Conditions: Atopic Dermatitis
Keywords: ANB020 etokimab eczema moderate to severe
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 302
Healthy volunteers: no

Brief summary:
This study is designed to evaluate the efficacy, safety, and pharmacokinetic (PK) profiles of multiple doses of etokimab in adult participants with atopic dermatitis (AD).

Detailed description:

Arms:
arm 1: Participants received matching placebo to etokimab, administered subcutaneously (SC) every 4 weeks (Q4W) for up to 16 weeks. arm 2: Participants received etokimab 20 milligrams (mg) administered SC Q4W for up to 16 weeks. arm 3: Participants received a 300 mg loading dose of etokimab on Day 1 then 150 mg etokimab administered SC every 8 weeks (Q8W) for up to 16 weeks. At Weeks 4 and 12 participants received placebo. arm 4: Participants received a 300 mg loading dose of etokimab on Day 1 then 150 mg etokimab administered SC Q4W for up to 16 weeks. arm 5: Participants received a 600 mg loading dose of etokimab on Day 1 then 300 mg etokimab administered SC Q4W for up to 16 weeks.

Interventions: intervention 1: Etokimab intervention 2: Placebo
Intervention descriptions: intervention 1: Humanized monoclonal antibody, administered by subcutaneous injection intervention 2: Administered by subcutaneous injection

Protocol document:
Prot_000.pdf: 
CLINICAL STUDY PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-
Ranging Study Investigating the Efficacy, Safety, and Pharmacokinetic 
Profile of ANB020 Administered to Adult Subjects with Moderate-to-Severe 
Atopic Dermatitis 
Short Title: 
Efficacy, Safety, and Pharmacokinetic Profile of  
 
ANB020 in Adults with Moderate-to-Severe 
 
Atopic Dermatitis 
Protocol Number: 
ANB020-005 
Amendment Number: 
Amendment 3 
Product: 
Etokimab (also known as ANB020) 
National Clinical Trial (NCT)  
Identified Number:   
NCT03533751 
Study Phase: 
2b 
EudraCT Number: 
2018-000331-27 
IND Number: 
137426 
IND Sponsor:  
AnaptysBio, Inc. 
 
10421 Pacific Center Court, Suite 200 
 
San Diego, CA  92121 United States 
Version Number:   
v.2.0 
Protocol Date:  
02 Jul 2019 
 
 
CONFIDENTIALITY STATEMENT 
This confidential information in this document is provided to you as an Investigator or consultant for 
review by you, your staff, and the applicable Institutional Review Board. Your acceptance of this 
document constitutes agreement that you will not disclose the information contained herein to others 
without written authorization from the Sponsor. 
 
 
 


Etokimab for Treatment of Atopic Dermatitis 
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02 Jul 2019  
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SUMMARY OF CHANGES FROM PREVIOUS VERSION 
One global protocol amendment and 3 country-specific amendments have been issued since the original 
protocol was issued on 19 March 2018 (see below). 
 
Version 
Date 
Original Protocol 
 
19 March 2018 
Global Protocol Amendments: 
Amendment 2 
 
23 October 2018 
Country-specific Protocol Amendments: 
Amendment 1 (Czech Republic) 
 
01 August 2018 
Amendment 1 (Germany) 
 
31 July 2018 
Amendment 1 (UK) 
 
20 June 2018 
 
Refer to Appendix A for Amendment 2 revisions and for all Amendment 1 revisions.  
Substantive changes to Amendment 3, a global protocol amendment, are summarized in Table 1.  
The overall rationale for this amendment reflects an update in statistical approach to the data analysis for 
this study. A hierarchical listing according to priority testing procedure will be employed for the primary 
and secondary endpoints, and thus, the secondary endpoints have been reorganized. Some previously 
secondary endpoints have become exploratory endpoints, and some previously exploratory endpoints 
have become secondary endpoints and clarifying time points for analysis have been added to some 
endpoints. In addition, an interim analysis has been introduced for the analysis of efficacy data at 
Week 16. The primary efficacy endpoint is the percent change in EASI score from Baseline to Week 16. 
The interim analysis will be performed once all subjects have completed the Week 16 visit and will 
comprise all efficacy data collected through Week 16 and all safety data collected as of the date of data 
cut-off. These updates and others are summarized in Table 1. 
Table 1. Summary of Changes for ANB020-005 Protocol Amendment 3 
Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
Entire protocol 
Editorial updates made to fix errors, make the 
document more navigable, and to be consistent 
with AnaptysBio Style Guide. 
Consistency, correctness, and readability  
Entire protocol 
Removed the term violation in regard to 
protocol deviations. Only the term deviation is 
now used. 
Consistency with reporting terminology. 
Sponsor Signature 
Page 
Updated statement of Sponsor’s compliance 
and approval of protocol 
Consistent with ICH expectations of 
Sponsor obligations and AnaptysBio use of 
Common Protocol Template 


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Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
Synopsis 
Section 3 
Re-ordered secondary and exploratory 
endpoints. Added clarifying time points to 
some endpoints. Added the safety and 
tolerability endpoints to the synopsis. Added 
additional endpoints of: 
 
Incidence of treatment-emergent adverse 
events 
 
Adverse events leading to discontinuation 
of study drug 
 
Adverse events resulting in death 
To align with changes to the statistical 
analyses 
Synopsis 
Added sample size and statistical methods 
sections to the synopsis 
Standard synopsis sections to note key 
statistical considerations. 
Section 3 
Revised the PK endpoints description for 
clarity 
Increased clarity for SAP 
Section 4.4 
Revised the definition of the end of study. 
Revised for clarity. 
Section 6.5.2 
Section 7.2 
Section 9.5.4 
Clarified definition of rescue 
medication/therapy and how subjects who 
receive rescue medication are to be handled. 
Clarified that systemic rescue medication is a 
reason for withdrawal from treatment. 
Increased clarity and instruction for study 
centers. Defines nonresponders for data 
analysis. 
Section 6.1.2 
Updated Tables 3 and 5 to clarify that the 
300/150 mg Q8W treatment group receives 
placebo at doses 2 and 4. 
Consistency with protocol body text. 
Section 6.4 
Section 7.1 
Section 7.2 
Clarified that subjects who miss 2 consecutive 
doses after the loading dose will be considered 
noncompliant with study drug and will be 
discontinued from the study. 
Clarification of study drug compliance 
Section 7.2 
Clarified that subjects who discontinue for 
pregnancy should also complete safety follow-
up assessments 
Accuracy and completeness 
Section 8.6.5 
Added text that clarifies Medical Monitor 
actions following an SAE entry into the eCRF. 
Clarifies the safety reporting process. 
Section 8.6.7 
Revised instructions for the treatment of a 
potential overdose of study treatment 
A protocol clarification letter on this subject 
was issued to study centers on 22 Jan 2019. 
This change aligns the protocol with the 
issued clarification letter language. 


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Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
Section 9 
Section 9.1 
Section 9.2 
Section 9.4 
Section 9.5 
Section 9.5.1 
Section 9.5.2 
Section 9.5.3 
Section 9.5.4 
Section 9.6 
Section 9.6.1 
Section 9.6.2 
Section 9.6.4 
Section 9.6.5 
These sections were significantly revised and 
re-ordered to reflect changes in the approach 
to statistical analysis for this study. Secondary 
efficacy endpoints now reflect a hierarchical 
testing procedure and other sections have been 
compressed or renamed to reflect the 
comprehensive update to the statistical 
analysis for this study.  
A hierarchical testing procedure will be 
employed for the primary and secondary 
endpoints, and thus, the secondary endpoints 
have been reorganized. Some previously 
secondary endpoints have become 
exploratory endpoints, and some previously 
exploratory endpoints have become 
secondary endpoints. Because of the 
comprehensive nature of the change to the 
statistical approach, the text of the statistical 
analysis sections required significant 
changes. 
Section 9.3 
(formerly Section 
9.2) 
Removed the ITT analysis set and revised the 
definitions of other analysis sets. 
Changes to the analysis sets made in 
conjunction with the changes to the 
statistical analyses. 
Section 9.7 
(formerly Section 
9.6) 
An interim analysis has been added  
The interim analysis was added in 
preparation for dose selection in the Phase 3 
study. 
Section 9.7.1 
This section, formerly titled Tabulation of 
Individual Participant Data has been deleted. 
This standalone section was removed as 
superfluous and information regarding the 
tabulation of individual participant data is 
covered in other sections. 
Section 10.1.2 
Added text that failure of the investigator to 
comply with ICH-GCP guidelines and FDA 
guidelines/regulations may result in early 
closure of the study center. 
Added for completeness and clarity. 
Section 10.1.5 
Updated Medical Monitor 
The Sponsor Medical Monitor for this study 
has changed, so the protocol has been 
updated to reflect the new Medical Monitor 
information. 
Section 10.1.6 
Updated DSMB information 
With the addition of the Week 16 interim 
analysis, subsets of data review provided to 
the DSMB are clarified. 
Section 10.1.9.2 
Clarified that study records should not be 
destroyed without prior authorization from the 
Sponsor. 
Revised for clarity and completeness. 
Section 10.1.10 
Added a list of protocol deviations that may 
affect the primary analysis 
The major protocol deviations according to 
ICH guidelines have been added, any 
additional deviations will be determined per 
discussion at the time of data review prior to 
database lock. 
Section 10.4 
Removed Section 10.4  
Improved information flow.  


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Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
Appendices 
Moved the Hanifin and Rajka Guidelines from 
Appendix B to Appendix N 
There were previously 2 Appendix B’s, this 
move retains the appendix numbering for 
the remaining appendices.  




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INVESTIGATOR’S AGREEMENT 
PROTOCOL TITLE:  A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-
Ranging Study Investigating the Efficacy, Safety, and Pharmacokinetic 
Profile of ANB020 Administered to Adult Subjects with Moderate-to-Severe 
Atopic Dermatitis 
PROTOCOL NO: ANB020-005 
AMENDMENT NO: Amendment 3 
This protocol is a confidential communication of the Sponsor. I confirm that I have read this 
protocol, I understand it, and I will work according to this protocol. I will also work consistently 
with the ethical principles that have their origin in the Declaration of Helsinki and that are 
consistent with Good Clinical Practices (GCPs) and the applicable laws and regulations. 
Acceptance of this document constitutes my agreement that no unpublished information contained 
herein will be published or disclosed without prior written approval from the Sponsor. 
 
Instructions to the Investigator:  Please SIGN and DATE this signature page. PRINT your name, title, and the name  
           of the study center in which the study will be conducted. Return the signed copy   
           to the Sponsor or designee. 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
Signature of Investigator:      ______________________________ 
Date:  _________________ 
Printed Name: 
______________________________ 
Investigator Title: 
______________________________ 
 
Name/Address of Center:  
______________________________ 
 
______________________________ 
 
______________________________ 
 
______________________________ 
 


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Table of Contents 
SUMMARY OF CHANGES FROM PREVIOUS VERSION ..................................................................... ii 
SPONSOR SIGNATURE PAGE................................................................................................................. vi 
INVESTIGATOR’S AGREEMENT .......................................................................................................... vii 
STATEMENT OF COMPLIANCE .............................................................................................................. 1 
1 
PROTOCOL SUMMARY ................................................................................................................ 2 
1.1 
Synopsis ................................................................................................................................... 2 
1.2 
Schema ..................................................................................................................................... 6 
1.3 
Schedule of Activities (SoA) ................................................................................................... 6 
2 
INTRODUCTION ............................................................................................................................. 9 
2.1 
Study Rationale ........................................................................................................................ 9 
2.2 
Background .............................................................................................................................. 9 
2.2.1 
Background of Disease ..................................................................................................... 9 
2.2.2 
Background of Etokimab ............................................................................................... 10 
2.3 
Risk/Benefit Assessment ....................................................................................................... 13 
2.3.1 
Known Potential Risks ................................................................................................... 13 
2.3.2 
Known Potential Benefits ............................................................................................... 14 
2.3.3 
Assessment of Potential Risks and Benefits................................................................... 14 
3 
OBJECTIVES AND ENDPOINTS ................................................................................................. 15 
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 .................................................................................................................. 19 
5.1 
Inclusion Criteria ................................................................................................................... 19 
5.2 
Exclusion Criteria .................................................................................................................. 20 
5.3 
Lifestyle Considerations ........................................................................................................ 22 
5.4 
Screen Failures....................................................................................................................... 22 
5.5 
Strategies for Recruitment and Retention .............................................................................. 22 
6 
STUDY INTERVENTION ............................................................................................................. 23 
6.1 
Study Intervention(s) Administration .................................................................................... 23 
6.1.1 
Study Intervention Description ...................................................................................... 23 
6.1.2 
Dosing and Administration ............................................................................................ 23 
6.2 
Preparation/Handling/Storage/Accountability ....................................................................... 25 
6.2.1 
Acquisition and accountability ....................................................................................... 25 
6.2.2 
Formulation, Appearance, Packaging, and Labeling ..................................................... 25 
6.2.3 
Product Storage and Stability ......................................................................................... 26 
6.2.4 
Preparation ..................................................................................................................... 26 
6.2.5 
Dosing Instructions ........................................................................................................ 26 
6.3 
Measures to Minimize Bias: Randomization and Blinding ................................................... 27 
6.3.1 
Randomization ............................................................................................................... 27 
6.3.2 
Blinding .......................................................................................................................... 27 


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6.4 
Study Intervention Compliance ............................................................................................. 28 
6.5 
Concomitant Therapy ............................................................................................................ 28 
6.5.1 
Allowed Medications ..................................................................................................... 28 
6.5.2 
Rescue Medicine ............................................................................................................ 29 
6.6 
Dose Modification ................................................................................................................. 29 
6.7 
Treatment After the End of the Study .................................................................................... 29 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ....................................................................................... 30 
7.1 
Discontinuation of Study Intervention ................................................................................... 30 
7.2 
Participant Discontinuation/Withdrawal from the Study ....................................................... 30 
7.3 
Lost to Follow-Up .................................................................................................................. 31 
8 
STUDY ASSESSMENTS AND PROCEDURES .......................................................................... 31 
8.1 
Efficacy Assessments ............................................................................................................ 32 
8.1.1 
Eczema Area and Severity Index (EASI) ....................................................................... 32 
8.1.2 
Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD™) 32 
8.1.3 
Severity Scoring of Atopic Dermatitis (SCORAD) ....................................................... 33 
8.1.4 
Dermatology Life Quality Index (DLQI) ....................................................................... 33 
8.1.5 
Patient Oriented Eczema Measure (POEM) ................................................................... 33 
8.1.6 
Numerical Rating Scale for Pruritus .............................................................................. 33 
8.1.7 
Asthma Control Questionnaire-6 ................................................................................... 34 
8.1.8 
Body Surface Area ......................................................................................................... 34 
8.2 
Safety Assessments ................................................................................................................ 34 
8.2.1 
Physical Examinations ................................................................................................... 34 
8.2.2 
Vital Signs ...................................................................................................................... 35 
8.2.3 
12-Lead ECG ................................................................................................................. 35 
8.2.4 
Clinical Laboratory Data ................................................................................................ 35 
8.2.5 
Pregnancy Testing .......................................................................................................... 36 
8.3 
Pharmacokinetics ................................................................................................................... 36 
8.4 
Biomarkers ............................................................................................................................. 37 
8.5 
Immunogenicity ..................................................................................................................... 37 
8.6 
Adverse Events and Serious Adverse Events ........................................................................ 38 
8.6.1 
Definition of Adverse Events (AE) ................................................................................ 38 
8.6.2 
Time Period and Frequency for Collecting AE and SAE Information .......................... 38 
8.6.3 
Method of Detecting AEs and SAEs .............................................................................. 38 
8.6.4 
Follow-Up of AEs and SAEs ......................................................................................... 38 
8.6.5 
Regulatory Reporting Requirements for SAEs .............................................................. 39 
8.6.6 
Pregnancy ....................................................................................................................... 39 
8.6.7 
Overdose of Study Drug ................................................................................................. 40 
8.7 
Unanticipated Problems ......................................................................................................... 40 
8.7.1 
Definition of Unanticipated Problems ............................................................................ 40 
8.7.2 
Unanticipated Problem Reporting .................................................................................. 41 
8.7.3 
Reporting Unanticipated Problems to Participants ........................................................ 41 
9 
STATISTICAL CONSIDERATIONS ............................................................................................ 41 


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9.1 
Sample Size ........................................................................................................................... 42 
9.2 
Statistical Hypothesis ............................................................................................................. 42 
9.3 
Populations for Analyses ....................................................................................................... 43 
9.4 
Baseline Definition ................................................................................................................ 43 
9.5 
Efficacy Analyses .................................................................................................................. 43 
9.5.1 
Primary Efficacy Endpoint ............................................................................................. 44 
9.5.2 
Secondary and Exploratory Endpoints ........................................................................... 44 
9.5.3 
Multiplicity ..................................................................................................................... 44 
9.5.4 
Handling of Dropouts and Missing Data ........................................................................ 44 
9.6 
Safety Analyses ..................................................................................................................... 45 
9.6.1 
Adverse events and serious adverse events .................................................................... 45 
9.6.2 
Deaths ............................................................................................................................. 45 
9.6.3 
Physical examinations, 12-lead ecg, Vital signs, and clinical safety laboratory tests 
(hematology, biochemistry, and urinalysis) ................................................................. 46 
9.6.4 
Subject disposition ......................................................................................................... 46 
9.6.5 
Subject characteristics and medical history .................................................................... 46 
9.6.6 
Concomitant medications ............................................................................................... 46 
9.7 
Interim Analyses .................................................................................................................... 47 
9.8 
SubGroup Analyses ............................................................................................................... 47 
9.9 
Immunogenicity Analyses ..................................................................................................... 47 
9.10 
Other Analyses....................................................................................................................... 47 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .................. 48 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ..................................................... 48 
10.1.1 
Informed Consent Process .............................................................................................. 48 
10.1.2 
Study Discontinuation and Closure ................................................................................ 49 
10.1.3 
Confidentiality and Privacy ............................................................................................ 49 
10.1.4 
Future Use of Stored Specimens and Data ..................................................................... 50 
10.1.5 
Key Roles and Study Governance .................................................................................. 50 
10.1.6 
Data and Safety Monitoring Board ................................................................................ 51 
10.1.7 
Clinical Monitoring ........................................................................................................ 51 
10.1.8 
Quality Assurance and Quality Control ......................................................................... 52 
10.1.9 
Data Handling and Record Keeping ............................................................................... 52 
10.1.10 
Protocol Deviations ........................................................................................................ 54 
10.1.11 
Publication and Data Sharing Policy .............................................................................. 55 
10.1.12 
Conflict of Interest Policy .............................................................................................. 55 
10.2 
Additional Considerations ..................................................................................................... 55 
10.2.1 
Regulatory and Ethical Considerations .......................................................................... 55 
10.2.2 
Amendment Policy ......................................................................................................... 56 
10.3 
Abbreviations ......................................................................................................................... 57 
11 
REFERENCES ................................................................................................................................ 59 
APPENDICES ............................................................................................................................................ 60 
Appendix A: Summary of Changes for (Country-Specific) Amendment 1 ................................................ 60 
Appendix B: Clinical Laboratory Tests ...................................................................................................... 68 




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STATEMENT OF COMPLIANCE 
 
The trial will be conducted in accordance with the protocol, International Conference on 
Harmonisation Good Clinical Practice (ICH GCP) and applicable United States (US) Code of 
Federal Regulations (21 CFR). The Principal Investigator (PI) will assure that no deviation from, 
or changes to the protocol will take place without prior agreement from the Investigational New 
Drug (IND) Sponsor, funding agency and documented approval from the Institutional Review 
Board (IRB)/Independent Ethics Committees (IECs), except where necessary to eliminate 
an immediate hazard(s) to the trial participants. All personnel involved in the conduct of this 
study have completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent forms (ICFs), recruitment materials, and all participant materials 
will be submitted to the IRB/IEC for review and approval. Approval of both the protocol and the 
informed consent form must be obtained before any participant is enrolled. Any amendments to 
the protocol, ICFs, recruitment materials, and all participant materials will require review and 
approval by the IRB/IEC before the changes are implemented to the study. All changes to the 
ICF will be IRB and IEC approved prior to implementation; a determination will be made 
regarding whether a new informed consent needs to be obtained from participants who provided 
informed consent, using a previously approved ICF. 
 
 


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PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
Title: 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 
Dose-Ranging Study Investigating the Efficacy, Safety, and 
Pharmacokinetic Profile of ANB020 Administered to Adult Subjects with 
Moderate-to-Severe Atopic Dermatitis 
Short Title: 
Efficacy, Safety, and Pharmacokinetic Profile of ANB020 in Adults with 
Moderate-to-Severe Atopic Dermatitis 
Protocol Number: 
 
ANB020-005 
Study Description: 
This is a randomized, double blind, placebo controlled, parallel group, dose 
ranging, Phase 2b study designed to assess the efficacy of different doses 
and dose regimens of ANB020 (etokimab) compared to placebo in adult 
subjects with moderate to severe atopic dermatitis (AD). This study will 
also assess the efficacy, safety, tolerability, and pharmacokinetics (PK) of 
etokimab. This study will monitor the effects of etokimab on moderate to 
severe AD subjects over a period of 24 weeks. 
The study will have a screening period of up to 4 weeks (Week -4 to 0) 
prior to administration of study drug on Day 1, treatment period of 16 
weeks (Week 0 to 16), and safety follow-up period of 8 weeks (Week 16 to 
24). 
During the screening period, all subjects will undergo evaluation for 
eligibility. The subjects will be randomized on Day 1 to one of the 
following 5 treatment arms in a 1:1:1:1:1 ratio: 
• 
Etokimab 20 mg subcutaneous (SC) every 4 weeks (Q4W) 
• 
Etokimab 300 mg load + 150 mg SC Q4W 
• 
Etokimab 300 mg load + 150 mg SC every 8 weeks 
• 
Etokimab 600 mg load + 300 mg SC Q4W 
• 
Placebo 
The subjects will be administered study drug SC during onsite visits on 
Day 1 (Week 0), Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 
12). The subjects will remain on site for 2 hours for postdose assessments at 
Weeks 0, 4, 8, and 12. Additional visits will occur at Day 5 (Week 1), 
Day 15 (Week 2), Day 92 (Week 13), and Day 113 (Week 16) during the 
treatment period. 
For the safety follow-up visit, the subject will return to the study center on 
Day 141 (Week 20) and Day 169 (Week 24). The End of Study (EOS) visit 
will be on Day 169 (Week 24) (see Section 1.3). 
The subject’s disease activity (response to study treatment) will be 
evaluated using the Eczema Area and Severity Index (EASI), Validated 
Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD), and 
Scoring Atopic Dermatitis (SCORAD) assessments. The patient reported 
outcome measurements (Patient Oriented Eczema Measure [POEM], 
Asthma Control Questionnaire-6 [ACQ-6], and Dermatology Life Quality 
Index [DLQI]) will be performed first at visits mentioned in the Schedule 
of Activities (SOA) (see Section 1.3) before any other study procedures 
(except informed consent at screening visit). Dermatology Life Quality 


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Index and POEM questionnaire will be administered only to the subset of 
subjects who can read and understand a language in which questionnaire is 
presented (based on availability of validated translations in participating 
countries). The ACQ-6 will be assessed only in subjects with active asthma 
disease whose primary language is (based on availability of validated 
translations in participating countries). The numerical rating scale (NRS) 
for pruritus, also a patient reported outcome measurement, will be 
completed daily via an electronic patient reported outcomes (ePRO) device. 
Serum samples for PK and immunogenicity will be collected before the 
administration of study drug and at the other time points specified in the 
SOA (see Section 1.3). 
Safety assessments including adverse event (AE)/serious adverse event 
(SAE) monitoring, vital signs, physical examination, electrocardiograms 
(ECGs), and laboratory measurements will be performed as specified in 
SOA (see Section 1.3). A Data Safety Monitoring Board (DSMB) will be 
instituted to periodically review and evaluate the study data for subject’s 
safety and advise the Sponsor of potential safety signals (see Section 
10.1.6). 
Objectives: 
 
Primary Objective: 
 
To evaluate the effects of etokimab on skin lesions 
 
Secondary Objectives:   
 
To evaluate the safety and tolerability of etokimab 
 
To evaluate the effects of etokimab on pruritus symptoms 
 
To evaluate the effects of etokimab on quality of life (QoL) 
Endpoints: 
Primary Endpoint: 
 
Percent change in EASI score from Baseline to Week 16. 
Secondary Efficacy Endpoints: 
At Week 16 and other clinical assessment time points, unless otherwise 
indicated: 
 
Proportion of subjects with EASI-50 (≥50% improvement from 
Baseline) 
 
Proportion of subjects with EASI-75 (≥75% improvement from 
Baseline) 
 
Proportion of subjects with EASI-90 (>90% improvement from 
Baseline) 
 
Proportion of subjects who achieve vIGA-AD score reduction of ≥2 
 
Proportion of subjects who achieve vIGA-AD response of 0 (clear) 
or 1 (almost clear) 
 
Proportion of subjects who achieve NRS for pruritus score 
reduction from Baseline of ≥4 
 
Percent change in peak weekly averaged NRS for pruritus score 
from Baseline  
 
Percent change in SCORAD scores from Baseline  
 
Change from Baseline in DLQI  
Safety and Tolerability Endpoints: 
 
Incidence of AEs 
 
Incidence of SAEs 


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 
Incidence of Treatment Emergent Adverse Events (TEAEs) 
 
AEs leading to discontinuation of study drug 
 
AEs leading to withdrawal from the study 
 
AEs resulting in death 
 
Changes in vital signs (blood pressure [BP], temperature, 
respiration rate, heart rate [HR], and weight) 
 
Changes in clinical safety laboratory tests (hematology, chemistry, 
and urinalysis) 
 
Changes in ECG parameters 
 
Immunogenicity (anti-drug antibody [ADA] and neutralizing ADA) 
Study Population: 
Approximately 300 adults between the ages of 18 and 75 years of age with 
clinically diagnosed AD based on Hanifin/Rajka criteria with symptoms 
present for at least 6 months prior to Baseline. Eligible subjects must also 
have a body mass index of 18 ≤35 kg/m2, and an EASI score of ≥16, body 
surface area (BSA) involvement of ≥10%, and a vIGA-AD score (5-point 
scale) ≥3 at screening and Baseline.  
Phase: 
2b 
Description of 
Sites/Facilities 
Enrolling Participants: 
Approximately 83 investigators and study centers across the United States, 
Canada, and Europe are expected to participate in this study.  
Approximately 300 subjects will be randomly assigned to study treatment 
for an estimated total of approximately 60 evaluable subjects per treatment 
group. 
Description of Study 
Intervention: 
Etokimab or matching placebo for SC injection: 
 
Sterile etokimab in single-use glass vials; each vial will contain 
100 mg/mL of etokimab 
 
Sterile placebo in single-use glass vials; each vial will contain no 
active drug product 
See Figure 1 for dosing regimen.  
Study Duration: 
Study duration will last approximately 12 months.  
Participant Duration: 
The study will have a screening period of up to 4 weeks (Weeks -4 to 0), 
treatment period of 16 weeks (Week 0 to 16), and safety follow-up period 
of 8 weeks (Week 16 to 24). 
Sample Size 
The expected efficacy response (and variability) for active and placebo 
response (related with percent change from Baseline in EASI score to 
Week 16) was estimated after review of 5 previous studies in subjects with 
moderate-to-severe AD subjects not taking topical corticosteroids.  
In this way, a total sample of approximately 300 subjects (60 subjects per 
treatment arm) achieves more than 95% power to detect differences among 
the means versus the alternative of equal means using an F test with a 
0.05000 significance level. The size of the variation in the means is 
represented by their standard deviation which is 18.59. The common 
standard deviation within a group is assumed to be 50.00. 
The hypothesized means used to compute the sample size derived from the 
studies mentioned before are: -20 -44. -65.4 -66.4 -68 (for placebo and each 
active treatment arm respectively) with a covariate R-squared of 0.300. 


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Statistical Methods 
All data listings, summaries, and analyses will be performed under the 
guidance and approval of the Sponsor.  
Descriptive statistics will be used for all variables, as appropriate. 
Continuous variables will be summarized by the number of observations, 
mean, standard deviation, median, minimum, and maximum. Categorical 
variables will be summarized by frequency counts and percentages for each 
category. Unless otherwise stated, percentages will be calculated out of the 
total population for each treatment arm.  
The primary endpoint will be assessed using ANCOVA with baseline EASI 
score as a covariate. Endpoints involving differences in proportion will be 
assessed using logistic regression with baseline EASI score and treatment 
type as a covariate. 
All safety data will be summarized using descriptive statistics.  
An Interim Analysis (IA) will be performed when 100% of subjects 
complete their 16-Week for final assessment of all primary and secondary 
efficacy endpoints (for Week 16) and all safety data available (up to 
Week 24). Final database lock will include exploratory efficacy and safety 
analysis for all subjects for Weeks 20 and 24. 
Additional details about the statistical methods including, but not limited, 
analysis sets, missing data strategies, etc. will be provided in the body of 
the protocol and the Statistical Analysis Plan (SAP) which will be prepared 
as a separate document prior to database lock.  








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k Pharmacokinetics blood samples will be collected at the following time points:  
 
Visit 2: prior to dosing. 
 
Visit 3: any time during the visit. Visit 3 must occur 3 to 5 days after Visit 2 regardless of visit window. 
 
Visit 4: any time during the visit.  
 
Visits 5, 6, and 7: prior to dosing. 
 
Visits 8: any time during the visit. Visit 8 must occur 2 to 13 days after Visit 7 regardless of visit window. 
 
Visits 9, 10, and 11: any time during each visit. 
Samples should be obtained prior to administering study drug if an administration coincides with the visit. 
l 
Immunogenicity blood samples will be collected for all subjects at the following time points:  
 
Visits 2, 5, 6, and 7: prior to dosing. 
 
Visits 9, 10, and 11: any time during each visit. 
 
Samples should be obtained prior to administering study drug if an administration coincides with the visit. 
m Subject will be instructed to perform this assessment daily in their ePRO device. Subject will be retrained as needed to be compliant with these assessments 
upon review at each visit by staff.  
n 
Patient-reported outcome measurements should be done first at mentioned visits before any other study procedures (except informed consent at screening 
visit). 
o The ACQ-6 will be assessed only in subjects with an active asthma disease, whose primary language is English (based on availability of validated translations 
in participating countries). 
p Subject is required to remain on site for 2 hours post injection at Weeks 0, 4, 8, and 12 for observation. 
q The ePRO device will be dispensed to the subject at the screening visit with training on login and completion of scales/questions. The subjects should bring 
ePRO device to each visit. The ePRO device should be returned to the site at the Week 24 (EOS) visit. If the Subject is discontinued from the study for any 
reason, the ePRO device will be returned to the site within 7 days of subject notification, otherwise the ePRO device will be collected at EOS. 
r 
Concomitant therapy will include pharmacologic and nonpharmacologic therapies. 


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2 
 
INTRODUCTION 
 
2.1 
STUDY RATIONALE  
Current therapy for moderate to severe atopic dermatitis (AD) is limited. Typical treatment modalities 
include nonsystemic treatment with emollients, topical corticosteroids, topical phosphodiesterase 
4 inhibitors, and topical calcineurin inhibitors. The majority of patients achieve disease control with these 
standard nonsystemic treatments. However, due to disease severity, treatment-related adverse reactions, 
or other factors, some patients do not achieve adequate disease control. Thus, there is need for long-term 
therapeutic control in moderate to severe AD. The IL-33 plays an important role in T-helper 2 
(Th2)-mediated cellular immunity, and in the pathogenesis of AD.1,2,3 It functions as a pleiotropic 
inflammatory cytokine orchestrating a diverse array of cellular immune responses and potently drives 
production of Th2 cell associated cytokines such as IL-4, IL-5 and IL-13. Monoclonal antibodies (mAbs) 
targeting such cytokines might represent a novel approach to control AD. Etokimab is a humanized mAb 
that specifically neutralizes human IL-33, thereby blocking the interaction of IL-33 with the IL-33 
receptor, ST2, and subsequently inhibiting IL-33 driven downstream signaling and cellular responses. 
Targeting IL-33 with etokimab should impact the downstream Th2 cell cytokines involved in AD 
pathogenesis, and may provide a novel beneficial therapy to subjects with AD. This study is designed to 
evaluate the efficacy, safety, and pharmacokinetic (PK) profile of etokimab in subjects with moderate to 
severe AD.  
2.2 
BACKGROUND  
2.2.1 BACKGROUND OF DISEASE 
Atopic dermatitis is a common chronic inflammatory skin disease that affects both children and adults 
with a prevalence of 30% and 10%, respectively.4 The hallmarks of AD are chronic, relapsing episodes of 
skin inflammation with disturbance of epidermal barrier function that culminates in dry skin.5 AD is often 
associated with elevated serum immunoglobulin (IgE) levels and a personal or family history of Type 1 
allergies, allergic rhinitis, or asthma.6 The etiology of AD is not entirely understood but involves a 
multiplicity of factors, including skin barrier abnormalities, defects in innate immunity response, Th2-
skewed adaptive immune response, and altered skin resident microbial flora. AD is often associated with, 
or is a prelude to the development of asthma, and other allergic diseases. The combination of these 
conditions and their interleaved progression has been defined as the atopic march. The interconnectivity 
among all these conditions, forming the atopic march, suggests that common pathogenic mechanisms are 
shared amongst all these conditions. In this context, growing evidence indicates that IL-33 is one of the 
key initiators of this shared pathogenic cascade. 
Current therapies for AD have limited efficacy in moderate to severe disease and most are focused on 
topical treatments such as corticosteroids and calcineurin inhibitors. Majority of the subjects achieve 
disease control with these standard nonsystemic treatments. However, there is a significant need for new 
effective systemic therapies for AD that is not controlled with optimal topical therapy. Biologics have 
been considered for the treatment of subjects with severe AD. Dupilumab, an mAb that blocks the action 
of the Th2 cytokines, IL-4, and IL-13, has been tested in clinical studies in AD. The results of these 
clinical studies have indicated that this mAb provided reduction in the signs and symptoms of disease and 


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led to its approval for the treatment of AD in the United States and European Union. This is encouraging 
for the development of etokimab, which targets IL-33, upstream of IL-4, IL-13, and other Th2 cytokines. 
Etokimab would offer an additional treatment approach to this disease where there remains a need for 
novel effective therapies. 
2.2.2 BACKGROUND OF ETOKIMAB 
Etokimab has been adopted as the non-proprietary name for ANB020. Therefore, ANB020 will be 
referred to as etokimab, interchangeably, in this clinical study protocol.  
Etokimab is a first-in-class, anti-interleukin-33 therapeutic antibody to treat Th2 cell driven inflammatory 
diseases with underlying interleukin (IL)-33 dysregulation. Etokimab is a humanized immunoglobulin 
subtype G1/kappa (IgG1/kappa) mAb that specifically neutralizes the biological effects of human IL-33, a 
member of the IL-1 superfamily7 and a multifunctional cytokine that plays an important role in Th2 
mediated cellular immunity and in the pathogenesis of atopic diseases.1,2 Etokimab binds to and inhibits 
the interaction of IL-33 with its specific cell surface receptor (ST2) thereby blocking IL-33 driven 
downstream signaling and subsequent cellular responses. It is being developed for the treatment of atopic 
diseases, such as eosinophilic asthma and chronic rhinosinusitis with nasal polyps. 
2.2.2.1 NONCLINICAL STUDIES WITH ETOKIMAB 
Etokimab is being developed by AnaptysBio Inc. as a lead drug candidate and exhibits strong inhibitory 
activity for human as well as cynomolgus monkey IL-33. Nonclinical data obtained from studies with 
etokimab in primary human and cynomolgus monkey cells, and from in vivo nonhuman primate studies 
demonstrated that: 
• 
Etokimab shows reactivity with human and cynomolgus monkey IL-33 (dissociation constant of 
1 pM vs 37 pM, respectively), but not with mouse or rat IL-33. 
• 
In primary human and cynomolgus monkey cell populations, in peripheral blood mononuclear cells 
and human whole blood, etokimab inhibited IL-33 induced interferon gamma (IFN-γ) production. In 
human basophils, etokimab also inhibited IL-33 induced IL-5 production. 
• 
Etokimab can reduce eosinophilia in mice treated with human IL-33. 
• 
The observed serum apparent terminal half-life (t1/2) of etokimab in cynomolgus monkeys was 
160 hours after a single intravenous (IV) dose administration, and 187 hours after a single 
subcutaneous (SC) dose administration at 10 mg/kg, consistent with the anticipated PK characteristics 
for a human IgG1 scaffold mAb in the monkey. 
• 
A multiple dose, good laboratory practice compliant toxicology and toxicokinetic study (4- and 
13-week duration with recovery phase) has been conducted with etokimab administered by SC and 
intravenous (IV) injection to cynomolgus monkeys. These studies produced no significant test article 
related effects and established a No Observed Adverse Effect Level of 50 mg/kg, the highest dose 
tested. 


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These data, together with nonclinical safety data generated, supported a strong scientific rationale for 
advancing etokimab into clinical development. 
For detailed nonclinical experience with etokimab, refer to the Etokimab Investigator’s Brochure (IB). 
2.2.2.2 CLINICAL STUDIES WITH ETOKIMAB 
Etokimab has been administered to humans in 2 phase 1 healthy volunteer studies (ANB020-001 and 
ANB020-BA-01) and a phase 2a proof-of-concept study (ANB020-002) in patients with moderate to 
severe AD. Detailed clinical experience with etokimab is provided in the Etokimab IB.  
2.2.2.2.1 STUDY ANB020-001 
Study ANB020-001 was a first-in-human (FIH), phase 1 study in healthy subjects. In the single ascending 
dose (SAD) phase of the study, 64 healthy subjects were enrolled into 8 treatment arms of 8 subjects each 
(6 etokimab + 2 placebo per treatment arm). Of these 64 subjects, 24 subjects received etokimab by SC 
injection (6 each at dose levels of 10, 40, 100, and 300 mg); 24 subjects received etokimab by IV infusion 
(6 each at dose levels of 40, 100, 300 and 750 mg); 8 subjects received placebo by SC injection; and 
8 subjects received placebo by IV infusion. In the single-dose portion of the study, etokimab was 
generally well tolerated in male and female healthy volunteers, ages 19 to 44 years of age, when 
administered as a single dose of etokimab of up to 300 mg SC and up to 750 mg IV. A total of 81% of 
subjects in the placebo group and 79% of subjects in the etokimab group had at least 1 treatment-
emergent adverse event (TEAE) during the study. The most commonly reported TEAEs were upper 
respiratory tract infection (etokimab 48%, placebo 50%), headache (etokimab 27%, placebo 31%), 
abdominal pain (etokimab 6%, placebo 0%), nausea (etokimab 4%, placebo 0%), vomiting (etokimab 4%, 
placebo 0%), urticaria (etokimab 4%, placebo 0%), and fatigue (etokimab 4%, placebo 0%). 
In the SAD cohort, 1 serious adverse event/suspected unexpected severe adverse reaction (SAE/SUSAR) 
occurred in a subject who was randomly assigned to etokimab (750 mg) as a single IV injection. The 
subject developed severe neutropenia (
 
 on Day 22 post-dose. The neutrophils level remained 
clinically significantly low (
 
) on Day 24, but the level returned to normal range by Day 29. 
The subject reported to have had prodromal viral symptoms prior the neutropenia episode and clear 
clinical manifestations (adenoapathy) of an ongoing viral infection. This might indicate that concomitant 
(viral infection) factors could have triggered the neutropenia episode. However, it cannot be formally 
excluded that IL-33 neutralization might have had a contributing role in the neutropenic episode. 
The multiple ascending dose (MAD) phase of the study, 32 subjects were enrolled into 4 treatment arms 
of 8 subjects each (6 etokimab + 2 placebo per treatment arm). Of the 32 subjects enrolled, 18 subjects 
received etokimab by IV infusion (6 each at dose levels of 40, 100, and 300 mg weekly); 6 subjects 
received etokimab by SC injection (at a dose level of 100 mg weekly); 6 subjects received multiple doses 
of placebo by IV infusion; and 2 subjects received multiple doses of placebo by SC injection. In the 
multiple dose portion of the study, etokimab was well tolerated in healthy male and female adult 
volunteers ages 18 to 45 years, when administered once-weekly for 4 weeks at 100 mg SC and at up to 
300 mg as a multiple-dose IV. A total of 24 subjects (75%) had at least 1 TEAE, including, 5 of 


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6 subjects (83%) following SC injection of etokimab, 13 of 18 subjects (72%) following IV infusion of 
etokimab, and 6 of 8 subjects (75%) following administration of placebo, with a total of 45 TEAEs.  
Most adverse events (AEs) were mild in severity (25 of 45 AEs, 56% of all AEs); 19 AEs (42%) were 
classified as moderate; and 1 AE was classified as severe (2%). Treatment-emergent AEs deemed to be 
related to study drug administration were reported in 17 of 32 subjects (53%). Of the TEAEs deemed to 
be related to study drug, 2 AEs were reported in 2 subjects (33%) who received etokimab SC, 14 AEs 
were reported in 11 subjects (61%) who received etokimab via IV infusion, and 4 AEs were reported in 
4 subjects (50%) who received placebo. Of the AEs deemed related to study drug, 8 AEs were mild in 
severity, 12 AEs were moderate in severity and 1 was considered severe.  
2.2.2.2.2 STUDY ANB020-BA-01 
Study (ANB020-BA-01) was a phase 1 study to assessed PK, safety, and tolerability of a single 100 mg 
SQ or IV dose of etokimab (current new formulation compared to Study ANB020-001) in healthy male 
and female subjects. The PK results of Study ANB020-BA-01 are consistent with results of Study 
ANB020-001. Administration of a single dose of etokimab 100 mg SQ injection or IV infusion was safe 
and well-tolerated in healthy male and female subjects. There were no new or unexpected safety findings 
compared to Study ANB020-001.  
2.2.2.2.3 STUDY ANB020-002 
Study ANB020-002 was a phase 2a, proof-of-concept, placebo-controlled, open-label study that evaluated 
the etokimab activity upon house dust mite skin challenge in 12 subjects with moderate to severe AD at a 
single center in the United Kingdom. This study was also conducted to assess the safety and tolerability 
of etokimab in patients with moderate to severe AD. 
All 12 subjects included in the Safety Analysis Set experienced at least 1 TEAE during the study. During 
the placebo period (from Day 1 to Day 8 prior to etokimab administration), 8 (66.7%) subjects 
experienced at least 1 TEAE and after administration of etokimab (on Day 8), 11 (91.7%) subjects 
experienced at least 1 TEAE. A total of 10 (83.3%) subjects experienced at least 1 TEAE considered 
related to etokimab by the Investigator. Only 1 (8.3%) subject experienced an SAE (exacerbation of 
pre-existing depression) after etokimab administration of severe intensity and considered to be unrelated 
to study drug. None of the subjects discontinued the study due to a TEAE. The most commonly reported 
TEAEs were dizziness and headache (3 subjects [25%] each) followed by upper respiratory tract 
infection, urinary tract infection, peripheral swelling, cough, and urticaria (2 subjects [16.7%] each).  
The mean total Eczema Area and Severity Index (EASI) score decreased statistically significantly after 
the administration of etokimab. On Day 15, the mean total EASI score was 19.2 and the mean treatment 
difference from Baseline in the total EASI score was -10.8. On Day 22 and Day 36, the mean treatment 
difference from Baseline in the total EASI score was -16.3 (p-value<0.0001) and -17.5 (p-value=0.0008), 
respectively.  


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2.3 
RISK/BENEFIT ASSESSMENT   
 
2.3.1 KNOWN POTENTIAL RISKS  
Etokimab has been extensively tested in animals and there were no etokimab-related adverse findings. 
The administration of etokimab had no effect on hematology, coagulation, clinical chemistry, or 
urinalysis test results. Etokimab was found to be safe and well tolerated in a phase 1 study (ANB020-001) 
in healthy subjects. There were no deaths during the study. In the phase 1 SAD study, no change in vital 
signs (blood pressure [BP], heart rate [HR], electrocardiogram [ECG], or body temperature) were noted. 
Hematology parameters, such as erythrocyte, white blood cell and platelets counts were all within the 
normal range except in 1 volunteer in the 750 mg dose group who reported a SAE of neutropenia 
considered as possibly related to the study treatment. All others did not show any modification or trend 
related to etokimab dosing.  
Serum chemistry results were also all in the normal range. A total of 81% subjects in the placebo group 
and 79% subjects in the etokimab group had at least 1 TEAE during the study. The most commonly 
reported TEAEs of mild to moderate intensity included upper respiratory tract infection (50% versus 48% 
in placebo and etokimab group, respectively) and headache (32% versus 27% in placebo and ANB020 
group, respectively). Of all the AEs reported across all dose groups, 44% were reported as possible 
related and 36% were reported as unrelated. One SAE of decreased neutrophils was reported in the 
750 mg dose group which resolved prior to the study completion with no sequelae. No other observations 
of decreased neutrophils were observed. No dose dependent AE presentation was evident. 
There were no SAEs in MAD phase of the study. One severe AE of elevated transaminase was reported in 
the MAD phase of the study. Of the 32 subjects, 24 reported a total of 45 TEAEs; 5 of 6 subjects (83%) 
following SC administration, 13 of 18 subjects (72%) following IV administration, and 6 of 8 subjects 
(75%) following placebo administration. Most of the AEs were mild in severity (25 of 45 [56%] 
subjects), 19 (42%) AEs were considered moderate and 1 AE was classified as severe AE (2%). Of the 
32 subjects, 17 subjects (53%) reported TEAEs considered related to the study drug. Of these, 2 AEs were 
reported in 2 subjects (33%) who received etokimab via IV infusion and 4 AEs were reported in 
4 subjects who received placebo. The most commonly reported AEs were headache, upper respiratory 
tract infection, and abdominal pain. 
One SAE of hospitalization for depression (exacerbation of pre-existing depression) of severe intensity 
was reported in Study ANB020-002. A 
r-old 
 patient with a moderate to severe AD 
who experienced the SAE 157 days after receiving a single dose of etokimab 300 mg IV. The event was 
considered unlikely related to the study drug by the Investigator and Sponsor. 
Although there is no evidence to date for an allergic/anaphylactic reaction to etokimab, such a reaction to 
either the active protein or excipients is possible. Some symptoms of allergic reactions are rash, wheezing 
or difficulty breathing, dizziness or fainting (also a possible outcome of a drop in BP), swelling around 
the mouth, throat or eyes, a fast HR, or sweating. Subjects with true allergic/anaphylactic reactions should 
not receive further doses of the product. 
Monoclonal antibodies may also be associated with reactions that are clinically indistinguishable from 
true allergic/anaphylactic reactions, but which are mediated through direct release of cytokines or other 


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pro-inflammatory mediators. Such reactions may be termed infusion-related reactions. Infusion-related 
reactions typically occur with the first administration of a monoclonal antibody product and are generally 
less frequent and/or less severe with subsequent doses. 
Allergic/anaphylactic reactions and infusion-related reactions typically begin during, or within several 
hours of dose administration. The onset of symptoms may be rapid, and some reactions may be life 
threatening. Etokimab should be administered in an environment under close supervision of a physician 
and where full resuscitation facilities are immediately available. 
Resistance to the therapeutic effects of mAbs can occur in rare cases due to development of neutralizing 
antibodies by the patient's immune system. 
Details about specific risks for subjects in this clinical trial can be found in the etokimab IB and informed 
consent form (ICF). 
2.3.2 KNOWN POTENTIAL BENEFITS  
A subject with AD may or may not receive direct benefit from participating in this study. Details about 
specific benefits for subjects in this clinical study are provided in the Etokimab IB and ICF. 
Based upon the inhibition of IL-33 by the study drug and pre-clinical study and early phase 2 results, 
subjects with AD who are randomized to active treatment may benefit from treatment with etokimab. 
Participation in this study may help develop important scientific knowledge that could contribute to the 
development of a new novel medication to be used in the treatment of subjects who suffer from AD, 
asthma, and food allergies. 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
In clinical development to date, etokimab (administered by SC or IV) has been shown to be generally well 
tolerated at all dose levels without any systemic or local safety concerns.  






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Safety and Tolerability Endpoints:  
The safety and tolerability endpoints of this study are as follows: 
 
Incidence of AEs. 
 
Incidence of SAEs  
 
Incidence of TEAEs 
 
AEs leading to discontinuation of study drug 
 
AEs leading to withdrawal from the study 
 
AEs resulting in death 
 
Changes in vital signs (BP, temperature, respiration rate, HR, and weight). 
 
Changes in clinical safety laboratory tests (hematology, chemistry, and urinalysis). 
 
Changes in ECG parameters. 
 
Immunogenicity (anti-drug antibody [ADA] and neutralizing ADA). 
Pharmacokinetic Endpoints (exploratory):  
A limited sampling strategy to collect samples of whole blood will be implemented for the determination 
of etokimab in human serum for PK assessment following SC administration. PK concentration data 
collected from the study may be included in a population PK-based (meta-) analysis, using non-linear 
mixed effects modeling. 
The PK endpoints for this study are as follows: 
 
Apparent clearance (CL/F) of etokimab  
 
Apparent volume of distribution (Vd/F) of etokimab  
 
Area under the curve (AUC) for the first and last dose 
 
Maximum concentration (Cmax) for the first and last dose 
 
tmax for the first and last dose  
 
t1/2 for the last dose 
4 
STUDY DESIGN  
 
4.1 
OVERALL DESIGN 
This is a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging, phase 2b study 
designed to assess the efficacy of different doses and dose regimens of etokimab compared to placebo in 
adult subjects with moderate to severe AD. This study will also assess the efficacy, safety, tolerability, 
and PK of etokimab. This study will monitor the effects of etokimab on moderate to severe AD subjects 
over a period of 24 weeks. 
The study will have a screening period of up to 4 weeks (Week -4 to 0) prior to administration of study 
drug on Day 1, treatment period of 16 weeks (Week 0 to 16) and safety follow-up period of 8 weeks 
(Week 16 to 24). 


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During the screening period, all subjects will undergo evaluation for eligibility. The subjects will be 
randomized on Day 1 to one of the following 5 treatment arms in a 1:1:1:1:1 ratio. 
 
Etokimab 20 mg SC every 4 weeks (Q4W) 
 
Etokimab 300 mg load + 150 mg SC Q4W 
 
Etokimab 300 mg load + 150 mg SC every 8 weeks (Q8W) 
 
Etokimab 600 mg load + 300 mg SC Q4W 
 
Placebo 
The subjects will be administered study drug SC during onsite visits on Day 1 (Week 0), Day 29 
(Week 4), Day 57 (Week 8), and Day 85 (Week 12). The subjects will remain on-site for 2 hours for 
postdose assessments at Weeks 0, 4, 8 and 12. Additional visits will occur at Day 5 (Week 1), Day 15 
(Week 2), Day 92 (Week 13), and Day 113 (Week 16) during the treatment period. 
For the safety follow-up visit, the subject will return to the study center on Day 141 (Week 20) and 
Day 169 (Week 24). The end of study (EOS) Visit will be on Day 169 (Week 24) (see Section 1.3). 
The subject’s disease activity (response to study treatment) will be evaluated using the EASI, vIGA-AD, 
and SCORAD assessments. The patient reported outcome measurements (POEM, ACQ-6, and DLQI will 
be performed first at visits specified in the Schedule of Activities (SOA;see Section 1.3) before any other 
study procedures (except informed consent at screening visit). Dermatology Life Quality Index and 
POEM questionnaires will be administered only to the subset of subjects who can read and understand a 
language in which questionnaire is presented (based on availability of validated translations in 
participating countries). The ACQ-6 will be assessed only in subjects with active asthma disease who can 
read and understand English. The NRS (numerical rating scale) for pruritus , also a patient reported 
outcome, will be completed daily via electronic patient reported outcome (ePRO) device. 
Serum samples for PK and immunogenicity will be collected before the administration of study drug and 
at the other time points specified in the SOA (see Section 1.3). 
Safety assessments including AE/SAE monitoring, vital signs, physical examination, ECGs, and 
laboratory measurements will be performed as specified in SOA (see Section 1.3). A Data Safety 
Monitoring Board will be instituted to periodically review and evaluate the study data for subject’s safety 
and advise the Sponsor of potential safety signals. 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
Etokimab, is a first-in-class, anti-IL-33 therapeutic antibody developed to treat Th2 cell driven 
inflammatory diseases with underlying IL-33 dysregulation. Preliminary evidence of this compound’s 
significant pharmacodynamic (PD) activity in terms of cytokine modulation has been demonstrated in 
nonclinical and clinical studies, justifying its further development in subjects with AD. Subjects with 
moderate to severe AD often have inadequate disease control from currently available topical treatments 
and uncontrolled AD significantly affects their quality of life. Systemic immunomodulatory therapy 
including oral corticosteroids has been used to treat these subjects but have significant side effects. The 
use of more targeted immune modulators such as etokimab may reduce the Th2 specific inflammation 


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triggering disease with fewer side effects. Other monoclonal Th2 immune modulators such as dupilumab 
have shown promising results in clinical studies.  
This study is a dose-ranging study aiming to assess the effects of etokimab compared to placebo in 
subjects with AD and provide evidence of a desired short-term clinical outcome. This study will use a 
placebo arm to allow for comparative efficacy assessments. Most of the subjects will be randomized to an 
active treatment arm. The t1/2 of etokimab was approximately 2 weeks in phase 1 studies in healthy 
subjects. Following subjects for 8 weeks after the last etokimab administration will allow time for 
additional PK, and safety assessments. 
4.3 
JUSTIFICATION FOR DOSE 
Data from the phase 1 study (ANB020-001) and phase 2a study (ANB020-002) are the basis for the 
selection of dose of etokimab for the current study. The dose range of etokimab selected for this study has 
been used safely in Study ANB020-001. Etokimab pharmacodynamic activity, measured as inhibition of 
ex-vivo IL-33 stimulated INF-γ production, can be inferred from the correlation with PK data. All the 
selected dose levels of etokimab are predicted to induce full IL-33 inhibition within 2 days for at least 9 to 
10 days after dosing. The administration of the loading doses of etokimab will allow systemic 
concentrations to reach serum concentrations sustaining more than 95% IL-33 inhibition faster, and 
potentially reduce the time to onset of clinical effect. Data from the phase 2a study show a clinical 
response 1 week after etokimab administration (300 mg IV), and the dose was found to be safe and well 
tolerated. One month after etokimab administration, the average EASI score reduction was 61% and the 
average pruritus reduction was 32% relative to Baseline. Sustained clinical response was observed 
2 months after etokimab administration.  
4.4 
END OF STUDY DEFINITION 
A subject is considered to have completed the study if he or she has completed all scheduled study visits, 
including the last visit on Day 169 (see Section 1.3) or the last scheduled assessment (see Section 6.7). 
The study is considered completed at the time the last subject has undergone all procedures associated 
with the last visit. 
5 
STUDY POPULATION 
 
5.1 
INCLUSION CRITERIA 
Subjects are eligible to be included in the study only if all of the following criteria apply: 
1. Male or female subjects must be 18 to 75 years of age, at the time of signing the informed 
consent.  
2. Body mass index (BMI) of 18 to ≤35 kg/m2 at screening. 
3. Clinically confirmed diagnosis of AD based on the Hanifin/Rajka criteria (see Appendix N) with 
symptoms present for at least 6 months prior to Baseline. 


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4. Eczema Area and Severity Index (EASI) score ≥16, BSA involvement ≥10%, and a vIGA-AD 
score (5-point scale) ≥3 at screening and Baseline. 
5. Subjects with a history (within 1 year prior to screening) of 1 or more of the following:  
a. Inadequate response to topical treatment,  
b. Use of systemic treatments to treat AD, and/or  
c. For whom topical treatments are otherwise medically inadvisable (eg, because of important 
side effects or safety risks). 
 
6. Has continued daily routine of applying non-medicated emollient (moisturizer) without any 
changes for a period of at least 7 days prior to Baseline. 
7. Contraception and pregnancy: 
a. A male subject must agree to use contraception as detailed in Appendix C of this protocol 
during the treatment period and for at least 3 months after the last dose of study treatment and 
refrain from donating sperm during this period. 
 
b. A female subject must have a negative serum pregnancy test (-human chorionic 
gonadotropin) at screening and a negative urine pregnancy test at Baseline (see Appendix C), 
is not lactating, and at least one of the following conditions applies: 
 
i. Not a woman of childbearing potential (WOCBP) as defined in Appendix C OR 
ii. A WOCBP who agrees to follow the contraceptive guidance in Appendix C during the 
treatment period and for at least 3 months after receiving the last dose of study treatment 
and refrain from donating oocytes (eggs) during this period. The female subject’s selected 
form of contraception must be effective by the time the female subject enters into the 
study (eg, hormonal contraception should be initiated at least 28 days before Day 1). 
 
8. Capable of giving signed informed consent and understanding the requirements and restrictions 
listed in the informed consent form (ICF) and in this protocol. 
5.2 
EXCLUSION CRITERIA  
Subjects are excluded from the study if any of the following criteria apply: 
1. Treatment with topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), or crisaborole 
within 2 weeks before dosing (Day 1), or, in the opinion of the Investigator, likely to require such 
treatment(s) during the first 2 weeks of study treatment. 
2. History of prior exposure to an anti-IL-33 antibody. 
3. Exposure to an investigational or licensed or other anti Th2 type cytokine or cytokine receptor 
antagonist (eg, IL-4, IL-5, IL-13, IL-31, ST2, and thymic stromal lymphopoietin [TSLP]) within 
16 weeks or 5 half-lives before screening, whichever is longer. 
4. History of prior exposure to any investigational or biologic systemic treatment within 5 half-lives 
before screening or is currently enrolled in another clinical study. 


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5. Have received systemic treatment (including systemic corticosteroids, immunosuppressants or 
immunomodulating drugs, or phototherapy or use of a tanning booth) within 4 weeks before 
screening. 
6. Treatment with a live vaccine within 4 weeks before screening through Day 1. 
7. History of hypersensitivity or allergic reactions to polysorbate 80 a component of etokimab 
formulation or the inactive ingredients (excipients). 
8. History of severe allergic or anaphylactic reactions to human, humanized, chimeric, or murine 
monoclonal antibodies. 
9. History of parasitic infections within 12 months before screening. 
10. Have concomitant dermatological (eg, psoriasis, scabies, seborrheic dermatitis, contact dermatitis 
(irritant or allergic), congenital ichthyoses, cutaneous T-cell lymphoma, photosensitivity 
dermatoses, immune deficiency diseases, erythroderma of other causes etc.) or medical 
condition(s) which may interfere with the Investigator’s ability to evaluate the subject's response 
to the study drug from an efficacy or safety perspective. 
11. Bacterial infections of the skin which requires hospital admission within 4 weeks before 
screening through Day 1. 
12. Any acute or chronic infection requiring systemic antibiotics, antivirals, or antifungals (IV or 
oral) within 2 weeks before screening or topical within 1 week before screening. 
13. Positive blood screen for hepatitis C antibody, hepatitis B surface antigen or core antibody, or 
human immunodeficiency virus (HIV) 1 or 2 antibodies. 
14. Immunodeficiency disorders (eg, IgA deficiency) or known or suspected history of 
immunosuppression, including history of invasive opportunistic infections (eg, active or latent 
tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocytosis, aspergillosis) 
despite infection resolution or unusually frequent, recurrent, or prolonged infections, per 
Investigator’s judgement. NOTE: Suspected active or latent tuberculosis will be based on medical 
history, physical examination, and standard of care diagnostic methods. Subjects with a positive 
interferon-gamma (IFN-γ) release assay (IGRA) at screening are not eligible for this study. 
15. History of malignancy within 5 years before screening, except completely treated in situ 
carcinoma of the cervix or treated and non-metastatic squamous or basal cell carcinoma of the 
skin. 
16. Laboratory findings at screening: 
a) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 times the upper 
limit of normal (ULN). 
b) Hemoglobin is <11 g/dL. 
c) Neutrophils <1.5 × 103/µL. 
d) Platelets <150 × 103/µL. 
17. Evidence of drug/substance abuse that would pose a risk to subject safety, interfere with the 
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protocol, including but not limited to evidence of misuse of addictive drugs, such as opioids, 
outside of prescribed medications for a medical condition.  
18. Have any other physical, mental, or medical conditions which, in the opinion of the Investigator, 
make study participation inadvisable or could confound study assessments. 
5.3 
LIFESTYLE CONSIDERATIONS 
No lifestyle restrictions are required. 
5.4 
SCREEN FAILURES 
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently entered in the study. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure subjects to meet the Consolidated Standards of Reporting Trials 
publishing requirements and to respond to queries from regulatory authorities. Minimal information 
includes demography, screen failure details, eligibility criteria, and any SAE. 
Subjects who do not meet the criteria for participation in the study (screen failure) may be rescreened 
once. 
Examples of rescreening:  
• 
A subject who needs to be treated with rescue medications during screening that is a topical 
steroid. The subject may be rescreened after resolution of the exacerbation that prompted 
treatment and after 14 days of completing treatment with TCS, TCI, and/or crisaborole. 
• 
Subjects who do not meet Inclusion criteria “Has continued daily routine of applying 
nonmedicated emollient (moisturizer) without any changes for a period of 7 days up to Baseline.” 
• 
Subjects who would continue use of antihistamines, or moisturizers containing additives or 
filaggrin breakdown products that were not initiated 2 weeks prior to the screening visit. They 
may be rescreened after they have been on a stable antihistamine regimen and/or moisturizer for 
2 weeks.  
• 
Any further queries for rescreening must be discussed with the Medical Monitor and approved by 
the Sponsor.  
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
The recruitment and retention plan for this study will be provided in a separate document. 


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6 
STUDY INTERVENTION 
 
6.1 
STUDY INTERVENTION(S) ADMINISTRATION 
 
6.1.1 STUDY INTERVENTION DESCRIPTION 
Etokimab, is a humanized IgG1/kappa mAb that specifically neutralizes mAb hIL-33. It was selected 
from a panel of mouse mAb humanized by complementarity determining region grafting, optimized and 
matured via mammalian cell display and somatic hyper mutation using AnaptysBio’s (SHM) XEL™ 
system to achieve a desired functional inhibitory potency. 
Placebo contains no active ingredient and will be similar to etokimab in appearance. 
6.1.2 DOSING AND ADMINISTRATION 
All eligible subjects will be randomized on Day 1 to 1 of 5 treatment arms, ie, placebo or 1 of the 
treatment arms dosed with etokimab in a 1:1:1:1:1 ratio followed by remaining study drug dose 
administration on Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12). 
The dosing details are presented in Table 2, Table 3, Table 4, and Table 5. 
Table 2 Dosing Details for Week 0 (Dose 1) 
 
 
 
 
Etokimab 100 mg/mL solution in 1.2 mL vials 
Dosing Arm
Dose 1 
Week 0 
Total 
injections # 
Total 
injection 
Volume 
Injection 1a 
Injection 2a 
Injection 3a 
Injection 4a 
20 mg Q4W
20 mg 
4 
6 mL 
0.2 mL etokimab 
+ 1.3 mL placebo = 
1.5 mL 
1.5 mL placebo 1.5 mL placebo 1.5 mL placebo
300/150 mg 
Q4W 
300 mg 
4 
6 mL 
1.5 mL etokimab
1.5 mL 
etokimab 
1.5 mL placebo 1.5 mL placebo
300/150 mg 
Q8W 
300 mg 
4 
6 mL 
1.5 mL etokimab
1.5 mL 
etokimab 
1.5 mL placebo 1.5 mL placebo
600/300 mg 
Q4W 
600 mg 
4 
6 mL 
1.5 mL etokimab
1.5 mL 
etokimab 
1.5 mL 
etokimab 
1.5 mL 
etokimab 
Placebo Q4W
Placebo 
4 
6 mL 
1.5 mL placebo 
1.5 mL placebo 1.5 mL placebo 1.5 mL placebo
a 
The numbering of injections in this table does not correspond to the order in which the injections will be administered. These 
will be prepared by an unblinded pharmacist or designee (examples include a state/country approved physician, registered nurse, 
etc.) and administered by blinded site staff. 


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Table 3 Dosing Details for Week 4 (Dose 2) 
 
 
 
 
Etokimab 100 mg/mL solution in 1.2 mL vials 
Dosing Arm
Dose 2  
Week 4 
Total 
injections # 
Total injection 
Volume 
Injection 1a 
Injection 2a 
20 mg Q4W 
20 mg 
2 
3 mL 
0.2 mL etokimab + 
1.3 mL placebo = 1.5 mL 
1.5 mL placebo 
300/150 mg 
Q4W 
150 mg 
2 
3 mL 
1.5 mL etokimab 
1.5 mL placebo 
300/150 mg 
Q8Wb 
Placebo 
2 
3 mL 
1.5 mL placebo 
1.5 mL placebo 
600/300 mg 
Q4W 
300 mg 
2 
3 mL 
1.5 mL etokimab 
1.5 mL etokimab 
Placebo Q4W
Placebo 
2 
3 mL 
1.5 mL placebo 
1.5 mL placebo 
a 
The numbering of injections in this table does not correspond to the order in which the injections will be administered. These 
will be prepared by an unblinded pharmacist or designee (examples include a state/country approved physician, registered nurse, 
etc.) and administered by blinded site staff. 
b 
At Week 4, the 300/150 mg Q8W dosing arm will receive a placebo dose. No etokimab will be administered at this visit. 
 
Table 4 Dosing Details for Week 8 (Dose 3) 
 
 
 
 
Etokimab 100 mg/mL solution in 1.2 mL vials 
Dosing Arm 
Dose 3  
Week 8 
Total 
injections # 
Total injection 
Volume 
Injection 1a 
Injection 2a 
20 mg Q4W 
20 mg 
2 
3 mL 
0.2 mL etokimab + 
1.3 mL placebo = 1.5 mL 
1.5 mL placebo 
300/150 mg 
Q4W 
150 mg 
2 
3 mL 
1.5 mL etokimab 
1.5 mL placebo 
300/150 mg 
Q8W 
150 mg 
2 
3 mL 
1.5 mL etokimab 
1.5 mL placebo 
600/300 mg 
Q4W 
300 mg 
2 
3 mL 
1.5 mL etokimab 
1.5 mL etokimab 
Placebo Q4W 
Placebo 
2 
3 mL 
1.5 mL placebo 
1.5 mL placebo 
a 
The numbering of injections in this table does not correspond to the order in which the injections will be administered. These 
will be prepared by an unblinded pharmacist or designee (examples include a state/country approved physician, registered nurse, 
etc.) and administered by blinded site staff. 
 
 


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Table 5 Dosing Details for Week 12 (Dose 4) 
 
 
 
 
Etokimab 100 mg/mL solution in 1.2 mL vials 
Dosing Arm 
Dose 4 
Week 12 
Total 
injections # 
Total injection 
Volume 
Injection 1a 
Injection 2a 
20 mg Q4W 
20 mg 
2 
3 mL 
0.2 mL etokimab + 
1.3 mL Placebo = 1.5 mL 
1.5 mL placebo 
300/150 mg 
Q4W 
150 mg 
2 
3 mL 
1.5 mL etokimab 
1.5 mL placebo 
300/150 mg 
Q8Wb 
Placebo 
2 
3 mL 
1.5 mL placebo 
1.5 mL placebo 
600/300 mg 
Q4W 
300 mg 
2 
3 mL 
1.5 mL etokimab 
1.5 mL etokimab 
Placebo Q4W
Placebo 
2 
3 mL 
1.5 mL placebo 
1.5 mL placebo 
a 
The numbering of injections in this table does not correspond to the order in which the injections will be administered. These 
will be prepared by an unblinded pharmacist or designee (examples include a state/country approved physician, registered nurse, 
etc.) and administered by blinded site staff. 
b 
At Week 12, the 300/150 Q8W dosing arm will receive a placebo dose. No etokimab will be administered at this visit. 
 
6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
 
6.2.1 ACQUISITION AND ACCOUNTABILITY 
The Investigator, institution, or the head of the medical institution (where applicable) is responsible for 
study treatment accountability, reconciliation, and record maintenance (ie, receipt, reconciliation, and 
final disposition records). The Investigator or designee must confirm appropriate temperature conditions 
have been maintained during transit for all study treatment received and any discrepancies are reported 
and resolved before use of the study treatment. 
Only subjects enrolled in the study may receive study treatment and only authorized study center staff 
may supply or administer study treatment. 
Further guidance and information for the final disposition of unused study treatment are provided in the 
Pharmacy Manual. 
Drug accountability forms must be available for inspection at any time. 
6.2.2 FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
Etokimab is a sterile, white to slightly opalescent solution that is formulated at 100 mg/mL in 30 mM 
histidine, 240 mM proline, and 0.01% polysorbate 80 at pH 6.0. Each single-use vial contains 1.2 mL of 
solution.  


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Placebo is formulated as a sterile solution of 30 mM histidine, 240 mM proline, and 0.01% polysorbate 
80 at pH 6.0. Each single use glass vial contains 1.2 mL of solution.  
All investigational product vials will be packaged and labeled as required per country requirements. 
6.2.3 PRODUCT STORAGE AND STABILITY 
All study treatments 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 center staff. 
The etokimab vials must be refrigerated at 2°C to 8°C (36°F to 46°F) until the day of use. Etokimab vials 
may be stored at room temperature (>8°C to 25°C [46°F to 77°F]) for up to 8 hours. Once etokimab has 
been diluted with placebo, the solution may be stored at room temperature (>8°C to 25°C [46°F to 77°F]) 
for up to 8 hours. Etokimab may be stored at room temperature in the undiluted and/or diluted state for a 
maximum of 8 hours. Vials are intended for single-use only; therefore, any remaining solution should be 
discarded. 
6.2.4 PREPARATION 
Investigational product (study drug or placebo) will be prepared by a trained, unblinded dose preparer to 
maintain blinding of the study investigators and study subjects. Dose preparation records will be 
completed and securely maintained by the dose preparer. Both the etokimab and the placebo have the 
same appearance in the syringe, thereby ensuring that the Principal Investigator (PI) administering the 
study injections will remain blinded to study treatment. Syringes of etokimab and placebo will be 
prepared based on treatment group assignment. 
6.2.5 DOSING INSTRUCTIONS 
Study drug (etokimab and placebo) will be administered by SC route at 1.5 mL per injection. Etokimab 
will be administered by SC route at 100 mg/mL concentration: 
 
Study drug (etokimab and placebo) should be prepared by drawing up the required dosing volume 
into suitable sized syringe and attaching a dosing needle. 
 
Subcutaneous injection sites should be alternated among the different quadrants of the abdomen 
(avoiding navel and waist areas), upper thighs, and upper arms, so that the same site is not 
injected for 2 consecutive months.  
 
To allow for adequate assessment of possible injection site reactions, study drug should be 
administered only into areas of normal looking skin; injections should be at least 2 inches (5 cm) 
apart.  
 
The loading dose should be administered into at least two different locations (eg, different 
quadrants of the abdomen) to avoid administration of more than 2 injections into the same 
location. 
 
Subcutaneous injections should not be given into moles, scars, tattoos or areas where the skin is 
tender, bruised, red, hard, or not intact. 


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6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
6.3.1 RANDOMIZATION 
This is a randomized, double blind, placebo-controlled study with limited access to the randomization 
code. All subjects will be centrally assigned to randomized study treatment using an Interactive Web 
Response System (IXRS). As subjects become eligible they will be assigned sequential randomization 
numbers which will be used to assign the allocated treatment based on a randomization schedule. Before 
the study is initiated, the log in information and directions for the IXRS will be provided to each study 
center. Study treatment will be prepared and dispensed at the study visits by an unblinded pharmacist or 
designee as summarized in Section 6.1 and the Pharmacy Manual; the visits at which this will occur are 
summarized in Section 1.3. Returned study treatment should not be re dispensed to the subjects. 
Eligible subjects will be randomized on Day 1 to one of the 5 treatment arms, ie, placebo or one of the 
treatment arms dosed with etokimab in a 1:1:1:1:1 ratio. Etokimab and placebo will be identical in 
physical appearance. The Sponsor, Investigator, site staff, and subjects will be blinded to treatment 
assignment and only the unblinded pharmacist or designee (examples include a state/country approved 
physician, registered nurse, etc.) will be aware of treatment assignment (etokimab or placebo). The IXRS 
will be responsible for providing the randomization number to the unblinded pharmacist or designee. The 
treatment codes will be held by the Sponsor’s designated vendor. 
6.3.2 BLINDING 
The IXRS will be programmed with blind-breaking instructions. In case of an emergency, the Investigator 
has the sole responsibility for determining if unblinding of a subject’s treatment assignment is warranted. 
Subject’s safety must always be the first consideration in making such a determination and unblinding 
should be performed only if the subject’s well-being requires knowledge of the subject’s treatment 
assignment, or if requested by the Data Safety Monitoring Board (DSMB). 
All entries resulting in an unblinding event are recorded and reported by the IXRS. If a subject’s 
treatment assignment is unblinded, the Sponsor must be notified within 24 hours after breaking the blind 
without informing the Sponsor of the treatment assignment. The date and reason that the blind was 
broken, but not the treatment assignment must be recorded in the source documentation and electronic 
case report form (eCRF), as applicable.  


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6.4 
STUDY INTERVENTION COMPLIANCE 
The assigned dosage, timing, and mode of administration may not be changed. Any departures from the 
intended regimen must be captured in the eCRFs and will be recorded as a protocol deviation. 
Subjects who miss 2 consecutive doses after the loading dose will be considered noncompliant and will 
be discontinued from the study. Missing the loading dose will also result in discontinuation from the 
study. 
6.5 
CONCOMITANT THERAPY 
For this protocol, a prescription medication is defined as a medication that can be prescribed only by a 
properly authorized/licensed clinician. 
Any medication, moisturizer, or vaccine (including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements) that the subject is receiving at the time of enrollment and during the study 
must be recorded on the eCRF.  
The Medical Monitor should be contacted if there are any questions regarding concomitant or prior 
therapy. 
A list of excluded medications is provided in Appendix D. 
6.5.1 ALLOWED MEDICATIONS 
Treatment with concomitant therapies for AD during the study is permitted only as outlined in the 
inclusion criteria (see Section 5.1)/exclusion criteria (see Section 5.2) and as described below. Subjects 
taking permitted medications should be on stable doses at the baseline visit (Week 0, Day 1) as specified 
in Section 5.2. 
• 
Throughout the treatment period, subjects will continue to apply their daily routine emollient 
without any changes at least once daily to all dry areas. 
• 
Women of childbearing potential are to continue using a highly effective form of contraception 
throughout the study. 
• 
Medications used to treat chronic disease such as diabetes, hypertension, and asthma are also 
permitted. 
The Investigator must record the use of all concomitant medications, both prescribed and over the 
counter, into the eCRF and subject’s medical records. This includes medications used on both a regular 
and an as needed basis. Subjects should be discouraged from starting any new medication, both 
prescribed and over the counter, without consulting the Investigator, unless the new medication is 
required for emergency use or has been prescribed for clinical need. If there is any question whether a 
medication may be used during the study the site should contact the Medical Monitor. 
A list of excluded medications/therapy is provided in Appendix D. 


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6.5.2 RESCUE MEDICINE 
The use of topical and systemic corticosteroids, immunosuppressant/immunomodulating treatments and 
phototherapy or use of a tanning booth are prohibited during the course of the study (Table 13). If any of 
these medications are needed to control intolerable AD symptoms, they may be given/utilized at the 
discretion of the Investigator and will be considered rescue medication/therapy. The Sponsor will not 
supply any rescue medication or support the cost of rescue therapy.  
Subjects who receive any exclusionary topical rescue treatment for more than 2 consecutive days, or for 
more than 3 days within two consecutive weeks, or for more than 6 days during the treatment period will 
be considered nonresponders; however, they are allowed to continue study treatment. Subjects who 
receive phototherapy rescue treatment or utilize tanning booths will be considered nonresponders, but will 
be allowed to continue study treatment. However, if a subject receives systemic rescue treatment, study 
treatment is to be immediately discontinued.  
All subjects who receive rescue medication/therapy should complete the study assessments according to 
Section 1.3 whether or not they continue study treatment. 
The date and time of any rescue medication administration or treatment, as well as the name and dosage 
regimen of the rescue medication or treatment, must be recorded.  
Anti-inflammatory topical rescue therapy should be administered to lesional skin only. The choice of the 
corticosteroid should be based upon standard of care considerations (eg, body area involved, severity of 
skin inflammation). A list of representative topical corticosteroids is provided in Appendix E. Low 
potency corticosteroids (Class 6/7) cream or ointment are suggested. For more severe inflammation, 
moderate potency corticosteroids (Class 4/5) are suggested. Topical calcineurin inhibitors (eg, tacrolimus 
0.1%) may be an alternative to TCS, in particular, for the treatment of the face, neck, and skin folds.  
6.6 
DOSE MODIFICATION 
No dose modification is allowed in this study. Study treatment can be interrupted temporarily or 
permanently if deemed necessary as per the Investigator’s discretion. Any interruption should be 
discussed with the Medical Monitor in advance but no later than 24 hours after it has occurred. 
6.7 
TREATMENT AFTER THE END OF THE STUDY 
All subjects will return to the study center for the EOS (Day 169) or early termination visit (ETV) for 
final safety and EOS assessments. After this visit, subjects should be treated according to the 
Investigator’s clinical judgment. Care after EOS/ETV will not be provided by the Sponsor. Any AE 
which in the opinion of the Investigator is related to the study drug, SAE, or pregnancy occurring within 


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30 days after the EOS visit should be reported to the IQVIA Lifecycle Safety team and followed up until 
it has a resolved or stable outcome or subject is lost to follow-up. 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
Study treatment can be interrupted temporarily in case of an AE as per the Investigator’s discretion. The 
Medical Monitor should be informed. Restarting of study treatment at the next scheduled administration 
study visits can be done after discussion with the Medical Monitor. 
Discontinuation from study intervention does not mean discontinuation from the study, and remaining 
study procedures should be completed as indicated by the study protocol. If a clinically significant finding 
is identified (including, but not limited to changes from Baseline) after enrollment, the Investigator or 
qualified designee will determine if any change in participant management is needed. Any new clinically 
relevant finding will be reported as an AE. 
In case of early withdrawal from the study or if the subject has missed 2 consecutive doses following the 
Day 1 loading dose, the subject will be required to return to the study center for an ETV. Procedures 
should be completed in accordance with the SOA (see Section 1.3) Week 24/ETV. 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
The subject can be discontinued or withdrawn from study due to following reasons: 
 
A subject may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the Investigator or Sponsor for safety (eg, 
occurrence of an AE or SAE or a protocol deviation), lack of efficacy, behavioral, lack of 
compliance, or administrative reasons. Prior to study drug administration, the Investigator 
decides that the subject should be withdrawn or is at risk. If this decision is made because of 
an AE or a clinically significant laboratory value, the study drug should not be administered, 
and appropriate measures are to be taken. AnaptysBio Inc. and/or IQVIA is to be notified 
immediately. 
 
Lost to follow-up. 
 
An anaphylactic or other serious allergic reaction. 
 
Occurrences of emergency unblinding. 
 
Use of any excluded/prohibited medications (see Appendix D) that in the opinion of the 
Investigator or Sponsor necessitates the subject being withdrawn. 
 
Laboratory abnormalities: 
o ALT or AST >5 times ULN for more than 2 weeks. 
o ALT or AST >3 times ULN AND bilirubin >2 times ULN (total bilirubin >4 times ULN 
in case of documented Gilbert’s syndrome). 
 
Use of systemic rescue medication. Patients should be withdrawn from treatment, but not 
necessarily from the study (see Section 6.5.2). 


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 
Termination of the study by the Investigator or Sponsor. 
 
Pregnancy (see Appendix C and Section 8.2.5). 
 
Noncompliance with study treatment (Section 6.4) 
Any subject who have received at least 1 dose of the study drug, should complete the ETV assessments 
and return for the safety follow-up assessments. 
If a subject 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 subject withdraws from the study, he/she may request destruction of any samples taken and not tested, 
and the Investigator must document this in the study center study records. 
In subjects who are discontinued for pregnancy, after completing ETV assessments and safety follow-up, 
they should be followed up until outcome of the pregnancy is known (see Section 8.2.5 and Appendix C). 
See SOA (Section 1.3) for data to be collected at the time of study discontinuation and follow-up and for 
any further evaluations that need to be completed. 
Subjects may be replaced in certain circumstances (eg, limited exposure to study drug). The final decision 
for replacement of subjects will be done on a case by case basis in consultation with Medical Monitor at 
the Sponsor’s designated contract research organization and/or with the Sponsor’s Medical Director. 
7.3 
LOST TO FOLLOW-UP 
A subject will be considered lost to follow-up if he or she fails to return for scheduled visits and is unable 
to be contacted by the study site staff.  
The following actions must be taken if a subject fails to return to the clinic for a required study visit: 
 
The study center personnel must attempt to contact the subject and reschedule the missed visit as 
soon as possible and counsel the subject on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the subject wishes to and/or should continue in the study. If 
the re-scheduled visit falls within the next visit’s window, then the visit should be considered a 
missed visit and the subject should come in for the next scheduled visit as planned. Missed visits 
must be captured in the eCRFs and will be recorded as a protocol deviation. 
 
Before a subject is deemed lost to follow-up, the Investigator or designee will make every effort 
to regain contact with the subject (where possible, 3 telephone calls and, if necessary, a certified 
letter to the subject’s last known mailing address or local equivalent methods). These contact 
attempts should be documented in the subject’s medical record or study file.  
 
Should the subject continue to be unreachable, he or she will be considered to have withdrawn 
from the study with a primary reason of lost to follow-up. 
 
8 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their scheduling are summarized in the Schedule of Activities (see Section 1.3). 
The study assessment details are presented below: 


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 
Assessments scheduled on the day of study treatment administration must be performed prior to 
the study treatment injection unless otherwise noted (see Section 1.3). 
 
There are visits where the protocol requires more than 1 procedure to be completed at the same 
time point. When indicated, the procedure must follow specific order of events, see Section 1.3 
for instructions. 
 
Immediate safety concerns should be discussed with the Sponsor/designee immediately upon 
occurrence or awareness to determine if the subject should continue or discontinue in the study. 
 
Adherence to the study design requirements, including those specified in Section 1.3, is essential 
and required for study conduct. 
 
All screening evaluations must be completed and reviewed to confirm that potential subjects meet 
all eligibility criteria. The Investigator will maintain a screening log to record details of all 
subjects screened and to confirm eligibility or record reasons for screening failure, as applicable 
and the log will be sent weekly to clinical lead. 
 
The maximum amount of blood collected from each subject over the duration of the study, 
including any extra assessments that may be required, is approximately 126 mL. Repeat or 
unscheduled samples may be taken for safety reasons or for technical issues with the samples. 
8.1 
EFFICACY ASSESSMENTS  
Severity of AD from Baseline through EOS follow-up will be assessed by the Investigator and/or the 
subject using the EASI, vIGA-AD, SCORAD, DLQI, POEM, and NRS for Pruritus. In addition, the 
ACQ-6 will be obtained in subjects with a history of asthma at Baseline. 
It is recommended that the same Investigator/Sub-investigator completes the scales and questionnaires for 
all time points for a given subject. Patient reported outcome assessments (ie, SCORAD, DLQI, POEM, 
and ACQ-6) should be obtained prior to any other assessments at each visit as per Section 1.3, except for 
signing of the ICF. 
8.1.1 ECZEMA AREA AND SEVERITY INDEX (EASI) 
The EASI is an Investigator assessment measuring the severity of clinical signs in AD. The EASI is 
considered one of the best validated outcome measures for AD. The EASI score assesses the severity and 
extent of erythema; induration, papulation, and edema; excoriations; and lichenification. The  EASI 
scores range from 0 to 72, with higher scores indicating greater severity and extent of AD7, 8. The EASI 
score will be recorded at the time points indicated in the SOA (see Section 1.3). The EASI will be 
captured in electronic clinical outcome assessment (eCOA) tablet. The EASI instructions and forms are in 
Appendix F. 
8.1.2 VALIDATED INVESTIGATOR GLOBAL ASSESSMENT SCALE FOR ATOPIC 
DERMATITIS (VIGA-AD™) 
The vIGA-AD is a static 5-point scale to evaluate AD disease severity globally and is frequently assessed 
in clinical studies. Investigator’s vIGA-AD responses will be captured in eCOA tablet. The vIGA-AD 
result will be recorded at the time points indicated in the Section 1.3. The vIGA-AD scale to be used is in 
Appendix G. 


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8.1.3 SEVERITY SCORING OF ATOPIC DERMATITIS (SCORAD) 
The SCORAD index, a validated assessment of AD, was developed to standardize the evaluation of the 
extent and severity of AD. There are 3 components to the assessment: A = extent or affected BSA, B = 
severity, and C = subjective symptoms. The extent of AD is assessed as a percentage of each defined 
body area and reported as the sum of all areas (assigned as “A” in the overall SCORAD calculation). The 
severity of 6 specific symptoms of AD (redness, swelling, oozing/crusting, excoriation, skin 
thickening/lichenification, and dryness) is assessed using the following scale: none (0), mild (1), moderate 
(2), or severe (3) (for a maximum of 18 total points, assigned as “B” in the overall SCORAD calculation). 
Subjective assessment of itch and sleeplessness is recorded for each symptom by the subject on a visual 
analog scale, where 0 is no itch (or sleeplessness) and 10 is the worst imaginable itch (or sleeplessness), 
with a maximum possible score of 20. This parameter is assigned as “C” in the overall SCORAD 
calculation. 
The SCORAD score is calculated as: A/5 + 7B/2 + C (see Appendix H for more information). Subjects 
will undergo this assessment at time points specified in Section 1.3. The SCORAD will be captured in 
eCOA tablet. 
8.1.4 DERMATOLOGY LIFE QUALITY INDEX (DLQI) 
The DLQI is a 10-item, validated questionnaire used in clinical trials to assess the impact of AD disease 
symptoms and treatment on quality of life. The format is a simple response (0 to 3 where 0 is “not at all” 
and 3 is “very much”) to 10 questions, which assess quality of life (QoL) over the past week, with an 
overall scoring system of 0 to 30; a high score is indicative of a poor QoL.11 The questionnaire will be 
administered only to the subset of subjects who can read and understand a language in which 
questionnaire is presented (based on availability of validated translations in participating countries). The 
subject should complete the DLQI in Appendix I at the time points indicated in the SOA (see 
Section 1.3). The DLQI will be captured in eCOA tablet. 
8.1.5 PATIENT ORIENTED ECZEMA MEASURE (POEM) 
The POEM is a 7-item, validated questionnaire used in clinical trials to assess the severity of eczema as 
experienced by the subject. The format is a response to 7 items (dryness, itching, flaking, cracking, sleep 
loss, bleeding, and weeping) based on frequency during the past week (ie, 0 = no days, 1 = 1 to 2 days, 
2 = 3 to 4 days, 3 = 5 to 6 days, and 4 = all days) with a scoring system of 0 to 28; the total score reflects 
disease-related morbidity12. The questionnaire will be administered only to the subset of subjects who can 
read and understand a language in which questionnaire is presented (based on availability of validated 
translations in participating countries). The subject should complete the POEM at the time points 
indicated in the SOA (see Section 1.3). The POEM will be captured in eCOA tablet. The subject should 
complete the POEM questionnaire (see Appendix J).  
8.1.6 NUMERICAL RATING SCALE FOR PRURITUS 
The NRS for Pruritus is a simple assessment tool that subjects will use to report the intensity of their 
pruritus (itch) during a daily recall period using an ePRO device. Subjects will be asked 2 questions:  


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 
For average itch intensity: “On a scale of 0 to 10, with 0 being ‘no itch’ and 10 being the ‘worst 
imaginable itch’, how would you rate your itch overall (on average) during the previous 
24 hours?” 
 
For maximum itch intensity: “On a scale of 0 to 10, with 0 being ‘no itch’ and 10 being the ‘worst 
imaginable itch’, how would you rate your itch at the worst moment during the previous 
24 hours?” 
The subject should complete the NRS for each of the 2 questions at the time points indicated in the SOA 
(see Section 1.3). Subjects will be instructed on using ePRO device to record their NRS score. Subjects 
will complete the rating scale daily through the last study visit. Study center will receive alerts when 
subjects do not complete the NRS items. Study center will be expected to contact subjects who have 
missed two consecutive entries to encourage compliance. The NRS for Pruritus will be captured on ePRO 
handheld device. 
8.1.7 ASTHMA CONTROL QUESTIONNAIRE-6 
The ACQ-6 will be used in this study to assess the asthma symptoms (night time waking, symptom on 
waking, activity limitation, and shortness of breath, wheezing, and short acting β agonist [SABA] usage) 
in subjects with active asthma disease. Subject will be asked to recall their experiences during the 
previous week by responding to 5 symptom related questions and 1 question related to bronchodilator 
use. Questions will be scored from 0 (totally controlled) to 6 (severely uncontrolled). The questionnaire 
will be administered only in subjects with active asthma disease whose primary language is English 
(based on availability of validated translations in participating countries). The subject should complete the 
ACQ-6 (see Appendix K) at the time points indicated in the SOA (see Section 1.3). The ACQ-6 responses 
will be captured by subjects on paper and transcribed into the eCRF.  
8.1.8 BODY SURFACE AREA  
The BSA affected by AD will be assessed for each major section of the body including the head, trunk, 
upper extremities, and lower extremities and will be reported as the added total of percentage of all major 
body sections combined. The subject’s BSA will be assessed in Part A of SCORAD assessment. 
8.2 
SAFETY ASSESSMENTS 
Planned time points for all safety assessments are provided in the SOA (see Section 1.3). 
Unscheduled safety assessments may be performed at any time during the study.  
8.2.1 PHYSICAL EXAMINATIONS 
Complete physical examinations will be performed at the time points specified in the SOA (see 
Section 1.3). 
 
A complete physical examination includes assessments of general appearance; skin; head/neck; 
pulmonary, cardiovascular, gastrointestinal, external genitourinary, lymphatic, and 
musculoskeletal system; extremities; eyes (inspection and vision control); nose; throat; and 


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neurologic status and will be performed only at screening. All other physical examinations should 
be abbreviated examinations and address associated complaints or findings, and any other 
assessments required to evaluate adverse events. 
 
A detailed examination of the skin should be performed at the time points specified in the SOA 
(see Section 1.3) for the efficacy assessments (eg, EASI, vIGA-AD, SCORAD). 
 
Height (in inches) will be measured only at the Screening visit.  
8.2.2 VITAL SIGNS 
Vital signs will be performed at the time points specified in the SOA (see Section 1.3). 
 
Body temperature, HR, BP, respiratory rate, and weight will be assessed and entered in eCRF. 
 
Weight will be measured at time points specified in Schedule of Activities (see Section 1.3).  
 
NOTE: Body mass index will be calculated automatically using formula BMI=weight 
(kg)/(height[m2]) as specified in specified in the SOA (see Section 1.3). 
 
Blood pressure and pulse rate measurements will be assessed in the seated position with a 
completely automated device. Manual techniques will be used only if an automated device is not 
available. 
 
Blood pressure and pulse rate measurements should be preceded by approximately 5 minutes of 
rest for the subject in a quiet setting without distractions (eg, television, cell phones etc.). 
8.2.3 12-LEAD ECG 
A single 12-lead ECG will be obtained at the time points specified in SOA (see Section 1.3). 
 
12-lead ECG will be obtained using a validated ECG machine that automatically calculates the 
HR and measures PR, QRS, QT, and QTcF intervals.  
 
The ECG will be reviewed by the central laboratory team and the instructions and guidelines for 
collection (eg, equipment), transmission, and archiving of ECG data will be provided in the ECG 
Manual. 
 
The ECG will be reviewed by the Investigator or an authorized representative who is experienced 
in the evaluation of ECGs and assessed for clinical significance. 
8.2.4 CLINICAL LABORATORY DATA 
Clinical safety laboratory assessments will be performed as below:  
 
See Appendix B for the list of clinical laboratory tests to be performed and the SOA (see 
Section 1.3) for the timing and frequency of the tests. 
 
A central laboratory will be used to perform all laboratory tests, except urine pregnancy dipstick 
test, which will be assessed by the site staff. However, local laboratory tests will be allowed if the 
central laboratory results will not be available immediately because the Investigator will need to 
make an immediate decision for any safety concerns based on laboratory results.  
 
The Investigator must review the laboratory report, document this review with date of review and 
their initials/signature, and record any clinically relevant changes occurring during the study in 


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the AE section of the eCRF. The laboratory reports must be filed with the source documents. 
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 
subject’s condition. 
 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study including the subject’s last EOS visit should be repeated until the values return to 
normal or Baseline or are no longer considered clinically significant or judged medically 
stabilized by the Investigator or Medical Monitor. Clinically significant abnormal laboratory 
results should be reported as an AE or SAE if applicable. 
 
If such values do not return to normal/Baseline within a period judged reasonable by the 
Investigator, the etiology should be identified, and the Sponsor must be notified. 
 
All protocol-required laboratory assessments, as defined in Appendix B, must be conducted in 
accordance with the Laboratory Manual and the SOA (see Section 1.3). 
o If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in subject management or are considered 
clinically significant by the Investigator (eg, SAE or AE or dose modification), then the 
results must be recorded in the eCRF and the laboratory reports must be filed with the source 
documents. 
8.2.5 PREGNANCY TESTING 
All WOCBP will have a serum pregnancy test (SPT) at screening and urine pregnancy test (UPT) at all 
designated post-screening timepoints as indicated in the SOA (Section 1.3). If UPT is positive, a serum 
pregnancy test will be performed to confirm. If any result is positive prior to investigational product 
administration, the subject will not receive study drug and will be discontinued. Follicle stimulating 
hormone (FSH) may be used to confirm menopausal status in female subjects as needed. Refer to 
Appendix C for further information. 
8.3 
PHARMACOKINETICS 
Whole blood samples of approximately 5 mL will be collected for measurement of serum concentrations 
of etokimab at time points as specified in the SOA (see Section 1.3). A maximum of 2 samples may be 
collected at additional time points during the study if warranted and agreed upon between the Investigator 
and Sponsor. Instructions for the collection and handling of biological samples will be provided by the 
Sponsor. The actual date and time (24-hour clock time) of each sample will be recorded in the eCRF. 
Samples will be used to evaluate the PK of etokimab. Each serum sample will be divided into 2 aliquots 
(1 each for PK and a back-up). Samples collected for analyses of etokimab serum concentration may also 
be used to correlate exposure to safety or efficacy aspects related to concerns arising during or after the 
study. 
Measurement of concentrations of etokimab will be performed using a validated assay method. Only 
samples which are within the window of sample stability will be analyzed. Placebo samples will not be 
analyzed. The time points for PK sample collection are given in Appendix L. 


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While PK and immunogenicity samples must be collected from subjects assigned to the placebo arm to 
maintain the blinding of treatment assignment, PK and immunogenicity assay results for these subjects 
are not needed for the safe conduct or proper interpretation of this trial and the samples will therefore not 
be analyzed. Personnel responsible for performing PK assays will be unblinded to subjects’ treatment 
assignments in order to identify appropriate PK and immunogenicity samples to be analyzed. Samples 
from subjects assigned to the placebo arm may be analyzed upon request (ie, to evaluate a possible error 
in dosing). 
Genetic analyses will not be performed on these samples unless consent for this was included in the ICF. 
Subject confidentiality will be maintained. Drug concentration information that may unblind the study 
will not be reported to study centers or blinded personnel until the study has been unblinded. Any changes 
in the timing or addition of time points for any planned study assessments must be documented and 
approved by the relevant study team member and then archived in the Sponsor and study center study 
files but will not constitute a protocol amendment. The Institutional Review Board (IRB)/Independent 
Ethics Committee (IEC) will be informed of any safety issues that require alteration of the safety 
monitoring scheme or amendment of the ICF. If a subject refuses blood collection for PK analysis, this 
will not be considered a protocol deviation as the PK analysis is an exploratory objective. 
8.4 
BIOMARKERS 
Biomarkers are not evaluated in this study. 
8.5 
IMMUNOGENICITY 
Antibodies to etokimab will be evaluated in serum samples collected from all subjects according to the 
SOA (See Section 1.3). Additionally, serum samples should also be collected at the final visit from 
subjects who discontinued study treatment or were withdrawn from the study. These samples will be 
tested by the Sponsor or Sponsor’s designee. Each serum sample will be divided into 2 aliquots (1 each 
for immunogenicity testing and a back-up). 
Serum samples will be screened for antibodies binding to etokimab and the titer of confirmed positive 
samples will be reported. Other analyses may be performed to verify the stability of antibodies to study 
treatment and/or to further characterize the immunogenicity of study treatment.  
The detection and characterization of antibodies to etokimab will be performed using a validated assay 
method by or under the supervision of the Sponsor. Only samples which are within the window of sample 
stability will be analyzed. The time points for ADA sample collection is given in Appendix L.  
Samples that are confirmed positive for antibodies binding to etokimab with a titer greater than one may 
be further characterized and/or evaluated for their ability to neutralize the activity of the study treatment 
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8.6.5 REGULATORY REPORTING REQUIREMENTS FOR SAES 
Regulatory reporting requirements for SAE are as below: 
 
Prompt notification by the Investigator to the IQVIA Lifecycle Safety team of an SAE is essential 
so that legal obligations and ethical responsibilities towards the safety of subjects and the safety 
of a study treatment under clinical investigation are met.  
 
The IQVIA Lifecycle Safety team has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study treatment under clinical 
investigation. 
 
The IQVIA Lifecycle Safety team will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, Institutional review board/Independent 
Ethics Committee, and Investigators. Investigator safety reports must be prepared for suspected 
unexpected serious adverse reactions according to local regulatory requirements and IQVIA 
Lifecycle Safety policy and forwarded to Investigators as necessary. 
 
An Investigator who receives an Investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the IQVIA Lifecycle Safety team will 
review and then file it along with the IB and will notify the IRB/IEC, if appropriate according to 
local requirements. 
Upon checking serious on the AE eCRF, a notification will be sent to the Medical Monitor and/or designee. 
Relevant eCRFs, including the subject’s Medical History, Concomitant Medications, and other AEs must 
also be completed to provide supporting documentation for the SAE. If there are additional documents that 
support the SAE (eg, clinic or hospital records or procedure reports), they should be uploaded to the AE 
eCRF. 
After review of the initial SAE report, the Medical Monitor may request additional documentation. The 
Sponsor is responsible for notifying the relevant Regulatory Authorities of certain events. It is the 
Investigator’s responsibility to notify the IRB/IEC of all SAEs that occur at his or her site. Investigators 
will also be notified of all unexpected, serious, study drug-related events that occur during any other clinical 
trial of etokimab. The Investigator is responsible for notifying its IRB/IEC of these additional SAEs. 
8.6.6 PREGNANCY 
 
Details will be collected on all pregnancies occurring from after the start of study treatment and 
until at least 16 weeks after the last dose. 
 
Details of all pregnancies in female partners of male subjects will be collected while the male 
subject is in this study and until at least 16 weeks after the last dose. 
 
If a pregnancy is reported, the Investigator should inform IQVIA Lifecycle Safety within 24 
hours of learning of the pregnancy and should follow the procedures outlined in Appendix C. 
 
If a pregnancy occurs, it will be followed-up to determine the outcome, but no longer than 4 
weeks after the estimated delivery date. 
 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, and ectopic pregnancy) are considered SAEs. 


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8.6.7 OVERDOSE OF STUDY DRUG  
For subject overdose (ie, dosing errors resulting in the administration of an SC dose that is more 
than 2 times the assigned dose), the Investigator or designee should: 
1. Monitor the subject clinically:  
 Supportive measures are to be undertaken as clinically indicated. 
 Electrocardiography and clinical laboratory evaluations (ie, blood glucose, hepatic 
enzymes, creatinine, blood urea nitrogen, creatine kinase, and complete blood count) are 
to be performed and, if abnormal, followed until all values return to baseline levels and 
AEs subside. 
 Upon evaluation of the subject, the Investigator or designee should contact the Medical 
Monitor to discuss continued participation.  
2. Record a protocol deviation. 
3. If the event meets the definition of an AE or SAE, as per Appendix M: 
 Document and report an AE/SAE associated with the overdose. 
 Contact the Medical Monitor immediately (within 24 hours of learning of the event 
[Section 8.6.5]).  
8.7 
UNANTICIPATED PROBLEMS 
 
8.7.1 DEFINITION OF UNANTICIPATED PROBLEMS  
According to ICH and Industry requirements this protocol considers unanticipated problems (UPs) 
involving risks to participants or others to include, in general, any incident, experience, or outcome that 
meets all of the following criteria: 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the IRB-approved research protocol and 
informed consent document; and (b) the characteristics of the participant population being 
studied; 
 
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
 
• 
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized. 
 


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8.7.2  UNANTICIPATED PROBLEM REPORTING  
 
The Investigator will report UPs to the reviewing IRB/IEC and to IQVIA Lifecycle Safety team. The UP 
report will include the following information: 
 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB/IEC project 
number; 
 
• 
A detailed description of the event, incident, experience, or outcome;  
 
• 
An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP;  
 
• 
A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP. 
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline:   
• 
UPs that are serious adverse events (SAEs) will be reported to the IRB/IEC and to IQVIA 
Lifecycle Safety team within 24 hours of the Investigator becoming aware of the event. 
• 
Any other UP will be reported to the IRB/IEC and to IQVIA Lifecycle Safety team within 7 days 
of the Investigator becoming aware of the problem.  
 
• 
All UPs should be reported to appropriate institutional officials (as required by an institution’s 
written reporting procedures), the supporting agency head (or designee), and the FDA within 
14 days of the IRB’s/IEC’s receipt of the report of the problem from the Investigator. 
 
8.7.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
The Sponsor will disclose clinical trial data to individuals, to investigators at sites, and publicly as 
aggregate summaries, in accordance with applicable regulations and requirements. 
 
9 
STATISTICAL CONSIDERATIONS  
All data listings, summaries, and analyses will be performed under the guidance and approval of the 
Sponsor. 
Descriptive statistics will be used for all variables, as appropriate. Continuous variables will be 
summarized by the number of observations, mean, standard deviation, median, minimum, and maximum. 
Categorical variables will be summarized by frequency counts and percentages for each category. Unless 
otherwise stated, percentages will be calculated out of the total population for each treatment arm. 
The Statistical Analysis Plan (SAP) will be developed and finalized before database lock and will provide 
details about describe the subject analysis data sets to be included in the analyses of the primary, 
secondary and exploratory endpoints, and missing data strategies/procedures for accounting for missing, 
unused, and spurious data, testing strategies, among other details. 


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PK analyses will be detailed in the Pharmacokinetic Analysis Plan. This section is a summary of the 
planned statistical analyses of the primary and secondary endpoints. Ad hoc exploratory analysis may be 
performed in addition to those specified, but no claims or conclusions will be drawn other than 
hypotheses to be tested in future clinical trials. 
The statistical analysis will be performed using statistical analysis system (SAS®) Version 9.4 or higher 
if available. All details regarding the statistical analysis and the preparation of tables, listings and figures 
will be described in the SAP. 
The default summary statistics for continuous variables includes number of contributing observations (n), 
mean, standard deviation (SD), median, minimum, and maximum or as described in the respective 
section. 
For categorical variables, the number and percentage (the percentage of subjects in each category relative 
to the total number of subjects in the relevant analysis set or relative to the total number of subjects in the 
relevant analysis set, with assessments available [where appropriate]) in each category will be the default 
summary presentation. 
9.1 
SAMPLE SIZE 
The expected efficacy response (and variability) for active and placebo response (related with percent 
change from Baseline in EASI score to Week 16) was estimated after review of 5 previous studies in 
subjects with moderate-to-severe AD subjects not taking topical corticosteroids.  
In this way, a total sample of approximately 300 subjects (60 subjects per treatment arm) achieves more 
than 95% power to detect differences among the means versus the alternative of equal means using an 
F test with a 0.05000 significance level. The size of the variation in the means is represented by their 
standard deviation which is 18.59. The common standard deviation within a group is assumed to be 
50.00. 
The hypothesized means used to compute the sample size derived from the studies mentioned before are: 
-20 -44. -65.4 -66.4 -68 (for placebo and each active treatment arm respectively) with a covariate 
R-squared of 0.300. 
9.2 
STATISTICAL HYPOTHESIS 
Statistical hypotheses and testing utilized will be defined in the SAP, including the null and alternative 
hypotheses. Primary, secondary, and exploratory endpoint analyses will all be included in the SAP. 


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9.3 
POPULATIONS FOR ANALYSES 
For purposes of analysis, the analysis sets are defined in Table 6. 
Table 6. 
Analysis Sets 
Analysis Set 
Description 
Safety Analysis Set (SAF) 
The SAF will include all randomized subjects who receive at least 
1 dose of etokimab or placebo. The safety analysis set will be used for 
all safety analyses. Subjects will be analyzed as treated. 
Full Analysis Set (FAS) 
The FAS will be based on the intent to treat principle and will include 
all randomized subjects who receive at least 1 dose of etokimab or 
placebo and have Baseline and postbaseline EASI score. The full 
analysis set will be used for all efficacy analyses. Subjects will be 
analyzed as randomized. 
PP Analysis Set (PPS) 
The PPS will include all subjects in the FAS who do not have major 
protocol deviations (See Section 10.1.10).  
Pharmacokinetic (PK) 
Analysis Set 
The PK analysis set will include all etokimab treated-subjects in the 
safety analysis set who have at least one quantifiable postdose PK 
sample available and who do not have events or protocol deviations or 
events with the potential to affect PK concentrations. The PK analysis 
set will be used for all PK analyses. 
 
 
9.4 
BASELINE DEFINITION 
Unless otherwise specified, Baseline is defined as the last observed value of the parameter of interest 
prior to the first intake of study drug (this includes unscheduled visits). For numerical variables, change 
from Baseline will be calculated as the difference between the value of interest and the corresponding 
baseline value. 
9.5 
EFFICACY ANALYSES 
Descriptive statistics for absolute and change from Baseline by visit will be provided for all continuous 
primary, secondary, and exploratory efficacy endpoints. 
Categorical end points will be summarized using frequency and percentage. By-subject listings will also 
be provided. Primary, secondary, and exploratory endpoints will be analyzed as described below. 


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9.5.1 PRIMARY EFFICACY ENDPOINT 
Percent change in EASI score from Baseline to Week 16 will be analyzed using an ANCOVA model 
adjusting for baseline EASI score in the FAS. 
The primary comparison will be least squares (LS) mean difference between active treatment group(s) 
and placebo at 16 weeks. Treatment differences will be presented with corresponding p values and 95% 
confidence interval.  
9.5.2 SECONDARY AND EXPLORATORY ENDPOINTS 
All secondary binary endpoints will be analyzed using a logistic regression adjusting for baseline EASI 
score. 
For all continuous endpoints, an ANCOVA model (similar to the analysis for the primary endpoint) will 
be used. 
9.5.3 MULTIPLICITY 
For the primary endpoint, a hierarchical testing procedure will be used, from the highest dose to the 
lowest dose until statistical significance at the 5% level is not achieved.  
Note: comparisons between active treatment doses are not intended in this study. In case 2 or more dose 
level results are positive, then the Sponsor will decide the optimal dose based on the risk / benefit profile 
for each dose level. 
Testing of secondary Endpoints: 
A gatekeeping procedure around the primary endpoint will be used: if at least 1 of the comparisons 
between the active treatments vs placebo crosses the 0.05 alpha boundary (statistical significance) then all 
secondary endpoints will be tested in a hierarchical approach. The order / sequence for testing all 
secondary endpoints will be described in the SAP.  
9.5.4 HANDLING OF DROPOUTS AND MISSING DATA 
Every effort should be made to minimize dropouts and missing assessment data. Subjects should be 
reminded of the importance of providing assessments as per protocol, and study personnel should be 
vigilant in ensuring assessments are completed as scheduled. 
Nonetheless, as subjects may elect to be withdrawn from study treatments or evaluations without 
prejudice, it is inevitable that there will be missing data. 
For subjects who receive rescue therapy and are considered nonresponders according to Section 6.5.2, the 
data collected after rescue treatment is initiated will be treated as missing. 
Missing efficacy data will be imputed using Multiple Imputation (MI) Procedure which will be detailed in 
the SAP. Additional missing data strategies will be used as deemed appropriate. 
Safety data will not be imputed. 


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9.6 
SAFETY ANALYSES 
For safety and tolerability, AEs, SAEs, vital signs, ECGs, ADA, neutralizing antibodies, and clinical 
laboratory assessments at specific time points will be evaluated. All safety data will be summarized 
descriptively. Number and percentage of AEs will be presented for each treatment group by preferred 
term and system organ class of the current Medical Dictionary for Regulatory Authorities (MedDRA).  
Individual listings of all SAEs and AEs leading to discontinuation from the study drug will be 
summarized using the current MedDRA. Summaries and listings of data for vital signs, hematology, 
clinical chemistry and urinalysis laboratory tests, and ECGs will be presented. Appropriate descriptive 
statistics will be summarized for the observed value at each scheduled assessment and for the 
corresponding change from Baseline. The Baseline will be the last assessment obtained before the first 
dose. 
Additional safety analysis will be also provided as deemed appropriate. Details will be provided in the 
SAP. 
9.6.1 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
A treatment-emergent adverse event (TEAE) is defined as: 
• 
A new event that occurs during or after first dose of study treatment or, 
• 
Any event present at Baseline that worsens in either intensity or frequency after first dose of 
study treatment. 
Only TEAEs will be summarized. 
Adverse events will be coded using MedDRA. Number of events and percentage will be tabulated by 
preferred term (PT) and system organ class (SOC). An event that occurred 1 or more times during a 
treatment period will contribute 1 observation to the numerator. The denominator will consist of all 
subjects in the SAF. If the intensity or seriousness of the AE changes, the overall intensity or seriousness 
will be the maximum intensity or seriousness of the multiple occurrences. The AEs, SAEs, TEAEs, 
TEAEs leading to treatment discontinuation, TEAEs leading to withdrawal of subject, and TEAEs leading 
to death will be listed and summarized by SOC and PT. Summaries will also be presented by relatedness 
to the study drug and severity. 
Injection site reactions will be reported separately by treatment. 
9.6.2 DEATHS 
The following death summaries will be generated: 
• 
Number (%) of subjects who died by study period (TEAE, on-study) and reasons for death 
summarized for the SAF by treatment received. 
 
• 
Death in nonrandomized subjects or randomized and not treated subjects. 


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9.6.3 PHYSICAL EXAMINATIONS, 12-LEAD ECG, VITAL SIGNS, AND CLINICAL 
SAFETY LABORATORY TESTS (HEMATOLOGY, BIOCHEMISTRY, AND 
URINALYSIS) 
Summaries and listings of data for both limited and complete physical examination findings, vital signs, 
hematology, biochemistry, and urinalysis laboratory tests will be presented. Appropriate descriptive 
statistics will be summarized for the observed value at each scheduled assessment and for the 
corresponding change from Baseline. 
For hematology and biochemistry tests, listings of subject data will also flag up any abnormal or out-of-
range values. Clinically significant changes in the laboratory test parameters will be summarized and 
listed. Hematology and clinical laboratory data will be reported in System International units. 
Descriptive statistics will be used to present the safety outcomes including, physical examination results, 
weight, BMI, 12-lead ECG, vital signs measurements, and clinical laboratory test results. 
Change from Baseline will also be summarized for vital signs measurements, and clinical laboratory test 
results. 
All ECG data results (normal/abnormal) will be summarized using frequency and percentages. Clinically 
significant abnormalities will be presented in by-subject listings. 
9.6.4 SUBJECT DISPOSITION 
A summary of subject disposition will be provided using the SAF. It will include the number of subjects 
screened, randomized, treated, completed as well as the number of dropouts, with reasons for 
discontinuation, and major protocol deviations. 
A listing will be presented to describe date of screening, assigned treatment, screen failed with reason, 
completion or early withdrawal, and the reason for early discontinuation, if applicable, for each subject. A 
list of protocol deviations will be identified and approved by the Investigator and Sponsor during the dry 
run to categorize deviations as major or minor. 
9.6.5 SUBJECT CHARACTERISTICS AND MEDICAL HISTORY 
Subject characteristics obtained at screening will be summarized for all subjects taking etokimab. Subject 
characteristics may include, but are not limited to age, gender, ethnicity, race, height, weight, and BMI. 
Summaries will include descriptive statistics for continuous variables (sample size [n], mean, SD, median, 
minimum, and maximum) and for categorical variables (sample size, frequency, and percent). 
Medical history will be coded using the MedDRA dictionary latest version and listed for all subjects. 
9.6.6 CONCOMITANT MEDICATIONS 
All medications will be coded using the World Health Organization Drug Dictionary. Each medication 
will be classified as prior medication if it is stopped prior to the first dose of study drug, or as concomitant 


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medication if it is ongoing at the time of the first dose or is started after the first dose of study drug. Prior, 
concomitant, and rescue medications will be summarized by ATC level 2 categories, and preferred name.  
9.7 
INTERIM ANALYSES  
An Interim Analysis (IA) will be performed when all active subjects complete their Week 16 visit for 
final assessment of all primary and secondary efficacy endpoints (for Week 16) and all safety data 
available (up to Week 24). Final database lock will include exploratory efficacy and safety analysis for all 
subjects for Weeks 20 and 24. 
9.8 
SUBGROUP ANALYSES 
Subgroup analyses will be detailed in the SAP. 
9.9 
IMMUNOGENICITY ANALYSES 
Observed values for ADA levels/status will be listed by subject and summarized with descriptive 
statistics based on the Safety Analysis Set. If data permits, correlation will be analyzed between 
ADA levels and safety and efficacy endpoints. 
9.10 OTHER ANALYSES 
Pharmacokinetic analyses will be described in a PK modeling and simulation analysis plan, separate from 
the SAP, and finalized before database lock. The population PK analysis will be presented separately 
from the main clinical study report in a PK modeling and simulation report.  
Serum etokimab concentrations will be listed and summarized for each sampling time point using 
appropriate descriptive statistics. Pharmacokinetic concentration data collected from the study may be 
included in a population PK based (meta-) analysis, using non-linear mixed effects modeling. The data 
from this study may be combined with data collected from other studies for population PK model 
development.  
The primary PK parameters of CL/F and Vd/F will be estimated by population PK modeling from 
etokimab serum concentrations after SC administrations. Secondary PK parameters (AUC, Cmax, and tmax 
for the first dose, and AUC, Cmax, tmax, and t1/2 for the last dose) will also be calculated for etokimab after 
SC administrations, where possible, using a Bayesian post-hoc estimation approach based upon the 
aforementioned population PK model. The PK parameters will be listed and summarized using 
appropriate descriptive statistics. A covariate screen of subject specific factors (eg, demographic and 
clinical characteristics) will be included in the analyses. 


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10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
10.1.1 INFORMED CONSENT PROCESS 
 
10.1.1.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED 
TO PARTICIPANTS 
Consent forms describing in detail the study intervention, study procedures, and risks are given to the 
subject and written documentation of informed consent is required prior to starting study intervention.  
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
Informed Consent Process is as follows: 
 
The Investigator or his/her representative will explain the nature of the study to the subject or 
his/her legally authorized representative and answer all questions regarding the study.  
 
Subjects must be informed that their participation is voluntary. Subjects or their legally 
authorized representative will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act requirements, where applicable, and the IRB/IEC or study center.  
 
The medical record must include a statement that written informed consent was obtained before 
the subject 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. 
 
Subjects 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 subject or the subject’s legally authorized 
representative. 
 
Subjects who are rescreened are required to sign a new ICF. 
The ICF will contain a separate section that addresses the use of remaining mandatory samples for 
optional exploratory research. The Investigator or authorized designee will explain to each subject the 
objectives of the exploratory research. Subjects will be told that they are free to refuse to participate and 
may withdraw their consent at any time and for any reason during the storage period. A separate signature 
will be required to document a subject’s agreement to allow any remaining specimens to be used for 
exploratory research. Subjects who decline to participate in this optional research will not provide this 
separate signature. 


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10.1.2 STUDY DISCONTINUATION AND CLOSURE 
The Sponsor designee reserves the right to close the study center or terminate the study at any time for 
any reason at the sole discretion of the Sponsor. Reasons may include safety, among others. Should the 
Sponsor decide to terminate the study, the Investigator(s) will be notified in writing. 
Study centers will be closed upon study completion. A study center is considered closed when all required 
documents and study supplies have been collected and a study center closure visit has been performed. 
The Investigator may initiate study center 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 center by the Sponsor or Investigator may include but are not 
limited to: 
 
Failure of the Investigator to comply with the protocol, with International Conference on 
Harmonisation-Good Clinical Practice (ICH-GPC) guidelines, the requirements of the IRB/IEC or local 
health authorities, the Sponsor’s procedures, FDA guidelines and regulations, or GCP guidelines. 
 
Inadequate recruitment of subjects by the Investigator. 
 
Discontinuation of further study treatment development. 
10.1.3 CONFIDENTIALITY AND PRIVACY  
Subject confidentiality and privacy are strictly held in trust by the participating investigators, their staff, 
and the Sponsor(s) and their interventions. This confidentiality is extended to cover testing of biological 
samples and genetic tests in addition to the clinical information relating to subjects. Therefore, the study 
protocol, documentation, data, and all other information generated will be held in strict confidence. 
No information concerning the study or the data will be released to any unauthorized third party without 
prior written approval of the Sponsor.  
All research activities will be conducted in as private a setting as possible. 
The study monitor, other authorized representatives of the Sponsor, representatives of the IRB/IEC, 
regulatory agencies or pharmaceutical company supplying study drug may inspect all documents and 
records required to be maintained by the Investigator, including but not limited to, medical records 
(office, clinic, or hospital) and pharmacy records for the subjects in this study. The clinical study center 
will permit access to such records. 
The study subject’s contact information will be securely stored at each clinical study center for internal 
use during the study. At the end of the study, all records will continue to be kept in a secure location for 
as long a period as dictated by the reviewing IRB/IEC, Institutional policies, or Sponsor requirements. 
Study subject research data, which is for purposes of statistical analysis and scientific reporting, will be 
transmitted to and stored at the data management company responsible for data management, analysis, 
and reporting. This will not include the subject’s contact or identifying information. Rather, individual 
subjects and their research data will be identified by a unique study identification number. The study data 


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entry and study management systems used by clinical study sites and by data management research staff 
will be secured and password protected. At the end of the study, all study databases will be de-identified 
and archived by the Sponsor. 
All information generated in this study must be considered highly confidential and must not be disclosed 
to any persons not directly concerned with the study without written prior permission from the Sponsor. 
Authorized regulatory officials and Sponsor personnel (or their representatives) will be allowed full 
access to inspect and copy the records. All study investigational product, subject bodily fluids, and/or 
other materials collected shall be used solely in accordance with this protocol, unless otherwise agreed to 
in writing by the Sponsor. Subjects will only be identified by unique subject numbers on eCRFs. 
Every subject will be given a copy of each version of the form that he/she signs before and during the 
study. Each ICF may also include authorization allowing the institution, Investigator, and Sponsor to use 
and disclose personal health information in compliance with the Health Insurance Portability and 
Accountability Act of 1996 Health Information Portability and Accountability Act. 
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA  
Blood and serum specimen storage outside the study required assessments is optional and requires 
subjects to sign an ICF. Refusal to participate in this optional specimen storage does not affect a subject’s 
ability to be enrolled in the study. A subject may choose to participate in this specimen storage at 
screening or any time during the study up to and including the end of study visit.  
With the subject’s approval and as approved by local IRBs/IECs, de-identified biological samples will be 
stored at a certified, licensed central laboratory. These samples may be used to research the causes of AD, 
its complications and other conditions for which individuals with AD are at increased risk, and to improve 
treatment. The central lab will also be provided with a code-link that will allow linking the biological 
specimens with the phenotypic data from each subject, maintaining the blinding of the identity of the 
subject. 
During the conduct of the study, a subject may choose to withdraw consent to have biological specimens 
stored for future research.  
Samples will be stored at least until completion of study, which refers to signed CSR, with preference to 
store samples up to 5 years following EOS. If a subject withdraws from study prior to analysis, samples 
collected from the subject may be destroyed following written notification to Sponsor and Sponsor 
confirming approval to destroy in writing as well. Sponsor will also provide in writing any instructions if 
samples are to be destroyed sooner than the 5-year limit. 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
Table 7 lists the key personnel for this study. Additional study contact information will be provided in the 
Study Operations Manual. 


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Table 7. 
Key Study Personnel for Protocol ANB020-005 
Medical Monitor Sponsor 
AnaptysBio, Inc.
10421 Pacific Center Court, Suite 200, San Diego, CA 92121 USA
(858) 362-6295 (general line)
ANB020-005@anaptysbio.com 
10.1.6 DATA AND SAFETY MONITORING BOARD 
An independent DSMB will be constituted by the contract research organization (CRO) to oversee the 
safety aspects of this study. The DSMB will also include a specialist from different disciplines/specialties 
as per the written charter. The DSMB will examine the safety data emerging from the study and provide 
its recommendations to the Sponsor who will then pass these on to PIs and/or the IEC/IRB according to 
requirements and regulations. DSMB members will not be investigators in the study nor will they have 
any conflict of interest with the Sponsor. 
The planned approach for data provided to the DMSB is as follows: 

DSMB DRM #1 approximately 25% Enrollment

DSMB DRM #2 approximately 50% Treatment Completers

DSMB DRM #3 100% W16 Treatment Completers (Planned directly after Interim Analysis (IA)
with IA data

DSMB DRM #4 Final Data – 100% W24 Completion of Study.
The identification/affiliation of DSMB members, roles and responsibilities of the DSMB, the operational 
procedures, data review meeting (DRM) schedules, data cutoff period/dates for review and method of 
communication with the CRO and/or Sponsor will be described in a separate DSMB charter. 
10.1.7 CLINICAL MONITORING 
Sponsor has engaged the services of a contract research organization, IQVIA, to perform all monitoring 
functions within this clinical study. IQVIA Monitors will work in accordance with IQVIA standard 
operating procedures (SOPs). The Monitor will establish and maintain regular contact between the 
Investigator and Sponsor. 
Monitoring will be carried out as determined by risk assessment process conducted on the study. 
The Monitor will evaluate the competence of the study center, informing the Sponsor about any problems 
relating to facilities, technical equipment, or medical staff. During the study, the Monitor will check that 
written informed consent has been obtained from all subjects correctly and that data are recorded 
correctly and completely. The Monitor is also entitled to compare entries in eCRFs with corresponding 
source data and to inform the Investigator of any errors or omissions. The Monitor will also assess and 
control adherence to the protocol and ICH/GCP guidelines at the study center. The Monitor will arrange 
for the supply of study treatment, ensure proper study treatment dispensing/accountability, and 
appropriate storage conditions are maintained. 


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Monitoring visits will be conducted according to all applicable regulatory requirements and standards. 
Regular monitoring visits will be made to each center while subjects are enrolled in the study. 
During monitoring visits, all entries in the eCRFs will be compared with the original source documents 
(source data verification). For the following and all other items, this check will be 100%: 
 
Subject identification number. 
 
Subject consent obtained. 
 
Subject eligibility criteria (inclusion and exclusion criteria). 
 
Efficacy variables. 
 
Safety variables. 
 
Medical record of AE. 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
According to the Guidelines of GCP (CPMP/ICH/135/95), IQVIA is responsible for implementing and 
maintaining quality assurance and quality control systems with written standard operating procedures 
(SOPs). Quality control will be applied to each stage of data handling. 
The following steps will be taken to ensure the accuracy, consistency, completeness, and reliability of the 
data: 
 
Central laboratories for clinical laboratory parameters. 
 
Center Initiation visit and/or participation in an Investigator Meeting. 
 
Early center visits post-enrollment. 
 
Routine center monitoring. 
 
Ongoing center communication and training. 
 
Data management quality control checks. 
 
Continuous data acquisition and cleaning. 
 
Internal review of data. 
 
Quality control check of the final clinical study report. 
In addition, Sponsor and/or IQVIA Clinical Quality Assurance Department may conduct periodic audits 
of the study processes, including, but not limited to study center, central laboratories, vendors, clinical 
database, and final clinical study report. When audits are conducted, access must be authorized for all 
study related documents including medical history and concomitant medication documentation to 
authorized Sponsor’s representatives and regulatory authorities. 
10.1.9 DATA HANDLING AND RECORD KEEPING  
 
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
Data generated within this clinical study will be handled according to the relevant SOPs of the Data 
Management and Biostatistics departments of IQVIA. 


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Electronic data capture (EDC) will be used for this study, meaning that all eCRF data will be entered in 
electronic forms at the study center. Data collection will be completed by authorized study center staff 
designated by the Investigator. Appropriate training and security measures will be completed with the 
Investigator and all authorized study center staff prior to the study being initiated and any data being 
entered into the system for any study subjects. 
All data must be entered in English. The eCRFs should always reflect the latest observations on the 
subjects participating in the study. Therefore, the eCRFs are to be completed as soon as possible during or 
after the subject’s visit. To avoid inter observer variability, every effort should be made to ensure that the 
same individual who made the initial baseline determinations completes all efficacy and safety 
evaluations. The Investigator must verify that all data entries in the eCRFs are accurate and correct. If 
some assessments are not done, or if certain information is not available or not applicable or unknown, 
the Investigator should indicate this in the eCRF. The Investigator will be required to electronically sign 
off on the clinical data. 
The Clinical Site Monitor will review the eCRFs and evaluate them for completeness and consistency. 
The eCRF will be compared with the source documents to ensure that there are no discrepancies between 
critical data. All entries, corrections and alterations are to be made by the responsible Investigator or 
his/her designee. The Monitor cannot enter data in the eCRFs. Once clinical data of the eCRF have been 
submitted to the central server, corrections to the data fields will be audit trailed, meaning that the reason 
for change, the name of the person who performed the change, together with time and date will be logged. 
Roles and rights of the center staff responsible for entering the clinical data into the eCRF will be 
determined in advance. If additional corrections are needed, the responsible Monitor or Data Manager 
will raise a query in the EDC application. The appropriate study center staff will answer queries sent to 
the Investigator. This will be audit trailed by the EDC application meaning that the name of 
investigational staff, time and date stamp are captured. 
The eCRF is essentially considered a data entry form and should not constitute the original (or source) 
medical records unless otherwise specified. Source documents are all documents used by the Investigator 
or hospital that relate to the subject’s medical history, that verify the existence of the subject, the 
inclusion and exclusion criteria and all records covering the subject’s participation in the study. They 
include but are not limited to laboratory notes, ECG results, memoranda, pharmacy dispensing records, 
subject files, etc. Source data should be attributable, legible, contemporaneous, original, accurate, and 
complete. Changes to source data should be traceable, should not obscure the original entry, and should 
be explained if necessary (eg, via an audit trail). 
The Investigator is responsible for maintaining source documents. These will be made available for 
inspection by the study Monitor at each monitoring visit. The Investigator must submit a completed eCRF 
for each subject who receives study treatment, regardless of duration. All supportive documentation 
submitted with the eCRF, such as laboratory or hospital records, should be clearly identified with the 
study and subject number. Any personal information, including subject name, should be removed or 
rendered illegible to preserve individual confidentiality. 
Electronic case report form records will be automatically appended with the identification of the creator, 
by means of their unique User ID. Specified records will be electronically signed by the Investigator to 
document his/her review of the data and acknowledgement that the data are accurate. This will be 


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facilitated by means of the Investigator’s unique User ID and password; date and time stamps will be 
added automatically at time of electronic signature. If an entry on an eCRF requires change, the correction 
should be made in accordance with the relevant software procedures. All changes will be fully recorded in 
a protected audit trail, and a reason for the change will be required. 
10.1.9.2 STUDY RECORDS RETENTION  
The Investigator must maintain essential study documents (protocol and protocol amendments, completed 
eCRFs, signed ICFs, relevant correspondence, and all other supporting documentation). The study center 
should plan on retaining such documents for approximately 15 years after study completion. The study 
center should retain such documents until at least 2 years after the last approval of a marketing application 
in an ICH region and until there are no pending or contemplated marketing applications in an ICH region 
or at least 2 years after the formal discontinuation of clinical development of the study treatment 
(etokimab). These documents should be retained for a longer period if required by the applicable 
regulatory requirements or the hospital, institution, or private practice in which the study is being 
conducted. Subject identification codes (subject names and corresponding study numbers) will be retained 
for this same period of time. These documents may be transferred to another responsible party, acceptable 
to Sponsor, who agrees to abide by the retention policies. Written notification of transfer must be 
submitted to Sponsor. No study records should be destroyed without prior authorization from the 
Sponsor. 
10.1.10 
PROTOCOL DEVIATIONS  
A protocol deviation is any noncompliance with the clinical trial protocol, ICH GCP, or Clinical 
Operations Plan requirements. The noncompliance may be either on the part of the subject, the 
Investigator, or the study site staff. As a result of deviations, corrective actions are to be developed by the 
site and implemented promptly.  
It is the responsibility of the study center Investigator to use continuous vigilance to identify and report 
deviations as soon as possible. All deviations must be addressed in study source documents and must be 
sent to the reviewing IRB per their policies. The site Investigator is responsible for knowing and adhering 
to the reviewing IRB requirements.  
Major protocol deviations considered to affect the primary analysis include, but are not limited to, the 
following:  
 
Failure to meet inclusion/exclusion criteria as defined by protocol 
 
Mishandling of the study drug which could have impacted the integrity of the study data such as 
non-allowable temperature deviations during storage or dispensing of study drug to the wrong 
subject 
 
Partial dosing of study treatment 
 
Use of prohibited concomitant medications unless defined as rescue medication per protocol 
 
Study procedures done outside protocol-specified window period that are judged to affect study 
efficacy data 
 
Assessments for primary endpoint not done. 


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Protocol deviations will be reviewed prior to unblinding and individual subjects having protocol 
deviations will be evaluated for inclusion in the PPS. Any additional deviations not listed above will be 
documented at this time. Further details about the handling of protocol deviations will be included in the 
Protocol Deviation Plan, Clinical Operations Plan, Medical Monitoring Plan, Safety Management Plan, 
and SAP. 
This study will be conducted as described in this protocol, except for an emergency situation in which the 
protection, safety, and well-being of the subject requires immediate intervention, based on the judgment 
of the Investigator (or a responsible, appropriately trained professional designated by the Investigator). In 
the event of a significant deviation from the protocol due to an emergency, accident, or mistake, the 
Investigator or designee must contact the Medical Monitor and the Sponsor at the earliest possible time by 
telephone. This will allow an early joint decision regarding the subject’s continuation in the study. This 
decision will be documented by the Investigator and the Medical Monitor. 
10.1.11 
PUBLICATION AND DATA SHARING POLICY 
The data generated by this study are confidential information of the Sponsor. The Sponsor will make the 
results of the study publicly available. The publication policy with respect to the Investigator and study 
center will be set forth in the Clinical Trial Agreement. 
10.1.12 
CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence is critical. Therefore, any actual 
conflict of interest of persons who have a role in the design, conduct, analysis, publication, financial 
interest, or any aspect of this trial will be disclosed and managed. Furthermore, persons who have a 
perceived conflict of interest will be required to have such conflicts managed in a way that is appropriate 
to their participation in the design and conduct of this trial. The study leadership has established policies 
and procedures for all study group members to disclose all conflicts of interest and will establish a 
mechanism for the management of all reported dualities of interest. Investigators and Sub-investigators 
will provide the Sponsor with sufficient, accurate financial information as requested to allow the Sponsor 
to submit complete and accurate financial certification or disclosure statements to the appropriate 
regulatory authorities. Investigators are responsible for providing information on financial interests in 
accordance to local requirements and laws during the course of the study and for 1 year after completion 
of the study. 
10.2 ADDITIONAL CONSIDERATIONS 
10.2.1 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 Good Clinical Practice (GCP) Guidelines. 


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 
Applicable laws and regulations. 
The protocol, protocol amendments, ICF, IB, and other relevant documents (eg, advertisements) must 
be submitted to an IRB/IEC by the Investigator and reviewed and approved by the IRB/IEC before 
the study is initiated. 
10.2.2 AMENDMENT POLICY 
The protocol, protocol amendments, ICF, IB, and other relevant documents (eg, advertisements) must be 
submitted to an IRB/IEC by the Investigator and reviewed and approved by the IRB/IEC before the study 
is initiated. 


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10.3 ABBREVIATIONS 
 
Abbreviation
Definition 
ACQ-6
Asthma Control Questionnaire-6
AD
Atopic dermatitis
ADA
Anti-drug antibody
AE
Adverse event
ALT
Alanine aminotransferase
AST
Aspartate aminotransferase
AUC
Area under the concentration-time curve for a dosing interval 
BMI
Body mass index
BP
Blood pressure
BSA
Body surface area
CFR
Code of Federal Regulations
CL/F
Apparent clearance
Cmax
Maximum concentration
CRO
Contract Research Organization
DLQI
Dermatology Life Quality Index
DSMB
Data Safety Monitoring Board
EASI
Eczema Area and Severity Index
ECG
Electrocardiogram
eCOA
Electronic Clinical Outcome Assessments
eCRF
Electronic case report forms
EOS
End of Study
ePRO
Electronic patient reported outcome
ETV
Early termination visit
FAS
Full analysis set
FSH
Follicle stimulating hormone
GCP
Good Clinical Practice
HIV
Human immunodeficiency virus
HR
Heart rate
HRT
Hormone replacement therapy
IB
Investigators Brochure
ICF
Informed consent form
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IFN- γ
Interferon gamma
IgA
Immunoglobulin A
IgE
Immunoglobulin E
IGRA
Interferon-gamma release assay
IL
Interleukin
IND
Investigational New Drug Application
IRB
Institutional Review Board
IXRS
Interactive Web Response System
mAb
Monoclonal antibody
MAD
Multiple ascending dose
MedDRA
Medical Dictionary for Regulatory Activities
MCID
Minimal clinically important difference


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Abbreviation
Definition 
NCT
National Clinical Trial
NRS
Numerical rating scale
PI
Principal investigator
PK
Pharmacokinetics
POEM
Patient Oriented Eczema Measure
PPS
Per protocol Analysis Set
Q4W
Every 4 weeks
Q8W
Every 8 weeks
QoL
Quality of life
SAD
Single ascending dose
SAE
Serious adverse event
SAF
Safety Analysis Set
SAP
Statistical Analysis Plan
SC
Subcutaneous(ly)
SCORAD
Scoring Atopic Dermatitis
SD
Standard deviation
SOA
Schedule of Activities
SOC
System organ class
SOP
Standard Operating Procedure
ST2
IL-33 receptor
t1/2
Apparent terminal half-life
TB
Tuberculosis
TCI
Topical calcineurin inhibitors
TCS
Topical corticosteroids
TEAE
Treatment-emergent adverse event
Th2
T helper type 2
tmax
Time of maximum concentration
ULN
Upper limit of normal
UP
Unanticipated problem
US
United States
Vd/F
Apparent volume of distribution
vIGA-AD
Validated Investigator Global Assessment Scale for Atopic Dermatitis
WOCBP
Woman of childbearing potential
 


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11 REFERENCES  
 
1. Nabe, T. Interleukin (IL)-33: New Therapeutic Target for Atopic Diseases. J Pharmacol Sci. 2014; 
126(2): 85-91.  
2. Liew Fy. Il-33: A Janus Cytokine. Ann Rheum Dis. 2012 Apr; 71(Suppl 2): I101-I104. 
3. Takatori H, Makita S, Ito T, Matsuki A, Nakajima H. Regulatory mechanisms of IL-33-ST2-mediated 
allergic inflammation. Front Immunol. 2018; 9:2004. 
4. Montes Torres A, Llamas Velasco M, Pérez-Plaza A, Solano López G and Sánchez Pérez J. 
Biological Treatments in Atopic Dermatitis. J Clin Med. 2015 Apr 3; 4(4):593 601. 
5. Leung D, Bieber T. Atopic Dermatitis. Lancet 2003 Jan 11; 361(9352):151-60. 
6. Eichenfield et al, J Am Acad Dermatol. 2014, Feb; 70 (2): 338 351. 
7. Pastorelli L., Garg RR, Hoang SB., Spina L, Mattioli B., Scarpa M., et al. Epithelial-derived IL 33 
and its receptor ST2 are dysregulated in ulcerative colitis and in experimental Th1/Th2 driven 
enteritis. Proc. Natl. Acad. of Sci USA. 2010 Apr 27;107(17):8017-8022. 
8. Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The eczema area and severity 
index (EASI): assessment of reliability in atopic dermatitis. Exp Dermatol 2001; 10: 11 8. 
9. Schram ME, Spuls PI, Leeflang MM, Lindeboom R, Bos JD, Schmitt J. EASI, (objective) SCORAD 
and POEM for atopic eczema: responsiveness and minimal clinically important difference. Allergy 
2012; 67: 99-106. 
10. Copyright ©2017 Eli Lilly and Company – Used with the permission of Eli Lilly and Company under 
a Creative Commons Attribution-NoDerivatives 4.0 International License - 
https://creativecommons.org/licenses/by-nd/4.0/. 
11. European Task Force on Atopic Dermatitis. Severity scoring of atopic dermatitis: the SCORAD 
index: Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology 1993; 186: 
23-31. 
12. Badia X, Mascaro JM, et al. Measuring health-related quality of life in patients with mild to moderate 
eczema and psoriasis: clinical validity, reliability and sensitivity to change of the DLQI. Br J 
Dermatol 1999; 141:698-702. 
13. Charman CR, Venn AJ, et al. The patient-oriented eczema measure. Arch Dermatol 2004; 140:1513 
1519. 
 
 


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APPENDICES 
 
APPENDIX A: SUMMARY OF CHANGES FOR (COUNTRY-SPECIFIC) 
AMENDMENT 1 
 
The summary of changes for global amendment 2 are shown in Table 8. 
 
Table 8. 
Summary of Changes for ANB020-005 Protocol Amendment 2 
Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
Entire protocol 
 Sections and Appendices reordered, added, 
and/or deleted
 Consistency with new Common Protocol 
Template 
Sponsor Signature 
Page 
 Updated statement of Sponsor’s 
compliance and approval of protocol 
 Consistent with ICH expectations of 
Sponsor obligations and AnaptysBio use 
of Common Protocol Template 
Synopsis, 
Sections 1.3 
(footnote ‘o’), 8.7 
 Revised description of administration of 
ACQ-6 to subjects whose primary 
language is English and availability of 
validated translations in participating 
countries
 Accuracy and completeness 
Synopsis, 
Section 4.1 
 Added statement that DSMB would also 
advise the Sponsor of potential safety 
signals
 Accuracy and completeness 
Synopsis 
 Revised the number of study centers and 
added the geographic regions of study 
centers
 Accuracy and completeness 
Figure 1 
 Revised figure caption and simplified study 
population bullet in figure
 Accuracy and completeness 
Section 1.3 
(SOA table) 
 Deleted ‘Optional items informed consent’ 
at screening from table 
 Revised footnote ‘g’ to specify that a 
negative pregnancy test result must be 
obtained at Visits 1 and 2 before subject 
may be randomized into study 
 Revised table and footnote ‘h’ to include 
TB testing, on a country-by-country basis 
 Clarified and revised timepoints for 
hematology and chemistry blood samples 
(footnote ‘I’), urinalysis (footnote ‘j’), and 
PK blood samples (footnote ‘k’)
 Provide clarification the optional ICF is 
not a separate item from the informed 
consent 
 Assuring patient safety requirement and 
compliance with health authority 
requests 
 Accuracy and completeness 
Section 2.1 
 Revised the description of the mechanism 
of action of etokimab with respect to IL-33 
inhibition and added 2 new references.
 Consistency with Etokimab IB version 7  


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Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
Section 2.2.2 
 Added statement that etokimab and 
ANB020 are used interchangeably 
throughout the study protocol 
 Updated atopic diseases that etokimab is 
being developed to treat
 Accuracy and completeness 
 Consistency with Etokimab IB version 7  
Section 2.2.2.2 
 Added summary statement 
 Completeness 
Section 2.2.2.2.1 
 Updated summary of Study ANB020-001 
results
 Consistency with version 7 of the 
Etokimab IB 
Section 2.2.2.2.2 
 Added summary of Study ANB020-BA-01 
results
 Consistency with version 7 of the 
Etokimab IB 
Section 2.2.2.2.3 
 Added summary of Study ANB020-002 
results
 Consistency with version 7 of the 
Etokimab IB 
Section 2.3.1 
 Updated known potential risks of etokimab 
 Consistency with version 7 of the 
Etokimab IB 
Section 3 
 Provided justification for endpoints 
 Accuracy and clarification 
Section 4.3 
 Justification of dose 
 Health authority request for clarity and 
completeness 
Section 4.4  
 Revised end of study definition to include 
last visit on Day 169 or the last scheduled 
procedure
 Aligning with industry standard 
definition 
Section 5.1 
 Inclusion Criterion #2: Revised maximum 
BMI to ≤35 kg/m2 for all subjects  
 Inclusion Criterion #4: Expanded EASI 
score at screening and Baseline from ≥12 
to ≥16 at screening and Baseline  
 Inclusion Criterion #7.b.ii: Added 
restriction to WOCBP to refrain from 
donating oocytes during treatment period 
and at least 3 months after last dose of 
study drug 
 Focusing on patient safety and aligning 
criteria in patients being enrolled 
 Input provided by participating clinical 
investigators with strong patient 
management experience 
 Complying with the Health Authorities 
request 
Section 5.2 
 Exclusion Criterion #14: Added note to 
better define how TB will be diagnosed 
and deleted text about TB retesting. 
 Exclusion Criterion #16: Revised 
permissible hemoglobin, neutrophils, and 
platelets levels at screening 
 Exclusion Criterion #17: Replaced history 
of drug abuse criterion with a new 
drug/substance abuse criterion
 Complying with the Health Authority 
requests. 
 Providing clarification on drug, alcohol 
or other substance abuse criteria.  
Section 5.4 
 Updated number of re-screens allowed 
 Correction 
Section 6.2.2 
 Updated description of etokimab 
formulation 
 Consistency with Etokimab IB version 
7.0  
Section 6.2.4 
 Added IP preparation details 
 Clarification regarding site expectation 
to comply with IP preparation and 
preserving blind. 


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Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
Section 6.2.5 
 Added additional dosing instructions 
 Health authority requests to assure no 
overlap between injection sites.  
Section 6.5.2 
 Added details regarding anti-inflammatory 
topical rescue therapy
 Provide clarification 
Section 7.1 
 Added details to better define 
discontinuation of study intervention
 Provide clarification 
Section 7.2 
 Revised ALT or AST criteria for 
discontinuation/withdrawal from study 
 Assuring patient safety requirement and 
compliance with health authority 
requests 
Section 7.3 
 Revised description of rescheduled and 
missed visits
 Provide clarification 
Section 8.2 
 Added statement that unscheduled safety 
assessments may be performed at any time 
during the study.
 Provide clarification 
Section 8.3 
 Updated PK and ADA processing 
 Clarification 
Sections 8.7, 
8.7.1, 8.7.2, 8.7.3 
 Added new section for Unanticipated 
Problems 
 Consistent with new Common Protocol 
Template language 
Section 9.1 
 Updated statistical hypothesis  
 Clarification 
Section 9.3.2 
 Modified the endpoint to NRS for pruritus 
score reduction from Baseline of 4.
 Per scientific advice per the health 
authority 
Section 9.3.2.4 
 Added new section for the handling of 
dropouts and missing data
 Clarification and aligning with industry 
practice 
Section 9.3.6 
 Added new section for subgroup analyses 
 Common Protocol Template language 
Section 9.3.9 
 Revised PK parameters and identified the 
Bayesian post-hoc estimation approach as 
the PK simulation model to be used
 Accuracy and completeness 
Section 10.1.2 
 Added examples to possible study 
discontinuation and closure
 Assuring Sponsor obligation to oversee 
and manage site performance. 
Section 10.1.4 
 Added guidelines around sample storage 
and notification of destruction 
 Provide clarification and assuring site 
understanding of process 
Section 10.1.10 
 Added section for protocol deviations 
 Consistent with new Common Protocol 
Template 
Appendix A 
 Added new appendix for Amendment 1 
Summary of Changes
 Provide clarification 
 
 
 
 
 
The Summary of Changes for each of the 3 country-specific protocol amendments for ANB020-005 
Protocol Amendment 1 are shown in Table 9. (Czech Republic), Table 10 (Germany), and Table 11 
(the UK). 


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Table 9. 
Protocol Amendment 1 for Czech Republic (dated 01 August 2018) 
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Original Text 
New Text 
Rationale 
1.3 Schedule of Activities and 
footnote 
(p. 15) 
 
In addition, tuberculosis 
testing by interferon-
gamma (IFN-γ) release 
assay (IGRA) will be 
performed on a country-by-
country basis if required by 
regulatory authorities (eg, 
Czech Republic) or ethics 
boards.
Added IGRA test to exclude 
latent forms of TBC if 
negative test result is required 
for eligibility. 
4.3 Justification for Dose 
(p. 26) 
Emergent data from the 
Phase I study (ANB020-001) 
and 
Phase IIa 
study 
(ANB020-002) are the basis 
for the section of dose of 
ANB020 for the current 
study. The 300 mg IV dose 
was found to be safe and well 
tolerated in healthy subjects 
and in subjects with AD. An 
interim 
analysis 
of 
the 
Phase IIa study indicated that 
a 
clinical 
response 
was 
observed 
2 weeks 
post 
ANB020 
administration 
(300 mg IV). One month 
post 
ANB020 
administration, the average 
EASI score reduction was 
61% and the average pruritus 
reduction was 32 % relative 
to 
Baseline. 
Sustained 
clinical 
response 
was 
observed 
after 
2 months 
post-ANB020 
administration.  
 
The Phase I study in healthy 
subjects is completed. The 
dose range of ANB020 
(excluding the expected sub-
therapeutic 20 mg, and 
placebo arms) selected for 
this study has provided 
complete inhibition of IL-33 
induced cytokine release, 
and has been used safely in 
study ANB020-001. 
Data from the Phase I study 
(ANB020-001) and 
Phase IIa study (ANB020-
002) are the basis for the 
selection of dose of 
ANB020 for the current 
study. The dose range of 
ANB020 selected for this 
study has been used safely 
in study ANB020 001. 
ANB020 pharmacodynamic 
activity, measured as 
inhibition of ex-vivo IL-33 
stimulated INF-γ 
production, can be inferred 
from the correlation with 
PK data. All of the selected 
dose levels of ANB020 are 
predicted to induce full IL-
33 inhibition within 2 days 
for at least 9-10 days after 
dosing. The administration 
of the loading doses of 
ANB020 will allow 
systemic concentrations to 
reach serum concentrations 
sustaining more than 95% 
IL-33 inhibition faster, and 
potentially reduce the time 
to onset of clinical effect. 
Data from the Phase IIa 
study show a clinical 
response 1 week post 
ANB020 administration 
(300 mg IV), and the dose 
was found to be safe and 
well tolerated. One month 
post ANB020 
administration, the average 
EASI score reduction was 
61% and the average 
pruritus reduction was 32 % 
relative to Baseline. 
Sustained clinical response 
was observed after 
2 months post-ANB020 
administration. 
Provided additional 
clarification on rationale for 
dose. 
Exclusion criteria  
(p. 29) 
14. Immunodeficiency 
disorders (eg, IgA 
deficiency) or known or 
14. Immunodeficiency 
disorders (eg, IgA 
deficiency) or known or 
Provided additional 
clarification on eligibility for 


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Affected Section 
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New Text 
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suspected history of 
immunosuppression, 
including history of invasive 
opportunistic infections (eg, 
tuberculosis, histoplasmosis, 
listeriosis, 
coccidioidomycosis, 
pneumocytosis, 
aspergillosis) despite 
infection resolution or 
unusually frequent, 
recurrent, or prolonged 
infections, per Investigator’s 
judgement. 
 
suspected history of 
immunosuppression, 
including history of 
invasive opportunistic 
infections (eg, active or 
latent tuberculosis, 
histoplasmosis, listeriosis, 
coccidioidomycosis, 
pneumocytosis, 
aspergillosis) despite 
infection resolution or 
unusually frequent, 
recurrent, or prolonged 
infections, per 
Investigator’s judgement. 
NOTE: Suspected active or 
latent tuberculosis will be 
based on medical history, 
physical examination, and 
standard of care diagnostic 
methods. Subjects with a 
positive interferon-gamma 
(IFN-γ) release assay 
(IGRA) at screening are not 
eligible for this study.
subjects with suspected 
tuberculosis. 
Exclusion criteria  
(p. 30) 
16. Laboratory findings at 
screening: 
 Alanine aminotransferase 
(ALT) or aspartate 
aminotransferase (AST) 
>3 times the upper limit 
of normal (ULN) and 
total bilirubin >2 times 
ULN (except in case of 
documented Gilbert’s 
syndrome) at screening. 
 Confirmed AST and/or 
ALT >5 × ULN. 
 Hemoglobin is <9 g/dL. 
 Neutrophils 
<1.0 × 103/µL. 
 Platelets <100 × 103/µL.
16. Laboratory findings at 
screening: 
 Alanine 
aminotransferase (ALT) 
or aspartate 
aminotransferase (AST) 
>3 times the upper limit 
of normal (ULN). 
 Hemoglobin is 
<11 g/dL. 
 Neutrophils 
<1.5 × 103/µL. 
 Platelets 
<100 × 103/µL. 
 
Changed requirements for 
laboratory findings at 
screening to exclude subjects 
with more severe 
abnormalities in their liver 
enzymes or hematology 
levels. 
Abbreviations 
(p. 60)
 
IGRA Interferon-gamma 
release assay
Added additional 
abbreviation.
Table 10 Protocol-required 
Safety Laboratory 
Assessments 
(p. 70)
 
Interferon-gamma release 
assay (if required on a 
country-by-country basis) 
Added IGRA test to exclude 
latent forms of TBC if 
negative test result is required 
for eligibility.
 
Table 10. 
Protocol Amendment 1 for Germany (dated 31 July 2018) 
Affected Section 
Original Text 
New Text 
Rationale 
4.3 Justification for Dose 
(p. 26) 
Emergent data from the 
Phase I study (ANB020-
001) and Phase IIa study 
(ANB020-002) are the basis 
for the section of dose of 
ANB020 for the current 
study. The 300 mg IV dose 
Data from the Phase I study 
(ANB020-001) and 
Phase IIa study (ANB020-
002) are the basis for the 
selection of dose of 
ANB020 for the current 
study. The dose range of 
Provided additional 
clarification on rationale for 
dose. 


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Affected Section 
Original Text 
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was found to be safe and 
well tolerated in healthy 
subjects and in subjects with 
AD. An interim analysis of 
the Phase IIa study indicated 
that a clinical response was 
observed 2 weeks post 
ANB020 administration 
(300 mg IV). One month 
post ANB020 
administration, the average 
EASI score reduction was 
61% and the average 
pruritus reduction was 32 % 
relative to Baseline. 
Sustained clinical response 
was observed after 2 months 
post-ANB020 
administration.  
 
The Phase I study in healthy 
subjects is completed. The 
dose range of ANB020 
(excluding the expected sub-
therapeutic 20 mg, and 
placebo arms) selected for 
this study has provided 
complete inhibition of IL-33 
induced cytokine release, 
and has been used safely in 
study ANB020-001. 
ANB020 selected for this 
study has been used safely 
in study ANB020-001. 
ANB020 pharmacodynamic 
activity, measured as 
inhibition of ex-vivo IL-33 
stimulated INF-γ 
production, can be inferred 
from the correlation with 
PK data. All of the selected 
dose levels of ANB020 are 
predicted to induce full IL-
33 inhibition within 2 days 
for at least 9-10 days after 
dosing. The administration 
of the loading doses of 
ANB020 will allow 
systemic concentrations to 
reach serum concentrations 
sustaining more than 95% 
IL-33 inhibition faster, and 
potentially reduce the time 
to onset of clinical effect. 
Data from the Phase IIa 
study show a clinical 
response 1 week post 
ANB020 administration 
(300 mg IV), and the dose 
was found to be safe and 
well tolerated. One month 
post ANB020 
administration, the average 
EASI score reduction was 
61% and the average 
pruritus reduction was 32 % 
relative to Baseline. 
Sustained clinical response 
was observed after 
2 months post-ANB020 
administration.
6.5.6 Rescue Medicine  
(pg. 37) 
Subjects who are rescued 
should receive low potency 
TCS over moderate or high 
potency TCS. 
Anti-inflammatory topical 
rescue therapy should be 
administered to lesional 
skin only. The choice of the 
corticosteroid should be 
based upon standard of care 
considerations (eg, body 
area involved, severity of 
skin inflammation). A list 
of representative topical 
corticosteroids is provided 
in Appendix 15. We 
suggest a low potency 
corticosteroids (Class 6/7) 
cream or ointment. If 
needed for more severe 
inflammation, we suggest 
moderate potency 
corticosteroids (Class 4/5). 
Topical calcineurin 
inhibitors (eg, tacrolimus 
Provided additional 
clarification on the rescue 
medications.  


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0.1%) may be an alternative 
to topical corticosteroids, in 
particular for the treatment 
of the face, neck, and skin 
folds. 
Appendix 2 Regulatory, 
Ethical, and Study Oversite 
Considerations 
(pg. 68) 
 
Reasons may include 
safety, among others. 
Should the sponsor decide 
to terminate the study, the 
investigator(s) will be 
notified in writing. 
Provided possible reasons for 
study termination by the 
Sponsor 
Appendix 15 WHO 
Classification of Topical 
Corticosteroids 
(pg. 95) 
 
WHO Classification of 
Topical Corticosteroids 
 
Topical corticosteroids 
have been ranked in terms 
of potency into four groups 
consisting of seven classes. 
Class I topical 
corticosteroids are the most 
potent and Class VII are the 
least potent. Representative 
preparations by group are 
listed in the table below. 
These groups may vary 
depending on the 
formulation and 
concentration and should be 
considered approximate.  
Reference provided as 
guidance to the rescue 
medication 
 
Table 11. 
Protocol Amendment 1 for the UK (dated 21 June 2018) 
Affected Section 
Original Text 
New Text 
Rationale 
Inclusion Criteria #7 ii  
(p. 27) 
A WOCBP who agrees to 
follow the contraceptive 
guidance in Appendix 6 
during the treatment period 
and for at least 3 months 
after receiving the last dose 
of study treatment. 
A WOCBP who agrees to 
follow the contraceptive 
guidance in Appendix 6 
during the treatment period 
and for at least 3 months 
after receiving the last dose 
of study treatment and 
refrain from donating 
oocytes (eggs) during this 
period.
It is not known whether 
ANB020 affects reproductive 
capacity. Therefore, women of 
childbearing potential should 
take necessary precautions to 
avoid pregnancy while 
receiving ANB020. This 
includes the donation of their 
eggs to achieve pregnancy in 
assisted reproductive care.
Exclusion Criteria #16  
(p. 29) 
Laboratory findings at 
Screening: 
 Alanine aminotransferase 
(ALT) or aspartate 
aminotransferase (AST) 
>3 times the upper limit 
of normal (ULN) and 
total bilirubin >2 times 
ULN (except in case of 
documented Gilbert’s 
syndrome) at screening. 
 Confirmed AST and/or 
ALT >5 × ULN. 
 Hemoglobin is <9 g/dL.
Laboratory findings at 
screening: 
 Alanine 
aminotransferase (ALT) 
or aspartate 
aminotransferase (AST) 
>3 times the upper limit 
of normal (ULN) and 
total bilirubin >1.5 
times ULN (total 
bilirubin >3 times ULN 
in case of documented 
Gilbert’s syndrome) at 
screening. 
The safety profile of ANB020 
is evolving and the minimum 
allowed hematology and 
bilirubin levels were at the 
limit of risk.  
Added a missing upper limit 
for total bilirubin in case of 
Gilbert’s syndrome (GS). GS 
is a benign condition 
characterized by higher than 
normal levels of unconjugated 
bilirubin, usually in the range 
of 1-3 × ULN (eg, after 
fasting). 


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Affected Section 
Original Text 
New Text 
Rationale 
 Neutrophils 
<1.0 × 103/µL. 
 Platelets <100 × 103/µL. 
 Confirmed AST and/or 
ALT >5 × ULN. 
 Hemoglobin is <10 
g/dL. 
 Neutrophils <1.5 × 
103/μL. 
 Platelets <150 × 103/μL. 
7.2 Subject Discontinuation/ 
Withdrawal from the Study  
(p. 37) 
 Laboratory abnormalities: 
o ALT or AST >5 times 
ULN for more than 
2 weeks. 
o ALT or AST >3 times 
ULN and bilirubin >2 
times ULN (unless 
related to Gilbert’s 
syndrome) at 
screening visit. 
 Laboratory 
abnormalities: 
o 
ALT or AST >5 
times ULN for 
more than 2 weeks. 
o 
ALT or AST >3 
times ULN and 
bilirubin >2 times 
ULN (total 
bilirubin >4 times 
ULN in case of 
documented 
Gilbert’s 
syndrome). 
Added upper limit for total 
bilirubin in case of Gilbert’s 
syndrome. Levels of bilirubin 
can fluctuate in people with 
Gilbert’s syndrome. They may 
be highest during certain 
conditions (eg, infection, 
fasting, or menstrual periods), 
but rarely exceed 4 × ULN in 
these patients. 
Appendix 6 Contraceptive 
Guidance – Female Subjects  
(p. 77) 
Female subjects of 
childbearing potential are 
eligible to participate if they 
agree to use highly effective 
methods of contraception 
consistently and correctly as 
described in the table below. 
Female subjects of 
childbearing potential are 
eligible to participate if 
they agree to use highly 
effective methods of 
contraception consistently 
and correctly as described 
in the table below and 
refrain from donating 
oocytes (eggs) for 3 months 
after receiving the last dose 
of study treatment 
Same as above (p. 27). 
 
 


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APPENDIX B: CLINICAL LABORATORY TESTS 
 
Clinical laboratory tests will be carried out at time points specified in the SOA (see Section 1.3). 
 
The tests detailed in Table 12 will be performed by the central laboratory. 
 
Local laboratory tests will be allowed in the event that the central laboratory results will not be 
available immediately and the Investigator needs to take an immediate decision for any safety 
concerns. If a local sample is required, it is important that the sample for central analysis is obtained 
at the same time. Urine pregnancy dipstick will be performed at the study center prior to study 
treatment administration. 
 
Protocol-specific requirements for inclusion or exclusion of subjects 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. 
Table 12. 
Protocol-required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Hematology 
Hemoglobin 
White blood cell count with differential 
Hematocrit 
Neutrophils 
Mean cell hemoglobin  
Lymphocytes 
Mean cell volume  
Monocytes 
Mean cell hemoglobin concentration  
Eosinophils 
Platelet count  
Basophils 
Red blood cell count  
Clinical Chemistry 
Alanine aminotransferase 
Creatinine 
Albumin 
Gamma glutamyl transferase  
Alkaline phosphatase  
Glucose 
Aspartate aminotransferase  
Potassium 
Bicarbonate 
Phosphate (Inorganic) 
Bilirubin (total) 
Protein (total) 
Bilirubin (direct-only if total is elevated) 
Sodium 
Calcium 
Blood urea nitrogen (urea) 
Chloride 
C-reactive protein 
Uric acid 
Triglycerides 
Lactate dehydrogenase 
Troponin-I 
Total cholesterol (fractions) 
Creatine kinase 
Serum pregnancy 
Human chorionic gonadotropin pregnancy test (as needed for women of childbearing potential) 
Follicle-stimulating 
hormone  
As needed in women of non-childbearing potential only (postmenopausal woman aged over 
45 years with at least 1 year of amenorrhea) 


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Laboratory 
Assessments 
Parameters 
Urine pregnancy 
Urine pregnancy dipstick (prior to study treatment administration) 
Urinalysis 
(dipstick test) 
Bilirubin  
pH 
Blood 
Protein 
Glucose 
Specific gravity 
Ketones 
Urobilinogen 
Leukocyte esterase 
Nitrites 
Immunoglobulin 
Immunoglobulin E 
 
Drugs of Abuse 
(Urine drug screen) 
Methamphetamine 
Benzodiazepines 
Cocaine 
Barbiturates 
Marijuana 
Phencyclidine 
MDMA 
Amphetamine 
Methadone 
Oxycodone 
Opiate 
TCA 
Ethanol 
Viral serology 
Hepatitis B surface antigen 
Hepatitis B and C Antibody 
 
 
HIV Antibodies (HIV 1 and 2) 
 
TB testing 
Interferon-gamma release assay (if required on 
a country-by-country basis) 
 
The results of each local test must be entered into the eCRF. 
Abbreviations: ADA = anti-drug antibody; eCRF = electronic case report form, HIV = Human Immunodeficiency Virus, 
MDMA = Methylenedioxymethamphetamine, PK = Pharmacokinetics and TCA=Tricyclic anti-depressants. 
NOTES: Please see Schedule of Activities (see Section 1.3) for laboratory tests time points. PK and ADA samples will be 
collected as detailed in the Schedule of Activities (see Section 1.3). Samples should be obtained prior to administering 
study drug if an administration coincides with the visit and before any hematology, or chemistry, samples to be drawn at 
that visit. The date and exact time of sample collection must be recorded. 
 
Investigators must document their review of each laboratory safety report. 


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APPENDIX C: CONTRACEPTIVE GUIDANCE AND COLLECTION OF 
PREGNANCY INFORMATION 
 
Definitions: 
 
 
Woman of Childbearing Potential (WOCBP) 
 
A woman is considered fertile following menarche and until becoming postmenopausal unless permanently sterile 
(see below). 
 
Women in the following categories are not considered WOCBP: 
 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
a) Documented hysterectomy. 
b) Documented bilateral salpingectomy. 
c) Documented bilateral oophorectomy. 
Note: Documentation can come from the study center personnel’s: review of the subject’s medical records, 
medical examination, or medical history interview. 
 
3. Postmenopausal female: 
a) A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high 
follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or hormonal replacement therapy (HRT). 
However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.  
b) Females on HRT and whose menopausal status is in doubt will be required to use 1 of the non-estrogen 
hormonal highly effective contraception methods if they wish to continue their HRT during the study. 
Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment. 
Contraception Guidance 
 
Male Subjects 
• 
Male subjects with female partners of childbearing potential are eligible to participate if they agree to ONE of 
the following (during the protocol-defined time frame in Section 5.1):  
o 
Are abstinent from penile vaginal intercourse as their usual and preferred lifestyle (abstinent on a long term 
and persistent basis) and agree to remain abstinent. 
 
o 
Agree to use a male condom plus partner use of a contraceptive method with a failure rate of < 1% per year 
when having penile vaginal intercourse with a WOCBP who is not currently pregnant. 
o 
In addition, male subjects must refrain from donating sperm for the duration of the study and for 3 months 
after the last dose of study treatment. 
 
• 
Male subjects with a pregnant or breastfeeding partner must agree to remain abstinent from penile vaginal 
intercourse or use a male condom during each episode of penile penetration for the duration of the study and for 
3 months after the last dose of study treatment. 
Female Subjects 


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• 
Female subjects must refrain from donating ova for the duration of the study and for 3 months after the last dose 
of study treatment. 
 
Female subjects of childbearing potential are eligible to participate if they agree to use highly effective 
methods of contraception consistently and correctly as described in the table below and refrain from 
donating oocytes (eggs) for 3 months after receiving the last dose of study treatment. 
Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User Dependent a  
Failure rate of <1% per year when used consistently and correctly.  
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation  
 Oral.  
 Intravaginal. 
 Transdermal. 
Progestogen only hormonal contraception associated with inhibition of ovulation 
 Oral. 
 Injectable.  
Highly Effective Methods That Are User Independent a  
Implantable progestogen only hormonal contraception associated with inhibition of ovulation 
 Intrauterine device. 
 Intrauterine hormone-releasing system. 
Hormone-free intrauterine device interfering with sperm transport and fertilization. 
Bilateral tubal occlusion or ligation. 
Vasectomized partner  
A vasectomy is a highly effective birth control method provided that the vasectomized partner is the sole male 
sexual partner of the WOCBP and the absence of sperm post vasectomy has been confirmed. If not, an additional 
highly effective method of contraception should be used.  
Sexual abstinence  
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study treatment. The reliability of sexual abstinence 
needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the subject.  
NOTES:  
a Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for subjects participating in clinical studies. 
 
Pregnancy Testing 
• 
Women of child bearing potential should only be included after a confirmed menstrual period and a negative 
highly sensitive serum pregnancy test at screening and urine pregnancy test on Day 1 (prior to study treatment 
administration). 
• 
Additional pregnancy testing should be performed as mentioned in the Schedule of Activities (see Section 1.3). 
• 
Pregnancy testing will be performed whenever a menstrual cycle is missed or when pregnancy is otherwise 
suspected. Positive urine pregnancy test result should be confirmed with a serum test. 
Collection of Pregnancy Information 
 
Male Subjects with Partners who Become Pregnant 


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• 
The Investigator will attempt to collect pregnancy information on any male subject’s female partner who 
becomes pregnant while the male subject is in this study. This applies only to male subjects who receive study 
treatment. 
• 
The Investigator will record pregnancy information on the appropriate pregnancy form and submit it to the 
Sponsor within 24 hours of learning of the partner’s pregnancy. The female partner will also be followed to 
determine the outcome of the pregnancy. Information on the status of the mother and child will be forwarded to 
the Sponsor. Generally, the follow-up will be no longer than 6 to 8 weeks following the estimated delivery date. 
Any termination of the pregnancy will be reported regardless of fetal status (presence or absence of anomalies) 
or indication for the procedure. 
Female Subjects who Become Pregnant  
• 
The Investigator will collect pregnancy information on any female subject who becomes pregnant while 
participating in this study. Information will be recorded on the appropriate form and submitted to the Sponsor 
within 24 hours of learning of a subject’s pregnancy. The subject will be followed to determine the outcome of 
the pregnancy. The Investigator will collect follow-up information on the subject and the neonate and the 
information will be forwarded to the Sponsor. Generally, follow-up will not be required for longer than 6 to 8 
weeks after the delivery date. Any termination of pregnancy will be reported, regardless of fetal status (presence 
or absence of anomalies) or indication for the procedure. 
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or elective 
termination of a pregnancy will be reported as an AE or SAE. A spontaneous abortion is always considered to 
be an SAE and will be reported as such. 
• 
Any post study pregnancy related SAE considered reasonably related to the study treatment by the Investigator 
will be reported to the Sponsor as described in Section 8.6.5. While the Investigator is not obligated to actively 
seek this information in former subjects, he or she may learn of an SAE through spontaneous reporting. 
• 
Any female subject who becomes pregnant while participating in the study will be withdrawn from the study.  
 
 


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APPENDIX D: EXCLUDED MEDICATIONS/THERAPY 
 
Excluded medications/therapy is listed below in Table 13. The use of an excluded medication/therapy is a 
protocol deviation and must be recorded in the eCRF. The following medications will not be permitted 
during the study: 
Table 13. 
Excluded Medication/Therapy 
Treatment 
Wash-out period 
Any topical medication containing corticosteroids (TCS), 
calcineurin inhibitor (TCI), or crisaborole. 
14 days prior to Day 1. 
Any systemic treatment for AD (including systemic 
corticosteroids, immunosuppressants, or immunomodulating 
drugs or phototherapy, or use of a tanning booth. 
4 weeks prior to screening. 
Live attenuated vaccine. 
4 weeks prior to screening through Day 1. 
Investigational systemic treatment or biologic systemic 
treatment. 
5 half-lives prior to screening. 
Investigational or licensed or other anti-Th2-type cytokine (eg, 
IL-31, IL-5, and TSLP) and anti-ST2. 
16 weeks or 5 half-lives (whichever is longer). 
Abbreviation: IL = Interleukin, ST2 = specific cell surface receptor, Th2 = T-helper cell, TSLP = Thymic stromal lymphopoietin. 
Note: Topical emollients are allowed during the study, except within 8 to 12 hours prior to the assessment. 
 
 
 


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APPENDIX E: WHO CLASSIFICATION OF TOPICAL CORTICOSTEROIDS 
Topical corticosteroids have been ranked in terms of potency into four groups consisting of seven classes. 
Class I topical corticosteroids are the most potent and Class VII are the least potent. Representative 
preparations by group are listed in the table below. These groups may vary depending on the formulation 
and concentration and should be considered approximate.  
Potency 
Class 
Topical corticosteroid 
Formulation 
Ultra high 
I 
Clobetasol propionate 
Cream, 0.05% 
Diflorasone diacetate 
Ointment, 0.05% 
High 
II 
Amcinonide 
Ointment, 0.1% 
Betamethasone dipropionate 
Ointment, 0.05% 
Desoximetasone 
Cream or ointment, 0.025% 
Fluocinonide 
Cream, ointment or gel, 0.05% 
Halcinonide 
Cream, 0.1% 
III 
Betamethasone dipropionate 
Cream, 0.05% 
Betamethasone valerate 
Ointment, 0.1% 
Diflorasone diacetate 
Cream, 0.05% 
Triamcinolone acetonide 
Ointment, 0.1% 
Moderate 
IV 
Desoximetasone 
Cream, 0.05% 
Fluocinolone acetonide 
Ointment, 0.025% 
Fludroxycortide 
Ointment, 0.05% 
Hydrocortisone valerate 
Ointment, 0.2% 
Triamcinolone acetonide 
Cream, 0.1% 
V 
Betamethasone dipropionate 
Lotion, 0.02% 
Betamethasone valerate 
Cream, 0.1% 
Fluocinolone acetonide 
Cream, 0.025% 
Fludroxycortide 
Cream, 0.05% 
Hydrocortisone butyrate 
Cream, 0.1% 
Hydrocortisone valerate 
Cream, 0.2% 
Triamcinolone acetonide 
Lotion, 0.1% 
Low 
VI 
Betamethasone valerate 
Lotion, 0.05% 
Desonide 
Cream, 0.05% 
  
Fluocinolone acetonide 
Solution, 0.01% 


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VII 
Dexamethasone sodium phosphate 
Cream, 0.1% 
  
Hydrocortisone acetate 
Cream, 1% 
  
Methylprednisolone acetate 
Cream, 0.25% 
 
 
 
 
 
The WHO Essential Medicines and Health Products Information Portal was designed and is maintained by Human 
Info NGO. Last updated: December 6, 2017 
 


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APPENDIX F: ECZEMA AREA AND SEVERITY INDEX SCORE FOR THE 
SEVERITY OF ATOPIC DERMATITIS (EASI) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 




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APPENDIX G: VALIDATED INVESTIGATOR GLOBAL ASSESSMENT SCALE FOR 
ATOPIC DERMATITIS (VIGA-AD™) 
 
The vIGA-AD is a static 5-point scale to evaluate AD disease severity globally and is frequently assessed 
in clinical studies. Investigator vIGA-AD responses will be captured in eCOA tablet. The vIGA-AD result 
will be recorded at the time points indicated in the Section 1.3.  
 
Score 
Morphological Description 
0- Clear 
No inflammatory signs of atopic dermatitis (no erythema, no 
induration/papulation, no lichenification, no oozing/crusting). Post-
inflammatory hyperpigmentation and/or hypopigmentation may be 
present. 
1-Almost clear 
 Barely perceptible erythema, barely perceptible 
induration/papulation, and/or minimal lichenification. No oozing or 
crusting. 
2-Mild  
 Slight but definite erythema (pink), slight but definite 
induration/papulation, and/or slight but definite lichenification. No 
oozing or crusting. 
3-Moderate  
 Clearly perceptible erythema (dull red), clearly perceptible 
induration/papulation, and/or clearly perceptible lichenification. 
Oozing and crusting may be present. 
4-Severe  
 Marked erythema (deep or bright red), marked induration/papulation, 
and/or marked lichenification. Disease is widespread in extent. 
Oozing or crusting may be present. 
Source: Eli Lilly and Company.10 
 




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B. Intensity 
A representative area of eczema is selected. In this area, the intensity of each of the following signs is 
assessed as:     0= absent     1= mild     2=moderate     3= severe  
Erythema (Redness) 
  0 
  1 
  2 
  3 
Edema/papulation (Swelling) 
  0 
  1 
  2 
  3 
Oozing / Crusting 
  0 
  1 
  2 
  3 
Excoriations (Scratch marks) 
  0 
  1 
  2 
  3 
Lichenification (Skin thickening) 
  0 
  1 
  2 
  3 
Dryness* 
  0 
  1 
  2 
  3 
 
*Dryness is evaluated on uninvolved areas 
 
C: Subjective Symptoms: Pruritus + Sleep Loss:  
Using a visual analogue scale where 0 is no itch (or no sleeplessness) and 10 is the worst imaginable itch 
(or sleeplessness), patient to indicate the average value for the last 48 hours. 
 
Patient facing: 
 
Subjective Symptoms:  Visual Analogue Scale Average for last 48 hours. Points from 0 to 10. 
 
Itching 
 
 
Trouble Sleeping 
 
 
 
SCORAD    A/5 + 7B/2 +C 
 
 
©1990 European Task Force on Atopic Dermatitis Published in "Dermatology in 1993; 186(1): 23-31 Consensus Report of the 
European Task Force on Atopic Dermatitis.11 
How to record a SCORAD score: 
Intensity 
 
Subjective Symptoms Pruritus + Sleep Loss 


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Area: 
To determine extent, the sites affected by eczema are shaded on a drawing of a body. The affected area (A) 
is calculated as a percentage of the whole body.  
 
Head 8% 
 
Upper limbs 9% each 
 
Lower limbs 18% each 
 
Hands 2% each 
 
Anterior trunk and neck 18% 
 
Back and neck 18%  
 
1% for genitals. 
The score for each area is added up. The total area is 'A', which has a possible maximum of 103%.  
Intensity: 
A representative area of eczema is selected. In this area, the intensity of each of the following signs is 
assessed as none (0), mild (1), moderate (2) or severe (3). 
 
Redness 
 
Swelling 
 
Oozing/crusting 
 
Scratch marks  
 
Skin thickening (lichenification) 
 
Dryness (this is assessed in an area where there is no inflammation) 
The intensity scores are added together to give 'B' (maximum 18). 
Subjective symptoms: 
Subjective symptoms ie, itch and sleeplessness, are each scored by the subject or relative using a visual 
analogue scale where 0 is no itch (or no sleeplessness) and 10 is the worst imaginable itch (or sleeplessness). 
These scores are added to give 'C' (maximum 20). 
Total score: 
The SCORAD for that individual is A/5 + 7B/2 + C 
 


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APPENDIX I: DERMATOLOGY LIFE QUALITY INDEX SCORE FOR SEVERITY 
OF ATOPIC DERMATITIS (DLQI) 
 
 
 
 
 
 
 
 
 
 
 
 
 DLQI 
Hospital No: 
 
 
 
 
Date: 
 
 
 
 
 
 
Name:  
 
 
 
 
 
 
 
 
Score: 
Address: 
 
 
 
 
Diagnosis: 
 
 
 
 
 
The aim of this questionnaire is to measure how much your skin problem has affected your life 
OVER THE LAST WEEK. Please tick   one box for each question. 
1. 
Over the last week, how itchy, sore,  
 
 
Very much 
 
 
painful or stinging has your skin  
  
 
A lot 
 
 
 
been?   
 
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
Not at all 
 
 
2. 
Over the last week, how embarrassed  
 
Very much 
 
 
or self-conscious have you been because  
 
A lot 
 
 
 
of your skin? 
 
  
 
 
 
A little  
 
 
 
 
 
 
 
 
 
Not at all 
 
 
3. 
Over the last week, how much has your   
 
Very much 
 
 
skin interfered with you going  
  
 
A lot 
 
 
 
shopping or looking after your home or  
 
A little  
 
 
garden?        
 
 
 
 
 
Not at all 
 
Not relevant  
 
4. 
Over the last week, how much has your   
 
Very much 
 
 
skin influenced the clothes  
 
 
 
A lot 
 
 
 
you wear? 
 
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
Not at all 
 
Not relevant  
 
5. 
Over the last week, how much has your   
 
Very much 
 
 
skin affected any social or  
 
 
 
A lot 
 
 
 
leisure activities? 
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
Not at all 
 
Not relevant  
 
6. 
Over the last week, how much has your   
 
Very much 
 
 
skin made it difficult for  
 
 
 
A lot 
 
 
 
you to do any sport? 
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
Not at all 
 
Not relevant  
 
7. 
Over the last week, has your skin prevented 
 
Yes 
 
 


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you from working or studying?  
 
 
No 
 
 
Not relevant  
 
 
If "No", over the last week how much has  
A lot 
 
 
 your skin been a problem at  
 
 
A little  
 
 
work or studying? 
 
 
 
Not at all 
 
 
8. 
Over the last week, how much has your   
 
Very much 
 
 
skin created problems with your  
 
 
A lot 
 
 
 
partner or any of your close friends 
 
 
A little  
 
 
or relatives?  
 
 
 
 
 
Not at all 
 
Not relevant  
 
9. 
Over the last week, how much has your   
 
Very much 
 
 
skin caused any sexual   
 
 
 
A lot 
 
 
 
difficulties? 
 
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
Not at all 
 
Not relevant  
 
10. 
Over the last week, how much of a  
 
 
Very much 
 
 
problem has the treatment for your 
 
 
A lot 
 
 
 
skin been, for example by making 
 
 
A little  
 
 
your home messy, or by taking up time?  
Not at all 
 
Not relevant  
 
Please check you have answered EVERY question. Thank you. 
 
©AY Finlay, GK Khan, April 1992  www.dermatology.org.uk. 
 
Badia et al.12 
 
 


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APPENDIX J: PATIENT ORIENTED ECZEMA MEASURE (POEM) 
 


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© www.nottingham.ac.uk/dermatology 
 
Charman et al.13 


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APPENDIX K: SAMPLE ASTHMA CONTROL QUESTIONNAIRE-6 (ACQ-6) 
 
ASTHMA CONTROL QUESTIONNAIRE-6 (ACQ-6) 
Asthma Control Questionnaire 
Subject ID: 
Date: 
Please answer questions 1-6 
Circle the number of the response that best describes how you have been during the past 
week. 
1. On average, during the past week, how 
often were you woken by your asthma 
during the night?  
0 
Never 
1 
Hardly ever 
2 
A few times 
3 
Several times 
4 
Many times 
5 
A great many times 
6 
Unable to sleep because of  
 
asthma 
2. On average, during the past week, how 
bad were your asthma symptoms when 
you woke up in the morning? 
0 
No symptoms 
1 
Very mild symptoms 
2 
Mild symptoms 
3 
Moderate symptoms 
4 
Quite severe symptoms 
5 
Severe symptoms 
6 
Very severe symptoms 
3. In general, during the past week, how 
limited were you in your activities 
because of your asthma? 
0 
Not limited at all 
1 
Very slightly limited 
2 
Slightly limited 
3 
Moderately limited 
4 
Very limited 
5 
Extremely limited 
6 
Totally limited 
4. In general, during the past week, how 
much shortness of breath did you 
experience because of your asthma? 
0 
None 
1 
A very little 
2 
A little 
3 
A moderate amount 
4 
Quite a lot 


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Asthma Control Questionnaire 
Subject ID: 
Date: 
5 
A great deal 
6 
A very great deal 
5. On average, during the past week, how 
many puffs/inhalations of short-acting 
bronchodilator (eg Ventolin/Bricanyl) 
have you used each day?  
(If you are not sure how to answer this 
question, please ask for help) 
0 
None 
1 
1-2 puffs/inhalations most days 
2 
3-4 puffs/inhalations most days 
3 
5-8 puffs/inhalations most days 
4 
9-12 puffs/inhalations most days 
5 
13-16 puffs/inhalations most days 
6 
More than 16 puffs/inhalations    
              most days 
6. In general, during the past week, how 
much of the time did you wheeze? 
0 
Not at all 
1 
Hardly any of the time 
2 
A little of the time 
3 
A moderate amount of the time 
4 
A lot of the time 
5 
Most of the time 
6 
All the time 
 
© 2001 QOL Technologies LTD. ACQ-SA-North American /English– Revised September 2010-Mapi Research Institute. 




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APPENDIX M: ADVERSE EVENTS: DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING 
 
AE Definition 
 
An AE is any untoward medical occurrence in a subject or subject, temporally associated 
with the use of study treatment, whether or not considered related to the study treatment. 
 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of study treatment. 
 
Events Meeting the AE Definition  
 
Any abnormal laboratory test results (hematology, biochemistry, or urinalysis) or other safety 
assessments (eg, ECG, radiological scans, and vital signs measurements), including those that 
worsen from Baseline, considered clinically significant in the medical and scientific judgment 
of the Investigator (ie, not related to progression of underlying disease). 
 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase 
in frequency and/or intensity of the condition. 
 
New conditions detected or diagnosed after study treatment administration even though it 
may have been present before the start of the study. 
 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study treatment or 
a concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an 
intentional overdose taken with possible suicidal/self-harming intent. Such overdoses should 
be reported regardless of sequelae. 
 
"Lack of efficacy" or "failure of expected pharmacological action" per se will not be reported 
as an AE or SAE. Such instances will be captured in the efficacy assessments. However, the 
signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as 
AE or SAE if they fulfill the definition of an AE or SAE.  
 
Events NOT Meeting the AE Definition  
 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments 
which are associated with the underlying disease, unless judged by the Investigator to be 
more severe than expected for the subject’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 subject’s condition. 
 
Medical or surgical procedure (eg, 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 pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
 


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Definition of SAE 
An SAE is defined as any untoward medical occurrence that, at any dose: 
a) Results in death 
b) Is life-threatening 
The term ‘life-threatening’ in the definition of “serious” refers to an event in which the subject 
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 subject has been detained (usually involving at least 
an overnight stay) at the hospital or emergency ward for observation and/or treatment that would 
not have been appropriate in the physician’s office or outpatient setting. Complications that occur 
during hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other 
serious criteria, the event is serious. When in doubt as to whether “hospitalization” occurred or 
was necessary, the AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
Baseline is not considered an AE. 
d) Results in persistent disability/incapacity 
 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
 
This definition is not intended to include experiences of relatively minor medical significance 
such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(eg, 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 


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f) Other situations: 
 
Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject 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. 
Recording and Follow-up of AE and/or SAE 
AE and SAE Recording 
 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event. 
 
The Investigator will then record all relevant AE/SAE information (including event term, 
start and stop dates, severity, relationship to study treatment, outcome, if serious or non-
serious) in the CRF. Each event must be recorded separately. 
 
It is not acceptable for the Investigator to send photocopies of the subject’s medical records 
to IQVIA Lifecycle Safety in lieu of completion of the AE/SAE CRF page. 
 
There may be instances when copies of medical records for certain cases are requested by 
IQVIA Lifecycle Safety/Sponsor. In this case, all subject identifiers, with the exception of the 
subject number, will be redacted on the copies of the medical records before submission to 
IQVIA Lifecycle Safety/Sponsor. 
 
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The Investigator will make an assessment of intensity for each AE and SAE reported during the 
study and assign it to 1 of the following categories:  
 
Mild: An event that is easily tolerated by the subject, causing minimal discomfort and not 
interfering with everyday activities. 
 
Moderate: An event that causes sufficient discomfort and interferes with normal everyday 
activities. 
 
Severe: An event that prevents normal everyday activities. An AE that is assessed as severe 
should not be confused with a SAE. Severe is a category utilized for rating the intensity of an 
event; and both AEs and SAEs can be assessed as severe. 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe. 
 


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Assessment of Causality 
 
The Investigator is obligated to assess the relationship between study treatment and each 
occurrence of each AE/SAE. The AE must be characterized as unrelated, possibly related, 
related  
o “Unrelated”: clinical event with an incompatible time relationship to study treatment 
administration, and that could be explained by an underlying condition or other drugs 
or chemicals or is incontrovertibly not related to the study treatment.  
o “Possibly related”: clinical event with a reasonable time relationship to study 
treatment administration, and that is unlikely to be attributed to concurrent condition 
or other drugs or chemicals. 
o “Related”: clinical event with plausible time relationship to study treatment 
administration and that cannot be explained by concurrent condition or other drugs or 
chemicals. 
 
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 treatment administration will be 
considered and investigated. 
 
The Investigator will also consult the IB in his/her assessment. 
 
For each AE/SAE, the Investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
 
There may be situations in which an SAE has occurred, and the Investigator has minimal 
information to include in the initial report to IQVIA Lifecycle Safety. 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 IQVIA Lifecycle Safety. 
 
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 IQVIA Lifecycle 
Safety 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 subject died during participation in the study, the Investigator will provide IQVIA 
Lifecycle Safety with a copy of any postmortem findings. 
 
New or updated information will be recorded in the originally completed CRF. 
 
The Investigator will submit any updated SAE data to the IQVIA Lifecycle Safety within 
24 hours of receipt of the information. 
 


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Reporting of SAEs 
SAE Reporting to IQVIA Lifecycle Safety via an Electronic Data Collection Tool 
 
The primary mechanism for reporting an SAE to IQVIA Lifecycle Safety will be the 
electronic data collection tool. 
 
If the electronic system is unavailable for more than 24 hours, then the study center will use 
the paper SAE data collection tool (see next section). 
 
The study center will enter the SAE data into the electronic system as soon as it becomes 
available. 
 
After the study is completed at a given study center, the EDC tool will be taken off-line to 
prevent the entry of new data or changes to existing data. 
 
If a study center receives a report of a new SAE from a subject or receives updated data on a 
previously reported SAE after the EDC tool has been taken off-line, then the study center can 
report this information on a paper SAE form (see next section) and send the paper SAE form 
to IQVIA Lifecycle Safety team via facsimile transmission or email. 
 
Contacts for SAE reporting can be found in SAE reporting form. 
 
SAE Reporting to IQVIA Lifecycle Safety via Paper Case Report Form 
 
Facsimile transmission of the SAE paper CRF is the preferred method to transmit this 
information to the IQVIA Lifecycle Safety team. 
 
In rare circumstances and in the absence of facsimile equipment, notification by telephone is 
acceptable with a copy of the SAE data collection tool sent by overnight mail or courier 
service. 
 
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 SAE reporting form. 
 
 


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APPENDIX N: HANIFIN AND RAJKA GUIDELINES FOR THE DIAGNOSIS OF 
ATOPIC DERMATITIS 
1. Must have three or more basic features described below: 
(1) 
Pruritus 
(2) 
Typical morphology and distribution 
• 
Flexural lichenification in adults 
• 
Facial and extensor eruptions in infants and children 
(3) 
Chronic or chronically relapsing dermatitis 
(4) 
Personal or family history of atopy (asthma, allergic rhinitis, and atopic dermatitis) 
2. Must have three or more following minor features: 
(1) 
Xerosis 
(2) 
Ichthyosis/palmar hyperlinearity, keratosis pilaris 
(3) 
Immediate (type I) skin test reaction 
(4) 
Elevated serum IgE 
(5) 
Early age of onset 
(6) 
Tendency toward cutaneous infections (especially Staph. aureus and Herpes simplex), impaired 
cell mediated immunity 
(7) 
Tendency toward non-specific hand or foot dermatitis 
(8) 
Nipple eczema 
(9) 
Cheilitis 
(10) Recurrent conjunctivitis 
(11) Dennie-Morgan infraorbital fold 
(12) Keratoconus 
(13) Anterior subcapsular cataracts 
(14) Orbital darkening 
(15) Facial pallor or facial erythema 
(16) Pityriasis alba 
(17) Anterior neck folds 
(18) Itch when sweating 
(19) Intolerance to wool ad lipid solvents 
(20) Perifollicular accentuation 
(21) Food intolerance 
(22) Course influenced by environmental and emotional factors 
(23) White dermographism or delayed blanch 
Source: Hanifin et al.8 
 

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Statistical Analysis Plan 
 
 
ANB020-005 
 
A 
RANDOMIZED, 
DOUBLE-BLIND, 
PLACEBO-CONTROLLED, 
PARALLEL-GROUP, DOSE-RANGING STUDY INVESTIGATING THE 
EFFICACY, SAFETY, AND PHARMACOKINETIC PROFILE OF ANB020 
ADMINISTERED TO ADULT SUBJECTS WITH MODERATE-TO-SEVERE 
ATOPIC DERMATITIS 
 
 
 
Author: 
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Version Number and Date: V1.1, 24OCT2019 
 
 
 


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Statistical Analysis Plan Signature Page 
Statistical Analysis Plan V1.1 (Dated 24OCT2019) for Protocol ANB020 -005. 
 
 
Name 
Signature 
Date 
Author: 
 
 
Position: 
 
Company: 
IQVIA 
 
Upon review of this document, the undersigned approves this version of the Statistical Analysis 
Plan, authorizing that the content is acceptable for the reporting of this study. 
 
Name 
Signature 
Date 
Approved By: 
 
 
Position: 
 
Company: 
AnaptysBio 
24Oct2019


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 List of Reviewers 
Reviewer Name 
Position/ Role 
Company 
IQVIATM 
AnaptysBio 
AnaptysBio 
AnaptysBio 
AnaptysBio 
AnaptysBio 
AnaptysBio 
 


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MODIFICATION HISTORY 
 
Unique 
Identifier for 
this Version 
Date of the 
Document 
Version 
Author 
Significant Changes from  
Previous Authorized Version 
1.0 
09APR2019 
 
Not Applicable – First Version 
1.0 
19JUL2019 
 
Sections have been renumbered. All section numbers 
below are from current numbering. 
Minor editorial changes throughout 
5 Updated study design section to match protocol. 
7.1 Added detail to DSMB section 
7.2 Added Interim Analysis 
8 Updated PPS definition 
8.4 Added Windowing conventions table 
8.9 Specified that data across sites will be pooled 
8.10 Updated missing data strategy 
8.11 Updated multiplicity strategy 
10 Updated disposition reporting 
11 Added list of major protocol deviations 
15 Updated study medication exposure reports 
16 Updated study and medication compliance 
definitions 
17.1 Added primary endpoint definition statement of 
null and alternative hypotheses 
17.1.1 Added multiple imputation description and 
updated primary endpoint analysis when using imputed 
data 
17.1.2 Added description of sensitivity analysis 
17.2 Added null and alternative hypotheses for 
Secondary efficacy endpoints and added definition of 
each secondary endpoint 
17.2.2 Added missing data handling for SCORAD and 
DLQI 
17.2.3 Updated analysis of secondary efficacy endpoints 


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17.3 Added null and alternative hypotheses for 
exploratory efficacy endpoints and added definition of 
each exploratory efficacy endpoint 
17.3.2.1 Added missing data handling for ACQ-6 
17.4 Updated analysis of exploratory efficacy endpoints 
18. Updated description of Safety outcomes 
18.2 Updated description of death listing and summaries 
18.6 Added description of physical examination 
reporting 
19 Added PK endpoints 
1.1 
09OCT2019 
 
3.4 Added Week 12 to applicable endpoints 
6 Added clarifying language around change vs. absolute 
change from baseline 
7.3 Clarified language that efficacy endpoints will be re-
executed during the Final Analysis 
8 Added Screen Failure population 
8.1 Clarified use of acute vs. chronic rescue medication 
8.10 Clarified that models with imputed data will be run 
and presented by Visit 
9 Clarified that models with imputed data will be run 
and presented by Visit 
17.1.1 Removed text about interaction terms and 
covariance testing 
17.1.2.2 Clarified use of Baseline Value through Week 
16 for Worst Case imputation; removed reporting of the 
number discontinued 
17.1.2.3 Added clarifying language around acute vs. 
chronic rescue medication use and trigger of non-
response as an endpoint 
17.2, 17.3 Updated count variables to start at j=2 
17.3 Added Week 12 to applicable endpoints 
APPENDIX 3 Corrected Proc Mixed and Proc Logistic 
code; added multiple imputation code 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
Abbreviation 
Definition  
ACQ 
Asthma Control Questionnaire 
AD 
Atopic dermatitis 
ADA 
Anti-drug antibodies 
AE  
Adverse event  
ANCOVA 
Analysis of covariance 
ATC 
Anatomical Therapeutic Chemical 
BLQ 
Below the lower limit of quantitation 
BMI  
Body mass index  
BSA 
Body surface area 
CI  
Confidence interval  
CS 
Clinically significant 
CTMS 
Clinical trial management system 
CV  
Coefficient of variation  
DLQI 
Dermatology Life Quality Index 
DSMB 
Data Safety Monitoring Board 
EASI 
Eczema Area and Severity Index 
ECG  
Electrocardiogram  
eCRF  
Electronic case report form  
EOS  
End of Study  
ET  
Early Termination 
FAS 
Full Analysis Set 
HR  
Heart rate  
IA 
Interim analysis 
LLOQ  
Lower limit of quantitation  
LS 
Least squares 
MCID 
Minimal clinically important difference 
MCMC 
Markov Chain Monte Carlo 
MedDRA  
Medical Dictionary for Regulatory Activities  
MI 
Multiple imputation 
n  
Sample size or number of observations  
NCS 
Not clinically significant 
ND 
Not determined 


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NRS 
Numerical rating scale  
PD 
Pharmacodynamic 
PK  
Pharmacokinetic(s) 
POEM 
Patient Oriented Eczema measure 
PPS 
Per Protocol Set 
PT 
Preferred term 
SAE  
Serious adverse event  
SAF 
Safety Analysis Set 
SAP  
Statistical analysis plan  
SAS  
Statistical analysis system  
SC 
Subcutaneous  
SCORAD 
Scoring Atopic Dermatitis 
SD  
Standard deviation  
SI 
System International 
SOA 
Schedule of Activities 
SOC 
System Order Class 
TEAE  
Treatment-emergent adverse event  
vIGA-AD 
Validated Investigator’s Global Assessment for Atopic Dermatitis 
WHO-DD 
World Health Organization Drug Dictionary 
 
 
 


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Table of Contents 
MODIFICATION HISTORY ..........................................................................................................4 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..................................................6 
TABLE OF CONTENTS .................................................................................................................8 
 
INTRODUCTION ...............................................................................................................11 
 
STUDY OBJECTIVES ........................................................................................................12 
 Primary Objective ................................................................................................................12 
 Secondary Objectives...........................................................................................................12 
 Exploratory Objectives ........................................................................................................12 
 
ENDPOINTS .......................................................................................................................13 
 Primary Endpoint: ................................................................................................................13 
 Secondary Efficacy Endpoints: ............................................................................................13 
 Safety and Tolerability Endpoints: ......................................................................................13 
 Exploratory Endpoints .........................................................................................................14 
 Pharmacokinetic Endpoints (Exploratory):..........................................................................15 
 
HYPOTHESIS .....................................................................................................................16 
 Primary Hypothesis ..............................................................................................................16 
 
STUDY DESIGN.................................................................................................................18 
 General Description .............................................................................................................18 
 Sample Size ..........................................................................................................................19 
 Schedule of Events ...............................................................................................................20 
 Changes to Analysis from Protocol .....................................................................................20 
 
STATISTICAL GENERAL CONSIDERATIONS .............................................................21 
 
PLANNED ANALYSIS ......................................................................................................23 
 Data Safety Monitoring Board .............................................................................................23 
 Interim Analysis ...................................................................................................................23 
 Final Analysis ......................................................................................................................23 
 
ANALYSIS SETS ...............................................................................................................24 
 Reference Start Date and Study Day ...................................................................................24 
 Baseline ................................................................................................................................25 
 Retests, Unscheduled Visits, and Early Termination Data ..................................................25 
 Windowing Conventions .....................................................................................................25 
 Statistical Tests ....................................................................................................................26 


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 Common Calculations ..........................................................................................................26 
 Software Version .................................................................................................................27 
 Adjustments for Covariates and Factors to be Included in Primary and Secondary Analyses
 
27 
 Multicenter Studies ..............................................................................................................27 
 
Missing Data .................................................................................................................27 
 
Testing Strategy and Adjustment for Multiplicity ........................................................28 
8.11.1. 
Testing Strategy for the Primary Endpoint ............................................................... 28 
8.11.2. 
Testing of Secondary Endpoints: .............................................................................. 28 
 
Examination of Subgroups ............................................................................................29 
 
OUTPUT PRESENTATIONS .............................................................................................30 
 
DISPOSITION AND WITHDRAWALS ............................................................................31 
 
PROTOCOL DEVIATIONS ...............................................................................................32 
 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS ..............................34 
 
MEDICAL HISTORY .........................................................................................................35 
 
CONCOMITANT THERAPIES .........................................................................................36 
 
STUDY MEDICATION EXPOSURE ................................................................................37 
 
Derivations ....................................................................................................................37 
 
COMPLIANCE....................................................................................................................38 
 
Compliance with Study Medication ..............................................................................38 
 
Compliance with the Protocol .......................................................................................38 
 
EFFICACY ENDPOINTS ...................................................................................................39 
 
Primary Efficacy Endpoint ............................................................................................39 
17.1.1. 
Missing Data Methods for Primary Efficacy Endpoint ............................................ 39 
17.1.2. 
Sensitivity Analysis for the Primary Efficacy Endpoint ........................................... 40 
 
Sensitivity analysis using the PPS ..........................................................................40 
 
Sensitivity analysis using Worst-Case Imputation method (FAS) .........................40 
 
Sensitivity analysis after chronic rescue medication (FAS) ...................................40 
 
Secondary Efficacy .......................................................................................................40 
17.2.1. 
Missing Data Methods for Secondary Efficacy Endpoints ....................................... 42 
17.2.2. 
Scoring and Missing Data for the Instruments Used for Secondary Endpoints ....... 43 
17.2.3. 
Analysis of Secondary Efficacy Variables ............................................................... 43 
 
Exploratory Efficacy Endpoints ....................................................................................44 
17.3.1. 
Missing Data Methods for Exploratory Efficacy Endpoints..................................... 46 
17.3.2. 
Scoring and Missing Data for the Instruments Used for Exploratory Endpoints ..... 46 


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Asthma Control Questionnaire 6 ............................................................................46 
 
Scoring Atopic Dermatitis ......................................................................................46 
 
Analysis of Exploratory Endpoints ...............................................................................47 
 
SAFETY ENDPOINTS .......................................................................................................48 
 
Adverse Events ..............................................................................................................48 
 
Deaths ............................................................................................................................50 
 
Laboratory Evaluations .................................................................................................50 
 
Electrocardiogram Evaluations .....................................................................................50 
 
Vital Signs .....................................................................................................................51 
 
Physical Examination ....................................................................................................51 
 
Immunogenicity ............................................................................................................52 
 
PHARMACOKINETIC ANALYSIS ..................................................................................53 
APPENDIX 1. PROGRAMMING CONVENTIONS FOR OUTPUTS....................................54 
APPENDIX 2. PARTIAL DATE CONVENTIONS .................................................................58 
APPENDIX 3. SAMPLE SAS CODE .......................................................................................62 
 
Tables 
Table 1 
Analysis Sets ................................................................................................................ 24 
Table 2 
Visit Windows .............................................................................................................. 26 
Table 3 
Hierarchical Order of Treatment Groups for Testing Strategy for Primary Endpoint at 
Week 16 ....................................................................................................................... 28 
Table 4 
List of Major Protocol Deviations................................................................................ 32 
 
Table of Figures 
Figure 1 Study Schematic ........................................................................................................... 19 
 
 
 


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 INTRODUCTION 
This statistical analysis plan (SAP) describes the rules and conventions to be used in the 
presentation and analysis of efficacy, pharmacokinetics (PK) and safety data for Protocol 
ANB020-005, Amendment 3, dated 02 July 2019. It describes the data to be summarized and 
analyzed, including specifics of the statistical analyses to be performed. 
Changes to the protocol that impact the design, the data collected, or the statistical methods and 
that occur after the finalization of this SAP may require amendment of the approved SAP. 
Similarly, changes to the planned analysis variables and/or statistical methods described in the 
approved SAP may also require amendment of the protocol. 
The Data Safety Monitoring Board (DSMB) SAP, PK modeling and simulation plan, and Blinded 
Data Review Meeting plan will be separately created for this study. 


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 STUDY OBJECTIVES 
 
Primary Objective 
• 
To evaluate the effects of etokimab on skin lesions 
 
Secondary Objectives 
• 
To evaluate the safety and tolerability of etokimab 
• 
To evaluate the effects of etokimab on pruritus symptoms 
• 
To evaluate the effects of etokimab on quality of life  
 
 Exploratory Objectives 
• 
To evaluate the immunogenicity of etokimab 
• 
To characterize the PK of etokimab 
• 
To evaluate the effects of etokimab on asthma symptoms 


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 ENDPOINTS 
 
Primary Endpoint: 
• 
Percent change in Eczema Area and Severity Index (EASI) score from Baseline to 
Week 16 
 
Secondary Efficacy Endpoints: 
At Week 16 and other clinical assessment time points, unless otherwise indicated: 
• 
Proportion of subjects with EASI-50 (≥50% improvement from Baseline) 
• 
Proportion of subjects with EASI-75 (≥75% improvement from Baseline) 
• 
Proportion of subjects with EASI-90 (>90% improvement from Baseline) 
• 
Proportion of subjects who achieve Validated Investigator’s Global Assessment for 
Atopic Dermatitis (vIGA-AD) score reduction of ≥2 
• 
Proportion of subjects who achieve vIGA-AD response of 0 (clear) or 1 (almost clear) 
• 
Proportion of subjects who achieve Numerical Rating Scale (NRS) for pruritus score1 
reduction from Baseline of ≥4 
• 
Percent change in peak weekly averaged NRS for pruritus score2 from Baseline 
• 
Percent change in Scoring Atopic Dermatitis (SCORAD) scores from Baseline 
• 
Change from Baseline in Dermatology Life Quality Index (DLQI) 
Notes: 
1 Using NRS for pruritus “itch intensity weekly average” 
2 Using NRS for pruritus “maximum itch intensity” 
   For NRS please refer to section 8.1.6 in the protocol for more details 
 
Safety and Tolerability Endpoints: 
• 
Incidence of AEs 
• 
Incidence of SAEs 
• 
Incidence of treatment-emergent adverse events (TEAEs) 
• 
AEs leading to discontinuation of study drug 
• 
AEs leading to withdrawal from the study 


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• 
AEs resulting in death 
• 
Changes in vital signs (blood pressure, temperature, respiration rate, heart rate [HR], and 
weight) 
• 
Changes in clinical safety laboratory tests (haematology, chemistry, and urinalysis) 
• 
Changes in electrocardiogram (ECG) parameters 
• 
Immunogenicity (anti-drug antibody [ADA] and neutralizing ADA) 
 
Exploratory Endpoints 
• 
Absolute change in EASI score from Baseline to Week 16 
• 
Percentage change in EASI score from Baseline to Weeks 4, 8, 12, 20, and 24 
• 
Percent change in body surface area (BSA) from Baseline to Weeks 4, 8, 12, 16, 20, and 
24 
• 
Absolute change in percent BSA from Baseline to Weeks 4, 8, 12, 16, 20, and 24 
• 
Change from Baseline in Asthma Control Questionnaire 6 (ACQ-6) Score at Weeks 4, 
8, 12, 16, and 24 
• 
Absolute change in SCORAD scores from Baseline to Weeks 4, 8, 12, 16, and 24 
• 
Change from Baseline in Patient Oriented Eczema Measure (POEM) at Weeks 4, 8, 12, 
16, 20, and 24 
• 
Absolute change in POEM scores from Baseline 
• 
Proportion of subjects with POEM change ≥ the minimal clinically important difference 
(MCID) 
• 
Proportion of subjects with DLQI change ≥MCID 
• 
Absolute change in peak weekly averaged NRS for Pruritus score from Baseline 
• 
Absolute change in mean weekly averaged NRS for Pruritus score from Baseline 
• 
Percent change in mean weekly averaged NRS for Pruritus score from Baseline 
• 
Proportion of subjects with NRS change ≥MCID 
• 
Proportion of subjects with EASI change ≥MCID 
• 
Proportion of subjects with SCORAD change ≥MCID 


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Pharmacokinetic Endpoints (Exploratory): 
A limited sampling strategy to collect samples of whole blood will be implemented for the 
determination of etokimab in human serum for PK assessment following subcutaneous (SC) 
administration. Pharmacokinetic concentration data collected from the study may be included in a 
population PK - based (meta-) analysis, using non-linear mixed effects modeling . 
The PK endpoints for this study are as follows: 
• 
Apparent clearance (CL/F) of etokimab 
• 
Apparent volume of distribution (Vd/F) of etokimab 
• 
Area under the curve (AUC) for the first and last dose 
• 
Maximum concentration (Cmax) for the first and last dose 
• 
Tmax for the first and last dose 
• 
T1/2 for the last dose 


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 HYPOTHESIS 
 
Primary Hypothesis 
Null Hypothesis (Ho): There are no differences between placebo treatment and any of the of the 
ANB020 treatment groups. 
Alternative Hypothesis (Ha): At least 1 of the EASI scores in the ANB020 treatment groups is 
different from placebo. 
Ho: 𝛿𝑃= 𝛿𝐸20/4 = 𝛿𝐸300+150/4 = 𝛿𝐸300+150/8 = 𝛿𝐸600+300/4, vs. 
HA: At least one 𝛿𝑇𝑖≠ 𝛿𝑃. 
Please see Table 3. 
Secondary Hypothesis 
On the selected dose (general approach): 
Ho: ANB020 treatment response = placebo response 
Ha: ANB020 treatment response different than placebo response 
 
General notation: 
Ho: p0 = pE20/4 = pE300+150/4 = pE300+150/8 = pE600+300/4, 
Ha: At least one pT ≠ p0. 
Note: similar approach for continuous endpoints 
 
For each of the endpoints below (in parenthesis) the following secondary hypothesis (Hi) will be 
tested (in sequential order). The assumption is the same for each case as in general approach 
above): 
• 
H1 (Improvement in proportion of subjects with EASI-50 (≥50% improvement from 
Baseline)) 
• 
H2 (Improvement in proportion of subjects with EASI-75 (≥75% improvement from 
Baseline)) 
• 
H3 (Improvement in proportion of subjects with EASI-90 (≥90% improvement from 
Baseline)) 
• 
H4 (Improvement in proportion of subjects who achieve vIGA-AD score reduction of 
≥2) 


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• 
H5 (Improvement in proportion of subjects who achieve vIGA-AD response of 0 or 1) 
• 
H6 (Improvement in proportion of subjects who achieve NRS for pruritus score reduction 
from Baseline of ≥4 ) 
• 
H7 (Percent change in peak weekly averaged NRS for pruritis score from Baseline) 
• 
H8 (Percent change in SCORAD score from Baseline) 
• 
H9 (Change from Baseline in DLQI) 


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 STUDY DESIGN 
 
General Description 
This is a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging, Phase 2b 
study designed to assess the efficacy of different doses and dose regimens of ANB020 (etokimab) 
compared to placebo in adult subjects with moderate to severe atopic dermatitis (AD). This study 
will also assess the efficacy, safety, tolerability, and PK of etokimab. This study will monitor the 
effects of etokimab on moderate to severe AD subjects over a period of 24 weeks. 
The study will have a screening period of up to 4 weeks (Week -4 to 0) prior to administration of 
study drug on Day 1, a treatment period of 16 weeks (Week 0 to 16), and a safety follow-up period 
of 8 weeks (Week 16 to 24). 
During the screening period, all subjects will undergo evaluation for eligibility. The subjects will 
be randomly assigned on Day 1 to one of the following 5 treatment groups in a 1:1:1:1:1 ratio as 
detailed in the protocol: 
• 
Etokimab 20 mg SC every 4 weeks (Q4W) 
• 
Etokimab 300 mg load + 150 mg SC Q4W 
• 
Etokimab 300 mg load + 150 mg SC every 8 weeks (Q8W) 
• 
Etokimab 600 mg load + 300 mg SC Q4W 
• 
Placebo 
The subjects will be administered study drug SC during onsite visits on Day 1 (Week 0), Day 29 
(Week 4), Day 57 (Week 8), and Day 85 (Week 12). The subjects will remain on site for 2 hours 
for postdose assessments at Weeks 0, 4, 8, and 12. Additional visits will occur at Day 5 (Week 1), 
Day 15 (Week 2), Day 92 (Week 13), and Day 113 (Week 16) during the treatment period. For the 
safety follow-up visit, the subject will return to the study center on Day 141 (Week 20) and 
Day 169 (Week 24). The End of Study (EOS) visit will be on Day 169 (Week 24). 
The subject’s disease activity (response to study treatment) will be evaluated using the EASI, 
vIGA-AD, and SCORAD assessments. The patient-reported outcome measurements (POEM, 
ACQ-6, and DLQI) will be performed first at visits mentioned in the Schedule of Activities (SOA) 
before any other study procedures (except informed consent at the screening visit). Dermatology 
Life Quality Index and POEM questionnaires will be administered only to the subset of subjects 
who can read and understand a language in which questionnaire is presented (based on availability 
of validated translations in participating countries). The ACQ-6 will be assessed only in subjects 
with active asthma disease whose primary language is a language in which questionnaire is 
presented (based on availability of validated translations in participating countries). The NRS for 
pruritus, also a patient-reported outcome measurement, will be completed daily via an electronic 


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patient reported outcomes device. 
Serum samples for PK and immunogenicity will be collected before the administration of study 
drug and at the other time points specified in the SOA. Safety assessments including adverse event 
(AE)/serious adverse event (SAE) monitoring, vital signs, physical examination, ECGs, and 
laboratory measurements will be performed as specified in SOA. A DSMB will be instituted to 
periodically review and evaluate the study data for subject’s safety and advise the Sponsor of 
potential safety signals. 
A study schematic for Protocol ANB020-005 is presented in Figure 1. 
 
Figure 1 
Study Schematic 
 
 
 
Sample Size 
The expected efficacy response (and variability) for active and placebo response (related with 
percent change from Baseline in EASI score to Week 16) was estimated after review of 5 previous 
studies in subjects with moderate to severe AD subjects not taking topical corticosteroids. 
In this way, in an analysis of covariance design, a total sample of approximately 300 subjects (60 


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subjects per treatment group) achieves more than 95% power to detect differences among the 
means versus the alternative of equal means using an F test with a 0.05000 significance level. 
The size of the variation in the means is represented by their standard deviation which is 18.59. 
The common standard deviation within a group is assumed to be 50.00. 
The hypothesized means used to compute the sample size derived from the studies mentioned 
before are: -20 -44. -65.4 -66.4 -68 (for placebo and each active treatment group respectively) with 
a covariate R-squared of 0.300. 
 
Schedule of Events 
The SOA can be found in Section 1.3 of the protocol. 
 
Changes to Analysis from Protocol 
There are no changes from the analysis mentioned in the protocol. 


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 STATISTICAL GENERAL CONSIDERATIONS 
All data listings, summaries, and analyses will be performed under the guidance and approval of 
the Sponsor and in consistency with this SAP. Data for patients excluded from an analysis set will 
be included in the data listings, but not in the summaries. 
Coding of AEs and medical history will be done by Medical Dictionary for Regulatory Activities 
(MedDRA) directory Version 22 (or higher) and medications data by the World Health 
Organization (WHO)-drug dictionary dated Mar2019 (or higher) by IQVIATM. 
The terms “change from Baseline” and “absolute change from Baseline” are used interchangeably 
throughout this document. 
The default summary statistics for continuous variables includes number of contributing 
observations (n), mean, standard deviation (SD), median, minimum, and maximum or as described 
in the respective section. For categorical variables, the number and percentage (the percentage of 
subjects in each category relative to the total number of subjects in the relevant analysis set or 
relative to the total number of subjects in the relevant analysis set, with assessments available 
[where appropriate]) in each category will be the default summary presentation. 
In general, for non-PK data, the number of decimal places displayed for each statistic will be 
determined as follows: 
• 
Mean and median: 1 more than the number of decimal places allotted in the raw data 
received from data management. 
• 
SD: 2 more than the number of decimal places allotted in the raw data. 
• 
Minimum and maximum: equal to the number of decimal places allotted in the raw data. 
• 
Percentages: All percentages between 0 and 100 will be rounded to 1 decimal unless 
there is a need to report more than 1 decimal for percentages. 
• 
Reference ranges will be reported to the same number of decimal places displayed by 
the laboratory. 
• 
P values and confidence intervals (CIs), if any, will be reported to 4 decimal places. 
P values less than 0.0001 will be presented as “<0.0001” and p value greater than 0.9999 
will be presented as “1.0000”. 
The following descriptive statistics by treatment (dose amount/schedule) and nominal study day 
will be presented in summary tables for the etokimab concentrations obtained in this study: number 
of non-missing observations (n), mean, SD, coefficient of variation (CV), minimum, median, and 
maximum. For etokimab concentrations, the number of observations above or equal to the lower 
limit of quantitation (LLOQ) will also be included. 
Concentration versus time summaries will be presented for all patients in the PK Analysis Set 


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(described in Table 1 Analysis Sets 
 Data from patients excluded from an analysis set will be included in the data listings, but not in 
the summaries. 
For etokimab concentration results, the data will be rounded as follows: 
• 
Etokimab concentrations will be reported in listing(s) and analyzed with the same 
precision as the source data regardless of how many significant figures or decimal places 
the data carry. Reporting of mean, SD, and median will carry 1 more significant 
figure/decimal place than the source data, according to the precision method used for 
source data. 
• 
Minimum and maximum will carry the same number of significant figures/decimal 
places as the source data. 
• 
Coefficient of variation will be reported to 1 decimal place. 
• 
Pharmacokinetic elapsed time variables will be reported with 2 decimal places with units 
of hours. 
Analysis plans for population PK modeling and potential pharmacodynamic (PD) and/or 
efficacy/safety correlative exploratory analyses will be described further in a separate modeling 
and simulation analysis plan. Results from any population PK analysis and correlation with 
PD/efficacy/safety results will be presented separately from the main clinical study report in a PK 
modeling and simulation report. 


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 PLANNED ANALYSIS 
 
Data Safety Monitoring Board  
A DSMB consisting of independent physicians and statisticians who are not Investigators in the 
study and who do not have a perceived conflict of interest with the conduct and administration of 
the study will be convened on a regular basis to evaluate the clinical study progress and review 
AEs. A DSMB SAP, describing the methodology and presentation of results and access to results, 
will be provided by IQVIA Biostatistics as a separate document. The data review meetings 
(DRMs) will follow the following schedule: 
• 
DSMB DRM #1 approximately 25% enrolment 
• 
DSMB DRM #2 approximately 50% Treatment Completers 
• 
DSMB DRM #3 100% W16 Treatment Completers (planned directly after interim 
analysis [IA] with IA data) 
• 
DSMB DRM #4 Final Data – 100% W24 completion of study 
 
Interim Analysis 
An IA will be performed when all active subjects complete their Week 16 visit which will be 
considered the final assessment of all primary and secondary efficacy endpoints (for Week 16). 
The IA will also consider all safety data available (up to Week 24). 
 
Final Analysis 
The Final Analysis (final database lock) will be executed once all subjects complete their Week 20 
and Week 24 safety and exploratory efficacy assessments and efficacy assessments for the primary 
and secondary endpoints will be re-executed, reporting Baseline, Week 16, Week 20, and Week 
24 results. 
The PK summaries, data listings, and PK figures will be the responsibility of the PK biostatistician 
at IQVIA. 


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 ANALYSIS SETS 
Agreement and authorization of subjects included/excluded from each analysis set (Table 1 below) 
will be conducted prior to the unblinding of the study for the IA to be performed when all subjects 
complete their safety and efficacy Week 16 assessments. 
Table 1 
Analysis Sets 
Analysis Set 
Description 
Safety Analysis Set (SAF) 
The SAF will include all randomized subjects who receive at 
least 1 dose of etokimab or placebo. The SAF will be used for all 
safety analyses. Subjects will be analyzed as treated. 
Full Analysis Set (FAS) 
The FAS will be based on the intent to treat principle and will 
include all randomized subjects who receive at least 1 dose of 
etokimab or placebo and have Baseline and postbaseline EASI 
score. The FAS will be used for all efficacy analyses. Subjects 
will be analyzed as randomized. 
PP Analysis Set (PPS) 
The PPS will include all subjects in the FAS who do not have 
major protocol deviations (See Section 10.1.10 in the Protocol).  
Pharmacokinetic (PK) 
Analysis Set 
The PK Analysis Set will include all etokimab treated subjects in 
the safety analysis set who have at least one quantifiable 
postdose PK sample available and who do not have events or 
protocol deviations with the potential to affect PK 
concentrations. The PK analysis set will be used for all PK 
analyses. The PK analysis is defined in detail in the 
Pharmacometric Plan. 
Additionally, Screen Failure (SF) patients are all patients who were screen failures and not 
randomized or dosed. 
 
 
Reference Start Date and Study Day 
Study Day will be calculated from the reference start date and will be used to show start/stop day 
of assessments and events. 
Reference start date is defined as the day of the first dose of study medication (Day 1 is the day of 
the first dose of study medication) and will appear in every listing where an assessment date or 
event date appears. 


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• 
If the date of the event is on or after the reference date, then: 
Study Day = (date of event – reference date) + 1 
• 
If the date of the event is prior to the reference date, then: 
Study Day = (date of event – reference date) 
• 
In the situation where the event date is partial or missing, Study Day, and any 
corresponding durations will appear partial or missing in the listings. 
 
Baseline 
The last nonmissing predose measurement taken prior to etokimab or placebo administration at 
randomization [Day 1] will be considered the baseline value.  
For NRS (numerical rating scale) for pruritus which will be completed daily via ePRO device (see 
details in section 8.1.6 in the protocol), two baseline average values will be computed:  one for the 
baseline average itch intensity, and the second one for the maximum itch intensity (or peak weekly 
average NRS at baseline.    
For all safety variables, Baseline will be last nonmissing measurement taken prior to reference 
start date (including unscheduled assessments or retests). If the predose measurement and the 
reference start date coincide, that measurement will be considered Baseline. 
 
Retests, Unscheduled Visits, and Early Termination Data 
In general, for by-visit summaries, data recorded at the nominal visit will be presented. 
Unscheduled measurements will not be included in by-visit summaries. In the case of a retest 
(same visit number is assigned), the latest available measurement for that visit will be used for 
by-visit summaries. Early termination data will be mapped to the next available visit number for 
by-visit summaries. 
Listings will include all scheduled, unscheduled, retest, and early discontinuation data collected in 
the electronic case report form (eCRF). 
 
Windowing Conventions 
Visit windows are assigned based on the Protocol SOA are presented in  
 


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Table 2. 
 
 
 


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Table 2 
Visit Windows 
Assigned Visit 
Assigned Study 
Week 
SOA day(s) 
Study day(s) 
1 (Screening) 
-4 to 0 
-28 to 0 
-28 to 0 
2 (Treatment) 
0 
1 
1 
3 (Treatment) 
1 
5 ± 1d 
4 to 6 
4 (Treatment) 
2 
15 ± 2d 
13 to 17 
5 (Treatment) 
4 
29±2d 
27 to 31 
6 (Treatment) 
8 
57±3d 
54 to 60 
7 (Treatment) 
12 
85±3d 
82 to 88 
8 (Treatment) 
13 
92±5d 
87 to 97 
9 (Treatment) 
16 
113±5d 
108 to 118 
10 (Safety Follow-Up) 
20 
141±5d 
136 to 146 
11 (Safety Follow-Up) 
24/EOS/ET 
169±5d 
164 to 174 
 
 
Statistical Tests 
The default significance level will be 0.05 two-sided; CIs will be 95% and all tests will be 
two-sided, unless otherwise specified in the description of the analyses. 
 
Common Calculations 
For quantitative measurements, change from baseline will be calculated as: 
 
• 
Test Value at Visit X – Baseline Value 
Percentage change from baseline will be calculated as: 
• 
(Test Value at Visit X – Baseline Value) *100/ Baseline Value 


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Software Version 
All analyses, statistics, and graphics reported in the clinical study report (including etokimab 
concentrations) will be conducted using Statistical Analysis System® (SAS) Version 9.4 or higher 
(SAS-Institute, Cary, North Carolina, USA). 
 
Adjustments for Covariates and Factors to be Included in Primary and Secondary 
Analyses 
The following covariates are used in the analyses. For details of their inclusion in the models, see 
the specific analysis section. 
• 
Baseline EASI score 
• 
Baseline vIGA-AD score 
• 
Baseline NRS score 
• 
Baseline SCORAD 
• 
Baseline DLQI score 
The following factors are used in the analyses. 
• 
Treatment 
• 
Visit 
 
Multicenter Studies 
Study centers across the United States, Canada, and Europe are expected to participate in this 
study. Data from all sites will be pooled for analysis. 
 Missing Data 
For duration of disease and birth date, the missing date will not be imputed. Missing safety data 
will not be imputed. Partial dates will be imputed as per APPENDIX 2. 
Missing efficacy data will be imputed using multiple imputation (MI) method described in Section 
17.1.1. Missing data will be imputed in a single step for all visits. For reporting and analysis, 
analysis models will be run “by visit”. 
For subjects who receive chronic rescue therapy and are considered non-responders according to 
protocol Section 6.5.2 (Rescue Medicine), the data collected after rescue therapy is initiated will 
be treated as missing. In addition, secondary and exploratory endpoints with responder/non-
responder outcomes will have data treated as missing after discontinuation due to chronic rescue 


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medication use.  However, their endpoint outcome will be defined as non-responder according to 
the date chronic rescue medication began.   
 
If a subject has acute rescue medication use, they will not be considered as non-responder by this 
criterion and all of their data will be used in the analysis.  Rescue medication use that meets the 
threshold of non-responder, as defined in protocol section 6.5.2, are considered ‘chronic’ use.  If 
it does not meet the threshold, it is considered ‘acute’ use.  
Details about missing data for primary and secondary endpoints are detailed in sections 17.1.1 and 
17.3.1 respectively. Assessments with missing data will be handled per the instructions provided 
by the author for each particular instrument, as described in Sections 17.2.1 and 17.3.1. Missing 
PK data will be handled as described in Section 19 of this plan. 
 Testing Strategy and Adjustment for Multiplicity 
8.11.1. Testing Strategy for the Primary Endpoint 
For the primary endpoint, a hierarchical testing procedure will be used, from the highest dose to 
the lowest dose until statistical significance at the 5% alpha level is not achieved. Hierarchical 
testing will occur in the following order: 
Table 3 
Hierarchical Order of Treatment Groups for Testing Strategy for Primary 
Endpoint at Week 16 
Sequence Arms to compare 
Alpha Level 
1 
Etokimab 600 mg load + 300 mg SC Q4W  
Vs. Placebo 
0.05 
2  
Etokimab 300 mg load + 150 mg SC Q4W 
Vs. Placebo 
0.05 
3  
Etokimab 300 mg load + 150 mg SC Q8W 
Vs. Placebo 
0.05 
4  
Etokimab 20 mg SC Q4W 
Vs. Placebo 
0.05 
Note: comparisons between active treatment doses are not intended in this study. In case that 2 or 
more dose levels results are positive then the Sponsor will select the optimal dose based on the 
risk / benefit profile for each dose level. 
8.11.2. Testing of Secondary Endpoints: 
A gatekeeping procedure in the primary endpoint will be used, only if at least 1 comparison 
between active treatments vs placebo for the primary endpoint crosses the α = 0.05 boundary for 
statistical significance, then the secondary endpoints will be tested in a hierarchical approach. For 


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example: 
• 
If the p value for the comparison between etokimab 300 mg load + 150 mg SC Q4W vs 
placebo is equal or smaller than 0.05 then: 
The secondary hypothesis (mentioned also in Section 4) will be tested sequentially. 
 
That is, for each of the j= 1, 2, …, 9 secondary hypotheses, 
 
If nominal p value H1 < 0.05, reject H1 and continue with H2; else stop. 
 
If nominal p value H2 < 0.05, reject H2 and continue with H3; else stop 
If nominal p value H3 < 0.05, reject H3 and continue with H4; else stop 
If nominal p value H4 < 0.05, reject H4 and continue with H5; else stop 
If nominal p value H5 < 0.05, reject H5 and continue with H6; else stop 
If nominal p value H6 < 0.05, reject H6 and continue with H7; else stop 
If nominal p value H7 < 0.05, reject H7 and continue with H8; else stop 
If nominal p value H8 < 0.05, reject H8 and continue with H9; else stop 
If nominal p value H9 < 0.05, reject H9 and stop 
  Examination of Subgroups 
Subgroup analyses may be performed as deemed appropriate. Any subgroup analysis will be 
considered Post Hoc. 
Subgroups may include, but are not limited to: 
• 
Age group 
• 
18 to <50 
• 
50 to <75 
• 
Gender 
• 
Race 
• 
Region 
• 
Disease status at Baseline 
• 
Moderate 
• 
Severe 
• 
Pruritis NRS at Baseline 
• 
ACQ-6 at Baseline 


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 OUTPUT PRESENTATIONS 
The templates provided with this SAP describe the presentations for this study and, therefore, the 
format and content of the summary tables, figures, and listings to be provided by IQVIA 
Biostatistics. 
All visit assessments will be presented according to the nominal visit name. For reporting and 
analysis of endpoints with imputed data, models will be run and presented “by visit”. 


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 DISPOSITION AND WITHDRAWALS 
All subjects who provide informed consent will be accounted for in this study. Subject disposition 
will be listed and summarized, including: 
• 
Total subjects screened 
• 
Number of screen failures (subjects who consent to participate in the clinical study but 
are not subsequently entered in the study) 
• 
Total of subjects in the FAS by treatment group 
• 
Total subjects randomized, but not treated by treatment group 
• 
Total subjects randomized and treated by treatment group 
• 
Total subjects ongoing (subjects ongoing at the time of the IA) by treatment group 
• 
Total number of subjects in the SAF by treatment group 
• 
Total number of subjects in the PPS  
• 
Total number of subjects in the PK Analysis Set 
• 
Total subjects who discontinue from study treatment by treatment group 
• 
Total subjects who discontinue from the study by treatment group 
• 
Total number of subjects who received chronic rescue medication by treatment group 
• 
Major protocol deviations and inclusion and exclusion criteria 


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 PROTOCOL DEVIATIONS 
All protocol deviations observed during study conduct will be captured in the Clinical Trial 
Management System (CTMS). 
The Investigator and Sponsor will review the protocol deviation records from the CTMS and 
provide confirmation on the categorization of deviations. 
Categorization definitions per the Protocol Deviation Plan are: 
Critical: A deviation from protocol-related procedures that threatens integrity of data, 
adversely affects subjects, and/or could invalidate acceptability of a project (or part of it). Such 
deviations require immediate action. 
Major: A deviation from protocol-related procedures that could affect integrity of the data or 
adversely affect subjects. Such deviations require timely action. 
Minor: A deviation from accepted procedures that will not adversely affect subjects or data 
integrity but should be dealt with appropriately.  
Major protocol deviations considered to affect the primary analysis include, but are not limited to, 
the following: 
Table 4 
List of Major Protocol Deviations 
No.  PD Group  
PD Description  
01 
Eligibility and Entry 
Criteria  
Not meeting either inclusion or exclusion criteria (at time 
of randomization)  
02 
Informed Consent  
Informed consent not signed  
03 
Compliance with 
Study Treatment 
Mishandling of the study drug which could have impacted 
the integrity of the study data such as non-allowable 
temperature deviations during storage or dispensing of 
study drug to the wrong subject 
04 
Compliance with 
Study Treatment 
Partial dosing of study treatment 
05 
Concomitant 
Medications  
Use of prohibited concomitant medications unless defined 
as rescue medication per protocol 
06 
Study Procedures 
Study procedures done outside protocol-specified window 
period that are judged to affect study efficacy data. 


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No.  PD Group  
PD Description  
Critical Protocol Deviations captured via CTMS will also 
be included.  
07 
Study 
Procedures/PK1 
Changes to the procedures or events which may impact 
the quality of the PK data will be considered significant 
protocol deviations or events and will be described within 
the clinical study report body text 
Note: 
These deviations or events will include any circumstances that will alter the evaluation of the PK. 
Examples include, but may not be limited to, sample processing errors that lead to inaccurate 
bioanalytical results and/or inaccurate/incomplete dosing for a dosing interval for which PK 
samples are collected. Other changes to the procedures or events which do not impact the quality 
of the PK data will not be considered significant protocol deviations. 
A frequency table for major protocol deviations will be provided for the SAF. 
Major protocol deviations or events that impact the quality of the PK and/or PD data will be listed 
only. 


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 DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
Demographics and other baseline characteristics will be listed and summarized for the SAF. No 
statistical testing will be carried out for demographic or other baseline characteristics data. 
• 
Summary statistics will be provided for: 
o Age (years) 
o Weight (kg) 
o Height (cm) 
o Body Mass Index (BMI [kg/m2]) 
• 
Frequency tables will be provided for: 
o Gender 
o Women of child bearing potential 
o Ethnicity 
o Race 
• 
Continuous variables will be summarized using count, mean, SD, median, minimum, 
and maximum 
• 
Categorical variables will be summarized using frequency and percentage 
• 
Separate summary table by EU states will be provided for European (EU) patients 
• 
Derivations 
o BMI (kg/ m2) = weight (kg)/ [height (m)]2 


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 MEDICAL HISTORY 
Medical history is collected only at Screening and will be listed and summarized for all the subjects 
by system organ class and preferred term. 


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 CONCOMITANT THERAPIES 
All medications (therapies) will be coded using the World Health Organization Drug Dictionary 
(WHO-DD). Each medication will be classified as prior medication if it is stopped prior to the first 
dose of study drug, or as concomitant medication if it is ongoing at the time of the first dose or is 
started after the first dose of study drug. Prior and concomitant medications will be summarized 
as counts and percentages by Anatomical Therapeutic Chemical (ATC) level 2 categories, and 
preferred name. 
Prior medications are subcategorized as Prior to Randomization and Prior Atopic Dermatitis 
Therapies. 
Concomitant medications are subcategorized as: Post randomization and rescue therapies. 
These will be reported in separate listings. 
See APPENDIX 2 for handling of partial dates for medications. In case it is not possible to define 
a medication as prior or concomitant, the medication will be classified conservatively as 
concomitant. 


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 STUDY MEDICATION EXPOSURE 
Duration of treatment exposure, average weekly and total dose will be listed and summarized by 
treatment groups using the SAF. 
 Derivations 
 
Duration of treatment exposure (weeks) = (Truncate (Date of last study medication 
administration – Date of first study medication administration)/7) + 4 weeks.  
 
 
 


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 COMPLIANCE 
 Compliance with Study Medication 
The assigned dosage, timing, and mode of administration may not be changed. Any departures 
from the intended regimen must be captured in the eCRFs and recorded as protocol deviations. 
Investigational Product Compliance will be listed and summarized, including number of subjects 
with planned and actual treatment for each visit. 
Missing the loading dose will result in discontinuation from the study. 
 Compliance with the Protocol 
Subjects who miss 2 consecutive doses after the loading dose will be discontinued from the study 
unless these subjects have received chronic rescue medication according to Section 6.5.2 of the 
protocol.  
Treatment compliance will be descriptively summarized by treatment group for the SAF, including 
the number and percentage of subjects who miss each assigned dose and number and percentage 
of subjects who are discontinued from the study due to one or more missed doses. 
 


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 EFFICACY ENDPOINTS 
 Primary Efficacy Endpoint 
Percent change in EASI score from Baseline to Week 16 will be analyzed using the FAS. 
Let the change (δ) from Baseline (B) in EASI at Week 16 (W16) be denoted for placebo (P) and 
each active treatment (Ti) group as: 
𝛿𝑃= 𝐸𝐴𝑆𝐼𝑊16,𝑃− 𝐸𝐴𝑆𝐼𝐵,𝑃 and 
𝛿𝑇= 𝐸𝐴𝑆𝐼𝑊16,𝑇𝑖− 𝐸𝐴𝑆𝐼𝐵,𝑇𝑖. 
Further, let each active treatment group (Ti) be denoted as: 
E20/4:  
 
Etokimab 20 mg SC every 4 weeks (Q4W) 
E300+150/4:  
Etokimab 300 mg load + 150 mg SC Q4W 
E300+150/8:  
Etokimab 300 mg load + 150 mg SC every 8 weeks 
E600+300/4:  
Etokimab 600 mg load + 300 mg SC Q4W 
 
Then the null and alternative hypotheses are stated as: 
Ho: 𝛿𝑃= 𝛿𝐸20/4 = 𝛿𝐸300+150/4 = 𝛿𝐸300+150/8 = 𝛿𝐸600+300/4, vs. 
HA: At least one 𝛿𝑇𝑖≠ 𝛿𝑃. 
 
17.1.1. Missing Data Methods for Primary Efficacy Endpoint 
Missing efficacy data for the primary endpoint will be handled using a MI procedure as follows: 
 
Step 1 – Imputation Phase: 
a. Creation of monotone missing data structure using 50 interactions (M), to ensure that the final 
results do not suffer from a relative efficiency loss (Van Buuren, 2012 cited by Patricia Berglund 
and Steven Heeringa in Multiple imputation using SAS 2014.): 
Intermediate (non-monotone) missing data (where some subjects may have missing records) will 
be imputed using the Markov Chain Monte Carlo (MCMC) method including treatment_arm, 
EASI_Baseline, EASI_Week1, EASI_Week2, EASI_Week4, EASI_Week8, EASI_Week12, and 
EASI_Week16 and assuming that the joint distribution of these variables is multivariate normal 
and the pattern for missing data is arbitrary. For this step the SAS procedure PROC MI with the 
MCMC option will be used. 


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b. Further imputations: 
The datasets, now with monotone missing data, will be imputed further, in a step-wise manner to 
impute each week’s EASI from Week 1 to Week 16 using the regression method (assuming 
missing at random). The model for each week will include terms for all of the previous weeks and 
follow the structure of the following model for each visit. 
Step 2 – Analysis Phase 
At this stage there are 50 imputed datasets with no missing data. For each imputed dataset, 
calculate the percent change in EASI score from Baseline to Week 16 and analyze using an analysis 
of covariance (ANCOVA) model adjusting for baseline EASI score (EASI_B). The primary 
comparison will be least squares (LS) mean difference between active treatment group(s) and 
placebo at 16 weeks. Treatment differences will be presented with corresponding p values and 
95% confidence interval (CI). 
Step 3 – Estimation and Inference for Imputed Data Sets 
This step will aim to perform a compute multiple imputation estimates of the descriptive statistics, 
model parameters and the variance of the MI estimates (computed in step 2) using Proc 
MIANALYZE. The pooled treatment difference, 95% CI, and p value will be reported. 
17.1.2. Sensitivity Analysis for the Primary Efficacy Endpoint 
 
Sensitivity analysis using the PPS 
The first sensitivity analysis will be performed as described for the primary efficacy analysis in 
Section 17.1, but using the PPS. Missing data approach will be the same as for the primary analysis. 
 
Sensitivity analysis using Worst-Case Imputation method (FAS) 
The second sensitivity analysis will use the FAS and worst-case imputation method. All subjects 
with missing data for Week 16 EASI will be imputed with their worst EASI score (including 
Baseline value).  
 
Sensitivity analysis after chronic rescue medication (FAS) 
To measure the impact on treatment effect of treating data as missing for those subjects who met 
the criteria of non-responder as the result of chronic rescue medication use, a sensitivity analysis 
using the FAS with all EASI data after initiation of chronic rescue medication will be performed.  
Missing data will be handled using the same approach as for the primary endpoint. 
 Secondary Efficacy 
For the interim analysis, reporting will reflect the time points through Week 16.  For the final 


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analysis, tables will include Baseline value and either Week 16 through Week 24 or Weeks 16, 20, 
and 24, as appropriate. 
Preliminaries: 
let p0= the proportion of subjects achieving the benchmark in the placebo group 
and 
pT= the proportion of subjects achieving the benchmark in a treatment group. 
Then 
Ho: p0 = pE20/4 = pE300+150/4 = pE300+150/8 = pE600+300/4, 
HA: At least one pT ≠ p0. 
Proportion of subjects with EASI-50 (≥50% improvement from Baseline) 
For each subject, define 
EASI50= 1 if [100*(EASI_16 – EASI_B)/ EASI_B] ≥ 50, 0 otherwise, 
where 
EASI_B = EASI at Baseline and EASI_16 = EASI at Week 16. 
EASI50 = 1 if subject achieved ≥50% improvement from Baseline, 0 otherwise. 
Then P_EASI50 for each treatment group is (Σ EASI50)/n.  
Proportion of subjects with EASI-75 (≥75% improvement from Baseline) 
For each subject, define 
EASI75= 1 if [100*(EASI_16 – EASI_B)/ EASI_B] ≥ 75, 0 otherwise, 
where 
EASI_B = EASI at Baseline and EASI_16 = EASI at Week 16. 
EASI75 = 1 if subject achieved ≥75% improvement from Baseline. 
Then P_EASI75 for each treatment group is (Σ EASI75/n). 
Proportion of subjects with EASI 90 (≥90% improvement from Baseline) 
For each subject, define 
EAS90= 1 if [100*(EASI_16 – EASI_B)/ EASI_B] ≥ 90, 0 otherwise, 
where 
EASI_B = EASI at Baseline and EASI_16 = EASI at Week 90. 
EASI90 = 1 if subject achieved ≥90% improvement from Baseline. 
Then P_EASI90 for each treatment group is (Σ EASI90/n). 
Proportion of subjects who achieve vIGA score reduction of ≥2 
For each subject, define 
VIGA2= 1 if (VIGA_16 – VIGA_B) ≥ 2, 0 otherwise, 
where 
VIGA_B = vIGA at Baseline and VIGA_16 = vIGA at Week 16. 
VIGA2 = 1 if subject achieved ≥2 improvement from Baseline, 0 otherwise. 


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Then P_VIGA2 for each treatment group is (Σ VIGA2)/n. 
Proportion of subjects who achieve vIGA-AD response of 0 (clear) or 1 (almost clear) 
For each subject, define 
VIGA01= 1 if VIGA_16
∈(0,1), 0 otherwise, 
where 
VIGA_16 = vIGA at Week 16. 
VIGA01 = 1 if subject achieved vIGA = 0 (clear) or 1 (almost clear), 0 otherwise. 
Then P_VIGA01 for each treatment group is (Σ VIGA01)/n. 
Proportion of subjects who achieve NRS for Pruritus score reduction from Baseline of ≥4 
For each subject, define 
NRSP4= 1 if (NRSP_16 – NRSP_B) ≥ 4, 0 otherwise, 
where 
NRSP_B = NRS for Pruritis score at Baseline and 
NRSP_16 = NRS for Pruritis score at Week 16. 
Then P_NRSP4 for each treatment group is (Σ NRSP4)/n. 
Percent change in peak weekly averaged NRS for Pruritus score from Baseline 
For each subject and week, define 
NRSP_peak_avg= (∑
𝑃𝑒𝑎𝑘 𝑁𝑅𝑆 𝑓𝑜𝑟 𝑃𝑟𝑢𝑟𝑖𝑡𝑖𝑠 𝑜𝑛 𝐷𝑎𝑦 𝑖
𝑘
𝑖=1
)/𝑘, 
where 
k = number of days NRS for Pruritis score was recorded for that week. 
Then for weeks j= 2, …, 16, 
NRSP_peak_Pct_Chg = (NRSP_ peak_avg – NRSP_B) * 100 / NRSP_B. 
Percent change in SCORAD score from Baseline 
For each subject, define 
SCORAD_pct_chg = (SCORAD_16 – SCORAD_B) *100/SCORAD_B 
where 
SCORAD_B= SCORAD at Baseline and SCORAD_16 = SCORAD at Week 16. 
Change from Baseline in DLQI at Week 16 
For each subject, define 
DLQI_chg = DLQI_16 – DLQI_B, 
where 
DLQI_B = DLQI at Baseline and DLQI_16= DLQI at Week 16. 
17.2.1. Missing Data Methods for Secondary Efficacy Endpoints 
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continuous endpoints and for categorical endpoints, the missing data will be included as patients 
not meeting the defined condition. 
17.2.2. Scoring and Missing Data for the Instruments Used for Secondary Endpoints 
Instruction provided by each owner/author of each instrument will be used as described below: 
SCORAD: The SCORAD index assesses disease extent and evaluates 6 clinical characteristics – 
erythema, edema/papulation, oozing/crusts, excoriation, lichenification and dryness – each on a 
scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe). SCORAD also assesses 
subjective symptoms of pruritus and sleep loss with visual analogue scales where 0 is no itch (or 
no sleeplessness) and 10 is the worst imaginable itch (or sleeplessness). These 3 aspects: extent of 
disease (A: range 0-102), disease severity (B; range 0-18) and subjective symptoms (C: range 
0-20) will be combined using, A/5 + 7*B/2 + C, to give a maximum possible score of 103.4. If a 
component (A, B, or C) cannot be calculated due missing data in a single question for that 
component, the missing question(s) for that component will be imputed using MI to calculate the 
component and total scores. If more than 1 question within a component is missing, then the 
SCORAD will be set to missing and imputed using MI as described in Section 17.1.1. 
DLQI: The DLQI is a 10- item questionnaire, each taking responses 0 to 3, for a maximum of 
30 points. If 1 question is unanswered, this is allocated a score of 0 and the DLQI score summed 
in the usual way, out of 30. If 2 or more questions are unanswered, the questionnaire is set to 
missing and imputed using MI as described in Section 17.1.1. 
NRS: For NRS, if a subject has less than 2 daily diary entries out of the 7 consecutive days prior 
to the visit, then the average will not be calculated and the NRS (i.e. weekly average peak score 
for that visit) will be considered missing.  Baseline NRS will be calculated from Day -6 to Day 0, 
unless that time frame includes fewer than 2 entries, in which case the Baseline value will be 
calculated from the most recent 2 entries prior to Day 0.  A Week 1 score will not be calculated 
because the time frame from Week 0 to Week 1 is less than the 7 days needed to obtain a weekly 
average. 
Missing NRS for that visit will be imputed by carrying forward the NRS from the previous visit. 
17.2.3. Analysis of Secondary Efficacy Variables 
The secondary efficacy analyses will be performed using the FAS. Continuous endpoints will be 
analyzed using ANCOVA models (similar to the analysis for the primary endpoint). 
For binary endpoints a logistic regression model adjusting for baseline score and including 
treatment, visit and all first order interaction terms will be used. Odds ratios, 95% CI and p value 
between treatment groups and placebo group will be presented. 


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 Exploratory Efficacy Endpoints 
Absolute change in EASI score from Baseline to Week 16 
For each subject, 
EASI_chg_16= EASI_16 – EASI_B, 
where 
EASI_B= EASI at Baseline and EASI_16 = EASI at Week 16. 
Percentage change in EASI score from Baseline to Weeks 4, 8, 12, 20, and 24 
For each subject, and for weeks j ∈ (4, 8, 12,16, 20, 24), 
EASI_j_pct_chg = (EASI_j – EASI_B) *100/EASI_B 
where 
EASI_B= EASI at Baseline and EASI_j = EASI at Week j. 
Percent change in BSA from Baseline to Weeks 4, 8, 12, 16, 20, and 24 
For each subject, and for weeks j ∈ (4, 8, 12, 16, 20, 24), 
BSA_j_pct_chg = (BSA_j – BSA_B) *100/BSA_B 
where 
BSA_B= BSA at Baseline and BSA_j = BSA at Week j. 
Absolute change in percent BSA from Baseline to Weeks 4, 8, 12, 16, 20, and 24 
For each subject, and for weeks j ∈ (4, 8, 12, 16, 20, 24), 
BSA_j_chg = (BSA_j – BSA_B) 
where 
BSA_B= BSA at Baseline and BSA_j = BSA at Week j. 
Absolute change from Baseline in ACQ-6 Score at Weeks 4, 8, 12, 16, 20 and 24 
For each subject, and for weeks j ∈ (4, 8, 12,16, 20, 24), 
ACQ6_j_chg = (ACQ6_j – ACQ6_B) 
where 
ACQ6_B= ACQ-6 score at Baseline and ACQ6_j = ACQ-6 score at Week j. 
Absolute change in SCORAD scores from Baseline to Weeks 4, 8, 12, 16, 20 and 24 
For each subject, and for weeks j ∈ (4, 8, 12, 16, 20, 24), 
SCORAD_j_chg = SCORAD_j – SCORAD_B 
where 
SCORAD_B= SCORAD at Baseline and SCORAD_j = SCORAD at Week j. 


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Absolute change from Baseline in POEM at Weeks 4, 8, 12,16, 20, and 24. 
For each subject, and for weeks j ∈ (4, 8, 12, 16, 20, 24), 
POEM_j_chg = POEM _j – POEM _B 
where 
POEM _B= POEM at Baseline and POEM _j = POEM at Week j. 
Proportion of subjects with POEM change ≥ the minimal clinically important difference (MCID) 
A change in POEM score of at least 3.4 points is considered clinically important. 
For each subject, 
POEM _MCID_16= 1 if POEM _16 – POEM _B ≥ 3.4, 0 otherwise 
where 
POEM _B= POEM at Baseline and POEM _16 = POEM at Week 16. 
Then P_ POEM _MCID_16 for each treatment group is (Σ POEM _MCID_16)/n. 
Proportion of subjects with DLQI change ≥MCID 
A change in DLQI score of at least 4 points is considered clinically important. 
For each subject, 
DLQI_MCID_16= 1 if DLQI_16 –DLQI_B ≥4, 0 otherwise 
where 
DLQI_B= DLQI at Baseline and DLQI_16 = DLQI at Week 16. 
Then P_ DLQI _MCID_16 for each treatment group is (Σ DLQI _MCID_16)/n. 
Absolute change in peak weekly averaged NRS for Pruritus score from Baseline 
For each subject and for weeks j=2, …, 24, define 
NRSP_peak_avg= (∑
𝑃𝑒𝑎𝑘 𝑁𝑅𝑆 𝑓𝑜𝑟 𝑃𝑟𝑢𝑟𝑖𝑡𝑖𝑠 𝑜𝑛 𝐷𝑎𝑦 𝑖
𝑘
𝑖=1
)/𝑘, where 
k = number of days NRS for Pruritis score was recorded for week j. 
Then 
NRSP__peak_Abs_Chg = (NRSP_peak_avg – NRSP_B). 
Absolute change in mean weekly averaged NRS for Pruritus score from Baseline 
For each subject and for weeks j=2, …, 24, define 
NRSP_j_avg= (∑
𝑁𝑅𝑆 𝑓𝑜𝑟 𝑃𝑟𝑢𝑟𝑖𝑡𝑖𝑠 𝑜𝑛 𝐷𝑎𝑦 𝑖
𝑘
𝑖=1
)/𝑘, where 
k = number of days NRS for Pruritis score was recorded for week j. 
Then 
NRSP_Avg = (∑
𝑁𝑅𝑆𝑃_𝑗_𝑎𝑣𝑔
𝑚
𝑖=1
)/𝑚, where m = the number of Weeks 
measured 
and 
NRSP_Abs_Avg = (NRSP_Avg – NRSP_B). 


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Percent change in mean weekly averaged NRS for Pruritus score from Baseline 
For each subject and for weeks j=2, …, 24, define 
NRSP_j_avg= (∑
𝑁𝑅𝑆 𝑓𝑜𝑟 𝑃𝑟𝑢𝑟𝑖𝑡𝑖𝑠 𝑜𝑛 𝐷𝑎𝑦 𝑖
𝑘
𝑖=1
)/𝑘, where 
k = number of days NRS for Pruritis score was recorded for Week j. 
Then 
NRSP_Avg = (∑
𝑁𝑅𝑆𝑃_𝑗_𝑎𝑣𝑔
𝑚
𝑖=1
)/𝑚, where m = the number of Weeks 
measured and NRSP_Pct_Avg = (NRSP_ Avg – NRSP_B) * 100 / NRSP_B. 
Proportion of subjects with EASI change ≥MCID 
A change in EASI score of at least 6.6 points is considered clinically important. 
For each subject, 
EASI _MCID_16= 1 if EASI _16 – EASI I_B ≥ 6.6, 0 otherwise 
where 
EASI _B= EASI at Baseline and EASI _16 = EASI at Week 16. 
Then P_ EASI _MCID_16 for each treatment group is (Σ EASI _MCID_16)/n. 
Proportion of subjects with SCORAD change ≥MCID 
A change in SCORAD score of at least 8.7 points is considered clinically 
important. 
For each subject, 
SCORAD _MCID_16= 1 if SCORAD _16 – SCORAD_B ≥ 8.7, 0 otherwise 
where 
SCORAD _B= EASI at Baseline and SCORAD _16 = EASI at Week 16. 
17.3.1. Missing Data Methods for Exploratory Efficacy Endpoints 
Missing data for exploratory efficacy endpoint will not be imputed. 
17.3.2. Scoring and Missing Data for the Instruments Used for Exploratory Endpoints 
 
Asthma Control Questionnaire 6 
The ACQ-6 contains 6 questions, each scored from 0 to 6. Responses are captured on paper forms 
and transcribed into the eCRF. The individual responses are averaged to obtain the total score. If 
1 or 2 responses are missing, the total score will be calculated as the average of the completed 
questions. If 3 or more responses are missing, the total score will be set to missing. 
 
Scoring Atopic Dermatitis 
Missing SCORAD components will be imputed similar as described in Section 17.2.2, but if a 
component (A, B or C) can not be computed in a single question for that component, then the 
entire component will be set as missing, in other words MI will not be executed. 


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 Analysis of Exploratory Endpoints 
Continuous endpoints will be analyzed using the ANCOVA model as described for the primary 
analysis. For the binary endpoints, a logistic regression model adjusting for baseline score (if 
available).  
 
 
 


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 SAFETY ENDPOINTS 
All safety data (AEs, SAEs, vital signs, ECGs, ADA, neutralizing antibodies, and clinical 
laboratory assessments at each specific time points) will be listed and summarized descriptively 
using the SAF. Number and percentage of AEs will be presented for each treatment group by 
preferred term and system organ class of the current Medical Dictionary for Regulatory Authorities 
(MedDRA). 
Individual listings of all SAEs and AEs leading to discontinuation from the study drug will be 
summarized using the current MedDRA. Summaries and listings of data for vital signs, 
haematology, clinical chemistry and urinalysis laboratory tests, and ECGs will be presented. 
Appropriate descriptive statistics will be summarized for the observed value at each scheduled 
assessment and for the corresponding change from Baseline. 
 Adverse Events 
AEs will be coded using MedDRA Version 22 and above. A TEAE is defined as: 
• 
A new event that occurs during or after first dose of study treatment or, 
• 
Any event present at Baseline that worsens in either intensity or frequency after first 
dose of study treatment. 
A non-TEAE will be defined as any AE that started on or after the date of informed consent and 
before the administration of study drug. 
Adverse events with missing start dates will be considered treatment-emergent. AEs with missing 
stop dates or with stop dates after the end of the study date will be considered to have been ongoing 
at the end of the study. 
The severity of AEs will be characterized as “mild, moderate, severe” according to the following 
definitions: 
• 
Mild events are usually transient and do not interfere with the patient’s daily activities. 
• 
Moderate events introduce a low level of inconvenience or concern to the patient and 
may interfere with daily activities. 
• 
Severe events interrupt the patient’s usual daily activity. 
• 
Missing severity will be assumed to be the worst severity case i.e. ‘severe’; however, in 
the listing, it will be displayed as missing. 
The causal relationship between the study drug and the AE will be characterized as Unrelated, 
Unlikely, Possible, Probable, and Unknown (unable to judge). Summaries will be presented as 
“Related” versus “Not Related”. Categories “Unrelated” and “Unlikely” will be mapped to “Not 
Related”, while the categories “Possible”, “Probable” and “Unknown” will be mapped to 


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Author: 
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Version Date:  
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Effective Date: 01Apr2018 
 
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to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly proh bited. 
“Related”. Missing relationship will be assumed to be the worst severity case (Related) in data 
summary tables; however, in listings it will be displayed as missing. 
A summary of the number and percentage of patients experiencing TEAEs for each treatment 
group will be provided. If patient has multiple TEAEs by severity and/or multiple relationships 
with the study drug, worst-case severity and the worst-case relationship to the study drug will used 
in the summary. 
 For TEAE by final outcome, if a patient has multiple TEAEs with different outcomes, the worst 
case will be reported, where ‘Fatal’ is the worst outcome. For Action Taken with the Drug, a 
patient can be counted in more than one category. 
The following summary tables will be provided by system order class (SOC) and preferred term 
(PT) for each treatment group and overall: 
• 
Number of patients with at least one TEAE 
• 
Number of patients with at least one serious TEAE 
• 
Number of patients with at least one TEAE by severity 
• 
Number of patients with at least one TEAE by relationship to study drug 
• 
Number of patients with at least one TEAE leading to permanent discontinuation of 
study drug 
• 
Number of patients with at least one TEAE leading to interruption of study drug 
• 
Number of patients with at least one TEAE leading to patient withdrawal from study 
• 
Number of patients with at least one TEAE leading to death 
• 
Number of patients with non-TEAE 
• 
TEAE occurring in ≥ 5% of subjects in any treatment group 
 
If an AE occurs more than once, the patient will be counted only once per SOC and once per PT 
within each SOC. If a patient reports a TEAE more than once within a SOC/PT, the AE with the 
worst-case severity will be used in the corresponding severity summaries and the worst-case 
relationship to the study drug will be used in the corresponding relationship summaries. 
Percentages will be calculated relative to the total number of patients in the SAF. The summaries 
will be sorted by descending frequencies of SOC and descending frequencies of PT with in SOC. 
Listings will be provided for TEAEs, Serious TEAEs, TEAEs leading to discontinuation from 
study or from study drug, and TEAEs leading to death for the SAF. 


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Version Date:  
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Effective Date: 01Apr2018 
 
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to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly proh bited. 
 Deaths 
Deaths will be listed and summarized as follows: 
• 
Number (%) of subjects who died by TEAE and study period and reasons for death will 
be summarized for the SAF by treatment received. 
• 
Death in nonrandomized subjects or randomized and not treated subjects. 
 Laboratory Evaluations 
The laboratory tests mentioned in SOA will be conducted throughout the study under laboratory 
evaluations. The actual and change from baseline values at scheduled assessments for each 
laboratory parameter will be summarized using appropriate descriptive statistics by treatment 
groups and all available visits. Frequency count and percentages will be provided for categorical 
variables. 
The following summaries also will be provided for laboratory data: 
• 
Incidence of abnormal values according to normal range criteria 
Shift table for laboratory test parameters from Baseline will be summarized at each visit. 
• 
Percentages will be based on the number of patients in the SAF population with data at 
Baseline and the visit of interest. 
Haematology and clinical chemistry data will be reported in System International (SI) units. 
 Electrocardiogram Evaluations 
Results from the central ECG Reading Center will be included in the reporting of this study. The 
following ECG parameters will be reported for this study: 
• 
PR Interval (msec) 
• 
QRS Interval (msec) 
• 
QT Interval (msec) 
• 
QTcF Interval (msec) 
• 
HR (bpm) 
• 
Normal 
• 
Abnormal, Not Significant (ANS) 
• 
Abnormal, Significant (AS) 
Electrocardiogram data will be listed using the actual and change from baseline values for the 


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to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly proh bited. 
above parameters and will be summarized using descriptive statistics (n, mean, SD, median, and 
range) by treatment groups and all available visits. 
The overall assessment of ECG data results (normal/abnormal) will be summarized using 
frequency and percentages. 
• 
Absolute values for QT and QTcF interval will be classified as: 
o ≥450 msec 
o ≥480 msec 
o ≥500 msec 
Since, there are different ranges for QTcF between the males and females, we will summarize the 
QTcF by gender as defined below: 
Absolute values of the QT interval as: Males: 431- 450 msec; Female: 451- 470 msec.  
• 
Abnormal values of the QT interval as: Males: > 450 msec Females: > 470 msec 
• 
Change from Baseline for QT and QTcF interval will be classified as: 
o >30 msec increase from Baseline 
o >60 msec increase from Baseline 
A listing of ECG parameters and of the overall assessment will be provided. 
 Vital Signs 
The following vital signs will be reported for this study: 
• 
Weight (kg) 
• 
Systolic and diastolic blood pressure (mmHg) 
• 
Heart rate (bpm) 
• 
Respiratory rate (breaths/min) 
• 
Temperature (⁰C) 
The actual and change from baseline values for the above parameters will be listed and summarized 
using descriptive statistics (n, mean, SD, median, and range) by treatment groups and all available 
visits. 
 Physical Examination 
Physical examination findings as collected in eCRF and associated abnormalities, along with 
clinical significance will be tabulated and presented in the listings for the SAF. 


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to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly proh bited. 
Baseline values and changes in the physical examination for the following parameters will be listed 
and summarized by treatment group and by visit using descriptive statistics: 
• 
General appearance 
• 
Head, eyes, ears, nose and throat 
• 
Respiratory system 
• 
Cardiovascular system 
• 
Lymph nodes 
• 
Extremities 
• 
Abdomen 
• 
Peripheral vascular system 
• 
Musculoskeletal system 
• 
Skin (excluding disease state per protocol AD) 
• 
Neurological system 
• 
Urogenital system 
The frequency and percentage of patients with normal, abnormal clinically significant (CS), and 
abnormal not clinically significant (NCS) assessments will be summarized by body system and 
treatment group at each available visit. 
 Immunogenicity 
Immunogenicity (ADA) results will be listed, including date/time of administration, results from 
the screening assay, confirmatory assay, titer, and neutralizing activity (if applicable). The number 
and frequency of subjects with confirmed ADA response and with confirmed neutralizing ADA 
response will be summarized by treatment and visit, as well as overall for a given treatment using 
the SAF. Efficacy results and/or safety results (such as AEs) may be presented by ADA status, as 
appropriate. If data permits, the correlation between ADA levels and safety and efficacy endpoints 
may be analyzed. 


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Effective Date: 01Apr2018 
 
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to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly proh bited. 
 PHARMACOKINETIC ANALYSIS 
The PK endpoints for this study are as follows: 
• 
Apparent clearance (CL/F) of etokimab 
• 
Apparent volume of distribution (Vd/F) of etokimab 
• 
Area under the curve (AUC) for the first and last dose 
• 
Maximum concentration (Cmax) for the first and last dose 
• 
tmax for the first and last dose 
• 
t1/2 for the last dose 
Patient listing(s) of PK sampling dates and times and all concentration-time data will be presented 
for the SAF. Concentrations which will fall outside the prespecified windows will be identified in 
the listings, for example: 
• 
If sample for Visit 3 occurs outside the protocol-specified window of 3 to 5 days after 
Visit 2 
• 
If samples scheduled for predose on Visits 2, 5, 6, and 7 are collected more than 1 hour 
after dosing 
• 
If sample for Visit 8 occurs outside the protocol-specified window of 2 to 13 days after 
Visit 7 
Concentration data of etokimab in serum will be summarized using descriptive statistics for the 
PK Analysis Set by treatment (dose amount/schedule) and nominal study day, as described in 
Section 6. Concentration-time data may be summarized by ADA status (confirmed ADA positive 
versus those without positive ADA response; patients with neutralizing ADAs). Samples collected 
outside of the above identified windows will be excluded from the concentration summaries. 
Concentrations below the LLOQ (BLQ) will be treated as zero for calculation of descriptive 
statistics. If the calculated mean concentration is BLQ, the mean value will be reported as BLQ, 
and the SD and CV will be reported as not determined (ND). If the calculated minimum, median, 
or maximum concentration is BLQ, it will be reported as BLQ. Missing data will not be imputed. 
If 1 or more concentrations at scheduled time points are missing, they will be reported as missing 
and will be omitted from the calculation of descriptive statistics. 
 


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Version Date:  
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Reference:  CS_WI_BS005 
Effective Date: 01Apr2018 
 
Copyright © 2009, 2010, 2012, 2016, 2018 IQVIA. All rights reserved. The contents of this document are confidential and proprietary 
to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly proh bited. 
APPENDIX 1. PROGRAMMING CONVENTIONS FOR OUTPUTS 
IQVIA Output Conventions 
Outputs will be presented according to the following Global Bios > Processes > GBIOS Processes 
- Implementation Guidelines and Templates > General Guidelines and Templates > Output 
Conventions 
Dates & Times 
Depending on data available, dates and times will take the form yyyy-mm-ddThh:mm:ss 
Spelling Format 
English US 
Presentation of Treatment Groups 
For outputs, treatment groups will be represented as follows and in this order: 
Treatment Group 
For Tables, Listings and Graphs 
 ETOKIMAB 20 mg SC Q4W 
 ETOKIMAB 20 mg SC Q4W 
 ETOKIMAB 300 mg load + 150 mg SC Q8W 
 ETOKIMAB 300 mg load + 150 mg SC Q8W 
 ETOKIMAB 300 mg load + 150 mg SC Q4W 
 ETOKIMAB 300 mg load + 150 mg SC Q4W 
 ETOKIMAB 600 mg load + 300 mg SC Q4W 
 ETOKIMAB 600 mg load + 300 mg SC Q4W 
Placebo 
 Placebo 


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Author: 
, PhD 
Version Number: 
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Version Date:  
24Oct2019 
Template No.:  CS_TP_BS016 Revision 5 
Reference:  CS_WI_BS005 
Effective Date: 01Apr2018 
 
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to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly proh bited. 
Presentation of Visits 
For outputs, visits will be represented as follows and in that order: 
Long Name (Default) 
Short Name  
Visit Number 
Screening (Day 0) 
Will be presented as  
1 
Baseline (Day 1) 
W0 
2 
Day 5, Week 1 
W1 
3 
Day 15, Week 2 
W2 
4 
Day 29, Week 4 
W4 
5 
Day 57, Week 8 
W8 
6 
Day 85, Week 12 
W12 
7 
Day 92, Week 13 
W13 
8 
Day 113, Week 16 
W16 
9 
Day 141, Week 20 
W20 
10 
Day 169, Week 24/EOS/ET 
EOS/ET 
11 
Unscheduled 
W#,Visit# 
 
 




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Document: 
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Author: 
, PhD 
Version Number: 
1.1 
 
Version Date:  
24Oct2019 
Template No.:  CS_TP_BS016 Revision 5 
Reference:  CS_WI_BS005 
Effective Date: 01Apr2018 
 
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to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly proh bited. 
 
Listings 
All listings will be ordered by the following: 
center-subject ID 
randomized treatment group (or treatment received if it is a safety output), first by active dose and 
then by placebo 
date (where applicable). 
 










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Document: 
\\ieedc-vnasc01\biosdata\AnaptysBio\ANB020\RYA20937_Blinded\Biostatistics\Documentation\SAP 
Author: 
, PhD 
Version Number: 
1.1 
 
Version Date:  
24Oct2019 
Template No.:  CS_TP_BS016 Revision 5 
Reference:  CS_WI_BS005 
Effective Date: 01Apr2018 
 
Copyright © 2009, 2010, 2012, 2016, 2018 IQVIA. All rights reserved. The contents of this document are confidential and proprietary 
to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly proh bited. 
APPENDIX 3. SAMPLE SAS CODE 
SAS code to impute missing values: 
/* creating monotone missing pattern */ 
proc mi data=adqs_trans nimpute=50 seed=1000  out=adqs_mono 
noprint; 
by treatment; 
    var baseline week1 week2 week4 week8 week12 week16; 
    mcmc chain=single impute=monotone; 
run; 
 
/* imputation */ 
proc mi data=adqs_mono out=adqs_monoimp nimpute=1 seed=1000; 
by _imputation_; 
    class  treatment; 
    var  treatment baseline week1 week2 week4 week8 week12 
week16; 
    monotone regression; 
run; 
 
 
SAS code for ANCOVA using imputed values: 
proc mixed data=<data_set_name> method=reml order=data; 
 
by _imputation visit_; 
    class treatment; 
    model response = treatment baseline /outp=outp ddfm=kr   
residual; 
    lsmeans treatment / cl diff; 
    ods output lsmeans=lsmeans diffs=diffs; 
run; 
*Where 
response = change from baseline 
treatment = treatment group (ETOKIMAB dose and Placebo); 
 
  
SAS code for logistic regression using imputed values: 
proc genmod data=<data_set_name> desc; 
by visit; 


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Version Date:  
24Oct2019 
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to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly proh bited. 
class treatment; 
model response=treatment baseline /dist=bin link=logit; 
lsmeans treatment/ diff cl exp; 
ods output lsmeans=lsmeans diffs=diffs; 
     output out=pred_resp reschi=resid; 
run; 
*Where 
response = binary response variable (Responder and Non-
responder) 
treatment = treatment groups (ETOKIMAB dose and Placebo) 
  
SAS code to pool the results of imputed test results: 
proc mianalyze data=mi_lsdiff; 
               by treatment _treatment; 
               modeleffects estimate; 
               stderr stderr; 
               ods output ParameterEstimates=est; 
run;