Clinical trial NCT03614923
Conditions: Chronic Rhinosinusitis
Keywords: ANB020 Etokimab CRSwNP
Sponsor: AnaptysBio, Inc.
Start date: 2018-11-29; Completion date: 2020-10-26
Enrollment: 105 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A study to evaluate the safety and efficacy of multiple doses of etokimab in adults with chronic rhinosinusitis with nasal polyps.

Detailed description:
This study is a randomized, placebo controlled, double-blind, multi-dose study to assess the efficacy of two different dose regimens of etokimab compared to placebo in adults with moderate-to-severe chronic sinusitis with nasal polyposis (CRSwNP).

During the screening period, all subjects will undergo evaluation for eligibility. A centralized reader will be used to confirm the diagnosis of CRSwNP as assessed by nasal endoscopy, computed tomography (CT) scan of sinuses, and symptom scoring to reduce the risk of interpretation variation.

Participants will also be provided mometasone furoate nasal spray (MFNS) for use during the trial and are required to undergo a minimum run-in period of 20 days prior to Day 1 with approximately 80% compliance.

Participants will be randomly assigned on Day 1 to one of the three treatment arms in a 1:1:1 ratio.

Arms: arm 1: Participants received a 300 mg loading dose of etokimab administered by subcutaneous injection at Week 0 then 150 mg etokimab by subcutaneous injection every 4 weeks (Q4W) up to Week 12 (Weeks 4, 8, and 12). Participants also used mometasone furoate nasal spray (MFNS) of 2 actuations (50 μg/actuation) in each nostril twice daily (BID). arm 2: Participants received a 300 mg loading dose of etokimab administered by subcutaneous injection at Week 0 then etokimab 150 mg by subcutaneous injection every 8 weeks (Q8W) up to Week 12 and placebo at Weeks 4 and 12. Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID. arm 3: Participants received placebo subcutaneous injection once every 4 weeks up to Week 12. Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
Interventions: intervention 1: Etokimab intervention 2: Placebo intervention 3: Mometasone Furoate Nasal Spray
Intervention descriptions: intervention 1: Administered by subcutaneous injection intervention 2: Administered by subcutaneous injection intervention 3: Mometasone Furoate Nasal Spray (MFNS) was used from 4 weeks prior to Day 1 (Run-in period) through the end of the study. Participants used 2 actuations (50 μg/actuation) in each nostril BID, total daily dose of 400 μg. Participants intolerant to BID intranasal corticosteroids (INCS) could use the lower dose regimen of 1 actuation in each nostril BID, total daily dose of 200 μg.

Protocol documents:
Prot_000.pdf: 
CLINICAL STUDY PROTOCOL 
A Phase 2, Double-Blind, Placebo-Controlled, Parallel-
Group, Multiple Dose Study to Investigate Etokimab 
(ANB020) in Adult Subjects with Chronic Rhinosinusitis 
with Nasal Polyposis 
 
Short Title: 
Efficacy, Safety, and Pharmacokinetic Profile of  
 
Etokimab in Adults with Chronic Rhinosinusitis 
 
with Nasal Polyposis 
Protocol Number: 
 ANB020-006 
National Clinical Trial (NCT)  
Identified Number:  
NCT03614923 
Lead Investigator:  
IND Sponsor:  
AnaptysBio, Inc. 
 
10421 Pacific Center Court, Suite 200 
 
San Diego, CA 92121 United States 
Amendment:  
3 
Protocol Date:  
06 February 2020 
Safety Reporting: 
 
 
CONFIDENTIALITY STATEMENT 
The information contained in this document is the property of AnaptysBio, Inc. and is confidential.  
This information may not be disclosed, reproduced, or distributed to anyone other than personnel directly 
involved in the conduct of the study and in response to a relevant Institutional Review Board and review by a 
Regulatory Authority as required by the applicable laws and regulations, without the written authorization of 
AnaptysBio, Inc. These restrictions will continue to apply after the study has closed. 
 


Etokimab for Treatment of CRSwNP 
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Sponsor Signature Page 
 
 
I confirm that I have read and approved this protocol in its entirety and will comply with the 
obligations as detailed in all applicable regulations and guidelines (eg, International Council on 
Harmonisation Good Clinical Practice [ICH GCP] guidelines) and the protocol. 
 
 
 
 
 
______________________________________ 
____________________ 
 
 
 Date 
Chief Medical Officer 
AnaptysBio, Inc. 
 
 
 
 
 


Etokimab for Treatment of CRSwNP 
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SUMMARY OF CHANGES FROM PREVIOUS VERSION 
Substantive changes to Amendment 3 are summarized below. 
The overall rationale for this amendment is to correct inconsistencies in objectives and endpoints listed 
throughout the document and correct administrative errors. 
Summary of Changes for ANB020-006 Protocol Amendment 3 
Affected Section(s) 
Summary of Revisions Made 
Rationale 
Global 
 Minor editorial and grammatical updates 
 Correction. 
Synopsis (secondary 
and exploratory 
objectives), Section 3 
 Moved Quality of Life (QoL) objective from 
secondary objectives to exploratory 
objectives 
 QoL endpoints will not be used 
for decision-making for future 
studies with etokimab. 
Synopsis (secondary 
and exploratory 
objectives), Section 3 
 Re-ordered secondary effectiveness 
endpoints to reflect the hierarchical order of 
statistical testing. 
 Identified secondary efficacy endpoints, 
which will undergo hierarchical statistical 
testing. All other efficacy endpoints were 
considered as exploratory endpoints. 
 Revised the list of endpoints in each section 
so that each relevant section of the protocol 
displays the same endpoints. 
 Hierarchical testing of 
secondary efficacy endpoints is 
being implemented as part of 
the Statistical Analysis Plan, 
therefore the protocol should 
also reflect the order of 
hierarchical testing of these 
endpoints. 
 All other secondary efficacy 
endpoints will not be used for 
decision making for future 
studies with etokimab. 
 The protocol was previously 
inconsistent in the presentation 
of endpoints in the different 
sections of the protocol. 


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Affected Section(s) 
Summary of Revisions Made 
Rationale 
Synopsis (Study 
Population),Section 
5.1 (inclusion #2) 
 Removed phrase “for both nostrils” from 
bilateral NPS score. 
 “Bilateral” and “both nostrils” 
are redundant. 
Synopsis (Participant 
Duration) 
 Updated the duration description to include 
the breakdown of the duration of each 
period in the study. 
 Clarification. 
Section 1.3 (Schedule 
of Activities, footnotes 
k and l), 
 Removed the sentence “Samples should be 
obtained prior to administering study drug if 
an administration coincides with the visit.” 
 Removed for redundancy. 
Section 1.3 (Schedule 
of Activities, footnote 
j), Section 6.2.5 
 Added language that subjects with ongoing 
TEAEs or treatment-emergent SAEs at the 
time of discharge after the first injection of 
study drug should remain at the study center 
until the Investigator has determined that 
these events have been resolved or deemed 
as not clinically significant.  
 Clarification for subject safety. 
Section 1.3 (Schedule 
of Activities, footnote 
w) 
 Added text to clarify that endoscopies 
performed onsite should be completed after 
all other study assessments and prior to 
dosing on that day. 
 Consistency. 
Section 2.2.2.1 
 Added text that GLP-compliant toxicology 
and toxicokinetic studies also included a 26-
week study. 
 Updated information. 
Section 3 
 Updated table to match the changes to the 
objectives and endpoints made in the 
Synopsis. Includes reduction of the number 
of secondary efficacy endpoints; moved 
remaining efficacy endpoints to exploratory, 
moved QoL objective to exploratory; wording 
revisions. 
 The protocol was previously 
inconsistent in the presentation 
of objectives and endpoints in 
the different sections of the 
protocol. 
Section 5.1 (Inclusion 
#3e) 
 Reworded the criterion 
 Clarification. 
Section 6.3.1 
 Updated the first sentence to match the 
study description 
 Consistency. 
Section 7.1 
 Clarified that subjects who discontinue early 
from study treatment, but not from the 
study as a whole, will be encouraged to 
complete their remaining clinic visits 
according to the SoA. 
 For internal consistency with 
the analysis described in 
Sections 9.4.2.1.1 and 9.4.2.3. 
Section 8.1.5 
 Corrected the timing of CT scans 
 Corrected for consistency. 
Section 8.1.6 
 Added text to clarify that the baseline biopsy 
should be obtained before administration of 
the study drug. 
 Clarification. 
Section 8.1.7 
 Added text that genomic analysis will us a 
validated assay and only samples within the 
window of sample stability will be analyzed. 
 Clarification. 


Etokimab for Treatment of CRSwNP 
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Affected Section(s) 
Summary of Revisions Made 
Rationale 
Section 8.1.8.2 
 Corrected number of levels in each 
dimension from 3 to 5. 
 Correction 
Section 8.2.4 
 Updated section to match the SOA 
 Consistency. 
Section 8.2.6 
 Added text to clarify that subjects only need 
to remain onsite for 2 hours following the 
first dose of study drug. 
 Clarification. 
Section 8.3 
 Deleted text that specified “approximately 5 
mL” of whole blood samples will be 
collected. 
 Detailed information about 
blood samples will be provided 
in the laboratory manual. 
Section 8.5 
 Specified that only samples from etokimab-
dosed subjects will be evaluated for anti-drug 
antibody (ADA). 
 Clarification. 
Section 9.1 
 Section was revised to only discuss co-
primary endpoints. 
 Details of secondary endpoint 
analyses will be provided in the 
Statistical Analysis Plan (SAP). 
Section 9.2 
 Corrected the percentage of dropouts 
expected from 15% to 18% in the sample size 
estimate. 
 Correction 
Section 9.3 
 Heading title was changed to “analysis sets.” 
 The ITT analysis set was removed. 
 Description of the full analysis set (FAS) and 
Per Protocol (PP) were corrected. 
 The term “analysis set” is being 
used throughout the protocol. 
 The ITT set is not being used for 
any planned analyses; the FAS 
set is being used for efficacy 
analyses. 
Section 9.4.2 and 
Table 3 
 Revised text of Section and Table 3 to reflect 
analysis of co-primary endpoints.  
 Updated Table 3 to reflect planned changes 
to the analysis of secondary endpoints and 
exploratory efficacy endpoints and the 
restructuring of the secondary/exploratory 
efficacy endpoints 
 In accordance with ICH E9, we 
are limiting the number of 
secondary endpoints and 
moving the additional endpoints 
being evaluated to exploratory. 
Section 9.4.2.1 
 Section heading was removed and text has 
become part of Section 9.4.2. 
 Changed for consistency. 
Section 9.4.2.1.1, 
Section 9.4.2.1.2 
 Updated text of the co-primary endpoints. 
 Changed the term “dropout” to “treatment 
discontinuation.” 
 Changed for consistency. 
 The term “treatment 
discontinuation” is more 
accurate in these sections as 
subjects could stop treatment 
but remain in the study. 
Section 9.4.4.1 
 Added the term “study discontinuations” to 
the description of the tabular presentation of 
subject disposition. 
 Clarification. 
Section 9.4.2.2 
 Heading changed to Analysis of the 
Secondary and Exploratory Endpoint(s). 
 Heading change reflects 
updated section content. 


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Amendment 3 
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Affected Section(s) 
Summary of Revisions Made 
Rationale 
 Modified text to indicate that details of 
secondary and exploratory analyses will be 
provided in the SAP. 
 Moved PK analysis text to this section and 
added a note that additional PK parameters 
may be evaluated if needed. 
 Most of the analysis details will 
be presented in the SAP and are 
not needed in the protocol. 
 PK endpoints are secondary, so 
the text was compressed into a 
single section. 
Section 9.4.2.3 
 Deleted section. 
 This text was not needed due to 
the changes made in Section 
9.4.2.2. 
Section 9.4.3.1 
 Clarified that TEAEs and SAEs will be 
presented as summaries; AEs (all) and SAEs 
will be presented as by-subject listings. 
 The previous text was unclear 
about what AE data would be 
presented as summaries vs 
listings. 
Section 9.4.3.2 
 Deaths will now be presented only as a by-
subject listing 
 The number of deaths is 
expected to be small, therefore 
a summary of deaths was not 
considered additive for 
assessing safety. 
Section 9.4.5 
 Interim analysis will now include both co-
primary endpoints. 
 Updated interim analysis to be performed 
when approximately 84 randomized subjects 
have completed Week 8  
 Text regarding the conditional power was 
deleted. 
 Details of the statistical analyses 
will be described in the SAP and 
in the DSMB analysis plan, as 
appropriate. 
Section 9.4.9 
 Deleted section. 
 Text from this section was 
moved to Section 9.4.2.2. 
 
Substantive changes to Amendment 2 are summarized below. 
The overall rationale for this amendment to correct inclusion and exclusion criteria based in input from 
participating Investigators, to update interim analysis details, and correct administrative errors. 
Summary of Changes for ANB020-006 Protocol Amendment 2 
Affected Section(s) 
Summary of Revisions Made 
Rationale 
Title Page 
 Lead investigator updated 
 Dr. Simon is not participating in 
the study 
Synopsis (1.1) 
Section 5.1 Inclusion Criteria 
number 2 
 
 Updated minimum bilateral 
Nasal Polyp Score from 5 to 4 
 Updated minimum score 
required from 2 to 1 in each 
nostril 
 Input provided by participating 
clinical Investigators with strong 
patient management experience 


Etokimab for Treatment of CRSwNP 
Amendment 3 
Protocol ANB020-006 
06 February 2020 
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Affected Section(s) 
Summary of Revisions Made 
Rationale 
Section 1.3 Schedule of Activities 
 Corrected footnote errors 
 Correction of errors and ensure 
alignment with 
Inclusion/Exclusion criteria 
Section 5.1 Inclusion Criteria 
 Increased upper limit of body 
mass index from 38 to 42 kg/m2 
 Subject safety and aligning 
criteria for enrolled subjects  
 Input provided by participating 
clinical Investigators with strong 
patient management experience 
Section 5.2 Exclusion Criteria 
 Updated method for confirming 
aspirin-exacerbated respiratory 
disease diagnosis (exclusion 4) 
 Reduced interventional 
treatment time restriction from 
6 months to 3 months 
(exclusion 7) 
 Clarified clinical significance for 
abnormal electrocardiogram 
findings (exclusion 10) 
 Clarified antibiotic treatment 
exclusion applies to systemic 
antibiotics (exclusion 12) 
 Updated smoking pack-years 
and clarified smoking 
restrictions (exclusion 15) 
 Clarified blood screening for 
hepatitis B (exclusion 16) 
 Updated QuantiFERON® test 
requirements (exclusion 17) 
 Clarified initiation of 
immunotherapy requirements 
(exclusion 24) 
 Focusing on subject safety and 
aligning criteria in subjects 
being enrolled 
 Input provided by participating 
clinical Investigators with strong 
patient management experience
 Clarifications 
 Corrections 
 
Section 5.4 Screen Failures 
 Added instruction for 
rescreening  
 Provide clarification  
Section 6.1.2 Dosing and 
Administration 
 Added instruction for injection 
site area 
 Provide clarification 
Section 6.2.2 Etokimab 
formulation, appearance, 
packaging, and labeling 
 Updated appearance 
information  
 Correction of error 
Section 8.1.3 
 Clarified timings for nasal peak 
inspiratory flow recordings 
 Clarification 
Section 8.1.5 
 Updated permitted computed 
tomography (CT) scans of the 
sinuses to allow scans collected 
within 3 months of screening to 
be used 
 Focusing on patient safety 
during rescreening process and 
for recently assessed subjects 


Etokimab for Treatment of CRSwNP 
Amendment 3 
Protocol ANB020-006 
06 February 2020 
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Affected Section(s) 
Summary of Revisions Made 
Rationale 
Section 9.2 Sample size 
determination 
 
 Added details of sample size 
calculation 
 Updated statistical power 
calculations to reduce 
percentage of dropouts from 
20% to 15% and the number of 
subjects per treatment arm 
from 35 to approximately 33 
 To clarify the hypothesis testing 
strategy for the co-primary 
endpoints 
 Review of available information 
indicates lower rate acceptable  
Section 9.4.2.1 Analysis of co-
primary endpoints 
9.4.2.1.1 First co-primary endpoint 
9.4.2.1.2 Second co-primary 
endpoint 
 Added confirmation of when 
statistical significance will be 
declared 
 Added details for hierarchical 
testing 
 Updated confidence interval 
and significance level 
 To clarify the hypothesis testing 
strategy for the co-primary 
endpoints 
Section 9.4.5 Planned interim 
analysis 
 Updated interim analysis to be 
performed when approximately 
100 randomized subjects have 
completed Week 8  
 Updated interim analysis to use 
conditional power instead of 
O’Brien-Fleming type 
boundaries 
 To avoid issues in boundary 
calculation based on Week 8 
completion 
Appendix A 
 Clarified instructions prohibited 
medications 
 Provide clarification 
  


Etokimab for Treatment of CRSwNP 
Amendment 3 
Protocol ANB020-006 
06 February 2020 
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Substantive changes to Amendment 1 are summarized below.  
The overall rationale for Amendment 1 reflects the key comments provided by clinical experts, safety 
staff, and provides clarity regarding procedures.  
Minor grammatical, editorial, formatting, and administrative changes not affecting the conduct of the 
study have been incorporated into this amendment for clarification and administrative purposes only 
and are not summarized below. 
Summary of Changes for ANB020-006 Protocol Amendment 1 
Affected Section(s) 
Summary of Revisions Made 
Rationale 
Entire protocol 
 Updated grammatical errors and 
clarified existing information 
 Accuracy and completeness 
Title Page 
 Added Safety Reporting Details 
 Accuracy and completeness 
Study Design, Schedule Of 
Events 
 Clarified screening window: Maximum 
31 days of screening 
 Clarification 
Study Design: 
Synopsis (1.1)  
Schedule of Activities (1.3) 
Overall Design (4.1) 
 Clarified mometasone furoate nasal 
spray (MFNS) use and run-in timeline  
 Added language on patient compliance 
of approximately 80% throughout the 
study including during Screening 
 Clarified that MFNS is provided by 
Sponsor 
 Clarified instruction on lowering dose 
if necessary 
 Accuracy and clarification 
Synopsis (1.1) 
 Corrected Secondary Endpoints to 
capture appropriate assessments and 
align with Section 3 (Objectives and 
Endpoints) 
 Correction 
Synopsis (1.1) 
 Updated study participants from 102 
to 105 
 Correction 
Figure 1 
 Updated patient arm descriptions and 
added MFNS to the diagram for clarity 
 Clarification 
Section 1.3 Schedule of 
Activities (SoA) 
 Removed Week 2/Day 15 
 Correction, removed unnecessary 
visit 
Section 1.3 Schedule of 
Activities (SoA) 
 Added additional procedures to SoA in 
accordance with existing protocol 
procedures  
 Provide clarification 
Section 1.3 Schedule of 
Activities (SoA) 
 Added additional detail on study 
windows and in footnotes  
 Provide clarification and accuracy  


Etokimab for Treatment of CRSwNP 
Amendment 3 
Protocol ANB020-006 
06 February 2020 
AnaptysBio, Inc. 
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Affected Section(s) 
Summary of Revisions Made 
Rationale 
Objectives: Section 3 
 Corrected Secondary Endpoints to 
capture appropriate assessments and 
align with Section 1.1 (Synopsis) 
 Added secondary endpoint  
 Corrected QoL sub-bullets 
 Added Exploratory Endpoint 
 Correction and improve accuracy 
 Assure assessments are analyzed 
correctly 
Section 5.1 Inclusion 
Criteria 
 Increased maximum age from 65 to 70 
years old at time of consent 
 Clarified bilateral scoring process 
 Clarified symptoms (bulleted 
symptoms) 
 Increased body mass index (BMI) from 
36 to 38 kg/m2 
 Added upper limit of normal (ULN) lab 
value criteria 
 Added compliance criteria for MFNS 
usage during Screening 
 Added compliance criteria for Nasal 
peak inspiratory flow (NPIF) 
completion during Screening  
 Focusing on patient safety and 
aligning criteria in patients being 
enrolled 
 Input provided by participating 
clinical Investigators with strong 
patient management experience 
 
Section 5.2 Exclusion 
Criteria 
 Increased SNOT-22 minimum score 
from < 7 to < 15 at Screening 
 Added Aspirin-exacerbated respiratory 
disease (AERD) diagnosis to exclusion 
criteria 
 Clarified nonsteroidal treatment 
exclusion details 
 Added additional detail to ischemic 
cardiovascular disease to clarify 
cerebrovascular events and time 
(within 1 year of Screening) 
 Added vaping to nonsmoking 
guidelines 
 Corrected reference to FEV1 percent 
predicted guidelines 
 Corrected high dose medication error 
 Clarified definition of nasal surgery 
 Removed maximum number of prior 
nasal polyp surgeries 
 Reduced time since last surgery from 6 
months to 3 months 
 Focusing on patient safety and 
aligning criteria in patients being 
enrolled 
 Input provided by participating 
clinical Investigators with strong 
patient management experience 
 Corrections 
 
Section 5.4 Screen Failures 
 Removed 30 day restriction for 
rescreening 
 Input provided by participating 
clinical Investigators  
Section 6.1.2 Dosing and 
Administration 
 Added instruction for subcutaneous 
injection procedures 
 Provide clarification 
6.2.4 Investigational 
Product Preparation 
 Updated header to specify 
“Investigational Product”  
 Correction 


Etokimab for Treatment of CRSwNP 
Amendment 3 
Protocol ANB020-006 
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Affected Section(s) 
Summary of Revisions Made 
Rationale 
 Removed “unblinded” team/preparer 
language 
Section 6.2.6 Mometasone 
Furoate Nasal Spray 
Formulation, Appearance, 
Packaging, and Labeling  
 Added information on MFNS 
 Provide clarification 
Section 6.2.6 Mometasone 
furoate Nasal Spray 
Formulation-dosing 
Instructions 
 Added information on dosing and 
instruction for decreasing, and 
compliance. 
 Provide clarification  
 Provide additional information on 
required MFNS usage 
6.3.1 Randomization 
 Removed unblinded staff language and 
explained kit assignment 
 Correction 
6.5.1 Rescue Medicine 
 Updated discontinuation language 
should subjects require rescue 
medication 
 Correction  
 Provide clarification 
7.1 Discontinuation of Study 
Intervention 
 Updated/added details to better 
define discontinuation of study 
intervention 
 Correction  
 Provide clarification 
7.2 Participant 
Discontinuation/Withdrawal 
from the Study 
 Updated section to require subject 
withdrawal for: 
o Pregnancy 
o Abnormal liver function tests as 
defined in the protocol 
 Removed language allowing optional 
continuation in the study treatment 
discontinuation 
 Assuring patient safety 
8.1.1 Nasal Endoscopy and 
Nasal Polyp Score (NPS) 
 Added details to clarify timing of 
procedure and study windows 
 Provide clarification 
8.1.3 Nasal Peak Inspiratory 
Flow 
 Added details to clarify collection 
procedures, timing, and compliance 
 Provide clarification 
8.1.5 Disease-Specific Tests 
and Assessments 
 Added details requirements and timing 
of procedure, and study windows 
 Provide clarification 
8.1.8.4 Excluded 
Medications Prior to Lung 
Function Assessments 
 Reduced asthma medication 
withholding timelines prior to 
spirometry from: 
o Twice daily and once daily inhalers 
(LABA/LAMA) reduced from 24 hrs. 
to 12 hrs 
o LTRA reduced from 24 hrs. to 12 hrs 
o Theophyllines reduced from 24hrs to 
12 hrs 
o Rescue SABA reduced from 6 hours 
to 4 hours 
 Focusing on patient safety  
 Input provided by participating 
clinical Investigators with strong 
patient management experience 
 
8.2.1 Clinical Laboratory 
Data 
 Removed incorrect information 
regarding antibody sample analysis  
 Correction 


Etokimab for Treatment of CRSwNP 
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Protocol ANB020-006 
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Affected Section(s) 
Summary of Revisions Made 
Rationale 
8.3 Pharmacokinetics,  
8.5 Immunogenicity 
 Updated sample collection information
 Updated PK and ADA processing 
 Clarification 
8.6.5 Adverse Event 
Reporting 
 Clarified requirements AE collection 
and recording 
 Provide clarification 
8.6.6 Serious Adverse Event 
Reporting 
8.6.9 Reporting of 
Pregnancy 
 Updated contact information 
 Correction 
Section 9 –Statistical 
Considerations 
 Corrected secondary endpoint analysis 
details 
 Updated number of subjects per arm 
 Full Analysis Set -Corrected 
typographical error  
 Secondary Efficacy Analysis: provided 
clarification 
 Exploratory Efficacy: provided 
clarification and detail 
 Corrections requested upon 
additional review of statistician 
 Correction/updates based on 
primary and secondary endpoints 
10.1.5 Key Roles and Study 
Governance 
 Updated Medical Monitor contact 
details 
 Correction 
Appendix B 
 Pregnancy testing: corrected 
confirmation requirements 
 Correction and clarification 
Appendix D 
 Updated Polyp Size descriptions for 
scoring  
 Provide clarification in definitions 
 Input provided by participating 
clinical Investigators with strong 
patient 
Appendix E 
 Updated Sino-Nasal Outcome Test 
(SNOT-22) Questionnaire 
 Correction received from license 
holder 
 
 


Etokimab for Treatment of CRSwNP 
Amendment 3 
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Investigator’s Agreement  
 
 
PROTOCOL TITLE:  A Phase 2, Double-Blind, Placebo-Controlled, Parallel Group, Multiple Dose 
Study to Investigate Etokimab (ANB020) in Adult Subjects with Chronic 
Rhinosinusitis with Nasal Polyposis 
PROTOCOL NO: 
ANB020-006 
VERSION:  
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:  ______________________________ 
 
______________________________ 
 
______________________________ 
 
______________________________ 
 


Etokimab for Treatment of CRSwNP 
Amendment 3 
Protocol ANB020-006 
06 February 2020 
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Table of Contents 
SUMMARY OF CHANGES FROM PREVIOUS VERSION ................................................................ iii 
STATEMENT OF COMPLIANCE ............................................................................................................ 1 
1 
PROTOCOL SUMMARY ............................................................................................................... 2 
1.1 
Synopsis ................................................................................................................................. 2 
1.2 
Schema ................................................................................................................................... 5 
1.3 
Schedule of Activities (SoA) ................................................................................................ 6 
2 
INTRODUCTION .......................................................................................................................... 10 
2.1 
Study Rationale ................................................................................................................... 10 
2.2 
Background .......................................................................................................................... 11 
 
Background of Disease .................................................................................... 11 
 
Background of Etokimab .................................................................................. 12 
2.3 
Risk/Benefit Assessment ................................................................................................... 16 
 
Known Potential Risks ...................................................................................... 16 
 
Known Potential Benefits ................................................................................. 17 
 
Assessment of Potential Risks and Benefits ................................................ 17 
3 
OBJECTIVES AND ENDPOINTS .............................................................................................. 18 
4 
STUDY DESIGN ........................................................................................................................... 20 
4.1 
Overall Design ..................................................................................................................... 20 
4.2 
Scientific Rationale for Study Design ............................................................................... 21 
4.3 
Justification for Dose .......................................................................................................... 21 
4.4 
End of Study Definition ....................................................................................................... 21 
5 
STUDY POPULATION ................................................................................................................. 22 
5.1 
Inclusion Criteria.................................................................................................................. 22 
5.2 
Exclusion Criteria ................................................................................................................ 23 
5.3 
Lifestyle Considerations ..................................................................................................... 25 
5.4 
Screen Failures ................................................................................................................... 25 
5.5 
Strategies for Recruitment and Retention ....................................................................... 26 
6 
STUDY INTERVENTION ............................................................................................................. 26 
6.1 
Study Intervention(s) Administration ................................................................................ 26 
 
Study Intervention Description ........................................................................ 26 
 
Dosing and Administration ............................................................................... 26 
6.2 
Preparation/Handling/Storage/Accountability ................................................................. 27 
 
Acquisition and Accountability ......................................................................... 27 
 
Etokimab Formulation, Appearance, Packaging, and Labeling ................. 27 
 
Etokimab Storage and Stability ....................................................................... 27 
 
Investigational Product Preparation ............................................................... 27 
 
Investigational Product Dosing Instructions .................................................. 27 
 
Mometasone Furoate Nasal Spray Formulation, Appearance, Packaging, 
and Labeling 
28 
 
Mometasone Furoate Nasal Spray Formulation-Dosing Instructions ....... 28 
6.3 
Measures to Minimize Bias: Randomization and Blinding ............................................ 28 
 
Randomization ................................................................................................... 28 


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Blinding 29 
6.4 
Study Intervention Compliance ......................................................................................... 30 
6.5 
Concomitant Therapy ......................................................................................................... 30 
 
Rescue Medicine ............................................................................................... 30 
6.6 
Dose Modification................................................................................................................ 30 
6.7 
Treatment After the End of the Study .............................................................................. 30 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ................................................................................................... 31 
7.1 
Discontinuation of Study Intervention .............................................................................. 31 
7.2 
Participant Discontinuation/Withdrawal from the Study ................................................ 31 
7.3 
Lost to Follow-Up ................................................................................................................ 32 
8 
STUDY ASSESSMENTS AND PROCEDURES ...................................................................... 33 
8.1 
Efficacy Assessments ........................................................................................................ 33 
 
Nasal Endoscopy and Nasal Polyp Score ..................................................... 33 
 
Sino-Nasal Outcome Test (SNOT-22) ........................................................... 34 
 
Nasal Peak Inspiratory Flow ............................................................................ 34 
 
University of Pennsylvania Smell Identification Test ................................... 35 
 
Disease-Specific Tests and Assessments .................................................... 35 
 
Polyp Biopsies ................................................................................................... 36 
 
Whole Blood Sampling and DNA Sampling .................................................. 36 
 
Quality of Life Assessments ............................................................................ 37 
8.2 
Safety and Other Assessments ........................................................................................ 39 
 
Clinical Laboratory Data ................................................................................... 40 
 
Pregnancy Testing ............................................................................................ 42 
 
Physical Examination ....................................................................................... 43 
 
Vital Signs .......................................................................................................... 43 
 
12-Lead ECG ..................................................................................................... 43 
 
Injection Site Evaluation ................................................................................... 43 
8.3 
Pharmacokinetics ................................................................................................................ 44 
8.4 
Biomarkers ........................................................................................................................... 44 
8.5 
Immunogenicity ................................................................................................................... 44 
8.6 
Adverse Events and Serious Adverse Events ................................................................ 45 
 
Definition of Adverse Events ........................................................................... 45 
 
Definition of Serious Adverse Events ............................................................. 46 
 
Classification of an Adverse Event ................................................................. 46 
 
Time Period and Frequency for Event Assessment and Follow-Up ......... 47 
8.6.5 
Adverse Event Reporting ................................................................................. 47 
8.6.6 
Serious Adverse Event Reporting .................................................................. 47 
8.6.7 
Reporting Events to Participants .................................................................... 48 
8.6.8 
Events of Special Interest ................................................................................ 48 
8.6.9 
Reporting of Pregnancy ................................................................................... 48 
8.7 
Unanticipated Problems ..................................................................................................... 49 
8.7.1 
Definition of Unanticipated Problems ............................................................. 49 


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8.7.2 
Unanticipated Problem Reporting ................................................................... 49 
8.7.3 
Reporting Unanticipated Problems to Participants ...................................... 50 
9 
STATISTICAL CONSIDERATIONS ........................................................................................... 51 
9.1 
Statistical Hypotheses ........................................................................................................ 51 
9.2 
Sample Size Determination ............................................................................................... 51 
9.3 
Analysis Sets ....................................................................................................................... 52 
9.4 
Statistical Analyses ............................................................................................................. 52 
9.4.1 
General Approach ............................................................................................. 52 
9.4.2 
Efficacy Analyses .............................................................................................. 53 
9.4.3 
Safety Analyses ................................................................................................. 58 
9.4.4 
Baseline Descriptive Statistics ........................................................................ 60 
9.4.5 
Planned Interim Analyses ................................................................................ 60 
9.4.6 
Subgroup Analyses ........................................................................................... 61 
9.4.7 
Tabulation of Individual Participant Data ....................................................... 61 
 
Immunogenicity Analyses ................................................................................ 61 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............. 61 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ............................................ 61 
10.1.1 
Informed Consent Process .............................................................................. 61 
 
Study Discontinuation and Closure ................................................................ 62 
10.1.3 
Confidentiality and Privacy .............................................................................. 62 
10.1.4 
Future Use of Stored Specimens and Data .................................................. 63 
10.1.5 
Key Roles and Study Governance ................................................................. 64 
10.1.6 
Data and Safety Monitoring Board ................................................................. 64 
10.1.7 
Clinical Monitoring ............................................................................................. 65 
10.1.8 
Quality Assurance and Quality Control .......................................................... 66 
10.1.9 
Data Handling and Record Keeping ............................................................... 66 
10.1.10 
Protocol Deviations ........................................................................................... 68 
10.1.11 
Publication and Data Sharing Policy .............................................................. 69 
10.1.12 
Conflict of Interest Policy ................................................................................. 70 
10.2 
Additional Considerations .................................................................................................. 70 
 
Ethics and Responsiblity .................................................................................. 70 
 
Amendment Policy ............................................................................................ 70 
10.3 
Abbreviations ....................................................................................................................... 72 
10.4 
Protocol Amendment History ............................................................................................ 74 
11 
REFERENCES .............................................................................................................................. 75 
APPENDICES ........................................................................................................................................... 78 
Appendix A: Prohibited Medications and Therapies during the course of the study ..................... 78 
Appendix B: Contraceptive Guidance and Collection of Pregnancy Information ........................... 79 
Appendix C: Pharmacokinetic and Anti-Drug Antibody Collection Timepoints ............................... 82 
Appendix D: Sample Endoscopic Nasal Polyp Score......................................................................... 83 
Appendix E: Sample 22-Item Sino-NASAL Outcome Test (SNOT-22) ........................................... 84 
Appendix F: Sample Short Form 36 Health Survey (SF-36) ............................................................. 85 
Appendix G: Sample EUROQOL-5D (EQ-5D) .................................................................................... 91 
Appendix H: Sample 7-Item Asthma Control Questionnaire (ACQ-7) ............................................. 93 


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Appendix I: Sample Nasal Polyp Related Resource Use Questionnaire ........................................ 95 
Appendix J: Sample Visual Analogue Scale ........................................................................................ 96 
 
 
LIST OF IN-TEXT TABLES 
Table 1. 
Clinical Laboratory Tests ................................................................................................. 40 
Table 2. 
Analysis Sets ..................................................................................................................... 52 
Table 3. 
Efficacy Analyses .............................................................................................................. 53 
Table 4. 
Key Study Personnel for Protocol ANB020-006 .......................................................... 64 
 
 
LIST OF IN-TEXT FIGURES 
Figure 1. 
 Study Schema for Protocol ANB020-006 ...................................................................... 5 
 
 
 


Etokimab for Treatment of CRSwNP 
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STATEMENT OF COMPLIANCE 
 
The trial will be conducted in accordance with the protocol, 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), 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 for review and approval. Approval of both the protocol 
and the ICFs 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 before the changes are implemented to the study. All changes to the ICF 
will be IRB 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. 
 
 


Etokimab for Treatment of CRSwNP 
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1 
 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
Title: 
A Phase 2, Double-Blind, Placebo-Controlled, Parallel Group, Multiple Dose 
Study to Investigate etokimab (ANB020) in Adult Subjects with Chronic 
Rhinosinusitis with Nasal Polyposis 
Study Description: 
This is a Phase 2, randomized, double-blind, placebo-controlled, 
parallel-group, multiple dose study designed to assess the efficacy of 
different doses and dose regimens of etokimab compared to placebo in 
adults with moderate to severe chronic rhinosinusitis with nasal polyposis 
(CRSwNP). This study will also assess the safety, tolerability, and 
pharmacokinetics (PK) of etokimab. The effects of etokimab on subjects 
with moderate to severe CRSwNP will be monitored over 24 weeks. 
All subjects will enter a run-in period of between 20 and 31 days on 
mometasone furoate nasal spray (MFNS) of 2 actuations (50 μg/actuation) 
in each alternate nostril twice daily (BID), total daily dose of 400 μg, at 
Visit 1, unless the subject is intolerant to BID intranasal corticosteroids 
(INCS) in which case, subjects can stay on the lower dose regimen (at the 
clinical judgment of the investigator). MFNS will be provided by the 
Sponsor. Compliance must be verified by the site prior to randomization.  
Objectives: 
 
Primary Objective: 
 
To evaluate the efficacy of etokimab compared to placebo in the 
treatment of subjects with CRSwNP following a 16-week 
treatment period (change from baseline using co-primary 
endpoints) 
 
Secondary Objectives:  
 
To evaluate the effectiveness of etokimab compared to placebo in 
subjects with CRSwNP in relieving clinical symptoms. 
 
To assess the safety and tolerability of etokimab in subjects with 
CRSwNP compared to placebo following a 16-week treatment 
period 
 
To assess the PK of etokimab in human serum in subjects with 
CRSwNP following subcutaneous (SC) administration 
Endpoints: 
Co-Primary Endpoints: 
 
Change from baseline to Week 16 in bilateral endoscopic Nasal 
Polyp Score (NPS) 
 
Change from baseline to Week 16 in Sino-Nasal Outcome Test 
(SNOT-22) scores 


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Secondary Efficacy Endpoints:
 
Time to first response (≥1 point improvement) in NPS 
 
Responder analysis: response defined as a reduction of at least 1 
point from baseline to Week 16 in NPS  
 
Responder analysis: response defined as a reduction of at least 12 
points from baseline to Week 16 in SNOT-22  
 
Change from baseline to Week 16 in sense of smell as assessed by 
the University of Pennsylvania Smell Identification Test (UPSIT) 
Other Secondary Endpoints 
 
Incidence of adverse events (AEs) and treatment-emergent AEs 
(TEAEs) 
 
Incidence of serious adverse events (SAEs) 
 
Changes in clinical laboratory tests (hematology, chemistry, and 
urinalysis) 
 
Changes in vital signs (blood pressure [BP], temperature, 
respiration rate, and pulse rate ) 
 
Changes in electrocardiogram (ECG) parameters 
 
Immunogenicity (anti-drug antibody [ADA} and neutralizing ADA) 
 
Apparent clearance (CL/F) 
 
Apparent volume of distribution 
 
Maximum concentration (Cmax) 
 
Time of maximum concentration (tmax) 
 
Area under the concentration-time curve from time 0 to the time 
of the last quantifiable concentration (AUCtau) 
 
Apparent terminal half-life (t1/2) will also be determined for 
etokimab after SC administrations, as possible  
Study Population: 
Approximately 100 adults between the ages of 18 and 70 years of age with 
CRSwNP with a minimum bilateral Nasal Polyp Score of 4 out of 8 
(maximum score) (with minimum score of 1 in each nostril) despite 
completion of a prior INCS treatment for at least 8 weeks before 
Screening. Presence of at least 2 of the following symptoms prior to 
Screening: nasal blockade/obstruction, nasal congestion, or nasal 
discharge (anterior/posterior nasal drip), facial pain/pressure, and/or 
reduction in or loss of smell. 
Phase: 
2 
Description of 
Sites/Facilities Enrolling 
Participants: 
Approximately 25 investigative sites across the United States (US) are 
expected to participate in this study.  
Approximately 100 subjects will be enrolled (approximately 33 evaluable 
subjects per treatment arm). 
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 identically matched single-use glass vials; each 
vial will contain no active drug product. 
See Figure 1 for dosing regimen.  


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Study Duration: 
Study duration will last approximately 12 months.  
Participant Duration: 
Participant duration includes: 
 
4-week screening period (maximum of 31 days) with a minimum 
MFNS run-in period of 20 days 
 
16-week treatment period 
 
8-week follow-up 
The total participant duration is expected to be up to 28 weeks. 
 
 


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1.2 
SCHEMA 
Figure 1. 
 
Study Schema for Protocol ANB020-006 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NOTE: MFNS will be provided to all subjects as standard of care for all 3 groups. 
Abbreviations: MFNS=Mometasone Furoate nasal spray  
 
SC=subcutaneous(ly) 
Arm 1:
Etokimab Q4W,  
~33 pts 
0 w
4w
8 w
12 w
16 w
300 mg 
SC 
Arm 3:
Placebo 
~33 pts 
 
150 mg 
SC 
150 mg
SC 
150 mg
SC 
24 w
20 w 
Screening
-4 weeks to Day -1
Follow up
(Randomization)
Arm 2:
Etokimab Q8W, 
Placebo 
~33pts 
Treatment
Legend: 
Etokimab = blue line 
Primary endpoints assessed = red type 
Placebo  =  yellow line 
Gray shading = nontreatment period 
MFNS


Etokimab for Treatment of CRSwNP 
 
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1.3 
SCHEDULE OF ACTIVITIES (SOA) 
 
 
Phase 
Screening 
Treatment 
Safety Follow-Up 
Week 
-4 to 0 
0 
1a 
4 
8 
12 
16/EOT 
20 
24/EOS/ETV 
Study Day 
-31 to -20* 
1d 
5± 1d 
29±3d 
57±3d 
85±3d 
113±5d 
141±5d 
169±5d 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
Informed Consent 
X 
 
 
 
 
 
 
 
 
IXRS: Subject Screening/Randomization/Drug 
Dispensing/Treatment Completion 
X 
X 
 
X 
X 
X 
X 
 
 
Inclusion/Exclusion Criteriab 
X 
X 
 
 
 
 
 
 
 
Medical History (Including Prior CRSwNP Therapy) 
X 
 
 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
 
Physical Examinationc 
X 
X 
 
 
 
 
X 
 
X 
Vital Signs Including Weightd 
X 
X 
 
X 
X 
X 
X 
X 
X 
12-Lead ECGe 
X 
X 
 
 
 
 
X 
 
X 
Follicle Stimulating Hormonef 
X 
 
 
 
 
 
 
 
 
Pregnancy Testg 
X 
X 
 
X 
X 
X 
X 
X 
X 
Drugs of Abuse (urine), HIV, Hepatitis B and C Viral Testing, 
TB Test (QuantiFERON® Gold)h 
X 
 
 
 
 
 
 
 
 
Hematology, Chemistryi 
X 
X 
X 
X 
X 
X 
X 
 
X 
Urinalysis 
X 
X 
 
 
 
 
X 
 
X 
Study Drug Injectionj 
 
X 
 
X 
X 
X 
 
 
 
Pharmacokineticsk 
 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicityl 
 
X 
 
X 
X 
X 
X 
X 
X 
FEV1 (Spirometry) m 
Xy 
X 
X 
X 
X 
 
 
ePRO Device Dispensation/Collectionn  
X 
 
 
 
 
 
 
X 


Etokimab for Treatment of CRSwNP 
 
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Phase 
Screening 
Treatment 
Safety Follow-Up 
Week 
-4 to 0 
0 
1a 
4 
8 
12 
16/EOT 
20 
24/EOS/ETV 
Study Day 
-31 to -20* 
1d 
5± 1d 
29±3d 
57±3d 
85±3d 
113±5d 
141±5d 
169±5d 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
NPIF readings collected via Diaryo 
 
Adverse Event Monitoring 
 
Concomitant Therapyp 
 
Nasal Endoscopy (centralized Nasal Polyp Score)b, w 
X 
X 
 
X 
X 
X 
X 
 
X 
CT Scan (Lund & 3D- correct accordingly)x 
 
X 
 
 
 
 
X 
 
 
Smell Test (UPSIT)q 
 
X 
X 
 
X 
 
SNOT-22 
X 
X 
X 
X 
X 
X 
 
X 
Visual Analogue Scale (VAS) 
 
X (Weekly via ePro Device) 
QoL (SF-36, EQ-5D) 
 
X 
X 
X 
X 
X 
 
X 
Nasal Polyps Related Resource Questionnaire 
 
X 
X 
X 
X 
X 
 
X 
ACQ-7r 
 
X 
X 
X 
X 
X 
 
X 
Nasal Polyp Biopsies s, t 
 
X 
 
 
 
 
X 
 
Stored DNA Sampling t, u  
 
X 
 
 
 
 
 
 
 
Whole Blood RNA Sampling t,u 
 
X 
X 
 
X 
 
X 
MFNS – distribute and verify usagev 
 
Abbreviations: ACQ-7 = 7-item Asthma Control Questionnaire; CRSwNP = Chronic Rhinosinusitis with Nasal Polyposis; d = day(s); CT = computed tomography; 
DNA = deoxyribonucleic acid; ECG = electrocardiogram; EOS = End of Study; ePRO = electronic patient-reported outcome; EQ-5D = EuroQol-5D for measuring 
QoL; ETV = Early Termination Visit; HIV = human immunodeficiency virus; IXRS = Interactive Web Response System; NPIF = nasal peak inspiratory flow; QoL = 
quality of life; SF-36 = Short Form-36 Health Assessment; SNOT-22 = Sino-Nasal Outcome Test; TB = tuberculosis; UPSIT = smell identification test; VAS = visual 
analogue scale. 
 
Footnotes on the next 2 pages. 
 
 


Etokimab for Treatment of CRSwNP 
 
Amendment 3 
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* During the screening window patients must use MFNS for a minimum of 20 days prior to Day 1 (maximum screening window is 31 days). Screening 
procedures can be conducted up to Day -1 if necessary. 
a Visit must occur 5 days (1 day) after Visit 2. 
b Inclusion/exclusion criteria are based on all screening assessments, Visit 1 nasal endoscopy, and laboratory results. Week 0/Day 1 pre-dose assessments are 
to be reviewed before enrollment. 
c A complete physical examination will be performed at the screening visit. All other physical examinations should be abbreviated and address associated 
complaints or findings and any other assessments required to evaluate adverse events. 
d Vital signs assessments should be performed before blood sampling and before injection of study drug at each study visit where administered. Blood 
pressure readings should be obtained after approximately 15 minutes of rest in a seated position. 
e 12-Lead ECG should be performed after 10 minutes of rest in a supine position and before the blood sample is collected. ECG must be conducted on ECG 
machine provided by ERT for the ANB020-006 clinical trial. 
f 
Follicle stimulating hormone may be used to confirm menopausal status in female subjects as needed. 
g Pregnancy testing is only required for women of childbearing potential (WOCBP). A serum test will be performed at the screening visit; urine pregnancy 
tests will be performed at treatment and follow-up visits. Testing must be performed before injection of study drug at Weeks 0, 4, 8, and 12. A negative 
result must be obtained at Visits 1 and 2 before subject may be randomized. 
h HIV 1 and 2, hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, and Mycobacterium tuberculosis (TB) will be assessed. Subjects with 
an indeterminate QuantiFERON® TB Gold result at Screening will be allowed 1 retest. 
i 
Hematology and chemistry: Blood samples will be taken before injection of study drug, after the ECG and vital signs assessments.  
j 
Subject is required to remain onsite for 2 hours post-dose for observation at Week 0 (Day 1). Subjects with any ongoing treatment-emergent AEs or SAEs at 
the time of scheduled discharge from the study center should remain at the study center until the Investigator has determined that these events have been 
resolved or deemed as not clinically significant. Subjects are not required to remain onsite after follow-up injections (Weeks 4, 8, and 12) unless deemed 
necessary by the Investigator, if there have been injection site reactions, or other AEs are noted. 
k Pharmacokinetics blood samples will be collected for all subjects at the following time points:  
 
Visit 2/Week 0: prior to dosing on Day 1. 
 
Visit 3/Week 1: Visit 3 can occur 3 to 5 days after Visit 2. 
 
Week 4, 8, 12: prior to dosing. 
 
Week 16, 20, and 24: any time at each visit. 
l 
Immunogenicity blood samples will be collected for all subjects at the following time points:  
 
Visits 2 (Week 0), 4 (Week 4), 5 (Week 8), and 6 (Week 12): prior to dosing. 
 
Visits 7 (Week 16), 8 (Week 20), and 9 (Week 24): any time at each visit. 


Etokimab for Treatment of CRSwNP 
 
Amendment 3 
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m All subjects should have the result of FEV1 (% of predicted normal as defined by the Global Initiative for Asthma) recorded in the source on Day 1 and at all 
the other scheduled visits during the treatment period. Every effort should be made to perform FEV1 assessment at the same time at each visit. If a subject 
with active asthma’s FEV1  60% on Day 1, then the subject will not be randomized. FEV1 assessment should be conducted on the spirometry machine 
provided by ERT for the ANB020-006 clinical trial. 
n The ePRO device will be provided to subjects on Day 1 upon confirmation of randomization. Subjects should be trained on log in and completion of NPIF 
distribution within the ePro device. The subjects should bring the ePRO device to each visit. The ePRO device should be returned to the site at the Week 24 
(EOS) visit. Detailed instructions will be provided separately in the Procedures Manual. 
o Peak Nasal Inspiratory Flow Meters will be provided to patients during the screening visit and patients will be instructed on use and recording requirements. 
NPIF values will be recorded on a paper diary during Screening (for 1 week/7 consecutive days). Diary must be returned to the study coordinator at the Day 
1 dosing visit. Following randomization, eDiaries will be distributed and NPIF values will be recorded directly in the device.  
p Concomitant therapy will include pharmacologic and nonpharmacologic therapies. 
q Testing must be performed before injection of study drug at Weeks 0 and 8. 
r  The ACQ-7 will be assessed only in subjects with an active asthma disease. 
s 
Optional polyp biopsies will be collected from subjects who indicate approval on ICF, in study centers with the capability to conduct the procedure. 
t 
Samples will be collected before injection of study drug on Day 1. 
u Optional sampling for exploratory analysis of DNA and RNA, requiring separate pharmacogenetic consent acknowledgment in ICF. 
V 
MFNS bottles will be distributed and used bottles collected at monthly visits to assess use. Subjects should be approximately 80% compliant with usage 
during Screening and throughout the study. During Screening subjects must complete a minimum of a 20 day run-in using MFNS prior to Day 1. 
w Endoscopy can utilize study windows to ensure procedure can be completed prior to dosing. Day 1 Endoscopy can occur up to 5 days prior to Day 1 clinic 
visit. If endoscopy is performed on site it should be completed after all other study assessments are done and prior to dosing on dose days. 
X 
Day 1 CT must be collected prior to dosing on Day 1. If necessary, the Day 1 CT can be collected during Screening, prior to Day 1, however all efforts should 
be made to conduct CT after subject screening labs have been reviewed and it is determined subject is likely eligible for the study. Note: CTs collected 
within 3 months prior to randomization (Day 1) can be utilized in lieu of a new Day 1 CT if the necessary imaging requirements are present. 
y 
Day 1 spirometry should be assessed prior to randomization to ensure inclusion/exclusion criteria are met 
 
 
 
 


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2 
 
INTRODUCTION 
 
2.1 
STUDY RATIONALE  
Chronic rhinosinusitis (CRS) is a heterogeneous disease which manifests with mucosal inflammation of 
the nasal cavity and paranasal sinuses. Chronic rhinosinusitis can be divided into 3 distinct clinical 
syndromes: CRS with nasal polyposis (CRSwNP) accounting for 20 to 33 percent of all CRS cases, and CRS 
without nasal polyposis and allergic fungal rhinosinusitis accounting for 60 to 65% and 8 to 12% of all 
CRS cases, respectively (Meltzer et al., 2004). CRSwNP is characterized by the presence of multiple 
polyps in the upper nasal cavity, originating from the ostiomeatal complex. It is the most aggressive 
form of CRS and causes significant morbidity and leads to a diminished quality of life in CRS patients.  
Current treatment options for CRSwNP are limited and typically include nonsystemic treatment with 
nasal corticosteroids, systemic corticosteroids, antibiotic therapy, and the surgical removal of polyps. 
Many 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. Relapses after surgery are common in patients with CRSwNP, and thus, there 
is need for long term therapeutic control in CRS patients.  
CRSwNP is often associated with other atopic diseases, with up to 50% of CRSwNP presenting with 
comorbid asthma (Jarvis et al., 2012) though the contributions of these acute conditions to the 
development of CRSwNP is not well understood. Asthma has been the most well-defined; approximately 
88% of patients with asthma also have radiographic evidence of sino-nasal inflammation and 
approximately 26 to 48% of patients with asthma also have been diagnosed with CRSwNP. Increased 
asthma severity has been linked to enhanced sino-nasal inflammation (Stevens, et al., 2016).  
The close association of CRSwNP with atopic disorders, particularly asthma, has led to a series of clinical 
studies with biologics that have shown efficacy in asthma. Two anti-IL-5 monoclonal antibodies 
(mepolizumab and reslizumab) and anti-immunoglobulin E (IgE) (omalizumab) have been tested in 
clinical studies in CRS patients with overall encouraging results (Chiarella et al., 2017). More recently 
dupilumab has also shown to provide benefit to CRSwNP patients (Pauwels et al., 2015). These studies 
have demonstrated the utility of biologics in CRSwNP as a viable option to provide much-needed new 
therapeutic approaches. 
The underlying pathophysiology of CRSwNP is not well-defined. Several factors are thought to 
contribute to both the development of the disease and complications of treatment. An impaired sino-
nasal epithelial barrier could allow for increased exposure to inhaled pathogens and antigens, which, in 
the setting of a dysregulated host-immune response, could encourage chronic inflammation (Stevens, et 
al., 2016).  
Interleukin-33 (IL-33), a tissue-derived cytokine that induces and amplifies eosinophilic inflammation, 
has emerged as a promising new drug target for asthma and allergic disease (Smith et al., 2017). Most 
recently, IL-33 has been detected in nasal polyps and a series of translational studies have highlighted 


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the potential central role of IL-33 in the pathogenesis of CRSwNP (Song et al., 2017; Poposki et al., 2017; 
Zhang et al., 2017). A recent study by Smith et al. resequenced 100 genes that were implicated in 
asthma to identify a novel sequence variant that directly correlated to eosinophil counts, as well as 
established asthma loci (IL-33 and IL1RL1) and demonstrated that asthma risk is mediated through IL-33 
and eosinophil counts are subsequently reduced, which could reduce the recurrence of nasal polyps 
following surgery. This study provided a sound rationale for the inhibition of the IL-33 pathway as an 
effective avenue to contain asthma. Since patients with concurrent CRSwNP and asthma require more 
sinus surgeries than patients with CRSwNP alone (Stevens, et al., 2016), a significant clinical need to 
isolate and inhibit the IL-3 pathway is warranted. 
Etokimab is a powerful and efficient inhibitor of IL-33, and thus, etokimab potentially offers an 
additional and novel treatment approach to treat severe CRSwNP patients who fail to respond to the 
current therapies. 
This Phase 2 study is intended to explore the activity of etokimab in adult subjects with CRSwNP. 
Etokimab is a highly effective inhibitor of IL-33, a cytokine that is considered to drive the pathogenic 
cascade in asthma, atopic dermatitis (AD), and CRSwNP. Interleukin-33 directly affects eosinophil counts 
and function by acting on the early phases of the atopic immune response, which is upstream of current 
asthma treatments with clinically validated targets such as IL-5, IL-4, and IL-13. The possibility to 
influence complementary and synergistic pathways involved in CRSwNP pathogenesis may provide a 
therapeutic improvement compared to the inhibition of single downstream pathways. This study will 
explore the effects of repeat doses of etokimab, administered subcutaneously (SC), compared to 
placebo on validated endpoints, such as the Nasal Polyp Score (NPS) and Sino-Nasal Outcome Test 
(SNOT-22). 
2.2 
BACKGROUND  
 
BACKGROUND OF DISEASE 
The main clinical symptoms observed in CRSwNP are nasal obstruction and congestion, reduction in or 
loss of sense of smell, anterior and posterior rhinorrhea, and facial pain. Patients with CRSwNP also 
report the presence of either anterior or posterior rhinorrhea, along with nasal congestion, hyposmia 
and/or facial pressure or pain lasting for >12 weeks in duration (Stevens, et al., 2016). CRSwNP is the 
most aggressive form of CRS and causes significant morbidity and leads to a diminished quality of life in 
CRS patients. It is most often diagnosed between 40 and 60 years of age and is more common in males, 
though females are often found to have a more aggressive disease course than males (Stevens, et al., 
2016). The polyps which occur are detected by a series of instrumental approaches mainly by endoscopy 
also supported by CT scans. 
CRSwNP is the most difficult type of CRS to be satisfactorily treated and often relapses even after 
surgical treatment. CRSwNP is a common condition observed in up to 5% percent of the US and 
European population (Stevens et al., 2016). Recently, it has been suggested that the severity of CRSwNP 
is associated with high levels of eosinophils and indeed the presence of eosinophils in tissue or airway 


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secretions greatly increases the risk of recurrent disease in CRSwNP patients after endoscopic sinus 
surgery (Vlaminck et al., 2014). 
Although the pathogenic cascade controlling CRSwNP has not yet been fully elucidated, mounting 
evidence indicates that CRSwNP shares common pathogenic pathways with asthma, particularly 
eosinophilic asthma. This is supported by the clinical evidence of CRSwNP severity correlating with 
eosinophils levels (Vlaminck et al., 2014). The close association of CRSwNP with atopic disorders, 
particularly asthma, has led to a series of clinical studies with biologics that have shown efficacy in 
asthma. Thus, 2 anti-IL-5 monoclonal antibodies (mepolizumab and reslizumab) have been tested in 
clinical studies in CRS patients (Chiarella et al., 2017). Also, anti-IgE (omalizumab) has been tested in 
these patients with overall encouraging results (Chiarella et al., 2017). More recently, dupilumab has 
also shown to provide benefit to CRS patients (Paulweis et al., 2015). All these studies have indicated 
that the use of biologics in CRSwNP patients is now considered a viable option to provide the much-
needed new therapeutic approaches.  
Although the pathogenesis of nasal polyps is not fully understood, it is believed that an atopic (Th2) 
response drives the cascade. Eosinophils are the predominant inflammatory cell found in the sinuses 
and nasal polyps and are frequently associated with asthma and aspirin sensitivity (Ponikau et al., 2005). 
Indeed, the large majority of CRSwNP patients have eosinophilic upper airway inflammation. There is 
evidence indicating that the magnitude of sinomucosal involvement, polyp size, and severity of nasal 
disease correlate with the extent of eosinophilic inflammation (Zacharek, et al, 2003). Therefore, 
eosinophils and eosinophilic products are considered the key players of the inflammatory response 
observed in nasal polyps. In this context, a series of cytokines (ie, IL-5) and mediators (cationic protein, 
eotaxin) involved in eosinophil activation are elevated in the nasal polyp specimens (Bhattacharyya et 
al., 2001).  
Most recently IL-33 has been detected in nasal polyps and a series of translational studies have 
highlighted the potential central role of IL-33 in the pathogenesis of CRSwNP (Soyka et al., 2015; Lam et 
al., 2015). Furthermore, in human subjects with a polymorphism of the IL-33 receptor (ST2), which 
confers protection from asthma, low levels of eosinophils have been observed in their periphery (Smith 
et al., 2017). Interleukin-33 also potentially activates innate lymphoid cell 2 (ILC2) to release cytokines 
such as IL-4, IL-13, and IL-5 which amplify the pathogenic Th2 response. Etokimab is a powerful and 
efficient inhibitor of IL-33, and thus, etokimab potentially offers an additional and novel treatment 
approach to treat severe CRSwNP patients who fail to respond to the current therapies. 
 
BACKGROUND OF ETOKIMAB 
Etokimab (previously known as ANB020) is a first-in-class, anti-IL-33 therapeutic antibody to treat Th2 
cell driven inflammatory diseases with underlying IL-33 dysregulation. Etokimab is a humanized 
immunoglobulin subtype G1/kappa (IgG1/kappa) monoclonal antibody (mAb) that specifically 
neutralizes the biological effects of human IL-33. Interleukin 33, a member of the IL-1 superfamily 
(Pastorelli et al., 2010) is a multifunctional cytokine that plays an important role in Th2 mediated cellular 
immunity and in the pathogenesis of atopic diseases (Liew et al., 2012; Nabe et al., 2014). Etokimab 


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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 asthma, AD, and food allergies. 
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 
, but not with mouse or rat IL-33. 
 
• 
In primary human and cynomolgus monkey cell populations, such as 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. 
 
• 
Multiple dose, good laboratory practice (GLP)- compliant toxicology and toxicokinetic studies (4-, 
13-, and 26-week duration with recovery phase) have 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
 the 
highest dose tested. 
These data, together with nonclinical safety data generated, support 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 
Currently, clinical findings from 2 completed clinical studies of etokimab (Studies ANB020-001 and 
ANB020-002) are available and summarized below. Detailed clinical experience with etokimab is 
provided in the etokimab IB.  


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2.2.2.2.1 STUDY ANB020-001 
Study ANB020-001 was a first-in-human, 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 well 
tolerated in male and female healthy volunteers, ages 19 to 44 years, when administered 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 SAE/SUSAR occurred in a subject who was randomly assigned to etokimab (750 mg) 
as a single IV injection. The subject developed severe neutropenia (0.2  109/L) on Day 22 postdose. The 
neutrophils level remained clinically significantly low (0.3  109/L) on Day 24, but the level returned 
within normal range by Day 29. No direct role of IL-33 inhibition was noted in this reported SAE of 
neutropenia. 
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 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.  
The PK data from the study have been utilized to determine route and dose to be used in this study. The 
PK data generated to date indicate that a linear PK profile is observed upon etokimab administration 


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regardless of the route. The predicted etokimab half-life is approximately 14 days. Results from the 
emergent data will serve as basis for the route of administration of Etokimab in future studies. 
2.2.2.2.2 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 (HDM) 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 subjects 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. No severe TEAE was reported, and no subject died during the 
study. 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). A total of 10 subjects experienced at 
least 1 TEAE considered related to etokimab by the Investigator during the study. The most commonly 
reported treatment-related TEAEs urinary tract infection, and urticaria (2 [16.7%] subjects each). 
Anti-drug antibodies titers were low and with no apparent effect on etokimab exposure.  
The mean (SD) total Eczema Area and Severity Index (EASI) score decreased statistically significantly 
after the administration of etokimab. On Day 15, the mean (SD) total EASI score was 19.2 (14.01) 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. The effect of etokimab showed a statistically significant decrease 
over time in total EASI scores as compared with baseline. 
After administration of etokimab (after Day 8 visit), no subject was reported by the Investigator to have 
an immunoglobulin A (IgA) score of Grade 5 and there was a trend over time for the IgA scores to 
become less severe. The shift table for the first post etokimab administration assessment on Day 15 
showed that 3 (25%) subjects who were Grade 5 at baseline improved to Grade 4; on Day 22, 3 (25%) 
subjects who were Grade 5 at baseline improved to Grade 4; and on Day 36, 2 (16.7%) subjects who 
were Grade 5 at baseline improved to Grade 4 and 1 (8.3%) subject who was Grade 5 at baseline 
improved to Grade 3. At the end of study (EOS) visit, most of the subjects (8 [66.7%] subjects) were 
Grade 4. Three (25%) subjects who were Grade 5 at baseline improved to Grade 4 at the EOS visit. 
The total Scoring Atopic Dermatitis (SCORAD) score decreased statistically significantly after the 
administration of etokimab. On Day 15, the mean (SD) total SCORAD score was 43.82 (17.753) and the 
mean treatment difference from baseline in the total SCORAD score was -16.23 (p-value<0.0001). On 


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Days 22 and 36, the mean treatment difference from baseline in the total SCORAD score was -19.20 (p-
value<0.0001) and -21.41 (p-value<0.0001), respectively. The change from baseline of total SCORAD 
score was statistically significant at all visits post etokimab administration. 
The Dermatology Life Quality Index and 5D Itch Scale scores indicated efficacy of etokimab at postdose 
visits particularly on Days 15, 22, and 36, but with declining efficacy at the later visits. 
2.3 
RISK/BENEFIT ASSESSMENT  
 
 
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 platelet 
counts were all within the normal range except in 1 volunteer in the 750 mg dose group, who reported a 
serious adverse event (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 etokimab 
group, respectively). No AEs were deemed by the Investigator to be related to etokimab. 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. 
Although there is no evidence to date for an allergic or immunologic reaction to etokimab, such a 
reaction to any drug is possible. Symptoms of allergic reactions can include rash, wheezing or difficulty 


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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. 
Based on clinical studies with other mAbs, subjects in this mAb study may experience symptoms of an 
immune reaction to the drug, also known as ‘cytokine release syndrome.’ These symptoms of this vary 
dramatically but can include: 
• 
Mild to moderate fever, chills, headache, nausea, and vomiting. 
• 
Moderate to severe symptoms such as edema (swelling of the skin), hypotension (low BP), and 
pulmonary infiltrates (eg, blood and mucus in the lung). 
Details about specific risks for subjects in this clinical trial can be found in the etokimab IB and ICF. 
 
KNOWN POTENTIAL BENEFITS  
A subject with CRSwNP 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 preclinical study and early Phase 2, results, 
subjects with CRSwNP 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. 
 
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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3 
OBJECTIVES AND ENDPOINTS 
 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary 
 
 
 
To evaluate the efficacy of 
etokimab compared to placebo in 
the treatment of subjects with 
CRSwNP following a 16-week 
treatment period  
 
Change from baseline to Week 16 in 
bilateral endoscopic NPS 
 
Change from baseline to Week 16 in 
Sino-Nasal Outcome Test (SNOT-22) 
scores  
Change in NPS and 
SNOT-22 are outcome 
measures that have been 
established as clinically 
relevant for assessing 
treatment response to 
mAbs for the 
management of CRSwNP 
symptoms 
 
Secondary 
 
 
 
To evaluate the effectiveness of 
etokimab compared to placebo in 
subjects with CRSwNP in relieving 
clinical symptoms 
 
Time to first response ( 1 point 
improvement) in NPS 
 
Responder analysis: response 
defined as a reduction of at least 1 
point from baseline to Week 16 in 
NPS  
 
Responder analysis: response 
defined as a reduction of at least 12 
points from baseline to Week 16 in 
SNOT-22  
 
Change from baseline to Week 16 in 
sense of smell as assessed by the 
University of Pennsylvania Smell 
Identification Test (UPSIT) 
 
These endpoints are 
outcome measures that 
have been established as 
clinically relevant for 
assessing treatment 
response of mAbs for the 
management of CRSwNP 
symptoms 
 
 
To assess the safety and 
tolerability of etokimab in 
subjects with CRSwNP compared 
to placebo following a 16-week 
treatment period 
 
 
Incidence of AEs and TEAEs 
 
Incidence of SAEs  
 
Changes in clinical laboratory tests 
(hematology, chemistry, and 
urinalysis) 
 
Changes in vital signs (BP, 
temperature, respiration rate, and 
pulse rate) 
 
Changes in ECG parameters 
 
Immunogenicity (ADA and 
neutralizing ADA) 
 
These endpoints are 
outcome measures that 
have been established as 
clinically relevant for 
assessing the safety and 
tolerability of mAbs for 
the management of 
CRSwNP symptoms 
 
 
To assess the pharmacokinetics 
(PK) of etokimab in human serum 
in subjects with CRSwNP 
following subcutaneous (SC) 
administration 
 
 
CL/F  
 
Apparent volume of distribution  
 
Cmax 
 
Time of maximum concentration 
(tmax) 
These PK endpoints are 
PK-specific outcome 
measures that have been 
established as clinically 
relevant for assessing the 
PK of mAbs for the 


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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
 
Area under the concentration-time 
curve from time 0 to the time of the 
last quantifiable concentration 
(AUCtau) 
 
Apparent terminal half-life (t1/2) will 
also be determined for etokimab 
after SC administrations, as possible 
 
management of CRSwNP 
symptoms 
 
Exploratory  
 
 
 
To assess improvement in Quality 
of Life (QoL) in subjects with 
CRSwNP treated with etokimab 
compared to placebo following a 
16-week treatment period 
 
QoL: 
o 
36-item Short Form Health 
Survey (SF-36) 
o 
European QoL scale (EQ-5D) 
o 
Patient-related rhinosinusitis 
symptoms severity using a 
visual analogue scale (VAS) 
o 
Number of nocturnal 
awakenings 
To assess the effect of 
etokimab on the patients’ 
symptoms and quality of 
life 
 
To assess other effects of 
etokimab compared to placebo in 
subjects with CRSwNP following a 
16-week treatment period 
 
 
Percent change from baseline to 
Week 16 in sinus opacification as 
assessed by CT scan using Lund-
Mackay score 
 
Change from baseline to Week 16 in 
nasal peak inspiratory flow (NPIF) 
 
Change from baseline to Week 16 in 
NPS in subjects with comorbid 
asthma 
 
Change from baseline to Week 16 in 
Sino-Nasal Outcome Test (SNOT-22) 
scores in subjects with comorbid 
asthma  
 
Percent change from baseline to 
Week 16 in 3-dimensional 
volumetric measurement of the 
maxillary sinus as assessed by CT 
scan 
 
Change from baseline to Week 16 in 
forced expiratory volume (FEV1) 
(overall and in subgroup with 
asthma) 
 
Change from baseline to Week 16 in 
FEV1 percent of predicted (overall 
and in subgroup with asthma) 
 
7-Item Asthma Control 
Questionnaire (ACQ-7) in asthma 
subgroup 
 
Reduction of eosinophils (blood 
eosinophil count) from baseline 
(Day 1 pre-dose) to Week 16 
All other efficacy 
endpoints have been re-
categorized as 
exploratory endpoints 
 
Additional measures of 
treatment response are 
established methods to 
characterize the clinical 
impact of treatment 
 
Patient-reported 
outcomes specific to 
CRSwNP provide 
additional evidence to 
support the physician 
assessment of outcome 


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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
 
Time to study treatment 
discontinuation 
 
Incidence of treatment 
discontinuation due to need for oral 
corticosteroids (OCS) or nasal polyp 
surgery 
 
Change in Nasal Polyp Resource 
Questionnaire from baseline to 
Week 16 
 
4 
STUDY DESIGN  
 
4.1 
OVERALL DESIGN 
This is a randomized, double-blind, placebo-controlled, parallel-group, multiple dose, Phase 2 study 
designed to assess efficacy, safety, tolerability, and PK of 2 different doses and dose regimens of 
etokimab following a 16-week treatment period compared to placebo in adults with moderate to severe 
CRSwNP. The total study duration will be approximately 28 weeks. 
A Sponsor-designated centralized reader will be used to confirm the diagnosis of CRSwNP as assessed by 
nasal endoscopy, CT scan of sinuses, and symptom scoring to reduce the risk of interpretation variation. 
This study has 3 periods: a 4-week screening period (maximum of 31 days), with a minimum MFNS 
run-in of 20 days prior to the administration of study drug on Day 1; a 16-week treatment period (Week 
0 to Week 16); and an 8-week safety follow-up period. 
During the screening period, all subjects will undergo evaluation for eligibility. Subjects will be randomly 
assigned on Day 1 to one of the following 3 treatment arms in a 1:1:1 ratio: 
 
Etokimab 300 mg load + 150 mg SC every 4 weeks (Weeks 0, 4, 8, and 12) 
 
Etokimab 300 mg load + 150 mg SC every 8 weeks (Weeks 0 and 8) and placebo (Weeks 4 
and 12) 
 
Placebo (Weeks 0, 4, 8, and 12) 
Eligible 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). Subjects will remain onsite for 2 hours for post-dose 
observation following the initial (Week 0/Day1) study drug injection. Additional visits will occur on Day 5 
(Week 1) and Day 113 (Week 16) during the treatment period. During the safety follow-up period, 
subjects will return to the study center on Day 141 (Week 20) and Day 169 (Week 24) EOS (see Section 
1.3). 
Subjects will also be provided MFNS for use during the trial and are required to undergo a minimum 
run-in period of 20 days prior to Day 1 with approximately 80% compliance. Subjects will use MFNS of 
2 actuations (50 μg/actuation) in each alternate nostril twice daily (BID), total daily dose of 400 μg, 


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throughout the study, unless they are intolerant to BID intranasal corticosteroids (INCS) in which case, 
subjects can stay on the lower dose regimen of 1 actuation (50 μg/actuation) in each nostril BID, total 
daily dose of 200 μg, additional decreases should be discussed with the Medical Monitor. If physician 
lowers dose regimen due to intolerance, compliance will be based on lower dose. Any changes to the 
MFNS must be documented and recorded in eCRF.  
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 examinations, ECGs, and 
laboratory measurements will be performed as specified in the SOA (see Section 1.3). 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
This Phase 2 study will explore the activity of etokimab in adult subjects with moderate to severe 
CRSwNP. Etokimab is a highly effective inhibitor of IL-33, a cytokine that is considered to drive the 
pathogenic cascade in asthma, AD, and CRSwNP. Interleukin-33 directly affects eosinophil counts and 
function by acting on the early phases of the atopic immune response, which is upstream of current 
asthma treatments with clinically validated targets such as IL-5, IL-4, and IL-13. The possibility to 
influence complementary and synergistic pathways involved in CRSwNP pathogenesis may provide a 
therapeutic improvement compared to the inhibition of single downstream pathways. This study will 
explore the effects of repeat doses of etokimab, administered SC over a 16-week treatment period, 
compared to placebo on validated endpoints, such as the NPS and SNOT-22. 
4.3 
JUSTIFICATION FOR DOSE 
Data from the etokimab Phase 1 (ANB020-001) and Phase 2a (ANB020-002) studies are the basis for the 
selection of the 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 of 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 etokimab loading doses will allow 
systemic concentrations to reach serum concentrations sustaining more than 95% IL-33 inhibition faster, 
potentially reducing 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 after 
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 or the last scheduled procedure, as shown in the Schedule of Activities 
(SoA), Section 1.3. 


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The end of the study is defined as the date of the last visit or procedure of the last subject in the study. 
5 
STUDY POPULATION 
 
5.1 
INCLUSION CRITERIA 
Subjects must meet all of the following criteria in order to be eligible to participate in this study: 
1. Male or female, aged 18 to 70 years at the time of consent. 
2. Present with a minimum bilateral total NPS of 4 out of 8 (maximum score), with minimum score 
of 1 in each nostril, despite completion of a prior INCS treatment at least 8 weeks before 
Screening. 
3. Present with at least 2 of the following symptoms prior to Screening: 
a. Nasal blockade/obstruction 
b. Nasal congestion  
c. Nasal discharge (anterior/posterior nasal drip) 
d. Facial pain/pressure, and 
e. Reduction in or loss of smell 
4. Body mass index (BMI) of 18 to 42 kg/m2 (inclusive) and total body weight > 50 kg (110 lb). 
5. Agrees to the following conditions regarding contraception and pregnancy: 
a. A male subject must agree to use contraception as detailed in the 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 of child bearing potential must have a negative serum pregnancy test 
(-human chorionic gonadotropin) at Screening and a negative urine pregnancy test at 
Baseline (Day 1), is not lactating, and at least one of the following conditions applies: 
 
i. Not a WOCBP as defined in the protocol, OR 
ii. A WOCBP who agrees to follow the contraceptive guidance in the protocol during the 
treatment period and for at least 3 months after receiving the last dose of study 
treatment. 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). 
6. Screening laboratory values must meet the following criteria:  
a. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels  3 x ULN 
b. Total bilirubin  1.5 x ULN 
c. Albumin  3 g/dL - lipase  1.5 ULN (if collected) 
If a subject has liver function tests (LFTs) within normal and defined limits at Screening and 
meets all other inclusion criteria at Screening and baseline, the subject can be dosed. 


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7. Capable of giving signed informed consent and understanding the requirements and restrictions 
listed in the ICF. 
8. Subject must use MFNS as provided by the Sponsor and be approximately 80% compliant during 
the screening period through Day 1. 
9. Willing to and capable of complying with the study protocol requirements. 
10. Able to read and to understand the study procedures and have the ability to communicate 
meaningfully with the Investigator and staff. 
11. Confirmation of completion of 1 week of daily NPIF recordings (twice daily) on Day 1, prior to 
randomization. (A minimum of approximately 5 days must be completed of the 7 consecutive 
days requested). 
 
5.2 
EXCLUSION CRITERIA  
Subjects are excluded from the study if any of the following criteria apply: 
1. Prior exposure to etokimab. 
2. SNOT-22 score < 15 at Screening. 
3. Use of other investigational drugs or prohibited therapy for this study within 8 weeks before 
screening or 5 half-lives, whichever is longer: 
a) Have required an increase of OCS or INCS drops within the 2 months before screening or are 
scheduled to receive OCS during the study period for another condition 
b) Have undergone any previous monoclonal antibody (mAb) or immunosuppressive treatment 
c) Leukotriene antagonists/modifiers for subjects who were not on a continuous treatment for 
 30 days prior to Screening 
4.  Have a documented history of aspirin-exacerbated respiratory disease (AERD) diagnosis as 
confirmed by a medical provider with an oral aspirin challenge. 
5. Have concomitant medical condition(s) that may interfere with the Investigator’s ability to 
evaluate the subject’s response to the investigational product (IP). 
6. Have experienced a severe life-threatening anaphylactic reaction to human, humanized, 
chimeric, or murine monoclonal antibodies. 
7. Have participated in any interventional study for the treatment of CRSwNP in the 3 months 
before Screening. 
8. Have received high dose systemic corticosteroids (equivalent to > 15 mg/day prednisone), 
prolonged nonsteroidal, immunosuppressant, or immunomodulating treatments within 8 weeks 
before Screening. 


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9. Have received treatment with biologics such as dupilumab, mepolizumab, or omalizumab within 
12 weeks or 5 half-lives (5 T1/2), whichever is longer, before Screening. 
10. Clinically significant abnormal ECG assessment at Screening (any abnormality that the 
Investigator believes is not safe for study participation). 
11. History of ischemic cardiovascular disease(s) or cerebrovascular event within 1 year of 
Screening. 
12. Have received any systemic antibiotic treatment within 4 weeks before Screening. 
13. Have a history of hypersensitivity or allergic reactions to
a component of the 
etokimab formulation or the inactive ingredients (excipients). 
14. If female, is pregnant or lactating, or intends to become pregnant during the study period. 
15. Current smokers or former smokers with a smoking history of ≥10 pack-years [(number of 
cigarettes per day/20) × number of years smoked]. A former smoker is defined as a subject who 
quit smoking at least 2 months prior to screening visit. This includes electronic cigarettes and 
vaping. Subjects who smoke medicinal marijuana can be enrolled at the Investigator’s discretion 
(conversion to edible forms of marijuana is preferred). Occasional smoking is permitted at the 
discretion of the Investigator (eg, cigar or pipe for significant event, occasional/rare weekend 
cigarette or marijuana use).  
16. Positive blood screen for hepatitis C virus antibody, hepatitis B virus core antibody, hepatitis B 
surface antigen, or human immunodeficiency virus (HIV) 1 and 2 antibodies (except subjects 
who test positive for hepatitis B surface antigen alone due to a hepatitis B vaccination). 
17. Presence of chronic or active infection at Screening including positive result for active 
tuberculosis (TB) (ie positive QuantiFERON® test result without any prior history of active nor 
latent TB infection and without evidence of active infection) where the subject has not 
completed prophylactic treatment. 
18. Any comorbidity that the Investigator believes is a contraindication to study participation. This 
includes, but is not limited to, any respiratory (eg, pulmonary fibrosis, eosinophilic 
granulomatosis with polyangiitis, allergic bronchopulmonary aspergillosis), cardiovascular, 
gastrointestinal, hematological, neurological, immunological, musculoskeletal, renal, infectious, 
neoplastic, or inflammatory condition that may place the safety of the subject at risk during the 
study, impact results of the study or their interpretation, or prevent subject from completing the 
study. 
19. Comorbid asthma when: 
a) Forced expiratory volume (FEV1) 60% of predicted normal as assessed on Day 1 as 
defined by the Global Lung Initiative (GLI) 
b) An exacerbation requiring systemic (oral and/or parenteral) corticosteroid treatment or 
hospitalization (> 24 hours) for treatment of asthma within 3 months prior to Screening 
c) A daily dose higher than 1000 g fluticasone or the equivalent of inhaled corticosteroids 


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20. Have any other physical, mental, or medical conditions that, in the opinion of the Investigator, 
makes study participation inadvisable or could confound study assessments. 
21. Receipt of live attenuated vaccine within 4 weeks before Screening. 
22. Planned surgery during the study or within 30 days before Screening. 
23. History of malignancy within 5 years, except non-melanoma skin cancer that has been fully 
treated with no current active disease. 
24. Initiation of allergen immunotherapy: 
a) Within 12 weeks prior to Screening  
b) Planned to begin therapy during the screening period 
c) Planned to begin during the randomized treatment period 
Subjects who started immunotherapy more than 12 weeks prior to Screening can continue the 
immunotherapy during the study providing dosing is at least 2 weeks prior to each dose of study 
drug. 
25. Undergone any nasal surgery (eg, any procedure with excision of tissue) within 3 months before 
randomization (Day 1).  
26. Evidence of drug/substance abuse that would pose a risk to subject safety, interfere with the 
conduct of the study, or affect the subject’s ability to participate in or comply with the study 
protocol, including but not limited to evidence of misuse of addictive drugs, such as opioids, 
outside of prescribed medications for a medical condition. 
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 trial but are not 
subsequently randomly assigned to the study intervention or entered in the study. A minimal set of 
screen failure information is required to ensure transparent reporting of screen failure participants, to 
meet the Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demography, screen 
failure details, eligibility criteria, and any SAE. 
Subjects who do not meet the criteria for participation in the study (screen failure) may be rescreened 
up to 2 more times during the enrollment period of the study. All requests for second rescreening must 
be discussed with the medical monitor and approved by the Sponsor.  


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5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
The recruitment and retention plan for this study will be provided in a separate Manual of Procedures 
(MOP). 
6 
STUDY INTERVENTION 
 
6.1 
STUDY INTERVENTION(S) ADMINISTRATION 
 
 
STUDY INTERVENTION DESCRIPTION 
Etokimab protein drug substance (DS) was produced using a conventional monoclonal antibody 
manufacturing process. Etokimab drug product (DP) was produced by sterile filtration and aseptic fill of 
drug substance into glass vials, without additional processing. The container closure system for the DP is 
a 2Rtype I glass vial with 13 mm chlorobutyl stoppers and 13 mm aluminum seals. Multiple DP lots may 
originate from a single DS lot. 
The identically matched placebo used in this study contains no active drug product. 
 
DOSING AND ADMINISTRATION 
Eligible subjects will be randomly assigned on Day 1 to 1 of 3 treatment arms in a 1:1:1 ratio: 
 
Etokimab 300 mg load + 150 mg SC every 4 weeks (Weeks 0, 4, 8, and 12) 
 
Etokimab 300 mg load + 150 mg SC every 8 weeks (Weeks 0 and 8) and placebo 
(Weeks 4 and 12) 
 
Placebo (Weeks 0, 4, 8, and 12) 
Study drug will be administered SC during onsite visits on Day 1 (Week 0), Day 29 (Week 4), Day 57 
(Week 8), and Day 85 (Week 12).  
Subcutaneous injection sites should be alternated among upper arms or, if necessary, the different 
quadrants of the abdomen (avoiding navel and waist areas). If possible, the same site should not be 
injected for 2 consecutive months. Study drug should be administered only into areas of normal-looking 
skin; if possible, Day 1 (loading dose) injections should be administered in separate upper arms. If both 
injections are administered in the same area, the injections should be spaced approximately 2 inches 
apart. Additional detail will be located in the Pharmacy Manual. 


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6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
 
 
ACQUISITION AND ACCOUNTABILITY 
Study centers are required to actively acknowledge receipt of shipment of IP and confirm that 
appropriate refrigeration was maintained during transit through accessing the temperature monitoring 
device(s) with each shipment. The Pharmacy Manual should be referred to for additional information 
and details. 
 
ETOKIMAB FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
Etokimab is a sterile, colorless to slightly yellowish solution that is formulated at
Each single-use vial contains
of 
solution and 
of etokimab.  
Identically matched placebo is supplied as a solution in single-use vials that contain active drug product. 
All IP vials will be packaged and labeled in accordance with all applicable laws and regulations. 
 
ETOKIMAB STORAGE AND STABILITY 
Etokimab or placebo vials must be refrigerated at 2°C to 8°C (36°F to 46°F) until the day of use. Etokimab 
or placebo should not be used beyond the retest or expiration date provided by the manufacturer. Vial 
contents should not be frozen or shaken. Etokimab or placebo may be stored at room temperature 
( 8°C to 25°C [46°F to 77°F]) 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. Compatibility 
testing has shown that etokimab is stable and does not adsorb to the polyethylene or polypropylene 
syringes or standard hypodermic needles. 
 
INVESTIGATIONAL PRODUCT PREPARATION 
Investigational product (study drug or placebo) will be prepared by a trained dose preparer. Dose 
preparation records will be completed and securely maintained by the dose preparer. Both etokimab 
and placebo have the same appearance in the syringe, thereby ensuring that the study team and 
subjects will remain blinded to study treatment. Syringes of etokimab and placebo will be prepared 
based on treatment group assignment. 
 
INVESTIGATIONAL PRODUCT DOSING INSTRUCTIONS 
Dosing instructions for study drug (etokimab and placebo) will be provided in the Pharmacy Manual. 
Injections of study drug will be administered following clinic procedures and blood collection at 
scheduled visits during the randomized treatment period (see SoA, Section 1.3).  
Subjects will be monitored for 2 hours by the Investigator or study personnel after the initial 
(Week 0/Day 1) injection of study drug, for any signs or symptoms of a local site injection or 


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hypersensitivity reaction. Subjects with any ongoing treatment-emergent AEs or SAEs at the time of 
scheduled discharge from the study center should remain at the study center until the Investigator has 
determined that these events have been resolved or deemed as not clinically significant. Subjects are 
not required to remain onsite after follow-up injections (Weeks 4, 8, and 12) unless deemed necessary 
by the Investigator, if there have been injection site reactions, or other AEs are noted. 
 
MOMETASONE FUROATE NASAL SPRAY FORMULATION, APPEARANCE, PACKAGING, 
AND LABELING 
Mometasone furoate, the active component of MFNS, 50 μg, is an anti-inflammatory corticosteroid 
having the chemical name, 9,21-Dichloro-11ß,17-dihydroxy-16α-methylpregna-1,4-diene-3,20-
dione17-(2 furoate). 
Mometasone furoate is a white to off-white powder, with a molecular formula of C27 H30 C12 O6 and a 
molecular weight of 521.43 g/mol. It is practically insoluble in water; slightly soluble in methanol, 
ethanol, and isopropanol; soluble in acetone and chloroform; and freely soluble in tetrahydrofuran. Its 
partition coefficient between octanol and water is >5000. 
Mometasone furoate nasal spray 50 μg is a metered-dose, manual pump spray unit containing an 
aqueous suspension of 0.05% w/w mometasone furoate in an aqueous medium containing 
benzalkonium chloride, citric acid, glycerin, microcrystalline cellulose and carboxymethylcellulose 
sodium, polysorbate 80 and sodium citrate. The pH is between 4.3 and 4.9. Each bottle contains 
120 metered sprays. 
 
MOMETASONE FUROATE NASAL SPRAY FORMULATION-DOSING INSTRUCTIONS 
Subjects will also be provided MFNS for use during the trial. Subjects will use MFNS of 2 actuations 
(50 μg/actuation) in each nostril twice daily (BID), total daily dose of 400 μg, throughout the study, 
unless they are intolerant to BID INCS in which case, subjects can stay on the lower dose regimen of 
1 actuation (50 μg/actuation) in each nostril twice daily (BID), total daily dose of 200 μg, additional 
decreases should be discussed with the Medical Monitor.  
If the Investigator lowers the dose regimen due to intolerance, compliance will be based on lower dose. 
Any changes to the MFNS must be documented and recorded in eCRF. 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
 
RANDOMIZATION 
This is a randomized, double-blind, placebo-controlled, parallel-group 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 


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randomization numbers which will be used to assign the allocated treatment based on a randomization 
schedule. Before the study is initiated, the telephone number and call-in directions for the IXRS and/or 
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 a pharmacist or designee as summarized in 
Section 6.2.4 and the Pharmacy Manual; the visits at which this will occur are summarized in the SoA 
(Section 1.3).  
Eligible subjects will be randomized on Day 1 to 1 of 3 treatment arms in a 1:1:1 ratio (see Section 6.1.2), 
based on a computer-generated randomization schedule prepared by or under the supervision of the 
Sponsor. The randomization will be stratified by asthma comorbidity. The IXRS will assign a unique 
treatment code, which will dictate the treatment assignment and matching study drug kit for the 
subject. The pharmacist or designee will not be aware of treatment assignment (etokimab or placebo) 
and will be provided only kit numbers to assign study drug. 
All calls 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 eCRF, as applicable. 
The assessments of efficacy will be performed by the Investigator or qualified designee, who is blinded 
to the subject’s treatment group assignment. When all of the study data have been entered into the 
study database and verified, the randomization code will be broken for data analysis.  
 
BLINDING 
Under normal circumstances, the blind should not be broken until all subjects have completed the 
double-blind phase of study and the database is finalized. Otherwise, the blind should be broken only if 
specific emergency treatment/course of action would be dictated by knowing the treatment the subject 
is receiving. In such cases, the Investigator may in an emergency determine the identity of the treatment 
by IXRS. Telephone contact with the Sponsor or its designee will be available 24 hours per day, 7 days 
per week.  
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).  
In the event the blind is broken, the Sponsor must be informed as soon as possible. The date, time, and 
reason for the unblinding must be documented by the Investigator in the appropriate section of the 
eCRF, and in the source document. The documentation received from the Interactive Web Response 
System indicating the code break must be retained with the subject’s source documents in a secure 
manner (eg, sealed envelope) so as not to unblind the treatment assignment to the study site, 


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Sponsor/contract research organization personnel. The Investigator is also advised not to reveal the 
study treatment assignment to the study site or Sponsor personnel. 
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. 
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. Medications to be reported in the eCRF are concomitant 
prescription medications, over-the-counter medications and supplements. 
Any medication, 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 prohibited medications is provided in Appendix A. 
 
RESCUE MEDICINE 
Use of rescue medication (eg, systemic corticosteroid) is not permitted in this study (except MFNS as 
supplied per protocol). If a subject receives systemic rescue treatment the subject will be discontinued 
from the study and should return for a final Early Termination Visit (ETV) within 30 days from last dose. 
Study procedures should be completed according to the ETV/EOS per Section 1.3. In the case of ongoing 
AEs/SAEs, the subject should be followed up until it has resolved or stable outcome or subject is lost to 
follow-up. The date and time of rescue medication administration, as well as the name and dosage 
regimen of the rescue medication, must be recorded into the eCRF/study database by study center 
personnel.  
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 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 


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is related to the study drug, SAE, or pregnancy occurring within 30 days after the EOS visit should be 
reported to the medical monitor and followed up until it has 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 study treatment at the next scheduled administration 
study visits can be done after discussion with the medical monitor. 
In the case of discontinuation from study treatment the subject should return for an ETV within 30 days 
from last dose and will be encouraged to complete their remaining clinic visits as planned. Study 
procedures should be completed according to the (ETV)/(EOV) per Section 1.3. Ongoing AEs/SAEs, the 
patient should be followed up until it has resolved or stable outcome or subject is lost to follow-up.  
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, the subject will be required to return as noted above for ETV. 
Procedures should be completed in accordance with the SoA (see Section 1.3) Week 24/ETV.  
If an ETV occurs within 7 days of the previous visit lab re-draws are not required unless clinically 
significant labs were noted.  
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Subjects are free to withdraw from participation in the study at any time upon request. 
An Investigator must discontinue or withdraw a subject from the study and follow for safety for the 
following reasons:  
 
Any subject becomes pregnant or indicates they are planning to become pregnant during the 
study 
 
Any LFT abnormality that meets the following criteria require discontinuation:  
o If a subject has at any time post-initial dose an AST or ALT >5-8x ULN for more than 2 weeks, 
discontinue dosing; or  
o AST or ALT >8x ULN, irrespective of duration discontinue dosing; or  
o Concurrent AST or ALT >3x ULN and total bilirubin >2x ULN discontinue dosing.  
An Investigator may discontinue or withdraw a subject from the study for the following reasons: 


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 
Significant study intervention noncompliance (eg, failure to follow study procedures or to keep 
follow-up appointments)  
 
If any clinical AE, laboratory abnormality, or other medical condition or situation occurs such 
that continued participation in the study would not be in the best interest of the subject 
 
Disease progression which requires discontinuation of the study intervention 
 
If the subject meets an exclusion criterion (either newly developed or not previously recognized) 
that precludes further study participation 
If the subject withdraws consent and discontinues from the study, the Investigator will attempt to 
determine the reason for discontinuation and record the reason in the subject’s study records and on 
the eCRF. If a subject withdraws consent because of an AE, that AE should be indicated as the reason for 
withdrawal. In the event of early discontinuation, the subject should be asked to return to the study 
center to complete the assessments specified in the ETV. 
If at any time during the study, the investigator determines that it is not in the best interest of the 
subject to continue, the subject will be discontinued from participation. The Investigator can discontinue 
a subject at any time if medically necessary. Appropriate documentation in the subject’s study record 
and eCRF regarding the reason for discontinuation must be completed. Prior to discontinuing a subject 
from study participation, the Investigator will discuss his/her intentions with the medical monitor or 
designee. 
All subjects who fail to return to the study center for the required follow-up visits will be contacted by 
phone to determine the reason(s) why the subject failed to return for the necessary visit or elected to 
discontinue from the study. If a subject is unreachable by telephone after a minimum of 2 documented 
attempts (one attempt on 2 different days), a registered letter will be sent requesting that contact be 
made with the Investigator. 
The Sponsor has the right to terminate or to stop the study at any time. Should this be necessary, both 
the Sponsor and the Investigator will ensure that proper study discontinuation procedures are 
completed. 
Subjects who sign the ICF and are randomized but do not receive the study intervention may be 
replaced. Subjects who sign the ICF, and are randomized and receive the study intervention, and 
subsequently withdraw, or are withdrawn or discontinued from the study, will not be replaced. 
7.3 
LOST TO FOLLOW-UP 
Study center personnel will attempt to contact the subject and reschedule any missed visit as soon as 
possible, if it does not fall within the next visit’s window, and counsel the subject on the importance of 
maintaining the assigned visit schedule and ascertain if 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. 


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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: 
 
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 
 
8.1 
EFFICACY ASSESSMENTS  
As part of study preparations, Investigators will receive standardized training on the efficacy 
assessments in this study. The same Investigator will perform all efficacy assessments for a given 
subject, as practical given the long study follow-up duration. 
 
NASAL ENDOSCOPY AND NASAL POLYP SCORE 
Nasal endoscopy is one of the co-primary endpoints in the study (ie, change in NPS from baseline to 
Week 16). It will be performed according to the SoA (see Section 1.3), if the endoscopy is performed 
onsite during the study visit, it should occur after study assessments (eg, QoL assessments, labs, UPSIT, 
etc.) have been completed and preceded by local administration of anesthetic drugs in combination 
with a decongestant. The nasal endoscopy must be performed prior to dosing on Day 1, Week 4, 
Week 8, and Week 12. The Day 1 endoscopy can be scheduled up to 5 days prior to the Day 1 visit; visit 
windows can be utilized for scheduling follow-up nasal endoscopies. For the analysis of primary 
endpoint, central reading of Day 1 will be used for comparison with central reading at Week 16. The 
sites will remove subject-identifying information from the imaging data header and label with subject ID 
prior to sending the imaging data to the central reader. 
Standard video sequences of the nasal endoscopy will be downloaded or sent to a Sponsor-designated 
centralized reader at the completion of the visit for adjudication. Nasal endoscopy will be performed 
using centralized imaging data assessments and scoring by an independent reviewer for the imaging 
data will be performed for all endoscopies. To confirm eligibility at Study Day 1, only the screening visit 
pass/fail results will be made available to the study center. The final results of central reading will be 
made available after the study. 
Further details on nasal endoscopy will be available in a separate operational manual provided to the 
sites. 
A sample NPS is provided in Appendix D. 


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SINO-NASAL OUTCOME TEST (SNOT-22) 
The SNOT-22 is one of the co-primary endpoints of the study (ie, change in SNOT-22 from baseline to 
Week 16). It is a 22-item outcome measure on a 5-category scale applicable to sino-nasal conditions and 
surgical treatments. The score ranges from 0 to 110. Higher total scores on the SNOT-22 imply greater 
impact of CRS on QoL. The questionnaire was found easy to use (time to completion is approximately 
7 minutes) and provided good discriminant validity (Hopkins et al., 2009). The SNOT-22 was validated 
and recommended for routine clinical practice. A Minimal Clinically Important Difference MCID is 
available:  8.90 (Chowdhury et al., 2017; Steele et al., 2016; and Rudmik et al., 2015).  
The SNOT-22 will be completed as indicated in the SoA (see Section 1.3) and is located on the clinical 
tablet. This frequent SNOT-22 might provide a kinetic profile of etokimab efficacy in subjects with 
CRSwNP.  
A sample SNOT-22 is provided in Appendix E. 
 
NASAL PEAK INSPIRATORY FLOW 
Nasal peak flow evaluation represents a physiologic measure of the air flow through both nasal cavities 
during forced inspiration and/or expiration expressed in liter per minute. The NPIF is the best validated 
technique for the evaluation of nasal flow through the nose. Nasal inspiration correlates most with the 
subjective feeling of obstruction and is the best validated technique for monitoring nasal flow in clinical 
trials. 
Taking the best of 3 outcomes with less than 10% variation is considered to be the best means of 
expression of the result (Juniper et al., 2004). All 3 values will be recorded by the subject in the diary, 
and the highest value will be used for evaluation. The procedure takes about 5 minutes. Baseline AM 
NPIF will be the mean AM measurement recorded for 7 consecutive days or 1 week during the screening 
period, prior to the first dose of IP, and baseline PM NPIF will be the mean PM measurement recorded 
for 7 consecutive days or 1 week during the screening period, and prior to the first dose of IP. Baseline 
will be the mean, averaged measurement from the 7-day period. 
At Screening (Visit 1), subjects will be issued an NPIF meter for recording morning (AM) and evening 
(PM) NPIF. Subjects will record values twice a day for 7 consecutive days during the screening period, 
and twice a day, every day throughout the treatment and safety follow-up period (Weeks 0-24), 
according to diary instructions. Subjects will be instructed on the use of the meter, and written 
instructions on the use of the NPIF meter will be provided to the subjects. In addition, the Investigator 
will instruct the subjects on how to record the following variables in the diary on a daily basis. 
 
AM NPIF should be performed approximately 15 minutes after arising prior to taking MFNS 
 
PM NPIF should be performed in the evening prior to taking MNFS 
Three NPIF efforts will be performed by the subject and recorded.  


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During the screening period NPIF recording will be collected on a paper diary provided to subjects. 
Subjects must return the paper diary to the site on Day 1. Subjects should complete the diary twice a 
day for 7 consecutive days during the screening window; however, at least 5 of the 7 days must be 
completed during the screening period to be eligible for enrollment.  
At Day 1 subjects will be provided an eDiary to collect NPIF recordings throughout the remainder of the 
trial. Diary compliance must be approximately 80% throughout the study duration. 
 
UNIVERSITY OF PENNSYLVANIA SMELL IDENTIFICATION TEST  
The UPSIT is a rapid and easy-to-administer method to quantitatively assess human olfactory function. It 
shows a high test-retest reliability (r: 0.981) and scores on this test are strongly correlated with the 
detection threshold for phenyl ethyl alcohol in the same individuals. When the UPSIT is administered in 
the standardized manner, clinical subjects show a high degree of uniformity in UPSIT performance when 
tested in different laboratories. 
The 40-odorant UPSIT is used in over 1500 clinics and laboratories throughout the US, Canada, South 
America, and Europe, and has been administered to nearly 200,000 people since its development in the 
early 1980s. A particular strength of this test is that it provides an olfactory diagnosis based on 
comparing the subject's test score with normative data, providing a percentile score of an individual 
relative to his or her age-matched normal group. Furthermore, a clinician can distinguish subjects with a 
normal sense of smell ("normosmia") from those with different levels of reduction ("mild, moderate and 
severe microsmia") or loss ("anosmia") (Juniper et al., 2004). 
 
DISEASE-SPECIFIC TESTS AND ASSESSMENTS 
Computed tomography of the sinuses should be performed at Day 1 (Week 0) and at Day 113 (Week 
16/EOT). Day 1 CT must be collected prior to dosing on Day 1. If necessary, the Day 1 CT can be collected 
prior to Day 1, however all efforts should be made to conduct CT after subject screening labs have been 
reviewed and it is determined subject is likely eligible for the study. Any CTs collected within 3 months 
of Visit 2 (Week 0) can be used for in lieu of a new CT at Day 1.  
For both Lund-Mackay scores and 3D volumetric measurement of the maxillary sinus, the same 
acquisitions (sequences) will be used for centralized imaging data assessments and scoring by an 
independent reviewer. Central reading of Visit 2 will be used for comparison with EOT. The final results 
of central reading will be made available after the study. Details on CTs will be available in a separate 
operational manual provided to the sites.  
8.1.5.1 LUND-MACKAY SCORE 
Lund-Mackay system is based on localization with points given for degree of opacification:  
0 = normal, 1 = partial opacification, 2 = total opacification. These points are then applied to the 
maxillary, anterior ethmoid, posterior ethmoid, sphenoid, frontal sinus on each side. The osteomeatal 


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complex is graded as 0 = not occluded, or 2 = occluded deriving a maximum score of 12 per side (Lund 
and MacKay, 1993). This scoring system has been validated in several studies (Metson et al., 1997; 
Oluwole et al., 1996). For patients in whom the osteomeatal complex (OC) is missing (because of a 
previous surgery) the reader should consider the location of the former OC and provide a scoring (as if 
the OC was there). 
8.1.5.2 3-DIMENSIONAL VOLUMETRIC MEASUREMENT OF THE MAXILLARY SINUS 
This method is used to calculate: (Deeb et al., 2011) 
 
the volume of the air (mL) 
 
the volume of mucosa (mL) 
 
% occupied by disease 
 
thickness of lateral wall 
For the analysis, central reading before V2 will be used for comparison with EOT reading. The sites will 
remove subject-identifying information from the imaging data header prior to sending the imaging data 
to the central reader. The percent change in opacification from baseline to EOT will be calculated. 
 
POLYP BIOPSIES 
Study centers with the capability to perform a nasal polyp biopsy and with consent of the subject, will 
collect samples as noted below. 
A baseline biopsy will be obtained at Day 1 (Week 0) of the study (before injection of the study drug). 
After randomization, another biopsy of nasal polyp tissue will be obtained at Week 16. 
The complete details on tissue collection and processing will be provided separately. Briefly, the 
biopsied polyp tissue will be weighed (mg) and then cut into cubes of approximately 0.5 cm in each 
dimension. All but one cube will be individually placed into labeled cryotubes and immediately frozen 
with liquid nitrogen, and then maintained at -70C or colder until shipped on dry ice to a central storage 
site or laboratory. Nasal polyp tissue will be subsequently assessed for various biomarkers of 
inflammation and disease process or response. Any remaining tissue will be discarded within 5 years of 
the completion of the last visit for the last patient in the study. Additional information on collection, 
processing, storage, and shipment of samples is located in the laboratory manual. 
 
WHOLE BLOOD SAMPLING AND DNA SAMPLING 
For those subjects who consent to whole blood RNA and DNA sampling, blood samples will be collected 
at timepoints as indicated in the SoA (Section 1.3) and sent to the central laboratory according to 
laboratory procedures. Genomic analysis will be performed using a validated assay method under the 
supervision of the Sponsor. Only samples which are within the window of sample stability will be 
analyzed. 


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QUALITY OF LIFE ASSESSMENTS 
8.1.8.1 SHORT FORM 36 HEALTH SURVEY (SF-36) 
The SF-36 is a generic questionnaire measuring general health status (QoL) in the last 4 weeks before 
completing the questionnaire. The SF-36 is a 36-item questionnaire that measures 8 multi-item 
dimensions of health: physical functioning (10 items) social functioning (2 items) role limitations due to 
physical problems (4 items), role limitations due to emotional problems (3 items), mental health 
(5 items), energy/vitality (4 items), pain (2 items), and general health perception (5 items). 
For each dimension, item scores are coded, summed, and transformed on to a scale from 0 
(worst possible health state measured by the questionnaire) to 100 (best possible health state). 
Two standardized summary scores can also be calculated from the SF-36; the physical component 
summary and the mental health component summary. The time for completion is 5 to 10 minutes. 
The SF-36 will be completed as indicated in the SoA (see Section 1.3) and is located on the clinical tablet. 
A sample SF-36 is provided in Appendix F. 
8.1.8.2 EUROPEAN QOL SCALE (EQ-5D) 
The EQ-5D is a standardized health-related QoL questionnaire developed by the EuroQol Group in order 
to provide a simple, generic measure of health for clinical and economic appraisal and inter-disease 
comparisons. The EQ-5D is designed for self-completion by subjects and takes only a few minutes to 
complete. 
The EQ-5D was used to study the impact on QoL for filgrastim administration in CRS patients, the scores 
improved though they were not statistically significant (Van Agthoven et al., 2001).  
The EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, 
pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problem, some problems, 
severe problems. The EQ VAS records the respondent’s self-rated health on a vertical visual analogue 
scale. The EQ VAS ‘thermometer’ has endpoints of 100 (Best imaginable health state) at the top and 0 
(Worst imaginable health state) at the bottom. 
The EQ-5D will be completed as indicated in the SoA (see Section 1.3) and is located on the clinical 
tablet. 
A sample EQ-5D is provided in Appendix G. 
8.1.8.3 7-ITEM ASTHMA CONTROL QUESTIONNAIRE (ACQ-7) 
The ACQ-7 will be used in this study to assess the asthma symptoms (nocturnal waking, symptom on 
waking, activity limitation, and shortness of breath, wheezing, and short acting β agonist [SABA] usage) 
and FEV1 measurement in subjects with active asthma disease. Subject will be asked to recall their 


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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. The 
subject should complete the ACQ 7 at the time points indicated in the SoA (see Section 1.3) and is 
located on the clinical tablet. 
A sample ACQ-7 is provided in Appendix H. 
8.1.8.4 EXCLUDED MEDICATIONS PRIOR TO LUNG FUNCTION ASSESSMENTS 
For subjects taking asthma medications, asthma medications should be withheld prior to lung function 
tests on study visit days: 
• 
Short acting bronchodilators (eg, albuterol [salbutamol] or ipratropium) should be withheld for 
at least 6 hours before spirometry. 
 
• 
Twice daily long-acting bronchodilator (LABA or long-acting muscarinic antagonist [LAMA] 
containing therapies) should be withheld for 12 hours and once daily long-acting bronchodilator 
(LABA or LAMA containing therapies) for > 12 hours before spirometry. 
 
• 
Leukotriene receptor antagonists (LTRA) should be restricted for > 12 hours. 
 
• 
Twice daily theophylline should be withheld for at least 12 hours and once daily theophylline for 
> 12 hours before spirometry.  
 
• 
If a subject has taken rescue SABA within 4 hours of the planned spirometry study center visit, 
they should either: 
o Remain at the study center until the 4-hour withholding time has been reached OR  
o Return on the following day (or within study window) for lung function assessments. 
8.1.8.5 NASAL POLYP RELATED RESOURCE USE QUESTIONNAIRE 
The Nasal Polyp Related Resource Use Questionnaire is a questionnaire of health care resource 
utilization for nasal polyposis (eg, specialist visits, emergency care visits, sick leaves, days off) will be 
completed as indicated in the SoA (see Section 1.3) and is located on the clinical tablet. 
A sample Nasal Polyp Related Resource Use Questionnaire is provided in Appendix I. 
8.1.8.6 SPIROMETRY (FEV1 MEASUREMENT) 
Spirometry will be performed on all subjects at the time points indicated in the SoA (see Section 1.3) and 
according to the ATS/ERS guidelines. Sites should perform spirometry using the spirometer provided by 
ERT. The spirometer should be calibrated per ATS/ERS guidelines prior to the start of the lung function 


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assessment on each study center visit day. The spirometer should be set to use the Global Lung Function 
Initiative reference equations, results will be over read by ERT.  
Pre-bronchodilator spirometry will be performed after appropriate bronchodilator withholding period in 
the morning. Patients with active asthma should withhold their usual asthma therapy prior to lung 
function tests on the study visit days spirometry is performed. See Section 8.1.8.4 for prohibited 
medications prior to lung function assessments. 
Subjects should have spirometry performed at approximately the same time on each study center visit 
day. Forced expiratory maneuvers should be performed with the patient seated in an upright position. 
If this is not comfortable for the patient, standing is permitted; however, the same position should be 
used by the patient for each forced expiratory maneuver from Screening through EOS visit. Three 
acceptable maneuvers should be obtained for each test. Additional details are provided in the lung 
function testing manual provided by the vendor. 
8.1.8.7 VISUAL ANALOGUE SCALE  
The VAS for rhinosinusitis is used to evaluate the total severity and is validated in adult CRS (Fokkens et 
al., 2012). 
The subject is asked to indicate on a VAS the answer to the question: “How troublesome are your 
symptoms of rhinosinusitis?“ The VAS ranks from 0 (Not troublesome) to 10 (Worst thinkable 
troublesome).  
The disease can be divided into mild, moderate, and severe based on total severity VAS score (0 to 10 
cm): 
MILD = VAS 0-3 
MODERATE = VAS >3-7 
SEVERE = VAS >7-10  
The VAS will be used as indicated in the SoA (see Section 1.3). 
The VAS scale will be collected weekly in the eDiary. On Day 1, the eDiary must be provided to the 
subject prior to dosing and the subject must complete the VAS scale before receiving study drug. 
A sample VAS is provided in Appendix J. 
8.2 
SAFETY AND OTHER ASSESSMENTS 
Unscheduled safety assessments may be performed at any time during the study to assess any 
perceived safety concerns.  


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CLINICAL LABORATORY DATA 
Table 1 lists the clinical laboratory tests to be assessed in this study. As outlined in the SoA (Section 1.3), 
non-fasting samples for serum chemistry, hematology, pregnancy test, serum antibodies and urinalysis 
will be collected at designated study timepoints. Blood and urine specimens will be collected using 
applicable safety precautions and processed according to clinical laboratory instructions.  
Table 1. 
Clinical Laboratory Tests 
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 
ALT
Creatinine
Albumin
Gamma glutamyl transferase 
Alkaline phosphatase 
Glucose
AST
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
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) 
Serum pregnancy 
Human chorionic gonadotropin pregnancy test (as needed for WOCBP)
Urine pregnancy 
Urine pregnancy dipstick (prior to study treatment administration)
 


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Laboratory 
Assessments 
Parameters
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 antibodies
 
HIV antibodies (HIV 1 and 2)
Tuberculosis B (TB) 
test 
Subjects with an indeterminate QuantiFERON® TB Gold result at Screening 
will be allowed one retest. purified protein derivative (PPD) test is permitted 
as repeat test in subjects who have never had a bacille Calmette-Guerin (BCG) 
vaccination. 
The results of each local test must be entered into the eCRF. 
Abbreviations: ADA = anti-drug antibody; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
eCRF = electronic case report form, HIV = Human Immunodeficiency Virus, MDMA = 
Methylenedioxymethamphetamine, PK = Pharmacokinetics and TCA=Tricyclic anti-depressants. 
NOTES: Please see SoA (see Section 1.3) for laboratory tests time points. PK and ADA samples will be collected 
as detailed in the SoA (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. 
 
It is the Investigator’s responsibility to review the results of all laboratory tests as they become 
available. For each laboratory test result outside the reference range, the Investigator must 
ascertain if the abnormal lab result is a clinically significant result for that individual subject. 
Likewise, if laboratory tests are taken at follow-up visits, the Investigator must ascertain if this is 
an abnormal and clinically significant change posttreatment for that individual subject. The 
Investigator may repeat the laboratory test or request additional tests to verify the results of the 
original laboratory test.  
 
 
The Investigator or qualified designee must sign and date all written laboratory results 
(chemistry, hematology plus pregnancy test, and urinalysis) and note Not Clinically Significant 
(NCS) or Clinically Significant (CS) for each out-of-range laboratory value. If a laboratory value is 


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determined to be a CS result for that subject, this may be considered an AE. Record any clinically 
relevant changes occurring during the study in the AE section of the eCRF. The laboratory 
reports must be filed with the source documents. Clinically significant abnormal laboratory 
findings are those that are not associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the subject’s condition.  
 
 
A central laboratory will be used to perform all laboratory tests except urine pregnancy dipstick 
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 needs to 
make an immediate decision for any safety concerns based on laboratory results.  
 
 
All laboratory tests with values considered CS 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 CS 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 notified. 
 
 
All protocol-required laboratory assessments, as defined above, must be conducted in 
accordance with the Laboratory Manual and the SoA (see Section 1.3). 
 
 
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 CS 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. 
 
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 SPT will 
be performed to confirm. If any result is positive prior to IP administration, the subject will not be 
allowed to participate. Follicle stimulating hormone may be used to confirm menopausal status in 
female subjects as needed. Refer to Appendix B for further information. 


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PHYSICAL EXAMINATION 
A complete physical examination will include examination of the following parameters and body 
systems: skin, neck (including thyroid), head, eyes, ears, nose, throat, heart, lungs, abdomen, back, 
lymph nodes, extremities, vascular and neurological. If indicated based on medical history and/or 
symptoms, rectal, external genitalia, breast, and/or pelvic exams may be performed. 
At Screening, a complete physical examination will be performed. At baseline and posttreatment visits, 
the physical examination may be abbreviated, as deemed medically appropriate at the discretion of the 
Investigator. 
Significant physical examination findings which meet the definition of an adverse event will be recorded 
on the AE page posttreatment; significant findings that are present prior to IP administration are 
included on the medical history page. 
 
VITAL SIGNS 
Vital signs captured include body temperature, respiration rate, sitting radial pulse rate, and sitting 
systolic and diastolic BPs. Vitals should be collected before blood sampling and before injection of study 
drug at each visit where administered (see Section 1.3). Blood pressure is collected after 15 minutes of 
rest in a seated position. 
 
12-LEAD ECG 
A single, standard, supine 12-lead ECG will be obtained after a subject has rested quietly for at least 
10 minutes, using equipment provided from the central reader. The ECG is to be repeated up to 2 times 
if the result is abnormal, as clinically appropriate. ECGs must be collected on the ECG machine provided 
by ERT. ECG data will be submitted and reviewed by the central reader. The ECG will also be reviewed by 
the investigator or an authorized representative who is experienced in the evaluation of ECGs and 
assessed for clinical significance. 
Instructions and guidelines for collection (eg, equipment), transmission, and archiving of ECG data will 
be provided in the ECG Manual. A 12-lead ECG will be obtained using a validated ECG machine that 
automatically calculates the HR and measures pulse rate, QRS, QT, and QTc intervals. 
 
INJECTION SITE EVALUATION 
Subjects must remain onsite for 2 hours postdose for observation at the Day 1 (Week 0) visit. Injection 
sites will be evaluated to determine if there are any injection site reactions to the IP. Any injection-
related pain, redness, bruising or swelling, etc., will be reported as an AE. 


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8.3 
PHARMACOKINETICS 
Whole blood samples will be collected for measurement of serum concentrations of etokimab at time 
points as specified in the SoA (see Section 1.3). Instructions for the collection and handling of biological 
samples will be provided by BARC central laboratory and analyzed by Q2 Solutions. 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 for a primary PK sample and 1 
for a back-up PK sample). 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. The time points for PK sample 
collection is given in Appendix D. 
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 the separate pharmacogenomics 
consent has been signed. 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 IRB 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 a secondary objective. 
8.4 
BIOMARKERS 
No specific or exploratory biomarkers will be collected or analyzed in this study. 
8.5 
IMMUNOGENICITY 
Antibodies to etokimab will be evaluated in serum samples collected from all etokimab-dosed 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 


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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 tested in a multi-tiered approach. A validated screening assay for antibodies 
binding to etokimab will be initially used to assess serum samples. Samples that are determined putative 
positive in the screening assay will then be subjected to a confirmatory assay to demonstrate that 
antibodies are specific to etokimab. Samples that are identified as positive in the confirmatory assay will 
be further characterized in a validated titer assay 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 C.  
Samples that are confirmed positive for antibodies binding to etokimab with a titer greater than the 
minimum required dilution of the validated assay may be further characterized and/or evaluated for 
their ability to neutralize the activity of the study treatment using a validated cell based neutralizing 
antibody assay method. 
8.6 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
 
DEFINITION OF ADVERSE EVENTS 
For this protocol, an AE is any untoward medical occurrence (eg, sign, symptom, disease, syndrome, 
intercurrent illness, CS abnormal laboratory finding, injury, or accident) that emerges or worsens 
following administration of the study drug and until the EOS participation. The untoward medical 
occurrence may not necessarily have a causal relationship to the administration of the IP. An AE can 
therefore be any unfavorable and/or unintended sign (including a CS abnormal laboratory result), 
symptom, or disease temporally associated with the use of a medicinal (investigational) product, 
whether or not related to the medicinal (investigational) product. A treatment-emergent AE is one that 
occurs after any exposure to treatment. 
A pre-existing condition is one that is present prior to the start of the study and is to be reported as part 
of the subject’s medical history. It should be reported as an AE only if the frequency, intensity, or the 
character of the condition worsens during the study. 
Any CS change in the study safety evaluations, (eg, vital signs, physical/neurological examinations, etc.) 
post injection must be reported as an AE. 
For each laboratory test result outside the reference range, the Investigator must ascertain if the 
abnormal lab result is a CS result for that individual subject. This determination, however, does not 
necessarily need to be made the first time an abnormal value is observed; the Investigator may repeat 


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the laboratory test or request additional tests to verify the results of the original laboratory test. If a 
laboratory value is determined to be a CS result for a subject, this may be considered an AE. 
 
DEFINITION OF SERIOUS ADVERSE EVENTS  
A SAE includes any event that results in any of the following outcomes: 
• 
Death 
• 
Life-threatening (ie, the subject was, in the opinion of the Investigator, at immediate risk of death 
from the event as it occurred. It does not apply to an AE that hypothetically might have caused 
death if it were more severe.) 
• 
Persistent or significant disability/incapacity or substantial disruption of the subject’s ability to 
carry out normal life functions 
• 
Requires in-patient hospitalization or prolongs hospitalization (ie, a prolonged hospitalization 
beyond the expected length of stay; hospitalizations for elective medical/surgical procedures, 
scheduled treatments, or routine check-ups are not SAEs by this criterion) 
• 
Congenital anomaly/birth defect (ie, an adverse outcome in a child or fetus of a subject exposed to 
the molecule or IP before conception or during pregnancy) 
• 
Does not meet any of the above serious criteria but based upon appropriate medical judgment may 
jeopardize the subject or may require medical or surgical intervention to prevent one of the 
outcomes listed above (ie, is a significant or important medical event) 
 
CLASSIFICATION OF AN ADVERSE EVENT 
8.6.3.1 SEVERITY OF EVENT 
The Investigator is responsible for evaluating all AEs and determining the severity of the event. Severity 
will be categorized as mild, moderate, or severe according to the following definitions: 
• 
Mild: Event may be noticeable to subject; does not influence daily activities; usually does not 
require intervention. 
 
• 
Moderate: Event may be of sufficient severity to make a subject uncomfortable; performance of 
daily activities may be influenced; intervention may be needed. 
 
• 
Severe: Event may cause severe discomfort; usually interferes with daily activities; subject may not 
be able to continue in the study; treatment or other intervention usually needed. 
8.6.3.2 RELATIONSHIP TO STUDY INTERVENTION 
 
Relationship of an AE to IP will be assessed as follows: 
• 
Definite: There is a clinically plausible time sequence between the onset of the AE and the 
administration of IP when the event responds to withdrawal of IP and recurs with re-
administration of IP. 


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• 
Related: There is a clinically plausible time sequence between the onset of the AE and the 
administration of IP; the AE is unlikely to be caused by the concurrent/underlying illness, other 
drugs or procedures. 
 
• 
Possibly Related: There may or may not be a clinically plausible time sequence between the 
onset of the AE and the administration of IP and a cause cannot be ruled out. 
 
• 
Unrelated: There is not a temporal or causal relationship to IP administration. 
8.6.3.3 EXPECTEDNESS  
The PI/designee will be responsible for determining whether an AE is expected or unexpected. An 
unexpected AE is one not identified in nature, severity, or frequency in the current protocol or IB. 
 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
SAEs that are identified on the last scheduled contact must be recorded on the AE eCRF page and 
reported to the Sponsor or the authorized representative according to the reporting procedures 
outlined in Section 8.6.6. This may include unresolved previously reported SAEs, or new SAEs. The 
Investigator should follow these SAEs until the events are resolved, or the subject is lost to follow-up. 
The Investigator should continue to report any significant follow-up information to the Sponsor or the 
authorized representative, and the IRB, up to the point the event has been resolved. Resolution means 
the subject has returned to the baseline state of health, or the Investigator does not expect any further 
improvement or worsening of the subject’s condition. 
Any new SAEs reported by the subject to the Investigator that occur after the last scheduled contact and 
are determined by the Investigator to be reasonably associated with the administration of IP should be 
reported to the Sponsor or the authorized representative, and the IRB, as required. 
8.6.5 ADVERSE EVENT REPORTING  
The Investigator will assess subjects at each study visit and posttreatment per protocol for the 
occurrence of AEs. In order to avoid bias in eliciting AEs, subjects should be asked the following 
nonleading question: “How have you felt since your last visit?” All AEs (serious and non-serious) 
reported by the subject must be recorded on the source documents and eCRFs. 
Adverse Events will be recorded beginning from the time of consent. Adverse Events that occur prior to 
dosing will also be noted in the medical history. 
8.6.6 SERIOUS ADVERSE EVENT REPORTING  
The Investigator will report any SAE to th
Pharmacovigilance within 24 hours 
of being made aware of it, whether or not considered study intervention related, including those listed 


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in the protocol or IB and must include an assessment of whether there is a reasonable possibility that 
the study intervention caused the event. Study endpoints that are serious adverse events (eg, all-cause 
mortality) must be reported in accordance with the protocol unless there is evidence suggesting a causal 
relationship between the study intervention and the event (eg, death from anaphylaxis). In that case, 
the Investigator must report the event to the Sponsor in the shortest possible time. 
All SAEs will be followed until satisfactory resolution or until the study center Investigator deems the 
event to be chronic or the participant is stable. Other supporting documentation of the event may be 
requested by the local or centralized IRB and study Sponsor and should be provided as soon as possible. 
The study Sponsor will be responsible for notifying the Food and Drug Administration (FDA) of any 
unexpected fatal or life-threatening suspected adverse reaction as soon as possible, but in no case later 
than 7 calendar days after the Sponsor's initial receipt of the information and in compliance with the 15 
day requirement. In addition, the Sponsor must notify FDA and all participating Investigators in an IND 
safety report of potential serious risks, from clinical trials or any other source, as soon as possible, but in 
no case later than 15 calendar days after the Sponsor determines that the information qualifies for 
reporting. 
8.6.7 REPORTING EVENTS 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. 
8.6.8 EVENTS OF SPECIAL INTEREST  
Not applicable. 
8.6.9 REPORTING OF PREGNANCY  
During the trial, all WOCBP should be instructed to contact the Investigator immediately (within 
24 hours) if they suspect they might be pregnant (eg, missed or late menstrual cycle). The Investigator 
must immediately notify 
Pharmacovigilance of any female subject who 
becomes pregnant any time during study participation, record the information on the Pregnancy 
Notification Form and send the form to the authorized representative. The study center will be asked to 
follow-up with the subject periodically during the pregnancy for ongoing health and safety information 
through term, as applicable. Subjects who become pregnant during the study will be discontinued. 
In the case of male subject’s female partner becoming pregnant while the male subject is in this study, 
the Investigator should attempt to collect pregnancy information on the male subject’s female partner. 
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 


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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. 
 
8.7 
UNANTICIPATED PROBLEMS 
 
8.7.1 DEFINITION OF UNANTICIPATED PROBLEMS 
The Office for Human Research Protections (OHRP) considers unanticipated problems 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. 
 
8.7.2  UNANTICIPATED PROBLEM REPORTING  
 
The Investigator will report unanticipated problems (UPs) to the reviewing IRB and to the Data 
Coordinating Center (DCC)/lead PI. The UP report will include the following information: 
 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB 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 SAEs will be reported to the IRB and to the DCC/study Sponsor within 24 hours of 
the Investigator becoming aware of the event. 
• 
Any other UP will be reported to the IRB and to the DCC/study Sponsor within <7 days of the 
Investigator becoming aware of the problem.  
 


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• 
All UPs should be reported to appropriate institutional officials (as required by an institution’s 
written reporting procedures), and the supporting agency head (or designee) within 14 days of 
the IRB’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. 


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9 
STATISTICAL CONSIDERATIONS  
 
9.1 
STATISTICAL HYPOTHESES 
The primary objective of this study is to evaluate the efficacy of etokimab compared to placebo in the 
treatment of subjects with CRSwNP following a 16-week treatment period (change from baseline using 
co-primary endpoints). The hypotheses for the co-primary efficacy endpoints are delineated below. 
Co-Primary Efficacy Endpoints:  
Statistical hypotheses associated with the co-primary efficacy endpoints are as follows: 
 
Treatment of adults diagnosed with CRSwNP using etokimab will result in a significantly greater 
reduction of Week 16 NPS from baseline when compared to placebo, and 
 
 
Treatment of adults diagnosed with CRSwNP using etokimab will result in a significantly greater 
reduction of Week 16 SNOT-22 score from baseline when compared to placebo 
 
9.2 
SAMPLE SIZE DETERMINATION 
Sample size estimates were calculated based on the following assumptions: 
 
Overall alpha=0.05 
 
Co-primary endpoints 
 
Hierarchical testing of the 2 active treatment arms versus placebo 
 
At least 85% power to detect a clinically meaningful difference between etokimab and placebo 
Based on data from similar trials conducted in adult subjects with CRSwNP, a difference in NPS of 1.3 
between the etokimab change from Baseline to Week 16 and the placebo group change from Baseline 
to Week 16 will be clinically meaningful (Bachert et al. 2016). Assuming a standard deviation (SD) of 1.5, 
and a significance level of 5%, a sample size of n=27 for each treatment arm will provide approximately 
87% power to detect the stipulated difference. In order to account for the dilution of treatment effect 
due to 18% dropouts and missing data, approximately 33 subjects are planned to be randomized equally 
to each of the 3 treatment arms. 
The second co-primary endpoint is SNOT-22 total score. In a trial of adults with CRSwNP, the difference 
in mean change from Baseline to Week 16 between active and placebo was 18.1. Assuming a common 
standard deviation of 19.2, and 2-sided significance level of 5%, the sample size of 27 subjects provides 
92% power to detect the stipulated treatment difference. Hence, adjusting for 18% dropouts and 
missing data, n=33 subjects will provide >85% desired power to detect a clinically meaningful difference 
in this endpoint between each active arm and placebo. 


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9.3 
ANALYSIS SETS 
The analysis sets for evaluating the efficacy, safety, and pharmacokinetics of etokimab are defined in 
Table 2. 
Table 2. 
Analysis Sets 
Analysis Set 
Description 
Safety Analysis Set 
The safety analysis set will include all randomized subjects who 
receive 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 
The full analysis set (FAS) will include all randomized subjects who 
receive 1 dose of etokimab or placebo and have baseline and at least 
1 post baseline NPS and/or SNOT-22 scores up to Week 16. The full 
analysis set will be used for all efficacy analyses. Subjects will be 
analyzed as randomized. 
PP Analysis Set 
The PP (Per Protocol) analysis set will include all subjects in the FAS 
analysis set who do not have major protocol violations that would 
affect the evaluation of the primary efficacy endpoints. 
PK Analysis Set 
The PK analysis set will include all 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. 
Abbreviations: FAS = Full analysis set, PP = Per protocol, PK = Pharmacokinetics. 
 
9.4 
STATISTICAL ANALYSES 
 
9.4.1 GENERAL APPROACH 
The final statistical analysis will be performed after all reportable data have been collected, queries 
resolved, and the database locked. The Statistical Analysis Plan (SAP) will be developed and finalized 
before the database lock and will provide full details of all statistical analyses, including procedures for 
accounting for missing, unused, and spurious data. This section summarizes the planned statistical 
analyses of the primary and secondary endpoints. 
The statistical analyses will be performed using statistical analysis system (SAS®) version 9.4 or higher if 
available. All details regarding the statistical analyses and the preparation of tables, listings and figures 
will be described in the SAP.  
In general, continuous variables will be summarized with descriptive statistics including n, mean, SD, 
median, minimum, and maximum. Categorical variables will be summarized by the number and 
percentage of subjects in the relevant analysis set and treatment group falling into each category. 


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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. 
Unless otherwise specified, all formal statistical tests will be 2-sided at the 5% significance level. Point 
estimates will be accompanied with 2-sided 95% confidence intervals (CIs), where applicable. In the case 
of normality assumption violations, appropriate nonparametric methods will be used for analysis. 
All data will be presented in by subject and treatment listings. 
9.4.2 EFFICACY ANALYSES 
A summary of the efficacy endpoints (co-primary, secondary, and exploratory) and the statistical 
methods that will be used to analyze these endpoints is provided in Table 3. The co-primary efficacy 
analyses will be performed on the FAS. Additionally, the co-primary efficacy analyses will be repeated on 
the PP Analysis set. 
Table 3. 
Efficacy Analyses 
Endpoint 
Statistical Analysis Methods 
Co-Primary Efficacy: 
Change from baseline to Week 16 in bilateral 
endoscopic NPS  
General linear mixed effects model with repeated 
measures (MMRM) including the change from 
baseline in NPS as dependent variable; treatment 
group, stratification factor, time (Weeks 4, 8, 12, 
and 16), treatment by stratification factor, and 
treatment by time interaction as fixed effect 
factors; baseline NPS score as covariate; and 
subject as random effect. 
Change from baseline to Week 16 in 
SNOT-22 scores  
MMRM as above for NPS will be applied for SNOT-
22 score. 
 
Secondary Efficacy: 
Time to first response (1 point reduction in 
NPS) 
Log rank test to compare the time to first response 
for the treatments 
Responder analysis: response defined as a 
reduction of ≥1point from baseline to Week 16 
in NPS 
Logistic regression modeling the response as 
dependent variable, treatment, baseline NPS, and 
asthma comorbidity as covariates 
Responder analysis response defined as a 
reduction of ≥12 points from baseline to Week 
16 in SNOT-22  
Logistic regression modeling the response as 
dependent variable, treatment, baseline SNOT-22 
score, and asthma comorbidity as covariates 
Change from baseline to Week 16 in UPSIT 
MMRM proposed for NPS will be applied for UPSIT. 


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Endpoint 
Statistical Analysis Methods 
Exploratory Efficacy 
Change from baseline to Week 16 in sinus 
opacification as assessed by CT scan using 
Lund-Mackay score 
Analysis of covariance (ANCOVA) modeling the 
change from baseline in Lund-MacKay score at 
Week 16 as dependent variable; baseline Lund-
MacKay score as covariate; and treatment as a 
factor 
Change from baseline to Week 16 in AM NPIF 
MMRM, including the change from baseline in AM 
NPIF as the dependent variable; treatment group, 
stratification factor, time (Weeks 4, 8, 12, and 16), 
treatment by stratification factor, and treatment by 
time interaction as fixed effect factors; baseline AM 
NPIF score as covariate; and subject as a random 
effect 
Change from baseline to Week 16 in PM NPIF 
MMRM, including the change from baseline in PM 
NPIF as the dependent variable; treatment group, 
stratification factor, time (Weeks 4, 8, 12, and 16), 
treatment by stratification factor, and treatment by 
time interaction as fixed effect factors; baseline PM 
NPIF score as covariate; and subject as a random 
effect 
Change from baseline to Week 16 in bilateral 
endoscopic NPS in subjects with comorbid 
asthma 
MMRM including the change from baseline in NPS 
as dependent variable; treatment group, time 
(Weeks 4, 8, 12, and 16), and treatment by time 
interaction as fixed effect factors; baseline NPS 
score as covariate; and subject as random effect 
Change from baseline to Week 16 in SNOT-22 
in subjects with comorbid asthma 
MMRM as above for NPS will be applied for SNOT-
22 score 
Change from baseline to Week 16 in the 
percent of 3-dimentional volumetric maxillary 
sinus occupied by disease (%VMSOD) as 
assessed by CT scan 
Analysis of covariance (ANCOVA) modeling the 
change from baseline in %VMSOD score at Week 16 
as dependent variable; baseline %VMSOD score as 
covariate; and treatment as a factor 
Change from baseline to Week 16 in SF-36 
physical component summary (PCS) 
MMRM including the change from baseline in SF-36 
PCS score as dependent variable; treatment group, 
stratification factor, time (Weeks 4, 8, 12, and 16), 
treatment by stratification factor, and treatment by 
time interaction as fixed effect factors; baseline SF-
36 PCS score as covariate; and subject as a random 
effect 
Change from baseline to Week 16 in SF-36 
mental component summary (MCS) 
MMRM as above for SF-36 PCS will be applied for 
SF-36 MCS 


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Endpoint 
Statistical Analysis Methods 
Change from baseline to Week 16 in EQ-5D 
index score 
MMRM including the change from baseline in EQ-
5D index score as dependent variable; treatment 
group, stratification factor, time (Weeks 4, 8, 12, 
and 16), treatment by stratification factor, and 
treatment by time interaction as fixed effect 
factors; baseline EQ-5D index score as covariate; 
and subject as a random effect 
Change from baseline to Month 4 in VAS 
MMRM including the change from baseline in VAS 
score as dependent variable; treatment group, 
stratification factor, time (Months 1, 2, 3, and 4), 
treatment by stratification factor, and treatment by 
time interaction as fixed effect factors; baseline 
VAS score as covariate; and subject as a random 
effect 
Number of nocturnal awakenings (in subgroup 
with comorbid asthma) 
Cochran Mantel-Hanszel statistics testing the row 
mean scores differ between treatment groups at 
each visit 
Change from baseline to Week 16 in FEV1 
(overall and in subgroup with asthma) 
MMRM including the change from baseline in FEV1 
score as dependent variable; treatment group, 
stratification factor, time (Weeks 4, 8, 12, and 16), 
treatment by stratification factor, and treatment by 
time interaction as fixed effect factors; baseline 
FEV1 score as covariate; and subject as a random 
effect 
Change from baseline to Week 16 in % 
predicted FEV1 (overall and in subgroup with 
asthma) 
MMRM including the change from baseline in 
%predicted FEV1 score as dependent variable; 
treatment group, stratification factor, time (Weeks 
4, 8, 12, and 16), treatment by stratification factor, 
and treatment by time interaction as fixed effect 
factors; baseline %predicted FEV1 score as 
covariate; and subject as a random effect 
Change from baseline to Week 16 in ACQ-7 
total score in subjects with comorbid asthma 
MMRM including the change from baseline in ACQ-
7 score (mean of the responses to all 7 questions) 
as dependent variable; treatment group, time 
(Weeks 4, 8, 12, and 16), and treatment by time 
interaction as fixed effect factors; baseline ACQ-7 
score as covariate; and subject as a random effect 


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Endpoint 
Statistical Analysis Methods 
Change from baseline to Week 16 in blood 
eosinophil count  
MMRM modeling the change from baseline in 
blood eosinophil count at Week 16 as dependent 
variable; treatment group, stratification factor, 
time (Weeks 4, 8, 12, and 16), treatment by 
stratification factor, and treatment by time 
interaction as fixed effect factors; baseline blood 
eosinophil count as covariate; and subject as a 
random effect 
Time to study treatment discontinuation 
Log rank test to compare the time to study 
treatment discontinuation  
Incidence of treatment discontinuation due to 
need for OCS or nasal polyp surgery 
Fisher’s exact test comparing the proportion of 
subjects with treatment discontinuation due to 
need for OCS or nasal polyp surgery 
Nasal Polyp Resource Questionnaire at each 
visit 
Descriptive statistics (number, percentage) to be 
provided per questionnaire item per visit 
Abbreviations: ANCOVA = analysis of covariance, CT = computed tomography, EOT = end of treatment, 
EQ-5D = EuroQoL-5D Scale, MMRM = mixed effects model with repeated measures, MPS = mental component 
summary, NPIF = nasal peak inspiratory flow, NPS = Nasal Polyp Score, PCS = physical component summary, SF-
36 = Short Form 36 Health Survey, SNOT-22 = Sino-Nasal Outcome Test, UPSIT = University of Pennsylvania Smell 
Identification Test, VMSOD = volumetric maxillary sinus occupied by disease 
Statistical significance for the co-primary efficacy endpoints will be declared if both p-values for the tests 
of the individual hypotheses, as described below, are < 0.05. 
9.4.2.1.1 FIRST CO-PRIMARY ENDPOINT 
The first co-primary endpoint is the change from Baseline to Week 16 in bilateral endoscopic NPS while 
on treatment.  
Baseline endoscopic NPS is the sum of the left and right nasal polyposis score at the randomization visit. 
The NPS is also measured every 4 weeks during treatment and at end of treatment (Week 16). A general 
linear MMRM using change from baseline in NPS scores at Weeks 4, 8, 12, and 16 as response, 
stratification factor, treatment group as fixed effect (3 levels), treatment by stratification factor, and 
treatment by time interaction as fixed effects, Baseline (Day 1) NPS score as fixed continuous covariate, 
and subject as a random effect, will be used to obtain least squares means at EOT, to compare the 
etokimab treatment arms with the placebo arm.  
No imputation of data for missing data due to treatment discontinuation will be implemented in the 
primary analysis. Comparison of the treatment arms will be based on the Week 16 least squares means 
of the treatment arms. An unstructured covariance matrix will be assumed and estimated in order to 
obtain associated standard errors for least squares means and to carry out the treatment comparisons. 
In case of convergence problems for the maximum likelihood estimates, other covariance structures 
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Comparison of each treatment arm with placebo will be based on the Week 16 least squares means 
obtained from the MMRM, where missing data due to treatment discontinuation are regarded as 
missing at random. Testing will be conducted in a hierarchical manner such that the comparison of the 
etokimab every 4 weeks treatment arm versus placebo will be conducted first. If the results of the 
comparison of the etokimab every 4 weeks treatment arm versus placebo are statistically significant, the 
etokimab every 8 weeks treatment arm will be compared to placebo. The p-value for the comparison 
will be obtained and compared to the significance level of 5%. An associated 2-sided 95% confidence 
interval will be obtained for the active minus placebo change from baseline to week 16 in the NPS for 
each treatment arm tested. No further adjustment will be made for testing each dosing regimen with 
placebo. 
In order to assess the impact of missing data due to treatment discontinuation, a sensitivity analysis may 
be performed where their data after dropout will be imputed using multiple imputation and the 
statistical analysis using MMRM will be repeated. Another sensitivity analysis may be performed where 
observed values of the NPS score obtained during study but after treatment discontinuation, if available, 
will be used. The MMRM model will be utilized where the treatment discontinuations are regarded as 
not missing at random (NMAR). Full details will be specified in the SAP. 
9.4.2.1.2 SECOND CO-PRIMARY ENDPOINT 
The second co-primary endpoint is the change from Baseline to Week 16 in SNOT-22 scores.  
An MMRM as described above for NPS, using the Baseline (Day 1) SNOT-22 score as fixed covariate, will 
be utilized for the SNOT-22. 
Baseline endoscopic NPS is the sum of the left and right nasal polyposis score at the randomization visit.  
Comparison of each treatment arm with placebo will be based on the Week 16 least squares means 
obtained from the MMRM. The p-value for the comparison will be obtained and compared to the 
significance level of 5%. An associated 2-sided 95% CI will be obtained for the active minus placebo 
change from baseline to Week 16 in the SNOT-22. No further adjustment will be made for testing each 
dosing regimen with placebo. 
In order to assess the impact of missing data due to treatment discontinuation, a sensitivity analysis may 
be performed where their data after treatment discontinuation will be imputed using multiple 
imputation and the statistical analysis using MMRM will be repeated. Another sensitivity analysis may 
be performed where observed values of the SNOT-22 score obtained during study but after treatment 
discontinuation, if available, will be used. The MMRM model will be utilized where the treatment 
discontinuations are regarded as NMAR. Full details will be specified in the SAP. 
9.4.2.2 ANALYSIS OF THE SECONDARY AND EXPLORATORY ENDPOINT(S) 
Analysis of secondary efficacy endpoints will be performed in a hierarchical order as listed in Section 3 to 
adjust for statistical multiplicity. More details for multiplicity adjustment will be described in SAP.  


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For the secondary PK endpoints, primary PK parameters of CL/F and volume of distribution will be 
estimated by population PK modeling from ANB020 serum concentrations after SC administrations. 
Secondary PK parameters of AUCtau, Cmax, tmax, for the first dose and AUCtau, Cmax, tmax and T1/2 for the last 
dose will also be calculated for ANB020 after SC administrations, where possible, using a Bayesian post-
hoc estimation approach based on the aforementioned population PK model. Other parameters may be 
evaluated, if needed. The PK parameters will be listed and summarized 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. A covariate 
screen of subject specific factors (eg, demographic and clinical characteristics) will be included in the 
analyses. Any population PK analysis plan will be described in detail in a pharmacometric analysis plan.  
All secondary and exploratory efficacy analyses will be performed on the FAS. Table 3 includes a 
summary of the statistical methods to be used in analyzing efficacy endpoints (co-primary, secondary, 
and exploratory). Full details of statistical analysis for all secondary and exploratory endpoints will be 
provided in the SAP.  
9.4.2.3 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. Subjects who elect to discontinue their 
randomized treatment but consent to continue in the study may provide on-study but off-treatment 
assessments which will aid in providing sensitivity analyses for the co-primary endpoints. 
The handling of missing data in the statistical analyses of the efficacy endpoints will be fully detailed in 
the SAP.  
No imputation of values for safety endpoints will be made. The SAP will provide methods for handling 
partial or completely missing assessment dates or missing adverse event severity.  
9.4.3 SAFETY ANALYSES 
9.4.3.1 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
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. 
TEAEs and SAEs will be summarized. 


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Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). The 
incidence and percentage will be tabulated by preferred term (PT) and system organ class (SOC). An 
event that occurred 1 or more times on treatment period will contribute 1 observation to the numerator 
and denominator comprise all safety subjects exposed to etokimab. If the intensity or seriousness of the 
TEAE changes, the overall intensity or seriousness will be the maximum intensity or seriousness of the 
multiple occurrences. The TEAEs, SAEs, TEAEs leading to treatment discontinuation, and TEAEs leading 
to withdrawal of subject will be tabulated for each treatment group. Summaries will also be presented 
by relatedness to the study drug and the severity of the TEAE. 
Listings of AEs, TEAEs, TEAEs leading to death, SAEs, and TEAEs that led to discontinuation from the 
study or of the study drug will be presented.  
Injection site reaction will be reported separately by treatment. 
9.4.3.2 DEATHS 
Subject deaths will be presented in a by-subject listing. 
9.4.3.3 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 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. 


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9.4.4 BASELINE DESCRIPTIVE STATISTICS 
9.4.4.1 SUBJECT DISPOSITION 
A tabular presentation of the subject disposition will be provided. It will include the number of subjects 
screened, randomized, treated, completed as well as the number of study discontinuations, with 
reasons for discontinuation, and major protocol deviations or violations. 
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/violations will be identified and discussed with the Investigator and Sponsor 
in dry run to categorize as major or minor and the same will be reported. 
9.4.4.2 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, 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. 
9.4.4.3 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 
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 Anatomic Therapeutic Chemical 
(ATC) level 2 categories, and preferred name.  
9.4.5 PLANNED INTERIM ANALYSES  
An interim analysis of co-primary data is planned when approximately 84 randomized subjects have 
completed Week 8 of the study. The rationale for this analysis is to assist in making decisions for the 
Phase 3 program. No adjustments to the current protocol are planned as a result of the interim analysis. 
Therefore, overall alpha is expected to be maintained at 0.05, 2-sided, for the co-primary efficacy 
endpoints.  
Full details on the interim analysis process, procedures for maintaining confidentiality of the interim 
analysis results will be described in the SAP and in the DSMB analysis plan, as appropriate. 


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9.4.6 SUBGROUP ANALYSES 
Subgroup analysis are planned for subjects with asthma comorbidity as indicated in Section 9.4.2. Any 
other subgroup analyses will be detailed in the SAP. 
9.4.7 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
All individual subject data will be listed by treatment group in the appendices. 
 
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. 
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 
intervention/administering study intervention.  
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
Informed consent is a process that is initiated prior to the subject’s agreeing to participate in the study 
and continues throughout the subject’s study participation. Written informed consent will be obtained 
from all subjects before any study-related procedures (including any pre-treatment screening 
procedures) are performed. The Investigator may discuss the study and the possibility for entry with a 
potential subject without first obtaining consent. However, a subject wishing to participate must give 
written informed consent prior to any study-related procedures being conducted, including those 
performed solely for the purpose of determining eligibility for study participation, and including 
withdrawal from current medication (if required prior to study entry). The Investigator has both the 
ethical and legal responsibility to ensure that each subject being considered for inclusion in this study 
has been given a full explanation of the procedures and expectations for study participation. 
When applicable, the study center-specific informed consent must be forwarded to the Sponsor for 
approval prior to submission to an IRB that is registered with appropriate local or federal agencies as 
required. Each subject will sign the consent form that has been approved by the same IRB that was 
responsible for protocol approval. Each informed consent document must adhere to the ethical 


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principles stated in the Declaration of Helsinki and will include the elements required by FDA regulations 
in 21 CFR Part 50, as well as the elements required by the International Council on Harmonisation (ICH) 
GCP guideline, and applicable federal and local regulatory requirements. The consent form must also 
include a statement that the Sponsor, their designees, and auditing regulatory agencies will have direct 
access to the subject’s records and medical history for study-related purposes. 
Once the appropriate essential information has been provided to the subject and fully explained by the 
Investigator (or a qualified designee) and it is felt that the subject understands the implications and risks 
of participating in the study, the IRB approved consent document shall be signed and dated by both the 
subject and the person obtaining consent (Investigator or designee), and by any other parties required 
by the IRB or other regulatory authorities. The subject will be given a copy of the signed informed 
consent document with the original kept on file by the Investigator. All of the above activities must be 
completed before any study-related procedures are conducted (including any screening study 
procedures). 
 STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party to study subjects, Investigator, the IND Sponsor and 
regulatory authorities. If the study is prematurely terminated or suspended, the PI will promptly inform 
study subjects, the IRB, and Sponsor and will provide the reason(s) for the termination or suspension. 
Study subjects will be contacted, as applicable, and be informed of changes to study visit schedule. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
 
Determination of unexpected, significant, or unacceptable risk to subjects 
 
Demonstration of efficacy that would warrant stopping  
 
Insufficient compliance to protocol requirements 
 
Data that are not sufficiently complete and/or evaluable 
 
Determination that the primary endpoint has been met 
 
Determination of futility 
 
The study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the Sponsor, IRB and/or FDA. 
10.1.3 CONFIDENTIALITY AND PRIVACY  
Subject confidentiality and privacy is 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.  


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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, 
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, 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 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 IP, 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 (HIPAA). 
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 a separate ICF. Refusal to participate in this optional DNA collection and specimen 
storage does not affect a subject’s ability to be enrolled in the study. A subject may choose to 
participate in this DNA collection and/or specimen storage at Screening or any time during the study up 
to and including the EOS visit.  
With the subject’s approval and as approved by local IRBs, de-identified biological samples will be stored 
at a certified, licensed central laboratory. These samples may be used to research the causes of 
CRSwNP, its complications and other conditions for which individuals with CRSwNP and asthma are at 
increased risk, and to improve treatment. The central lab will also be provided with a code-link that will 


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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.  
Once samples have been analyzed specimens will be destroyed. If no analyses have been completed 
within 5 years following EOS, samples will be destroyed. 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
Table 4 lists the key personnel for this study. Additional study contact information will be provided in 
the Study Operations Manual. 
Table 4. 
Key Study Personnel for Protocol ANB020-006 
 
10.1.6 DATA AND SAFETY MONITORING BOARD 
A DSMB, or otherwise called Independent Data Monitoring Committee, will be set up, prior to the first 
subject being enrolled in the study, as an independent body to review accumulating data in the study. 
The DSMB is comprised of 3 independent clinicians (2 pulmonologists, 1 ENT specialist) and 1 
independent statistician. Members of the DSMB will not be Investigators in the study, and will be free of 
any conflicts of interest with the Sponsor or study outcome. 
The DSMB will periodically examine the safety data emerging from the study and provide its 
recommendations to the Sponsor. The roles and responsibilities of the DSMB, their operational 
procedures, and method of communication with Sponsor will be described in a separate DSMB charter.  
The first DSMB meeting is expected to occur prior to the Investigators Meeting. A formal review of the 
accumulating data is planned for every quarter thereafter, unless an ad hoc meeting is required. 


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10.1.7 CLINICAL MONITORING 
All aspects of the study will be monitored by the Sponsor or authorized representatives of the Sponsor 
according to GCP and Standard Operating Procedures (SOPs) for compliance with applicable government 
regulations, (ie, Informed Consent Regulations [US 21CFR, Part 50] and IRB regulations [US 21CFR, Part 
56.103]). Access to all records, both during the study and after study completion, should be made 
available to the Sponsor at any time for review and audit to ensure the integrity of the data. The 
Investigator must notify Sponsor immediately if the responsible IRB has been disqualified or if 
proceedings leading to disqualification have begun. 
The Investigator must conduct the protocol in accordance with applicable GCP regulations and 
guidelines; applicable informed consent regulations (US 21CFR, Part 50); and in compliance with the 
Declaration of Helsinki. Every attempt must be made to follow the protocol and to obtain and record all 
data requested for each subject at the specified times. If data are not recorded per protocol, the reasons 
must be clearly documented on the eCRF/records. 
Before study initiation, at a study center initiation visit or at a meeting with the Investigator(s), a 
representative from the Sponsor will review the protocol and study eCRFs with the Investigator(s) and 
their staff. During the study, the study monitor will visit the study center regularly to check the 
completeness of subject records, the accuracy of entries on the eCRFs, the adherence to the protocol 
and to GCP, the progress of enrollment, and to ensure that consent is being sought and obtained in 
compliance with applicable regulations, and that the IP is being stored, dispensed and accounted for 
according to specifications. The Investigator and key trial personnel must be available to assist the 
monitor during these visits. 
The Investigator must give the monitor access to relevant hospital or clinical records, to confirm their 
consistency with the eCRF entries. No information in these records about the identity of the subjects will 
leave the study center. Monitoring standards require full verification for the presence of informed 
consent, adherence to the inclusion/exclusion criteria, documentation of SAEs, and the recording of 
primary efficacy and safety variables. Additional checks of the consistency of the source data with the 
eCRFs will be performed according to the study-specific monitoring plan. 
The Investigator must promptly complete the eCRFs after the subject’s visit. The monitor is responsible 
for reviewing them and clarifying and resolving any data queries. A copy of the eCRFs will be retained by 
the investigator who must ensure that it is stored in a secure place with other study documents, such as 
the protocol, the IB, and any protocol amendments. 
The Investigator must provide the Sponsor and the responsible IRB with a study summary shortly after 
study completion, or as designated by the Sponsor. 


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10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
Each clinical study center will perform internal quality management of study conduct, data and 
biological specimen collection, documentation and completion. An individualized quality management 
plan will be developed to describe a study center’s quality management. 
Quality control (QC) procedures will be implemented beginning with the data entry system and data QC 
checks that will be run on the database will be generated. Any missing data or data anomalies will be 
communicated to the site(s) for clarification/resolution. 
Following written SOPs, the monitors will verify that the clinical trial is conducted and data are 
generated and biological specimens are collected, documented (recorded), and reported in compliance 
with the protocol, ICH GCP, and applicable regulatory requirements (eg, GLP, Good Manufacturing 
Practices [GMP]).  
The study center will provide direct access to all study-related sites, source data/documents, and 
reports for the purpose of monitoring and auditing by the Sponsor, and inspection by local and 
regulatory authorities. 
10.1.9 DATA HANDLING AND RECORD KEEPING  
 
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
All protocol-specified data will be recorded in the source documents, and data will be entered on the 
eCRFs from the source documents. In addition to signature confirmation that a subject meets the study 
eligibility criteria, upon each subject’s completion of the study, the Investigator will sign a statement 
indicating that all pages of the subject’s case report have been reviewed. Signature stamps and “per 
signatures” are not acceptable.  
It is Sponsor’s policy that the study data be verifiable with the source data that necessitates access to all 
original recordings, laboratory reports, and other records for each subject. The Investigator must 
therefore agree to allow access to subjects’ records, and source data must be made available for all 
study data. Subjects (or their legal representatives) must also allow access to their medical records. 
Subjects will be informed of the importance of increased record access and permission granted by 
signature on the informed consent document prior to Screening. 
Checks will be performed to ensure the quality, consistency, and completeness of the data. Instances of 
missing or uninterpretable data will be resolved with the Investigator or study coordinator. Data 
queries, documented on data query forms, will be sent to the research facility. Site personnel will be 
responsible for providing resolutions to the data queries and for correcting the eCRFs, as appropriate. All 
unused Sponsor source documents and binders must be returned to the Sponsor upon completion of 
the study. 


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The Investigator must keep written or electronic source documents for every subject participating in the 
clinical study. The subject file that identifies the study in which the subject is participating must include 
the subject’s available demographic and medical information including:  
• 
Name 
• 
Contact information 
• 
Date of birth 
• 
Sex 
• 
Medical history 
• 
Concomitant diseases 
• 
Concomitant therapies/medication 
• 
Study visit dates 
• 
Performed examinations, evaluations, and clinical findings 
• 
IP administration 
• 
AEs, SAEs, or pregnancy (as applicable) 
Additionally, any other documents with source data, especially original printouts of data that were 
generated by technical equipment must be included in the subject’s source document (eg, laboratory 
value listings). All these documents must have at least the subject’s study number, and the date of the 
evaluation.  
The data recorded during the course of the study will be documented in the eCRF and/or the study-
specific forms. Before or at study termination, all data must be forwarded to the Sponsor. The data will 
then be recorded, evaluated, and stored in anonymous or coded form in accordance with data-
protection regulations. 
Subjects will authorize the use of their protected health information during the informed consent 
process in accordance with the applicable privacy requirements. Subjects who deny permission to use 
and disclose protected health information will not be eligible to participate in the study. The Investigator 
will ensure that the study documents forwarded to the Sponsor, and any other documents, contain no 
mention of subject names. 
Any amendments and corrections necessary will be undertaken in both the source documents and 
eCRFs (as appropriate) and countersigned by the Investigator, or documented designee, stating the date 
of the amendment/correction. Errors must remain legible and may not be deleted with correction aids. 
The Investigator must state his/her reason for the correction of any data. In the case of missing 
data/remarks, the entry spaces provided in the eCRF should be cancelled out so as to avoid unnecessary 
follow-up inquiries. 
Regulatory authorities, the IRB and/or the Sponsor’s Quality Assurance group (or designee) may request 
access to all source documents, eCRFs, and other study documentation for onsite audit or inspection. 
The Investigator must guarantee direct access to these documents. eCRFs will be kept by the Sponsor or 
an authorized designee in a secured area. Clinical data will be recorded in a computer format for 
subsequent statistical analyses. Data files will be stored on electronic media with a final master data file 


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kept by the Sponsor after descriptive and statistical analyses and reports have been generated and are 
complete. 
It is the responsibility of the Investigator to ensure that the study center file is maintained in accordance 
with the ICH Guidance for Industry E6(R2) GCP: Consolidated Guidance, Section 8 – Essential Documents 
for the Conduct of a Clinical Trial. 
10.1.9.2 STUDY RECORDS RETENTION  
Study documents should be retained for a minimum of 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 until at least 2 years have elapsed since the formal discontinuation of clinical development 
of the study intervention. These documents should be retained for a longer period, however, if required 
by local regulations. No records will be destroyed without the written consent of the Sponsor, if 
applicable. It is the responsibility of the Sponsor to inform the Investigator when these documents no 
longer need to be retained. 
The Investigator must not dispose of any records or essential documents relevant to this study without 
either (1) written permission from the Sponsor, or (2) providing an opportunity for the Sponsor to 
collect such records. The Investigator shall take responsibility for maintaining adequate and accurate 
electronic or hard copy source documents of all observations and data generated during this study. Such 
documentation is subject to inspection by the Sponsor and relevant regulatory agencies. If the 
Investigator withdraws from the study (eg, relocation, retirement) all study-related records should be 
transferred to a mutually agreed upon designee. Notice of such transfer will be provided to the Sponsor 
in writing. 
10.1.10 
PROTOCOL DEVIATIONS  
A protocol deviation is any noncompliance with the clinical trial protocol, ICH GCP, or MOP 
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. Further details about the handling of protocol deviations will be 
included in the MOP, Clinical Monitoring Plan, Medical 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 


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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 
This study will be conducted in accordance with the following publication and data sharing policies and 
regulations: 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to the 
published results of NIH funded research. It requires scientists to submit final peer-reviewed journal 
manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for 
publication. 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-funded 
Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As 
such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be 
submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in 
peer-reviewed journals. Data from this study may be requested from other researchers up to 5 years 
after the completion of the primary endpoint by contacting the Sponsor.  
It is understood by the Investigator that the information generated in this study will be used by Sponsor 
in connection with the development of the product. To allow for the use of information derived from 
the study, it is understood that the Investigator is obliged to provide the Sponsor with complete test 
results, all study data, and access to all study records.  
Any results of medical investigations with Sponsor’s products and/or publication/lecture/manuscripts 
based thereon, shall be exchanged and discussed by the Investigator and Sponsor representative(s) 
30 days before submission for publication or presentation. Due regard shall be given to Sponsor’s 
legitimate interests for example, manuscript authorship, obtaining optimal patent protection, 
coordinating and maintaining the proprietary nature of submissions to health authorities, coordinating 
with other ongoing studies in the same field, and protecting confidential data and information. The 
Sponsor shall be furnished with a copy of any proposed publication. Comments shall be rendered 
without undue delay. 
In cases of publications or presentations of material arising from multicenter clinical investigations, the 
Sponsor is to serve as coordinator and referee. Individual Investigators who are part of a multicenter 
investigation may not publish or present data that are considered common to a multicenter 
investigation without the consent of the other participating Investigators and the prior review of the 
Sponsor. 
In case of disagreement among the Investigators participating in a multicenter investigation, the 
Sponsor will be the final arbiter. Comments shall be given without undue delay. If they are not accepted, 
the senior author of the manuscript and representatives of the Sponsor shall promptly meet to discuss 
further and endeavor to agree mutually on the final wording and/or disposition of the publication. The 


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above procedure also applies to information on prematurely discontinued and other non-completed 
studies. 
Results from investigations shall not be made available to any third party by the investigating team 
outside the publication procedure as outlined previously. The Sponsor will not quote from publications 
by Investigators in its scientific information and/or promotional material without full acknowledgment 
of the source (ie, author and reference). 
 
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. All persons with 
direct financial interest in this trial are prohibited to have direct involvement. 
10.2 ADDITIONAL CONSIDERATIONS 
 ETHICS AND RESPONSIBLITY 
This study must be conducted in compliance with the protocol, the ICH Guidance for Industry E6(R2) 
GCP: Consolidated Guidance, the Declaration of Helsinki, IRB requirements, and all applicable national 
and local regulatory requirements. Investigators must submit all essential regulatory documentation, as 
required by local and national regulations (including approval of the protocol and ICF by an HHS-
registered IRB) to the Sponsor before IP will be shipped to the study site. 
 AMENDMENT POLICY 
Only the Sponsor may modify the protocol. Protocol amendments will be made after consultation 
between the Sponsor and the Investigator(s). Amendments must be approved by all applicable national 
and local committees including, but not limited to, the government regulatory authorities and/or 
regional IRB before implementation. The only exception is when an Investigator considers that a subject 
may be harmed and immediate action] is necessary. Under these circumstances, approval of the 
chairman of the IRB, or an authorized designee, must be sought immediately. The Investigator should 
inform the Sponsor, and the full IRB, no later than 5 working days after the emergency occurs.  
Protocol-specified safety reporting requirements must be adhered to independent of any other 
variables. All amendments that have an impact on subject risk, the study objectives or that require 
revision of the informed consent document must be approved by the IRB before implementation. 
Administrative changes to the protocol and/or changes that do not impact subject safety, risk, or 


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comfort may be implemented prior to IRB approval if local institutional policy permits. A copy of the 
written approval of the IRB, which becomes part of the essential study documents file, must be given to 
the study monitor. Examples of amendments requiring such approval are: 
• 
A significant change in the study design 
• 
An increase in the number of invasive procedures to which subjects are exposed 
• 
An addition or deletion of a test procedure 
The PI at each study center must sign the Investigator’s Agreement page of the amended protocol. 
 


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10.3 ABBREVIATIONS 
 
ACQ-7
7-Item Asthma Control Questionnaire 
AD
Atopic dermatitis
ADA
Anti-drug antibody
AE
Adverse event
AERD
Aspirin-exacerbated respiratory disease
AUC[tau]
Area under the concentration-time curve from time 0 to the time of the last quantifiable 
concentration 
BMI
Body mass index
BP
Blood pressure
CFR
Code of Federal Regulations
CI
Confidence interval
CL/F
Apparent clearance
Cmax
Maximum concentration
CRS
Chronic rhinosinusitis
CRSwNP
Chronic rhinosinusitis with nasal polyposis
CT
Computed tomography
DNA
Deoxyribonucleic acid
DP 
Drug product
DS
Drug substance
DSMB
Data Safety Monitoring Board
ECG
Electrocardiogram
eCRF
Electronic case report forms
EOS
End of study
EOT
End of treatment
ePRO
Electronic patient-reported outcome
EQ-5D
EuroQoL-5D Scale
ETV
Early termination visit
FAS
Full analysis set
FDA
Food and Drug Administration
FEV1
Forced expiratory volume 
GCP 
Good Clinical Practice
GLP
Good Laboratory Practices
GMP
Good Manufacturing Practices
HIPAA 
Health Insurance Portability and Accountability Act 
HIV
Human immunodeficiency virus
HR
Heart rate
IB
Investigator’s Brochure 
ICF
Informed consent form
ICH 
International Council for Harmonisation of Technical Requirements for Pharmaceuticals 
for Human Use  
IgA
Immunoglobulin A
IgE
Immunoglobulin E
INCS
Intranasal corticosteroid
IND
Investigational New Drug Application


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IP
Investigational product
IRB
Institutional Review Board
IXRS
Interactive Web Response System
mAb
Monoclonal antibody
MAD
Multiple ascending dose
MedDRA
Medical Dictionary for Regulatory Activities
MFNS
Mometasone furoate nasal spray
MMRM
Mixed effects model with repeated measures
NCT
National Clinical Trial
NMAR
Not missing at random
NP
Nasal polyposis
NPIF
Nasal peak inspiratory flow
NPS
Nasal Polyp Score
OCS
Oral corticosteroids
OHRP
Office for Human Research Protections
PI
Principal Investigator
PK
Pharmacokinetics
PP
Per protocol
Q4W
Every 4 weeks
Q8W
Every 8 weeks
QC
Quality control
QoL
Quality of life
SAD
Single ascending dose
SAE
Serious adverse event
SAP
Statistical Analysis Plan
SC
Subcutaneous(ly)
SF-36
Short Form 36 Health Survey
SNOT-22
Sino-Nasal Outcome Test
SoA
Schedule of Activities
SOC
System organ class
SOP
Standard Operating Procedure
t1/2
Apparent terminal half-life 
TCA
Tricyclic antidepressant drugs
TEAE
Treatment-emergent adverse event
TB
Tuberculosis
Th2
T helper type 2
tmax
Time of maximum concentration
UP
Unanticipated problem
UPSIT
University of Pennsylvania Smell Identification Test
US
United States
VAS
Visual Analogue Scale
Vd/F
Apparent volume of distribution
WOCBP
Woman of childbearing potential
 


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10.4 PROTOCOL AMENDMENT HISTORY 
 
Version
Date
Description of Change
Brief Rationale
Original Protocol 
21 September 2018 
 
 
Amendment 1 
15 February 2019 
Administrative 
corrections, updated 
Inclusion/exclusion 
criteria, clarified 
procedures. See 
Summary of Changes for 
complete summary. 
Improving patient safety, 
aligning criteria in patients 
enrollment, and improving 
protocol based on input 
provided by DSMB and 
participating clinical 
Investigators with strong 
patient management 
experience. 
Amendment 2 
15 August 2019 
Updated 
inclusion/exclusion 
criteria; clarified 
procedures; updates on 
statistical 
considerations, dropout 
rate and sample size; 
administrative 
corrections. See 
Summary of Changes for 
complete summary. 
Providing clarification, 
improving patient safety and 
improving protocol based on 
input provided by 
participating clinical 
Investigators with strong 
patient management 
experience. 
Amendment 3 
06 February 2020 
Corrected inconsistencies 
in objectives and endpoints 
listed throughout the 
document and corrected 
administrative errors. 
The synopsis, Section 3, and 
statistical sections were not 
consistent for the objectives 
and endpoints listed.  
 


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Bachert C, Mannent L, Naclerio RM, Mullo J, Ferguson BJ, Gevaert P, et al. Effect of subcutaneous 
dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis – a randomized 
clinical trial. JAMA. 2016;315(5):469-479. 
 
Bhattacharyya N, Vyas DK, Fechner FP, Gliklich RE, Metson R. Tissue Eosinophilia in Chronic 
SinusitisQuantification Techniques. Arch Otolaryngol Head Neck Surg. 2001;127(9):1102–1105. 
doi:10.1001/archotol.127.9.1102 
 
Chiarella, Sy, Peters. Monoclonal antibody therapy in sino-nasal disease. Am J Rhinol Allergy. 2017 Mar 
1; 31(2):93-95. 
 
Chowdhury N, Mace J, Bodner T, Alt J, Deconde A, Levy J, et al. Investigating the minimally clinically 
important difference for SNOT-22 symptom domains in surgically managed chronic rhinosinusitis. Int 
Forum Allergy Rhinol. 2017; 7(12):1149-1155. 
 
Deeb R, Malani PN, Gil B, Jafari-Khouzani K, Soltanian-Zadeh H, Patel S, et al. Three dimensional 
 volumetric measurements and analysis of the maxillary sinus. Am J Rhinol Allergy. 2011; 25(3); 152-56. 
 
Fokkens W, Lund VJ, Mullol J., Bachert C, Alobid I, Baroody F, et al. European position paper on 
rhinosinusitis and nasal polyps 2012. Rhinol Suppl. 2012; 23: 1-298. 
 
Hopkins C, Gillett S, Slack R, Lund VJ and Browne JP. Psychometric validity of the 22- item sinonasal 
outcome test. Clin Otolaryngology. 2009; 34: 447-454. 
 
Jarvis D, Newson R, Lotvall J, Hastan D, Tomassen P, Keil T, et al. Asthma in adults and its association 
with chronic rhinosinusitis: the GA2LEN survey in Europe. Allergy. 2012 Jan;67(1):91-8. 
 
Juniper EF, Svensson K, Mörk AC, Ståhl E. Measurement properties and interpretation of 
three shortened versions of the asthma control questionnaire. Respir Med. 2005 May; 99 (5): 
553-558. Epub 2004 Nov 26. 
 
Lam M, Hull L, Imrie A, Snidvongs K, Chin D, Pratt E, et al. Interleukin-25 and interleukin-33 as mediators 
of eosinophilic inflammation in chronic rhinosinusitis. Am J Rhinol Allergy. 2015; 29:175–81. 
 
Liew Fy. IL-33: A Janus Cytokine. Ann Rheum Dis. 2012;71 Suppl 2:I101-I104. 
 
Lund VJ, Mackay IS. Staging in rhinosinusitus. Rhinology. 1993;31(4):183-184. 
 
Meltzer et al. Rhinosinusitis: establishing definitions for clinical research and patient care. J Allergy Clin 
Immunol. 2004;114(6 Suppl):155. 
 
Metson R, Gliklich RE, Stankiewicz JA, Kennedy DW, Duncavage JA, Hoffman SR, et al. Comparison of 
sinus computed tomography staging systems. American Academy of Otolaryngology-Head and Neck 
Surgery. 1997; 117(4):372-379. 


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Nabe, T. Interleukin (IL)-33: New Therapeutic Target for Atopic Diseases. J. Pharmacol Sci. 2014; 126: 85-
91. 
 
O’Brien PC and Fleming TR. A multiple testing procedure for clinical trials. Biometrics. 1979; 35: 549-556. 
 
Oluwole M, Russell N, Tan L, Gardiner Q, White P. A comparison of computerized tomographic staging 
systems in chronic sinusitis. Clin Otolaryngol. 1996; 21(1): 91-95. 
 
Pastorelli L., Garg L, Hoang S, 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, PNAS, Proc. Natl. 
Acad. Of Sci, 2010, Vol.1 107, no.17, 8017 – 8022. 
 
Pauwels B, Jonstam K, Bachert C. Emerging biologics for the treatment of chronic rhinosinusitis. Expert 
Rev Clin Immunol. 2015 Mar;11(3):349-61. 
 
Ponikau J.U., Sherris D.A., Kephart G.M., Kern E.B., Congdon D.J., Adolphson C.R., et al. Striking 
deposition of toxic eosinophil major basic protein in mucus: Implications for chronic rhinosinusitis. 
Journal of Allergy and Clinical Immunology, 2005; 116 (2), pp. 362-369. 
 
Poposki et al. Group 2 innate lymphoid cells are elevated and activated in chronic rhinosinusitis with 
nasal polyps. Immun Inflamm Dis. 2017 Sep;5(3):233-243. 
 
Rudmik L, Hopkins C, Peters A, Smith T, Schlosser R, Soler Z. Patient-reported outcome measures for 
adult chronic rhinosinusitis: A systemic review and quality assessment. J Allergy Clin Immunol. 2015; 
(136(6):1532-1540. 
 
Smith D, Helgason H, Sulem P, Bjornsdottir US, Lim AC, Sveinbjornsson G, et al. (2017) A rare IL33 loss-
of-function mutation reduces blood eosinophil counts and protects from asthma. PLoS Genet 13(3): 
e1006659. https://doi.org/10.1371/journal.pgen.1006659  
 
Song et al. IL-33 Expression in Chronic Rhinosinusitis with Nasal Polyps and Its Relationship with Clinical 
Severity. ORL J Otorhinolaryngol Relat Spec. 2017;79(6):323-330. 
 
Soyka MB, Holzmann D, Basinski TM, Wawrzyniak M, Bannert C, Bürgler S, et al. The induction of IL-33 in 
the sinus epithelium and its influence on T-helper cell responses. PLoS One. 2015;10:0123-163. 
 
Steele T, Rudmik L, Mace J, DeConde A, Alt J, Smith T. Patient-centered decision making – the role of the 
baseline SNOT-22 in predicting outcomes for medical management of chronic rhinosinusitis. Int Forum 
Allergy Rhinol. 2016; 6(6):590-596. 
 
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Van Agthoven M, Fokkens WJ, Van de Merwe JP, Van Bolhuis EM, Uyl-de Groot CA, Busschbach JJV. 
Quality of life of patients with refractory chronic rhinosinusitis: effects of filgrastim treatment. Am J 
Rhinol. 2001 Aug; 15(4):231-237. 
 
Vlaminck et al. The importance of local eosinophilia in the surgical outcome of chronic rhinosinusitis: a 
3-year prospective observational study. Am J Rhinol Allergy. 2014 May-Jun;28(3):260-4. 
 
Zacharek MA, Krouse JH. The role of allergy in chronic rhinosinusitis. Curr Opin Otolaryngol Head Neck 
Surg. 2003 Jun;11(3):196-200. 
 
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APPENDICES 
 
APPENDIX A: PROHIBITED MEDICATIONS AND THERAPIES DURING THE COURSE OF THE 
STUDY 
Excluded medications/therapies are listed below. The use of an excluded medication/therapy is a 
protocol violation and must be recorded in the eCRF. The following medications will not be permitted 
during the study: 
• 
Biologics, monoclonal antibodies including but not limited to: anti-immunoglobulin E (IgE) therapy 
(omalizumab), anti-IL-5 therapy (mepolizumab, benralizumab) anti-IL-4/13 (dupilumab)  
 
Any immunosuppressive treatment including but not limited to: methotrexate, cyclosporine, 
mycophenolate, tacrolimus, gold, penicillamine, sulfasalazine, hydroxychloroquine, azathioprine, 
cyclophosphamide 
• 
Aspirin or nonsteroidal anti-inflammatory (NSAID) in patients with hypersensitivity to aspirin or 
NSAID 
• 
Systemic corticosteroid 
• 
Decongestion (topical or systemic) is not allowed, except before endoscopy 
• 
Long term use of systemic antibiotics (for 2 weeks or more) 
• 
Lipoxygenase inhibitors 
 
Use of intranasal medication that could interfere with the symptoms of diseases are prohibited (this 
includes but is not limited to: chronic use of INCSs, antihistamines, nasal atropine, ipratropium 
bromide, nasal cromolyn)  
 
Chronic use of nasal antihistamines within 8 weeks of Screening is prohibited (however acute 
episodic use within 8 weeks of Screening is permitted. Oral antihistamines and nasal saline are 
permitted both during Screening and while on-study). 
 
Polypectomy (allowed as part of medical history up to 3 months prior to randomization)  
 
 


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APPENDIX B: 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. 


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Female Subjects 
• 
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. 
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 negative highly 
sensitive SPT at Screening and UPT on Day 1 (prior to study treatment administration). 
• 
Additional pregnancy testing should be performed as mentioned in the SOA (see Section 1.3). 
• 
Pregnancy testing will be performed whenever a menstrual cycle is missed or when pregnancy is otherwise 
suspected. Positive UPT result should be confirmed with a serum test. 


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Collection of Pregnancy Information 
 
Male Subjects with Partners who Become Pregnant 
• 
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 8.6.6. 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 C: PHARMACOKINETIC AND ANTI-DRUG ANTIBODY COLLECTION TIMEPOINTS 
 
Study Day 
Study Visit 
PK Sample Time Point 
(Serum) 
Sample Time 
Point for ADA 
Day 1/Week 0 
etokimab/Placebo dosing 
2 
Predose 
Predose 
 
Day 5/Week 1 
3 
Must occur 3 to 5 days after 
Day 1 dosing (Visit 2) 
 
 
Day 29/Week4 
5 
Predose 
Predose 
 
Day 57/Week 8 
6 
Predose 
Predose 
 
Day 85/Week 12 
7 
Predose 
Predose 
 
Day 113/Week 16 
8 
PK can be pulled at any time 
during the study visit 
 
 
Day 141/Week 20 
9 
Anytime during the study visit 
Anytime during 
the study visit 
 
Day 169/Week 24/EOS/ET 
10 
Anytime during the study visit 
Anytime during 
the study visit 
Abbreviation: ADA = Anti-drug antibody; EOS = End of study; ETV = Early termination visit and PK=Pharmacokinetic 
  
 
 


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APPENDIX D: SAMPLE ENDOSCOPIC NASAL POLYP SCORE 
Sample Endoscopic Nasal Polyp Score 
Polyp Score 
Polyp Size 
0 
No polyps 
1 
Polyps in the middle meatus not reaching below the lower border of the 
middle turbinate 
2 
Polyps reaching below the lower border of the middle turbinate 
3 
Polyps reaching the lower border of the inferior turbinate or polyps medial 
to the middle turbinate 
4 
Polyps causing complete obstruction of the inferior nasal cavity 
Total NPS Score: 
NPS Left ______ + NPS Right _______ = Total __________ 
 
The NPS score is the sum of the right and left nostril scores, as evaluated by means of nasal endoscopy. 
NP is graded based on polyp size described in the table above. 
 


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APPENDIX E: SAMPLE 22-ITEM SINO-NASAL OUTCOME TEST (SNOT-22) 
 
 


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APPENDIX F: SAMPLE SHORT FORM 36 HEALTH SURVEY (SF-36) 
 


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APPENDIX G: SAMPLE EUROQOL-5D (EQ-5D) 
 
 


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APPENDIX H: SAMPLE 7-ITEM ASTHMA CONTROL QUESTIONNAIRE (ACQ-7) 
 
7-ITEM ASTHMA CONTROL QUESTIONNAIRE (ACQ-7) 
Please answer questions 1to 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  
0 
Never 
woken by your asthma during the night?  
1 
Hardly ever 
 
2 
A few minutes 
 
 
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  
0 
No symptoms 
asthma symptoms when you woke up in the morning? 
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  
0 
Not limited at all 
in your activities because of your asthma?  
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  
0 
None 
breath did you experience because of you asthma?  
1  
A very little 
 
2 
A little 
 
3 
A moderate amount  
 
4 
Quite a lot 
 
5 
A great deal 
 
6 
A very great deal  
 
5. 
In general, during the past week, how much of the time did  
0 
Not at all 
you wheeze?  
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  
 
6. 
On average, during the past week, how many puffs of  
0 
None 
short-acting bronchodilator (eg. Ventolin) have you  
1 
1-2 puffs most days 
used each day?  
2 
3-4 puffs most days 
 
3 
5-8 puffs most days 
 
4 
9-12 puffs most days 
 
5 
13-16 puffs most days 
 
6 
More than 16 puffs most days 
 


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To be completed by a member of the clinic staff  
7. 
FEV1 pre-bronchodilator:...................................  
0 
>95% predicted 
 
1 
95-90% 
FEV1 predicted....................................................... 
2 
89-80% 
FEV1 % predicted.................................................... 
3 
79-70% 
(Record actual values on the dotted lines  
4 
69-60% 
and score the FEV1 % predicted in the next  
5 
59-50% 
column)  
6 
< 50% predicted 
 
 
 
The Asthma Control Questionnaire is copyrighted. It may not be changed, translated or sold (paper or software) 
without the permission of Elizabeth Juniper. 
 


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APPENDIX I: SAMPLE NASAL POLYP RELATED RESOURCE USE QUESTIONNAIRE 
 
 


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APPENDIX J: SAMPLE VISUAL ANALOGUE SCALE  
 
 

SAP_001.pdf: 
 
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Statistical Analysis Plan for Interventional Studies 
 
Sponsor Name: AnaptysBio Inc. 
 
Protocol Number: ANB020-006 
Protocol Title: A Phase 2, Double-Blind, Placebo Controlled, Parallel Group, Multiple Dose Study to 
Investigate etokimab (ANB020) in Adult Subjects with Chronic Rhinosinusitis with Nasal Polyposis 
 
Protocol Version and Date: Amendment3_v.4.0 (28-Feb-2020) 
 
roject Code: 7001287 
 
Authors:
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notice of Confidential and Proprietary Information: 
The information contained in this document is confidential belonging to AnaptysBio, Inc.   Acceptance of this 
document constitutes agreement by the recipient that no information contained herein will be published or 
disclosed without prior written authorization from an official of AnaptysBio, Inc.  However, this document may 
be disclosed to appropriate Institutional Review Board and Ethics Committees or duly authorized 
representatives of a national regulatory authority under the condition that they are requested to keep it 
confidential. In the event of an actual or suspected breach of this obligation,
should be notified 
promptly. 
National Clinical Trial (NCT) 
Identified Number: NCT03614923 


Statistical Analysis Plan for Interventional Studies 
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REVISION HISTORY 
Version # 
Date 
(DD-Mmm-YYYY) 
Document Owner 
Revision Summary 
V.0.1 
02June2019 
Initial Release Version  
V0.2 
09Sept2019 
Changes according to Amendment 2 15AUG2019 and 
update according to Sponsor’s requests 
V0.3 
28Feb2020 
Changes according to Amendment 3 06FEB2020 and 
update according to Sponsor’s requests 
V1.0 
03Apr2020 
Added: ACQ-5 analysis. 
Updated: Nocturnal awaking analysis based on eDiary 
data, not from ACQ-7. 
Administration changes: updated sponsor reviewer, minor 
changes throughout. 
 
 
 


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I confirm that I have reviewed this document and agree with the content. 
Approvals 
pproval 
 
 
 
 
 
 
 
Signature 
 
Date (DD-MMM-YYYY) 
 
Signature 
 
Date (DD-MMM-YYYY) 
Sponsor Approvals 
 
 
 
 
 
 
Signature 
 
Date (DD-MMMYYYY) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature 
 
Date (DD-MMM-YYYY) 
 
 
 
 
 
 












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Abbreviation 
Description 
ePRO 
Electronic subject reported outcome 
EQ-5D 
EuroQoL-5D Scale 
ETV 
Early termination visit 
FAS 
Full analysis set 
FEV1 
Forced expiratory volume 
GCP 
Good Clinical Practice 
HIV 
Human immunodeficiency virus 
IA 
Interim Analysis 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation  
IDMC 
Independent Data Monitoring Committee 
IgA 
Immunoglobulin A 
IgE 
Immunoglobulin E 
INCS 
Intranasal corticosteroid 
IP 
Investigational product 
IXRS 
Interactive Web Response System 
LFTs 
Liver Function Tests 
mAb 
Monoclonal antibody 
MAR 
Missing at Random 
Max 
Maximum 
MCAR 
Missing Completely at Random 
MCID 
Minimal Clinically Important Difference 
MedDRA 
Medical Dictionary for Regulatory Activities 
MFNS 
Mometasone furoate nasal spray 
Min 
Minimum 
MMRM 
Mixed effects model with repeated measures 
MOP 
Manual of Procedures 
N/A 
Not Applicable 


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Abbreviation 
Description 
NA 
Not Applicable 
NMAR 
Not missing at random 
NP 
Nasal polyposis 
NPIF 
Nasal peak inspiratory flow 
NPS 
Nasal polyp score 
OCS 
Oral corticosteroids 
PI 
Principal investigator 
PK 
Pharmacokinetics 
PP 
Per protocol 
PR 
Pulse rate 
PT 
Preferred Term 
Q4W 
Every 4 weeks 
Q8W 
Every 8 weeks 
QC 
Quality Control 
QoL 
Quality of life 
QTc 
Corrected QT Interval 
QTcF 
QT corrected by Fridericia's formula 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous(ly) 
SD 
Standard Deviation 
SE 
Standard Error 
SF-36 
Short Form 36 Health Survey 
SI 
Standard International System of Units 
SNOT-22 
Sino-Nasal Outcome Test 
SOA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 


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Abbreviation 
Description 
t1/2 
Apparent terminal half-life 
TEAE 
Treatment-emergent Adverse Event 
TB 
Tuberculosis 
TFL 
Tables, Figures, and Listings 
tmax 
Time of maximum concentration 
ULN 
Upper Limit Normal 
TTFR 
Time to First Response 
UPSIT 
University of Pennsylvania Smell Identification Test 
US 
United States 
VAS 
Visual Analogue Scale 
Vd/F 
Apparent volume of distribution 
VMSOD 
Volumetric Maxillary Sinus Occupied by Disease 
WHO 
World Health Organization 
WOCBP 
Woman of childbearing potential 
 










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10. Clinically significant abnormal ECG assessment at screening (any abnormality that the investigator 
believes is not safe for study participation).  
11. History of ischemic cardiovascular disease(s) or cerebrovascular event within 1 year of screening. 
12. Have received any systemic antibiotic treatment within 4 weeks before screening.  
13. Have a history of hypersensitivity or allergic reactions to polysorbate 80, a component of the etokimab 
formulation or the inactive ingredients (excipients). 
14. If female, is pregnant or lactating, or intends to become pregnant during the study period. 
15. Current smokers or former smokers with a smoking history of ≥ 10 pack-years [(number of cigarettes 
per day/20) × number of years smoked]. A former smoker is defined as a subject who quit smoking at 
least 2 months prior to Screening visit. This includes electronic cigarettes and vaping. Subjects who 
smoke medicinal marijuana can be enrolled at the investigator’s discretion (conversion to edible forms 
of marijuana is preferred). Occasional smoking is permitted at the discretion of the investigator (e.g., 
cigar or pipe for significant event, occasional/rare weekend cigarette or marijuana use).  
16. Positive blood screen for hepatitis C virus antibody, hepatitis B virus core antibody, hepatitis B surface 
antigen, or human immunodeficiency virus (HIV) 1 and 2 antibodies (except subjects who test positive 
for hepatitis B surface antigen alone due to a hepatitis B vaccination).  
17.  Presence of chronic or active infection at screening including positive result for active tuberculosis 
(TB) (i.e. positive QuantiFERON® test result without any prior history of active nor latent TB infection 
and without evidence of active infection) where the subject has not completed prophylactic treatment.  
18. Any co-morbidity that the investigator believes is a contraindication to study participation. This 
includes, but is not limited to, any respiratory (e.g., pulmonary fibrosis, eosinophilic granulomatosis 
with polyangiitis, allergic bronchopulmonary aspergillosis), cardiovascular, gastrointestinal, 
hematological, neurological, immunological, musculoskeletal, renal, infectious, neoplastic, or 
inflammatory condition that may place the safety of the subject at risk during the study, impact results 
of the study or their interpretation, or prevent subject from completing the study. 
19. Comorbid asthma when: 
a) Forced expiratory volume (FEV1)  60% of predicted normal as assessed on Day 1 and defined by 
the Global Lung Initiative (GLI) 
b) An exacerbation requiring systemic (oral and/or parenteral) corticosteroid treatment or 
hospitalization (> 24 hours) for treatment of asthma within 3 months prior to screening. 
c) A daily dose higher than 1000 g fluticasone or the equivalent of inhaled corticosteroids. 
20. Have any other physical, mental, or medical condition that, in the opinion of the investigator, makes 
study participation inadvisable or could confound study assessments. 
21. Receipt of live attenuated vaccine within 4 weeks before screening. 
22. Planned surgery during the study or 30 days before screening. 
23. History of malignancy within 5 years, except non-melanoma skin cancer that has been fully treated 
with no current active disease. 
24. Initiation of allergen immunotherapy: 
a) Within 12 weeks prior to screening 






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Subcutaneous injection sites should be alternated among upper arms or, if necessary, the different quadrants of 
the abdomen (avoiding navel and waist areas). If possible, the same site should not be injected for 2 consecutive 
months. Study drug should be administered only into areas of normal-looking skin; if possible, Study Day 1 
(loading dose) injections should be administered in separate upper arms. If both injections are administered in 
the same area, the injections should be spaced approximately 2 inches apart. Additional detail will be located 
in the Pharmacy Manual.




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* During the screening window patients must use MFNS for a minimum of 20 days prior to Day 1 (maximum screening window is 31 days). Screening 
procedures can be conducted up to Day -1 if necessary. 
a Visit must occur 5 days (1 day) after Visit 2. 
b Inclusion/exclusion criteria are based on all screening assessments, Visit 1 nasal endoscopy, and laboratory results. Week 0/Day 1 pre-dose assessments 
are to be reviewed before enrollment. 
c 
A complete physical examination will be performed at the screening visit. All other physical examinations should be abbreviated and address associated 
complaints or findings and any other assessments required to evaluate adverse events. 
d Vital signs assessments should be performed before blood sampling and before injection of study drug at each study visit where administered. Blood 
pressure readings should be obtained after approximately 15 minutes of rest in a seated position. 
e 12-Lead ECG should be performed after 10 minutes of rest in a supine position and before the blood sample is collected. ECG must be conducted on 
ECG machine provided by ERT for the ANB020-006 clinical trial. 
f 
Follicle stimulating hormone may be used to confirm menopausal status in female subjects as needed. 
g Pregnancy testing is only required for women of childbearing potential (WOCBP). A serum test will be performed at the screening visit; urine pregnancy 
tests will be performed at treatment and follow-up visits. Testing must be performed before injection of study drug at Weeks 0, 4, 8, and 12. A negative 
result must be obtained at Visits 1 and 2 before subject may be randomized. 
h HIV 1 and 2, hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, and Mycobacterium tuberculosis (TB) will be assessed. Subjects 
with an indeterminate QuantiFERON® TB Gold result at Screening will be allowed 1 retest. 
i 
Hematology and chemistry: Blood samples will be taken before injection of study drug, after the ECG and vital signs assessments.  
j 
Subject is required to remain onsite for 2 hours post-dose for observation at Week 0 (Day 1). Subjects with any ongoing treatment-emergent AEs or 
SAEs at the time of scheduled discharge from the study center should remain at the study center until the Investigator has determined that these 
events have been resolved or deemed as not clinically significant. Subjects are not required to remain onsite after follow-up injections (Weeks 4, 8, and 
12) unless deemed necessary by the Investigator, if there have been injection site reactions, or other AEs are noted. 
k Pharmacokinetics blood samples will be collected for all subjects at the following time points:  
 
Visit 2/Week 0: prior to dosing on Day 1. 
 
Visit 3/Week 1: Visit 3 can occur 3 to 5 days after Visit 2. 
 
Week 4, 8, 12: prior to dosing. 
 
Week 16, 20, and 24: any time at each visit. 
l 
Immunogenicity blood samples will be collected for all subjects at the following time points:  
 
Visits 2 (Week 0), 4 (Week 4), 5 (Week 8), and 6 (Week 12): prior to dosing. 
 
Visits 7 (Week 16), 8 (Week 20), and 9 (Week 24): any time at each visit. 
m All subjects should have the result of FEV1 (% of predicted normal as defined by the Global Initiative for Asthma) recorded in the source on Day 1 and at 
all the other scheduled visits during the treatment period. Every effort should be made to perform FEV1 assessment at the same time at each visit. If a 
subject with active asthma’s FEV1  60% on Day 1, then the subject will not be randomized. FEV1 assessment should be conducted on the spirometry 
machine provided by ERT for the ANB020-006 clinical trial. 


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n The ePRO device will be provided to subjects on Day 1 upon confirmation of randomization. Subjects should be trained on log in and completion of 
NPIF distribution within the ePro device. The subjects should bring the ePRO device to each visit. The ePRO device should be returned to the site at the 
Week 24 (EOS) visit. Detailed instructions will be provided separately in the Procedures Manual. 
o Peak Nasal Inspiratory Flow Meters will be provided to patients during the screening visit and patients will be instructed on use and recording 
requirements. NPIF values will be recorded on a paper diary during Screening (for 1 week/7 consecutive days). Diary must be returned to the study 
coordinator at the Day 1 dosing visit. Following randomization, eDiaries will be distributed and NPIF values will be recorded directly in the device.  
p Concomitant therapy will include pharmacologic and nonpharmacologic therapies. 
q Testing must be performed before injection of study drug at Weeks 0 and 8. 
r  The ACQ-7 will be assessed only in subjects with an active asthma disease. 
s 
Optional polyp biopsies will be collected from subjects who indicate approval on ICF, in study centers with the capability to conduct the procedure. 
t 
Samples will be collected before injection of study drug on Day 1. 
u Optional sampling for exploratory analysis of DNA and RNA, requiring separate pharmacogenetic consent acknowledgment in ICF. 
V 
MFNS bottles will be distributed and used bottles collected at monthly visits to assess use. Subjects should be approximately 80% compliant with usage 
during Screening and throughout the study. During Screening subjects must complete a minimum of a 20 day run-in using MFNS prior to Day 1. 
w Endoscopy can utilize study windows to ensure procedure can be completed prior to dosing. Day 1 Endoscopy can occur up to 5 days prior to Day 1 
clinic visit. If endoscopy is performed on site it should be completed after all other study assessments are done and prior to dosing on dose days. 
X 
Day 1 CT must be collected prior to dosing on Day 1. If necessary, the Day 1 CT can be collected during Screening, prior to Day 1, however all efforts 
should be made to conduct CT after subject screening labs have been reviewed and it is determined subject is likely eligible for the study. Note: CTs 
collected within 3 months prior to randomization (Day 1) can be utilized in lieu of a new Day 1 CT if the necessary imaging requirements are present. 
y 
Day 1 spirometry should be assessed prior to randomization to ensure inclusion/exclusion criteria are met 
 
















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• 
If there is no scheduled visit/day for the analysis visit window and there is a tie between the data in the 
number of days/hours before and after the scheduled day, the later data will be used.  
The summary by visit will use “analyzed records” only ---at most one per subject per parameter. 
An unscheduled visit that does not fall under any window will remain in the database and will be included in 
the listings.  The data not flagged as the “analyzed record” will be included in subject listings. Tables 2a to 2f 
display visit windows for multiple analyses.  
Table 2a: Visit Windows for Assigning ET Visits to an Analysis Visit for Nasal Endoscopy, SNOT-22, 
QoL, Nasal Polyps Resource Questionnaire, and ACQ-7 
 
Study Period 
 
Analysis Visit 
 
Target Day 
Window 
for 
Reassignment to  Analysis 
Visit 
Baseline 
Baseline 
1 
≤1 
Treatment Period 
Week 4 
29 
2-42 
 
Week 8 
57 
43-70 
 
Week 12 
85 
71-98 
 
Week 16/EOT 
113 
99-126 
Safety Follow-up Period 
Week 24/EOS/ETV** 
169 
127-182 
 
**The last observation in the time window will be used. [This is an exception from the rule regarding closest to target.] 
Table 2b: Visit Windows for Assigning ET Visits to an Analysis Visit for Spirometry 
 
Study Period 
 
Analysis Visit 
 
Target Day 
Window for 
Reassignment to  
Analysis Visit 
Baseline 
Baseline 
1 
≤1 
Treatment Period 
Week 4 
29 
2-42 
 
Week 8 
57 
43-70 
 
Week 12 
85 
71-98 
 
Week 16/EOT** 
113 
99-126 
**The last observation in the time window will be used. [This is an exception from the rule regarding closest to target.] 
Table 2c: Visit Windows for Assigning ET Visits to an Analysis Visit for Hematology and Chemistry 
 
Study Period 
 
Analysis Visit 
 
Target Day 
Window for 
Reassignment to 
Scheduled Analysis Visit 
Baseline 
Baseline 
1 
≤1 
Treatment Period 
Week 1 
5 
2-10 
 
Week 4 
29 
11-42 
 
Week 8 
57 
43-70 
 
Week 12 
85 
71-98 
 
Week 16 
113 
99-126 
Safety Follow-up Period 
Week 24/EOS/ETV** 
169 
155-182 


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**The last observation in the time window will be used. [This is an exception from the rule regarding closest to target.] 
Table 2d: Visit Windows for Assigning PW Visits to an Analysis Visit for Immunogenicity and Vital Signs 
 
Study Period 
 
Visit 
 
Target Day 
Window for 
Reassignment to 
Scheduled Visit 
Baseline 
Baseline 
1 
≤1 
Treatment Period 
Week 4 
29 
2-42 
 
Week 8 
57 
43-70 
 
Week 12 
85 
71-98 
 
Week 16/EOT 
113 
99-126 
Safety Follow-up Period 
Week 20 
141 
127-154 
 
Week 24/EOS/ETV** 
169 
155-182 
**The last observation in the time window will be used. [This is an exception from the rule regarding closest to target.] 
 
Table 2e: Visit Windows for Assigning PW Visits to an Analysis Visit for UPSIT and Lund-MacKay 
Scores 
 
Study Period 
 
Visit 
 
Target Day 
Window for 
Reassignment to 
Scheduled Visit 
Baseline 
Baseline 
1 
≤1 
Treatment Period 
Week 8* 
57 
43-84 
 
Week 16/EOT 
113 
85-126 
*UPSIT only. Lund-MacKay score is not assessed at Week 8. 
**UPSIT and Lund-MacKay scores do allow gaps between analysis visits. 
 
Table 2f: Visit Windows for Assigning PW Visits to an Analysis Visit for EQ-VAS, Nocturnal Awakenings, 
and NPIF 
 
Study Period 
 
Visit 
 
Target Day* 
Window for 
Reassignment to 
Scheduled Visit 
Baseline 
Baseline 
1 
≤1 
Treatment Period 
Week 1 
5 
2-7 
 
Week 2 
11 
8-14 
 
Week 3 
18 
15-21 
 
Week 4 
25 
22-28 
 
… 
… 
… 
 
Week 16/EOT 
102 
99-105 
Safety Follow-up Period 
Week 20 
130 
127-133 
 
… 
… 
… 
 
Week 24/EOS/ETV** 
158 
155-161 
*Except for Week 1, Target Day for the rest weekly analysis visits is the mid-week day. 
**The last observation in the time window will be used. [This is an exception from the rule regarding closest to target.] 












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be obtained at each visit during Treatment Period (Week 4, 8, 12 and 16), and at the end of the Safety Follow-
up Period (Week 24).  
A listing of nasal endoscopy performance, nasal polyp scores, and change from baseline scores will be provided 
per visit per subject for the Full Analysis set. 
8.1.1.1. 
Definition of Estimand 
Subjects who permanently stopped the study medication are not required to withdraw from the study. Subjects 
were informed that if they decided to discontinue study medication, they had the option of providing clinic 
assessments at scheduled office visits or by phone contact until the planned end of their study visits.  
Thus, the (co)primary estimand chosen here is the de facto or treatment policy estimand, which uses the 
available on-treatment NPS values during Treatment period. The primary time point is Week 16. 
The NPS is also measured every 4 weeks during treatment and at end of treatment (Week 16). A general linear 
mixed model with repeated measures (MMRM) will be used to obtain least squares means of change in NPS at 
Week 16 from baseline, to compare the etokimab treatment arms with the placebo arm.  
Summary statistics for each time point will include n, mean, standard deviation, median, minimum, and 
maximum, for baseline, each time of measurement, and the change from baseline calculated as post-baseline 
value minus the baseline value. 
8.1.1.2. 
Primary Statistical Analysis for NPS 
Statistical analysis of this endpoint will employ a general linear model with repeated measures (also called a 
mixed model with repeated measures, MMRM), with the change from baseline in NPS as the dependent 
variable;  baseline (Day 1) NPS score as a covariate, treatment group (3 levels), stratification factor, treatment 
by stratification factor, categorical time points (Weeks 4, 8, 12 and 16) and treatment by time interaction as 
fixed effect factors, and subject as a random effect in the model.  Assuming treatment (trtpn) is coded as 
Placebo=1, Eto Q8W=2, Eto Q4W=3, and that the time variable  (weekn) is ordered as 4, 8, 12, and 16, we can 
write the SAS model of interest to be performed with SAS PROCEDURE MIXED as follows:   
PROC MIXED DATA = DATASETNAME; 
CLASS USUBJID WEEKN TRTPN STRAT; 
MODEL CFB = BASE STRAT TRTPN STRAT*TRTPN WEEKN WEEKN*TRTPN / SOLUTION DDFM=KR; 
REPEATED WEEKN / SUBJECT=USUBJID TYPE=UN; 
LSMEANS WEEKN*TRTPN / CL ALPHA=0.05; 
RUN; 
 
The (co)primary hypothesis to be tested for this estimand is that treatment of adults diagnosed with CRSwNP 
using etokimab will result in a significantly greater reduction of Week 16 NPS from baseline when compared 
to placebo. 
This hypothesis will be tested by comparing the least squares adjusted means for each etokimab dose group 
with placebo, at the week 16 time point.  Comparison of each treatment arm with placebo will be based on the 
change in least squares means at Week 16 obtained from the MMRM. Testing will be conducted in a hierarchical 
manner such that the comparison of the etokimab Q4W treatment arm versus placebo will be conducted first. 


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If the results of the comparison of the eetokimab Q4W treatment arm versus placebo are statistically significant, 
the etokimab Q8W treatment arm will be compared to placebo.  
While the treatment group means at each visit are estimated by the model, the standard deviations are nuisance 
parameters and must also be estimated in order to carry out the hypothesis tests and/or obtain confidence interval 
estimates for means and contrasts.  An unstructured covariance matrix will be assumed and estimated in order 
to obtain associated standard errors for least squares means and to carry out the treatment comparisons. In case 
the model does not converge with the unstructured covariance structure, the heterogeneous Toeplitz structure 
(TOEPH) will be used instead. In case the model will not converge with the heterogeneous Toeplitz structure, 
heterogeneous compound symmetry (CSH) will be used instead. The denominator degrees of freedom will be 
computed using the Kenward-Roger method. 
The p-value for the comparison will be obtained and compared to the significance level of 5%, two-sided. An 
associated 2-sided 95% confidence interval will be obtained for the active minus placebo change from baseline 
to week 16 in the NPS for each treatment arm tested. Comparison of multiple treatment groups versus placebo 
will be performed in a hierarchical manner so further adjustment will not be made for testing each dosing 
regimen with placebo. Statistical significance (two-sided p-value < 0.05) for a treatment contrast will be taken 
to infer a difference in efficacy versus placebo for that etokimab dosing regimen. The direction of difference 
will determine whether that dosing regimen of etokimab is better or worse than the placebo group at that 
specified level of significance. 
Graphical displays of the results will be presented. The (by-time point) least squares means and two-sided 95% 
confidence intervals for each treatment will be plotted against time, and the p-values for the Week 16 
comparisons will be displayed on the Week 16 time point.  
8.1.1.3. 
Supplementary Statistical Analysis for NPS 
In order to assess the impact of missing data due to dropouts on the inference for the co-primary endpoints, a 
sensitivity analysis will be performed in 2 ways. First, NPS data after dropout will be imputed using multiple 
imputation and the statistical analysis using MMRM will be repeated. Multiple imputation analyses will be 
performed based on both Missing at Random (i.e. the missing data are assumed to follow the same model as 
the other patients in their respective treatment arm) and Missing Not at Random assumptions. Second, an 
ANCOVA will be performed only for the subjects who have completed Week 16 assessment (ie., completers 
analysis). 
MI analysis with Missing at Random (MAR) assumption: In the analysis of each of the co-primary 
endpoints, subjects with missing data at post-baseline visits will have data imputed using multiple imputation 
(MI) methodology using the total study sample. MI will be performed under the assumption of MAR. 
Intermittent missing value(s) will also be replaced using MI. MI will impute 10 integer values using Markov 
Chain Monte Carlo (MCMC) methods assuming nonmonotone missing, a pre-specified seed number, 500 
burn-in iterations, 100 iterations between imputations, and a non-informative prior. The imputation models 
based on all subjects (regardless of treatment group) will include the randomization stratification factor, the 
baseline value of the endpoint, and all previous values of the endpoint at each time point. Results from the 
analysis of each of the 10 imputed datasets will be combined using Rubin’s imputation rules (Rubin 1987) to 
produce a pooled least squares mean (LSM) estimate of treatment difference. 












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For the PCS and MCS separately, the change from baseline  at Weeks 4, 8, 12 and 16 will be modeled using an 
MMRM with baseline SF-36 as covariate, treatment group (3 levels), stratification factor, treatment by 
stratification factor, categorical time point (Weeks 4, 8, 12 and 16) and treatment by time interaction as fixed 
effect factors, and subject as a random effect. Treatment comparisons will be based on the week 16 least squares 
means and standard errors. Associated 95% confidence limits for the LS means and the p-value for comparison 
of each etokimab dose group with the Placebo group will be displayed.  
8.3.1.2. 
European Quality of Life Scale (EQ-5D) 
The impact of CRSwNP on the quality of life of the patient will be assessed using the EQ-5D questionnaire. 
This questionnaire has two components: health state description and evaluation.  
In the description part, the EQ-5D-5L health questionnaire is a health-related quality of life instrument with 5 
dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 
5 possible levels: no problems, slight problems, moderate problems, severe problems and extreme problems.  
The summary of results will follow the EQ-5D-5L guidelines for results presentation. For the “Health Profiles” 
descriptive system summary results will show the number, and proportion (%) of subjects in each Item score 
(No Problems, Slight Problems, Moderate Problems, Severe Problems, Extreme Problems) by treatment at 
baseline and at each visit (Weeks 4, 8, 12, and 16).  
No formal statistical testing will be carried out for the EQ-5D-5L. 
In the evaluation part, the EQ-VAS measures overall self-rated health status on a 0-100 scale, with 0=worst 
health you can imagine and 100=best health you can imagine.  Thus higher scores are suggestive of better health 
status.  
Summary statistics will be presented for the EQ-VAS score showing number of subjects, mean, standard 
deviation, median, minimum and maximum for each treatment group at baseline and each visit (Weeks 4, 8, 12 
and 16), and change from baseline.  
An MMRM with the baseline EQ-VAS score as covariate, and treatment (3 levels), stratification factor, 
treatment by stratification factor, categorical time point (Weeks 4, 8, 12, and 16), and treatment by time 
interaction as fixed effect factors, and subject as a random effect will be used to obtain least squares estimates 
for the change from baseline in EQ-5D VAS score in Week 16 for each treatment group.  Each etokimab dose 
group will be compared to the Placebo group using the Week 16 least squares means and standard errors 
obtained from the model.  Associated 95% confidence limits for the LS means and p-values for the treatment 
comparisons will be displayed. 
8.3.1.3. 
Patient Related Rhinosinusitis Severity Using Visual Analog Scale (VAS) 
The Visual Analogue Scale (VAS) for rhinosinusitis is used to evaluate the total severity. The patient is asked 
to indicate on a continuous scale (VAS) the answer to the question: “How troublesome are your symptoms of 
rhinosinusitis?” The VAS score ranges from 0 (Not troublesome) to 10 (Worst thinkable troublesome).  
The disease severity can be divided into MILD, MODERATE and SEVERE based on total severity visual 
analogue scale (VAS) score (0 to 10 cm): 






























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2. A negative pre-dose immunogenicity assessment and a confirmed positive immunogenicity response 
after dosing. 
3. A positive pre-dose immunogenicity assessment and a confirmed positive immunogenicity response 
after dosing. 
Observed values for ADA levels/status and the neutralizing antibody levels/status will be listed by subject and 
summarized with descriptive statistics based on the Safety Analysis Set. The frequency and percentage of 
confirmed positive immunogenicity response will be summarized by treatment groups.  If data permits, 
correlation will be assessed between ADA levels and safety and efficacy endpoints.  
Titer values will be summarized by treatment using mean and median. The frequency and percentage of patients 
with categorical result assessments will be summarized by treatment groups at each available visit and time 
point. 










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2 
25 
 
3 
50 
 
4 
75 
 
5 
100 
*Precoded response choices as printed in the questionnaire 
 
Scoring the SF-36: Step 2 – Averaging Items to Form Scales 
Scale 
Number of 
Items 
After recoding average the 
following items 
Item numbers on 
original questionnaire 
Physical functioning 
10 
3, 4, 5, 6, 7,8, 9, 10, 11, 12 
Qu. 3 a-j 
Role limitations due to 
physical health 
4 
13, 14, 15, 16 
Qu. 4 a-d 
Role limitations due to 
emotional health 
3 
17, 18, 19 
Qu. 5 a-c 
Energy/fatigue 
4 
23, 27, 29, 31 
Qu. 9 a, e, g, i 
Emotional well-being 
5 
24, 25, 26, 28, 30 
Qu. 9 b, c, d, f, h 
Social functioning 
2 
20, 32 
Qu. 6; Qu. 10 
Pain 
2 
21, 22 
Qu. 7; Qu.8 
General health 
5 
1, 33, 34, 35, 36 
Qu. 1; Qu. 11 a-d