Conditions: Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP) Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)
Keywords: GB001 Gossamer Bio Gossamer Nasal Polyposis CRSwNP CRSsNP
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 97
Healthy volunteers: no

Brief summary:
A Phase 2a, randomized, double-blind, placebo-controlled, multi-center study to evaluate the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of GB001 compared with placebo over 16 weeks of treatment in patients with chronic rhinosinusitis with or without nasal polyposis (NP).

Detailed description:

Arms:
arm 1: GB001 40 mg once per day (QD) for 16 weeks arm 2: Placebo QD for 16 weeks

Interventions: intervention 1: GB001 intervention 2: Placebo
Intervention descriptions: intervention 1: film-coated oral tablet intervention 2: film-coated oral tablet

Protocol document:
Prot_000.pdf: 
GB001, Inc. 
GB001 
Protocol GB001-2101 
Version 5.0, 16 Apr 2020 
1 
CONFIDENTIAL 
CLINICAL STUDY PROTOCOL 
Protocol Title:  
A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Multi-
Center Study to Evaluate the Effect of GB001 in Patients with Chronic 
Rhinosinusitis with or without Nasal Polyps 
Protocol Number:  
GB001-2101 
Compound Number:  
GB001 
Study Phase:  
Phase 2a 
Short Title: 
Sponsor Name: 
GB001 in Adult Subjects with Chronic Rhinosinusitis 
GB001, Inc., a wholly owned subsidiary of Gossamer Bio, Inc. 
Legal Registered 
Address: 
3013 Science Park Road, Suite 200 
San Diego, CA 92121, USA 
Regulatory Agency 
Identifier Number: 
 
 
EudraCT:          2019-001682-33 
 
Version: 
5.0 
Approval Date: 
16 April 2020 
 
Confidential 
This document contains proprietary and confidential information of GB001, Inc. Acceptance of 
this document constitutes agreement by the recipient that no previously unpublished information 
contained herein will be published or disclosed without the prior written approval of GB001, 
Inc. The following exceptions may occur under the condition that the party has agreed to keep 
this information confidential: 1) disclosure of information to the extent necessary to obtain 
informed consent, 2) disclosure of the document to study personnel under your supervision who 
need to know the contents for conducting the study, and 3) disclosure of the document to 
appropriate Institutional Review Boards (IRBs)/Independent Ethics Committees (IEC). The 
foregoing shall not apply to disclosure required by governmental regulations or laws; however, 
GB001, Inc. shall be promptly notified of any such disclosure. 


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SPONSOR’S AUTHORIZED REPRESENTATIVE SIGNATURE PAGE 
 
 
 
 
 
 
 
Gossamer Bio Services, Inc. on behalf of GB001, Inc, 
a wholly owned subsidiary of Gossamer Bio, Inc. 
 
Medical Monitor name and contact information will be provided separately. 
 


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INVESTIGATOR AGREEMENT 
GB001-2101: A Phase 2a, randomized, double-blind, placebo-controlled, multi-center study to 
evaluate the effect of GB001 in patients with chronic rhinosinusitis with or without nasal polyps 
I, the undersigned, have read this protocol and agree to conduct this protocol in accordance with 
ethical principles as outlined in the International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use (ICH) guidelines on Good Clinical Practice, 
any applicable laws and requirements and any additional conditions mandated by a regulatory 
authority and/or Institutional Review Board/Independent Ethics Committee (IRB/IEC). 
I acknowledge that I am responsible for the overall study conduct and I agree to personally 
conduct or supervise the described clinical study. 
I agree to ensure that the confidential information contained in this document will not be used for 
any purpose other than the evaluation or conduct of the clinical investigation without the prior 
written consent of GB001, Inc. 
 
 
 
 
 
Signature 
 
 
 
Name of Investigator 
 
Date 




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Section # and Name  
Description of Change  
Brief Rationale  
the risks to trial integrity during 
the COVID-19 pandemic 
Global Change 
Minor revisions to text 
Administrative clarifications were 
incorporated, and typographical 
errors were corrected 


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TABLE OF CONTENTS 
SPONSOR’S AUTHORIZED REPRESENTATIVE SIGNATURE PAGE ...................................2 
INVESTIGATOR AGREEMENT...................................................................................................3 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................4 
1. 
PROTOCOL SUMMARY ..........................................................................................11 
1.1. 
Synopsis ......................................................................................................................11 
1.2. 
Schema ........................................................................................................................13 
1.3. 
Schedule of Activities .................................................................................................14 
2. 
INTRODUCTION ......................................................................................................18 
2.1. 
Study Rationale ...........................................................................................................18 
2.2. 
Background .................................................................................................................18 
2.3. 
Benefit/Risk Assessment ............................................................................................19 
2.3.1. 
GB001 Benefit/Risk Assessment ................................................................................19 
2.3.2. 
Study Design Benefit/Risk Assessment ......................................................................20 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................21 
4. 
STUDY DESIGN .......................................................................................................23 
4.1. 
Overall Design ............................................................................................................23 
4.1.1. 
Study Design ...............................................................................................................23 
4.1.2. 
Unscheduled Visit .......................................................................................................24 
4.2. 
Scientific Rationale for Study Design ........................................................................24 
4.2.1. 
Study Population .........................................................................................................24 
4.2.2. 
Choice of Control Group ............................................................................................25 
4.2.3. 
Efficacy Endpoint Selection .......................................................................................25 
4.3. 
Justification for Dose ..................................................................................................25 
4.4. 
End of Study Definition ..............................................................................................25 
5. 
STUDY POPULATION .............................................................................................26 
5.1. 
Inclusion Criteria ........................................................................................................26 
5.2. 
Exclusion Criteria .......................................................................................................26 
5.3. 
Randomization Criteria ...............................................................................................29 
5.4. 
Screen or Run-In Failures ...........................................................................................30 
6. 
INVESTIGATIONAL PRODUCT ............................................................................30 
6.1. 
Investigational Product Administered ........................................................................30 


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6.2. 
Preparation/Handling/Storage/Accountability ............................................................31 
6.3. 
Randomization and Blinding ......................................................................................31 
6.3.1. 
Randomization ............................................................................................................31 
6.3.2. 
Assignment of Investigational Product Bottle Numbers ............................................31 
6.3.3. 
Unblinding of an Individual Subject ...........................................................................31 
 
 
6.4. 
Investigational Product Compliance ...........................................................................32 
6.5. 
Concomitant Therapy .................................................................................................33 
6.5.1. 
Prohibited and Restricted Medications Prior to the Screening Visit and 
Throughout the Study .................................................................................................33 
6.6. 
Dose Modification ......................................................................................................33 
6.7. 
Intervention After the End of the Study .....................................................................33 
7. 
DISCONTINUATION OF INVESTIGATIONAL PRODUCT AND 
SUBJECT DISCONTINUATION/WITHDRAWAL ................................................33 
7.1. 
Discontinuation of Investigational Product ................................................................33 
7.1.1. 
Pregnancy ...................................................................................................................34 
7.1.2. 
Liver Safety ................................................................................................................34 
7.2. 
Subject Withdrawal from the Study ...........................................................................34 
7.3. 
Lost to Follow-up .......................................................................................................35 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................35 
8.1. 
Efficacy Assessments .................................................................................................37 
8.1.1. 
SNOT-22 .....................................................................................................................37 
8.1.2. 
Computer Tomography (CT) ......................................................................................38 
8.1.3. 
Bilateral Endoscopic Nasal Polyp Score ....................................................................38 
8.1.4. 
Disease-specific, Daily Symptom Assessments .........................................................39 
8.1.5. 
Smell Test: University of Pennsylvania Smell Identification Test (UPSIT) ..............39 
8.1.6. 
CRS Exacerbation .......................................................................................................40 
8.1.7. 
Visual Analog Scale (VAS) ........................................................................................40 
8.1.8. 
Nitric Oxide Measurement .........................................................................................40 
8.1.9. 
Other Assessments ......................................................................................................40 
8.2. 
Safety Assessments .....................................................................................................41 
8.2.1. 
Physical Examinations ................................................................................................41 
8.2.2. 
Vital Signs ..................................................................................................................41 


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8.2.3. 
Electrocardiograms .....................................................................................................41 
8.2.4. 
Clinical Safety Laboratory Assessments ....................................................................41 
8.3. 
Adverse Events, Serious Adverse Events, and Adverse Events of Interest ................42 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE Information .......................42 
8.3.2. 
Method of Detecting AEs and SAEs ..........................................................................42 
8.3.3. 
Follow-up of AEs and SAEs .......................................................................................43 
8.3.4. 
Regulatory Reporting Requirements for SAEs ...........................................................43 
8.3.5. 
Pregnancy ...................................................................................................................43 
8.3.6. 
Death Events ...............................................................................................................43 
8.3.7. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as 
AEs or SAEs ...............................................................................................................43 
 
 
8.4. 
Treatment of Overdose ...............................................................................................44 
8.5. 
Pharmacokinetics ........................................................................................................44 
8.6. 
Pharmacodynamics and Biomarkers...........................................................................45 
8.6.1. 
Nasal Biomarker Sample ............................................................................................45 
8.6.2. 
Blood Biomarker Analyses .........................................................................................45 
8.6.3. 
RNA Transcriptome Research ....................................................................................45 
 
 
8.7. 
Pharmacogenetics .......................................................................................................46 
9. 
STATISTICAL CONSIDERATIONS .......................................................................46 
9.1. 
Statistical Hypotheses .................................................................................................46 
9.2. 
Sample Size Determination ........................................................................................46 
9.3. 
Populations for Analyses ............................................................................................46 
9.4. 
Statistical Analyses .....................................................................................................47 
9.4.1. 
Efficacy Analyses .......................................................................................................47 
9.4.1.1. 
Primary Efficacy Analysis ..........................................................................................47 
9.4.1.2. 
Secondary Efficacy Analysis ......................................................................................47 
9.4.2. 
Safety Analyses ..........................................................................................................48 
9.5. 
Interim Analyses .........................................................................................................48 
10. 
APPENDICES ............................................................................................................49 
10.1. 
Appendix 1:  Regulatory, Ethical, and Study Oversight Considerations (site 
responsibilities) ...........................................................................................................49 


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10.1.1. 
Regulatory and Ethical Considerations ......................................................................49 
10.1.2. 
Informed Consent Process ..........................................................................................49 
10.1.3. 
Data Protection ...........................................................................................................50 
10.1.4. 
Dissemination of Clinical Study Data ........................................................................50 
10.1.5. 
Data Quality Assurance ..............................................................................................50 
10.1.6. 
Source Documents ......................................................................................................51 
10.1.7. 
Study and Site Closure................................................................................................51 
10.1.8. 
Publication Policy .......................................................................................................52 
10.2. 
Appendix 2:  Clinical Laboratory Tests ......................................................................53 
10.3. 
Appendix 3:  Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow up, and Reporting ........................................................................55 
10.3.1. 
Definition of AE .........................................................................................................55 
10.3.2. 
Definition of SAE .......................................................................................................56 
10.3.3. 
Adverse Events of Interest ..........................................................................................56 
10.3.4. 
Recording and Follow Up of Adverse Events and Serious Adverse Events ..............57 
10.3.5. 
Reporting of SAEs ......................................................................................................59 
10.4. 
Appendix 4:  Contraceptive Guidance and Collection of Pregnancy 
Information .................................................................................................................60 
10.5. 
Appendix 5:  Genetics ................................................................................................64 
10.6. 
Appendix 6:  Liver Safety - Actions and Follow-up Assessments .............................65 
10.7. 
Appendix 7:  Visual Analog scale (VAS) ...................................................................68 
10.8. 
Appendix 8:  ACQ-5 Questionnaire ...........................................................................69 
10.9. 
Appendix 9:  SNOT-22 Questionnaire .......................................................................72 
10.10. 
Appendix 10:  Prohibited and Restricted Medications and Treatments .....................74 
10.11. 
Appendix 11:  Guidance to Address a Pandemic or Other Global Health 
Emergencies and Potential Impact on the Clinical Study ...........................................79 
10.12. 
Appendix 12:  Abbreviations ......................................................................................80 
10.13. 
Appendix 13: Protocol Amendment History ..............................................................83 
11. 
REFERENCES ...........................................................................................................91 
 


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LIST OF TABLES 
Table 1: 
Investigational Product Formulation by Treatment Group .........................................30 
Table 2: 
Endoscopic Nasal Polyp Score ...................................................................................39 
Table 3: 
Protocol-Required Safety Laboratory Assessments ...................................................53 
Table 4: 
Liver Safety Laboratory Assessments ........................................................................54 
Table 5: 
Liver Chemistry Criteria Requiring Additional Monitoring with Possible 
Interruption of Investigational Product .......................................................................65 
Table 6: 
Liver Chemistry Criteria Requiring Investigational Product Interruption and 
Additional Monitoring ................................................................................................66 
Table 7: 
Prohibited Medications and Treatments .....................................................................74 
Table 8: 
Restricted Medications Associated with an Increased Risk of Liver Injury ..............75 
Table 9: 
Prohibited Medications Associated with CYP3A4 Induction or Inhibition ...............76 
Table 10: Prohibited Food and Herbal Supplements Associated with CYP3A4 
Induction or Inhibition ................................................................................................78 
 


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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A Phase 2a, randomized, double-blind, placebo-controlled, multi-center study to 
evaluate the effect of GB001 in patients with chronic rhinosinusitis with or without nasal polyps 
Short Title: GB001 in adult subjects with chronic rhinosinusitis 
Rationale: 
GB001 is a highly potent and selective oral prostaglandin D2 receptor (DP2) antagonist. DP2 is 
expressed on a variety of cells implicated in the allergic process including eosinophils, basophils, 
and epithelial cells (Kupczyk, 2017; Singh, 2017) as well as Group 2 innate lymphoid cells 
(ILC2) and T Helper cell type 2 (Th2) cells (Kato, 2019). GB001 is being developed as a once-
daily oral add-on maintenance treatment for patients with moderate to severe eosinophilic asthma 
and related diseases. 
The purpose of this Phase 2a study is to evaluate the efficacy, safety, pharmacokinetics (PK), 
and pharmacodynamics (PD) of GB001 compared with placebo in patients with chronic 
rhinosinusitis with or without bilateral nasal polyps (NP).  




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Overall Design: 
This is a Phase 2a, randomized, double-blind, placebo-controlled, multi-center study to evaluate 
GB001 in patients with chronic rhinosinusitis with or without bilateral nasal polyps (NP). 
A schematic of the study design is presented in Section 1.2. All subjects will be maintained on a 
stable background therapy of mometasone furoate nasal spray for the duration of the study. 
Number of Subjects: 
This study will randomize approximately 100 subjects, with approximately 50 per treatment 
group. Approximately 64 subjects will have presence of nasal polyps (chronic rhinosinusitis with 
nasal polyps [CRSwNP]), and approximately 36 subjects will have absence of bilateral NP 
(chronic rhinosinusitis without nasal polyps [CRSsNP]). 
Intervention Groups and Duration: 
Treatment groups: 
• GB001 40 mg once per day (QD)  
• Matching placebo once per day (QD) 
Total duration for study participation per subject is 24 weeks (includes a Screening visit; 
followed by up to 4-weeks Run-in period to allow for collection of baseline Diary data; 
a 16-week Double-Blind, Placebo-Controlled period; and 4-week Follow-up period). 
Independent Data Monitoring Committee (IDMC): No 
 
1.2. 
Schema 
 
 
Note: Randomization will be stratified by country, the presence or absence of NP (CRSwNP and CRSsNP), and the 
presence or absence of comorbid asthma among CRSwNP subjects. The CRSwNP stratum will consist of 
approximately 64 subjects, and the CRSsNP stratum will consist of approximately 36 subjects.  






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Procedure 
Screening Visit 
Randomization 
 
 
Double-Blind 
Placebo-
Controlled Period 
Early Withdrawal 
from Study 
Early 
Discontinuation of 
IP 
Follow-up 
(after W16 or EW 
from study) 
Notes 
Visit  
1 
2 
2.5 
3 
3.5 
4 
4.25 
4.5 
5 
6 
7 
If 
needed 
If 
needed 
Follow    
up 
 
Week 
-4 to -2 
0 
1 
2 
3 
4 
5 
6 
8 
12 
16 
If 
needed 
If 
needed 
20 or 
as 
needed 
Every visit window +/- 3 days 
(except for visit 3 which is +/- 2 
days); The Screening period 
includes up to a 4 weeks Run-in 
period 
Hematology with differential 
X 
X
* 
 
 
 
 
 
 
X 
 
X 
X 
X 
X 
See Appendix 2 (Section 10.2).  
Coagulation test (INR only) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
See Appendix 2 (Section 10.2). 
*Includes INR at Visit 2 
Hepatitis B surface antigen and 
Hepatitis C antibody 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
If Hepatitis C test is positive or 
indeterminant, a confirmatory 
test will be reflexively performed 
to confirm the results. 
Clinical chemistry  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
See Appendix 2 (Section 10.2), 
Table 4 and Appendix 6 
(Section 10.6). Includes total bile 
acids at every visit.  
If ALP > 1xULN, include 
fractionation of ALP  
Urinalysis 
X 
 
 
 
 
 
 
 
 
 
X 
X 
X 
 
See Appendix 2 (Section 10.2). 
Nasal mucosal lining fluid sample  
 
X 
 
 
 
 
 
 
X 
 
X 
X 
X 
 
See Section 8.6.1.  
Pharmacokinetic (PK) sample 
 
 
 
 
 
X 
 
 
 
X 
X 
X 
X 
 
Subject to record time of last 
morning dose taken at home prior 
to Week 4, 12, and 16 visits. For 
Week 4, 12, and 16 visits, subject 
to bring the dose to clinic to be 
taken after the PK blood draw. 
See Section 8.5. At Week 4 visit, 
an additional PK sample will be 
taken at approximately 2.5 hours 
post-dose. 
Biomarker sample (blood, urine) 
 
X 
 
 
 
 
 
 
X 
 
X 
X 
X 
 
See Sections 8.6.2 and 8.6.3.  
RNA transcriptome research 
 
X 
 
 
 
 
 
 
 
 
X 
X 
X 
 
See Section 8.6.3.  


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Procedure 
Screening Visit 
Randomization 
 
 
Double-Blind 
Placebo-
Controlled Period 
Early Withdrawal 
from Study 
Early 
Discontinuation of 
IP 
Follow-up 
(after W16 or EW 
from study) 
Notes 
Visit  
1 
2 
2.5 
3 
3.5 
4 
4.25 
4.5 
5 
6 
7 
If 
needed 
If 
needed 
Follow    
up 
 
Week 
-4 to -2 
0 
1 
2 
3 
4 
5 
6 
8 
12 
16 
If 
needed 
If 
needed 
20 or 
as 
needed 
Every visit window +/- 3 days 
(except for visit 3 which is +/- 2 
days); The Screening period 
includes up to a 4 weeks Run-in 
period 
Pharmacogenetic sample 
 
X
* 
 
 
 
* 
 
 
* 
* 
* 
 
 
 
* If consent provided, sample 
can be collected at any visit 
post-randomization or any bio-
sample used for this purpose; see 
Section 8.7.  
Other Administrative Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dispense investigational product (IP) 
 
X 
 
 
 
X 
 
 
X 
X 
 
 
 
 
If subject discontinues IP, but 
stays on study, do not dispense IP 
at subsequent visits (Section 7.1). 
Collect used IP/conduct accountability 
 
 
 
 
 
X 
 
 
X 
X 
X 
X 
 
 
 
Dispense MFNS for use as background 
therapy 
X 
X 
 
 
 
X 
 
 
X 
X 
X 
 
 
 
 
Instruct subjects on Diary use, if all 
screening eligibility criteria are met 
 
 
<============================> 
Eligible subjects enter the Run-in 
period and complete morning and 
evening Diary until Week 20. 
Review Diary 
 
X 
 
X 
 
X 
 
 
X 
X 
X 
X 
X 
X 
 
Complete eCRF 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Abbreviations:  CRS = chronic rhinosinusitis; CT = computed tomography; eCRF = electronic case report form; EW = early withdrawal; 
IP =investigational product; MFNS = mometasone furoate nasal spray; RNA = ribonucleic acid. 


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2. 
INTRODUCTION 
2.1. 
Study Rationale 
GB001 is a highly potent and selective oral prostaglandin D2 receptor (DP2) antagonist. DP2 is 
expressed on a variety of cells implicated in the allergic process including eosinophils, basophils, 
and epithelial cells (Kupczyk, 2017; Singh, 2017) as well as Group 2 innate lymphoid cells 
(ILC2) and T Helper cell type 2 (Th2) cells (Kato, 2019). GB001 is being developed as a once-
daily oral add-on maintenance treatment for patients with moderate to severe eosinophilic asthma 
and related diseases, and for patients with chronic rhinosinusitis with or without nasal polyps 
(NP). 
The purpose of this study is to evaluate the efficacy, safety, pharmacokinetics (PK), and 
pharmacodynamics (PD) of GB001 compared with placebo in patients with chronic 
rhinosinusitis with or without bilateral NP. 
2.2. 
Background 
Chronic rhinosinusitis (CRS) is defined as any inflammatory condition of the paranasal sinuses 
and associated nasal mucosa for more than 12 weeks (Fokkens, 2007). The loss of epithelial 
barrier function plays an essential role in the pathogenesis of CRS, with the loss of tight 
junctions permitting access to the sinus stromal tissue by allergens, bacteria, and bacteria-derived 
antigens. Clinical symptoms include nasal obstruction and congestion, reduction in or loss of 
sense of smell, anterior and posterior rhinorrhea, and facial pain. These symptoms can impact 
greatly upon a patient’s quality of life. 
Current recommendations for phenotyping CRS are based on the presence of nasal polyps 
(chronic rhinosinusitis with nasal polyps [CRSwNP]) or absence of nasal polyps (chronic 
rhinosinusitis without nasal polyps [CRSsNP]) (Fokkens, 2007). In a multinational study 
undertaken by the Global Allergy and Asthma European Network, the total prevalence of 
CRSwNP and CRSsNP has been estimated at 15.5% and 10.9% in the USA and Europe, 
respectively (Collins, 1997; Hastan, 2011). Patients with CRSwNP and comorbid asthma (~30%) 
have a poor therapeutic response and a high recurrence rate, and their disease tends to be more 
resistant to treatment (Thomas, 2008; Fokkens, 2007).  
Within the group of patients with aspirin sensitivity, nasal polyps are found in 36% to 60% of 
patients. Patients with aspirin sensitivity, asthma, and NP, also known as aspirin-exacerbated 
respiratory disease (AERD), are usually non-atopic and the disease prevalence increases over the 
age of 40 years. Notably, these patients have an increased expression of DP2 (Rothenberg, 2017). 
Eicosanoid changes in paranasal sinus diseases, including AERD, are generally characterized by 
an up-regulation of cysteinyl leukotrienes (CysLTs), lipoxin A4 (LXA4), and prostaglandin D2 
(PGD2) and a down-regulation of cyclooxygenase 2 (COX-2) and prostaglandin E2 (PGE2).  
Classification of CRS by nasal polyp phenotype is based on the observation that nasal polyp 
disease is more likely to be associated with an eosinophil-mediated Th2-high (IL-4, IL-5, 
and IL-13) cytokine profile. In contrast, CRSsNP is thought to present as a non-eosinophilic 
disease (Crombruggen, 2011). Emerging data, however, suggest that NP status alone can often 
be inadequate for defining a Th2-high/IL-5–high eosinophilic phenotype (Tan, 2017). The Tan 


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study examined tissue concentrations of IL-5 and eosinophil cationic protein (ECP) as surrogate 
markers for tissue eosinophilia. While values were significantly greater in patients with 
CRSwNP, there was extensive overlap in ECP concentrations between patients with and without 
NPs. Similarly, in a cluster analysis, expression of IL-5 in patients with CRS was identified in 
clusters with and without NPs (Tomassen, 2016).  
Within these two groups, CRSwNP and CRSsNP, patients with an eosinophilic phenotype, 
eosinophilic CRS (eCRS) have a subtype of chronic sinusitis that is thought to occur secondary 
to chronic and systemic eosinophil activation. Patients with eCRS show overlapping mechanisms 
for eosinophilia and tend to have a poor response to medical and surgical management 
(Ferguson, 2004). In a recent cross-sectional study of adult patients with CRS (N = 345) 
undergoing endoscopic sinus surgery, eCRS was defined by histopathological assessment 
showing > 10 eosinophils/high-power field on sinus mucosal biopsy. Blood tests were performed 
preoperatively and assessed for a full blood count including eosinophils as well as markers of 
inflammation and atopy. Comparisons between eCRS and non-eCRS patients were performed. 
Among all cases with CRS, 60% were identified as eCRS, of which 41% had asthma and 47% 
had nasal polyps. Receiver operating characteristic (ROC) curve analysis predicted high tissue 
eosinophilia at blood eosinophil levels ≥ 240 cells/μL (sensitivity 70.9%, specificity 78.4%, area 
under the curve [AUC]: 0.792, p < 0.01). There was no association with other markers of 
inflammation and atopy (Ho, 2018). 
Evidence from treatment with biologics inhibiting Type 2 inflammation have demonstrated 
clinical benefits in patients with CRSwNP (Bachert, 2017; Bachert, 2016). The treatment effect 
of GB001 has been demonstrated in patients with asthma and particularly Type 2 inflammation. 
Specifically, in a Phase 2 study in Japanese subjects (Study PTR-36-201), GB001 reduced 
asthma worsening (32.7%, GB001 5 mg; 20.8%, GB001 20 mg) compared with placebo 
(52.8%, p < 0.05 for both dose levels). This effect was enhanced in subjects with eosinophils 
≥ 300 cells/μL.  
In a recent post-hoc analysis of 36 subjects with mild to moderate atopic asthma receiving a total 
daily dose of fluticasone propionate ≤ 500 μg or equivalent, who were randomized (2:1) to 30 
mg of GB001 or placebo once daily for 28 days, lung function was analyzed by baseline 
fractional exhaled nitric oxide (FeNO, < 35 and ≥ 35 ppb) and blood eosinophil (< 250 and ≥ 
250/µL) subgroups (Ortega, 2019; Skolnick, 2019). In the overall population, GB001 had an 
effect on forced expiratory volume in 1 second (FEV1) at Day 28 (difference in mean change for 
GB001 versus placebo of 102 mL, n = 36). Changes in FEV1 were also observed in the high 
baseline FeNO (n=14) and high baseline eosinophil (n=11) subgroups (differences of 207 mL 
and 133 mL, respectively). These results suggest that GB001 influences lung function in subjects 
with markers of eosinophilic inflammation. 
It is anticipated that GB001 has the potential to provide clinical benefit in patients with 
eosinophilic chronic rhinosinusitis. 
2.3. 
Benefit/Risk Assessment 
2.3.1. 
GB001 Benefit/Risk Assessment 
GB001, an oral DP2 antagonist, is being developed as a controller therapy in asthma. The clinical 
development of GB001 includes 9 completed clinical studies and 2 ongoing clinical studies. 


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As of 29 August 2019, a total of 459 subjects have received at least 1 dose of GB001 at any dose 
level. Of these, 98 subjects received a single dose of GB001 ranging from 1 mg to 200 mg, and 
361 subjects received multiple doses from 5 mg to 160 mg. Of the 361 subjects who received 
multiple doses, about half (n = 159) were subjects with asthma in the completed Phase 2 studies 
who received either GB001 20 mg for up to 12 weeks, including 2 weeks with concurrent dosing 
of montelukast 10 mg daily (Study ADC3680-07), or GB001 22.73 mg daily for up to 4 weeks 
(Study ADC3680-04) or up to 16 weeks concurrent with ICS withdrawal and discontinuation 
(Study PTR-36-201).  
Based on evaluation of asthma worsening (Study PTR-36-201), GB001 at a 20 mg dose showed 
efficacy in the overall population and the greatest efficacy in the subgroup of patients with 
eosinophil counts ≥ 300 cells/μL. This is consistent with the current understanding of the biology 
regarding this pathway.  
As of 29 August 2019, a total of 459 subjects have received at least 1 dose of GB001 at any dose 
level. Drug induced liver injury is considered a potential risk of GB001 due to the occurrence of 
two Hy’s Law cases, one was a liver disorder (preferred term) in a healthy subject at 160 mg in 
Study PTR-36-101 and one was hepatic enzyme increased (preferred term) in Study 
GB001-2001 which remains blinded. Details are provided in the IB. Liver monitoring is critical 
for the safe management of subjects. Investigators should have a low threshold for discontinuing 
study drug with any suspicion of drug-induced liver injury. Safety will be closely monitored by 
the Sponsor.  
In a study with another DP2 antagonist (OC000459) which evaluated 35 subjects allergic to grass 
pollen, subjects were exposed to grass pollen for 6 hours on the 2nd and 8th days of treatment. 
During the first treatment period, there was a significant reduction in the total nasal symptom 
score compared with placebo (Horak, 2012). These data support the role of DP2 in upper airway 
disease and provide a foundation for potential therapeutic benefits by blocking this pathway in 
patients with upper airway inflammatory disease.  
2.3.2. 
Study Design Benefit/Risk Assessment 
This study is designed to assess the effect of GB001 on the Sino-Nasal Outcome Test-22 
(SNOT-22) in comparison to placebo. 
To minimize any potential risk to subjects, stringent criteria are utilized during screening to 
exclude subjects with a history of significant comorbidities that could impact subjects’ safety. 
All participating subjects on active or placebo will be frequently and closely monitored during 
the study with optimized standard of care.  
This study proposes to minimize the number of subjects to be exposed to GB001, while still 
being able to assess potential effects on CRS disease. Based upon the study design and the close 
monitoring from the Sponsor and/or designee, the benefits of participation in GB001-2101 
outweigh the potential risks of exposure to GB001. The study will provide the basis of a first 
benefit/risk assessment of GB001 in patients with chronic rhinosinusitis with or without bilateral 
nasal polyps.  




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Objectives 
Endpoints 
• To evaluate the effect of GB001 on 
maxillary CT opacification  
• Change from baseline to Week 16 in 
percentage of maxillary sinus volume 
occupied by disease on CT scan 
• To evaluate the effect of GB001 on 
worsening of CRS requiring the use 
of antibiotics 
• Proportion of subjects with antibiotic use due 
to worsening CRS by Week 16 
• To evaluate pharmacokinetics (PK) 
of GB001 
• Plasma concentration of GB001 
• To evaluate the effect of intervention 
on, as a function of, the 
pharmacodynamic markers (PD) 
• Correlation between baseline markers and 
safety, tolerability, and efficacy parameters  
• Change in PD markers over time 
• To evaluate the relationship between 
safety, efficacy, and exposure 
parameters and pharmacogenetics 
(PGx) 
• Correlation between baseline characteristics 
and single nucleotide polymorphisms  
• Change from baseline in safety, efficacy, 
and exposure parameters as a function of 
single nucleotide polymorphisms  
 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase 2a, randomized, double-blind, placebo-controlled, multi-center study to evaluate 
GB001 administered once a day for 16 weeks in subjects with chronic rhinosinusitis with or 
without bilateral nasal polyps. 
A schematic of the study design is presented in Section 1.2. 
4.1.1. 
Study Design 
Prior to screening, subjects must be on a stable regimen of intranasal corticosteroids (INCS) for 
≥ 2 months. If the subject is using an INCS product other than mometasone furoate nasal spray 
(MFNS) prior to the Screening visit, the Investigator must switch the subject to MFNS at the 
Screening visit. All subjects will be maintained on a stable background therapy of mometasone 
furoate nasal spray for the duration of the study. 
Screening Visit (Visit 1): Informed consent will be obtained, and inclusion and exclusion 
criteria will be assessed. Informed consent may be obtained prior to the day of the Screening 
visit to allow for medication washouts or for other logistical reasons such as obtaining 
documentation of exacerbations, if necessary. All other screening procedures should be 
completed, where possible, on the day of the Screening visit. Subjects not meeting the eligibility 
criteria will be deemed screen failures and will not continue participation in the study (see 
Section 5.4). The Run-in period commences with completion of all Screening visit procedures 
and concludes at the Randomization visit (Visit 2). During the Run-in period of up to 4 weeks, 
subjects will capture nasal symptoms and MFNS use in a Diary daily (morning and evening): 
• Subject’s treatment regimen with MFNS should remain stable. 
• 2 actuations (50 µg/actuation) in each nostril twice daily (total daily dose of 400 µg), 
unless subject is intolerant to a twice daily (BID) regimen of MFNS in which case, 
they can stay on the dose regimen in place prior to screening. 
• The only dose modification of MFNS during the Run-in period may be for subjects 
who were switched from another INCS to MFNS and need to change to a QD 
regimen due to intolerability. 
Randomization Visit (Day 1/Week 0/Visit 2): Subjects who meet the randomization eligibility 
criteria will be randomized in a 1:1 ratio to receive one of the following double-blind treatments 
for 16 weeks: 
• GB001 40 mg once per day (QD)  
• Matching placebo once per day (QD) 
Randomization will be stratified by country, the presence or absence of NP (CRSwNP and 
CRSsNP), and the presence or absence of comorbid asthma among CRSwNP subjects. Presence 
of NP is defined by a minimum NPS of 4 out of a maximum score of 8 with a score of at least 2 
for each nostril. Absence of NP is defined as an absence of NP based on visual examination or an 
NPS of 0 based on nasal endoscopy. Presence of comorbid asthma is defined as a diagnosis of 
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or prior to study entry. The CRSwNP stratum will consist of approximately 64 subjects, and the 
CRSsNP stratum will consist of approximately 36 subjects. 
Subjects will continue on mometasone furoate: MFNS two actuations in each nostril BID (or QD 
in case subject cannot tolerate the high dose) during the course of the study. 
Following initiation of investigational product (IP) at the clinic, subjects will visit the clinic 
weekly for the first 6 weeks and approximately every 4 weeks thereafter through week 20, for a 
total of 10 additional visits (refer to Schedule of Activities, Section 1.3). 
Early Discontinuation of IP and Early Withdrawal from Study: Subjects will be requested to 
attend the Early Discontinuation of IP or Early Withdrawal (EW) visit, as appropriate, and will 
be strongly encouraged to complete any remaining study visits as per the Schedule of Activities 
(SoA; Section 1.3). Subjects who permanently discontinue IP and continue in the study will 
complete the Early Discontinuation of IP visit at the time of IP discontinuation and then return 
for the next visit in the visit sequence. At the visits after the Early Discontinuation of IP visit, 
study procedures will be completed except for dispensation/return of IP. Subjects who withdraw 
early from the study, regardless of the reason, will be requested to return to the clinic to complete 
the EW visit. All subjects who remain on IP through and including Visit 7 (Week 16) or who 
complete the EW visit will be asked to return for a Follow-up visit approximately 4 weeks after 
their last dose of IP to assess subject safety. 
Follow-up Period: Subjects can continue treatment with the stable dose of MFNS maintained 
over the Double-Blind, Placebo-Controlled period, or modify treatment based on medical 
judgment.  
Total duration for study participation per subject is up to 24 weeks (includes a Screening visit, 
followed by an up to 4-weeks Run-in period to allow for collection of baseline Diary data; 
a 16-week Double-Blind, Placebo-Controlled period; and 4-week Follow-up period). 
4.1.2. 
Unscheduled Visit 
There may be a need to have a subject return to clinic for an unscheduled visit for a variety of 
reasons, including but not limited to: repeat of a lab test, replacement of IP, or evaluation of an 
AE. Any procedure that is conducted during a regularly scheduled on-treatment visit may be 
performed at an unscheduled visit. 
4.2. 
Scientific Rationale for Study Design 
4.2.1. 
Study Population 
The study population is comprised of: symptomatic CRS subjects with CRSsNP, defined as an 
absence of NP based on visual examination or an NPS of 0 based on nasal endoscopy, and 
evidence of an eosinophilic phenotype (eCRS), defined as a blood eosinophil count of  ≥ 250 
cells/μL; and symptomatic CRS subjects with CRSwNP, defined as a minimum NPS of 4 out of 
a maximum of 8, with at least a score of 2 for each nostril, as assessed by endoscopic diagnosis 
by a blinded central reader. Subjects with historical evidence of neutrophilic predominant polyp 
disease will be excluded considering that the mechanism of action of GB001 is thought to be 
linked to eosinophilic Type 2 inflammation. The overall study population will consist of 
approximately 64 CRSwNP subjects and 36 CRSsNP subjects. 


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GB001 will be administered as an additional treatment on top of a stable standard of care (SOC) 
regimen of mometasone furoate nasal spray (MFNS). 
4.2.2. 
Choice of Control Group 
All subjects will be on background SOC. The study is placebo-controlled to minimize bias 
and provide an inactive control group to which the efficacy of GB001 can be compared. 
Comparisons between the GB001 and placebo treatment groups will facilitate differentiation of 
the GB001 safety profile from that of the SOC. Lastly, a placebo group, as opposed to an active 
control, will help to understand whether the occurrence of an AE in the GB001 group is different 
from that which would occur in this population in the absence of GB001. 
4.2.3. 
Efficacy Endpoint Selection 
The primary endpoint is the change from baseline to Week 16 in SNOT-22. This instrument has 
been used in multiple clinical studies to demonstrate the impact of different types of treatment 
interventions in subjects with CRS. 
In addition, this study will explore the impact of GB001 on bilateral nasal polyps and associated 
sinus symptoms, using specific assessments and questionnaires.  
4.3. 
Justification for Dose 
This study will assess 40 mg of GB001 in adult subjects with chronic rhinosinusitis with or 
without bilateral nasal polyps. In a previous asthma study (PTR-36-201), GB001 5 mg and 
20 mg doses were evaluated. While both doses of GB001 were effective compared to placebo 
in decreasing the proportion of subjects with asthma worsening/exacerbations in a treatment 
withdrawal design, the 20 mg dose produced a larger treatment effect (20 mg: 20.8%; 5 mg: 
32.7%; placebo: 52.8%). In addition, only the 20 mg dose demonstrated statistical significance 
for the endpoints of asthma control, Asthma Control Questionnaire (ACQ-5), and time to asthma 
worsening relative to placebo. However, no improvements in lung function were observed, 
suggesting that higher doses are needed to achieve clinical benefit across different endpoints, 
including lung function. A comparable safety profile was observed across all treatment arms 
(including placebo) in this study. Considering that patients with chronic rhinosinusitis with 
eosinophilic inflammation manifest with more inflammation and disease severity than patients 
with asthma in general, a dose of 40 mg should be adequate and safe to investigate the efficacy 
and safety of GB001 in this patient population. The selection of this dose encompasses the 
totality of PK, efficacy, and safety data of GB001 available to date. 
4.4. 
End of Study Definition 
Subjects will be regarded to have completed the study if he/she completes the Week 16 visit. 
The end of the study is defined as the date of the last visit of the last subject in the study. 


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5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
a protocol waiver or exemption, is not permitted. 
5.1. 
Inclusion Criteria 
Prior to randomizing a subject, additional randomization criteria in Section 5.3 must be met. 
Subjects are eligible to enter the Run-in period only if all of the following criteria are met: 
1. Informed Consent: Capable of giving signed informed consent which includes 
compliance with the requirements and restrictions listed in the informed consent form 
(ICF) and in this protocol. 
2. Age: ≥ 18 to 75 years of age at the time of Screening visit. 
3. Sex: Males or females: 
a. Women of childbearing potential (WOCBP) must use an acceptable method of 
contraception (see Appendix 4, Section 10.4) at least 1 month prior to screening 
through 28 days after the last dose of IP. 
4. Diagnosis: Diagnosis of chronic rhinosinusitis with or without bilateral nasal polyps for 
at least 12 weeks prior to Visit 1. 
5. Nasal symptoms: Presence of at least two of the following symptoms prior to Visit 1:  
• nasal blockade/obstruction/congestion  
• nasal discharge (anterior/posterior nasal drip) 
• facial pain/pressure 
• reduction or loss of smell  
6. INCS: Subjects must be on a stable administration of intranasal corticosteroids (INCS) 
for ≥ 2 months prior to Visit 1. For subjects using a specialized delivery device (eg, 
XHANCE™) or corticosteroids administered via irrigation (eg, budesonide + sterile 
saline), they must be on MFNS for ≥ 2 weeks prior to screening. 
5.2. 
Exclusion Criteria 
Subjects are excluded from the study if any of the following criteria apply: 
1. Nasal symptoms: SNOT-22 score < 20 as assessed at screening. 
2. Prior polyp surgery: Subjects who have undergone any nasal surgery (excluding 
polypectomy performed as an outpatient procedure) within 4 months before screening or 
have had ≥ 4 sinonasal surgeries in the past.  
3. Comorbidities: Presence of a known pre-existing clinically important condition 
including: active tuberculosis, pulmonary fibrosis, bronchopulmonary aspergillosis, 
eosinophilic granulomatous polyangiitis (Churg-Strauss syndrome), Young’s syndrome, 
Kartagener’s syndrome or dyskinetic ciliary syndromes, and cystic fibrosis. Clinically 
significant endocrine, autoimmune, metabolic, neurological, renal (calculated creatinine 


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clearance < 60 mL/min), gastrointestinal, hepatic, cardiovascular, hematological, or any 
other system abnormalities that are uncontrolled with standard treatment. 
4. Malignancy: A current malignancy or previous history of cancer in remission for less 
than 5 years prior to screening (subjects will not be excluded if they had localized 
carcinoma of the skin that was resected for cure). 
5. Liver Disease: Known pre-existing liver disorders (ie, non-alcoholic fatty liver disease 
(NALFD) or Gilbert’s syndrome), or unstable liver disease (as defined by the presence of 
ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices 
or persistent jaundice), cirrhosis, or known biliary abnormalities. 
6. Prior anti-inflammatory treatment: Subjects who have required a burst of systemic 
corticosteroids (eg, oral, intravenous, intramuscular corticosteroids) within the 1 month 
before screening or are scheduled to receive systemic corticosteroids during the study 
period for another condition, or who have required intranasal corticosteroid drops within 
1 month prior to screening.  
7. Intolerant to mometasone furoate nasal spray. 
8. Specific conditions/concomitant diseases:  Subjects with conditions such as: 
antrochoanal polyps, nasal septal deviation that would occlude at least one nostril; acute 
sinusitis, invasive fungal rhinosinusitis, neutrophilic polyposis, nasal infection or upper 
respiratory infection at screening or in the 2 weeks before screening. Subjects requiring 
chronic systemic antibiotic treatment for rhinosinusitis. 
9. Ongoing rhinitis medicamentosa. 
10. ECG Assessment: Subjects with QTcF ≥ 450 msec for males or QTcF ≥ 470 msec for 
females on the Screening visit ECG. However, if QTcF is above this prespecified limit 
and there are no other clinically significant ECG abnormalities in the opinion of the 
Investigator, the assessment can be repeated in triplicate. The triplicate QTcF values 
should be averaged by the Investigator to determine eligibility of the subject to enter the 
Run-in period. However, if any of the triplicate ECGs show a clinically significant 
abnormality in the opinion of the Investigator, the subject should be excluded, regardless 
of the average QTcF of the triplicates.  
11. Alcohol/Marijuana/Illicit Drugs/Substance Abuse: A known or suspected history of 
alcohol misuse, marijuana, illicit drugs, or substance abuse within 12 months prior to 
Screening visit.  
12. Smoking history: Asthma or COPD patients that are current smokers (any substance), 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 6 months prior to Screening visit. This includes electronic cigarettes and 
vaping. 
13. Immunodeficiency: A known immunodeficiency, including that due to human 
immunodeficiency virus (HIV), other than that explained by systemic corticosteroid use. 
14. Investigational medications: Subjects who have received treatment with an 
investigational medication within the past 30 days or within 5 half-lives of the 


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medication, whichever is longer, prior to Screening visit (this also includes 
investigational formulations of marketed products). 
15. Receiving prohibited medications: Refer to Appendix 10 (Section 10.10) for more 
details. 
a. Regular use of systemic corticosteroids or immunosuppressive therapies including 
methotrexate or azathioprine 
b. Monoclonal antibodies used in the treatment of asthma  
c. Medications, food or drink that are moderate or strong CYP3A4 inhibitors or inducers 
d. Other medications that have the potential for interaction with GB001 
e. Medications that have a black-box warning for hepatic toxicity. 
16. Prior participation in a study with GB001: Subjects who previously participated in 
a study with GB001 (also named PTR-36 or ADC3680). 
17. Hypersensitivity: A known sensitivity to GB001 or any of its excipients. Subjects with 
rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, 
or glucose-galactose malabsorption. Subjects with mild-moderate lactose intolerance 
are not excluded. Subjects with sensitivity or intolerance to aspirin (ie, subjects with 
aspirin-exacerbated respiratory disease [AERD] with or without desensitization). 
18. Pregnancy: Subjects who are pregnant or breastfeeding. Subjects should not be enrolled 
if they are planning to become pregnant during the time of study participation. A serum 
pregnancy test is required of all females of child-bearing potential at Screening. 
19. Adherence: Subjects who have a known lack of adherence to medications such as INCS. 
20. Body Mass Index (BMI): BMI is ≥ 40 kg/m2. 
21. Participation: Subject has any other condition or reason that, in the opinion of the 
Investigator, would prohibit the subject from participating in the study. 
22. Participation in another clinical study: Subjects currently participating in an 
interventional clinical study with a biologic agent or who have received study drug in 
another clinical study are not to be considered for participation until the completion of the 
safety follow-up visit or following a non-investigational drug period of no less than five 
half-lives. Subjects may not participate in another interventional clinical trial while 
enrolled in this study. 


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5.3. 
Randomization Criteria 
Subjects must fulfill the following criteria to be randomized to study treatment: 
1. Diary compliance: Compliance with completion of the Diary as defined as: 
a. Completion of questions on 4 or more of the last 7 days immediately prior to Visit 2 
(includes the morning of Visit 2). 
b. Note: If the Diary was completed on < 4 days due to technical challenges, the Visit 2 
may be delayed up to an additional 3 days to allow for completion of the Diary 
parameters above. 
2. Eosinophilic Phenotype: Subjects must meet at least one of the criteria below. 
• Blood eosinophil count ≥ 250 cells/μL obtained at Visit 1.  
OR 
• Minimum NPS of 4 out of a maximum score of 8 with a score of at least 2 for each 
nostril as assessed by a blinded central reader. Subjects with an NPS of 1-3 are not 
eligible for randomization.  
3. CRS exacerbation: Subjects who experience a CRS exacerbation during the Run-in 
period should have their Randomization Visit (Visit 2) delayed until the investigator 
considers the subject has returned to their baseline status. If a 4-week Run-in period has 
elapsed before the subject is back to baseline status, then the subject will be considered a 
Run-in failure. CRS exacerbation is defined in Section 8.1.6. 
4. Laboratory abnormality: No evidence of clinically significant abnormality in the 
hematological, biochemical, or urinalysis at Screening visit, as judged by the investigator. 
5. Hepatitis status: No diagnosis of chronic hepatitis B or C, as evidenced by a negative 
hepatitis B surface antigen (HBsAg) or hepatitis C antibody screen at Screening visit. 
6. Chemistry and hematology obtained at Screening visit: 
• ALT ≤ 1 × the upper limit of normal (ULN) 
• AST ≤ 1 × ULN 
• Alkaline phosphatase < 2 × ULN 
• Bilirubin < 1 × ULN 
• Absolute eosinophil count < 1,500 cells/μL 
• White blood cell count < 15,000 cells/μL 
7. Pregnancy test: For WOCBP, both the serum pregnancy test at the Screening visit and 
the urine pregnancy test at Visit 2 must be negative. 
8. Use of MFNS: Subject newly switched onto MFNS during screening should tolerate 
MFNS during Run-in. 
9. Nasal symptoms: SNOT-22 score ≥ 17 as assessed at randomization. 
10. ECG overread: ECG overread by the central ECG reader confirms the QTcF interval is 
< 450 msec for males or QTcF < 470 msec for females. 


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5.4. 
Screen or Run-In Failures 
Subjects will be assigned a subject number at the time of signing the ICF and entry into the 
online registration system (IRT).  Subjects who do not enter the Run-in period will be labeled as 
screen failures. 
Subjects who enter the Run-in period but are not randomized will be designated as Run-in 
failures, even if they complete the Run-in period.  
A minimal set of Screen failure/Run-in failure information is required to ensure transparent 
reporting of Screen/Run-in failure subjects to meet the Consolidated Standards of Reporting 
Trials (CONSORT) publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, Screen/Run-in failure details, eligibility 
criteria, and any serious adverse event (SAE). 
Subjects who are not randomized may be eligible to rescreen upon approval by the Sponsor 
and/or designated Medical Monitor. A new subject number will be assigned if approved to 
rescreen. One rescreen is permitted. 
6. 
INVESTIGATIONAL PRODUCT 
6.1. 
Investigational Product Administered 
 
Table 1: 
Investigational Product Formulation by Treatment Group 
Treatment 
Groups 
GB001 40 mg 
 
Placebo 
Dose 
Formulation 
20 mg Film-Coated Tablet 
Matched Placebo Film-Coated Tablet 
Unit Dose 
Strength(s) 
2 × 20 mg tablet 
2 × placebo tablet 
Dosage Level(s) 
40 mg 
Placebo 
Route of 
Administration 
and Instructions 
Oral, in the morning 
on an empty stomacha 
Oral, in the morning 
on an empty stomacha 
Packaging and 
Labeling 
GB001 and placebo film-coated tablets will be packaged in a blinded manner in 
high-density polyethylene (HDPE) 50 mL bottles. The bottles will be labeled as 
required per country requirement. 
Storage 
Requirements 
IP should be stored at room temperature (20–25°C) in the original packaging. 
Protect from moisture. 
IP stored at site will be maintained under controlled, temperature monitored 
conditions. Excursions between 15–30°C are permitted. Any other excursion from 
the required storage condition will be reported to the Sponsor as soon as practical. 
a No food intake. Liquids are acceptable. 
 


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6.2. 
Preparation/Handling/Storage/Accountability 
1. The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all IP received and any discrepancies are reported and 
resolved before use of the IP. 
2. Only subjects enrolled in the study may receive IP and only authorized site staff may 
supply IP. All IP must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized site staff. 
3. The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for IP accountability, reconciliation, and record maintenance (ie, receipt, 
reconciliation, and final disposition records). 
4. Further guidance and information for the final disposition of IP are provided in the 
Pharmacy Manual. 
6.3. 
Randomization and Blinding 
6.3.1. 
Randomization 
All subjects will be centrally randomized to IP treatment group using an Interactive Response 
Technology (IRT). Before the study is initiated, directions for use of the system will be provided 
to the sites. 
Randomization will be stratified by country, the presence or absence of NP (CRSwNP and 
CRSsNP), and the presence or absence of comorbid asthma among CRSwNP subjects. Presence 
of NP is defined by a minimum NPS of 4 out of a maximum score of 8 with a score of at least 2 
for each nostril. Absence of NP is defined as an absence of NP based on visual examination or an 
NPS of 0 based on nasal endoscopy. Presence of comorbid asthma is defined as a diagnosis of 
asthma by a physician according to Global Initiative for Asthma (GINA) guidelines at screening 
or prior to study entry. The CRSwNP stratum will consist of approximately 64 subjects, and the 
CRSsNP stratum will consist of approximately 36 subjects. 
6.3.2. 
Assignment of Investigational Product Bottle Numbers 
IP will be dispensed at the study visits as summarized in SoA. At the Randomization Visit, the 
IRT system will assign an IP bottle number based on the subject’s randomized treatment group. 
For subsequent visits when IP is dispensed, the IRT system will assign new IP bottle numbers 
based on the subject’s randomized treatment group. 
6.3.3. 
Unblinding of an Individual Subject 
The IRT system will be programmed with blind-breaking instructions. In case of a medical 
emergency, the investigator has the sole responsibility for determining if unblinding of 
a subject’s treatment assignment is warranted. Subject safety must always be the first 
consideration in making such a determination. If the investigator decides that unblinding is 
warranted, the investigator, when possible, should make an effort to contact the Sponsor to 
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6.5. 
Concomitant Therapy 
Subjects should remain on their stable dosing treatment (mometasone furoate [eg, NASONEX® 
or a generic such as other mometasone furoate nasal sprays (eg, as available from Apotex Corp, 
Amneal Pharmaceuticals, LLC, Sandoz Inc)] 50 micrograms/actuation Nasal Spray) for the 
duration of their time on study. If a subject discontinues from IP or withdraws from the study due 
to lack of efficacy, SOC therapy should not be adjusted until after the Safety Follow-up visit. 
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 or receives 
during the study must be recorded along with: 
• Reason for use 
• Dates of administration including start and end dates 
• Dosage information including dose and frequency 
The Medical Monitor should be contacted if there are any questions regarding concomitant 
or prior therapy. 
6.5.1. 
Prohibited and Restricted Medications Prior to the Screening Visit and 
Throughout the Study 
Please refer to Appendix 10 (Section 10.10) for prohibited and restricted medications and other 
treatments. 
6.6. 
Dose Modification 
Dose modifications of IP are not permitted. Subjects who are unable to tolerate their assigned 
dose of IP must be discontinued from IP. 
6.7. 
Intervention After the End of the Study 
There is no plan for intervention following the end of the study. 
7. 
DISCONTINUATION OF INVESTIGATIONAL PRODUCT AND 
SUBJECT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Investigational Product 
Permanent discontinuation of IP does not mean withdrawal from the study, and the subject will 
be encouraged to remain in the study and continue to complete all study visits and diaries as per 
the SoA (Section 1.3). If a subject permanently discontinues IP prior to Visit 6 (Week 12) and 
remains in the study through Visit 7 (Week 16), the subject will not need to return for the 
Follow-up Visit (Week 20) as the Week 16 Visit will serve as an acceptable Follow-up visit. 
Mandatory criteria for permanent discontinuation of IP are documented in Appendix 6 
Section 10.6. A subject must permanently discontinue IP if the subject experiences a drug-
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For subjects who simultaneously discontinue IP and withdraw early from the study, the EW Visit 
procedures should be conducted (Section 1.3), and a separate Early Discontinuation of IP Visit is 
not needed. The subjects should be encouraged to return for the Follow-up Visit. 
7.1.1. 
Pregnancy 
A subject must permanently discontinue IP if the subject becomes pregnant. See Appendix 4 
Section 10.4 and Section 8.3.5 for additional details. 
The Early Discontinuation of IP Visit procedures should be conducted, as shown in the SoA 
(Section 1.3), and a separate Early Withdrawal from Study Visit is not needed. 
7.1.2. 
Liver Safety 
A subject must permanently discontinue IP if the subject meets the liver chemistry criteria that 
are specified in Appendix 6 Section 10.6. 
7.2. 
Subject Withdrawal from the Study 
A subject may withdraw or be withdrawn from the study for the following reasons: 
• Physician decision 
• Adverse event 
• Noncompliance with study drug  
• Withdrawal by subject 
• Study terminated by the Sponsor 
• Site terminated by Sponsor 
• Lost to follow-up 
• Lack of efficacy 
• Pregnancy 
The reason for subject withdrawal from the study will be recorded in the eCRF. 
If a subject is withdrawn from the study and has previously discontinued IP, if possible, the EW 
Visit should be conducted, as shown in the SoA (Section 1.3). If the subject is simultaneously 
discontinuing IP and withdrawing early from the study, the EW visit should be conducted. 
The subjects should be encouraged to return for the Follow-up Visit. See SoA for data to be 
collected at the time of study withdrawal and at follow-up and for any further evaluations that 
need to be completed. 
If a subject withdraws from the study, he/she may request destruction of any samples taken and 
not tested, and the investigator must document this in the site study records. 


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7.3. 
Lost to Follow-up 
A subject will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site. 
The following actions must be taken if a subject fails to return to the clinic for a required study 
visit: 
• The site must attempt to contact the subject and reschedule the missed visit as soon as 
possible and counsel the subject on the importance of maintaining the assigned visit 
schedule and ascertain whether the subject wishes to and/or should continue in the 
study. 
• Before a subject is deemed lost to follow up, the investigator or designee must 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. 
• The Sponsor may also attempt to ascertain vital status on subjects deemed lost to 
follow up. 
• Should the subject continue to be unreachable, he/she will be considered to have 
withdrawn from the study. The subject’s data and biosamples may still be assayed, in 
accordance with his/her original informed consent. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarized in the SoA. Protocol waivers 
or exemptions are not allowed. 
• Safety concerns should be discussed with the Sponsor immediately upon occurrence 
or awareness to determine if the subject should continue or discontinue IP. 
• Adherence to the study design requirements, including those specified in the SoA, 
is essential and required for study conduct. 
All screening and randomization evaluations must be completed and reviewed to confirm that 
potential subjects meet all eligibility criteria. The Investigator will maintain a log to record 
details of all subjects screened to either confirm eligibility or record reasons for screening 
or Run-in failures, as applicable. The suggested order of study procedures should be as follows. 
(Note: this list is not all inclusive. Review the SoA and the Study Reference Manual for 
additional guidance.) 


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Screening Visit (Visit 1):  
(The list may not be all inclusive. Review the SoA and the Study Reference Manual for 
additional guidance) 
• Informed consent 
• Demography 
• Administer SNOT-22 
• Medical/surgical history 
• Concomitant medication review including confirmation of INCS use for more than 
8 weeks prior to screening 
• Vital signs 
• Physical exam including visual exam of nose for polyps 
• 12-lead electrocardiogram 
• Review of inclusion/exclusion criteria 
• Collect urine and blood samples 
• Record adverse events, if any 
• Dispense Diary and train subject in its use including responding to the morning and 
evening CRS symptom questions and daily MFNS use 
• Ensure subject has MFNS (or equivalent for non-US sites) for use as required 
background therapy throughout the study. 
• Perform nasal endoscopy (subset of subjects). Endoscopy (including use of 
decongestants and/or anesthetics before the procedure) will be performed after all 
other efficacy assessments have been completed at each visit; video sequences will be 
downloaded by the investigator to the blinded central reader’s secure Internet site. For 
eligibility in the CRSwNP stratum, blinded central reading of the Visit 1 endoscopy 
will be used. 
• Remind patient to bring diary materials to the next visit 
• Complete eCRF 
Note: During the Run-in period, the site should review the central endoscopy overread report 
and the laboratory results. If the overread or laboratory results indicate that the subject is not 
eligible for randomization, the subject should be contacted to return all study provided materials 
to the site. 


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Randomization Visit (Visit 2): 
(The list may not be all inclusive. Review the SoA and the Study Reference Manual for 
additional guidance)    
• Review Diary to assess eligibility and remind subject to bring the materials to the 
next visit 
• Review randomization eligibility criteria including results from blinded central reader 
of Visit 1 nasal endoscopy to confirm entry criteria 
• Have subject complete questionnaires including SNOT-22 
• Concomitant medication and adverse event review 
• Vital signs 
• Reconfirm eligibility based on review of Inclusion/Exclusion Criteria (Section 5.3) 
• Collect lab samples  
• Perform CT scan. If a qualifiable CT scan has been performed within 30 days on the 
qualified equipment consistent with the study imaging protocol and allowing 
appropriate interpretation/assessment and the image sequences are available for 
upload to the imaging core laboratory, then a CT scan on Visit 2 is not required. If a 
historic CT scan is to be used this CT scan must be uploaded to the Imaging Core 
Laboratory at a minimum of 14 days prior to the randomization visit to ensure image 
quality and appropriate quantification. 
• Perform nasal endoscopy (only on subjects categorized as CRSwNP) 
• Perform nitric oxide measurements on all subjects.  
• Dispense IP 
• Complete eCRF 
8.1. 
Efficacy Assessments 
8.1.1. 
SNOT-22 
The SNOT-22 (Section 10.9) is a validated questionnaire to assess the impact of chronic 
rhinosinusitis on quality of life and utilizes a 2-week recall period. It is a 22-item outcome 
measure on a 5-point category scale applicable to sinonasal conditions and surgical treatments. 
The total scores range from 0 to 110 with higher total scores implying greater impact of CRS 
on quality of life. A Minimal Clinically Important Difference (MCID) is available: 8.90 
(Hopkins, 2009). 


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8.1.2. 
Computer Tomography (CT) 
CT of the sinuses will be performed at Randomization, at end of treatment (Visit 7) and if 
a patient is withdrawn early. 
For the accurate assessment of Lund-Mackay scores and 3D volumetric measurement of the 
maxillary sinus, the same acquisitions (sequences) will be performed and used for centralized 
imaging data assessments and scored by the imaging core laboratory.  
Blinded central reading of the Visit 2 assessment will be used for comparison with the Week 16 
visit. The final results of blinded central reading will be made available after the study. 
Details on CT will be available in a separate operational manual provided to the sites. 
The 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 complex is graded as 0 = not occluded, or 2 = occluded deriving a maximum score 
of 12 per side (Lund, 1993). This scoring system has been validated in several studies 
(Scadding, 2011; Hopkins, 2009). 
For subjects in whom the osteomeatal complex (OC) is missing (because of a previous surgery) 
the blinded central reader should consider the location of the former OC and provide a scoring 
(as if the OC was there). 
Three-Dimensional volumetric measurement of the maxillary sinus will be performed at the 
imaging core laboratory. 
This method is used to calculate: 
• volume of the air (mL) 
• volume of mucosa (mL) 
• percent occupied by disease 
• thickness of lateral wall 
For the analysis, blinded central reading of the CT at Visit 2 will be used for comparison with 
Week 16. The sites will remove subject-identifying information from the imaging data header 
prior to sending the imaging data to the imaging core laboratory. The percent change in 
opacification from baseline to end of treatment will be calculated (Van Agthoven, 2001). 
If a prior CT within 60 days of the Randomization visit is available and the Imaging Core 
Laboratory confirms their quality criteria are met, this CT may be acceptable. 
8.1.3. 
Bilateral Endoscopic Nasal Polyp Score 
The bilateral endoscopic nasal polyp score (NPS) is the sum of the right and left nostril scores, as 
evaluated by means of blinded, centrally read nasal endoscopy. NP is graded based on polyp size 
described in the Table 2 below: 


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Table 2: 
Endoscopic Nasal Polyp Score 
Polyp Score 
Polyp Size 
0 
No polyps 
1 
Small polyps in the middle meatus not reaching below the inferior border of the 
middle turbinate 
2 
Polyps reaching below the lower border of the middle turbinate 
3 
Large polyps reaching the lower border of the inferior turbinate or polyps medial to 
the middle turbinate 
4 
Large polyps causing complete obstruction of the inferior nasal cavity 
Nasal endoscopy should be performed at the end of the scheduled visits and preceded by local 
administration of anesthetic drugs in combination with a decongestant. Standard video sequences 
will be downloaded or sent to the centralized reader. Centralized imaging data assessments and 
scoring by an independent physician reviewer for the imaging data will be performed for all 
endoscopies. To confirm eligibility at Visit 2 (baseline), only the Visit 1 blinded central reading 
will be made available to the site. The final results of blinded central reads will be made 
available after the study. 
8.1.4. 
Disease-specific, Daily Symptom Assessments 
On a daily basis, from Visit 1 and throughout the study, the subject will use a Diary to: 
Respond to the morning and evening individual rhinosinusitis symptom questions using a 0–3 
categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms 
and 3 = severe symptoms) for the following symptoms: 
• congestion and/or obstruction 
• anterior rhinorrhea (runny nose) 
• posterior rhinorrhea (post-nasal drip) 
• loss of sense of smell 
The Diary is provided at Visit 1 and information is collected on the days/times indicated in the 
Schedule of Activities. Diary entries are to be completed until the Follow-up visit (Week 20). 
The TSS is the sum of the scores from the 4 symptom categories and ranges from 0–12. For each 
rhinosinusitis symptom category and the TSS, the average of the available scores recorded 
during the last 7 days before Visit 2 (up to 14 scores, including the morning of Visit 2) will be 
used to determine the baseline value. A minimum of 4 days of the previous 7 days must be 
completed (inclusive of the morning entry on the day of randomization) in order to qualify for 
randomization (see Section 5.3). 
8.1.5. 
Smell Test: University of Pennsylvania Smell Identification Test (UPSIT) 
The test consists of four booklets, each containing 10 odorants with one odorant per page 
(Doty, 1984). The test-time is about 15 minutes. The stimuli are embedded in 10–50 μm 
diameter plastic microcapsules on brown strips at the bottom of each page. Above each odorant 


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strip is a multiple-choice question with four alternative words to describe the odor. The subject is 
asked to release the odorant by rubbing the brown-strip with the tip of a pencil and to indicate 
which of four words best describes the odor. An UPSIT result is scored out of 40 where a higher 
score indicates better olfaction.  
8.1.6. 
CRS Exacerbation 
Chronic rhinosinusitis exacerbation is defined as deterioration of CRS symptoms requiring 
treatment with an antibiotic, an anti-inflammatory drug, or a symptom reliever; an Emergency 
Department visit; or hospitalization (Kuiper, 2018; Meltzer, 2006; Rosenfeld, 2015). 
The date of onset of a CRS exacerbation will be considered to be the first date of treatment 
with an antibiotic, an anti-inflammatory drug, or a symptom reliever, the date of Emergency 
Department visit, or the date of hospitalization, whichever occurs first. The end date of 
a CRS exacerbation will be considered to be the last date of treatment with an antibiotic, 
an anti-inflammatory drug, or a symptom reliever, or 6 days after the date of onset (for a total 
duration of 7 days), whichever is later. Courses of treatment separated by 7 or more days will be 
counted as separate exacerbations. 
8.1.7. 
Visual Analog Scale (VAS)  
The visual analog scale (VAS) for rhinosinusitis is used to evaluate the total severity and is only 
validated in adult CRS to date (Fokkens, 2007). 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), see Appendix 7, 
Section 10.7. 
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 
8.1.8. 
Nitric Oxide Measurement 
Nitric oxide may be measured at the visits specified in the SoA utilizing equipment provided by 
a central vendor. Nitric oxide will be measured both by oral (fractional exhaled nitric oxide 
[FeNO]) and nasal (nasal nitric oxide [nNO]) methods. For more details, please refer to the 
Study Reference Manual. 
8.1.9. 
Other Assessments 
Asthma control will be assessed at visits (Visits 2, 5, and 7, EW, early discontinuation) using 
the ACQ-5 questionnaire. These assessments will be conducted only in subjects who reported 
a diagnosis of asthma at the Screening visit.  


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8.2. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA. 
8.2.1. 
Physical Examinations 
• A complete physical examination will be conducted as designated in the SoA 
(see Section 1.3). 
• Height and weight will also be measured and recorded as noted in the SoA (see 
Section 1.3). 
8.2.2. 
Vital Signs 
• Pulse rate, respiratory rate, temperature, and blood pressure will be assessed. 
• Blood pressure and pulse measurements should be preceded by at least 5 minutes of 
rest for the subject in a quiet setting without distractions (eg, television, cell phones). 
• Blood pressure and pulse measurements will be assessed with the subject in a sitting 
position with a completely automated device. Manual techniques will be used only if 
an automated device is not available. 
• Vital signs will be measured prior to ECG measurements. 
8.2.3. 
Electrocardiograms 
• Assessment of a single 12-lead ECG will be obtained as outlined in the SoA 
(see Section 1.3) to determine heart rate and measure PR, QRS, QT, and QTc 
intervals. The test can be repeated in triplicate if the QTcF value is slightly above the 
threshold. 
8.2.4. 
Clinical Safety Laboratory Assessments 
• See Appendix 2 (Section 10.2) for the list of clinical laboratory tests to be performed 
at the visits designated in the SoA. Details for collection, processing and shipping of 
samples to the central laboratory are provided in a separate Laboratory Manual. 
• The investigator must review the laboratory report, document this review, and record 
any clinically relevant changes occurring during the study in the AE section of the 
eCRF. The laboratory reports must be filed with the source documents. Clinically 
significant abnormal laboratory findings are those which are not associated with the 
underlying disease, unless judged by the investigator to be more severe than expected 
for the subject's condition. 
• All laboratory tests with values considered abnormal and clinically significant during 
participation in the study should be repeated until the values return to normal 
or baseline or are no longer considered clinically significant by the investigator 
or Medical Monitor. For additional liver safety monitoring, refer to Appendix 6 
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− If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified, and the Sponsor 
notified. 
• All protocol-required laboratory assessments, as defined in Appendix 2 
(Section 10.2), must be conducted in accordance with the Laboratory Manual 
and the SoA. 
• If laboratory values from non-protocol specified laboratory assessments performed at 
the institution’s local laboratory require a change in subject management or are 
considered clinically significant by the investigator (eg, SAE or AE or dose 
modification), then the results must be recorded in the source document. 
8.3. 
Adverse Events, Serious Adverse Events, and Adverse Events of 
Interest 
The definitions of an AE, SAE, and AE of Interest can be found in Appendix 3 (Section 10.3). 
AE will be reported by the subject (or, when appropriate, by a caregiver, surrogate, 
or the subject's legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE, SAE, or AE of Interest. 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE Information 
Treatment-emergent adverse events will be collected from the first dose of IP until the end of 
follow up. Serious adverse events will be collected beginning at the time of consent until the end 
of follow up. Medical occurrences that begin after obtaining informed consent and before the 
first dose of IP will be recorded on the Medical History/Current Medical Conditions section of 
the eCRF and not the AE section. 
All SAEs will be recorded and reported to the Sponsor or designee immediately upon the site 
learning of an event and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3 (Section 10.3.5). The investigator will submit any updated SAE data to the Sponsor 
within 24 hours of it being available. 
Investigators are not obligated to actively seek AEs or SAEs that start after conclusion of the 
study participation. However, if the investigator learns of any SAE, including a death, at any 
time after a subject has been discharged from the study, and he/she considers the event to be 
reasonably related to the IP or study participation, the investigator must promptly notify the 
Sponsor. 
8.3.2. 
Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 3 (Section 10.3). 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the subject is the preferred method to inquire about 
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8.3.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each subject 
at subsequent visits/contacts. All SAEs and events of interest (defined in Section 10.3) will be 
followed until resolution, stabilization, the event is otherwise explained, or the subject is lost to 
follow up (as defined in Section 7.3). Further information on follow-up procedures is given in 
Appendix 3 (Section 10.3). 
8.3.4. 
Regulatory Reporting Requirements for SAEs 
• Prompt notification by the investigator to the Sponsor of a SAE is essential so that 
legal obligations and ethical responsibilities towards the safety of subjects and the 
safety of the IP under clinical investigation are met. 
• The Sponsor has a legal responsibility to notify both the local regulatory authority 
and other regulatory agencies about the safety of an IP under clinical investigation. 
The Sponsor will comply with country-specific regulatory requirements relating to 
safety reporting to the regulatory authority, Institutional Review Boards 
(IRB)/Independent Ethics Committees (IEC), and investigators. 
• Investigator safety reports must be prepared for SUSAR according to local regulatory 
requirements and Sponsor policy and forwarded to investigators as necessary. 
• An Investigator who receives an Investigator safety report from the Sponsor 
describing a SAE or other specific safety information (eg, summary or listing of 
SAEs) will review and then file it along with the IB. The Investigator will then notify 
the IRB/IEC, if appropriate according to local requirements. 
8.3.5. 
Pregnancy 
• Details of all pregnancies will be collected as outlined in Appendix 4 (Section 10.4). 
• If a pregnancy is reported, the investigator should inform the Sponsor within 24 hours 
of learning of the pregnancy and should follow the procedures outlined in Appendix 4 
(Section 10.4). 
• Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. 
8.3.6. 
Death Events 
Timelines for reporting of death events are identical to the requirements for SAE reporting. 
(Section 10.3.5). 
8.3.7. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs  
CRS exacerbation is an efficacy assessment that is a disease-related outcome not qualifying as an 
AE unless the investigator considers the CRS exacerbation to have met the definition of an SAE 
(Appendix 3; Section 10.3.2). CRS exacerbation meeting the definition of an SAE will be 
reported in the appropriate eCRF (Appendix 3; Section 10.3.5). CRS exacerbation not meeting 
the definition of an SAE should not be reported as an AE. CRS exacerbations, as captured by 








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• Intent-to-treat (ITT) population: All subjects who are randomized and receive 
at least one dose of IP, with subjects grouped according to randomized treatment. 
This population will be used for all efficacy analyses. 
• Safety population: All subjects who receive at least 1 dose of IP, with subjects 
grouped according to their actual treatment. This population will be used for safety 
analyses. 
9.4. 
Statistical Analyses 
In general, continuous variables will be summarized using the number of subjects with 
non-missing data, mean, standard deviation, minimum, and maximum. Continuous variable 
summaries will include standard error, where appropriate. Categorical variables will be 
summarized using counts and percentages. Baseline value will be defined as the last non-missing 
value on or before the date of the first dose of IP. 
Analyses will generally be performed for the overall population and by stratum (CRSwNP 
and CRSsNP), other than endpoints associated with outcomes that are specific to the CRSwNP 
stratum (eg, NPS). 
All statistical hypothesis testing will be at an 0.050 two-sided level of significance. 
9.4.1. 
Efficacy Analyses 
9.4.1.1. 
Primary Efficacy Analysis 
The primary endpoint of change from baseline to Week 16 in SNOT-22 score will be 
analyzed by a mixed-effects model with repeated measures (MMRM) using a restricted 
maximum-likelihood (REML)-based approach. The MMRM model will include change from 
baseline scores up to Week 16 as the response variable; the fixed, categorical effects of treatment 
group, randomization strata defined by the presence or absence of NP and comorbid asthma 
(ie, CRSwNP with comorbid asthma, CRSwNP without comorbid asthma, and CRSsNP), 
country, visit, and treatment group by visit interaction; and the continuous, fixed covariates of 
baseline SNOT-22 score and baseline SNOT-22 score by visit interaction. An unstructured 
covariance structure will be used to model within-subject error. If this analysis fails to converge, 
a compound symmetric or first-order autoregressive covariance structure will be utilized for the 
primary analysis, based on the covariance structure converging to better fit as determined based 
on Akaike’s information criterion.  
Statistical inference for treatment group comparison of GB001 40 mg versus placebo at Week 16 
will be derived from the above MMRM model, with results presented in terms of a least squares 
mean difference, along with the corresponding 95% confidence interval (CI) and p-value.  
9.4.1.2. 
Secondary Efficacy Analysis 
The secondary endpoints of change from baseline to Week 16 in Lund-Mackay total score and in 
UPSIT score will be analyzed utilizing analysis of covariance (ANCOVA) models including 
covariates for baseline score, presence or absence of bilateral NP, and treatment group.  Results 
will be presented in terms of least squares mean differences, along with corresponding 95% CIs 
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The secondary endpoints of change from baseline to Week 16 in NPS, NC, and TSS will be 
analyzed with MMRM using an REML approach, employing a similar methodological approach 
as the analysis of the primary endpoint. The analysis of change from baseline to Week 16 in NPS 
will be conducted in the CRSwNP stratum, with the fixed, categorical effect for randomization 
strata in the MMRM model defined by presence of NP and comorbid asthma (ie, CRSwNP with 
comorbid asthma and CRSwNP without comorbid asthma). For NC and TSS, the average of the 
scores recorded during the last 7 days before a given visit (14 scores, including the morning of 
the visit) will be used to determine the value for that visit. 
The secondary endpoint of time to first response (≥ 1 point improvement from baseline) in NPS 
will be conducted in the CRSwNP stratum and will be analyzed using a stratified Cox 
proportional hazards model, stratified on the basis of the presence or absence of comorbid 
asthma, adjusted for country, baseline NPS, and treatment group. Subjects without a response 
in NPS will be censored at their last NPS assessment. The secondary endpoint of time to first 
CRS exacerbation will be analyzed using a stratified Cox proportional hazards model, stratified 
on the basis of the presence or absence of NP and comorbid asthma (ie, CRSwNP with comorbid 
asthma, CRSwNP without comorbid asthma, and CRSsNP), adjusted for country and treatment 
group. Subjects without a CRS exacerbation will be censored at their last assessment for CRS 
exacerbation. Kaplan-Meier estimates and curves will be provided for both time to first response 
in NPS and time to first CRS exacerbation. 
9.4.2. 
Safety Analyses 
Safety and tolerability will be examined based on AEs, clinical laboratory results, vital signs, 
and 12-lead ECG assessments. 
Safety analyses will be focused on TEAEs, defined as AEs with onset on or after the first dose of 
IP. The incidence of AEs and SAEs will be summarized by treatment group, including the 
incidence by system organ class and preferred term. In addition, the incidence of AEs by 
severity, the incidence of treatment-related AEs, and the incidence of AEs leading to study drug 
discontinuation/study withdrawal will be summarized by system organ class and preferred term. 
Laboratory, vital signs, and ECG data will be analyzed by treatment group using summary 
statistics for actual values of and change from baseline in continuous parameters. The number 
and frequency of subjects with pre-defined abnormalities considered clinically significant will be 
presented. For laboratory parameters, the number and frequency of subjects with shifts from 
baseline to low or high values based on normal ranges will also be presented. 
9.5. 
Interim Analyses 
No formal interim analyses are planned. 
See Section 6.3.3 regarding unblinded analyses to be performed by Sponsor individuals not 
directly involved in the conduct of the study to inform further development of GB001.  


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10. 
APPENDICES 
10.1. 
Appendix 1:  Regulatory, Ethical, and Study Oversight 
Considerations (site responsibilities) 
10.1.1. 
Regulatory and Ethical Considerations 
• This study will be conducted in accordance with the protocol and with the following: 
− Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
− Applicable ICH Good Clinical Practice (GCP) Guidelines 
− Applicable laws and regulations 
• The protocol, protocol amendments, ICF, IB, Diary and other relevant documents 
(eg, advertisements) must be submitted to an IRB/IEC by the investigator and 
reviewed and approved by the IRB/IEC before the study is initiated. 
• Any amendments to the protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes necessary 
to eliminate an immediate hazard to study subjects. 
• The investigator will be responsible for the following: 
− Providing written summaries of the status of the study to the IRB/IEC annually 
or more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC 
− Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
− Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR (or equivalent for non-IND sites), ICH guidelines, the 
IRB/IEC, European regulation 536/2014 for clinical studies (if applicable), and all 
other applicable local regulations 
10.1.2. 
Informed Consent Process 
• The investigator or his/her representative will explain the nature of the study to the 
subject or his/her legally authorized representative and answer all questions regarding 
the study. 
• Subjects must be informed that their participation is voluntary. Subjects or their 
legally authorized representative will be required to sign a statement of informed 
consent that meets the requirements of 21 CFR 50 (or equivalent for non-IND sites), 
local regulations, ICH guidelines, Health Insurance Portability and Accountability 
Act (HIPAA) requirements, where applicable, and the IRB/IEC or study center. 


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• The medical record must include a statement that written informed consent was 
obtained before the subject entered the study and the date the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the 
ICF. 
• Subjects must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
• A copy of the ICF(s) must be provided to the subject or the subject’s legally 
authorized representative. 
• A pharmacogenetics (PGx) consent form must be offered to all subjects and the 
process must be documented, unless prohibited by local regulations. 
10.1.3. 
Data Protection 
• Subjects will be assigned a unique identifier by the Sponsor. Any subject records or 
datasets that are transferred to the Sponsor will contain the identifier only; subject 
names or any information which would make the subject identifiable will not be 
transferred. 
• The subject must be informed that his/her personal study-related data will be used by 
the Sponsor in accordance with local data protection law. The level of disclosure must 
also be explained to the subject. 
• The subject must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
Sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
10.1.4. 
Dissemination of Clinical Study Data 
• A clinical study report (CSR) will be developed by the Sponsor at completion of data 
analysis. This report will be a clinical and statistical integrated report, according to 
the ICH E3 guidelines. 
• Sponsor will register the study and post study results regardless of outcome on 
a publicly accessible website in accordance with the applicable laws and regulations. 
10.1.5. 
Data Quality Assurance 
• All subject data relating to the study will be recorded on printed or electronic eCRF 
unless transmitted to the Sponsor or designee electronically (eg, laboratory data). 
The investigator is responsible for verifying that data entries are accurate and correct 
by physically or electronically signing the eCRF. 
• The investigator must maintain accurate documentation (source data) that supports 
the information entered in the eCRF. 
• The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents. 


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• Monitoring details describing strategy (eg, risk-based initiatives in operations and 
quality such as Risk Management and Mitigation Strategies and Analytical Risk-
Based Monitoring), methods, responsibilities and requirements, including handling of 
noncompliance issues and monitoring techniques (central, remote, or on-site 
monitoring) are provided in the Monitoring Plan. 
• The Sponsor or designee is responsible for the data management of this study 
including quality checking of the data. 
• The Sponsor assumes accountability for actions delegated to other individuals 
(eg, Contract Research Organizations). 
• Study monitors will perform ongoing source data verification to confirm that data 
entered into the eCRF by authorized site personnel are accurate, complete, 
and verifiable from source documents; that the safety and rights of subjects are being 
protected; and that the study is being conducted in accordance with the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
• Records and documents, including signed ICFs, pertaining to the conduct of this 
study must be retained by the investigator per ICH-GCP and local regulations 
or institutional policies. No records may be destroyed during the retention period 
without the written approval of the Sponsor. No records may be transferred to another 
location or party without written notification to the Sponsor. 
10.1.6. 
Source Documents 
• Source documents provide evidence for the existence of the subject and substantiate 
the integrity of the data collected. Source documents are filed at the investigator’s 
site. 
• Data entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained. 
The investigator may need to request previous medical records or transfer records, 
depending on the study. Also, current medical records must be available. 
• Source documents are original documents, data, and records from which the subject’s 
eCRF data are obtained. These include but are not limited to hospital records, clinical 
and office charts, laboratory and pharmacy records, diaries, microfiches, radiographs, 
and correspondence. 
10.1.7. 
Study and Site Closure 
• The Sponsor designee reserves the right to close the study site or terminate the study 
at any time for any reason at the sole discretion of the Sponsor. Study sites will be 
closed upon study completion. A study site is considered closed when all required 
documents and study supplies have been collected and a study-site closure visit has 
been performed. 
• The investigator may initiate study-site closure at any time, provided there is 
reasonable cause and sufficient notice is given in advance of the intended termination. 


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• Reasons for the early closure of a study site by the Sponsor or investigator may 
include but are not limited to: 
− Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the Sponsor's procedures, or GCP guidelines 
− Inadequate recruitment of subjects by the investigator 
− Discontinuation of further IP development 
10.1.8. 
Publication Policy 
• The publication policy is located within the Clinical Study Agreement with the 
Investigator and/or Institution. 
















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10.4. 
Appendix 4:  Contraceptive Guidance and Collection of Pregnancy 
Information 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below). 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of IP, additional evaluation should be considered. 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry. 
Note: Documentation can come from the site personnel’s: review of the subject’s medical 
records, medical examination, or medical history interview. 
3. Postmenopausal female 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause.  
− A high follicle stimulating hormone (FSH) level (eg, > 40 IU/L) 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, confirmation with more 
than one FSH measurement is required.  
• Females on HRT and whose menopausal status is in doubt will be required to use one 
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. 


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Contraception Guidance: 
• A female subject is eligible to participate if she is not pregnant or breastfeeding, 
and at least one of the following conditions applies: 
− Is not a woman of childbearing potential (WOCBP) 
OR 
− Is a WOCBP and using a contraceptive method that is highly effective 
(with a failure rate of < 1% per year), preferably with low user dependency 
(see table below), at least 1 month prior to Screening, during the intervention 
period, and for 28 days after the last dose of IP, and agrees not to donate eggs 
(ova, oocytes) for the purpose of reproduction during this period. The investigator 
should evaluate the effectiveness of the contraceptive method in relationship to 
the first dose of IP. 
− A WOCBP must have a negative highly sensitive pregnancy test (urine or serum 
as required by local regulations) within 24 hours before the first dose of IP. 
− If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum 
pregnancy test is required. In such cases, the subject must be excluded from 
participation if the serum pregnancy result is positive. 
Contraceptive use should be consistent with local regulations regarding the use of contraceptive 
methods for those participating in clinical studies. 


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Highly Effective Methodsa  That Have Low User Dependency  
• 
Implantable progestogen-only hormone contraception associated with inhibition of ovulationb  
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS)b 
• 
Bilateral tubal occlusion 
• 
Vasectomized partner 
• 
(Vasectomized partner is a highly effective contraceptive method provided that the partner is the 
sole sexual partner of the woman of childbearing potential and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be used. 
Spermatogenesis cycle is approximately 90 days.) 
Highly Effective Methodsa That Are User Dependent  
• 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation 
− 
oral 
− 
intravaginal 
− 
transdermal 
− 
injectable 
• 
Progestogen-only hormone contraception associated with inhibition of ovulationb 
− 
oral 
− 
injectable 
• 
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 IP. 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.) 
a  Failure rate of < 1% per year when used consistently and correctly. Typical use failure rates differ from those 
when used consistently and correctly 
b  If locally required, in accordance with Clinical Trial Facilitation Group (CTFG) guidelines, acceptable 
contraceptive methods are limited to those which inhibit ovulation as the primary mode of action 
Note: Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception for 
this study. Male condom and female condom should not be used together (due to risk of failure with friction). 


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Collection of Pregnancy Information 
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 beyond the estimated 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 intervention by the investigator will be reported to the sponsor as described in 
Section 10.3.5. While the investigator is not obligated to actively seek this 
information in former study subjects, he or she may learn of an SAE through 
spontaneous reporting. 
• Any female subject who becomes pregnant while participating in the study will 
discontinue IP or be withdrawn from the study. 


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10.5. 
Appendix 5:  Genetics 
Use and Analysis of DNA 
• Genetic variation may impact a subject’s response to IP, susceptibility to, and severity 
and progression of disease. Variable response to IP may be due to genetic 
determinants that impact drug absorption, distribution, metabolism, and excretion; 
mechanism of action of the drug; disease etiology; and/or molecular subtype of the 
disease being treated. Therefore, where local regulations and IRB/IEC allow, a 
biosample may be collected for DNA analysis from consenting subjects. 
• DNA samples may be used for research related to the relationship between safety, 
efficacy, and exposure parameters collected in this study, as they related to placebo, 
GB001, CRS, and related diseases. They may also be used to develop tests/assays 
including diagnostic tests related to GB001 and DP2 inhibitors and/or atopic disease.  
• Genetic research may consist of the analysis of candidate polymorphisms, 
prespecified in the statistical analysis plan. 
• The samples may be analyzed as part of a multi-study assessment of genetic factors 
involved in the response to GB001 of this class to understand study disease or related 
atopic conditions. 
• The results of genetic analyses may be reported in a separate study summary. 
• The Sponsor will store the samples in a secure storage space with adequate measures 
to protect confidentiality. 
• The samples will be retained while research on GB001 continues but no longer than 
8 years or other period as per local requirements. 


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10.6. 
Appendix 6:  Liver Safety - Actions and Follow-up Assessments 
Liver chemistry will be evaluated as specified in the SoA (Section 1.3) and Appendix 2 
(Section 10.2). Parameters will include ALT, AST, GGT, bilirubin, total bile acids, and ALP. 
For subjects with ALT or AST > 1 × ULN and < 3 × ULN or total bilirubin or direct bilirubin 
> 1 × ULN and ≤ 1.5 × ULN, confirm the value within 24 to 48 hours. Contact the Medical 
Monitor to determine the appropriate liver monitoring schedule (eg, weekly or twice a week). 
The criteria requiring additional liver monitoring with possible interruption of study intervention 
are detailed in Table 5. 
Table 5: 
Liver Chemistry Criteria Requiring Additional Monitoring with Possible 
Interruption of Investigational Product 
Criterion 
Actions 
ALT or AST ≥ 3 × ULN and < 5 × ULN 
or total bilirubin or direct bilirubin > 1.5 
× ULN without symptoms believed to be 
related to liver injury or hypersensitivity, 
and who can be monitored weekly for 4 
weeks 
• 
Notify the Medical Monitor within 24 hours of 
learning of the abnormality to discuss subject safety.  
“Additional Liver Panel” in Table 6 may be requested 
by the Medical Monitor 
• 
Confirm values within 24 to 48 hours via repeat labs. 
If unable to obtain repeat labs within 48 hours, 
discontinue IP. 
• 
Decision to continue or interrupt study intervention 
will be determined by the Investigator and the Medical 
Monitor 
• 
Subject must return weekly or more frequently for 
repeat liver chemistry tests (ALT, AST, GGT, ALP, 
total bile acids, and bilirubin) until the abnormalities 
resolve, stabilize, or return to baseline. 
• 
If at any time the subject meets liver chemistry 
interruption criteria (as specified in Table 6), then 
follow the instructions in “Actions and  Follow-up 
Assessments” in  Table 6 and in consultation with the 
Medical Monitor initiate relevant assessment 
procedures. 
In the case of AEs of interest (Section 10.3.3), potential re-challenge will be restricted to 
potential DILI cases that have been assessed as unlikely or not related to IP by the HAC and after 
liver enzymes have returned to baseline levels. When re-challenging with IP, obtain repeat liver 
chemistries twice weekly in the first 2 weeks and then weekly for 6 weeks after the re-challenge. 
If there is a rise in liver enzymes > 2 × ULN, the IP should be discontinued permanently. 
The criteria requiring interruption of IP with additional liver monitoring is detailed in Table 6.  


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Table 6: 
Liver Chemistry Criteria Requiring Investigational Product Interruption 
and Additional Monitoring 
 
 
Liver Chemistry – IP Interruption Criteria 
ALT/AST (single occurrence) 
ALT or AST ≥ 5 × ULN 
ALT/AST 
ALT or AST ≥ 3 × ULN persists for ≥ 4 weeks 
+ Bilirubin a,b 
ALT or AST ≥ 3 × ULN and bilirubin > 2 × ULN (> 35% direct bilirubin) 
+ INR b 
ALT or AST ≥ 3 × ULN and international normalized ratio (INR) > 1.5, if 
INR measured 
+ Cannot Monitor 
ALT or AST ≥ 3 × ULN and cannot be monitored weekly for 4 weeks 
+ Symptomatic c 
ALT or AST ≥ 3 × ULN associated with symptoms (new or worsening) 
believed to be related to liver injury or hypersensitivity 
Actions and Follow-up Assessments  
Actions 
Follow-Up Assessments 
• 
Immediately discontinue IP 
• 
Report the event to the Medical Monitor within 
24 hours 
• 
Complete the liver event eCRF and complete an SAE 
data collection tool if the event also met the criteria 
for an SAEb 
• 
Perform liver chemistry follow-up assessments. 
• 
Monitor the subject until liver chemistry test 
abnormalities resolve, stabilize, or return to baseline 
(see MONITORING) 
• 
Do not restart/rechallenge subject with IP unless 
Medical Monitor approval is granted 
• 
If restart/rechallenge not granted, permanently 
discontinue IP and continue subject in the study for 
any protocol specified follow up assessments 
 
MONITORING: 
 
• 
Repeat liver chemistry tests (include ALT, AST, 
GGT, alkaline phosphatase, total bile acids, bilirubin, 
and INR) and perform liver event follow-up 
assessments within 24 hours 
• 
Monitor subject twice weekly until liver chemistry 
test abnormalities resolve, stabilize, or return to 
baseline 
• 
A specialist or hepatology consultation is 
recommended 
 
Additional Liver Panel 
• 
Viral hepatitis serology d 
• 
Obtain INR and recheck with each liver 
chemistry assessment until the ALT and/or AST 
values show downward trend 
• 
Obtain blood sample for pharmacokinetic (PK) 
analysis  
• 
Serum creatine phosphokinase (CPK) 
and lactate dehydrogenase (LDH) 
• 
Fractionate bilirubin, if total bilirubin 
> 2 × ULN 
• 
Obtain complete blood count with differential to 
assess eosinophilia 
• 
Record the appearance or worsening of clinical 
symptoms of liver injury, or hypersensitivity, on 
the adverse event (AE) report form 
• 
Record use of concomitant medications 
(including acetaminophen, herbal remedies, and 
other over-the-counter medications) on the 
concomitant medications eCRF 
• 
Record alcohol use on the liver event alcohol 
intake eCRF 
• 
Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney microsomal 
antibodies, and quantitative total 
immunoglobulin G (IgG) or gamma globulins 
• 
Serum acetaminophen assay 
• 
Liver imaging (ultrasound, magnetic resonance, 
or computerized tomography) and/or liver 
biopsy to evaluate liver disease 
a.    Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue IP if ALT or AST ≥ 3 × ULN and bilirubin > 2 × ULN. Additionally, if 
serum bilirubin fractionation testing is unavailable, record the absence/presence of detectable urinary 
bilirubin on dipstick which is indicative of direct bilirubin elevations suggesting liver injury. 


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b. All events of ALT or AST  ≥ 3 × ULN and bilirubin > 2 × ULN (> 35% direct bilirubin) or ALT 
or AST ≥ 3 × ULN and INR > 1.5 may indicate severe liver injury (possible ‘Hy’s Law’) and must be 
reported as an SAE (excluding studies of hepatic impairment or cirrhosis). The INR stated threshold value 
will not apply to subjects receiving anticoagulants. INR is not part of routine laboratory assessments in this 
study. 
c.  
New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness, or jaundice) or hypersensitivity (such as fever, rash, or eosinophilia). 
d. Includes: expanded viral hepatitis serology (Section 10.2 Table 4) 
 


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10.7. 
Appendix 7:  Visual Analog scale (VAS) 
To evaluate the total severity, the subject is asked to indicate on a VAS the answer to the 
question: 
How troublesome are your symptoms of rhinosinusitis? 
 
    Not troublesome  
 
 
 
 
Worst thinkable troublesome 
 
Example, not for use. Not to scale. 


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10.8. 
Appendix 8:  ACQ-5 Questionnaire 
The ACQ-5 questionnaire is located on the following page. 


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ASTHMA CONTROL QUESTIONNAIRE© 
PATIENT ID: 
(LANGUAGE VERSION FOR COUNTRY) 
DATE: 
Page 1 of 1 
ACQ-5 - Canada/English - Mapi. 
ACQ-5_AU1.0_eng-CAori.doc 
Please answer questions 1 - 5. 
Circle the number of the response that best describes how you have been during the past week. 
1.
On average, during the past week,
how often were you woken by your
asthma during the night?
0 
Never 
1 
Hardly ever 
2 
A few times 
3 
Several times 
4 
Many times 
5 
A great many times 
6 
Unable to sleep because of asthma 
2.
On average, during the past week,
how bad were your asthma symptoms
when you woke up in the morning?
0 
No symptoms 
1 
Very mild symptoms 
2 
Mild symptoms 
3 
Moderate symptoms 
4 
Quite severe symptoms 
5 
Severe symptoms 
6 
Very severe symptoms 
3.
In general, during the past week, how
limited were you in your activities
because of your asthma?
0 
Not limited at all 
1 
Very slightly limited 
2 
Slightly limited 
3 
Moderately limited 
4 
Very limited 
5 
Extremely limited 
6 
Totally limited 
4.
In general, during the past week, how
much shortness of breath did you
experience because of your asthma?
0 
None 
1 
A very little 
2 
A little 
3 
A moderate amount 
4 
Quite a lot 
5 
A great deal 
6 
A very great deal 
5.
In general, during the past week, how
much of the time did you wheeze?
0 
Not at all 
1 
Hardly any of the time 
2 
A little of the time 
3 
A moderate amount of the time 
4 
A lot of the time 
5 
Most of the time 
6 
All the time 
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10.9. 
Appendix 9:  SNOT-22 Questionnaire 
The SNOT-22 questionnaire is located on the following page. 














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10.11. 
Appendix 11:  Guidance to Address a Pandemic or Other Global 
Health Emergencies and Potential Impact on the Clinical Study 
In the occurrence of a global health pandemic affecting the conduct of the ongoing study, such as 
the COVID-19 pandemic, study conduct may be adjusted due to subjects being in self-
isolation/quarantine, limited access to public places (including hospitals) due to the risk of 
spreading infections, and health care professionals being committed to critical tasks (FDA, 2020; 
EMA, 2020; Health Canada, 2020; MHRA, 2020). 
Adjustments to the GB001-2101 protocol may be made as described below, in line with global 
regulatory authorities guidance in order to ensure the safety of study participants, maintain 
compliance with GCP, and minimize the risks to trial integrity during the COVID-19 pandemic 
(FDA, 2020; EMA, 2020; Health Canada, 2020; MHRA, 2020). Member states within the 
National Competent Authorities may issue their own guidance requiring country specific 
recommendations to be followed.  
• In the case of missed visits due to COVID-19 (or other health pandemic) related 
reasons: 
− The site should make every effort to contact the subject to confirm and document 
the reason for the missed visit, and at minimum evaluate AEs/SAEs, concomitant 
medications, and the SNOT-22 questionnaire in order to assess subject status.  
− The subject should continue to collect the daily morning and evening symptom 
diary as described in Section 8.1.4.  
• Alternative methods of collecting study assessments may be considered where 
possible: 
− Questionnaires, including SNOT-22, UPSIT, and ACQ-5, may be self-
administered by the subject at home. 
− In certain situations, with Sponsor approval, a local laboratory may be used. 
• Alternative methods of supplying IP to study subjects (eg, direct-to-patient shipment 
from site) may be considered where possible. 
− With prior sponsor approval, IP may be supplied via alternative methods provided 
that laboratory assessments are able to be performed prior to the delivery of IP. In 
all cases, study subjects must provide consent for alternative delivery methods. 
Documentation of consent will be captured in the subject’s study records.  
 


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10.12. 
Appendix 12:  Abbreviations 
Abbreviation Term 
Description 
ACQ-5 
Asthma Control Questionnaire 
AE 
adverse event  
AERD 
aspirin-exacerbated respiratory disease 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
BID 
twice daily 
BMI 
body mass index  
BUN 
blood urea nitrogen  
CI 
confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences  
CONSORT 
Consolidated Standards of Reporting Trials 
COX-2 
cyclooxygenase 2 
CRS 
chronic rhinosinusitis 
CRSsNP 
chronic rhinosinusitis without nasal polyps 
CRSwNP 
chronic rhinosinusitis with nasal polyps 
CSR 
clinical study report  
CT 
Computed Tomography 
CTFG 
Clinical Trial Facilitation Group  
CysLT 
cysteinyl leukotriene 
DILI 
drug induced liver injury 
DP2 
prostaglandin D2 receptor 
ECG 
electrocardiogram  
ECP 
eosinophil cationic protein 
eCRF 
electronic case report form 
eCRS 
eosinophilic chronic rhinosinusitis 
EW 
early withdrawal 
FeNO 
fractional exhaled nitric oxide 
FEV1 
forced expiratory volume in 1 second 


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Abbreviation Term 
Description 
FSH 
follicle-stimulating hormone  
GCP 
Good Clinical Practice  
GGT 
gamma-glutamyl transferase  
GINA 
Global Initiative for Asthma 
HAC 
Hepatology Assessment Committee 
HBcAb 
Hepatitis B core antibody  
HBsAg 
Hepatitis B surface antigen 
hCG 
human chorionic gonadotropin  
HDPE 
high-density polyethylene 
HIV 
human immunodeficiency virus 
HIPAA 
Health Insurance Portability and Accountability Act  
HRT 
hormonal replacement therapy  
IB 
Investigator’s Brochure  
ICF 
informed consent form 
ICH 
International Council for Harmonisation  
IDMC 
Independent Data Monitoring Committee  
IEC 
Independent Ethics Committee 
IL 
interleukin (IL-4, IL-5, IL-13) 
ILC2 
Group 2 innate lymphoid cells 
INCS  
intranasal corticosteroids 
INR 
international normalized ratio  
IP 
investigational product 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
ITT 
intent-to-treat 
IUD 
intrauterine device 
IUS 
intrauterine hormone-releasing system 
LAM 
lactational amenorrhoea method  
LDH 
lactate dehydrogenase  
LXA4 
lipoxin A4 
MCID 
minimal clinically important difference  
MFNS 
mometasone furoate nasal spray 


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Abbreviation Term 
Description 
MMRM 
mixed-effects model with repeated measures 
NAFLD 
non-alcoholic fatty liver disease 
NC 
nasal congestion 
nNO 
nasal nitric oxide 
NP   
nasal polyps 
NPS  
nasal polyp score 
OC 
osteomeatal complex 
PD 
pharmacodynamic  
PGD2 
prostaglandin D2 
PGE2 
prostaglandin E2 
PGx 
pharmacogenetics 
PK 
pharmacokinetic 
QD 
once daily 
QTcF 
Fridericia's correction formula for QT interval (interval between Q wave 
and T wave) 
RBC 
red blood cell  
REML 
restricted maximum-likelihood 
RNA 
ribonucleic acid  
SAE 
serious adverse event  
SNOT-22 
Sino-Nasal Outcome Test 
SoA 
schedule of activities  
SOC 
standard of care  
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
Th2 
T Helper cell type 2 
TSS 
total symptom score 
ULN 
upper limit of normal  
UPSIT 
University of Pennsylvania Smell Identification Test 
VAS 
visual analog scale 
WBC 
white blood cell  
WOCBP 
women of childbearing potential 
 


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10.13. 
Appendix 13: Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents (TOC). 
DOCUMENT HISTORY  
Document  
Date  
Amendment 4 (v4.0) 
18 Feb 2020 
Amendment 3 (v3.0) 
28 Aug 2019 
Amendment 2 (v2.1) 
02 May 2019 
Amendment 1 (v2.0.0)  
05 Apr 2019  
Original Protocol (v1.0.0)  
24 Jan 2019  
Amendment 4 (v4.0; 18 Feb 2020)  
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for the Amendment:  
The primary purpose of this amendment is to enhance monitoring of liver parameters during the 
conduct of the trial and provide clarification on eligibility criteria. 
Section # and Name  
Description of Change  
Brief Rationale  
Section 1.3 Schedule of 
Activities; 
Section 1.2 Schema 
Addition of a Week 1 visit (Visit 
2.5) serum chemistry panel 
following Randomization (Visit 
2). Added CRS exacerbation 
review at Visits 1, 2, and 2.5.  
Week 1 visit was added to 
enhance laboratory monitoring 
during the first month following 
IP initiation. Clarified that CRS 
exacerbation review is performed 
at every visit. 
Section 4.1.1 Study Design; 
Section 4.2.1 Study 
Population; 
Section 6.3.1 Randomization 
Added visual examination as a 
method of confirming absence of 
nasal polyps 
Clarified definition of absence of 
nasal polyps 
Section 5.3  
Randomization Criteria #6   
Modification of the 
randomization criteria from ALT 
and AST < 2 × ULN to ALT and 
AST ≤ 1 × ULN 
Enhance safety characterization 
of the study population 
Section 6.3.4 Unblinded 
Sponsor Medical Monitor 
Added new monitoring guidelines 
To enable unblinded medical 
monitoring of liver and other 
laboratory parameters of interest 
by a designated Sponsor Medical 
Monitor in order to protect 
subject safety 
Section 10.3.3 Adverse 
Events of Interest 
Updated language describing 
adverse events of interest 
Clarified definition of adverse 
events of interest 


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Section # and Name  
Description of Change  
Brief Rationale  
Section 10.6 Appendix 6: 
Liver Safety - Actions and 
Follow-up Assessments 
Modified: 
• 
Discussion of possible 
Investigational Product (IP) 
continuation or 
discontinuation if ALT or 
AST ≥ 3 × ULN or total 
bilirubin or direct bilirubin > 
1.5 × ULN and potential 
triggering of appropriate 
follow-up to include Liver 
Safety Laboratory 
assessments 
• 
ALT or AST > 1 × ULN and 
< 3 × ULN or total bilirubin 
or direct bilirubin > 1 × ULN 
and ≤ 1.5 × ULN, confirm the 
value within 24 to 48 hours 
To enhance monitoring of liver 
parameters during the conduct of 
the trial 
Global Change 
Minor revisions to text 
Administrative updates were 
incorporated, and typographical 
errors were corrected 
 


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Amendment 3 (v3.0; 28 Aug 2019)  
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for the Amendment:  
The primary purpose of this amendment is to enhance monitoring of liver parameters during the 
conduct of the trial and to provide guidance on drugs that may be associated with hepatoxicity 
and provide clarification on eligibility criteria. 
Section # and Name  
Description of Change  
Brief Rationale  
Section 1.3 Schedule of 
Activities; 
Section 1.2 Schema 
• 
Notes on total bile acid, 
international normalized ratio 
(INR), and fractionation of 
ALP if ALP > 1xULN were 
added. 
• 
Added assessment of clinical 
chemistry at Week 3.  
• 
Added separate line for 
concomitant medications.  
 
• 
Addition of INR 
measurement at baseline. 
Collection of a total bile acid   
sample at every visit, and 
fractionation of ALP if ALP 
> 1xULN. 
• 
Week 3 visit was added to 
enhance laboratory 
monitoring during the first 
month following IP initiation. 
• 
Clarified timing of 
concomitant medications. 
Section 2.3.1 GB001 
Risk/Benefit Assessment 
Revised data for GB001. 
Clarified risk/benefit profile. 
Section 5.1  
Inclusion Criterion #2  
Maximum age was increased. 
Higher maximum age allowed 
because no additional risk is 
expected in this extended 
population. 
Section 5.2  
Exclusion Criteria #2 
Clarified polypectomy performed 
as an outpatient procedure will 
not exclude subject from study. 
Polypectomy performed as an 
outpatient procedure is 
considered a minor surgery. 
Section 5.2  
Exclusion Criteria #5   
 
Added known history of non-
alcoholic fatty liver disease 
(NAFLD) or Gilbert’s Syndrome. 
Clarified liver-related pre-existing 
conditions. 
Section 5.3  
Randomization Criteria #2  
Updated nasal polyp score (NPS) 
range for exclusion from 
randomization. 
Clarified that subjects with NPS 
of 0 are eligible for 
randomization. 
Section 5.3  
Randomization Criteria #6   
Added maximum absolute 
eosinophil count and white blood 
cell (WBC) count criteria. 
Enhance safety characterization 
of the study population 
Section 6.5.1 Prohibited 
Medications Prior to the 
Screening Visit and 
Throughout the Study; 
• 
Added the concept of 
restricted medications. 
Referred investigators to list 
of medications in Appendix 
10 which include those 
• 
Increased awareness of 
medications which may 
impact liver effects and those 
drugs/agents that may inhibit 
or induce CYP3A. 


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Section # and Name  
Description of Change  
Brief Rationale  
Section 10.10 Appendix 10: 
Prohibited Medications and 
Treatments 
medications known to have 
the potential for drug induced 
liver injury (DILI) as well as 
CYP3A inhibitors and 
inducers. 
• 
Removed XHANCE™ as a 
prohibited medication. 
• 
Intranasal corticosteroid 
delivered via a specialized 
device will be allowed under 
Inclusion Criteria #6. 
Section 8 Study Assessments 
and Procedures 
Added language on nasal 
endoscopy and nitric oxide 
measurement at Randomization 
visit. 
Clarified which subjects should 
receive nasal endoscopy and that 
all subjects should have nitric 
oxide measurement. 
Section 8.1.2 Computed 
Tomography (CT) 
Updated language that prior CT 
may be acceptable under specific 
conditions. 
Clarification that a prior CT 
within 60 days of the 
Randomization visit of 
satisfactory quality may be 
acceptable. 
Section 10.2 Appendix 2: 
Clinical Laboratory Tests 
Table 3  
Total bile acid, INR, and 
fractionation of ALP if ALP > 
1xULN were added.  
To enhance monitoring of liver 
parameters during the conduct of 
the trial. 
Global Change 
Minor revisions to text. 
Administrative updates were 
incorporated, and typographical 
errors were corrected. 


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Amendment 2 (v2.1; 02 May 2019)  
This amendment is considered to be nonsubstantial based on the criteria set forth in Article 10(a) 
of Directive 2001/20/EC of the European Parliament and the Council of the European Union 
because it neither significantly impacts the safety or physical/mental integrity of participants nor 
the scientific value of the study. 
Overall Rationale for the Amendment:  
The primary purpose of this amendment is to remove assessment of nitric oxide at the Screening 
visit. 
Section # and Name  
Description of Change  
Brief Rationale  
Section 1.3 Schedule of Activities 
Removed assessment of nitric 
oxide at Screening visit. 
Nasal nitric oxide (nNO) 
and fractional exhaled nitric 
oxide (FeNO) tests are not 
required at the time of 
screening. 
Section 2.2 Background 
Added results from a recent 
poster. 
Updated with results which 
suggest that GB001 
influences lung function in 
subjects with markers of 
eosinophilic inflammation. 
Section 7.1 Discontinuation of 
Investigational Product 
Included separate section on 
liver safety. 
Clarification on liver 
chemistry criteria that will 
result in permanent 
discontinuation of 
investigational product. 
Section 8.1.2 Computed Tomography 
(CT) 
Updated text to imaging core 
laboratory. 
Clarification that imaging 
core laboratory will analyze 
CT sequences. 
Section 10.3.5 Reporting of SAEs 
Contact information was 
updated. 
Updated contact information 
for sites outside North 
America. 
Global Change 
Minor revisions to text. 
Administrative updates were 
incorporated, and 
typographical errors were 
corrected. 


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Amendment 1 (v2.0.0; 5 Apr 2019)  
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union based 
on the criteria set forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and 
the Council of the European Union.  
Overall Rationale for the Amendment:  
The primary purpose of this amendment is to increase the sample size of the study, include an 
exclusion criterion for AERD, incorporate additional objectives and endpoints, and revise the 
statistical considerations section to reflect the increased sample size and additional endpoints. 
Section # and Name  
Description of Change  
Brief Rationale  
Section 1.1 Synopsis; 
Section 1.2 Schema; 
Section 4.1.1 Study Design; 
Section 4.2.1 Study Population; 
Section 6.3.1 Randomization; 
Section 9 Statistical Considerations 
Total sample size increased to 
100. Added text on 
randomization and 
stratification. 
Increased total number of 
subjects by 30 to enable 
better characterization of 
benefit-risk profile in 
subjects with nasal polyps. 
Clarification on 
randomization and 
stratification. 
Section 1.1 Synopsis; 
Section 1.3 Schedule of Activities;  
Section 3 Objectives and Endpoints; 
Section 8.1.9 Other Assessments; 
Section 9.4.1.2 Secondary Efficacy 
Analysis 
Included additional secondary 
endpoint and clarified 
previous endpoints. 
Added and clarified 
secondary endpoints to 
evaluate data including 
exacerbations, time to first 
response in NPS, and change 
in total symptom score to 
better characterize CRS. 
Section 1.3 Schedule of Activities  
Hepatitis B surface antigen 
and Hepatitis C antibody text 
was updated. 
Clarification to include 
indeterminate test result. 
Section 1.3 Schedule of Activities; 
Section 4.1.1 Study Design; 
Section 4.2.1 Study Population; 
Section 5.3 Randomization Criteria; 
Section 8 Study Assessments and 
Procedures 
Added use of mometasone 
furoate nasal spray (MFNS) 
equivalent. 
MFNS may not be available 
in some ex-US countries and 
therefore an equivalent 
product may be used. 
Section 3 Objectives and Endpoints  
Included additional 
exploratory endpoints. 
Added 3 exploratory 
endpoints to further 
understand the role of 
GB001 in CRS.   
Section 4.1.1 Study Design   
Written informed consent text 
was updated. 
The modification was made 
to clarify that informed 
consent may be obtained 
prior to Visit 1 to allow for 
medication washouts and 


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Section # and Name  
Description of Change  
Brief Rationale  
obtaining historical medical 
records when necessary.  
Section 4.2.1 Study Population; 
Section 5.2 Exclusion Criteria 
Add aspirin-exacerbated 
respiratory disease (AERD) 
exclusion criterion. 
Remove subjects with 
AERD to maintain a more 
homogeneous study 
population. 
Section 5.2 Exclusion Criteria 
Text around ECG assessment 
was updated. 
This modification was made 
to improve clarity that ECG 
assessment could be 
repeated. 
Section 5.2 Exclusion Criteria 
Text was added to exclude 
smoking of any substance. 
This clarification was made 
to include marijuana, its 
components, and any other 
substances which may be 
smoked. 
Section 5.3 Randomization Criteria; 
Section 8 Study Assessments and 
Procedures; 
Section 8.3.7 Disease-Related Events 
and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs 
Added criterion for subjects 
who experience an 
exacerbation. 
Added definition of an 
exacerbation and clarification 
regarding adverse event 
qualification. 
Clarification on timing of 
randomization for subjects 
who experience an 
exacerbation. Definition was 
added to characterize 
worsening of disease 
(exacerbations) that may 
occur during the study. 
Section 5.4 Screen or Run-In Failures 
Text added to clarify 
designation of Run-in failure. 
Clarification on Run-in 
failure definition for this 
study. 
Section 6.3.3 Unblinding of an 
Individual Subject; 
Section 9.5 Interim Analyses 
Text added to clarify 
conditions for unblinding. 
Clarification of procedures 
to protect samples and data 
for unblinding. 
Section 7.1.1 Pregnancy 
Updated text on Follow-up 
visit. 
Clarification on procedures 
if the subject who becomes 
pregnant. 
Section 7.2 Subject Withdrawal from 
the Study 
Updated text to provide 
further clarity. 
Clarification on reasons for 
subject withdrawal from 
study. 
Section 8 Study Assessments and 
Procedures 
Changed order of assessments Arranged assessments such 
that efficacy assessments 
follow the ordering of 
endpoints. 
Section 8.6.3 RNA Transcriptome 
Research 
Text was updated. 
Clarification that not all 
samples may be analyzed. 


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Section # and Name  
Description of Change  
Brief Rationale  
Section 10.10 Appendix 10:  
Prohibited Medications and 
Treatments 
Clarification in reference to a 
medication. 
Replaced company name 
(Optinose) with trade name 
(XHANCE). 
Global Change 
Minor revisions to text. 
Typographical errors were 
corrected. 
 


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11. 
REFERENCES 
Bachert C, Sousa AR. Lund JV, et al. Reduced need for surgery in severe nasal polyposis with 
mepolizumab: Randomized trial. J Allergy Clin Immunol 2017;140:1024-1031. 
Bachert C, Mannent L, Naclerio RM, et al. Effect of subcutaneous dupilumab on nasal polyp 
burden in patients with chronic sinusitis and nasal polyposis: a randomized clinical trial. JAMA 
2016;315:469-479. 
Björnsson, ES. Hepatotoxicity by Drugs: The Most Common Implicated Agents. Int J Mol Sci. 
2016;17(2):224.  
Collins JG. Prevalence of selected chronic conditions: United States, 1990–1992. Vital Health 
Stat 1997;194:1–89. 
Crombruggen K, Zhang N, Gevaert P, Tomassen P, Bachert C. Pathogenesis of chronic 
rhinosinusitis: Inflammation. J Allergy Clin Immunol 2011;128:728-732. 
Doty RL, Shaman P, Kimmelman CP, Dann MS. University of Pennsylvania Smell Identification 
Test: a rapid quantitative olfactory function test for the clinic. Laryngoscope 1984;94:176-178. 
EMA, Points to consider on implications of Coronavirus disease (COVID-19) on methodological 
aspects of ongoing clinical trials. Amsterdam, The Netherlands: Committee for Human 
Medicinal Products; March 2020. 
FDA, Guidance for Industry. Drug-Induced Liver Injury: Premarketing Clinical Evaluation. 
Rockville, MD: Center for Drug Evaluation and Research, Food and Drug Administration, US 
Dept of Health and Human Services; July 2009. 
FDA, FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 
Pandemic. Rockville, MD: Center for Drug Evaluation and Research, Food and Drug 
Administration, US Dept of Health and Human Services; April 2020. 
Ferguson BJ. Categorization of eosinophilic chronic rhinosinusitis. Curr Opin Otolaryngol Head 
Neck Surg 2004;12:237-242. 
Fokkens W, Lund V, Mullol J. European position paper on rhinosinusitis and nasal polyps 2007. 
Rhinol Suppl 2007;20:1-136. 
Hastan D, Fokkens WJ, Bachert C, et al. Chronic rhinosinusitis in Europe – an underestimated 
disease. A GA(2)LEN study. Allergy 2011;9:1216–1223. 
Health Canada, Management of clinical trials during the COVID-19 pandemic: Notice to clinical 
trial sponsors. 2020. https://www.canada.ca/en/health-canada/services/drugs-health-
products/drug-products/announcements/management-clinical-trials-during-covid-19-
pandemic.html. Accessed April 13, 2020. 
Ho J, Hamizan WA, Alvarado R, et al. Systemic predictors of eosinophilic chronic rhinosinusitis. 
Am J Rhinol Allergy 2018;32:252-257. 
Hopkins C, Gillett S, Slack R, Lund VJ, Browne JP. Psychometric validity of the 22- item 
sinonasal outcome test. Clin Otolaryngology 2009;34:447-454.  


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Horak F, Zieglmayer P, Zieglmayer R, Lemell P, et al. The CRTH2 antagonist OC000459 
reduces nasal and ocular symptoms in allergic subjects exposed to grass pollen, a randomised, 
placebo-controlled, double-blind trial. Allergy 2012;67:1572–1579. 
Kato A. Group 2 innate lymphoid cells in airway diseases. Chest 2019;156:141-149. 
Kuiper JR, Hirsch AG, Bandeen-Roche K, et al. Prevalence, severity, and risk factors for acute 
exacerbations of nasal and sinus symptoms by chronic rhinosinusitis status. Allergy 
2018;73(6):1244-1253. 
Kupczyk, M. and Kuna, P. Targeting the PGD2/CRTH2/DP1 Signaling pathway in asthma and 
allergic disease: current status and future perspectives. Drugs 2017;77:1281-1294 
Lund VJ, Mackay IS. Staging in rhinosinusitus. Rhinology. 1993;31:183-184. 
Meltzer EO1, Hamilos DL, Hadley JA, et al. Rhinosinusitis: developing guidance for clinical 
trials. J Allergy Clin Immunol 2006;118(5 Suppl):S17-61. 
MHRA, Guidance: Managing clinical trials during Coronavirus (COVID-19). 2020. 
https://www.gov.uk/guidance/managing-clinical-trials-during-coronavirus-covid-19. Accessed 
April 13, 2020. 
Ortega H, Fitzgerald M, Bhakta N, Raghupathi K, Singh D. Reduction of exhaled nitric oxide by 
the DP2 antagonist GB001 in patients with mild atopic asthma. J Allergy Clin Immunol. 
2019a;143(2):AB104. 
Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, et al. Clinical practice guideline (update): adult 
sinusitis. Otolaryngol Head Neck Surg 2015;152(2 Suppl):S1-S39. 
Rothenberg ME, Saito H, Peebles RS. Advances in mechanisms of allergic disease in 2016. J 
Allergy Clin Immunol 2017;140:1622-1631. 
Scadding G, Hellings P, Alobid I, Bachert C, Fokkens W, Van Wijk RG, et al. Diagnostic tools 
in Rhinology EAACI position paper. Clin Transl Allergy 2011:2;1-39. 
Singh D, Ravi A, Southworth T. CRTH2 antagonists in asthma: current perspectives. Clin 
Pharmacol 2017;9:165-173. 
Skolnick BE, Ortega H, Raghupathi K, Tompkins C, Fitzgerald M, Singh D. Markers of 
eosinophilic inflammation are associated with response to the DP2 antagonist GB001. American 
Rhinologic Society Annual Meeting; September 13-14, 2019; New Orleans, LA. 
Tan BK, Klingler AI, Poposki JA, Stevens WW, Peters AT, Suh LA, et al. Heterogeneous 
inflammatory patterns in chronic rhinosinusitis without nasal polyps in Chicago, Illinois. J 
Allergy Clin Immunol 2017;139:699-703. 
Thomas M, Yawn BP, Price D, Lund V, Mullol J, Fokkens W. EPOS Primary Care Guidelines: 
European position paper on the primary care diagnosis and management of rhinosinusitis and 
nasal polyps 2007 - a summary. Primary Care Respiratory Journal 2008;17:79-89. 
Tomassen P, Vandeplas G, Van Zele T, Cardell LO, Arebro J, Olze H, et al. Inflammatory 
endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. J Allergy Clin 
Immunol 2016;137:1449-1456. 


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van Agthoven M1, Fokkens WJ, van de Merwe JP, Marijke van Bolhuis E, Uyl-de Groot CA, 
Busschbach JJ. Quality of life of patients with refractory chronic rhinosinusitis: effects of 
filgrastim treatment. Am J Rhinol. 2001;15:231-237. 
 

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Statistical Analysis Plan 
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Page 2 of 50 
VERSION CONTROL 
Version Number 
Date 
Comments/Changes 
1.0 
01 September 2020 
Final 
 
 


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Page 4 of 50 
TABLE OF CONTENTS 
VERSION CONTROL ....................................................................................................................2 
APPROVALS ..................................................................................................................................3 
LIST OF ABBREVIATIONS ..........................................................................................................7 
1. 
PURPOSE OF THE ANALYSIS ................................................................................10 
2. 
PROTOCOL SUMMARY ...........................................................................................11 
2.1. 
Objectives and Endpoints ............................................................................................11 
2.2. 
Overall Study Design and Plan ....................................................................................12 
2.3. 
Study Population ..........................................................................................................13 
2.4. 
Randomization and Treatment Regimens ....................................................................14 
2.5. 
Sample Size Determination..........................................................................................14 
3. 
GENERAL ANALYSIS AND REPORTING CONVENTIONS................................15 
3.1. 
Visit Windowing ..........................................................................................................16 
3.2. 
Standard Calculations ..................................................................................................17 
3.3. 
Considerations Related to the COVID-19 Pandemic ...................................................18 
4. 
ANALYSIS POPULATIONS .....................................................................................20 
4.1. 
All Enrolled Population ...............................................................................................20 
4.2. 
Run-in Period Population .............................................................................................20 
4.3. 
Intent-to-Treat Population ............................................................................................20 
4.4. 
Safety Population .........................................................................................................20 
5. 
STUDY PATIENTS ....................................................................................................21 
5.1. 
Disposition of Patients .................................................................................................21 
5.2. 
Protocol Deviations ......................................................................................................21 
6. 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS ......................22 
6.1. 
Demographic Characteristics .......................................................................................22 
6.2. 
Baseline Disease Characteristics ..................................................................................22 
6.3. 
Atopic/Allergic Conditions ..........................................................................................23 
6.4. 
Efficacy-Related Baseline Characteristics ...................................................................24 
6.5. 
Biomarker Baseline Characteristics .............................................................................24 
6.6. 
Medical History ...........................................................................................................25 
6.7. 
Prior Medications .........................................................................................................25 
6.8. 
Concomitant Medications ............................................................................................25 


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7. 
EXTENT OF EXPOSURE, COMPLIANCE, AND TIME ON STUDY ....................27 
7.1. 
Extent of Exposure .......................................................................................................27 
7.2. 
Compliance ..................................................................................................................27 
7.3. 
Time on Study ..............................................................................................................27 
8. 
EFFICACY EVALUATION .......................................................................................28 
8.1. 
Overview of Efficacy Analysis Issues .........................................................................28 
8.1.1. 
Handling of Dropouts or Missing Data ........................................................................28 
8.1.2. 
Multicenter Studies ......................................................................................................28 
8.2. 
Efficacy Endpoints .......................................................................................................28 
8.3. 
Analysis Methods.........................................................................................................32 
8.3.1. 
Primary Efficacy Analyses ..........................................................................................32 
8.3.1.1. 
MMRM without MI .....................................................................................................32 
8.3.1.2. 
MMRM with MI ..........................................................................................................33 
8.3.1.3. 
ANCOVA without MI .................................................................................................34 
8.3.1.4. 
ANCOVA with MI ......................................................................................................34 
8.3.1.5. 
Additional Analyses of the Primary Endpoint .............................................................34 
8.3.2. 
Secondary Efficacy Analyses ......................................................................................35 
8.3.2.1. 
Change from Baseline to Week 16 Endpoints .............................................................35 
8.3.2.1.1. Lund-Mackay and UPSIT Scores ................................................................................35 
8.3.2.1.2. NPS and Symptom Scores ...........................................................................................36 
8.3.2.2. 
Time to Event Endpoints .............................................................................................37 
8.3.3. 
Exploratory and Additional Analyses ..........................................................................39 
8.3.3.1. 
Change from Baseline to Week 16 Endpoints .............................................................39 
8.3.3.2. 
Change from Baseline to Week 16 Including All Data Endpoints ..............................39 
8.3.3.3. 
Annualized Rate of CRS Exacerbations ......................................................................40 
8.3.3.4. 
Proportion of Subjects with Antibiotic Use Due to Worsening CRS by Week 16 ......41 
8.3.3.5. 
Other Endpoints ...........................................................................................................41 
8.3.3.5.1. Nitric Oxide .................................................................................................................41 
8.3.3.5.2. ACQ-5 Score ................................................................................................................41 
8.3.3.5.3. PK Concentrations .......................................................................................................42 
8.4. 
Examination of Subgroups ...........................................................................................42 
8.4.1. 
Examination of CRSsNP and CRSwNP Subgroups ....................................................42 


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8.4.2. 
Examination of Other Subgroups.................................................................................43 
9. 
SAFETY EVALUATION ...........................................................................................45 
9.1. 
Adverse Events ............................................................................................................45 
9.2. 
Clinical Laboratory Evaluation ....................................................................................46 
9.3. 
Vital Signs and Other Observations Related to Safety ................................................47 
9.3.1. 
Vital Signs ....................................................................................................................47 
9.3.2. 
Other Safety Measures .................................................................................................47 
9.3.2.1. 
Electrocardiograms ......................................................................................................47 
10. 
REFERENCES ............................................................................................................49 
 
LIST OF TABLES 
Table 1:  Efficacy Endpoints and Analysis Methods .....................................................................29 
Table 2:  Vital Sign Parameter Abnormality Criteria ....................................................................47 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ACQ-5 
Asthma Control Questionnaire 
AE 
adverse event 
ALT 
alanine aminotransferase 
AM 
morning 
ANCOVA 
analysis of covariance 
ANOVA 
analysis of variance 
AST 
aspartate aminotransferase 
ATC 
anatomical therapeutic chemical 
BID 
twice daily 
BLQ 
below limit of quantification 
BMI 
body mass index 
BPM 
beats per minute 
CI 
confidence interval 
COVID-19 
Coronavirus Disease 2019 
CRS 
chronic rhinosinusitis  
CRSsNP 
chronic rhinosinusitis without nasal polyps 
CRSwNP 
chronic rhinosinusitis with nasal polyps 
CSR 
clinical study report 
CT 
computed tomography 
CTS 
continuous 
CV 
coefficient of variation 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
eDISH 
evaluation of Drug-Induced Serious Hepatotoxicity 
EM 
expectation-maximization 
EMA 
European Medicines Agency 
EW 
early withdrawal 
FDA 
Food and Drug Administration 
FeNO 
fractional exhaled nitric oxide 


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Abbreviation 
Definition 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transferase 
GINA 
Global Initiative for Asthma 
ICH 
International Conference on Harmonisation 
INCS 
intranasal corticosteroids 
IP 
investigational product 
ITT 
intent-to-treat 
LABA 
long-acting beta-agonist 
LAMA 
long-acting muscarinic antagonist 
LLOQ 
lower limit of quantification 
LS 
least squares 
MCID 
minimal clinically important difference 
MCMC 
Markov Chain Monte Carlo 
MedDRA 
Medical Dictionary for Regulatory Activities 
MFNS 
mometasone furoate nasal spray 
MI 
multiple imputation 
MMRM 
mixed-effects model with repeated measures 
NC 
nasal congestion 
nNO 
nasal nitric oxide 
NP 
nasal polyps 
NPS 
nasal polyp score 
OR 
odds ratio 
PD 
pharmacodynamics 
PGx 
pharmacogenetics 
PM 
evening 
PK 
pharmacokinetics 
PT 
preferred term 
QD 
once daily 
QOL 
quality of life 
QTcF 
Fridericia’s correction formula for QT interval 


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Abbreviation 
Definition 
REML 
restricted maximum-likelihood 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SE 
standard error 
SNOT-22 
Sino-Nasal Outcome Test 
SoA 
schedule of activities 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
TSS 
total symptom score 
ULN 
upper limit of normal 
UPSIT 
University of Pennsylvania Smell Identification Test 
VAS 
visual analog scale 
WHO 
World Health Organization 


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1. 
PURPOSE OF THE ANALYSIS 
This statistical analysis plan (SAP) provides a comprehensive and detailed description of the 
statistical methodology to be used for reporting of the study results for use in the clinical study 
report (CSR) and is based on protocol version 5.0.  The purpose of this SAP is to describe the 
methodology, procedures, rules, and conventions to be used for the reporting of results.  Results 
to be reported will include summaries of subject disposition, demographic and baseline 
characteristics, significant protocol deviations, prior and concomitant medications, study 
treatment exposure and compliance, primary, secondary, and select tertiary/exploratory efficacy 
endpoints, pharmacokinetic (PK) concentrations, and safety endpoints, including adverse events 
(AEs), serious AEs (SAEs), and laboratory, vital sign, and electrocardiogram (ECG) parameters.   
If additional analyses are required to supplement the planned analyses described in this SAP, 
they may be completed and will be identified in the CSR as post hoc. 
The last two “Exploratory” objectives and endpoints in Section 2.1 will not be addressed in this 
SAP.  
This SAP was written with due consideration of the recommendations outlined in the most recent 
International Conference on Harmonisation (ICH) E9 Guideline (ICH E9, 1998) entitled 
Guidance for Industry E9 Statistical Principles for Clinical Trials and the most recent ICH E3 
Guideline (ICH E3, 1995) entitled Guidance for Industry Structure and Content of Clinical Study 
Reports and was finalized prior to study unblinding.  
In this document, investigational product (IP) and study treatment have the same meaning. 
 






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obtained prior to the day of the Screening visit to allow for medication washouts or for other 
logistical reasons such as obtaining documentation of exacerbations, if necessary.  All other 
screening procedures should be completed, where possible, on the day of the Screening visit.  
Subjects not meeting the eligibility criteria will be deemed screen failures and will not continue 
participation in the study.  The Run-in period commences with completion of all Screening visit 
procedures and concludes at the Randomization visit (Visit 2).  During the Run-in period of up to 
4 weeks, subjects will capture nasal symptoms and MFNS use in an online daily Diary (morning 
[AM] and evening [PM]): 
• Subject’s treatment regimen with MFNS should remain stable. 
• 2 actuations (50 µg/actuation) in each nostril twice daily (BID; total daily dose of 400 
µg), unless subject is intolerant to a BID regimen of MFNS in which case, they can 
stay on the dose regimen in place prior to screening. 
• The only dose modification of MFNS during the Run-in period may be for subjects 
who were switched from another intranasal corticosteroids (INCS) to MFNS and need 
to change to a once daily (QD) regimen due to intolerability. 
After the Randomization visit, subjects will enter the Double-Blind, Placebo-Controlled period 
which will be followed by a Follow-up period.   
Total duration for study participation per subject is up to 24 weeks (includes a Screening visit; 
followed by an up to 4-week Run-in period to allow for collection of baseline Diary data and 
standardized MFNS treatment regimen; a 16-week Double-Blind, Placebo-Controlled period; 
and a 4-week Follow-up period). 
Subjects who permanently discontinue IP or withdraw early from the study will be requested to 
attend the Early Discontinuation of IP visit or Early Withdrawal (EW) visit, as appropriate, and 
will be strongly encouraged to complete any remaining study visits as per the Schedule of 
Activities (SoA). 
The first dose of double-blind IP will be administered in the clinic on Day 1.  All subsequent 
doses will be taken orally, in the AM on an empty stomach.  Following initiation of IP, subjects 
will visit the clinic for assessments per protocol.  Subjects will continue on mometasone furoate:  
MFNS two actuations in each nostril BID (or QD in case subject cannot tolerate the high dose) 
during the course of the study. 
All subjects will complete a daily Diary from the Screening visit through the Follow-up visit, 
responding to the AM and PM CRS symptom questions and documenting twice daily MFNS use.   
The protocol contains further details related to the study design and conduct. 
2.3. 
Study Population 
The study population is comprised of: symptomatic subjects with CRS without NP (CRSsNP), 
defined as an absence of NP based on visual examination or an NPS of 0 based on nasal 
endoscopy, and evidence of an eosinophilic phenotype, defined as a blood eosinophil count of 


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≥ 250 cells/μL; and symptomatic subjects with CRS with NP (CRSwNP), defined as a minimum 
NPS of 4 out of a maximum of 8, with at least a score of 2 for each nostril, as assessed by 
endoscopic diagnosis by a blinded central reader.  Subjects will be male or female and ≥ 18 to 75 
years of age at the time of the Screening visit.  Subjects with historical evidence of neutrophilic 
predominant polyp disease will be excluded considering that the mechanism of action of GB001 
is thought to be linked to eosinophilic Type 2 inflammation.   
2.4. 
Randomization and Treatment Regimens 
This study will randomize approximately 100 subjects, with approximately 50 subjects per 
treatment group, randomized in a 1:1 ratio to the following treatment groups: 
• GB001 40 mg QD 
• Matching placebo QD 
Randomization will be stratified by country, the presence or absence of NP (CRSwNP and 
CRSsNP), and the presence or absence of comorbid asthma among CRSwNP subjects.  Presence 
of NP is defined by a minimum NPS of 4 out of a maximum score of 8 with a score of at least 2 
for each nostril.  Absence of NP is defined as an absence of NP based on visual examination or 
an NPS of 0 based on nasal endoscopy.  Presence of comorbid asthma is defined as a diagnosis 
of asthma by a physician according to Global Initiative for Asthma (GINA) guidelines at 
screening or prior to study entry.  The CRSwNP stratum will consist of approximately 64 
subjects, and the CRSsNP stratum will consist of approximately 36 subjects. 
2.5. 
Sample Size Determination 
A total sample size of approximately 100 subjects (approximately 50 per treatment group, 
randomized in a 1:1 ratio) is estimated to provide approximately 90% power to detect a treatment 
difference of 12.0 between GB001 and placebo at a 0.050 two-sided level of significance for the 
primary endpoint of change from baseline to Week 16 in SNOT-22 score, assuming a common 
standard deviation (SD) of 16.8 and a dropout rate of 15% using a two-sided t-test. 
A total sample size of approximately 64 subjects in the CRSwNP stratum (approximately 32 
per treatment group, randomized in a 1:1 ratio) is estimated to provide approximately 80% power 
to detect a treatment difference of 1.3 between GB001 and placebo at a 0.050 two-sided level of 
significance for the secondary endpoint of change from baseline to Week 16 in NPS, assuming 
a common SD of 1.7 and a dropout rate of 15% using a two-sided t-test. 
Therefore, the total sample size of approximately 100 subjects overall will consist of 
approximately 64 subjects in the CRSwNP stratum and 36 subjects in the CRSsNP stratum. 


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3. 
GENERAL ANALYSIS AND REPORTING CONVENTIONS 
All analyses will be performed using SAS® System (SAS Institute Inc., Cary, NC) version 9.4 or 
later. 
Categorical variables will be summarized using counts (n) and percentages (%) and will be 
presented in the format “n (xx.x)”.  If a count is 0, no percentage will be shown.  To ensure 
completeness, summaries for categorical and discrete variables may include all categories, even 
if no subjects had a value in a particular category.  Additionally, for missing data, a category of 
“Missing” will be presented as needed. 
Continuous variables, unless otherwise stated, will be summarized using descriptive statistics: 
number of subjects with non-missing data (n), mean, standard deviation (SD), median, 25th and 
75th percentiles, minimum, and maximum.  Descriptive statistics on select measures may also 
include the standard error (SE) and 95% confidence interval (CI) for the mean.  In general, 
rounding rules for reporting continuous descriptive summary statistics are as follows: 
• If the original values have 0 or 1 decimal places: mean, median, 25th and 75th 
percentiles will be reported to one more decimal place than the original values, and 
SD and SE will be reported to 2 more decimal places than the original values 
• If the original values have 2 or more decimal places: mean, median, 25th and 75th 
percentiles, SD, and SE will all be reported to 3 decimal places 
Minimum and maximum will always be reported to the same decimal places as the original 
values, up to a maximum of 3 decimal places.  Percent change from baseline will be reported to 1 
more decimal place than change from baseline, up to a maximum of 3 decimal places. 
Efficacy results will be summarized by various measures including but not limited to least 
squares (LS) means, differences in LS means, SEs, odds ratios (ORs), hazard ratios, rate ratios, 
p-values, and two-sided 95% CIs.  The SEs, LS means, differences in LS means and 
corresponding CIs will be reported per the rules above, with the CIs following the same rounding 
rules as the mean, ORs, hazard ratios, rate ratios, and corresponding CIs will be reported to 3 
decimal places, and percentage reductions and corresponding CIs will be reported to 1 decimal 
place.  P-values will be reported to 4 decimal places, with values less than 0.0001 displayed as < 
0.0001 and values greater than 0.9999 displayed as > 0.9999.  All statistical hypothesis testing 
will be at an 0.050 two-sided level of significance.     
In general, all analyses will be performed for the overall population, with the exception of 
efficacy endpoints based on NPS, which will be performed only for the randomized CRSwNP 
subgroup. 
Disposition, demographic and baseline characteristics, significant protocol deviations, and 
medical history tables will be presented by randomized treatment group and will include an 
overall column combining both treatment groups.  Prior and concomitant medication tables will 
be presented by either randomized treatment group or actual treatment group, depending on the 
analysis, and will include an overall column combining both treatment groups.  Select analyses 
among these will be performed for the randomized CRSwNP and CRSsNP subgroups.   


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Efficacy tables will be presented by randomized treatment group only and select efficacy 
analyses will be performed for the randomized CRSwNP and CRSsNP subgroups.  Safety tables 
will be presented by actual treatment group and select safety analyses will be performed for the 
actual CRSwNP and CRSsNP subgroups. 
When appropriate, sorting in disposition, demographic, and baseline characteristics tables will be 
based on decreasing incidence within the overall column.  In general, AE tables that are 
displayed by system organ class (SOC) and preferred term (PT) will be sorted by the 
internationally agreed order for SOC, and by decreasing incidence and then alphabetically for PT 
within the GB001 40 mg column.  Otherwise, safety tables, when applicable, will be sorted by 
decreasing incidence within the GB001 40 mg column. 
Assessments at the Randomization Visit are to be performed prior to the first dose of study 
treatment.  Therefore, for all measures, the baseline value is defined as either the last non-
missing value before the first dose of study treatment, the mean over the last 7 days of the Run-in 
period including the value on Day 1 (AM endpoints collected in the daily Diary), or the mean 
over the last 7 days of the Run-in period excluding the value on Day 1 (PM endpoints collected 
in the Diary).  
If multiple evaluations occur on the same day, the average of these evaluations will be used for 
analysis excluding maximum post-baseline, abnormality, and outlier analyses.   
For all shift from baseline analyses, percentages will be based on the number of subjects in each 
baseline category and also having at least one post-baseline measurement. 
Values with “<” or “>” signs will be analyzed without the signs in tables and figures.  In by-
subject data listings, values will be reported as collected with the sign. 
Dates in by-subject data listings will be displayed as yyyy-mm-dd (e.g., 2015-01-24).  In general, 
by-subject data listings will be sorted by randomized treatment group and subject number. 
3.1. 
Visit Windowing 
Subjects do not always strictly adhere to the visit schedule timing in protocols.  Therefore, the 
designation of visits (or timepoints) will generally be based on the actual day of evaluation 
relative to the date of first dose of study treatment (Day 1), rather than the nominal visit, for 
analyses conducted by visit. 
Mutually exclusive visit windows containing no gaps will generally be utilized to assign visits 
for by visit analysis and will correspond to post-baseline visits specified in the protocol.  Visits 
for analysis will be assigned by using a windowing scheme as described below. 
The upper bound of the baseline visit window is Day 1 (up to the time of the first dose for 
assessments with time collected), and the lower bound of the first post-baseline visit window is 
Day 1 after the time of the first dose for assessments with time collected and Day 2 for 
assessments without time collected.  For all other lower and upper bounds of visit windows, 
windows will end at the midpoint between scheduled visit timepoints, with the midpoint in the 


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latter visit window with the exception of the Week 16 visit for the efficacy endpoints, which will 
include Day 120 as the upper bound of the visit window.   
If a subject’s last observation is after the date of first dose of study treatment but prior to the first 
scheduled visit, data from an EW visit will be assigned to the first scheduled visit.  If two or 
more evaluations occur in the same visit window, the evaluation closest to the target visit day 
will be selected for inclusion in the analysis.  If multiple evaluations are equally close to the 
target visit day, then the latest evaluation will be selected for inclusion in the analysis.  The 
target visit day for Week 1 and on is defined as the week number specified in the SoA of the 
protocol multiplied by 7 plus 1.   
3.2. 
Standard Calculations 
Standard calculations are described as follows:  
Age: 
If age is not collected on the electronic case report form (eCRF), age at screening will be 
calculated in years using the date of birth and the date of the Screening visit (Visit 1), rounded 
down to the nearest integer.   
Duration: 
Duration between two dates date1 and date2 will be calculated as follows: 
date2 – date1 + 1, when expressed in days 
(date2 – date1 + 1)/7, when expressed in weeks 
(date2 – date1 + 1)/365.25, when expressed in years 
Change/Percent Change from Baseline: 
Change from baseline will be calculated as:  Value at post-baseline visit – value at baseline 
Percent change from baseline will be calculated as:  (Change from baseline/value at baseline) * 
100% 
Note: Change from baseline summaries will only include subjects with a baseline value and at 
least one post-baseline value.  If the value at baseline is 0, percent change from baseline will be 
missing. 
Study Day: 
Study day will be calculated as follows: 
assessment date – date of the first dose of study treatment, where assessment date < date of the 
first dose of study treatment 


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assessment date – date of the first dose of study treatment + 1, where assessment date ≥ date of 
the first dose of study treatment 
Date Imputation: 
If complete dates are unavailable, July 2 (midpoint of a non-leap year) will be utilized in 
calculations in cases where both month and day are missing, and the 15th will be utilized in 
calculations in cases where only day is missing. 
3.3. 
Considerations Related to the COVID-19 Pandemic 
Screening of subjects for this study began in April 2019, and the last subject completed their 
participation in the study in August 2020.  As such, a portion of this study’s conduct was 
affected by the global Coronavirus Disease 2019 (COVID-19) pandemic. 
At the time of finalization of this SAP in September 2020, several regulatory authorities have 
issued guidance related to trial conduct and associated methodological issues related to the effect 
of the COVID-19 pandemic, including, but not limited to, the Food and Drug Administration 
(FDA) (References: FDA Guidance on Conduct of Clinical Trials of Medical Products during 
COVID-19 Pandemic, March 2020, updated on July 2, 2020 and Statistical Considerations for 
Clinical Trials During the COVID-19 Public Health Emergency, June 2020) and European 
Medicines Agency (EMA) (References: Guidance on the Management of Clinical Trials during 
the COVID-19 (Coronavirus) pandemic, Version 3 (28/04/2020) and Points to consider on 
implications of Coronavirus disease (COVID-19) on methodological aspects of ongoing clinical 
trials, 26 June 2020). 
Potential effects on conduct of this study related to the COVID-19 pandemic include, but are not 
limited to, the following:  subject discontinuation of study treatment and/or withdrawal from 
study; inability or reduced ability for subjects to continue on IP due to disruptions in IP 
dispensing; missed visits or missed assessments; alternative procedures (e.g., telephone visit or 
virtual visit) used for collection of critical efficacy and/or safety assessments; and inability for 
sites to complete entry of data in the electronic case report form (eCRF) and/or collect data via 
other sources (e.g., eDiary). 
A determination will be made at the end of study if additional statistical analyses are warranted 
as part of the final analysis, should participation of subjects or endpoint ascertainment be 
affected by the COVID-19 pandemic to a substantial degree.  These additional analyses would be 
undertaken to enable an understanding of the potential impact of the COVID-19 pandemic on 
study results. 
A non-exhaustive list of examples of such additional analyses is as follows: 
• Analysis of compliance: 
o By subgroup of subjects who received direct IP shipment due to the COVID-19 
pandemic versus those that did not 
• Analyses of primary and select secondary efficacy endpoints: 


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o By subgroup of subjects whose study participation was affected by the COVID-19 
pandemic versus was not affected; 
o Excluding only data that is missing for reasons related to the COVID-19 
pandemic (but including imputation of data missing for other reasons); and 
o By subgroup of subjects who had an alternative method of collection for an 
assessment contributing to a particular endpoint (e.g., SNOT-22 completed by 
subject at home via virtual visit) versus subjects who did not have an alternative 
method of collection 
• Analysis of AEs: 
o Incidence of AEs by subgroup of subjects whose study participation was affected 
by the COVID-19 pandemic versus was not affected; 
o Incidence of AEs that were collected via an alternative method versus incidence 
of AEs that were not collected via an alternative method 
• Analysis of laboratory values: 
o By subgroup of subjects whose study participation was affected by the COVID-19 
pandemic versus was not affected; 
o Excluding values resulting from local collection due to reasons related to the 
COVID-19 pandemic; and 
o Including only values resulting from local collection due to reasons related to the 
COVID-19 pandemic 
In addition, by-subject listings indicating subjects whose study participation was affected by the 
COVID-19 pandemic, subjects with missing data related to the COVID-19 pandemic, and/or 
subjects with an alternative method of collection for specific assessments may be provided. 


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4. 
ANALYSIS POPULATIONS 
4.1. 
All Enrolled Population 
The all enrolled population will include all subjects with a non-missing date of informed consent.  
The all enrolled population will be utilized for disposition summaries. 
4.2. 
Run-in Period Population 
The run-in period population will include all enrolled subjects who are not screen failures and 
enter the Run-in period.  The run-in period population will be presented in disposition 
summaries. 
4.3. 
Intent-to-Treat Population 
The intent-to-treat (ITT) population will include all subjects who are randomized and receive at 
least 1 dose of study treatment, with subjects grouped according to randomized treatment.  The 
ITT population will be utilized for efficacy analyses. 
4.4. 
Safety Population 
The safety population will include all subjects who receive at least 1 dose of study treatment, 
with subjects grouped according to their actual treatment.  If GB001 was taken, based on kit and 
study treatment accountability data, subjects will be included in the GB001 40 mg group.  The 
safety population will be utilized for safety and PK analyses. 
 


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5. 
STUDY PATIENTS 
5.1. 
Disposition of Patients 
The disposition of subjects will be summarized for the all enrolled population.  The number and 
percent of subjects who are screened, screen failures, run-in period participants, completed run-
in period, run-in period failures, and randomized in error, along with screen failure reasons, run-
in period failure reasons, reasons not randomized, and eligibility or randomization criteria not 
met will be summarized overall.  In addition, the number and percent of subjects who are 
randomized, treated, completed study treatment, discontinued study treatment, completed the 
study, and withdrew from the study, along with associated reasons, and in each analysis 
population, will be summarized by treatment group and overall.   
Disposition data will also be presented in a by-subject data listing.  In addition, a listing of the 
randomization scheme will be presented. 
5.2. 
Protocol Deviations 
Protocol deviations will be identified and reviewed on an ongoing basis by the study team and 
entered into a Clinical Trial Management System.  Significant protocol deviations are defined as 
those that can affect efficacy and/or safety assessments, the safety or mental integrity of a 
subject, or the scientific value of the study.   Protocol deviations will be classified as significant 
or non-significant and will be assigned a protocol deviation type prior to unblinding.  The 
number and percent of subjects with at least 1 significant protocol deviation overall and for each 
protocol deviation type will be summarized for the ITT population.  In addition, COVID-19 
related and non-COVID-19 related significant protocol deviations will be summarized. 
Protocol deviations will also be presented in a by-subject data listing.  In addition, subjects who 
were randomized in error and subjects who were mis-stratified based on the presence or absence of 
NP (CRSwNP and CRSsNP) or on the presence or absence of comorbid asthma among CRSwNP 
subjects at randomization will be presented in a by-subject data listing. 


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6. 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
6.1. 
Demographic Characteristics 
Demographic characteristics will be summarized for the ITT population for the following 
parameters: 
• Age (years; continuous [cts]; ≥ 18-< 50, ≥ 50-< 65, ≥ 65) 
• Sex (male, female) 
• Race (White, Black or African American, American Indian or Alaska Native, Native 
Hawaiian or Other Pacific Islander, Asian, Other) 
• Ethnicity (Hispanic or Latino, Not Hispanic or Latino, Not Reported) 
• Height (cm; cts) 
• Weight (kg; cts) 
• Body mass index (BMI [kg/m2; cts; < 18.5, ≥ 18.5-< 25, ≥ 25-< 30, ≥ 30]) 
• Country (Czech Republic, Ukraine, United States) 
• Region (United States, Eastern Europe [Czech Republic, Ukraine]) 
Demographic characteristics will also be presented in a by-subject data listing. 
6.2. 
Baseline Disease Characteristics 
Baseline disease characteristics will be summarized for the ITT population for the following 
parameters: 
• Disease status strata at randomization and actual (CRSwNP [overall, with comorbid 
asthma, without comorbid asthma], CRSsNP) 
• CRS/NP Surgical History 
o Any prior surgery (cts) 
o Prior functional endoscopic sinus surgery (number of surgeries and years since 
most recent surgery; cts; 0, 1, 2, ≥ 3 for number of surgeries) 
o Prior NP surgery (number of surgeries and years since most recent surgery; cts; 0, 
1, 2, ≥ 3 for number of surgeries) 
o Prior stent placement (number of surgeries and years since most recent surgery; 
cts; 0, 1, ≥ 2 for number of surgeries) 
o Prior nasal septum surgery (number of surgeries and years since most recent 
surgery; cts; 0, 1, ≥ 2 for number of surgeries) 
o Prior rhinoplasty surgery (number of surgeries and years since most recent 
surgery; cts; 0,  ≥ 1 for number of surgeries) 


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• CRS/NP History  
o CRS duration (years; cts) 
o History of NP (never had, ongoing, past; NP duration for CRSwNP subjects 
[years; cts]) 
o Comorbid asthma (yes, no) 
o Fungal sinusitis current or prior history (yes, no) 
o Inadequate response to vaccines (yes, no) 
o Nasal blockade/obstruction/congestion (yes, no) 
o Nasal discharge (yes, no) 
o Reduction or loss of smell (yes, no) 
o Facial pain/pressure (yes, no) 
o Loss of sleep (yes, no) 
o Sinus CT scan in past 2 years (yes, no) 
o Sinus X-ray in past 2 years (yes, no) 
o Prior anti-fungal treatment (yes, no) 
o Prior saline nasal irrigations (yes, no) 
o Chronic antibiotic use in the past (yes, no) 
o Chronic antibiotic use currently (yes, no) 
• Polyps present (based on visual exam by investigator) in right/left nostril for 
CRSwNP subjects (yes, no) 
• Smoking history (never, former, current; cigarette pack-years for former and current 
smokers) 
• Alcohol history (never, former, current) 
Baseline disease characteristics will also be presented in by-subject data listings. 
6.3. 
Atopic/Allergic Conditions 
Atopic/allergic conditions will be summarized for the ITT population for the following 
parameters: 
• Chronic Rhinosinusitis, Asthma, Seasonal Allergic Rhinitis, Perennial Allergic Rhinitis, 
Chronic Spontaneous Urticaria, Eosinophilic granulomatosis with polyangiitis (Churg 
Strauss Syndrome) (none, ongoing, past) 
Atopic/allergic conditions will also be presented in a by-subject data listing. 


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6.4. 
Efficacy-Related Baseline Characteristics 
Efficacy-related baseline characteristics will be summarized for the ITT population for the 
following parameters: 
• SNOT-22 total score and 5 domain (Nasal, Ear, Sleep, General and Practical, and 
Emotional) scores (cts; ≤ Median, > Median of ITT population for total score) 
• Bilateral Endoscopic NPS at Screening for CRSwNP subjects (cts; 4, 5 - 6, 7 - 8) 
• Bilateral Endoscopic NPS at Baseline for CRSwNP subjects (cts; ≤ 4, 5 - 6, 7 - 8) 
• TSS (AM, PM; cts; ≤ Median, > Median of ITT population for AM TSS) 
• NC score (AM, PM; cts; ≤ Median, > Median of ITT population for AM NC) 
• Anterior rhinorrhea score (AM, PM; cts) 
• Posterior rhinorrhea score (AM, PM; cts) 
• Loss of sense of smell score (AM, PM; cts) 
• UPSIT score (cts; Anosmia = 0 – 18, Severe Microsmia = 19 – 25, Moderate 
Microsmia = 26 – 30, Mild Microsmia = 31 – 34, Normal = 35 - 40) 
• VAS score (cts; mild, moderate, severe, using categories defined in Section 8.3.3.1) 
• Lund-Mackay score (cts) 
• Volume of the air (mL; cts) 
• Volume of mucosa (mL; cts) 
• Percentage of maxillary sinus volume occupied by disease on CT scan (cts) 
• Thickness of lateral wall (mm; cts) 
• ACQ-5 score for asthma subjects (cts; < 1.5, ≥ 1.5) 
Efficacy-related baseline characteristics will also be presented in a by-subject data listing. 
6.5. 
 Biomarker Baseline Characteristics 
Biomarker baseline characteristics will be summarized for the ITT population for the following 
parameters: 
• Blood eosinophils at Screening (10^9/L; cts; <0.25, ≥ 0.25) 
• Blood eosinophils at Baseline (10^9/L; cts; <0.25, ≥ 0.25) 
• Screening and Baseline blood eosinophils (10^9/L; ≥ 0.25 and < 0.25) 
• Maximum blood eosinophils value prior to randomization visit for CRSsNP subjects 
(10^9/L; cts; ≥ 0.25, ≥ 0.30, ≥ 1.50)  
• Fractional exhaled nitric oxide (FeNO) at Baseline (ppb; cts; < 25, ≥ 25) 


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• Chloride at Baseline (mmol/L; cts; ≤ Quartile 1, > Quartile 1 - ≤ Quartile 2, > 
Quartile 2 - ≤ Quartile 3, > Quartile 3, where quartiles are based on the ITT 
population)   
Biomarker baseline characteristics will also be presented in a by-subject data listing. 
6.6. 
Medical History 
Verbatim targeted and general medical history terms will be coded to a SOC and PT using the 
Medical Dictionary for Regulatory Activities (MedDRA) Version 21.0 or later.  Counting will be 
at the subject level for each level of summarization (e.g., any medical history, SOC, and PT), 
with subjects experiencing more than one occurrence of a SOC or PT counted only once.  
Ongoing and past medical history will be summarized for the ITT population. 
Medical history will also be presented in a by-subject data listing. 
6.7. 
Prior Medications 
Verbatim prior medication terms will be coded to a drug class (anatomical therapeutic chemical 
[ATC2]) and PT using World Health Organization (WHO)Drug Global B3 March 2018 or later.  
Prior medications are defined as all medications that started prior to the date of first dose of 
study treatment.  In general, if it is not clear whether a medication is prior due to missing or 
incomplete medication start date, the medication will be considered to be prior unless the non-
missing portions of the start date indicate otherwise.  Counting will be at the subject level for 
each level of summarization (e.g., any medication, ATC2, and PT), with subjects receiving more 
than one medication counted only once. 
Prior medications will be summarized for the safety population. 
In addition, MFNS use prior to informed consent, MFNS use between screening and 
randomization, prior ICS use overall and separately for between screening and randomization, 
further broken down by ICS alone and ICS + long-acting beta-agonist (LABA) and/or long-
acting muscarinic antagonist (LAMA), and prior systemic corticosteroid use will be summarized 
for the ITT population. 
6.8. 
Concomitant Medications 
Verbatim concomitant medication terms will be coded to a drug class (ATC2) and PT using 
WHODrug Global B3 March 2018 or later. 
Concomitant medications are defined as all medications that started on or after the date of first 
dose of study treatment or that started prior to the date of first dose of study treatment and 
stopped on or after the date of first dose of study treatment or were ongoing.  In general, if it is 
not clear whether a medication is concomitant due to missing or incomplete medication start 


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and/or end dates, the medication will be considered to be concomitant unless the non-missing 
portions of the start and end dates indicate otherwise.   
A medication may be considered as both prior and concomitant, i.e. prior and concomitant 
medications are not mutually exclusive.  Counting will be at the subject level for each level of 
summarization (e.g., any medication, ATC2, and PT), with subjects receiving more than one 
medication counted only once.   
Concomitant medications will be summarized for the safety population.  In addition, concomitant 
MFNS use will be summarized for the ITT population. 
Prior and concomitant medications will also be presented in a by-subject data listing and will 
include an indicator, identifying each medication as prior and/or concomitant.   
Concurrent procedures will be presented in a by-subject data listing. 
 


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7. 
EXTENT OF EXPOSURE, COMPLIANCE, AND TIME ON STUDY 
7.1. 
Extent of Exposure 
Duration of study treatment (days, weeks, and subject-years) will be summarized for the safety 
population using descriptive statistics and categorically (every 4 weeks).  Duration of study 
treatment will also be presented in a by-subject data listing. 
7.2. 
Compliance 
Compliance with study treatment will be assessed using the following formula: 
Treatment compliance (%) = (# of actual tablets taken/# of expected tablets) x 100, 
where # of actual tablets taken = (# of tablets dispensed - # of tablets returned) and # of expected 
tablets is based on actual duration of study treatment 
Compliance will be summarized for the safety population using descriptive statistics and 
categorically (< 80, ≥ 80-100, > 100-< 120, ≥ 120). 
Compliance with study treatment will also be presented in a by-subject data listing.  In addition, 
IP accountability including kit information will be presented in a by-subject data listing. 
7.3. 
Time on Study 
Time on study (days and weeks, and subject-years) will be summarized for the safety population 
using descriptive statistics and categorically (every 4 weeks).  The latest assessment date for 
each subject will be used in the calculation of time on study.  Time on study will also be 
presented in a by-subject data listing. 


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8. 
EFFICACY EVALUATION 
8.1. 
Overview of Efficacy Analysis Issues 
8.1.1. 
Handling of Dropouts or Missing Data 
A variety of methodological approaches will be applied for handling subjects with missing data; 
full details are provided in Section 8.3.   
8.1.2. 
Multicenter Studies 
Data from all countries and sites will be pooled for the purpose of analyses. 
8.2. 
Efficacy Endpoints 
Table 1 provides a summary of the statistical models/methods of primary and sensitivity analyses 
to be used for the primary, secondary, and select exploratory endpoints.  For all efficacy 
analyses, disease status stratification factor values used for randomization (CRSwNP with 
comorbid asthma, CRSwNP without comorbid asthma, and CRSsNP) and region (United States, 
Eastern Europe) will be used as covariates and results will be summarized for the ITT 
population, unless otherwise stated.   
 
 


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Table 1:  Efficacy Endpoints and Analysis Methods 
Efficacy 
Endpoints 
Missing 
Data 
Thresholda 
MMRM 
ANCOVA  
Cox 
Propor- 
tional 
Hazards 
Negative 
Binomial 
Regressionb 
Logistic 
Regression 
without 
MI 
with 
MI 
without 
MI 
with 
MI 
Primary 
Change from 
baseline to Week 
16 in SNOT-22 
total score 
< 10% 
P 
 
 S      
 
 
 
 
≥ 10% 
S 
P 
 
S       
 
 
 
Secondary 
 
 
 
 
 
 
 
 
Change from 
baseline to Week 
16 in Lund-
Mackay score 
< 10% 
 
 
P 
 
 
 
 
≥ 10% 
 
 
S 
P 
 
 
 
Change from 
baseline to Week 
16 in NPSc 
< 10% 
P    
 
S      
 
 
 
 
≥ 10% 
S    
P 
 
S 
 
 
 
Time to first 
response (≥ 1 
point 
improvement 
from baseline) in 
NPSc 
 
 
 
 
 
P 
 
 
Change from 
baseline to Week 
16 in AM NC 
score 
< 10% 
P    
 
S      
 
 
 
 
≥ 10% 
S    
P 
 
S 
 
 
 
Change from 
baseline to Week 
16 in AM TSS 
< 10% 
P    
 
S      
 
 
 
 
≥ 10% 
S    
P  
 
S 
 
 
 
Change from 
baseline to Week 
16 in UPSIT score 
< 10% 
 
 
P 
 
 
 
 
≥ 10% 
 
 
S 
P 
 
 
 
Time to first CRS 
exacerbation 
 
 
 
 
 
P 
 
 
Exploratory 
 
 
 
 
 
 
 
 
Change from 
baseline to Week 
16 in VAS score 
 
 
 
P 
 
 
 
 
Annualized rate of 
CRS 
exacerbations 
 
 
 
 
 
 
P 
 
Change from 
baseline to Week 
16 in percentage 
of maxillary sinus 
volume occupied 
by disease on CT 
scan 
 
 
 
P 
 
 
 
 


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Efficacy 
Endpoints 
Missing 
Data 
Thresholda 
MMRM 
ANCOVA  
Cox 
Propor- 
tional 
Hazards 
Negative 
Binomial 
Regressionb 
Logistic 
Regression 
without 
MI 
with 
MI 
without 
MI 
with 
MI 
Proportion of 
subjects with 
antibiotic use due 
to worsening CRS 
by Week 16 
 
 
 
 
 
 
 
 
P 
Change from 
baseline to Week 
16 in FeNO and 
nNO 
 
 
 
P 
 
 
 
 
Percent change 
from baseline to 
Week 16 in FeNO 
and nNO 
 
 
 
P 
 
 
 
 
Additional 
 
 
 
 
 
 
 
 
Change from 
baseline in 
SNOT-22 total 
score including all 
data 
< 10% 
P 
 
 
 
 
 
 
≥ 10% 
 
P 
 
    
 
 
 
Proportion of 
subjects with a ≥ 
9 point decrease 
from baseline at 
Week 16 in 
SNOT-22 total 
score 
 
 
 
 
 
 
 
P 
Change from 
baseline in Lund-
Mackay score 
including all data 
< 10% 
 
 
P 
 
 
 
 
≥ 10% 
 
 
 
P 
 
 
 
Change from 
baseline in NPSc 
including all data 
< 10% 
P    
 
  
 
 
 
 
≥ 10% 
   
P 
 
 
 
 
 
Proportion of 
subjects with a 
reduction from 
baseline of ≥ 1 in 
NPSc at Weeks 8 
and 16 
 
 
 
 
 
 
 
P 
Change from 
baseline to Week 
16 in PM NC 
score  
 
P 
 
 
 
 
 
 
Change from 
baseline to Week 
16 in PM TSS 
 
P 
 
 
 
 
 
 


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Efficacy 
Endpoints 
Missing 
Data 
Thresholda 
MMRM 
ANCOVA  
Cox 
Propor- 
tional 
Hazards 
Negative 
Binomial 
Regressionb 
Logistic 
Regression 
without 
MI 
with 
MI 
without 
MI 
with 
MI 
Change from 
baseline to Week 
16 in AM and PM 
anterior 
rhinorrhea, 
posterior 
rhinorrhea, and 
loss of sense of 
smell scores  
 
P 
 
 
 
 
 
 
Change from 
baseline to Week 
16 in volume of 
the air, volume of 
mucosa, and 
thickness of 
lateral wall 
 
 
 
P 
 
 
 
 
Change from 
baseline to Week 
16 in ACQ-5 
score  
 
 
 
P 
 
 
 
 
ACQ-5 = asthma control questionnaire; AM = morning; ANCOVA = analysis of covariance; CRS = chronic 
rhinosinusitis; CRSwNP = chronic rhinosinusitis with nasal polyps; CT = computed tomography; FeNO = fractional 
exhaled nitric oxide; ITT =intent-to-treat; MMRM = mixed-effects model with repeated measures; MI = multiple 
imputation; NC = nasal congestion; nNO = nasal nitric oxide; NPS = nasal polyp score; P = primary; PM = evening; S 
= sensitivity; SNOT-22 = Sino-Nasal Outcome Test; TSS = total symptom score; UPSIT = University of Pennsylvania 
Smell Identification Test; VAS = visual analog scale 
a The analysis approach depends on the amount of missing data for the endpoint in the ITT population. 
b If the distribution of severe exacerbation data is underdispersed, or if the negative binomial regression model fails to 
converge, a Poisson regression model will be used instead. 
c Assessed in subjects in the randomized CRSwNP stratum. 
 
 
 


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8.3. 
Analysis Methods 
8.3.1. 
Primary Efficacy Analyses 
The primary endpoint is the change from baseline to Week 16 in SNOT-22 total score. 
SNOT-22 is a validated questionnaire to assess the impact of CRS on quality of life (QOL) and 
utilizes a 2-week recall period.  It is a 22-item outcome measure on a 5-point category scale 
applicable to sinonasal conditions and surgical treatments. The questionnaire consists of 22 items 
across 5 domains:  Nasal, Ear, Sleep, General and Practical, and Emotional.  A scale ranging 
from 0 (no problem) to 5 (problem as bad as it can be) is used to respond to each item in the 
questionnaire. The total scores range from 0 to 110 with higher total scores implying greater 
impact of CRS on QOL. A Minimal Clinically Important Difference (MCID) is available: 8.90 
(Hopkins, 2009).     
Total and domain scores will be derived by taking the sum of the non-missing item responses at 
each visit.   
If the number of subjects overall with a missing change from baseline to Week 16 SNOT-22 total 
score is < 10%:  
• The primary analysis will be mixed-effects model with repeated measures (MMRM) 
without multiple imputation (MI).   
• As a sensitivity analysis, analysis of covariance (ANCOVA) without MI will also be 
performed.   
If the number of subjects overall with a missing change from baseline to Week 16 SNOT-22 total 
score is ≥ 10%:  
• The primary analysis will be MMRM with MI.   
• As sensitivity analyses, MMRM without MI and ANCOVA with MI will also be 
performed. 
8.3.1.1. 
MMRM without MI 
MMRM will be performed using a restricted maximum-likelihood (REML)-based approach.  
The MMRM model will include change from baseline scores through Week 16 as the response 
variable; the fixed, categorical covariates of treatment group, disease status stratification factor 
values used for randomization (CRSwNP with comorbid asthma, CRSwNP without comorbid 
asthma, and CRSsNP), region (United States, Eastern Europe), visit, and treatment group by visit 
interaction; and the continuous, fixed covariates of baseline SNOT-22 total score and baseline 
SNOT-22 total score by visit interaction.  An unstructured covariance structure will be used to 
model within-subject error.   
If the analysis fails to converge due to the complexity of model specification, the following will 
be considered to enable model convergence:  1) use of maximum likelihood estimation instead of 
REML; and/or 2) a compound symmetric or first-order autoregressive covariance structure will 


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be utilized, based on the covariance structure converging to better fit as determined based on 
Akaike’s information criterion (Akaike, 1973); and/or 3) reduced models.  In the case of 3), if 
the full model does not converge after using maximum likelihood estimation or different 
covariance structures, reduced models will be fit using REML and an unstructured covariance 
structure.  The reduced model will include treatment group, visit, and treatment group by visit 
interaction.     
Parameters will be estimated using REML with the Newton-Raphson algorithm.  Treatment 
comparisons will be derived from the MMRM.  The number and percent of subjects contributing 
to the MMRM analysis and descriptive statistics along with the LS means, SEs, and 
corresponding 95% CIs for each treatment group will be provided.  The difference in LS means, 
SE, corresponding 95% CI, and p-value with Kenward-Roger adjustment (Kenward, 1997) will 
also be provided for comparison for the GB001 40 mg group versus placebo.  Results will be 
presented for the total score only, for change from baseline to Week 16 and separately for change 
from baseline to all visits through Week 16 (excluding descriptive statistics). 
A bar graph of the LS mean change from baseline to Week 16 by treatment group, including 95% 
CIs, for the total score will be provided.  A figure of LS mean change from baseline in the total 
score, including 95% CIs, by visit will also be provided.  The figures reporting model-based results 
will use the primary analysis approach based on the amount of missing data as described in 
Table 1.  Lastly, a bar graph of the mean change from baseline to Week 16 by treatment group, 
including SE bars, for each domain score will be provided using as observed data.      
Actual, change from baseline, and percent change from baseline values in total and domain 
scores will be descriptively summarized by visit using as observed data.       
SNOT-22 total and domain scores will also be presented in a by-subject data listing. 
8.3.1.2. 
MMRM with MI 
Missing SNOT-22 total scores at post-baseline visits will be imputed using an MI approach.  
Missing SNOT-22 total scores at baseline will not be imputed. 
The following steps will be performed: 
• Step 1:  Intermittent missing values will be imputed using the Markov Chain Monte 
Carlo (MCMC) method (Schafer, 1997), using a noninformative prior (Jeffreys) for 
the prior information for the means and covariances and expectation-maximization 
(EM) for the initial mean and covariance estimates. 
• Step 2:  Monotone missing values will then be imputed using a linear regression 
model (Allison, 2005) including the imputed intermittent missing values in step 1.  A 
monotone missing pattern is such that in the event that a variable is missing it is 
implied that all subsequent variables are also missing (e.g., once a subject withdraws 
from study, no additional data is expected for that subject). 
• For each step, MI will be performed within each treatment group with covariates for 
disease status stratification factor values used for randomization (CRSwNP with 


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comorbid asthma, CRSwNP without comorbid asthma, and CRSsNP), region (United 
States, Eastern Europe), and non-missing values for baseline SNOT-22 total score 
and Weeks 4, 8, 12, and 16 SNOT-22 total scores.  Should convergence issues occur 
due to small cell size for the categorical covariates at either step, the categorical 
variable(s) causing convergence issues will be removed from the model. 
• Missing change from baseline and percent change from baseline in SNOT-22 total 
scores will be computed from the imputed SNOT-22 total scores. 
• The analysis of the primary endpoint as described in Section 8.3.1 will be performed 
for each complete, imputed dataset. 
• For step 1, fifty imputations will be performed.  For step 2, 1 imputation will be 
performed if 50 imputations were performed for step 1.  Fifty imputations will be 
performed for step 2 if step 1 was skipped (e.g., for assessments only collected once 
post-baseline or for endpoints without intermittent missing values). 
• Results of the MMRM on the multiple imputed data sets will be combined to generate 
an overall estimate and associated variance using Rubin’s rules (Rubin, 1987). 
Results will be presented as described in Section 8.3.1.1 but using the MI data and the number 
and percent of subjects with an MI value or an observed value for each treatment group will also 
be provided.  In addition, actual, change from baseline, and percent change from baseline values 
in total and domain scores will be descriptively summarized by visit using MI data.  
8.3.1.3. 
ANCOVA without MI 
For ANCOVA without MI, the models will include covariates for treatment group, disease status 
stratification factor values used for randomization (CRSwNP with comorbid asthma, CRSwNP 
without comorbid asthma, and CRSsNP), region (United States, Eastern Europe), and baseline 
SNOT-22 total score. 
Descriptive statistics for change from baseline to Week 16 along with the LS means, SEs, and 
corresponding 95% CIs for each treatment group will be provided.  The difference in LS means, 
SE, corresponding 95% CI, and p-value for the GB001 40 mg group versus placebo will also be 
constructed from the ANCOVA model.  Results will be presented for the total score only.   
8.3.1.4. 
ANCOVA with MI 
The imputed data described in Section 8.3.1.2 will be used for the ANCOVA with MI analyses. 
Covariate adjustment will be the same as in Section 8.3.1.3. 
Results will be presented as described in Section 8.3.1.3 but using the MI data. 
8.3.1.5. 
Additional Analyses of the Primary Endpoint 
The proportion of subjects with a ≥ 9 point decrease from baseline at Week 16 in SNOT-22 total 
score will be analyzed in the subset of the ITT population who have a non-missing baseline and 
at least one post-baseline value.  Logistic regression modeling will be used to compare the 


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GB001 40 mg group with placebo using as observed data with covariates for treatment group, 
disease status stratification factor values used for randomization (CRSwNP with comorbid 
asthma, CRSwNP without comorbid asthma, and CRSsNP), region (United States, Eastern 
Europe), and baseline SNOT-22 total score.     
The number and proportion of subjects with a ≥ 9 point decrease from baseline at Week 16 in 
SNOT-22 total score and corresponding 95% Wilson (Score) CIs (Wilson, 1927) will be 
summarized by treatment group.  The OR, corresponding asymptotic 95% CI along with the 
absolute difference in proportions and corresponding 95% CI, and p-value will be summarized 
for the GB001 40 mg group versus placebo.  The 95% CI for the absolute difference will be 
Newcombe continuity-corrected CI (Newcombe, 1998).  The percentage reduction in odds and 
corresponding 95% CI will also be provided. 
The number and proportion of subjects with a ≥ 9 point decrease from baseline in SNOT-22 total 
score will also be summarized by visit as described above at Week 16.   
8.3.2. 
Secondary Efficacy Analyses 
The secondary efficacy endpoints are listed in Table 1 and will be analyzed as described below. 
8.3.2.1. 
Change from Baseline to Week 16 Endpoints 
8.3.2.1.1. 
Lund-Mackay and UPSIT Scores 
Lund-Mackay scores are based on the centralized imaging data assessments and scored by 
blinded central reading at the imaging core laboratory.  The 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 each sinus (maxillary, anterior ethmoid, 
posterior ethmoid, sphenoid, and frontal sinus) on each side.  The osteomeatal complex on each 
side is graded as 0 = not occluded, or 2 = occluded, deriving a maximum score of 12 per side, for 
a total score ranging from 0 to 24 (Lund, 1993).  Of note, an aplastic (absent) frontal sinus 
receives a score of 0. 
The UPSIT test consists of four booklets, each containing 10 odorants with one odorant per page 
(Doty, 1984).  The test-time is about 15 minutes.  The stimuli are embedded in 10–50 μm 
diameter plastic microcapsules on brown strips at the bottom of each page.  Above each odorant 
strip is a multiple-choice question with four alternative words to describe the odor.  The subject 
is asked to release the odorant by rubbing the brown-strip with the tip of a pencil and to indicate 
which of four words best describes the odor.  An UPSIT score will only be derived if all 40 
responses are non-missing.  A higher UPSIT score indicates better olfaction.  Anosmia 
categories for the UPSIT score are defined as:  
• Anosmia = 0 - 18 
• Severe Microsmia = 19 – 25 
• Moderate Microsmia = 26 - 30 
• Mild Microsmia = 31 – 34 


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• Normal = 35 – 40 
For the change from baseline to Week 16 in Lund-Mackay and UPSIT scores, the primary 
analysis will be ANCOVA without MI if the number of subjects overall with a missing change 
from baseline value to Week 16 is < 10% for the respective endpoint.  If the number of subjects 
overall with a missing change from baseline value to Week 16 is ≥ 10% for the respective 
endpoint, the primary analysis will be ANCOVA with MI, with an MI procedure similar to that 
described in Section 8.3.1.2, and ANCOVA without MI will be performed as a sensitivity 
analysis.  For the Lund-Mackay and UPSIT score multiple imputation, step 1 for imputing 
intermittent missing values will be skipped since Lund-Mackay and UPSIT scores can only be 
monotone missing, as they are only collected at Weeks 0 and 16.  The ANCOVA models will be 
analogous to those described in Sections 8.3.1.3 and 8.3.1.4, with the baseline score specific to 
each endpoint included as a covariate.   
Bar graphs of the LS mean change from baseline to Week 16 by treatment group, including 95% 
CIs, for Lund-Mackay and UPSIT scores will be provided, using the primary analysis approach 
for each endpoint based on the amount of missing data as described in Table 1.   
The number and proportion of subjects in each anosmia category will be summarized by visit, 
including baseline, using as observed data.   
CT scan and UPSIT data will also be presented in by-subject data listings. 
8.3.2.1.2. 
NPS and Symptom Scores  
The bilateral endoscopic NPS is the sum of the right and left nostril scores, as evaluated by 
means of blinded, centrally read nasal endoscopy and ranges from 0-8.  NP is graded based on 
polyp size:  0 = No polyps, 1 = Small polyps in the middle meatus not reaching below the 
inferior border of the middle turbinate, 2 = Polyps reaching below the lower border of the middle 
turbinate, 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial 
to the middle turbinate, and 4 = Large polyps causing complete obstruction of the inferior nasal 
cavity. 
On a daily basis, from Visit 1 and throughout the study, the subject will use a Diary to: 
Respond to the AM and PM individual rhinosinusitis symptom questions using a 0–3 categorical 
scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe 
symptoms) for the following symptoms: 
• congestion and/or obstruction (i.e. NC score) 
• anterior rhinorrhea (runny nose) 
• posterior rhinorrhea (post-nasal drip) 
• loss of sense of smell 
The above symptom scores will be recorded directly in the daily Diary.  For post-baseline visits, 
the average of the daily symptom scores over the prior 4 weeks will be used to determine the 
value for that visit, if at least 50% of the scores were completed over the prior 4 weeks, and will 


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be calculated separately for AM and PM scores.  The TSS is the sum of the scores from the 4 
symptom categories (congestion and/or obstruction, anterior rhinorrhea, posterior rhinorrhea, 
loss of sense of smell), ranges from 0–12, and will be calculated separately for AM and PM 
scores.  
For the change from baseline to Week 16 in NPS, AM NC score, and AM TSS, the primary 
analysis approach will depend on the amount of missing data for each endpoint, based on the 
same criteria for the primary endpoint as described in Section 8.3.1.  The MMRM models will be 
similar to those described in Sections 8.3.1.1 and 8.3.1.2, with the baseline score specific to each 
endpoint included as a covariate.  For NC and TSS MI, Week 20 (Follow-up) values will be 
included as a covariate in the multiple imputation.  For monotone regression, MI is performed 
sequentially, meaning only the data from weeks prior to the study week with missing data will 
inform the MI.  Therefore, values at Week 20 (Follow-up) will not inform prior weeks.  If the 
analyses fail to converge due to the complexity of model specification, the approaches described 
in Section 8.3.1.1 will be implemented.  The ANCOVA models will be analogous to those 
described in Sections 8.3.1.3 and 8.3.1.4, with the baseline score specific to each endpoint 
included as a covariate.  For the NPS endpoint, the analysis will be conducted within the 
randomized CRSwNP stratum.   
For the change from baseline to Week 16 and change from baseline to all visits through Week 16 
in PM NC score, PM TSS, AM and PM anterior rhinorrhea, AM and PM posterior rhinorrhea, 
and AM and PM loss of sense of smell, the MMRM without MI models described in Section 
8.3.1.1 will be used with the baseline score specific to each endpoint included as a covariate.   
Actual, change from baseline, and percent change from baseline values in NPS, AM NC score, 
and AM TSS will be descriptively summarized by visit using MI data if MI is performed.  
Actual, change, and percent change from baseline values in NPS, NC scores, anterior rhinorrhea 
scores, posterior rhinorrhea scores, loss of sense of smell scores, and TSS for AM and PM will 
be descriptively summarized by visit using as observed data.     
Bar graphs of the LS mean change from baseline to Week 16 by treatment group, including 95% 
CIs, for NPS, AM and PM NC scores, AM and PM anterior rhinorrhea, AM and PM posterior 
rhinorrhea, AM and PM loss of sense of smell, and AM and PM TSS at Week 16 will be 
provided.  Figures of LS mean change from baseline, including 95% CIs, by visit for each of 
these endpoints will also be provided.  The figures will use the primary analysis approach for each 
endpoint based on the amount of missing data as described in Table 1.   
Nasal endoscopy and diary data will also be presented in by-subject data listings. 
8.3.2.2. 
Time to Event Endpoints 
Time to first response in NPS is defined as the time from the date of the first dose of study 
treatment to the first date with ≥ 1 point improvement in NPS from baseline for subjects in the 
randomized CRSwNP stratum.  Subjects in the randomized CRSwNP stratum who do not 
experience ≥ 1 point improvement in NPS from baseline will be censored at their last post-
baseline NPS assessment, or on Day 1 if no baseline NPS assessment or no post-baseline NPS 
assessment was performed.     


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CRS exacerbation is defined as deterioration of CRS symptoms requiring treatment with an 
antibiotic, an anti-inflammatory drug, or a symptom reliever; an Emergency Department visit; or 
hospitalization (Kuiper, 2018).  Time to first CRS exacerbation is defined as the time from the 
date of the first dose of study treatment to the first date of treatment with an antibiotic, an anti-
inflammatory drug, or a symptom reliever, the date of Emergency Department visit, or the date 
of hospitalization, whichever occurs first.  Subjects without a CRS exacerbation will be censored 
at their last post-baseline CRS exacerbation assessment, or on Day 1 if no post-baseline CRS 
exacerbation assessment was performed. 
For the primary analysis of both time to event endpoints, all data through Week 16 will be 
included;  a sensitivity analysis of both time to event endpoints will be performed including all 
data. 
The number and proportion of subjects with a response in NPS will be summarized for subjects 
in the randomized CRSwNP stratum.  Time to first response in NPS will be compared between 
treatment groups using a Cox proportional hazards model and will include covariates for 
treatment group, disease status stratification factor values used for randomization (CRSwNP with 
comorbid asthma, CRSwNP without comorbid asthma, and CRSsNP), region (United States, 
Eastern Europe), and baseline NPS.   
The number and proportion of subjects with CRS exacerbations will be summarized.  Time to 
first CRS exacerbation will be analyzed using a Cox proportional hazards model and will include 
covariates for treatment group, disease status stratification factor values used for randomization 
(CRSwNP with comorbid asthma, CRSwNP without comorbid asthma, and CRSsNP), and 
region (United States, Eastern Europe). 
The exact method will be used to handle ties in event times.   
For both time to event endpoints, estimates of the hazard ratio for the GB001 40 mg group versus 
placebo, corresponding 95% CIs, and p-values will be provided from the model.  Percentage 
reductions and corresponding 95% CIs will also be provided.  Kaplan-Meier summaries of the 
proportion of subjects with response in NPS and separately for the proportion of subjects with a 
CRS exacerbation over time will also be presented and displayed graphically.  The median event 
time (and other quartiles), if estimable, and corresponding 95% CI based on the Brookmeyer and 
Crowley method (Brookmeyer, 1982) using the log-log transformation (Kalbfleisch, 1980) will 
be provided for each treatment group and endpoint. 
An additional analysis of the proportion of subjects with a reduction from baseline of ≥ 1 in NPS 
at Weeks 8 and 16 in the randomized CRSwNP stratum will be analyzed using a logistic 
regression model to compare the GB001 40 mg group with placebo, using the approach 
described in Section 8.3.1.5 with NPS score at baseline included as a covariate. 
Time to event data will also be presented in by-subject data listings. 


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8.3.3. 
Exploratory and Additional Analyses 
The exploratory and additional endpoints are listed in Table 1 and will be analyzed as described 
below. 
8.3.3.1. 
Change from Baseline to Week 16 Endpoints 
The VAS for rhinosinusitis is used to evaluate the total severity and is only validated in adult 
CRS to date (Fokkens, 2007).  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) (as defined in Protocol Section 10.7).  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 
Percentage of maxillary sinus volume occupied by disease on CT scan, volume of the air (mL), 
volume of mucosa (mL), and thickness of lateral wall (mm) will be calculated each for the left 
and right sides and averaged for analysis, using the non-missing values at each visit.   
Change from baseline to Week 16 in VAS score and percentage of maxillary sinus volume 
occupied by disease on CT scan, volume of the air, volume of mucosa, and thickness of lateral 
wall will be analyzed using ANCOVA models without MI.  The ANCOVA models will be 
analogous to those described in Section 8.3.1.3, with the baseline value specific to each endpoint 
included as a covariate.  The models will include covariates for treatment group, disease status 
stratification factor values used for randomization (CRSwNP with comorbid asthma, CRSwNP 
without comorbid asthma, and CRSsNP), region (United States, Eastern Europe), and baseline 
value.  LS means, SEs, and corresponding 95% CIs for each treatment group, and differences in 
LS means, SEs, corresponding 95% CIs, and p-values for the GB001 40 mg group versus 
placebo will be provided.   
Actual values and change from baseline values in VAS scores will be descriptively summarized 
by visit using as observed data.   
VAS score, percentage of maxillary sinus volume occupied by disease on CT scan, volume of 
the air, volume of mucosa, and thickness of lateral wall data will be presented in by-subject data 
listings. 
8.3.3.2. 
Change from Baseline to Week 16 Including All Data Endpoints 
Additional analyses of change from baseline to Week 16 in SNOT-22 total score, NPS, and 
Lund-Mackay score will be performed including all data.  For these analyses, analysis visit 
windows will be the same as the primary analysis, except no upper bound will be applied to the 
Week 16 analysis visit window.  The primary analysis approach will depend on the amount of 
missing data for each endpoint, based on the same criteria for the primary endpoint as described 


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in Section 8.3.1.  The MMRM models for SNOT-22 total score and NPS will be similar to those 
described in Sections 8.3.1.1 and 8.3.1.2, with the baseline score specific to each endpoint 
included as a covariate.  The ANCOVA model for Lund-Mackay score will be analogous to 
those described in Sections 8.3.1.3 and 8.3.1.4, with the baseline score included as a covariate.  
For the NPS endpoint, the analysis will be conducted within the randomized CRSwNP stratum.   
8.3.3.3. 
Annualized Rate of CRS Exacerbations 
The date of onset of a CRS exacerbation will be considered to be the first date of treatment with 
an antibiotic, an anti-inflammatory drug, or a symptom reliever, the date of Emergency 
Department visit, or the date of hospitalization, whichever occurs first.  The end date of a CRS 
exacerbation will be considered to be the last date of treatment with an antibiotic, an anti-
inflammatory drug, or a symptom reliever, or 6 days after the date of onset (for a total duration 
of 7 days), whichever is later.  Courses of treatment separated by 7 or more days will be counted 
as separate exacerbations. 
The number and proportion of subjects with 0, 1, and ≥ 2 CRS exacerbations and the adjusted 
annualized rate of CRS exacerbations will be summarized by treatment group.  The unadjusted 
annualized rate of CRS exacerbations will be calculated as the total number of CRS 
exacerbations divided by the total number of subject-years of follow-up and will also be 
summarized by treatment group.   
The total number of CRS exacerbations will be analyzed using a negative binomial regression 
model, with the logarithmic transformation of follow-up time as the offset parameter.  The 
follow-up time is defined as the subject’s time on study through Day 120.  The model will 
include terms for treatment group, disease status stratification factor values used for 
randomization (CRSwNP with comorbid asthma, CRSwNP without comorbid asthma, and 
CRSsNP), and region (United States, Eastern Europe).  If the distribution of CRS exacerbation 
data is underdispersed, or if the negative binomial regression model fails to converge, a Poisson 
regression model will be used instead of the negative binomial regression model.   
The rate ratio for the GB001 40 mg group versus placebo, corresponding 95% CI, and p-value 
will be provided from the model.  The percentage reduction and corresponding 95% CI will also 
be provided.   
Lastly, the subject CRS exacerbation rate will be calculated as the number of CRS exacerbations 
for each subject divided by the number of years followed in the study for that subject and will be 
summarized by treatment group.  
Analyses of annualized rate of CRS exacerbations may also be presented by various time periods 
(Baseline through Week 8, Week 8 through Week 16, and Baseline through Week 20 [Follow-up]) in 
order to elucidate onset and durability of effect over time. 
CRS exacerbation data will also be presented in by-subject data listings. 


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8.3.3.4. 
Proportion of Subjects with Antibiotic Use Due to Worsening CRS by Week 
16 
The proportion of subjects with antibiotic use due to worsening of CRS by Week 16 will be 
analyzed using a logistic regression model to compare the GB001 40 mg group with placebo, 
using the approach described in Section 8.3.1.5, excluding baseline SNOT-22 total score as a 
covariate in the model. 
8.3.3.5. 
Other Endpoints 
8.3.3.5.1. 
Nitric Oxide 
Nitric oxide will be measured both by oral (FeNO) and nasal (nasal nitric oxide [nNO]) methods.  
nNO data will be analyzed for the same nostril, either left or right, per subject at all visits.  The 
primary nNO analysis will include subjects with a change from baseline to Week 16 value for a 
single nostril and subjects with change from baseline to Week 16 values for both nostrils where 
the nostril with the lower (i.e., worse) value at baseline is used.  In the case of ties at baseline, the 
nostril with the lower (i.e., worse) change from baseline at Week 16 will be selected for 
summary.  A sensitivity nNO analysis will include subjects with a change from baseline to Week 
16 value for a single nostril and subjects with change from baseline to Week 16 values for both 
nostrils where the nostril with the higher (i.e., better) value at baseline is used.  In the case of ties 
at baseline, the nostril with the higher (i.e., better) change from baseline at Week 16 will be 
selected for summary. 
Change from baseline to Week 16 in both FeNO and nNO and percent change from baseline to 
Week 16 in both FeNO and nNO will be analyzed using ANCOVA models without imputation.  
LS means, SEs, and corresponding 95% CIs for each treatment group, and differences in LS 
means, SEs, corresponding 95% CIs, and p-values for the GB001 40 mg group versus placebo 
will be provided. The models will include covariates for treatment group and baseline FeNO or 
nNO.  Analyses may be conducted using log transformed data in the case of non-normality. 
Actual, change from baseline, and percent change from baseline values in FeNO and nNO will 
be descriptively summarized by visit using as observed data.   
Nitric oxide data will also be presented in a by-subject data listing. 
8.3.3.5.2. 
ACQ-5 Score 
The ACQ-5 is a five-item questionnaire which has been developed as a measure of the subject’s 
asthma control that can be quickly and easily completed (Juniper, 2005). The response options 
for each of these questions consists of a zero (no impairment/limitation) to 6 (total 
impairment/limitation) scale with the total score ranging from 0 to 30.  ACQ-5 score is the 
average of the 5 non-missing items and will be calculated at each visit for each subject. The 
MCID is 0.5 points.  ACQ-5 will be conducted only in subjects who reported a diagnosis of 
asthma at the Screening visit. 
Change from baseline to Week 16 in ACQ-5 score will be analyzed using an ANCOVA model 
without MI.  The ANCOVA model will be analogous to the model described in Section 8.3.1.3, 


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and will include covariates for treatment group, region (United States, Eastern Europe), and 
baseline ACQ-5 score.  Actual and change from baseline values in ACQ-5 score will be 
descriptively summarized by visit using as observed data.   
ACQ-5 scores will also be presented in a by-subject data listing. 
8.3.3.5.3. 
PK Concentrations 
GB001 plasma concentrations will be summarized by visit/timepoint using the following 
descriptive statistics: number of subjects with non-missing data, arithmetic mean, SD, arithmetic 
% coefficient of variation (CV), geometric mean, geometric % CV, median, minimum, and 
maximum.  
For calculation of mean concentrations, all below limit of quantification (BLQ) values will be set 
to zero. If the number of values that are BLQ at a nominal timepoint exceed 50% of the 
observations collected at that nominal timepoint, summary statistics for the timepoint will not be 
calculated. If the mean concentration value is less than the lower limit of quantification (LLOQ) 
value, then the mean, median, minimum, and maximum concentration values will be set to BLQ.  
GB001 plasma concentrations will also be presented in a by-subject data listing. 
 
8.4. 
Examination of Subgroups 
8.4.1. 
Examination of CRSsNP and CRSwNP Subgroups 
Subgroup analyses of the primary and three secondary efficacy endpoints (i.e. change from 
baseline to Week 16 in SNOT-22 total score, Lund-Mackay score, AM NC score, and AM TSS) 
will be performed using the primary analysis approach (which is based on the amount of missing 
data as described in Table 1) for the randomized CRSsNP and CRSwNP subgroups.  The 
CRSwNP subgroup will be further broken down based on the presence or absence of comorbid 
asthma (CRSwNPsA and CRSwNPwA).   
Models used for the subgroup analyses will be similar to those used for the primary and 
secondary efficacy endpoints as specified in Sections 8.3.1 and 8.3.2.1, with the following 
additional covariates:  treatment group by disease status stratification factor values used for 
randomization (referred to as ‘strata’ henceforth in this section, for brevity) interaction, strata by 
visit interaction, and treatment group by strata by visit interaction for SNOT-22 total score, AM 
NC score, and AM TSS score; and treatment group by strata interaction for Lund-Mackay score.  
For SNOT-22 total score, AM NC score, and AM TSS, if the model does not converge, a 
reduced model excluding region, baseline score, and baseline score by visit interaction will be 
used.  For Lund-Mackay, if the model does not converge, a reduced model including only 
treatment group, strata, and treatment group by strata interaction will be used. 
Heterogeneity of treatment effect across the CRSsNP and CRSwNP subgroups (CRSsNP, 
CRSwNP, CRSwNPsA, CRSwNPwA) will be evaluated by presenting interaction p-values for 
the treatment group by strata by visit interaction for Week 16 for SNOT-22 total score, AM NC 
score and AM TSS score, and treatment group by strata interaction for Lund-Mackay score. The 


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interaction term will be used to test whether the treatment effects in the CRSsNP and CRSwNP 
subgroups are significantly different, using CRSsNP as the reference subgroup.  Additionally, 
the interaction term will be used to test whether the treatment effects in CRSwNPsA and 
CRSwNPwA are significantly different, using CRSwNPsA as the reference group.  
Actual, change from baseline, and percent change from baseline values in SNOT-22 domain 
scores will be descriptively summarized by visit for the randomized CRSsNP and CRSwNP 
subgroups using as observed data.   
8.4.2. 
Examination of Other Subgroups 
Subgroup analyses of the primary and three secondary efficacy endpoints (i.e. change from 
baseline to Week 16 in SNOT-22 total score, NPS, AM NC score, and AM TSS) will be 
performed using the primary analysis approach (which is based on the amount of missing data as 
described in Table 1) for all of the subgroups specified below.  For any subgroup level that does 
not comprise ≥ 20% of the ITT population, the SNOT-22 total score, AM NC score, and AM 
TSS analyses based on the models will not be performed.  For any subgroup level that does not 
comprise ≥ 20% of subjects in the ITT population with nasal polyps, the NPS analyses based on 
the models will not be performed.  The subgroups of interest are described below. 
Demographic characteristic subgroups: 
• Age (years; < 50, ≥ 50) 
• Sex (male, female) 
• BMI (kg/m2; < 30, ≥ 30) 
• Region (United States, Eastern Europe) 
Baseline disease characteristic and atopic/allergic condition subgroups: 
• SNOT-22 total score at Baseline (≤ Median, > Median, where median is based on the 
ITT population) for the SNOT-22 total score endpoint 
• NPS at Baseline (≤ 6, > 6) for the NPS endpoint 
• AM NC score at Baseline (≤ Median, > Median, where median is based on the ITT 
population) for the AM NC score endpoint 
• AM TSS score at Baseline (≤ Median, > Median, where median is based on the ITT 
population) for the AM TSS score endpoint 
• Prior NP surgery (yes, no) 
• Allergic Rhinitis (seasonal and/or perennial) at Baseline (yes, no) 
Biomarker baseline characteristic subgroups: 
• Blood eosinophils at Baseline (10^9/L; < 0.25, ≥ 0.25) 
• FeNO at Baseline (ppb; < 25, ≥ 25) 


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• Chloride at Baseline (mmol/L; ≤ Quartile 1, > Quartile 1-≤ Quartile 2, > Quartile 3-≤ 
Quartile 3, > Quartile 3, where quartiles are based on the ITT population) 
Models used for the subgroup analyses will be similar to those used for the primary and 
secondary efficacy endpoints as specified in Sections 8.3.1 and 8.3.2.1, with the following 
additional covariates:  subgroup (if different than the aforementioned covariates, i.e. region), 
treatment group by subgroup interaction, subgroup by visit interaction, and treatment group by 
subgroup by visit interaction.  If the model does not converge, a reduced model excluding strata, 
region (if not the subgroup), baseline score, and baseline score by visit interaction will be used.   
Heterogeneity of treatment effect across different levels of each subgroup will be evaluated by 
presenting interaction p-values for the treatment group by subgroup by visit interaction for Week 
16. The interaction term tests whether the treatment effect is significantly different across 
different levels of the subgroup (between males and females, for example). The least severe or 
lower subgroup level (where applicable) will be used as the reference subgroup, and the test will 
assess whether the treatment effect in the more severe level(s) or higher value level(s) differs 
from that in the reference subgroup. For subgroups without directionality (sex and region), male 
and United States, respectively, will be used as the reference subgroup.  
Forest plots of the treatment effect estimates, corresponding 95% CIs, subgroup p-values, and 
interaction p-values for the subgroup analyses described in Sections 8.4.1 and 8.4.2 will be 
provided. 


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9. 
SAFETY EVALUATION 
9.1. 
Adverse Events 
Verbatim AE terms will be coded to a SOC and PT using MedDRA Version 21.0 or later. 
All analyses of AEs will be based on the principle of treatment emergence.  An AE is considered 
to be treatment-emergent if it has a start date on or after the date of the first dose of study 
treatment.  In general, if the treatment emergence of an AE is not clear due to a missing or 
incomplete AE start date, the AE will be considered to be treatment-emergent unless the non-
missing portions of the start date and the end date indicate otherwise. 
In general, whenever a tabular summary of AEs is mentioned in this document, it is intended that 
the tabular summary is in reference to TEAEs, even though “treatment-emergent” may not be 
explicitly mentioned.  By-subject data listings of AEs will include all events regardless of 
treatment emergence and TEAEs will be identified.   
Counting will be at the subject level for each level of summarization (e.g., any AE, SOC, and 
PT), with subjects experiencing more than one AE counted only once.  In the summary of AEs 
by severity (mild, moderate, severe), subjects will be counted once at the highest severity 
reported at each level of summarization.  AEs that are missing severity will be presented in 
summary tables as “Missing”.  AEs that are missing relationship to study treatment will be 
presented in summary tables as “Related”. 
The following summaries will be presented for the safety population:  
• Overall Summary of AEs - showing the number and percent of subjects with an AE; a 
moderate or severe AE; a severe AE; a SAE; a treatment-related AE; a treatment-
related SAE; an AE leading to discontinuation of study treatment; an AE leading to 
withdrawal from study; an AE resulting in death; and an AE of interest (as defined in 
Protocol Section 10.3.3). 
• Incidence of AEs by SOC and PT 
• Incidence of AEs by PT 
• AEs with Incidence ≥ 5% in Either Treatment Group by PT 
• AEs with Incidence at Least ≥ 3% Higher in the GB001 40 mg Group Relative to the 
Placebo Group by Preferred Term   
• Incidence of SAEs by SOC and PT  
• Incidence of AEs by SOC, PT, and Maximum Severity 
• Incidence of Treatment-Related AEs by SOC and PT  
• Incidence of AEs Leading to Discontinuation of Study Treatment by SOC and PT 
• Incidence of AEs Leading to Withdrawal from Study by SOC and PT 
• Summary of Pruritus AEs 


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• Incidence of Liver Chemistry AEs by PT 
• Incidence of Liver Chemistry AEs Leading to Discontinuation of Study Treatment by 
PT 
• Incidence of AEs of Interest by SOC and PT 
All AEs, AEs leading to discontinuation of study treatment and/or withdrawal from study, AEs 
of interest, SAEs, and AEs resulting in death will be presented in by-subject data listings. 
9.2. 
Clinical Laboratory Evaluation 
Actual values and change from baseline values for quantitative laboratory parameters (clinical 
and liver chemistry, hematology, and urinalysis) will be summarized by visit for the safety 
population.   
Shift tables will be presented for clinical and liver chemistry, hematology, and qualitative 
urinalysis parameters summarizing shifts from baseline to high and low (or to abnormal for 
urinalysis) at any time post-baseline based on laboratory normal ranges. 
A summary of maximum post-baseline values > 1.0, > 1.5, and > 3.0 10^9/L for blood 
eosinophils will be presented.   
Summaries of maximum post-baseline values for liver chemistry parameters (alanine 
aminotransferase [ALT], aspartate aminotransferase [AST], ALT or AST, concurrent ALT or 
AST and total bilirubin, total bilirubin, direct bilirubin, indirect bilirubin, alkaline phosphatase, 
gamma-glutamyl transferase [GGT]), and bile acid according to categories based on multiples of 
upper limit of normal (ULN) will be presented.  Liver chemistry parameters according to 
categories based on multiples of ULN will also be presented by visit. 
For laboratory shift tables and summaries of maximum post-baseline values, only subjects with 
at least one post-baseline value will be included. 
The time to first elevation for ALT will be presented for subjects with an elevation in ALT.  An 
elevation for ALT will be defined as the first post-baseline value ≥ 1.5 x ULN for subjects with a 
baseline value ≤ ULN, and the first post-baseline value with a > 50% increase from baseline for 
subjects with a baseline value > ULN.  This analysis will also be repeated using a threshold of > 
1.0 x ULN.  In addition, the time to first elevation of AST will be summarized in the same 
manner as described above for time to first elevation of ALT. 
In addition, the following figures/plots will be provided: 
• Mean change from baseline values, including SE bars, by visit figures for liver 
chemistry parameters 
• Mean ratio of actual values to ULN, including SE bars, by visit figures for liver 
chemistry parameters 
• Evaluation of Drug-Induced Serious Hepatotoxicity (eDISH) (Merz, 2014) plots 


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• Mean actual values and mean change from baseline values, including SE bars, by 
visit figures for blood eosinophils 
• Maximum post-baseline values versus baseline values plot for blood eosinophils 
Laboratory parameters will also be presented in by-subject data listings.  In addition, liver event 
information including liver biopsy and liver imaging results will be presented in a by-subject 
data listing. 
9.3. 
Vital Signs and Other Observations Related to Safety 
9.3.1. 
Vital Signs 
Actual values and change from baseline values for vital sign parameters (systolic and diastolic 
blood pressure, pulse rate, respiratory rate, temperature, and weight) will be summarized by visit 
for the safety population. 
A summary table of the incidence of abnormalities in vital sign parameters will be presented 
according to the following abnormality criteria. 
Table 2:  Vital Sign Parameter Abnormality Criteria 
Vital Sign Parameter 
Abnormality Criteria 
Systolic Blood Pressure 
High or Increased:  > 180 mmHg post-baseline if ≤ 180 mmHg at baseline, or an 
increase from baseline of > 40 mmHg. 
 
 
Low or Decreased:  < 90 mmHg post-baseline if ≥ 90 mmHg at baseline, or a 
decrease from baseline of > 30 mmHg. 
Diastolic Blood Pressure 
High or Increased:  > 105 mmHg post-baseline if ≤ 105 mmHg at baseline, or an 
increase from baseline of > 30 mmHg. 
 
 
Low or Decreased:  < 50 mmHg post-baseline if ≥ 50 mmHg at baseline, or a 
decrease from baseline of > 20 mmHg. 
Pulse Rate 
High or Increased:  > 120 bpm post-baseline if ≤ 120 bpm at baseline, or an increase 
from baseline of > 20 bpm. 
 
 
Low or Decreased:  < 50 bpm post-baseline if ≥ 50 bpm at baseline, or a decrease 
from baseline of > 20 bpm. 
Temperature 
> 38 degrees C and an increase from baseline of at least 1 degree C. 
bpm = beats per minute   
Vital sign parameters will also be presented in a by-subject data listing and abnormalities will be 
flagged. 
9.3.2. 
Other Safety Measures 
9.3.2.1. 
Electrocardiograms 
Actual values and change from baseline values will be summarized by visit for the safety 
population for the following quantitative ECG parameters:  heart rate, PR interval, QRS duration, 


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QT interval (uncorrected), Fridericia's correction formula for QT interval (QTcF), and RR 
interval.   
Outlier analyses for QTcF intervals will be performed.  This will consist of a summary of the 
number and percent of subjects with a post-baseline QTcF interval greater than 450 msec, 480 
msec, and 500 msec and the number and percent of subjects with an increase from baseline in 
QTcF interval of greater than 30 msec and 60 msec. 
Each ECG will be assessed with an overall interpretation of normal, abnormal, or unable to 
evaluate.  Shift tables for overall interpretation will be presented, summarizing shifts from 
baseline to abnormal at any time post-baseline. 
ECG parameters will also be presented in a by-subject data listing and outliers will be flagged. 


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Protocol No. GB001-2101 
 
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