A Multi-centre, Single Arm, Open-label Extension Study to Evaluate the Long-term Safety of GSK3511294 (Depemokimab) in Adult and Adolescent Participants With Severe Asthma With an Eosinophilic Phenotype From Studies 206713 or 213744
Phase: PHASE3
Conditions: Asthma
Sponsor: GlaxoSmithKline

 
CONFIDENTIAL 
 
212895 
 
 
Protocol Amendment 2 
16 Jan 2025 
1 
TITLE PAGE 
Protocol Title: A multi-centre, single arm, open-label extension study to evaluate the 
long-term safety of GSK3511294 (Depemokimab) in adult and adolescent participants 
with severe asthma with an eosinophilic phenotype from studies 206713 or 213744 
Protocol Number: 212895 
Compound Number or Name: 
GSK3511294 
Brief Title: A Study of GSK3511294 (Depemokimab) in participants who were 
previously enrolled In 206713 or 213744; Open-Label Extension  
Study Phase: Phase 3A 
Sponsor Name and Legal Registered Address: 
GSK Research & Development Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
Manufacturer: GSK 
Regulatory Agency Identifying Number(s): 
IND: 146742 
EU CT number: 2023-505203-23 
Medical Monitor Name and Contact Information: Can be found in the Study 
Reference Manual. 
SPONSOR SIGNATORY: 
David A. Lipson, M.D. 
Vice President, Respiratory Disease Area Lead 
GSK Development Clinical Sciences 
Approval Date: 16 Jan 2025 
Copyright 2025 the GSK group of companies. All rights reserved. Unauthorized copying 
or use of this information is prohibited. 

 
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Protocol Investigator Agreement 
• 
To assume responsibility for the proper conduct of the study at this site. 
• 
That I am aware of and will comply with GCP and all applicable regulatory 
requirements. 
• 
That I will comply with the terms of the clinical study site agreement. 
• 
To ensure that all persons assisting me with the study are adequately informed about 
the GSK study intervention and other study-related duties and functions as described 
in the protocol. 
• 
To cooperate with representative(s) of GSK in the monitoring and data management 
processes of the study with respect to data entry and resolution of queries about the 
data. 

 
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Study identifier 
212895 
EU CT number 
2023-505203-23 
IND number 
146742 
Approval date 
16 Jan 2025 
Title 
A multi-centre, single arm, open-label extension 
study to evaluate the long-term safety of 
GSK3511294 (Depemokimab) in adult and 
adolescent participants with severe asthma with an 
eosinophilic phenotype from studies 206713 or 
213744 
Investigator name 
 
 
 
Signature 
 
 
 
Date of signature 
(DD Month YYYY) 
 

 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date of Issue 
Amendment 2 
16 Jan 2025 
Amendment 1 
12 January 2023 
Original Protocol 
30 July 2021 
Overall Rationale for the Amendment: This is an amendment for EU countries to 
include the EU CT number in accordance with EU CTR requirements. A description and 
rationale for all changes is provided below. 
Section # and Name 
Description of Change 
Brief Rationale 
Title page 
Replaced EudraCT number 
with EU CTR number 
Clarification 

 
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TABLE OF CONTENTS 
PAGE 
TITLE PAGE ................................................................................................................... 1 
PROTOCOL INVESTIGATOR AGREEMENT ................................................................. 2 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 4 
TABLE OF CONTENTS .................................................................................................. 5 
LIST OF TABLES ............................................................................................................ 9 
1. 
PROTOCOL SUMMARY ........................................................................................ 10 
1.1. 
Synopsis ..................................................................................................... 10 
1.2. 
Schema ...................................................................................................... 13 
1.3. 
Schedule of Activities (SoA) ........................................................................ 14 
2. 
INTRODUCTION .................................................................................................... 19 
2.1. 
Study Rationale .......................................................................................... 19 
2.2. 
Background ................................................................................................ 19 
2.3. 
Benefit/Risk Assessment ............................................................................ 20 
2.3.1. 
Risk Assessment ......................................................................... 21 
2.3.2. 
Benefit Assessment ..................................................................... 28 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 28 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 29 
3.1. 
Primary Estimand ....................................................................................... 30 
3.2. 
Secondary Estimands ................................................................................. 31 
4. 
STUDY DESIGN .................................................................................................... 32 
4.1. 
Overall Design ............................................................................................ 32 
4.2. 
Scientific Rationale for Study Design .......................................................... 33 
4.2.1. 
Participant Input into Design ........................................................ 34 
4.3. 
Justification for Dose .................................................................................. 34 
4.4. 
End of Study Definition ............................................................................... 35 
5. 
STUDY POPULATION ........................................................................................... 36 
5.1. 
Inclusion Criteria ......................................................................................... 36 
5.2. 
Exclusion Criteria ........................................................................................ 37 
5.3. 
Lifestyle Considerations .............................................................................. 39 
5.4. 
Screen Failures........................................................................................... 39 
5.5. 
Criteria for Temporarily Delaying Enrolment/ Administration of Study 
Intervention Administration ......................................................................... 39 
6. 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY .............................. 40 
6.1. 
Study Intervention(s) Administered ............................................................. 40 
6.1.1. 
Medical Devices ........................................................................... 41 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 41 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................... 42 
6.4. 
Study Intervention Compliance ................................................................... 42 
6.5. 
Dose Modification ....................................................................................... 42 

 
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6.6. 
Continued Access to Study Intervention after the End of the Study ............ 42 
6.7. 
Treatment of Overdose ............................................................................... 42 
6.8. 
Concomitant Therapy.................................................................................. 43 
6.8.1. 
Permitted Medications and Non-Drug Therapies .......................... 43 
6.8.2. 
Prohibited Medications and Non-Drug Therapies ......................... 44 
6.8.3. 
Rescue Medicine ......................................................................... 45 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 46 
7.1. 
Discontinuation of Study Intervention .......................................................... 46 
7.1.1. 
Liver Chemistry Stopping Criteria ................................................ 47 
7.1.2. 
Rechallenge ................................................................................. 48 
7.1.2.1. 
Study Intervention Restart or Rechallenge after 
liver stopping criteria met ............................................ 48 
7.1.3. 
QTc Stopping Criteria .................................................................. 49 
7.1.4. 
Temporary Discontinuation .......................................................... 49 
7.2. 
Participant Discontinuation/Withdrawal from the Study ............................... 50 
7.3. 
Lost to Follow Up ........................................................................................ 50 
7.4. 
Reasons for Study Intervention Discontinuation and/or Study 
Withdrawal .................................................................................................. 51 
7.5. 
Criteria for Follow-up of Potential Type III Hypersensitivity (Immune 
Complex Disease /Vasculitis) ...................................................................... 51 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 53 
8.1. 
Screening and Critical Baseline Assessments ............................................ 53 
8.1.1. 
Critical Assessments performed at Enrolment (Visit 1)................. 53 
8.1.2. 
Assessments performed if the time between the Exit Visit 
from the prior study (206713/213744) and Visit 1 is >7 
days ............................................................................................. 54 
8.2. 
Safety Assessments ................................................................................... 54 
8.2.1. 
Physical Examinations ................................................................. 55 
8.2.2. 
Vital Signs .................................................................................... 55 
8.2.3. 
Electrocardiograms ...................................................................... 55 
8.2.4. 
Clinical Safety Laboratory Assessments ...................................... 56 
8.2.5. 
Pregnancy Testing ....................................................................... 56 
8.3. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and Other 
Safety Reporting ......................................................................................... 57 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 57 
8.3.2. 
Method of Detecting AEs and SAEs ............................................. 58 
8.3.3. 
Follow-up of AEs and SAEs ......................................................... 58 
8.3.4. 
Regulatory Reporting Requirements for SAEs ............................. 58 
8.3.5. 
Pregnancy ................................................................................... 58 
8.3.6. 
Cardiovascular and Death Events ................................................ 59 
8.3.7. 
Adverse Events of Special Interest .............................................. 59 
8.3.8. 
Medical Device Deficiencies ........................................................ 60 
8.3.8.1. 
Time Period for Detecting Medical Device 
Deficiencies ................................................................ 60 
8.3.8.2. 
Follow-up of Medical Device Deficiencies ................... 60 
8.3.8.3. 
Prompt Reporting of Medical Device 
Deficiencies to Sponsor .............................................. 60 

 
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8.3.8.4. 
Regulatory Reporting Requirements for 
Medical Device Incidents ............................................ 61 
8.4. 
Efficacy Assessments ................................................................................. 61 
8.4.1. 
Efficacy Endpoints ....................................................................... 61 
8.4.2. 
Asthma Exacerbations ................................................................. 61 
8.4.3. 
Spirometry ................................................................................... 62 
8.4.4. 
Asthma Control Questionnaire (ACQ-5) ....................................... 62 
8.4.5. 
St. George’s Respiratory Questionnaire (SGRQ) ......................... 62 
8.5. 
Pharmacokinetics ....................................................................................... 62 
8.6. 
Genetics and Pharmacogenomics .............................................................. 63 
8.7. 
Biomarkers/Pharmacodynamic Markers ..................................................... 63 
8.8. 
Immunogenicity Assessments ..................................................................... 63 
8.9. 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 64 
9.1. 
Statistical Hypotheses................................................................................. 64 
9.2. 
Sample Size Determination ........................................................................ 64 
9.3. 
Analysis Sets .............................................................................................. 65 
9.4. 
Statistical Analyses ..................................................................................... 65 
9.4.1. 
General Considerations ............................................................... 65 
9.4.2. 
Primary Endpoints ....................................................................... 65 
9.4.3. 
Secondary Endpoints ................................................................... 66 
9.4.4. 
Other Endpoint(s) ........................................................................ 68 
9.5. 
Interim Analysis .......................................................................................... 68 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 69 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 69 
10.1.1. 
Regulatory and Ethical Considerations ........................................ 69 
10.1.2. 
Financial Disclosure ..................................................................... 69 
10.1.3. 
Informed Consent Process .......................................................... 70 
10.1.4. 
Data Protection ............................................................................ 70 
10.1.5. 
Committees Structure .................................................................. 71 
10.1.6. 
Dissemination of Clinical Study Data ........................................... 71 
10.1.7. 
Data Quality Assurance ............................................................... 72 
10.1.8. 
Source Documents ...................................................................... 73 
10.1.9. 
Study and Site Start and Closure ................................................. 73 
10.1.10. Publication Policy ......................................................................... 74 
10.2. 
Appendix 2: Clinical Laboratory Tests ......................................................... 75 
10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ....................................... 77 
10.3.1. 
Definition of AE ............................................................................ 77 
10.3.2. 
Definition of SAE .......................................................................... 78 
10.3.3. 
Definition of Cardiovascular Events ............................................. 79 
10.3.4. 
Recording and Follow-Up of AE and SAE .................................... 80 
10.3.5. 
Reporting of SAE to GSK ............................................................. 81 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ....................................... 83 
10.4.1. 
Definitions: ................................................................................... 83 
CCI
CCI
CCI

 
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10.4.2. 
Contraception Guidance: ............................................................. 84 
10.5. 
Appendix 5: Genetics .................................................................................. 86 
10.6. 
Appendix 6: Liver Safety: Required Actions, Monitoring and Follow-
up Assessments ......................................................................................... 87 
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 .................................. 91 
10.7.1. 
Definition of Medical Device AE and ADE .................................... 91 
10.7.2. 
Definition of Medical Device SAE, SADE and USADE ................. 91 
10.7.3. 
Definition of Device Deficiency ..................................................... 92 
10.7.4. 
Recording and Follow-Up of AE and/or SAE and Device 
Deficiencies ................................................................................. 93 
10.7.5. 
Reporting of SAEs ....................................................................... 95 
10.7.6. 
Reporting of SADEs ..................................................................... 96 
10.8. 
Appendix 8: Anaphylaxis Criteria ................................................................ 97 
10.9. 
Appendix 9: Recommended Measures Related to COVID-19 
Pandemic.................................................................................................... 98 
10.10. Appendix 10: Country-specific requirements ............................................. 107 
10.11. Appendix 11: Protocol amendment history ................................................ 108 
10.12. Appendix 12: Abbreviations and Trademarks ............................................ 113 
11. REFERENCES ..................................................................................................... 117 
 

 
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LIST OF TABLES 
PAGE 
Table 1 
Overview of Study Intervention ............................................................... 40 
Table 2 
Probabilities of observing a given number of adverse events or 
more (k) ................................................................................................. 64 
Table 3 
Protocol-Required Safety Laboratory Tests ............................................ 75 
Table 4 
Schedule of Activities (SoA) Indicating Assessments that may be 
Conducted Outside of a Clinical Study Site .......................................... 102 
 

 
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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A multi-centre, single arm, open-label extension study to evaluate the 
long-term safety of GSK3511294 (Depemokimab) in adult and adolescent participants 
with severe asthma with an eosinophilic phenotype from studies 206713 or 213744 
Brief Title: A Study of GSK3511294 (Depemokimab) in participants who were 
previously enrolled in 206713 or 213744; Open-Label Extension 
Rationale: 
The efficacy and safety of GSK3511294 in participants with severe uncontrolled asthma 
with an eosinophilic phenotype will be evaluated in the placebo-controlled studies 
206713 and 213744. The purpose of this open-label 12 month extension study is to 
continue to characterize the long-term safety, efficacy and immunogenic profile of 
GSK3511294 in participants with severe asthma with an eosinophilic phenotype 
following completion of clinical studies 206713 or 213744. Participants who have 
completed either of these prior studies will receive two doses (at Week 0 and Week 26) 
of add-on study intervention (either GSK3511294 100 mg or placebo) by subcutaneous 
(SC) injection over a 52-week treatment period. In this open-label extension study, all 
participants will receive two doses (at Week 0 and Week 26) of GSK3511294 100 mg SC 
over a study intervention period of 52 weeks. 
Objectives and Endpoints 
Primary (Safety) 
• 
To describe the long-term safety profile of 
GSK3511294 100 mg (SC) every 26 weeks in 
participants with severe asthma with an 
eosinophilic phenotype on top of existing asthma 
therapy over a 12 month open label extension 
phase 
• 
Incidence of adverse events (AEs)/ serious 
adverse events (SAEs) over 52 weeks 
• 
Incidence of immunogenicity as measured by the 
presence of anti-drug antibody (ADA)/ neutralising 
antibody (Nab) to GSK3511294 over 52 weeks 
Secondary (Efficacy) 
• 
To evaluate the effects of long-term dosing of 
GSK3511294 100 mg (SC) every 26 weeks on a 
range of clinical markers of asthma control and 
additional efficacy assessments on top of existing 
asthma therapy over a 12 month open label 
extension phase 
• 
Annualized rate of clinically significant 
exacerbations over 52 weeks 
• 
Change from Baseline in Asthma Control 
Questionnaire-5 (ACQ-5) score at discrete 
timepoints during the 52 week period 
• 
Change from Baseline in St. George's Respiratory 
Questionnaire (SGRQ) total score at Week 26 and 
Week 52 
• 
Change from Baseline in pre-bronchodilator FEV1 
at Week 26 and Week 52 

 
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Overall Design: 
This is a multicentre, single-arm, open-label 12-month extension study to evaluate the 
long-term safety of GSK3511294 100 mg administered SC, in addition to standard of 
care (SoC), in participants who have severe asthma with an eosinophilic phenotype. All 
participants who completed either study 206713 or 213744 will have the opportunity to 
participate in this study. The number of participants participating in this trial will not be 
greater than the combined number randomised into studies 206713 and 213744. 
Brief Summary: 
All participants who completed either study 206713 or 213744 will have the opportunity 
to enrol in this study, regardless of which treatment they were randomized to in the 
previous studies. Participants will be eligible to screen to enter the Open-label Extension 
(OLE) Study 212895 if he/she: 
• 
has received both doses of study intervention (at Visit 2 and Visit 10), AND 
• 
completed the scheduled Exit Visit of the parent protocol (Visit 17), AND 
• 
did not meet any of the study intervention discontinuation conditions during the 
study. 
The Exit Visit in 206713/213744 will serve as the Baseline Visit (Visit 1) for this study 
(212895). If the Exit Visit in 206713/213744 is on the same day or within 7 days of Visit 
1 for study 212895 then some assessments from the Exit Visit will be used as the baseline 
for 212895. If the Visit 1 is performed >7 days (maximum 14 days) after the Exit Visit in 
206713/213744 several of the assessments need to be repeated. A delayed administration 
of the study intervention may be considered (maximum 4 weeks) in consultation with the 
GSK Medical Monitor. 
After giving informed consent for this study, eligibility will be assessed. The assessments 
at this baseline visit will include informed consent, updated medical history and change 
in smoking status. 
Those participants meeting all the inclusion criteria and none of the exclusion criteria will 
receive their first open-label dose of GSK3511294 SC at Visit 1. Participants will receive 
a second dose of GSK3511294 SC approximately 26 weeks after Visit 1. 
Number of Participants: 
This study is an extension of Study 206713 and Study 213744. Participants must 
complete study 206713 or 213744 prior to entering this study. The maximum number of 
participants who are potentially eligible to take part in this study is not greater than the 
total number of participants enrolled in studies 206713 and 213744 (approximately 750 
participants). 

 
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Intervention Groups and Duration: 
Eligible participants will be requested to participate in the study for a maximum of 
56 weeks (Visit 1 to the Follow-up visit/call, inclusive). There will be a single treatment 
arm and all participants will receive open-label GSK3511294 100 mg SC at enrolment 
(Week 0) and at Week 26. The study consists of two phases described below: 
• 
Intervention Period: (Duration - 52 weeks). Participants who meet the eligibility 
criteria will enter the open-label 52-week treatment period and receive GSK3511294 
100 mg SC administered via a prefilled safety syringe, at enrolment (Week 0) and at 
Week 26. The Exit Visit will occur at Week 52. Following enrolment, visits will 
occur at Week 4 and approximately every 4 weeks (with some exceptions) thereafter 
with a visit at Week 26 for the administration of the second dose of GSK3511294 
100 mg SC. 
• 
Follow-up Period: (Duration – 4 weeks). Participants will be contacted 4 weeks 
after the Exit Visit. A participant will be regarded as having completed the study if 
they complete the treatment administration and Exit Visit and the Follow up 
visit/call, 4 weeks after the Exit Visit. 
Study visits may be conducted remotely or virtually, however, in-person clinic visits are 
required for those visits with study drug administration, 12-lead ECG or spirometry 
assessments, as detailed in the Schedule of activities (SoA): Visit 1, Visit 2, Visit 6, Visit 
7, Exit Visit 12 and Withdraw from Study (WS) Visit (if applicable). For WOCBP the 
follow up visit should be conducted as onsite visit or home visit (where applicable). 
Follow-up phone call is only applicable for male and WONCBP. 
Data Monitoring/ Other Committee: Yes 

 
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1.2. 
Schema 
Follow-up - 
Visit/Call# 
GSK3511294 100 mg SC** 
Week 
Visit 
0 
1 
4 
2 
12 
4 
20 
5 
26 
6 
7 
28 
8 
32 
36 
9 
40 
10 
11 
48 
12 
52 
Study Intervention Period 
52 Weeks 
1 st Dose 
2 nd Dose 
8 
3 
Exit Visit 
Exit Visit for Study 
206713/213744* 
56 
13 
F/U 
Follow-up 
4 Weeks 
*The Exit Visit in 206713/213744 will serve as the Baseline Visit (Visit 1) for this study (212895) 
** Participants will remain on standard of care asthma therapy, which may be adjusted during the study at the discretion of 
their physician.  
# Follow-up phone call is only applicable for male and WONCBP 

 
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1.3. 
Schedule of Activities (SoA) 
Protocol Activity 
 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-up 
visit/call 
 or Withdrawal 
Visit 
(7 days 
Notes 
 
Visit 
V1 * V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 V11 
Exit 
Visit 
V12 
FUi WS Visit b 
FU=Follow-up visit 
WS=Withdrawn from study visit 
 
Study Week  
0 
4 
8 
12 
20 
26 
28 
32 
36 
40 
48 
52 
56 
Study Day  
1 
28 
56 
84 
140 182 196 224 252 280 336 
364 392 
 
 
General Eligibility Assessments 
Informed Consenta 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
See footnote a. 
Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography data collection 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Changes including cardiovascular (CV), 
CV risk factors, asthma including 
exacerbations, vasculitis, allergies and 
anaphylaxis 
Smoking Status 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Parasitic screening 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Parasitic screening should have been 
performed prior to treatment in the OLE 
only if the participant has travelled to 
high risk countries in the past six 
months. For details refer to study 
reference manual (SRM).  
Safety assessments 
Concomitant Medication Assessment c 
X 
X 
X 
X 
X 
X 
X 
X 
Xh 
X 
Xh 
X 
 
X 
See footnote c. 
Physical Examination  
(X)  
 
 
 
 
 
 
 
 
 
 
 X  
 
 X  
 

 
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Protocol Activity 
 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-up 
visit/call 
 or Withdrawal 
Visit 
(7 days 
Notes 
 
Visit 
V1 * V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 V11 
Exit 
Visit 
V12 
FUi WS Visit b 
FU=Follow-up visit 
WS=Withdrawn from study visit 
 
Study Week  
0 
4 
8 
12 
20 
26 
28 
32 
36 
40 
48 
52 
56 
Study Day  
1 
28 
56 
84 
140 182 196 224 252 280 336 
364 392 
 
 
Vital Signs  
Xd 
 
X 
 
X 
X 
X 
 
 
X 
 
Xd 
 
Xd 
See footnote d. 
12-lead ECG 
(X) 
X 
 
 
 
X 
X 
 
 
 
 
X 
 
X 
ECG must be performed and assessed 
pre-dose. Twelve-lead ECG central 
overread values should be used at all 
visits with the exception of Visit 1 and 
Visit 6 where 12-lead ECG machine 
read values should be used. 
Adverse Events/Serious Adverse Event 
Assessment 
X e 
X  
X 
X 
X 
X 
X 
X 
Xh 
X 
Xh 
X 
X 
X 
See footnote e. 
Laboratory Assessments 
Urine Pregnancy Testf  
(WOCBP only) 
X 
X 
X 
X 
X 
X 
X 
X 
Xh 
X 
Xh 
X 
X 
X 
See footnote f. 
All WOCBP as determined in prior study 
(206713/ 213744) must continue their 
highly effective contraceptive method 
without any interruptions between prior 
study and enrolment in this study. See 
Section 5.1 and Section 8.2.5 for 
additional details 

 
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Protocol Activity 
 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-up 
visit/call 
 or Withdrawal 
Visit 
(7 days 
Notes 
 
Visit 
V1 * V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 V11 
Exit 
Visit 
V12 
FUi WS Visit b 
FU=Follow-up visit 
WS=Withdrawn from study visit 
 
Study Week  
0 
4 
8 
12 
20 
26 
28 
32 
36 
40 
48 
52 
56 
Study Day  
1 
28 
56 
84 
140 182 196 224 252 280 336 
364 392 
 
 
Urinalysis 
(X) 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
Note: Urinalysis to be performed using 
dipstick test. If results are abnormal a 
second urine sample should be taken 
and sent to central laboratory. 
China Only: 
For China sites the urine specimen may 
be sent to the central laboratory for 
routine urinalysis instead of performing 
a local urine dipstick. 
Clinical Chemistry  
(X) 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
Include liver chemistry. 
Immunogenicity sample 
(X) 
 
 
X 
 
X 
 
 
 
X 
 
X 
 
X 
 
 
Efficacy Assessments 
Review of exacerbations 
X 
X 
X 
X 
X 
X 
X 
X 
Xh 
X 
Xh 
X 
X 
X 
 
CCI
CCI

 
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Protocol Activity 
 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-up 
visit/call 
 or Withdrawal 
Visit 
(7 days 
Notes 
 
Visit 
V1 * V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 V11 
Exit 
Visit 
V12 
FUi WS Visit b 
FU=Follow-up visit 
WS=Withdrawn from study visit 
 
Study Week  
0 
4 
8 
12 
20 
26 
28 
32 
36 
40 
48 
52 
56 
Study Day  
1 
28 
56 
84 
140 182 196 224 252 280 336 
364 392 
 
 
Spirometry (pre-bronchodilator FEV1) 
(X) 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
FEV1=Forced expiratory volume in 1 
second; Spirometry should not be 
conducted for participants with 
confirmed/suspected COVID-19 
ACQ-5 
(X) 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
ACQ-5=Asthma Control Questionnaire 
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 hypersensitivity 
for at least 2 h after IP administration. 
For details refer to study reference 
manual (SRM). 
Worksheets/eCRF 
Provide worksheet 
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 
Dispense Rescue medication  
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
 
 
 
 
Register Visit in the IRT system 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
IRT=interactive response technology 
Complete electronic Case Report Form (eCRF) 
X 
X 
X 
X 
X 
X 
X 
X 
Xh 
X 
Xh 
X 
 
X 
 
HRQoL: PRO and Health Outcomes Assessments 
SGRQ 
(X) 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
SGRQ=St. George’s Respiratory 
Questionnaire 

 
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Protocol Activity 
 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-up 
visit/call 
 or Withdrawal 
Visit 
(7 days 
Notes 
 
Visit 
V1 * V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 V11 
Exit 
Visit 
V12 
FUi WS Visit b 
FU=Follow-up visit 
WS=Withdrawn from study visit 
 
Study Week  
0 
4 
8 
12 
20 
26 
28 
32 
36 
40 
48 
52 
56 
Study Day  
1 
28 
56 
84 
140 182 196 224 252 280 336 
364 392 
 
 
*: If the Exit Visit in 206713/213744 is on the same day, or within 7 days of Visit 1 for study 212895 then the assessments in brackets above do not need to be performed and the 
assessments from the Exit Visit from 206713/213744 will be used as the baseline for 212895. Information will be transferred accordingly. If the Visit 1 performed greater >7 days 
(maximum 14 days) after the Exit Visit in 206713/213744 then the assessments in brackets needs to be performed (For details refer to Section 8). A delayed administration of 
the study intervention (maximum 4 weeks) may be considered in consultation with the GSK Medical Monitor. 
a. 
Informed Consent must be obtained prior to initiating any study assessments.  
b. 
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 participant withdraws before the second dose of study intervention, or at Week 52 if the second dose of study intervention was received.  
c. 
Ensure maintenance asthma medications from the previous trial to Visit 1 and all current medications are reviewed. 
d. 
Vital signs including height and weight should be conducted at Visit 1. Height can be omitted for subsequent visits.  
e. 
SAEs must be collected after signing of Informed Consent. 
f. 
Urine pregnancy testing is only required for women of childbearing potential (WOCBP). Serum pregnancy test is required at the Exit Visit of the parent protocols for all WOCBP. 
g. 
For haematology samples 
 the absolute and differential (%) values of eosinophils, lymphocytes, basophils, neutrophils and monocytes will be blinded to site staff 
and sponsor to protect the blind from the previous study. Starting at 
 haematology samples are no longer blinded. Sites will be sent total white blood counts throughout 
the study. Samples should be taken pre-dose on dosing days. 
h. 
Week 36 and Week 48 are phone visits. In France, Week 36 and Week 48 are phone visits for all participants except WOCBP who will perform both visits, including the Follow 
Up visit, onsite. 
i. 
A follow-up visit/call should be conducted 30 weeks after the last dose of study intervention for AE/SAE assessments and pregnancy testing. For WOCBP the follow up visit 
should be conducted as onsite visit or home visit (where applicable). Follow-up phone call is only applicable for male and WONCBP. 
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2. 
INTRODUCTION 
2.1. 
Study Rationale  
Interleukin-5 (IL5) mediates the growth and differentiation of eosinophils in the bone 
marrow and their recruitment and activation within tissues [Corren, 2012]. Eosinophils 
circulate in the blood with a half-life of 8 to 18 hours and can persist in tissues for longer 
(days to weeks) [Kovalszki, 2016]. Therefore, inhibiting IL5 will remove a key 
eosinophil growth factor, and given the short half-life of eosinophils, will cause a rapid 
reduction in the circulating population. Reduction in eosinophils has been identified as a 
therapeutic strategy for numerous disorders with monoclonal antibodies (mAbs) targeting 
IL5, such as mepolizumab [Legrand, 2015]. Anti-IL5 therapies have an established 
efficacy and long-term safety profile and are a cornerstone of severe asthma management 
for patients with an eosinophilic phenotype. Three antagonists, of IL5 (mepolizumab and 
reslizumab) or its receptor (IL5R) (benralizumab) are approved for severe eosinophilic 
asthma, as an add-on treatment administered every 4 to 8 weeks. 
GSK3511294 (Depemokimab) is being developed as a long-acting (LA) SC injectable 
anti-IL5 therapy and is anticipated to deliver an efficacy and safety profile similar to the 
current anti-IL5 therapies with a reduced dosing frequency (once every 26 weeks). The 
long-term safety, efficacy and immunogenic profile of GSK3511294 has not been 
characterised. 
The aim of this study is to provide long-term safety data for GSK3511294 following 
completion of treatment in clinical trial 206713 or 213744. Participants in these prior 
studies will receive either GSK3511294 100 mg subcutaneously (SC) or placebo. In this 
open-label extension study, all participants will receive GSK3511294 100 mg SC for 52 
weeks; therefore, participants that received GSK3511294 in clinical trial 206713 or 
213744 will have received approximately 104 weeks of GSK3511294 exposure after 
completion of 212895. 
2.2. 
Background 
Persistent eosinophilic inflammation is a feature of more than 50% of the 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 (IL5) or its receptor 
(IL5R): mepolizumab (Nucala), reslizumab (Cinqair/Cinqaero), and benralizumab 
(Fasenra), respectively. All three, by utilizing blood eosinophils as a biomarker to predict 
patients likely to respond to therapy, have been shown to reduce asthma exacerbations 
and improve lung function and health-related quality of life (HrQoL) in patients with 
asthma with an eosinophilic phenotype [Haldar, 2009; Castro, 2011; Pavord, 2012; Bel, 
2014; Ortega, 2014; Castro, 2015; Bleecker, 2016; FitzGerald, 2016; Chupp, 2017]. 

 
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Evidence supporting the tolerability of targeting IL5/5R is provided by long-term 
extension studies of mepolizumab [Lugogo, 2016; Khatri, 2019; Khurana, 2019], 
reslizumab [Murphy, 2017], and benralizumab [Busse, 2019] as well as efficacy data of 
mepolizumab in real-world evidence settings [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 IL5 pathway are both 
highly effective and well tolerated. Based on this established efficacy and safety, anti-
IL5/5R 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 IL5 binding to its 
receptor and belongs to the established class of anti-IL5 therapies for severe asthma 
management. Compared with mepolizumab, GSK3511294 contains 7 amino acid 
substitutions in the heavy chain sequence: 4 amino acid changes introduced in the heavy 
chain variable region, and 3 amino acid changes (YTE) in the Fc region. The resulting 
antibody has increased affinity and half-life. Evidence to date indicate that these amino 
acid changes extend the PK and pharmacology of GSK3511294 to enable less frequent 
dosing with an anticipated similar safety and efficacy profile relative to mepolizumab 
(administered chronically). 
Long-acting (LA) 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 deliver similar efficacy and safety as 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, efficacy and safety of 
GSK3511294 is provided in the current Investigator’s Brochure (IB) [GSK Document 
Number RPS-CLIN-044550 or later]. 
2.3. 
Benefit/Risk Assessment 
Summaries of findings from non-clinical studies conducted with GSK3511294 and 
completed first time in humans (FTIH) study 205722 can be found in the current IB 
[GSK Document Number RPS-CLIN-044550 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 Standardised 
MedDRA Queries (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 National Institute of 
Allergy and Infectious Disease 
(NIAID)/ Food Allergy and 
Anaphylaxis Network (FAAN) 2nd 
Symposium on Anaphylaxis to collect 
data on reports of anaphylaxis (see 
Appendix 8). 

 
 
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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
• 
Participants will be monitored in clinic 
for immediate hypersensitivity and any 
other untoward effects for a minimum 
of 2 hours post-injection (both at Visit 
1 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. 
• 
Participants with severe allergic 
reaction/anaphylaxis with no 
alternative explanation after the first 
dose will not receive another dose. 

 
 
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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
• 
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 to from 
enrolment if diagnosed (Section 5.2). 
• 
Daily monitoring of serious adverse 
events (SAEs) 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. 
• 
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 
open-label dose will not receive 
another dose of study intervention (see 
Section 7.1). 
• 
Immunogenicity, anti-drug antibodies 
(ADAs) 
• 
Biopharmaceutical products may elicit 
ADAs and neutralising antibodies 
(NAb), which have the potential to 
modulate PK or PD, or to produce 
adverse reactions. 
• 
Blood samples will be collected for 
detection of both ADA and Nab (See 
Section 8.8). 

 
 
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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
• 
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 IL5 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. Neutralizing 
antibodies were not tested in this 
study. 
• 
Local injection site reactions 
• 
A potential risk of any drug delivered 
via injection. 
• 
No injection site reactions were noted 
in the preclinical studies. 
• 
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. 

 
 
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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
• 
In the GSK3511294 FTIH study 
(205722), injection site reactions were 
reported by one (3%) participant who 
received 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), a total of 2 participants had 
an elevated post-baseline QTcF value 
of potential clinical importance based 
on average from triplicate assessment: 
one on GSK3511294 100mg SC 
[Week 2: 467 msec (all subsequent 
assessments were <450 msec and Day 
1 pre-dose was 450 msec)] and one on 
placebo [Week 36: 455 msec (last 
assessment on study and Day 1 pre-
dose was 414 msec)] 
• 
ECGs will be performed according to 
time points specified in SoA Section 
1.3 and assessment will be done as 
specified in Section 8.2.3. 
• 
Participants with QTc prolongation at 
visit 1 will be excluded (criterion 6, 
Section 5.2). 
• 
Participants who meet QTc stopping 
criteria as specified in Section 7.1.3 
after the first open-label dose will not 
receive the second open-label dose. 

 
 
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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
• 
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.  
• 
Participants who are pregnant, 
breastfeeding, or plan to become 
pregnant during the study are excluded 
(criterion 10, Section 5.2). Participants 
who become pregnant during the study 
will not receive another dose of study 
intervention (see Section 7.1). 
• 
For all female participants of 
childbearing potential continuation of 
highly effective contraceptive method 
between the previous study 
(206713/213744) and enrolment into 
this study without any interruptions is 
required and must continue until 30 
weeks after the last dose. 
• 
In case the highly effective 
contraceptive method was interrupted 
prior to enrolment in this study, the 
reason must be discussed with medical 
monitor and the following must be 
done: 
➢ Highly effective contraceptive 
method must be restarted and 
continued for at least 14 days prior 
to first dose 

 
 
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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
• 
In addition, there is a low reproductive 
risk associated with the IL5 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 
monoclonal antibody (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. 
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. The 
safety profile of anti-IL5/5R mAbs is favourable. Based on the positive benefit: risk, 
anti-IL5/5R mAbs have been approved as add-on maintenance treatment for severe 
eosinophilic asthma. 
As a long-acting anti-IL5 mAb, GSK3511294 is anticipated to provide the same clinical 
benefit with a similar safety profile compared with others in its class and with the added 
benefit of 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 taken to minimise risk to participants enrolled in this 
study, the potential risks identified in association with GSK3511294 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 safety and efficacy of GSK3511294 is justified in study 212895 with a positive 
benefit: risk ratio. 

 
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3. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary (Safety) 
• 
To describe the long-term safety 
profile of GSK3511294 100 mg (SC) 
every 26 weeks in participants with 
severe asthma with an eosinophilic 
phenotype on top of existing asthma 
therapy over a 12 month open label 
extension phase 
• 
Incidence of AEs/SAEs over 52 
weeks 
• 
Incidence of immunogenicity as 
measured by the presence of 
ADA/NAb to GSK3511294 over 52 
weeks 
Secondary (Efficacy) 
• 
To evaluate the effects of long-term 
dosing of GSK3511294 100 mg (SC) 
every 26 weeks on a range of clinical 
markers of asthma control and 
additional efficacy assessments on 
top of existing asthma therapy over a 
12 month open label extension phase 
• 
Annualized rate of Clinically 
significant exacerbations over 52 
weeks 
• 
Change from Baseline in Asthma 
Control Questionnaire-5 (ACQ-5) 
score at discrete timepoints during the 
52 week period 
• 
Change from Baseline in St. George's 
Respiratory Questionnaire (SGRQ) 
total score at Week 26 and Week 52. 
• 
Change from Baseline in pre-
bronchodilator FEV1 at Week 26 and 
Week 52 
Other 
• 
To describe the long-term safety 
profile of GSK3511294 100 mg (SC) 
every 26 weeks in participants with 
severe asthma with an eosinophilic 
phenotype on top of existing asthma 
therapy over a 12 month open label 
extension phase 
• 
ECG assessments at discrete 
timepoints during the 52 week period 
o 
Change from baseline in ECG 
values 
o 
Maximum QTc values post 
baseline  
o 
Maximum increase in QTc 
values post baseline  
o 
ECG findings 
• 
Change from baseline in vital signs 
including blood pressure (BP), body 
temperature, and pulse rate at discrete 
timepoints during the 52 week period 

 
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Objectives 
Endpoints 
• 
Change from baseline in laboratory 
parameters (including 
haematological, clinical chemistry) 
and hepatobiliary laboratory 
abnormalities, at discrete timepoints 
during the 52 week period 
Pharmacodynamic (PD) 
3.1. 
Primary Estimand 
Treatment: open-label GSK3511294 + SoC 
• 
open-label GSK3511294 + SoC and on GSK3511294 + SoC in previous study 
• 
open-label GSK3511294 + SoC and on placebo + SoC in previous study 
Population: Adult and adolescent participants with severe asthma with an eosinophilic 
phenotype following the strategy outlined for dealing with the main intercurrent events 
that are anticipated. 
Endpoints: 
• 
Incidence of AEs/SAEs 
• 
Incidence of immunogenicity measured by the presence of ADA/NAb to 
GSK3511294 
Main intercurrent events anticipated: 
• 
Study intervention discontinuation due to reasons unrelated to the COVID 19 
pandemic: while on-treatment strategy i.e. using data up until 26 weeks after last 
dose of GSK3511294. This strategy is to summarise the events while the participants 
are exposed to the treatment. 
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• 
Study intervention discontinuation due to reasons related to the COVID-19 
pandemic: while on-treatment strategy i.e. using data up until 26 weeks after last 
dose of GSK3511294 
• 
Change in maintenance therapy or use of prohibited medications: 
 
 
Summary measures: 
• 
Number and percentage of participants with any AEs and incidence rate of AEs 
• 
Number and percentage of participants with incidence of immunogenicity as 
measured by the presence of ADA/NAb to GSK3511294 and mean titre results 
3.2. 
Secondary Estimands 
Treatment: open-label GSK3511294 + SoC 
• 
open-label GSK3511294 + SoC and on GSK3511294 + SoC in previous study 
• 
open-label GSK3511294 + SoC and on placebo + SoC in previous study 
Population: Adult and adolescent participants with severe asthma with an eosinophilic 
phenotype following the strategy outlined for dealing with the main intercurrent events 
that are anticipated. 
Endpoints: 
• 
Annualised rate of clinically significant exacerbations over 52 weeks 
• 
Change from Baseline in ACQ-5 score at discrete timepoints during the 52-week 
period 
• 
Change from Baseline in SGRQ total score at Week 26 and Week 52. 
• 
Change from Baseline in pre-bronchodilator FEV1 at Week 26 and Week 52 
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: treatment 
 
 
Summary measures: 
• 
Annualised rate of clinically significant exacerbations 
• 
Mean Change from Baseline in SGRQ total score, ACQ-5 score, pre-bronchodilator 
FEV1 at discrete timepoints during the 52-weeks period 
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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a multicentre, single-arm, open-label 12- month extension study to evaluate the 
long-term safety of GSK3511294 100 mg administered SC, in addition to standard of 
care, in participants who have severe asthma with an eosinophilic phenotype. Participants 
who completed either study 206713 or 213744 will have the opportunity to participate in 
this study, regardless of which treatment they were previously randomized. The number 
of participants enrolled in this trial will not be greater than the combined number 
randomised into Studies 206713 and 213744. Participants will be eligible to screen to 
enter the open-label extension (OLE) Study 212895 if he/she: 
• 
has received both doses of study intervention (at Visit 2 and Visit 10) AND 
• 
completed the scheduled Exit Visit (Visit 17) AND 
• 
did not meet any of the study intervention discontinuation conditions during the 
study. 
Visit 1 will serve as the Baseline Visit for this study (212895). If the Exit Visit in 
206713/213744 is on the same day or within 7 days of Visit 1 for study 212895 then 
some assessments from the Exit Visit will be used as the baseline for 212895. If the Visit 
1 is performed >7 days (maximum 14 days) after the Exit Visit in 206713/213744 several 
of the assessments need to be repeated (for details refer to Section 8). A delayed 
administration of the study intervention may be considered (maximum 4 weeks) in 
consultation with the GSK Medical Monitor. 
After giving informed consent for this study, eligibility will be assessed. The assessments 
at this baseline visit will include informed consent, updated medical history, and change 
in smoking status. 
Those participants meeting all the inclusion criteria and none of the exclusion criteria will 
receive their first open-label dose of GSK3511294 SC at Visit 1. Participants will receive 
a second open-label dose of GSK3511294 SC 26 weeks after Visit 1, providing up to 
52 weeks of treatment. Participants who experience any of the study intervention 
discontinuation conditions (listed in Section 7.1) will not receive another dose of study 
intervention. 
Participants will remain on standard of care asthma therapy, which may be adjusted 
during the study at the discretion of their physician. The use of any other anti-IL-5/5R 
therapy mepolizumab (Nucala), benralizumab (Fasenra), reslizumab (Cinqair/Cinqaero) 
or any other monoclonal antibody including omalizumab (Xolair) and dupilumab 
(Dupixent), will not be permitted during the course of the study. 
Serum samples for anti-GSK3511294 antibody measurements will be obtained from all 
participants according to the time points specified in SoA (Section 1.3). Any sample 
obtained for anti-GSK3511294 antibody testing that tests positive will be tested for 
neutralizing antibody. 

 
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Participants will be monitored for a minimum of two hours after each dose and safety and 
efficacy will be assessed according to the time points specified in the SoA (Section 1.3). 
The Asthma Control Questionnaire-5 (ACQ-5) and SGRQ will be used to assist the 
investigator in assessing the participant’s asthma status along with spirometry. As some 
subjects may have previously received placebo while participating in the 206713 and 
213744 studies and are naïve to GSK3511294, safety lab monitoring will be more 
frequent after each dose administration. Participants will be regarded as having 
completed the current study if they complete the 52-week treatment administration, Exit 
Visit and an additional Follow-up visit/call, 4 weeks after the Exit Visit. 
For WOCBP the follow up visit should be conducted as onsite visit or home visit (where 
applicable). Follow-up phone call is only applicable for male and WONCBP. 
Study visits may be conducted remotely or virtually, however, in-person clinic visits are 
required for those visits with study drug administration, 12-lead ECG or spirometry 
assessments, as detailed in the SoA (Section 1.3): Visit 1, Visit 2, Visit 6, Visit 7, Exit 
Visit 12, 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 9). 
4.2. 
Scientific Rationale for Study Design 
This study will allow participants that completed Study 206713 and Study 213744 to 
initiate GSK3511294 100 mg SC treatment if they were previously randomised to 
placebo, or continue with GSK3511294 if previously randomised to receive 
GSK3511294 100 mg SC. This will increase the overall number of participants exposed 
to GSK3511294 by permitting participants previously on placebo to be treated with 
GSK3511294 100 mg SC, while allowing exposure of up to a total of 104 weeks for 
participants previously receiving GSK3511294 in Study 206713 and 213744.  
GSK3511294 100 mg SC will be administered as adjunctive therapy to the participant’s 
usual treatment. Investigators should continue participants on their maintenance asthma 
therapy and adjust this therapy as needed in response to improving or worsening asthma. 
All changes in asthma therapy will be captured in the source and electronic case report 
form (eCRF). 
Participants will be evaluated in the clinic after each dosing occasion and approximately 
every 4 weeks (with some exceptions) thereafter. The Asthma Control Questionnaire-5 
(ACQ-5) and SGRQ will be used to assist the investigator in assessing the participant’s 
asthma status along with spirometry. 

 
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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 [GSK 
Document Number RPS-CLIN-044550] that investigated single SC doses of 
GSK3511294 ranging from 2 mg to 300 mg. The FTIH study was designed to collect 
robust blood eosinophil pharmacology data (including washout) in a relevant population 
(mild to moderate asthma and a blood eosinophil count ≥200 cells/μL at screening) and 
inform dose selection in late-phase development using Model-informed drug 
development (MIDD) principles [Wang, 2019; Marshall, 2019]. The precedence of using 
blood eosinophil reduction as a predictor of efficacy in severe asthma with an 
eosinophilic phenotype was established in two mepolizumab Phase 3 studies, which 
consistently reduced annualised exacerbation rate by approximately 50%, for associated 
reductions in blood eosinophils of 84% in the MENSA trial [Ortega, 2014] and 78% in 
the MUSCA trial [Chupp, 2017], compared with placebo. Since GSK3511294 targets the 
same IL-5 epitope as mepolizumab, establishing the same reduction in blood eosinophils 
as mepolizumab via the same IL-5 neutralisation is expected to generate the same clinical 
efficacy in the same patient population (i.e., severe asthma with an eosinophilic 
phenotype with a previous history of two or more exacerbations in the past 12 months). 
In addition, given the precedented safety profile of IL-5 neutralisation comparable to 
placebo, targeting previous mepolizumab pharmacology is both valid and expeditious in 
selecting the dose of GSK3511294. 
A comprehensive analysis of the clinical effects of GSK3511294 on blood eosinophils 
from Study 205722 was therefore conducted to identify the dose and frequency of dosing 
that match previous Phase 3 mepolizumab target pharmacology most closely. To this end, 
a Bayesian non-linear mixed-effects dose-time response model was used to analyse blood 
eosinophil data. This model was then used to calculate the posterior probability of 
achieving reductions of 78% for the MUSCA trial [Chupp, 2017] and 84% for the 
MENSA trial [Ortega, 2014] compared with placebo. Doses deemed suitable were 
defined as having a probability of exceeding MUSCA in excess of 80% while doses 
deemed unsuitable as having a probability of exceeding MENSA of less than 10%. 

 
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Based on the comprehensive analysis of the clinical effects of GSK3511294 on blood 
eosinophils, a dose of 100 mg SC GSK3511294 administered every 26 weeks has been 
selected to match the pharmacology seen with mepolizumab in two Phase 3 studies at the 
approved therapeutic dose, but over an extended period of 26 weeks [GSK Document 
Number 2019N418119_00]. 
4.4. 
End of Study Definition 
The end of the study is defined as the date of the last follow-up visit/call for the last 
participant in the trial. 
Participants will be considered to have completed the study if he/she has completed the 
Exit Visit and the Follow-up visit/call, 4 weeks after the Exit Visit, 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: 
TYPE OF PARTICIPANT AND DISEASE CHARACTERISTICS 
1. Participants: Participants who completed the double-blind study intervention 
treatment during Study 206713 or Study 213744. 
2. Age: Adults and adolescents ≥12 years of age, at the time of signing the informed 
consent/assent. 
 
 
  
 
. 
 
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SEX 
 
INFORMED CONSENT 
4. Informed Consent: Capable of giving signed informed consent/assent which 
includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol. 
5. French participants: In France, a participant will be eligible for inclusion in this 
study only if either affiliated to or a beneficiary of a social security category. 
 
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
MEDICAL CONDITIONS 
1. Health Status: Clinically significant change in health status during Study 206713 
or Study 213744 which in the opinion of the investigator would make the 
participant unsuitable for participation in this study. 
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MEDICAL CONDITIONS 
2. Malignancy: A current malignancy or a malignancy that developed during Study 
206713 or Study 213744 (participants who had localised carcinoma of the skin 
that was resected for cure will not be excluded).  
3. Participants who have other clinically significant medical conditions uncontrolled 
with SoC therapy not associated with Asthma, e.g., uncontrolled cardiovascular 
disease or ongoing active infectious disease which in the opinion of the 
investigator makes them unsuitable for the study. 
4. Participants with known parasitic (helminth) infections within 6 months prior to 
Visit 1 will be excluded from the study or required to be adequately treated for 
helminth infections before initiation of GSK3511294.  
5. Liver chemistry test: Participants who meet the following based results of week 48 
assessment from Study 206713 or Study 213744 or from a later result: 
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) 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. 
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 eligibility criteria. 
6. 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. 
7. ECG Assessment: QTcF ≥450 msec or QTcF ≥480 msec for participants with 
Bundle Branch Block in the 12-lead ECG machine read at Visit 1. 
 
OTHER EXCLUSIONS 
8. Smoking status: Current smokers 
9. Hypersensitivity: Participants with allergy/intolerance to the excipients of 
GSK3511294 in Section 6.1, a monoclonal antibody, or biologic. 
10. 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 8.2.5. 

 
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OTHER EXCLUSIONS 
11. Permanent Discontinuation of study intervention in Previous Study: Participants 
who for any reason permanently discontinued study treatment in the previous 
study 206713/213744 will be excluded from this study. 
12. Other investigational product/clinical study: 
• 
Participants who have received treatment with an investigational agent 
(biologic or non-biologic) within the past 30 days or 5 drug half-lives 
whichever is longer, prior to the first dose, other than Study 206713/213744 
study treatment. The term “investigational” applies to any drug not approved 
for sale for the disease/indication to treat in the country in which it is being 
used or investigational formulations of marketed products 
• 
Participants who are currently participating in any other interventional clinical 
study 
5.3. 
Lifestyle Considerations 
No Lifestyle restrictions are required. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently entered in the study. A minimal set of screen failure information 
is required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes 
demography, screen failure details, eligibility criteria, any protocol deviations and any 
serious adverse events (SAEs). 
Individuals who do not meet the criteria for participation in this study (screen failure) 
may not be rescreened. 
5.5. 
Criteria for Temporarily Delaying Enrolment/ Administration 
of Study Intervention Administration 
A delayed administration of the study intervention (>14 days after the Exit Visit in 
206713/213744 and up to a maximum of 4 weeks) may be considered in consultation 
with the GSK Medical Monitor. 

 
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6. 
STUDY INTERVENTION(S) AND CONCOMITANT 
THERAPY 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol. 
Study intervention will only be administered in the clinic; hence, Visit 1 (Week 0) and 
Visit 6 (Week 26) are required to be in-clinic visits. 
6.1. 
Study Intervention(s) 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 Type I 
glass syringe (with a 1/2-inch, 29-gauge thin wall, staked needle and sealed with a latex-
free rubber plunger). 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 in 1.0 mL sterile liquid formulation. The formulation 
contains L-histidine, trehalose dihydrate, L-arginine hydrochloride, disodium edetate 
(EDTA), water for injection and polysorbate 80. 
An overview of study intervention is provided in Table 1. 
Table 1 
Overview of Study Intervention 
ARM Name 
GSK3511294 100 mg 
Intervention Name 
GSK3511294 100 mg SC 
Type  
Biologic 
Dose Formulation 
Sterile liquid formulation in single-use PFS 
Unit Dose 
Strength(s) 
100 mg/mL; 1.0 mL (deliverable) 
Dosage Level(s) 
100 mg once every 26 weeks (Week 0 and Week 26) 
Route of 
Administration 
SC injection 
Use 
Experimental 
IMP and NIMP 
IMP 
Sourcing 
Provided centrally by the Sponsor  
Packaging and 
Labelling 
Study Intervention will be provided in PFS. Each PFS will be labelled 
as required per country requirement. 
PFS=Pre-filled safety syringe, IMP=Investigational Medicinal Product 

 
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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 device. The devices used in the 
study are representative of the devices planned to be marketed for the product. 
• 
The components that comprise the pre-filled syringe (glass barrel with pre-staked 
needle and plunger) are sourced from Becton Dickinson. The pre-filled syringe is 
filled and assembled at GSK, Barnard Castle. 
• 
The safety syringe components are manufactured by Becton Dickinson. The safety 
syringe components are assembled with the pre-filled syringe at GSK, Barnard 
Castle. 
The Instruction for use (IFU) of the injection device will be provided. The instructions 
were developed and optimised as a result of formative human factors studies for 
mepolizumab and are representative of those that are planned for GSK3511294. 
All device deficiencies (including malfunction, use error and inadequate labelling) shall 
be documented, and reported by the investigator throughout the clinical investigation (see 
Section 8.3.8) and appropriately managed by GSK. 
6.2. 
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. 
• 
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 Study Reference Manual.  
• 
Under normal conditions of handling and administration, study intervention is not 
expected to pose significant safety risks to site staff. Take adequate precautions to 
avoid direct eye or skin contact and the generation of aerosols or mists. In the case of 
unintentional occupational exposure, notify the monitor, Medical Monitor and/or 
GSK study contact. 

 
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• 
A Material Safety Data Sheet (MSDS)/equivalent document describing occupational 
hazards and recommended handling precautions either will be provided to the 
investigator, where this is required by local laws, or is available upon request from 
GSK. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
This is an open-label study, randomization is not applicable. In order to maintain the 
blind from previous studies, WBC differential (% and total) will be blinded at screening 
. Sites to continue the blinding strategy from 206713 and 213744 
studies 
 
6.4. 
Study Intervention Compliance 
GSK3511294 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 event (For details refer to SRM). 
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. 
6.5. 
Dose Modification 
Dose modification is not allowed. 
6.6. 
Continued Access to Study Intervention after the End of the 
Study 
Participants will not receive any additional treatment from GSK after completion 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. 
6.7. 
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 [GSK Document Number RPS-CLIN-044550 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). 
Each PFS will enable the delivery of a single dose of study intervention (see Section 6.1). 
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In the event of an overdose, the investigator should: 
• 
Contact the Medical Monitor immediately. 
• 
Treat the patient 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. 
6.8. 
Concomitant Therapy 
At enrolment, information on the participant’s baseline SoC asthma therapy will be 
collected and recorded in the eCRF. 
Any medication or vaccine (including over the counter or prescription medicines, 
recreational drugs, vitamins, and/or herbal supplements) that the participant is receiving 
at the time of enrolment or receives during the study must be recorded along with: 
• 
reason for use 
• 
dates of administration including start and end dates 
• 
dosage information including dose and frequency 
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
6.8.1. 
Permitted Medications and Non-Drug Therapies 
Throughout the study, participants are to be maintained on SoC asthma treatment. During 
the study, adjustments may be made to participant’s asthma maintenance therapy based 
on the investigator’s judgment. 
If uncertain whether a medication is permitted, please confirm with the Medical Monitor. 
Albuterol/salbutamol is permitted throughout the study but should, if possible, be 
withheld in the 6-hour period prior to spirometry assessments. 
LABAs, LAMAs, ICS/LABA or ICS/LABA/LAMA fixed dose combinations should be 
withheld for ≥12 hours prior to spirometry, if possible. 

 
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Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure 
(BiPAP) for the treatment of obstructive sleep apnoea is permitted. This treatment must 
be captured in the eCRF. 
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. 
COVID-19 vaccination is permitted and should follow local regulations. COVID-19 
vaccine administration and the study site injection should be separated by 14 days if 
possible, in order to be able to properly assess study injection site/treatment reactions. 
6.8.2. 
Prohibited Medications and Non-Drug Therapies 
The following medications are not allowed during the study: 
Medication 
Monoclonal antibodies and Investigational drugs 
• 
Any investigational drug/vaccine. 
• 
Mepolizumab [Nucala], reslizumab [Cinqair/Cinqaero], benralizumab [Fasenra], 
Omalizumab [Xolair], dupilumab [Dupixent] 
• 
Other monoclonal antibodies 
• 
Experimental anti-inflammatory drugs (non-biologicals) 
Immunosuppressive medications such as those listed below (not all inclusive) 
• 
Regular systemic (oral or parenteral) and intramuscular, long-acting depot 
corticosteroids if used to treat a condition other than asthma 
• 
Methotrexate, cyclosporin, azathioprine  
• 
Oral gold 
• 
Chemotherapy used for conditions other than asthma 
Additionally, Bronchial Thermoplasty and Radiotherapy are excluded throughout the 
study. 

 
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6.8.3. 
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. 
Low dose ICS-formoterol as rescue medication is not allowed. 
Participants will be dispensed an MDI at Visit 1 to be used primarily to treat asthma 
symptoms on an as needed basis (see Section 8.4.3). 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 delayed, if possible, for at least 6 hours prior to the 
spirometry assessments. 

 
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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: 
• 
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 7.1.3) 
• 
Pregnancy: Positive pregnancy test (see Section 8.2.5) 
• 
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 7.4). 
If a participant meets any of the treatment discontinuation conditions or chooses (for any 
reason) not to receive an additional dose of study intervention before the end of the 
protocol specified 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 Visit and 
Follow-up Visit/call.  
• 
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 to have regularly scheduled 
in-clinic visits or to have regularly scheduled phone visits. The required study 
assessments will depend on whether the participant is attending an in-clinic visit or a 
scheduled phone visit. 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, if 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. 
7.1.2. 
Rechallenge 
7.1.2.1. 
Study Intervention Restart or Rechallenge after liver stopping criteria 
met 
Study intervention restart or rechallenge after liver chemistry stopping criteria are met by 
any participant in this study is not allowed. 

 
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7.1.3. 
QTc Stopping Criteria 
Details on performing ECG assessments can be found in Section 8.2.3. 
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. 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 Visit 1 should be used as 
baseline QTcF value for any changes from baseline calculations during the study. 
Twelve-lead ECG central overread values should be used at all visits with the exception 
of Visit 1 and Visit 6 where 12-lead ECG machine read values should be used. After 
Visit 1 12-lead ECG central over-read values should be used to assess QTc stopping 
criteria, with the exception of Visit 6 (Week 26) where 12-lead ECG machine read values 
should be used. 
7.1.4. 
Temporary Discontinuation 
For this study, a temporary discontinuation refers to a delayed administration of the 
second open-label dose of study intervention at Week 26. 
A delayed administration of the study intervention may be considered in consultation 
with the GSK Medical Monitor due to clinical or safety reasons (eg. 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). 

 
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7.2. 
Participant Discontinuation/Withdrawal from the Study 
• 
Participants are strongly encouraged to remain in the study for the entire duration but 
may prematurely discontinue study intervention product and withdraw from the 
study at any time at his/her own request, at the request of their legally authorised 
representative (LAR), or at any time at the discretion of the investigator for safety, 
behavioural, compliance or administrative 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 assessment. WOCBP will need to 
perform the follow up visit as onsite visit or home visit. 
Note: This includes any participants who initially discontinue IP and remain in the 
study (Section 7.1) but later decide to withdraw from the study. 
• 
Participants who permanently discontinue IP are not required to withdraw from the 
study. If a participant must permanently discontinue IP, every effort should be made 
by the Investigator/site staff to keep the participant in the study to collect important 
safety and efficacy data. Participants who have permanently discontinued IP and 
have not withdrawn consent may continue in the study to complete all remaining 
protocol specified visits by continued in-clinic visits or by phone contact. 
• 
For participants who discontinue IP and withdraw from the study, the Withdraw 
from Study Visit should be conducted as per SoA.  
• 
If the participant withdraws consent for disclosure of future information, the sponsor 
may retain and continue to use any data collected before such a withdrawal of 
consent. 
• 
If a participant withdraws from the study, he/she may request destruction of any 
samples taken and not tested, and the investigator must document this in the site 
study records. 
7.3. 
Lost to Follow Up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits (or scheduled phone calls, if applicable) and is unable to be contacted by 
the study site. 

 
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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 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 a 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. If possible, ADA, C3, and C4 samples may be 
taken at the time of the event along with haematology, clinical chemistry and urinalysis. 
Symptoms potentially suggestive of vasculitis include but are not limited to: 
• 
persistent* fever (*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 

 
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• 
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 heterogeneous with 
respect to the time course over which they develop, organ involvement and the 
constellation of symptoms and severity. Early recognition of potential events of vasculitis 
is important to timely diagnosis and subsequent treatment.  
The precise management will depend on the clinical evaluation at the time of presentation 
and ongoing assessment including consideration of relevant differential diagnoses. Given 
that there is often a differential for presenting symptoms such as infection, and indeed 
such factors may also precipitate immune related AEs, these factors (infectious, 
neoplastic, metabolic, toxic) should be given due consideration and ruled out.  
Serological, immunological, and histological (biopsy) data should be considered to 
support the diagnosis and consultation with the GSK medical monitor, and an appropriate 
medical specialist should be considered when investigating a possible immune related 
AE. 
Unscheduled ADA, C3 and C4 samples may be taken at the time of the event and 
samples may be taken for additional biomarkers (e.g., ANA, anti-neutrophil cytoplasmic 
antibodies [ANCA]) in the setting of clinical concern regarding the possibility of immune 
complex disease. If necessary, testing for biomarkers, e.g., ANA, ANCA (anti-
myeloperoxidase [MPO] antibody and anti-proteinase 3 [PR3] antibody), may also be 
conducted using the frozen baseline serum samples from the preceding study 206713 or 
213744 (that were collected and stored prior to administration of study intervention) to 
allow for evaluation of interval change for participants with suspected vasculitis (see 
Section 8.7.2 ). Other possible causative or differential factors for abnormal clinical or 
laboratory observations may also have to be investigated including testing to exclude 
infection.  
If clinically indicated, the patient 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 1.3. 
• 
Protocol waivers or exemptions are not allowed. 
• 
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or 
discontinue study intervention. 
• 
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
• 
All enrolment 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. 
• 
For haematology samples 
, the absolute and differential (%) values of 
eosinophils, lymphocytes, basophils, neutrophils and monocytes will be blinded to 
site staff and sponsor to protect the blind from the previous study.  
• 
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. 
Critical Assessments performed at Enrolment (Visit 1) 
The following assessments must be performed for all participants at Visit 1: 
• 
Informed consent 
• 
Assessment of inclusion/exclusion criteria 
• 
Record demographic data such as year of birth, sex, race, and ethnicity in the 
participant’s eCRF. Collection of sex, race and ethnicity data is necessary to assess 
and monitor the diversity of the trial participants, and to determine if the trial 
participants are truly representative of the impacted population. 
• 
Review and document any changes in Medical History 
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• 
Review of prior/concomitant medication 
• 
Review and document any change in Smoking Status 
• 
Review for exacerbations. If Visit 1 for 212895 is not on the same day as the exit 
visit for the preceding study (206713 or 213744) then any asthma exacerbations that 
occurred between the two studies should be recorded as historical asthma 
exacerbations for study 212895. 
• 
Urine pregnancy test for females of childbearing potential 
• 
Provide medical problems and healthcare utilisation worksheet (see Section 8.9) 
8.1.2. 
Assessments performed if the time between the Exit Visit from 
the prior study (206713/213744) and Visit 1 is >7 days 
The following assessments need only be performed if the time between the Exit Visit 
from the prior study (206713/213744) and Visit 1 is >7 days: 
• 
Physical Examination 
• 
12-lead ECG 
• 
Urine analysis 
• 
Blood sampling for: 
o 
Complement C3/C4 
o 
Hematology 
o 
Clinical chemistry 
o 
Immunogenicity 
• 
Spirometry (pre-bronchodilator FEV1) 
• 
ACQ-5 
• 
SGRQ 
All clinic visits from Visit 1 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, 6 and WS visit 
must be registered in the IRT. 
8.2. 
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. 

 
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8.2.1. 
Physical Examinations 
• 
A complete physical examination will include, at a minimum, assessments of the 
skin, eyes, cardiovascular, respiratory, gastrointestinal and neurological systems. 
• 
Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
8.2.2. 
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. 
• 
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. 
• 
Vital signs including height and weight should be conducted at Visit 1. Height can be 
omitted for subsequent visits. 
8.2.3. 
Electrocardiograms 
• 
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 7.1.3 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 patient should be enrolled or discontinued from the study intervention 
(but not from the study). Refer to Section 5.2 for exclusion criteria related to ECG 
assessment and Section 7.1.3 for QTc withdrawal criteria and additional QTc 
readings that may be necessary. 
• 
ECG measurements will be made after the subject 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 
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• 
Paper ECG traces are required to be maintained at the site with other source 
documents. 
8.2.4. 
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 if applicable) should be 
repeated until the values return to normal or baseline or are no longer considered 
significantly abnormal by the investigator or medical monitor. If 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. 
• 
All protocol-required laboratory tests, as defined in Section 10.2, must be conducted 
in accordance with the laboratory manual and the SoA (Section 1.3). 
• 
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 or dose 
modification), then the results must be recorded. 
• 
For haematology samples 
, the absolute and differential (%) values of 
eosinophils, lymphocytes, basophils, neutrophils and monocytes will be blinded to 
site staff and sponsor to protect the blind from the previous study. 
8.2.5. 
Pregnancy Testing 
• 
Refer to Section 5.1 Inclusion Criteria for pregnancy testing entry criteria. 
• 
Urine pregnancy testing should be conducted as per SoA (Section 1.3) during study 
intervention period. 
• 
For all WOCBP, serum pregnancy test should be done at Exit Visit of 
206713/213744 study and urine pregnancy testing must be performed at Visit 1 prior 
to receiving first dose. 
• 
A final urine pregnancy test should be conducted for all WOCBP, 30 weeks after the 
last dose of study intervention 
• 
Participants who withdraw early from the study should have a urine pregnancy test, 4 
weeks after the WS Visit 
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• 
Additional serum or urine pregnancy tests may be performed, as determined 
necessary by the investigator or required by local regulation, to establish the absence 
of pregnancy at any time during the participant’s participation in the study. 
8.3. 
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. 
Adverse events 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. 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• 
All SAEs will be collected from the start of intervention until the Follow-up 
Visit/call 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 Follow-up Visit/call 
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. 

 
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• 
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. 
8.3.2. 
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. 
8.3.3. 
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 8.3.7), 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. 
8.3.4. 
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 Investigator’s Brochure 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. 
8.3.5. 
Pregnancy 
• 
Details of all pregnancies in female participants will be collected after the start of 
study intervention and until 30 weeks after the last study drug administration. 

 
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• 
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 
reasons will be reported as an AE or SAE. 
• 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, foetal death, stillbirth, 
congenital anomalies, and 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 8.3.4. 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. 
• 
Any female participant who becomes pregnant while participating in the study will 
discontinue study intervention and if possible, remain in the study and continue with 
all remaining study visits. 
8.3.6. 
Cardiovascular and Death Events 
For any cardiovascular events detailed in Appendix 3 and all deaths, whether or not they 
are considered SAEs, specific Cardiovascular (CV) and Death sections of the CRF will 
be required to be completed. These sections include questions regarding cardiovascular 
(including sudden cardiac death) and non-cardiovascular death. 
The CV CRFs pages are presented as queries in response to reporting of certain CV 
MedDRA terms. The CV information should be recorded in the specific cardiovascular 
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. 
8.3.7. 
Adverse Events of Special Interest 
Adverse events of special interest 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) 

 
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• 
Local injection site reactions 
• 
QTc prolongation 
See Section 2.3.1 for additional details. 
8.3.8. 
Medical Device Deficiencies 
Medical devices (PFS) are being provided for use in this study as a delivery method for 
GSK3511294. 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. 
8.3.8.1. 
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.  
• 
If the investigator learns of any device deficiency at any time after a participant has 
been discharged from the study, and such device deficiency is considered reasonably 
related to a medical device provided for the study, the investigator will promptly 
notify the sponsor. 
• 
The method of documenting Medical Device Incidents is provided in Section 10.7. 
8.3.8.2. 
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. 
8.3.8.3. 
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. 

 
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8.3.8.4. 
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. 
• 
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. 
8.4. 
Efficacy Assessments 
8.4.1. 
Efficacy Endpoints 
Efficacy endpoints are listed in Section 3. 
8.4.2. 
Asthma Exacerbations 
Clinically significant exacerbations of asthma are defined by worsening of asthma which 
requires: 
• 
use of systemic CSs or 
• 
hospitalisation or Emergency Department (ED) visit, requiring systemic steroids. 
For all participants, IV or oral steroids (e.g., prednisone) for at least 3 days or a single 
IM corticosteroid dose is required. For participants on maintenance systemic 
corticosteroids, at least double the existing maintenance dose for at least 3 days is 
required. 
Exacerbations separated by less than 7 days will be treated as a continuation of the same 
exacerbation. 
Details of each asthma exacerbation, including medications used to treat exacerbations 
should be recorded in the eCRF. 
Asthma exacerbations should not be recorded as an AE unless they meet the definition of 
a SAE. 
The time period for collection of exacerbation information in the eCRF will be from the 
time that the ICF is signed until the Exit Visit or Follow-up Visit/call or Withdraw from 
Study Visit as applicable. 

 
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8.4.3. 
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), and at scheduled in clinic- visits 
according to the SoA (Section 1.3). At each visit where spirometry is performed, 
spirometry should be performed at the same time of the day (1 hour) as the assessment 
performed at Visit 1 (the baseline assessment). Participants should try to withhold short-
acting beta-2-agonists (SABAs) for ≥6 hours and LABAs/LAMAs for ≥12 hours prior to 
the clinic visit, if possible. 
Spirometry should not be conducted for participants with confirmed/suspected COVID-
19 infection. 
8.4.4. 
Asthma Control Questionnaire (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 
according to the SoA (Section 1.3). 
8.4.5. 
St. George’s Respiratory Questionnaire (SGRQ) 
The St. George’s Respiratory Questionnaire 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 according to the SoA (Section 1.3). 
8.5. 
Pharmacokinetics 
Not applicable. 
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8.6. 
Genetics and Pharmacogenomics 
Not applicable. 
8.7. 
Biomarkers/Pharmacodynamic Markers 
8.8. 
Immunogenicity Assessments 
Antibodies to GSK3511294 will be evaluated in serum samples collected from all 
participants according to the SoA (Section 1.3). Additionally, serum samples should also 
be collected at the final visit from participants who discontinued study intervention or 
were withdrawn from the study. Processing, storage and shipping procedures are 
provided in the SRM. 
In the immunogenicity assessment for GSK3511294, a tiered analyses approach will use 
a validated binding ADA assay (screening, confirmation and titration assays) and a 
validated neutralization antibody (NAb) assay. If necessary, further immune response 
characterization may be performed as needed. 
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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
Because the study has a single treatment arm, statistical analyses of treatment effect will 
not be performed. Therefore, no hypotheses have been defined for this study. 
9.2. 
Sample Size Determination 
There is no sample size calculation for this study since this is an estimation study with the 
primary aim to estimate long-term safety outcomes. The sample size will be determined 
by the number of available participants who were randomised into Study 206713 and 
Study 213744 and are eligible for the current study based on inclusion and exclusion 
criteria. 
This study is an extension of Study 206713 and Study 213744. Participants must have 
completed the study intervention during Study 206713 or 213744 prior to entering this 
study. The maximum number of participants who are potentially eligible to take part in 
this study is approximately 750. Assuming 15% drop out rate, 637 will be enrolled into 
this open label safety study. 
The primary endpoints are incidence of AE/SAE and incidence of immunogenicity as 
measured by the presence of ADA/NAb to GSK3511294. Table 2 gives the probability of 
observing various numbers of events over an averaged on-treatment observation period, 
e.g., AE, for different anticipated population risks given a sample size of 637. For 
example, for a risk of an AE of 1/1000, we would have approximately 50% chance of 
observing at least one AE over an averaged on-treatment observation time period. Also, 
for a risk of 1/10,000, would have 6.5% chance of seeing at least one AE over an 
averaged on-treatment observation time period 
Table 2 
Probabilities of observing a given number of adverse events or more 
(k) 
 
Risk of an Event 
k 
0.0200 
0.0100 
0.0050 
0.0020 
0.0010 
0.0001 
1 
>0.9999 
0.9983 
0.9590 
0.7206 
0.4713 
0.0617 
2 
>0.9999 
0.9877 
0.8276 
0.3640 
0.1342 
0.0019 
3 
0.9997 
0.9534 
0.6176 
0.1368 
0.0269 
<0.0001 
4 
0.9988 
0.8801 
0.3942 
0.0404 
0.0041 
 
5 
0.9958 
0.7628 
0.2164 
0.0098 
0.0005 
 
6 
0.9879 
0.6128 
0.1032 
0.0020 
0.0001 
 
7 
0.9711 
0.4532 
0.0433 
0.0004 
<0.0001 
 
8 
0.9400 
0.3079 
0.0162 
0.0001 
 
 
9 
0.8901 
0.1923 
0.0054 
<0.0001 
 
 
10 
0.8190 
0.1107 
0.0016 
 
 
 

 
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9.3. 
Analysis Sets 
Analysis Set 
Description 
Screened 
All participants who were screened for eligibility 
Enrolled 
All participants who entered the study (who received 
study intervention or underwent a post screening 
study procedure).  
Note screening failures 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. 
Safety 
All participants who receive at least one dose of 
open-label GSK3511294. 
9.4. 
Statistical Analyses 
The statistical analysis plan will include a more technical and detailed description of the 
statistical analyses described in this section. This section is a summary of the planned 
statistical analyses of the most important endpoints including primary and key secondary 
endpoints. 
9.4.1. 
General Considerations 
9.4.2. 
Primary Endpoints  
Treatment 
• 
open-label GSK3511294 + SoC  
Results will also be summarised according to treatment group in studies 
206713/213744: 
• 
open-label GSK3511294 + SoC and on GSK3511294 + SoC in 
previous study 
• 
open-label GSK3511294 + SoC and on placebo + SoC in previous 
study 
Target Patient 
Population 
Adult and adolescent participants with severe asthma with an 
eosinophilic phenotype following the strategy outlined for dealing with 
the main intercurrent events that are anticipated 
Primary Endpoints 
• 
Incidence of AEs/SAEs 
• 
Incidence of immunogenicity measured by the presence of 
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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: while on-treatment strategy i.e. using data up 
to 26 weeks after last dose of GSK3511294  
b) Study intervention discontinuation due to reasons related to the 
COVID-19 pandemic: while on-treatment strategy, i.e. using data up 
to 26 weeks after last dose of GSK3511294. 
c) 
Change in maintenance therapy or use of prohibited medications: 
 
 
Summary 
measures 
• 
Number and percentage of participants with any AE/SAE will be 
summarized and incidence rate of AE/SAE will also be summarized. 
• 
Number and percentage of participants with positive anti-
GSK3511294 binding anti-body status will be summarized. 
Summary statistics for titre results will also be presented. 
9.4.3. 
Secondary Endpoints  
Treatment 
open-label GSK3511294 + SoC  
Results will also be summarised according to treatment group in studies 
206713/213744: 
• 
open-label GSK3511294 + SoC and on GSK3511294 + SoC in 
previous study 
• 
open-label GSK3511294 + SoC and on placebo + SoC in previous 
study 
Target Patient 
Population 
Adult and adolescent participants with severe asthma with an 
eosinophilic phenotype following the strategy outlined for dealing with 
the main intercurrent events that are anticipated 
Endpoint 
Annualized rate of clinically significant exacerbations. Clinically 
significant exacerbations are defined in Section 8.4.2 
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 
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pandemic: 
 
  
c) 
Change in maintenance therapy or use of prohibited medications: 
 
 
Summary measure 
Annualized exacerbation rate and 95% confidence interval (CI) 
Analysis Method 
The primary analysis of the number of clinically significant exacerbations 
will use a negative binomial model. Covariates included will be region, 
and treatment group during 206713/213744 with loge(time in study in 
years) as an offset variable. 
Handling of 
missing data and 
data to be excluded 
due to intercurrent 
events 
a) For participants that discontinue study intervention due to reasons 
related to the COVID-19 pandemic, 
 
 
 
 
. 
b) For participants that withdraw from the study, preventing 
assessment of the endpoint, 
 
 
 
 
Treatment 
• 
open-label GSK3511294 + SoC  
Results will also be summarised according to treatment group in studies 
206713/213744: 
• 
open-label GSK3511294 + SoC and on GSK3511294 + SoC in 
previous study 
• 
open-label GSK3511294 + SoC and on placebo + SoC in previous 
study 
Target Patient 
Population 
Adult and adolescent participants with severe asthma with an eosinophilic 
phenotype the strategy outlined for dealing with the main intercurrent 
events that are anticipated 
Endpoints 
• 
Change from Baseline in ACQ-5 score at discrete timepoints during 
the 52 week period 
• 
Change from Baseline in SGRQ total score at Week 26 and Week 52. 
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• 
Change from Baseline in pre-bronchodilator FEV1 at Week 26 and 
Week 52 
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: 
 
  
Summary measure  Mean and 95% CIs.  
Analysis Method  
The analysis will be performed using a repeated measures mixed 
model. Covariates included will be region, treatment group during 
206713/213744 and visit, plus interaction terms for visit by treatment group 
during 206713/213744 group. Baseline values for each assessment 
(unless otherwise specified) will be the Visit 1 pre-dose assessment.  
Handling of missing 
data and data to be 
excluded due to 
intercurrent events  
a) For participants that discontinue study intervention due to reasons 
related to the COVID-19 pandemic, 
 
 
 
  
b) For participants that withdraw from the study, preventing assessment 
of the endpoint, 
 
 
). 
9.4.4. 
Other Endpoint(s) 
The statistical analysis plan will provide a detailed description of the planned analyses for 
other endpoints. 
9.5. 
Interim Analysis 
As the study will be still ongoing at the time of regulatory submission, interim analyses 
will be performed in order to provide open-label safety and efficacy data in an interim 
Clinical Study Report (CSR) to inform the risk-benefit assessment of GSK3511294 in 
severe asthma. The Statistical Analysis Plan will describe the planned interim analyses in 
greater detail. 
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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: 
o 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
o 
Applicable ICH Good Clinical Practice (GCP) Guidelines 
o 
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: 
o 
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 
o 
Notifying the IRB/IEC of SAE or other significant safety findings as required by 
IRB/IEC procedures 
o 
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 
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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/assent 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 authorized 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 
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. 
GSK (alone or working with others) may use participant’s coded study data and samples 
and other information to carry out this study; understand the results of this study; learn 
more about GSK3511294 or about the study disease; publish the results of these research 
efforts; work with government agencies or insurers to have the GSK3511294 approved 
for medical use or approved for payment coverage. 
In case of unexpected pregnancy, participant must be informed that personal information 
such as [year of birth, sex] of the baby will be collected as part of safety follow-up. 
Consent for the baby may be obtained from the participant and/or their partner as per 
local regulations. 
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. 

 
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• 
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. 
10.1.5. 
Committees Structure 
An IDMC will review safety data from Studies 206713, 213744 and 206785 and Study 
212895 until sponsor unblinding of Studies 206713, 213744 and 206785. After sponsor 
unblinding of Studies 206713, 213744 and 206785, safety data from Study 212895 will 
be reviewed by GSK and not by the IDMC. 
The IDMC will not issue recommendations for the conduct of Study 212895. GSK will 
evaluate if IDMC recommendations from Studies 206713, 213744 and 206785 will 
require changes to Study 212895 
An Independent IDMC comprised of clinical experts external to GSK will review 
unblinded data from the parent studies (studies 206713 and 213744) and 206785 at 
defined timepoints during the study. Data from Study 212895 is being provided for 
information to the IDMC as potential supporting data for the overall assessment of safety 
for use of GSK3511294 in the 206713, 213744 and 206785 study population. 
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 Study 212895 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 participants 
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 participant 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. 

 
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• 
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 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 participant 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. 
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 right, 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 
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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 
available. 
• 
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: 
• 
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For site termination: 
• 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
• 
Inadequate or no recruitment 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 participant 
therapy and/or follow-up 
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 multicenter studies only in their entirety and not as individual site 
data. In this case, a coordinating investigator will be designated by mutual 
agreement. 
• 
Authorship will be determined by mutual agreement and in line with International 
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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). 
The tests detailed in Table 3 will be performed by the central laboratory. 
Local laboratory results may be required in the event that the central laboratory results 
are not available in time – for example: 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. 
Table 3 
Protocol-Required Safety Laboratory Tests 
Laboratory 
Assessments 
Parameters 
Hematology1 
Platelet Count  
RBC Indices: 
WBC count with Differential: 
(post-dose results blinded 
 
 as described in footnote 
1) 
 
RBC Count 
MCV 
WBC 
 
Haemoglobin 
MCH 
Neutrophils 
 
Haematocrit 
%Reticulocytes 
Lymphocytes 
 
 
 
Monocytes 
 
Eosinophils 
Basophils 
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Laboratory 
Assessments 
Parameters 
Clinical 
Chemistry2 
BUN 
Potassium 
AST(SGOT) 
Total and direct 
bilirubin 
 
Creatinine 
Sodium 
ALT (SGPT) 
Total Protein 
 
Glucose  
Calcium 
Alkaline phosphatase3 
Albumin 
Magnesium 
GGT 
 
Routine 
Urinalysis 
 
• 
Specific gravity 
• 
pH, glucose, protein, blood, ketones by dipstick 
• 
Microscopic examination and UACR (if blood or protein is abnormal 
[evidence of microalbuminuria or haematuria of ≥1+]) 
Pregnancy 
testing 
• 
Highly sensitive urine pregnancy test at Visit 1 and as per SoA (Section 
1.3) during study intervention period and at the Follow up Visit for 
WOCBP4 ; Highly sensitive serum pregnancy test at Exit Visit of 
206713/213744 study for all WOCBP. 
NOTES: 
ALT = Alanine Aminotransferase; AST = Aspartate Aminotransferase; BUN = Blood urea nitrogen; FSH = Follicle-
stimulating hormone; GGT= Gamma glutamyl transferase; hBsAg – hepatitis B surface antigen; hBc = hepatitis B core 
antibody; hCG = human chorionic gonadotropin; hsCRP = highly sensitive C-reactive protein; MPO=myeloperoxidase; 
PR3=proteinase 3; RBC = red blood cell; SGOT = Serum Glutamic-Oxaloacetic Transaminase; SGPT = Serum 
Glutamic-Pyruvic Transaminase; UACR = urinary albumin-creatinine ratio; WBC = white blood cell; WOCBP = women 
of childbearing potential; WONCBP = women of non-childbearing potential. 
1. 
To maintain the treatment blind, the following post-dose results will not be reported to investigators and blinded 
Sponsor representatives: absolute and percentage values of eosinophils, neutrophils, lymphocytes, monocytes, 
and basophils (Unblinded at 
  
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 normalized ratio (INR) >1.5, if 
INR measured, which may indicate severe liver injury (possible Hy’s Law), must be reported to GSK as an SAE. 
3. 
If alkaline phosphatase is elevated, consider fractionating. 
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 
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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., hospitalization 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 hospitalization or prolongation of existing hospitalization 
• 
In general, hospitalization signifies that the participant has been admitted 
(usually involving at least an overnight stay) at the hospital or emergency 
ward for observation and/or treatment that would not have been appropriate in 
the physician’s office or outpatient setting. Complications that occur during 
hospitalization are AE. If a complication prolongs hospitalization or fulfils 
any other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered 
serious. 
• 
Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 

 
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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 
• 
Revascularization 

 
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10.3.4. 
Recording and Follow-Up of AE and SAE 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory, and diagnostics reports) 
related to the event. 
• 
The investigator will then record all relevant AE/SAE information. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the GSK required form. 
• 
There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to GSK. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 
• 
Mild: 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. 
• 
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. 

 
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Assessment of Causality 
• 
The investigator will also consult the current IB, 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. 
 
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. 

 
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SAE Reporting to GSK via Electronic Data Collection Tool 
• 
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 at the beginning of this protocol on the 
Sponsor/Medical Monitor Contact Information page. 

 
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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-estrogen hormonal highly effective contraception methods if 
they wish to continue their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrolment. 
• 
Permanent sterilization methods (for the purpose of this study) include: 
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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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 (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulationc 
• 
oral 
• 
intravaginal 
• 
transdermal 
• 
injectable 
Progestogen-only hormone contraception associated with inhibition of ovulation 
• 
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 monoclonal antibody 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 
Not applicable. 

 
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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: 
• 
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. 

 
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Liver Chemistry Stopping Criteria 
If ALT ≥3xULN AND total bilirubin ≥2xULN or 
INR >1.5:  
• 
Repeat liver chemistries (include ALT, 
AST, alkaline phosphatase, total bilirubin 
and INR) and perform liver event follow-up 
assessments within 24 hours 
• 
Monitor 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. 
• 
Fractionate bilirubin, if total 
bilirubin≥2xULN 
• 
Obtain complete blood count with 
differential to assess eosinophilia. 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 SRM 

 
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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. 

 
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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. 
 
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. 

 
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A Medical Device SAE is any serious adverse event that: 
A permanent impairment of a body structure or a body function. 
Inpatient or prolonged hospitalization. Planned hospitalization for a pre-existing 
condition, or a procedure required by the protocol, without serious deterioration in 
health, is not considered an SAE. 
Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function 
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 describe 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. 
• 
Other measures to evaluate AEs and SAEs may be utilised (e.g., National Cancer 
Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE]). 

 
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Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE/device deficiency 
• 
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 current 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 SAE coordinator by 
telephone. 
• 
Contacts for SAE reporting can be found in SRM. 
 
SAE Reporting to GSK via Paper Data Collection Tool 
• 
Facsimile transmission of the SAE data collection tool is the preferred method to 
transmit this information to the [GSK medical monitor 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 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 in SRM. 

 
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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., dyspnea, wheeze-bronchospasm, stridor, reduced 
peak expiratory flow [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., dyspnea, wheeze-bronchospasm, stridor, reduced 
PEF, hypoxemia) 
c) Reduced BP or associated symptoms (e.g., hypotonia [collapse], syncope, 
incontinence) 
d) Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting) 
3) Reduced BP after exposure to known allergen for that patient (minutes to several 
hours): 
a) Adolescents (aged 12-17): low systolic BP (age specific) or greater than 30% 
decrease in systolic BP 
b) Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from 
that person’s baseline. 

 
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10.9. 
Appendix 9: 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 enrollment 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 
responsibility of the investigator to inform GSK when this occurs and to document in 
source notes. 

 
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• 
Remote visits may be performed at the participant’s home by qualified study 
personnel or at a local medical facility, unless the Investigator deems that a site visit 
is necessary. 
• 
Additional unscheduled safety assessments such as routine blood sampling may be 
performed at the discretion of the Investigator including in the participant’s home, if 
deemed necessary. Biological samples may be collected at a different location, other 
than the study site (e.g., at participant’s home) by qualified study personnel or at a 
local medical facility according to standard operating procedures and applicable 
regulations (see note). Biological samples should not be collected if they cannot be 
processed in a timely manner or appropriately stored until the intended use.  
• 
If visits to a site/home are not feasible, then the medical evaluation of the 
participant’s 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. 
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 Interventions and Concomitant 
Therapy), a maximum dose interval 
 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 utilization 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 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 utilized during the study for each study participant is complete and 
consistent with source documents throughout the study (ICH GCP 4.9.1 4.9.2). The 
PI may sign/re-sign the eCRF from any computer/location by accessing InForm (or 
other eDC platform) using his/her unique eCRF log-in credentials. The PI may 
delegate this activity to another medically qualified and trained sub-investigator and 
this must be documented on the Delegation of Responsibilities (DoR) Log. It is 
recommended that the PI identifies a sub-investigator as a back-up for eCRF 
signatures. The sub-investigator must be appropriately trained on the protocol and 
eCRF requirements (with training documented), and the DoR log updated 
accordingly. 
• 
Essential Document Sign Off Process: If an investigator is unable to print and sign 
essential documents such as Protocol /Amendment signature page then Email 
approval can be accepted by replying to the relevant email that is sent by GSK. 
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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. 
• 
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 4 
Schedule of Activities (SoA) Indicating Assessments that may be Conducted Outside of a Clinical Study Site 
Protocol Activity 
 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-up 
visit/call 
 or Withdrawal 
Visit 
(7 days 
Notes 
 
Visit 
V1 * V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 V11 
Exit 
Visit 
V12 
FUi WS Visit b 
FU=Follow-up visit 
WS=Withdrawn from study visit 
 
Study Week  
0 
4 
8 
12 
20 
26 
28 
32 
36 
40 
48 
52 
56 
Study Day  
1 
28 
56 
84 
140 182 196 224 252 280 336 
364 392 
 
 
General Eligibility Assessments 
Informed Consenta 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
See footnote a. 
Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography data collection 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Changes including cardiovascular (CV), 
CV risk factors, asthma including 
exacerbations, vasculitis, allergies and 
anaphylaxis 
Smoking Status 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Parasitic screening 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Parasitic screening should have been 
performed prior to treatment in the OLE 
only if the participant has travelled to 
high risk countries in the past six 
months. For details refer to study 
reference manual (SRM).  
Safety assessments 
Concomitant Medication Assessment c 
X 
X 
X 
X 
X 
X 
X 
X 
Xh 
X 
Xh 
X 
 
X 
See footnote c. 
Physical Examination  
(X)  
 
 
 
 
 
 
 
 
 
 
 X  
 
 X  
 
Vital Signs  
X d 
 
X 
 
X 
X 
X 
 
 
X 
 
X d 
 
X d 
See footnote d. 

 
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Protocol Activity 
 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-up 
visit/call 
 or Withdrawal 
Visit 
(7 days 
Notes 
 
Visit 
V1 * V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 V11 
Exit 
Visit 
V12 
FUi WS Visit b 
FU=Follow-up visit 
WS=Withdrawn from study visit 
 
Study Week  
0 
4 
8 
12 
20 
26 
28 
32 
36 
40 
48 
52 
56 
Study Day  
1 
28 
56 
84 
140 182 196 224 252 280 336 
364 392 
 
 
12-lead ECG 
(X) 
X 
 
 
 
X 
X 
 
 
 
 
X 
 
X 
ECG must be performed and assessed 
pre-dose. Twelve-lead ECG central 
overread values should be used at all 
visits with the exception of Visit 1 and 
Visit 6 where 12-lead ECG machine 
read values should be used. 
Adverse Events/Serious Adverse Event 
Assessment 
X e 
X  
X 
X 
X 
X 
X 
X 
Xh 
X 
Xh 
X 
X 
X 
See footnote e. 
Laboratory Assessments 
Urine Pregnancy Testf  
(WOCBP only) 
X 
X 
X 
X 
X 
X 
X 
X 
Xh 
X 
Xh 
X 
X 
X 
See footnote f. 
All WOCBP as determined in prior study 
(206713/ 213744) must continue their 
highly effective contraceptive method 
without any interruptions between prior 
study and enrolment in this study. See 
Section 5.1 and Section 8.2.5 for 
additional details 

 
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Protocol Activity 
 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-up 
visit/call 
 or Withdrawal 
Visit 
(7 days 
Notes 
 
Visit 
V1 * V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 V11 
Exit 
Visit 
V12 
FUi WS Visit b 
FU=Follow-up visit 
WS=Withdrawn from study visit 
 
Study Week  
0 
4 
8 
12 
20 
26 
28 
32 
36 
40 
48 
52 
56 
Study Day  
1 
28 
56 
84 
140 182 196 224 252 280 336 
364 392 
 
 
Urinalysis 
(X) 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
Note: Urinalysis to be performed using 
dipstick test. If results are abnormal a 
second urine sample should be taken 
and sent to central laboratory. 
China Only: 
For China sites the urine specimen may 
be sent to the central laboratory for 
routine urinalysis instead of performing 
a local urine dipstick.  
Clinical Chemistry  
(X) 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
Include liver chemistry. 
Immunogenicity sample 
(X) 
 
 
X 
 
X 
 
 
 
X 
 
X 
 
X 
 
Efficacy Assessments 
Review of exacerbations 
X 
X 
X 
X 
X 
X 
X 
X 
Xh 
X 
Xh 
X 
X 
X 
. 
Spirometry (pre-bronchodilator FEV1) 
(X) 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
FEV1=Forced expiratory volume in 1 
second; Spirometry should not be 
conducted for participants with 
confirmed/suspected COVID-19 
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Protocol Activity 
 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-up 
visit/call 
 or Withdrawal 
Visit 
(7 days 
Notes 
 
Visit 
V1 * V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 V11 
Exit 
Visit 
V12 
FUi WS Visit b 
FU=Follow-up visit 
WS=Withdrawn from study visit 
 
Study Week  
0 
4 
8 
12 
20 
26 
28 
32 
36 
40 
48 
52 
56 
Study Day  
1 
28 
56 
84 
140 182 196 224 252 280 336 
364 392 
 
 
ACQ-5 
(X) 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
ACQ-5=Asthma Control Questionnaire 
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 hypersensitivity 
for at least 2 h after IP administration. 
For details refer to study reference 
manual (SRM). 
Worksheets/eCRF 
Provide worksheet 
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 
Dispense Rescue medication  
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
 
 
 
 
Register Visit in the IRT system 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
IRT=interactive response technology 
Complete electronic Case Report Form (eCRF) X 
X 
X 
X 
X 
X 
X 
X 
Xh 
X 
Xh 
X 
 
X 
 
HRQoL: PRO and Health Outcomes Assessments 
SGRQ 
(X) 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
SGRQ=St. George’s Respiratory 
Questionnaire 
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Protocol Activity 
 
Intervention Period and Exit Visit (visit window is 7 days) 
Follow-up 
visit/call 
 or Withdrawal 
Visit 
(7 days 
Notes 
 
Visit 
V1 * V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 V11 
Exit 
Visit 
V12 
FUi WS Visit b 
FU=Follow-up visit 
WS=Withdrawn from study visit 
 
Study Week  
0 
4 
8 
12 
20 
26 
28 
32 
36 
40 
48 
52 
56 
Study Day  
1 
28 
56 
84 
140 182 196 224 252 280 336 
364 392 
 
 
*: If the Exit Visit in 206713/213744 is on the same day, or within 7 days of Visit 1 for study 212895 then the assessments in brackets above do not need to be performed and the 
assessments from the Exit Visit from 206713/213744 will be used as the baseline for 212895. Information will be transferred accordingly. If the Visit 1 performed greater >7 days 
(maximum 14 days) after the Exit Visit in 206713/213744 then the assessments in brackets needs to be performed (For details refer to Section 8). A delayed administration of the 
study intervention (maximum 4 weeks) may be considered in consultation with the GSK Medical Monitor. 
a. 
Informed Consent must be obtained prior to initiating any study assessments.  
b. 
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 participant withdraws before the second dose of study intervention, or at Week 52 if the second dose of study intervention was received.  
c. 
Ensure maintenance asthma medications from the previous trial to Visit 1 and all current medications are reviewed. 
d. 
Vital signs including height and weight should be conducted at Visit 1. Height can be omitted for subsequent visits.  
e. 
SAEs must be collected after signing of Informed Consent. 
f. 
Urine pregnancy testing is only required for women of childbearing potential (WOCBP). Serum pregnancy test is required at the Exit Visit of the parent protocols for all WOCBP. 
g. 
For haematology samples 
, the absolute and differential (%) values of eosinophils, lymphocytes, basophils, neutrophils and monocytes will be blinded to site staff 
and sponsor to protect the blind from the previous study. 
. Sites will be sent total white blood counts throughout 
the study. Samples should be taken pre-dose on dosing days. 
h. 
Week 36 and Week 48 are phone visits. In France, Week 36 and Week 48 are phone visits for all participants except WOCBP who will perform both visits, including the Follow 
Up visit, onsite. 
i. 
A follow-up visit/call should be conducted 30 weeks after the last dose of study intervention for AE/SAE assessments and pregnancy testing. For WOCBP the follow up visit 
should be conducted as onsite visit or home visit (where applicable). Follow-up phone call is only applicable for male and WONCBP. 
 
CCI
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10.10. 
Appendix 10: Country-specific requirements 
Czech Republic specific requirements: 
1. Protocol Section 8.4.2 is supplemented with following requirement: Asthma 
exacerbations should be treated in accordance with current clinical practice in the 
Czech Republic and with the current GINA recommendations. 
2. The Protocol 10.9 Appendix 9 with Recommended Measures Related to COVID-19 
Pandemic is supplemented with following requirement: These recommendations 
apply only if they are in accordance with national laws and the opinions of the State 
Institute for Drug Control- SUKL. 

 
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10.11. 
Appendix 11: Protocol amendment history 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the table of contents (TOC). 
Amendment 1: 12 January 2023 
This amendment is considered to be substantial based on the criteria set forth in Article 
10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union. 
Overall rationale for the Amendment: 
The protocol was amended in response to France EC recommendation and to include 
country specific changes in Germany, UK and Czech Republic and to provide added 
clarity to the ECG process. Additionally, it provides clarification on the use of a central 
lab for urinalyses in China. 
The Key changes are: 
• 
Clarification on urinalysis in China 
• 
Country specific changes in Germany, UK, France and Czech Republic 
• 
Follow up visit should be conducted as onsite visit or home visit (where applicable) 
for WOCBP. Administrative change to SOA table to be clear on assessment that can 
be done at home vs site 
• 
ECG updates 
• 
AGILE safety data will be included in the Independent Data Monitoring Committee 
(IDMC) review as supporting data. 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.2 and Schema  
Added footnote # Follow-up phone 
call is only applicable for male and 
WONCBP. 
Clarification 
Section 1.1 and Synopsis, Section 
1.3 and Schedule of Activities (SoA), 
Section 4.1 and Overall design, 
Section 5.5 and Criteria for 
Temporarily Delaying Enrolment/ 
Administration of Study Intervention 
Administration, 
Section 10.9 Appendix 9: 
Recommended Measures Related to 
COVID-19 Pandemic (Table 4) 
Existing text: 
A delayed administration of the 
study intervention may be 
considered (maximum 4 weeks) 
due to clinical or safety reasons in 
consultation with the GSK Medical 
Monitor. 
 
Revised text: 
A delayed administration of the 
study intervention may be 
considered (maximum 4 weeks) in 
consultation with the GSK Medical 
Monitor. 
Clarification 

 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 1.1 Synopsis, Section 4.1 
Overall design 
 
Removed reference to week 0, 
week 26 and week 52 from the 
parent studies (206713 or 213744) 
and added reference to Visits 2, 10 
and 17 instead. 
Clarification 
Section 1.3 and Schedule of 
Activities (SoA),  
Section 10.9 Appendix 9: 
Recommended Measures Related to 
COVID-19 Pandemic (Table 4) 
Moved note (see footnote d) from 
Physical examination to Vital signs. 
 
Clarification 
Section 1.3 and Schedule of 
Activities (SoA),  
Section 10.9 Appendix 9: 
Recommended Measures Related to 
COVID-19 Pandemic (Table 4) 
Administer Study intervention: 
Modified the text in notes as 
follows: 
Study intervention will only be 
administered in the clinic. Any 
scheduled assessments or sample 
draws should be performed 
beforehand. Monitor participant for 
hypersensitivity for at least 2 h after 
IP administration. For details 
refer to study reference manual 
(SRM). 
Clarification 
Section 1.3 and Schedule of 
Activities (SoA),  
Section 10.9 Appendix 9: 
Recommended Measures Related to 
COVID-19 Pandemic (Table 4) 
Add notes to SoA referencing for 
ECG and new wording as below, 
ECG must be performed and 
assessed pre-dose. Twelve-lead 
ECG central overread values 
should be used at all visits with the 
exception of Visit 1 and Visit 6 
where 12-lead ECG machine read 
values should be used. 
Clarification on ECG to be 
performed at pre-dose and to give 
clarification on usage of twelve-lead 
ECG central overread and machine 
read values for QTcF exclusion and 
discontinuation criteria.  
Section 1.1 and Synopsis, Section 
1.3 and Schedule of Activities (SoA), 
Section 4.1 Overall design, Section 
10.9 Appendix 9: Recommended 
Measures Related to COVID-19 
Pandemic (Table 4) 
Added new footnote “i” with new 
wording as below: 
For WOCBP the follow up visit 
should be conducted as onsite visit 
or home visit (where applicable). 
Follow-up phone call is only 
applicable for male and WONCBP. 
Clarification 
Section 1.3 and Schedule of 
Activities (SoA), Section 10.9 
Appendix 9: Recommended 
Measures Related to COVID-19 
Pandemic (Table 4) 
Updated footnote “h” with new 
wording as below: 
In France, Week 36 and Week 48 
are phone visits for all participants 
except WOCBP who will need to 
perform both visits, including the 
Follow Up visit, onsite. 
France EC recommendations 
Section 1.3 and Schedule of 
Activities (SoA), Section 10.9 
Appendix 9: Recommended 
Measures Related to COVID-19 
Pandemic (Table 4) 
Removed follow up visit/call 
conducted 30 weeks after the last 
dose of study intervention for 
AE/SAE assessments and 
pregnancy testing from footnote “b” 
and added as a new footnote “i”. 
Clarification 
Section 5.1 and Inclusion Criteria 
Added note to Germany and UK 
participants. 
Note: German and UK Participants: 
In Germany and UK only adult 
participants (≥18 years) are to be 
Country requirements 

 
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Section # and Name 
Description of Change 
Brief Rationale 
included in this clinical trial. 
Section 5.2 and Exclusion Criteria 
Criteria 7 revised as follows: 
ECG Assessment: QTcF ≥450 
msec or QTcF ≥480 msec for 
participants with Bundle Branch 
Block in the 12-lead ECG machine 
read at Visit 1. 
Clarification 
Section 6.3 and Measures to 
Minimize Bias: Randomization and 
Blinding 
Added the following text: 
Sites to continue the blinding 
strategy from 206713 and 213744 
studies up to 
 
Clarification 
Section 6.4 and Study Intervention 
Compliance 
Modified the below text 
Participants will be monitored in 
clinic for a minimum of 2 hours 
post-dose to monitor for immediate 
hypersensitivity and any other 
untoward event (For details refer 
to SRM). 
Clarification 
Section 7.1.3 and QTc Stopping 
Criteria 
Added the following text: 
The QTcF value from the 12-lead 
ECG central over-read at Visit 1 
should 
be used as baseline QTcF value for 
any changes from baseline 
calculations during the 
study. Twelve-lead ECG central 
overread values should be used at 
all visits with the exception of Visit 1 
and Visit 6 where 12-lead ECG 
machine read values should be 
used. After Visit 1 12-lead ECG 
central over-read values should be 
used to 
assess QTc stopping criteria, with 
the exception of Visit 6 (Week 26) 
where 12-lead 
ECG machine read values should 
be used. 
Clarification 
Section 7.2 and Participant 
Discontinuation/Withdrawal from the 
Study 
Added the text to follow-up visit as 
follows: 
WOCBP will need to perform the 
follow up visit as onsite visit or 
home visit. 
Clarification 
Section 8.1.1 and Critical 
Assessments performed at 
Enrolment (Visit 1) 
Added below point: 
Record demographic data such as 
year of birth, sex, race, and 
ethnicity in the participant’s eCRF. 
Collection of sex, race and ethnicity 
data is necessary to assess and 
monitor the diversity of the trial 
participants, and to determine if the 
trial participants are truly 
representative of the impacted 
population. 
As per audit findings from other 
studies 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 8.1.2 and Assessments 
performed if the time between the 
Exit Visit from the prior study 
(206713/213744) and Visit 1 is >7 
days 
Added new section heading for 
existing text. 
 
Removed below assessments: 
• 
SAEs/AEs 
• 
Vital Signs 
Clarification 
Section 8.2.1 and Physical 
Examination 
Removed below text: 
Height (screening only) and weight 
will also be measured and recorded 
Clarification 
Section 8.2.2 and Vital Signs 
Added below text: 
Vital signs including height and 
weight should be conducted at Visit 
1. Height can be omitted for 
subsequent visits. 
Clarification 
Section 8.2.3 and 
Electrocardiograms 
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 patient should be 
enrolled or discontinued from the 
study intervention (but not from the 
study). Refer to Section 5.2 for 
exclusion criteria related to ECG 
assessment and Section 7.1.3 for 
QTc withdrawal criteria and 
additional QTc readings that may 
be necessary. 
Clarification 
Section 8.4.2 and Asthma 
Exacerbations 
Existing text: 
Clinically significant exacerbations 
of asthma are defined by: 
Worsening of asthma that requires 
use of systemic corticosteroids1 
and/or hospitalization and/or 
Emergency Department (ED) visits. 
 
Revised text: 
Clinically significant exacerbations 
of asthma are defined by worsening 
of asthma which requires: 
•use of systemic CSs or  
•hospitalisation or Emergency 
Department (ED) visit, requiring 
systemic steroids. 
Clarification 
Section 10.1.3 and Informed Consent 
Process 
Added text: 
In case of unexpected pregnancy, 
participant must be informed that 
personal information such as [year 
of birth, sex] of the baby will be 
collected as part of safety follow-up. 
Consent for the baby may be 
obtained from the participant and/or 
their partner as per local 
regulations. 
As per new protocol template 
instructions 
Section 10.1.5 and Committees 
Structure 
Structure of IDMC included. 
Study data provided as supporting 
data for the IDMC review. 

 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 1.3 and Schedule of 
Activities (SoA), Section 
10.2.Appendix 2: Clinical Laboratory 
Tests, Section 10.9 Appendix 9: 
Recommended Measures Related to 
COVID-19 Pandemic (Table 4) 
Note: Urinalysis to be performed 
using dipstick test. If results are 
abnormal a second urine sample 
should be taken and sent to central 
laboratory. 
 
For China sites the urine specimen 
may be sent to the central 
laboratory for routine urinalysis 
instead of performing a local urine 
dipstick. 
Country specific procedure 
Section 1.3 and Schedule of 
Activities (SoA), Section 
10.2.Appendix 2: Clinical Laboratory 
Tests, Section 10.9 Appendix 9: 
Recommended Measures Related to 
COVID-19 Pandemic (Table 4) 
Haematology with white blood cells 
count: 
 
Added Note: Site should continue 
with the blinding strategy from 
206713 and 213744 studies up to 
 
Clarification 
Section 10.10 Appendix 10: Country-
specific requirements 
Added Czech Republic specific 
requirements: 
 
1. 
Protocol Section 8.4.2 is 
supplemented with following 
requirement: Asthma 
exacerbations should be 
treated in accordance with 
current clinical practice in the 
Czech Republic and with the 
current GINA 
recommendations. 
 
2. 
The Protocol 10.9 Appendix 9 
with Recommended 
Measures Related to COVID-
19 Pandemic is 
supplemented with following 
requirement: These 
recommendations apply only 
if they are in accordance with 
national laws and the 
opinions of the State Institute 
for Drug Control- SUKL. 
Country requirements 
Throughout 
Minor editorial and document 
formatting revisions 
Minor, therefore have not been 
summarized. 
CCI

 
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10.12. 
Appendix 12: 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  
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  
CL  
Clearance  
cm  
Centimeter  
CONSORT  
Consolidated Standards of Reporting Trials  
CPAP  
Continuous positive airway pressure  
CPK  
Creatine phosphokinase  
CRF  
Case report form  
CRP  
C-reactive protein  
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  
FAAN  
Food Allergy and Anaphylaxis Network  
FEV1  
Forced expiratory volume in 1 second  
FSH  
Follicle stimulating hormone  
FTIH  
First Time in Humans  
FVC  
Forced vital capacity  
g  
Grams  
GCP  
Good Clinical Practice  
GGT  
Gamma glutamyl transferase  
GINA  
Global Initiative for Asthma  
GLDH  
Glutamate dehydrogenase  
GSK 
GlaxoSmithKline 

 
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h  
Hours  
HBc  
Hepatitis B core  
HBsAg  
Hepatitis B surface antigen  
hCG  
Human chorionic gonadotropin  
HRQoL  
Health-related quality of life  
HRT  
Hormone replacement therapy  
hsCRP  
High sensitivity C-reactive protein  
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  
Ig  
Immunoglobulin  
IL-5  
Interleukin-5  
IL-5R  
Interleukin-5 receptor  
IM  
Intramuscular  
IMP  
Investigational medicinal product  
INR  
International normalized ratio  
IRB  
Institutional Review Board  
IRT  
Interactive response technology  
IUS  
Intrauterine hormone-releasing system  
IV  
Intravenous  
K 
Probabilities of observing a given number of adverse 
events or more 
kg  
kilogram  
L  
Litre  
LA  
Long-acting  
LABA  
Long acting -agonist  
LAMA  
Long acting muscarinic antagonist  
LDH  
Lactate dehydrogenase  
LFT  
Liver function test  
mAb  
Monoclonal antibody  
MAR  
Missing at random  
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  

 
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NIAID  
National Institute of Allergy and Infectious Disease  
NIH  
National Institutes of Health  
NIMP  
Non-investigational medicinal product  
OLE  
Open-label extension  
PCR  
Polymerase chain reaction  
PD  
Pharmacodynamics  
PEF  
Peak expiratory flow  
PFS  
Pre-filled safety syringe  
PK  
Pharmacokinetics  
PR3  
Proteinase 3  
PRO  
Patient-reported outcomes  
QTcF  
QTc corrected by Fridericia’s formula  
QTL  
Quality tolerance limits  
RNA  
Ribonucleic acid  
RBC  
Red blood cell  
SABA  
Short acting beta-2-agonist  
SADE  
Serious adverse device event  
SAE  
Serious Adverse Event  
SC  
Subcutaneous  
SGPT  
Serum glutamic pyruvic transaminase  
SGOT  
Serum glutamic oxaloacetic transaminase  
SGRQ  
St. George’s Respiratory Questionnaire  
SoA  
Schedule of assessments  
SoC  
Standard of care  
SOC  
System organ class  
SRM  
Study Reference Manual  
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  
L 
Microlitre  
CCI

 
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Trademark Information 
Trademarks of the GSK group of companies 
 
Trademarks not owned by the GSK group of 
companies 
NUCALA 
 
CINQAERO 
 
 
CINQAIR/ CINQAERO 
 
 
DUPIXENT 
 
 
FASENRA 
 
 
MedDRA 
 
 
SAS 
 
 
XOLAIR 

 
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11. 
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