A Randomised, Double-blind, Parallel Group Phase III Study to Assess the Efficacy and Safety of 100 mg SC Depemokimab in Patients With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) - ANCHOR-1 (depemokimAb iN CHrOnic Rhinosinusitis)
Phase: PHASE3
Conditions: Nasal Polyps
Sponsor: GlaxoSmithKline

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GSK group of companies  
 
Protocol Amendment 5 Final 
26 Jun 2024 
1 
TITLE PAGE 
Protocol Title: A randomised, double-blind, parallel group Phase III study to assess the 
efficacy and safety of 100 mg SC depemokimab in patients with chronic rhinosinusitis 
with nasal polyps (CRSwNP) – ANCHOR-1 (depemokimAb iN CHrOnic Rhinosinusitis) 
Protocol Number: 217095/Amendment 5 
Regulatory Agency Identifying Number(s): 
Registry 
ID 
IND 
146742 
EudraCT 
2021-005037-16 
Compound Number or Name: GSK3511294 (Depemokimab) 
Approval Date: 
26 Jun 2024 
Brief Title: Efficacy and safety of subcutaneous depemokimab in patients with chronic 
rhinosinusitis with nasal polyps 
Study Phase: Phase 3 
Sponsor Name and Legal 
Registered Address: 
 
GSK Research & Development Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
Sponsor Signatory: 
Angela Davis, MD 
Sr Clinical Development Director, 
Clinical Science Respiratory 
GSK 
Medical Monitor Name and Contact Information can be found in the Study Reference 
Manual. 
©2024 GSK group of companies or its licensor. All rights reserved. Unauthorized 
copying or use of this information is prohibited. 

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
Document Identifier 
Amendment 5 
26 Jun 2024 
TMF-19443864 
Amendment 4 
12 March 2024 
TMF-18580353 
Amendment 3 
18 October 2023 
TMF-16242628 
Amendment 2 
26 October 2022 
TMF-14934311 
Protocol Clarification Letter 
08 July 2022 
TMF-14822401 
Protocol Clarification Letter 
29 April 2022 
TMF-14646867 
Amendment 1 
09 February 2022 
TMF-14446861 
Protocol Clarification Letter 
07 January 2022 
TMF-14395957 
Original Protocol 
24 November 2021 
TMF-13802260 
Amendment 5 (26 Jun 2024) 
Overall rationale for the current Amendment: The protocol has been amended to 
update the primary and secondary estimand strategy to handle the initiation of 
medications that may modulate the disease course of CRSwNP intercurrent event with a 
composite strategy in alignment with FDA guidelines [FDA, 2023]. The previously 
defined primary estimand, which handled this intercurrent event with a treatment policy 
strategy, becomes a supplementary estimand to the primary estimand for the co-primary 
endpoints and to the secondary estimand for the pooled secondary endpoints related to 
nasal surgery. The pooled secondary endpoints related to nasal surgery have an additional 
supplementary estimand to handle the initiation of medication that may modulate the 
disease course of CRSwNP with a hypothetical strategy to reflect global differences in 
availability of biologics for CRSwNP. Additionally, the definition of non-continuous 
endpoints has been expanded to refer to the presence or absence of intercurrent events 
being handled with a composite strategy in alignment with the estimand framework. 
LIST OF MAIN CHANGES IN THE PROTOCOL AND THEIR RATIONALE: 
Section # and title  
Description of change  
Brief rationale  
Section 1.1. Synopsis, 
Section 3.2. Objectives and 
Endpoints for Pre-
specified Pooled Analysis 
Across Studies 217095 
(This Study) and 218079 
(Replicate Study) 
Non-continuous (binary and time-to-event) 
endpoints including Other efficacy endpoints 
and Pooled Secondary and Other efficacy 
endpoints have been expanded to refer to the 
presence or absence of intercurrent events 
being handled with a composite strategy. 
To reflect the composite 
strategy in the endpoint 
definition, in alignment with the 
estimand framework. 
Section 1.1. Synopsis, 
Section 3.1. Objectives and 
Endpoints and 
Section 8.2.6.1. Sino-Nasal 
Outcome Test (SNOT-22) 
Questionnaire  
The SNOT-22 responder definition has been 
corrected to require a decrease in score of 
“≥8.9” instead of “>8.9”.  
To align with the published 
clinically meaningful 
difference.  
Section 1.1. Synopsis, 
Section 3.2. Objectives and 
Endpoints for Pre-
specified Pooled Analysis 
The asthma control objectives have been 
corrected to describe the asthma population 
with an ACQ-5 score of >0.75 as having 
To more accurately describe 
the asthma population in 
alignment with published 

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Section # and title  
Description of change  
Brief rationale  
Across Studies 217095 
(This Study) and 218079 
(Replicate Study)  
“partially or not well controlled” asthma 
instead of “uncontrolled” asthma.  
interpretations of the ACQ-5 
score.  
Section 1.1. Synopsis and 
Section 3.2 Objectives and 
Endpoints for Pre-
specified Pooled Analysis 
Across Studies 217095 
(This Study) and 218079 
(Replicate Study)  
Additional pooled other endpoint: Number of 
courses of antibiotics to treat sinus-related 
infection up to Week 52  
To capture the results of these 
data as an endpoint.  
Section 1.3. Schedule of 
Activities (SoA)  
The recall period for the PGIS has been 
corrected from “the last week” to “the last 
4 weeks”.  
To align the recall period as 
described in Section 8.2.6.2.  
Section 2.2. Introduction  Replaced references to Clinical Study 
Reports with the published articles.  
To cite published data.  
Section 3.3. Primary 
Estimands, Section 3.4. 
Secondary Estimands and 
Section 3.5. Secondary 
Estimands for Prespecified 
Pooled Analysis Across 
Studies 217095 (This 
Study) and 218079  
The primary estimand has been updated to 
handle the initiation of medications that may 
modulate the disease course of CRSwNP 
intercurrent event with a composite strategy, 
in which participants who experience the 
intercurrent event are considered to have an 
unfavorable outcome.  
To align with FDA guidelines 
on developing drugs for 
treatment of CRSwNP.  
Section 3.3. Primary 
Estimands  
The previously defined primary estimand, in 
which all changes in background medication 
or start of a prohibited medication (including 
those medications that may modulate the 
disease course of CRSwNP) to be handled 
with a treatment policy strategy, becomes a 
supplementary estimand to the primary 
estimand for the co-primary endpoints.  
To align with FDA guidelines 
on developing drugs for 
treatment of CRSwNP.  
Section 3.5 Secondary 
Estimands for Pre-
specified Pooled Analysis 
Across Studies 
The estimand strategy has been updated to 
handle the initiation of medications that may 
modulate the disease course of CRSwNP 
intercurrent event with a composite strategy, 
in which participants who experience the 
intercurrent event are considered to have an 
unfavorable outcome.  
The previously defined primary estimand, in 
which all changes in background medication 
or start of a prohibited medication (including 
those medications that may modulate the 
disease course of CRSwNP) to be handled 
with a treatment policy strategy, becomes a 
supplementary estimand to the primary 
estimand for the pooled surgery endpoints. 
And additional supplemental estimand was 
added to handle the initiation of medications 
that may modulate the disease course of 
CRSwNP with a hypothetical strategy  
To align with FDA guidelines 
on developing drugs for 
treatment of CRSwNP.  
To reflect global differences in 
availability of biologics for 
CRSwNP 

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Section # and title  
Description of change  
Brief rationale  
gSection 9.3.1. Co-Primary 
and Key Secondary 
Endpoint(s) Analyses  
Addition of a tipping point sensitivity analysis 
for the coprimary endpoints.  
To explore the impact of 
missing data.  
Section 9.5 Sample Size 
Determination 
Updates to power calculations. 
To account for updated 
estimand strategy  
All sections  
Other minor editorial corrections.  
NA  

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TABLE OF CONTENTS 
PAGE 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 2 
LIST OF MAIN CHANGES IN THE PROTOCOL AND THEIR RATIONALE: ............ 2 
LIST OF ABBREVIATIONS AND TRADEMARKS ......................................................... 13 
1. 
PROTOCOL SUMMARY ........................................................................................ 25 
1.1. 
Synopsis ..................................................................................................... 25 
1.2. 
Schema ...................................................................................................... 32 
1.3. 
Schedule of Activities (SoA) ........................................................................ 32 
2. 
INTRODUCTION .................................................................................................... 43 
2.1. 
Study Rationale .......................................................................................... 43 
2.2. 
Background ................................................................................................ 43 
2.2.1. 
The Role of Anti IL5 Therapy in CRSwNP.................................... 45 
2.2.1.1. 
Depemokimab (GSK3511294) Long-Acting IL-
5 ................................................................................. 46 
2.3. 
Benefit/Risk Assessment ............................................................................ 47 
2.3.1. 
Risk Assessment ......................................................................... 48 
2.3.2. 
Benefit Assessment ..................................................................... 55 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 55 
3. 
OBJECTIVES, ENDPOINTS AND ESTIMANDS .................................................... 56 
3.1. 
Objectives and Endpoints ........................................................................... 56 
3.2. 
Objectives and Endpoints for Pre-specified Pooled Analysis Across 
Studies 217095 (This Study) and 218079 (Replicate Study) ....................... 59 
3.3. 
Primary Estimands ...................................................................................... 61 
3.4. 
Secondary Estimands ................................................................................. 62 
3.5. 
Secondary Estimands for Pre-specified Pooled Analysis Across 
Studies 217095 (This Study) and 218079 ................................................... 62 
3.5.1. 
Secondary estimand for surgery endpoints .................................. 62 
3.5.2. 
Secondary estimand for systemic steroids endpoint .................... 64 
3.5.3. 
Secondary estimand for ACQ-5 ................................................... 65 
4. 
STUDY DESIGN .................................................................................................... 66 
4.1. 
Overall Design ............................................................................................ 66 
4.2. 
Scientific Rationale for Study Design .......................................................... 67 
4.2.1. 
Participant Input into Design ........................................................ 67 
4.3. 
Justification for Dose .................................................................................. 68 
4.4. 
End of Study Definition ............................................................................... 70 
5. 
STUDY POPULATION ........................................................................................... 70 
5.1. 
Inclusion Criteria ......................................................................................... 71 
5.2. 
Exclusion Criteria ........................................................................................ 73 
5.3. 
Randomization Criteria ............................................................................... 76 
5.4. 
Lifestyle Considerations .............................................................................. 77 
5.5. 
Screen/Run-in Failures ............................................................................... 77 
5.6. 
Criteria for Temporarily Delaying Randomization / Initiation of Study 
Intervention Administration ......................................................................... 77 

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6. 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY .............................. 78 
6.1. 
Study Intervention(s) Administered ............................................................. 78 
6.1.1. 
Medical Devices ........................................................................... 79 
6.1.2. 
Treatment Assignment ................................................................. 79 
6.2. 
Preparation, Handling, Storage and Accountability ..................................... 79 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................... 80 
6.3.1. 
Controlled Early Access to Unblinded PK and PKPD Data .......... 81 
6.4. 
Study Intervention Compliance ................................................................... 81 
6.5. 
Dose Modification ....................................................................................... 81 
6.6. 
Continued Access to Study Intervention after the End of the Study ............ 81 
6.7. 
Treatment of Overdose ............................................................................... 81 
6.8. 
Prior and Concomitant Therapy .................................................................. 82 
6.8.1. 
Permitted CRSwNP and Asthma Medications .............................. 82 
6.8.2. 
Prohibited Medications ................................................................. 83 
6.8.3. 
COVID-19 Vaccines and treatments ............................................ 84 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 84 
7.1. 
Discontinuation of Study Intervention .......................................................... 84 
7.1.1. 
Specified Study Intervention Discontinuation Criteria ................... 85 
7.1.2. 
Liver Chemistry Stopping Criteria ................................................ 85 
7.1.3. 
QTc Stopping Criteria .................................................................. 87 
7.1.4. 
Temporary Discontinuation .......................................................... 88 
7.1.5. 
COVID-19 Testing ....................................................................... 88 
7.2. 
Participant Discontinuation/Withdrawal from the Study ............................... 88 
7.3. 
Lost to Follow Up ........................................................................................ 89 
7.4. 
Criteria for Follow-up of Potential Type III Hypersensitivity (Immune 
Complex Disease /Vasculitis) ...................................................................... 90 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 91 
8.1. 
Administrative and general/baselines procedures ....................................... 91 
8.1.1. 
Collection of demographic data .................................................... 91 
8.1.2. 
Medical history ............................................................................. 92 
8.2. 
Efficacy Assessments ................................................................................. 92 
8.2.1. 
Endoscopic NP Score .................................................................. 92 
8.2.2. 
Symptoms .................................................................................... 92 
8.2.2.1. 
Individual Symptoms Verbal Response Scale 
(VRS) ......................................................................... 92 
8.2.2.2. 
Overall Visual Analogue Scale (VAS) 
Symptoms Score ........................................................ 93 
8.2.2.3. 
Nasal Obstruction Symptoms VAS ............................. 93 
8.2.3. 
Computed Tomography (CT) Scan .............................................. 93 
8.2.4. 
NP Surgery .................................................................................. 94 
8.2.5. 
Corticosteroid Medication ............................................................ 94 
8.2.6. 
Health-Related Quality of Life (HRQoL) Assessments ................. 94 
8.2.6.1. 
Sino-Nasal Outcome Test (SNOT-22) 
Questionnaire ............................................................. 95 
8.2.6.2. 
Patient Global Impression of Change and 
Severity of Nasal Polyp Symptoms ............................. 95 
8.2.7. 
For Asthmatic Participants Only: .................................................. 95 
8.2.7.1. 
Asthma Control Questionnaire (ACQ-5) ...................... 95 
8.2.7.2. 
Asthma Exacerbations ................................................ 96 

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8.3. 
Safety Assessments ................................................................................... 96 
8.3.1. 
Physical Examinations ................................................................. 96 
8.3.2. 
Vital Signs .................................................................................... 96 
8.3.3. 
Electrocardiograms ...................................................................... 97 
8.3.4. 
Clinical Safety Laboratory Tests .................................................. 97 
8.3.5. 
Pregnancy Testing ....................................................................... 98 
8.4. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and Other 
Safety Reporting ......................................................................................... 98 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 99 
8.4.2. 
Method of Detecting AEs and SAEs ............................................. 99 
8.4.3. 
Follow-up of AEs and SAEs ....................................................... 100 
8.4.4. 
Regulatory Reporting Requirements for SAEs ........................... 100 
8.4.5. 
Pregnancy ................................................................................. 100 
8.4.6. 
Cardiovascular and Death Events .............................................. 101 
8.4.7. 
Disease-Related Events and/or Disease-Related 
Outcomes Not Qualifying as SAEs............................................. 101 
8.4.8. 
Adverse Events of Special Interest ............................................ 101 
8.4.9. 
Medical Device Deficiencies ...................................................... 102 
8.4.9.1. 
Time Period for Detecting Medical Device 
Deficiencies .............................................................. 102 
8.4.9.2. 
Follow-up of Medical Device Deficiencies ................. 102 
8.4.9.3. 
Prompt Reporting of Medical Device 
Deficiencies to the Sponsor ...................................... 103 
8.4.9.4. 
Regulatory Reporting Requirements for Device 
Deficiencies .............................................................. 103 
8.5. 
Pharmacokinetics ..................................................................................... 103 
8.6. 
Pharmacodynamics/Biomarkers ............................................................... 103 
8.6.1. 
Blood Eosinophil Counts ............................................................ 104 
8.6.2. 
Total IL-5 Levels ........................................................................ 104 
8.6.3. 
Complement, IgE and Inflammatory Biomarkers ........................ 104 
8.6.4. 
Exploratory Biomarkers .............................................................. 104 
8.6.4.1. 
Serum: Soluble Marker Analysis ............................... 105 
8.6.4.2. 
Whole Blood: Gene Expression Analysis 
(Transcriptomics) ...................................................... 105 
8.6.4.3. 
Nasal Samples ......................................................... 105 
8.6.4.3.1. 
Surgical ................................................ 105 
8.6.4.3.2. 
Nasal Biopsy ........................................ 105 
8.7. 
Genetics ................................................................................................... 106 
8.8. 
Immunogenicity Assessments ................................................................... 106 
8.9. 
Medical Resource Utilization and Health Economics ................................ 106 
8.9.1. 
Short Form-36 (SF-36) Questionnaire (Version 2) ..................... 106 
8.9.2. 
Work Productivity and Activity Impairment Questionnaire 
(WPAI) ....................................................................................... 107 
9. 
STATISTICAL CONSIDERATIONS ...................................................................... 108 
9.1. 
Statistical Hypotheses............................................................................... 108 
9.1.1. 
Multiplicity Adjustment ............................................................... 108 
9.2. 
Analysis Sets ............................................................................................ 110 
9.3. 
Statistical Analyses ................................................................................... 111 
9.3.1. 
Co-Primary and Key Secondary Endpoint(s) Analyses .............. 111 
9.3.2. 
Safety Analysis .......................................................................... 112 

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9.3.3. 
Pharmacokinetic Analysis .......................................................... 113 
9.3.4. 
Pharmacodynamic and 
Pharmacokinetic/Pharmacodynamic Analysis ............................ 113 
9.4. 
Interim Analysis ........................................................................................ 113 
9.5. 
Sample Size Determination ...................................................................... 114 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................. 115 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations .......................................................................................... 115 
10.1.1. 
Regulatory and Ethical Considerations ...................................... 115 
10.1.2. 
Financial Disclosure ................................................................... 116 
10.1.3. 
Informed Consent Process ........................................................ 116 
10.1.4. 
Recruitment Strategy ................................................................. 117 
10.1.5. 
Data Protection .......................................................................... 117 
10.1.6. 
Committees Structure ................................................................ 118 
10.1.7. 
Dissemination of Clinical Study Data ......................................... 118 
10.1.8. 
Data Quality Assurance ............................................................. 119 
10.1.9. 
Source Documents .................................................................... 120 
10.1.10. Study and site start and closure ................................................. 120 
10.1.11. Publication Policy ....................................................................... 121 
10.2. 
Appendix 2: Clinical Laboratory Tests ....................................................... 121 
10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ..................................... 123 
10.3.1. 
Definition of AE .......................................................................... 123 
10.3.2. 
Definition of SAE ........................................................................ 124 
10.3.3. 
Definition of Cardiovascular Events ........................................... 125 
10.3.4. 
Recording and Follow-Up of AE and SAE .................................. 126 
10.3.5. 
Reporting of SAE to GSK ........................................................... 128 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ..................................... 129 
10.4.1. 
Definitions: ................................................................................. 129 
10.4.2. 
Contraception Guidance: ........................................................... 130 
10.5. 
Appendix 5: Genetics ................................................................................ 132 
10.6. 
Appendix 6: Liver Safety: Required Actions and Follow-up 
Assessments ............................................................................................ 133 
10.6.1. 
Liver Chemistry Stopping Criteria and Required Follow-up 
Assessments ............................................................................. 133 
10.6.2. 
Liver Chemistry Increased Monitoring Criteria with 
Continued Study Intervention ..................................................... 136 
10.7. 
Appendix 7: AEs, ADEs, SAEs, SADEs, USADEs and Device 
Deficiencies: Definition and Procedures for Recording, Evaluating, 
Follow-up, and Reporting in Medical Device Studies ................................ 137 
10.7.1. 
Definition of Medical Device AE and ADE .................................. 137 
10.7.2. 
Definition of Medical Device SAE, SADE and USADE ............... 137 
10.7.3. 
Definition of Device Deficiency ................................................... 138 
10.7.4. 
Recording and Follow-Up of AE and/or SAE and Device 
Deficiencies ............................................................................... 138 
10.7.5. 
Reporting of SAEs ..................................................................... 141 
10.7.6. 
Reporting of SADEs ................................................................... 141 
10.7.7. 
Reporting of Medical Device Deficiencies for Associated 
Person ....................................................................................... 142 
10.8. 
Appendix 8: Anaphylaxis Criteria .............................................................. 143 

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10.9. 
Appendix 9: Lund-Mackay CT score ......................................................... 143 
10.10. Appendix 10: Country-specific requirements ............................................. 144 
10.11. Appendix 11: Recommended Measures Related to COVID-19 
Pandemic.................................................................................................. 145 
10.11.1. Overall Rationale for this Appendix: ........................................... 145 
10.11.2. Study Procedures During COVID-19 Pandemic ......................... 145 
10.11.3. Protocol Defined Procedures/Visits: ........................................... 145 
10.11.4. Study Intervention: ..................................................................... 146 
10.11.5. Data Management/Monitoring: ................................................... 147 
10.11.6. Assessments that can be Conducted Outside Clinical 
Study Site: ................................................................................. 147 
10.12. Appendix 12: Protocol Amendment History ............................................... 147 
11. REFERENCES ..................................................................................................... 158 
 

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LIST OF TABLES 
PAGE 
Table 1 
Schedule of Activities Table ................................................................... 33 
Table 2 
Predicted Exposure for Depemokimab 100 mg SC Q26W Versus 
Measured Exposure in Phase 1 study 205722 and Measured 
Exposure with the NOAEL Dose (100 mg/kg, highest dose tested 
in the 26 weeks study in cynomolgus monkeys) ..................................... 69 
Table 3 
Description of Depemokimab and Placebo ............................................. 78 
Table 4 
Prohibited medications ........................................................................... 83 

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LIST OF FIGURES 
PAGE 
Figure 1 
Study Schematic .................................................................................... 32 
Figure 2 
Liver Chemistry Stopping Criteria Algorithm ........................................... 86 
Figure 3 
Liver Chemistry Increased Monitoring Algorithm with Continued 
Study Intervention for Participants with ALT ≥3x ULN but 
<8xULN and do not meet any of the liver stopping criteria...................... 87 
Figure 4 
Conceptualisation of Statistical Testing Strategy Across Studies 
217095 and 218079 ............................................................................. 109 

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LIST OF APPENDIX TABLES 
PAGE 
Appendix Table 1 
Protocol-Required Safety Laboratory Tests ............................... 122 
 

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LIST OF ABBREVIATIONS AND TRADEMARKS 
Abbreviations 
Abbreviation 
Definition 
ACQ-5 
Asthma Control Test 
ADA 
Anti-drug antibodies 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ALT 
Alanine aminotransferase 
ANA 
Antinuclear antibodies 
ANCA 
Antineutrophil cytoplasmic antibodies 
AUC 
Area under the curve 
CA 
Competent Authority 
CF 
Cystic fibrosis 
Cmax 
Maximum plasma concentration 
CONSORT 
Consolidated Standards of Reporting Trials 
CRS 
Chronic rhinosinusitis 
CRSwNP 
Chronic rhinosinusitis with nasal polyps 
CS(s) 
Corticosteroid(s) 
CT 
Computerised tomography 
CV 
Cardiovascular 
DNA 
Deoxyribonucleic acid 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
ECRS 
Eosinophilic chronic rhinosinusitis 
eDiary 
Electronic diary 

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Abbreviation 
Definition 
EGPA 
Eosinophilic granulomatosis with polyangiitis 
EPOS 
European Position Paper on Rhinosinusitis and Nasal Polyps 
ESS 
Endoscopic sinus surgery 
EW 
Early withdrawal 
FPFV 
First-participant-first-visit 
FTIH 
First-time-in-human 
GCSP 
Global Clinical Safety and Pharmacovigilance 
GGT 
Gamma-glutamyl transferase 
HES 
Hypereosinophilic Syndrome 
HIV 
Human immunodeficiency virus 
HRQoL 
Health-related quality of life 
ICF 
Informed consent form 
ICS/ETN 
Inhaled corticosteroids exhalation through nose 
ICSR 
Individual Case Safety Reports 
IDMC 
Independent Data Monitoring Committee 
IgG 
Immunoglobulin G 
IL-5 
Interleukin-5 
IL-5R 
Interleukin-5 receptor 
INCS 
Intranasal corticosteroid 
INR 
International normalised ratio 
IRT 
Interactive response technology 
IV 
Intravenous  
JESREC 
Japanese Epidemiological Survey of Refractory Eosinophilic Chronic 
Rhinosinusitis 

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Abbreviation 
Definition 
LMK 
Lund Mackay 
LTRA 
Leukotriene receptor antagonist 
mAb(s) 
Monoclonal antibody(ies) 
MCID 
Minimal clinically important difference 
MCS 
Mental component summary 
MedDRA 
Medical Dictionary for Regulatory Activities 
MPO 
Myeloperoxidase 
NAb 
Neutralising antibodies 
NP 
Nasal polyps 
OC 
Osteomeatal complex 
OCS 
Oral corticosteroid 
PCS 
Physical component summary 
PD 
Pharmacodynamic 
PFS 
Pre-filled safety syringe 
PGIC 
Patient Global Impression of Change  
PGIS 
Patient Global Impression of Severity  
PI 
Principal Investigator 
PK 
Pharmacokinetic  
PR3 
Anti-proteinase 3  
QTcB 
QT interval corrected for heart rate according to Bazett’s formula 
QTcF 
QT interval corrected for heart rate according to Fridericia’s formula 
RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SC 
Subcutaneous 

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Abbreviation 
Definition 
SCS 
Systemic corticosteroids 
SDAC 
Statistical Data Analysis Centre 
SF-36 
Short Form (36) Health Survey 
SGRQ 
St. George's Respiratory Questionnaire 
SNOT-22 
Sino-nasal Outcome Test 
SoA 
Schedule of activities 
SoC 
Standard of care 
SRM 
Study reference manual 
SSD 
Safety syringe device 
TB 
Tuberculosis 
ULN 
Upper limit of normal 
URTI 
Upper respiratory tract infection 
US 
The United States 
VAS 
Visual analogue scale 
VRS 
Verbal response scale 
WOCBP 
Woman of childbearing potential 
WONCBP 
Woman of non-childbearing potential 
WPAI 
Work Productivity and Activity Impairment Questionnaire 

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Terms 
Term 
Definition 
Adverse Drug Reaction 
An adverse event where a causal relationship 
between a medicinal product and the adverse event is 
at least a reasonable possibility, i.e., the relationship 
cannot be ruled out.  
a. 
In the context of a clinical trial, an ADR can be 
serious or non-serious. Serious ADRs may be 
subject to expedited reporting if they are 
considered unexpected (see SUSAR definition). 
b. For marketed products, ADRs are subject to 
expedited reporting within the country where 
they are authorized 
Auxiliary Medicinal Product 
(AxMP) 
a. 
Authorised AxMP 
b. Unauthorized AxMP 
Medicinal products used in the context of a clinical 
trial but not as investigational medicinal products, 
such as medicinal products used for background 
treatment, challenge agents, rescue medication, or 
used to assess end-points in a clinical trial. Auxiliary 
medicinal products should not include concomitant 
medications, that is medications unrelated to the 
clinical trial and not relevant for the design of the 
clinical trial. 
a. 
Medicinal product authorized in accordance with 
Regulation (EC) No 726/2004, or in any Member 
State concerned in accordance with Directive 
2001/83/EC, irrespective of changes to the 
labelling of the medicinal product. Safety 
reporting with regard to auxiliary medicinal 
products shall be made in accordance with 
Chapter 3 of Title IX of Directive 2001/83/EC. 
b. Medicinal product not authorized in accordance 
with Regulation (EC) No 726/2004. Safety 
reporting for unauthorised auxiliary medicinal 
products will follow the same processes and 
procedures as SUSAR safety reporting. 

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Term 
Definition 
Background treatment 
Type of medicinal product administered to each of 
the clinical trial participants, regardless of 
randomization group, to treat the indication that is the 
object of the study. Background treatment is 
generally considered to be the current standard care 
for the particular indication. In these trials, the IMP is 
given in addition to the background treatment and 
safety and efficacy are assessed. The protocol may 
require that the IMP plus the background treatment is 
compared with an active comparator or with placebo 
plus background treatment. 
Blinding 
A procedure in which 1 or more parties to the study 
are kept unaware of the intervention assignment in 
order to reduce the risk of biased study outcomes. 
The level of blinding is maintained throughout the 
conduct of the study, and only when the data are 
cleaned to an acceptable level of quality will 
appropriate personnel be unblinded or when required 
in case of a SAE. 
In a double-blind study, the participant, the 
investigator and sponsor staff who are involved in the 
treatment or clinical evaluation of the participants 
and the review or analysis of data are all unaware of 
the intervention assignment. 
Caregiver 
A ‘caregiver’ is someone who 
• 
lives in the close surroundings of a participant 
and has a continuous caring role or 
• 
has substantial periods of contact with a 
participant and is engaged in their daily health 
care (e.g., a relative of the participant, a nurse 
who helps with daily activities in case of 
residence in a nursing home). 
In the context of a clinical study, a caregiver could 
include an individual appointed to oversee and 
support the participant's compliance with protocol-
specified procedures. 

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Term 
Definition 
Certified copy 
A copy (irrespective of the type of media used) of the 
original record that has been verified (i.e. by a dated 
signature or by generation through a validated 
process) to have the same information, including data 
that describe the context, content, and structure, as 
the original. 
Co-administered (concomitant) 
products 
A product given to clinical trial participants as 
required in the protocol as part of their standard care 
for a condition which is not the indication for which 
the IMP is being tested and is therefore not part of the 
objective of the study. 
Combination product 
Combination product comprises any combination of  
• 
drug  
• 
device  
• 
biological product  
Each drug, device and biological product included in 
a combination product is a constituent part. 
Comparator 
Any product used as a reference (including placebo, 
marketed product, GSK or non-GSK) for an 
investigational product being tested in a clinical trial. 
This is any product that is being used to assess the 
safety, efficacy, or other measurable value against the 
test product (IMP). 
Decentralized Trial Platform 
A digital engagement technology allowing for the 
remote delivery and access to trials for participants, 
sites, and sponsors. 
Direct-from-Participant 
Shipments 
Home pickup of collected biological specimens, or 
pickup and return of unused/partially used/expired 
trial materials for return to investigator site. 
Direct-to-Participant 
Shipments 
Shipping of Investigational Product, lab kits, devices, 
etc., to the participant’s residence under secure and 
controlled conditions. 
eDiary 
Electronically registered patient data and automated 
data entries on, for example, a handheld mobile 
device, tablet or computer. 

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Term 
Definition 
Eligible 
Qualified for enrollment into the study based upon 
strict adherence to inclusion/exclusion criteria. 
Essential documents 
Documents which individually and collectively 
permit evaluation of the conduct of a study and the 
quality of the data produced. 
Home Healthcare Services 
Deployment of mobile health care professional(s) 
(nurses or phlebotomists) to perform study activities 
remotely. 
Intercurrent event 
Event occurring after study intervention initiation 
that affects either the interpretation or the existence 
of the measurements associated with the clinical 
question of interest. 
Intervention number 
A number identifying an intervention to a participant, 
according to intervention allocation. 
Investigational medicinal 
product 
An IMP is a pharmaceutical form of an active 
substance or placebo being tested or used as a 
reference in a clinical study, including products 
already with a marketing authorization but used or 
assembled (formulated or packaged) in a way 
different from the authorized form, or when used for 
an unauthorized indication, or when used to gain 
further information about the authorized form. 
Medicinal products with a marketing authorization 
are IMPs when they are to be used as the test 
substance, reference substance, or comparator in a 
clinical study, provided the requirement(s) in the 
definition is/are met. 
Investigator 
A person responsible for the conduct of the clinical 
study at a study site. If a study is conducted by a team 
of individuals at a study site, the investigator is the 
responsible leader of the team and may be called the 
principal investigator. 
The investigator can delegate study-related duties and 
functions conducted at the study site to qualified 
individual or party to perform those study-related 
duties and functions. 

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Term 
Definition 
Legally acceptable 
representative 
An individual, judicial or other body authorized 
under applicable law to consent on behalf of a 
prospective participant to the participant's 
participation in the clinical study. 
The terms legal representative or legally authorized 
representative are used in some settings. 
LSLV 
The date on which the last participant in a clinical 
study was examined or received an 
intervention/treatment to collect final data for the 
primary outcome measures, secondary outcome 
measures, and AEs (that is, the last participant’s last 
visit or LSLV). 
Medicinal products used to 
assess endpoints 
A product given to the participant in a Clinical Trial 
as a tool to assess a relevant clinical trial endpoint; it 
is not being tested or used as a reference in the 
clinical trial. 
NIMP/ AxMP 
A NIMP or AxMP is a medicinal product that is not 
classified as an IMP in a study, but may be taken by 
participants during the study, e.g., concomitant or 
rescue/escape medication used for preventive, 
diagnostic, or therapeutic reasons or medication 
given to ensure that adequate medical care is 
provided for the participant during a study. 
Participant 
Term used throughout the protocol to denote an 
individual who has been contacted to participate or 
who participates in the clinical study as a recipient of 
the study intervention (product(s)/control). 
Synonym: subject 
Participant number 
A unique identification number assigned to each 
participant who consents to participate in the study. 

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Term 
Definition 
Pharmacogenomics 
The ICH E15 Guidance for Industry defines 
pharmacogenomics as the “Study of variation of 
DNA and RNA characteristics as related to drug or 
treatment response.” 
Pharmacogenetics, a subset of pharmacogenomics, is 
“the study of variations in DNA sequence as related 
to drug response.” Pharmacogenomic biomarkers 
include germline (host) DNA and RNA as well as 
somatic changes (e.g., mutations) that occur in cells 
or tissues. 
Pharmacogenomic biomarkers are not limited to 
human samples but include samples from viruses and 
infectious agents as well as animal samples. The term 
pharmacogenomic experiment includes both the 
generation of new genetic or genomic (DNA and/or 
RNA) data with subsequent analysis as well as the 
analysis of existing genetic or genomic data to 
understand drug or treatment response (PK, safety, 
efficacy or effectiveness, mode of action). 
Proteomic and metabolomic biomarker research is 
not pharmacogenomics. 
Placebo 
An inactive substance or treatment that looks the 
same as, and is given in the same way as, an active 
drug or intervention/treatment being studied. 
Primary Completion Date 
The date on which the last participant in a clinical 
study was examined or received an intervention to 
collect final data for the primary outcome measure. 
Whether the clinical study ended according to the 
protocol or was terminated does not affect this date. 
For clinical studies with more than one primary 
outcome measure with different completion dates, 
this term refers to the date on which data collection is 
completed for all the primary outcome measures. 
Randomization 
Process of random attribution of intervention to 
participants to reduce selection bias. 
Remote visit 
This term refers to the visit conducted in the place 
other than the study site. 

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Term 
Definition 
Rescue medication 
Medicines identified in the protocol as those that may 
be administered to the participants when the efficacy 
of the IMP is not satisfactory, or the effect of the IMP 
is too great and is likely to cause a hazard to the 
patient, or to manage an emergency situation. 
Self-contained study 
Study with objectives not linked to the data of 
another study. 
Source data 
All information in original records and certified 
copies of original records of clinical findings, 
observations, or other activities in a clinical study 
necessary for the reconstruction and evaluation of the 
study. Source data are contained in source documents 
(original records or certified copies). 
Standard of Care 
Medicine(s) for a specific indication, or a component 
of the standard care for a particular medical 
indication, based on national and/or international 
consensus; there is no regulatory significance to this 
term. 
Products/regimens considered standard of care may 
differ country to country, depending on consensus in 
individual countries. 
Study completion date 
The date on which the last participant in a clinical 
study was examined or received an 
intervention/treatment to collect final data for the 
primary outcome measures, secondary outcome 
measures, and AEs (that is, the last participant's last 
visit or LSLV). 
Study intervention 
Term used throughout the clinical study to denote a 
set of investigational product(s) or marketed 
product(s) or placebo intended to be administered to 
a participant. 
Note: “Study intervention” and “study treatment” are 
used interchangeably unless otherwise specified. 
Study monitor 
An individual assigned by the sponsor and 
responsible for assuring proper conduct of clinical 
studies at 1 or more investigational sites. 

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Term 
Definition 
Subcohort 
A group of participants for whom specific study 
procedures are planned as compared to other 
participants or a group of participants who share a 
common characteristic (e.g., ages, vaccination 
schedule, etc.) at the time of enrollment. 
SUSAR 
Suspected Unexpected Serious Adverse Reaction; in 
a clinical trial, a serious adverse reaction that is 
considered unexpected, i.e., the nature or severity of 
which is not consistent with the reference safety 
information (e.g., Investigator's Brochure for an 
unapproved investigational medicinal product). All 
adverse drug reactions (ADRs) that are both serious 
and unexpected are subject to expedited reporting. 
Telemedicine 
The use of electronic information and 
telecommunications technologies (both video-based 
and audio-only) to facilitate remote health care 
delivery, participant and professional health-related 
education, public health and health administration. 
Virtual visit 
This term refers to study visits conducted using 
multimedia or technological platforms. 
TRADEMARK INFORMATION 
Trademarks of the GSK group of 
companies 
 
Trademarks not owned by the GSK 
group of companies 
Nucala 
 
Cinqair/Cinqaero 
 
 
Dupixent 
 
 
Fasenra 
 
 
Xolair 
 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title:  
A randomised, double-blind, parallel group Phase III study to assess the efficacy and 
safety of 100 mg SC depemokimab in patients with chronic rhinosinusitis with nasal 
polyps (CRSwNP) – ANCHOR-1 (depemokimAb iN CHrOnic Rhinosinusitis) 
Brief Title: Efficacy and safety of subcutaneous depemokimab in patients with chronic 
rhinosinusitis with nasal polyps 
Rationale: 
Interleukin-5 (IL-5) is the predominant cytokine in nasal polyps (NP) associated with 
tissue eosinophilia. IL-5 is increased in NP tissue of patients with chronic rhinosinusitis 
with nasal polyps (CRSwNP) compared with that in healthy controls and correlates with 
the degree of tissue eosinophilia. Reduction in eosinophils has been identified as a 
therapeutic strategy for numerous disorders. 
Several monoclonal antibodies (mAbs) targeting eosinophil inflammation have received 
marketing authorization for asthma with an eosinophilic phenotype, including three 
targeting either IL-5 or its receptor (IL-5R): mepolizumab (Nucala), reslizumab 
(Cinqair/Cinqaero) and benralizumab (Fasenra). All three, by utilizing blood eosinophils 
as a biomarker to predict patients likely to respond to therapy, have been shown to reduce 
asthma exacerbations and improve lung function and health-related quality of life 
(HRQoL) in patients with asthma with an eosinophilic phenotype. 
The recently completed Phase III study of mepolizumab in adults with CRSwNP 
(SYNAPSE, study 205687) demonstrated the efficacy of mepolizumab 100 mg SC by 
showing statistically significant and clinically meaningful improvement in the co-primary 
endpoints of total endoscopic nasal polyp score and symptoms of nasal obstruction 
associated with chronic rhinosinusitis (CRS) compared with placebo when administered 
every 4 weeks for up to 52 weeks in addition to standard of care (SoC) therapy. Nucala 
has been recently approved for the treatment of CRSwNP in a few countries including the 
United States and the EU. 
Depemokimab (GSK3511294) is an immunoglobulin G (IgG)-1 allotype three antibody 
with increased serum half-life. It blocks IL-5 binding to the IL-5 receptor complex, 
causing a reduction in the circulating population of eosinophils. The extended 
pharmacokinetic (PK) and pharmacology characteristics of depemokimab have been 
achieved by reducing clearance and increasing affinity for IL-5. This will potentially 
enable a single administration every 26 weeks, as opposed to the current regimen of 
every 4 weeks for mepolizumab. 

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Depemokimab is anticipated to confer a similar efficacy and benefit: risk profile as other 
IL-5 targeting mAbs, while being administered with a dosing interval of up to 6 months. 
As such, depemokimab may offer the convenience of an improved dosing schedule.  
This study is to assess the efficacy and safety, over a 52-week treatment period of 
depemokimab 100 mg SC +SoC given once every 26 weeks as add-on maintenance to 
participants with CRSwNP. 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
 
To evaluate the efficacy of 
depemokimab 100mg SC + SoC 
compared to placebo + SoC at 
Week 52 in participants with a 
diagnosis of CRSwNP  
Co-primary endpoints:  
a) Change from baseline in total endoscopic 
NP score at Week 52 (centrally read) 
b) Change from baseline in mean nasal 
obstruction score (verbal response scale 
[VRS]) from Week 49 through to Week 52 
Secondary 
To evaluate the efficacy of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC at 
Week 52 in terms of symptom 
scores for rhinorrhoea (runny nose) 
and loss of smell  
• 
Change from baseline in mean symptom 
score for rhinorrhoea (runny nose) (VRS) 
from Week 49 through to Week 52 
• 
Change from baseline in mean symptom 
score for loss of smell (VRS) from 
Week 49 through to Week 52 
To evaluate the efficacy of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC at 
Week 52 in terms of the Lund 
Mackay CT score 
• 
Change from baseline in Lund Mackay CT 
score at Week 52 
To evaluate the impact on quality of 
life of depemokimab 100 mg SC + 
SoC compared to placebo + SoC at 
Week 52 in patients with a diagnosis 
of CRSwNP  
• 
Change from baseline in SNOT-22 total 
score at Week 52 
To evaluate the efficacy of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC prior to 
Week 26 in participants with a 
diagnosis of CRSwNP 
• 
Change from baseline in mean nasal 
obstruction score (VRS) from Week 21 
through to Week 24 
• 
Change from baseline in total endoscopic 
NP score at Week 26 

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Objectives 
Endpoints 
Other 
To evaluate the efficacy of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC on 
individual NP symptoms 
• 
Change from baseline in mean overall 
symptom (VAS) score from Week 49 
through to Week 52 
• 
Achieving a one point or greater decrease 
from baseline in NP Score at Week 52 
without first having nasal surgery (actual) 
or disease-modulating medication for 
CRSwNP 
• 
Change from baseline in mean individual 
symptom (VRS) score for facial pain from 
Week 49 through to Week 52 
• 
Change from baseline in mean individual 
symptom (VRS) score for mucus in throat 
from Week 49 through to Week 52 
To evaluate the efficacy of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC on 
composite symptom endpoints 
• 
Change from baseline in the mean nasal 
polyps symptoms composite score 
(combining VRS scores for nasal 
obstruction, rhinorrhoea (runny nose), loss 
of smell, and mucus in throat) from 
Week 49 through to Week 52 
• 
Change from baseline in mean CRS 
symptoms and facial pain composite score 
(combining VRS scores for nasal 
obstruction, rhinorrhoea (runny nose), loss 
of smell, and facial pain) from Week 49 
through to Week 52 
• 
Achieving a meaningful decrease from 
baseline in their mean individual symptoms 
VRS and composite VRS from Week 49 
through to Week 52 without first having 
nasal surgery (actual) or disease-
modulating medication for CRSwNP.  
To evaluate the efficacy of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC on 
health-related quality of life  
• 
Achieving an 8.9 point or greater decrease 
from baseline in SNOT-22 total score at 
Week 52 without first having nasal surgery 
(actual) or disease-modulating medication 
for CRSwNP 
• 
Achieving a 28 point or greater decrease 
from baseline in SNOT-22 total score at 
Week 52 without first having nasal surgery 

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Objectives 
Endpoints 
(actual) or disease-modulating medication 
for CRSwNP 
• 
Change from baseline in SF-36 Mental 
Component Summary (MCS) score, 
Physical Component Summary (PCS) 
score and eight domains at Week 52  
• 
Change from baseline in WPAI-GH scores 
at Week 52 
safety 
To evaluate the safety and 
tolerability of depemokimab 100 mg 
SC + SoC every 26 weeks, 
compared to placebo + SoC in 
patients with a diagnosis of 
CRSwNP 
• 
Incidence of Adverse events (AEs)/ 
Serious adverse events (SAEs)  
• 
Change from baseline in vital signs (heart 
rate, systolic and diastolic blood pressure, 
body temperature) at discrete timepoints 
during the 52-week period 
• 
Change from baseline in ECG values at 
discrete timepoints during the 52-week 
period 
• 
Change from baseline in laboratory 
parameters (including haematological and 
clinical chemistry parameters) and 
hepatobiliary laboratory abnormalities at 
discrete timepoints during the 52-week 
period 
• 
Incidence of immunogenicity as measured 
by the presence of antidrug antibody 
(ADA) and neutralising antibodies (NAb) 
to depemokimab 
Pharmacokinetics and Pharmacodynamics 
To evaluate the pharmacokinetics 
and pharmacodynamics of 
depemokimab 100 mg SC + SoC in 
participants with a diagnosis of 
CRSwNP 
• 
Depemokimab plasma concentration at 
measured timepoints during the 52-week 
period 
• 
 Ratio to baseline in absolute blood 
eosinophil count at measured timepoints 
during the 52-week period. 

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Objectives and Endpoints for Pre-Specified Pooled Analysis Across Studies 217095 
(this study) and 218079 (replicate study) 
Objectives 
Endpoints 
Secondary: Pre-specified pooled analysis across studies 217095 (this study) and 
218079 (replicate study) 
To evaluate the impact of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC on 
the requirement for nasal surgery 
(actual or planned) at Week 52 in 
patients with a diagnosis of 
CRSwNP 
• 
Time to first nasal surgery (actual or entry on 
waiting list) or disease-modulating 
medication for CRSwNP up to Week 52 
• 
Time to first nasal surgery (actual) or disease-
modulating medication for CRSwNP up to 
Week 52 
To evaluate the impact on use of 
systemic corticosteroids of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC up to 
Week 52 in patients with a 
diagnosis of CRSwNP 
• 
Requiring at least 1 course of systemic 
corticosteroids or disease-modulating 
medication for CRSwNP or nasal surgery 
(actual) during the Week 52 treatment period 
To evaluate the impact on asthma 
control of depemokimab 100 mg 
SC + SoC compared to placebo + 
SoC at Week 52 in the subgroup 
of participants with partially or 
not well-controlled (ACQ-5 Score 
>0.75) asthma and a diagnosis of 
CRSwNP 
• 
Change from baseline in Asthma Control 
Questionnaire (ACQ-5) score at Week 52 
Other: Pre-specified pooled analysis across studies 217095 (this study) and 218079 
(replicate study) 
To evaluate the impact of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC on 
nasal surgery and oral 
corticosteroid (OCS) use in 
patients with a diagnosis of 
CRSwNP 
• 
Time to first nasal surgery (actual) or course 
of systemic CS or disease-modulating 
medication for CRSwNP up to Week 52 
• 
Time to first nasal surgery (actual or entry on 
waiting list) or course of systemic CS or 
disease-modulating medication for CRSwNP 
up to Week 52 

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Objectives 
Endpoints 
To evaluate the impact on nasal 
surgery (actual or reduced need 
for) of depemokimab 100 mg SC 
+ SoC compared to placebo + 
SoC in patients with a diagnosis 
of CRSwNP 
• 
Participants no longer having a need for nasal 
surgery, defined as meeting all of the 
following: 
o 
NP score <5 at Week 52 (centrally read) 
o 
Mean overall VAS symptom score ≤7 
during Week 49 to Week 52 
o 
No surgery during the treatment period 
up to Week 52 
o 
No use of disease-modulating medication 
for CRSwNP up to Week 52 
To evaluate the efficacy of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC on 
systemic steroid or antibiotic use 
as part of SoC in patients with a 
diagnosis of CRSwNP 
• 
Number of courses of systemic steroid 
therapy for CRSwNP up to Week 52 
• 
Number of courses of systemic steroid 
therapy, regardless of indication, up to Week 
52 
• 
Total systemic steroid exposure (mg of 
prednisolone equivalent) regardless of 
diagnosis up to Week 52 
• 
Time to first course of systemic CS or 
disease-modulating medication for CRSwNP 
up to Week 52 
• 
Number of courses of antibiotics to treat 
sinus-related infection up to Week 52 
To evaluate the effect of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC on 
asthma control in the subgroup of 
participants with partially or not 
well-controlled (ACQ-5 Score 
≥0.75) asthma and a reduction in 
exacerbation frequency in all 
participants with comorbid 
asthma 
The following asthma related endpoints will be 
assessed: 
• 
Achieving a meaningful decrease from 
baseline in ACQ-5 score of 0.5 points or 
greater at 52 weeks without first having nasal 
surgery (actual) or disease-modulating 
medication for CRSwNP 
• 
Number of clinically significant asthma 
exacerbations defined as worsening of asthma 
requiring systemic corticosteroids 
(intravenous [IV] or oral steroid) for at least 
3 days or a single intramuscular (IM) 
corticosteroid dose and/or ED visit and/or 
hospitalization for asthma up to Week 52 

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Overall Design: 
• 
This is a randomized, double-blind, placebo-controlled, parallel group, Phase III 
study of depemokimab + SoC in adults with CRSwNP. The objective of the study is 
to evaluate the efficacy and safety of depemokimab 100 mg, administered SC by the 
site staff, via a pre-filled safety syringe device (SSD) every 6 months + SoC for 52 
weeks. Efficacy of depemokimab will be assessed using co-primary endpoints of 
change from baseline in total endoscopic NP score at Week 52 and change from 
baseline in mean nasal obstruction VRS (verbal response scale) score from Week 49 
through to Week 52. Nasal surgery will be assessed from a pre-specified pooled 
analysis of study 217095 (this study) and study 218079. 
• 
The study population will consist of adult participants (18 years of age) with 
CRSwNP. In addition, participants must have an endoscopic NP score of at least 5 
out of a maximum score of 8, with a minimum score of 2 in each nasal cavity. 
Participants must also have a prior treatment with systemic corticosteroids (SCS) 
anytime within the past 2 years; and/or have a medical contraindication/intolerance 
to SCS; and/or had a documented history of prior surgery for NP at the Screening 
Visit. 
• 
The study will include an approximate 4-week run-in period followed by 
randomization to a 52-week treatment period. Randomization will be stratified based 
on occurrence of previous surgery for nasal polyps and country. Participants will be 
randomized in a 1:1 ratio into one of the two treatment groups, receiving 100 mg of 
depemokimab SC + SoC or placebo + SoC for a total of 2 doses (26 weeks apart). 
• 
Throughout the entire study, participants will be on the SoC for CRSwNP. 
Depending on local practice1, SoC can include intranasal corticosteroids (INCS), 
saline nasal douching, occasional short courses of systemic corticosteroids (except 
during the run-in period), and/or antibiotics. With the exception of participants in 
Japan, participants should take INCS throughout the study. 
• 
Participants in this study who use inhaled corticosteroids exhalation through nose 
(ICS/ETN) method of administration for their asthma and NP disease are required to 
maintain this method throughout the study period. 
 
 
1 Note: Use of INCS is mandatory for all participants except for those in Japan (INCS is 
not part of current SoC for CRSwNP in Japan). In Japan, participants not on INCS at 
screening will be permitted to start INCS, if required for symptom management. In Japan, 
once participants are on INCS, then they should remain on INCS for the remainder of the 
study. 

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Number of Participants: 
Approximately 417 participants will be screened to ensure 250 randomly assigned 1:1 to 
depemokimab 100 mg SC + SoC or placebo + SoC (approximately 125 participants per 
treatment group). 
Data Monitoring/ Other Committee: Yes (see Appendix 1 in Section 10.1 for details). 
An Independent Data Monitoring Committee (IDMC) will be utilized in this study to 
ensure external objective review of the safety data in order to protect the ethical and 
safety interests of participants and to protect the scientific validity of the study 
(Section 10.1 – Appendix 1). 
1.2. 
Schema 
Figure 1 
Study Schematic 
 
1.3. 
Schedule of Activities (SoA) 
The Schedule of Activities (SoA) for this study are provided in Table 1. Study visits will 
include:  
• 
In-clinic visits (with a marker of “a” in Table 1) 
• 
Telemedicine visits (with a marker of “b”), where permitted by local regulations 
• 
Optional home nursing visits (with a marker of “c”), where permitted by local 
regulations 
Refer to study reference manual (SRM) for further details. 
 

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Table 1 
Schedule of Activities Table 
Procedure 
Screening (Visit 1)a, d 
Treatment Period 
Withdraw/Follow Up 
Notes 
Week 
EW Visit Follow-up 
0 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 26 or 52 
30/56 
Visit (±7 days) 
2a 3a 4c 5a 6b 7a 8b 9a 10a 11a 12b 13a 14b 15a 16a 
a, e 
b, e 
Eligibility Assessments 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
To be signed before any study 
procedures. Can occur at a 
separate visit, prior to 
Screening, if preferred. 
Optional Genetic Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not applicable for China. 
Informed consent for optional 
genetics sample must be 
obtained before collecting a 
sample. 
Optional Biomarker Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not applicable for China. 
Informed consent for optional 
exploratory biomarkers must 
be obtained before collecting 
a sample. 
Inclusion and exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history; Past and current medical conditions 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history includes past 
and current medical conditions 
for the preceding 12 months 
including cardiovascular 
medical history as well as 
family history of premature 
cardiovascular disease, 
CRSwNP disease, 
CRSwNP/eosinophilic chronic 
rhinosinusitis (ECRS) and 

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Procedure 
Screening (Visit 1)a, d 
Treatment Period 
Withdraw/Follow Up 
Notes 
Week 
EW Visit Follow-up 
0 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 26 or 52 
30/56 
Visit (±7 days) 
2a 3a 4c 5a 6b 7a 8b 9a 10a 11a 12b 13a 14b 15a 16a 
a, e 
b, e 
asthma therapy, substance 
usage, smoking history, 
asthma and exacerbation 
history, and concomitant 
medications for the preceding 
12 months. 
History of NP surgery 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
History of systemic CS use including for CRSwNP 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization & Study Intervention 
Review of randomization criteria 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization Day is Day 1. 
Study Intervention Administration 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
A minimum of 2 hours 
observation post-injection (at 
randomization and at Week 
26; V9). 
Device deficiencies review 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Safety Assessments 
Physical exam 
X 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
 
Height to be measured at 
Screening (V1) only. Weight 
does not need to be 
collected at V9. At V2 and 
V9, physical examination to 
be performed prior to dosing. 
Vital signs 
X 
X 
 
X 
 
 
X 
 
X 
X 
 
 
X 
 
X 
X 
X 
 
Temperature, systolic and 
diastolic blood pressure and 
heart rate. 
12-lead ECG 
X 
X 
X 
 
 
 
 
 
X 
X 
 
 
 
 
 
X 
X 
 
ECG must be performed and 
assessed pre-dose. Twelve-
lead ECG central over-read 

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Procedure 
Screening (Visit 1)a, d 
Treatment Period 
Withdraw/Follow Up 
Notes 
Week 
EW Visit Follow-up 
0 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 26 or 52 
30/56 
Visit (±7 days) 
2a 3a 4c 5a 6b 7a 8b 9a 10a 11a 12b 13a 14b 15a 16a 
a, e 
b, e 
values should be used at all 
visits with the exception of 
V2 and V9 where 12-lead 
ECG machine read values 
should be used. 
SAE review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Any SAEs assessed as 
related to study procedures or 
related to a GSK product will 
be recorded from the time a 
participant consents to 
participate in the study. 
AE review 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Concomitant medication review (including INCS) 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Efficacy Assessment 
Assessment of endoscopic NP score 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
 
For V2, the nasal endoscopy 
assessment may be 
performed up to 7 days prior 
to the clinic visit. Nasal 
endoscopy must occur prior to 
randomization. For all other 
visits the nasal endoscopy 
assessment must not exceed 
the protocol defined windows 
of ±7 days from the nominal 
study visit. 
CT Scan 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
CT scan is mandatory unless 
not approved by local ethics 
committee or institutional 
review board. The first CT 

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Procedure 
Screening (Visit 1)a, d 
Treatment Period 
Withdraw/Follow Up 
Notes 
Week 
EW Visit Follow-up 
0 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 26 or 52 
30/56 
Visit (±7 days) 
2a 3a 4c 5a 6b 7a 8b 9a 10a 11a 12b 13a 14b 15a 16a 
a, e 
b, e 
scan must be performed prior 
to randomization and should 
be the last assessment 
performed, where possible. If 
the first CT scan cannot be 
performed as the last 
assessment before 
randomization, the subject 
should have completed their 
screening visit and all 
screening lab results, the 
central NP score and ECG 
central over-read results 
should be assessed by the PI 
before a CT scan is 
conducted. The second CT 
scan should be performed at 
V16 or EW visit (up to 14 days 
prior to the nominal study 
visit). Note: If a participant is 
permanently discontinued 
both from the study 
intervention and from the 
study, and the second dose of 
study intervention was not 
received, decision on 
performing CT scan during 
EW visit at Week 26 will be 
made by the investigator in 
consultation with the Medical 

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Procedure 
Screening (Visit 1)a, d 
Treatment Period 
Withdraw/Follow Up 
Notes 
Week 
EW Visit Follow-up 
0 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 26 or 52 
30/56 
Visit (±7 days) 
2a 3a 4c 5a 6b 7a 8b 9a 10a 11a 12b 13a 14b 15a 16a 
a, e 
b, e 
Monitor. 
Please refer to Pregnancy test 
(WOCBP only). 
Assessment of Actual NP Surgery or planned NP 
Surgery 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Wherever possible (and when 
optional consent provided for 
exploratory biomarkers), the 
removed tissue from a nasal 
surgery will be collected and 
stored. Not applicable for 
China. 
Assessment of systemic CS and antibiotics dose and 
duration including for CRSwNP 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Patient-Reported Outcomes 
Dispensing and Training of the eDiary 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
eDiary Compliance Check 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
eDiary Collection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
 
Individual symptom scores (including nasal 
obstruction, rhinorrhea [runny nose], loss of smell, 
facial pain, and mucus in throat) (VRS)f 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Performed using eDiary. eDiary 
will be completed by 
participants in the morning 
between Screening Visit (V1) 
and V16. 
Overall symptoms score (VAS)f 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Performed using eDiary. eDiary 
will be completed by participants
in the morning between 
Screening Visit (V1) and V16. 
Nasal obstruction score (VAS)f 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
 
Performed using eDiary. 
SNOT-22f 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Performed using eDiary. 
PGISf 
 
X 
X 
X 
X 
 
 
X 
 
 
 
 
X 
 
 
X 
X 
 
Performed using eDiary. The 
PGIS will ask the patient to 

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Procedure 
Screening (Visit 1)a, d 
Treatment Period 
Withdraw/Follow Up 
Notes 
Week 
EW Visit Follow-up 
0 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 26 or 52 
30/56 
Visit (±7 days) 
2a 3a 4c 5a 6b 7a 8b 9a 10a 11a 12b 13a 14b 15a 16a 
a, e 
b, e 
rate the severity of their nasal 
polyps symptoms over the last 
4 weeks. 
PGICf 
 
 
X 
X 
X 
 
 
X 
 
 
 
 
X 
 
 
X 
X 
 
Performed using eDiary. The 
PGIC will ask the patient to 
rate the change in their nasal 
symptoms since the start of 
trial medication. 
ACQ-5f 
 
X 
 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
X 
X 
X 
 
For asthmatic participants 
only. Performed using eDiary. 
Review for asthma exacerbations 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
For asthmatic participants 
only. An asthma exacerbation 
is defined as worsening of 
asthma requiring systemic 
corticosteroids (IV or oral 
steroid) for at least 3 days or a 
single IM CS dose and/or 
emergency department visit, 
or hospitalization. 
SF-36f 
 
X 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
 
Performed using eDiary. 
WPAI-GHf 
 
X 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
 
Performed using eDiary. 
Laboratory Assessments 
Parasitic screening 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Parasitic screening is only 
required in countries with high-
risk or for participants who have 
visited high-risk countries in the 
past 6 months. Please refer to 
SRM for full list of high-risk 
countries. Sites should use local 

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Procedure 
Screening (Visit 1)a, d 
Treatment Period 
Withdraw/Follow Up 
Notes 
Week 
EW Visit Follow-up 
0 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 26 or 52 
30/56 
Visit (±7 days) 
2a 3a 4c 5a 6b 7a 8b 9a 10a 11a 12b 13a 14b 15a 16a 
a, e 
b, e 
laboratories. 
If sites wish to use central 
laboratories, they should note 
that the central test is stool 
microscopy for ova and 
parasites. For details of the 
organisms detected by this test 
refer to the parasitic screening 
section of the SRM. 
Clinical chemistry (including liver chemistry) 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
 
 
X 
 
 
X 
X 
 
 
Urinalysish 
X 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
 
Urinalysis to be performed at 
local laboratories using 
dipstick test. If results are 
abnormal (blood or protein is 
abnormal [evidence of 
microalbuminuria or hematuria 
of ≥1+]) a second urine 
sample should be taken and 
sent to central laboratory. 
Hematology 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
 
X 
 
X 
X 
X 
 
For hematology samples 
collected after Randomization, 
the absolute and differential 
(%) values of eosinophils, 
lymphocytes, basophils, 
neutrophils and monocytes 
will not be reported to site staff 
and Sponsor (to maintain the 
treatment blind). However, 
sites will be sent total white 
blood counts throughout the 

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Procedure 
Screening (Visit 1)a, d 
Treatment Period 
Withdraw/Follow Up 
Notes 
Week 
EW Visit Follow-up 
0 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 26 or 52 
30/56 
Visit (±7 days) 
2a 3a 4c 5a 6b 7a 8b 9a 10a 11a 12b 13a 14b 15a 16a 
a, e 
b, e 
study. Samples should be 
taken prior to dosing at V2 
and V9. 
Pregnancy test (WOCBP only) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
For WOCBP, a serum 
pregnancy test should be 
done at Screening Visit, at 
V16, and EW Visit. Highly 
sensitive urine pregnancy 
tests should be done for all 
other time points. Urine 
pregnancy test should also be 
performed within 24 hours 
prior to any CT scan and 
results assessed prior to the 
CT scan. If a urine test cannot 
be confirmed as negative 
(e.g., an ambiguous result), a 
serum pregnancy test is 
required. Participants who 
withdraw early from the study 
should have a urine 
pregnancy test 4 weeks after 
the EW Visit. 
PK samples 
 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
 
X 
 
 
X 
X 
 
Must be performed pre-dose 
at V2 and V9. PK samples at 
Week 52 (Visit 16/EW Visit) 
will be collected for 
approximately 200 
participants; sites will be 
notified once 200 samples 

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Procedure 
Screening (Visit 1)a, d 
Treatment Period 
Withdraw/Follow Up 
Notes 
Week 
EW Visit Follow-up 
0 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 26 or 52 
30/56 
Visit (±7 days) 
2a 3a 4c 5a 6b 7a 8b 9a 10a 11a 12b 13a 14b 15a 16a 
a, e 
b, e 
have been collected. 
IL-5 samples 
 
X 
X 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
 
Must be performed pre-dose 
at V2 and V9. 
Complement C3 and C4 sample 
 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
 
 
Total IgE sample 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Anti-MPO antibody, anti-PR3 antibody, ANA including 
anti-dsDNA Ab 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collected baseline (pre-dose) 
serum sample will be stored 
and may be tested for ANCA, 
(anti-MPO antibody, anti-PR3 
antibody) and ANA including 
anti-dsDNA Ab, if necessary 
(Section 8.6.3) 
Immunogenicity 
 
X 
X 
X 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
 
Must be performed pre-dose 
at V2 and V9. 
Optional Samples g, h 
Optional Genetics sample 
 
X 
 
 
Genetics sample can be 
collected at V2 or at any visit 
during the Treatment Period. 
Not applicable for China. 
Optional Exploratory Blood Biomarker samples 
 
X 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
Must be performed pre-dose 
at V2 and V9. Not applicable 
for China. 
A whole blood sample for 
transcriptomics (Section 
8.6.4.2) is collected at V2 and 
V16 only. 
Collect NP surgery samples – Optional 
 
X 
 
 
Wherever possible, the 
removed tissue from a nasal 
surgery will be collected and 

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Procedure 
Screening (Visit 1)a, d 
Treatment Period 
Withdraw/Follow Up 
Notes 
Week 
EW Visit Follow-up 
0 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 26 or 52 
30/56 
Visit (±7 days) 
2a 3a 4c 5a 6b 7a 8b 9a 10a 11a 12b 13a 14b 15a 16a 
a, e 
b, e 
stored. Not applicable for 
China. 
Optional Nasal Biopsy sample 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Only in participating countries 
and sites. 
Abbreviations: Ab, antibody; ACQ, asthma control questionnaire; AE, adverse event; ANA, antinuclear antibodies; ANCA, antineutrophil cytoplasmic antibodies; CV, cardiovascular, 
CRSwNP, chronic rhinosinusitis with nasal polyps; dsDNA, double stranded Deoxyribonucleic acid; ECG, electrocardiogram; eDiary, electronic diary; EW, early withdrawal; INCS, 
intranasal corticosteroids; NP, nasal polyps; MPO, myeloperoxidase; PGIS, patient global impression of severity; PGIC, patient global impression of change; PI: Principal 
Investigator; PK, pharmacokinetic; PR3, proteinase 3; SAE, serious adverse event; SF-36, 36 item short form health survey; SNOT-22, 22-item sinonasal outcomes test; SRM, 
study reference manual; VAS, visual analogue scale; VRS, verbal response scale; WPAI-GH, workers productivity and activity impairment – general health; WOCBP, women of 
childbearing potential; V, Visit. 
a. 
In-clinic visit. 
b. 
Telemedicine visit. 
c. 
Optional home nursing visit (Week 8; V4 only). 
d. 
Screening window should be 28 days ± 7 days i.e., maximum of 35 days from Day 1 and minimum of 21 days. 
e. 
If a participant withdraws from the study, then the EW Visit should be conducted 26 weeks after the last administered dose of study intervention, i.e., at Week 26 if the second 
dose of study intervention was not received, or at Week 52 if the second dose of study intervention was received. A follow-up visit/call should also be conducted 30 weeks after 
the last dose of study intervention for AE/SAE assessments, concomitant medication review and pregnancy testing (i.e., at Week 30 or 56). 
f. 
All questionnaires should be performed before any other assessments on each particular visit. 
g. 
Informed consent for optional genetics sample or optional exploratory biomarker samples (blood, surgery or nasal biopsy) must be obtained before collecting any samples. 
h. 
China only: Optional samples (genetics, exploratory biomarkers, surgery and nasal biopsy samples) will not be collected from participants in China. Urine dipstick will not be 
performed in China, all urine sample will instead be sent for central laboratory urinalysis. Investigators should be aware of the time needed for central laboratories to return 
results, and should perform appropriate local investigations if any urgent result is required. 

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2. 
INTRODUCTION 
2.1. 
Study Rationale 
Depemokimab is a humanised mAb (IgG1, kappa) antagonist of IL-5 with an extended 
pharmacology. It blocks IL-5 binding to the IL-5 receptor complex, causing a reduction 
in the circulating population of eosinophils. Treatment with anti-IL-5 mAbs such as 
mepolizumab, administered every 4 weeks, is well tolerated and is approved as an add-on 
maintenance treatment in patients with severe eosinophilic asthma.  
The recently completed Phase III study of mepolizumab in adults with CRSwNP 
(SYNAPSE, study 205687) demonstrated the efficacy of mepolizumab 100 mg SC by 
showing statistically significant and clinically meaningful improvement in the co-primary 
endpoints of total endoscopic nasal polyp score and symptoms of nasal obstruction 
associated with NP compared with placebo when administered every 4 weeks for up to 52 
weeks in addition to SoC therapy [Han, 2021]. 
Depemokimab is anticipated to confer a similar efficacy and benefit: risk profile as other 
IL-5 targeting monoclonal antibodies, while being administered with a dosing interval of 
up to 6 months. As such, depemokimab may offer the convenience of an improved dosing 
schedule.  
This study is to assess the efficacy and safety, over a 52-week treatment period of 
depemokimab 100 mg SC + SoC given once every 26 weeks as add-on maintenance 
therapy to participants with CRSwNP. 
2.2. 
Background 
Background on CRSwNP / eosinophilic chronic rhinosinusitis (ECRS) 
Nasal polyposis (NP) is a chronic inflammatory disease of the nasal passage linings 
and/or sinuses leading to soft tissue growth in the upper nasal cavity. The resultant 
swellings which can grow in both nostrils (bilateral), greatly impact a patient’s health-
related quality of life through increases in nasal obstruction, loss of smell, facial pain, 
facial pressure and nasal discharge. The persistence of these symptoms due to NP leads to 
CRS. The condition is therefore also described as CRS with NP (CRSwNP). The 
European Position Paper on Rhinosinusitis and NP [Fokkens, 2020] defines the severity 
of disease using a total severity visual analogue scale (VAS) in which a patient is asked 
to indicate on a 10 cm VAS how troublesome they consider their symptoms. An overall 
VAS symptom score of 0-3 is defined as mild disease, >3-7 as moderate and >7-10 as 
severe [Lim, 2007; Fokkens, 2020]. Symptoms are invariably accompanied with findings 
of inflammation of the nasal mucosa and the presence of a polyp seen through nasal 
endoscopy or positive imaging findings, for example using computerized tomography 
(CT). The aetiology of CRSwNP is currently unknown. 

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The current SoC for CRSwNP is treatment with saline washes, INCS and, for severe 
symptoms, when short term relief is required, intermittent courses of systemic 
corticosteroids [Fokkens, 2020]. Antibiotic courses may also be required for intercurrent 
sinus infection, which often complicates severe NP. Although many patients with 
CRSwNP can be adequately controlled with simple medical care (INCS and oral 
corticosteroid [OCS], occasional nasal douching and antibiotic courses) [Alobid, 2012; 
Newton, 2008], progression to surgery as a result of severe symptoms and disruption to 
quality of life is common. Surgery, when ultimately indicated, involves the removal of 
the polyp tissue and diseased mucosa, restoring aeration of the nasal passage and sinuses. 
Over 250,000 NP surgeries are performed in the US annually [Bhattacharyya, 2010]. 
However, polyps have a strong tendency to recur, often requiring repeat surgery  
[Levine, 1990; Larsen, 1997; Rucci, 2003; Wynn, 2004; Jankowski, 2006; Brescia, 2015, 
DeConde, 2017; Loftus, 2020] with a timescale that can vary from a few months to years. 
Data suggests patients with NP associated with tissue eosinophilia constitute the majority 
of those who have a recurrence after surgery [Brescia, 2015]. Repeat (revision) surgery is 
associated with diminishing success and a higher potential for adverse effects 
[Bhattacharyya, 2004; Chu, 1997], hence alternative treatment options are needed for this 
patient group.  
While the recurrence of bilateral NP despite surgery is common and known to be 
associated with the IL-5/eosinophilic pathway in adults, this is less so for children  
[Jones, 1999; Fokkens, 2020]. The number of eosinophils and cells expressing messenger 
RNA for IL-4, IL-5 and IL-10 is higher in patients with CRS excluding cystic fibrosis 
(CF) versus those with CF and controls [Fokkens, 2020]. Anetrochoanal polyps are also 
another form of NP more common in children that are usually unilateral and associated 
with low eosinophil tissue levels [Fokkens, 2020]. 
CRSwNP in Japan and China 
In Japan, CRS is recognized as a common chronic disease [Tokunaga, 2015]. In recent 
years, cases of CRSwNP associated with eosinophilic infiltration have increased in Japan 
due to westernization of eating habits and environments [Tokunaga, 2015]. Patients are 
diagnosed as ECRS using the Japanese Epidemiological Survey of Refractory 
Eosinophilic Chronic Rhinosinusitis (JESREC) scoring system based on the presence of 
bilateral NP, CT findings, and eosinophilia in peripheral blood. This scoring system 
provides a criterion to diagnose and classify ECRS without the use of biopsy or 
operational specimens. A patient is diagnosed as having ECRS if the JESREC score is 11 
out of 17 points or higher. Patients with ECRS (JESREC score 11) are further classified 
into three groups according to blood eosinophilia, ethmoid-dominant shadow in CT, and 
comorbidity (bronchial asthma, AI, NSAIDs intolerance). These groups were 
significantly correlated with the rate of NP recurrence and refractory disease  
[Tokunaga, 2015].  
Similarly, CRS is among the most prevalent chronic diseases in China with an estimated 
prevalence of 8.0% [Shi, 2015]. A recent report found that the proportion of eosinophilic 
CRSwNP patients significantly increased over 11 years [Wang, 2019]. Although there are 
no established diagnosis criteria for eosinophilic CRSwNP in China so far, these patients 
differ significantly from non-eosinophilic patients in clinical characteristics and treatment 

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outcomes: they have higher risk of having comorbid allergic rhinitis and asthma, are 
frequently associated with extensive sinus disease, and have higher polyp recurrence rate 
after surgery. Hence, precision medicine on inflammatory endotypes by verification and 
mapping of the eosinophilic disease are of great importance to optimize care pathways in 
Asia. 
Standard of care (SoC) for ECRS is systemic corticosteroids in Japan and there is a trend 
to use orally inhaled corticosteroids exhalation through nose (ICS/ETN) method of 
administration for the management of NP for patients with both ECRS and concomitant 
asthma disease [Kobayashi, 2018]. Although longer term effects on nasal polyp disease 
are yet to be fully evaluated, the short term effects of ICS/ETN on NP size can be 
significant. Of note, in Japan INCS is not licensed for ECRS. 
2.2.1. 
The Role of Anti IL5 Therapy in CRSwNP 
IL-5 is the predominant cytokine in NP associated with tissue eosinophilia, promoting the 
activation and prolonged survival of eosinophils [Bachert, 1997; Bachert, 1998]. IL-5 is 
increased in NP tissue compared with that in healthy controls, and correlates with the 
degree of tissue eosinophilia, strongly suggesting a rationale for anti-IL-5 therapy in this 
condition [Bachert, 1997]. 
Inhibition of IL-5 will remove a key eosinophil growth factor, and given the short 
circulating half-life of eosinophils, it will result in a rapid reduction in the circulating 
population. Reduction in eosinophils has been identified as a therapeutic strategy for 
numerous disorders, with mAbs targeting IL-5, such as mepolizumab, currently approved 
for the treatment of severe eosinophilic asthma, eosinophilic granulomatosis with 
polyangiitis (EGPA), CRSwNP, and hypereosinophilic syndrome (HES) and in 
development for other indications [Legrand, 2015]. 
The current clinical data from approved anti-IL-5/5R mAbs (mepolizumab, reslizumab, 
and benralizumab) demonstrate clinical utility in the treatment of conditions associated 
with elevated eosinophil levels, such as severe asthma with an eosinophilic phenotype. 
Mepolizumab 100 mg SC (every 4 weeks) is approved as an add-on maintenance 
treatment for severe asthma with an eosinophilic phenotype. The safety profile of 
mepolizumab is favourable. 
The recently completed Phase III study of mepolizumab in CRSwNP (SYNAPSE, study 
205687) demonstrated the efficacy of mepolizumab 100 mg SC by showing statistically 
significant and clinically meaningful improvement in the co-primary endpoints of total 
endoscopic nasal polyp score and symptoms of nasal obstruction associated with CRS 
compared with placebo when administered every 4 weeks for up to 52 weeks in addition 
to SoC therapy [Han, 2021]. 

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2.2.1.1. 
Depemokimab (GSK3511294) Long-Acting IL-5 
Depemokimab is an extended pharmacology humanised mAb. It inhibits IL-5 signalling 
by blocking human IL-5 binding to the IL-5 receptor complex, which is expressed on the 
eosinophil cell surface. Treatment with anti-IL-5 monoclonal antibodies such as 
mepolizumab, administered every 4 weeks, is well tolerated and is approved as an add-on 
maintenance treatment in patients with severe eosinophilic asthma, EGPA, HES, and 
CRSwNP. Depemokimab is anticipated to confer a similar efficacy and benefit: risk 
profile as other IL-5 targeting monoclonal antibodies, while being administered with a 
longer dosing interval. 
Depemokimab demonstrated an approximately 29-fold increase in IL-5 potency 
compared to mepolizumab in a cell-based in vitro assay and approximately 2-fold 
reduction in clearance in a single-dose pharmacokinetic (PK)/pharmacodynamic (PD) 
study in cynomolgus monkeys. Consistent with the in vitro data, in cynomolgus 
monkeys, depemokimab demonstrated approximately 30-fold greater IL-5 binding 
affinity compared with mepolizumab, as evaluated by the serum total IL-5 profile and 
duration of blood eosinophil suppression. The reversal to 50% of the maximal inhibition 
of blood eosinophils was observed at around Day 169 for depemokimab (1 mg/kg) and at 
Day 29 for mepolizumab (1 mg/kg). 
The safety profile of depemokimab (10 and 100 mg/kg doses) has been evaluated in a 
4-week single-dose and a 26-week repeat dose toxicity (2 doses 3 months apart given at 
Day 1 and Week 14) studies, administered by the subcutaneous route to cynomolgus 
monkeys. Depemokimab binding assessed by immunohistochemistry did not demonstrate 
specific positive staining in any of the tissues examined with the staining restricted to the 
positive control material (IL-5 coated coupled beads), suggesting little likelihood for 
nonpharmacological effects.  
As a long-acting anti-IL-5 mAb, depemokimab is anticipated to provide the same clinical 
benefit with a similar safety profile compared with mepolizumab and others in its class 
and with the added benefit of an extended duration of action requiring less frequent SC 
dosing (once every 6 months). As such, depemokimab may offer the convenience of an 
improved dosing schedule. 
Depemokimab in the clinic:  
GSK has completed a single ascending dose first-time-in-human (FTIH) study (Study 
205722) to investigate the safety, tolerability, immunogenicity, PK and PD of 
depemokimab administered subcutaneously in participants with mild- to -moderate 
asthma. Eligible participants had a screening blood eosinophil level of ≥200 cells/μL for 
relevance to the target population and facilitate investigation of the blood eosinophil 
profile following single doses of depemokimab. The study 205722 showed depemokimab 
to be well tolerated in adult participants with mild/moderate asthma who received a 
single SC dose of depemokimab up to 300 mg [Singh, 2022]. 
A detailed description of the chemistry, pharmacology and safety of depemokimab is 
provided in the current Investigator’s Brochure (IB) [GSK3511294 Clinical 
Investigator’s Brochure]. 

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2.3. 
Benefit/Risk Assessment 
The benefit-risk of depemokimab in this trial is favourable. Summaries of findings from 
nonclinical studies conducted with depemokimab and completed FTIH study 205722, as 
well as more detailed information about the known and expected benefits and risks and 
reasonably expected AEs of depemokimab can be found in the current IB [GSK3511294 
Clinical Investigator’s Brochure] or later. 
 

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The following section outlines the risk  assessment and mitigation strategy for this protocol: 
2.3.1. 
Risk Assessment 
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Study Intervention Depemokimab (GSK3511294) 
Allergic reactions including anaphylaxis 
• 
Allergic reactions with the most severe form being 
anaphylaxis (see Appendix 8 in Section 10.8), are 
potential risks associated with mAbs. 
• 
No allergic reactions or anaphylaxis have been 
reported with depemokimab in FTIH study 205722 in 
participants with mild to moderate asthma. One 
participant reported an event under Hypersensitivity 
SMQ with preferred term of rash verbatim “localised 
rash both bends of arms”, 82 days post 30 mg SC 
dose of depemokimab. The event was non-serious, 
of mild intensity, resolved within 10 days and was 
considered unrelated to the study intervention by the 
investigator. 
• 
Daily monitoring of serious adverse events (SAEs) 
by Medical Monitor; regular systematic review of 
AE/SAE data from ongoing studies by a GSK safety 
review team. 
• 
Use of criteria of Joint National Institute of Allergy 
and Infectious Disease (NIAID)/Food Allergy and 
Anaphylaxis Network (FAAN) 2nd Symposium on 
Anaphylaxis to collect data on reports of anaphylaxis 
(see Appendix 8 in Section 10.8). 
• 
Use of standardized CRFs to collect relevant data 
on systemic reactions. 
• 
Participants will be monitored in the clinic for 
immediate hypersensitivity and any other untoward 
effects for a minimum of 2 hours post-injection (both 
at randomization and at Week 26). In the event of an 
acute severe reaction (e.g., anaphylaxis) following 
administration of study intervention, there are 
personnel/staff onsite at the treatment facility who 
are appropriately trained in basic life support to 
manage the participant including administration of 
medications (e.g., epinephrine), and have access to 

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a system that can promptly transport the participant 
to another facility for additional care if appropriate. 
• 
An independent data monitoring committee (IDMC) 
will review unblinded safety data at regular intervals. 
• 
Participants with severe allergic 
reaction/anaphylaxis with no alternative explanation 
after the first dose will not receive another dose. 
Type III Hypersensitivity (Immune 
complex disease/vasculitis) 
• 
Adverse effects of vascular inflammation consistent 
with immune complex disease were observed in one 
female monkey in the 1-month toxicity study after 
administration of 10 mg/kg. A further monkey had a 
minimal focal inflammation after administration of 
100 mg/kg. Immune complex disease was not 
observed in the 6-month repeat dose (2 doses) 
study at the same doses. It is unknown if this will 
translate to humans as preclinical models are not 
necessarily predictive of clinical findings in humans. 
• 
No AEs of Type III hypersensitivity have been 
reported with depemokimab in FTIH study 205722 in 
participants with mild to moderate asthma (36 
participants received depemokimab; 12 participants 
received placebo). 
• 
Participants with current diagnosis of vasculitis will 
be excluded. Participants with high clinical suspicion 
of vasculitis at screening will be evaluated and 
excluded from enrolment if diagnosed (Section 5.2). 
• 
Daily monitoring of SAEs will be done by Medical 
Monitor; regular systematic review of AE/SAE data 
from ongoing studies will be performed by a GSK 
safety review team. 
• 
IDMC will review unblinded safety data at regular 
intervals; any events suggestive of immune complex 
disease will be reviewed by a relevant medical 
expert (member of the IDMC). 
• 
Protocol guidance on early identification of vasculitis 
events is provided (see Section 7.4). 
• 
Participants with confirmed vasculitis or suspected 
vasculitis with no alternative explanation after the 
first dose will not receive another dose of study 
intervention (see Section 7.1.1). 
Immunogenicity, anti-drug antibodies 
(ADAs) 
• 
Biopharmaceutical products may elicit ADAs and 
neutralising antibodies (NAb), which have the 
• 
Blood samples will be collected for detection of both 
ADA and NAb (see Section 8.8). 

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potential to modulate PK or PD, or to produce 
adverse reactions. 
• 
In FTIH study 205722, none of the participants 
tested positive for ADA at baseline. Overall, 9 
participants (25%) had confirmed positive results for 
ADA at any time post-baseline, primarily in the 
depemokimab 30 mg dose group (5 participants), 
which was also the group with the highest total 
serum IL-5 concentrations. This apparent correlation 
warrants further investigation. There were no major 
differences observed in the depemokimab plasma 
concentration-time and blood eosinophil count-time 
profiles as well as AE reporting between ADA-
positive and ADA- negative participants. Neutralizing 
antibodies were not tested in this study. 
Local injection site reactions. 
• 
A potential risk of any drug delivered via injection. 
• 
No injection site reactions were noted in the 
preclinical studies. 
• 
In the depemokimab FTIH study 205722, injection 
site reactions were reported by one (3%) participant 
who received depemokimab and one (8%) 
participant who received placebo. 
• 
Daily monitoring of SAEs by Medical Monitor; 
regular systematic review of AE/SAE data from 
ongoing studies by GSK study team and/or GSK 
safety review team. 
• 
Use of standardized CRFs to collect relevant data 
on local injection site reactions. 
• 
The IDMC will review unblinded safety data at 
regular intervals. 
QTc prolongation 
• 
Four out of six monkeys in the 6-month repeat dose 
monkey study administered 100 mg/kg every 3 
months (2 doses) were observed to have QTc 
• 
ECGs will be performed according to timepoints 
specified in the SoA (Section 1.3) and the 
assessment will be done as specified in Section 
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prolongation (mean change of 18 msec relative to 
vehicle control value) during Week 14. 
• 
In the depemokimab FTIH study (205722), no 
treatment effect for ECG parameters including 
corrected QT interval (QTcF) was observed across 
the depemokimab treatment groups (n=36). No 
participants met QTcF protocol specified criteria 
(QTcF >500 msec or increase from baseline >60 
msec, or uncorrected QT >600 msec) that would 
require additional monitoring.  
• 
Analysis of the relationship between depemokimab 
plasma concentrations and change from baseline 
QTcF data collected in FTIH 205722 study did not 
reveal any clinically or statistically significant trends 
of concern with increasing depemokimab dose up to 
300 mg. The predicted increase in mean QTcF 
change from baseline with depemokimab plasma 
concentrations point estimates remained below 
10 msec [FDA, 2005] up to concentrations of 100 
ug/mL, with a 95% lower CI consistent with zero 
change from baseline (i.e. the 95% lower bound of 
the CI is below zero) [ GSK Document Number 
2020N457410_00]. 
• 
Participants with QTc prolongation on screening will 
be excluded (criterion 30, Section 5.2). 
• 
Participants with clinically significant cardiac 
abnormalities that are uncontrolled with standard 
treatment are  excluded (criterion 18, Section 5.2). 
• 
Participants who meet QT stopping criteria as 
specified in Section 7.1.3 will not receive another 
dose of study intervention. 
• 
The IDMC will review unblinded safety data at 
regular intervals. 
Risk of depemokimab affecting an unborn 
baby 
• 
Reproductive studies have not been conducted with 
depemokimab; however, in the 6-month repeat dose 
monkey study no changes were observed in 
reproductive organs. Seminiferous tubules were 
• 
Participants who are pregnant, breastfeeding, or 
plan to become pregnant at  screening are excluded 
(criterion 28, Section 5.2). Participants who become 

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evaluated with respect to their stage in the 
spermatogenic cycle and the integrity of the various 
cell types present within the different stages in 
sexually mature males. No cell or stage specific 
abnormalities were noted. 
• 
In addition, there is a low reproductive risk 
associated with the IL-5 target mechanism (as 
shown in pre-clinical reproductive toxicology studies 
of mepolizumab and reslizumab), a low genotoxic 
concern for mAbs in general, and a low transfer of 
mAbs into semen due to the inability of large 
molecular weight proteins such as depemokimab to 
access pivotal cells in the testes [Setchell, 1975; 
Pollanen, 1995; Pollanen, 1989; Setchell, 2001; 
Sohn, 2016], the risk of adverse effects on 
spermatogenesis is considered minimal. Therefore, 
male participants are not required to use 
contraception. 
pregnant during the study will not receive another 
dose of study intervention (see Section 7.1.1). 
• 
All female participants will be assessed at screening 
to determine childbearing status. Female 
participants of childbearing potential must be using a 
highly effective contraceptive method from at least 
14 days prior to first dose and until 30 weeks after 
the last administered dose as described in Section 
10.4.2. 
Study Procedures 
Potential risk for injury with phlebotomy 
• 
Risks with phlebotomy include bruising, bleeding, 
infection, nerve damage. 
• 
Procedures to be performed by trained personnel 
(i.e., study nurse). 
Exposure of subjects to ionising radiation 
from Sinus CT 
• 
Two sinus CT scans are included at baseline (as a 
last assessment prior to randomization, where 
possible) and at Visit 16, or Early Withdrawal, if 
appropriate (see Section 8.2.3). 
• 
The minimum number of CT procedures will be 
performed to achieve study objectives (with 
approximately 52 weeks spacing between 
procedures).  
• 
The first CT scan must be performed prior to 
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• 
The total effective radiation dose from the two sinus 
CT procedures is estimated to be 2mSv per study 
(i.e., 1mSv per scan). 
• 
The average annual global background radiation 
dose is 2.4mSv and therefore the total estimated 
dose from study procedures is less than 1-years of 
background radiation. The additional risk of 
developing a fatal malignancy as a result of this 
radiation exposure is around 1 in 10000. 
performed, where possible. If the first CT scan 
cannot be performed as the last assessment before 
randomization, the subject should have completed 
their screening visit and all screening lab results, the 
central NP score and ECG central over-read results 
should be assessed by the Principal Investigator (PI) 
before a CT scan is conducted. The second CT 
scan should be performed at V16 or EW visit (up to 
14 days prior to the nominal study visit). Note: If a 
participant is permanently discontinued both from 
the study intervention and from the study, and the 
second dose of study intervention was not received, 
decision on performing CT scan during EW visit at 
Week 26 will be made by the investigator in 
consultation with the Medical Monitor 
• 
Please refer to Section 8.3.5 for Pregnancy testing 
requirements (WOCBP only) 
• 
Application of an increased minimum age for 
inclusion in the study was considered to further 
mitigate the risks. However, such a restriction is 
impracticable in this population and might also result 
in the study sample being skewed and 
unrepresentative. Therefore, given the moderate 
radiation dose, a minimum age for inclusion of 18 
years is considered justifiable. 
• 
Participants who have been exposed to 
ionising radiation in excess of 10mSv above 

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background over the previous three-year 
period as a result of occupational exposure or 
previous participation in research studies are 
excluded (criterion 22, Section 5.2). 
• 
Participants are asked about any occupational 
exposure or previous participation in research 
studies at screening so that dose estimates 
can be obtained, where necessary. 
Exposure of foetus to ionising radiation 
from Sinus CT 
• 
As the study procedure is a sinus CT, the abdomen 
is out of the field of view and in the event of an 
undetected pregnancy the foetal radiation dose will 
be limited to scatter and hence very small. 
Nevertheless, steps are required to avoid accidental 
exposure of pregnant subjects. 
• 
WOCBP will be required to have a negative highly 
sensitive urine pregnancy test within the 24 hours 
before each CT scan. If a urine test cannot be 
confirmed as negative (e.g., an ambiguous result), a 
serum pregnancy test is required. In such cases, the 
participant will be excluded from participation if the 
serum pregnancy result at screening is positive. 

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2.3.2. 
Benefit Assessment 
Current clinical data from approved anti-IL-5/5R mAbs (mepolizumab, reslizumab, and 
benralizumab) demonstrate clinical utility in the treatment of conditions associated with  
elevated eosinophil levels, such as severe asthma with an eosinophilic phenotype. 
Mepolizumab 100 mg SC (every 4 weeks) has been approved for the treatment of severe 
asthma with an eosinophilic phenotype and CRSwNP and mepolizumab 300 mg SC 
(every 4 weeks) has been approved for eosinophilic granulomatosis with polyangiitis 
(EPGA) and HES in several different countries. The benefit: risk profile of mepolizumab 
is favourable. Considering a precedented mechanism of action and demonstrated efficacy 
of mepolizumab in patients with CRSwNP along with good tolerability and a favourable 
safety profile, as well as clinical safety results from the completed FTIH study 205722 
with depemokimab, proposed depemokimab CRSwNP therapy is expected to deliver an 
efficacy and safety profile similar to mepolizumab, with the added benefit of an extended 
duration of action requiring less frequent SC dosing (once every 6 months). As such, 
depemokimab may offer the convenience of an improved dosing schedule. 
2.3.3. 
Overall Benefit: Risk Conclusion 
Taking into account the measures being implemented to minimize risk to participants in 
this study, the potential risks of participating in this study are justified by the anticipated 
benefits that may be afforded to participants with CRSwNP. Therefore, the Sponsor 
considers that the investigation of the efficacy and safety of depemokimab is justified in 
this study with a positive benefit: risk ratio. 

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3. 
OBJECTIVES, ENDPOINTS AND ESTIMANDS 
3.1. 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
 
To evaluate the efficacy of 
depemokimab 100mg SC + SoC 
compared to placebo + SoC at 
Week 52 in participants with a 
diagnosis of CRSwNP  
Co-primary endpoints:  
• 
Change from baseline in total endoscopic 
NP score at Week 52 (centrally read) 
• 
Change from baseline in mean nasal 
obstruction score (verbal response scale 
[VRS]) from Week 49 through to Week 52 
Secondary 
To evaluate the efficacy of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC at 
Week 52 in terms of symptom 
scores for rhinorrhoea (runny nose) 
and loss of smell  
• 
Change from baseline in mean symptom 
score for rhinorrhoea (runny nose) (VRS) 
from Week 49 through to Week 52 
• 
Change from baseline in mean symptom 
score for loss of smell (VRS) from 
Week 49 through to Week 52 
To evaluate the efficacy of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC at 
Week 52 in terms of the Lund 
Mackay CT score 
• 
Change from baseline in Lund Mackay CT 
score at Week 52 
To evaluate the impact on quality of 
life of depemokimab 100 mg SC + 
SoC compared to placebo + SoC at 
Week 52 in patients with a diagnosis 
of CRSwNP  
• 
Change from baseline in SNOT-22 total 
score at Week 52 
To evaluate the efficacy of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC prior to 
Week 26 in participants with a 
diagnosis of CRSwNP 
• 
Change from baseline in mean nasal 
obstruction score (VRS) from Week 21 
through to Week 24 
• 
Change from baseline in total endoscopic 
NP score at Week 26 

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Objectives 
Endpoints 
Other 
To evaluate the efficacy of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC on 
individual NP symptoms 
• 
Change from baseline in mean overall 
symptom (VAS) score from Week 49 
through to Week 52 
• 
Achieving a one point or greater decrease 
from baseline in NP Score at Week 52 
without first having nasal surgery (actual) 
or disease-modulating medication for 
CRSwNP 
• 
Change from baseline in mean individual 
symptom (VRS) score for facial pain from 
Week 49 through to Week 52 
• 
Change from baseline in mean individual 
symptom (VRS) score for mucus in throat 
from Week 49 through to Week 52 
To evaluate the efficacy of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC on 
composite symptom endpoints 
• 
Change from baseline in the mean nasal 
polyps symptoms composite score 
(combining VRS scores for nasal 
obstruction, rhinorrhoea (runny nose), loss 
of smell, and mucus in throat) from 
Week 49 through to Week 52 
• 
Change from baseline in mean CRS 
symptoms and facial pain composite score 
(combining VRS scores for nasal 
obstruction, rhinorrhoea (runny nose), loss 
of smell, and facial pain) from Week 49 
through to Week 52 
• 
Achieving a meaningful decrease from 
baseline in their mean individual symptoms 
VRS and composite VRS from Week 49 
through to Week 52 without first having 
nasal surgery (actual) or disease-
modulating medication for CRSwNP 
To evaluate the efficacy of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC on 
health-related quality of life 
• 
Achieving an 8.9-point or greater decrease 
from baseline in SNOT-22 total score at 
Week 52 without first having nasal surgery 
(actual) or disease-modulating medication 
for CRSwNP 
• 
Achieving a 28 point or greater decrease 
from baseline in SNOT-22 total score at 
Week 52 without first having nasal surgery 

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Objectives 
Endpoints 
(actual) or disease-modulating medication 
for CRSwNP 
• 
Change from baseline in SF-36 Mental 
Component Summary (MCS) score, 
Physical Component Summary (PCS) 
score and eight domains at Week 52 
• 
Change from baseline in WPAI-GH scores 
at Week 52 
Safety 
To evaluate the safety and 
tolerability of depemokimab 100 mg 
SC + SoC every 26 weeks, 
compared to placebo + SoC in 
patients with a diagnosis of 
CRSwNP 
• 
Incidence of AEs/ Serious adverse events 
(SAEs)  
• 
Change from baseline in vital signs (heart 
rate, systolic and diastolic blood pressure, 
body temperature) at discrete timepoints 
during the 52-week period 
• 
Change from baseline in ECG values at 
discrete timepoints during the 52-week 
period  
• 
Change from baseline in laboratory 
parameters (including haematological and 
clinical chemistry parameters) and 
hepatobiliary laboratory abnormalities at 
discrete timepoints during the 52-week 
period 
• 
Incidence of immunogenicity as measured 
by the presence of ADA and neutralising 
antibodies (NAb) to depemokimab 
Pharmacokinetics and Pharmacodynamics 
To evaluate the pharmacokinetics 
and pharmacodynamics of 
depemokimab 100 mg SC + SoC in 
participants with a diagnosis of 
CRSwNP 
• 
Depemokimab plasma concentration at 
measured timepoints during the 52-week 
period 
• 
Ratio to baseline in absolute blood 
eosinophil count at measured timepoints 
during the 52-week period. 

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3.2. 
Objectives and Endpoints for Pre-specified Pooled Analysis 
Across Studies 217095 (This Study) and 218079 (Replicate 
Study) 
Objectives 
Endpoints 
Secondary: Pre-specified pooled analysis across studies 217095 (this study) and 
218079 (replicate study) 
To evaluate the impact of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC on the 
requirement for nasal surgery (actual 
or planned) at Week 52 in patients 
with a diagnosis of CRSwNP 
• 
Time to first nasal surgery (actual or entry 
on waiting list) or disease-modulating 
medication for CRSwNP up to Week 52 
• 
Time to first nasal surgery (actual) or 
disease-modulating medication for 
CRSwNP up to Week 52 
To evaluate the impact on use of 
systemic corticosteroids of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC up to 
Week 52 in patients with a diagnosis 
of CRSwNP 
• 
Requiring at least 1 course of systemic 
corticosteroids or disease-modulating 
medication for CRSwNP or nasal surgery 
(actual) during the Week 52 treatment 
period 
To evaluate the impact on asthma 
control of depemokimab 100 mg SC 
+ SoC compared to placebo + SoC 
at Week 52 in the subgroup of 
participants with partially or not 
well-controlled (ACQ-5 Score 
>0.75) asthma and a diagnosis of 
CRSwNP 
• 
Change from baseline in Asthma Control 
Questionnaire (ACQ-5) score at Week 52 
Other: Pre-specified pooled analysis across studies 217095 (this study) and 218079 
(replicate study) 
To evaluate the impact of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC on nasal 
surgery and OCS use in patients 
with a diagnosis of CRSwNP 
• 
Time to first nasal surgery (actual) or 
course of systemic CS or disease-
modulating medication for CRSwNP up to 
Week 52 
• 
Time to first nasal surgery (actual or entry 
on waiting list) or course of systemic CS or 
disease-modulating medication for 
CRSwNP up to Week 52 

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Objectives 
Endpoints 
To evaluate the impact on nasal 
surgery (actual or reduced need for) 
of depemokimab 100 mg SC + SoC 
compared to placebo + SoC in 
patients with a diagnosis of 
CRSwNP 
• 
Participants no longer having a need for 
nasal surgery, defined as meeting all of the 
following: 
− 
NP score <5 at Week 52 (centrally 
read) 
− 
Mean overall VAS symptom score ≤7 
during Week 49 to Week 52 
− 
No surgery during the treatment period 
up to Week 52 
− 
No use of disease-modulating 
medication for CRSwNP up to 
Week 52 
To evaluate the efficacy of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC on 
systemic steroid or antibiotic use as 
part of SoC in patients with a 
diagnosis of CRSwNP 
• 
Number of courses of systemic steroid 
therapy for CRSwNP up to Week 52 
• 
Number of courses of systemic steroid 
therapy, regardless of indication, up to 
Week 52 
• 
Total systemic steroid exposure (mg of 
prednisolone equivalent) regardless of 
diagnosis up to Week 52 
• 
Time to first course of systemic CS for 
CRSwNP up to Week 52 
• 
Number of courses of antibiotics to treat 
sinus-related infection up to Week 52 
To evaluate the effect of 
depemokimab 100 mg SC + SoC 
compared to placebo + SoC on 
asthma control in the subgroup of 
participants with partially or not 
well-controlled (ACQ-5 Score 
>0.75) asthma and a reduction in 
exacerbation frequency in all 
participants with co-morbid asthma 
The following asthma related endpoints will be 
assessed: 
• 
Achieving a meaningful decrease from 
baseline in ACQ-5 score of 0.5 points or 
greater at 52 weeks without first having 
nasal surgery (actual) or disease-
modulating medication for CRSwNP 
• 
Number of clinically significant asthma 
exacerbations defined as worsening of 
asthma requiring systemic corticosteroids 
(intravenous [IV] or oral steroid) for at 
least 3 days or a single intramuscular (IM) 
corticosteroid dose and/or ED visit and/or 
hospitalization for asthma up to Week 52 
 

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3.3. 
Primary Estimands 
The primary estimands are defined as follows: 
Treatment Comparison: depemokimab 100 mg SC + SoC compared to placebo + SoC  
Population: Participants with a diagnosis of CRSwNP / ECRS  
Co-primary variables/endpoints:  
• 
Change from baseline in total endoscopic NP score at Week 52 (centrally read) 
• 
Change from baseline in mean nasal obstruction score (verbal response scale [VRS]) 
from Week 49 through to Week 52 
Summary measure: Difference in means between treatment groups - depemokimab 100 
mg SC + SoC versus placebo + SoC 
Main Intercurrent events (ICE) anticipated: 
• 
Surgery, which includes any procedure involving instruments resulting in incision 
and removal of tissue from the nasal cavity (e.g., polypectomy and endoscopic sinus 
surgery (ESS)) – to be handled using a composite strategy by incorporating 
occurrence of the event into the definition of the endpoint. Specifically, participants 
who undergo surgery will be assigned the worst possible value of the relevant score 
for all assessments following surgery (i.e., the worst value that it is possible to select 
on the given scale).  
• 
Premature discontinuation of study treatment – to be handled using a treatment 
policy strategy 
• 
Initiation of a medication that may modulate the disease course of CRSwNP by 
reduction of blood eosinophils or type II inflammation to be handled using a 
composite strategy by incorporating the occurrence of the event into the definition of 
the endpoint. Medications that may modulate the disease course to be selected either 
based on published evidence or mechanism of action, and to include the initiation of 
some biologics, chronic SCS and INCS. Specifically, participants who start a 
medication that may modulate the disease course of CRSwNP will be assigned the 
worst possible value of the relevant score for all assessments following the start of 
the medication (i.e., the worst value that is possible to select on the given scale). 
• 
All other changes in background medication or start of a prohibited medication – to 
be handled using a treatment policy strategy 
• 
COVID-19 related events – to be handled using a treatment policy strategy 
• 
Course(s) of systemic CS for any reason – to be handled using a treatment policy 
strategy 

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Supplementary estimand strategy for co-primary endpoints: In addition, the 
intercurrent event for all changes in background medication or start of medication that 
may modulate the disease course of CRSwNP to be handled under the treatment policy 
strategy will be considered as a supplementary estimand to the primary estimand. 
3.4. 
Secondary Estimands 
The secondary estimands are defined as follows: 
Treatment Comparison: As for primary estimand 
Population: As for primary estimand 
Variables/endpoints:  
• 
Change from baseline in mean symptom score for rhinorrhea (runny nose) (VRS) 
from Week 49 through to Week 52 
• 
Change from baseline in mean symptom score for loss of smell (VRS) from Week 49 
through to Week 52 
• 
Change from baseline in Lund Mackay CT score at Week 52 
• 
Change from baseline in SNOT-22 total score at Week 52 
• 
Change from baseline in mean nasal obstruction score (VRS) from Week 21 through 
to Week 24 
• 
Change from baseline in total endoscopic NP score at Week 26 
Summary measure: As for primary estimand 
Main Intercurrent events (ICE) anticipated: As for primary estimand 
3.5. 
Secondary Estimands for Pre-specified Pooled Analysis 
Across Studies 217095 (This Study) and 218079 
3.5.1. 
Secondary estimand for surgery endpoints 
The secondary estimand for time to first nasal surgery (actual or entry on waiting list) or 
disease-modulating medication  up to Week 52 and for time to first nasal surgery (actual) 
or disease-modulating medication up to Week 52 is defined as follows: 
Treatment Comparison: depemokimab 100 mg SC + SoC compared to placebo + SoC  
Population: participants with a diagnosis of CRSwNP / ECRS  

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Variable/endpoint:  
• 
Time to first nasal surgery (actual or entry on waiting list) or disease-modulating 
medication for CRSwNP up to Week 52  
• 
Time to first nasal surgery (actual) or disease-modulating medication for CRSwNP 
up to Week 52 
Summary measure: Hazard ratio between treatment groups - depemokimab 100 mg SC 
+ SoC versus placebo + SoC 
Main Intercurrent events (ICE) anticipated: 
• 
Premature discontinuation of study treatment – to be handled using a treatment 
policy strategy 
• 
Initiation of a medication that may modulate the disease course of CRSwNP by 
reduction of blood eosinophils or type II inflammation to be handled using a 
composite strategy by incorporating the occurrence of the event into the definition of 
the endpoint. Medications that may modulate the disease course to be selected either 
based on published evidence or mechanism of action, and to include the initiation of 
some biologics, chronic SCS and INCS. Specifically, participants who start a 
medication that may modulate the disease course of CRSwNP will be counted as 
requiring surgery at the time the medication was started. 
• 
All other changes in background medication or start of a prohibited medication – to 
be handled using a treatment policy strategy 
• 
COVID-19 related events – to be handled using a treatment policy strategy 
• 
Course(s) of systemic CS for any reason – to be handled using a treatment policy 
strategy 
Supplementary estimand strategy for pooled secondary endpoints related to nasal 
surgery: 
• 
Supplementary estimand 1: In addition, the intercurrent event for all changes in 
background medication or start of medication (including those medications that may 
modulate the disease course of CRSwNP) to be handled under the treatment policy 
strategy will be considered as a supplementary estimand to the primary estimand. 
• 
Supplementary estimand 2: In addition, the intercurrent event for initiation of a 
medication that may modulate the disease course of CRSwNP by reduction of blood 
eosinophils or type II inflammation to be handled under the hypothetical strategy by 
censoring participants after the initiation of a disease-modulating medication for 
CRSwNP. Medications that may modulate the disease course to be selected either 
based on published evidence or mechanism of action, and to include the initiation of 
some biologics, chronic SCS and INCS.  
o 
All other changes in background medication or start of a prohibited medication 
to be handled using a treatment policy strategy 

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3.5.2. 
Secondary estimand for systemic steroids endpoint  
The secondary estimand for requiring at least 1 course of systemic corticosteroids or 
disease-modulating medication for CRSwNP or nasal surgery (actual) during the 
Week 52 treatment period is defined as follows: 
Treatment Comparison: depemokimab 100 mg SC + SoC compared to placebo + SoC  
Population: participants with a diagnosis of CRSwNP / ECRS  
Variable/endpoint:  
• 
Requiring at least 1 course of systemic corticosteroids or disease-modulating 
medication for CRSwNP or nasal surgery (actual) during the Week 52 treatment 
period  
Summary measure: Odds ratio between treatment groups - depemokimab 100 mg SC + 
SoC versus placebo + SoC 
Main Intercurrent events (ICE) anticipated: 
• 
Surgery, which includes any procedure involving instruments resulting in incision 
and removal of tissue from the nasal cavity (e.g., polypectomy and ESS) – to be 
handled using a composite strategy by incorporating occurrence of the event into the 
definition of the endpoint. Specifically, participants who undergo surgery will be 
counted as requiring systemic corticosteroids during the Week 52 treatment period. 
• 
Premature discontinuation of study treatment – to be handled using a treatment 
policy strategy 
• 
Initiation of a medication that may modulate the disease course of CRSwNP by 
reduction of blood eosinophils or type II inflammation to be handled using a 
composite strategy by incorporating the occurrence of the event into the definition of 
the endpoint. Medications that may modulate the disease course to be selected either 
based on published evidence or mechanism of action, and to include the initiation of 
some biologics, chronic SCS and INCS. Specifically, participants who start a 
medication that may modulate the disease course of CRSwNP will be counted as 
requiring corticosteroids during the 52-week treatment period. 
• 
All other changes in background medication or start of a prohibited medication – to 
be handled using a treatment policy strategy 
• 
COVID-19 related events – to be handled using a treatment policy strategy 
• 
Course(s) of systemic CS for any reason – to be handled using a treatment policy 
strategy 

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3.5.3. 
Secondary estimand for ACQ-5 
The secondary estimand for change from baseline in ACQ-5 score at Week 52 is defined 
as follows: 
Treatment Comparison: depemokimab 100 mg SC + SoC compared to placebo + SoC 
Population: Participants with a diagnosis of CRSwNP / ECRS and partially or not well-
controlled asthma with an ACQ-5 score >0.75 at baseline 
Variable/endpoint: 
• 
Change from baseline in ACQ-5 score at Week 52 
Summary measure: Difference in means between treatment groups - depemokimab 
100 mg SC + SoC versus placebo + SoC 
Main Intercurrent events (ICE) anticipated: 
• 
Surgery, which includes any procedure involving instruments resulting in incision 
and removal of tissue from the nasal cavity (e.g., polypectomy and endoscopic sinus 
surgery (ESS)) – to be handled using a composite strategy by incorporating 
occurrence of the event into the definition of the endpoint. Specifically, participants 
who undergo surgery will be assigned a score of 6, the worst possible value of ACQ-
5 for all assessments following surgery. 
• 
Premature discontinuation of study treatment – to be handled using a treatment 
policy strategy 
• 
Initiation of a medication that may modulate the disease course of CRSwNP by 
reduction of blood eosinophils or type II inflammation to be handled using a 
composite strategy by incorporating the occurrence of the event into the definition of 
the endpoint. Medications that may modulate the disease course to be selected either 
based on published evidence or mechanism of action, and to include the initiation of 
some biologics, chronic SCS and INCS. Specifically, participants who start a 
medication that may modulate the disease course of CRSwNP will be assigned the 
worst possible value of the relevant score for all assessments following the start of 
the medication (i.e., the worst value that is possible to select on the given scale). 
• 
All other changes in background medication or start of a prohibited medication – to 
be handled using a treatment policy strategy 
• 
COVID-19 related events – to be handled using a treatment policy strategy 
• 
Course(s) of systemic CS for any reason – to be handled using a treatment policy 
strategy 

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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a randomized, double-blind, placebo-controlled, parallel group, Phase III study of 
depemokimab 100 mg + SoC in approximately 250 adults with CRSwNP. The objective 
of the study is to evaluate the efficacy and safety of depemokimab 100 mg, administered 
SC by the site staff, via a pre-filled safety syringe device every 6 months + SoC for 52 
weeks. Efficacy of depemokimab will be assessed using co-primary endpoints of change 
from baseline in total endoscopic NP score at Week 52 and change from baseline in mean 
nasal obstruction VRS score from Week 49 through to Week 52. Nasal surgery will be 
assessed from a pre-specified pooled analysis of study 217095 (this study) and study 
218079. 
The study population will consist of adult participants (≥18 years of age) with CRSwNP. 
In addition, participants must have an endoscopic NP score of at least 5 out of a 
maximum score of 8, with a minimum score of 2 in each nasal cavity. Participants must 
also have a prior treatment with SCS anytime within the past 2 years; and/or have a 
medical contraindication/intolerance to SCS; and/or had a documented history of prior 
surgery for NP at the Screening Visit. 
The study will include a 4-week run-in period followed by randomization to a 52-week 
treatment period as a double-blind, placebo-controlled phase. The total study duration 
will be approximately 56 weeks. Randomization will be stratified based on occurrence of 
previous surgery for nasal polyps and country. Participants will be randomized in a 
1:1 ratio into one of the two treatment groups, receiving 100 mg of depemokimab SC or 
placebo (both in addition to SoC) for a total of two doses (26 weeks apart). 
Throughout the entire study, participants will be on the SoC for CRSwNP. Depending on 
local practice*, SoC can include INCS, saline nasal douching, occasional short courses of 
systemic corticosteroids (except during the run-in period), and/or antibiotics. With the 
exception of participants in Japan, participants should take INCS throughout the study. 
There is a trend, especially in Japan, to use orally ICS/ETN method of administration for 
the management of NP for participants with both ECRS and concomitant asthma disease 
[Kobayashi, 2018]. Although longer term effects on CRSwNP disease are yet to be fully 
evaluated, short-term effects of ICS/ETN on NP size can be significant. Therefore, 
participants in this study who use ICS/ETN method of administration for their asthma 
and NP disease are required to maintain this method throughout the study period. 
(*Note: Use of INCS is mandatory for all participants, except for those in Japan [INCS is 
not part of current SoC for CRSwNP in Japan]. In Japan, participants not on INCS at 
screening will be permitted to start INCS, if required for symptom management. In Japan, 
once participants are on INCS, then they should remain on INCS for the remainder of the 
study.) 

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4.2. 
Scientific Rationale for Study Design 
Current data from mepolizumab pre-clinical and clinical development indicate the ability 
of mepolizumab to inhibit IL-5 leading to consistent reduction in blood eosinophils, with 
demonstration of clinical benefit in the treatment of conditions associated with 
eosinophilic inflammation. Data from Phase II and Phase III studies of mepolizumab in 
CRSwNP have shown efficacy in both NP score and symptoms as well as impact on the 
need for surgery.  
In addition, data from the Phase III asthma programme with mepolizumab demonstrate, 
compared with placebo, a reduction in asthma exacerbations, improvements in asthma 
control and quality of life (as measured by the Asthma Control Test (5-item) [ACQ-5] 
and St. George's Respiratory Questionnaire [SGRQ], respectively), improvements in lung 
function and a reduction in oral corticosteroid (OCS) use in those participants on chronic 
OCS treatment. No new safety issues were identified in the Study 205687 (SYNAPSE 
study) in addition to those already identified in the severe asthma studies. Since 
depemokimab targets the same IL-5 epitope as mepolizumab, it therefore follows that 
establishing the same reduction in blood eosinophils as mepolizumab, via the same IL-5 
neutralization is expected to generate similar clinical efficacy in the CRSwNP patient 
population selected for this study. Safety in depemokimab is expected to be similar to 
that of mepolizumab. 
4.2.1. 
Participant Input into Design 
Sixteen CRSwNP patients who met the proposed Inclusion Criteria provided input into 
the study design: 4 from the United States, 4 from Argentina, 3 from Germany and 5 
from the United Kingdom. 
Insights were gained via a 25-minute online qualitative survey.  
The questions included in the survey were centred around:  
1. Understanding patient’s motivations for participating  
2. Study Assessments and Procedures 
3. Retention and ongoing support required  
In line with the feedback received there will be clear explanations for all study specific 
procedures provided in the informed consent form (ICF), suggested recruitment and 
retention techniques will be explored and flexibility/support with visit scheduling (e.g., 
telemedicine visits and concierge services) will be implemented where allowed by local 
regulations.  

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4.3. 
Justification for Dose 
Using model-informed drug development (MIDD) principles, GSK has identified that the 
dose and dosing frequency of depemokimab that matches phase 3 mepolizumab-like 
blood eosinophil pharmacology (seen in SYNAPSE) for the entire length of treatment, in 
the CRSwNP population, is 100 mg SC administered every 26 weeks. Further analysis 
shows that there will be limited additional benefit, in term of eosinophil reduction, 
beyond this dose [GSK Document Number 2021N475816_00]. 
The depemokimab 100 mg SC every 26 weeks dosing regimen is further supported by the 
Bayesian dose-time exposure-response analysis [GSK Document Number 
2019N418119_00] focussed on asthma and utilized to select a dose of 100 mg SC every 
26 weeks for the Phase III trials (206713 and 213744). The clinical pharmacology of 
mepolizumab was similar in participants with nasal polyps and severe asthma, and the 
same is anticipated to be valid for depemokimab. 
Since depemokimab targets the same IL-5 epitope as mepolizumab, it therefore follows 
that establishing the same reduction in blood eosinophils as mepolizumab, via the same 
IL-5 neutralization is expected to generate similar clinical efficacy in the CRSwNP 
patient population selected for this study. Furthermore, given the precedented safety 
profile of IL-5 neutralization is comparable to placebo, it also follows that targeting 
previous mepolizumab pharmacology is both valid and expeditious in selecting the dose 
of depemokimab. 
The proposed 100 mg SC dose is 3 times lower than the highest dose tested in the Phase 1 
study 205722 (300 mg SC) and approximately 70 times lower than the no observed 
adverse effect level dose (NOAEL). The safety margins are detailed in Table 2 for i) a 
typical 70 kg individual, ii) a 66.7 kg individual (average male body weight in adult 
Japanese [Statistics of Japan, 2021]), iii) a 53.2 kg individual (average female body 
weight in adult Japanese [Statistics of Japan, 2021]) and iv) a 29 kg individual (lowest 
body weight in adult Japanese [Statistics of Japan, 2021]). Based on the wide safety 
margins described above, the favourable safety profile in the Phase 1 study 205722, 
including at the 300 mg dose and the large clinical and real-world experience with 
compounds targeting IL5/IL5R, the proposed dose is anticipated to be safe and adequate. 

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Table 2 
Predicted Exposure for Depemokimab 100 mg SC Q26W Versus 
Measured Exposure in Phase 1 study 205722 and Measured 
Exposure with the NOAEL Dose (100 mg/kg, highest dose tested in 
the 26 weeks study in cynomolgus monkeys) 
Body 
Weight (kg) 
Predicted 
Ph3 
exposure1 
Measured 
in Ph12 
Ratio 
(measured in 
Ph1 to 
predicted 
Ph3) 
Measured 
NOAEL3 
Ratio (measured 
NOAEL to 
predicted Ph3) 
AUC (ug*day/mL) 
70.0 
754.3 
(678.8-838.4) 
1873.7 
(1439.3, 
2439.1) 
2.5x 
46666.7 
(37416.7-
53750.0) 
61.9x 
66.7 
782.5 
(704.0-869.8) 
2.4x 
59.6x 
53.3 
926.9 
(833.5-
1030.6) 
2.0x 
50.3x 
29.0 
1463.7 
(1315.4-
1628.6) 
1.3x 
31.9x 
Cmax (ug/mL) 
70.0 
11.6 
(10.4-12.8) 
28.6 
(22.5-36.4) 
2.5x 
1390 
(1090-1610) 
119.8x 
66.7 
12.1 
(10.9-13.4) 
2.4x 
114.9x 
53.3 
15.0 
(13.6-16.7) 
1.9x 
92.7x 
29.0 
27.2 
(24.4-30.3) 
1.1x 
51.1x 
1 Geometric mean (95%CI of predicted geometric mean), predicted after second dose at week 26 using the popPK 
model developed on Ph1, including typical value of parameter estimates and their uncertainty 
2 Geometric mean (95%CI) of 300mg dose, determined via NCA. AUC refers to AUC(0-inf) 
3 Mean (range), gender averaged of 100 mg/kg dose, highest dose tested in cynomolgous monkeys. Cmax and AUC 
measured after second dose at week 14. 
The potential impact of ethnic differences on depemokimab exposure, pharmacology, 
efficacy and safety is considered low based on the evidence accumulated with 
mepolizumab and with monoclonal antibodies targeting soluble ligands.  

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Mepolizumab PK showed no apparent ethnic differences, and neither race, nor ethnicity, 
nor country was identified as a covariate of mepolizumab exposure in the population PK 
meta-analysis of 13 mepolizumab studies across various eosinophilic conditions. 
Consistent with those pharmacokinetic observations, the efficacy, safety and 
pharmacodynamics of mepolizumab at the dose used for severe eosinophilic asthma have 
been profiled in participants of North East Asian ancestry and confirmed to be of low 
ethnic sensitivity [GSK Document Number 2020N460984_00].  
Depemokimab is catabolised by proteolytic enzymes, not restricted to hepatic tissue and 
does not undergo target-mediated clearance, similarly to mepolizumab and other 
therapeutic monoclonal antibodies. Inter-ethnic differences are not anticipated in the 
clearance of depemokimab via these ubiquitous proteolytic enzymes. These observations 
are consistent with other therapeutic monoclonal antibodies for which only small inter-
ethnic differences in pharmacokinetics between East Asian and White/Caucasian 
populations have been reported, mostly attributed to the well-established population 
differences in body weight [Chiba, 2014; Matsushima, 2015; Ogasawara, 2019].  
Based on this evidence, the same benefit/ risk is expected for depemokimab for all 
participants administered the same dosing regimen, and no clinically significant effect of 
body weight (in the range of body weight included in this trial) and ethnicity is 
anticipated. Thus, no dose adjustment is recommended.  
Depemokimab’s potential for drug-drug interaction is deemed low in light of its 
elimination pathways. In addition, there is no in vivo evidence that neutralisation of IL-5 
alters expression of cytochrome P450s or transporters [GSK3511294 Clinical 
Investigator’s Brochure].  
4.4. 
End of Study Definition 
The end of the study is defined as the date of the last visit of the last participant in the 
study or last scheduled procedure shown in Table 1 for the last participant in the trial 
globally, whichever is earlier. 
A participant is considered to have completed study treatment dosing if he/she receives 
study treatment at Visit 9 (Week 26). A participant is considered to have completed the 
study if he/she has completed the visit at Week 52, regardless of whether the second dose 
of study intervention (at Week 26) was received. 
5. 
STUDY POPULATION 
Participants with CRSwNP as per inclusion exclusion criteria will be enrolled into the 
study. Prospective approval of protocol deviations to recruitment and enrolment criteria, 
also known as protocol waivers or exemptions, is not permitted. Deviations from 
inclusion and exclusion criteria are not allowed because they can potentially jeopardize 
the scientific integrity of the study, regulatory acceptability or participant safety. 
Therefore, adherence to the criteria as specified in the protocol is essential. 

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5.1. 
Inclusion Criteria 
In order to confirm eligibility, the investigator must review each participant’s medical 
records prior to a participant entering the run-in period. To be randomized into the study, 
participants will be required to meet the additional randomization criteria  
(see Section 5.3). Participants are eligible to be included in the study only if all of the 
following criteria apply at screening: 
AGE 
1. 18 years of age and older inclusive, at the time of signing the informed consent. 
CRSwNP / ECRS DIAGNOSIS 
2. Endoscopic bilateral NP score of at least 5 out of a maximum score of 8 (with a 
minimum score of 2 in each nasal cavity) assessed by the investigator (see Clario 
Video Guideline) 
3. Participants who have had at least one of the following at Visit 1: 
− 
previous nasal surgery for the removal of NP,  
− 
have used at least three consecutive days of systemic corticosteroids in the 
previous 2 years for the treatment of NP, 
− 
medically unsuitable or intolerant to systemic corticosteroid. 
4. Participants (except for those in Japan) must be on daily treatment with INCS 
(including intranasal liquid steroid wash/douching) for at least the 8 weeks 
immediately prior to screening. 
5. Participants presenting with severe NP symptoms defined as symptoms of nasal 
congestion/blockade/obstruction with moderate or severe severity and loss of 
smell or rhinorrhoea (runny nose) based on clinical assessment by the investigator.  
6. Presence of symptoms of chronic rhinosinusitis as described by at least 2 different 
symptoms for at least 12 weeks prior to Visit 1, one of which should be either 
nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal 
drip), plus 
− 
facial pain/pressure 
and/or 
− 
reduction or loss of smell 

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GENDER 
7. Male or eligible female participants:  
Female Participants: 
− 
A female participant is eligible to participate if she is not pregnant or 
breastfeeding, and one of the following conditions applies: 
o 
Is a woman of non-childbearing potential (WONCBP) as defined in 
Appendix 4  
OR 
o 
Is a woman of childbearing potential (WOCBP) and using a contraceptive 
method that is highly effective, with a failure rate of <1%, as described in 
Appendix 4, from at least 14 days prior to the first dose of study 
intervention until at least 30 weeks after the last administered dose of 
study intervention. 
− 
A WOCBP must have a negative highly sensitive serum pregnancy test at 
Screening Visit 1 and a negative highly sensitive urine pregnancy test within 
24 hours before the first dose of study intervention. Additional requirements 
for pregnancy testing are located in the SoA (Section 1.3). 
− 
Contraceptive use by WOCBP should be consistent with local regulations 
regarding the methods of contraception for those participating in clinical 
studies. 
− 
The investigator should evaluate the potential for contraceptive method failure 
(e.g., noncompliance, recently initiated in relationship to the first dose of 
study intervention). 
− 
The investigator is responsible for review of medical history, menstrual 
history, and recent sexual activity to decrease the risk for inclusion of a 
woman with an early undetected pregnancy. 
INFORMED CONSENT 
8. Capable of giving signed informed consent which includes compliance with the 
requirements and restrictions listed in the ICF and in this study protocol. 
French participants: In France, a participant will be eligible for inclusion in this 
study only if either affiliated to or a beneficiary of a social security category. 
 

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5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
CONCURRENT CONDITIONS/MEDICAL HISTORY  
1. As a result of medical interview, physical examination, or screening investigation 
the physician responsible considers the participant unfit for the study  
2. Cystic fibrosis 
3. Antrochoanal polyps 
4. Nasal cavity tumor (malignant or benign) 
5. Fungal rhinosinusitis 
6. Severe nasal septal deviation occluding one nostril preventing full assessment of 
nasal polyps in both nostrils 
7. Participants who had a sino-nasal or sinus surgery changing the lateral wall 
structure of the nose making impossible the evaluation of nasal polyp score  
8. Acute sinusitis or upper respiratory tract infection (URTI) at screening or in 2 
weeks prior to screening 
9. Ongoing rhinitis medicamentosa (rebound or chemical induced rhinitis) 
10. Participants who have had an asthma exacerbation requiring admission to hospital 
within 4 weeks of Screening 
11. Participants who have undergone any intranasal and/or sinus surgery (for example 
polypectomy, balloon dilatation or nasal stent insertion) within 6 months prior to 
Visit 1; nasal biopsy prior to Visit 1 for diagnostic purposes only is excepted. 
12. Participants where NP surgery is contraindicated in the opinion of the Investigator 
13. Eosinophilic Diseases: Participants with other conditions that could lead to 
elevated eosinophils such as hyper-eosinophilic syndromes including (but not 
limited to) EGPA (formerly known as Churg-Strauss Syndrome) or Eosinophilic 
Esophagitis  
14. Parasitic infection: Participants with a known, pre-existing parasitic infestation 
within 6 months prior to Visit 1 
15. Immunodeficiency: A known immunodeficiency (e.g., human immunodeficiency 
virus – HIV), other than that explained by the use of corticosteroids (CSs) taken as 
therapy for asthma 
16. Malignancy: A current malignancy or previous history of cancer in remission for 
less than 12 months prior to screening (NOTE: Participants that had localised 
carcinoma of the skin which was resected for cure will not be excluded). 

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CONCURRENT CONDITIONS/MEDICAL HISTORY  
17. Liver Disease:  
− 
Alanine aminotransferase (ALT) >2x ULN 
− 
Total bilirubin >1.5x ULN (isolated bilirubin >1.5xULN is acceptable if 
bilirubin is fractionated and direct bilirubin <35%) 
− 
Cirrhosis or current unstable liver or biliary disease per investigator 
assessment defined by the presence of ascites, encephalopathy, coagulopathy, 
hypoalbuminemia, oesophageal or gastric varices, persistent jaundice.  
NOTE: Stable non-cirrhotic chronic liver disease (including Gilbert’s 
syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C) are 
acceptable if participant otherwise meets entry criteria. 
18. Other Concurrent Medical Conditions: Participants who have known, pre-
existing, clinically significant cardiac, endocrine, autoimmune, metabolic, 
neurological, renal, gastrointestinal, hepatic, haematological or any other system 
abnormalities that are uncontrolled with standard treatment. 
19. Vasculitis: Participants with current diagnosis of vasculitis. Participants with high 
clinical suspicion of vasculitis at screening will be evaluated and current vasculitis 
must be excluded prior to enrolment. 
20. Hypersensitivity: Participants with allergy/intolerance to the excipients of 
depemokimab in Section 6.1, a monoclonal antibody, or biologic. 
21. COVID-19: Participants that, according to the investigator's medical judgment, 
are likely to have active COVID-19 infection must be excluded. Participants with 
known COVID-19 positive contacts within the past 14 days must be excluded for 
at least 14 days following the exposure during which the participant should remain 
symptom-free. Reported smell/ taste complications from COVID-19 must be used 
as exclusion.  
22. Participants that have been exposed to ionising radiation in excess of 10mSv 
above background over the previous 3-year period as a result of occupational 
exposure or previous participation in research studies. NOTE: Clinically justified 
therapeutic or diagnostic exposures are not included in this cumulative calculation.  
PRIOR/CONCURRENT CLINICAL STUDY EXPERIENCE 
23. Previous participation: Previously participated in any study with mepolizumab, 
reslizumab, or benralizumab and received study intervention (including placebo) 
within 12 months prior to Visit 1. 
24. Investigational Medications (Biologics or non-biologics): Participants currently 
enrolled in another clinical study OR participants who have received treatment 
with an investigational drug within the specified washout periods (refer to  
Section 6.8.2) prior to Visit 1 (this also includes investigational formulations of 
marketed products).  

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PRIOR/CONCOMITANT THERAPY 
25. Monoclonal antibodies targeting IL-5/5R: Participants who have received 
mepolizumab (Nucala), reslizumab (Cinqair/Cinqaero), or benralizumab (Fasenra) 
within 12 months prior to Visit 1. 
26. Other mAbs in the treatment of asthma or CRSwNP: Participants who have 
received omalizumab (Xolair) or dupilumab (Dupixent) within 130 days prior to 
Visit 1. 
27. Other mAbs not used for the treatment of asthma or CRSwNP: Participants 
who have received any mAb within 5 half-lives of Visit 1 (with the exception of 
mAbs for the treatment of COVID-19, which are permitted, unless experimental).  
For a full list of prohibited medication see Section 6.8.2 
PREGNANCY: 
28. Women who are pregnant or lactating or are planning on becoming pregnant 
during the study. Requirements for pregnancy testing are provided in  
Section 8.3.5. 
OTHER DISEASES/ABNORMALITIES:  
29. Any participant who is considered unlikely to survive the duration of the study 
period or has any rapidly progressing disease or immediate life-threatening illness 
(e.g., cancer). In addition, any participant who has any other condition (e.g., 
neurological condition) that is likely to affect respiratory function should not be 
included in the study. 
DIAGNOSTIC ASSESSMENTS: 
30. ECG Assessment: QTcF ≥450 msec or QTcF ≥480 msec for participants with 
Bundle Branch Block in the 12-lead ECG central over-read from Screening Visit 
1. See Section 8.3.3 for further ECG guidance. 
DRUG OR ALCOHOL ABUSE:  
31. A known or suspected history of alcohol or drug abuse within 2 years prior to 
Screening (Visit 1) that in the opinion of the investigator would prevent the 
participant from completing the study procedures. 
ADHERENCE: 
32. Participants who have known evidence of lack of adherence to controller 
medications and/or ability to follow physician’s recommendations. 
AFFILIATION WITH INVESTIGATOR SITE:  
33. Is an investigator, sub-investigator, study coordinator, employee of a participating 
investigator or study site, or immediate family member of the aforementioned that 
is involved in this study. 

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INABILITY TO READ:  
34. In the opinion of the investigator, any subject who is unable to read and/or would 
not be able to complete a questionnaire. 
5.3. 
Randomization Criteria 
Those participants who meet the randomization criteria below will be randomized into 
the study until the target of approximately 250 randomized participants is reached.  
In rare instances and following consultation with the Medical Monitor a participant can 
be rescreened. Rescreened participants are required to sign a new ICF. 
At the end of the run-in period, study participants must fulfill the following additional 
criteria in order to be randomized to study treatment: 
1. Endoscopic bilateral NP score of at least 5 out of a maximum score of 8 (with a 
minimum score of 2 in each nasal cavity) taken at Visit 1 as assessed at central 
laboratory 
2. Mean nasal obstruction VRS of 2 or greater over the last 7 days preceding Visit 2 
(excluding Visit 2) (from electronic diary [eDiary]) 
3. eDiary compliance for at least 4 out of the last 7 days preceding Visit 2 (excluding 
Visit 2). 
4. Not had any NP surgery between Visit 1 and Visit 2 and not on a waiting list for NP 
surgery at the time of randomization. 
5. Laboratory abnormality: No evidence of clinically significant abnormality in the 
haematological, biochemical or urinalysis screen at Visit 1, as judged by the 
investigator. 
6. Liver Chemistry Tests: obtained at Visit 1: 
− 
ALT ≤ 2x upper limit of normal (ULN) 
− 
Bilirubin ≤ 1.5x ULN (isolated bilirubin >1.5x ULN is acceptable if bilirubin is 
fractionated and direct bilirubin <35%) 
7. ECG: QTcF < 450 msec, or QTcF < 480 msec for participants with Bundle Branch 
Block, in the 12-lead ECG machine-read at Randomization Visit 2. No evidence of a 
clinically significant abnormality in the central over-read of the 12-lead ECG 
conducted at Screening Visit 1 that would impact the participant’s participation 
during the study, based on the evaluation of the Investigator. See Section 8.3.3 for 
further ECG guidance.  
8. Asthma Exacerbation: No asthma exacerbations during run-in period. An 
exacerbation is defined as worsening of asthma requiring the use of systemic 
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visit, or hospitalization. 
9. Maintenance Therapy: No new systemic corticosteroids for CRSwNP have been 
started during the run-in period. 
10. If the participant has an URTI or cold during run-in, then run-in should be extended 
to have the Visit 2, 2 weeks post the resolution of the cold but no greater than a total 
of 6 weeks from Visit 1. Participants with colds that are not resolved within the 4th 
week of the nominal run-in period (28 days after screening) will be ineligible for 
randomization as they would have exceeded the 6 weeks period. 
5.4. 
Lifestyle Considerations 
Not applicable for this study. 
5.5. 
Screen/Run-in Failures 
Screen/run-in failures are defined as participants who consent to participate in the clinical 
study but are not subsequently randomized. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes 
demography, screen failure details, eligibility criteria, any protocol deviations and any 
serious adverse events (SAEs). 
For the purposes of this study, screening failures will be sub-divided as follows: 
• 
Participants will be assigned a study number at the time of signing the informed 
consent.  
• 
Those participants that complete at least one Visit 1 (Screening) procedure but do not 
enter the run-in period will be designated as screen failures. 
• 
Those participants that enter the run-in period, but are not randomized, will be 
designated as run-in failures. 
Rescreening of participants will be permitted, however, advanced approval to proceed 
with rescreening the participant must be obtained from the Medical Monitor (for contact 
details, see study reference manual [SRM]). Rescreened participants should sign a new 
ICF and should be assigned a new participant number for every screening/rescreening 
event. 
5.6. 
Criteria for Temporarily Delaying Randomization / Initiation 
of Study Intervention Administration 
Initiation of the study intervention administration could be temporarily delayed at Week 0 
(Visit 2) and Week 26 (Visit 9), such as due to parasitic infection (see Section 7.1.4). A 
delayed administration of the study intervention may be considered in consultation with 
the GSK Medical Monitor. 

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6. 
STUDY INTERVENTION(S) AND CONCOMITANT 
THERAPY 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol. 
6.1. 
Study Intervention(s) Administered 
The term ‘study intervention’ is used throughout the protocol to describe any 
combination of products received by the participant as per the protocol design. Study 
intervention may therefore refer to the individual study treatments or the combination of 
those study treatments. 
Depemokimab is a humanised IgG antibody (IgG1, kappa) with human heavy and light 
chain frameworks. Depemokimab Injection, 100 mg/mL, drug product is supplied as a 
sterile, preservative-free aqueous solution of purified mAb in a Type I glass syringe. The 
drug product and syringe will be assembled in a single use, disposable pre-filled syringe 
(PFS) to enable delivery of the drug product. The formulation contains L-histidine, 
trehalose dihydrate, L-arginine hydrochloride, disodium edetate, water for injection and 
polysorbate 80. 
The placebo in this study will be 0.9% sodium chloride solution contained in a PFS also 
supplied by GSK. 
Description of depemokimab and placebo is provided in Table 3. 
Table 3 
Description of Depemokimab and Placebo  
Arm Name 
Depemokimab 100 mg 
Placebo 
Intervention Name 
Depemokimab 100 mg SC 
Placebo 
Type 
Biologic 
N/A 
Dose Formulation 
Sterile liquid formulation in single- use 
PFS 
Sterile 0.9% (w/v) sodium chloride 
solution in single use PFS 
Unit Dose Strength(s) 
100 mg/mL; 1.0 mL (deliverable) 
N/A, 1.0 mL (deliverable) 
Dosage Level(s) 
100 mg once every 26 weeks 
(Week 0 and Week 26) 
Placebo once every 26 weeks 
(Week 0 and Week 26) 
Route of Administration 
SC injection 
SC injection 
Use 
IMP 
Placebo 
Non-IMP 
NA 
NA 
Authorized 
AxMP/Unauthorized AxMP 
NA 
NA 
Sourcing 
Provided centrally by the Sponsor 
Provided centrally by the Sponsor 
Packaging and Labelling 
Study Intervention will be provided in 
PFS. Each PFS will be labelled as 
required per country requirement. 
Study Intervention will be provided in 
PFS. Each PFS will be labelled as 
required per country requirement. 
Abbreviations: PFS, Pre-filled safety syringe; IMP, Investigational Medicinal Product; N/A, not applicable 

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GSK will provide or reimburse the sites for SoC such as INCS and courses of OCS. 
6.1.1. 
Medical Devices 
Depemokimab Injection, 100 mg/mL, is supplied as a sterile, preservative-free aqueous 
solution in a 3 mL Type I untreated borosilicate clear glass vial with a 13 mm 
fluorinated-polymer coated grey bromobutyl rubber stopper and a 13 mm aluminium 
overall seal with a plastic flip-off cap, or in a 1 mL long Type I glass siliconized barrel 
with a 29G thin wall stainless steel needle sealed with rubber plugger stopper. The 
prefilled syringe is assembled in an SSD. 
6.1.2. 
Treatment Assignment 
Participants eligible to enter the study will be assigned to treatment randomly via an 
interactive response technology (IRT) system. The randomization schedule will be 
generated using the GSK validated randomization software RAMOS NG. Randomization 
will be stratified based on occurrence of previous surgery for nasal polyps. A separate 
randomization list will be developed for each country. Participants will be assigned to 
study treatment in accordance with the randomization schedule. Once a randomization 
number has been assigned to a participant, it cannot be reassigned to any other participant 
in the study. 
6.2. 
Preparation, Handling, Storage and Accountability 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are 
reported and resolved before use of the study intervention. 
Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study interventions 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labelled storage conditions with access limited to 
the investigator and authorized site staff. 
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(i.e., receipt, reconciliation, and final disposition records). 
Further guidance and information for the final disposition of unused study intervention 
are provided in the SRM.  
Under normal conditions of handling and administration, study intervention is not 
expected to pose significant safety risks to site staff. Take adequate precautions to avoid 
direct eye or skin contact and the generation of aerosols or mists. In the case of 
unintentional occupational exposure notify the monitor, Medical Monitor and/or GSK 
study contact. 

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A Material Safety Data Sheet (MSDS)/equivalent document describing occupational 
hazards and recommended handling precautions either will be provided to the 
investigator, where this is required by local laws, or is available upon request from GSK. 
Precaution will be taken to avoid direct contact with the study intervention. A MSDS 
describing occupational hazards and recommended handling precautions will be provided 
to the investigator. In the case of unintentional occupational exposure notify the monitor, 
Medical Monitor and/or GSK study contact. 
The recommended storage condition is 2 - 8°C, protected from light. The expiry date, 
where required, is stated on the product label. 
Depemokimab Injection, 100 mg/mL (PFS SSD), should not be administered 
concomitantly with other drugs in the same syringe or administration assembly. 
For subcutaneous administration, Depemokimab Injection, 100 mg/mL (PFS SSD) and 
matching placebo in-use instructions are provided in the SRM. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
A participant may continue in the study if that participant’s treatment assignment is 
unblinded by the investigator or treating physician, but will not receive the second dose 
of study intervention at Week 26 (if not already received). The primary reason for 
discontinuation from study intervention (the event or condition which led to the 
unblinding) will be recorded in the eCRF. Every effort should be made to ensure the data 
of the participant are collected when possible. 
The RAMOS NG will be programmed with blind-breaking instructions. In case of an 
emergency, the investigator has the sole responsibility for determining if unblinding of a 
participants’ intervention assignment is warranted. Participant safety must always be the 
first consideration in making such a determination. If a participant’s intervention 
assignment is unblinded GSK must be notified within 24 hours after breaking the blind. 
The date and reason for the unblinding must be recorded in the source documentation and 
case report form (CRF), as applicable. 
To maintain the blind, data on IL-5 levels and haematology data (absolute and % values 
of eosinophils, lymphocytes, basophils, neutrophils, and monocytes) from post-
randomization samples will not be reported to the site or the central study team, prior to 
the unblinding of the study. 
GSK’s Pharma Safety staff may unblind assignment for any participant with an SAE. If 
the SAE requires that an expedited regulatory report be sent to one or more regulatory 
agencies, a copy of the report, identifying the participant’s treatment assignment, may be 
sent to investigators in accordance with local regulations and/or GSK policy. 

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6.3.1. 
Controlled Early Access to Unblinded PK and PKPD Data 
Designated independent representative(s) may be unblinded for performing population 
PK and PKPD dataset preparation and draft PK and PKPD model development using 
scrambled (random reassignment of subject identification numbers) PK and PKPD 
unblinded datasets, including baseline demographic characteristics. 
6.4. 
Study Intervention Compliance 
• 
Participants will receive study treatment directly from the investigator or designee, 
under medical supervision. The date and time of each dose administered in the clinic 
will be recorded in the source documents. The dose of study treatment and study 
participant identification will be confirmed at the time of dosing by a member of the 
study site staff other than the person administering the study treatment. 
• 
Participants will be monitored for a minimum of 2 hours (both at randomization and 
at Week 26) after study intervention administrations in the clinic. In the event of an 
acute severe reaction (e.g., anaphylaxis) following administration of study treatment, 
there are personnel/staff onsite at the treatment facility who are appropriately trained 
in basic life support to manage the participant including administration of 
medications (e.g., epinephrine), and have access to a system that can promptly 
transport the patient to another facility for additional care if appropriate. 
• 
Administration will be documented in the source documents and reported in the 
eCRF. 
6.5. 
Dose Modification 
Not applicable for this study. 
6.6. 
Continued Access to Study Intervention after the End of the 
Study 
There are no plans to provide depemokimab following study completion. 
The investigator is responsible for ensuring that consideration has been given to the post-
study care of the participant’s medical condition, whether or not GSK is providing 
specific post-study treatment. 
6.7. 
Treatment of Overdose 
The dose of depemokimab that is considered to be an overdose has not been defined. 
There are no known antidotes and there is no specific treatment for a suspected overdose. 
In FTIH study 205722 [GSK Document Number 2019N411063_00], single SC doses of 
depemokimab up to 300 mg were well tolerated in adult participants with mild/moderate 
asthma (6 participants received a 300 mg SC dose). 
Each PFS will enable the delivery of a single dose of study intervention (Section 6.1). 
In the event of a potential overdose, the investigator should: 

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• 
Contact the Medical Monitor immediately. 
• 
Treat the participant with active supportive care as dictated by the participant’s 
clinical status in the knowledge of the long half-life (approximately 41 days) of 
depemokimab. 
• 
Closely monitor the participant for AE/SAE and laboratory abnormalities for 
30 weeks following the last administered dose of depemokimab/placebo (either at 
randomization [Day 1] or Visit 9 [Week 26]). 
• 
Document the quantity of the excess dose as well as the duration of the 
overdosing in the CRF. 
Decisions regarding discontinuation or delay of another dose of depemokimab/placebo 
will be made by the investigator in consultation with the Medical Monitor based on the 
clinical evaluation of the participant. 
6.8. 
Prior and Concomitant Therapy 
Any medication or vaccine (including over the counter or prescription medicines, 
vitamins, and/or herbal supplements, and vaccine) that the participant is receiving 12 
months prior to enrolment, or receives during the study, must be recorded along with: 
• 
reason for use 
• 
dates of administration including start and end dates 
• 
dosage information including dose and frequency 
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
Initiation or changes in the dosing regimen of allergen immunotherapy from screening to 
end of the study are not allowed.  
With the exception of participants in Japan, daily INCS treatment is an inclusion 
criterion, and participants should continue INCS treatment throughout the study. 
Participants in Japan who are not on INCS at screening are permitted to start INCS while 
on study, if required for symptom management.  
Initiation or changes in the dosing regimen of leukotriene receptor antagonist from 
screening to end of the study are allowed, if required for symptom management.  
6.8.1. 
Permitted CRSwNP and Asthma Medications 
The following medications may be used for all participants: 
1. Short courses of systemic corticosteroids (for example of systemic corticosteroids for 
treatment of CRSwNP) are permitted prior to Screening and after Randomization, 
but not during the Run-in period. Although the use of rescue medications such as 
systemic CS is allowable during the treatment phase of the study (Visit 2 and 
onwards); the date and time of rescue medication administration as well as the name 

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and dosage regimen (dose and duration) of the rescue medication must be recorded 
in the eCRF for NP as well as for other comorbidities. 
2. Throughout the study, asthmatic participants are to be maintained on their baseline 
SoC asthma treatment. 
3. Courses of antibiotics and saline nasal douches are permitted at any time. For 
antibiotic treatment for CRSwNP / ECRS, the type, dose and duration must also be 
recorded in the eCRF. 
4. INCS are allowed with no interruption throughout the study duration. If a 
participant in Japan is not on INCS prior to screening, the participant is 
permitted to start INCS during the study, if required for symptom 
management. Once on INCS, the participant should remain on INCS for the 
remainder of the study. 
6.8.2. 
Prohibited Medications 
The following medications are not allowed prior to screening (Visit 1), according to the 
following schedule, or during the study (Table 4): 
Table 4 
Prohibited medications 
Prohibited Medication 
Time Period Prior to Screening Visit 
Investigational products (non-biologic) 
30 days or 5 half-lives whichever is longer  
Investigational products (biologic) 
3 months or 5 half-lives whichever is longer  
Omalizumab [Xolair] 
130 days 
Dupilumab [Dupixent] 
130 days 
Mepolizumab [Nucala], reslizumab 
[Cinqair/Cinqaero], benralizumab [Fasenra] 
12 months 
Other monoclonal antibodies (other than for the 
treatment of COVID-19, see Section 6.8.3) 
5 half-lives 
Immunosuppressive medications such as those listed below (not all inclusive) 
Chronic systemic corticosteroids including oral, 
intramuscular, long-acting depot 
1 month 
Methotrexate, cyclosporin, Azathioprine 
1 month 
Oral gold 
3 months 
Chemotherapy used for conditions other than 
asthma 
12 months 
Insertion of any non-drug or drug eluting nasal 
stents such as Propel stents 
6 months 
Direct steroid injections into CRSwNP / ECRS 
6 months 

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6.8.3. 
COVID-19 Vaccines and treatments 
Participants can be vaccinated against SARS-CoV-2 infection using authorized 
COVID-19 vaccines in line with local/national guidelines for COVID-19 vaccines. 
Experimental COVID-19 vaccines are not permitted. 
Any COVID-19 treatment (including monoclonal antibodies) approved by local 
government (in line with local/national guidelines) is permitted. 
Experimental COVID-19 treatments are not permitted. 
COVID-19 vaccine administration and the study site injection should be separated by 
14 days if possible, in order to be able to properly assess study injection site/treatment 
reactions. 
Refer to the SRM for further details. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
At the point of informed consent prior to screening, participants will be requested to 
provide permission and agree to be contacted even after study withdrawal/study 
intervention discontinuation to collect information relating to any surgical intervention to 
the NP. Every effort will be made to have all participants attend study visits up to 
Week 52 even if they discontinue study treatment in order to capture NP scores, symptom 
score, any subsequent surgical procedures or entry into a waiting list for NP surgery. 
7.1. 
Discontinuation of Study Intervention 
A participant may discontinue from study intervention at any time at his/her own request, 
or at the discretion of the investigator. If study treatment is permanently discontinued (for 
any reason), the participants are encouraged to remain in the study until the completion of 
the Week 52 Visit assessments (Table 1; refer to the SRM for further details). If this not 
possible, the investigator should encourage the participant to participate in as much of the 
study as they are willing (or able) to. 
The participant’s NP surgical status will be tracked for the duration of the study. The 
participants are also allowed to have nasal surgery during the study without 
discontinuation from study intervention.  
All participants will be followed up for the study duration. As a minimum the participants 
should agree to be contacted by telephone to enquire regarding any safety assessments 
and any NP surgery events. The primary reason for discontinuation of study intervention 
(and sub-reason, if applicable) will be recorded in the eCRF. If for any reason, the 
participant later chooses to withdraw from the study, a Withdraw from Study Visit (see 
Section 7.2) should be conducted according to Table 1. 

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7.1.1. 
Specified Study Intervention Discontinuation Criteria  
A participant must be discontinued from study intervention if any of the following 
stopping criteria are met:  
• 
Liver Chemistry: Meets any of the protocol defined liver chemistry stopping criteria 
(see Section 7.1.2 and Appendix 6) 
• 
QTc: Meets any of the protocol defined QTc stopping criteria (see Section 7.1.3) 
• 
Pregnancy: Positive pregnancy test (see Section 8.4.5 and Appendix 4) 
• 
Severe allergic reaction/anaphylaxis: Participants with severe allergic 
reaction/anaphylaxis with no clear alternative cause (see Appendix 8 in 
 Section 10.8). 
• 
Vasculitis: Participants with confirmed vasculitis or suspected vasculitis with no 
alternative explanation (see Section 7.4). 
• 
Study treatment unblinded: Unblinding of the study treatment assigned to a 
participant by the investigator or treating physician (see Section 6.3).  
7.1.2. 
Liver Chemistry Stopping Criteria 
Liver chemistry stopping, and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event aetiology. 
Discontinuation of study intervention for abnormal liver tests is required when: 
• 
a participant meets one of the conditions outlined in Figure 2 and Figure 3 
OR 
• 
in the presence of abnormal liver chemistry not meeting protocol specified stopping 
rules, if the investigator believes that it is in the best interest of the participant.  
Study treatment restart or rechallenge after liver chemistry stopping criteria are met by 
any participant in this study is not allowed. 
Details of liver chemistry stopping criteria, required actions, and follow-up assessments 
after liver stopping or monitoring event are given in Appendix 6. 

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Figure 2 
Liver Chemistry Stopping Criteria Algorithm 
 
Abbreviations: ALT, alanine transaminase; INR, international normalised ratio; Tbili, total bilirubin; SAE, serious 
adverse event; ULN, upper limit of normal 

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Figure 3 
Liver Chemistry Increased Monitoring Algorithm with Continued 
Study Intervention for Participants with ALT ≥3x ULN but <8xULN 
and do not meet any of the liver stopping criteria 
 
Abbreviations: ALT, alanine transaminase; INR, international normalised ratio; Tbili, total bilirubin; SAE, serious 
adverse event; ULN, upper limit of normal  
7.1.3. 
QTc Stopping Criteria 
The QT interval corrected for heart rate by Fredericia’s formula (QTcF) must be used for 
each individual participant to determine eligibility for the study and discontinuation from 
study treatment. This formula may not be changed or substituted for the duration of the 
study. 
For this study, the following QTc stopping criteria will apply: 
• 
QTcF >500 msec or uncorrected QT >600 msec 
• 
Change from baseline: QTcF >60msec 
• 
For participants with bundle branch block, follow the criteria listed below:  
− 
QTcF >500 msec (if baseline QTcF <450 msec) 
− 
QTcF ≥530 msec (if baseline QTcF 450-480 msec) 
The QTcF value from the 12-lead ECG central over-read at randomization visit 2 should 
be used as baseline QTcF value for any changes from baseline calculations during the 
study. 

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• 
After randomization 12-lead ECG central over-read values should be used to assess 
QTc stopping criteria, with the exception of Visit 9 (Week 26) where 12-lead ECG 
machine read values should be used. 
7.1.4. 
Temporary Discontinuation 
For this study, a temporary discontinuation refers to a delayed administration of the 
second dose of study intervention beyond Week 26. 
For example, if a participant becomes infected (parasitic infection) during the study 
treatment period before receiving the second dose of study intervention and does not 
respond to antihelminth treatment, a delayed administration of the study intervention may 
be considered in consultation with the GSK Medical Monitor. 
7.1.5. 
COVID-19 Testing 
Participants that test positive for COVID-19 do not have to discontinue study 
intervention. Participants are encouraged to remain in the study and be followed up per 
study schedule as participants well-being allows. Every effort should be made by the 
Investigator/site staff to keep the participant in the study until their nominal 52 weeks 
post randomization date. 
• 
COVID-19 tests during the study may be performed, as determined by the 
investigator or local guidelines.  
• 
All positive COVID-19 tests should be reported on the relevant eCRFs and the 
AE/SAE eCRFs, as appropriate.  
• 
Positive tests should be reported to the appropriate local government authorities, per 
local regulations.  
7.2. 
Participant Discontinuation/Withdrawal from the Study 
Participants are strongly encouraged to remain in the study for the entire duration but 
may prematurely withdraw from the study at any time at his/her own request, at the 
request of their legally authorized representative (LAR), or may be withdrawn at any time 
at the discretion of the investigator for safety, behavioural, or compliance reasons.  
Participants who prematurely withdraw from the study should attend:  
• 
Early Withdrawal (EW) Visit, 26 weeks after the last administered dose of study 
intervention (at Week 26 or Week 52) AND 
• 
Follow-up visit/call, 30 weeks after the last administered dose of study intervention 
for AE/SAE and pregnancy assessments. 
Note: this includes any participants who initially discontinue study intervention and 
remain in the study (Section 7.1) but later decide to withdraw from the study. 
Participants who are prematurely withdrawn from study should be encouraged to 
complete their eDiary up until their EW Visit. 

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See SoA (Section 1.3) for data to be collected at the time of study withdrawal and follow-
up and for any further evaluations that need to be completed. 
The participant will be permanently discontinued from the study intervention and the 
study at that time. 
If the participant withdraws consent for disclosure of future information, the sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
If a participant withdraws from the study, he/she may request destruction of any samples 
taken and not tested, and the investigator must document this in the site study records. 
7.3. 
Lost to Follow Up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• 
The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study. 
• 
Before a participant is deemed lost to follow up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls/other contact methods, and if necessary, a certified letter to the participant’s last 
known mailing address or local equivalent methods). These contact attempts should 
be documented in the participant’s medical record. 
• 
Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study.  
• 
Site personnel, or an independent third party, will attempt to collect the vital status 
information of the participant within legal and ethical boundaries for all participants 
randomized, including those who did not get study intervention. Public sources may 
be searched for vital status information. If vital status is determined as deceased, this 
will be documented along with other relevant study information. Sponsor personnel 
will not be involved in any attempts to collect vital status information. 

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7.4. 
Criteria for Follow-up of Potential Type III Hypersensitivity 
(Immune Complex Disease /Vasculitis) 
Owing to the adverse findings of arterial inflammation that were observed in the 1 month, 
but not 6-month, nonclinical toxicology studies, events potentially representing type III 
hypersensitivity/immune complex disease/vasculitis should be promptly reported to GSK, 
and consultation with the Medical Monitor is encouraged. Treatment for the event will be 
given as medically required. If possible, PK, ADA, C3, and C4 samples may be taken at 
the time of the event along with haematology, clinical chemistry and urinalysis. 
Symptoms potentially suggestive of vasculitis include but are not limited to: 
• 
persistent* fever  
• 
persistent* muscle and joint pain 
• 
persistent* rash 
• 
persistent* fatigue 
• 
symptoms of peripheral neuropathy, like numbness or weakness 
• 
laboratory abnormalities, e.g., decreased platelets, elevated creatinine, decrease in 
complement C3/C4, abnormal urinary albumin/creatinine ratio 
(*Note: persistent is considered to be a duration of ≥2 days.) 
Participants who experience any of the above events should be monitored until the event 
resolves and/or a diagnosis is established. 
The symptoms and clinical features are often non-specific and heterogenous with respect 
to the time course over which they develop, organ involvement and the constellation of 
symptoms and severity. Early recognition of potential events of vasculitis is important to 
timely diagnosis and subsequent treatment. 
The precise management will depend on the clinical evaluation at the time of presentation 
and ongoing assessment including consideration of relevant differential diagnoses. Given 
that there is often a differential for presenting symptoms such as infection, and indeed 
such factors may also precipitate immune related AEs, these factors (infectious, 
neoplastic, metabolic, toxic) should be given due consideration and ruled out. 
Serological, immunological, and histological (biopsy) data should be considered to 
support the diagnosis and consultation with the GSK Medical Monitor, and an 
appropriate medical specialist should be considered when investigating a possible 
immune related AE. 
Unscheduled PK, ADA, C3 and C4 samples may be taken at the time of the event and 
samples may be taken for additional biomarkers (e.g., antinuclear antibodies [ANA], 
antineutrophil cytoplasmic antibodies [ANCA]) in the setting of clinical concern 
regarding the possibility of immune complex disease. If necessary, testing for 
biomarkers, e.g., ANA, ANCA (anti-myeloperoxidase [MPO] antibody and 
anti-proteinase 3 [PR3] antibody), may also be conducted using the frozen baseline serum 
samples (that were collected and stored prior to administration of study intervention) to 

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allow for evaluation of interval change for participants with suspected vasculitis (see 
Section 8.6.3). Other possible causative or differential factors for abnormal clinical or 
laboratory observations may also have to be investigated including testing to exclude 
infection. 
If clinically indicated, the participant may be referred to a specialist for further 
management, which may include organ biopsy. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
• 
Study procedures and their timing are summarized in Table 1.  
• 
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 participant should continue or 
discontinue study intervention. 
• 
Adherence to the study design requirements, including those specified in Table 1, is 
essential and required for study conduct. 
• 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening 
log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable.  
• 
Procedures conducted as part of the participant’s routine clinical management (e.g., 
blood count) and obtained before signing of the ICF may be utilized for Screening or 
baseline purposes provided the procedure met the protocol specified criteria and was 
performed within the time frame defined in the SoA (Section 1.3). 
• 
Following randomization, laboratory results that could unblind the participant’s 
intervention assignment will not be reported to investigative sites or other blinded 
personnel until the study has been unblinded. 
• 
Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples. 
• 
When permitted by local regulations, all effort will be made so that whenever 
possible the study visits will be home nursing visits (when a study nurse will visit the 
participant at home instead of the participant having to go to the site) or telemedicine 
(virtual visit, typically video or voice call). Please follow Table 1 for information on 
the optional home nursing visits or telemedicine visits. 
8.1. 
Administrative and general/baselines procedures 
8.1.1. 
Collection of demographic data 
Record demographic data including year of birth, sex, race, and ethnicity in the 
participant’s eCRF, where permitted by local regulations. 

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8.1.2. 
Medical history 
Obtain the participant’s medical history by interviewing the participant and/or review of 
the participant’s medical records. Record pre-existing conditions of interest per the 
eCRF, prior to study start.  
8.2. 
Efficacy Assessments 
8.2.1. 
Endoscopic NP Score 
Endoscopic NP score will be assessed at study visits as described in Table 1. This score is 
graded based on NP size and recorded as the sum of the right and left nostril scores with a 
range of 0-8; higher scores indicate worse status. 
Endoscopic NP score will be performed at the site by trained health care professional 
(usually ENT surgeon). All image recordings of endoscopies will be sent to an 
independent reviewer at Clario, the central lab for blinded NP scoring. There is potential 
for the site score to differ from the central score. In such cases, the output from the 
central labs is considered final and will be utilized for patient eligibility and for the 
analysis of this endpoint (for additional details refer to the Clario Video Guideline). 
For Visit 2, the nasal endoscopy assessment may be performed up to 7 days prior to the 
clinic visit but must occur prior to randomization. For all other visits the nasal endoscopy 
assessment must not exceed the protocol defined windows of ±7 days from the nominal 
study visit. 
8.2.2. 
Symptoms 
Clario will provide the eDiary for administering electronic Patient-Reported Outcome 
(ePRO) on the study. 
8.2.2.1. 
Individual Symptoms Verbal Response Scale (VRS) 
All VRS symptom scores will be administered using the eDiary and will be collected 
daily in the morning from screening to the end of the Treatment Period. 
Every day, the participant will be asked to indicate on a VRS, the severity of 4 nasal 
polyposis symptoms at their worst over the last 24 hours (one VRS for each symptom): 
1. nasal obstruction; 2. rhinorrhoea (runny nose); 3. loss of smell; 4. facial pain; 5. mucus 
in the throat. 
A 4-point Likert scale will be used, with appropriate verbal response options of no 
symptoms, mild symptoms, moderate symptoms, and severe symptoms. Participants will 
be instructed on how to use the scale prior to use. 
Please refer to the SRM for further details on the phrasing of these questions and 
response options. 

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8.2.2.2. 
Overall Visual Analogue Scale (VAS) Symptoms Score 
The overall symptoms VAS to be used in the study will be administered using the eDiary 
and will be collected daily in the morning from screening to the end of the treatment 
period. 
Every day, the participant will be asked to indicate on a VAS, the overall severity of 
nasal polyposis symptoms at their worst over the last 24 hours. 
The left-hand side of the scale (0) represents “None” and the right-hand side of the scale 
(100) represents “As bad as you can imagine”. The participant selects a point on the line 
that represents their current experience on the continuum. The eDiary will be suitably 
pixilated to allow the selection of all integers from 0 to 100. Participants will be 
instructed on how to use the scale prior to use. The final VAS scores that are reported 
will be derived from the electronically captured score by dividing each score by 10 and 
will range between 0 and 10. 
8.2.2.3. 
Nasal Obstruction Symptoms VAS 
A Nasal Obstruction VAS score will be administered using the eDiary at key timepoints 
to facilitate understanding and interpretation of the Nasal Obstruction VRS (see Table 1). 
Through run-in, baseline and 4 weeks prior to Week 24 (i.e., from Week 21 through to 
Week 24) and Week 52 (i.e., from Week 49 through to Week 52) the participant will be 
asked to indicate on a VAS the Nasal Obstruction symptoms at their worst. 
8.2.3. 
Computed Tomography (CT) Scan 
CT scan is mandatory unless not approved by local ethics committee or institutional review 
board. The first CT scan must be performed prior to randomization and should be the last 
assessment performed, where possible. If the first CT scan cannot be performed as the 
last assessment before randomization, the subject should have completed their screening 
visit, and all screening lab results, the central NP score and ECG central over-read results 
should be assessed by the PI before a CT scan is conducted. The second CT scan should 
be performed at V16 or EW visit (up to 14 days prior to the nominal study visit). Note: 
If a participant is permanently discontinued both from the study intervention and from the 
study, and the second dose of study intervention was not received, decision on 
performing CT scan during Early Withdrawal visit at Week 26 will be made by the 
investigator in consultation with the Medical Monitor. 
The Lund Mackay (LMK) CT scoring system is based on localization with points given 
for degree of opacification: 0 = normal, 1 = partial opacification, 2 = total opacification. 
These points are applied to the maxillary, anterior ethmoid, posterior ethmoid, sphenoid, 
frontal sinus on each side. The osteomeatal complex (OC) is graded as 0 = not occluded, 
or 2 = occluded deriving a maximum score of 12 per side. This scoring system has been 
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All image recordings of CT scans will be sent to an independent reviewer at Clario for 
centralized blinded data assessment and central reading for LMK scoring will be used for 
analysis. 
For participants in whom the OC is missing (because of a previous surgery) the reader 
should consider the location of the former OC and provide a scoring (as if the OC was 
there). 
Detailed information on the CT assessment will be available in a separate operational 
manual provided to the sites. CT scans central reading for LMK scoring will be used in 
the statistical analysis. 
8.2.4. 
NP Surgery 
At each visit, it will be recorded whether the participant is on a waiting list for NP 
surgery and whether the participant has received confirmed documented surgery. As an 
endpoint, for the purpose of this study, NP surgery is defined as any procedure involving 
instruments resulting in incision and removal of tissue from the nasal cavity 
(polypectomy/ESS). Dilatation of the air passages in the nasal cavity (e.g., balloon 
sinuplasty) will not be included in this endpoint. Procedures occurring on the same date 
will be considered as part of the same surgery event.  
Wherever possible the removed tissue from a nasal surgery will be collected and stored. 
Detailed processing and storage instructions are provided in the laboratory manual. 
8.2.5. 
Corticosteroid Medication 
The dose and duration of courses of systemic steroids (for NP and for any other reason) 
will be recorded in the eCRF. The dose and duration of the course of systemic CS will be 
according to the participants SoC for systemic CS use for its NP condition.  
For the purpose of this study courses of systemic corticosteroids separated by less than 7 
days will be considered to be one continuous course.  
8.2.6. 
Health-Related Quality of Life (HRQoL) Assessments 
Participants should complete all questionnaires in a quiet location, free from distraction, 
prior to the completion of other study procedures. All questionnaires will be completed 
on an electronic handheld device provided by Clario. Site staff can provide limited advice 
if required, however participants should not be guided or directed in answering questions. 
During training participants should be instructed to select the single response option for 
each question that most closely reflects their health over the time period indicated for 
each questionnaire. Participants will not be able to skip or miss questions. 

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8.2.6.1. 
Sino-Nasal Outcome Test (SNOT-22) Questionnaire 
SNOT-22 is a 22-item measure of disease specific HRQoL. It will be completed by the 
participant at study visits according to Table 1 on the eDiary. 
The SNOT-22 has been shown to be a reliable outcome measure for successful septal 
surgery [Buckland, 2003]. It is also recommended as a suitable questionnaire in CRS 
management [Morley, 2006] and its routine use is recommended as a tool to evaluate 
outcomes in NP [Browne, 2006]. 
Participants will be asked to rate the severity of their condition on each of the 22 items 
over the previous 2 weeks using a 6-point rating scale of 0-5 including: 0 = Not 
present/no problem; 1 = Very mild problem; 2 = Mild or slight problem; 3 = Moderate 
problem; 4 = Severe problem; 5 = Problem as “bad as it can be”. The total score range for 
the SNOT-22 is 0-110, where higher scores indicate greater disease impact. Psychometric 
analyses of data from the 205687 study (SYNAPSE) indicate that a decrease of 28 points 
or greater is a clinically meaningful within participant change [Han, 2021]. The 
previously published minimum clinically important difference (MCID) of a difference of 
≥8.9 will also be reported [Hopkins, 2009]. In addition to the overall score, the SNOT-22 
provides two summary scores of symptoms and impacts and 6 domain scores of nasal 
symptoms, ear and facial symptoms, non-nasal symptoms, fatigue, impact on sleep and 
emotional. 
8.2.6.2. 
Patient Global Impression of Change and Severity of Nasal Polyp 
Symptoms 
Two single item patient global impression scales will be completed by participants to 
assess change and severity of nasal polyps symptoms, according to Table 1. Both items 
will have a 5-point Likert response scale. The primary objective of these scales is to 
provide anchors for subsequent in trial psychometric analyses. 
• 
The Patient Global Impression of Change (PGIC) will ask the patient to rate the 
change in their nasal polyps symptoms since the start of trial medication. 
• 
The Patient Global Impression of Severity (PGIS) will ask the patient to rate the 
severity of their nasal polyps symptoms over the last 4 weeks.  
8.2.7. 
For Asthmatic Participants Only: 
8.2.7.1. 
Asthma Control Questionnaire (ACQ-5) 
The ACQ-5 is a 5-item questionnaire, which has been developed as a measure of 
patients’ asthma control that can be quickly and easily completed [Juniper, 1999;  
Juniper, 2005]. The questions are designed to be self-completed by the participant. The 5 
questions enquire about the frequency and/or severity of asthma symptoms over the 
previous week (nocturnal awakening on waking in the morning, activity limitation, and 
shortness of breath, wheeze). The response options for all these questions consist of a 
zero (no impairment/limitation) to six (total impairment/ limitation) scale. The recall 
period is the past week.  

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ACQ-5 will be assessed during the study according to Table 1. 
8.2.7.2. 
Asthma Exacerbations 
Clinically significant exacerbations of asthma are defined by: 
• 
Worsening of asthma which requires use of systemic CSs* and/or hospitalization 
and/or Emergency Department visit. 
(*Note: For all participants, IV or oral steroids (e.g., prednisone) for at least 3 days or a 
single IM CS dose is required. For participants on maintenance systemic CSs, at least 
double the existing maintenance dose for at least 3 days is required.) 
Exacerbations separated by less than 7 days will be treated as a continuation of the same 
exacerbation. 
Details of each asthma exacerbation, including medications used to treat exacerbations 
should be recorded in the eCRF. 
Asthma exacerbations should not be recorded as an AE unless they meet the definition of 
an SAE. 
The time period for collection of exacerbation information in the eCRF will be from the 
start of study intervention until the Exit Visit or Follow-up Visit if applicable. 
8.3. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA. Where possible, 
these should be aligned with SoC. 
8.3.1. 
Physical Examinations 
• 
A physical examination will include, at a minimum, assessments of the skin, eyes, 
cardiovascular (CV), respiratory, gastrointestinal and neurological systems. Height 
(screening only) and weight will also be measured and recorded. 
• 
Investigators should pay special attention to clinical signs related to previous serious 
illness. 
8.3.2. 
Vital Signs 
• 
Temperature, systolic and diastolic blood pressure and heart rate will be assessed. 
• 
Blood pressure and heart rate measurements will be assessed in the resting state with 
a completely automated device. Manual techniques will be used only if an automated 
device is not available. 
• 
Blood pressure and heart rate measurements should be preceded by at least 5 minutes 
of rest for the participant in a quiet setting without distractions (e.g., television, cell 
phones) and should be taken before blood collection for laboratory tests. 

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8.3.3. 
Electrocardiograms 
• 
12-lead ECG will be obtained as outlined in Table 1 using an ECG machine, 
provided by GSK via Clario the designated central laboratory, that automatically 
calculates the heart rate and measures PR, QRS, QT, and QTc intervals.  
• 
The QTcF formula must be used for each individual participant to determine 
eligibility. This formula may not be changed or substituted once the participant has 
been enrolled. 
• 
If an ECG demonstrates a prolonged QT interval, obtain two more ECGs over a brief 
period, and then use the averaged QTcF values of the three ECGs to determine 
whether the participant should be screened/ randomized/ discontinued from the study 
intervention (but not from the study). Refer to Section 5.2 and Section 5.3 for 
exclusion and randomization criteria related to ECG assessment, and Section 7.1.3 
for QTc stopping criteria. 
• 
ECG measurements will be made after the participant has rested in the supine 
position for 5 minutes and should be obtained after the vital signs assessments. 
Collection shortly after a meal or during sleep should be avoided since QT 
prolongation can occur at these times. 
• 
Paper ECG traces will be recorded at a standard paper speed of 25 mm/sec and gain 
of 10 mm/mV, with a lead II rhythm strip. There will be electronic capture and 
storage of the data by a validated method (for additional details refer to the Vendor 
Manual). 
• 
Paper ECG traces are required to be maintained at the site with other source 
documents. 
− 
For further details please refer to the SRM. 
8.3.4. 
Clinical Safety Laboratory Tests 
• 
Q2 Solutions is the central laboratory service provider for this study. 
• 
All protocol-required laboratory assessments, as defined in Appendix 2, must be 
conducted in accordance with the central laboratory manual and the SoA. The timing 
and frequency are provided in Table 1. 
• 
The investigator must review the laboratory report, document this review, and record 
any clinically significant 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 participant’s condition. 
• 
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study until the Exit Visit (or Follow-up visit/call if applicable) 
should be repeated until the values return to normal or baseline or are no longer 
considered significantly abnormal by the investigator or Medical Monitor. If 
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judged reasonable by the investigator, the aetiology should be identified, and the 
Sponsor notified. 
• 
If laboratory values from non-protocol specified laboratory tests performed at the 
institution’s local laboratory require a change in participant management or are 
considered clinically significant by the investigator (e.g., SAE or AE), then the 
results must be recorded. 
• 
To maintain the treatment blind, the site and the central study team will not be sent 
information on haematology differential (absolute and % values of eosinophils, 
lymphocytes, basophils, neutrophils, and monocytes) from any visits post-
randomization. 
8.3.5. 
Pregnancy Testing 
• 
Pregnancy testing entry criteria are provided in Section 5.1. 
• 
Serum pregnancy test should be conducted for all WOCBP at Screening Visit, at 
Week 52 Visit, and at Early Withdrawal Visit. In addition, urine pregnancy tests 
should be performed at the timepoints specified in Table 1, including at the Follow-
up Visit/call (if applicable).  
• 
To mitigate risk of exposure of foetus to ionising radiation from Sinus CT, highly 
sensitive urine pregnancy test should also be performed within 24 hours prior to the 
CT scan and results to be assessed prior to CT scan.  
• 
If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum 
pregnancy test is required and the result assessed prior to the CT scan. 
• 
A final urine pregnancy test should be conducted for all WOCBP, 30 weeks after the 
last administered dose of study intervention: 
− 
Participants should have a urine pregnancy test at the Follow-up Visit/call 
(Week 56). A self-reported home urine pregnancy test result is acceptable if the 
follow-up is conducted as a phone call visit. 
− 
Participants who withdraw early from the study should have a urine pregnancy 
test, 4 weeks after the Early Withdrawal Visit. 
• 
Additional serum or urine pregnancy tests may be performed, as determined 
necessary by the investigator or required by local regulation, to establish the absence 
of pregnancy at any time during the participant’s participation in the study. 
8.4. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and 
Other Safety Reporting 
The definitions of an AE and SAE can be found in Appendix 3. 
The definitions of device-related safety events, adverse device effects (ADEs) and  
serious adverse device effects (SADEs) can be found in Appendix 7. 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant's LAR). 

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The investigator or their designees are responsible for detecting, documenting and 
reporting events that meet the definition of an AE or SAE and remain responsible for 
following up.  
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3. 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• 
All SAEs will be collected from the start of intervention (Day 1) until the follow-up 
visit at the timepoints specified in Table 1. However, any SAEs assessed as related to 
study participation (e.g., study intervention, protocol-mandated procedures, invasive 
tests, or change in existing therapy) or related to a GSK product will be recorded 
from the time a participant consents to participate in the study.  
• 
All SAEs will be recorded and reported to the sponsor or designee immediately and 
under no circumstance should this exceed 24 hours, as indicated in Appendix 3. The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it 
being available. 
• 
All AEs will be collected from the start of intervention (Day 1) until the follow-up 
visit at the timepoints specified in Table 1. 
• 
Medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will be recorded as medical history/current medical 
conditions not as AEs. 
• 
Investigators are not obligated to actively seek information on AEs or SAEs after 
conclusion of the study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the study, 
and he/she considers the event to be reasonably related to the study intervention or 
study participation, the investigator must promptly notify the sponsor. 
NOTE: The method of recording, evaluating and assessing causality of AEs and SAEs 
and procedures for completing and transmitting SAE reports to GSK are provided in 
Appendix 3.  
8.4.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended 
and non-leading verbal questioning of the participant is the preferred method to inquire 
about AE occurrence. Appropriate questions include:  
“How are you feeling?”  
“Have you had any (other) medical problems since your last visit/contact?”  
“Have you taken any new medicines, other than those provided in this study, since your 
last visit/contact?”  

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8.4.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs will be followed until resolution, until 
the condition stabilizes, until the event is otherwise explained, or until the participant is 
lost to follow-up (as defined in Section 7.3). Further information on follow-up procedures 
is given in Appendix 3. 
8.4.4. 
Regulatory Reporting Requirements for SAEs 
• 
Prompt notification by the investigator to the sponsor of an SAE is essential so that 
legal obligations and ethical responsibilities towards the safety of participants and 
the safety of a study intervention 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 a study intervention under clinical 
investigation. The sponsor will comply with country-specific regulatory 
requirements relating to safety reporting to the regulatory authority, IRB/IEC, and 
investigators. 
• 
An investigator who receives an investigator safety report describing an SAE or 
other specific safety information (e.g., summary or listing of SAEs) from the sponsor 
will review and then file it along with the IB and will notify the IRB/IEC, if 
appropriate according to local requirements. 
• 
Investigator safety reports must be prepared for suspected unexpected serious 
adverse reactions according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 
8.4.5. 
Pregnancy 
• 
Investigator will collect pregnancy information on any female participants, who 
becomes pregnant while participating in this study. 
• 
Details of all pregnancies in female participants will be collected from the start of  
study intervention and until 30 weeks after the last administered dose of study  
intervention. 
• 
If a pregnancy is reported, the investigator will record pregnancy information on the 
appropriate form and submit to GSK within 24 hours of learning of the female 
participant’s pregnancy. While pregnancy itself is not considered to be an AE or 
SAE, any pregnancy complication or elective termination of a pregnancy for medical 
reasons will be reported as an AE or SAE. 
• 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs and will be reported 
as such. 
• 
The participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on the participant and the neonate and 
the information will be forwarded to the sponsor. 

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• 
Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in 
Section 8.4.4 and Appendix 3. While the investigator is not obligated to actively seek 
this information in former study participants, he or she may learn of an SAE through 
spontaneous reporting. 
• 
Any female participant who becomes pregnant while participating in the study will 
immediately discontinue study medication. 
8.4.6. 
Cardiovascular and Death Events 
For any cardiovascular events detailed in Appendix 3 and all deaths, whether or not they 
are considered SAEs, specific cardiovascular (CV) and death sections of the eCRF will 
be required to be completed. These sections include questions regarding CV (including 
sudden cardiac death) and non-CV death.  
The CV eCRFs are presented as queries in response to reporting of certain CV Medical 
Dictionary for Regulatory Activities (MedDRA) terms. The CV information should be 
recorded in the specific CV section of the eCRF within 1 week of receipt of a CV event 
data query prompting its completion.  
The death eCRF is provided immediately after the occurrence or outcome of death is 
reported. Initial and follow-up reports regarding death must be completed within 1 week 
of when the death is reported.  
8.4.7. 
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as SAEs 
Not applicable for this study. 
8.4.8. 
Adverse Events of Special Interest 
Adverse events of special interest (AESI) include: 
• 
Allergic reactions including anaphylaxis 
Note: these events will be assessed by the investigator as to whether they meet the 
diagnostic criteria for anaphylaxis as outlined by the 2006 Joint National Institute of 
Allergy and Infectious Disease (NIAID)/Food Allergy and Anaphylaxis Network 
(FAAN) Second Symposium on Anaphylaxis [Sampson, 2006] (Appendix 8). 
• 
Type III hypersensitivity (immune complex disease/vasculitis) reactions 
• 
Local injection site reactions 
• 
QTc prolongation 
See Section 2.3.2 for additional details. 

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8.4.9. 
Medical Device Deficiencies 
Medical devices are being provided for use in this study. To fulfill regulatory reporting 
obligations worldwide, the investigator is responsible for the detection and 
documentation of events meeting the definitions of device deficiency that occur during 
the study with such devices.  
If the sites use non-sponsor medical devices, i.e., medical devices not provided by GSK, 
then the investigators are obligated to report any device deficiencies to the legal 
manufacturer of the devices directly. 
The definition of a Medical Device Deficiency can be found in Appendix 7. 
NOTE: Deficiencies fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Appendix 3. 
8.4.9.1. 
Time Period for Detecting Medical Device Deficiencies 
• 
Medical device deficiencies that result in an incident will be detected, documented, 
and reported during all periods of the study in which the medical device is used.  
• 
If the investigator learns of any device deficiency at any time after a participant has 
been discharged from the study, and such a device deficiency is considered 
reasonably related to a medical device provided for the study, the investigator will 
promptly notify the sponsor. 
• 
Medical device deficiencies and any associated AE/SAEs for associated person (i.e., 
spouse, caregiver, site staff) will be collected. The associated person will be provided 
with a safety reporting information and authorization letter. 
• 
The method of documenting medical device deficiencies is provided in Appendix 7. 
8.4.9.2. 
Follow-up of Medical Device Deficiencies 
• 
Follow-up applies to all participants, including those who discontinue study 
intervention or the study, and associated persons. 
• 
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency. 
• 
New or updated information will be recorded on the originally completed form with 
all changes signed and dated by the investigator. 

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8.4.9.3. 
Prompt Reporting of Medical Device Deficiencies to the Sponsor 
• 
Device deficiencies will be reported to the sponsor within 24 hours after the 
investigator determines that the event meets the protocol definition of a device 
deficiency. 
• 
The medical device deficiency report form will be sent to the sponsor electronically. 
If this primary method is unavailable, then alternative method should be utilized 
(notification by telephone with a copy of the SAE paper data collection, see 
Appendix 7 for details). 
• 
The sponsor will be the contact for the receipt of device deficiency reports. 
8.4.9.4. 
Regulatory Reporting Requirements for Device Deficiencies 
• 
The investigator will promptly report all device deficiencies occurring with any 
medical device provided for use in the study in order for the sponsor to fulfill the 
legal responsibility to notify appropriate regulatory authorities and other entities 
about certain safety information relating to medical devices being used in clinical 
studies. 
• 
The investigator, or responsible person according to local requirements (e.g., the 
head of the medical institution), will comply with the applicable local regulatory 
requirements relating to the reporting of device deficiencies to the IRB/IEC. 
8.5. 
Pharmacokinetics 
To characterize the PK in patients with CRSwNP, blood samples for analysis of 
depemokimab plasma concentration will be obtained at visits specified in Table 1. 
Samples obtained at Visit 2 (Day 1) and at Visit 9 (Week 26) should be drawn prior to 
dosing. Samples at Visit 16 / EW Visit (Week 52) will be collected for approximately 
200 participants. No requirement to fast prior to sample being taken. The date and exact 
time of collection for each sample will be documented in the eCRF. 
Details for collection, processing, storage, and shipping procedures are provided in the 
laboratory manual. PK samples will be analysed using an appropriately validated assay 
method under the supervision of the sponsor. Study Intervention concentration 
information that would unblind the study will not be reported to investigative sites or 
blinded personnel until the study has been unblinded. 
8.6. 
Pharmacodynamics/Biomarkers 
Collection, processing, storage and shipping procedures for biomarker and PD samples 
are provided in the laboratory manual. 

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8.6.1. 
Blood Eosinophil Counts 
In order to investigate the PD effects of depemokimab, blood eosinophil counts will be 
measured as part of the standard haematological assessments according to Table 1. 
(Section 1.3). For haematology samples collected after Randomization, the absolute and 
differential (%) values of eosinophils, lymphocytes, basophils, neutrophils and 
monocytes will not be reported to site staff and Sponsor (to maintain the treatment blind). 
However, sites will be sent total white blood counts throughout the study. 
8.6.2. 
Total IL-5 Levels 
To characterize the binding of depemokimab to IL-5 in patients with CRSwNP, blood 
samples will be collected for measurement of total serum IL-5 levels at the visits 
specified in Table 1. Total IL-5 samples will be analysed using an appropriately validated 
assay method under the supervision of the sponsor. Intervention concentration 
information that would unblind the study will not be reported to investigative sites or 
blinded personnel until the study has been unblinded. 
8.6.3. 
Complement, IgE and Inflammatory Biomarkers  
Blood samples will be collected to measure complement (C3 and C4) and total IgE, 
according to the SoA (Section 1.3). 
A baseline serum sample will be collected at Visit 2 and stored. If necessary, this sample 
may be analysed for the presence of ANCA (using anti-MPO antibody and anti-PR3 
antibody tests), and ANA, including anti-dsDNA antibodies. 
After dosing, repeat of these analytes as well as additional biomarkers (as determined by 
clinical presentation) may be considered on an ad-hoc basis should there be clinical 
concerns regarding an immune-mediated AE (see Section 7.4). 
8.6.4. 
Exploratory Biomarkers 
Participation in exploratory biomarker research is optional. Participants who do not wish 
to participate in the exploratory biomarker research may still participate in the study. 
China only: Exploratory biomarker samples will not be collected from participants from 
China. 
With the participant’s consent, surgically removed polyp tissues, nasal fluid and blood 
samples collected during this study may be used for the purposes of measuring novel 
biomarkers to identify factors that may influence the disease under treatment, and/or 
medically related conditions, as well as the biological and clinical responses to 
depemokimab. If relevant, this approach will be extended to include the identification of 
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GSK may store samples for up to 15 years after the end of the study to achieve study 
objectives. Additionally, with participants consent, samples may be used for further 
research by GSK or others such as universities or other companies to contribute to the 
understanding of CRSwNP or related diseases, the development of related or new 
treatments or research methods. 
8.6.4.1. 
Serum: Soluble Marker Analysis 
Serum samples will be collected to explore changes in levels of soluble markers in 
response to depemokimab and may be used to identify novel candidate biomarkers of the 
biological responses associated with disease. 
8.6.4.2. 
Whole Blood: Gene Expression Analysis (Transcriptomics) 
Whole blood will be collected into PaxGene RNA tubes and transcriptomic analysis may 
be conducted using RNA Sequencing technology, facilitating the simultaneous 
measurement of the relative abundances of thousands of RNA species resulting in a 
transcriptome profile for a blood sample. The same samples may also be used to confirm 
findings by application of alternative technologies. 
8.6.4.3. 
Nasal Samples 
8.6.4.3.1. Surgical 
Whenever possible, surgical samples from participants undergoing surgery while on the 
study will be collected for the purposes of measuring PD biomarkers to understand the 
biological and clinical responses to depemokimab. The surgical samples may be analysed 
histologically for immune cell infiltration and transcriptional analysis may be performed 
to evaluate the changes in gene profiles that may correlate with biological and clinical 
responses to depemokimab. These samples may also be used to advance our 
understanding of disease pathogenesis as well as patient heterogeneity and may also be 
used for assay validation purposes. Instructions for the collection and handling of 
biological samples will be described in the laboratory manual. 
8.6.4.3.2. Nasal Biopsy 
Nasal biopsy samples will be collected from participants who consent to this optional 
procedure at Visit 16 (Week 52) in participating countries and sites. Nasal biopsy 
samples will be collected during endoscopy for the purposes of measuring biomarkers to 
better understand the biological responses to depemokimab within the tissue and the 
relationship to clinical responses. Instructions for the collection and handling of 
biological samples will be described in the laboratory manual. 

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8.7. 
Genetics 
China only: Genetic blood samples will not be collected from participants in China.  
Up to 6 mL blood sample for deoxyribonucleic acid (DNA) isolation will be collected 
from participants who have consented to participate in the genetics analysis component of 
the study. Participation is optional. Participants who do not wish to participate in the 
genetic research may still participate in the study. 
In the event of DNA extraction failure, a replacement genetic blood sample may be 
requested from the participant. Signed informed consent will be required to obtain a 
replacement sample unless it was included in the original consent. 
Please see Appendix 5 for information regarding genetic research. Details on processes 
for collection and shipment and destruction of these samples can be found in laboratory 
manual. 
8.8. 
Immunogenicity Assessments 
Antibodies to depemokimab will be evaluated in serum samples collected from 
participants according to Table 1. Additionally, serum samples should also be collected at 
the Exit Visit, or the final in-clinic visit for participants who withdraw early from the 
study. Processing, storage and shipping procedures are provided in the laboratory manual. 
In the immunogenicity assessment for depemokimab under supervision by GSK, a tiered 
analyses approach will use a validated binding ADA assay (screening, confirmation and 
titration assays) and a validated neutralising antibody (NAb) assay. If necessary, further 
immune response characterisation may be performed as needed. Intervention information 
that would unblind the participant’s intervention assignment will not be reported to 
investigative sites or blinded personnel until the study has been unblinded. 
8.9. 
Medical Resource Utilization and Health Economics 
Health Economics/Medical Resource Utilization and Health Economics parameters are 
evaluated in this study by means of the Short Form-36 (SF-36) and the Work Productivity 
and Activity Impairment Questionnaire (WPAI) questionnaires. 
8.9.1. 
Short Form-36 (SF-36) Questionnaire (Version 2) 
SF-36 will be performed by the participants at study visits described in Table 1. 
SF-36 is one of the most widely used generic questionnaires. It consists of 36 
self-administered questions that cover 8 health domains: physical functioning, role 
physical, bodily pain, and general health, vitality, role emotional, social functioning, and 
mental health with a recall of 4 weeks. Scale scores range from 0 to 100 and higher 
scores indicate better QoL. In addition, the PCS and the MCS scores can be derived 
following the original authors’ recommendations [Ware, 1994]. 

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Radenne [Radenne, 1999], demonstrated a high internal validity and reliability in patients 
with NP and reported that NP impaired QoL in all SF-36 domains. Khan [Khan, 2019] 
also found that patients with CRSwNP had significantly lower mean SF-36 PCS and 
MCS scores than the general population, demonstrating that CRSwNP negatively affects 
HRQoL. 
Alobid [Alobid, 2005] showed that a significant improvement was observed in all 
domains of SF-36 after medical and surgical treatment. Both mental and physical health 
reached population levels. Combined steroid treatment and ESS had similar long-term 
outcomes on QoL. Radenne [Radenne, 1999] showed that steroids and ESS improved the 
symptoms and the QoL in patients with NP especially in body pain, general health, 
vitality, social functioning, and mental health domains with no significant differences 
between both treatment regimes. 
8.9.2. 
Work Productivity and Activity Impairment Questionnaire (WPAI) 
WPAI will be assessed by the participant at study visits described in Table 1. 
The WPAI questionnaire is an instrument to measure impairments in both paid work and 
unpaid work [Reilly, 2002]. It measures absenteeism, presenteeism as well as the 
impairments in unpaid activity because of health problem during the past seven days. It 
has been validated to quantify work impairments for numerous diseases such as asthma, 
psoriasis, irritable bowel syndrome, ankylosing spondylitis and Crohn's disease  
[Reilly, 2004; Reilly, 2010; Reilly, 2008]. In addition, the WPAI questionnaire has been 
used to compare work impairments between treatment groups in clinical studies and trials 
or between participants with different disease severity levels [Reilly, 2004; Reilly, 2010; 
Reilly, 2008; Revicki, 2007; Pearce, 2006; Chen, 2008]. 
The WPAI-GH consists of six questions: 1 = currently employed; 2 = hours missed due 
to health problems; 3 = hours missed other reasons; 4 = hours actually worked; 5 = 
degree health affected productivity while working (using a 0 to 10 VAS); 6 = degree 
health affected productivity in regular unpaid activities (VAS) [Reilly, 1993]. The recall 
period for the questions 2 to 6 is 7 days. Four main outcomes can be generated from the 
WPAI: 1) percent work time missed due to health for those who were currently 
employed; 2) percent impairment while working due to health for those who were 
currently employed and actually worked in the past seven days; 3) percent overall work 
impairment due to health for those who were currently employed; 4) percent activity 
impairment due to health for all respondents [Reilly, 2002]. For those who missed work 
and did not actually work in the past seven days, the percent overall work impairment due 
to health will be equal to the percent work time missed due to health. 

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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
The study is designed to test the inequality of depemokimab 100 mg SC vs. placebo (both 
in addition to SoC) in both co-primary endpoints of total endoscopic NP score at Week 
52 and mean nasal obstruction VRS symptom score from Week 49 through to Week 52. 
Each co-primary endpoint will be tested at the two-sided 5% alpha level, both tests are 
required to be significant to achieve the primary objective of this study.  
Demonstration of efficacy for each of these tests will be based on a hypothesis testing 
approach, whereby the null hypothesis is that there is no difference between treatment 
groups for the endpoint of interest and the alternative hypothesis is that there is a 
difference between treatment groups. 
9.1.1. 
Multiplicity Adjustment 
Hypotheses to be tested will be structured as shown in Figure 4. The co-primary 
endpoints will be tested first and if these comparisons are both significant at the two-
sided 5% level, testing will continue within the study according to the testing procedure 
detailed in Figure 4. Testing of endpoints will be carried out in a hierarchical manner, 
dependent on statistical significance having been achieved for the previous endpoint in 
the hierarchy. 
A pre-specified pooled analysis of data from this study (217095) and study 218079 is 
planned for the secondary endpoints of time to first nasal surgery (actual or entry on 
waiting list) or disease-modulating medication for CRSwNP, time to first nasal surgery 
(actual) or disease modulating medication for CRSwNP, proportion of participants 
requiring at least 1 course of systemic corticosteroids or disease-modulating medication 
for CRSwNP or nasal surgery (actual), and ACQ-5 Score. This pooled analysis will be 
carried out after both studies have completed and only if statistical significance is 
achieved for both co-primary endpoints within both studies. Endpoints in the pooled 
analyses will be tested in a hierarchical manner at a significance level of α - α2 (4.75%) 
[Bretz, 2019]. The time to first nasal surgery (actual) or disease-modulating medication 
for CRSwNP will only be tested if statistical significance is achieved for time to first 
nasal surgery (actual or entry on waiting list) or disease-modulating medication for 
CRSwNP. The proportion of participants requiring at least 1 course of systemic 
corticosteroids or disease-modulating medication for CRSwNP or nasal surgery (actual) 
will only be tested if statistical significance is achieved for both time to first nasal surgery 
(actual or entry on waiting list) or disease-modulating medication for CRSwNP and time 
to first nasal surgery (actual) or disease-modulating medication for CRSwNP. Similarly, 
the ACQ-5 Score will only be tested if statistical significance is achieved for time to first 
nasal surgery (actual or entry on waiting list) or disease-modulating medication for 
CRSwNP, time to first nasal surgery (actual) or disease modulating medication for 
CRSwNP, and proportion of participants requiring at least 1 course of systemic 
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Figure 4 
Conceptualisation of Statistical Testing Strategy Across Studies 
217095 and 218079 
 
Note: Endpoint names in Figure 4 are abbreviated. Refer to Section 3 for full nomenclature of endpoints. 
The treatment comparisons defined as part of the multiple testing strategy will be limited 
to the specified key comparisons shown in Figure 4. Other pairwise comparisons will be 
performed but will not form part of the multiple testing strategy. Analyses of other 
efficacy measures are nested under the secondary efficacy measures and no multiplicity 
adjustment is planned for these other efficacy endpoints. 
If significance is achieved for both of the co-primary efficacy endpoints within this study, 
then the secondary endpoints within the study will be tested in a closed-testing manner 
using the pre-defined hierarchy. If significance is also achieved for each of the secondary 
efficacy endpoints within the study, then all other efficacy endpoints for the study will be 
tested without multiplicity adjustment. 
If significance is achieved for both of the co-primary efficacy endpoints in both this study 
(217095) and study 218079, then the 4 secondary endpoints that are pre-specified to be a 
pooled analysis across both studies will be tested in a closed testing manner according to 
the pre-defined hierarchy. If significance is achieved at the α - α2 (4.75%) level for all 4 
of these endpoints, then all of the other efficacy endpoints that are pre-specified to be a 
pooled analysis across both studies will also be tested at the α - α2 (4.75%) significance 
level without any multiplicity adjustment. 

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9.2. 
Analysis Sets 
For the purposes of analysis, the following analysis sets are defined: 
Participant Analysis 
Set 
Description 
Screened 
All participants screened and for whom a record exists on the study 
database. 
Screened-China 
All participants screened and for whom a record exists on the study 
database from China. 
Screened-Japan 
All participants screened and for whom a record exists on the study 
database from Japan. 
Randomized 
All randomized participants. 
Full Analysis Set (FAS) 
All randomized participants who take at least 1 dose of study 
treatment excluding participants from site 255388a. Participants will 
be analysed according to the treatment they are allocated at 
randomization. 
FAS-China 
All participants in the FAS population who are enrolled from China. 
FAS-Japan 
All participants in the FAS population who are enrolled from Japan 
and are of Japanese heritage only. 
FAS-Modified 
All participants in the FAS population plus randomised participants 
from site 255388a who receive at least one dose of study treatment. 
Safety 
All randomised participants who take at least 1 dose of study 
treatment excluding participants from site 255388a. Participants will 
be analysed according to the treatment they are allocated at 
randomisation, unless the participant receives a different treatment to 
randomized active treatment at all protocol-defined administrations at 
which study medication was received, in which case the participant 
will be analysed according to the actual treatment they received. 
Safety-China 
All participants in the Safety population who are enrolled from China. 
Safety-Japan 
All participants in the Safety population who are enrolled from Japan 
and are of Japanese heritage only. 
Safety-Modified 
All participants in the safety population plus randomised participants 
from site 255388a who receive at least 1 dose of study treatment. 
Participants will be analysed according to the treatment they are 
allocated at randomisation, unless the participant receives a different 
treatment to randomized active treatment at all protocol-defined 
administrations at which study medication was received, in which 
case the participant will be analysed according to the actual treatment 
they received. 
PK 
All participants in the FAS population for whom at least one 
pharmacokinetic sample was obtained, analysed and was 
measurable, including imputed values that were below the limit of 
quantification. Participants will be analysed according to the 
treatment they received. 
a. 
The Japan Ministry of Health, Labour and Welfare (MHLW) confirmed GCP violations in several studies 
involving Medipharma, a Japanese Site Management Organisation (SMO). Medipharma provided site 
management services to site 255388 in Study 217095. 

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9.3. 
Statistical Analyses 
The statistical analysis plan will include a more technical and detailed description of the 
statistical analyses described in this section. This section is a summary of the planned 
statistical analyses of the most important endpoints including primary and key secondary 
endpoints. 
9.3.1. 
Co-Primary and Key Secondary Endpoint(s) Analyses 
The treatment comparison of depemokimab 100 mg SC + SoC vs. placebo + SoC is of 
interest for the co-primary and secondary endpoints. Multiplicity arising from the 
multiple secondary endpoints will be controlled as detailed in Section 9.1.1. 
Endpoint 
Statistical Analysis Methods 
Co-
Primaries 
The comparison of depemokimab 100 mg SC + SoC with placebo + SoC will be 
expressed as a difference in means in change from baseline values presented with 
corresponding 95% confidence intervals, the p-value for the difference in means 
between treatment groups and will be based on a mixed model repeated measures 
(MMRM) analysis with covariates of treatment group, baseline score, baseline 
blood eosinophil count, region, previous surgery for nasal polyps, visit and 
interaction terms for visit by baseline score and visit by treatment group. Off-
treatment data from participants who withdrew early from interventional product 
and continued in the study will be included in the analyses, missing data will be 
assumed to be missing at random (MAR). 
A sensitivity analysis using MMRM with multiple imputation will be performed for 
each co-primary endpoint to assess the potential impact of choices for handling 
missing data in the primary analysis. For the sensitivity analysis, participants with 
missing data at Week 52 who had taken their Week 26 dose of interventional 
product (and therefore considered on-treatment at Week 52) will have missing data 
imputed under the assumption of MAR. Participants with missing data at Week 52 
who had not taken their Week 26 dose of interventional product (and therefore 
considered off-treatment at Week 52) will have missing data imputed using a jump 
to reference (J2R) approach. Implementation of the J2R method assumes that for 
participants in the experimental treatment group (Depemokimab) with missing data, 
their imputed mean response is that of the reference treatment group (Placebo). 
An additional tipping point sensitivity analysis will explore the impact of missing 
data by using differing assumptions for each of the co-primary endpoints. 
Assumptions about missing values on the experimental treatment arm and placebo 
arm will vary independently, and will include scenarios where participants with 
missing data in the experimental treatment arm have worse outcomes than 
participants with missing data in the placebo arm. This analysis will allow for 
determination of ‘tipping point(s)’ of the values for missing data that would cause a 
change in the statistical significance of the result of the treatment comparison. The 
deltas (small numerical shifts in the values of missing data) investigated will cover 
a range that this is plausible for the respective endpoint under the MAR 

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Endpoint 
Statistical Analysis Methods 
assumption and will be investigated on final data to ensure it supports a tipping 
point range. 
Subgroup analyses for each of the co-primary endpoints will be performed for age, 
gender, race, region and baseline blood eosinophil category. 
Full details of all analyses will be provided in the statistical analysis plan. 
Secondary The pooled analysis of time to first nasal surgery (actual or entry on waiting list) or 
disease-modulating medication for CRSwNP and time to first nasal surgery (actual) 
or disease-modulating medication for CRSwNP will be analysed using Cox’s 
proportional hazards model allowing for covariates of treatment group, baseline 
total endoscopic nasal polyps score, baseline nasal obstruction score (VRS), 
baseline blood eosinophil count, region, study and previous surgery for nasal 
polyps. Missing values will be considered censored at random. Summaries and 
graphs of Kaplan-Meier estimates of the proportion of participants requiring surgery 
over time will be provided.  
Change from baseline in mean rhinorrhoea (runny nose) score, mean loss of smell 
score, Lund Mackay CT score and SNOT-22 total score will be analysed in a 
similar manner to the co-primary endpoints. The pooled analysis of proportion of 
participants requiring at least 1 course of systemic corticosteroids or disease-
modulating medication for CRSwNP or nasal surgery (actual) will be analysed 
using a logistic regression model with covariates for treatment group, number of 
courses of systemic corticosteroids in 12 months prior to screening (0, 1, >1 as 
ordinal), baseline blood eosinophil count, baseline total endoscopic nasal polyps 
score, baseline nasal obstruction score (VRS), region, study and previous surgery 
for nasal polyps. The pooled analysis of ACQ-5 will be based on MMRM with MAR 
assumption for missing data with covariates for treatment group, baseline score, 
baseline blood eosinophil count, region, previous surgery for nasal polyps, study, 
visit and interaction terms for visit by baseline score and visit by treatment group.  
 
 
9.3.2. 
Safety Analysis 
All safety analyses will be performed on the Safety Population. 
AEs will be coded using the MedDRA coding dictionary and summarised by preferred 
term and treatment. Separate summaries will be provided for all AEs, drug-related AEs, 
SAEs and for AEs leading to permanent discontinuation of study intervention or 
withdrawal from the study.  
Immunogenicity data, ECG, vital signs, and laboratory data will be summarised 
descriptively. 
Further details will be given in the statistical analysis plan.  

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9.3.3. 
Pharmacokinetic Analysis 
All randomized participants will be sampled for plasma depemokimab levels. Assessment 
of depemokimab concentration will be performed at the timepoints indicated in Table 1. 
Results will be presented using appropriate graphic and tabular summaries. Plasma 
depemokimab concentration data obtained from this study, and other studies with 
depemokimab, will be used in a population PK analysis, which will be reported 
separately. Potential effects of covariates on depemokimab PK including, but not limited 
to, demographic, disease characteristics and baseline eosinophil count, ethnicity and 
geographic region, and anti-drug-antibodies will be evaluated. Derived PK parameters 
will include clearance and AUC.  
9.3.4. 
Pharmacodynamic and Pharmacokinetic/Pharmacodynamic 
Analysis 
All randomized participants will be sampled for blood eosinophil count at the timepoints 
indicated in Table 1.  
Results will be presented using appropriate graphic and tabular summaries.  
Plasma depemokimab concentration and blood eosinophil count data obtained from this 
study, and other studies with depemokimab, will be used in a population PKPD analysis, 
which will be reported separately. Potential effects of covariates including, but not 
limited to, demographic and disease characteristics, ethnicity and geographic region, and 
baseline eosinophil count will be evaluated. Derived PKPD parameters will include 
maximum eosinophils suppression.  
9.4. 
Interim Analysis 
A safety IDMC is being implemented for the study, the IDMC charter is available on 
request and will detail the schedule for any planned interim safety analyses and the 
analysis plan for the IDMC review. Members of the IDMC and the independent 
Statistical Data Analysis Centre (SDAC) responsible for preparing results for the IDMC 
will have access to unblinded randomization codes and any interim safety results.  
Blinded interim data will be used to facilitate validation, including estimation of 
meaningful score changes, of the patient-reported outcomes (e.g., VRS) included in this 
trial. No assessment of efficacy or safety will be included in this validation assessment. 
The study statistician, investigators, and GSK personnel involved in monitoring of the 
study will not have access to randomized treatment codes until the study completes as 
planned or is terminated.  
No other interim analysis is planned, however if recruitment is significantly slower than 
anticipated GSK may conduct a single unblinded interim analysis to assess futility. Any 
unblinded interim analysis for futility will be performed by an SDAC in conjunction with 
an IDMC to maintain study integrity. In the case where a futility interim will be 

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implemented, full details of the timing and stopping boundary will be included in a 
statistical analysis plan and updated IDMC charter, and these will be submitted to 
regulatory agencies as appropriate prior to any futility analysis being performed. 
9.5. 
Sample Size Determination 
The sample size for this study is based on the co-primary efficacy endpoints of total 
endoscopic nasal polyps score at Week 52 and mean nasal obstruction VRS symptoms 
score from Week 49 through to Week 52, and a pre-specified pooled analysis of data 
from study 217095 (this study) and study 218079 for the key secondary endpoint of time 
to nasal surgery (actual or entry on waiting list) or disease-modulating medication for 
CRSwNP. 
Approximately 250 participants will be randomized in this study in a ratio of 1:1 giving 
125 randomised participants per arm. This sample size allows for up to 5% of 
randomized participants to be non-evaluable, providing a minimum of 118 evaluable 
participants per arm in the analyses of primary and secondary endpoints. 
For the co-primary efficacy endpoint of total endoscopic nasal polyps score at Week 52, 
the study has >99% power assuming a true population difference of -1.10 between 
depemokimab and placebo. This assumes a standard deviation of 1.665 with significance 
declared at the two-sided 5% significance level. The smallest observed effect which is 
predicted to result in a statistically significant difference between depemokimab 100 mg 
SC + SoC and placebo + SoC is a treatment difference of –0.42. 
For the co-primary efficacy endpoint of mean nasal obstruction VRS score during Weeks 
49-52, the study has >99% power assuming a true population difference of -0.70 between 
depemokimab and placebo. This assumes a standard deviation of 0.84 with significance 
declared at the two-sided 5% significance level. The smallest observed effect which is 
predicted to result in a statistically significant difference between depemokimab 100 mg 
SC + SoC and placebo + SoC is a treatment difference of –0.21. 
The overall power for both co-primary endpoints is >99%. 
The planned number of patients recruited within this study is not sufficient to adequately 
assess whether depemokimab significantly reduces the risk of nasal surgery compared to 
placebo. A pre-specified pooled analysis of data from this study (217095) and study 
218079 is planned for the endpoint of time to first surgery (actual or entry on waiting list) 
or disease-modulating medication for CRSwNP. The proportion of participants in the 
pooled placebo group expected to require surgery or disease-modulating medication for 
CRSwNP is 23%. Assuming a true population hazard ratio of 0.38 (62% reduction in risk 
of required surgery) this pooled analysis has >90% power to observe statistical 
significance at the 2-sided 4.75% level. In the pooled analysis, the smallest observed 
effect which is predicted to result in a statistically significant difference between 
depemokimab 100 mg SC + SoC and placebo + SoC is a hazard ratio of 0.64 (36% 
reduction in risk of surgery). 

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The overall power for both co-primary endpoints and the pre-specified pooled analysis of 
time to first surgery (actual or entry on waiting list) or disease-modulating medication for 
CRSwNP using data from this study (217095) and study 218079 is >90%. 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• 
This study will be conducted in accordance with the protocol and with: 
− 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) international ethical guidelines 
− 
Applicable ICH Good Clinical Practice (GCP) guidelines 
− 
Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., 
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 IEC/IRB approval before 
implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study participants.  
• 
Protocols and any substantial amendments to the protocol will require health 
authority approval prior to initiation except for changes necessary to eliminate an 
immediate hazard to study participants. 
• 
The investigator will be responsible for the following: 
− 
Providing written summaries of the status of the study to the IRB/IEC annually 
or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB/EC 
− 
Notifying the IRB/IEC of SAE 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), European Medical Device 
Regulation 2017/745 for clinical device research (if applicable), and all other 
applicable local regulations 

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10.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 
10.1.3. 
Informed Consent Process 
• 
The investigator or his/her representative will explain the nature of the study, 
including the risk and benefit, to the participant or their LAR and answer all 
questions regarding the study.  
• 
Participants must be informed that their participation is voluntary. Participants or 
their LAR will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, privacy and data 
protect requirements, where applicable, and the IRB/IEC or study centre.  
• 
The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF. 
• 
Participants must be re-consented to the most current version of the ICF(s) during 
their participation in the study.  
• 
A copy of the ICF(s) must be provided to the participant or their LAR. Participants 
who are rescreened are required to sign a new ICF.  
• 
If follow-up information from a treating physician or other licensed medical  
practitioner is required for a medical device incident with an AE/SAE involving  
an associated person(s), the Associated Person Safety Reporting Information and  
Authorization Letter must be signed by the associated person to obtain consent.  
• 
GSK (alone or working with others) may use participant’s coded study data and 
samples and other information to carry out this study; understand the results of this 
study; learn more about depemokimab or about the study disease; publish the results 
of these research efforts; work with government agencies or insurers to have 
depemokimab approved for medical use or approved for payment coverage. 
• 
The ICF contains a separate section that addresses the use of participant data and 
remaining samples for optional further research. The investigator or authorized 
designee will inform each participant of the possibility of further research not related 
to the study/disease. Participants 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 participant’s agreement 
to allow any participant data or samples to be used for further research not related to 
the study/disease. Participants who decline further research will tick the 
corresponding “No” box. 

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10.1.4. 
Recruitment Strategy 
Recruitment will be competitive. Recruitment will be performed by the investigators at 
the participating sites. The Sponsor will NOT participate in recruitment of participants to 
the study. In addition, the study will be published in public databases such as 
ClinicalTrials.gov. 
10.1.5. 
Data Protection 
• 
Participants will be assigned a unique identifier by the sponsor. Any participant 
records or datasets that are transferred to the sponsor will contain the identifier only; 
participant names or any information which would make the participant identifiable 
will not be transferred.  
• 
GSK will ensure protection of the personal data of the investigator and site staff 
which is collected within the framework of and for the purpose of the study. 
• 
The participant must be informed that his/her personal study-related data will be 
used by the sponsor in accordance with local data protection law. The level of 
disclosure must also be explained to the participant who will be required to give 
consent for their data to be used as described in the informed consent.  
• 
The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
• 
The contract between sponsor and study sites specifies responsibilities of the parties 
related data protection, including handling of data security breaches and respective 
communication and cooperation of the parties. 
• 
Information technology systems used to collect, process, and store study-related data 
are secured by technical and organizational security measures designed to protect 
such data against accidental or unlawful loss, alteration, or unauthorized disclosure 
or access. GSK and/or trusted third parties working on behalf of GSK and/or 
institutions working with GSK for the purposes of this study are contractually bound 
to protect participant coded data. GSK will protect participant coded data and will 
only share it as described in the ICF. 
• 
GSK has a global, internal policy that requires all GSK staff and complementary 
workers to report data incidents or breaches immediately, using dedicated tools. 
Clear procedures are defined for assessing and investigating data breaches to identify 
and to take appropriate remediation steps, to contain and to mitigate any risks for 
individuals resulting from a breach, in compliance with applicable laws. 

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10.1.6. 
Committees Structure 
An IDMC comprised of clinical experts external to GSK will review unblinded data at 
defined timepoints during the study. If deemed appropriate by the IDMC, or upon request 
by GSK or investigators, additional timepoints for review may be added. 
Details of the structure and function of the IDMC, and analysis plan for IDMC reviews, 
are outlined in the IDMC Charter, which is available upon request. 
In addition to the IDMC, the GSK SRT will review blinded safety data at regular 
intervals throughout the study to ensure participant safety, which includes safety signal 
detection at any time during the study. Details of the SRT process will be available in 
relevant SRT documents. The SRT will inform the IDMC if any safety signals are 
identified. 
10.1.7. 
Dissemination of Clinical Study Data 
• 
The key design elements of this protocol and results summaries will be posted on 
www.ClinicalTrials.gov and/or GSK Study Register in compliance with applicable 
regulations/GSK policy. GSK will aim to register protocols summaries prior to study 
start and target results summaries submission within 12 months of primary/ study 
completion date. Where external regulations require earlier disclosure, GSK will 
follow those timelines.  
• 
Where required by regulation, summaries will also be posted on applicable national 
or regional clinical study registers. 
• 
Where required by applicable regulatory requirements, an investigator signatory will 
be identified for the approval of the study report, and provided reasonable access to 
statistical tables, figures, and relevant reports. GSK will also provide the investigator 
with the full summary of the study results, including a summary of trial results 
understandable to laypersons. The investigator is encouraged to share the layperson 
summary of results with the study participants, as appropriate. The full study report 
will be made available upon request, after decision on marketing authorization by 
regulatory authorities. 
• 
Where required by regulation, the names of the sponsor signatory and investigator 
signatory will be made public. 
• 
GSK will provide the investigator with the randomization codes and participant-level 
line listings for their site only after completion of the full statistical analysis. 
• 
The procedures and timing for public disclosure of the protocol and results summary 
and for development of a manuscript for publication for this study will be in 
accordance with GSK Policy. 
• 
GSK intends to make anonymized participant-level data from this study available to 
external researchers for scientific analyses or to conduct further research that can 
help advance medical science or improve patient care. This helps ensure the data 
provided by study participants are used to maximum effect in the creation of 
knowledge and understanding. Data will be shared with researchers in a non-

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identifying way, and appropriate measures will be taken to protect PI; these measures 
will comply with data protection and privacy laws that apply. 
• 
Requests for access may be made through www.clinicalstudydatarequest.com. 
• 
A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge. 
10.1.8. 
Data Quality Assurance 
• 
All participant data relating to the study will be recorded on printed or eCRF unless 
transmitted to the sponsor or designee electronically (e.g., laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the eCRF.  
• 
Guidance on completion of eCRFs will be provided in eCRF Completion Guidelines. 
• 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.  
• 
Quality tolerance limits (QTLs) will be pre-defined in the Integrated Quality Risk 
Management Plan (IQRMP) to identify systematic issues that can impact participant 
safety and/or reliability of study results. These pre-defined parameters will be 
monitored during and at the end of the study and all deviations from the QTLs and 
remedial actions taken will be summarized in the clinical study report. 
• 
Monitoring details describing strategy including definition of study critical data 
items and processes (e.g., 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 Clinical Monitoring Plan. 
• 
The sponsor or designee is responsible for the data management of this study 
including quality checking of the data. Detailed information about study data 
collection and management process including systems used can be found in the Data 
Management Plan. 
• 
The sponsor assumes accountability for actions delegated to other individuals (e.g., 
Contract Research Organizations). 
• 
Records and documents, including signed ICF, pertaining to the conduct of this study 
must be retained by the investigator for 25 years from the issue of the final Clinical 
Study Report (CSR)/equivalent summary unless local regulations or institutional 
policies require a different retention period. No records may be destroyed during the 
retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. 
• 
When copies of source documents are shared externally for review by a central 
reader mechanism (e.g., endpoint adjudication committee; expert reader), documents 
are stored by the external body for 25 years. 

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10.1.9. 
Source Documents 
• 
Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
• 
Data reported on the eCRF or 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. 
• 
Definition of what constitutes source data, and its origin can be found in the site-
specific Source Data Acknowledgment. 
• 
The investigator must maintain accurate documentation (source data) that supports 
the information entered in the eCRF. 
• 
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 participants are being 
protected; and that the study is being conducted in accordance with the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements.  
10.1.10. 
Study and site start and closure 
First Act of Recruitment 
The start of study is defined as first subject first visit (FSFV) at a country-level. 
Study/Site Termination 
GSK or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK. 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: 
For study termination: 
• 
Discontinuation of further study intervention development 

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For site termination: 
• 
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 or no recruitment (evaluated after a reasonable amount of time) of 
participants by the investigator 
• 
Total number of participants included earlier than expected 
If the study is prematurely terminated or temporarily suspended, the sponsor shall 
promptly inform the investigators, the IECs/IRBs, the regulatory authorities, and any 
contract research organization(s) used in the study of the reason for termination or 
temporary suspension, as specified by the applicable regulatory requirements. The 
investigator shall promptly inform the participant and should assure appropriate 
participant therapy and/or follow-up. 
10.1.11. 
Publication Policy 
• 
GSK seeks to publish medically or scientifically significant results in searchable 
peer-reviewed scientific literature within 18 months from LSLV. We follow 
International Committee of Medical Journal Editors standards for authorship and use 
Good Publications practices to guide our publications.  
• 
The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally 
support publication of multicenter studies only in their entirety and not as individual 
site data. In this case, a coordinating investigator will be designated by mutual 
agreement. 
• 
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 
10.2. 
Appendix 2: Clinical Laboratory Tests 
• 
The tests detailed in Appendix Table 1 will be performed by the central laboratory 
Q2 Solutions.  
• 
Local laboratory results are only required in the event that the central laboratory 
results are not available in time for either study intervention administration and/or 
response evaluation. If a local sample is required, it is important that the sample for 
central analysis is obtained at the same time. Additionally, if the local laboratory 
results are used to make either a study intervention decision or response evaluation, 
the results must be recorded.  
• 
Protocol-specific requirements for inclusion or exclusion of participants are detailed 
in Section 5 of the protocol. 
• 
Additional tests may be performed at any time during the study as determined 
necessary by the investigator or required by local regulations. 
• 
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Appendix Table 1 
Protocol-Required Safety Laboratory Tests 
Laboratory 
Assessments 
Parameters 
Haematology
1 
Platelet Count 
RBC Indices: 
WBC count with Differential: 
(post-dose results blinded as described in 
footnote 1) 
RBC Count 
MCV 
WBC 
Haemoglobin 
MCH 
Neutrophils 
Haematocrit 
%Reticulocytes 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Clinical Chemistry
2 BUN 
Potassium 
AST(SGOT) 
Total and direct bilirubin 
Creatinine 
Sodium 
ALT (SGPT) 
Total Protein 
Glucose (non-
fasting) 
Calcium 
Alkaline phosphatase
3 
Albumin 
Magnesium 
GGT 
Routine Urinalysis Specific gravity 
pH, glucose, protein, blood, ketones by dipstick 
Microscopic examination and UACR (if blood or protein is abnormal [evidence of 
microalbuminuria or haematuria of ≥1+]) UACR will require a separate urine sample to 
be sent to central laboratory for analysis. 
Pregnancy  testing Highly sensitive serum pregnancy test at Screening Visit 1, Exit Visit and at Early 
Withdrawal Visit; highly sensitive urine pregnancy tests for other assessments at time 
points specified in Table 1, and additionally within 24 hours prior to CT scan (as needed 
for WOCBP)
4 
Other Tests 
FSH (if required to confirm postmenopausal status, see Section 10.4) 
Parasitic Screening (only required in regions with high-risk or for participants who have 
visited high-risk regions in the past 6 months). Sites should use local laboratories. If 
sites wish to use central laboratories, they should note that the central test is stool 
microscopy for ova and parasites. For details of the organisms detected by this test 
refer to the parasitic screening section of the SRM.  
Total IgE 
Complement (C3 and C4) 
Serum samples collected at baseline will be frozen and stored for later analyses, if 
necessary: anti-MPO antibody, anti-PR3 antibody, ANA including anti-dsDNA antibody 
Abbreviations: ALT, alanine aminotransferase; ANA, anti-nuclear antibody; AST, aspartate aminotransferase; BUN, 
blood urea nitrogen; FSH, follicle-stimulating hormone; MPO, myeloperoxidase; PR3, proteinase 3; SGOT, serum 
glutamic-oxaloacetic transaminase; SGPT, serum glutamic-pyruvic transaminase; UACR, urinary albumin- 
creatinine ratio; WBC, white blood cell; WOCBP, women of childbearing potential; WONCBP, women of non- 
childbearing potential; GGT, Gamma-glutamyl transferase. 
1. 
To maintain the treatment blind, the following data for post-randomization samples will not be reported to 
investigators and blinded Sponsor representatives: absolute and percentage values of eosinophils, neutrophils, 
lymphocytes, monocytes, and basophils. 
2. 
Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping or 
monitoring event are given in Section 7.1.2 and Appendix 6. All events of ALT ≥3 × upper limit of normal (ULN) 
and total bilirubin ≥2 × ULN (>35% direct bilirubin) or ALT ≥3 × ULN and international normalized ratio (INR) >1.5, 
if INR measured, which may indicate severe liver injury (possible Hy’s Law), must be reported to GSK as an SAE. 
3. 
If alkaline phosphatase is elevated, consider fractionating. 

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4. 
Local urine testing will be standard for all visits (except Screening Visit and Exit Visit) unless serum testing is 
required by local regulation or IRB/IEC. 
10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.3.1. 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study intervention, whether or not 
considered related to the study intervention. 
• 
NOTE: An AE can therefore be any unfavourable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a study intervention. 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (e.g., ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not 
related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• 
New condition detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected intervention- intervention 
interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae. 
• 
“Lack of efficacy” or “failure of expected pharmacological action” per se will not 
be reported as an AE or SAE. Such instances will be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting 
from lack of efficacy will be reported as AE or SAE if they fulfil the definition of 
an AE or SAE.  
 

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Events NOT Meeting the AE Definition  
• 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition. 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
10.3.2. 
Definition of SAE 
An SAE is defined as any untoward medical occurrence that, at any dose, meets 
one or more of the criteria listed: 
a. Results in death 
b. Is life-threatening 
The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in which 
the participant was at risk of death at the time of the event. It does not refer to an 
event, which hypothetically might have caused death, if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
− 
In general, hospitalization signifies that the participant has been admitted 
(usually involving at least an overnight stay) at the hospital or emergency 
ward for observation and/or treatment that would not have been appropriate in 
the physician’s office or outpatient setting. Complications that occur during 
hospitalization are AE. If a complication prolongs hospitalization or fulfills 
any other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered 
serious. 
− 
Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
d. Results in persistent or significant disability/incapacity 
− 
The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. 
− 
This definition is not intended to include experiences of relatively minor 
medical significance such as uncomplicated headache, nausea, vomiting, 
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An SAE is defined as any untoward medical occurrence that, at any dose, meets 
one or more of the criteria listed: 
interfere with or prevent everyday life functions but do not constitute a 
substantial disruption. 
e. 
Is a congenital anomaly/birth defect 
f. 
Is a suspected transmission of any infectious agent via an authorized 
medicinal product 
g. Other situations: 
− 
Possible Hy’s Law case: ALT≥3x ULN AND total bilirubin ≥2x ULN (>35% 
direct bilirubin) or INR >1.5 must be reported as SAE 
− 
Medical or scientific judgment should be exercised by the investigator in 
deciding whether SAE reporting is appropriate in other situations such as 
significant medical events that may jeopardize the participant or may require 
medical or surgical intervention to prevent one of the other outcomes listed in 
the above definition. These events should usually be considered serious. 
− 
Examples of such events include invasive or malignant cancers, intensive 
treatment for allergic bronchospasm, blood dyscrasias, convulsions, or 
development of intervention dependency or intervention abuse. 
10.3.3. 
Definition of Cardiovascular Events 
Cardiovascular Events (CV) Definition: 
Investigators will be required to fill out the specific CV event page of the CRF for the 
following AEs and SAEs: 
• 
Myocardial infarction/unstable angina 
• 
Congestive heart failure 
• 
Arrhythmias 
• 
Valvulopathy 
• 
Pulmonary hypertension 
• 
Cerebrovascular events/stroke and transient ischemic attack 
• 
Peripheral arterial thromboembolism 
• 
Deep venous thrombosis/pulmonary embolism 
• 
Revascularization 

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10.3.4. 
Recording and Follow-Up of AE and SAE 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory, and diagnostics reports) 
related to the event. 
• 
The investigator will then record all relevant AE/SAE information. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the GSK required form. 
• 
There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to GSK. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories:  
• 
Mild: Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
• 
Moderate: Minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental Activities of Daily Living (ADL). Instrumental ADL 
refers to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc. 
• 
Severe: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling, limiting 
self-care ADL. Self-care ADL refers to bathing, dressing and undressing, feeding 
self, using the toilet, taking medications, and not bedridden. 
 

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Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE. The investigator will use clinical judgment 
to determine the relationship. 
• 
A reasonable possibility of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• 
The investigator will also consult the IB and/or Product Information (for marketed 
products), in his/her assessment.  
• 
For each AE/SAE, the investigator must document in the medical notes that 
he/she has reviewed the AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred, and the investigator has 
minimal information to include in the initial report to GSK. However, it is very 
important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to GSK. 
• 
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
Follow-up of AE and SAE 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK 
to elucidate the nature and/or causality of the AE or SAE as fully as possible. This 
may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals. 
• 
If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide GSK with a copy of any 
postmortem findings including histopathology.  
• 
New or updated information will be recorded in the originally submitted 
documents. 
• 
The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
 

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10.3.5. 
Reporting of SAE to GSK 
SAE Reporting to GSK via Electronic Data Collection Tool 
• 
The primary mechanism for reporting SAE to GSK will be the electronic data 
collection tool. 
• 
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) to report the event within 24 hours. 
• 
The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• 
After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data. 
• 
If a site receives a report of a new SAE from a study participant or receives 
updated data on a previously reported SAE after the electronic data collection tool 
has been taken off-line, then the site can report this information on a paper SAE 
form (see next section) or to the Medical Monitor by telephone. 
• 
If the site during the course of the study or poststudy becomes aware of any 
serious, nonserious AEs, pregnancy exposure, related to any GSK product that is 
not part of the study design, they will report these events to GSK or to the 
concerned Competent Authority (CA) via the national spontaneous reporting 
system. These will be classified as spontaneous Individual Case Safety Reports 
(ICSR). 
• 
Contacts for SAE reporting can be found in the SRM. 
SAE Reporting to GSK via Paper Data Collection Tool 
• 
Facsimile transmission of the SAE paper data collection tool is the preferred 
method to transmit this information to the Medical Monitor. 
• 
In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service. 
• 
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE data collection tool within the designated reporting 
time frames. 
• 
Contacts for SAE reporting can be found in the SRM. 

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10.4. 
Appendix 4: Contraceptive and Barrier Guidance  
10.4.1. 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
Women in the following categories are considered WOCBP (fertile): 
1. Following menarche 
2. From the time of menarche until becoming post-menopausal unless permanently 
sterile (see below) 
Notes: 
• 
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 
enrolment. 
• 
Permanent sterilization methods (for the purpose of this study) include: 
− 
Documented hysterectomy 
− 
Documented bilateral salpingectomy 
− 
Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (e.g., Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), investigator 
discretion should be applied to determining study entry. 
Note: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview. 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation should 
be considered. 

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Woman of Non-childbearing Potential (WONCBP) 
Women in the following categories are considered WONCBP: 
1. Premenopausal female with permanent infertility due to one of the following (for the 
purpose of this study): 
− 
Documented hysterectomy 
− 
Documented bilateral salpingectomy 
− 
Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (e.g., Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), 
investigator discretion should be applied to determining study entry. 
Note: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview. 
2. Postmenopausal female 
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
− 
A high FSH level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal 
contraception or 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 must discontinue 
HRT 
to allow confirmation of postmenopausal status before study enrolment. 
10.4.2. 
Contraception Guidance: 
Female participants 
Use of effective contraceptive methods will be required from at least 14 days prior to first 
dose and until 30 weeks after the last administered dose: 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsb That Have Low User Dependency Failure rate of <1% 
per year when used consistently and correctly. 
a. 
Implantable progestogen-only hormone contraception associated with 
inhibition of ovulationc 
b. Intrauterine device (IUD) 
c. 
Intrauterine hormone-releasing system (IUS)c 
d) Bilateral tubal occlusion 

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CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
e. 
Azoospermic partner (vasectomized or due to a medical cause) 
Azoospermia is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the WOCBP, 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.  
Note: documentation of azoospermia for a male participant can come from the 
site personnel’s review of the participant’s medical records, medical 
examination, or medical history interview. 
Highly Effective Methodsb That Are User Dependent Failure rate of <1% per year 
when used consistently and correctly. 
f) 
Combined (estrogen- and progestogen-containing) hormonal contraception 
associated with inhibition of ovulationc 
• 
oral 
• 
intravaginal 
• 
transdermal 
• 
injectable 
g) Progestogen-only hormone contraception associated with inhibition of 
ovulationc 
• 
oral 
• 
injectable 
h) Sexual abstinence 
• 
Sexual abstinence is considered a highly effective method only if defined 
as refraining from heterosexual intercourse during the entire period of 
risk associated with the study intervention. 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 participant 
i) 
Contraceptive use by men or women should be consistent with local 
regulations regarding the use of contraceptive methods for those participating 
in clinical studies. 
j) 
Failure rate of <1% per year when used consistently and correctly. Typical 
use failure rates differ from those when used consistently and correctly. 
k) Male condoms must be used in addition to hormonal contraception. 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, sympto-thermal, post-ovulation methods), 
withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method 

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CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
(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 from friction) 
Male participants 
As depemokimab is a mAb that is not anticipated to interact directly with 
deoxyribonucleic acid (DNA) or other chromosomal material and minimal 
exposure through semen is expected, male participants will not be required to use 
contraception during the study.  
10.5. 
Appendix 5: Genetics 
USE/ANALYSIS OF DNA 
• 
Genetic variation may impact a participant’s response to study intervention, 
susceptibility, severity and progression of disease. Variable response to study 
intervention 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 blood sample will be collected for DNA 
analysis. 
• 
DNA samples will be used for research related to depemokimab or CRSwNP. 
Genetic research may consist of the analysis of one or more candidate genes or the 
analysis of genetic markers throughout the genome. 
• 
Additional analyses of DNA samples may be conducted if it is hypothesized that this 
may help further understand the clinical data.  
• 
DNA samples will be analysed. Additional analyses may be conducted if it is 
hypothesized that this may help further understand the clinical data.  
• 
The samples may be analyzed as part of a multi-study assessment of genetic factors 
involved in the response to depemokimab or study interventions of this class. The 
results of genetic analyses may be reported in the clinical study report 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 depemokimab (or study interventions 
of this class) or CRSwNP continues but no longer than 15 years after the last subject 
last visit or other period as per local requirements. 

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10.6. 
Appendix 6: Liver Safety: Required Actions and Follow-up 
Assessments  
Liver Chemistry Stopping Criteria and Increased Monitoring Criteria are designed t 
o assure participant safety and evaluate liver event aetiology. 
10.6.1. 
Liver Chemistry Stopping Criteria and Required Follow-up 
Assessments 
Liver Chemistry Stopping Criteria- Liver Stopping Event 
ALT Absolute 
ALT ≥ 8xULN 
ALT Increase 
ALT ≥ 5xULN but <8xULN persists for ≥2 weeks 
ALT ≥ 3xULN but <5xULN persists for ≥ 4 weeks 
Bilirubin1, 2 
ALT ≥ 3xULN and total bilirubin ≥ 2xULN (>35% direct bilirubin)  
INR2  
ALT ≥ 3xULN and INR>1.5 
Cannot 
Monitor 
ALT ≥ 5xULN but <8xULN and cannot be monitored weekly for ≥2 weeks 
ALT ≥ 3xULN but <5xULN and cannot be monitored weekly for ≥ 4 weeks 
Symptomatic3 
ALT ≥ 3xULN associated with symptoms (new or worsening) believed to be related to 
liver injury or hypersensitivity 
Required Actions, Monitoring and Follow up Assessments 
Actions 
Follow Up Assessments 
• 
Immediately discontinue study intervention 
• 
Report the event to GSK within 24 hours 
• 
Complete the liver event form and 
complete SAE data collection tool if the 
event also meets the criteria for an SAE2 
• 
Perform liver event follow up assessments 
as described in the Follow up Assessment 
column 
• 
Viral hepatitis serology4 
• 
Obtain INR and recheck with each liver 
chemistry assessment until the 
aminotransferases values show downward 
trend 
• 
Obtain blood sample for pharmacokinetic (PK) 
analysis, within a week of meeting increased 
liver monitoring criteria5 
• 
Obtain a Serum creatine phosphokinase (CPK) 
and lactate dehydrogenase (LDH), gamma 

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Liver Chemistry Stopping Criteria- Liver Stopping Event 
• 
Monitor the participant until liver 
chemistries resolve, stabilize, or return to 
within baseline (see MONITORING) 
MONITORING: 
If ALT ≥3xULN AND total bilirubin ≥2xULN or 
INR >1.5:  
• 
Repeat liver chemistries (include ALT, 
AST, alkaline phosphatase, total bilirubin, 
and INR) and perform liver event follow up 
assessments within 24 hours 
• 
Monitor participants twice weekly until liver 
chemistries resolve, stabilize or return to 
within baseline 
• 
A specialist or hepatology consultation is 
recommended 
For All other criteria (total bilirubin <2xULN 
and INR ≤1.5):  
• 
Repeat liver chemistries (include ALT, 
AST, alkaline phosphatase, total bilirubin, 
and INR) and perform liver event follow up 
assessments within 24-72 hours 
• 
Monitor participants weekly until liver 
chemistries resolve, stabilize or return to 
within baseline 
RESTART/RECHALLENGE 
Do not restart/rechallenge participant with 
study intervention since not allowed per 
protocol; continue participant in the study for 
any protocol specified follow up assessments. 
glutamyl transferase [GGT], glutamate 
dehydrogenase [GLDH], and serum albumin 
• 
Fractionate bilirubin, if total bilirubin ≥2xULN 
• 
Obtain complete blood count with differential to 
assess eosinophilia. This blood sample will be 
sent to the central laboratory to maintain the 
blind while study is ongoing. Results will be 
provided only if unblinding of a participant’s 
treatment assignment is required. Also note that 
the mechanism of action of depemokimab leads 
to lowering of eosinophils 
• 
Record the appearance or worsening of clinical 
symptoms of liver injury, or hypersensitivity, on 
the liver event form 
• 
Record use of concomitant medications on the 
concomitant medications report form including 
acetaminophen, herbal remedies, recreational 
drugs and other over the counter medications 
• 
Record alcohol use on the liver event alcohol 
intake form 
If ALT ≥3xULN AND total bilirubin ≥2xULN or INR 
>1.5 obtain the following in addition to the 
assessments listed above: 
o 
Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney microsomal 
antibodies, and quantitative total 
immunoglobulin G (IgG) or gamma globulins. 
o 
Serum acetaminophen adduct assay should be 
conducted (where available) to assess potential 
acetaminophen contribution to liver injury unless 
acetaminophen use is very unlikely in the 
preceding week. (e.g., where the participant has 
been resident in the clinical unit throughout).  

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Liver Chemistry Stopping Criteria- Liver Stopping Event 
o 
Liver imaging (ultrasound, magnetic resonance, 
or computerized tomography) to evaluate liver 
disease: complete Liver Imaging form. 
o 
Liver biopsy may be considered and discussed 
with local specialist if available, for instance: 
o 
In patients when serology raises the 
possibility of autoimmune hepatitis (AIH) 
o 
In patients when suspected DILI 
progresses or fails to resolve on 
withdrawal of study intervention 
o 
In patients with acute or chronic atypical 
presentation:  
o 
If liver biopsy conducted complete liver biopsy 
form. 
1. 
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study intervention for that participant if ALT ≥3xULN and total bilirubin ≥ 
2xULN. Additionally, if serum bilirubin fractionation testing is unavailable, record presence of detectable urinary 
bilirubin on dipstick, indicating direct bilirubin elevations and suggesting liver injury. 
2. 
All events of ALT ≥3xULN and bilirubin ≥2xULN (>35% direct bilirubin) or ALT ≥ 3xULN and INR>1.5 which may 
indicate severe liver injury (possible ‘Hy’s Law’), must be reported to GSK as an SAE; the INR threshold value 
stated will not apply to participants receiving anticoagulants 
3. 
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 believed to be related to hypersensitivity (such as fever, rash or 
eosinophilia). 
4. 
Includes: hepatitis A Immunoglobulin M (IgM) antibody; HbsAg and HbcAb; hepatitis C RNA; cytomegalovirus IgM 
antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, heterophile antibody or monospot 
testing); and hepatitis E IgM antibody. In those with underlying chronic hepatitis B at study entry (identified by 
positive hepatitis B surface antigen) quantitative hepatitis B DNA and hepatitis delta antibody. If hepatitis delta 
antibody assay cannot be performed, it can be replaced with a polymerase chain reaction (PCR) of hepatitis D 
RNA virus (where needed) [Le Gal, 2005]. 
5. 
Record the date/time of the PK blood sample draw and the date/time of the last dose of study intervention prior to 
the PK blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the participant’s best 
approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot be collected in 
the time period indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are in 
the central laboratory manual. 

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10.6.2. 
Liver Chemistry Increased Monitoring Criteria with Continued 
Study Intervention 
Liver Chemistry Increased Monitoring Criteria and Actions with Continued Study Intervention Liver 
Monitoring Event 
Criteria 
Actions 
ALT ≥ 5xULN and <8xULN and total bilirubin 
<2xULN or INR≤1.5 without symptoms believed 
to be related to liver injury or hypersensitivity, and 
who can be monitored weekly for 2 weeks. 
OR 
ALT ≥ 3xULN and <5xULN and total bilirubin 
<2xULN or INR≤1.5 without symptoms believed 
to be related to liver injury or hypersensitivity, 
and who can be monitored weekly for 4 weeks. 
o 
Notify the GSK Medical Monitor within 24 hours of 
learning of the abnormality to discuss participant 
safety. 
o 
Participant can continue study intervention. 
o 
Participant must return weekly for repeat liver 
chemistries (ALT, AST, alkaline phosphatase, total 
bilirubin and INR) until they resolve, stabilise or 
return to within baseline. 
o 
If at any time participant meets the liver chemistry 
stopping criteria, proceed as described above. 
o 
If ALT decreases from ALT ≥ 5xULN and <8xULN to 
≥3xULN but <5xULN, (total bilirubin <2xULN and 
INR ≤1.5) continue to monitor liver chemistries 
weekly. 
o 
If, after 4 weeks of monitoring, ALT <3xULN and total 
bilirubin <2xULN and INR ≤1.5, monitor participants 
twice monthly until liver chemistries resolve or return 
to within baseline. 
Reference 
Le Gal F, Gordien E, Affolabi D, Hanslik T, Alloui C, Dény P, et al. Quantification of 
Hepatitis Delta Virus RNA in Serum by Consensus Real-Time PCR Indicates Different 
Patterns of Virological Response to Interferon Therapy in Chronically Infected Patients. J 
Clin Microbiol. 2005;43(5):2363–2369. 

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10.7. 
Appendix 7: AEs, ADEs, SAEs, SADEs, USADEs and Device 
Deficiencies: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting in Medical Device 
Studies 
• 
The definitions and procedures detailed in this appendix are in accordance with ISO 
14155 and the European Medical Device Regulation (MDR) 2017/745 for clinical 
device research (if applicable).  
• 
Both the investigator and the sponsor will comply with all local medical device 
reporting requirements for medical devices. 
• 
The detection and documentation procedures described in this protocol apply to all 
GSK medical devices provided for use in the study (see Section 6.1.1 for the list of 
GSK medical devices). 
10.7.1. 
Definition of Medical Device AE and ADE 
Medical Device AE and ADE Definition  
• 
A medical device AE is any untoward medical occurrence, in a clinical study 
participant, users, or other persons, temporally associated with the use of study 
intervention whether or not considered related to the investigational medical 
device. An AE can therefore be any unfavourable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of an investigational medical device. This 
definition includes events related to the investigational medical device or 
comparator and events related to the procedures involved except for events in 
users or other persons, which only include events related to investigational 
devices. 
• 
An ADE is defined as an AE related to the use of an investigational medical 
device. This definition includes any AE resulting from insufficient or inadequate 
instructions for use, deployment, implantation, installation, or operation, or any 
malfunction of the investigational medical device as well as any event resulting 
from use error or from intentional misuse of the investigational medical device. 
10.7.2. 
Definition of Medical Device SAE, SADE and USADE 
A Medical Device SAE is any serious adverse event that: 
a. 
Led to death  
b. Led to serious deterioration in the health of the participant, that either resulted in: 
− 
A life-threatening illness or injury. The term ‘life-threatening’ in the 
definition of ‘serious’ refers to an event in which the participant was at risk of 
death at the time of the event. It does not refer to an event, which 
hypothetically might have caused death, if it were more severe. 
− 
A permanent impairment of a body structure or a body function. 

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A Medical Device SAE is any serious adverse event that: 
− 
Inpatient or prolonged hospitalization. Planned hospitalization for a pre-
existing condition, or a procedure required by the protocol, without serious 
deterioration in health, is not considered an SAE. 
− 
Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function. 
− 
Chronic disease (MDR 2017/745). 
c. 
Led to fetal distress, fetal death or a congenital abnormality or birth defect 
d. Is a suspected transmission of any infectious agent via a medicinal product 
SADE definition 
• 
A SADE is defined as an ADEs that has resulted in any of the consequences 
characteristic of an SAE. 
• 
Any device deficiency that might have led to an SAE if appropriate action had not 
been taken, intervention had not occurred, or circumstances had been less 
fortunate. 
Unanticipated SADE (USADE) definition 
• 
An USADE (also identified as UADE in US Regulations 21 CFR 813.3), is 
defined as a serious ADEs that by its nature, incidence, severity or outcome has 
not been identified in the current version of the risk analysis report  
(see Section 2.3). 
10.7.3. 
Definition of Device Deficiency 
Device Deficiency Definition 
• 
A device deficiency is an inadequacy of a medical device with respect to its 
identity, quality, durability, reliability, safety, or performance. Device deficiencies 
include malfunctions, use errors, and inadequacy of the information supplied by 
the manufacturer. 
10.7.4. 
Recording and Follow-Up of AE and/or SAE and Device 
Deficiencies 
AE, SAE and Device Deficiency Recording 
• 
When an AE/SAE/device deficiency occurs, it is the responsibility of the 
investigator to review all documentation (e.g., hospital progress notes, laboratory 
reports, and diagnostics reports) related to the event. 
• 
The investigator will then record all relevant AE/SAE/device deficiency 
information in the participant’s medical records, in accordance with the 
investigator’s normal clinical practice, and on the appropriate form. 

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AE, SAE and Device Deficiency Recording 
• 
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the AE/SAE/device deficiency 
form. 
• 
There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to GSK. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE. 
• 
For device deficiencies, it is very important that the investigator describes any 
corrective or remedial actions taken to prevent recurrence of the deficiency. 
• 
A remedial action is any action other than routine maintenance or servicing of a 
medical device where such action is necessary to prevent recurrence of a device 
deficiency. This includes any amendment to the device design to prevent 
recurrence. 
• 
If the site during the course of the study becomes aware of any serious, nonserious 
incident (including device deficiencies and malfunctions) related to any GSK 
product that is not part of the study design, they will report these events to GSK or 
to the concerned CA via the national spontaneous reporting system. These will be 
classified as spontaneous ICSRs. 
Assessment of Intensity 
• 
The investigator will make an assessment of intensity for each AE/SAE/device 
deficiency reported during the study and assign it to one of the following 
categories:  
• 
Mild: Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
• 
Moderate: Minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental ADL. Instrumental ADL refers to preparing meals, 
shopping for groceries or clothes, using the telephone, managing money, etc. 
• 
Severe: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling, limiting self 
care ADL. Self care ADL refers to bathing, dressing and undressing, feeding self, 
using the toilet, taking medications, and not bedridden. 
• 
Other measures to evaluate AEs and SAEs may be used (e.g., National Cancer 
Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE]). 
 

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Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE/device deficiency. The investigator will use 
clinical judgment to determine the relationship. 
• 
A reasonable possibility of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• 
The investigator will also consult the IB and/or Product Information, in his/her 
assessment. 
• 
For each AE/SAE/device deficiency, the investigator must document in the 
medical notes that he/she has reviewed the AE/SAE/device deficiency and has 
provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK. However, it is very 
important that the investigator always make an assessment of causality for every 
event before the initial transmission of the SAE data to GSK. 
• 
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
Follow-up of AE/SAE/device deficiency 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK 
to elucidate the nature and/or causality of the AE/SAE/device deficiency as fully 
as possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health care 
professionals. 
• 
If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide GSK with a copy of any post-
mortem findings including histopathology. 
• 
New or updated information will be recorded in the originally completed eCRF. 
• 
The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 

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10.7.5. 
Reporting of SAEs 
SAE Reporting to GSK via an Electronic Data Collection Tool 
• 
The primary mechanism for reporting an SAE to GSK will be the electronic data 
collection tool. 
• 
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next table) in order to report the event within 24 hours. 
• 
The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• 
After the study is completed at a given site, the electronic data collection tool will 
be taken offline to prevent the entry of new data or changes to existing data. 
• 
If a site receives a report of a new SAE from a study participant or receives 
updated data on a previously reported SAE after the electronic data collection tool 
has been taken off-line, then the site can report this information on a paper SAE 
form (see next section) or to the GSK Medical Monitor by telephone. 
• 
If the site during the course of the study becomes aware of any serious, nonserious 
incident (including device deficiencies and malfunctions) related to any GSK 
product that is not part of the study design, they will report these events to GSK or 
to the concerned CA via the national spontaneous reporting system. These will be 
classified as spontaneous ICSRs. 
• 
Contacts for SAE reporting can be found in the SRM. 
SAE Reporting to GSK via Paper Data Collection Tool 
• 
Facsimile transmission of the SAE data collection tool is the preferred method to 
transmit this information to the GSK Medical Monitor. 
• 
In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE paper data collection tool sent by 
overnight mail or courier service. 
• 
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE paper data collection tool within the designated 
reporting time frames. 
• 
Contacts for SAE reporting can be found in the SRM. 
10.7.6. 
Reporting of SADEs 
SADE Reporting to GSK  
• 
NOTE: There are additional reporting obligations for medical device deficiencies 
that are potentially related to SAEs that must fulfill the legal responsibility to 
notify appropriate regulatory authorities and other entities about certain safety 
information relating to medical devices being used in clinical studies.  

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SADE Reporting to GSK  
• 
Any device deficiency that is associated with an SAE must be reported to GSK 
within 24 hours after the investigator determines that the event meets the 
definition of a device deficiency. 
• 
GSK will review all device deficiencies and determine and document in writing 
whether they could have led to an SAE. These device deficiencies will be reported 
to the regulatory authorities and IRBs/IECs as required by national regulations. 
• 
Refer to the paper medical device deficiency report form for details on 
transmission of this information to the Sponsor. 
10.7.7. 
Reporting of Medical Device Deficiencies for Associated Person 
Reporting to GSK  
• 
If an Associated Person (i.e., e.g., spouse, caregiver, site staff) experiences a 
device deficiency, the medical device deficiency information, and any associated 
AE/SAE information will be reported to GSK. The associated person will be 
provided with the authorization to contact physician letter. 
• 
If follow up information is required, authorization to contact physician (or other 
licensed medical practitioner’ must be signed to obtain consent. 
• 
Medical device deficiencies that are not related to an AE or SAE should be 
reported via email to gsk-rd.complaints@gsk.com, using the medical device 
deficiency report form.  
• 
If the medical device deficiency is related to a non-serious AE and not linked to an 
SAE, please send the medical device deficiency report form with details of the 
associated AE via email to gsk-rd.complaints@gsk.com only. 
• 
If the device incident is linked to an SAE, please email the medical device 
deficiency report form, within 24 hours, to both uk.gsk-rd-gcsp-ctsm-
admin@gsk.com (or fax +44(0)20 8754 7822) and gsk-rd.complaints@gsk.com. 
The associated SAE form should also be reported to uk.gsk-rd-gcsp-ctsm-
admin@gsk.com (or fax +44(0)20 8754 7822). 
• 
GSK will review all device deficiencies and determine and document in writing 
whether they could have led to an SAE. These device deficiencies will be reported 
to the regulatory authorities and IRBs/IECs as required by national regulations. 
• Contacts for Medical Device Deficiency reporting can be found in the medical 
device deficiency report form. 

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10.8. 
Appendix 8: Anaphylaxis Criteria 
Joint National Institute of Allergy and Infectious Disease (NIAID)/ FAAN Second 
Symposium on Anaphylaxis [Sampson, 2006]. The criteria do not make a distinction 
based on underlying mechanism. These criteria are summarised as follows: 
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, 
mucosal tissue, or both (e.g., generalized hives, pruritus or flushing, swollen 
lips-tongue-uvula), and at least one of the following: 
a) Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced 
PEF, hypoxemia) 
b) Reduced blood pressure (BP) or associated symptoms of end-organ dysfunction 
(e.g., hypotonia [collapse], syncope, incontinence) 
2. Two or more of the following that occur rapidly after exposure to a likely allergen 
for that patient (minutes to several hours): 
a) Involvement of the skin-mucosal tissue (e.g., generalized hives, itch-flush, 
swollen lips-tongue-uvula) 
b) Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced  
PEF, hypoxemia) 
c) Reduced BP or associated symptoms (e.g., hypotonia [collapse], syncope, 
incontinence) 
d) Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting) 
3. Reduced BP after exposure to known allergen for that patient (minutes to several 
hours): 
a) Adolescents (aged 12-17): low systolic BP (age specific) or greater than 30% 
decrease in systolic BP 
b) Adults: systolic BP of less than 90 mmHg or greater than 30% decrease from 
that person’s baseline 
10.9. 
Appendix 9: Lund-Mackay CT score 
Change in the Lund-Mackay CT score percentage of maxillary sinus volume occupied by 
disease will be assessed in all participants. 
The Lund-Mackay CT score evaluates the patency of each sinus using a 0 to 2 scale (0 = 
normal; 2 = total opacification) and has a total score range from 0 to 24 (higher scores 
indicate more opacification) [Lund, 1993; Bhattacharyya, 1999].  

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Sinus 
Right sinus 
Left sinus 
Frontal 
0-2 
0-2 
Anterior ethmoids 
0-2 
0-2 
Posterior ethmoids 
0-2 
0-2 
Maxillary 
0-2 
0-2 
Sphenoid 
0-2 
0-2 
Ostiomeatal complex 
0 or 2 
0 or 2 
Total 
0-12 
0-12 
For the sinuses: 0 = no opacification; 1 = partial opacification; 2 = total opacification. 
For the ostiomeatal complex: 0 = not occluded; 2 = occluded. 
Maximum total score: 24 
10.10. 
Appendix 10: Country-specific requirements  
Country-specific local requirements will be added, as and when applicable. 
Japan-specific requirements 
Additional Japan-specific requirements will be captured within a separate addendum. The 
content of the Japan addendum is considered administrative.  
China-specific requirements 
Urinalysis: Urine dipstick will not be performed in China, all urine sample will instead 
be sent for central laboratory urinalysis. Investigators should be aware of the time needed 
for central laboratories to return results, and should perform appropriate local 
investigations if any urgent result is required.  
Exploratory biomarkers: Exploratory biomarkers samples will not be collected from 
participants in China.  
Genetics: Genetic Informed Consent will not be collected from participants in China.  
France-specific requirements  
Informed Consent: In France, a participant will be eligible for inclusion in this study 
only if he/she is either affiliated to or a beneficiary of a social security category. 

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10.11. 
Appendix 11: Recommended Measures Related to COVID-19 
Pandemic 
10.11.1. 
Overall Rationale for this Appendix: 
COVID-19 pandemic may impact the conduct of clinical studies. Challenges may arise 
from quarantines, site closures, travel limitations, interruptions to the supply chain for the  
study intervention or other considerations if site personnel or study participants become 
infected with COVID-19. These challenges may lead to difficulties in meeting protocol- 
specified procedures, including administering or using the study intervention or adhering 
to protocol-mandated visits and laboratory/diagnostic testing. 
This protocol appendix outlines measures that may be applicable for any site impacted by 
the COVID-19 pandemic. The purpose of the appendix is to provide information on the 
measures to be taken to protect participants’ safety, welfare and rights, and promote data 
integrity. 
10.11.2. 
Study Procedures During COVID-19 Pandemic 
During the special circumstances caused by the current COVID-19 pandemic, you should 
consider specific public health guidance, the impact of any travel restrictions 
implemented by local/regional health authorities and local institutions, and individual 
benefit /risk when making enrolment and treatment decisions for trial participants. 
Every effort should be made to adhere to protocol specified assessments for participants 
on study intervention, including follow-up however when not possible, for the duration of 
these special circumstances, the following measures may be implemented for enrolled 
participants. 
• 
Clinical investigators should document in site files and in participant 
notes/Electronic Health Records as appropriate how restrictions related to COVID-
19 led to the changes in study conduct and duration of those changes and indicate 
which trial participants were impacted and how those trial participants were 
impacted (as per the current local COVID-19 related regulatory guidance). 
• 
Missing protocol required data/visits due to COVID-19 should be noted in 
participant notes and recorded as a COVID-19 protocol deviation. 
10.11.3. 
Protocol Defined Procedures/Visits: 
• 
Where applicable country and local regulations and infrastructure for home 
healthcare allow, home healthcare may take place at a location other than the clinical 
trial site to perform study assessments, which may include collection of blood and 
urine samples, measurement of vital signs and weight, and preparation and 
administration of study drug (at the discretion of the investigator). It is the 
responsibility of the investigator to inform GSK when this occurs and to document in 
source notes. 

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• 
Remote visits may be performed at the participant’s home by qualified study 
personnel or at a local medical facility, unless the investigator deems that a site visit 
is necessary. 
• 
Additional unscheduled safety assessments such as routine blood sampling may be 
performed at the discretion of the investigator including in the participant’s home, if 
deemed necessary. Biological samples may be collected at a different location, other 
than the study site (e.g., at participant’s home) by qualified study personnel or at a 
local medical facility according to standard operating procedures and applicable 
regulations (see note). Biological samples should not be collected if they cannot be 
processed in a timely manner or appropriately stored until the intended use. 
• 
If visits to a site/home are not feasible, then the medical evaluation of the 
participant’s CRSwNP may take place by telemedicine which will use secure video 
conferences, phone calls, and a web portal and/or mobile application as a way of 
communicating with and monitoring the participant’s progress. GSK will be 
accountable for working with the vendor to ensure the site has the required 
equipment, training and support for this model and should be notified as soon as 
possible by the investigator that the service is required. 
• 
The study investigator is responsible for ensuring that the identification, 
management, and reporting of AEs and SAEs are completed in accordance with the 
protocol and applicable regulations. AEs are first reported by participants to the 
investigator/study team or may be identified by the study team during interactions 
with the participants via telemedicine encounters. In addition, mobile nurses may 
identify AEs as well and report them to the investigator for evaluation. Additionally, 
AEs may be identified from lab reports, imaging or ECG  reports, and other records. 
As determined by the investigator, the appropriate medical intervention, therapeutic 
intervention, and/or support measures are instituted, as necessary. 
• 
The participant should be informed of the plan and any potential risks associated with 
the virtual medium and sign a revised Informed Consent Form if required. 
IRB/Ethics committee should be informed and/or approve of this change in approach 
and the process documented in study files. 
• 
The revised schedule of study activities is provided in the SoA in Section 1.3. 
Note: If the investigator wishes to conduct a trial visit at a location that has not been 
previously assessed by GSK, it is the investigator’s responsibility to identify an adequate 
alternate location and to notify GSK of the alternate location. The investigator should 
ensure that this alternate location meets ICH GCP requirements, is well-equipped to 
perform study procedures and covered by an adequate insurance. Furthermore, the 
investigator should have sufficient oversight to ensure that the staff at the alternate 
location are trained to perform study procedures. Refer to and follow most recent local 
guidance and regulations if available or refer to FDA or EMA guidance available at time. 
10.11.4. 
Study Intervention: 
• 
If despite best efforts it is not possible to administer the dose of study intervention as 
defined in the protocol (see Section 6 Study Intervention and Concomitant Therapy), 
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• 
In-clinic visits are required for administration of the study intervention (Week 0 and 
Week 26). 
• 
In some cases, trial participants who no longer have access to study intervention or 
the investigational site may need additional safety monitoring (e.g., on withdrawal of 
an active investigational treatment). 
10.11.5. 
Data Management/Monitoring: 
• 
If the eDiary was provided to the participant, it may be returned to the site by 
conventional mail after the end of the relevant data collection period (Visit 17 Exit 
Visit). 
• 
If on site monitoring is no longer permitted, GSK will consider remote Source Data 
Verification/Source Document Review (SDV/SDR) where permitted by the clinical 
site/institution. Remote SDV/SDR will be proposed to study sites to meet a patient 
and/or critical quality need, e.g., to assess participant safety or to ensure data 
integrity. In case of remote SDV/SDR, GSK will work with the site to ensure 
participant privacy. 
• 
eCRF/CRF Final or Interim Sign off Process: The PI is responsible for ensuring that 
the data within the eCRF casebook and any other data sources utilized during the 
study for each study participant is complete and consistent with source documents 
throughout the study (ICH GCP 4.9.1 4.9.2). The PI may sign/re-sign the eCRF from 
any computer/location by accessing InForm (or other eDC platform) using his/her 
unique eCRF log-in credentials. The PI may delegate this activity to another 
medically qualified and trained sub-investigator and this must be documented on the 
Delegation of Responsibilities (DoR) Log. It is recommended that the PI identifies a 
sub-investigator as a back-up for eCRF signatures. The sub- investigator must be 
appropriately trained on the protocol and eCRF requirements (with training 
documented), and the DoR log updated accordingly. 
• 
Essential Document Sign Off Process: If an investigator is unable to print and sign 
essential documents such as Protocol /Amendment signature page then Email 
approval can be accepted by replying to the relevant email that is sent by GSK. 
10.11.6. 
Assessments that can be Conducted Outside Clinical Study Site: 
Activities/assessments that may be conducted outside of a clinical study site are indicated 
in Table 1. 
10.12. 
Appendix 12: Protocol Amendment History 
Amendment 4 (12 March 2024) 
Overall rationale for the current Amendment: The protocol has been amended 
primarily to change the pooled analysis endpoint of time to first nasal surgery (actual) 
from ‘Other’ to ‘Secondary’ to address feedback from the FDA. Additional participant 
analysis sets have been added and updates to existing analysis sets have been made to 
exclude data from sites managed by Medipharma, a Japanese Site Management 

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Organisation, in response to the Japan Ministry of Health, Labour and Welfare (MHLW) 
confirming GCP violations in several studies involving Medipharma. Other changes to 
the protocol reflect updates to the GSK protocol template. 
LIST OF MAIN CHANGES IN THE PROTOCOL AND THEIR RATIONALE: 
Section # and title 
Description of change 
Brief rationale 
Abbreviations 
Addition of abbreviations 
Added abbreviations introduced in this 
protocol amendment. 
Terms 
Addition of terms 
For clarification of terms used in the 
protocol. 
Section 1.1 Synopsis, 
Section 3.2 Objectives and 
Endpoints for Pre-specified 
Pooled Analysis Across 
Studies 217095 (This 
Study) and 218079 
(Replicate Study) 
Changed the pooled analysis 
endpoint of ‘time to first 
nasal surgery (actual)’ from 
‘Other’ to ‘Secondary’. 
Based on regulatory authority feedback. 
Section 1.1 Synopsis, 
Section 3.2 Objectives and 
Endpoints for Pre-specified 
Pooled Analysis Across 
Studies 217095 (This 
Study) and 218079 
(Replicate Study) 
Added ‘for CRSwNP’ for the 
endpoint related to systemic 
corticosteroids. 
For clarification of endpoint assessment. 
Section 1.1 Synopsis, 
Section 3.2 Objectives and 
Endpoints for Pre-specified 
Pooled Analysis Across 
Studies 217095 (This 
Study) and 218079 
(Replicate Study) 
Added ‘up to Week 52’ for 
the endpoint related to need 
for surgery. 
For clarification of endpoint assessment. 
Section 2.2.1.1 
Depemokimab 
(GSK3511294) Long-Acting 
IL-5 and Section 2.3 
Benefit/Risk Assessment 
Reference to the 
Investigator’s Brochure has 
been updated to the latest 
effective version of the IB.  
To update to the current effective IB 
version 5.0.  
Section 3.5 Secondary 
Estimands for 
Pre-specified Pooled 
Analysis Across Studies 
217095 (This study) and 
218079 
Addition of estimand 
definition for the pooled 
secondary endpoint of ‘Time 
to first nasal surgery 
(actual)’.  
To provide the estimand definition for 
this endpoint, which is now a pooled 
analysis secondary endpoint. 
Section 6.1 Study 
Intervention(s) 
Administered 
Table 3 
Updated to indicate 
‘Depemokimab’ as IMP 
instead of ‘Experimental’ and 
that Non-IMP and authorized 
AxMP/unauthorized AxMP 
are Not Applicable. 
Updated for clarity and to reflect 
changes made to the GSK protocol 
template. 
Section 6.8.2 Prohibited 
Medications 
Corrected the washout 
period prior to Screening 
Editorial correction. 

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Section # and title 
Description of change 
Brief rationale 
Table 4 
visit for non-biologic and 
biologic investigational 
products; corrected the 
dupilumab trade name. 
Section 7.2 Participant 
Discontinuation/Withdrawal 
from the Study 
Updated terminology: 
replaced ‘study 
discontinuation’ with ‘study 
withdrawal’. 
To provide clarity and consistency in 
terminology between “discontinuing 
treatment” and “withdrawal from study” 
and to reflect changes made to the GSK 
protocol template. 
Section 7.3 Lost to Follow 
Up 
Updated to clarify that other 
contact methods can be 
used along with telephone 
calls for follow up. 
For clarification and to reflect changes 
made to the GSK protocol template. 
Section 8.4.9 Medical 
Device Deficiencies 
Updated to clarify that if the 
sites use non-sponsor 
medical devices, then the 
investigators are obligated to 
report any device 
deficiencies to the legal 
manufacturer of the devices 
directly. 
For clarification and to reflect changes 
made to the GSK protocol template. 
Section 9.1.1 Multiplicity 
Adjustment and Figure 4 
This section and the figure 
were updated to reflect the 
addition of time to first nasal 
surgery (actual) as a 
secondary endpoint for the 
pooled analysis. Updates to 
indicate that the time to first 
nasal surgery (actual) will 
only be tested if statistical 
significance is achieved for 
time to first nasal surgery 
(actual or entry on waiting 
list). Updated the number of 
secondary endpoints to 4. 
To align with changes to the statistical 
hierarchy.  
Section 9.2 Analysis Sets 
Update to the Full Analysis 
Set (FAS) to exclude 
participants from sites 
managed by Medipharma, 
and addition of modified 
analysis sets including these 
participants. 
Added additional participant 
analysis sets for PK and 
specific analysis sets for 
China and Japan. 
Updated to align with the Statistical 
analysis plan in response to the Japan 
Ministry of Health, Labour and Welfare 
(MHLW) confirming GCP violations in 
several studies involving Medipharma 
and to describe analysis sets required 
for PK analyses and submissions in 
China and Japan. 
Section 9.3.1 Co-primary 
and Key Secondary 
Endpoint(s) Analyses 
Added the time to first nasal 
surgery (actual) endpoint 
under secondary pooled 
analyses and detailed the 
pooled analysis description. 
Updated to align with updates in other 
sections of the protocol and Statistical 
analysis plan.  

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Section # and title 
Description of change 
Brief rationale 
Section 10.1.5 Data 
Protection 
Added a statement related to 
GSK internal policy for 
reporting data incidents or 
breaches. 
To comply with requirements to protect 
personal data and to reflect changes 
made to the GSK protocol template. 
Section 10.1.7 
Dissemination of Clinical 
Study Data 
• 
Updated plain language 
terminology to layperson 
summary of results. 
• 
Added a statement that 
where required by 
regulation, the names of 
the sponsor signatory 
and investigator 
signatory will be made 
public. 
• Deleted the wording 
related to SHARE 
initiative. 
• Added a statement 
related to data sharing 
and protecting PI.  
Updated to align with GSK’s disclosure 
requirement and regulatory disclosure 
requirement and to reflect changes 
made to the GSK protocol template. 
Section 10.1.11 Publication 
Policy 
Updated wording around 
GSK seeking to publish 
medically or scientifically 
significant results in peer-
reviewed scientific literature. 
Updated to align with the new policy on 
Ethical Scientific Research and to reflect 
changes made to the GSK protocol 
template. 
Section 10.3.5 Reporting of 
SAE to GSK; Section 10.7.4 
Recording and Follow-Up 
of AE and/or SAE and 
Device Deficiencies; 
Section 10.7.5 Reporting of 
SAEs 
Additional instruction to the 
site to report to the 
concerned Competent 
Authority via the national 
spontaneous reporting 
system if they become 
aware of any serious, 
nonserious AEs, pregnancy 
exposure, related to any 
GSK product/device that is 
not part of the study design. 
Updated for clarification and to reflect 
changes made to the GSK protocol 
template. 
Section 11 References 
Deleted references (Bretz 
2009, Wang 2003) which 
were not cited in the protocol 
Correction as these references were not 
cited.  
All sections 
Other minor editorial changes to improve readability.  
Amendment 3 (18 October 2023)  
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: 

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• 
To reduce the number of participants required to provide PK samples at Week 52 
(Visit 16/EW Visit) to approximately 200. 
• 
To add an optional nasal biopsy sample collection at Week 52 (Visit 16). 
• 
To update the statistical testing hierarchy. 
• 
To move the asthma-related endpoints to the pooled analyses. 
• 
To amend the definition of the nasal surgery endpoint included in the pooled analysis 
statistical hierarchy from ‘actual’ to ‘required’. 
• 
Other changes include clarification on NP Scoring guidance and updates to language 
related to regulatory, ethical, and study oversight considerations. 
List of Main Changes in the Protocol and Their Rationale: 
Section # and title 
Description of Change 
Brief Rationale 
Terms 
Addition of terms and definitions. 
For clarification of terms used in 
the protocol. 
Section 1.1. Synopsis,  
Section 3.1. Objectives and 
Endpoints,  
Section 3.2. Objectives and 
Endpoints for Pre-specified 
Pooled Analysis Across 
Studies 217095 (This Study) 
and 218079 (Replicate 
Study),  
Section 3.4. Secondary 
Estimands, 
Section 3.5. Secondary 
Estimands for Pre-specified 
Pooled Analysis Across 
Studies 217095 (This Study) 
and 218079 
To move the asthma-related 
endpoints (ACQ-5 Score and 
exacerbations) to the pooled 
analyses. 
To amend the definition of the 
nasal surgery objective and 
endpoint included in the pooled 
analysis statistical hierarchy from 
‘actual’ to ‘required’. To update 
the definition of the ‘Other’ 
objective and endpoint for nasal 
surgery to count actual surgery 
only. 
To ensure sufficient power for the 
asthma-related endpoint analyses. 
To account for (1) the fact that 
there may be some delay between 
the requirement for surgery and 
actually having a surgery, during 
which time participants will be on a 
waiting list and (2) country-level 
variations in medical practices 
including potential for extended 
waiting list durations. 
Section 1.3. Schedule of 
Activities (SoA) 
PK samples at Week 52 
(Visit 16/EW Visit) will be 
collected for approximately 
200 participants rather than all 
participants. 
Optional nasal biopsy sample 
collection added at Week 52. 
Samples from approximately 
200 participants at Visit 16 are 
sufficient for PK analysis. 
To better understand the biological 
responses to depemokimab within 
the tissue and the relationship to 
clinical responses. 
Section 2.3.1. Risk 
Assessment,  
Section 10.3.5. Reporting of 
SAE to GSK,  
Section 10.7.5. Reporting of 
SAEs 
Deleted reference to the SAE 
Coordinator. 
The SAE Coordinator role no 
longer exists. 

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Section # and title 
Description of Change 
Brief Rationale 
Section 3.5. Secondary 
Estimands for Pre-specified 
Pooled Analysis Across 
Studies 217095 (This Study) 
and 218079 
Addition of secondary estimand 
information for the ACQ-5 Score 
endpoint. 
To align with changes to the 
statistical hierarchy. 
Section 4.4. End of Study 
Definition 
Updates to the definition of study 
completion. 
For clarification and alignment 
across the clinical development 
program. 
Section 5.1. Inclusion 
Criteria 
Replaced reference to 
"Appendix 10" with "Clario Video 
Guideline". 
To clarify the endoscopic NP 
scoring guidance used by sites and 
central reader. 
Section 5.3. Randomization 
Criteria 
Updated Randomization 
Criteria 9 on maintenance 
therapy to prohibit new use of 
systemic corticosteroids during 
the run-in period. 
To clarify what medications are 
permitted during the run-in period. 
Section 6.8.1. Permitted 
CRSwNP and Asthma 
Medications 
Added clarifications on the use of 
short courses of systemic 
corticosteroids, antibiotics, and 
saline nasal douches during the 
study. 
To clarify what medications are 
permitted during the study. 
Section 7.2. Participant 
Discontinuation/Withdrawal 
from the Study 
Participants who are prematurely 
withdrawn from study should be 
encouraged to complete their 
eDiary up until their EW Visit. 
To clarify eDiary requirements for 
participants who are withdrawn 
from study. 
Section 8. Study 
Assessments and 
Procedures 
Removed requirement for NP 
scores to be blinded to study and 
site staff. 
NP scores do not pose a risk of 
unblinding the participant’s 
intervention assignment. 
Section 8.2.1. Endoscopic 
NP Score 
Replaced reference to “Vendor 
manual” with “Clario Video 
Guideline”. 
To clarify the endoscopic NP 
scoring guidance used by sites and 
central reader. 
Section 8.5 
Pharmacokinetics 
PK samples at Week 52 
(Visit 16/EW Visit) will be 
collected for approximately 
200 participants rather than all 
participants. 
Samples from approximately 
200 participants at Visit 16 are 
sufficient for PK analysis. 
Section 8.6.4.3.2. Nasal 
Biopsy 
Optional nasal biopsy sample 
collection added at Week 52. 
To better understand the biological 
responses to depemokimab within 
the tissue and the relationship to 
clinical responses. 
Section 9.1.1. Multiplicity 
Adjustment 
Text and Figure 4 updated: 
ACQ-5 Score endpoint moved to 
the pooled analysis statistical 
hierarchy and definition of the 
nasal surgery secondary 
endpoint in the pooled analysis 
hierarchy updated to include 
entry on waiting list. 
To align with changes to the 
statistical hierarchy. 
Section 9.2. Analysis Sets 
The “modified Intent-to-treat” 
population has been renamed as 
the “Full Analysis Set”. 
To align on analysis set naming 
across the clinical development 
program. 

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Section # and title 
Description of Change 
Brief Rationale 
Section 9.5. Sample Size 
Determination 
Updates to assumptions and 
power to reflect inclusion of entry 
on waiting list as an event for the 
nasal surgery secondary 
endpoint. 
To align with the updated definition 
of the nasal surgery secondary 
endpoint included in the statistical 
hierarchy. 
Section 10.1.5. Data 
Protection 
Added a statement related to 
protection of the personal data of 
the investigator and site staff. 
To comply with requirements to 
protect personal data. 
Section 10.1.7. 
Dissemination of Clinical 
Study Data 
Added timing for disclosure of 
clinical study data. 
To align with sponsor policies on 
the dissemination of clinical study 
data. 
Section 10.1.8. Data Quality 
Assurance 
Added a statement related to 
external sharing of source 
documents for review and 
storage. 
To state how long documents will 
be stored by the external body. 
Previous Section 10.10 
Appendix 10: Endoscopic 
NP Score 
Deleted Appendix 10 (nasal 
polyps scoring). 
Now referencing ‘Clario Video 
Guideline’ to clarify the endoscopic 
NP scoring guidance used by sites 
and central reader. 
Throughout 
Minor editorial and document 
formatting revisions. 
Minor, therefore, have not been 
summarized. 
Amendment 2 (26 October 2022) 
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:  
This protocol was modified following release of a protocol clarification letter in April 
2022. All details included in the protocol clarification letter are now incorporated into the 
study protocol. Protocol changes are described in the table below. 
Section  
Description of Change 
Brief Rationale 
Section 1.3 Schedule of Activities 
Updated notes for  
• 
Medical history; Past and 
current medical conditions’ 
• 
Physical exam 
• 
12-lead ECG 
• 
Assessment of endoscopic 
NP score 
• 
CT Scan 
• 
eDiary Compliance Check 
• 
Parasitic Screening 
Modified to align with the 
corresponding amendments 
made in rest of the protocol.  

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Section  
Description of Change 
Brief Rationale 
• 
Urinalysis 
• 
Pregnancy test (WOCBP 
only) 
• 
Footnote  
Deleted row on Optional Nasal 
filter samples for biomarkers 
Section 1.3 Schedule of Activities 
Physical examination to be 
performed prior to dosing at Visit 
9 as well 
Correction/Clarification 
Section 1.3 Schedule of Activities 
Updated footnote to provide 
information on urinalysis in China 
To comply with local policy 
Section 5.1 Inclusion Criteria 
Updated definition of severe NP 
symptoms 
Clarification 
Section 5.2. Exclusion Criteria 
Exclusion criteria 24 on 
prior/concurrent clinical study 
experience updated to include 
washout period for non-biologics 
besides biologics, by adding a 
reference to Section 6.8.2  
Clarification 
Section 6.8 Concomitant Therapy  
Modified heading to “Prior and 
Concomitant therapy” 
Correction 
Section 6.8.2 Table 4 
Table 4 Prohibited medicated 
updated to include more clarity 
on ‘time period prior to screening 
visit’ for non-biologic and biologic 
products  
Correction/ Clarification 
Section 6.8.3. COVID-19 Vaccines 
and treatments 
Updated information on the 
permitted COVID-19 treatment 
Clarification 
Section 7.1.3.QTc Stopping Criteria Added the definition for baseline 
QTcF value and the procedure to 
assess QTc stopping criteria after 
randomization and at Visit 9 
(Week 26) 
Clarification 
Section 8.2.1. Endoscopic NP 
Score 
Updated window period for nasal 
endoscopic assessment 
Correction 
Section 8.2.2.2. Overall Visual 
Analogue Scale (VAS) Symptoms 
Score 
Update regarding final VAS 
scores assessment/interpretation 
Correction/ Clarification 

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Section  
Description of Change 
Brief Rationale 
Section 8.2.3. Computed 
Tomography (CT) Scan 
Text modified to clarify that CT 
scan must be performed prior to 
randomization and should be the 
last assessment performed, 
where possible. Protocol updated 
to outline minimum criteria that 
need to be verified prior to the 
first CT scan, if it cannot be 
performed as the last 
assessment before 
randomization, in line with a 
protocol clarification letter 
released in April 2022. 
Correction/ Clarification 
Section 8.6.4.3. Surgical Samples 
Section on Nasal Filter Samples 
removed 
Correction 
Section 9.1. Statistical Hypotheses 
Replaced the statistical term 
superiority with inequality  
Clarification 
Section 10.1.4. Recruitment 
Strategy 
New section added on 
recruitment strategy employed for 
the study 
To comply with EU CTR 
Section 10.1.5. Data Protection 
More information added on data 
protection as per the new 
protocol template 
To comply with EU CTR 
Section 10.1.10. Study and site 
start and closure 
Added a new appendix section 
10.1.10 on Study and Site start 
and closure as per new protocol 
template (effective 29 June 2022) 
To comply with EU CTR 
Section 10.2.  
Appendix 2: Clinical Laboratory 
Tests 
Appendix Table 1 updated with 
the visit days for pregnancy 
testing, and the parasitic 
screening tests (stool microscopy 
for ova and parasites) for central 
laboratory testing. 
Clarification 
Section 10.11. Appendix 11: 
Country-specific requirements 
Updated that urine samples from 
China will be sent for central 
laboratory urinalysis  
Clarification 
All sections 
Other minor, grammatical, or typographical corrections made to 
improve readability. 
Amendment 1 (09 February 2022) 

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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:  
This protocol was modified in response to a regulatory agency request and alignment 
with the new draft FDA guidelines on clinical development in CRSwNP. The main 
changes are (1) addition of an inclusion criterion: participants (except for those in Japan) 
are required to be on daily INCS for at least 8 weeks before screening as this reflects the 
global SoC (except in Japan); (2) removal of text (in Section 4.1 for participants in Japan) 
stating “if a participant is not on INCS or LTRA prior to screening, the participant is 
prohibited to start any INCS or LTRA during the study”; (3) clarification that participants 
in Japan are permitted to start INCS during the study if required for symptom 
management and that those participants who start INCS should remain on INCS for the 
duration of the study; (4) addition of 2 exclusion criteria: participants with a concurrent 
condition or medical history of (a) nasal cavity tumor and (b) fungal rhinosinusitis; (5) 
addition of subgroup analyses (age, gender, race, region, and baseline blood eosinophil 
category) for the co-primary endpoints. Protocol changes are described in the table 
below. 
Section # and 
Name 
Description of Change 
Brief Rationale 
Section 1.1 
Synopsis 
Added text to clarify that participants (except 
those in Japan) should take INCS throughout the 
study per SoC. 
Clarification and alignment with 
added inclusion criterion 4. 
Section 1.2 
Schema 
Revised footnote to clarify that participants 
(except those in Japan) should take INCS 
throughout the study per SoC. 
Clarification and alignment with 
added inclusion criterion 4. 
Section 1.3 
Schedule of 
Activities 
Added note for exploratory blood biomarker 
samples to clarify that a serum sample will be 
collected at the indicated visits, while a whole 
blood sample is collected at Visits 2 and 16 only. 
Clarification. 
Section 3 
Objectives, 
Endpoints and 
Estimands 
Corrected text to reflect that start of INCS 
therapy is not prohibited in Japan. 
Correction. 
Section 4.1 
Study Design 
Added text to clarify that participants (except 
those in Japan) should take INCS throughout the 
study per SoC. Revised text to clarify that 
participants in Japan are permitted to start INCS 
(and should remain on INCS if started) during 
the study.  
Alignment with added inclusion 
criterion 4 and regulatory 
request. 

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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 5.1 
Inclusion Criteria 
Added inclusion criterion 4: participants (except 
those in Japan) must be on treatment with daily 
INCS for at least 8 weeks prior to screening. 
Reflects the use of INCS as 
SoC globally (except Japan). 
Section 5.2 
Exclusion 
Criteria 
Added exclusion criterion 4: Concurrent 
condition or medical history of nasal cavity tumor 
(malignant or benign). 
Regulatory request. 
Section 5.2 
Exclusion 
Criteria 
Added exclusion criterion 5: Concurrent 
condition or medical history of fungal 
rhinosinusitis. 
Regulatory request. 
Section 5.2 
Exclusion 
Criteria 
In “nasal biopsy prior to Visit 0 for diagnostic 
purposes only is excepted”: corrected Visit 0 to 
Visit 1. 
Correction. 
Section 5.3 
Randomisation 
Criteria 
Revised randomisation criterion 9: Removed the 
list of CRSwNP maintenance therapies and 
removed the requirement for dose and regimen 
to remain unchanged during the run-in period. 
Clarification. 
Section 6.8 
Concomitant 
Therapy; Section 
6.8.1 Permitted 
Medications; 
Section 6.8.2 
Prohibited 
Medications 
Added text to align with inclusion criterion 4. 
Revised text to clarify that participants in Japan 
are permitted to start INCS (and should remain 
on INCS if started) during the study. Added 
statement that initiation or changes in dosing 
regimen of leukotriene receptor antagonist are 
permitted. Removed row in prohibited medication 
table specifying changes in INCS treatment. 
Alignment with added inclusion 
criterion 4 and regulatory 
request. 
Section 8.5.1. 
Blood Eosinophil 
Counts 
Modified text to clarify that absolute and 
differential (%) values of eosinophils, 
lymphocytes, basophils, neutrophils and 
monocytes will not be reported to site staff and 
Sponsor (to maintain the treatment blind). 
However, sites will be sent total white blood 
counts throughout the study. 
Clarification. 
Section 9.2 
Analysis Sets 
Removed “enrolled” analysis set and added 
“screened” and “randomised” analysis sets. 
Consistency with terminology in 
other protocols. 
Section 9.3.1 Co-
Primary and Key 
Secondary 
Endpoint(s) 
Analyses 
Added statement that subgroup analyses (age, 
gender, race, region, and baseline blood 
eosinophil category) will be conducted for the co-
primary endpoints. 
Regulatory request. 
All sections 
Other minor, grammatical, or typographical corrections to improve readability. 

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11. 
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