Clinical trial NCT03683576
Conditions: Asthma
Keywords: GB001 eosinophilic asthma moderate asthma severe asthma
Sponsor: GB001, Inc, a wholly owned subsidiary of Gossamer Bio, Inc.
Start date: 2018-10-22; Completion date: 2020-08-18
Enrollment: 481 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A randomized, double-blind, placebo-controlled, dose-ranging, multi-center study to evaluate the efficacy and safety of GB001 when added to standard-of care (SOC) asthma maintenance therapy in adults with moderate to severe asthma and an eosinophilic phenotype with respect to asthma worsening at the end of 24 weeks of treatment.

Detailed description:

Arms: arm 1: Placebo once per day (QD) for 24 weeks arm 2: GB001 20 mg QD for 24 weeks arm 3: GB001 40 mg QD for 24 weeks arm 4: GB001 60 mg QD for 24 weeks
Interventions: intervention 1: GB001 intervention 2: Placebo
Intervention descriptions: intervention 1: film-coated oral tablet intervention 2: film-coated oral tablet

Protocol documents:
Prot_000.pdf: 
GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
1 
CONFIDENTIAL 
CLINICAL STUDY PROTOCOL 
 
 
Protocol Title:  
A Phase 2b, randomized, double-blind, placebo-controlled, 
dose-ranging, multi-center study to evaluate the efficacy and safety of 
GB001 as maintenance therapy in adult subjects with moderate to 
severe asthma 
Short Title: 
GB001 in adult subjects with moderate to severe asthma 
Protocol Number:  
GB001-2001 
Compound Number:  
GB001 
Study Phase:  
Phase 2b 
Sponsor Name: 
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(s): 
 
EudraCT:        2018-002242-36 
Version: 
5.0 
Approval Date: 
16 Apr 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document constitutes agreement by the recipient that no previously unpublished information contained 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. 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
2 
CONFIDENTIAL 
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.   


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
3 
CONFIDENTIAL 
INVESTIGATOR AGREEMENT 
GB001-2001: A Phase 2b, randomized, double-blind, placebo-controlled, dose-ranging, 
multi-center study to evaluate the efficacy and safety of GB001 as maintenance therapy in adult 
subjects with moderate to severe asthma 
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 (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 




GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
5 
CONFIDENTIAL 
Section # and Name  
Description of Change  
Brief Rationale  
compliance with good 
clinical practice (GCP), 
and minimizing 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 
 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
6 
CONFIDENTIAL 
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 ........................................................................................................................14 
1.3. 
Schedule of Activities .................................................................................................15 
2. 
INTRODUCTION ......................................................................................................19 
2.1. 
Study Rationale ...........................................................................................................19 
2.2. 
Background .................................................................................................................19 
2.3. 
Benefit/Risk Assessment ............................................................................................21 
2.3.1. 
GB001 Risk/Benefit Assessment ................................................................................21 
2.3.2. 
Study Design Risk/Benefit Assessment......................................................................21 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................22 
4. 
STUDY DESIGN .......................................................................................................24 
4.1. 
Overall Design ............................................................................................................24 
4.1.1. 
Study Design ...............................................................................................................24 
4.1.2. 
Unscheduled Visit .......................................................................................................25 
4.2. 
Scientific Rationale for Study Design ........................................................................26 
4.2.1. 
Study Population .........................................................................................................26 
4.2.2. 
Placebo Rationale .......................................................................................................26 
4.2.3. 
Primary Endpoint Selection ........................................................................................27 
4.3. 
Justification for Dose ..................................................................................................27 
4.4. 
End of Study Definition ..............................................................................................27 
5. 
STUDY POPULATION .............................................................................................28 
5.1. 
Inclusion Criteria ........................................................................................................28 
5.2. 
Exclusion Criteria .......................................................................................................29 
5.3. 
Randomization Criteria ...............................................................................................31 
5.4. 
Screen or Run-In Failures ...........................................................................................32 
6. 
INVESTIGATIONAL PRODUCT ............................................................................33 
6.1. 
Preparation/Handling/Storage/Accountability ............................................................33 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
7 
CONFIDENTIAL 
6.2. 
Measures to Minimize Bias: Randomization and Blinding ........................................34 
6.2.1. 
Assignment of a Subject Number ...............................................................................34 
6.2.2. 
Randomization ............................................................................................................34 
6.2.3. 
Assignment of Investigational Product Kit Numbers .................................................34 
6.2.4. 
Unblinding of an Individual Subject ...........................................................................34 
 
 
6.3. 
Investigational Product Compliance ...........................................................................35 
6.4. 
Concomitant Therapy .................................................................................................35 
6.4.1. 
Prohibited Medications Prior to the Screening Visit and Throughout the 
Study ...........................................................................................................................35 
6.4.2. 
Restricted Medications ...............................................................................................36 
6.4.3. 
Rescue Medicine .........................................................................................................36 
6.5. 
Dose Modification ......................................................................................................36 
6.6. 
Intervention After the End of the Study .....................................................................36 
7. 
DISCONTINUATION OF INVESTIGATIONAL PRODUCT AND 
SUBJECT WITHDRAWAL FROM THE STUDY ...................................................36 
7.1. 
Discontinuation of Investigational Product ................................................................36 
7.1.1. 
QTc Stopping Criteria .................................................................................................36 
7.1.2. 
Pregnancy ...................................................................................................................37 
7.2. 
Subject Withdrawal from the Study ...........................................................................37 
7.3. 
Lost to Follow up ........................................................................................................37 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................38 
8.1. 
Efficacy Assessments .................................................................................................40 
8.1.1. 
Asthma Worsening (Primary Endpoint) .....................................................................40 
8.1.2. 
eDiary Asthma Parameters and Alerts ........................................................................40 
8.1.3. 
Pulmonary Function Testing including Reversibility .................................................41 
8.1.4. 
Asthma Control Questionnaire-5 ................................................................................41 
8.1.5. 
Asthma Quality of Life Questionnaire- Standardized (AQLQ-S) ..............................42 
8.1.6. 
Sino-Nasal Outcome Test ...........................................................................................42 
8.1.7. 
Hair Assessment .........................................................................................................42 
8.2. 
Safety Assessments .....................................................................................................43 
8.2.1. 
Physical Examinations ................................................................................................43 
8.2.2. 
Vital Signs ..................................................................................................................43 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
8 
CONFIDENTIAL 
8.2.3. 
Electrocardiograms .....................................................................................................43 
8.2.4. 
Clinical Safety Laboratory Assessments ....................................................................44 
8.3. 
Adverse Events, Serious Adverse Events, and Adverse Events of Interest ................44 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE Information .......................44 
8.3.2. 
Method of Detecting AEs and SAEs ..........................................................................45 
8.3.3. 
Follow-up of AEs and SAEs .......................................................................................45 
8.3.4. 
Pregnancy ...................................................................................................................46 
8.3.5. 
Death Events ...............................................................................................................46 
8.3.6. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as 
AEs or SAEs ...............................................................................................................46 
 
 
8.4. 
Treatment of Overdose ...............................................................................................46 
8.5. 
Pharmacokinetics ........................................................................................................47 
8.6. 
Pharmacodynamics and Biomarkers...........................................................................47 
8.6.1. 
Induced Sputum ..........................................................................................................47 
8.6.2. 
Fractional Exhaled Nitric Oxide .................................................................................48 
8.6.3. 
RNA Transcriptome Research ....................................................................................48 
 
 
8.6.5. 
Blood Biomarker Analyses .........................................................................................48 
 
 
8.6.7. 
Exhaled Breath Condensate Assessment ....................................................................49 
8.7. 
Genetics ......................................................................................................................49 
9. 
STATISTICAL CONSIDERATIONS .......................................................................50 
9.1. 
Statistical Hypotheses .................................................................................................50 
9.2. 
Sample Size Determination ........................................................................................50 
9.3. 
Populations for Analyses ............................................................................................50 
9.4. 
Statistical Analyses .....................................................................................................50 
9.4.1. 
Efficacy Analyses .......................................................................................................51 
9.4.1.1. 
Primary Efficacy Analysis ..........................................................................................51 
9.4.1.2. 
Secondary Efficacy Analysis ......................................................................................51 
 
 
9.4.2. 
Safety Analyses ..........................................................................................................52 
9.4.3. 
Other Analyses ............................................................................................................52 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
9 
CONFIDENTIAL 
9.5. 
Interim Analyses .........................................................................................................52 
9.5.1. 
Independent Data Monitoring Committee ..................................................................53 
10. 
APPENDICES ............................................................................................................54 
10.1. 
Appendix 1:  Regulatory, Ethical, and Study Oversight Considerations ...................54 
10.1.1. 
Regulatory and Ethical Considerations ......................................................................54 
10.1.2. 
Informed Consent Process ..........................................................................................54 
10.1.3. 
Data Protection ...........................................................................................................55 
10.1.4. 
Dissemination of Clinical Study Data ........................................................................55 
10.1.5. 
Data Quality Assurance ..............................................................................................55 
10.1.6. 
Source Documents ......................................................................................................56 
10.1.7. 
Study and Site Closure................................................................................................57 
10.1.8. 
Publication Policy .......................................................................................................57 
10.2. 
Appendix 2:  Clinical Laboratory Tests ......................................................................58 
10.3. 
Appendix 3:  Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow up, and Reporting ........................................................................60 
10.3.1. 
Definition of AE .........................................................................................................60 
10.3.2. 
Definition of SAE .......................................................................................................61 
10.3.3. 
Adverse Events of Interest ..........................................................................................62 
10.3.4. 
Recording and Follow Up of Adverse Events and Serious Adverse Events ..............62 
10.3.5. 
Reporting of SAEs ......................................................................................................65 
10.4. 
Appendix 4:  Contraceptive Guidance and Collection of Pregnancy 
Information .................................................................................................................66 
10.5. 
Appendix 5:  Genetics ................................................................................................70 
10.6. 
Appendix 6:  Liver Safety - Actions and Follow-up Assessments .............................71 
10.7. 
Appendix 7:  Daily Asthma Symptom Score .............................................................74 
10.8. 
Appendix 8:  Prohibited Medications and Treatments ...............................................75 
10.9. 
Appendix 9:  Restricted Medications and Treatments ................................................77 
10.10. 
Appendix 10:  Estimated Clinical Comparability of Medium and High Doses 
of Inhaled Corticosteroids ...........................................................................................78 
10.11. 
Appendix 11:  Assessment of Hair Loss.....................................................................79 
10.12. 
Appendix 12:  Guidance to Address a Pandemic or Other Global Health 
Emergencies and Potential Impact on the Clinical Study ...........................................80 
10.13. 
Appendix 13:  Abbreviations ......................................................................................81 
10.14. 
Appendix 14: Protocol Amendment History ..............................................................84 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
10 
CONFIDENTIAL 
11. 
REFERENCES ...........................................................................................................91 
 
LIST OF TABLES 
Table 1: 
Investigational Product Formulation by Treatment Group .........................................33 
Table 2: 
Protocol-Required Safety Laboratory Assessments ...................................................58 
Table 3: 
Liver Safety Laboratory Assessments ........................................................................59 
Table 4: 
Liver Chemistry Criteria Requiring Additional Monitoring with Possible 
Interruption of Investigational Product .......................................................................71 
Table 5: 
Liver Chemistry Criteria Requiring Investigational Product Interruption and 
Additional Monitoring ................................................................................................72 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
11 
CONFIDENTIAL 
1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A Phase 2b, randomized, double-blind, placebo-controlled, dose-ranging, 
multi-center study to evaluate the efficacy and safety of GB001 as maintenance therapy in adult 
subjects with moderate to severe asthma 
Short Title: GB001 in adult subjects with moderate to severe asthma 
Rationale: 
GB001 is a potent and highly selective oral prostaglandin D2 receptor (DP2) antagonist. DP2 is 
expressed on a variety of cells implicated in the allergic process including eosinophils and 
epithelial cells (Kupczyk, 2017; Singh, 2017). GB001 is being developed as a once daily oral 
add-on maintenance treatment for moderate to severe eosinophilic asthma. 
The purpose of this Phase 2b study is to evaluate the efficacy, safety, pharmacokinetics, and 
pharmacodynamics of 3 GB001 dose levels compared with placebo in subjects with moderate to 
severe asthma and an eosinophilic phenotype. The study will assess the efficacy of GB001 
relative to placebo in reducing asthma worsening when added to standard of care (SOC) asthma 
maintenance therapy.  




GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
13 
CONFIDENTIAL 
Overall Design: 
This is a Phase 2b, randomized, double-blind, placebo-controlled, dose-ranging, multi-center 
study to evaluate the efficacy and safety of GB001 as maintenance therapy in a moderate to 
severe eosinophilic asthma population. GB001 will be added to the subject’s standard-of-care 
asthma treatment. 
An interim analysis to inform further development of GB001 will be conducted after the first 
320 subjects have completed the study or have prematurely withdrawn from the study. 
A schematic of the study design is presented in Section 1.2. 
Disclosure Statement: 
This is a parallel group treatment study with 4 arms that is participant, Investigator, and Sponsor 
blinded. 
Number of Participants: 
This study will randomize approximately 480 subjects, with approximately 120 subjects per 
treatment group. 
Intervention Groups and Duration: 
Treatment groups: 
• GB001 60 mg daily 
• GB001 40 mg daily 
• GB001 20 mg daily 
• Matching placebo daily 
Total duration for study participation per subject is up to 34 weeks (includes a Screening visit; 
followed by a 2-week to 6-week Run-in period to allow for collection of baseline eDiary data; a 
24-week Double-Blind, Placebo-Controlled period; and 4-week Follow-up period). 
Independent Data Monitoring Committee (IDMC): Yes 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
14 
CONFIDENTIAL 
1.2. 
Schema 
 
 










GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
19 
CONFIDENTIAL 
2. 
INTRODUCTION 
2.1. 
Study Rationale 
GB001 is a potent and highly selective oral prostaglandin D2 receptor (DP2) antagonist. DP2 is 
expressed on a variety of cells implicated in the allergic process including eosinophils and 
epithelial cells (Kupczyk, 2017; Singh, 2017). GB001 is being developed as a once daily oral 
add-on maintenance treatment for moderate to severe eosinophilic asthma. 
The purpose of this Phase 2b study is to evaluate the efficacy, safety, pharmacokinetics, and 
pharmacodynamics of 3 GB001 dose levels compared with placebo in subjects with moderate to 
severe asthma and an eosinophilic phenotype. The study will assess the efficacy of GB001 
relative to placebo in reducing asthma worsening when added to standard of care (SOC) asthma 
maintenance therapy. 
2.2. 
Background 
More than 300 million people around the globe are diagnosed with asthma, a heterogenous 
chronic disease characterized by variable airflow obstruction and symptoms of cough, wheeze, 
and dyspnea. Inhaled corticosteroids (ICS) are the cornerstone of asthma maintenance therapy, 
with or without additional controllers (GINA, 2018). However, not all patients have a complete 
resolution of the underlying inflammation, and some continue to have severe asthma 
exacerbations. Prevention of severe asthma exacerbations is of utmost importance in the 
treatment of asthma. The significance of preventing severe asthma exacerbations is highlighted 
as 1 of the 7 key conclusions in the recent Lancet Commission Report (Pavord, 2018). Severe 
exacerbations create anxiety for the patient and their families, place stress on the healthcare 
system, and may result in more rapid decline in lung function (Reddel, 2009; O'Byrne, 2011; 
Ortega, 2018). From a societal perspective, asthma exacerbations result in millions of days of 
lost work each year (Botturi, 2011; Catley, 2011). The occurrence of asthma worsening or severe 
asthma exacerbations (asthma attack) is not infrequent. Approximately 45% of working adults in 
the United States with a diagnosis of asthma experienced at least one episode over the 5-year 
period from 2011-2016 (Mazurek, 2018). In summary, there continues to be an unmet medical 
need to provide novel therapies to reduce asthma worsening and severe asthma exacerbations. 
New biologics have recently entered the market to address, in part, the unmet medical need. 
However, these medications are given by injection, which currently requires a patient to visit a 
clinic every 2 to 8 weeks and may require multiple injections per dose. In addition, these 
medications may not be available to every patient who needs them. Lastly, biologic medications 
are restricted to patients who require Global Initiative for Asthma (GINA) guideline step 5 
treatment (GINA, 2018) and have exhausted other asthma therapies. It would be beneficial to 
have an effective therapy for reducing severe exacerbations as an option at earlier GINA steps. 
The class of compounds known as DP2 antagonists which act through the DP2 receptor may offer 
the potential to become an add-on oral maintenance therapy at GINA step 4 or earlier to decrease 
the occurrence of asthma exacerbations. DP2 has been implicated as a pathway that has a direct 
effect upon specific cell types that are associated with severe asthma, specifically mast cells and 
eosinophils. Importantly, it has been demonstrated that asthma patients with more severe disease 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
20 
CONFIDENTIAL 
or a history of an exacerbation in the prior year had upregulation of the prostaglandin D2 (PGD2)-
DP2 pathway and had the highest expression of the DP2 receptor in bronchial biopsy samples 
(Fajt, 2013). It is anticipated that GB001 will reduce recruitment and activation of airway 
eosinophils, with consequent reduction in airway inflammation including effects on fractional 
exhaled nitric oxide (FeNO). In a recent post-hoc analysis of 36 subjects (ADC3680-04) 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 FeNO (< 35 and ≥ 35 ppb) and blood eosinophil 
(< 200 and ≥ 200/µL) subgroups (Ortega, 2019a; Ortega, 2019b). In the overall population, 
GB001 had a favorable 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 = 16) 
subgroups (differences of 207 mL and 81 mL, respectively). These results suggest that GB001 
favorably influences lung function in subjects with markers of eosinophilic inflammation. 
Two important studies with the oral DP2 antagonist fevipiprant provide further support for the 
development of this class of compounds for the reduction of asthma exacerbations in patients 
with severe asthma and markers of eosinophilic inflammation. In the first study conducted by 
Gonem et al, fevipiprant (compared to placebo) significantly reduced eosinophilic inflammation 
as measured by a reduction in sputum eosinophils in patients receiving ICS and having either an 
ACQ-7 score of at least 1.5 at randomization or a severe asthma exacerbation in the prior year 
(Gonem, 2016). The magnitude of reduction in sputum eosinophils with fevipiprant treatment for 
12 weeks is consistent with that of the biologic mepolizumab (Haldar, 2009; Pavord, 2012). The 
second Phase 2 study is a large dose-ranging study that evaluated the effect of a wide range of 
fevipiprant doses in comparison to placebo and montelukast in a population with moderate to 
severe asthma. The primary efficacy outcomes were based upon FEV1 which demonstrated 
improvements in lung function from baseline over 12 weeks. Additionally, a post-hoc analysis 
investigated the reduction in asthma worsening/exacerbations in over 1000 patients. Despite the 
short treatment duration of 12 weeks, a trend for reduction of asthma worsening and asthma 
exacerbation events was seen when all doses (1 mg to 450 mg) were pooled (Bateman, 2017). 
The effect of GB001 in reducing asthma worsening has been studied in a Phase 2 study in 
Japanese subjects (Study PTR-36-201). This study enrolled subjects who were taking a 
medium-dose ICS or medium-dose ICS/LABA. Prior to start of the Run-in, subjects taking ICS/ 
long-acting beta agonist (LABA) were required to switch to ICS only. At baseline, subjects 
evaluated for efficacy had a mean ACQ score of 0.795 and a mean eosinophil count of 319 
cells/µL. Following a Run-in period, subjects were randomized to double-blind treatment with 
GB001 20 mg, GB001 5 mg, or placebo for 16 weeks. During the first 8 weeks on study (ie, 4-
week Run-in and 4 weeks of the double-blind treatment period), background ICS treatment was 
tapered and ultimately withdrawn. Subjects then continued for an additional 12 weeks on 
monotherapy. The proportion of subjects with asthma worsening was significantly lower in the 2 
GB001 groups (32.7% GB001 5 mg, 20.8% GB001 20 mg) compared with the placebo group 
proportion of 52.8% (p < 0.05 for both dose levels). Collectively, these data along with the data 
from fevipiprant support further investigation of GB001 to reduce asthma exacerbations. 
The results of other GB001 clinical studies are available in the Investigator’s Brochure. 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
21 
CONFIDENTIAL 
2.3. 
Benefit/Risk Assessment 
2.3.1. 
GB001 Risk/Benefit Assessment 
GB001, an oral DP2 antagonist, is being developed as a maintenance therapy in asthma. Despite 
the recent availability of injectable biologics to manage asthma patients with poor control and 
exacerbations, there continues to be a paucity of oral agents to help manage and control asthma. 
The mechanism of GB001 is to antagonize the DP2 receptor and thereby reduce the T helper cell 
type 2 (Th2) response while affecting other cells relevant in the inflammatory and allergic 
cascade with corresponding improvements in asthma control, lung function and exacerbations 
(Hall, 2015; Gonem, 2016; Bateman, 2017). Ultimately these physiologic effects could result in 
an improvement in the overall quality of life of patients with moderate to severe asthma. 
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 the current study 
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 
and the Independent Data Monitoring Committee (IDMC). 
2.3.2. 
Study Design Risk/Benefit Assessment 
This study is designed to assess the effect of GB001 on asthma worsening, while maintaining 
asthma controller therapy. Since this study employs an add-on therapy design, subjects will be 
maintained on their stable SOC regimen throughout the study. 
To minimize the potential risk to subjects, stringent criteria are utilized during screening to 
exclude subjects with a history of significant other pulmonary disease, liver disease or other 
comorbidities that could impact subjects’ safety. In addition, subjects will be closely monitored 
with regards to liver function following current guidelines. All subjects will be closely monitored 
throughout the study through daily home morning peak expiratory flow (PEF) and eDiary 
monitoring. Alerts are programmed into the eDiary that trigger in the event of potential loss of 
asthma control. Upon receiving an alert, subjects will be instructed to contact their study 
physician and if necessary go to the site for further evaluation.  
Exacerbations are recognized as a common clinical manifestation in patients with severe asthma 
(GINA, 2018). Currently, management of acute exacerbations includes high doses of systemic 
corticosteroids, which is coupled with the known health risks associated with steroids 
(Dalal, 2016). This study offers the potential benefit for subjects receiving GB001 to experience 
fewer exacerbations and consequently have a reduction in the total cumulative dose of systemic 
corticosteroids (eg, prednisone), thereby minimizing the risk of acute systemic side effects of 
corticosteroids. As an additional potential benefit, all participating subjects on active or placebo 
will be frequently and closely monitored during the duration of the study with optimized 
standard of care. Furthermore, in patients who complete the study, an extension follow-up study 
may be offered in which all subjects will receive GB001. 






GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
24 
CONFIDENTIAL 
4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase 2b, randomized, double-blind, placebo-controlled, dose-ranging, multi-center 
study to evaluate the efficacy and safety of GB001 as maintenance therapy in a moderate to 
severe eosinophilic asthma population. GB001 will be added to the subject’s standard-of-care 
asthma treatment. 
An interim analysis to inform further development of GB001 will be conducted after the first 
320 subjects have completed the study or have prematurely withdrawn from the study (see 
Section 9.5). 
A schematic of the study design is presented in Section 1.2. 
4.1.1. 
Study Design 
The study will commence with a Screening visit (Visit 1), at which 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 or historical reversibility, if necessary. 
All other screening procedures should be completed 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). Eligible subjects will enter a Run-in period of a 
minimum of 2 weeks and a maximum of 6 weeks and will remain on their SOC regimen. The 
Run-in period commences with completion of all Screening visit procedures and concludes at the 
Randomization visit. During the Run-in period, subjects will capture PEF and asthma symptoms 
in an eDiary daily. Subjects who experience an asthma exacerbation during the Run-in period 
will receive appropriate treatment and remain in the Run-in period until their asthma status has 
returned to baseline status for at least 1 week. Subjects who are not able/eligible to be 
randomized due to ongoing asthma exacerbation at the end of the Run-in period will be 
discontinued from study participation and be labeled as Run-in failures. Subjects will remain on 
their SOC therapy during the Run-in period. 
At Visit 2 (Week 0, Day 1), subjects who meet the randomization eligibility criteria will be 
randomized in a 1:1:1:1 ratio to receive one of the following double-blind treatments for 
24 weeks: 
• GB001 60 mg daily 
• GB001 40 mg daily 
• GB001 20 mg daily 
• Matching placebo daily 
Randomization will be stratified by baseline ICS dose (medium or high, as defined in 
Appendix 10; Section 10.10) and country. 
The first dose of double-blind investigational product (IP) will be administered in the clinic on 
Day 1. All subsequent doses will be taken orally at home at bedtime on an empty stomach. 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
25 
CONFIDENTIAL 
Following initiation of IP, subjects will visit the clinic for assessments at Weeks 2, 3, and 4, 
followed by visits approximately every 4 weeks for an additional 5 visits. Subjects should remain 
on their stable current SOC therapy (ie, medium or high dose ICS plus additional controller 
therapy) through the duration of their time on study (refer to Schedule of Activities, Section 1.3). 
Subjects will be provided with an eDiary which is programmed to alert the subject of potential 
asthma worsening: 
1. On 2 consecutive days, AM PEF ≤ 75% of mean AM PEF measured over the last 7 days 
of the Run-in period 
2. Increase in rescue medication use of ≥ 6 puffs/day (last 24 hours) on 2 consecutive days 
compared to mean use over the last 7 days of the Run-in period 
3. Nighttime awakening due to asthma symptoms requiring rescue medication for at least 2 
of 3 successive nights 
4. An asthma symptom score of 4 for at least 2 of 3 successive days.  
Upon receiving an alert, the subject should contact the site staff as soon as practical to assess the 
subject’s asthma status. The subject may be asked to return to the clinic when necessary to have 
their asthma status evaluated. 
Subjects who permanently discontinue IP will be requested to attend the Early Discontinuation 
of IP visit 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 Double-Blind, Placebo-Controlled visit 
sequence. At the visits subsequent to the Early Discontinuation of IP visit, study procedures will 
be completed except for dispensation/return of IP. Subjects who withdraw from the study, 
regardless of the reason, will be requested to return to the clinic to complete the Early 
Withdrawal (EW) from Study visit. All subjects who remain on IP through and including Visit 9 
(Week 24) or who complete the EW from Study visit will be asked to return for a Follow-up visit 
approximately 4 weeks after their last dose of IP to assess subject safety. 
Total duration for study participation per subject is up to 34 weeks (includes a Screening visit, 
followed by a 2-week to 6-week Run-in period to allow for collection of baseline eDiary data; a 
24-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 kit, evaluation of an 
adverse event (AE), or evaluation of asthma status. Any procedure that is conducted during a 
regularly scheduled on-treatment visit may be performed at an unscheduled visit. 
If a subject returns to the clinic between regularly scheduled visits to assess asthma status, the 
following should be conducted: 
• Review eDiary data to confirm if asthma worsening has occurred; and 
• Have the subject complete the ACQ-5 and spirometry if possible to determine if 
asthma worsening has occurred. 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
26 
CONFIDENTIAL 
4.2. 
Scientific Rationale for Study Design 
4.2.1. 
Study Population 
The target population is patients with moderate to severe asthma who are currently receiving 
GINA step 4 or 5 therapy and have evidence of eosinophilic inflammation. Reducing 
eosinophilic inflammation within the lungs, assessed by measuring sputum eosinophils, has been 
associated with a reduction in asthma exacerbations (Haldar, 2009; Pavord, 2012). It is 
anticipated that GB001, as a DP2 antagonist, will reduce sputum eosinophilia and consequently 
asthma exacerbations. As measurement of sputum eosinophils is cumbersome and requires sites 
experienced with this procedure to obtain appropriate samples, a surrogate measure of lung 
eosinophils, namely peripheral blood eosinophils, will be used in this study. The cut-off 
threshold of 250 cells/µL has been selected for this study as it is predicted to have a sensitivity of 
84% and a specificity of 91% to differentiate less than versus ≥ 3% sputum eosinophils 
(Wagener, 2015). 
Based upon regulatory guidance, patients with a history of asthma exacerbations should be 
recruited in studies where the primary endpoint is exacerbation reduction (EMA, 2015). Patients 
with a history of exacerbations are more likely to experience future exacerbations. Therefore, 
this study will be recruiting subjects with a history of at least 1 asthma exacerbation in the 
previous 12 months. 
In addition, DP2 antagonists might have an effect in a subset of subjects with inflammation 
beyond the lower airways such as upper airways and skin. Thus, exploratory assessments 
targeting these tissues will evaluate additional beneficial effects as a result of treatment with 
GB001. 
4.2.2. 
Placebo Rationale 
A placebo-controlled design is necessary because asthma is a disease that waxes and wanes over 
time, and the endpoint of asthma worsening has a subjective component. Therefore, it is 
important to be able to differentiate the efficacy of GB001 compared to the “placebo effect,” 
which may be as high as 30% to 50% depending on the endpoint chosen (Castro, 2007). 
Importantly, placebo-controlled studies require fewer subjects than active-controlled studies to 
demonstrate superiority of the experimental treatment. In addition, comparisons between the 
GB001 and placebo treatment groups will facilitate differentiation of the GB001 safety profile 
from that of the subject’s SOC therapy. Lastly, a placebo group, as opposed to an active control, 
will help to understand whether the occurrence of an AE in a GB001 group is different from that 
which would occur in the asthma population in the absence of GB001. 
An IDMC will periodically convene to review unblinded efficacy and safety data. The first 
IDMC meeting at which results are reviewed will occur after approximately 50 subjects have 
been randomized and have completed 12 weeks on study or within 12 months of the first subject 
randomized. 
A placebo-controlled design for this study is consistent with the European Medicines Agency 
regulatory guideline on the clinical investigation of IP for the treatment of asthma (EMA, 2015), 
wherein the following statement is made: “If the drug is not intended to be substituted for ICSs, 
add-on designs where the new drug is compared with placebo on top of standard background 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
27 
CONFIDENTIAL 
medication are required.” As such, GB001-2001 includes a placebo group in addition to the 
subject’s SOC therapy. 
4.2.3. 
Primary Endpoint Selection 
The use of proportion of subjects with worsening of asthma as an endpoint has been employed 
successfully in previous asthma studies (Wenzel, 2013; Castro, 2014), including a Phase 2 study 
with GB001 (PTR-36-201). This composite endpoint has the potential to reduce the sample size 
and duration of a study relative to an endpoint of severe exacerbations, while providing a 
clinically meaningful output. At the same time, this allows fewer subjects to be exposed to an 
investigational product in development when the efficacy and safety have not been fully 
established. The parameters included in the asthma worsening composite endpoint include 
changes in lung function (FEV1 and PEF), rescue medication use, asthma control and symptoms. 
These markers of asthma control are closely related to signs and symptoms associated to 
exacerbations. 
4.3. 
Justification for Dose 
This study will assess the dose-response relationship of 3 doses of GB001 (60 mg, 40 mg, and 
20 mg) in adult subjects with moderate to severe asthma. 
The GB001 40 mg dose was selected based on the anticipated pharmacokinetics (PK) and 
exposure levels extrapolated from the results of two Phase 2 studies with GB001 (Study PTR-36-
201 and ADC3680-07) and based on prior efficacy and safety results from these studies. In 
Study PTR-36-201, GB001 20 mg and 5 mg doses were evaluated in an asthma treatment 
withdrawal design. Both doses of GB001 were effective in decreasing the proportion of subjects 
with asthma worsening/exacerbations as compared to placebo, with the 20 mg dose producing 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 (ACQ-5) 
and time to asthma worsening relative to placebo. No improvements in lung function were 
observed, while less worsening of lung function was seen in the GB001 groups compared to 
placebo. A comparable safety profile was observed across all treatment arms (including placebo) 
in this study. Based on this data, the 40 mg dose has been selected for the current study. 
To characterize the dose-response curve, 1 dose level below and 1 dose level above the 40 mg 
dose are included in the current study. The 20 mg dose has been included as a potentially 
suboptimal dose based on data generated from a Phase 2 study of GB001 versus placebo 
(Study ADC3680-07). This study found that GB001 20 mg daily produced some efficacy, as 
measured by improvements in ACQ scores, but this dose level did not result in improvements in 
lung function. The 60 mg dose is included to assess whether greater efficacy may be achieved 
beyond that of the 40 mg dose, since no improvements have been seen in lung function with 
lower doses to date. 
4.4. 
End of Study Definition 
Subjects will be regarded to have completed the study if he/she completes the Week 24 visit. The 
end of the study is defined as the date of the last visit of the last subject in the study. 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
28 
CONFIDENTIAL 
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 
To confirm eligibility, a review of each subject’s medical records should be performed prior to 
the subject entering the Run-in period. Prior to randomization, additional randomization criteria 
(including blood eosinophils ≥ 250 cells/µL; Section 5.3) must be met. 
Subjects are eligible to enter the Run-in period only if all 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 and < 75 years of age at the time of Screening visit. 
3. Gender: 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. Weight: at least 40 kg. 
5. Diagnosis of asthma:  A diagnosis of asthma by a physician according to GINA 
guidelines of at least 12 months prior to Screening. 
6. ICS plus additional controller: Subjects with a documented requirement for regular 
treatment with medium or high dose ICS and at least one other controller medication for 
at least 12 months prior to Visit 1. Subjects must maintain a stable ICS dose regimen 
during the 4 weeks prior to Visit 1. 
a. Medium dose ICS is defined as an ICS dose equivalent to fluticasone propionate 
> 250 to 500 mcg/day and high dose is defined as an  ICS dose equivalent to 
fluticasone propionate > 500 mcg/day (for equivalent ICS doses see Appendix 10, 
Section 10.10) 
b. An additional controller medication such as LABA, long-acting muscarinic antagonist 
(LAMA), or leukotriene receptor antagonist (LTRA).  
7. FEV1: a pre-bronchodilator FEV1 of ≤ 85% of predicted normal. 
8. Reversibility/Airway Hyperresponsiveness:  
• At least 12% in FEV1 following 4 puffs of albuterol 400 μg ex-US (360 μg US) or 1 
equivalent nebulized dose/salbutamol 100 mcg at Screening. Reversibility is to be 
assessed in all subjects at Screening. 
•  If a subject does not reverse at least 12% at Screening, the site may submit historical 
documentation of one of the following for review and approval by the Medical 
Monitor: 
− reversibility in the 24 months prior to Screening visit, OR 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
29 
CONFIDENTIAL 
− airway hyperresponsiveness demonstrated by a positive methacholine, histamine, 
or mannitol challenge. 
9. Evidence of uncontrolled asthma: demonstration of uncontrolled asthma by one of the 
following: 
a. Previously confirmed history of 2 or more asthma exacerbations requiring treatment 
with systemic corticosteroids in the 12 months prior to Screening visit. 
OR 
b. Previously confirmed history of 1 asthma exacerbation requiring treatment with 
systemic corticosteroids in the 12 months prior to Screening visit and ACQ-5 of ≥ 1.5 
at Screening visit. 
10. Are willing and able to comply with the requirements for participation in the study. 
5.2. 
Exclusion Criteria 
Subjects are excluded from the study if any of the following criteria apply: 
1. Smoking history: Current smokers (any substance), or former smokers with a smoking 
history of ≥ 10 pack-years [(number of cigarettes per day/20) x 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. 
2. Concurrent Respiratory Disease: Presence of a known pre-existing clinically important 
lung condition other than asthma. This includes current infection, active tuberculosis 
infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis or 
diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease 
other than asthma) or a history of lung cancer. 
3. 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.) 
4. 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. 
5. Other Concurrent Medical Conditions: Known, pre-existing clinically significant 
endocrine, autoimmune, metabolic, neurological, renal (calculated creatinine clearance 
< 60 mL/min), gastrointestinal, hepatic, cardiovascular, hematological, or any other 
system abnormalities that are uncontrolled with standard treatment. 
6. Eosinophilic Disease: Subjects with any other condition that could lead to elevated 
eosinophils such as hypereosinophilic syndrome, including eosinophilic granulomatosis 
with polyangiitis. 
7. ECG Assessment: QTcF ≥ 450 msec for males or QTcF ≥ 470 msec for females at the 
Screening visit. If QTcF is above the prespecified limit and there are no other clinically 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
30 
CONFIDENTIAL 
significant abnormalities, the assessment can be repeated in triplicate and the three results 
will be averaged for eligibility. 
8. Alcohol/Substance Abuse: A history or suspected history of alcohol misuse or substance 
abuse, including marijuana, within 12 months prior to Screening visit. 
9. Immunodeficiency: A known immunodeficiency, including that due to human 
immunodeficiency virus (HIV), other than that explained by systemic corticosteroid use. 
10. Investigational medications: Subjects who have received treatment with an 
investigational medication within the past 30 days or within 5 half-lives of the 
medication, whichever is longer, prior to Screening visit. (This also includes 
investigational formulations of marketed products.) 
11. DP2 (CRTh2) antagonist studies: Participated in another DP2 (CRTh2) antagonist study 
in the 12 months prior to Screening visit or known prior intolerance or inadequate 
response in a prior DP2 antagonist study. 
12. Receiving prohibited medications or treatments: (refer to Appendix 8, Section 10.8, 
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 such as reslizumab, 
mepolizumab, omalizumab or benralizumab 
c. Medications, food or drink that are moderate or strong CYP3A4 inhibitors or inducers 
d. Medications that have the potential for interaction with GB001 
e. Bronchial thermoplasty and radiotherapy are excluded in the 12 months prior to 
Screening 
13. Prior participation in a study with GB001: Subjects who previously participated in a 
study with GB001 (also named PTR-36 or ADC3680) are not eligible for this study. 
14. Hypersensitivity: A known sensitivity to GB001 or any of its excipients. Patients with 
rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or 
glucose-galactose malabsorption are not eligible for this study. Subjects with 
mild-moderate lactose intolerance are not excluded. 
15. 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. 
16. Adherence: Subjects who have a known lack of adherence to controller medications. 
17. Body Mass Index (BMI): BMI is ≥ 40 kg/m2. 
18. Have any other condition or reason that, in the opinion of the Investigator, would prohibit 
the subject from participating in the study, including participation in another clinical trial 
while participating in this study. 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
31 
CONFIDENTIAL 
5.3. 
Randomization Criteria 
At the end of the Run-in period, study subjects must fulfill the following criteria to be 
randomized to study treatment: 
1. Eosinophilic asthma: A peripheral blood eosinophil count of ≥ 250 cells/µL measured at 
the Screening visit. NOTE: In a subject with prior evidence of an eosinophilic 
phenotype, as assessed by the Investigator, an eosinophil count < 250 may be repeated 
during Run-in upon approval by the Medical Monitor. 
2. FEV1: The morning percent predicted FEV1 must be ≤ 85% of the predicted normal at 
both the Screening visit and Randomization visit. 
3. FEV1 overread: The Screening visit overread by vendor must confirm eligibility was 
met. 
4. eDiary compliance: Compliance with completion of the eDiary as defined as: 
• Completion of rescue medication use question on 4 or more of the last 7 days 
immediately prior to Visit 2 (includes the morning of Visit 2). 
AND 
• Completion of AM PEF on 4 or more of the last 7 mornings immediately prior to 
Visit 2 (includes the morning of Visit 2). 
• Note: If the eDiary 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 eDiary 
parameters above. 
5. ACQ-5: The ACQ-5 assessment has been completed in the eDiary in clinic during the 
Randomization visit. 
6. Laboratory abnormality: No evidence of clinically significant abnormality in the 
hematological, biochemical, or urinalysis at Screening visit, as judged by the 
Investigator.  
7. Hepatitis status: No evidence of chronic hepatitis B or C, as evidenced by a negative 
hepatitis B surface antigen (HbsAg) or hepatitis C test at the Screening visit. Note: if 
hepatitis C antibody test is positive or indeterminate at screening, the confirmatory test 
result must be negative for Hepatitis C. 
8. Chemistry and hematology obtained at Screening visit: 
• ALT must be < 2x the upper limit of normal (ULN) 
• AST must be < 2x ULN 
• Alkaline phosphatase must be < 2x ULN 
• Bilirubin must be < 1x ULN 
• Absolute eosinophil count must be < 1,500 cells/μL 
• White blood cell count must be < 15,000 cells/μL 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
32 
CONFIDENTIAL 
9. ECG overread: The screening ECG overread confirms the QTcF interval is < 450 msec 
for males or QTcF < 470 msec for females.  
10.  Asthma exacerbation: 
Subjects who experience an asthma 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 asthma status. If a 6-week Run-in period has elapsed before the 
subject is back to baseline status, then the subject will be considered a Run-in failure. An 
asthma exacerbation is defined as worsening of asthma requiring the use of systemic 
corticosteroids for at least 3 days, hospitalization, or an Emergency Department visit. 
11. Compliance with the subject’s SOC asthma therapy as evidenced by: 
• No changes in the dose or regimen of the Run-in asthma therapy (except for treatment 
of an asthma exacerbation). 
AND 
• Subjects must have demonstrated ≥ 75% compliance with their SOC therapy during 
Run-in. 
12.  Pregnancy test:  For WOCBP, both the serum pregnancy test at the Screening visit and 
the urine pregnancy test at Visit 2 must be negative. 
5.4. 
Screen or Run-In Failures 
Subjects will be assigned a subject number at the time of signing the ICF. 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 Medical 
Monitor. A new subject number will be assigned if approved to rescreen. 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
33 
CONFIDENTIAL 
6. 
INVESTIGATIONAL PRODUCT 
Table 1: 
Investigational Product Formulation by Treatment Group 
Treatment 
Groups 
GB001 60 mg 
GB001 40 mg 
GB001 20 mg 
Placebo 
Dose 
Formulation 
Film-Coated 
Tablet 
Film-Coated 
Tablet 
Film-Coated 
Tablet 
Film-Coated 
Tablet 
Unit Dose 
Strength(s) 
3 x 20 mg tablet 
2 x 20 mg tablet 
and 
1 x placebo tablet 
1 x 20 mg tablet 
and 
2 x placebo tablet 
3 x placebo tablet 
Dosage Level(s) 
60 mg at bedtime 
40 mg at bedtime 
20 mg at bedtime 
Placebo at 
bedtime 
Route of 
Administration 
and Instructions 
Oral on an empty 
stomach 
Oral on an empty 
stomach 
Oral on an empty 
stomach 
Oral on an empty 
stomach 
Packaging and 
Labeling 
GB001 and Placebo film-coated tablets will be packaged in blinded dosing kits. 
Each kit will consist of a labeled wallet containing 2 blister cards with 24 tablets 
each (ie, 48 tablets per kit), which will provide sufficient doses for 16 days of 
treatment (14 days + 2 days for the visit window). Individual kits have been 
packaged to deliver 3 tablets per day of the appropriate combination of 20 mg and 
placebo tablets as described in “unit dose strength” above. Subjects will receive 1 
or 2 kits at each visit based on the timing of the subsequent visit. The kits 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 15-30oC are permitted. Any other excursion from 
the required storage condition will be reported to the Sponsor as soon as practical. 
 
6.1. 
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 study medications. All study medication 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). 






GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
36 
CONFIDENTIAL 
6.4.2. 
Restricted Medications 
Restricted medications are defined as medications which should be avoided, if possible; 
however, they are not prohibited during this study if stable for at least one month before 
screening. If such medications are required, consider switching to another medication in the class 
that is not restricted. Please refer to Appendix 9 (Section 10.9) for restricted medications. 
6.4.3. 
Rescue Medicine 
Subjects will be provided with albuterol/salbutamol for use as needed. The rescue medication 
will be locally sourced or reimbursed. Subjects are permitted to use the study-provided 
albuterol/salbutamol or any other short-acting bronchodilator. All rescue medication use is to be 
captured in the eDiary. For the purposes of data capture within the eDiary, one nebule should be 
captured as 4 puffs of rescue medication. 
 If the subject requires medication in addition to a short-acting bronchodilator for treating asthma 
symptoms, the subject should contact the study site for evaluation of their asthma status. 
6.5. 
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. 
6.6. 
Intervention After the End of the Study 
Subjects who complete the study and meet the eligibility criteria for the Extension Study (ES) 
may be offered the opportunity to receive active treatment in the ES when the study is available. 
7. 
DISCONTINUATION OF INVESTIGATIONAL PRODUCT AND 
SUBJECT WITHDRAWAL FROM THE STUDY 
7.1. 
Discontinuation of Investigational Product 
Permanent discontinuation of IP does not mean withdrawal from the study, and remaining study 
procedures should be completed as indicated by the study protocol. If study IP is permanently 
discontinued, the subject will be encouraged to remain in the study and continue to complete all 
study visits as per the SoA (Section 1.3). If a subject permanently discontinues IP prior to Visit 8 
(Week 20) and remains in the study through Visit 9 (Week 24), the subject will not need to 
return for the Follow-up visit. 
Sections 7.1.1 and 7.1.2 define mandatory criteria for permanent discontinuation of IP. 
For subjects who simultaneously discontinue IP and withdraw from the study, 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. The subjects should be 
encouraged to return for the Follow-up visit. 
7.1.1. 
QTc Stopping Criteria 
Subjects must permanently discontinue IP if QTcF > 500 msec.  


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
37 
CONFIDENTIAL 
7.1.2. 
Pregnancy 
A subject must permanently discontinue IP if the subject becomes pregnant. See Appendix 4 
Section 10.4 and Section 8.3.4 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.  
7.2. 
Subject Withdrawal from the Study 
A subject may withdraw or be withdrawn from the study for the following reasons: 
• Physician decision 
• AE  
• Noncompliance with study drug 
• Withdrawal by subject 
• Study terminated by 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. 
At the time of withdrawal from the study, if possible, an Early Withdrawal from Study visit 
should be conducted, as shown in the SoA (Section 1.3). See SoA for data to be collected at the 
time of study withdrawal and follow-up and for any further evaluations that need to be 
completed. 
For subjects who simultaneously discontinue IP and withdraw from the study, 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. The subjects should be 
encouraged to return for the Follow-up visit. 
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. 
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 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
38 
CONFIDENTIAL 
schedule and ascertain whether or not 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. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed. 
• Immediate 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 
(Section 1.3), 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.) 
Screening Visit (Visit 1): all procedures should be completed on the same day with the exception 
of the Informed Consent, which should be obtained prior to the Visit: 
• Informed consent 
• Demography 
• Concomitant medications and medical history 
• Vital signs 
• Physical exam 
• 12-lead electrocardiogram 
• Fractional exhaled nitric oxide (FeNO) 
• Spirometry pre and post bronchodilator 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
39 
CONFIDENTIAL 
• Have subject complete the ACQ-5 within the eDiary and download the completed 
questionnaire PRIOR to the subject leaving the clinic 
• Review of inclusion/exclusion criteria 
• Collect urine and blood samples 
• Record adverse events, if any 
• Ensure subject has a rescue inhaler 
• Dispense eDiary and train subject in its use 
• Complete eCRF 
Note: During the Run-in period, the site should review the vendor overread of the ECG and 
spirometry report and the laboratory results, including the blood eosinophil count. If the 
overread or laboratory results indicates that the subject is not eligible for randomization, the 
subject should be contacted to return all study provided materials to the site. However, in a 
subject with prior evidence of an eosinophilic phenotype, as assessed by the Investigator, an 
eosinophil count < 250 cells/µL may be repeated during Run-in upon approval by the 
Medical Monitor. 
Randomization Visit (Visit 2): All procedures should be completed on the same day. Sputum 
induction and Exhaled Breath Condensate may be conducted on the next calendar day when 
necessary, followed by the first dose in clinic and post PK sample. Randomization should be 
performed on the day of first dose in clinic. (List is not all inclusive. Review the SoA and the 
Study Reference Manual for additional guidance.) 
• Download the eDiary and check if today’s diary has been completed 
• Review eDiary to assess eligibility 
• Review randomization eligibility criteria 
• Have subject complete questionnaires 
• Exacerbation review 
• Concomitant medications and adverse event review 
• Vital signs 
• FeNO 
• Exhaled breath condensate (EBC) analysis (only at select sites that are properly 
trained and qualified) 
• Spirometry (pre-bronchodilator only) 
• Collect lab samples and predose PK sample 
• Sputum induction (only at select sites that are properly trained and qualified) 
• Register visit in the eCRF 
• Ensure subject has a rescue inhaler  


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
40 
CONFIDENTIAL 
• Dispense IP 
• Collect post-dose PK sample at 2.5 hours post-dose 
• Complete eCRF 
Other visits when these procedures are part of the visit: 
• Have the subject complete questionnaires 
• Vital signs 
• ECG 
• FeNO 
• EBC analysis (only at select sites that are properly trained and qualified) 
• Spirometry (pre-bronchodilator only) 
• Collect lab samples and predose pharmacokinetic sample 
• Sputum induction (only at select sites that are properly trained and qualified) 
8.1. 
Efficacy Assessments 
8.1.1. 
Asthma Worsening (Primary Endpoint) 
At each visit, the Investigator or designee will:  
• Download and review the eDiary report for alerts for AM PEF, rescue medication 
use, and asthma symptoms 
• Have the subject complete the ACQ-5 in clinic and review to assess for an increase in 
ACQ-5 score ≥ 0.5 compared to baseline 
• Measure spirometry at each visit except Visit 3 (Week 2), and the FEV1 will be 
assessed to look for a decrease of > 20% from baseline 
• Interview the subject to inquire about recent use of systemic corticosteroids (for 3 or 
more days) for asthma, or an Emergency Department visit or hospitalization for 
asthma.  If the criteria for a severe asthma exacerbation are met, the site staff will 
complete the exacerbation page within the eCRF. Courses of systemic corticosteroids 
separated by 7 or more days will be counted as separate severe exacerbations. 
8.1.2. 
eDiary Asthma Parameters and Alerts 
The subject will be asked to record the following parameters daily in the eDiary from the 
Screening visit through the Follow-up visit: 
• Morning peak flow (best of three efforts) before rescue medication usage (L/min) 
• Puffs of rescue medication used over the previous 24 hours 
• Asthma symptom score over the previous 24-hours using a 6-point scale (Appendix 7 
in Section 10.7) 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
41 
CONFIDENTIAL 
• Frequency of awakening due to asthma symptoms requiring rescue medication use 
The eDiary is programmed to alert the subject about potential asthma worsening. Please refer to 
Section 4.1.1 for alert criteria. 
Subjects will be issued a paper worksheet to record new medical problems and medications taken 
during the study. This will be used to assist subject recall in discussions with the Investigator or 
designee. 
The eDiary information is to be downloaded and reviewed at each visit for potential asthma 
worsening, asthma exacerbations, and to assess compliance with eDiary completion. The subject 
diary data should be archived by site at the end of the study. 
8.1.3. 
Pulmonary Function Testing including Reversibility 
Pre-albuterol/salbutamol morning FEV1 will be measured using electronic spirometry between 
5:00 AM and 12:00 noon and within ± 1 hour from the time of the Screening visit FEV1 
measurement time. Spirometry will be measured at all visits except Visit 3. Subjects should 
withhold short-acting beta-agonist (SABA) use for ≥ 6 hours prior to measurement of 
spirometry, long-acting beta-agonists (LABAs) for ≥ 12 hours prior to spirometry and ultra-
LABA (eg, vilantrol) > 24 hours prior to spirometry. Additionally, forced vital capacity (FVC), 
FEV1/FVC, PEF and forced expiratory flow at 25% to 75% (FEF25-75) will be recorded. For 
predicted values, the Global Lung Initiative will be used. Additional details for pulmonary 
function testing will be available in the Study Reference Manual. 
Reversibility 
At the Screening visit, reversibility in FEV1 will be measured before and within 30 minutes (± 15 
minutes) of albuterol/salbutamol 360/400 µg via metered dose inhaler (MDI) or one nebulized 
treatment of albuterol/salbutamol. The subject must improve by at least 12% in FEV1 to be 
eligible to enter the Run-in period. If the target is not met, historical documentation of 
reversibility in the 24 months prior to Screening visit or historical documentation of airway 
hypersensitivity may be allowed upon review and approval by the Medical Monitor. 
Reversibility in FEV1 will also be assessed at Visit 9 (Week 24) or the Early Discontinuation of 
IP visit. 
8.1.4. 
Asthma Control Questionnaire-5 
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 questions are 
designed to be self-completed by the subject. The five questions enquire about the frequency 
and/or severity of symptoms in the prior week (nocturnal awakening, activity limitation, 
shortness of breath, wheeze). The response options for each of these questions consists of a zero 
(no impairment/limitation) to 6 (total impairment/limitation) scale. The minimal clinically 
important difference (MCID) is 0.5 points. 
The subject should be provided with a quiet area in which to complete the questionnaire within 
the eDiary. The Investigator or designee should ask the subject to complete the questions as 
accurately as possible. If the subject requests assistance or clarification for any of the questions, 
he/she will be asked to reread the instructions and to select the answer that best reflects how 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
42 
CONFIDENTIAL 
he/she felt over the prior week. The subject should be assured that there are no right or wrong 
answers. The Investigator should not provide the subject with any answer or attempt to interpret 
any portion of a question. 
It is recommended that the ACQ be administered at the same time during each visit. To avoid 
biasing responses, the subject should not be told the results of diagnostic tests prior to 
completing the ACQ and the ACQ should be performed prior to any procedures that might 
influence the subject’s responses. Adequate time should be allowed to complete all items on the 
ACQ. 
8.1.5. 
Asthma Quality of Life Questionnaire- Standardized (AQLQ-S) 
The AQLQ-S is a disease-specific, self-administered quality of life questionnaire developed to 
evaluate the impact of asthma on the subject’s quality of life (Juniper, 1993). The questionnaire 
contains 32 items in 4 domains with a 2-week recall period: activity limitation (11 items), 
symptoms (12 items), emotional function (five items) and environmental stimuli (4 items). 
Additionally, each of the 32 responses are averaged to produce an overall quality of life score. 
Responses are scored on a seven-point scale with a value of 1 indicating total impairment and 
7 indicating no impairment. The minimal clinically important difference (MCID) is 0.5 points 
(Juniper, 1994). 
The AQLQ-S will be completed at the visits specified in the SoA (Section 1.3). The AQLQ-S 
should be completed at approximately the same time during each visit. Subjects should not be 
told the results of any assessments or study procedures before the questionnaire is completed to 
avoid biasing the results. 
Subjects should complete all questions within the AQLQ-S as accurately as possible. If the 
subject requests assistance or clarification for completing the question responses, he/she will be 
asked to reread the question and instructions and encouraged to give the answer that best reflects 
their current feeling. The subject should be reassured that there are no right or wrong answers. 
8.1.6. 
Sino-Nasal Outcome Test 
Sino-Nasal Outcome Test (SNOT-22) is a quality of life instrument to assess the impact of 
chronic rhinosinusitis and utilizes a 2-week recall period (Hopkins, 2009). The questionnaire will 
only be completed by subjects with a prior history of sinusitis, nasal polyps, or allergic rhinitis to 
assess whether GB001 has an impact on this common comorbidity in patients with asthma. 
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 with the total global score ranging from 0 to 
110. The global MCID is 8.9. 
8.1.7. 
Hair Assessment 
The DP2 pathway has been implicated as being involved in androgenic alopecia and antagonizing 
this pathway has shown benefit as a potential treatment for alopecia (Garza, 2012; Nieves, 2014). 
Therefore, subjects will be assessed for the presence or absence of scalp hair loss at baseline and 
at conclusion of IP treatment. 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
43 
CONFIDENTIAL 
A visual scale (Norwood classification for male subjects and Savin classification for female 
subjects) to characterize the degree of scalp hair loss at baseline and at the end of the study will 
be used (Gupta, 2016). This information will be complemented with a modified questionnaire to 
assess patient perceptions of scalp hair growth at the end of the study (Appendix 10; 
Section 10.11). This questionnaire includes 2 simple questions to describe possible scalp hair 
growth changes during the study period. 
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 including but not limited to an evaluation of the 
lungs and cardiovascular systems as well as visualization of nose for polyps will be 
conducted as designated in the SoA (see Section 1.3). The presence or absence of hair 
loss will also be assessed. The results of the physical examination will be recorded in 
the subject’s notes and any significant unfavorable change from the screening exam 
will be recorded as an AE both in the subject’s notes and in the eCRF. 
• Height and weight will also be measured and recorded. 
• The physical exam should be conducted prior to spirometry. 
8.2.2. 
Vital Signs 
• Pulse rate, respiratory rate, temperature and blood pressure will be assessed. 
• 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. 
• 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). 
• Vital signs will be measured after 5 minutes rest and prior to spirometry and ECG 
measurements. 
8.2.3. 
Electrocardiograms 
• Single 12-lead ECG will be obtained as outlined in the SoA (see Section 1.3) using an 
ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, 
and QTc intervals. Refer to Section 7.1.1 for QTc stopping criteria. 
• ECG will be centrally read by the Sponsor’s designee via the electronic portal. 
• Subjects with evidence of a significant abnormality in the 12-lead ECG obtained at 
screening, including prolongation of the QTc interval will not be eligible to 
randomize into the study. 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
44 
CONFIDENTIAL 
8.2.4. 
Clinical Safety Laboratory Assessments 
• See Appendix 2 (Section 10.2) for the list of clinical laboratory tests to be performed 
and to the SoA for the timing and frequency. 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 clinically significantly abnormal during 
participation in the study should be repeated until the values return to normal or 
baseline or are no longer considered clinically significant by the Investigator or 
Medical Monitor. For additional liver safety monitoring, refer to Appendix 6 
(Section 10.6). 
− 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 eCRF. 
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 
All AEs/SAEs will be collected from the time of signing the ICF until 4 weeks after the last IP 
dose. For subjects who permanently discontinue IP early but remain in the study, AEs will 
continue to be collected until the completion of Visit 9 (Week 24) or 4 weeks after the last dose 
of IP, whichever occurs later. 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
45 
CONFIDENTIAL 
Medical occurrences that begin before the start of IP but after obtaining informed consent will be 
recorded on the Medical History/Current Medical Conditions section of the eCRF 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 
AE occurrences. 
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 liver events 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). 
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 an 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 Investigator’s Brochure. The 
Investigator will then notify the IRB/IEC, if appropriate according to local 
requirements. 




GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
47 
CONFIDENTIAL 
In the event of an overdose, the Investigator should: 
1. Contact the Medical Monitor as soon as possible. 
2. Closely monitor the subject for any AE/SAE and laboratory abnormalities. 
3. Document the quantity of the excess dose as well as the duration of the overdose. 
Decisions regarding dose interruptions or modifications will be made by the Investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the subject. 
8.5. 
Pharmacokinetics 
• Blood samples of approximately 6 mL will be collected for measurement of plasma 
concentrations of GB001 and possibly metabolites of GB001 as specified in the SoA 
(see Section 1.3): 
− At the Randomization visit, the PK samples will be collected predose and 
approximately 2.5 hours postdose. 
− For all other visits where PK samples are collected, the sample will be collected at 
any time during the visit. The subject will be instructed to take their dose in the 
evening at their regular dosing time and to record the time of dosing on a paper 
worksheet. 
• Each plasma sample will be divided into 3 aliquots. 
Drug concentration information that may unblind the study will not be reported to investigative 
sites or blinded personnel until the study has been unblinded. 
8.6. 
Pharmacodynamics and Biomarkers 
Blood, nasal, and urine samples will be collected at the designated times specified in the SoA 
(see Section 1.3) and may be used as the basis for multiple exploratory assays to evaluate the 
effect of GB001 on a range of potential target engagement and PD biomarkers. 
Airway samples (eg, nasosorption, sputum, EBC) may be collected at the designated times 
specified in the SoA at properly trained and qualified sites. These samples may be used for 
multiple exploratory assays to evaluate the effect of GB001 on potential target engagement and 
PD biomarkers. 
Samples may be stored at a facility selected by the Sponsor, to enable further analysis of 
biomarker responses to GB001, for a maximum of 8 years (or according to local regulations) 
following the last subject’s last visit for the study. 
Residual blood, airway and urine samples may be stored for potential future identification of 
factors or profiles that correlate with measures of response to GB001. 
For more details on the procedures, please refer to the study specific Laboratory Manual. 
8.6.1. 
Induced Sputum 
Induced sputum may be collected at selected trained and qualified sites in a subset of subjects 
with baseline ≥ 2%) with a goal of achieving approximately 20 subjects per treatment group and 






GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
50 
CONFIDENTIAL 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
This study is designed to demonstrate the superiority of GB001 versus placebo, when added to 
SOC therapy, on the primary endpoint of the proportion of subjects who experience worsening of 
asthma by Week 24. 
9.2. 
Sample Size Determination 
A total sample size of approximately 480 subjects (approximately 120 per treatment group, 
randomized in a 1:1:1:1 ratio) is estimated to provide 80% power to detect a reduction in odds of 
66% between each GB001 group and placebo at an 0.050 two-sided level of significance for the 
primary endpoint of the proportion of subjects who experience worsening of asthma by Week 24. 
This assumes the proportion of subjects who experience worsening of asthma by Week 24 is 
25% in the placebo group and 10.2% in each GB001 group and a dropout rate of 8%. 
Randomization will be stratified by baseline ICS dose (medium or high, as defined in 
Appendix 9; Section 10.9) and country. 
9.3. 
Populations for Analyses 
The following major analysis populations are defined: 
• All enrolled population:  All subjects who consent to study participation. This 
population will be utilized for summaries of subject disposition. 
• Run-in period population:  All enrolled subjects who enter the Run-in period. This 
population will be utilized for summaries of subject disposition. 
• Intent-to-treat (ITT) population:  All subjects who are randomized and receive at least 
1 dose of IP, with subjects grouped according to randomized treatment. 
• Per-protocol (PP) population:  All subjects in the ITT population who do not violate 
terms of the protocol that may affect primary or secondary efficacy outcomes. The 
criteria for the PP population will be determined prior to unblinding and will be 
described in detail in the Statistical Analysis Plan (SAP). 
• Safety population:  All subjects who receive at least 1 dose of IP, with subjects 
grouped according to their actual treatment. 
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. This section is a summary of the planned 
statistical analyses of the primary and secondary endpoints. 






GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
53 
CONFIDENTIAL 
Given that the interim analysis is administrative, will not result in any statistical inferences being 
made, and is not intended to result in any modification to the study (ie, the study will be 
continued and completed regardless of the interim analysis results), no Type I error will be 
allocated to the interim analysis. 
9.5.1. 
Independent Data Monitoring Committee 
An IDMC will regularly monitor overall safety and emerging efficacy results, as well as general 
aspects of study conduct, to ensure that the benefits and risks of study participation remain 
acceptable. Following an initial organizational IDMC meeting, the first IDMC meeting at which 
results are reviewed will occur after approximately 50 subjects have been randomized and have 
completed 12 weeks on study or within 12 months of the first subject randomized. 
Based on these regular reviews of emerging results, the IDMC will recommend to the Sponsor 
continuation, modification, or termination of the study. 
Meeting structure, schedule, and procedures, including communication between the Sponsor and 
the IDMC, the content and format of IDMC reports, and other relevant details, will be 
determined in consultation with IDMC members and detailed in a separate IDMC charter.  


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
54 
CONFIDENTIAL 
10. 
APPENDICES 
10.1. 
Appendix 1:  Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• This study will be conducted in accordance with the protocol and with the following: 
− Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
− Applicable ICH Good Clinical Practice (GCP) Guidelines 
− Applicable laws and regulations 
• The protocol, protocol amendments, ICF, Investigator Brochure, eDiary 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, 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. 
• Participants must be informed that their participation is voluntary. Participants or 
their legally authorized representative will be required to sign a statement of informed 
consent that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, 
Health Insurance Portability and Accountability Act (HIPAA) requirements, where 
applicable, and the IRB/IEC or study center. 
• The medical record must include a statement that written informed consent was 
obtained before the subject entered the study and the date the written consent was 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
55 
CONFIDENTIAL 
obtained. The authorized person obtaining the informed consent must also sign the 
ICF. 
• Participants must be re-consented to the most current version of the ICF(s) during 
their participation in the study. 
• A copy of the ICF(s) must be provided to the subject or the subject’s legally 
authorized representative. 
• Subjects who are rescreened are required to sign a new ICF. 
• The ICF will contain a separate section that addresses the use of remaining mandatory 
samples for optional exploratory research. The Investigator or authorized designee 
will explain to each subject the objectives of the exploratory research. Subjects will 
be told that they are free to refuse to participate and may withdraw their consent at 
any time and for any reason during the storage period. A separate signature will be 
required to document a subject's agreement to allow any remaining specimens to be 
used for exploratory research. Subjects who decline to participate in this optional 
research will not provide this separate signature. 
• 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 
• Participants 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 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 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
56 
CONFIDENTIAL 
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. 
• 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. 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
57 
CONFIDENTIAL 
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. 
• 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. 


















GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
66 
CONFIDENTIAL 
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 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. 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
67 
CONFIDENTIAL 
Contraception Guidance 
Female Subjects: 
• 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 by men or women should be consistent with local regulations regarding the 
use of contraceptive methods for those participating in clinical studies. 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
68 
CONFIDENTIAL 
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 
o 
oral 
o 
intravaginal 
o 
transdermal 
o 
injectable 
• 
Progestogen-only hormone contraception associated with inhibition of ovulationb 
o 
oral 
o 
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). 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
69 
CONFIDENTIAL 
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. The subject will be followed until birth 
or termination of pregnancy. 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 
IP 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. 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
70 
CONFIDENTIAL 
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 will be collected for DNA analysis from consenting subjects.
•
Samples may be used for research related to GB001 and/or asthma and related
diseases. They may also be used to develop tests/assays including diagnostic tests
related to GB001 and DP2 inhibitors and atopic disease. Genetic research may consist
of the analysis of prespecified candidate polymorphisms.
•
Samples may be analyzed for variation in candidate genes which dramatically affect
the pharmacokinetics of GB001, the safety, and/or efficacy profile. Often times, a
large variability in the plasma concentration–time profiles of any medicine can be
linked to loss of function mutations in the drug metabolizing enzymes and/or
transporters. For example, substantial efforts have been made in reducing the risk of
drug–drug interactions related to cytochrome P450 enzymes and variability caused by
polymorphic expression of cytochrome P450 enzymes (eg, CYP2D6). The effects of
single nucleotide polymorphisms on the PK of GB001 uncovered in the course of this
study may help guide future clinical studies and regulatory review of GB001.
Additional pharmacogenetic analyses may be conducted if it is hypothesized that
doing so may help resolve issues with the clinical data, eg, safety and/or efficacy
observations during the life of the study.
•
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 the CSR or in a separate study
summary.
•
The Sponsor will store the DNA 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.
The following genetic parameters may be evaluated in this study: 
•
Genetics (DNA):
SNPs in a) drug metabolizing and enzymes, b) DP2 pathway genes, c) asthma &
atopic pathway genes, e.g. vitamin D


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
71 
CONFIDENTIAL 
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 4. 
Table 4: 
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 5 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 5), then 
follow the instructions in “Actions and Follow-up 
Assessments” in Table 5 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, then IP should be discontinued permanently.The 
criteria requiring interruption of IP with additional liver monitoring is detailed in Table 5. 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
72 
CONFIDENTIAL 
Table 5: 
Liver Chemistry Criteria Requiring Investigational Product Interruption 
and Additional Monitoring 
 
 
Liver Chemistry – IP Interruption Criteria 
ALT/AST (single occurrence) 
ALT or AST ≥ 5x ULN 
ALT/AST 
ALT or AST ≥ 3x ULN persists for ≥ 4 weeks 
+ Bilirubin a,b 
ALT or AST ≥ 3x ULN and bilirubin > 2x ULN (> 35% direct bilirubin) 
+ INR b 
ALT or AST ≥ 3x ULN and international normalized ratio (INR) > 1.5, if 
INR measured 
+ Cannot Monitor 
ALT or AST ≥ 3x ULN and cannot be monitored weekly for 4 weeks 
+ Symptomatic c 
ALT or AST ≥ 3x 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 > 2x 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 ≥ 3x ULN and bilirubin > 2x ULN. Additionally, if serum 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
73 
CONFIDENTIAL 
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. 
b All events of ALT or AST  ≥ 3x ULN and bilirubin > 2x ULN (> 35% direct bilirubin) or ALT or AST ≥ 3x 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 (Table 3). 
 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
74 
CONFIDENTIAL 
10.7. 
Appendix 7:  Daily Asthma Symptom Score 
Each morning subjects will record in the eDiary an assessment of the severity of their asthma 
symptoms during the prior 24 hours using the following scale: 
• 0 = No symptoms 
• 1 = Symptoms for one short period 
• 2 = Symptoms for two or more short periods 
• 3 = Symptoms for most of the prior 24 hours which did not affect my ability to carry 
out my daily activities 
• 4 = Symptoms for most of the prior 24 hours which did affect my ability to carry out 
my daily activities 
• 5 = Symptoms so severe that I could not go to work/school or complete my normal 
daily activities 










GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
79 
CONFIDENTIAL 
10.11. 
Appendix 11:  Assessment of Hair Loss 
Questionnaire to Assess Patient Perceptions of Hair Growth 
1. Do you lose hair to the point that this is concerning?  
 Yes   
 No 
2. Do you have any bald spots?  
 Yes   
 No 
Note: If the subject answered “Yes” to any of the questions above, the site will complete the 
graphical visual assessment for male and female subjects (Norwood and Savin Scales), 
respectively. 
In those subjects who completed the above information, at the end of the study (Last IP Visit) 
the following questions should be completed, please check only one box: 
a. Since initiation of the study, I noticed my bald spot is getting smaller: 
Strongly agree 
 
Agree 
 
A little better 
 
The same 
 
A little worse 
 
Somewhat worse 
 
A lot worse 
 
 
b. Overall, since initiation of the study, I noticed that the growth of my hair is: 
Greatly increased 
 
Moderately increased 
 
Slightly increased 
 
The same 
 
Slightly decreased 
 
Moderately decreased 
 
Greatly decreased 
 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
80 
CONFIDENTIAL 
10.12. 
Appendix 12:  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 GB001-2001 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 asthma exacerbations in order to assess subject status.  
− The subject should continue to collect the daily AM PEF and eDiary responses on 
the eDiary. The eDiary will provide an alert to potential asthma worsening, as 
described in Section 4.1.1. In the event of an alert, the subject should contact the 
site staff as soon as practical to assess the subject’s asthma status. 
• Alternative methods of collecting study assessments may be considered where 
possible: 
− Questionnaires, including ACQ-5, AQLQ, and SNOT-22, 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.  


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
81 
CONFIDENTIAL 
10.13. 
Appendix 13:  Abbreviations 
Abbreviation Term 
Description 
ACQ 
Asthma Control Questionnaire 
AE 
adverse event  
ALT 
alanine aminotransferase 
AM 
morning  
ANCOVA 
analysis of covariance 
AQLQ-S 
Asthma Quality of Life Control Questionnaire (standardized) 
AST 
aspartate aminotransferase 
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 
CPK 
serum creatine phosphokinase  
CRTh2 
chemoattractant receptor-homologous molecule expressed on Th2 
CSR 
clinical study report  
CTFG 
Clinical Trial Facilitation Group  
DILI 
drug induced liver injury 
DP2 
prostaglandin D2 receptor 
DPI 
dry powder inhaler 
EBC 
exhaled breath condensate  
EC 
Ethics Committee 
ECG 
electrocardiogram  
eCRF 
electronic case report form 
EDC 
electronic data capture 
eDiary 
electronic diary 
ES 
extension study 
EW 
early withdrawal 
FEF25-75 
forced expiratory flow at 25% to 75% 
FeNO 
fractional exhaled nitric oxide 
FEV1 
forced expiratory volume in 1 second 
FSH 
follicle-stimulating hormone  


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
82 
CONFIDENTIAL 
Abbreviation Term 
Description 
FVC 
forced vital capacity 
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  
HIV 
human immunodeficiency virus 
HIPAA 
Health Insurance Portability and Accountability Act  
HPLC 
high performance liquid chromatography  
HRT 
hormonal replacement therapy  
IB 
Investigator’s brochure  
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation  
ICS 
inhaled corticosteroid 
IDMC 
Independent Data Monitoring Committee  
IEC 
Independent Ethics Committee 
IgG 
immunoglobulin G  
IgM 
immunoglobulin M  
INR 
international normalized ratio  
IP 
investigational product 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
ITT 
intent-to-treat 
IUD 
intrauterine device 
IUS 
hormone-releasing system  
LABA 
long-acting beta agonist 
LAM 
lactational amenorrhoea method  
LAMA 
long-acting muscarinic antagonist 
LDH 
lactate dehydrogenase  
LTRA 
leukotriene receptor antagonist 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
83 
CONFIDENTIAL 
Abbreviation Term 
Description 
MCID 
minimal clinically important difference  
MDI 
metered dose inhaler 
OR 
odds ratio 
PD 
pharmacodynamic  
PEF 
peak expiratory flow 
PGD2 
prostaglandin D2 
PK 
pharmacokinetic 
PP 
Per-protocol 
PRO 
patient reported outcomes 
QTcF 
Fridericia's correction formula for QT interval (interval between Q wave 
and T wave) 
RBC 
red blood cell  
RNA 
ribonucleic acid  
SABA 
short-acting beta-agonist 
SAE 
serious adverse event  
SAP 
Statistical Analysis Plan 
SNOT-22 
Sino-Nasal Outcome Test 
SNP 
single nucleotide polymorphism 
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 
ULN 
upper limit of normal  
VOC 
volatile organic compounds  
WBC 
white blood cell  
WOCBP 
women of childbearing potential 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
84 
CONFIDENTIAL 
10.14. 
Appendix 14: 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 3 (v4.0) 
18-Feb-2020 
Amendment 2 (v3.0) 
28-Aug-2019 
Amendment 1 (v2.0.0)  
28-Feb-2019  
Original Protocol (v1.0.0)  
02-Aug-2018  
Amendment 3 (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 purpose of this amendment is to enhance monitoring of liver parameters during the conduct 
of the trial. 
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 (liver) 
following Randomization 
(Visit 2) 
Week 1 visit was added to 
enhance laboratory 
monitoring during the first 
month following IP 
initiation 
Section 6.2.5 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 
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 
To enhance monitoring of 
liver parameters during 
the conduct of the trial 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
85 
CONFIDENTIAL 
Section # and Name  
Description of Change  
Brief Rationale  
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 
 
Global Change 
Minor revisions to text. 
Administrative 
clarifications were 
incorporated, and 
typographical errors were 
corrected. 
 
Amendment 2 (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 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 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, to provide 
clarification on eligibility criteria, and to evaluate annualized rate of severe asthma exacerbations 
as a secondary (rather than exploratory) endpoint. 
Section # and Name  
Description of Change  
Brief Rationale  
Section 1.1 Synopsis; 
Section 3 Objectives and Endpoints; 
Section 9.4.1.2 Secondary Efficacy Analysis 
Updated annualized rate 
of severe asthma 
exacerbations from 
tertiary/exploratory to 
secondary endpoint. 
Given the clinical 
importance of the 
assessment of severe 
asthma exacerbation, this 
has been elevated to a 
secondary endpoint. 
Section 1.3 Schedule of Activities  
• 
Notes on total bile 
acid, international 
normalized ratio 
• 
Addition of INR 
measurement at 
baseline. Collection of 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
86 
CONFIDENTIAL 
Section # and Name  
Description of Change  
Brief Rationale  
(INR), and 
fractionation of ALP 
if ALP > 1xULN 
were added.  
• 
Added assessment of 
clinical chemistry at 
Week 3. 
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. 
 
Section 2.2 Background 
 
Added recent results from 
post-hoc analyses. 
 
Updated with results 
which suggest that GB001 
favorably influences lung 
function in subjects with 
Type 2 markers of 
inflammation. 
Section 2.3.1 GB001 Risk/Benefit 
Assessment 
Revised data for GB001. 
Clarified risk/benefit 
profile. 
Section 5.1 Inclusion Criterion #8 
Criterion for airway 
hyperresponsiveness was 
updated. 
Extended period of 
reversibility and added 
historical demonstration 
of airway 
hyperresponsiveness. 
Section 5.2 Exclusion Criteria #4  
 
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 #8  
Added absolute eosinophil 
count and white blood cell 
(WBC) count criteria. 
Enhance safety 
characterization of the 
study population with 
eosinophilic asthma. 
Section 6.4.2 Restricted Medications; 
Section 10.9 Appendix 9: Restricted 
Medications and Treatments 
 
 
Added to the list of 
restricted medications 
those that are known to 
have potential for liver 
toxicity.  
Increased awareness of 
medications which may 
impact liver effects. 
Section 9.4.1.2 Secondary Efficacy Analysis 
Added statistical analysis 
methodology for 
annualized rate of severe 
asthma exacerbation. 
Included statistical 
analysis methodology 
given this has been 
elevated to a secondary 
endpoint. 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
87 
CONFIDENTIAL 
Section # and Name  
Description of Change  
Brief Rationale  
Section 10.2 Appendix 2: Clinical 
Laboratory Tests Table 2 
Total bile acid, INR, and 
fractionation of ALP if 
ALP > 1xULN were 
added. Clarified 
urinalysis. 
To enhance monitoring of 
liver parameters during 
the conduct of the trial. 
Global Change 
Minor revisions to text. 
Administrative 
clarifications were 
incorporated, and 
typographical errors were 
corrected. 
 
Amendment 1 (v2.0.0; 28 Feb 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 purpose of this amendment is to provide clarification on Inclusion/Exclusion criteria, 
incorporate new information based on the GB001-1901 study, and to make administrative 
protocol clarifications. 
Section # and Name  
Description of Change  
Brief Rationale  
Section 1.3 Schedule of Activities; 
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 obtaining 
historical medical records 
when necessary.  
Section 1.3 Schedule of Activities  
Hepatitis B surface 
antigen and Hepatitis C 
antibody text was 
updated. 
Clarification to include 
indeterminate test result. 
 
At-home RNA 
Transcriptome Research 
text was updated. 
Test removed from Early 
Discontinuation visit due 
to logistics. 
 
Nasal sample collection 
was separately listed. 
Clarification to avoid 
confusion so that all 
subjects provide sample. 
 
Notes on sputum 
eosinophil and neutrophil 
Clarification on timing of 
sputum and exhaled 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
88 
CONFIDENTIAL 
Section # and Name  
Description of Change  
Brief Rationale  
and exhaled breath 
condensate assessments at 
Randomization visit were 
added. 
breath condensate analysis 
and first dose. 
Section 3 Objectives and Endpoints 
The text on 
pharmacokinetic (PK) 
analysis was updated. 
Exploratory endpoint was 
added. 
The minor update 
clarified that PK samples 
would be collected from 
plasma. 
Exacerbations was added 
as exploratory endpoint. 
Section 4.2.2 Placebo Rationale 
Text added on timing of 
IDMC meeting. 
Clarification of timing of 
IDMC meeting. 
Section 5.1 Inclusion Criteria #3; 
Section 8.3.4 Pregnancy; 
Section 10.4 Appendix 4:  Contraceptive 
Guidance and Collection of Pregnancy 
Information 
Criterion for male 
contraception was 
removed. 
Data on pregnancies of 
male partners of female 
subjects will no longer be 
collected.  
Contraceptive guidance 
for male subjects was 
removed. Collection of 
information from male 
subjects with partners 
who become pregnant has 
been removed. 
Per CTFG Guidance 
Section 2.3, no male 
contraception is required. 
Section 5.1 Inclusion Criteria #6 
Criteria for ICS plus 
additional controller was 
updated. 
Clarification on length of 
prior treatment with 
medium or high dose ICS 
and clarification of the use 
of additional controller 
medication. 
Section 5.1 Inclusion Criteria #7; 
Section 5.3 Randomization Criteria 
The lower limit for FEV1 
criterion was removed. 
Studies in subjects with 
severe asthma have been 
conducted without lower 
limit of FEV1. Exclusion 
of subjects with low 
FEV1 will be based on 
PI’s assessment. 
Section 5.1 Inclusion Criteria #8 
Text on reversibility was 
revised. 
Clarification on use of 
equivalent dose of 
nebulized bronchodilator. 
Section 5.2 Exclusion Criteria #1 
Text was added to exclude 
smoking of any substance. 
This clarification was 
made to include 
marijuana, its 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
89 
CONFIDENTIAL 
Section # and Name  
Description of Change  
Brief Rationale  
components, and any 
other substances which 
may be smoked. 
Section 5.2 Exclusion Criteria #7 
Text around ECG 
assessment was updated. 
This modification was 
made to clarify that ECG 
assessment could be 
repeated. 
Section 5.2 Exclusion Criteria #18 
Text added to clarify 
criterion. 
Clarification on reasons 
for excluding subjects 
who may participate in 
another 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 6.2.4 Unblinding of an Individual 
Subject 
Text added to clarify 
conditions for unblinding. 
Clarification of 
procedures to protect 
samples and data for 
unblinding. 
Section 6.4.2 Rescue Medicine 
Text was updated to 
provide additional details. 
This modification was 
made to clarify use of 
rescue medication and 
data capture. 
Section 7.1.2 Pregnancy 
Removed 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 
Text was added to 
description of Screening 
and Randomization visits. 
Clarification on timing of 
procedures. 
Section 8.1.1 Asthma Worsening 
Text was added to clarify 
the timing/duration of 
exacerbations. 
Clarification of the 
interval between two 
exacerbations. 
Section 8.6.3 RNA Transcriptome Research 
Text was updated. 
Clarification that not all 
samples may be analyzed. 
Section 8.6.5 Blood Biomarker Analyses 
Text was updated. 
Simplification and 
clarification of possible 
analyses. 
Section 9.3 Populations for Analyses 
Text added for clarity. 
Clarification of 
populations for analyses. 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
90 
CONFIDENTIAL 
Section # and Name  
Description of Change  
Brief Rationale  
Section 9.4 Statistical Analyses 
Text added for clarity. 
Clarification on 
summaries of variables. 
Section 9.4.1 Efficacy Analyses 
Subheading was added on 
efficacy analyses. 
Clarification of the 
population for efficacy 
analyses. 
Section 10.1.2 Informed Consent Process 
Text was added to 
describe 
pharmacogenetics consent 
form. 
Clarification of the 
process for collecting PGx 
informed consent. 
Section 10.2 Appendix 2: Clinical 
Laboratory Tests Table 3;  
Section 10.6 Appendix 6 Table 5  
Specific acetaminophen 
assay was removed. 
Type of acetaminophen 
assay is no longer 
specified to allow 
flexibility in assay 
performed.  
Section 10.3.5 Reporting of SAEs 
Contact information and 
paper submission of SAE 
report was updated. 
Update and clarification 
of contact information and 
on paper submission of 
SAE report. 
Section 10.6 Appendix 6: Liver Safety - 
Actions and Follow-up Assessments 
“Not required in China” 
was removed. 
Updated. 
Section 10.8 Appendix 8: Prohibited 
Medications and Treatments 
Table was updated. 
New data indicated that 
GB001 is not expected to 
have clinically significant 
drug-drug interactions 
with substrates of 
CYP2C8, CYP2C9, 
OATP1B1/1B3, and Pg-p. 
These data supported 
change in prohibited 
medications and 
treatments. 
Section 10.9 Appendix 9: Estimated Clinical 
Comparability of Medium and High Doses 
of Inhaled Corticosteroids 
Table was updated. 
Update due to availability 
of new products. 
Global Change 
Minor revisions to text. 
Typographical errors were 
corrected. 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
91 
CONFIDENTIAL 
11. 
REFERENCES 
Bateman ED, Guerreros AG, Brockhaus F, Holzhauer B, Pethe A, Kay RA, et al. Fevipiprant, an 
oral prostaglandin DP2 receptor (CRTh2) antagonist, in allergic asthma uncontrolled on low-
dose inhaled corticosteroids. Eur Respir J. 2017;50(2). 
Björnsson ES. Hepatotoxicity by drugs: the most common implicated agents. Int J Mol Sci. 
2016;17(2):224. 
Botturi K, Langelot M, Lair D, Pipet A, Pain M, Chesne J, et al. Preventing asthma 
exacerbations: what are the targets? Pharmacol Ther. 2011;131(1): 114-129. 
Castro M. Placebo versus best-available-therapy control group in clinical trials for 
pharmacologic therapies: which is better? Proc Am Thorac Soc. 2007;4(7):570-573. 
Castro M, King TS, Kunselman SJ, Cabana MD, Denlinger L, Holguin F, et al. Effect of vitamin 
D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: 
the VIDA randomized clinical trial. JAMA 2014;311(20): 2083-2091. 
Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P, et al. Reslizumab for 
inadequately controlled asthma with elevated blood eosinophil counts: results from two 
multicentre, parallel, double-blind, randomised, placebo-controlled, Phase 3 trials. Lancet Respir 
Med. 2015;3(5): 355-366. 
Catley MC, Coote J, Bari M, and Tomlinson KL. Monoclonal antibodies for the treatment of 
asthma. Pharmacol Ther. 2011;132(3): 333-351. 
Dalal AA, Duh MS, Gozalo L, et al. Dose-Response Relationship Between Long-Term Systemic 
Corticosteroid Use and Related Complications in Patients with Severe Asthma. J Manag Care 
Spec Pharm. 2016;22(7): 833-847. 
EMA, Guideline on the clinical investigation of medicinal products for the treatment of asthma. 
Committee for Medicinal Products for Human Use (CHMP). CHMP/EWP/2922/01 Rev.1 
Published 22 October 2015. London, UK. Available from: 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/12/WC500
198877.pdf. 
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. 
Fajt ML, Gelhaus SL, Freeman B, et al. Prostaglandin D(2) pathway upregulation: relation to 
asthma severity, control, and TH2 inflammation. J Allergy Clin Immunol. 2013;131(6): 1504-
1512. 
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. 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
92 
CONFIDENTIAL 
Garza LA, Liu Y, Yang Z, et al. Prostaglandin D2 inhibits hair growth and is elevated in bald 
scalp of men with androgenetic alopecia. Sci Transl Med. 2012;4(126): 126ra134. 
GINA, Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention,  
2018. Available from: http://www.ginasthma.org/. 
Gonem S, Berair R, Singapuri A, et al. Fevipiprant, a prostaglandin D2 receptor 2 antagonist, in 
patients with persistent eosinophilic asthma: a single-centre, randomised, double-blind, parallel-
group, placebo-controlled trial. Lancet Respir Med. 2016;4(9): 699-707. 
Gupta M and Mysore V. Classifications of Patterned Hair Loss: A Review. J Cutan Aesthet Surg. 
2016;9(1): 3-12. 
Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory 
eosinophilic asthma. N Engl J Med. 2009;360(10): 973-984. 
Hall IP, Fowler AV, Gupta A, et al. Efficacy of BI 671800, an oral CRTH2 antagonist, in poorly 
controlled asthma as sole controller and in the presence of inhaled corticosteroid treatment. Pulm 
Pharmacol Ther. 2015;32: 37-44. 
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. 
Hopkins C, Gillett S, Slack R, Lund VJ and Browne JP. Psychometric validity of the 22-item 
Sinonasal Outcome Test. Clin Otolaryngol. 2009;34(5): 447-454. 
Juniper EF, Guyatt GH, Ferrie PJ and Griffith LE. Measuring quality of life in asthma. Am Rev 
Respir Dis. 1993;147(4): 832-838. 
Juniper EF, Guyatt GH, Willan A and Griffith LE. Determining a minimal important change in a 
disease-specific Quality of Life Questionnaire. J Clin Epidemiol. 1994;47(1): 81-87. 
Juniper EF, Svensson K, Mork AC and Stahl E. Measurement properties and interpretation of 
three shortened versions of the asthma control questionnaire. Respir Med. 2005;99(5): 553-558. 
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(12): 1281-1294. 
Lacombe M, Marie-Desvergne C, Combes F, et al. Proteomic characterization of human exhaled 
breath condensate. J Breath Res. 2018;12(2): 021001. 
Maniscalco M, Paris D, Melck DJ, et al. Differential diagnosis between newly diagnosed asthma 
and COPD using exhaled breath condensate metabolomics: a pilot study. Eur Respir J. 
2018;51(3). 
Mazurek JM, Syamlal G. Prevalence of Asthma, Asthma Attacks, and Emergency Department 
Visits for Asthma Among Working Adults-National Health Interview Survey, 2011-2016. 
MMWR Morb Mortal Wkly Rep. 2018(67):377-386. 
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. 


GB001, Inc. 
GB001 
Protocol GB001-2001 
Version 5.0, 16 Apr 2020 
93 
CONFIDENTIAL 
Nieves A and Garza LA. Does prostaglandin D2 hold the cure to male pattern baldness? Exp 
Dermatol. 2014;23(4): 224-227. 
O'Byrne PM. Therapeutic strategies to reduce asthma exacerbations. J Allergy Clin Immunol. 
2011;128(2): 257-263. 
Ortega H, Yancey SW, Keene ON, Gunsoy NB, Albers, FC and Howarth PH. Asthma 
Exacerbations Associated with Lung Function Decline in Patients with Severe Eosinophilic 
Asthma. J Allergy Clin Immunol Pract. 2018;6(3): 980-986 e981. 
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. 
Ortega H, Fitzgerald M, Raghupathi K, Bhakta N, Singh D. Reduction of exhaled nitric oxide by 
the DP2 antagonist GB001 in patients with mild atopic asthma. American Academy of Allergy, 
Asthma & Immunology Annual Meeting; February 22-25, 2019b; San Francisco, CA. 
Pavord ID, Beasley R, Agusti A, , et al. After asthma: redefining airways diseases. Lancet. 
2018;391(10118): 350-400. 
Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a 
multicentre, double-blind, placebo-controlled trial. Lancet. 2012;380(9842): 651-659. 
Reddel HK, Taylor DR, Bateman ED, et al. An official American Thoracic Society/European 
Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for 
clinical asthma trials and clinical practice. Am J Respir Crit Care Med. 2009;180(1): 59-99. 
Singh D, Ravi A, Southworth T. CRTH2 antagonists in asthma: current perspectives. Clin 
Pharmacol. 2017;9: 165-173. 
Uchida Y, Soma T, Kobayashi T, Nakagome K and Nagata M. Differential features of pro-
inflammatory eicosanoids in exhaled breath condensate and sputum from asthmatics. J Allergy 
Clin Immunol. 2018;141(2): AB110. 
Wagener AH, de Nijs SB, Lutter R, et al. External validation of blood eosinophils, FE(NO) and 
serum periostin as surrogates for sputum eosinophils in asthma. Thorax. 2015;70(2): 115-120. 
Wenzel S, Ford L, Pearlman D, et al. Dupilumab in persistent asthma with elevated eosinophil 
levels. N Engl J Med. 2013;368(26): 2455-2466. 

SAP_001.pdf: 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 2 of 47 
VERSION CONTROL 
 
Version Number 
Date 
Comments/Changes 
1.0 
11 April 2020 
Final 
 
 
 
 
 
 
 
 
 
 




GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 4 of 47 
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 .........................................................................................................14 
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 .................................................................................................16 
3.3. 
Considerations Related to the COVID-19 Pandemic .................................................17 
4. 
ANALYSIS POPULATIONS ....................................................................................19 
4.1. 
All Enrolled Population ..............................................................................................19 
4.2. 
Run-in Period Population ...........................................................................................19 
4.3. 
Intent-to-Treat Population ..........................................................................................19 
4.4. 
Per Protocol Population ..............................................................................................19 
4.5. 
Safety Population ........................................................................................................19 
5. 
STUDY PATIENTS ...................................................................................................20 
5.1. 
Disposition of Patients ................................................................................................20 
5.2. 
Protocol Deviations ....................................................................................................20 
6. 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS .....................21 
6.1. 
Demographic Characteristics ......................................................................................21 
6.2. 
Baseline Disease Characteristics ................................................................................21 
6.3. 
Atopic/Allergic Conditions .........................................................................................22 
6.4. 
Efficacy-Related Baseline Characteristics ..................................................................22 
6.5. 
Biomarker Baseline Characteristics ............................................................................23 
6.6. 
Prior Medications ........................................................................................................23 
6.6.1. 
Prior Asthma Medications ..........................................................................................23 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 5 of 47 
6.7. 
Concomitant Medications ...........................................................................................24 
6.7.1. 
Concomitant Asthma Medications .............................................................................24 
7. 
EXTENT OF EXPOSURE, COMPLIANCE, AND TIME ON STUDY ..................25 
7.1. 
Extent of Exposure .....................................................................................................25 
7.2. 
Compliance .................................................................................................................25 
7.3. 
Time on Study .............................................................................................................25 
8. 
EFFICACY EVALUATION ......................................................................................26 
8.1. 
Overview of Efficacy Analysis Issues ........................................................................26 
8.1.1. 
Handling of Dropouts or Missing Data ......................................................................26 
8.1.2. 
Multicenter Studies .....................................................................................................26 
8.1.3. 
Multiple Comparisons/Multiplicity ............................................................................26 
8.2. 
Efficacy Endpoints ......................................................................................................26 
8.3. 
Analysis Methods .......................................................................................................28 
8.3.1. 
Primary Efficacy Analyses .........................................................................................28 
8.3.1.1. 
Sensitivity Analyses ....................................................................................................30 
8.3.1.2. 
Evaluation of Dose Response for the Primary Endpoint ............................................32 
8.3.1.3. 
Additional Analyses of the Primary Endpoint ............................................................32 
8.3.2. 
Secondary Efficacy Analyses .....................................................................................32 
8.3.2.1. 
Change from Baseline to Week 24 Endpoints ............................................................32 
8.3.2.2. 
Time to First Asthma Worsening ...............................................................................35 
8.3.2.3. 
Annualized Rate of Severe Asthma Exacerbations ....................................................35 
8.3.3. 
Tertiary/Exploratory Analyses ....................................................................................36 
8.3.3.1. 
PRO Endpoints ...........................................................................................................36 
8.3.3.2. 
Additional Markers of Asthma Control ......................................................................38 
8.3.3.3. 
Biomarkers ..................................................................................................................39 
8.3.3.4. 
PK Concentrations ......................................................................................................39 
8.4. 
Examination of Subgroups .........................................................................................40 
9. 
SAFETY EVALUATION ..........................................................................................42 
9.1. 
Adverse Events ...........................................................................................................42 
9.2. 
Clinical Laboratory Evaluation ...................................................................................43 
9.3. 
Vital Signs and Other Observations Related to Safety ...............................................44 
9.3.1. 
Vital Signs ..................................................................................................................44 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 6 of 47 
9.3.2. 
Other Safety Measures ................................................................................................44 
9.3.2.1. 
Electrocardiograms .....................................................................................................44 
10. 
REFERENCES ...........................................................................................................46 
 
LIST OF TABLES 
Table 1: 
Efficacy Endpoints and Analysis Methods .................................................................27 
Table 2: 
Criteria for determination of asthma worsening status for subjects who 
prematurely withdraw from the study without experiencing asthma 
worsening ....................................................................................................................29 
Table 3: 
Summary of Primary and Sensitivity Analyses of the Primary Endpoint ..................30 
Table 4: 
Vital Sign Parameter Abnormality Criteria ................................................................44 
 
  
 
 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 7 of 47 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ACQ 
asthma control questionnaire 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance 
ANOVA 
analysis of variance 
AQLQ-S 
asthma quality of life questionnaire-standardized 
AST 
aspartate aminotransferase 
ATC 
anatomical therapeutic chemical 
BLQ 
below limit of quantification 
BMI 
body mass index 
BPM 
beats per minute 
CI 
confidence interval 
COVID-19 
Coronavirus Disease 2019 
CSR 
clinical study report 
CTS 
continuous 
CV 
coefficient of variation 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
eDISH 
evaluation of Drug-Induced Serious Hepatotoxicity 
EMA 
European Medicines Agency 
FDA 
Food and Drug Administration 
FeNO 
fractional exhaled nitric oxide 
FEV1 
forced expiratory volume in 1 second 
FVC 
forced vital capacity 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transferase 
GINA 
Global Initiative for Asthma 
GMR 
geometric mean ratio 
ICH 
International Conference on Harmonisation 
ICS 
inhaled corticosteroid 
IgE 
immunoglobulin E 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 8 of 47 
Abbreviation 
Definition 
IM 
intramuscular 
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 
LTRA 
leukotriene receptor antagonist 
MCID 
minimal clinically important difference 
MCMC 
Markov Chain Monte Carlo 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
multiple imputation 
MMRM 
mixed-effects model with repeated measures 
OR 
odds ratio 
PD 
pharmacodynamics 
PEF 
peak expiratory flow 
PK 
pharmacokinetics 
PRO 
patient reported outcomes 
PT 
preferred term 
QOL 
quality of life 
QTcB 
Bazett’s correction formula for QT interval 
QTcF 
Fridericia's correction formula for QT interval 
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 
ULN 
upper limit of normal 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 9 of 47 
Abbreviation 
Definition 
WHO 
World Health Organization 
 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
Page 10 of 47 
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 4.0.  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 “Tertiary/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 at the interim analysis. 
In this document, investigational product (IP) and study treatment have the same meaning. 






GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 13 of 47 
Total duration for study participation per subject is up to 34 weeks (includes a Screening Visit; 
followed by a 2-week to 6-week Run-in period to allow for collection of baseline eDiary data; a 
24-week Double-Blind, Placebo-Controlled period; and 4-week Follow-up period). 
Subjects who permanently discontinue IP will be requested to attend the Early Discontinuation 
of IP Visit 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 at home at bedtime on an empty stomach. Following initiation of IP, 
subjects will visit the clinic for assessments at Weeks 2 and 4, followed by visits approximately 
every 4 weeks for an additional 5 visits. Subjects should remain on their stable current standard 
of care therapy (i.e., medium or high dose inhaled corticosteroid (ICS) plus additional controller 
therapy) through the duration of their time on study. 
All subjects will be closely monitored throughout the study through daily home morning PEF 
and eDiary monitoring. Subjects will be provided with an eDiary which is programmed to alert 
the subject of potential asthma worsening: 
1. On 2 consecutive days, AM PEF ≤ 75% of mean AM PEF measured over the last 7 days 
of the Run-in period 
2. Increase in rescue medication use of ≥ 6 puffs/day (last 24 hours) on 2 consecutive days 
compared to mean use over the last 7 days of the Run-in period 
3. Nighttime awakening due to asthma symptoms requiring rescue medication for at least 
2 of 3 successive nights 
4. An asthma symptom score of 4 for at least 2 of 3 successive days. 
Subjects will be asked to record the following parameters daily in the eDiary from the Screening 
Visit through the Follow-up Visit: 
• Morning peak flow (best of three efforts) before rescue medication usage (L/min) 
• Puffs of rescue medication used over the previous 24 hours 
• Asthma symptom score over the previous 24-hours using a 6-point scale (as defined 
in Protocol Section 10.7) 
• Frequency of awakening due to asthma symptoms requiring rescue medication use 
The protocol contains further details related to the study design and conduct. 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 14 of 47 
2.3. 
Study Population 
This study will enroll male and female subjects with moderate to severe asthma who are 
currently receiving Global Initiative for Asthma (GINA) step 4 or 5 therapy and have evidence 
of eosinophilic inflammation, and are ≥ 18 and < 75 years of age at the time of the Screening 
Visit.  Other key eligibility criteria include: 
• A peripheral blood eosinophil count of ≥ 250 cells/µL measured at the Screening 
Visit. Note: In a subject with prior evidence of an eosinophilic phenotype, as assessed 
by the investigator, an eosinophil count < 250 may be repeated during Run-in upon 
approval by the medical monitor. 
• Subjects with a documented requirement for regular treatment with medium or high 
dose ICS and at least one other controller medication for at least 12 months prior to 
Visit 1. Subjects must maintain a stable ICS dose regimen during the 4 weeks prior to 
Visit 1. 
• Demonstration of uncontrolled asthma by one of the following: 
a. Previously confirmed history of 2 or more asthma exacerbations requiring 
treatment with systemic corticosteroids in the 12 months prior to Screening Visit. 
OR 
b. Previously confirmed history of 1 asthma exacerbation requiring treatment with 
systemic corticosteroids in the 12 months prior to Screening Visit and ACQ-5 of 
≥ 1.5 at Screening Visit. 
2.4. 
Randomization and Treatment Regimens 
This study will randomize approximately 480 subjects, with approximately 120 subjects per 
treatment group, randomized in a 1:1:1:1 ratio to the following treatment groups: 
• GB001 60 mg daily 
• GB001 40 mg daily 
• GB001 20 mg daily 
• Matching placebo daily 
Randomization will be stratified by baseline ICS dose (medium or high, as defined in 
Protocol Section 10.10) and country. 
2.5. 
Sample Size Determination 
A total sample size of approximately 480 subjects (approximately 120 per treatment group, 
randomized in a 1:1:1:1 ratio) is estimated to provide 80% power to detect a reduction in odds of 
66% between each GB001 group and placebo at an 0.050 two-sided level of significance for the 
primary endpoint of the proportion of subjects who experience worsening of asthma by Week 24.  
This assumes the proportion of subjects who experience worsening of asthma by Week 24 is 
25% in the placebo group and 10.2% in each GB001 group and a dropout rate of 8%. 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 15 of 47 
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 (cts) 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).  Rounding rules for reporting cts 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.   
Efficacy results will be summarized by various measures including but not limited to odds ratios 
(ORs), hazard ratios, rate ratios, least squares (LS) means, differences in LS means, SEs, p-
values, and two-sided confidence intervals (CIs).  The ORs, hazard ratios, rate ratios, and 
corresponding CIs will be reported to 3 decimal places, percentage reductions and corresponding 
CIs will be reported to 1 decimal place, and SEs, LS means, differences in LS means and 
corresponding CIs will be reported per the rules above.  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 tests will be two-sided with a significance level 
of 0.050.  
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. 
Disposition, demographic and baseline characteristics, significant protocol deviations, and prior 
medication tables will be presented by randomized treatment group and will also include an 
overall column combining all treatment groups.  Efficacy tables will be presented by randomized 
treatment group only.  Safety tables will be presented by actual treatment group and, in general, 
will also include a total GB001 column combining all GB001 treatment groups.  Sorting in 
disposition, etc. tables will be based on decreasing incidence within the overall column.  In 
general, AE tables that are displayed by system organ class (SOC) and/or preferred term (PT) 
will be sorted by the internationally agreed order for SOC, and by decreasing incidence and then 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 16 of 47 
alphabetically for PT within the total GB001 column.  Otherwise, safety tables when applicable, 
will be sorted by decreasing incidence within the total GB001 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 on or before the first dose of study treatment or the mean over the last 7 days of 
the Run-in including the value on Day 1.    
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. 
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. 
3.1. 
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, and the lower bound of the first post-
baseline visit window is Day 1 after the time of the first dose.  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 latter visit window with the exception of the Week 24 visit for the 
efficacy endpoints, which will include Day 174 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 early withdrawal 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 2 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: 
Age will be calculated in years to two decimal places 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: 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 17 of 47 
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 
assessment date – date of the first dose of study treatment + 1, where assessment date ≥ date of 
the first dose of study treatment 
3.3. 
Considerations Related to the COVID-19 Pandemic 
Screening of subjects for this study began in October 2018, and the last subject is expected to 
complete their participation in the study around August-September 2020.  As such, a portion of 
this study’s conduct may be affected by the global Coronavirus Disease 2019 (COVID-19) 
pandemic. 
At the time of finalization of this SAP in April 2020, several regulatory authorities have recently 
issued guidance related to trial conduct and associated methodological issues related to the effect 
of the COVID-19 pandemic, including Food and Drug Administration (FDA) (Reference: FDA 
Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic, 
March 2020) and European Medicines Agency (EMA) (References: Guidance on the 
Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic, Version 2 
(27/03/2020) and Points to consider on implications of Coronavirus disease (COVID-19) on 
methodological aspects of ongoing clinical trials, 25 March 2020). 
Potential anticipated effects on conduct of this ongoing 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; 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). 
At the time of finalization of this SAP, it is acknowledged that it is not known the degree to 
which study conduct and subject participation may be affected by the COVID-19 pandemic, as 
the study is currently approximately 4-5 months from the last subject completing participation.  


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 18 of 47 
Given the COVID-19 pandemic is a developing and rapidly evolving situation, 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 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: 
− 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: 
− By subgroup of subjects whose study participation was affected by the COVID-19 
pandemic versus was not affected; 
− Excluding only data that is missing for reasons related to the COVID-19 
pandemic (but including imputation of data missing for other reasons); and 
− By subgroup of subjects who had an alternative method of collection for an 
assessment contributing to a particular endpoint (e.g., ACQ-5 completed by 
subject at home via virtual visit) versus subjects who did not have an alternative 
method of collection 
• Analysis of AEs: 
− Incidence of AEs by subgroup of subjects whose study participation was affected 
by the COVID-19 pandemic versus was not affected; 
− 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: 
− By subgroup of subjects whose study participation was affected by the COVID-19 
pandemic versus was not affected; 
− Excluding values resulting from local collection due to reasons related to the 
COVID-19 pandemic; and 
− 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. 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 19 of 47 
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. 
Per Protocol Population 
The per protocol population will include all subjects in the ITT population who do not violate 
terms of the protocol that may affect primary or secondary efficacy outcomes. The criteria for the 
per protocol population will be determined and documented prior to unblinding based on review 
of study data in a blinded manner. 
Programmatically-derived and/or manually reviewed criteria for exclusion from the per protocol 
population include, but are not limited to: 
• Subjects who do not meet the following eligibility criteria: 
− Inclusion Criteria 5, 6, 7, or 9 
− Exclusion Criteria 12 
− Randomization Criteria 1, 2, 4, 5, or 11 
• Poor study treatment compliance up to the last dose of study treatment defined as < 
80.0% compliance 
• Subjects at any site with good clinical practice (GCP) compliance issues identified, if 
applicable 
4.5. 
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, subjects will be 
grouped according to the highest dose of GB001 actually taken (20 mg, 40 mg, or 60 mg) based 
on kit and study treatment accountability data.  The safety population will be utilized for safety 
and PK analyses.  


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 20 of 47 
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 participants, completed run-in, and 
run-in failures, along with screen failure reasons, run-in failure reasons, and reasons not 
randomized 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. 
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 for ICS dose (medium or high) at 
randomization may be presented in a by-subject data listing.   


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 21 of 47 
6. 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
6.1. 
Demographic Characteristics 
Demographic characteristics will be summarized for the ITT and per protocol populations for the 
following parameters: 
• Age (years; 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 (Austria, Belgium, Canada, Czech Republic, France, Germany, Poland, 
Spain, Ukraine, United Kingdom, United States) 
• Region (North America [United States, Canada], Eastern Europe [Czech Republic, 
Poland, Ukraine], Western Europe [Austria, Belgium, France, Germany, Spain, 
United Kingdom])  
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 and per protocol populations for 
the following parameters: 
• ICS dose at Randomization and actual (medium, high) 
• Asthma duration (years; cts) 
• Triggers of exacerbations (air pollution, allergy, aspirin, etc.) 
• Total number of exacerbations in the past 12 months (cts; 0, 1, 2, 3, ≥ 4; overall and 
by exacerbation categories [treated with systemic corticosteroids, resulted in an 
emergency department visit, resulted in a hospitalization]) 
• Uncontrolled asthma demonstrated by the following: 
− 2 or more asthma exacerbations requiring treatment with systemic corticosteroids 
in the 12 months prior to Screening Visit  
− Previously confirmed history of 1 asthma exacerbation requiring treatment with 
systemic corticosteroids in the 12 months prior to Screening Visit and ACQ-5 
score of ≥ 1.5 at Screening Visit 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 22 of 47 
• Chronic Rhinosinusitis and Nasal Polyps (neither, chronic rhinosinusitis and nasal 
polys, chronic rhinosinusitis without nasal polys, nasal polys without chronic 
rhinosinusitis)  
• Smoking history (former smoker [yes, no]; cigarette pack-years) 
• 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 and per protocol populations for the 
following parameters: 
• Allergic Rhinitis, Anaphylactic Reaction, Aspirin-exacerbated Respiratory Disease, 
Atopic Dermatitis, Chronic Rhinosinusitis, Food Allergy, Nasal Polyps, Urticaria 
(none, ongoing, past) 
Atopic/allergic conditions will also be presented in a by-subject data listing. 
6.4. 
Efficacy-Related Baseline Characteristics 
Efficacy-related baseline characteristics will be summarized for the ITT and per protocol 
populations for the following parameters: 
• Pre-bronchodilator FEV1 at Screening and Baseline (L; cts) 
• Post-bronchodilator FEV1 at Screening (L; cts) 
• Pre-bronchodilator percent predicted FEV1 at Screening (%; cts; < 60, ≥ 60) 
• Post-bronchodilator percent predicted FEV1 at Screening (%; cts) 
• Pre-bronchodilator FEV1/forced vital capacity (FVC) at Screening and Baseline 
(ratio; cts; < 0.7, ≥ 0.7)  
• FEV1 reversibility at Screening (%; cts) 
• AM PEF over last 7 days of the Run-in (L/min; cts) 
• Rescue medication usage over last 7 days of the Run-in (puffs/day; cts) 
• ACQ-5 score at Baseline (cts; < 1.5, ≥ 1.5) 
Efficacy-related baseline characteristics will also be presented in a by-subject data listing. 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 23 of 47 
6.5. 
Biomarker Baseline Characteristics 
Biomarker baseline characteristics will be summarized for the ITT and per protocol populations 
for the following parameters: 
• Qualifying blood eosinophils (GI/L; cts; ≥ 0.25, ≥ 0.30, ≥ 1.50) 
• Blood eosinophils at Baseline (GI/L; cts; < 0.20, ≥ 0.20; < 0.25, ≥ 0.25; < 0.30, ≥ 
0.30; < 1.50, ≥ 1.50) 
• Qualifying and Baseline blood eosinophils (GI/L; ≥ 0.25 and < 0.25; ≥ 0.30 and < 
0.30)   
• Fractional exhaled nitric oxide (FeNO) at Screening (ppb; cts; < 25, ≥ 25; < 30, ≥ 30; 
< 35, ≥ 35; < 50, ≥ 50) 
• FeNO at Baseline (ppb; cts; < 25, ≥ 25; < 30, ≥ 30; < 35, ≥ 35; < 50, ≥ 50) 
• Screening and Baseline FeNO (ppb; ≥ 25 and < 25; ≥ 30 and < 30; ≥ 35 and < 35; ≥ 
50 and < 50) 
• Baseline blood eosinophils and Baseline FeNO categories (all combinations for 0.25 
and 25; 0.25 and 30; 0.25 and 35; 0.25 and 50; repeat for 0.30) 
• Immunoglobulin E (IgE) at Baseline (IU/mL; cts; normal [≤ 158], high [> 158]) 
• 25-Hydroxyvitamin D at Baseline (ng/mL; cts; ≤ 20, > 20) 
• 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. 
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 by subject and at each 
level of summarization (e.g., any medication, ATC2, and PT), subjects receiving more than one 
medication will be counted only once.  
Prior medications will be summarized for the safety population.   
6.6.1. 
Prior Asthma Medications 
Prior asthma controller medications will be summarized for the ITT population. 
Prior asthma biologic medications will be summarized and include, but are not limited to, those 
with a PT in the following list: mepolizumab, benralizumab, omalizumab, and dupilumab. 
In addition, prior leukotriene receptor antagonist (LTRA) (e.g., montelukast) use will be 
summarized. 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 24 of 47 
Lastly, the number and percent of subjects who received an ICS plus a long-acting beta-agonist 
(LABA), who received an ICS plus a LABA plus a long-acting muscarinic antagonist (LAMA), 
and who received an ICS plus a LABA plus a LTRA will be summarized.    
6.7. 
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 
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 by subject and at each level of 
summarization (e.g., any medication, ATC2, and PT), subjects receiving more than one 
medication will be counted only once.   
Concomitant medications will be summarized for the safety 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. 
6.7.1. 
Concomitant Asthma Medications 
Concomitant asthma controller medications will be summarized for the ITT population. In 
addition, concomitant LTRA (e.g., montelukast) will be summarized for the ITT population. 
Lastly, the number and percent of subjects who received an ICS plus a LABA, who received an 
ICS plus a LABA plus a LAMA, and who received an ICS plus a LABA plus a LTRA will be 
summarized for the ITT population. 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 25 of 47 
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, 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. 




GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 27 of 47 
Table 1: 
Efficacy Endpoints and Analysis Methods 
Efficacy  
Endpoints 
Missing 
Data 
Thresholda 
Logistic 
Regression 
 
ANCOVA 
MMRM 
Cox 
Propor- 
tional 
Hazards 
Negative 
Binomial 
Regres-
sionb 
without  
MI 
with 
MI 
with 
MI 
without 
MI 
with 
MI 
without 
MI 
Primary 
Proportion of subjects 
who experience 
worsening of asthma 
by Week 24 
 
 
P, S 
 
S 
 
 
 
 
 
 
Secondary 
 
 
 
 
 
 
 
 
 
Change from baseline 
to Week 24 in  
ACQ-5 score 
< 5% 
 
 
 
P 
 
S 
 
 
≥ 5% 
 
 
P 
S 
S 
S 
 
 
Change from baseline 
to Week 24 in pre-
bronchodilator FEV1 
< 5% 
 
 
 
P 
 
S 
 
 
≥ 5% 
 
 
P 
S 
S 
S 
 
 
Time to first asthma 
worsening 
 
 
 
 
 
 
 
P 
 
Annualized rate of 
severe asthma 
exacerbations 
 
 
 
 
 
 
 
 
P, S 
Change from baseline 
to Week 24 in post-
bronchodilator FEV1 
< 5% 
 
 
 
P 
 
 
 
 
≥ 5% 
 
 
P 
S 
 
 
 
 
Change from baseline 
to Week 24 in AM 
PEF 
< 5% 
 
 
 
P 
 
S 
 
 
≥ 5% 
 
 
P 
S 
S 
S 
 
 
Tertiary/Exploratory 
 
 
 
 
 
 
 
 
 
PROs 
 
 
 
 
 
 
 
 
 
Proportion of subjects 
with a greater than or 
equal to 0.5 decrease 
in ACQ-5 score at any 
time post-baseline 
 
 
P 
 
 
 
 
 
 
 
Change from baseline 
to Week 24 in  
AQLQ-S 
 
 
 
 
P 
 
 
 
 
Change from baseline 
to Week 24 in  
SNOT-22  
 
 
 
 
P 
 
 
 
 
Change from baseline 
to Week 24 in hair-
loss assessmentc 
 
 
 
 
 
 
 
 
 
Additional Markers 
of Asthma Control 
 
 
 
 
 
 
 
 
 
Change from baseline 
to Week 24 in rescue 
medication use  
 
 
 
 
P 
 
 
 
 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 28 of 47 
Efficacy  
Endpoints 
Missing 
Data 
Thresholda 
Logistic 
Regression 
 
ANCOVA 
MMRM 
Cox 
Propor- 
tional 
Hazards 
Negative 
Binomial 
Regres-
sionb 
without  
MI 
with 
MI 
with 
MI 
without 
MI 
with 
MI 
without 
MI 
Change from baseline 
to Week 24 in daily 
asthma symptom 
scores  
 
 
 
 
P 
 
 
 
 
Change from baseline 
to Week 24 in 
awakening at night 
due to asthma 
symptoms requiring 
rescue medication use  
 
 
 
 
P 
 
 
 
 
Biomarkers 
 
 
 
 
 
 
 
 
 
Change from baseline 
to Week 24 in FeNO  
 
 
 
 
P 
 
 
 
 
Percentage change 
from baseline to Week 
24 in FeNO 
 
 
 
 
P 
 
 
 
 
Change from baseline 
to Week 24 in sputum 
eosinophils and 
neutrophils 
 
 
 
 
P 
 
 
 
 
ANCOVA = analysis of covariance; MMRM = mixed-effects model with repeated measures; MI = multiple imputation; 
P = primary; S = sensitivity 
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 Cross tabulations of the Baseline assessment versus the Week 24 assessment for Norwood classification (males) and 
Savin classification (females) separately. 
 
8.3. 
Analysis Methods 
8.3.1. 
Primary Efficacy Analyses 
The primary endpoint is the proportion of subjects who experience worsening of asthma by 
Week 24 as defined by at least one of the following: 
• On 2 consecutive days, AM PEF ≤ 75% of mean AM PEF measured over the last 7 
days of the Run-in  
• FEV1 < 80% of baseline (Visit 2)  
• Increase in rescue medication use of ≥ 6 puffs/day on 2 consecutive days compared to 
mean use over the last 7 days of the Run-in  
• Increase in ACQ-5 score of ≥ 0.5 compared to baseline (Visit 2)  
• The occurrence of a severe asthma exacerbation (asthma attack) defined as 
deterioration of asthma that leads to the use of systemic corticosteroids for at least 3 
days, hospitalization, or an Emergency Department visit 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 29 of 47 
Logistic regression modeling will be used to compare each GB001 group with placebo.  The 
model will include covariates for treatment group, ICS dose (medium or high) at randomization, 
region (North America, Eastern Europe, Western Europe), baseline pre-bronchodilator FEV1, 
and baseline ACQ-5 score.  If the full model does not converge, a model with treatment group, 
ICS dose at randomization, and region as covariates will be utilized. If this reduced model does 
not converge, a model with treatment group and ICS dose at randomization will be used. In the 
rare case that convergence issues remain, only treatment group will be included in the model.  
The number and proportion of subjects meeting the primary endpoint and corresponding 95% 
Wilson (Score) CIs (Wilson, 1927) will be summarized by treatment group.  ORs, corresponding 
asymptotic 95% CIs along with the absolute differences and corresponding 95% CIs, and p-
values will be summarized for each GB001 group versus placebo. The 95% CIs for the absolute 
difference will be Newcombe continuity-corrected CIs (Newcombe, 1998). Percentage 
reductions and corresponding 95% CIs will also be summarized. Lastly, the number and 
proportion of subjects meeting each component of the primary endpoint, with observed 
worsening of asthma, and with an assigned status of asthma worsening will also be summarized 
by treatment group. Subjects can meet more than one component of the primary endpoint.  
A subject who prematurely withdraws from the study without experiencing asthma worsening 
will be assigned asthma worsening status by Week 24 (yes/no) based on their discontinuation of 
study treatment and withdrawal from study reasons as summarized below in Table 2.  If a 
subject’s reason for discontinuation of study treatment or withdrawal from study is indicative of 
lack of efficacy or is an AE indicative of asthma worsening, a determination will be made prior 
to study unblinding for the interim analysis regarding whether the subject should be considered 
to have had asthma worsening for the primary endpoint. Otherwise, subjects who prematurely 
withdraw from the study will be considered to have not experienced asthma worsening for the 
primary endpoint.  
Table 2: 
Criteria for determination of asthma worsening status for subjects who 
prematurely withdraw from the study without experiencing asthma 
worsening 
Reason for Discontinuation of Study Treatment and/or Withdrawal from Study 
Asthma Worsening 
Status Assigned 
(Yes/No) 
Lack of Efficacy 
Yes 
AE where the corresponding AE PT reflects asthma worsening including ‘asthma’ 
Yes 
Death where death is due to an SAE where the corresponding SAE PT reflects asthma 
worsening including ‘asthma’ 
Yes 
Lost to follow-up, Non-compliance with study drug, Physician decision, Protocol 
deviation, Withdrawal by Subject, or Other, where further details indicate asthma, asthma 
worsening, lack of efficacy or prescription of or switch to a new asthma treatment 
Yes 
AE where the corresponding AE PT does not reflect asthma worsening 
No 
Death where death is due to an SAE where the corresponding PT does not reflect asthma 
worsening 
No 
Lost to follow-up, Non-compliance with study drug, Physician decision, Protocol 
deviation, Withdrawal by Subject, or Other, where further details do not indicate asthma, 
asthma worsening, lack of efficacy or prescription of or switch to a new asthma treatment 
No 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 30 of 47 
A bar graph of the proportion of subjects meeting the primary endpoint by treatment group and a 
bar graph of the proportion of subjects meeting each component of the primary endpoint by 
treatment group will be provided. 
The primary endpoint and components will also be presented in a by-subject data listing. 
8.3.1.1. 
Sensitivity Analyses 
Table 3 provides an overview of the primary and sensitivity analyses of the primary endpoint.    
Table 3: 
Summary of Primary and Sensitivity Analyses of the Primary Endpoint 
Analysis 
Description 
Primary analysis 
Logistic regression where subjects with missing values are assigned 
asthma worsening status by Week 24 based on discontinuation of 
study treatment /withdrawal from study reasons 
Sensitivity analysis #1:  
Missing Status Imputed as Asthma 
Worsening 
Logistic regression where subjects with missing values are considered 
to have asthma worsening by Week 24 
Sensitivity analysis #2: 
Worse Case Imputation 
Logistic regression where placebo subjects with missing values are 
considered to NOT have asthma worsening by Week 24 and GB001 
subjects with missing values are considered to have asthma 
worsening by Week 24 
Sensitivity analysis #3: 
As Observed Analysis 
Logistic regression using only those subjects with an observed status 
for asthma worsening by Week 24 
Sensitivity analysis #4:  
MI 
Logistic regression using MI 
Sensitivity analysis #5: 
Per Protocol Population 
Logistic regression in per protocol population using the same 
approach as primary analysis 
MI = multiple imputation 
Sensitivity analyses of the primary endpoint will be conducted to evaluate the robustness of 
treatment effect under different assumptions and imputation algorithms. Sensitivity analyses will 
utilize the same logistic regression model as the primary analysis. 
In general, for all sensitivity analyses, the number and proportion of subjects meeting each 
component of the primary endpoint, with observed worsening of asthma, and with an assigned 
status of asthma worsening will be summarized. The exceptions are Sensitivity Analysis #3 
where the number of subjects with an assigned status will not be presented given that the analysis 
is among subjects with an observed status, and Sensitivity Analysis #4 where the number for 
each component will not be presented as multiple imputation (MI) will be performed for the 
overall asthma worsening status (yes/no). 
8.3.1.1.1. Sensitivity Analysis #1: Missing Status Imputed as Asthma Worsening  
A sensitivity analysis will be conducted with all subjects who prematurely withdraw from the 
study without experiencing asthma worsening by Week 24 considered as having experienced 
asthma worsening by Week 24. 
8.3.1.1.2. Sensitivity Analysis #2: Worst Case Imputation 
A worst case sensitivity analysis will be conducted where all placebo subjects who withdraw 
from study without experiencing asthma worsening are considered as not having asthma 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 31 of 47 
worsening by Week 24 and all GB001 subjects who withdraw from study without experiencing 
asthma worsening are considered as having asthma worsening by Week 24. 
8.3.1.1.3. Sensitivity Analysis #3: As Observed Analysis 
An as observed sensitivity analysis will be conducted where only subjects with an observed 
status for asthma worsening by Week 24 are included. 
8.3.1.1.4. Sensitivity Analysis #4: Multiple Imputation 
If the number of subjects overall with a missing observed status for asthma worsening by Week 
24 is ≥ 5%, then the following MI approach will be conducted as a sensitivity analysis.   
The dichotomous outcome of asthma worsening by Week 24 will be imputed for subjects who 
have withdrawn from study without having experienced asthma worsening using a MI approach 
assuming that these subjects with a missing dichotomous outcome would have similar outcomes 
to subjects who had an observed status of asthma worsening by Week 24.  The dichotomous 
outcome will be imputed directly as opposed to imputing the individual components of the 
primary endpoint and then deriving the composite outcome. 
The following steps will be performed: 
• Intermittent missing values will first be imputed using the Fully Conditional 
Specification method, which is appropriate for non-monotonic missing data for binary 
data.  
• The monotone missing values will then be multiply imputed using the monotone 
logistic regression imputation method (Allison, 2005). 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 (i.e. once a subject withdraws from study, no additional 
data is expected for that subject). 
• For each stage, MI will be performed within treatment group with covariate 
adjustment the same as the primary analysis of the primary endpoint and non-missing 
outcomes for asthma worsening. Should convergence issues occur due to small cell 
size for the categorical covariates at either stage, they will be removed from the 
model. 
• The primary analysis of the primary endpoint as described in Section 8.3.1 will be 
performed for each complete, imputed dataset. 
• Fifty imputations will be performed. 
• Results of the logistic regression on the multiple imputed data sets will be combined 
to generate an overall estimate and associated variance using Rubin’s rules 
(Rubin, 1987). 
The imputed data logistic regression model-based estimates of the proportion of subjects with 
asthma worsening, ORs, corresponding 95% CIs, and p-values will be reported. Percentage 
reductions and corresponding 95% CIs will also be provided. 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 32 of 47 
8.3.1.1.5. Sensitivity Analysis #5: Per Protocol Population 
If ≥ 5% of subjects in the ITT population are excluded from the per protocol population, then a 
sensitivity analysis will be conducted in which the primary analysis of the primary endpoint will 
be repeated in the per protocol population. 
8.3.1.2. 
Evaluation of Dose Response for the Primary Endpoint 
A dose response analysis will be conducted to evaluate the relationship between increasing dose 
and the effect of GB001, using the primary analysis method of the primary endpoint.  
A one-sided, asymptotic, Cochran-Armitage test for trend (Cochran, 1954; Armitage, 1955) will 
be used to test if the response proportion with asthma worsening decreases linearly with 
increasing dose level (placebo, 20 mg, 40 mg, 60 mg). The p-value from the test will be reported. 
For this test, the null hypothesis, H0 (Π0 = Π20 = Π40 = Π60) is: There is no linear trend in 
binomial proportions of response across increasing levels of dosage.    
The alternative hypothesis, (H1) (Π0  ≥ Π20  ≥  Π40  ≥  Π60) is: There is a decreasing trend in 
binomial proportions of response across increasing levels of dosage.  
To further evaluate the dose response relationship, the ORs and corresponding 95% CIs for the 3 
pairwise comparisons among each of the GB001 treatment groups will be provided (60 mg vs 20 
mg, 60 mg vs 40 mg, 40 mg vs 20 mg). Percentage reductions and corresponding 95% CIs will 
also be provided. 
8.3.1.3. 
Additional Analyses of the Primary Endpoint 
Logistic regression modeling based on an as observed analysis using the same logistic regression 
model as Sensitivity Analysis #3 will be used to compare each GB001 group with placebo for the 
following: 
• Each individual component of the primary endpoint separately.  An individual 
component will not be analyzed if < 5 total subjects meet the criterion in the ITT 
population. 
• The AM PEF and FEV1 components only, as they represent worsening of asthma 
related to lung function. 
• The rescue medication, ACQ-5 score, and severe asthma exacerbation components 
only, as they represent worsening of asthma related to asthma control. 
Lastly, the primary endpoint will be analyzed in a manner similar to the primary analysis, but for 
the timeframe of by the Follow-up Visit (Week 28) rather than by Week 24. 
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 24 Endpoints 
Change from baseline to Week 24 in ACQ-5 score, pre-bronchodilator FEV1, post- 
bronchodilator FEV1, and AM PEF will be analyzed as described below. 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 33 of 47 
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 E. F., 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 
minimal clinically important difference (MCID) is 0.5 points. 
For AM PEF, the baseline value is defined as the mean over the last 7 days of the Run-in 
including the value on Day 1 and Week 24 is defined as the mean over the last 7 days prior to 
Week 24 including the value on the day of the Week 24 visit. For the other endpoints, the 
baseline value is defined as the last non-missing value on or before the date of the first dose of 
study treatment. 
If the number of subjects overall with a missing change from baseline value is < 5% for a 
particular endpoint:  
• The primary analysis will be analysis of covariance (ANCOVA) without MI.   
• As a sensitivity analysis, mixed-effects model with repeated measures (MMRM) 
without MI will also be performed.   
If the number of subjects overall with a missing change from baseline value is ≥ 5% for a 
particular endpoint:  
• The primary analysis will be ANCOVA with MI.   
• As sensitivity analyses, MMRM with MI, ANCOVA without MI, and MMRM 
without MI will also be performed.   
Post-bronchodilator FEV1 will not be analyzed using MMRM as it is collected at only one post-
baseline timepoint. 
Each secondary endpoint of change from baseline to Week 24 will be analyzed using ANCOVA 
models. For this analysis, the MI procedure analogous to that described in Section 8.3.1.1.4 will 
be performed if the number of subjects overall with a missing change from baseline value is ≥ 
5% with the following modifications for cts data: (1) intermittent missing values will be imputed 
using the Markov Chain Monte Carlo (MCMC) method (Schafer, 1997), and (2) monotone 
missing values will be imputed using a regression model.  Covariate adjustment will be the same 
as for the primary endpoint for ACQ-5 score and pre-bronchodilator FEV1. For post-
bronchodilator FEV1 and AM PEF, the covariates used in the model will be the same as for the 
primary endpoint except that baseline pre-bronchodilator FEV1 will be replaced with baseline 
post-bronchodilator FEV1 or baseline AM PEF, depending on the endpoint of interest.  
ANCOVA without MI will be performed similarly as described above without the imputation of 
values. 
Descriptive statistics for change from baseline to Week 24 along with the LS means, SEs, and 
corresponding 95% CIs for each treatment group will be presented.  Differences in LS means, 
SEs, corresponding 95% CIs, and p-values for each GB001 group versus placebo will also be 
constructed from the ANCOVA models. 
In addition, each secondary endpoint of change from baseline to Week 24 will be analyzed by 
MMRM except for change from baseline to Week 24 in post-bronchodilator FEV1.  MMRM will 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 34 of 47 
be performed using a restricted maximum-likelihood (REML)-based approach and an 
unstructured covariance structure to model within-subject error. The MMRM model will include 
change from baseline values up to Week 24 as the response variable; the fixed, categorical 
effects of treatment group, ICS dose (medium or high) at randomization, region, visit, and 
treatment group by visit interaction; and the cts, fixed covariates of baseline value and baseline 
value by visit interaction.  
Parameters will be estimated using REML with the Newton-Raphson algorithm. Treatment 
comparisons will be derived from the MMRM. Differences in LS mean changes from baseline, 
the corresponding 95% CIs, and p-values with Kenward-Roger adjustment (Kenward, 1997) will 
be provided for comparison for each GB001 group versus placebo. LS means will be reported 
along with SEs and corresponding 95% CIs, and differences between treatment groups reported 
with LS means, SEs, corresponding 95% CIs, and p-values. 
If a given 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 be utilized, based on the covariance structure converging to better fit as determined 
based on Akaike’s information criterion (Akaike, 1973). 
Actual values and change from baseline values for ACQ-5 score, pre-bronchodilator FEV1, post- 
bronchodilator FEV1, and AM PEF will be summarized by visit.  Differences in means, SEs, and 
corresponding 95% CIs constructed from analysis of variance (ANOVA) models adjusting for 
treatment group only will also be presented. In addition, figures of mean actual values and mean 
change from baseline values, including SE bars, for ACQ-5 score and pre-bronchodilator FEV1 
by visit will be provided.  Lastly, bar graphs of the LS means and CIs for Week 24 for ACQ-5 
score and pre-bronchodilator FEV1 will be provided. 
Lastly, a sensitivity analysis with a different method of handling pre-bronchodilator FEV1 
measurements confounded by systemic corticosteroid use will be performed. Pre-bronchodilator 
FEV1 measurements collected from systemic corticosteroid start date to systemic corticosteroid 
end date + 14 days will be excluded in order to reduce the confounding effect of systemic 
corticosteroids. If the number of subjects overall with a missing change from baseline is < 5%, 
then only ANCOVA without MI will be performed.  If the number of subjects overall with a 
missing change from baseline value is ≥ 5%, ANCOVA with MI and MMRM with MI will be 
performed. 
ACQ-5 score, pre-bronchodilator FEV1, post- bronchodilator FEV1, and AM PEF data will also 
be presented in by-subject data listings. 
8.3.2.1.1. Evaluation of Dose Response for ACQ-5 and Pre-Bronchodilator FEV1 
A dose response analysis for change from baseline to Week 24 in ACQ-5 score and pre-
bronchodilator FEV1 will be conducted to evaluate the relationship between increasing dose and 
the effect of GB001, using the primary analysis method of these secondary efficacy endpoints. 
Differences in LS means and SEs for all pairwise comparisons will be provided.  In addition, 
Tukey’s multiple comparisons test (i.e. Tukey’s honest significance difference) will be used to 
compare all possible pairwise means to test which pairwise means differ while adjusting nominal 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 35 of 47 
type 1 error at 5%.  The simultaneous 95% CIs and p-values from Tukey’s test will be reported.  
Box plots for mean change from baseline to Week 24 by treatment group will be presented. 
8.3.2.2. 
Time to First Asthma Worsening 
Time to first asthma worsening is defined as the time from the date of the first dose of study 
treatment to the first date that any of the components of the asthma worsening endpoint is met.  
Subjects who do not experience asthma worsening will be censored on the date of their last 
assessment for any of the components of asthma worsening.  For the primary analysis of time to 
first asthma worsening, all data up to Week 24 will be utilized; a sensitivity analysis of time to 
first asthma worsening will be performed utilizing all data up to the Follow-up Visit (Week 28). 
For subjects who experience asthma worsening, the date of the event is defined for each 
component as: 
• AM PEF and rescue medication use – date of event is considered to be on the first of 
2 consecutive days where the respective criterion is met 
• FEV1 and ACQ-5 score – date of event is considered to be on the date of the 
qualifying assessment 
• Severe exacerbation – date of event is considered to be on the date of onset of 
exacerbation as captured on the Severe Asthma Exacerbations eCRF 
The number and proportion of subjects with asthma worsening will be summarized. The number 
and proportion of subjects meeting each component will also be summarized with subjects 
counted only once for the component first met. 
Time to asthma worsening will be compared between treatment groups using a Cox proportional 
hazards model. The exact method will be used to handle ties in event times.  Covariate 
adjustment will be the same as for the primary endpoint. Estimates of the hazard ratio for each 
GB001 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 asthma worsening 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) will 
be provided for each treatment arm. 
Time to asthma worsening data will also be presented in a by-subject data listing. 
8.3.2.3. 
Annualized Rate of Severe Asthma Exacerbations 
A severe asthma exacerbation is defined as deterioration of asthma that leads to the use of 
systemic corticosteroids for at least 3 days, hospitalization, or an Emergency Department visit. 
Exacerbations for which the courses of systemic corticosteroids are separated by 7 or more days 
will be counted as separate severe asthma exacerbations. 
The number and proportion of subjects with 0, 1, and ≥ 2 severe exacerbations and the 
annualized rate of severe asthma exacerbations will be summarized. The unadjusted annualized 
rate of severe exacerbations will be calculated as the total number of severe exacerbations 
divided by the total number of subject-years of follow-up and will also be summarized.  


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 36 of 47 
The total number of severe 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 up to and including Day 174.  The model 
will include terms for treatment group, ICS dose (medium or high) at randomization, region, age 
at screening, and the number of exacerbations in the past 12 months.  If the distribution of severe 
exacerbation data is under dispersed, or if the negative binomial regression model fails to 
converge, a Poisson regression model will be used instead of the negative binomial regression 
model. Exacerbations for which the courses of systemic corticosteroids are separated by 7 or 
more days will be counted as separate exacerbations.  
Rate ratios for each GB001 group versus placebo, corresponding 95% CIs, and p-values will be 
provided from the model.  In addition, the rate ratios and corresponding 95% CIs for the 3 
pairwise comparisons among each of the GB001 treatment groups will be provided (60 mg vs 
20 mg, 60 mg vs 40 mg, 40 mg vs 20 mg). Lastly, percentage reductions and corresponding 95% 
CIs will also be provided. 
A sensitivity analysis will be performed to include asthma exacerbations that were treated with 
an intramuscular (IM) injection of systemic corticosteroids for less than 3 days.  In this analysis, 
a severe asthma exacerbation will be defined as deterioration of asthma that leads to the use of oral 
or intravenous systemic corticosteroids for at least 3 days, the use of IM systemic corticosteroids for 
at least 1 day, hospitalization, or an Emergency Department visit.  
Lastly, analyses of annualized rate of severe exacerbations will also be presented for the primary 
definition of severe asthma exacerbation by various time periods (Baseline to Week 12, Week 12 
to Week 24, and Baseline through the Follow-up Visit [Week 28]) in order to elucidate onset and 
durability of effect over time. 
This data will also be presented in a by-subject data listing. 
8.3.3. 
Tertiary/Exploratory Analyses 
The tertiary/exploratory endpoints are listed in Table 1 and will be analyzed as described below. 
8.3.3.1. 
PRO Endpoints 
8.3.3.1.1. Proportion of Subjects with a ≥ 0.5 Decrease in ACQ-5 Score from Baseline 
The proportion of subjects with a ≥ 0.5 decrease from baseline in ACQ-5 score at any time post-
baseline by Week 24 will be analyzed in the subset of the ITT population who have a non-
missing baseline value and at least one post-baseline value. Logistic regression modeling will be 
used to compare each GB001 group with placebo as for the primary endpoint. ORs, 
corresponding asymptotic 95% CIs along with the absolute differences and corresponding 95% 
CIs, and p-values will be summarized for each GB001 group versus placebo. Percentage 
reductions and corresponding 95% CIs will also be provided.  
The number and proportion of subjects with a ≥ 0.5 decrease from baseline in ACQ-5 score and 
corresponding 95% CIs will also be summarized by visit. 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 37 of 47 
8.3.3.1.2. Change from Baseline in AQLQ-S 
The AQLQ-S is a disease-specific, self-administered quality of life (QOL) questionnaire 
developed to evaluate the impact of asthma on the subject’s QOL (Juniper, 1993). The 
questionnaire contains 32 items in 4 domains with a 2-week recall period: activity limitations (11 
items), symptoms (12 items), emotional function (5 items), and environmental stimuli (4 items). 
Additionally, each of the 32 responses are averaged to produce an overall QOL score. Responses 
are scored on a seven-point scale with a value of 1 indicating total impairment and 7 indicating 
no impairment. The MCID is 0.5 points (Juniper, 1994). 
Overall and domain scores will be derived by taking the average of the item responses at each 
visit. The activity limitations and symptoms domain scores will only be derived if there is ≤ 1 
missing item response per domain. The emotional function and environmental stimuli domain 
scores will only be derived if there are no missing item responses per domain. Overall score will 
only be derived if all 4 domain scores are non-missing. Overall and domain scores will be 
summarized by visit.  
Change from baseline to Week 24 in AQLQ-S will be analyzed using an ANCOVA model 
without MI. Covariate adjustment will be the same as for the primary endpoint except that 
baseline pre-bronchodilator FEV1 will be replaced with baseline AQLQ-S. LS means will be 
reported along with SEs and corresponding 95% CIs, and differences between treatment groups 
reported with LS means, SEs, corresponding 95% CIs, and p-values. Results will be presented 
for the overall score only. 
AQLQ-S overall and domain scores will also be presented in a by-subject data listing. 
8.3.3.1.3. Change from Baseline in SNOT-22 
SNOT-22 is a QOL instrument to assess the impact of chronic rhinosinusitis and utilizes a 
2-week recall period (Hopkins, 2009). The questionnaire will only be completed by subjects with 
a prior history of sinusitis, nasal polyps, or allergic rhinitis to assess whether GB001 has an 
impact on this common comorbidity in patients with asthma. 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 with the total global score ranging from 0 to 110. The global MCID is 8.9. 
Overall and domain scores will be derived by taking the sum of the non-missing item responses 
at each visit. Overall and domain scores will be summarized by visit. 
Change from baseline to Week 24 in SNOT-22 will be analyzed using an ANCOVA model 
without MI. Covariate adjustment will be the same as for the primary endpoint except that 
baseline pre-bronchodilator FEV1 will be replaced with baseline SNOT-22. LS means will be 
reported along with SEs and corresponding 95% CIs, and differences between treatment groups 
reported with LS means, SEs, corresponding 95% CIs, and p-values. Results will be presented 
for the overall score only. 
Subgroup analyses will be performed for the following:  
• Subjects with sinusitis (regardless of nasal polyps) 
• Subjects with sinusitis and nasal polyps 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 38 of 47 
• Subjects with sinusitis and without nasal polyps 
SNOT-22 overall and domain scores will also be presented in a by-subject data listing. 
8.3.3.1.4. Change from Baseline in Hair-Loss Assessment 
A visual scale (Norwood classification for male subjects and Savin classification for female 
subjects) to characterize the degree of scalp hair loss at baseline and at the end of the study will 
be used (Gupta, 2016). This information will be complemented with a modified questionnaire to 
assess patient perceptions of scalp hair growth at the end of the study. This questionnaire 
includes 2 simple questions to describe possible scalp hair growth changes during the study 
period. 
Cross tabulations of the Baseline assessment versus the Week 24 assessment will be presented 
for the Norwood classification for males and Savin classification for females separately. 
Hair-loss assessment data will also be presented in a by-subject data listing. 
8.3.3.2. 
Additional Markers of Asthma Control 
8.3.3.2.1. Change from Baseline in Daily Rescue Medication Use, Daily Asthma Symptom 
Scores, and Awakening at Night Due to Asthma Symptoms Requiring Rescue 
Medication Use 
Rescue medications include the study-provided salbutamol/albuterol or any other short-acting 
bronchodilator. All rescue medication use is to be captured in an eDiary. 
Change from baseline to Week 24 in daily rescue medication use, daily asthma symptoms scores, 
and awakening at night due to asthma symptoms requiring rescue medication use will be 
analyzed using an ANCOVA model without MI.  Covariate adjustment is the same as the 
primary endpoint except that baseline pre-bronchodilator FEV1 will be replaced with baseline 
rescue medication use, baseline daily symptom score, or baseline awakening at night due to 
asthma symptoms requiring rescue medication use, depending on the endpoint of interest. 
Daily rescue medication use is collected as the number of puffs during the past 24 hours.  The 
baseline rescue medication value is defined as the mean number of puffs over the last 7 days of 
the Run-in including the value on Day 1 and Week 24 is defined as the mean number of puffs 
over the last 7 days prior to Week 24 including the value on the day of the Week 24 visit.  
Similarly, the value at all other post-baseline visits is defined as the mean number of puffs over 
the last 7 days prior to that visit including the day of the visit. 
Daily asthma symptom score over the previous 24 hours is assessed by subjects using a 6-point 
scale, with higher values indicating greater symptom severity, and is captured in the same eDiary 
as rescue medication use.  Subjects also record the number of times they had awakening at night 
due to asthma symptoms requiring rescue medication use in this same eDiary. 
Baseline and post-baseline visit values for daily symptom scores and awakening at night are 
defined as for daily rescue medication use.  In order for the mean to be calculated at a visit, 4 out 
of the 7 days must have non-missing values.  If < 4 of 7 days are available, the mean is 
considered missing. 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 39 of 47 
Actual values and change from baseline values will be summarized by visit. Differences in 
means, SEs, and corresponding 95% CIs constructed from ANOVA models adjusting for 
treatment group only will also be presented.  These data will also be presented in by-subject data 
listings. 
8.3.3.3. 
Biomarkers 
8.3.3.3.1. FeNO 
Actual values, change from baseline values, and percent change from baseline values will be 
summarized by visit. LS means, SEs, and corresponding 95% CIs for each treatment group and 
differences in LS means, SEs, and corresponding 95% CIs for each GB001 group versus placebo 
will be constructed from ANCOVA models without MI for both change and percent change from 
baseline to Week 24. The models will include covariates for treatment group and baseline FeNO. 
FeNO data will also be presented in a by-subject data listing. 
8.3.3.3.2. Sputum Eosinophils and Neutrophils 
As sputum eosinophils and neutrophils are known to follow a log-normal distribution, analyses 
will be based on a log10-transformed scale, with results back-transformed to obtain the following 
statistics: 
• Baseline geometric means and % coefficients of variation (CV), and corresponding 
95% CIs by treatment group 
• Week 24 geometric means, % CV, and corresponding 95% CIs by treatment group 
• Within-treatment group geometric mean ratios (GMRs) for LS means for change 
from baseline to Week 24, using an ANCOVA model adjusting for log of baseline 
value, SEs, and corresponding 95% CIs  
• Percent reduction in the above within-treatment group GMRs for LS means for 
change from baseline to Week 24 for each GB001 group versus placebo, 
corresponding 95% CIs, and p-values from the ANCOVA model 
Sputum eosinophils and neutrophils will also be presented in a by-subject data listing. 
8.3.3.4. 
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 
% 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. 
PK concentrations will also be presented in a by-subject data listing. 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 40 of 47 
8.4. 
Examination of Subgroups 
Subgroup analyses of the primary and two secondary (ACQ-5 score and pre-bronchodilator 
FEV1) efficacy endpoints will be performed for all of the subgroups specified below. In addition, 
subgroup analyses of the secondary efficacy endpoint of annualized rate of severe asthma 
exacerbations will also be performed for select subgroups as specified below. For any subgroup 
level that does not comprise ≥ 10% of the ITT population, the analyses based on the models will 
not be performed. The subgroups of interest are described below. 
Demographic and general baseline characteristic subgroups: 
• Age (years; < 65, ≥ 65) 
• Sex (male, female) 
• BMI (kg/m2; < 30, ≥ 30) 
• Baseline ICS dose ([per randomization and per actual value]; medium, high, 
including comparison of GB001 medium to Placebo high) 
• Region (North America, Eastern Europe, Western Europe) 
• Total number of exacerbations in the past 12 months (1, > 1)  
Efficacy-related baseline characteristic subgroups: 
• Pre-bronchodilator percent predicted FEV1 at Screening (%; < 60, ≥ 60) 
• ACQ-5 score at Baseline (< 1.5, ≥ 1.5) 
Biomarker baseline characteristic subgroups: 
• Blood eosinophils at Baseline (GI/L; < 0.20, ≥ 0.20; < 0.25, ≥ 0.25 [including for 
annualized rate of severe asthma exacerbations]; < 0.30, ≥ 0.30) 
• FeNO at Baseline (ppb; < 25, ≥ 25 [including for annualized rate of severe asthma 
exacerbations]; < 30, ≥ 30; < 35, ≥ 35; < 50, ≥ 50) 
• Blood eosinophils and FeNO at Baseline ([blood eosinophils < 0.25 GI/L and FeNO 
< 25 FeNO ppb] vs [blood eosinophils ≥ 0.25 GI/L and/or FeNO ≥ 25 ppb] 
{including for annualized rate of severe asthma exacerbations}; repeat for 0.25 vs 30, 
0.25 vs 35, and 0.25 vs 50) 
• Blood eosinophils and FeNO at Baseline ([blood eosinophils < 0.25 GI/L and FeNO 
< 25 FeNO ppb] vs [blood eosinophils < 0.25 GI/L and FeNO ≥ 25 ppb] vs [blood 
eosinophils ≥ 0.25 GI/L and FeNO < 25 ppb] vs [blood eosinophils ≥ 0.25 GI/L and 
FeNO ≥ 25 ppb]; including for annualized rate of severe asthma exacerbations) 
• IgE (IU/mL; normal [≤ 158], high [> 158]) 
• 25-Hydroxyvitamin D at Baseline (ng/mL; ≤ 20, > 20) 
• 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) 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 41 of 47 
Models used for the subgroup analyses will be the same as those used for the primary and 
secondary efficacy endpoints as specified in Section 8.3.1 and Section 8.3.2.1 with covariates for 
the subgroup (if different than the aforementioned covariates i.e. baseline ICS dose (medium or 
high) at randomization and region; for the efficacy-related baseline characteristic subgroups, 
baseline pre-bronchodilator FEV1 or baseline ACQ-5 score will be replaced with a categorical 
subgroup variable) and treatment group by subgroup interaction added.  If the model does not 
converge, a reduced model including only treatment group, ICS dose at randomization, and 
region will be used. 
Heterogeneity of treatment effect across different levels of each subgroup will be evaluated by 
presenting p-values for the treatment by subgroup interaction. The interaction term tests whether 
the treatment effect is significantly different across different levels of the subgroup, between 
males and females, for example. If a subgroup variable has more than two levels then the least 
severe level (where applicable) will be used as the reference subgroup, and the test will assess 
whether the treatment effect in the more severe levels differs from that in the reference subgroup. 
Forest plots of the treatment effect estimates and corresponding 95% CIs from the subgroup 
analyses will be provided. 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 42 of 47 
9. 
SAFETY EVALUATION 
9.1. 
Adverse Events 
Verbatim AE terms will be coded to a SOC and PT using the Medical Dictionary for Regulatory 
Activities (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 by subject, not event, and at 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 including asthma worsening-related 
terms; a SAE excluding asthma worsening-related terms; 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 
• AEs with Incidence ≥ 5% in Any Treatment Group by PT   
• Incidence of SAEs by SOC and PT Including Asthma Worsening-Related Terms 
• Incidence of SAEs by SOC and PT Excluding Asthma Worsening-Related Terms  
• 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 
• Incidence of Liver Chemistry AEs by PT 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 43 of 47 
• 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 and hematology parameters 
summarizing shifts from baseline to high and low at any time post-baseline based on laboratory 
normal ranges. A shift table will also be presented for urinalysis parameters summarizing shifts 
from baseline to positive at any time post-baseline based on laboratory normal ranges. 
A summary of maximum post-baseline values > 1.0, > 1.5, and > 3.0 GI/L for blood eosinophils 
will be presented.  
Summaries of maximum post-baseline values for liver chemistry parameters (alanine 
aminotransferase [ALT], aspartate aminotransferase [AST], concurrent ALT/AST and total 
bilirubin, total bilirubin, direct bilirubin, indirect bilirubin, alkaline phosphatase, and gamma-
glutamyl transferase [GGT]) 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 
• 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 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 44 of 47 
Laboratory parameters will also be presented in by-subject data listings. 
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 4: 
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, 
QT interval (uncorrected), Fridericia's correction formula for QT interval (QTcF), Bazett’s 
correction formula for QT interval (QTcB), 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. 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 45 of 47 
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. 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 46 of 47 
10. 
REFERENCES 
Akaike, H. (1973). Information theory and an extension of the maximum likelihood principle. 
Second International Symposium on Information Theory, 267-281. 
 
Allison, P. (2005). Imputation of categorical variables with PROC MI. Presented at 30th 
Meeting of SAS User Group International, April 10-13. Philadelphia, PA. 
 
Armitage, P. (1955). Tests for linear trends in proportion and frequencies. Biometrics, 11, 375-
386. 
 
Brookmeyer R, C. J. (1982). A confidence interval for the median survival time. Biometrics, 29-
41. 
 
Cochran, W. G. (1954). Some methods of strengthening the common x2 tests. Biometrics, 10, 
417-451. 
 
FDA (2020).  FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-
19 Pandemic. Guidance for Industry, Investigators, and Institutional Review Boards. Published 
March 2020, Updated 02 April 2020. Available from: 
https://www.fda.gov/media/136238/download. 
 
EMA (2020). Guidance on the Management of Clinical Trials during the COVID-19 
(Coronavirus) pandemic. Version 2 (27/03/2020) Published 27 March 2020. Amsterdam, The 
Netherlands. Available from: https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-
10/guidanceclinicaltrials_covid19_en.pdf.   
 
EMA (2020). Points to consider on implications of Coronavirus disease (COVID-19) on 
methodological aspects of ongoing clinical trials. Committee for Medicinal Products for Human 
Use (CHMP). EMA/158330/2020 Published 25 March 2020. Amsterdam, The Netherlands. 
Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/points-consider-
implications-coronavirus-disease-covid-19-methodological-aspects-ongoing-clinical_en.pdf. 
 
Gupta, M. a. (2016). Classifications of Patterned Hair Loss: A Review. J Cutan Aesthet Surg, 
9(1), 3-12. 
 
Hopkins, C. G. (2009). Psychometric validity of the 22-item Sinonasal Outcome Test. Clin 
Otolaryngol , 34(5), 447-454. 
 
ICH Harmonised Tripartite Guideline: Statistical Principles for Clinical Trials E9. Step 4. 1998. 
(n.d.). Retrieved from https://database.ich.org/sites/default/files/E9_Guideline.pdf 
 
ICH Harmonised Tripartite Guideline: Structure and content of clinical study reports E3. Step 4. 
1995. (n.d.). Retrieved from https://database.ich.org/sites/default/files/E3_Guideline.pdf 
 
Juniper, E. F. (1993). Measuring quality of life in asthma. Am Rev Respir Dis, 147(4), 832-838. 
 


GB001 
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol No. GB001-2001 
 
 
 
 
 
      11 April 2020 
Version: GB001-2001_Final_Statistical_Analysis_Plan_v1.0.doc 
 
Page 47 of 47 
Juniper, E. F. (1994). Determining a minimal important change in a disease-specific Quality of 
Life Questionnaire. J Clin Epidemiol, 47(1), 81-87. 
 
Juniper, E. F. (2005). Measurement properties and interpretation of three shortened versions of 
the asthma control questionnaire. Respir Med, 99(5), 553-558. 
 
Kenward, M. G. (1997). Small sample inference for fixed effects from restricted maximum 
likelihood. Biometrics, 53, 983-997. 
 
Merz. (2014). Drug Saf, 37(Suppl 1), S33-S45. 
 
Newcombe, R. G. (1998). Interval Estimation for the Difference Between Independent 
Proportions: Comparison of Eleven Methods. Statistics in Medicine, 17, 873-890. 
 
Rubin, D.B. (1987), Multiple Imputation for Nonresponse in Surveys, New York: John Wiley & 
Sons, Inc. 
 
Schafer, J.L. (1997), Analysis of Incomplete Multivariate Data, New York: Chapman and Hall. 
 
Wilson, E. B. (1927). Probable inference, the law of succession, and statistical inference. J. 
Amer. Stat. Assoc., 22, 209-212.