Conditions: Asthma
Keywords: GSK3511294 (Depemokimab) Eosinophilic phenotype Severe uncontrolled asthma Exacerbations Placebo
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 395
Healthy volunteers: no

Brief summary:
This is a multi-center, randomized, placebo-controlled, double-blind, parallel group study that aims to assess the efficacy and safety of GSK3511294 (Depemokimab) in participants with severe uncontrolled asthma with an eosinophilic phenotype

Detailed description:

Arms:
arm 1: Participants received a 100 milligram (mg) dose of GSK3511294 SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study. arm 2: Participants received placebo subcutaneous (SC) injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma standard of care (SOC) treatment throughout the study.

Interventions: intervention 1: GSK3511294 (Depemokimab) intervention 2: Placebo
Intervention descriptions: intervention 1: GSK3511294 (Depemokimab) will be administered using a pre-filled syringe. intervention 2: Matching placebo will be administered as a normal saline using a pre-filled syringe.

Protocol document:
Prot_000.pdf: 
TMF-14449557 
CONFIDENTIAL 
206713  
The GlaxoSmithKline group of companies 
 
Protocol Amd 02  
1 
TITLE PAGE 
Protocol Title: A 52-week, randomised, double-blind, placebo-controlled, parallel-
group, multi-centre study of the efficacy and safety of GSK3511294 adjunctive therapy 
in adult and adolescent participants with severe uncontrolled asthma with an eosinophilic 
phenotype  
Protocol Number: 206713/Amendment 02 
Compound Number or Name: GSK3511294 
Brief Title: Placebo-controlled efficacy and safety study of GSK3511294 
(depemokimab) in participants with severe asthma with an eosinophilic phenotype 
Study Phase: Phase 3A 
Sponsor Name and Legal Registered Address:  
GlaxoSmithKline Research & Development Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
Medical Monitor Name and Contact Information can be found in the Study Reference 
Manual (SRM). 
Sponsor Signatory: 
David Lipson 
Vice President and Disease Area Lead, Respiratory 
Manufacturer: GlaxoSmithKline  
Regulatory Agency Identifying Number(s):  
IND: 146742 
EudraCT: 2020-003632-25 
Approval Date: 08 Apr 2022 
 
Copyright 2022 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited.


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
Document Number 
Amendment 02 
08 Apr 2022 
TMF-14449557 
Amendment 01 
17-AUG-2021 
TMF-13331263 
Original Protocol 
01-Oct-2020 
TMF-2125331 
(2020N439965_00) 
Amendment 02: 08 Apr 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:  
Amendment 02 is a global amendment to include details about 
 
 
 and the use of blinded interim data to complete a psychometric analysis 
of the Asthma Daily/Nightly Symptom Diary (ADSD/ANSD) and 
. 
Additional changes include repeated spirometry assessment and/or additional lab test if 
randomisation criteria are not met during screening, change in the ratio of medium/high 
ICS dose, allowance/permittance of authorized COVID-19 treatments, Global Initiative 
for Asthma (GINA) inhaled corticosteroid (ICS) doses update, and QT prolongation 
clarifications. Added note for exclusion of adolescents in Germany, United Kingdom 
(UK), Russia. Text added related to special procedure for the urinalysis in China sites. 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.3 Schedule of 
Activities (SoA) 
Added new footnote “h” 
spirometry retest allowed during 
the run in period if a patient fails 
the protocol-specified reversibility 
criterion or FEV1 inclusion criteria 
 
Added text to clarify that 
pregnancy text should be done at 
screening Visit 1 and Exit 
Visit/Withdraw from study visit  
 
Updated text in footnote “e” the 
Screening Visit laboratory 
assessment can be repeated 
during the run in period if a 
patient does not meet the blood 
To add flexibility in screening 
tests; current information 
suggests this change is expected 
to result in improved screening 
while maintaining the integrity of 
the patient population 
 
Clarification 
 
 
 
 
To add flexibility in screening 
tests; current information 
suggests this change is expected 
to result in improved screening 
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Section # and Name 
Description of Change 
Brief Rationale 
eosinophil count eligibility criteria 
at the Screening Visit test result 
 
Added text to clarify that, 
electrocardiogram (ECG) must 
be performed and assessed pre-
dose 
 
Added text to clarify that 12-lead 
ECG central over-read values 
should be used at all visits with 
the exception of Visit 2 and Visit 
10 where 12-lead ECG machine 
read values should be used  
while maintaining the integrity of 
the patient population  
 
 
 
Clarification 
 
 
Clarification 
Section 1.3 Schedule of 
Activities SoA 
(Urinalysis) 
 
10.2 Appendix 2: Clinical 
Laboratory Tests 
 
Section 10.11 Appendix 
11: Recommended 
measures Related to 
COVID-19 Pandemic 
(Table 6) 
Text added to clarify that for 
China sites the urine specimen 
may be sent to the central 
laboratory for routine urinalysis 
instead of performing a local 
urine dipstick. Urinalysis should 
be performed at Visit 1 so that 
results are available before 
randomisation at Visit 2. 
Country specific procedure 
Section 2.3.1 Risk 
Assessment (QTc 
prolongation) 
Removed text related to post-
baseline QTcF value of potential 
clinical importance from first time 
in human (FTIH) study (205722) 
 
Updated text related to ECG 
parameters including corrected 
QT interval using Fridericia’s 
formula (QTcF) for depemokimab 
treatment groups in the FTIH 
study (205722) 
 
Updated wordings related to 
analysis of the relationship 
between depemokimab plasma 
concentrations and change from 
baseline QTcF data collected in 
FTIH 205722 study 
 
Modified text related to ECG 
parameters in the FTIH study 
(205722) for better clarity. No 
new safety information.  


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Section # and Name 
Description of Change 
Brief Rationale 
Section 4.1 Overall 
Design 
 
Section 6.4.1 Treatment 
Assignment 
Changed the ratio of 
medium/high ICS dose from 25% 
medium ICS dose and 75% high 
ICS dose to aiming up to 50% 
approximately of participants on 
medium ICS dose 
To better reflect dosing in clinical 
practice while maintaining the 
integrity of the patient population 
Section 5.1 Inclusion 
Criteria 
Added note to clarify that, in UK, 
Russia and Germany only adult 
participants (≥18 years) are to be 
included in this clinical trial 
 
Clarification 
Section 5.2 Exclusion 
Criteria 
(Prior/Concomitant 
therapy)  
Text added in exclusion criteria 
no. 12 to clarify that Authorized 
monoclonal antibodies (mAbs) 
treatments for COVID-19 are 
permitted 
 Allowance of treatments for 
COVID-19 is not expected to 
impact the overall interpretability 
of the data generated from this 
study or lead to any safety 
concern with concomitant use of 
IMP 
 
Section 5.2 Exclusion 
Criteria (Diagnostic 
Assesments) 
Text added in exclusion criteria 
no.15 to clarify that the 12-lead 
ECG central over-read QTcF 
value is to be used 
Clarification 
 
Section 5.3.2 
Randomisation 
Exclusion Criteria  
Text added in randomisation 
exclusion criteria no. 3 to clarify 
that the 12-lead ECG machine 
read QTcF value is to be used at 
Visit 2. The central over-read of 
the Screening Visit 1 12-lead 
ECG should be used to review 
ECG findings at Visit 2. 
Clarification 
 
Section 6.9.1 Permitted 
Medications and Non-
Drug Therapies 
“Additional asthma medications 
such as theophyllines and anti-
leukotrienes will be permitted as 
maintenance provided that they 
have been taken regularly in the 
3 months prior to screening (Visit 
1)”. 
 
Clarification 
 
 
 
 
 
 
 
Repeated text removed  
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Section # and Name 
Description of Change 
Brief Rationale 
Removed repeated wordings 
about vaccination against SARS-
CoV-2 infection using authorized 
COVID-19 vaccines  
 
Text added to clarify that 
participants can be treated for 
SARS-CoV-2 infection using 
authorized COVID-19 treatments 
(including mAbs) in line with 
local/national guidelines. 
Experimental COVID-19 
treatments are not permitted 
 
 
 
 
 
Allowance of treatments for 
COVID-19 is not expected to 
impact the overall interpretability 
of the data generated from this 
study or lead to any safety 
concern with concomitant use of 
IMP 
Section 7.1.2 QTc 
Stopping Criteria 
Text added to clarify that the 
QTcF value from the 12-lead 
ECG central over-read at 
randomisation Visit 2 should be 
used as baseline QTcF value for 
any changes from baseline 
calculations during the study 
 
Text added to clarify that after 
randomisation 12-lead ECG 
central over-read values should 
be used to assess QTc stopping 
criteria, with the exception of Visit 
10 (Week 26) where 12-lead 
ECG machine read values 
should be used 
Clarification 
 
 
 
 
 
 
 
Clarification 
Section 8.1.2 Critical 
Assessment performed 
at Screening (Visit 1) 
Added new text to clarify that if 
the Screening Visit test result 
does not meet the blood 
eosinophil count eligibility criteria, 
the laboratory  assessment may 
be repeated, at the discretion of 
the investigator 
 
Added text for spirometry to 
clarify that if a patient fails the 
protocol-specified reversibility 
criterion or FEV1 inclusion 
criteria, spirometry restest is  
allowed during the run-in period 
 
To add flexibility in screening 
tests; current information 
suggests this change is expected 
to result in improved screening 
while maintaining the integrity of 
the patient population 
 
 
To add flexibility in screening 
tests; current information 
suggests this change is expected 
to result in improved screening 
while maintaining the integrity of 
the patient population 


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Section # and Name 
Description of Change 
Brief Rationale 
Section 8.3.3 
Electrocardiograms 
(ECGs) 
Updated text related to additional 
ECGs to be performed if an ECG 
demonstrates a prolonged QTcF 
interval  
Revised wording for clarification 
Section 9.2.1 Sample 
Size Assumptions 
Added text regarding the 
possibility that greater than 375 
participants will be randomised in 
the study due to local country 
requests or requirements 
Clarification 
Section 9.2.3 Sample 
Size Re-estimation or 
Adjustment 
Text related to the data to be 
used for clinical study report has 
been deleted.  
All data (pre and post- target 
enrolment) would be used for 
clinical study report  
Section 9.3 Analysis 
Sets 
Updated text related to screened, 
enrolled, randomised, full 
analysis set, and safety 
population  
Revised description of Analysis 
sets 
 
 
Section 9.4.5 Safety 
Analyses 
Safety population used for Safety 
analyses instead of mITT  
To provide clarification that all 
safety analyses will be performed 
on the Safety Population  
Section 9.6
 
 
 
 
 
 
 
 
 
Added text to describe that  
blinded interim data will be used 
to complete a psychometric 
analysis of the ADSD/ANSD and 
 
 
 
 
 
 
 
 
 
As part of the validation of the 
ADSD/ANSD and 
 
 a blinded, data cut 
off will be used to complete a 
psychometric analysis of the 
measures  
10.7.4 Recording and 
Follow-up of AE and/or 
SAE and Device 
Deficiencies 
(Assessment of Intensity) 
Text deleted “other measures to 
evaluate AEs and SAEs may be 
utilised”. 
Clarification 
Appendix 10 Medium 
and High Daily Doses of 
Inhaled Corticosteroids 
Footnote added to clarify GINA 
2021 guidelines updates  
Update as per GINA 2021 
guidelines  
Section 11 References 
Added and updated the 
reference  
 
Updated the references  
Throughout 
Minor editorial and document 
formatting revisions 
 
Minor, therefore have not been 
summarized 
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TABLE OF CONTENTS 
PAGE 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 1 
1. 
PROTOCOL SUMMARY ........................................................................................ 10 
1.1. 
Synopsis ..................................................................................................... 10 
1.2. 
Schema ...................................................................................................... 12 
1.3. 
Schedule of Activities (SoA) ........................................................................ 13 
2. 
INTRODUCTION .................................................................................................... 22 
2.1. 
Study Rationale .......................................................................................... 22 
2.2. 
Background ................................................................................................ 22 
2.3. 
Benefit: Risk Assessment ........................................................................... 23 
2.3.1. 
Risk Assessment ......................................................................... 24 
2.3.2. 
Benefit Assessment ..................................................................... 30 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 30 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 31 
3.1. 
Primary Estimand ....................................................................................... 33 
3.2. 
Secondary Estimands ................................................................................. 34 
4. 
STUDY DESIGN .................................................................................................... 35 
4.1. 
Overall Design ............................................................................................ 35 
4.1.1. 
Study Phases, Duration and Treatment Arms .............................. 36 
4.1.2. 
Treatment after the End of Study ................................................. 37 
4.1.3. 
Independent Data Monitoring Committee (IDMC) ........................ 37 
4.2. 
Scientific Rationale for Study Design .......................................................... 38 
4.2.1. 
Participant Input into Design ........................................................ 39 
4.3. 
Justification for Dose .................................................................................. 39 
4.4. 
End of Study and Study Completer Definition ............................................. 40 
5. 
STUDY POPULATION ........................................................................................... 41 
5.1. 
Inclusion Criteria ......................................................................................... 41 
5.2. 
Exclusion Criteria ........................................................................................ 43 
5.3. 
Randomisation Criteria ............................................................................... 45 
5.3.1. 
Randomisation Inclusion Criteria ................................................. 45 
5.3.2. 
Randomisation Exclusion Criteria ................................................ 47 
5.4. 
Lifestyle Considerations .............................................................................. 47 
5.5. 
Pre-screen/Screen/Run-in Failures ............................................................. 48 
5.6. 
Criteria for Temporarily Delaying Randomisation ........................................ 48 
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY .................................. 49 
6.1. 
Study Intervention Administered ................................................................. 49 
6.1.1. 
Medical Devices ........................................................................... 50 
6.2. 
Packaging and Labelling ............................................................................. 50 
6.3. 
Preparation/Handling/Storage/Accountability .............................................. 50 
6.4. 
Measures to Minimise Bias: Randomisation and Blinding ........................... 51 
6.4.1. 
Treatment Assignment ................................................................. 51 
6.4.2. 
Blinding ........................................................................................ 51 
 
 
6.5. 
Study Intervention Compliance ................................................................... 52 
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6.6. 
Dose Modification ....................................................................................... 52 
6.7. 
Continued Access to Study Intervention after the End of the Study ............ 53 
6.8. 
Treatment of Overdose ............................................................................... 53 
6.9. 
Concomitant Therapy.................................................................................. 54 
6.9.1. 
Permitted Medications and Non-Drug Therapies .......................... 54 
6.9.2. 
Prohibited Medications and Non-Drug Therapies ......................... 55 
6.9.3. 
Rescue Medicine ......................................................................... 55 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 56 
7.1. 
Discontinuation of Study Intervention .......................................................... 56 
7.1.1. 
Liver Chemistry Stopping Criteria ................................................ 57 
7.1.1.1. 
Study Intervention Restart or Rechallenge after 
liver stopping criteria met ............................................ 58 
7.1.2. 
QTc Stopping Criteria .................................................................. 58 
7.1.3. 
Temporary Discontinuation .......................................................... 59 
7.2. 
Participant Discontinuation/Withdrawal from the Study ............................... 59 
7.3. 
Lost to Follow-Up ........................................................................................ 60 
7.4. 
Reasons for Study Intervention Discontinuation and/or Study 
Withdrawal .................................................................................................. 60 
7.5. 
Criteria for Follow-up of Potential Type III Hypersensitivity (Immune 
Complex Disease /Vasculitis) ...................................................................... 60 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 62 
8.1. 
Screening and Critical Baseline Assessments ............................................ 62 
8.1.1. 
Pre-screening Visit (Visit 0) .......................................................... 62 
8.1.2. 
Critical Assessments performed at Screening (Visit 1) ................. 63 
8.1.3. 
Critical Assessments performed at Randomisation (Visit 2) ......... 64 
8.2. 
Efficacy Assessments ................................................................................. 65 
8.2.1. 
Efficacy Endpoints ....................................................................... 65 
8.2.2. 
Asthma Exacerbations ................................................................. 65 
8.2.3. 
Pulmonary Function Testing/ Spirometry ..................................... 66 
8.2.3.1. 
Reversibility using the Maximum Post-
Bronchodilator Method ............................................... 66 
8.2.4. 
St. George’s Respiratory Questionnaire (SGRQ) ......................... 66 
8.2.5. 
Asthma Control Questionnaire-5 (ACQ-5) .................................... 67 
 
 
8.2.10. 
Asthma Daily Symptom Diary/Asthma Nightly Symptom 
Diary (ADSD/ANSD) .................................................................... 68 
 
 
8.3. 
Safety Assessments ................................................................................... 69 
8.3.1. 
Physical Examinations ................................................................. 69 
8.3.2. 
Vital Signs .................................................................................... 69 
8.3.3. 
Electrocardiograms (ECGs) ......................................................... 70 
8.3.4. 
Clinical Safety Laboratory Assessments ...................................... 70 
8.3.5. 
Pregnancy Testing ....................................................................... 71 
8.4. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and Other 
Safety Reporting ......................................................................................... 72 
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8.4.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 72 
8.4.2. 
Method of Detecting AEs and SAEs ............................................. 73 
8.4.3. 
Follow-up of AEs and SAEs ......................................................... 73 
8.4.4. 
Regulatory Reporting Requirements for SAEs ............................. 73 
8.4.5. 
Pregnancy ................................................................................... 73 
8.4.6. 
Cardiovascular and Death Events ................................................ 74 
8.4.7. 
Adverse Events of Special Interest .............................................. 74 
8.4.8. 
Medical Device Deficiencies ........................................................ 75 
8.4.8.1. 
Time Period for Detecting Medical Device 
Deficiencies ................................................................ 75 
8.4.8.2. 
Follow-up of Medical Device Deficiencies ................... 75 
8.4.8.3. 
Prompt Reporting of Medical Device 
Deficiencies to Sponsor .............................................. 75 
8.4.8.4. 
Regulatory Reporting Requirements for Medical 
Device Incidents ......................................................... 75 
8.5. 
Pharmacokinetics ....................................................................................... 76 
8.6. 
Genetics and Pharmacogenomics .............................................................. 76 
 
 
 
 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 78 
9.1. 
Statistical Hypotheses................................................................................. 78 
9.2. 
Sample Size Determination ........................................................................ 78 
9.2.1. 
Sample Size Assumptions ........................................................... 78 
9.2.1.1. 
Primary Endpoint ........................................................ 78 
9.2.1.2. 
Secondary Endpoints ................................................. 79 
9.2.2. 
Sample Size Sensitivity ................................................................ 79 
9.2.3. 
Sample Size Re-estimation or Adjustment ................................... 79 
9.3. 
Analysis Sets .............................................................................................. 80 
9.4. 
Statistical Analysis ...................................................................................... 80 
9.4.1. 
General Considerations ............................................................... 80 
9.4.2. 
Primary Endpoint ......................................................................... 81 
9.4.2.1. 
Main Estimand ............................................................ 81 
9.4.3. 
Secondary Endpoints ................................................................... 82 
9.4.3.1. 
Main Estimands .......................................................... 82 
9.4.4. 
Other Endpoints ........................................................................... 83 
9.4.5. 
Safety Analyses ........................................................................... 83 
9.5. 
Multiple Testing Strategy ............................................................................ 84 
9.6. 
 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 85 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 85 
10.1.1. 
Regulatory and Ethical Considerations ........................................ 85 
10.1.2. 
Financial Disclosure ..................................................................... 85 
10.1.3. 
Informed Consent Process .......................................................... 86 
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10.1.4. 
Data Protection ............................................................................ 86 
10.1.5. 
Committees Structure .................................................................. 87 
10.1.6. 
Dissemination of Clinical Study Data ........................................... 87 
10.1.7. 
Data Quality Assurance ............................................................... 88 
10.1.8. 
Source Documents ...................................................................... 88 
10.1.9. 
Study and Site Start and Closure ................................................. 89 
10.1.10. Publication Policy ......................................................................... 90 
10.2. 
Appendix 2: Clinical Laboratory Tests ......................................................... 91 
10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ....................................... 93 
10.3.1. 
Definition of AE ............................................................................ 93 
10.3.2. 
Definition of SAE .......................................................................... 94 
10.3.3. 
Definition of Cardiovascular Events ............................................. 95 
10.3.4. 
Recording and Follow-Up of AE and SAE .................................... 96 
10.3.5. 
Reporting of SAE to GSK ............................................................. 98 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ....................................... 99 
10.4.1. 
Definitions: ................................................................................... 99 
10.4.2. 
Contraception Guidance: ........................................................... 100 
10.5. 
Appendix 5: Genetics ................................................................................ 102 
10.6. 
Appendix 6: Liver Safety: Required Actions, Monitoring and Follow-
up Assessments ....................................................................................... 103 
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 ................................ 107 
10.7.1. 
Definition of Medical Device AE and ADE .................................. 107 
10.7.2. 
Definition of Medical Device SAE, SADE and USADE ............... 108 
10.7.3. 
Definition of Device Deficiency ................................................... 108 
10.7.4. 
Recording and Follow-Up of AE and/or SAE and Device 
Deficiencies ............................................................................... 109 
10.7.5. 
Reporting of SAEs ..................................................................... 111 
10.7.6. 
Reporting of SADEs ................................................................... 112 
10.8. 
Appendix 8: Anaphylaxis Criteria .............................................................. 113 
10.9. 
 
10.10. Appendix 10: Low, Medium and High Daily Doses of Inhaled 
Corticosteroids .......................................................................................... 115 
10.11. Appendix 11: Recommended Measures Related to COVID-19 
Pandemic.................................................................................................. 116 
10.12. Appendix 12: Country-specific requirements ............................................. 129 
10.13. Appendix 13: Abbreviations and Trademarks ............................................ 130 
10.14. Appendix 14: Protocol Amendment History ............................................... 134 
10.14.1. Amendment 1: 17-Aug-2021 ...................................................... 134 
11. REFERENCES ..................................................................................................... 138 
 
 
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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A 52-week, randomised, double-blind, placebo-controlled, parallel-group, 
multi-centre study of the efficacy and safety of GSK3511294 adjunctive therapy in adult 
and adolescent participants with severe uncontrolled asthma with an eosinophilic 
phenotype  
Brief Title: Placebo-controlled efficacy and safety study of GSK3511294 (depemokimab) 
in participants with severe asthma with an eosinophilic phenotype 
Rationale: 
GSK3511294 is being developed as a long-acting (LA) subcutaneous (SC) injectable anti-
interleukin-5 (anti-IL-5) therapy and is expected to deliver an efficacy and safety profile 
similar to current anti-IL-5 therapies with a reduced dosing frequency (once every 26 
weeks). The aim of this study is to investigate the efficacy and safety, over a 52-week 
treatment period, of GSK3511294 100 mg SC given once every 26 weeks as adjunctive 
therapy in participants with uncontrolled severe asthma with an eosinophilic phenotype. 
Objectives and Endpoints:  
Objectives 
Endpoints 
Primary 
 
• To evaluate the efficacy of GSK3511294 
100 mg (SC) every 26 weeks versus 
placebo in participants with severe 
uncontrolled asthma with an eosinophilic 
phenotype on top of existing asthma 
therapy 
• Annualised rate of clinically significant 
exacerbationsa over 52 weeks 
Secondary 
 
• To evaluate GSK3511294 100 mg (SC) 
every 26 weeks versus placebo on health-
related quality of life (HRQoL) and 
additional efficacy assessments on top of 
existing asthma therapy 
• Change from baseline in St. George's 
Respiratory Questionnaire (SGRQ) total 
score at Week 52  
• Change from baseline in Asthma Control 
Questionnaire-5 (ACQ-5) score at Week 52 
• Change from baseline in pre-bronchodilator 
forced expiratory volume in one second 
(FEV1) at Week 52 
• Annualised rate of exacerbations requiring 
hospitalisation and/or Emergency 
Department (ED) visit over 52 weeks 
a. Clinically significant exacerbations will be defined as worsening of asthma requiring the use 
of systemic corticosteroids (IM, IV or oral) and/or hospitalisation and/or ED visit (see Section 
8.2.2). 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.   


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Overall Design: 
This study employs a multi-centre, randomised, placebo-controlled, double-blind, parallel 
group design to assess the efficacy and safety of GSK3511294 in participants with severe 
uncontrolled asthma with an eosinophilic phenotype despite standard of care (SoC) 
treatment with medium to high dose inhaled corticosteroid (ICS) plus at least one 
additional controller. All participants will receive study intervention as an adjunct therapy 
while remaining on their existing asthma therapy throughout the study. 
Brief Summary: 
The purpose of this study is to assess the efficacy and safety of GSK3511294 as an 
adjunctive therapy in participants with severe uncontrolled asthma with an eosinophilic 
phenotype. During the 52-week treatment period, participants will receive two doses (at 
Week 0 and Week 26) of add-on study intervention (GSK3511294 100 mg or matching 
placebo) by SC injection, while remaining on their existing maintenance asthma therapy 
(that excludes biologics) throughout the study. Assessments will include the annualised 
rate of clinically significant exacerbations and measures of lung function, asthma control, 
and safety. 
Number of Participants: 
Approximately 540 participants with severe uncontrolled asthma with an eosinophilic 
phenotype will be screened to ensure the randomisation of 375 participants in a 2:1 ratio 
to GSK3511294 (n=250) and matching placebo (n=125).  
Intervention Groups and Duration: 
The study will consist of a pre-screen period (0-2 weeks), a run-in period (1-6 weeks), and 
a study intervention period (52 weeks). After the run-in period, participants will be 
randomised in a 2:1 ratio using an interactive response technology (IRT) system in a 
blinded manner to receive either GSK3511294 100 mg or placebo by SC injection. 
Randomisation will be stratified based on baseline ICS dose (medium or high dose). Two 
doses of study intervention will be administered in the clinic: the first at randomisation 
Visit 2 (Week 0) and the second at Visit 10 (Week 26). Participants will be assessed at 
each scheduled visit (a total of 17 study visits) during the 52-week treatment phase. Study 
visits may be conducted remotely (by a home healthcare professional) or virtually, 
however, in-person clinic visits are required for the following: pre-screening Visit 0, 
screening Visit 1, randomisation Visit 2, Visit 3, Visit 10, Visit 11 Exit Visit 17, and WS 
Visit (if applicable).  
Participants who receive both doses of study intervention and complete the Exit Visit will 
be eligible to participate in an open-label extension (OLE) study (Study 212895), during 
which they will receive two doses of open-label GSK3511294 100 mg SC over another 52 
weeks. Participants who do not enter the OLE study will have a follow-up visit/call at 
Week 56.  
 
Independent Data Monitoring Committee: Yes 


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1.2. 
Schema 
 
 


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1.3. 
Schedule of Activities (SoA) 
Protocol Activity 
Pre-
Screenin
g 
Screenin
g/Run-in 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-
up 
/Withdra
w  
(7 days) 
Notes 
Visit 
V0 a 
Visit 1 a V2b 
R* V3 V4 V5 V6 V7 V8 V9 V1
0 
V1
1 
V1
2 
V1
3 
V1
4 
V1
5 
V1
6 
Exit 
V17 WSc FU 
R* =Randomisation 
WS=Withdraw from study visit  
(see footnote c) 
FU=Follow-up visit/call (only required for 
participants not entering OLE study) 
Study Week 
-8 to -6 -6 to -1 
0 
2 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 
26 
or 
52 
56 
Study Day 
-56 to -
42 
-42 to -7 1 14 28 56 84 112 140 168 182 196 224 252 280 308 336 364 
 
392 
General Eligibility Assessments 
Informed consent 
a 
X 
(X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Conduct at Visit 1 if not completed at Visit 
0; See footnote a.  
Genetic sample 
informed consent 
d 
X 
(X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Conduct at Visit 1 if not completed at Visit 
0; See footnote d. 
Demography data 
collection 
X 
(X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Conduct at Visit 1 if not completed at Visit 
0; All females must be assessed at Visit 1 
to determine childbearing potential. 
Inclusion/Exclusio
n criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Historical blood 
eosinophil count 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
See footnote e. 
Medical history  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Include cardiovascular (CV), CV risk 
factors, asthma, exacerbations, 
vasculitis, allergies and anaphylaxis. 
Smoking status 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Protocol Activity 
Pre-
Screenin
g 
Screenin
g/Run-in 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-
up 
/Withdra
w  
(7 days) 
Notes 
Visit 
V0 a 
Visit 1 a V2b 
R* V3 V4 V5 V6 V7 V8 V9 V1
0 
V1
1 
V1
2 
V1
3 
V1
4 
V1
5 
V1
6 
Exit 
V17 WSc FU 
R* =Randomisation 
WS=Withdraw from study visit  
(see footnote c) 
FU=Follow-up visit/call (only required for 
participants not entering OLE study) 
Study Week 
-8 to -6 -6 to -1 
0 
2 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 
26 
or 
52 
56 
Study Day 
-56 to -
42 
-42 to -7 1 14 28 56 84 112 140 168 182 196 224 252 280 308 336 364 
 
392 
Parasite 
screening 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Only required in regions with high-risk or 
for participants who have visited a high-
risk region in the past 6 months. Use 
local laboratories for this test. For details 
refer to study reference manual (SRM). 
eDiary registration 
and training 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Conduct thorough eDiary training at 
Screening Visit 1 and throughout the 
study on as-needed basis.   
Randomisation 
criteria 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assess prior to randomisation; see 
footnote e. 
Efficacy Assessments 
Review for 
exacerbations 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X Collection of exacerbations at Visit 1 is 
historical data. 
Spirometry (pre- 
and post-
bronchodilator 
FEV1)h 
 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
 
FEV1=Forced expiratory volume in 1 
second; Spirometry should not be 
conducted for participants with 
confirmed/suspected COVID-19 (see 
Section 8.2.3). 
ACQ-5 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
ACQ-5=Asthma Control Questionnaire-5 


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Protocol Activity 
Pre-
Screenin
g 
Screenin
g/Run-in 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-
up 
/Withdra
w  
(7 days) 
Notes 
Visit 
V0 a 
Visit 1 a V2b 
R* V3 V4 V5 V6 V7 V8 V9 V1
0 
V1
1 
V1
2 
V1
3 
V1
4 
V1
5 
V1
6 
Exit 
V17 WSc FU 
R* =Randomisation 
WS=Withdraw from study visit  
(see footnote c) 
FU=Follow-up visit/call (only required for 
participants not entering OLE study) 
Study Week 
-8 to -6 -6 to -1 
0 
2 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 
26 
or 
52 
56 
Study Day 
-56 to -
42 
-42 to -7 1 14 28 56 84 112 140 168 182 196 224 252 280 308 336 364 
 
392 
HRQoL: PRO and Health Outcomes Assessments 
SGRQ 
 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
 
SGRQ=St. George’s Respiratory 
Questionnaire  
Complete 
ADSD/ANSD 
 
=========   daily   
=========→ 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
ADSD/ANSD=Asthma Daily/Nightly 
Symptom Diary; To be completed daily 
during Run-in phase through Week 16, 
then to be completed for 1 full week 
during the week preceding each visit 
thereafter. 
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Protocol Activity 
Pre-
Screenin
g 
Screenin
g/Run-in 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-
up 
/Withdra
w  
(7 days) 
Notes 
Visit 
V0 a 
Visit 1 a V2b 
R* V3 V4 V5 V6 V7 V8 V9 V1
0 
V1
1 
V1
2 
V1
3 
V1
4 
V1
5 
V1
6 
Exit 
V17 WSc FU 
R* =Randomisation 
WS=Withdraw from study visit  
(see footnote c) 
FU=Follow-up visit/call (only required for 
participants not entering OLE study) 
Study Week 
-8 to -6 -6 to -1 
0 
2 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 
26 
or 
52 
56 
Study Day 
-56 to -
42 
-42 to -7 1 14 28 56 84 112 140 168 182 196 224 252 280 308 336 364 
 
392 
Safety Assessments 
Concomitant 
Medication 
Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Ensure maintenance asthma medications 
from the year prior to Screening Visit 1, 
all medications within the 3 months prior 
to Screening Visit 1 and all current 
medications are reviewed. 
Physical 
Examination 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Include height and weight for the 
complete physical exam at Screening 
Visit 1. Height can be omitted for 
subsequent visits. 
Vital Signs 
 
X 
X 
 
 
X 
 
 
X 
 
X 
X 
 
 
X 
 
X 
X 
X 
 
 
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Protocol Activity 
Pre-
Screenin
g 
Screenin
g/Run-in 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-
up 
/Withdra
w  
(7 days) 
Notes 
Visit 
V0 a 
Visit 1 a V2b 
R* V3 V4 V5 V6 V7 V8 V9 V1
0 
V1
1 
V1
2 
V1
3 
V1
4 
V1
5 
V1
6 
Exit 
V17 WSc FU 
R* =Randomisation 
WS=Withdraw from study visit  
(see footnote c) 
FU=Follow-up visit/call (only required for 
participants not entering OLE study) 
Study Week 
-8 to -6 -6 to -1 
0 
2 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 
26 
or 
52 
56 
Study Day 
-56 to -
42 
-42 to -7 1 14 28 56 84 112 140 168 182 196 224 252 280 308 336 364 
 
392 
12-lead ECG 
 
X 
X 
X 
 
 
 
 
 
 
X 
X 
 
 
 
 
 
X 
X 
 
ECG must be performed and assessed 
pre-dose. Twelve-lead ECG central over-
read values should be used at all visits 
with the exception of Visit 2 and Visit 10 
where 12-lead ECG machine read values 
should be used. 
AE/SAE 
Assessment 
X g 
X g 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X AE=Adverse events; SAE=Serious 
adverse events; see footnote g. 
Laboratory Assessments  
Total IgE 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test 
(WOCBP only) 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Serum pregnancy test should be done at 
screening Visit 1 and Exit Visit/ Withdraw 
from study visit; urine pregnancy tests 
should be done for all other 
assessments; WOCBP=Women of 
childbearing potential; See Section 8.3.5 
for additional information. 
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Protocol Activity 
Pre-
Screenin
g 
Screenin
g/Run-in 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-
up 
/Withdra
w  
(7 days) 
Notes 
Visit 
V0 a 
Visit 1 a V2b 
R* V3 V4 V5 V6 V7 V8 V9 V1
0 
V1
1 
V1
2 
V1
3 
V1
4 
V1
5 
V1
6 
Exit 
V17 WSc FU 
R* =Randomisation 
WS=Withdraw from study visit  
(see footnote c) 
FU=Follow-up visit/call (only required for 
participants not entering OLE study) 
Study Week 
-8 to -6 -6 to -1 
0 
2 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 
26 
or 
52 
56 
Study Day 
-56 to -
42 
-42 to -7 1 14 28 56 84 112 140 168 182 196 224 252 280 308 336 364 
 
392 
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Protocol Activity 
Pre-
Screenin
g 
Screenin
g/Run-in 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-
up 
/Withdra
w  
(7 days) 
Notes 
Visit 
V0 a 
Visit 1 a V2b 
R* V3 V4 V5 V6 V7 V8 V9 V1
0 
V1
1 
V1
2 
V1
3 
V1
4 
V1
5 
V1
6 
Exit 
V17 WSc FU 
R* =Randomisation 
WS=Withdraw from study visit  
(see footnote c) 
FU=Follow-up visit/call (only required for 
participants not entering OLE study) 
Study Week 
-8 to -6 -6 to -1 
0 
2 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 
26 
or 
52 
56 
Study Day 
-56 to -
42 
-42 to -7 1 14 28 56 84 112 140 168 182 196 224 252 280 308 336 364 
 
392 
Immunogenicity 
sample 
 
 
X 
X 
X 
X 
X 
 
 
 
X 
X 
X 
X 
X 
 
 
X 
X 
 
 
Genetics sample 
 
 
=============  
The genetics sample can be 
collected at Visit 2 or any visit 
after 
=============→ 
 
 
See footnote d. 
Study intervention 
Administer study 
intervention 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Study intervention will only be 
administered in the clinic. Any scheduled 
assessments or sample draws should be 
performed beforehand. Monitor 
participant for at least 2h after 
administration (see Section 6.5). 
eCRF/worksheets/other 
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Protocol Activity 
Pre-
Screenin
g 
Screenin
g/Run-in 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-
up 
/Withdra
w  
(7 days) 
Notes 
Visit 
V0 a 
Visit 1 a V2b 
R* V3 V4 V5 V6 V7 V8 V9 V1
0 
V1
1 
V1
2 
V1
3 
V1
4 
V1
5 
V1
6 
Exit 
V17 WSc FU 
R* =Randomisation 
WS=Withdraw from study visit  
(see footnote c) 
FU=Follow-up visit/call (only required for 
participants not entering OLE study) 
Study Week 
-8 to -6 -6 to -1 
0 
2 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 
26 
or 
52 
56 
Study Day 
-56 to -
42 
-42 to -7 1 14 28 56 84 112 140 168 182 196 224 252 280 308 336 364 
 
392 
Provide 
worksheet 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
The worksheet is a medical problems and 
healthcare utilisation worksheet. 
Review worksheet 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
eDiary close out  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
 
Complete eCRF 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
eCRF=electronic Case Report Form 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a. 
Informed Consent must be obtained prior to initiating any study assessments. Pre-screening Visit 0 can occur any time from 0 to 14 days before Screening Visit 1. 
b. 
Randomisation Visit 2 is 1 week after Screening Visit 1 but can be extended to up to 6 weeks after Visit 1 if, for example, a participant has an exacerbation during the run-in 
period. Results from Screening Visit 1 procedures must be available for review of randomisation criteria.  
c. 
If a participant withdraws from the study, then the Withdraw from Study (WS) 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 and pregnancy testing.  
d. 
Informed Consent for optional genetics research must be obtained before collecting a sample. China only:  Genetic Informed Consent will not be collected from participants in 
China. Genetic blood samples will not be collected from participants in China. 
e. 
To be randomised, participants without a historical blood eosinophil count of ≥300 cells/µL in the 12 months prior to Screening Visit 1, must have a blood eosinophil count of ≥150 
cells/µL at Screening Visit 1. If the Screening Visit test result does not meet the blood eosinophil count eligibility criteria, the laboratory  assessment may be repeated, at the 
discretion of the investigator, if it is judged to be likely in the eligible range for study inclusion within the run-in period prior to Visit 2. 
f. 
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g. 
SAEs must be collected from signing of Informed Consent if considered related to study procedures 
h. 
If a patient fails the protocol-specified reversibility criterion or FEV1 inclusion criteria, spirometry retest is allowed during the run-in period. 
 


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2. 
INTRODUCTION 
2.1. 
Study Rationale  
Anti-IL-5 therapies have an established efficacy and long-term safety profile and are a 
cornerstone of severe asthma management for patients with an eosinophilic phenotype 
[GINA, 2020]. Three antagonists of IL-5 (mepolizumab and reslizumab) or its receptor 
(IL-5R) (benralizumab) are approved for severe asthma with an eosinophilic phenotype, 
as an add-on treatment administered every 4 to 8 weeks.  
GSK3511294 (depemokimab) is being developed as a LA SC injectable anti-IL-5 therapy 
and is anticipated to deliver an efficacy and safety profile similar to current anti-IL-5 
therapies with a reduced dosing frequency (once every 26 weeks). The aim of this study 
is to investigate the efficacy and safety, over a 52-week treatment period, of 
GSK3511294 100 mg SC given once every 26 weeks as adjunctive therapy to 
participants with uncontrolled severe asthma with an eosinophilic phenotype. 
2.2. 
Background 
Persistent eosinophil inflammation is a feature of more than 50% of patients with severe 
asthma [Chung, 2014]. Several monoclonal antibodies (mAbs) targeting eosinophil 
inflammation have received marketing authorisation for asthma with an eosinophilic 
phenotype, including 3 targeting either interleukin-5 (IL-5) or its receptor (IL-5R): 
mepolizumab (Nucala), reslizumab (Cinqair/Cinqaero), and benralizumab (Fasenra). All 
three, by utilising 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 [Haldar, 2009; Castro, 2011; Pavord, 2012; Bel, 2014; Ortega, 2014; Castro, 
2015; Bleecker, 2016; FitzGerald, 2016; Chupp, 2017].  
Evidence supporting the tolerability of targeting IL-5/5R is provided by long-term 
extension studies for mepolizumab [Lugogo, 2016; Khatri, 2019; Khurana, 2019], 
reslizumab [Murphy, 2017], and benralizumab [Busse, 2019] as well as efficacy data in 
real-world evidence settings for mepolizumab [Harrison, 2020; Bagnasco, 2019; Pertzov, 
2019; Schleich, 2020]. Clinical trial data over more than 10 years combined with real-
world evidence, have demonstrated that treatments targeting the IL-5 pathway are both 
highly effective and well-tolerated. Based on this established efficacy and safety, anti-IL-
5/5R therapies are now a cornerstone of severe asthma management and are endorsed by 
international guidelines for appropriate patients that continue to exacerbate despite 
optimised care with Step 4 or Step 5 treatment (medium and high dose ICS) [GINA, 
2020]. 
GSK3511294 is a humanised, affinity matured mAb that blocks human IL-5 binding to 
its receptor and belongs to the established class of anti-IL-5 therapies for severe asthma 
management. 
 
 
. The resulting 
antibody has increased affinity and half-life. Evidence to date indicate that these amino 
acid changes extend the pharmacokinetics (PK) and pharmacology of GSK3511294 to 
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enable less frequent dosing with an anticipated similar efficacy and safety profile relative 
to mepolizumab (administered chronically).  
Long-acting alternatives that can be administered on a less frequent basis are recognised 
as successful approaches for chronic indications. As a LA anti-IL-5 therapy, 
GSK3511294 is anticipated to have an efficacy and safety profile that is similar to those 
of the currently-approved therapies in its class, but with a single administration every 
26 weeks, as opposed to the current regimen of every 4 weeks for mepolizumab and 
reslizumab, or every 8 weeks for benralizumab (every 4 weeks for the first 3 doses).  
A detailed description of the chemistry, pharmacology, and safety of GSK3511294 is 
provided in the current Investigator’s Brochure (IB) [GlaxoSmithKline Document 
Number 2016N295843_03 or later]. 
2.3. 
Benefit: Risk Assessment 
Summaries of findings from non-clinical studies conducted with GSK3511294 and 
completed FTIH study 205722 can be found in the current IB [GlaxoSmithKline 
Document Number 2016N295843_03 or later]. The following section outlines the risk 
assessment and mitigation strategy for this protocol: 
 


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2.3.1. 
Risk Assessment 
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Study Intervention GSK3511294 
• Allergic reactions including anaphylaxis. 
• Allergic reactions with the most severe form 
being anaphylaxis (see Appendix 8), are 
potential risks associated with mAbs. 
• No allergic reactions or anaphylaxis have 
been reported with GSK3511294 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 GSK3511294. 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/SAE 
coordinator; regular systematic review of 
adverse event (AE)/SAE data from ongoing 
studies by a GSK safety review team. 
• Use of Joint NIAID/FAAN 2nd 
Symposium on Anaphylaxis to collect data 
on reports of anaphylaxis (see Appendix 8). 
• Participants will be monitored in clinic for 
immediate hypersensitivity and any other 
untoward effects for a minimum of 2 hours 
post-injection (both at randomisation 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 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. 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
• 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 1 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 GSK3511294 in FTIH 
study 205722 in participants with mild to 
moderate asthma (36 participants received 
GSK3511294; 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/SAE coordinator; regular 
systematic review of adverse event 
(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 rheumatologist (member of the IDMC).   
• Protocol guidance on early identification of 
vasculitis events is provided (see 
Section 7.5). 
• 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). 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
• Immunogenicity, anti-drug antibodies 
(ADAs) 
• Biopharmaceutical products may elicit 
ADAs and neutralising antibodies (NAb), 
which have the potential to modulate PK or 
pharmacodynamics (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 
GSK3511294 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 GSK3511294 
plasma concentration profiles and blood 
eosinophil count-time profiles as well as AE 
reporting between ADA-positive and ADA-
negative participants. Neutralising 
antibodies were not tested in this study.  
• Blood samples will be collected for 
detection of both ADA and NAb (see 
Section 8.8). 
• 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 GSK3511294 FTIH study 205722, 
injection site reactions were reported by one 
(3%) participant who received 
• Daily monitoring of SAEs by Medical 
Monitor/SAE coordinator; regular 
systematic review of AE/SAE data from 
ongoing studies by GSK study team and/or 
GSK safety review team. 
• The IDMC will review unblinded safety 
data at regular intervals. 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
GSK3511294 and one (8%) participant who 
received placebo. 
• QTc prolongation 
• Four monkeys in the 6-month repeat dose 
monkey study administered 100 mg/kg 
every 3 months (2 doses) were observed to 
have QTc prolongation (mean change of 18 
msec relative to vehicle control value) 
during Week 14. 
• 
In the GSK3511294 FTIH study (205722), 
no treatment effect for ECG parameters 
including corrected QT interval (QTcF) 
was observed across the GSK3511294 
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 
GSK3511294 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 GSK3511294 dose 
up to 300 mg. The predicted increase in 
mean QTcF change from baseline with 
GSK3511294 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 
• ECGs will be performed according to 
timepoints specified in the SoA 
(Section 1.3) and the assessment will be 
done as specified in Section 8.3.3. 
• Participants with QTc prolongation on 
screening will be excluded (criterion 15, 
Section 5.2). 
• Participants with a pre-existing clinically 
significant cardiac medical condition are 
excluded (criterion 7, Section 5.2). 
• Participants who meet QT stopping criteria 
as specified in Section 7.1.2 will not receive 
another dose of study intervention. 
• The IDMC will review unblinded safety 
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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
bound of the CI is below zero) [GSK 
Document Number: 2020N457410_00]. 
• Risk of GSK3511294 affecting an unborn 
baby. 
• Reproductive studies have not been 
conducted with GSK3511294; however, in 
the 6-month repeat dose monkey study no 
changes were observed in reproductive 
organs. Seminiferous tubules were 
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 
GSK3511294 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. 
• Participants who are pregnant, 
breastfeeding, or plan to become pregnant at 
Screening are excluded (criterion 19, 
Section 5.2). Participants who become 
pregnant during the study will not receive 
another dose of study intervention (see 
Section 7.1).  
• 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. 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
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). 
 


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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) is approved as an add-on maintenance 
treatment for severe asthma with an eosinophilic phenotype. The safety profile of 
mepolizumab is favourable. 
As a LA anti-IL-5 mAb, GSK3511294 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, GSK3511294 may offer the convenience of an improved 
dosing schedule.  
2.3.3. 
Overall Benefit: Risk Conclusion 
Taking into account the measures being implemented to minimise 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 severe uncontrolled asthma with an 
eosinophilic phenotype; therefore, the Sponsor considers that the investigation of the 
efficacy, and safety of GSK3511294 is justified in this study with a positive benefit: risk 
ratio.  


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3. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
 
• To evaluate the efficacy of GSK3511294 
100 mg (SC) every 26 weeks versus 
placebo in participants with severe 
uncontrolled asthma with an eosinophilic 
phenotype on top of existing asthma 
therapy 
• Annualised rate of clinically significant 
exacerbationsa over 52 weeks 
Secondary 
 
• To evaluate GSK3511294 100 mg (SC) 
every 26 weeks versus placebo on health-
related quality of life (HRQoL) and 
additional efficacy assessments on top of 
existing asthma therapy 
• Change from baseline in St. George's 
Respiratory Questionnaire (SGRQ) total 
score at Week 52  
• Change from baseline in Asthma Control 
Questionnaire-5 (ACQ-5) score at Week 52 
• Change from baseline in pre-bronchodilator 
forced expiratory volume in one second 
(FEV1) at Week 52 
• Annualised rate of exacerbations requiring 
hospitalisation and/or Emergency 
Department (ED) visit over 52 weeks 
Other 
 
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Objectives 
Endpoints 
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Objectives 
Endpoints 
Safety 
• To evaluate the safety and tolerability of 
GSK3511294 100 mg (SC) every 26 weeks 
versus placebo in participants with severe 
uncontrolled asthma with an eosinophilic 
phenotype on top of existing asthma 
therapy 
• Incidence of AEs/SAEs  
• Laboratory parameters, including 
haematological and clinical chemistry 
parameters  
• Vital signs including blood pressure (BP), 
body temperature, and pulse rate  
• ECG assessments  
• Incidence of immunogenicity as measured 
by the presence of ADA/NAb to 
GSK3511294  
 
 
a. Clinically significant exacerbations will be defined as worsening of asthma requiring the use 
of systemic corticosteroids (IM, IV or oral) and/or hospitalisation and/or ED visit (see Section 
8.2.2). 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.   
3.1. 
Primary Estimand 
Population: Adult and adolescent participants with severe uncontrolled asthma with an 
eosinophilic phenotype following the strategy outlined below for dealing with the main 
intercurrent events that are anticipated. 
Treatment comparison: GSK3511294 + SoC compared with placebo + SoC 
Endpoint: Annualised rate of clinically significant exacerbations over 52 weeks 
Main intercurrent events anticipated: 
• Study intervention discontinuation due to reasons unrelated to the COVID-19 
pandemic: 
 
 
• Study intervention discontinuation due to reasons related to the COVID-19 
pandemic:
 
 
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• Change in maintenance therapy or use of prohibited medications (listed in 
Section 6.9.2): 
 
 
Summary measure: Ratio of the rates of clinically significant exacerbations between 
GSK3511294 + SoC and placebo + SoC 
For further details, see (Section 9.4 
3.2. 
Secondary Estimands 
Population: Adult and adolescent participants with severe uncontrolled asthma with an 
eosinophilic phenotype following the strategy outlined below for dealing with the main 
intercurrent events that are anticipated. 
Treatment comparison: GSK3511294 + SoC compared with placebo + SoC 
Endpoints: 
• Change from baseline in SGRQ at Week 52  
• Change from baseline in ACQ-5 at Week 52 
• Change from baseline in pre-bronchodilator FEV1 at Week 52 
• Annualised rate of clinically significant exacerbations requiring hospitalisation 
and/or ED visit over 52 weeks 
Main intercurrent events anticipated: 
• Study intervention discontinuation due to reasons unrelated to the COVID-19 
pandemic: 
 
 
• Study intervention discontinuation due to reasons related to the COVID-19 
pandemic: 
 
 
• Change in maintenance therapy or use of prohibited medications (listed in 
Section 6.9.2): 
 
 
Summary measures: 
• Difference in mean change from baseline in SGRQ at Week 52 
• Difference in mean change from baseline in ACQ-5 at Week 52 
• Difference in mean change from baseline in pre-bronchodilator FEV1 at Week 52 
• Ratio of the rates of clinically significant exacerbations requiring hospitalisation 
and/or ED visit  
between GSK3511294 + SoC and placebo + SoC. 
For further details, see (Section 9.4) 
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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This study employs a multi-centre, randomised, placebo-controlled, double-blind, parallel 
group design. The study will recruit adults and adolescents (12 years) with a confirmed 
diagnosis of severe asthma with an eosinophilic phenotype and who are on a regimen of 
medium to high dose ICS (440 mcg fluticasone propionate [FP] hydrofluoroalkane 
product [HFA] daily, or clinically comparable [GINA, 2020; see Appendix 10]) plus at 
least one additional controller medication, with evidence of bronchodilator reversibility 
or airway hyperresponsiveness as measured by methacholine/histamine challenge. 
Eligible participants must have uncontrolled asthma with a history of repeat 
exacerbations (2 exacerbations in the previous 12 months) while on their existing 
maintenance asthma therapy that excludes any biologics. Participants will be required to 
have a blood eosinophil count of 150 cells/µL at screening or 300 cells/µL 
documented in the 12 months prior to screening. Participants who have received any anti-
IL-5/5R mAb therapy within the last 12 months will be excluded from this study. 
Participants will attend a Pre-screen Visit (Visit 0) to sign consent and a Screening Visit 
(Visit 1; may be done on the same day as Visit 0) for eligibility assessments (see Section 
8.1). At the conclusion of the run-in period (Visit 2), participants who meet the pre-
defined criteria (see Section 5.1 and Section 5.3) will be randomised in a 2:1 ratio to 
receive either GSK3511294 100 mg or placebo, administered SC (at Week 0 and Week 
26) in the clinic via a pre-filled safety syringe (PFS) as an adjunct therapy. 
Randomisation will be stratified based on baseline ICS dose (aiming to up to 50% 
approximately of participants on medium ICS dose; see Appendix 10). Participants will 
remain on their existing stable maintenance asthma therapy throughout the study (See 
Section 6.9 for details on concomitant medications). See Section 4.1.1 for additional 
details on the study phases, duration, and treatment arms. 
The primary outcome measure will be the annualised rate of clinically significant 
exacerbations (i.e. exacerbations requiring systemic CSs and/or hospitalisation and/or ED 
visit [see Section 8.2.2]) measured over the 52-week treatment period. Additional 
efficacy assessments will include lung function (pre- and post-bronchodilator FEV1), 
asthma control (ACQ-5), HRQoL measured with SGRQ, 
 
 
 daytime and night-time asthma symptoms 
(ADSD/ANSD), 
 
 (see Section 8.2).  
The study will include safety (see Section 8.3 and Section 8.4) and immunogenicity (see 
Section 8.8) assessments to characterise the safety profile of GSK3511294 100 mg SC 
following repeat dosing. 
 
 
 
After randomisation, all participants will be encouraged to remain in the study and 
complete all scheduled visits, regardless of whether they receive the second dose of study 
intervention at Week 26. Participants who experience any of the study intervention 
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discontinuation conditions (listed in Section 7.1) will not receive another dose of study 
intervention. 
Study visits may be conducted remotely (by a home healthcare professional) or virtually, 
however, in-person clinic visits are required for the following: pre-screening Visit 0, 
screening Visit 1, randomisation Visit 2, Visit 3, Visit 10, Visit 11 Exit Visit 17, and WS 
Visit (if applicable). Participants who are unable to attend their scheduled clinic visits due 
to COVID-19 restrictions or other unexpected events may complete some visits at home 
(see Appendix 11). Note: study intervention will only be administered in the clinic (at 
Week 0 and Week 26 visits).  
4.1.1. 
Study Phases, Duration and Treatment Arms 
At pre-screening, participants will be requested to participate in the study for a maximum 
of 60 weeks (Visit 0 to the Exit Visit, inclusive) or 64 weeks if not continuing into the 
OLE Study 212895 (Visit 0 to the Follow-up Visit, inclusive). 
During the study, participants will remain on their existing maintenance asthma therapy 
whilst completing all phases of the study described in Table 1.  
Table 1 
Study Phases 
Phase Phase Title 
Duration 
Description 
1 
Pre-screening 
(Visit 0) 
0-2 weeks 
Details about the study and procedures will be 
explained through the informed consent process. The 
Pre-screening Visit (Visit 0) can occur on the same day 
as the Screening Visit (Visit 1) but must be completed 
prior to initiating any Visit 1 procedures 
2 
Screening 
(Visit 1) and 
Run-in 
1-6 weeks 
Participants who meet all the eligibility criteria at 
Screening (Visit 1) will enter the run-in period for a 
minimum of 1 week and a maximum of 6 weeks. 
The run-in is intended to assess the participant’s 
compliance with study-related procedures and 
continued eligibility for the study as well as to collect 
baseline eDiary data. 
Participants who experience an asthma exacerbation 
during the run-in period should receive treatment for 
their exacerbation and remain in the run-in period until 
the investigator considers that the participant has 
returned to their baseline asthma status for at least one 
week.  
The participants that are not eligible to continue in the 
study at the end of the run-in period will be deemed 
run-in failures, but may be rescreened after 
consultation with the Medical Monitor (Section 5.5). 


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Phase Phase Title 
Duration 
Description 
3 
Study 
Intervention 
(Visit 2-Visit 
17) 
52 weeks 
Participants who meet the randomisation criteria will 
enter the 52-week treatment period and will be 
randomised to receive either add-on GSK3511294 
(100 mg) or matching placebo in a 2:1 ratio.  
During the treatment phase, a total of 2 doses of study 
medication will be administered SC via PFS: at 
Week 0 (Visit 2) and Week 26 (Visit 10).a 
Study visits will occur at Week 0, Week 2, Week 4 and 
every 4 weeks thereafter with an additional study visit 
at Week 26 for the administration of the second dose 
of study intervention. The study intervention period will 
conclude with the Exit Visit at Week 52 (Visit 17). 
Only participants who choose not to enter the OLE study will complete the phase below: 
4 
Follow-up 
4 weeks 
Participants will complete a Follow-up visit/call 4 weeks 
after the Exit Visit; this visit/call will capture AE/SAE 
assessments and a urine pregnancy test result.  
At the end of the Follow-up visit/call, participants will be 
prescribed appropriate alternative asthma therapy at 
the physician’s discretion, if required. 
a. Participants who experience any of the study intervention discontinuation conditions listed in 
Section 7.1 will not receive another dose of study intervention but will be encouraged to 
remain in the study and complete their remaining scheduled visits/assessments.  
4.1.2. 
Treatment after the End of Study  
Participants who receive both doses of double-blind treatment and complete the Week 52 
Exit Visit will be eligible to participate in the OLE study 212895. See Section 6.7 for 
details. 
Participants who are not entering the OLE study 212895 will enter a 4-week follow-up 
period and complete the study with a Follow-up visit/call at Week 56. After study 
completion, appropriate alternative asthma therapy may be prescribed at the physician’s 
discretion.  
4.1.3. 
Independent Data Monitoring Committee (IDMC) 
An IDMC will be utilised in this study to ensure external objective review of the data in 
order to protect the ethical and safety interests of participants and to protect the scientific 
validity of the study (see Section 10.1.5).  


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4.2. 
Scientific Rationale for Study Design 
Population: This study is designed to evaluate the efficacy and safety of GSK3511294 
100 mg SC as an adjunct therapy in participants with severe uncontrolled asthma with an 
eosinophilic phenotype. Participants should have uncontrolled asthma, as evidenced by 
repeat exacerbations, despite treatment with optimised background therapy consisting of 
maintenance ICS treatment and at least one additional controller. Participants are also 
required to have the requisite elevated blood eosinophil count (see randomisation 
criterion 1, Section 5.3) that is indicative of asthma with an eosinophilic phenotype. This 
population has been shown to benefit from add-on anti-IL-5 therapies such as 
mepolizumab [Pavord, 2012, Ortega, 2014; Chupp, 2017] and is therefore anticipated to 
benefit from GSK3511294.  
Blood eosinophil count screening: A Screening blood eosinophil count threshold of 
150 cells/μL at Screening Visit 1 or 300 cells/µL in the previous 12 months has been 
selected as a criterion to identify participants likely to respond to treatment with anti-IL-5 
therapy, consistent with findings from previous trials with mepolizumab. 
Primary efficacy endpoint: A primary efficacy endpoint of annualised rate of clinically 
significant exacerbations has been selected as a robust and clinically relevant measure of 
the direct benefit of GSK3511294 to a population with severe uncontrolled asthma with 
an eosinophilic phenotype. In the current study, the definition of clinically significant 
exacerbations (see Section 8.2.2), i.e. exacerbations treated with systemic CSs 
(intramuscular [IM], intravenous [IV], or oral) for 3 or more days and/or hospitalisation 
and/or ED visit, is consistent with previous trials with mepolizumab [Pavord, 2012; 
Ortega, 2014] and reslizumab [Castro, 2015]. 
Placebo-control design: An established randomised, double-blind and parallel-group 
study design will allow for a robust determination of participant response to 
GSK3511294 as an adjunct therapy to their maintenance asthma therapy. As such, the 
comparator arm in this study will be placebo plus continued maintenance asthma 
treatment. A 2:1 randomisation will be used in order to limit the number of participants 
randomised to placebo treatment and to provide more safety information on 
GSK3511294. All participants will continue to receive their optimised and stable 
maintenance asthma therapy throughout the entire duration of the study regardless of 
intervention arm assignment. The stable maintenance asthma therapy (per the inclusion 
criteria) will consist of medium to high dose ICS (440 mcg FP HFA daily, or clinically 
comparable [GINA, 2020; see Appendix 10]) with at least one additional controller 
medication e.g., long-acting beta-2-agonist (LABA), with or without maintenance oral 
corticosteroids (OCS). Participants who are treated with medium dose ICS will also need 
to be treated with LABA to qualify for inclusion. 
Study Duration: A 52-week treatment period should allow sufficient time to assess 
whether GSK3511294 100 mg SC, administered as two repeat doses 26 weeks apart (at 
Week 0 [randomisation] and at Week 26), can reduce the annualised rate of clinically 
significant exacerbations to a similar extent to that observed with other anti-IL-5 mAbs. 
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Run-in Period: The one-week (maximum 6 weeks) Run-in period allows for the 
assessment of participant understanding and compliance with the daily eDiary, to 
establish Baseline symptoms, and to allow adequate time for receipt of results from 
assessments collected at Screening Visit 1.  
Open-label extension study: Following study completion, all eligible participants will 
have the option to participate in the OLE study to provide additional safety data (see 
Section 6.7). 
Data collection after discontinuation from study intervention: The protocol objective 
is to collect data over the full study period, whether participants continue on study 
intervention or in the case of premature discontinuation from study intervention. 
However, the decision to continue in the study after premature discontinuation from 
study intervention remains the prerogative of the participant. Participants who agree to 
continue in the study after premature discontinuation from study intervention (for any 
reason) will continue to be contacted by the study site, either through in clinic visits or by 
phone as agreed with the participant, on a monthly basis (aligned to their study schedule) 
until the end of their planned 52-week participation and follow up contact 4 weeks later, 
to enable capture of post-intervention information. 
4.2.1. 
Participant Input into Design 
Participant involvement in the study design was obtained from 10 patients (6 in Italy, 1 in 
UK, and 3 in US [1 adolescent]) using 2 online qualitative surveys containing 
17 questions over a period of 2 weeks. Based on the participant feedback, the following 
design elements will be implemented: 
• Reduced number of laboratory samples and patient-reported outcomes (PRO) 
assessments  
• A hybrid trial model, allowing for home visits and virtual/telemedicine visits at 
key assessments which will reduce the burden of onsite visits and offer some 
flexibility in visit timing for the participant’s schedule 
4.3. 
Justification for Dose 
The dose rationale for this study is supported by the FTIH Study 205722 
[GlaxoSmithKline Document Number 2019N411063_00] that investigated single SC 
doses of GSK3511294 ranging from 2 mg to 300 mg. 
 
 
 
 
 
 
 
 
 
 
 
 
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4.4. 
End of Study and Study Completer Definition 
The end of the study is defined as the date of the last visit of the last participant in the 
study. 
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.  
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5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrolment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
AGE 
1. Age: Adults and adolescents ≥12 years of age, at the time of signing the informed 
consent/assent. 
TYPE OF PARTICIPANT AND DISEASE CHARACTERISTICS  
2. Asthma: Participants must have a documented physician diagnosis of asthma for 
≥2 years that meets the National Heart, Lung, and Blood Institute guidelines 
[NHLBI, 2007] or GINA guidelines [GINA, 2020] AND 
a) Eosinophilic phenotype: Have, or with high likelihood of having, asthma 
with an eosinophilic phenotype as per Randomisation Criteria 1 and 2 (see 
Section 5.3) 
AND 
b) Exacerbation history: Have previously confirmed history of 2 
exacerbations requiring treatment with systemic CS (IM, IV, or oral), in the 
12 months prior to Visit 1, despite the use of medium to high-dose ICS (see 
criterion 4). For participants receiving maintenance CS, the CS treatment for 
the exacerbations must have been a two-fold dose increase or greater. 
3. Airflow obstruction: Persistent airflow obstruction as indicated by: 
a) For participants 18 years of age at Visit 1, a pre-bronchodilator FEV1 <80% 
predicted (NHANES III) recorded at Visit 1 
b) For participants 12-17 years of age at Visit 1: 
• A pre-bronchodilator FEV1 <90% predicted (NHANES III) recorded at 
Visit 1  
OR 
• FEV1:Forced Vital Capacity (FVC) ratio <0.8 recorded at Visit 1 
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ASTHMA MAINTENANCE THERAPY  
4. Inhaled Corticosteroid: A well-documented requirement for regular treatment 
with medium to high dose ICS (in the 12 months prior to Visit 1 with or without 
maintenance OCS). The maintenance ICS dose must be 440 mcg FP HFA daily, 
or clinically comparable [GINA, 2020; see Appendix 10]. Participants who are 
treated with medium dose ICS will also need to be treated with LABA to qualify 
for inclusion. 
5. Additional Controller Medication: Current treatment with at least one 
additional controller medication, besides ICS, for at least 3 months [e.g., LABA, 
long-acting muscarinic antagonist (LAMA), leukotriene receptor antagonist 
(LTRA), or theophylline]. 
 
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SEX 
INFORMED CONSENT 
7
5.2. Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
MEDICAL CONDITIONS 
1. Concurrent Respiratory Disease: Presence of a known pre-existing, clinically 
important lung condition other than asthma. This includes (but is not limited to) 
current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary 
aspergillosis, or diagnoses of emphysema or chronic bronchitis (chronic 
obstructive pulmonary disease other than asthma) or a history of lung cancer. 
2. Eosinophilic Diseases: Participants with other conditions that could lead to 
elevated eosinophils such as hyper-eosinophilic syndromes including (but not 
limited to) Eosinophilic Granulomatosis with Polyangiitis (EGPA, formerly 
known as Churg-Strauss Syndrome) or Eosinophilic Esophagitis.   
3. Parasitic infection: Participants with a known, pre-existing parasitic infestation 
within 6 months prior to Visit 1. 
4. Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency 
virus – HIV), other than that explained by the use of CSs taken as therapy for 
asthma. 
5. Malignancy: A current malignancy or previous history of cancer in remission for 
less than 12 months prior to screening (Participants that had localised carcinoma 
of the skin which was resected for cure will not be excluded).  
6. Liver Disease: Cirrhosis or current unstable liver or biliary disease per 
investigator assessment defined by the presence of ascites, encephalopathy, 
coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent 
jaundice.  
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MEDICAL CONDITIONS 
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. 
 
7. 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.  
8. 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. 
9. COVID-19: Participants that, according to the investigator's medical judgment, 
are likely to have active COVID-19 infection should be excluded. Participants 
with known COVID-19 positive contacts within the past 14 days should be 
excluded for at least 14 days following the exposure during which the participant 
should remain symptom-free. 
 
PRIOR/CONCOMITANT THERAPY 
10. 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 or who have a previous documented 
failure with anti-IL-5/5R therapy. 
11. Other mAbs in the treatment of asthma: Participants who have received 
omalizumab (Xolair) or dupilumab (Dupixent) within 130 days prior to Visit 1. 
12. Other mAbs not used for the treatment of asthma: Participants who have 
received any mAb within 5 half-lives of Visit 1. Authorized treatments for 
COVID-19 are permitted. 
13. Investigational Medications: Participants who have received treatment with an 
investigational drug within the past 30 days or five terminal phase half-lives of 
the drug whichever is longer, prior to Visit 1 (this also includes investigational 
formulations of marketed products). 
 
PRIOR/CONCURRENT CLINICAL STUDY EXPERIENCE 
14. 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.  


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DIAGNOSTIC ASSESSMENTS 
15. 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.   
 
OTHER EXCLUSIONS 
16. Smoking history: Current smokers or former smokers with a smoking history of 
10 pack years (number of pack years = (number of cigarettes per day / 20) x 
number of years smoked). A former smoker is defined as a participant who quit 
smoking at least 6 months prior to Visit 1. 
17. Alcohol/Substance Abuse: A history (or suspected history) of alcohol misuse or 
substance abuse within 2 years prior to Visit 1. 
18. Hypersensitivity: Participants with allergy/intolerance to the excipients of 
GSK3511294 in Section 6.1 or any mAb or biologic. 
19. Pregnancy: Participants who are pregnant or breastfeeding. Participants should 
not be enrolled if they plan to become pregnant during the time of study 
participation. Requirements for pregnancy testing are located in Section 8.3.5. 
20. Adherence: Participants who have known evidence of lack of adherence to 
controller medications and/or ability to follow physician’s recommendations. 
5.3. 
Randomisation Criteria 
At the end of the run-in period, study participants must fulfil all of the randomisation 
inclusion/exclusion criteria below in order to be randomised to study intervention.  
5.3.1. 
Randomisation Inclusion Criteria 
RANDOMISATION INCLUSION CRITERIA 
1. Blood eosinophil count: 
a) An elevated peripheral blood eosinophil count of 300 cells/L demonstrated 
in the past 12 months prior to Visit 1 that is related to asthma 
OR 
b) An elevated peripheral blood eosinophil count of 150 cells/L at Screening 
Visit 1 that is related to asthma. 
2. Asthma: Evidence of airway reversibility or responsiveness as documented by 
either:  
a) Airway reversibility (FEV112% and 200 ml) demonstrated at Visit 1 or 
Visit 2 using the Maximum Post Bronchodilator Procedure OR 


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RANDOMISATION INCLUSION CRITERIA 
b) Airway reversibility (FEV112% and 200ml) documented in the 24  months 
prior to Visit 2 (randomisation visit) OR  
c) Airway hyperresponsiveness (methacholine: PC20 of <8 mg/mL, histamine: 
PD20 of <7.8 mol, mannitol: decrease in FEV1 as per the labelled product 
instructions) documented in the 24 months prior to Visit 2 (randomisation 
visit)  
3. 
 
 
 
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5.3.2. 
Randomisation Exclusion Criteria 
RANDOMISATION EXCLUSION CRITERIA 
1. Laboratory abnormality: Evidence of clinically significant abnormality in the 
haematological, biochemical or urinalysis screen at Visit 1, as judged by the 
investigator.  
2. Liver chemistry test: Participants who meet the following based on results from 
sample taken at Screening Visit 1: 
a) Alanine aminotransferase (ALT) >2x upper limit of normal (ULN) 
b) Total bilirubin >1.5x ULN (isolated bilirubin >1.5xULN is acceptable if 
bilirubin is fractionated and direct bilirubin <35%) 
c) Cirrhosis or current unstable liver or biliary disease per investigator 
assessment defined by the presence of ascites, encephalopathy, coagulopathy, 
hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice. 
NOTES: Stable non-cirrhotic chronic liver disease (including Gilbert’s 
syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C) is 
acceptable if the participant otherwise meets entry criteria. 
3. ECG: QTcF ≥450msec, or QTcF ≥480 msec for participants with Bundle 
Branch Block, in the 12-lead ECG machine read at randomisation Visit 2 are 
excluded. Participants are excluded if an abnormal ECG finding from central 
over-read of the 12-lead ECG conducted at Screening Visit 1 is considered to 
be clinically significant and would impact the participant’s participation during 
the study, based on the evaluation of the Investigator. 
4. Unstable Asthma: Participants with a clinically significant asthma exacerbation 
in the 7 days prior to randomisation should have their randomisation visit delayed 
until the investigator considers the participant's asthma to be stable (see 
Section 5.6).  
5. Maintenance Asthma Therapy: Any changes in the dose or regimen of baseline 
ICS and/or additional controller medication (except for treatment of an 
exacerbation) during the run-in period. 
5.4. 
Lifestyle Considerations 
No lifestyle restrictions are required for this study. 


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5.5. 
Pre-screen/Screen/Run-in Failures 
Pre-screen/screen/run-in failures are defined as participants who consent to participate in 
the clinical study but are not subsequently randomised. 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 SAEs. 
For the purposes of this study, pre-screen/screen/run-in failures will be defined as 
follows: 
Pre-screen Failures 
Screen Failures 
Run-in Failures 
Participants who are assigned 
a study number at the time of 
signing the informed consent 
(pre-screen visit) but do not 
progress to the screening 
visit. 
Participants who complete at 
least one additional Visit 1 
(Screening) procedure but do 
not enter the run-in period. 
Participants who enter the 
run-in period but are not 
subsequently randomised. 
Re-screening of participants will be permitted; however, advance written approval to 
proceed with re-screening a participant must be obtained from the Medical Monitor. 
Re-screened participants should be assigned a new participant number for every 
screening/rescreening event. 
5.6. 
Criteria for Temporarily Delaying Randomisation 
Participants who experience a clinically significant asthma exacerbation during the run-in 
period should receive treatment for their exacerbation, have their randomisation visit 
delayed and remain in the run-in period (up to 6 weeks) until the investigator considers 
the participant to have returned to their baseline asthma status for at least 7 days.  
A clinically significant exacerbation is defined as worsening of asthma requiring the use 
of systemic CS and/or hospitalisation and/or ED visit (Section 8.2.2). 
A participant who is not eligible to continue in the study at the end of the run-in period, 
should be considered a run-in failure but may be rescreened after consultation with the 
Medical Monitor (Section 5.5).  


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6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY 
Study intervention is defined as any investigational intervention(s)/product(s) (IP), 
marketed product(s), placebo, or medical device(s) intended to be administered to a study 
participant according to the study protocol. 
Study intervention will only be administered in the clinic; hence Visit 2 (Week 0) and 
Visit 10 (Week 26) are required to be in-clinic visits. 
6.1. 
Study Intervention Administered 
GSK3511294 is a humanised IgG antibody (IgG1, kappa) with human heavy and light 
chain frameworks. GSK3511294 liquid drug product will be supplied by GSK in a Type I 
glass syringe 
 The drug product and syringe will be assembled in a single use, 
disposable safety syringe to enable delivery of the drug product. Each device enables SC 
delivery of 100 mg GSK3511294 
 sterile liquid formulation. 
 
 
  
The placebo in this study will be 0.9% sodium chloride solution contained in a PFS also 
supplied by GSK.  
An overview of study intervention is provided in Table 2. 
Table 2 
Overview of Study Intervention 
ARM Name 
GSK3511294 100 mg 
Placebo 
Intervention Name 
GSK3511294 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 
Experimental 
Placebo 
IMP and NIMP 
IMP 
IMP 
Sourcing 
Provided centrally by the 
Sponsor  
Provided centrally by the 
Sponsor  
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ARM Name 
GSK3511294 100 mg 
Placebo 
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. 
PFS=Pre-filled safety syringe, IMP=Investigational Medicinal Product, N/A=not applicable 
6.1.1. 
Medical Devices 
The GSK manufactured medical devices (or devices manufactured for GSK by a third 
party) provided for use in this study are injection devices: 
• A pre-filled syringe contained within a safety syringe. 
 
. 
• The components that comprise the pre-filled syringe (glass barrel with pre-staked 
needle and plunger) 
 
 
 
• 
 
 
 
The Instruction for use (IFU) of the injection device will be provided. 
 
 
  
All device deficiencies, (including malfunction, use error and inadequate labelling) shall 
be documented, and reported by the investigator throughout the clinical investigation (see 
Section 8.4.8) and appropriately managed by GSK. 
6.2. 
Packaging and Labelling 
The contents of the label will be in accordance with all applicable regulatory 
requirements.  
6.3. 
Preparation/Handling/Storage/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 
authorised 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 authorised site staff. 
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• 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. 
• 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. 
6.4. 
Measures to Minimise Bias: Randomisation and Blinding 
6.4.1. 
Treatment Assignment 
• Eligible participants will be centrally randomised using an IRT system.  
• 
 
 Separate randomisation schedules will be created for each 
country. Participants will be assigned to study intervention in accordance with the 
randomisation schedule. Once a randomisation number has been assigned to a 
participant, it cannot be reassigned to any other participant in the study.  
• Randomisation will be stratified according to the participant’s baseline ICS dose 
(aiming to up to 50% approximately of participants on medium ICS dose; see 
Appendix 10). 
• At Visit 2 (Week 0), those participants who meet the randomisation criteria will be 
randomised in a 2:1 ratio to receive one of the following study treatments in addition 
to their stable maintenance asthma treatment: 
o GSK3511294 100 mg SC 
o Placebo SC 
• Study intervention will be administered in the clinic at Visit 2 (Week 0) and Visit 10 
(Week 26) as per the SoA (Section 1.3).  
6.4.2. 
Blinding 
• The IRT system will be programmed with blind-breaking instructions. In case of an 
emergency, the investigator has the sole responsibility for determining if unblinding 
of a participant’s intervention assignment is warranted. Participant safety must always 
be the first consideration in making such a determination. If the investigator decides 
that unblinding is warranted, the investigator should make every effort to contact 
GSK prior to unblinding a participant’s intervention assignment unless this could 
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delay emergency intervention of the participant. If a participant’s intervention 
assignment is unblinded, GSK must be notified within 24 hours after breaking the 
blind. The date and reason that the blind was broken must be recorded in the source 
documentation and case report form (CRF), as applicable. 
• Investigators will remain blinded to each participant’s assigned study intervention 
throughout the course of the study. 
 
. 
• If a participant’s intervention code is unblinded by the investigator or treating 
physician, that participant will continue with all study visits but will not receive the 
second dose of study intervention at Week 26. The primary reason for the event or 
condition which led to the unblinding will be recorded in the CRF (see Section 7.1).  
• 
 
 
.  
• GSK’s Global Clinical Safety and Pharmacovigilance (GCSP) staff may unblind the 
intervention 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 intervention assignment, may be sent to 
investigators in accordance with local regulations and/or GSK policy. 
6.5. 
Study Intervention Compliance 
Both doses of GSK3511294 or placebo will be administered under medical supervision 
via SC injection to participants by the investigator or designee at the study site. Dose 
administration details (date and time) will be recorded in the source documents and 
reported in the CRF. 
Participants will be monitored in clinic for a minimum of 2 hours post-dose to monitor 
for immediate hypersensitivity and any other untoward effects. In the event of an acute 
severe reaction (e.g., anaphylaxis) following administration of GSK3511294, 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 participant to 
another facility for additional care if appropriate. 
6.6. 
Dose Modification 
Dose modification is not allowed. 
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6.7. 
Continued Access to Study Intervention after the End of the Study 
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. 
At the end of the study, participants will be eligible to screen to enter the OLE Study 
212895 and have continued access to open-label GSK3511294 if he/she: 
• has received both doses of study intervention (at Week 0 and Week 26), AND 
• completed the scheduled Exit Visit at Week 52, AND 
• did not meet any of the study intervention discontinuation conditions (Section 7.1) 
during the study. 
For participants who enrol into the 12-month OLE study, the Day 1 visit of the OLE 
study can occur on the same day as the Exit Visit of the current study. Specific details on 
the OLE study will be documented separately. 
Participants who do not enter the OLE study will complete a follow-up visit/call and be 
prescribed alternative asthma therapy if needed and as determined by the study 
investigator.  
6.8. 
Treatment of Overdose 
The dose of GSK3511294 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 (refer to the current IB [GlaxoSmithKline Document Number 
2016N295843_03 or later]),  single SC doses of GSK3511294 up to 300 mg were well 
tolerated by adult participants with mild/moderate asthma (6 participants received a 
300 mg SC dose). 
 (see Section 6.1). 
In the event of an overdose, the investigator should: 
• 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 
GSK3511294.  
• Closely monitor the participant for AE/SAE and laboratory abnormalities for 
30 weeks following the last administered dose. 
• 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 study intervention will be 
made by the investigator in consultation with the Medical Monitor based on the clinical 
evaluation of the participant.  
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6.9. 
Concomitant Therapy 
At pre-screening and/or screening, information on the participant’s baseline maintenance 
asthma therapy will be collected and recorded in the eCRF.  
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) that the participant is receiving at the time of 
enrolment or receives during the study must be recorded in the eCRF along with: 
• reason for use 
• dates of administration including start and end dates 
• dosage information including dose and frequency (any dose changes are to be 
recorded for OCS) 
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
6.9.1. 
Permitted Medications and Non-Drug Therapies 
Throughout the study, participants are to be maintained on their baseline maintenance 
asthma treatment consisting of ICS plus at least one other controller, e.g. LABA, LAMA, 
with or without maintenance OCS (see inclusion criteria 4 and 5, Section 5.1). It is 
recognised that in a year-long study, changes may need to be individualised if clinically 
crucial for a participant. The investigator is encouraged to discuss any cases with the 
Medical Monitor before initiating changes to a participant’s maintenance asthma 
medication. 
Additional asthma medications such as theophyllines and anti-leukotrienes will be 
permitted as maintenance provided that they have been taken regularly in the 3 months 
prior to screening (Visit 1). If uncertain whether a medication is permitted, please 
confirm with the Medical Monitor.  
Albuterol/salbutamol is permitted throughout the study but should be withheld in the 
6-hour period prior to spirometry assessments, if possible. Study-provided 
albuterol/salbutamol should not be recorded in the eCRF, only in the eDiary.  
LABAs, LAMAs, and fixed dose combinations of ICS/LABA or ICS/LABA/LAMA 
should be withheld for 12 hours prior to spirometry, if possible.  
Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure 
(BiPAP) for the treatment of obstructive sleep apnoea is permitted, if initiated prior to the 
Screening Visit (Visit 1). This treatment must be captured in the eCRF. 
Allergen-specific immunotherapy is permitted provided that it has been taken regularly in 
the 6 months prior to screening (Visit 1).  
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. 


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COVID-19 vaccine administration and the administration of the study intervention should 
be separated by 14 days if possible, in order to be able to properly assess study injection 
site/treatment reactions. 
Participants can be treated for SARS-CoV-2 infection using authorized COVID-19 
treatments (including monoclonal antibodies) in line with local/national guidelines.  
Experimental COVID-19 treatments are not permitted. 
6.9.2. 
Prohibited Medications and Non-Drug Therapies 
The following medications are not allowed prior to screening (Visit 1), according to the 
following schedule, or during the study: 
Medication 
Washout Time 
Prior to Screening Visit 
Investigational drugs 
1 month or 5 half-lives whichever is 
longer 
Omalizumab [Xolair], dupilumab [Dupixent] 
130 days 
Mepolizumab [Nucala], reslizumab [Cinqair/Cinqaero], 
benralizumab [Fasenra] 
12 months 
Other monoclonal antibodies 
5 half-lives 
Experimental anti-inflammatory drugs (non biologicals) 
3 months 
 
Immunosuppressive medications such as those listed below (not all inclusive) 
Corticosteroids if used to treat a condition other than asthma 
• Intramuscular, long-acting depot 
• Regular systemic (oral or parenteral) 
Methotrexate, cyclosporin, azathioprine  
Oral gold 
Chemotherapy used for conditions other than asthma 
Additionally, Bronchial Thermoplasty and Radiotherapy are excluded for 12 months 
prior to Visit 1 and throughout the study. CPAP, BiPAP, and oxygen therapy should not 
be initiated during the run-in period. 
6.9.3. 
Rescue Medicine 
Trade label albuterol/salbutamol metered dose inhalers (MDIs) will be provided as rescue 
medication throughout the study. Albuterol/salbutamol will be sourced for all centres. 
Use of low dose ICS-formoterol as rescue medication is not allowed during the study. 
Participants will be dispensed an MDI at Screening Visit 1 to be used primarily to treat 
asthma symptoms on an as needed basis and also during the reversibility assessments (see 
Section 8.2.3.1). The MDI should be replaced as needed.  
Although the use of rescue medications is allowable (at any time during the study), the 
use of rescue medications should be withheld, if possible, for at least 6 hours prior to the 
spirometry assessments. Rescue medication usage will be recorded in the eDiary. 


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7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Intervention 
No further doses of study intervention will be administered to participants who meet any 
of the following permanent treatment discontinuation conditions at any time during the 
study treatment period: 
• Liver Chemistry: Meets any of the protocol-defined liver chemistry stopping 
criteria (see Section 7.1.1) 
• ECG: Meets any of the protocol-defined QTc stopping criteria (see Section 7.1.2) 
• Pregnancy: Positive pregnancy test (see Section 8.4.5) 
• Severe allergic reaction/anaphylaxis: Participants with severe allergic 
reaction/anaphylaxis with no clear alternative cause (see Appendix 8) 
• Vasculitis: Participants with confirmed vasculitis or suspected vasculitis with no 
alternative explanation (see Section 7.5). 
• Study treatment unblinded: Unblinding of the study treatment assigned to a 
participant (see Section 6.4.2). 
If a participant meets any of the treatment discontinuation conditions or chooses (for any 
reason) not to receive another dose of study intervention before the end of the protocol 
specified randomised intervention period:  
• The investigator will make every effort to encourage the participant to remain in 
the study and to continue with all remaining study visits, including the Exit and 
Follow-up Visits.  
• The primary reason for discontinuation of study intervention (e.g., AE, lack of 
efficacy, protocol deviation, investigator discretion, consent withdrawn etc.) must 
be recorded in the eCRF.  
• Participants will be provided with the option to continue their scheduled visits 
in-clinic, at home, or by phone. The required study assessments will depend on 
whether the participant is attending the visit in-clinic, at home, or by phone. At a 
minimum, an assessment of exacerbations, AEs, SAEs, and concomitant 
medications will be completed.  
• 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 
the SoA (Section 1.3). 


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7.1.1. 
Liver Chemistry Stopping Criteria 
Liver chemistry stopping criteria, 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 the algorithm or  
• in the presence of abnormal liver chemistry not meeting protocol-specified 
stopping rules, the investigator believes that it is in the best interest of the 
participant.  
Liver Chemistry Stopping Criteria Algorithm 
 
Abbreviations: ALT = alanine transaminase; INR = international normalised ratio; SAE = 
serious adverse event; ULN = upper limit of normal, Tbili = Total bilirubin 
Refer to Appendix 6 for required Liver Safety Actions, Monitoring, and Follow-up 
Assessments. 


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Liver Chemistry Increased Monitoring Algorithm with Continued Study 
Intervention for Participants with ALT 3xULN but <8xULN and do not meet any 
of the liver stopping criteria 
 
Abbreviations: ALT = alanine transaminase; Tbili = total bilirubin; INR = international 
normalised ratio; SAE = serious adverse event; ULN = upper limit of normal, Tbili = 
Total bilirubin. 
Refer to Appendix 6 for required Liver Safety Actions, Monitoring and Follow-up 
Assessments. 
7.1.1.1. 
Study Intervention Restart or Rechallenge after liver stopping 
criteria met 
Study intervention restart or rechallenge after liver chemistry stopping criteria are met by 
a participant in this study will not be permitted.  
7.1.2. 
QTc Stopping Criteria 
Details on performing ECG assessments can be found in Section 8.3.3.  
The QT interval corrected using Fridericia’s formula (QTcF) must be used for each 
individual participant to determine eligibility for and discontinuation from the study 
intervention. This formula may not be changed or substituted once the participant has 
been enrolled. 


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For this study, the following QTc stopping criteria will apply: 
• QTcF >500 msec OR uncorrected QT >600 msec  
• Change from baseline of QTcF >60 msec 
For participants with underlying bundle branch block, follow the discontinuation criteria 
listed below: 
Baseline QTcF with Bundle Branch 
Block 
Discontinuation QTcF with Bundle 
Branch Block 
<450 msec 
>500 msec 
450 – 480 msec 
≥530 msec 
The QTcF value from the 12-lead ECG central over-read at randomisation Visit 2 should 
be used as baseline QTcF value for any changes from baseline calculations during the 
study. After randomisation 12-lead ECG central over-read values should be used to 
assess QTc stopping criteria, with the exception of Visit 10 (Week 26) where 12-lead 
ECG machine read values should be used. 
7.1.3. 
Temporary Discontinuation 
For this study, a temporary discontinuation refers to a delayed administration of the 
second dose of study intervention at Week 26.  
If a participant becomes infected (parasitic infection) during the study intervention period 
before receiving the second dose of study intervention and does not respond to anti-
helminth treatment, a delayed administration of the study intervention may be considered 
in consultation with the GSK Medical Monitor.  
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 authorised representative (LAR), or may be withdrawn at any 
time at the discretion of the investigator for safety, behavioural, or compliance 
reasons. This is expected to be uncommon. 
• Participants who prematurely withdraw from the study should attend: 
o a Withdraw from Study (WS) Visit, 26 weeks after the last administered dose of 
study intervention (at Week 26 or Week 52) AND 
o a 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.  


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• 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/she repeatedly fails to return for 
scheduled visits (or scheduled phone calls, if applicable) 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 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. A final attempt will be made to contact the 
participant for a safety follow-up 30 weeks after the last administered dose of 
study intervention. 
Discontinuation of specific sites or of the study as a whole are handled as part of 
Appendix 1. 
7.4. 
Reasons for Study Intervention Discontinuation and/or Study 
Withdrawal 
The primary reason for study intervention discontinuation and/or study withdrawal will 
be recorded in the eCRF. When a participant withdraws consent, the investigator must 
document the reason (if specified by the participant) in the eCRF.  
7.5. 
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. 
 
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Symptoms potentially suggestive of vasculitis include but are not limited to: 
• 
persistent* fever (*where persistent is considered to be a duration of 2 days) 
• 
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 
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. 
If clinically indicated, the participant may be referred to a specialist for further 
management, which may include organ biopsy. 
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8. 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarised in the SoA (Section 1.3).  
• As detailed in the SoA (Section 1.3), participants who are not entering the OLE study 
212895 should make every effort to complete the Week 56 follow-up visit/call on the 
scheduled day. The visit may be completed within 7 days of the scheduled time-point. 
• Every effort should be made to reduce missing data throughout the study. 
• Protocol waivers or exemptions are not allowed. 
• Immediate safety concerns should be discussed with the Medical Monitor 
immediately upon occurrence or awareness to determine if the participant should 
continue to receive the second scheduled dose of study intervention, if applicable.  
• Adherence to the study design requirements, including those specified in the SoA, 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 ICF may be utilised for screening or 
baseline purposes provided the procedure met the protocol-specified criteria and was 
performed within the time frame defined in the SoA. 
• 
 
 
 
 
• Repeat or unscheduled samples may be taken for safety reasons or for technical issues 
with the samples. 
• Participants should be provided a quiet space in which to complete patient-reported 
outcomes (PRO), prior to other assessments and procedures. Site staff can provide 
limited advice if required, however participants should not be guided or directed in 
answering questions. Family or friends should not influence the answers. Site staff 
should encourage participants to complete all questions. 
8.1. 
Screening and Critical Baseline Assessments 
8.1.1. 
Pre-screening Visit (Visit 0) 
Informed consent should be obtained at the Pre-screening Visit or the Screening Visit, 
prior to initiating any study assessments. A participant number will be assigned at the 
time the ICF is signed. Participants can conduct the Pre-screening Visit (Visit 0) up to 
2 weeks prior to the Screening Visit (Visit 1).  
The pre-screening procedures will include a review/assessment of: 
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• Inclusion/exclusion criteria (see Section 5.1 and Section 5.2) 
• Demographic information including gender, ethnic origin, race, and year of birth 
(can be conducted at Visit 1 instead, if necessary) 
• Childbearing status for all women (can be conducted at Visit 1 instead, if 
necessary); for WOCBP, contraception should be started at least 14 days prior to 
receiving the first dose of study intervention (see Appendix 4) 
• Therapy history and concomitant medications including maintenance asthma 
medications from the year prior to Screening Visit 1, all medications within the 
3 months prior to Screening Visit 1 and all current medications 
All clinic visits from Pre-screening Visit 0 to the Exit Visit (or if applicable, the WS Visit 
or the Follow-up Visit) should be completed in the relevant eCRF form. Visit 1, 2, 10 and 
WS visit must be registered in the IRT. 
Serious adverse events must be collected from signing of Informed Consent if considered 
related to study procedures.  
8.1.2. 
Critical Assessments performed at Screening (Visit 1) 
The following critical assessments will be conducted at Screening Visit 1: 
• Review inclusion/exclusion criteria (see Section 5.1 and Section 5.2) 
• Review therapy history and concomitant medications including maintenance 
asthma medications from the year prior to Screening Visit 1, all medications 
within the 3 months prior to Screening Visit 1 and all current medications. 
• Medical history including: 
o Asthma including current treatment, duration of asthma, courses of rescue 
CSs, history of previous intubations, asthma exacerbation history in previous 
year, asthma triggers  
o Cardiovascular (CV) medical history/risk factors (as detailed in the eCRF) 
o Vasculitis, allergies and anaphylaxis history 
o Smoking history and current status 
o Historical blood eosinophil count - participants without a documented blood 
eosinophil count ≥300 cells/µL in the 12 months prior to Screening Visit 1 
must show a blood eosinophil count ≥150 cells/µL, based on the sample 
collected at Visit 1 (see randomisation criterion 1, Section 5.3.1). If the 
Screening Visit test result does not meet the blood eosinophil count eligibility 
criteria, the laboratory assessment may be repeated, at the discretion of the 
investigator, if it is judged to be likely in the eligible range for study inclusion 
within the run-in period prior to Visit 2.  
• Spirometry including bronchodilator responsiveness testing using the Maximum 
Bronchodilator Procedure (see Section 8.2.3). If a patient fails the protocol-
specified reversibility criterion or FEV1 inclusion criteria, spirometry retest is 
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• 
 
• Safety Assessments including: 
o Physical exam (see Section 8.3.1) 
o Vital signs (see Section 8.3.2) 
o Resting 12-lead ECG (see Section 8.3.3) 
o AE/SAE assessment 
• 
• eDiary registration and training 
• 
(see Section 8.9) 
• Complete ADSD/ANSD (to be completed daily at home; see Section 8.2.10) 
8.1.3. 
Critical Assessments performed at Randomisation (Visit 2) 
The following critical assessments will be conducted at randomisation Visit 2: 
• Review of randomisation criteria (see Section 5.3), and data collected at Visit 1, 
including, if applicable, verification that the asthma-related peripheral blood 
eosinophil count is 150 cells/L, based on the sample collected at Visit 1 
• Review of concomitant medications 
• Spirometry (if airway reversibility was not demonstrated at Visit 1, the Maximum 
Bronchodilator Procedure may be repeated at Visit 2) (see Section 8.2.3) 
• SGRQ (see Section 8.2.4) 
• ACQ-5 (see Section 8.2.5) 
• 
 
• 
 
• 
 
• Safety assessments including: 
o Vital signs (see Section 8.3.2) 
o Resting 12-lead ECG (see Section 8.3.3) 
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o AE/SAE assessment 
•
o 
 
 
 
• Provide and review 
 (see 
Section 8.9) 
The following items will be completed at home: 
• 
 
• Complete ADSD/ANSD daily (see Section 8.2.10) 
8.2. 
Efficacy Assessments 
8.2.1. 
Efficacy Endpoints 
Efficacy endpoints and estimands are provided in Section 3. 
8.2.2. 
Asthma Exacerbations 
Clinically significant exacerbations of asthma are defined by: 
Worsening of asthma which requires use of systemic CSs1 and/or hospitalisation and/or 
Emergency Department (ED) visit.  
1For 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. 
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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 
a 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. 
8.2.3. 
Pulmonary Function Testing/ Spirometry  
Spirometry lung function assessments will be performed for all participants at specified 
visits to assess FEV1. At least 3 valid spirometry efforts should be attempted (with no 
more than 8 attempts) using the ATS guidelines [Miller, 2005]. Spirometry includes 
FEV1, percent predicted FEV1, Forced Vital Capacity (FVC) and FEV1/FVC. Spirometry 
assessments will be performed at screening (Visit 1), randomisation (Visit 2), and at 
scheduled in-clinic visits according to the SoA (Section 1.3). At each visit, spirometry 
should be performed at the same time of day (1 hour) as the assessment performed at 
Visit 2 (the baseline assessment). Participants should try to withhold short-acting beta-2-
agonists (SABAs) for 6 hours and LAMAs/LABAs for 12 hours prior to the clinic 
visit, if possible.  
Spirometry should not be conducted for participants with confirmed/suspected 
COVID-19.  
8.2.3.1. 
Reversibility using the Maximum Post-Bronchodilator Method 
Pre-bronchodilator measurements will be taken at the clinic visits specified in the SoA 
(Section 1.3): at screening, randomisation, Week 26 Visit, and Exit Visit (or EW Visit). 
In addition, post-bronchodilator values will be recorded following reversibility testing 
using the Maximum Post-Bronchodilator Method. Participants’ reversibility will be 
assessed at Visit 1 (Screening). For participants unable to achieve 12% reversibility and 
200 mL change at Visit 1, reversibility can be repeated at Visit 2 to confirm eligibility for 
the study (see randomisation criterion 2, Section 5.3.1). The procedures involved in the 
Maximum Post-Bronchodilator Method are those generated by the Pulmonary Physiology 
Subcommittee [Tepper, 2012]. Additional details on the reversibility testing procedures 
using the Maximum Post-Bronchodilator Method can be found in the spirometry section 
of the SRM. 
8.2.4. 
St. George’s Respiratory Questionnaire (SGRQ) 
The SGRQ is a well-established instrument, comprising 50 items  designed to measure 
Quality of Life in participants with diseases of airway obstruction [Jones, 1992]. The 
questionnaire will be administered as per guidance from the measure developers and 
completed electronically according to the SoA (Section 1.3).  


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8.2.5. 
Asthma Control Questionnaire-5 (ACQ-5) 
The ACQ-5 is a five-item questionnaire, which has been developed as a measure of 
participants’ asthma control that can be quickly and easily completed [Juniper, 2005]. 
The questions are designed to be self-completed by the participant. The five questions 
enquire about the frequency and/or severity of symptoms (nocturnal awakening on 
waking in the morning, activity limitation, and shortness of breath, wheeze) over the 
previous week. The response options for all these questions consist of a zero (no 
impairment/limitation) to six (total impairment/ limitation) scale. This will be completed 
electronically according to the SoA (Section 1.3). 
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8.2.9. 
  
The evaluations will be completed electronically at the visits specified in the SoA 
(Section 1.3). 
8.2.10. 
Asthma Daily Symptom Diary/Asthma Nightly Symptom Diary 
(ADSD/ANSD) 
The ADSD/ANSD is a 6-item self-administered patient-reported diary developed by the 
PRO Consortium’s Asthma Working Group (in accordance with the Food and Drug 
Administration’s PRO Guidance) to facilitate comprehensive and reliable assessment of 
asthma symptoms from a patient’s perspective [Gater, 2016]. 
The ADSD/ANSD is intended for use by adults and adolescents (aged 12 years and older) 
who are diagnosed with asthma to rate the severity of their symptoms in the three core 
categories: breathing symptoms (wheezing, shortness of breath), chest symptoms (chest 
tightness, chest pain) and cough.  
The ADSD/ANSD must be completed twice daily by the participant: 
• ADSD is to be completed before going to bed and refers to asthma symptoms 
during the day. 
• ANSD is to be completed upon waking and refers to asthma symptoms during the 
previous night.   
Participants are required to rate the six symptoms at their worst during the respective 
timeframes using an 11-point numeric rating scale (NRS) ranging from 0 (‘None’) to 10 
(‘As bad as you can imagine’). Responses will be captured electronically.  
The ADSD/ANSD questionnaire should only be administered to participants for whom 
an appropriate translation is available. Further details are contained in the SRM. 
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8.3. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.3) – 
where possible, these should be aligned with standard of care.  
8.3.1. 
Physical Examinations 
• A complete physical examination will include, at a minimum, assessments of the 
Skin, Eyes, 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 illnesses.  
8.3.2. 
Vital Signs  
• Temperature, pulse rate, and blood pressure will be assessed.  
• Blood pressure and pulse 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.  
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• Blood pressure and pulse 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. 
8.3.3. 
Electrocardiograms (ECGs) 
• Twelve-lead ECGs will be obtained at the time points specified in the SoA (see 
Section 1.3) using an ECG machine, provided by GSK via a 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. Refer to Section 7.1.2 for the QTcF formula. 
• 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/ randomised/ discontinued 
from the study intervention (but not from the study). Refer to Section 5.2 and 
Section 5.3.2 for exclusion/randomisation exclusion criteria related to ECG 
assessment and Section 7.1.2 for QTc withdrawal criteria and additional QTc 
readings that may be necessary. 
• ECG measurements will be made after the participant has rested in the supine 
position for 5 minutes. The ECG should be obtained after the vital signs 
assessments but before lung function testing followed by other study procedures. 
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. 
• Paper ECG traces are required to be maintained at the site with other source 
documents. 
8.3.4. 
Clinical Safety Laboratory Assessments 
• See Appendix 2 for the list of clinical laboratory tests to be performed and refer to 
the SoA (Section 1.3) for the timing and frequency.  
• The investigator must review the laboratory report, document this review, and 
record any clinically significant changes occurring during the study as an AE. The 
laboratory reports must be filed with the source documents.  
• Abnormal laboratory findings associated with the underlying disease are not 
considered clinically significant, 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 
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no longer considered significantly abnormal by the investigator or Medical 
Monitor. If clinically significant values do not return to normal/baseline within a 
period of time 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. 
• All protocol-required laboratory assessments, as defined in Section 10.2, must be 
conducted in accordance with the laboratory manual and the SoA (Section 1.3). 
• 
 
 
 
 
8.3.5. 
Pregnancy Testing 
• Refer to Section 5.1 Inclusion Criteria for pregnancy testing entry criteria. 
• A serum pregnancy test should be conducted for all WOCBP at the screening visit 
(Visit 1) and the Exit visit. In addition, a urine pregnancy test should be 
performed for all WOCBP prior to randomisation (Visit 2), on a monthly basis at 
the specified scheduled study visit, and at the Follow-up Visit/call (if applicable) 
as per the SoA (Section 1.3). 
• A final urine pregnancy test should be conducted for all WOCBP, 30 weeks after 
the last administered dose of study intervention:  
o Participants who enter the OLE study will have a urine pregnancy test 
prior to receiving the first dose of open-label GSK3511294. 
o Participants who do not enter the OLE study 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.  
o Participants who withdraw early from the study should have a urine 
pregnancy test, 4 weeks after the WS Visit (see Section 7.2). 
• 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. 
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8.4. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and Other 
Safety Reporting 
The definitions of adverse events (AE) or serious adverse events (SAEs) can be found in 
Section 10.3. Asthma exacerbations should not be recorded in the AE section of the 
eCRF unless they meet the definition of a SAE.  
The definitions of device-related safety events, (adverse device effects [ADEs] and 
serious adverse device effects [SADEs]), can be found in Section 10.7. Device 
deficiencies are covered in Section 10.7. 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant's legally authorised representative). 
The investigator and any qualified designees are responsible for detecting, documenting, 
and reporting events that meet the definition of an AE or SAE and remain responsible for 
following up all AEs that are serious, considered related to the study intervention or the 
study, or that caused the participant to discontinue the study (see Section 7).  
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 10.3. 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• All SAEs will be collected from the start of intervention (Visit 2) until the Exit Visit 
or follow-up visit/call (if applicable) at the time points specified in the SoA 
(Section 1.3). 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 AEs will be collected from the start of intervention until the Exit Visit or the 
follow-up visit/call (if applicable) at the time points specified in the SoA 
(Section 1.3). 
• Medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will be recorded as Medical History/Current Medical 
Conditions (in the eCRF) not as AEs. 
• 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 GSK within 24 hours of it being 
available. 
• Investigators are not obligated to actively seek information on AEs or SAEs after the 
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 GSK. 


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8.4.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AE and/or SAE. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrence.  
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 and non-serious AEs of special 
interest (as defined in Section 8.4.7), will be followed until the event is resolved, 
stabilised, otherwise explained, or 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 GSK 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.  
• GSK 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, Institutional Review Boards 
(IRB)/Independent Ethics Committees (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 GSK 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 (SUSAR) according to local regulatory requirements and GSK policy and 
forwarded to investigators as necessary. 
8.4.5. 
Pregnancy 
• Any female participant who becomes pregnant while participating in the study will 
not receive another dose of study intervention. 
• 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 it to GSK within 24 hours of learning of the female 
participant pregnancy. While pregnancy itself is not considered to be an AE or SAE, 
any pregnancy complication or elective termination of a pregnancy for medical 
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• Abnormal pregnancy outcomes (e.g., spontaneous abortion, foetal 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. 
• 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. 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. 
8.4.6. 
Cardiovascular and Death Events 
For any CV events detailed in Appendix 3 and all deaths, whether or not they are 
considered SAEs, specific CV and Death sections of the CRF will be required to be 
completed. These sections include questions regarding CV (including sudden cardiac 
death) and non-CV death.  
The CV CRF pages are presented as queries in response to reporting of certain CV 
MedDRA terms. The CV information should be recorded in the specific CV section of 
the CRF within one week of receipt of a CV Event data query prompting its completion.   
The Death CRF page is provided immediately after the occurrence or outcome of death is 
reported. Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported. 
8.4.7. 
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 NIAID/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 2.3.1 for additional details. 


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8.4.8. 
Medical Device Deficiencies 
Medical devices (PFS) are being provided for use in this study as a delivery method for 
GSK3511294 or matching placebo injections. To fulfil 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.  
The definition of a Medical Device Deficiency can be found in Section 10.7. 
NOTE: Deficiencies fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Section 10.3 of the protocol.  
8.4.8.1. 
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.  
• The method of documenting Medical Device Incidents is provided in Section 10.7. 
8.4.8.2. 
Follow-up of Medical Device Deficiencies 
• Follow-up applies to all participants, including those who discontinue study 
intervention or the study. 
• 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. 
8.4.8.3. 
Prompt Reporting of Medical Device Deficiencies to 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 by email. 
If email is unavailable, then fax should be utilised. 
• The Sponsor will be the contact for the receipt of device deficiency reports. 
8.4.8.4. 
Regulatory Reporting Requirements for Medical Device Incidents 
• The investigator will promptly report all deficiencies occurring with any medical 
device provided for use in the study in order for the Sponsor to fulfil 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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• 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 
• Blood samples will be collected for measurement of plasma concentrations of 
GSK3511294 as specified in the SoA (Section 1.3).  
• The actual date and time (24-hour clock time) of each sample will be recorded. 
Samples obtained at Visit 2 (Week 0) and Visit 10 (Week 26) should be drawn prior 
to dosing. 
• Collection, processing, storage and shipping procedures are provided in the central 
laboratory manual. 
• 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. 
Genetics and Pharmacogenomics 
China only: Genetic blood samples will not be collected from participants in China. 
A blood sample for 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. 
See Section 10.5 Genetics and Pharmacogenomics for Information regarding genetic 
research. Details on processes for collection and shipment and destruction of these 
samples can be found in the central laboratory manual. Additional country specific 
requirements are specified in the SRM. 
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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
The primary study objective is to test for the superiority of GSK3511294 100 mg SC 
+ SoC following two doses (at Week 0 and at Week 26) compared with placebo + SoC, 
assessed by the annualised rate of clinically significant exacerbations measured over the 
study intervention period of 52 weeks. 
The study will test at a 5% two-sided significance level the null hypothesis that there is 
no difference in annualised exacerbation rate between GSK3511294 and placebo. 
9.2. 
Sample Size Determination 
Approximately
 participants with severe uncontrolled asthma with an eosinophilic 
phenotype will be screened to ensure the randomisation of 
 participants in a 
ratio 
to GSK3511294 
 and matching placebo 
  
9.2.1. 
Sample Size Assumptions 
A sample size of 
participants 
 GSK3511294 to placebo allocation ratio) is based 
on sufficient power to conclude superiority on primary and key secondary endpoints. 
There is a possibility that greater than 
 participants will be randomised in the study 
due to local country requests or requirements, for example, the local competent authority 
specifying a minimum number to be enrolled. 
9.2.1.1. 
Primary Endpoint 
The assumed true annualised rate of exacerbations in the placebo arm is 1.18. Based on 
an assumed true treatment difference of a 
reduction in annualised exacerbation rate 
between GSK3511294 + SoC and placebo + SoC, a sample size of 
 randomised 
participants (
 to GSK3511294, 
to placebo) will provide 99% power for the 
primary endpoint at a 5% two-sided significance level [PASS, 2020]. 
The assumptions for the placebo rate and treatment effect are median values from an 
elicitation exercise which used Phase 3 anti-IL-5/5R historical data (~50% reduction in 
exacerbations) and expert opinion. The sample size is based also on an assumption of 
 
for the dispersion parameter which was observed in two mepolizumab studies [Pavord, 
2012; Ortega, 2014]. It was assumed that
 of participant-years data will be missing 
due to study withdrawal, which is also consistent with mepolizumab studies. 
Based on the assumptions above, the minimum observed treatment difference estimated 
to result in significance at the 5% two-sided significance level is a 
 reduction in 
exacerbations for GSK3511294 + SoC compared with placebo + SoC (rate ratio of 0.73). 
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9.2.1.2. 
Secondary Endpoints 
Table 3 describes the assumptions and power values for two key secondary endpoints. 
The assumptions are obtained from the Phase 3 mepolizumab studies [Pavord, 2012; 
Ortega, 2014; Chupp, 2017]. 
Table 3 
Power Calculations for Key Secondary Endpoints  
Endpoint 
Assumed treatment 
difference (GSK3511294 + 
SoC vs. placebo + SoC) 
Standard 
deviation 
Power 
9.2.2. 
Sample Size Sensitivity 
The sample size and power calculations are based on assumptions about the true values 
for parameters. The power of the study is dependent on changes in these assumptions, in 
particular the assumed annualised exacerbation rates. Table 4 illustrates how changes in 
assumptions for two parameters (placebo + SoC annualised exacerbation rate and 
treatment effect) affect the power. 
Table 4 
Estimates of Power for Assumed Placebo + SoC Exacerbation 
Rate and Assumed Percent Reduction with GSK3511294 + SoC 
Compared with Placebo + SoC 
Percent reduction in 
annualised exacerbation rate 
with GSK3511294 + SoC vs. 
placebo + SoC 
Placebo + SoC annualised exacerbation rate 
9.2.3. 
Sample Size Re-estimation or Adjustment 
There will be no sample size re-estimation. 
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9.3. 
Analysis Sets 
For the purpose of analyses, the following populations are defined  
Further populations to be used for other assessments will be defined in the statistical 
analysis plan (SAP). 
9.4. 
Statistical Analysis 
The SAP will be finalised prior to un-blinding and it 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. 
9.4.1. 
General Considerations 
The study will test at a 5% two-sided significance level the null hypothesis that there is 
no difference in annualised exacerbation rate between GSK3511294 + SoC and placebo 
+ SoC. 
Population 
Description 
Screened 
All participants who sign the ICF. 
Enrolled 
All participants who entered the study. 
 
Note screening failures (who never passed screening even if 
rescreened) and participants screened but never enrolled into the 
study (Met eligibility but not needed) are excluded from the 
Enrolled analysis set as they did not enter the study. 
 
Randomised 
All participants who were randomly assigned to study 
intervention in the study. 
Full Analysis Set (FAS) 
All randomised participants who receive at least one dose of 
study intervention. Participants will be analysed according to the 
intervention they are allocated at randomisation. This population 
will serve as the primary population for analyses of efficacy 
endpoints. 
Safety 
All randomised participants who receive at least one dose of 
study intervention. Participants will be analysed according to the 
intervention they are allocated at randomisation, unless a 
participant receives a different intervention to the randomised 
intervention at all protocol-defined administrations, in which case 
the participant will be analysed according to the actual 
intervention they received. This population will serve as the 
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9.4.2. 
Primary Endpoint 
9.4.2.1. 
Main Estimand 
Target Participant 
Population 
Adult and adolescent participants with severe uncontrolled asthma with 
an eosinophilic phenotype following the strategy outlined below for 
dealing with the main intercurrent events that are anticipated. 
Primary Endpoint 
Annualised rate of clinically significant exacerbations over 52 weeks. 
Clinically significant exacerbations are defined in Section 8.2.2. 
Intercurrent events 
and strategies 
The anticipated key intercurrent events and corresponding strategies 
are: 
a) Study intervention discontinuation due to reasons unrelated to the 
COVID-19 pandemic: 
 
 
b) Study intervention discontinuation due to reasons related to the 
COVID-19 pandemic: 
 
 
c) Change in maintenance therapy or use of prohibited medications 
(listed in Section 6.9.2): 
 
 
Summary measure 
Ratio of the rates of exacerbations between GSK3511294 + SoC and 
placebo + SoC. 
Analysis Method 
The primary analysis of the annualised rate of clinically significant 
exacerbations will use a negative binomial model. Covariates included 
will be baseline maintenance OCS therapy (OCS vs. no OCS), baseline 
ICS dose (medium or high dose, see Appendix 10), region, number of 
exacerbations in the year prior to the study, baseline % predicted FEV1 
and treatment group with loge(time in study in years) as an offset 
variable. The rate ratio and 95% confidence interval (CI) will be provided 
for the comparison between GSK3511294 + SoC and placebo + SoC. 
Handling of 
missing data and 
intercurrent events 
leading to 
exclusion of data 
Missing data or data excluded due to intercurrent events will be handled 
as follows: 
a) 
 
 
 
 
 
 
 
 
 
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Sensitivity analyses will be conducted to investigate the conclusions 
from deviations from these assumptions regarding missing data for (b) 
above. 
 
 
 
 
 
 
 
9.4.3. 
Secondary Endpoints 
9.4.3.1. 
Main Estimands 
Target Participant 
Population 
Adult and adolescent participants with severe uncontrolled asthma with 
an eosinophilic phenotype following the strategy outlined below for 
dealing with the main intercurrent events that are anticipated. 
Secondary 
Endpoints 
• Change from baseline in SGRQ total score at Week 52  
• Change from baseline in ACQ-5 score at Week 52 
• Change from baseline in pre-bronchodilator FEV1 at Week 52 
Intercurrent events 
and strategies 
The anticipated key intercurrent events and corresponding strategies: 
a) Study intervention discontinuation due to reasons unrelated to the 
COVID-19 pandemic:
 
 
b) Study intervention discontinuation due to reasons related to the 
COVID-19 pandemic: 
 
 
c) Change in maintenance therapy or use of prohibited medications 
(listed in Section 6.9.2): 
 
 
Summary measure 
Difference in means between GSK3511294 + SoC and placebo + SoC. 
Analysis Method 
The analysis will be performed using a repeated measures mixed model. 
Covariates included will be baseline, region, baseline maintenance OCS 
therapy (OCS vs. no OCS), baseline ICS dose (medium or high dose, 
see Appendix 10), number of exacerbations in the year prior to the 
study, baseline % predicted FEV1,treatment group and visit, plus 
interaction terms for visit by baseline and visit by treatment group. The 
difference in means and 95% CI will be provided for the comparison 
between GSK3511294 + SoC and placebo + SoC. 
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Handling of 
missing data and 
intercurrent events 
leading to 
exclusion of data 
Missing data or data excluded due to intercurrent events will be handled 
as follows: 
a) 
b) 
Sensitivity analyses will be conducted to investigate the conclusions 
from deviations from these assumptions regarding missing and excluded 
data for (b) above. 
 
 
 
 
 
 
The annualised rate of exacerbations requiring hospitalisation and/or ED visit over 
52 weeks will be evaluated using the same strategy as that described for the primary 
endpoint (see Section 9.4.2). 
9.4.4. 
Other Endpoints 
Full details of analysis methods to be used for other endpoints will be provided in the 
SAP. 
9.4.5. 
Safety Analyses 
All safety analyses will be performed on the Safety Population. Summaries of data will 
report data according to the nominal visit for which it was recorded. Occurrence of AEs, 
SAEs, AESIs, laboratory data, vital signs, and ECGs will be included in data displays in 
the form of listings, frequency tables, summary statistics, graphs, and statistical analyses 
where appropriate.  
Adverse Events (AEs) will be coded using the standard Medical Dictionary for 
Regulatory Activities (MedDRA) and will be grouped by system organ class (SOC). AEs 
will be summarised by frequency and percentage of participants, by SOC and preferred 
term within each treatment group. Separate summaries will be presented for all AEs, 
drug-related AEs, serious AEs (SAEs), AEs leading to permanent discontinuation of 
study intervention or withdrawal from study and for any AEs of special interest. 
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9.5. 
Multiple Testing Strategy 
The treatment comparison of interest for the primary and secondary endpoints is 
GSK3511294 100 mg SC + SoC vs placebo + SoC. A fixed sequence hierarchical testing 
procedure will be used to provide strong control of Type I error for multiplicity arising 
from the primary and multiple secondary endpoints. This will be carried out using a 
stepdown closed testing procedure where inference for an endpoint in the predefined 
hierarchy will be dependent on statistical significance having been achieved for the 
previous endpoints in the hierarchy. For example, for the primary endpoint, GSK3511294 
+ SoC will be compared to placebo + SoC at a two-sided 5% level. The next endpoint in 
the hierarchy (i.e. the first secondary endpoint) will be tested only if the test for the 
primary endpoint is significant at the two-sided 5% level. Testing will continue down the 
hierarchy for the remaining endpoints in an equivalent manner only if the previous 
endpoint in the hierarchy achieves statistical significance. 
The hierarchy of the primary and secondary endpoints to be tested is as follows: 
1. Annualised rate of clinically significant exacerbations over 52 weeks 
2. Change from baseline in SGRQ at Week 52 
3. Change from baseline in ACQ-5 at Week 52 
4. Change from baseline in clinic pre-bronchodilator FEV1 at Week 52 
5. Annualised rate of exacerbations requiring hospitalisation and/or ED visit over 
52 weeks 
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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 
10.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide GSK with sufficient, accurate financial 
information as requested to allow GSK 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. 


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10.1.3. 
Informed Consent Process 
• The investigator or his/her representative will explain the nature of the study to 
the participant or their legally authorised representative and answer all questions 
regarding the study.  
• Participants must be informed that their participation is voluntary. Participants or 
their legally authorised representative will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study centre.  
• For participants 12-17 years old, written informed assent must be obtained in 
addition to the legally authorised representative(s)' consent. Assent will be 
obtained in accordance with applicable country or IRB/Ethics Committee 
regulations. Written informed consent will be obtained from participants turning 
18 years of age to continue participation in the study.  
• The medical record must include a statement that written informed consent/assent 
was obtained before the participant was enrolled in the study and the date the 
written consent/assent was obtained. The authorised person obtaining the 
informed consent/assent must also sign the ICF. 
• Participants must be re-consented/re-assented 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 legally 
authorised representative.  
Participants who are rescreened are required to provide consent/assent and sign a new 
ICF/assent form. 
GSK (alone or working with others) may use a participant’s coded study data and 
samples and other information to carry out this study; understand the results of this study; 
learn more about GSK3511294 or about the study disease; publish the results of these 
research efforts; work with government agencies or insurers to have GSK3511294 
approved for medical use or approved for payment coverage.  
10.1.4. 
 Data Protection 
• Participants will be assigned a unique identifier by GSK. Any participant records 
or datasets that are transferred to GSK will contain the identifier only; participant 
names or any information which would make the participant identifiable will not 
be transferred.  
• The participant must be informed that his/her personal study-related data will be 
used by GSK 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 authorised personnel appointed by 
GSK, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 


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10.1.5. 
Committees Structure 
An Independent Data Monitoring Committee (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.  
10.1.6. 
Dissemination of Clinical Study Data 
• Where required by applicable regulatory requirements, an investigator signatory 
will be identified for the approval of the clinical study report. The investigator 
will be provided reasonable access to statistical tables, figures, and relevant 
reports and will have the opportunity to review the complete study results at a 
GSK site or other mutually agreeable location. 
• GSK will also provide all investigators who participated in the study with a 
summary of the study results and will tell the investigators what treatment their 
patients received. The investigator(s) is/are encouraged to share the summary 
results with the study participants, as appropriate. 
• Under the framework of the SHARE initiative, GSK intends to make anonymised 
participant-level data from this trial 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 trial participants are 
used to maximum effect in the creation of knowledge and understanding. 
Requests for access may be made through www.clinicalstudydatarequest.com. 
• GSK will provide the investigator with the randomisation codes 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 anonymised patient-level data from this trial 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 trial participants are used to maximum effect in the creation of 
knowledge and understanding 
• A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge. 


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10.1.7. 
Data Quality Assurance 
• All participant data relating to the study will be recorded on printed or electronic 
CRF 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 CRF.  
• Guidance on completion of CRFs will be provided in the CRF Guidelines. 
• Quality tolerance limits (QTLs) will be pre-defined in the QTL Plan 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 
summarised in the clinical study report. 
• The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents.  
• Monitoring details describing strategy 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 Monitoring Plan. 
• GSK or a designee is responsible for the data management of this study including 
quality checking of the data.  
• GSK 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 longer retention period. No records may be 
destroyed during the retention period without the written approval of GSK. No 
records may be transferred to another location or party without written 
notification to GSK.  
10.1.8. 
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 CRF 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 
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• Definition of what constitutes source data and its origin can be found in [Source 
Data Acknowledgment]. 
• The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF. 
• Study monitors will perform ongoing source data verification to confirm that data 
entered into the CRF by authorised 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.  
10.1.9. 
Study and Site Start and Closure 
First Act of Recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the first site open and will be the study start date. 
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 
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 of participants (evaluated after a reasonable amount 
of time) by the investigator 
• If the study is prematurely terminated or 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 
suspension, as specified by the applicable regulatory requirements. The 
investigator shall promptly inform the participant and should assure appropriate 
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10.1.10. 
Publication Policy 
• The results of this study may be published or presented at scientific meetings. If 
this is foreseen, the investigator agrees to submit all manuscripts or abstracts to 
the Sponsor before submission. This allows the Sponsor to protect proprietary 
information and to provide comments.  
• GSK will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, GSK will generally 
support publication of multicentre 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. 


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10.2. Appendix 2: Clinical Laboratory Tests 
All protocol required laboratory assessments must be conducted in accordance with the 
Laboratory Manual and the SoA (Section 1.3).  
Local laboratory results may be required in the event that the central laboratory results 
are not available in time for either study intervention administration and/or response 
evaluation to be performed – for example: when results from screening Visit 1 should be 
available before dosing on Visit 2, or at any time when a participant is unwell and results 
are required urgently.  
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 
in the CRF.  
 
 
 
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. 
For China sites the urine specimen may be sent to the central laboratory for routine 
urinalysis instead of performing a local urine dipstick. Urinalysis should be performed at 
Visit 1 so that results are available before randomisation at Visit 2. Urine pregnancy test 
must still be performed at the site. 
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Table 5 
Protocol-Required Safety Laboratory Tests 
NOTES: 
 
 
 
 
 
 
 
 
.  
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 and Section 10.6 All events of ALT 3 × upper 
limit of normal (ULN) and total bilirubin 2 × ULN (>35% direct bilirubin) or ALT 3 × ULN and 
international normalised 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. 
4. Local urine testing will be standard for the protocol unless serum testing is required by local 
regulation or IRB/IEC. 
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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 (haematology, 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 conditions 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 which 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 
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalisation for signs/symptoms of the disease under study, 
death due to progression of disease, etc.).  
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 hospitalisation or prolongation of existing hospitalisation 
• In general, hospitalisation 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 
hospitalisation are AE. If a complication prolongs hospitalisation or fulfils any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalisation” occurred or was necessary, the AE should be considered serious. 
• Hospitalisation for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 


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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: 
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, diarrhoea, 
influenza, and accidental trauma (e.g. sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
e. Is a congenital anomaly/birth defect  
f. Other situations: 
• Possible Hy’s Law case: ALT≥3xULN AND total bilirubin ≥2xULN (>35% direct 
bilirubin) or international normalised ratio (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 jeopardise 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. 
o 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 
• Revascularisation 


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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: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities. 
• Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities. 
• Severe: An event that prevents normal everyday activities. An AE that is assessed 
as severe should not be confused with an SAE. Severe is a category utilised for 
rating the intensity of an event; and both AE and SAE can be assessed as severe. 
• An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes 
as described in the definition of an SAE, NOT when it is rated as severe. 
 
Assessment of Causality 
The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. 
• 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. 
• The investigator will use clinical judgment to determine the relationship. 


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Assessment of Causality 
• Alternative causes, such as underlying diseases, 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 recognised 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 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 and send/fax it 
to the Medical Monitor. 
• 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 or the SAE coordinator by telephone. 
• 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 or the SAE coordinator. 
• 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. 
o 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.  
o Females on HRT and whose menopausal status is in doubt will be required to use 
one of the non-oestrogen 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 sterilisation methods (for the purpose of this study) include: 
o Documented hysterectomy 
o Documented bilateral salpingectomy 
o 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 Nonchildbearing 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): 
a) Documented hysterectomy 
b) Documented bilateral salpingectomy 
c) 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) 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. 
b) 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: 
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. 
• Implantable progestogen-only hormone contraception associated with inhibition of 
ovulationc 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS)c 
• Bilateral tubal occlusion 
• Azoospermic partner (vasectomised or due to a medical cause) 
Azoospermia is a highly effective contraceptive method provided that the partner 
is the sole sexual partner of the woman of childbearing potential and the absence 
of sperm has been confirmed. If not, an additional highly effective method of 


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CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
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. 
• Combined (oestrogen- and progestogen-containing) hormonal contraception 
associated with inhibition of ovulationc 
• oral 
• intravaginal 
• transdermal 
• injectable 
• Progestogen-only hormone contraception associated with inhibition of ovulationc 
• oral 
• injectable 
• Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the 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. 
a. Contraceptive use by men or women should be consistent with local regulations regarding 
the use of contraceptive methods for those participating in clinical studies. 
b. Failure rate of <1% per year when used consistently and correctly. Typical use failure rates 
differ from those when used consistently and correctly. 
c. 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 (LAM) are not 
acceptable methods of contraception. Male condom and female condom should not be used 
together (due to risk of failure from friction) 
Male participants: As GSK3511294 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.  


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10.5. Appendix 5: Genetics 
USE/ANALYSIS OF DNA 
China only: No genetic samples will be collected from participants in China. 
• 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 
aetiology; 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 GSK3511294 or asthma with an 
eosinophilic phenotype and related diseases. They may also be used to develop 
tests/assays including diagnostic tests) related to GSK3511294 or study interventions 
of this drug class, and indication. Genetic research may consist of the analysis of one 
or more candidate genes or the analysis of genetic markers throughout the genome or 
analysis of the entire genome (as appropriate). 
• Additional analyses of DNA samples may be conducted if it is hypothesised that this 
may help further understand the clinical data.  
• The samples may be analysed as part of a multi-study assessment of genetic factors 
involved in the response to GSK3511294 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 GSK3511294 (or study interventions 
of this class) or asthma with an eosinophilic phenotype continues but no longer than 
15 years after the last participant last visit or other period as per local requirements. 


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10.6. Appendix 6: Liver Safety: Required Actions, Monitoring and Follow-
up Assessments 
Liver Chemistry Stopping Criteria and Increased Monitoring Criteria are designed 
to assure participant safety and evaluate liver event aetiology. 
Liver Chemistry Stopping criteria and Required Follow-up Assessments  
Liver Chemistry Stopping Criteria  
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 
an SAE data collection tool if the event also 
meets the criteria for an SAE2 
• Perform follow-up assessments as 
described in the Follow-up Assessment 
column. 
• Monitor the participant until liver chemistries 
resolve, stabilise, or return to within 
baseline (see MONITORING below) 
MONITORING: 
If ALT 3xULN AND total bilirubin 2xULN or 
INR >1.5:  
• 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 criteria.5 
• Obtain a serum creatine phosphokinase 
(CPK), lactate dehydrogenase (LDH), 
gamma glutamyl transferase [GGT], 
glutamate dehydrogenase [GLDH], and 
serum albumin. 
• Fractionate bilirubin, if total 
bilirubin2xULN 


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Liver Chemistry Stopping Criteria  
• Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, total bilirubin and 
INR) and perform liver event follow-up 
assessments within 24 hours 
• Monitor participant twice weekly until liver 
chemistries resolve, stabilise or return to 
within baseline 
• A specialist or hepatology consultation is 
recommended 
For all other stopping 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 participant weekly until liver 
chemistries resolve, stabilise or return to 
within baseline 
RESTART/RECHALLENGE 
• Do not restart/rechallenge participant with 
study intervention since it is not allowed 
per protocol; continue participant in the 
study for any protocol specified follow-up 
assessments. 
• 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 
GSK3511294 leads to lowering of 
eosinophils. 
• Record the appearance or worsening of 
clinical symptoms of liver injury, or 
hypersensitivity, on 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: 
• Anti-nuclear antibody, anti-smooth 
muscle antibody, Type 1 anti-liver kidney 
microsomal antibodies, and quantitative 
total immunoglobulin G (IgG) or gamma 
globulins. 
• Serum acetaminophen 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)  
• Liver imaging (ultrasound, magnetic 
resonance, or computerised tomography) 
to evaluate liver disease; complete Liver 
Imaging form 


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Liver Chemistry Stopping Criteria  
• 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:  
• 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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Liver Chemistry Increased Monitoring Criteria with Continued Study Intervention 
Liver Chemistry Increased Monitoring Criteria and Actions with Continued Study 
Intervention 
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. 
 
• Notify the GSK Medical Monitor within 24 hours 
of learning of the abnormality to discuss 
participant safety.  
• Participant can continue study intervention. 
• 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. 
• If at any time participant meets the liver chemistry 
stopping criteria, proceed as described above 
• 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.  
• 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. 
References 
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 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  
• 
An 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. 
• 
An adverse device effect (ADE) is 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. 


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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. 
• 
Inpatient or prolonged hospitalisation. Planned hospitalisation 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. 
c. 
Led to foetal distress, foetal 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 adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event. 
• 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 a 
serious adverse device effect 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 information supplied by the manufacturer. 


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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. 
• 
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. 
o 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. 
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: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities. 
• Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities. 
• Severe: An event that prevents normal everyday activities. An AE that is assessed 
as severe should not be confused with an SAE. Severe is a category used for rating 
the intensity of an event; both AEs and SAEs can be assessed as severe. 
• An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes 
as described in the definition of an SAE, not when it is rated as severe. 


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Assessment of Causality 
• The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE/device deficiency 
• 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. 
• The investigator will use clinical judgment to determine the relationship. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• The investigator will also consult the IB 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. 
• New or updated information will be recorded in the originally completed CRF. 
• 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 Medical Monitor or the SAE coordinator by telephone. 
• 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 Medical Monitor or the SAE coordinator. 
• 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. 


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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 fulfil the legal responsibility to notify 
appropriate regulatory authorities and other entities about certain safety 
information relating to medical devices being used in clinical studies.  
• 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. 
• Contacts for SAE reporting can be found at the beginning of this protocol on the 
Sponsor/Medical Monitor Contact Information page. 
 
 


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10.8. Appendix 8: Anaphylaxis Criteria 
Joint National Institute of Allergy and Infectious Disease (NIAID)/ Food Allergy and 
Anaphylaxis Network (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., generalised hives, pruritus or flushing, swollen lips-
tongue-uvula), and at least one of the following: 
a) Respiratory compromise (e.g., dyspnoea, 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., generalised hives, itch-flush, 
swollen lips-tongue-uvula) 
b) Respiratory compromise (e.g., dyspnoea, 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 mm Hg or greater than 30% decrease from that 
person’s baseline 
 
 


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10.9. 
 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party 
copyright laws and therefore have been excluded.
CCI


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10.10. Appendix 10: Low, Medium and High Daily Doses of Inhaled 
Corticosteroids 
Daily medium and high dose ICS options for adults and adolescents (12 years and older) 
are shown in Figure 1.  
Figure 1 
Low, medium and high daily doses of inhaled corticosteroids  
  
Reproduced with permission from Global Initiative for Asthma [GINA, 2020]). 
• 
The medium to high dose for Japanese adolescent subjects 15 years or younger will be ≥200 µg/day of FP 
or other ICSs of equivalent dose) as per the Japanese asthma pediatric guidelines. 
• 
Updates as per GINA 2021: 
• 
Beclometasone dipropionate (pMDI, extrafine particle, HFA) changed to Beclometasone dipropionate (DPI or 
pMDI, extrafine particle, HFA) 
• 
Budesonide (DPI) changed to Budesonide (DPI, or pMDI, standard particle, HFA) 
• 
Mometasone Furoate (DPI) Low, Medium and High total daily ICS doses reference to product information 
as it depends on DPI device.


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10.11. Appendix 11: Recommended Measures Related to COVID-19 
Pandemic 
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. 
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 Heath 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.  
• 
Spirometry should not be conducted for participants with confirmed/suspected 
COVID-19. 
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 


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responsibility of the investigator to inform GSK when this occurs and to 
document in source notes. 
• 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 asthma 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 Table 6.   
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. 


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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), 
a maximum dose interval of 28 weeks may be used.  
• 
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). 
Data Management/Monitoring: 
• The medical problems and healthcare utilisation worksheet may be transmitted from 
and to the investigator by electronic mail and or conventional mail. If copies/scans of 
the paper worksheet are sent to the investigator by electronic mail, the participant 
should be instructed to maintain the original documents and to return them to the site 
when a visit to the site will be allowed. 
• If the eDiary device 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 Principal Investigator (PI) is 
responsible for ensuring that the data within the eCRF casebook and any other data 
sources utilised 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. 


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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 6. 
• 
White boxes represent activities/assessments that are to be done during visits to the 
clinical study centre (pre-screening Visit 0, screening Visit 1, randomisation Visit 2, 
Visit 3, Visit 10, Visit 11 Exit Visit 17, and WS Visit if applicable). 
• 
Grey boxes represent activities/assessments during study visits (Visits 4-9, Visits 
12-16, and the FU Visit) that may be conducted by a home healthcare professional, 
where applicable country and local regulations and infrastructure allow (at the 
discretion of the investigator, based on safety and tolerability). 
• 
The FU Visit may be conducted as a remote/home visit or as a phone call.  
• 
During home visits, the scheduled collection of samples for laboratory and other 
assessments may be performed by a home healthcare professional. 
 


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Table 6 
Schedule of Activities (SoA) Indicating Assessments that may be Conducted Outside of a Clinical Study 
Site 
Protocol Activity 
Pre-
Screenin
g 
Screenin
g/Run-in 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-
up 
/Withdra
w  
(7 days) 
Notes 
Visit 
V0 a 
Visit 1 a V2b 
R* V3 V4 V5 V6 V7 V8 V9 V1
0 
V1
1 
V1
2 
V1
3 
V1
4 
V1
5 
V1
6 
Exit 
V17 WSc FU 
R* =Randomisation 
WS=Withdraw from study visit  
(see footnote c) 
FU=Follow-up visit/call (only required for 
participants not entering OLE study) 
Study Week 
-8 to -6 -6 to -1 
0 
2 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 
26 
or 
52 
56 
Study Day 
-56 to -
42 
-42 to -7 1 14 28 56 84 112 140 168 182 196 224 252 280 308 336 364 
 
392 
General Eligibility Assessments 
Informed consent 
a 
X 
(X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Conduct at Visit 1 if not completed at Visit 
0; See footnote a.  
Genetic sample 
informed consent 
d 
X 
(X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Conduct at Visit 1 if not completed at Visit 
0; See footnote d. 
Demography data 
collections  
X 
(X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Conduct at Visit 1 if not completed at Visit 
0; All females must be assessed at Visit 1 
to determine childbearing potential. 
Inclusion/Exclusio
n criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Historical blood 
eosinophil count 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
See footnote e. 
Medical history  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Include cardiovascular (CV), CV risk 
factors, asthma, exacerbations, 
vasculitis, allergies and anaphylaxis. 
Smoking status 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Protocol Activity 
Pre-
Screenin
g 
Screenin
g/Run-in 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-
up 
/Withdra
w  
(7 days) 
Notes 
Visit 
V0 a 
Visit 1 a V2b 
R* V3 V4 V5 V6 V7 V8 V9 V1
0 
V1
1 
V1
2 
V1
3 
V1
4 
V1
5 
V1
6 
Exit 
V17 WSc FU 
R* =Randomisation 
WS=Withdraw from study visit  
(see footnote c) 
FU=Follow-up visit/call (only required for 
participants not entering OLE study) 
Study Week 
-8 to -6 -6 to -1 
0 
2 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 
26 
or 
52 
56 
Study Day 
-56 to -
42 
-42 to -7 1 14 28 56 84 112 140 168 182 196 224 252 280 308 336 364 
 
392 
Parasite 
screening 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Only required in regions with high-risk or 
for participants who have visited a high-
risk region in the past 6 months. Use 
local laboratories for this test. For details 
refer to study reference manual (SRM). 
eDiary registration 
and training 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Conduct thorough eDiary training at 
Screening Visit 1 and throughout the 
study on as-needed basis.   
Randomisation 
criteria 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assess prior to randomisation; see 
footnote e. 
Efficacy Assessments 
Review for 
exacerbations 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X Collection of exacerbations at Visit 1 is 
historical data. 
Spirometry (pre- 
and post-
bronchodilator 
FEV1)h 
 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
 
FEV1=Forced expiratory volume in 1 
second; Spirometry should not be 
conducted for participants with 
confirmed/suspected COVID-19 (see 
Section 8.2.3). 
ACQ-5 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
ACQ-5=Asthma Control Questionnaire-5 


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Protocol Activity 
Pre-
Screenin
g 
Screenin
g/Run-in 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-
up 
/Withdra
w  
(7 days) 
Notes 
Visit 
V0 a 
Visit 1 a V2b 
R* V3 V4 V5 V6 V7 V8 V9 V1
0 
V1
1 
V1
2 
V1
3 
V1
4 
V1
5 
V1
6 
Exit 
V17 WSc FU 
R* =Randomisation 
WS=Withdraw from study visit  
(see footnote c) 
FU=Follow-up visit/call (only required for 
participants not entering OLE study) 
Study Week 
-8 to -6 -6 to -1 
0 
2 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 
26 
or 
52 
56 
Study Day 
-56 to -
42 
-42 to -7 1 14 28 56 84 112 140 168 182 196 224 252 280 308 336 364 
 
392 
HRQoL: PRO and Health Outcomes Assessments 
SGRQ 
 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
 
SGRQ=St. George’s Respiratory 
Questionnaire  
Complete 
ADSD/ANSD 
 
=========   daily   
=========→ 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
ADSD/ANSD=Asthma Daily/Nightly 
Symptom Diary; To be completed daily 
during Run-in phase through Week 16, 
then to be completed for 1 full week 
during the week preceding each visit 
thereafter. 
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Protocol Activity 
Pre-
Screenin
g 
Screenin
g/Run-in 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-
up 
/Withdra
w  
(7 days) 
Notes 
Visit 
V0 a 
Visit 1 a V2b 
R* V3 V4 V5 V6 V7 V8 V9 V1
0 
V1
1 
V1
2 
V1
3 
V1
4 
V1
5 
V1
6 
Exit 
V17 WSc FU 
R* =Randomisation 
WS=Withdraw from study visit  
(see footnote c) 
FU=Follow-up visit/call (only required for 
participants not entering OLE study) 
Study Week 
-8 to -6 -6 to -1 
0 
2 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 
26 
or 
52 
56 
Study Day 
-56 to -
42 
-42 to -7 1 14 28 56 84 112 140 168 182 196 224 252 280 308 336 364 
 
392 
Safety Assessments 
Concomitant 
Medication 
Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Ensure maintenance asthma medications 
from the year prior to Screening Visit 1, 
all medications within the 3 months prior 
to Screening Visit 1 and all current 
medications are reviewed. 
Physical 
Examination 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Include height and weight for the 
complete physical exam at Screening 
Visit 1. Height can be omitted for 
subsequent visits. 
Vital Signs 
 
X 
X 
 
 
X 
 
 
X 
 
X 
X 
 
 
X 
 
X 
X 
X 
 
 
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Protocol Activity 
Pre-
Screenin
g 
Screenin
g/Run-in 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-
up 
/Withdra
w  
(7 days) 
Notes 
Visit 
V0 a 
Visit 1 a V2b 
R* V3 V4 V5 V6 V7 V8 V9 V1
0 
V1
1 
V1
2 
V1
3 
V1
4 
V1
5 
V1
6 
Exit 
V17 WSc FU 
R* =Randomisation 
WS=Withdraw from study visit  
(see footnote c) 
FU=Follow-up visit/call (only required for 
participants not entering OLE study) 
Study Week 
-8 to -6 -6 to -1 
0 
2 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 
26 
or 
52 
56 
Study Day 
-56 to -
42 
-42 to -7 1 14 28 56 84 112 140 168 182 196 224 252 280 308 336 364 
 
392 
12-lead ECG 
 
X 
X 
X 
 
 
 
 
 
 
X 
X 
 
 
 
 
 
X 
X 
 
ECG must be performed and assessed 
pre-dose. Twelve-lead ECG central over-
read values should be used at all visits 
with the exception of Visit 2 and Visit 10 
where 12-lead ECG machine read values 
should be used. 
AE/SAE 
Assessment 
X g 
X g 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X AE=Adverse events; SAE=Serious 
adverse events; see footnote g. 
Laboratory Assessments  
Total IgE 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test 
(WOCBP only) 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Serum pregnancy test should be done at 
screening Visit 1 and Exit Visit/ Withdraw 
from study visit; urine pregnancy tests 
should be done for all other 
assessments; WOCBP=Women of 
childbearing potential; See Section 8.3.5 
for additional information. 
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Protocol Activity 
Pre-
Screenin
g 
Screenin
g/Run-in 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-
up 
/Withdra
w  
(7 days) 
Notes 
Visit 
V0 a 
Visit 1 a V2b 
R* V3 V4 V5 V6 V7 V8 V9 V1
0 
V1
1 
V1
2 
V1
3 
V1
4 
V1
5 
V1
6 
Exit 
V17 WSc FU 
R* =Randomisation 
WS=Withdraw from study visit  
(see footnote c) 
FU=Follow-up visit/call (only required for 
participants not entering OLE study) 
Study Week 
-8 to -6 -6 to -1 
0 
2 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 
26 
or 
52 
56 
Study Day 
-56 to -
42 
-42 to -7 1 14 28 56 84 112 140 168 182 196 224 252 280 308 336 364 
 
392 
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Protocol Activity 
Pre-
Screenin
g 
Screenin
g/Run-in 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-
up 
/Withdra
w  
(7 days) 
Notes 
Visit 
V0 a 
Visit 1 a V2b 
R* V3 V4 V5 V6 V7 V8 V9 V1
0 
V1
1 
V1
2 
V1
3 
V1
4 
V1
5 
V1
6 
Exit 
V17 WSc FU 
R* =Randomisation 
WS=Withdraw from study visit  
(see footnote c) 
FU=Follow-up visit/call (only required for 
participants not entering OLE study) 
Study Week 
-8 to -6 -6 to -1 
0 
2 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 
26 
or 
52 
56 
Study Day 
-56 to -
42 
-42 to -7 1 14 28 56 84 112 140 168 182 196 224 252 280 308 336 364 
 
392 
Genetics sample 
 
 
=============  
The genetics sample can be 
collected at Visit 2 or any visit 
after 
=============→ 
 
 
See footnote d. 
Study intervention 
Administer study 
intervention 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Study intervention will only be 
administered in the clinic. Any scheduled 
assessments or sample draws should be 
performed beforehand. Monitor 
participant for at least 2h after 
administration (see Section 6.5). 
eCRF/worksheets/other 
Dispense Rescue 
medication  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
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Protocol Activity 
Pre-
Screenin
g 
Screenin
g/Run-in 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-
up 
/Withdra
w  
(7 days) 
Notes 
Visit 
V0 a 
Visit 1 a V2b 
R* V3 V4 V5 V6 V7 V8 V9 V1
0 
V1
1 
V1
2 
V1
3 
V1
4 
V1
5 
V1
6 
Exit 
V17 WSc FU 
R* =Randomisation 
WS=Withdraw from study visit  
(see footnote c) 
FU=Follow-up visit/call (only required for 
participants not entering OLE study) 
Study Week 
-8 to -6 -6 to -1 
0 
2 
4 
8 12 16 20 24 26 28 32 36 40 44 48 52 
26 
or 
52 
56 
Study Day 
-56 to -
42 
-42 to -7 1 14 28 56 84 112 140 168 182 196 224 252 280 308 336 364 
 
392 
Provide 
worksheet 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
The worksheet is a medical problems and 
healthcare utilisation worksheet. 
Review worksheet 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
eDiary close out  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
 
Complete eCRF 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
eCRF=electronic Case Report Form 
a. 
Informed Consent must be obtained prior to initiating any study assessments. Pre-screening Visit 0 can occur any time from 0 to 14 days before Screening Visit 1. 
b. 
Randomisation Visit 2 is 1 week after Screening Visit 1 but can be extended to up to 6 weeks after Visit 1 if, for example, a participant has an exacerbation during the run-in 
period. Results from Screening Visit 1 procedures must be available for review of randomisation criteria.  
c. 
If a participant withdraws from the study, then the Withdraw from Study (WS) 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 and pregnancy testing.  
d. 
Informed Consent for optional genetics research must be obtained before collecting a sample. China only:  Genetic Informed Consent will not be collected from participants in 
China. Genetic blood samples will not be collected from participants in China. 
e. 
To be randomised, participants without a historical blood eosinophil count of ≥300 cells/µL in the 12 months prior to Screening Visit 1, must have a blood eosinophil count of ≥150 
cells/µL at Screening Visit 1. If the Screening Visit test result does not meet the blood eosinophil count eligibility criteria, the laboratory  assessment may be repeated, at the 
discretion of the investigator, if it is judged to be likely in the eligible range for study inclusion within the run-in period prior to Visit 2. 
f. 
 
 
. 
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g. 
SAEs must be collected from signing of Informed Consent if considered related to study procedures. 
h. 
If a patient fails the protocol-specified reversibility criterion or FEV1 inclusion criteria, spirometry retest is allowed during the run-in period. 
 


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10.12. Appendix 12: Country-specific requirements 
 
 
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10.13. Appendix 13: Abbreviations and Trademarks 
Abbreviations 
ACQ 
Asthma Control Questionnaire 
ADA 
Anti-drug antibody 
AE 
Adverse event 
ALT 
Alanine transaminase 
ANA 
Antinuclear antibodies 
ANCA 
Anti-neutrophil cytoplasmic antibody 
ADE 
Adverse device events 
ADSD 
Asthma Daily Symptom Diary 
ANSD 
Asthma Nightly Symptom Diary 
Anti-HBc 
Hepatitis B core antibody 
Anti-IL-5 
Anti-Interleukin-5  
Anti-IL-5R 
Anti-Interleukin-5 receptor 
AST 
Aspartate aminotransferase 
BiPAP 
Bilevel positive airway pressure 
BP 
Blood pressure 
BUN 
Blood urea nitrogen 
CI 
Confidence interval 
CIOMS 
Council for International Organizations of Medical 
Sciences 
COVID-19 
Coronavirus disease 2019 
cm 
Centimetre 
CONSORT 
Consolidated Standards of Reporting Trials 
CPAP 
Continuous positive airway pressure 
CPK 
Creatine phosphokinase 
CRF 
Case report form 
CS 
Corticosteroid 
CSR 
Clinical study report 
CTFG 
Clinical Trial Facilitation Group 
CV 
Cardiovascular 
DNA 
Deoxyribonucleic acid 
eCRF 
Electronic case report form 
ECG 
Electrocardiogram 
ED 
Emergency department 
eDiary 
Electronic diary 
EDTA 
Ethylenediaminetetraacetic acid or disodium edetate 
EGPA 
Eosinophilic granulomatosis with polyangiitis 
FAAN 
Food Allergy and Anaphylaxis Network 
FAS 
Full Analysis Set 
FEV1 
Forced expiratory volume in 1 second 
FP 
Fluticasone propionate 
FSH 
Follicle stimulating hormone 
FTIH 
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FVC 
Forced vital capacity 
g 
Grams  
GCP 
Good Clinical Practice 
GCSP 
Global Clinical Safety and Pharmacovigilance 
 
 
GINA 
Global Initiative for Asthma  
GLDH 
Glutamate dehydrogenase 
GSK 
GlaxoSmithKline 
h 
Hours 
HBc 
Hepatitis B core 
HBsAg 
Hepatitis B surface antigen 
HFA 
Hydrofluoroalkane product 
HIV 
Human immunodeficiency virus 
HRQoL 
Health-related quality of life 
HRT 
Hormone replacement therapy 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Council on Harmonization of Technical 
Requirements for Registration of Pharmaceuticals for 
Human Use 
ICS 
Inhaled corticosteroid 
IDMC 
Independent data monitoring committee 
IEC 
Independent Ethics Committee 
IFU 
Instruction for use 
Ig 
Immunoglobulin  
IL-5 
Interleukin-5 
IL-5R 
Interleukin-5 receptor 
IM 
Intramuscular 
IMP 
Investigational medicinal product 
INR 
International normalised ratio 
IP 
Investigational Product 
IRB 
Institutional Review Board 
IRT 
Interactive response technology 
IUD 
Intrauterine device 
IUS 
Intrauterine hormone-releasing system 
IV 
Intravenous 
kg 
kilogram 
L 
Litre 
LA 
Long-acting 
LABA 
Long-acting -agonist 
LAM 
Lactational amenorrhea method 
LAMA 
Long-acting muscarinic antagonist  
LDH 
Lactate dehydrogenase 
LTRA 
Leukotriene receptor antagonist 
mAb 
Monoclonal antibody 
MAR 
Missing at random 
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mcg (g) 
Microgram 
MDI 
Metered dose inhaler 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligrams 
mL 
Millilitres 
mm Hg 
Millimetre of mercury 
mol 
Mole 
MPO 
myeloperoxidase 
MSDS 
Material Safety Data Sheet 
msec 
Milliseconds 
NAb 
Neutralising antibody 
NHANES 
National Health and Nutrition Examination Survey 
NHLBI 
National Heart, Lung, and Blood Institute 
NIAID 
National Institute of Allergy and Infectious Disease 
NIH 
National Institutes of Health 
NIMP 
Non-investigational medicinal product 
OCS 
Oral corticosteroid 
OLE 
Open-label extension 
PC20 
Provocative concentration causing a 20% fall in FEV1 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamics 
PD20 
Provocative dose that decreases FEV1 by 20% 
PEF 
Peak expiratory flow 
PFS 
Pre-filled safety syringe 
PRO 
Patient-reported outcomes 
QTcF 
QTc corrected by Fridericia’s formula 
QTL 
Quality tolerance limits 
R&D 
Research and Development 
RNA 
Ribonucleic acid 
RBC 
Red blood cell 
SABA 
Short-acting -agonist 
SADE 
Serious adverse device event 
SAE 
Serious Adverse Event 
SAP 
Statistical analysis plan 
SC 
Subcutaneous 
SDAC 
Statistical data analysis centre 
SGRQ 
St. George’s Respiratory Questionnaire 
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SoA 
Schedule of assessments 
SoC 
Standard of care 
SOC 
System organ class 
SRM 
Study Reference Manual 
SRT 
Safety review team 
SUSAR 
Suspected unexpected serious adverse reaction 
UACR 
Urinary albumin-creatinine ratio 
UK 
United Kingdom 
ULN 
Upper Limit of Normal 
WBC 
White blood cell 
WOCBP 
Women of childbearing potential 
WONCBP 
Women of non-childbearing potential 
w/v 
Weight/volume 
μL 
Microlitre 
Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
NUCALA 
 
CINQAERO 
 
 
CINQAIR 
 
 
DUPIXENT 
 
 
FASENRA 
 
 
MedDRA 
 
 
SAS 
 
 
XOLAIR 


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10.14. Appendix 14: Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents. 
10.14.1. 
Amendment 1: 17-Aug-2021 
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: Amendment 01 is a global amendment to 
include modifications based on regulatory suggestion and additional changes were 
incorporated which align with program revisions and/or updates as listed in table below.   
Section # and Name Description of Change 
Brief Rationale 
Title page, Section 
1.1 Synopsis and 
Section 2.1 Study 
Rationale 
Addition of name “depemokimab” 
To update the protocol with the 
recently approved generic name 
of GSK3511294 
Section 1.3 Schedule 
of Activities and 
Table 6 of Appendix 
11 
Term “Demography and 
childbearing status” modified to 
“Demography data collection” 
 
Added text “Collection of 
exacerbations at Visit 1 is historical 
data” 
 
 
 
 
 
 
 
 
 
Minor modification for more 
clarity 
Text “-56 to -7” modified to “-56 to -
42”, “Week -8 to –1” modified to 
“Week -8 to -6” 
Clarification 
Inclusion of an ECG at week 2 and 
week 28 
Revision to address request of 
health authority 
Only screening, randomization, 
dispensing and withdrawal visits 
need interactive response 
technology (IRT), hence corrections 
Visits which require IRT 
registration were clarified 
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Section # and Name Description of Change 
Brief Rationale 
made accordingly 
Added 
 at 
week 48 
Added a 
 visit at 
week 48 
Modification with respect to the 
planned open label extension 
study 
Section 1.1 
Synopsis, Section 
4.1 Overall design 
and 
Appendix 11 
Added Visits 3 and 11 as in-person 
clinic visits. 
Due to the inclusion of an ECG 
at week 2 and week 28 these 
visits can not be conducted 
remotely or virtually. 
Section 4.1.1 Study 
Phases, Duration 
and Treatment Arms 
(Table 1) 
Term “Clinic” modified to “Study” 
Clarification 
Section 5.1 Inclusion 
Criteria 
Added text in inclusion criteria 
related to pregnancy  
Clarification 
Section 5.2 
Exclusion Criteria 
Exclusion of participants with 
allergy/intolerance to the excipients 
of GSK3511294 in Section 6.1 
Updated wording for more clarity 
for study intervention and its 
excipients 
Section 5.3.1 
Randomization 
Inclusion Criteria 
Airway reversibility or Airway 
hyperresponsiveness documented 
in the 24 months prior to Visit 2 
instead of previous 12 months 
To provide flexibility for enrolling 
participants that have 
demonstrated airway 
reversibility/hyperresponsiveness 
Section 5.3.2 
Randomization 
Exclusion Criteria 
Revised QTc criteria 
Revised wording for clarification 
Section 6.9.1 
Permitted 
Medications and 
Non-Drug Therapies 
Text added for permission to receive 
COVID-19 Vaccine 
Clarification considering the 
COVID-19 pandemic situation 
Section 6.9.2 
Prohibited 
Medications and 
Non-Drug Therapies 
Removed “troleandomycin” from 
prohibited medication 
As per the program level 
updated troleandomycin is no 
longer a prohibited medication 
Section 6.9.3. 
Rescue Medicine 
Low dose ICS/LABA is not permitted 
as rescue medication. Rescue 
medication usage will be recorded in 
the eDiary. 
Revised wording for providing 
more clarity 
Section 8.1.1 Pre-
screening Visit (Visit 
0) 
Only screening (Visit 1), 
randomization (Visit 2), dispensing 
(Visit 10) and withdrawal visits need 
IRT, hence corrections made 
accordingly 
Visits which require IRT 
registration were clarified 
Section 8.2.2 Asthma Text deleted “Additional details on 
Text removed to align with the 
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Section # and Name Description of Change 
Brief Rationale 
Exacerbations 
the process for determination of 
clinically significant exacerbations 
can be found in the SAP”. 
Statistical Analysis Plan 
8.2.3.1. Reversibility 
using the Maximum 
Post-Bronchodilator 
Method 
Current “The procedures involved in 
the Maximum Post-Bronchodilator 
Method are those generated by the 
Pulmonary Physiology 
Subcommittee “ 
Previously “The procedures involved 
in the Maximum Post-Bronchodilator 
Method are those generated by the 
and not by Asthma Clinical 
Research Network”  
 
Current “Details of reversibility 
procedure mentioned in SRM” 
Previously “Details of reversibility 
procedure mentioned in in third 
party vendor manual” 
Clarification 
Section 8.2.4. St. 
George’s Respiratory 
Questionnaire 
(SGRQ) 
The SGRQ will contain 50 items 
instead of previous 51. 
Clarification 
Section 8.2.10. 
Asthma Daily 
Symptom 
Diary/Asthma Nightly 
Symptom Diary 
(ADSD/ANSD) 
 
 
 
Clarification 
Section 8.2.10. 
Asthma Daily 
Symptom 
Diary/Asthma Nightly 
Symptom Diary 
(ADSD/ANSD) 
Updated the information regarding 
use of ADSD and ANSD 
Correction of the timeframe for 
completing 
 
Section 8.3.2 Vital 
Signs 
Text “Oral or skin Temperature” 
modified to “Temperature” 
Clarification 
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Section # and Name Description of Change 
Brief Rationale 
Section 8.6 Genetics 
and 
Pharmacogenomics, 
Section 9.3 Analysis 
sets  
mITT description updated, Safety 
Population deleted 
Revised description of mITT 
population to provide clarification 
that mITT population will be used 
as primary population for some 
other endpoints apart from 
efficacy. 
Clarification of analysis populations 
which will be defined in SAP. 
Clarification 
Appendix 2 Clinical 
Laboratory Tests 
Added 
 
to the table of protocol-required 
clinical laboratory test parameters. 
Added to align with clinical 
laboratory worksheet. 
Section 10.3.2 
Definition of SAE 
Modified definition of SAE 
Revised as per the latest 
definition of SAE. 
Section 10.3.5 
Reporting of SAE to 
GSK 
Removed the requirement of SAE 
reporting in eCRF within 72 hours  
Removal of additional step of 
eCRF check. 
Throughout 
Minor editorial and document 
formatting revisions 
Minor, therefore have not been 
summarized 
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11. 
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Ther. 2019;105(4):899-911. 

SAP_001.pdf: 
Statistical Analysis Plan Amendment 2
Study ID:  206713
Official Title of Study: A 52-week, randomised, double-blind, placebo-controlled, 
parallelgroup, multi-centre study of the efficacy and safety of GSK3511294 
adjunctive therapy in adult and adolescent participants with severe uncontrolled 
asthma with an eosinophilic phenotype
NCT ID: NCT04719832
Date of Document: 14-DEC-2023


CONFIDENTIAL 
The GlaxoSmithKline group of companies 
 
206713 
 
 
 
 
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Division 
: Worldwide Development 
Information Type 
: Statistical Analysis Plan (SAP) 
TITLE PAGE 
Protocol Title: A 52-week, randomised, double-blind, placebo-controlled, parallel-
group, multi-centre study of the efficacy and safety of GSK3511294 (Depemokimab) 
adjunctive therapy in adult and adolescent participants with severe uncontrolled asthma 
with an eosinophilic phenotype   
Protocol Number: 206713 
Compound Number:  GSK3511294 
Short Title: Placebo-controlled efficacy and safety study of GSK3511294 
(Depemokimab) in participants with severe asthma with an eosinophilic phenotype  
Acronym: SWIFT-1 
Sponsor Name: GlaxoSmithKline Research & Development Limited 
Regulatory Agency Identifier Number(s)  
Registry 
ID 
IND 
146742 
EudraCT  
2020-003612-28 
SAP Author(s): 
Author 
 
Principal Statistician, Dev Biostats Stats Dev 
 
Statistical Leader, Dev Biostats Stats Dev 
SAP Biostatistics Line Approval (Pharma TMF eSignature): 
Approver 
 
,  Dev Biostats Stats Dev 
 
Copyright 2023 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited. 
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TABLE OF CONTENTS 
PAGE 
1. 
INTRODUCTION ...................................................................................................... 8 
1.1. 
Objectives, Estimands and Endpoints ........................................................... 8 
1.1.1. 
Objectives and Endpoints .............................................................. 8 
1.1.2. 
Estimands .................................................................................... 12 
1.2. 
Study Design .............................................................................................. 25 
2. 
STATISTICAL HYPOTHESES ............................................................................... 26 
2.1. 
Multiplicity Adjustment ................................................................................ 26 
3. 
ANALYSIS SETS ................................................................................................... 27 
4. 
STATISTICAL ANALYSES ..................................................................................... 29 
4.1. 
General Considerations .............................................................................. 29 
4.1.1. 
General Methodology .................................................................. 29 
4.1.2. 
Baseline Definition ....................................................................... 30 
4.1.3. 
Multicenter Studies ...................................................................... 32 
4.2. 
Primary Endpoint Analyses ......................................................................... 32 
4.2.1. 
Definition of endpoint ................................................................... 32 
4.2.2. 
Main analytical approach ............................................................. 33 
 
 
4.3. 
Secondary Endpoints Analyses .................................................................. 34 
4.3.1. 
Definition of endpoint(s) ............................................................... 34 
4.3.2. 
Main analytical approach for SGRQ total score, ACQ-5 
score and pre-bronchodilator FEV1 .............................................. 35 
4.3.3. 
Main analytical approach for annualised rate of 
exacerbations requiring hospitalisation and/or ED visit 
over 52 weeks ............................................................................. 36 
4.3.4. 
Sensitivity analyses ..................................................................... 36 
4.4. 
Other Endpoints Analyses .......................................................................... 36 
4.4.1. 
Time to first clinically significant exacerbation and Time to 
first clinically significant exacerbation requiring 
hospitalisation and/or ED visit ...................................................... 36 
4.4.2. 
Change from baseline in SGRQ total score and in ACQ-5 
score at discrete timepoints during the 52-week period................ 37 
4.4.3. 
SGRQ total score responder status at Week 52 and ACQ-
5 score responder status at Week 52 ........................................... 38 
4.4.4. 
Change from baseline in pre-bronchodilator FEV1 and 
post-bronchodilator FEV1 ............................................................. 39 
 
 
4.4.7. 
Patient-rated response to therapy during the 52-week 
period .......................................................................................... 40 
4.4.8. 
Clinician-rated response to therapy during the 52-week 
period .......................................................................................... 40 
4.4.10. 
ADSD/ANSD ................................................................................ 41 
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4.4.11. 
Mean number of occasions of rescue medication per day ............ 43 
4.4.12. 
Awakenings at night due to asthma symptoms requiring 
rescue medication use ................................................................. 43 
4.5. 
CLINICAL PHARMACOLOGY DATA ANALYSES ...................................... 44 
 
 
 
 
4.6. 
Safety Analyses .......................................................................................... 45 
4.6.1. 
Extent of Exposure ...................................................................... 45 
4.6.2. 
Adverse Events............................................................................ 45 
4.6.3. 
Additional Safety Assessments .................................................... 47 
4.6.4. 
Additional Safety Analyses .......................................................... 48 
4.7. 
 
4.8. 
 
4.10. 
Analyses on China Subpopulation .............................................................. 50 
4.11. 
 
4.11.1. 
IDMC Safety Review .................................................................... 51 
4.11.2. 
 
4.11.3. 
Blinded Data Analysis for Validation Questionnaires .................... 55 
4.12. 
Changes to Protocol Defined Analyses ....................................................... 55 
5. 
SAMPLE SIZE DETERMINATION ......................................................................... 55 
5.1. 
Sample Size Assumptions .......................................................................... 55 
5.1.1. 
Primary Endpoint ......................................................................... 55 
5.1.2. 
Secondary Endpoints ................................................................... 56 
5.2. 
Sample Size Sensitivity ............................................................................... 57 
5.3. 
Sample Size Re-estimation or Adjustment .................................................. 57 
6. 
SUPPORTING DOCUMENTATION ....................................................................... 58 
6.1. 
 
6.2. 
Appendix 1 Abbreviations and Trademarks ................................................. 59 
6.2.1. 
List of Abbreviations .................................................................... 59 
6.2.2. 
Trademarks ................................................................................. 60 
7. 
REFERENCES ....................................................................................................... 61 
 
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VERSION HISTORY 
Table 1 
SAP Version History Summary 
SAP 
Version 
Document 
Date 
Protocol 
Version 
(Date) on 
which SAP 
is Based 
Change 
Rationale 
1 
22-Jan-
2021 
Version 01 
Approval 
Date: 
 01-OCT-
2020 
Not Applicable 
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Amendment 
01 
02-Aug-22 
 
Amendment 
02 
Approval 
Date:  
08-APR 
2022 
1. 
Section 1.1.2 Estimand: 
updated intercurrent event 
strategy for change in 
maintenance therapy  
 
 
 
 
 
2. 
Section 3 Analysis Sets: 
Updated text related to 
enrolled, randomised, full 
analysis set, and safety 
population. Added China sub-
population. 
 
3. 
Section 4.3.2: updated model 
checking method 
4. 
Section 4.4.9: removed 
statistical analysis of 
 endpoints 
 
5. 
Section  4.4.10 ADSD/ANSD: 
 
6. 
Section 4.5.2: updated 
imputation method for non-
detectable blood eosinophil 
values of 0 GI/L, or results 
below the limit of quantification. 
7. 
Section 4.6.3.3: adding two 
visits for ECG reporting and 
modified wording for categories 
to be reported 
8. 
Section 4.9: Added 
 
 
blinded analysis for validation 
of questionaries  
9. 
Section 4.10: removed that 
Table of ‘Changes to Protocol 
Defined Analyses’. 
10. Section 4.4.15: added a 
summary of systemic 
corticosteroids use associated 
with  clinically significant 
exacerbations 
1. 
Different strategies to be 
applied to intercurrent 
event of change in 
maintence therapy and 
use of prohibited 
medication for PD 
endpoint. Also added 
clarification for this 
intercurrent event.  
2. 
Revision of Analysis sets 
based on the new SAP 
template description. To 
included China reporting 
into this analysis plan. 
 
 
3. 
Correct the checking 
method 
4. 
Only need summary 
 
 
 
5. 
Clarification 
 
6. 
Clarification 
 
 
 
 
7. 
Update  due to protocol 
amendment 
 
 
8. 
Update  due to protocol 
amendment 
 
 
9. 
Update  due to protocol 
amendment 
 
 
10. Update in order  to include 
all type of corticosteroids 
use 
 
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Amendment 
02 
14-Dec-
2023 
Amendment 
02 
Approval 
Date:  
05-APR 
2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1. 
Section 1.1.1 Endpoints and 
Section 2.1 Multiplicity 
Adjustment 
 
 
2. 
Section 1.1.2:updated for the 
endpoints with descriptive 
summaries, 
 
 
. And 
removed safety endpoints from 
the table.  
3. 
Section 3 updated FAS and 
Safety analysis sets . Added 
FAS-modified and Safety-
modifitied analysis sets. 
4. 
Section 4.1.2 Baseline 
Definition: changed from ‘Day -
7 to Day 1’ to ‘Day -6 to Day 1’ 
5. 
Section 4.2.2, 4.3.2, 4.4, Main 
Analytical Approach, removed 
the covariate of ‘ baseline 
maintenance OCS therapy 
(OCS vs. no OCS)’ from the 
analysis model 
6. 
Section 4.2.3.2 removed 
condition for performing 
 
 
7. 
Section 4.4.10.2. Added 
analysis for responder based 
ADSD/ANSD 
8. 
Section 4.4.13. Added a 
 
plot 
9. 
Section 4.4.15. Removed the 
 
 
 
 
10. Section 4.9 added the section 
for Risk Benefit forest plot  
11. Section 4.3.2, 4.4.3, 4.4.10 
added suggestion for how to 
exclude timepoints from 
analysis when the model does 
not converge. 
12. Section 4.10 added clarification 
for analyses on China 
subpopulation 
13. Section 4.1.1 added 
clarification for covaiates 
 
1. 
 
 
 
 
 
 
 
2. 
Clarification. 
 
 
 
 
 
 
3. 
To exclude patients from 
the site that had GCP 
non-compliance for the 
main analyses.   
 
4. 
Clarification 
 
 
5. 
This covariate is not 
needed because >95% 
subjects were not on 
maintenance OCS 
therapy at baseline. 
 
6. 
 
 
 
7. 
 
 
 
8. 
 
 
9. 
 
 
 
 
10. additional plot required for 
CSR 
11. Clarification 
 
 
 
 
12. Clarification 
 
 
13. Clarification 
 
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14. Section 4.3.3 added condition 
for performing analysis 
14. Clarification 
 


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1. 
INTRODUCTION 
The purpose of this SAP is to describe the planned analyses to be included in the Clinical 
Study Report (CSR) for Study 206713. Details of the planned final analyses are provided. 
Descriptive study population analyses such as summary of demography and baseline 
characteristics and additional detail with regards to data handling conventions and the 
specification of data displays will be provided in the Output and Programming 
Specification (OPS) document. 
1.1. 
Objectives, Estimands and Endpoints 
1.1.1. 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
 
• 
To evaluate the efficacy of GSK3511294 
100 mg (SC) every 26 weeks versus 
placebo in participants with severe 
uncontrolled asthma with an eosinophilic 
phenotype on top of existing asthma 
therapy 
• 
Annualised rate of clinically significant 
exacerbationsa over 52 weeks 
Secondary 
 
• 
To evaluate GSK3511294 100 mg (SC) 
every 26 weeks versus placebo on health-
related quality of life (HRQoL) and 
additional efficacy assessments on top of 
existing asthma therapy 
• 
Change from baseline in St. George's 
Respiratory Questionnaire (SGRQ) total 
score at Week 52  
• 
Change from baseline in Asthma Control 
Questionnaire-5 (ACQ-5) score at Week 52 
• 
Change from baseline in pre-
bronchodilator forced expiratory volume in 
one second (FEV1) at Week 52 
• 
Change from baseline in Asthma Daily 
Symptom Diary (ADSD)/ Asthma Nightly 
Symptom Diary (ANSD) weekly mean score 
at Week 52 
• 
Annualised rate of exacerbations requiring 
hospitalisation and/or Emergency 
Department (ED) visit over 52 weeks 
Other 
 
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Objectives 
Endpoints 
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Objectives 
Endpoints 
Safety 
• 
To evaluate the safety and tolerability of 
GSK3511294 100 mg (SC) every 26 weeks 
versus placebo in participants with severe 
uncontrolled asthma with an eosinophilic 
phenotype on top of existing asthma 
therapy 
• 
Incidence of AEs/SAEs  
• 
Laboratory parameters, including 
haematological and clinical chemistry 
parameters  
• 
Vital signs including blood pressure (BP), 
body temperature, and pulse rate  
• 
ECG assessments  
• 
Incidence of immunogenicity as measured 
by the presence of ADA/NAb to 
GSK3511294  
a. 
Clinically significant exacerbations will be defined as worsening of asthma requiring the use of systemic 
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Objectives 
Endpoints 
corticosteroids (IM, IV or oral) and/or hospitalisation and/or ED visit. 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.   
 


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1.1.2. 
Estimands 
Table 2 
Estimands 
The following two attributes apply to all estimands: 
• Treatment comparison: GSK3511294 + SoC compared with placebo + SoC 
• Population: Adult and adolescent participants with severe uncontrolled asthma with an eosinophilic phenotype following the 
strategy outlined below for dealing with the main intercurrent events that are anticipated. 
 
Objectives 
Estimand 
Endpoint 
Intercurrent Event Strategy 
Population Level Summary 
Measure 
Primary objective: To evaluate the 
efficacy of GSK3511294 100 mg 
(SC) every 26 weeks versus 
placebo in participants with severe 
uncontrolled asthma with an 
eosinophilic phenotype on top of 
existing asthma therapy 
Annualised rate of clinically 
significant exacerbations over 52 
weeks 
• 
Study intervention 
discontinuation due to reasons 
unrelated to the COVID 19 
pandemic: 
 
 
 
• 
Study intervention 
discontinuation due to reasons 
related to the COVID-19 
pandemic: 
 
 
 
• 
Change in maintenance 
therapy (not important PDs): 
Ratio of the rates of exacerbations 
between GSK3511294 + SoC and 
placebo + SoC. 
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Objectives 
Estimand 
Endpoint 
Intercurrent Event Strategy 
Population Level Summary 
Measure 
 
 
 
• 
Concomitant medication 
important PDs (change in 
maintenance therapy or use of 
prohibited medications): 
 
 
 
Secondary objective: to evaluate 
GSK3511294 100 mg (SC) every 
26 weeks versus placebo on 
health-related quality of life 
(HRQoL) and additional efficacy 
assessments on top of existing 
asthma therapy 
a) Change from baseline in 
SGRQ total score at Week 52  
 
 
b) Change from baseline in ACQ-
5 score at Week 52 
 
 
 
c) Change from baseline in pre-
bronchodilator FEV1 at Week 
52 
• 
Study intervention 
discontinuation due to reasons 
unrelated to the COVID-19 
pandemic:
 
 
 
 
• 
Study intervention 
discontinuation due to reasons 
related to the COVID-19 
pandemic: 
 
 
 
 
a) Difference in mean change 
from baseline in SGRQ total 
score at Week 52 between 
GSK3511294 + SoC and 
placebo + SoC 
b) Difference in mean change 
from baseline in ACQ-5 score 
at Week 52 between 
GSK3511294 + SoC and 
placebo + SoC 
c) Difference in mean change 
from baseline in pre-
bronchodilator FEV1 at Week 
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Objectives 
Estimand 
Endpoint 
Intercurrent Event Strategy 
Population Level Summary 
Measure 
 
 
 
d) Change from baseline in 
ADSD/ ANSD weekly mean 
score at Week 52 
 
 
 
e) Annualised rate of clinically 
significant exacerbations 
requiring hospitalisation and/or 
ED visit over 52 weeks 
• 
Change in maintenance 
therapy (not important PDs): 
 
 
 
• 
Concomitant medication 
important PDs (change in 
maintenance therapy or use of 
prohibited medications): 
 
 
 
52 between GSK3511294 + 
SoC and placebo + SoC 
d) Difference in mean change 
from baseline in ADSD/ ANSD 
weekly mean score at Week 52 
between GSK3511294 + SoC 
and placebo + SoC 
e) Ratio of the rates of clinically 
significant exacerbations 
requiring hospitalisation and/or 
ED visit between GSK3511294 
+ SoC and placebo + SoC 
 
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Objectives 
Estimand 
Endpoint 
Intercurrent Event Strategy 
Population Level Summary 
Measure 
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Objectives 
Estimand 
Endpoint 
Intercurrent Event Strategy 
Population Level Summary 
Measure 
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Objectives 
Estimand 
Endpoint 
Intercurrent Event Strategy 
Population Level Summary 
Measure 
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Objectives 
Estimand 
Endpoint 
Intercurrent Event Strategy 
Population Level Summary 
Measure 
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Objectives 
Estimand 
Endpoint 
Intercurrent Event Strategy 
Population Level Summary 
Measure 
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Objectives 
Estimand 
Endpoint 
Intercurrent Event Strategy 
Population Level Summary 
Measure 
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Objectives 
Estimand 
Endpoint 
Intercurrent Event Strategy 
Population Level Summary 
Measure 
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Objectives 
Estimand 
Endpoint 
Intercurrent Event Strategy 
Population Level Summary 
Measure 
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Objectives 
Estimand 
Endpoint 
Intercurrent Event Strategy 
Population Level Summary 
Measure 
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Objectives 
Estimand 
Endpoint 
Intercurrent Event Strategy 
Population Level Summary 
Measure 
 
 
 
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1.2. 
Study Design 
Overview of Study Design and Key Features 
 
Design 
Features 
• 
Phase 3A 
• 
52-week treatment period 
• 
Randomised 
• 
Double-blind 
• 
Placebo-controlled 
• 
Parallel group 
• 
Multi-centre  
• 
Approximately 540 participants with severe uncontrolled asthma with an 
eosinophilic phenotype will be screened to ensure the randomisation of 
375 participants in a 2:1 ratio to GSK3511294 (n=250) and matching 
placebo (n=125). 
• 
A sample size of 375 randomised will provide 99% power to demonstrate 
superiority of GSK3511294 100 mg SC + SoC following two doses (at Week 
0 and at Week 26) compared with placebo + SoC in annualised rate of 
clinically significant exacerbations over 52 weeks, based on the true 
annualised rate of exacerbations in the placebo arm being 1.18 , an 
assumed true treatment difference of a 50% reduction and at a 5% two-
sided significance level. 
• 
Participants who receive both doses of study intervention and complete 
the Exit Visit will be eligible to participate in an open-label extension 
(OLE) study (Study 212895), during which they will receive two doses of 
open-label GSK3511294 100 mg SC over another 52 weeks. 
Study 
intervention 
and Study 
intervention 
Assignment 
The study will consist of a pre-screen period (0-2 weeks), a run-in period (1-6 
weeks), and a study intervention period (52 weeks). After the run-in period, 
participants will be randomised in a 2:1 ratio using an interactive response 
technology (IRT) system in a blinded manner to receive either GSK3511294 100 
mg or placebo by SC injection. Randomisation will be stratified based on baseline 
ICS dose (medium or high dose). Two doses of study intervention will be 
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Overview of Study Design and Key Features 
second at Visit 10 (Week 26). Participants will be assessed at each scheduled visit 
(a total of 17 study visits) during the 52-week treatment phase. Study visits may 
be conducted remotely (by a home healthcare professional) or virtually, however, 
in-person clinic visits are required for the following: pre-screening Visit 0, 
screening Visit 1, randomisation Visit 2, Visit 3, Visit 10, Visit 11, Exit Visit 17, and 
WS Visit (if applicable).  
Participants will remain on their existing stable maintenance asthma therapy 
throughout the study. 
 
 
• 
 
• 
A blinded data analysis is also planned to complete a psychometric 
analysis of the ADSD/ANSD and 
.  
• 
Regular IDMC reviews of safety data are planned.  
2. 
STATISTICAL HYPOTHESES  
The primary study objective is to test for the superiority of GSK3511294 100 mg SC + 
SoC following two doses (at Week 0 and at Week 26) compared with placebo + SoC, 
assessed by the annualised rate of clinically significant exacerbations measured over the 
study intervention period of 52 weeks. 
The study will test at a 5% two-sided significance level the null hypothesis that there is 
no difference in annualised exacerbation rate between GSK3511294 and placebo. 
2.1. 
Multiplicity Adjustment 
The treatment comparison of interest for the primary and secondary endpoints is 
GSK3511294 100 mg SC + SoC vs placebo + SoC. A fixed sequence hierarchical testing 
procedure will be used to provide strong control of Type I error for multiplicity arising 
from the primary and multiple secondary endpoints. This will be carried out using a 
stepdown closed testing procedure where inference for an endpoint in the predefined 
hierarchy will be dependent on statistical significance having been achieved for the 
previous endpoints in the hierarchy. For example, for the primary endpoint, GSK3511294 
+ SoC will be compared to placebo + SoC at a two-sided 5% level. The next endpoint in 
the hierarchy (i.e. the first secondary endpoint) will be tested only if the test for the 
primary endpoint is significant at the two-sided 5% level. Testing will continue down the 
hierarchy for the remaining endpoints in an equivalent manner only if the previous 
endpoint in the hierarchy achieves statistical significance. 
The hierarchy of the primary and secondary endpoints to be tested is as follows: 
1. Annualised rate of clinically significant exacerbations over 52 weeks 
2. Change from baseline in SGRQ at Week 52 
3. Change from baseline in ACQ-5 at Week 52 
4. Change from baseline in clinic pre-bronchodilator FEV1 at Week 52 
5. Change from baseline in ANSD at Week 52 
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6. Change from baseline in ADSD at Week 52 
7. Annualised rate of exacerbations requiring hospitalisation and/or ED visit over 52 
weeks 
 
3. 
ANALYSIS SETS 
Analysis Set 
Definition / Criteria 
Analyses Evaluated 
Screened 
All participants who sign the ICF. 
Study Population 
Enrolled 
All participants who entered the study. 
 
Note screening failures (who never passed 
screening even if rescreened) and 
participants screened but never enrolled into 
the study (Met eligibility but not needed) are 
excluded from the Enrolled analysis set as 
they did not enter the study. 
 
Study Population 
Randomised 
All participants who were randomly 
assigned to study intervention in the study. 
Study Population 
Full Analysis Set 
(FAS) 
All randomised participants who receive at 
least one dose of study intervention 
excluding participants from Site 
    
Data will be analysed according to 
randomised treatment arm.  
• 
Study Population 
• 
Efficacy 
• 
Immunogenicity  
• 
PD 
• 
 
FAS-
ADSD/ANSD 
All participants in the FAS population for 
whom at least one ADSD/ANSD 
questionnaire were administered 
• 
Efficacy (ADSD/ANSD) 
FAS-China 
All participants in the FAS population who 
are enrolled from China 
• 
Study Population 
• 
Efficacy 
• 
 
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Analysis Set 
Definition / Criteria 
Analyses Evaluated 
Safety 
All randomised participants who receive at 
least one dose of study intervention 
excluding participants from Site 
   
Participants will be analysed according to 
the intervention they are allocated at 
randomisation, unless a participant receives 
a different intervention to the randomised 
intervention at all protocol-defined 
administrations at which study medication 
was received,  in which case the participant 
will be analysed according to the actual 
intervention they received. This population 
will serve as the primary population for 
analyses of safety endpoints.  
• 
Safety 
Safety-China 
All participants in the Safety population who 
are enrolled from China 
• 
Safety 
• 
 
FAS-Modified 
All participants in the FAS population plus 
randomised participants from Site 
 
who receive at least one dose of study 
intervention.   
• 
Efficacy (Primary and Secondary) 
Safety-Modified 
All participants in the Safety population plus 
randomised particiants from Site 
 
who receive at least one dose of study 
intervention.  Participants will be analysed 
according to the intervention they are 
allocated at randomisation, unless a 
• 
Key Safety 
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Analysis Set 
Definition / Criteria 
Analyses Evaluated 
participant receives a different intervention 
to the randomised intervention at all 
protocol-defined administrations at which 
study medication was received,  in which 
case the participant will be analysed 
according to the actual intervention they 
received.  
FAS-
ADSD/ANSD-
Modified 
All participants in the FAS-ADSD/ANSD 
population plus randomised participants 
from Site 
 who receive at least one 
dose of study intervention.   
• 
Efficacy (ADSD/ANSD) 
Note: GCP non-compliance/significant data integrity concern at Site 
 was identified.  
 
4. 
STATISTICAL ANALYSES 
4.1. 
General Considerations 
4.1.1. 
General Methodology 
The Full Analysis Set (FAS) will be used for all Study Population, Efficacy, 
Immunogenicity and PD analyses, unless otherwise stated. The Safety analysis set will be 
used for safety analyses, unless otherwise stated. PK analysis sets will be used for PK 
data analysis. FAS-China, Safety-China and PK-China will be used for China outputs. 
The Output and Programming Specification (OPS) document will provide more details. 
Confidence intervals will use 95% confidence intervals (CI) unless otherwise specified. 
Unless otherwise specified, continuous data will be summarised using descriptive 
statistics: n, mean, standard deviation (std), median, minimum and maximum. 
Categorical data will be summarised as the number and percentage of participants in each 
category. 
For endpoints that are formally modelled, summary statistics will be provided. In the 
statistical analysis where covariates are included in the modelling, the following approach 
will be applied: 
• The covariate of exacerbation history is classified as 2, 3, 4+. In the event that 
exacerbation history is <2, it will be included in the category of ‘2’.  
• For the covariate of baseline pre-bronchodilator % predicted FEV1, screening pre-
bronchodilator % predicted FEV1 will be used if baseline value is missing. If both  
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sreeening and baseline pre-bronchodilator % predicted FEV1 are missing, a missing 
value will be assigned for this covariate.   
Where statistical models are used, if there are important departures from the 
distributional assumptions, transformations of covariates or alternative models may be 
explored as supporting analyses. 
Randomisation is stratified based on baseline ICS dose (medium or high). All statistical 
models will include this stratum as a covariate. In the case of wrong stratification 
assigned at the time of randomization, the analyses will be performed based on the data 
collected in the CRF, not the assigned stratum at randomization. 
 
Assessments collected at withdrawal visit will be included in summary tables but won’t 
be included in any statistical analysis. 
 
4.1.2. 
Baseline Definition 
Baseline values for visit based assessments and 
 assessments are defined in Table 
3. 
Unless otherwise stated, if baseline is missing, no derivation will be performed and 
baseline will be set to missing. 
Table 3 
Baseline Definitions & Derivations 
Parameter 
Study Assessments Collected 
Prior to Dosing 
Baseline Definition 
Screening 
(Visit 1) 
Day 1 Pre-Dose 
(Visit 2) 
 
Efficacy, Health Outcomes and Other 
SGRQ total and 
domain scores 
 
X 
Day 1 pre-dose 
ACQ-5 
  
X 
Day 1 pre-dose 
Pre-bronchodilator 
FEV1 
X 
X 
Day 1 pre-dose 
Post-bronchodilator 
FEV1 
X 
X 
Day 1 pre-dose 
ADSD/ANSD weekly 
mean score 
X (daily following Screening) 
 
Average of measurements from Day 
-7 to Day -1 inclusive (at least 4 days 
must be non-missing) 
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Parameter 
Study Assessments Collected 
Prior to Dosing 
Baseline Definition 
Screening 
(Visit 1) 
Day 1 Pre-Dose 
(Visit 2) 
 
Safety 
Blood pressure 
X 
X 
Values from most recent assessment 
prior to first dose of study treatment 
which records both systolic and 
diastolic BP  
Pulse rate 
X 
X 
Most recent individual value prior to 
first dose of study treatment  
ECG endpoints 
X 
X 
Values from most recent ECG 
conducted prior to first dose of study 
treatment  
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Parameter 
Study Assessments Collected 
Prior to Dosing 
Baseline Definition 
Screening 
(Visit 1) 
Day 1 Pre-Dose 
(Visit 2) 
 
Other  
Immunogenicity   
 
X 
Day 1 pre-dose 
NOTES : 
• 
Only records that have been assigned a treatment phase of ‘pre-treatment’ will be considered as baseline 
assessments. 
• 
ADSD is to be completed before going to bed and refers to asthma symptoms during the day. Day 1 assement of 
ADSD will not be pre-dose. Therefore an average of measurements from Day -7 to Day -1 is defined as the 
baseline for ADSD/ANSD. 
• 
Baseline Definitions will be used for derivations for endpoints / parameters and indicated on summaries and 
Listings. 
• 
Unless otherwise stated, if baseline data is missing no derivation will be performed and will be set to missing. 
4.1.3. 
Multicenter Studies 
For the purposes of covariate adjustment in the statistical analysis, countries will be 
grouped into regions. The following regions are defined: 
• European (Czechia, France, Germany, Italy, Ireland, Poland, Spain, UK) 
• US 
• Rest of World (Canada, China, Russia) 
 
If there are insufficient subjects in each region for the statistical procedures to converge 
satisfactorily, the combining of regions will be considered. 
4.2. 
Primary Endpoint Analyses 
4.2.1. 
Definition of endpoint 
The primary endpoint is the annualized rate of clinically significant exacerbations over 
the 52 weeks following randomisation. 
Clinically significant exacerbations of asthma are defined as worsening of asthma 
requiring the use of systemic corticosteroids (IM, IV or oral) and/or hospitalisation and/or 
ED visit (see protocol Section 8.2.2). 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 recorded in the eCRF are considered as verified clinically significant 
exacerbations and will be included in the primary analysis.  
Exacerbations separated by less than 7 days will be treated as a continuation of the same 
exacerbation. 
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4.2.2. 
Main analytical approach 
Primary Statistical Analyses 
Endpoint(s) 
• 
Annualized rate of clinically significant exacerbations over 52 weeks 
Model Specification 
• 
Generalized linear model assuming a negative binomial distribution 
• 
Terms in the model: 
• 
Response: number of recorded clinically significant exacerbations experienced per subject. 
• 
Categorical: treatment group, exacerbation history (variable (2, 3, 4+)), baseline ICS dose 
(medium, high), geographical region  
• 
Continuous: baseline pre-bronchodilator % predicted FEV1    
• 
Offset: Loge(total time in the study in years)    
Model Checking & Diagnostics 
• 
The fit of the regression models will be examined using “Q-Q” plots of the standardized residuals. 
Interpretation of these plots will be aided by the addition of simulation-generated tolerance 
boundaries. 
Results Presentation 
• 
Treatment group model estimated annualized exacerbation rates and associated 95% CI 
• 
pairwise treatment rate ratios and associated p-value and 95% CI.  
• 
pairwise treatment percent reductions in annual exacerbation rate and associated 95% CI  
 
Handling of missing data and data excluded due to intercurrent events 
Subgroup Analysis  
• 
By baseline ICS dose (medium, high) subgroup analysis will be performed.  
• 
Separate model will be fitted for each subgroup. 
Additional Analysis 
• 
The same primary endpoint analysis will be performed using FAS-modified analysis set 
 
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4.3. 
Secondary Endpoints Analyses 
4.3.1. 
Definition of endpoint(s) 
The secondary endpoints are: 
• Change from baseline in SGRQ total score at Week 52  
• Change from baseline in ACQ-5 score at Week 52 
• Change from baseline in pre-bronchodilator FEV1 at Week 52 
• Change from baseline in ANSD at Week 52 (see Section 4.4.10) 
• Change from baseline in ADSD at Week 52 (see Section 4.4.10) 
• Annualised rate of exacerbations requiring hospitalisation and/or Emergency 
Department (ED) visit over 52 weeks 
 
 
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4.3.2. 
Main analytical approach for SGRQ total score, ACQ-5 score and 
pre-bronchodilator FEV1 
Secondary Endpoints Analyses 
Endpoint(s) 
• 
Change from baseline in SGRQ total score at Week 52  
• 
Change from baseline in ACQ-5 score at Week 52 
• 
Change from baseline in pre-bronchodilator FEV1 at Week 52 
Model Specification 
• 
Mixed Models Repeated Measures (MMRM) model. 
• 
Terms in the model: 
• 
Response: SGRQ Total score or ACQ-5 score or pre-bronchodilator FEV1 at each visit. 
• 
Categorical: treatment group, baseline ICS dose (medium or high), exacerbation history (variable (2, 3, 
4+)), geographical region, visit  
• 
Continuous: baseline (SGRQ Total score, or ACQ-5 score, baseline pre-bronchodilator % predicted 
FEV1) 
• 
Interaction: baseline*visit, treatment group*visit 
• 
Repeated:  visit  
• 
The MMRM analysis for SGRQ total scores will include data collected at Weeks 4, 12, 26, 40 and 52.  
• 
The MMRM analysis for ACQ-5 score will include data collected at Weeks 2, 4, 8, 12, 16, 20, 24, 26, 
28, 32, 36, 40, 44, 48 and 52. In the event the model fails to run due to too many assessments 
timepoints, timepoints included in the analysis may be reduced by keeping the timepoints of most 
interest. Suggested order for dropping timepoints is week 44, 20, 36, 16, 32, 48, 24, 28. 
• 
The MMRM analysis for pre-bronchodilator FEV1 will include data collected at Weeks 26 and 52. 
• 
The model will be fit with an unstructured variance-covariance matrix. 
• 
The Kenward and Roger method (KR) for approximating the denominator degrees of freedom and 
correcting for bias in the estimated variance-covariance of the fixed effects will be used.  In the event 
the model fails to run using the KR method, then the residual method will be used instead. In the event 
the model fails to run using residual method and assessments are from many timepoints, timepoints 
included in the analysis may be reduced by keeping the timepoints/intervals of most interest. 
• 
Baseline is defined in Section 4.1.2 
• 
Two models will be fitted; one with a response variable of change from baseline and one with the 
response variable as the raw value. 
• 
 
Model Checking & Diagnostics 
• 
Distributional assumptions underlying the model used for analysis will be examined by obtaining a 
normal probability plot of the residuals and a plot of the residuals versus the fitted values (i.e. checking 
the normality assumption and constant variance assumption of the model respectively) to gain 
confidence that the model assumptions are reasonable. 
Results Presentation 
• 
Least-square (LS) means and LS mean change from baseline values for each treatment group will be 
presented with their associated standard errors as well as 95% CIs. The estimated treatment difference 
along with corresponding standard error, 95% CI and P-values for each visit will be presented. 
• 
The LS mean treatment differences (and associated 95% CIs) for all visits will also be presented 
graphically. 
• 
SGRQ total scores, ACQ-5 score and pre-bronchodilator FEV1 (absolute value and changes from 
baseline) will also be summarised by treatment group and visit. 
Handling of missing data and data excluded due to intercurrent events 
• 
 
 
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Secondary Endpoints Analyses 
Additional Analysis 
The same secondary endpoint analyses will be performed using FAS-modified analysis set 
 
4.3.3. 
Main analytical approach for annualised rate of exacerbations 
requiring hospitalisation and/or ED visit over 52 weeks 
The annualised rate of exacerbations requiring hospitalisation and/or ED visit over 52 
weeks will be analysed using a negative binomial generalised linear model, as described 
for the primary endpoint, Section 4.2.2 for details. This endpoint would only be analysed 
in the event that a total of 20 or more exacerbations requiring hospitalisation and/or ED 
visit occurred in the study. 
4.3.4. 
Sensitivity analyses 
The sensitivity analyses for the primary endpoint as described in Section 4.2.3 will also 
be performed for the secondary endpoints. 
4.4. 
Other Endpoints Analyses 
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4.5. 
CLINICAL PHARMACOLOGY DATA ANALYSES 
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4.6. 
Safety Analyses 
All safety analyses will be performed on the Safety Analysis Set unless otherwise 
specified. Summaries of data will report data according to the nominal visit for which it 
was recorded. Occurrence of Adverse Events (AEs), Serious Adverse Events (SAEs), 
Adverse Events of Special Interest (AESIs), laboratory data, vital signs, and ECGs will 
be included in data displays in the form of frequency Tables, summary statistics, graphs, 
and statistical analyses where appropriate.  
4.6.1. 
Extent of Exposure 
Two doses of study treatment will be administered during study treatment period: the 
first at randomisation Visit 2 (Week 0) and the second at Visit 10 (Week 26). Each dose 
is viewed as providing therapeutic coverage for 26 weeks (182 days). The number of 
treatments administered and the number of days exposure will be summarised 
descriptively and listed. Total subject-year exposure will also be presented.  
 
Number of days of exposure to study treatment will be calculated as follow:   
Duration of Exposure in Days = (Date of Final Dose) – (Date of First Dose) + 182 
Subject years exposure is calculated as follow: 
Subject Years Exposure = ((Date of Final Dose) – (Date of First Dose) + 182)/365.25 
The exposure summary will also be presented by age subgroup (12-17, 18-64, ≥65). 
4.6.2. 
Adverse Events 
Adverse events analyses including the analysis of adverse events (AEs), Serious AEs 
(SAEs) and other significant AEs will be based on GSK Core Data Standards.  
An overview summary of AEs, including counts and percentages of participants with any 
AE, AEs related to study intervention, AEs leading to permanent discontinuation of study 
intervention or withdrawal from study, study intervention related AEs leading to 
permanent discontinuation of study intervention or withdrawal from study, SAEs, SAEs 
related to study intervention, fatal SAEs, and fatal SAEs related to study intervention will 
be produced. These summaries will also be produced by age subgroup (12-17, 18-64, 
≥65). 
Adverse events will be coded using the standard Medical Dictionary for Regulatory 
Affairs (MedDRA dictionary). 
The frequency and percentage of AEs will be summarised in two ways: 1) in descending 
order by System Organ Class (SOC) and Preferred Term (PT), where exposure-adjusted 
incidence rate will also be summarised. 2) in descending order by PT only. 
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Common (>=3%) AEs will be summarised by overall frequency and summarised by time 
to onset. 
A separate summary will be provided for study intervention-related AEs. A study 
intervention-related AE is defined as an AE for which the investigator classifies the 
possible relationship to study intervention as “Yes”. A worst-case scenario approach will 
be taken to handle missing relatedness data, i.e. the summary Table will include events 
with the relationship to study intervention as ‘Yes’ or missing. The summary Table will 
be displayed in descending order by SOC and PT. 
All SAEs will be tabulated based on the number and percentage of participants who 
experienced the event. Separate summaries will also be provided for study intervention-
related SAEs. The summary Tables will be displayed in descending order by SOC and 
PT.   
A study intervention-related SAE is defined as an SAE for which the investigator 
classifies the relationship to study intervention as “Yes”. A worst-case scenario approach 
will be taken to handle missing data, i.e. the summary Table will include events with the 
relationship to study intervention as ‘Yes’ or missing. The summary Table will be 
displayed in descending order by SOC and PT. 
4.6.2.1. 
Adverse Events of Special Interest 
Adverse events of special interest (AESI) for GSK3511294 program include: 
• Allergic (Type 1 hypersensitivity)  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 NIAID/FAAN 
Second Symposium on Anaphylaxis. 
• Type III hypersensitivity (immune complex disease/vasculitis) reactions 
• Local injection site reactions 
• QTc prolongation 
AESI reported by the investigator as systemic reactions (further categorised by the 
investigator as either allergic [type I hypersensitivity] or other systemic reactions and 
assessed against Sampson criteria for anaphylaxis) are collected via targeted eCRF 
within the study. Vasculitis events and local injection site reactions are also collected 
via targeted eCRF within the study.  
Separate summary Tables showing the number and percent of subjects with each type 
of AESI (excluding QTc prolongation) broken down by preferred term will be created. 
 
For each type of AESI (excluding QTc prolongation) a profile summary Table will be 
produced containing information including, but not limited to, the number of 
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A summary of the incidence of serious adverse events and adverse events of special 
interest (excluding QTc prolongation) will be produced displaying the relative risk and 
risk difference and their 95% CIs between and GSK3511294  and placebo.   
AESI of QTc prolongation will be summarised as detailed in Section 4.6.3.3 ECG. 
 
 
4.6.3. 
Additional Safety Assessments  
4.6.3.1. 
Laboratory Data 
Summaries of laboratory data 
, and liver 
chemistry test data will be based on GSK Core Data Standards and unless otherwise 
specified will include on-treatment and post-treatment data. 
A scatter plot of maximum post-baseline ALT vs maximum post-baseline total bilirubin 
will be produced. In addition, if any liver stopping or liver monitoring events occur 
during the study, summaries of liver monitoring/stopping event reporting and 
hepatobiliary laboratory abnormalities will be produced. 
 
 
.  
The details of the planned displays will be in OPS. 
4.6.3.2. 
Vital Signs 
Pre-dose systolic blood pressure, diastolic blood pressure, pulse rate and body 
temperature including change from baseline at all visits will be summarised. 
4.6.3.3. 
ECG 
Change from baseline (for post-baseline timepoints) values for QTc(F),  and heart rate 
will be summarised by treatment for Baseline, Week 2,Week 26, Week 28, and Week 52. 
ECG findings will be summarised by visits. 
Individual maximum QTc(F)  values will also be summarised to show the number of 
subjects with maximum values (msec) post-baseline relative to baseline in the following 
categories: Decrease, no change or increase to <= 450, increase to 450 < to <= 480, 
increase to 480 < to <= 500, increase to 500< to <=530 and increase to > 530.  QT 
uncorrected values will be summarised to show the number of subjects with maximum 
values (msec) post-baseline relative to baseline in the following categories: Decrease, no 
change or increase  to <600 and increase to >=600. 
Additionally, individual maximum changes from baseline in QTc(F) values will be 
summarised to show the number of subjects with maximum changes (msec) in the 
categories: increase of <= 30, increase of 31 to 60 and increase of > 60. 
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All ECG values for participants with protocol defined QT stopping criteria will be listed.  
4.6.4. 
Additional Safety Analyses  
The following additional safety analysis will be provided on Safety-Modified analysis 
set: 
• 
Overview of all adverse events (including site 
 
• 
Summary of on-treatment serious adverse events and adverse events of special 
interest: incidence, relative risk and risk difference (including sites 
 
• 
Listing of all adverse events from site 
 
4.7. 
Immunogenicity Analysis 
All participants’ baseline immunogenicity samples will be analysed.  Post-baseline 
immunogenicity samples will only be analysed for participants receiving GSK3511294 
100 mg SC.   
The following descriptive summaries will be presented for GSK3511294 100 mg SC 
group by visit using FAS population.: 
• 
PPD
PPD
PPD
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• Summary of AE by highest post-baseline binding antibody confirmatory assay 
result  
The following descriptive summaries will be presented for the placebo group using FAS 
population: 
• Summary of binding antibody assay results for all baseline visit results. Summary 
will include categories for negative and positive results, and available titre value 
(min, median and max).  
• Summary of neutralizing antibody assay results for all baseline visit results. 
Summary will include categories for negative and positive results.  
Note: Visits will include pre-dose baseline visit and all post-baseline visits where 
immunogenicity assessments were performed. The binding antibody confirmatory assay 
results are categorised as negative or positive. The positive results will have two sub 
categories: transient positive (defined as a single confirmatory positive immunogenic 
response that does not occur at the final study assessment) or persistent positive (defined 
as a confirmatory positive immunogenic response for at least 2 consecutive assessments 
or a single result at the final study assessment).  For the summary of  highest post-
baseline binding antibody confirmatory assay result and neutralizing antibody assay 
result, subjects with both positive and negative results will be identified in the positive 
category. If a subject had titre results that fall into multiple titre result categories, they 
will be included in the highest category. 
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4.9. 
Risk Benefit Analyses  
A forest plot will be produced to display efficacy and safety data from analyses in 
adjacent panels using Full Analysis Set. 
The efficacy results will include primary endpoint (and its associated endpoint), i.e. 
clinically significant exacerbations (and exacerbations requiring hospitalisation and/or 
ED visit). The AE results will be obtained from the analyses as described in Section 
4.6.2.1for the following categories of AEs: 
• On-treatment SAE  
• Systemic Reactions 
o Allergic (Type 1 hypersensitivity) reactions  
▪ Anaphylaxis 
o Other systemic reactions 
• Type III hypersensitivity/vasculitis 
• Local injection site reactions  
4.10. 
Analyses on China Subpopulation 
The key study population, efficacy, safety and PK analyses and some exploratory 
analyses will be repeated in the following subpopulations (as defined in Section 3, 
Analysis Sets) respectively: 
FAS-China： All participants in the FAS population who are enrolled from China. 
Safety-China: All participants in the Safety population who are enrolled from China. 
PK-China: All participants in the PK population who are enrolled from China. 
The subpopulation analyses will employ the same model as the overall population 
analyses. For MMRM analyses, once the model cannot converge from original settings 
(including repeated visits and covariates in the models), those will be adjusted to ensure 
model convergence and obtain stable estimations. For secondary endpoint ACQ-5 
including data collected at Weeks 2, 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48 and 52, 
in the event the model fails to run due to too many assessment timepoints, timepoints 
included in the analysis may be reduced by keeping the timepoints of most interest. 
Suggested order for dropping timepoints is week 44, 20, 36, 16, 32, 8, 48, 24, 28. 
 
4.11. 
 
 
. Periodic 
review of safety data by an independent data monitoring committee (IDMC) will also be 
performed. Other than the emergency unblinding procedures described in the protocol, all 
personnel having direct responsibility for the conduct of the study will remain blinded to 
treatment groups for all data until the database is frozen. 
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4.11.1. 
IDMC Safety Review 
IDMC will periodically review unblinded safety data from the three Phase III studies in 
the severe asthma program: 206713 (this study), 213744 and 206785,  in accordance 
with the IDMC Charter. IDMC will also review safety data from study 212895, an open-
label extension study including participants who were previously enrolled in study 
206713 or 213744 when sufficient data is collected. 
The IDMC will review all safety data, including AEs and serious adverse events 
(SAEs) and adverse events of special interest (AESI), laboratory parameters, including 
haematological and clinical chemistry parameters and ECG assessments from the three 
studies for identification of any potential safety signals. The safety data analyses for the 
IDMC reviews will be performed by an independent Statistical Data Analysis Centre 
(SDAC).  
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5. 
SAMPLE SIZE DETERMINATION 
Approximately 
 participants with severe uncontrolled asthma with an eosinophilic 
phenotype will be screened to ensure the randomisation of 
 participants in a 
ratio 
to GSK3511294 
 and matching placebo 
.  
5.1. 
Sample Size Assumptions 
A sample size of
 participants (
 GSK3511294 to placebo allocation ratio) is based 
on sufficient power to conclude superiority on primary and key secondary endpoints. 
5.1.1. 
Primary Endpoint 
 
 
 
 
 
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5.1.2. 
Secondary Endpoints 
Table 5 describes the assumptions and power values for two key secondary endpoints. 
The assumptions are obtained from the Phase 3 mepolizumab studies [Pavord, 2012; 
Ortega, 2014; Chupp, 2017]. 
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Table 5 
Power Calculations for Key Secondary Endpoints  
Endpoint 
Assumed treatment difference 
(GSK3511294 + SoC vs. placebo + 
SoC) 
Standard 
deviation 
Power 
5.2. 
Sample Size Sensitivity 
The sample size and power calculations are based on assumptions about the true values 
for parameters. The power of the study is dependent on changes in these assumptions, in 
particular the assumed annualised exacerbation rates. Table 5 illustrates how changes in 
assumptions for two parameters (placebo + SoC annualised exacerbation rate and 
treatment effect) affect the power. 
Table 5 
Estimates of Power for Assumed Placebo + SoC Exacerbation Rate 
and Assumed Percent Reduction with GSK3511294 + SoC Compared 
with Placebo + SoC 
Percent reduction in 
annualised exacerbation rate 
with GSK3511294 + SoC vs. 
placebo + SoC 
Placebo + SoC annualised exacerbation rate 
5.3. 
Sample Size Re-estimation or Adjustment 
There will be no sample size re-estimation. 
There is a possibility for randomising greater than 
participants in the study. This is 
due to local country requests or requirements, for example, the local health authority 
specifying a minimum number to be enrolled. The primary analysis and clinical study 
report (CSR) will be based on the initial target enrolment. If the study target enrolment is 
reached before a local country enrolment requirement is met, then recruitment in that 
country may continue. Participants from those countries, who have already been enrolled 
at the time of reaching the target enrolment, will be included in the primary analysis. All 
data (pre- and post-target enrolment) will be analysed together but reported later in a 
supplement to the study report. Inferences will be drawn on the original study report 
based on the target enrolment.  
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6. 
SUPPORTING DOCUMENTATION 
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6.2. 
Appendix 1 Abbreviations and Trademarks 
6.2.1. 
List of Abbreviations 
Abbreviation 
Description 
ACQ 
Asthma Control Questionnaire 
ADA 
Anti-drug antibody 
ADSD 
Asthma Daily Symptom Diary 
ANSD 
Asthma Nightly Symptom Diary 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
Anti-IL-5 
Anti-Interleukin-5  
BP 
Blood pressure 
CI 
Confidence interval 
COVID-19 
Coronavirus disease 2019 
CPMS 
Clinical Pharmacology Modeling and Simulation 
CSR 
Clinical Study Report 
ECG 
Electrocardiogram 
eCRF 
Electronic Case report form 
ED 
Emergency Department 
eDiary 
Electronic diary 
FAS 
Full Analysis Set 
FEV1 
Forced expiratory volume in 1 second 
GSK 
GlaxoSmithKline 
HRQoL 
health-related quality of life  
ICS 
Inhaled corticosteroids 
IDMC 
Independent Data Monitoring Committee 
IgE 
Immunoglobulin E 
IL-5 
Interleukin-5 
LOS 
Length of Stay 
IM 
Intramuscular 
IV 
Intravenous 
KR method 
Kenward and Roger method  
LS Mean 
Adjusted mean for the treatment group 
LS Mean 
Change 
Adjusted mean change from baseline for the treatment group 
MAR 
Missing at Random 
MNAR 
Missing Not at Random 
Max 
Maximum 
MedDRA 
Medicinal dictionary for regulatory activities 
Min 
Minimum 
FAS 
Full Analysis Set 
Mg 
Milligram 
MMRM 
Mixed Models Repeated Measures 
NAb 
Neutralising antibody 
NHANES 
National Health and Nutrition Examination Survey 


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Abbreviation 
Description 
OCS 
Oral corticosteroids 
OPS 
Output and Programming Specification 
OR 
Odds ratio 
PD 
Pharmacodynamics 
PEF 
Peak expiratory flow 
PT 
Preferred Term  
PK 
Pharmacokinetics 
PRO 
Patient-reported outcomes 
QTcF 
QTc corrected by Fridericia’s formula 
RAP 
Reporting and Analysis Plan 
SAP 
Statistical Analysis Plan 
SAE 
Serious adverse event 
SAC 
Statistical Analysis Complete 
SC 
Subcutaneous 
SD 
Standard Deviation 
SE 
Standard Error 
SGRQ 
St George’s Respiratory Questionnaire 
SoC 
Standard of care 
SOC 
System Organ Class 
 
6.2.2. 
Trademarks 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
None  
 
SAS 
 
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7. 
REFERENCES 
Chupp G Bradford ES, Albers FC, Bratton DJ, Wang-Jairaj J, Nelsen LM, et al.Efficacy 
of mepolizumab add-on therapy on health-related quality of life and markers of asthma 
control in severe eosinophilic asthma (MUSCA): a randomised, double blind, placebo-
controlled, parallel-group, multicentre, phase 3b trial. Lancet. 2017;5(5):390-400. 
Keene, Roger et al. Missing data sensitivity analysis for recurrent event data using 
controlled imputation. Pharm Stat. Jul-Aug 2014;13(4):258-64. 
Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, et al.  
Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 
2014;371:1198-207.  
PASS 2020 Sample Size Software, NCSS.com. Tests for the Ratio of Two Negative 
Binomial Rates. Ch 438:1-17. Available at https://www.ncss.com/wp-
content/themes/ncss/pdf/Procedures/PASS/Tests_for_the_Ratio_of_Two_Negative_Bino
mial_Rates.pdf 
Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, et al. Mepolizumab for 
severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled 
trial. Lancet. 2012;380:651-9. 
Protocol: A 52-week, randomised, double-blind, placebo-controlled, parallel-group, 
multi-centre study of the efficacy and safety of GSK3511294 adjunctive therapy in adult 
and adolescent participants with severe uncontrolled asthma with an eosinophilic 
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