Clinical trial NCT03393806
Conditions: Asthma
Keywords: Asthma Control Questionnaire Allergic fungal airway disease Asthma Quality of Life Questionnaire Holter monitoring Asthma
Sponsor: GlaxoSmithKline
Start date: 2018-04-18; Completion date: 2020-01-06
Enrollment: 17 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study is multicenter, double-blinded parallel group design, where participants with moderate to severe asthma with AFAD will be enrolled. Participants will receive three doses of 10 milligrams/kilogram (mg/kg) of GSK3772847 every 4 Weeks versus placebo along with standard of care. Participants will be randomized in 1:1 ratio to receive either 10 mg/kg GSK3772847 intravenously (IV) or matching placebo IV. Participants will receive study treatment on Week 0 (Day 1), Week 4 and Week 8. The total duration of the study will be 28 Weeks and approximately 46 participants will be randomized.

Detailed description:

Arms: arm 1: Participants will be randomized to receive GSK3772847 as IV infusion. Participants will receive three doses ( Day 1, Day 29 and Day 57) of GSK3772847 every 4 weeks arm 2: Participants will be randomized to receive matching placebo as IV infusion
Interventions: intervention 1: GSK3772847 intervention 2: Placebo
Intervention descriptions: intervention 1: GSK3772847 will be available as 100 mg/vial, white to yellow, uniform lyophilized cake in a 5 milliliter (mL) clear glass vial with closure sealed by red metal and yellow overseal. intervention 2: Commercially sourced sterile normal saline will be provided as Placebo

Protocol documents:
Prot_000.pdf: 
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TITLE PAGE
Protocol Title: A double blind (sponsor open) placebo-controlled, stratified, parallel 
group study to evaluate the efficacy and safety of repeat doses of GSK3772847 in 
participants with moderate to severe asthma with allergic fungal airway disease (AFAD)
Protocol Number: 207972/02
Short Title: Repeat dose study of GSK3772847 in participants with moderate to severe 
asthma with allergic fungal airway disease (AFAD).
Compound Number:
GSK3772847
Sponsor Name and Legal Registered Address: 
GlaxoSmithKline Research & Development Limited
980 Great West Road
Brentford
Middlesex, TW8 9GS
UK
Medical Monitor Name and Contact Information can be found in the Study Reference 
Manual
Regulatory Agency Identifying Number(s): EudraCT number: 2017-003544-20
Approval Date: 10-OCT-2018
Copyright 2018 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited.


 
PPD
PPD


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document
Date
Amendment 2-2017N331706_03
10-OCT-2018
Amendment 1 RUS-1-2017N331706_02
26-JUL-2018
Amendment 1-2017N331706_01
05-FEB-2018
Original Protocol-2017N331706_00
01-SEP-2017
Amendment 2 10-OCT-2018
Overall Rationale for the Amendment: To include participants with severe asthma with 
AFAD treated with low dose oral corticosteroid who still demonstrate a lack of complete 
control as demonstrated by ACQ-5, FeNO and blood eosinophil levels. Also, a few 
clarifications were included.


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Section # and Name
Description of Change
Brief Rationale
Section 6.1 Inclusion Criteria; 
Section 6.2 Table 2; Section 
6.3 Run-in Exclusion Criteria; 
Section 6.5 Randomisation 
Exclusion Criteria; Section 
7.7.1 Permitted Medications 
and Non-Drug Therapies; 
Section 7.7.2 Prohibited 
Medications and Non-drug 
Therapies
Additional therapy: with low dose 
oral corticosteroid (10 mg/day 
prednisolone or equivalent) is 
permissible.
High dose oral corticosteroid is 
defined as >10 mg/day 
prednisolone or equivalent. 
It is not uncommon for 
severe asthma participants  
including those with allergic 
fungal airway disease to 
receive oral corticosteroids 
as maintenance treatment 
and still demonstrate a lack 
of complete asthma control. 
Section 6.1 Inclusion Criteria; 
Section 6.7 Screening/Run-
in/Randomisation Failures
Blood eosinophils of 250-
299 cells/microliters at screening 
but with documented evidence of 
300 cells /microliters within 5 
months of screening will be 
accepted.
There is no well-accepted 
low cutoff point for 
eosinophilia between 150-
300 cells/microliters. Blood 
eosinophils of 
250 cells/microliters at 
screening with documented 
evidence of eosinophilia will 
be adequate to demonstrate 
efficacy and safety. 
Section 9.1.2 Fractional 
Exhaled Nitric Oxide; Section 
9.1.4 Spirometry
Participants should withhold use 
of their SABA and LABA, ICS 
and OCS medications prior to 
FeNO and Spirometry 
assessments. 
Clarification to ensure that all 
participants perform key 
study assessments at the 
end of their SoC medication 
dosing intervals. 
Section 9.8.1 Exploratory 
Biomarkers
Participants should withhold use 
of their SABA and LABA, ICS 
and OCS medications prior to 
visits with sputum assessments, 
similar to spirometry restrictions.
To ensure that baseline and 
end-of-treatment sputum 
samples are taken in similar 
conditions. 
Section 2 Schedule of 
Activities; Section 9.8.2 
Immunogenicity Assessments
Clarified that immunogenicity 
assessments should be 
performed pre dose.
Immunogenicity 
assessments should be done 
pre dose at all dosing visits.
Section 2 Schedule of 
Activities
Clarified that serum pregnancy 
test is required at screening. 
WOCBP should only be 
included after a confirmed 
menstrual period and a 
negative highly sensitive 
serum pregnancy test.
Section 7.7.1 Permitted 
Medications and Non-Drug 
Therapies
Medications for rhinitis are 
disallowed 48 hours prior to ECG 
measurements
Reworded the sentence for 
clarification.
Section 7.7.2 Prohibited 
Medications and Non-drug 
Therapies
Methotrexate, troleandomycin, 
oral or parenteral gold, 
cyclosporin, azathioprine, 
cyclophosphamide, tacrolimus, 
mycophenolate mofetil, D-
penicillamine are not permitted.
Clarification to match Table 2 
list of Section 6.2 Exclusion 
Criteria. 


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TABLE OF CONTENTS
PAGE
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE.....................................3
1.
SYNOPSIS...............................................................................................................8
2.
SCHEDULE OF ACTIVITIES (SOA).......................................................................11
3.
INTRODUCTION....................................................................................................17
3.1.
Study Rationale ..........................................................................................17
3.2.
Background ................................................................................................17
3.3.
Benefit/Risk Assessment ............................................................................19
3.3.1.
Risk Assessment .........................................................................20
3.3.2.
Benefit Assessment.....................................................................27
3.3.3.
Overall Benefit:Risk Conclusion...................................................27
4.
OBJECTIVES AND ENDPOINTS...........................................................................28
5.
STUDY DESIGN ....................................................................................................30
5.1.
Overall Design ............................................................................................30
5.2.
Number of Participants ...............................................................................31
5.3.
Participant and Study Completion...............................................................31
5.4.
Scientific Rationale for Study Design ..........................................................32
5.5.
Dose Justification........................................................................................32
6.
STUDY POPULATION...........................................................................................35
6.1.
Inclusion Criteria.........................................................................................35
6.2.
Exclusion Criteria........................................................................................36
6.3.
Run-in Exclusion Criteria ............................................................................40
6.4.
Randomisation Inclusion Criteria ................................................................40
6.5.
Randomisation Exclusion Criteria ...............................................................40
6.6.
Lifestyle Restrictions...................................................................................41
6.6.1.
Caffeine, Alcohol, and Tobacco ...................................................41
6.6.2.
Activity .........................................................................................41
6.7.
Screening/Run-in/Randomisation Failures..................................................42
7.
TREATMENTS.......................................................................................................43
7.1.
Treatments Administered............................................................................43
7.1.1.
Medical Devices...........................................................................44
7.1.2.
Rescue medication ......................................................................44
7.2.
Dose Modification .......................................................................................44
7.3.
Method of Treatment Assignment ...............................................................44
7.4.
Blinding.......................................................................................................45
7.5.
Preparation/Handling/Storage/Accountability..............................................46
7.5.1.
Accountability ..............................................................................46
7.5.2.
Preparation, Storage and Handling..............................................46
7.6.
Treatment Compliance................................................................................47
7.7.
Concomitant Therapy..................................................................................47
7.7.1.
Permitted Medications and Non-Drug Therapies..........................47
7.7.2.
Prohibited Medications and Non-drug Therapies .........................48


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7.8.
Treatment after the End of the Study ..........................................................49
8.
DISCONTINUATION CRITERIA.............................................................................50
8.1.
Discontinuation of Study Treatment ............................................................50
8.1.1.
Liver Chemistry Stopping Criteria ................................................51
8.1.2.
QTc Stopping Criteria ..................................................................51
8.1.3.
Rechallenge.................................................................................52
8.1.3.1.
Study Treatment Restart or Rechallenge....................52
8.2.
Withdrawal from the Study..........................................................................52
8.3.
Lost to Follow Up........................................................................................53
9.
STUDY ASSESSMENTS AND PROCEDURES .....................................................54
9.1.
Efficacy Assessments.................................................................................54
9.1.1.
Blood Eosinophils ........................................................................54
9.1.2.
Fractional Exhaled Nitric Oxide (FeNO) .......................................54
9.1.3.
Questionnaires ............................................................................55
9.1.3.1.
Asthma Control Questionnaire (ACQ-5)......................55
9.1.3.2.
Asthma Quality of Life Questionnaire (AQLQ) ............55
9.1.4.
Spirometry ...................................................................................56
9.2.
Adverse Events...........................................................................................56
9.2.1.
Time Period and Frequency for Collecting AE and SAE 
Information...................................................................................56
9.2.2.
Method of Detecting AEs and SAEs.............................................57
9.2.3.
Follow-up of AEs and SAEs.........................................................57
9.2.4.
Regulatory Reporting Requirements for SAEs .............................57
9.2.5.
Cardiovascular and Death Events................................................57
9.2.6.
Pregnancy ...................................................................................58
9.3.
Treatment of Overdose...............................................................................58
9.4.
Safety Assessments ...................................................................................58
9.4.1.
Physical Examinations.................................................................59
9.4.2.
Vital Signs....................................................................................59
9.4.3.
Electrocardiograms......................................................................59
9.4.4.
Continuous ambulatory ECG (Holter)...........................................59
9.4.5.
Clinical Safety Laboratory Assessments ......................................60
9.4.6.
Diary assessments ......................................................................60
9.5.
Pharmacokinetics .......................................................................................60
9.6.
Pharmacodynamics ....................................................................................61
9.7.
Genetics .....................................................................................................61
9.8.
Biomarkers .................................................................................................61
9.8.1.
Exploratory Biomarkers................................................................61
9.8.2.
Immunogenicity Assessments......................................................61
9.9.
Medical Resource Utilization and Health Economics ..................................62
10. STATISTICAL CONSIDERATIONS........................................................................63
10.1.
Sample Size Determination ........................................................................63
10.2.
Populations for Analyses ............................................................................65
10.3.
Statistical Analyses.....................................................................................66
10.3.1.
Efficacy Analyses.........................................................................66
10.3.2.
Safety Analyses...........................................................................67
10.3.3.
Pharmacokinetic Analyses...........................................................67
10.3.4.
Pharmacodynamic Analyses........................................................67
10.3.5.
Other Analyses ............................................................................67


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10.3.6.
Interim Analyses ..........................................................................68
11. REFERENCES.......................................................................................................69
12. APPENDICES........................................................................................................71
12.1.
Appendix 1: Abbreviations and Trademarks................................................71
12.2.
Appendix 2: Clinical Laboratory Tests.........................................................74
12.3.
Appendix 3: Study Governance Considerations..........................................77
12.4.
Appendix 4: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .......................................81
12.5.
Appendix 5: Contraceptive Guidance and Collection of Pregnancy 
Information..................................................................................................87
12.6.
Appendix 6: Genetics..................................................................................90
12.7.
Appendix 7: Liver Safety: Required Actions and Follow-up 
Assessments ..............................................................................................91
12.8.
Appendix 8 : Protocol Amendment History..................................................94


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1.
SYNOPSIS
Protocol Title: A double blind (sponsor open) placebo-controlled, stratified, parallel 
group study to evaluate the efficacy and safety of repeat doses of GSK3772847 in 
participants with moderate to severe asthma with allergic fungal airway disease (AFAD).
Short Title: Repeat dose study of GSK3772847 in participants with moderate to severe 
asthma with allergic fungal airway disease (AFAD).
Rationale:
GSK3772847 (formerly CNTO 7160, which was in-licensed from Janssen) is a human 
immunoglobulin G2 sigma isotype (IgG2) antibody that binds Domain 1 of the cell-
surface interleukin-33 receptor (IL-33R). Inhibition of IL-33 signalling via blockade of 
the IL-33 receptor (Suppressor of tumorigenicity 2 [ST2], also known as Interleukin-1 
receptor like-1 [IL-1RL1]) presents a potential novel treatment for severe asthma as an 
add-on to standard of care. Agents targeting this mechanism could be expected to have 
effects on both type 2 (T2)-driven and non-T2-driven disease.
Allergic fungal airway disease (AFAD) is defined as Immunoglobulin E (IgE)
sensitisation to thermotolerant filamentous fungi particularly Aspergillus fumigatus. 
Clinical data suggest increased IL-33 levels in bronchoalveolar (BAL) fluid and 
endobronchial biopsy at baseline disease of children with severe asthma with fungal 
sensitisation and in lung tissue samples from patients with allergic bronchopulmonary 
aspergillosis [In-house unpublished data]. Recent data reported an association between 
IgE sensitisation to colonising thermotolerant filamentous fungi and the presence of lung 
damage as demonstrated by high-resolution computed tomography (HRCT) scanning in 
moderate to severe asthma. This study aims to evaluate the effects of GSK3772847 in 
moderate to severe asthma participants with AFAD on top of standard of care.
Objectives and Endpoints:
Objectives
Endpoints
Primary
To evaluate the efficacy of 3 doses of
GSK3772847 (administered every 4 weeks)
compared with placebo in moderate to severe 
asthma participants with allergic fungal airway 
disease (AFAD) who are currently on Standard 
of Care (SoC)

Change from baseline (Week 0) in blood 
eosinophils over time

Change from baseline (Week 0) in fractional 
exhaled nitric oxide (FeNO) over time
Secondary
To evaluate the serum pharmacokinetics (PK) of 
3 doses of GSK3772847 (administered every 4 
weeks) in moderate to severe asthma 
participants with AFAD 

Serum concentrations of GSK3772847
To evaluate the pharmacodynamics (PD) of 
GSK3772847 in moderate to severe asthma 
participants with AFAD 

Serum levels of free and total soluble ST2


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Objectives
Endpoints
To evaluate the levels and specificity of any 
anti-drug antibodies formed following dosing 
with GSK3772847

Incidence and titres of serum anti-
GSK3772847 antibodies post dosing
To evaluate the health status of moderate to 
severe asthma participants with AFAD currently on 
SoC, and who are treated with GSK3772847
compared with placebo-treated participants

Change from baseline (Week 0) in Asthma 
Control Questionnaire -5 (ACQ-5) absolute 
score at Weeks 2, 4, 8 and 12

Change from baseline (Week 0) in Asthma 
Quality of Life Questionnaire (AQLQ) total 
and domain scores at Weeks 2, 4, 8 and 12

Proportion of responders to ACQ-5. A 
responder to ACQ-5 will be defined as a 
subject who has a decrease from baseline in 
ACQ-5 score of 0.5 or more.

Proportion of responders to AQLQ. A 
responder to AQLQ will be defined as a 
subject who has an increase from baseline 
in AQLQ score of 0.5 or more.
To evaluate the effect on lung function of 
moderate to severe asthma participants with AFAD 
currently on SoC, treated with GSK3772847
compared with placebo

Change from baseline (Week 0) in 
spirometry parameters over time including 
but not limited to pre-bronchodilator Forced 
expiratory volume in 1 second (FEV1)
To evaluate the safety and tolerability of 
GSK3772847 compared with placebo in 
moderate to severe asthma participants with AFAD
Safety and tolerability parameters include:

Treatment emergent adverse events (AE)

Clinical Laboratory safety data 

Vital signs (blood pressure, heart rate)

12–Lead Electrocardiogram (ECG)
monitoring

24-hour Holter monitoring
Overall Design:
This is a randomised, multicentre, double blind (sponsor open), placebo-controlled, 
stratified, parallel group study evaluating 3 doses of 10 mg/kg GSK3772847 administered 
every 4 weeks versus placebo in addition to SoC. Participants who have been diagnosed 
as having moderate to severe asthma with allergic fungal airway disease shall be enrolled 
in the study. Moderate to severe asthmatics are defined as asthmatics who are well 
controlled with Step 3 or 4 treatment, respectively, based on Global Initiative for Asthma, 
2017 Guidelines. 
Number of Participants:
Approximately 46 participants with moderate to severe asthma will be randomised such 
that approximately 40 evaluable participants complete the study, where evaluable is 


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defined as subjects with at least one post-baseline measurement for both FeNO and blood 
eosinophils.
Treatment Groups and Duration:
Participants who meet the eligibility criteria at Screening (Visit 1) will enter a two-week 
Run-in period during which they will undergo one 24h Holter monitoring session and 
fulfil paper Diary requirements. Participants who meet the pre-defined randomisation 
criteria, will be randomised in a 1:1 ratio to one of the following treatment groups: 

10 mg/kg GSK3772847 administered intravenously 

Matching placebo administered intravenously
The randomisation will be stratified based on whether a participant is taking anti-fungal 
medication or not, determined at screening.  
Both treatments will be administered on Week 0 (Day 1), Week 4 and Week 8.
Each participant will: 

Be screened;

Attend a run-in visit (Visit 2) and enter the run-in period, approximately 14 days 
before the first treatment visit;

Receive a total of 3 doses, each one on separate study visits (Visits 3, 5 and 6); doses 
will be every 4 weeks starting at week 0;

Attend treatment period study visits at week 2 (Visit 4) and week 12 (Visit 7) but not 
receive study treatment during these visits; and

Have a follow-up visit (approximately 12 weeks after Visit 7).
Each participant will be involved in the study for approximately 28 weeks. 
At specified visits, each participant will undergo the following procedures: 

Sputum inductions at baseline (Visit 2) and end of treatment period (Visit 7). The 
sputum inductions may each be repeated once: for baseline at visit 3 and for end of 
treatment period at an extra visit after Visit 7;

24 h Holter monitoring at Visits 2 and 3 only.
During treatment period study visits, the participant will: 

Have blood drawn, for PD and/or PK assessments;

Undergo FeNO measurement and spirometry;

Have vital signs measured; and

Complete 2 Quality of Life (QoL) questionnaires.


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2.
SCHEDULE OF ACTIVITIES (SOA)
Procedure
Screening
(5days)
Run-in
(5days)
Treatment Period
(Visit window 3days)
End of Treatment / EW
(3days)
FU (3days)
Notes
Visit
V1
V2
V3
V4
V5
V6
V7
V8
Week
-4
-2
0
2
4
8
12
24
Day
-28
-14
1
15
29
57
85
169
Informed consent
X
May be obtained prior to Screening. 
Inclusion and exclusion criteria
X
X
X
Recheck clinical status before 1st dose of 
study medication.
Demography
X
Full physical examination 
X
To include height and weight
Medical/medication/
drug/alcohol/smoking history
X
Including smoking history, substance abuse, 
medical conditions and family history of 
premature cardiovascular disease; asthma 
disease duration and exacerbation history
Human 
immunodeficiency 
virus 
(HIV), Hepatitis B and C screening
X
If test otherwise performed within 3 months 
prior to first dose of study treatment, testing at 
screening is not required
Genetics
Informed 
consent 
for 
Pharmacogenetic blood sample
X


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Procedure
Screening
(5days)
Run-in
(5days)
Treatment Period
(Visit window 3days)
End of Treatment / EW
(3days)
FU (3days)
Notes
Visit
V1
V2
V3
V4
V5
V6
V7
V8
Week
-4
-2
0
2
4
8
12
24
Pharmacogenetic 
(PGx) 
blood 
sample
X
PGx sample may be drawn any time from 
Visit 3 onwards, pre-dose. Informed consent 
must be obtained before collecting a sample.
Study Treatment and Questionnaires
Randomisation
X
Study treatment
X
X
X
Dispense diary card
X
To be completed daily.
Diary card review
X
X
X
X
X
Collect diary card
X
Rescue medication dispensing
X
X1
X1
X1
X1
1.
As needed
ACQ-5 
X
X
X
X
X
X
Test to be performed before all other 
assessments
AQLQ 
X
X
X
X
X
Test to be performed immediately after ACQ-
5 
Efficacy 
Haematology (including eosinophil 
count)
X
X1
X
X
X
X
1.
Pre-dose
FeNO
X
X
X
X
X
X
Test to be performed pre-dose
Spirometry
X
X
X
X
X
X
Test to be performed pre-dose


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Procedure
Screening
(5days)
Run-in
(5days)
Treatment Period
(Visit window 3days)
End of Treatment / EW
(3days)
FU (3days)
Notes
Visit
V1
V2
V3
V4
V5
V6
V7
V8
Week
-4
-2
0
2
4
8
12
24
Free and total sST2 (serum)
X1
X
X2
X1
X3
X3
1.
Pre and Post Dose
2.
Pre Dose
3.
Anytime (5 days)
Pre-dose samples: within 2 hours from the 
planned dosing time
Post-dose samples as soon as possible after 
end of infusion but must be taken within 4 
hours.
Total & fungal specific IgE
X1
X2
X
X
X
X
1.
Fungal specific IgE only if no historical 
documented results available
2.
Pre-dose


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Procedure
Screening
(5days)
Run-in
(5days)
Treatment Period
(Visit window 3days)
End of Treatment / EW
(3days)
FU (3days)
Notes
Visit
V1
V2
V3
V4
V5
V6
V7
V8
Week
-4
-2
0
2
4
8
12
24
Induced sputum sample for 
biomarkers
X
X1,2
X3
1.
If no viable sample is produced at V2, 
induction should be repeated pre dose at 
V3
2.
If a participant does not produce a viable 
baseline sputum sample at visit 2 or at 
visit 3, the participant will not need to 
undergo a sputum induction at the end of 
the treatment period.
3.
If no viable sample is produced, induction 
should be repeated after a minimum of 72 
hrs but no later than 7 days after 
scheduled visit. 


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Procedure
Screening
(5days)
Run-in
(5days)
Treatment Period
(Visit window 3days)
End of Treatment / EW
(3days)
FU (3days)
Notes
Visit
V1
V2
V3
V4
V5
V6
V7
V8
Week
-4
-2
0
2
4
8
12
24
Pharmacokinetics
Serum blood sample for PK
X1
X
X2
X3
X4
X4
1.
Post Dose
2.
Pre Dose
3.
Pre and Post Dose
4.
Anytime (5 days)
Pre-dose samples: within 2 hours from the 
planned dosing time
Post-dose samples as soon as possible after 
end of infusion but must be taken within 4 
hours.
Safety
Laboratory assessments
X1,2
X1,3
X1
X1,3
X1
X1,3
X1
1.
Clinical chemistry (includes liver 
chemistry)
2.
Routine urinalysis at screening (Visit 1)
3.
Cardiac markers
Note: haematology assessments in efficacy 
section
Serum blood sample for 
immunogenicity
X1
X
X1
X1
X
X
1.
Pre Dose


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Procedure
Screening
(5days)
Run-in
(5days)
Treatment Period
(Visit window 3days)
End of Treatment / EW
(3days)
FU (3days)
Notes
Visit
V1
V2
V3
V4
V5
V6
V7
V8
Week
-4
-2
0
2
4
8
12
24
Urine or serum pregnancy test 
(WOCBP only)
X1
X
X
X
X
X
To be performed pre-dose during the 
treatment period
1. Serum pregnancy test required
12-lead ECG
X
X1
X1
X1
X
1. Test to be performed pre-dose and post-
dose within 30 mins after end of infusion.
24 hour Holter
X
X1
Holter monitor needs to be returned to the 
clinic at end of 24 hour recording (i.e. the next 
day).
1Place the Holter 30-60mins prior to dosing
Vital signs
X
X
X1
X1
X1
X
X
1.
Test to be performed prior to the 12-lead 
ECG (pre-dose and post dose)
AE review
===============================
SAE review
X
X
===============================
At V1 and V2 collect only SAEs considered as 
related to study participation.
Concomitant medication review
X
X
===============================
EW: Early Withdrawal. The list of assessments listed in this column should be completed for an early withdrawal visit. 


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3.
INTRODUCTION
GSK3772847 (formerly CNTO 7160, which was in-licensed from Janssen) is a human 
immunoglobulin G2 sigma isotype (IgG2) antibody that binds Domain 1 of the cell-
surface interleukin-33 receptor (IL-33R). Inhibition of IL-33 signalling via blockade of 
the IL-33 receptor (Suppressor of tumorigenicity 2 [ST2], also known as interleukin-1 
receptor like-1 [IL-1RL1]) presents a potential novel treatment for severe asthma as an 
add-on to standard of care. Agents targeting this mechanism could be expected to have 
effects on both type 2 (T2)-driven and non-T2-driven disease. 
At the time of writing this protocol, a two-part, single and multiple ascending dose first 
time in human study has completed dosing (GlaxoSmithKline Document Number 
2017N344518_00). The safety information from this study is included in the investigator 
brochure. 
Another study, a Phase IIa, multicentre, randomised, placebo-controlled, double-blind, 
stratified, parallel group study in moderately severe asthmatics started in September 2017
and aims to complete in late 2018. 
The present study is a Phase IIa study to provide supplemental efficacy, safety and 
tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of GSK3772847 
in patients with moderate to severe asthma with allergic fungal airway disease (AFAD).
3.1.
Study Rationale
This study aims to evaluate the effects of GSK3772847 in moderate to severe asthma 
participants with AFAD on top of standard of care. Evidence suggests that in order to 
observe the maximum benefit of targeting the IL-33 signalling pathway with 
GSK3772847, participants would need to be in a state of pulmonary cellular damage.
Clinical data suggest increased IL-33 levels in bronchoalveolar lavage (BAL) fluid and 
endobronchial biopsy at baseline disease of children with severe asthma with fungal 
sensitisation [Castanhinha, 2015]. Also, lung tissue samples from patients with allergic 
bronchopulmonary aspergillosis indicate a markedly increased IL-33 expression [In-
house unpublished data]. Recent data reported an association between immunoglobulin E 
(IgE) sensitisation to colonising thermotolerant filamentous fungi and the presence of 
graded lung damage as demonstrated by high-resolution computed tomography (HRCT)
scanning (such as bronchiectasis, bronchial wall thickness, air trapping, etc.) in moderate 
to severe asthma [Woolnough, 2016]. Therefore, the target population is moderate to 
severe asthmatics who have allergic fungal airway disease (defined as IgE sensitisation to 
thermotolerant filamentous fungi particularly Aspergillus fumigatus, including allergic 
bronchopulmonary aspergillosis [ABPA]) [Rick, 2016]. Moderate to severe asthmatics 
are defined as asthmatics who are well controlled with Step 3 or 4 treatment, respectively, 
based on Global Initiative for Asthma [GINA, 2017] Guidelines.
3.2.
Background
Asthma is a serious public health problem affecting about 300 million individuals 
worldwide. Asthma is a chronic inflammatory disorder of the airways, defined by a 


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history of respiratory symptoms of variable length and intensity together with variable 
airflow limitation. These symptoms are often triggered by allergen or irritant exposure, 
exercise or viral respiratory infections [GINA, 2017]. When uncontrolled, asthma can 
place severe limitations on daily life, and is sometimes fatal.
Severe asthma represents approximately 5-10% of the asthma population and is 
associated with a greater frequency of asthma exacerbations, decreased health-related 
quality of life and greater symptom burden [Chung, 2014], [Aburuz, 2007, Moore, 2007). 
Fungal exposure has been associated with asthma severity [O'Driscoll, 2005]. Moderate 
to severe asthmatics who are sensitised to Aspergillus fumigatus have impaired lung 
function, as demonstrated by reduced forced expiratory volume in 1 second (FEV1), more 
severe airway obstruction, and the requirement for higher doses of corticosteroids 
[Denning, 2006] [Menzies, 2011]. Aspergillus fumigatus (thermotolerant filamentous 
fungi) are able to colonise the airways and cause lung damage [Moss, 2014]. Susceptible 
hosts such as moderate to severe asthmatics with reduced mucocilliary clearance 
functions are unable to efficiently clear their respiratory epithelium of inhaled fungal 
spores. This leads to increased contact of fungal spores with the immune system, thereby 
facilitating fungal growth and mucosal colonisation [Tracy, 2016]. The resulting immune 
response in susceptible hosts is a deviation towards a Th2- driven immune response with 
increased production of Th2 cytokines, in part driven by IL-33 that is derived from the 
airway epithelium.
GSK3772847 binds to the extracellular domain of IL-33R and neutralizes IL-33-mediated 
IL-33R signalling. The IL-33R gene codes for both a soluble form (sST2) and a 
membrane-bound “long” form (ST2L or IL-33R). Soluble ST2 exists in the serum and is 
elevated in severe asthmatics during an exacerbation [Smithgall, 2008, Oshikawa, 2001].
IL-33R is expressed on a variety of immune and non-immune cells. IL-33 has been 
shown to be released after endothelial or epithelial cell damage during trauma, 
physicochemical / microbarometric stress or infection [Arshad, 2016]. The IL-33R 
pathway causes downstream production of Type 2 cytokines and contributes to Th2-
mediated pathologies and allergic responses [Yagami, 2010, Smithgall, 2008], but has 
also been shown to promote Th1- and Th17-mediated responses [Arshad, 2016, 
Smithgall, 2008]. Inhibition of IL-33 signalling may result in down regulation of immune 
cell responses and therefore presents a potential novel treatment for severe asthma on top 
of standard of care [Arshad, 2016].
In a 3-month good laboratory practice (GLP) toxicology study, GSK3772847 was 
administered to cynomolgus monkeys as a weekly 15-minute intravenous (IV) infusion 
(20 or 100 mg/kg) and was found to be well-tolerated at both doses. 
A Phase I randomised, double-blind, placebo-controlled, IV single ascending dose study 
in healthy participants and multiple ascending dose study in participants with asthma and 
participants with atopic dermatitis (Study CNTO7160ASH1001) has completed dosing. 
The final clinical study report is still pending. There are no efficacy data available to 
date.


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More information about the non-clinical and clinical studies is available in the 
GSK3772847 Investigator’s Brochure (IB) (GlaxoSmithKline (GSK) Document Number 
2017N316832_00).
3.3.
Benefit/Risk Assessment
More detailed information about the known and expected benefits and risks and 
reasonably expected adverse events of GSK3772847 may be found in the IB (GSK
Document Number 2017N316832_00).


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3.3.1.
Risk Assessment
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Investigational Product (IP) GSK3772847
Cardiovascular (CV)
There is evidence to suggest that the IL-33/ST2 
pathway may be protective in the cardiovascular 
system. Components of the IL-33/ST2 pathway 
are expressed in a number of cellular 
components of the heart and blood vessels in 
rodents and human patients.
Increased circulating levels of soluble ST2 are 
markers of a poor prognosis in patients with 
hemodynamic stress (e.g. hemodynamic-
hypertrophy, chamber dilation, fibrosis; ischemic-
apoptosis and infarct volume). The effect was 
abolished in rodents with genetic knockout of 
ST2. 
Atherosclerotic plaque development was 
significantly reduced in ApoE -/- mice given 
exogenous IL-33 while plaques were larger in 
mice treated with soluble ST2 (which binds and 
blocks IL-33).
Non-clinical:
No GSK3772847-related changes noted in (non-
GLP) IV and subcutaneous (SC) 4 week monkey 
study at doses ≤100 mg/kg/week, or in the GLP 
3 month IV repeat dose toxicity study at doses 
≤100 mg/kg/week) or SC administration. 
However, it should be noted that the animals in 
toxicity studies are healthy and, therefore, are 
unlikely to detect the potential target related CV 
liability.
Clinical:
In Janssen study CNTO 7160ASH1001, several 
episodes of sinus tachycardia on telemetry were
reported in a 20-year-old male healthy volunteer, 
between 1 and 9 hours post-dose (10 mg/kg), 
accompanied on one occasion by mild vertigo 
and malaise (no chest pain). Troponin I, N-
terminal prohormone of brain natriuretic peptide 
(NT-proBNP) were normal pre dose and Day 5, 
also normal ECG and vital signs including 
temperature. The event was considered by the 
investigator to be likely related to investigational 
product. No specific cause was identified. Data 
on this event was reviewed by GSK (Internal 
Cardiac Safety Panel and Chief Medical Officer), 
Exclude participants with existing clinically 
significant organic heart disease (e.g. Coronary 
artery disease [CAD], ACC/AHA Stage C/D, and 
New York Heart Association (NYHA) Class III/IV 
heart failure) and abnormal, clinically significant 
findings from 12-lead electrocardiogram (ECG)
and 24-hour Holter monitoring (Section 6.2 and 
Section 6.3). 
CV events will be monitored (including ECG and 
Holter monitoring) as specified in SoA (Section 
2). All cardiac-related adverse events (AEs) will 
be reviewed by an internal safety review 
committee (iSRC, see Appendix 3). Protocol-
defined stopping criteria are specified in Section 
8.1.


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
and was not considered to impact further clinical 
development.
During 12 hours post-dose telemetry monitoring 
in Part 1 of Janssen study CNTO7160ASH1001, 
6 out of 60 completed subjects were assessed to 
have abnormal findings by the investigator. The 
abnormalities were considered clinically 
significant and recorded as treatment emergent 
adverse events.
In Part 2 of the Janssen study CNTO
7160ASH1001, there were four reports of non-
sustained ventricular tachycardia. Of these 
reports, one participant received placebo and 
two received GSK3772847 at 3 mg/kg and one 
received GSK3772847 at 10 mg/kg. The events 
were non-symptomatic, and a monomorphic 
pattern (i.e., not Torsades de pointes), which is a 
pattern thought not to be indicative of increased 
risk for sudden ventricular tachycardia and 
sudden death. Heart rate (HR) analysis did not 
identify any safety concern (no pattern of 
increased HR suggestive of an increase in 
sympathetic tone). All 4 participants had normal 
results from exercise test and echocardiogram. 
Dosing was continued as planned, and the dose 
escalated to 10 mg/kg.


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Increased risk of infections & 
immunosuppression
Studies in mice indicate a potential role for IL-33 
in infection control. IL-33 was shown to activate 
neutrophils in BALB/c mice subjected to cecal 
ligation and puncture thus preventing 
polymicrobial sepsis. Similarly, IL-33 is thought 
to stimulate neutrophil recruitment from the bone 
marrow to the periphery in response to fungal 
infection. Mice infected with flu virus and 
administered an IL-33 inhibitor exhibited a lower 
number of clusters of differentiated CD90+ and 
cluster of differentiated CD25+ inate lymphoid 
cells with consequent impaired lung function 
compared to phosphate buffered saline treated 
controls. IL-33 has also been shown to be 
produced in the helminth infected cecum of 
parasite infected mice and is shown to be 
important in expulsion of the parasite. 
Preclinical:
No GSK3772847-related changes in clinical 
signs, white blood cell count or no microscopic 
changes (inflammatory cell infiltrates) in any 
tissues indicative of infection observed in 
monkey 4 week IV/SC or IV 3 month toxicity at 
doses ≤100 mg/kg/week. 
Clinical:
Safety data from Janssen study 
CNTO7160ASH1001 Single Ascending Dose 
has shown the most frequent AEs reported as 
infections, including nasopharyngitis, rhinitis, 
gastroenteritis and upper respiratory tract 
infection. The frequency of these events was 
similar in GSK3772847 and placebo groups 
(18/45 [40%] of participants administered 
GSK3772847 versus 6/17 [35%] administered 
placebo.)1
Safety data from Part 2 of the Janssen study 
CNTO7160ASH1001 have shown the System-
organ class with the most frequent AEs reported 
was ’Infections and infestations’. The number of 
asthma participants experiencing infections and 
infestations was similar between the group 
receiving GSK3772847 (9/18 [50%]) and the 
group receiving placebo (4/6 [66.7%]). The 
frequency of infection events in participants with 
Participants with a known, pre-existing parasitic
infestation within 6 months prior to Screening are 
excluded from participation in the study (Section 
6.2). 
Participants who develop an infection will be 
requested to seek medical advice, and subject to 
close monitoring.
European Union (EU) Regulatory guidance on 
development of asthma drugs request that 
agents that interact with the immune system 
should be investigated for their effect on the host 
response to infection and tumours. The 
incidence of infections will be monitored in 
clinical studies. Incidence of tumours and 
development of paradoxical immune responses 
(e.g. idiopathic thrombocytopenic purpura, 
autoimmune thyroiditis, multiple sclerosis-like 
syndrome) will be monitored in clinical trials and 
routinely as part of the post marketing 
pharmacovigilance process. 
Exclude participants with ongoing or recurrent 
infections. 
Close monitoring of infection AEs (including 
pneumonia). 


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
atopic dermatitis was greater in participants in 
the GSK3772847 group compared with the 
placebo group (6/11 [54.5%] versus 1/4 [25%]). 
The most frequently-reported infection was 
nasopharyngitis. 
Increased risk of hyper-sensitivity, 
anaphylaxis, cytokine release syndrome 
(CRS) 
Therapy with other monoclonal antibodies has 
been associated with hypersensitivity reactions 
which may vary in severity and time of onset. 
Nonclinical: 
Not observed in studies to date. 
Clinical: 
Not observed in Janssen study 
CNTO7160ASH1001 in healthy volunteers 
following single doses up to 10 mg/kg, and 
multiple doses in asthma and atopic dermatitis 
participants at doses up to 10 mg/kg (3 doses, 
once every two weeks over four weeks).
Based on in vitro cytokine release data and 
safety experience in Janssen study 
CNTO7160ASH1001 the risk of CRS is 
considered negligible. 
If a hypersensitivity or anaphylactic reaction 
occurs, infusion should be discontinued 
immediately and appropriate therapy instituted. 
Agents to treat reactions should be available 
immediately. Stopping & continuation criteria will
be included in protocols. Painkillers can be
prescribed for pain at site of injection. Patients
developing hypersensitivity, anaphylactic
reactions or anaphylactic shock will be withdrawn
from the study. All doses in this trial will be
administered in the clinic. 
Possible interaction with live virus or 
bacterial vaccines 
As GSK3772847 is an immunomodulator, there 
is a possibility that the participant will not mount 
an adequate immune response to a vaccine or 
even cause the infection the vaccine should 
protect against.
Vaccination also drives a systemic immune 
response to the pathogen antigen that runs the 
risk of causing some immunomodulation of the 
Non-clinical: 
In the monkey 13 week toxicity study no 
GSK3772847-related changes in the T cell 
dependent B cell response (Immunoglobulin M 
[IgM] or Immunoglobulin G [IgG]) was observed 
at doses ≤100 mg/kg/week. This data is 
indicative that healthy monkeys were able to 
mount a response against the antigen challenge 
during GSK3772847 administration at doses 
where near complete inhibition of IL-33 was 
In the study, participants should not be 
vaccinated with live or attenuated vaccines within 
4 weeks prior to receiving IP or up to 6 months 
after dose administration of GSK3772847. 
However, vaccines containing killed bacteria or 
inactivated virus will be permitted.


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
lung immune responses. This has been best 
studied in murine models where eosinophilic lung 
inflammation has been suppressed by systemic 
toll-like receptor activation.
anticipated. 
Based on this data GSK3772847 is considered 
unlikely to blunt/inhibit the generation of a 
response to vaccinations. 
Clinical: 
Not observed in Janssen study 
CNTO7160ASH1001 in healthy volunteers 
following single doses up to 10 mg/kg, and 
multiple doses in asthma and atopic dermatitis 
patients at doses up to 10 mg/kg (3 doses, once 
every two weeks over four weeks).
Gastrointestinal disorders

Nausea

Vomiting
Clinical
In Part 2 of Janssen study CNTO7160ASH1001, 
the incidence of gastrointestinal disorders was 
greater in participants in the GSK3772847 
groups compared with the placebo groups: 6/18 
(33.3%) participants in the asthma cohort and 
3/11 (27.3) participants in the atopic dermatitis 
cohort as compared with 0 participants in either 
the asthma cohort or atopic dermatitis cohort 
placebo groups. Gastrointestinal disorders 
events included nausea (1/18 participants in the 
asthma cohort, 2/11 participants in the atopic 
dermatitis cohort), vomiting, diarrhoea. 
The incidence and severity of nausea and 
vomiting will be monitored.


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Skin and subcutaneous tissue disorders

Contact dermatitis
Clinical
In Part 2 of Janssen study CNTO7160ASH1001, 
the incidence of contact dermatitis was greater in 
participants in the GSK3772847 groups 
compared with the placebo groups. In the 
asthma cohort, the number of participants with 
contact dermatitis was 4/18 (22.2%) in the 
combined GSK3772847 groups versus 1/6 
(16.7%) in the placebo group. In the atopic 
dermatitis, the number of participants with 
contact dermatitis was 3/11 (27.3%) in the 
combined GSK3772847 versus 0/4 (0%) in the 
placebo group.
The incidence and severity of contact dermatitis 
will be monitored.


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Procedures
Sputum Induction
Sputum production is stimulated by inhalation of 
increasing concentrations of saline solution. This 
inhalation may cause an increase in cough, 
which may lead to pain in the throat or chest as 
well as to breathlessness, due to irritation of the 
airways.
Participants will receive a bronchodilator (e.g. 
salbutamol) prior to the procedure to reduce 
discomfort. Lung function will be assessed at 
baseline (pre- and post-bronchodilator) and after 
each saline inhalation procedure. The procedure 
will be terminated if the FEV1 drops below 20% 
of the post-bronchodilator value. If the FEV1 falls 
by 10% of the post-bronchodilator value, the 
saline concentration will not be increased during 
the next inhalation period.
If the participant exhibits respiratory symptoms 
such as wheeze, shortness of breath or chest 
discomfort at any stage during the procedure, 
they may be given bronchodilator therapy as 
needed and the procedure terminated as 
appropriate.
1Values have been updated from an incorrect entry in the IB and risk management benefit plan. Both documents will be updated with these correct values at the next scheduled 
update.


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3.3.2.
Benefit Assessment
Efficacy of GSK3772847 has not yet been demonstrated and there are no existent data 
from molecules with the same or similar mode of action. Taking part in this study may or 
may not improve a participant’s health, and may or may not directly benefit a participant. 
This study will provide additional safety and efficacy information on GSK3772847. 
Whilst the in vivo models of T2 asthma support a role for IL-33 pathway in eosinophilic 
asthma disease, it is clear that IL-33 plays a significant role in other types of immune 
responses and cell types including amplification of Th1 and Th17 responses in 
combination with other cytokines [Arshad, 2016; Smithgall, 2008]. Agents targeting this 
mechanism could be expected to have effects on both type 2 (T2)-driven and non-T2-
driven disease.
All study participants will receive a rescue inhaler to use as needed for asthma symptom 
relief from Run-in to the end of the Treatment Period. Medical assessments are planned 
during the study to evaluate participants’ health status. The assessments include physical 
examination, vital signs, ECG, Holter monitoring, and clinical laboratory evaluation 
including liver chemistry and blood chemistry panel at a number of clinic visits. 
Participants’ health status will also be evaluated by ACQ-5 and AQLQ during the study. 
Participants’ safety will also be assured by having criteria for withdrawal from study 
medication in case of loss of asthma control. The aim will be to retain participants in the 
study post withdrawal of study medication to follow-up for safety.
3.3.3.
Overall Benefit:Risk Conclusion
Taking into account measures to minimize the risk to the participants participating in the 
study, the balance of anticipated benefits and apparent risks associated with GSK3772847 
continues to be acceptable. There is an opportunity to determine if there is a new drug 
that can be developed for patients with severe asthma who may benefit from the broad 
spectrum effects hypothesized for GSK3772847. 


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4.
OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary
To evaluate the efficacy of 3 doses of 
GSK3772847 (administered every 4 weeks) 
compared with placebo in moderate to severe 
asthma participants with allergic fungal airway 
disease (AFAD) who are currently on Standard 
of Care (SoC)

Change from baseline (Week 0) in blood 
eosinophils over time

Change from baseline (Week 0) in fractional 
exhaled nitric oxide (FeNO) over time
Secondary
To evaluate the serum pharmacokinetics (PK) of 
3 doses of GSK3772847 (administered every 4 
weeks) in moderate to severe asthma 
participants with AFAD 

Serum concentrations of GSK3772847
To evaluate the pharmacodynamics (PD) of 
GSK3772847 in moderate to severe asthma 
participants with AFAD 

Serum levels of free and total soluble 
suppressor of tumorigenicity 2 (ST2)
To evaluate the levels and specificity of any 
anti-drug antibodies formed following dosing 
with GSK3772847

Incidence and titres of serum anti-
GSK3772847 antibodies post dosing
To evaluate the health status of moderate to 
severe asthma participants with AFAD currently on 
SoC, and who are treated with GSK3772847
compared with placebo-treated participants

Change from baseline (Week 0) in Asthma 
Control Questionnaire -5 (ACQ-5) absolute 
score at Weeks 2, 4, 8 and 12

Change from baseline (Week 0) in Asthma 
Quality of Life Questionnaire (AQLQ) total 
and domain scores at Weeks 2, 4, 8 and 12

Proportion of responders to ACQ-5. A 
responder to ACQ-5 will be defined as a 
subject who has a decrease from baseline in 
ACQ-5 score of 0.5 or more.

Proportion of responders to AQLQ. A 
responder to AQLQ will be defined as a 
subject who has an increase from baseline 
in AQLQ score of 0.5 or more.
To evaluate the effect on lung function of 
moderate to severe asthma participants with AFAD 
currently on SoC, treated with GSK3772847
compared with placebo

Change from baseline (Week 0) in 
spirometry parameters over time including 
but not limited to pre-bronchodilator Forced 
expiratory volume in 1 second (FEV1)
To evaluate the safety and tolerability of 
GSK3772847 compared with placebo in 
moderate to severe asthma participants with AFAD
Safety and tolerability parameters include:

Treatment emergent adverse events (AE)

Clinical Laboratory safety data 

Vital signs (blood pressure, heart rate)

12–Lead Electrocardiogram (ECG) 
monitoring

24-hour Holter monitoring


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Objectives
Endpoints
Exploratory
To evaluate changes in exploratory biomarkers 
in the blood of moderate to severe asthma 
participants with AFAD who have been treated 
with GSK3772847 compared with placebo

Change over time in levels of serum total 
Immunoglobulin E (IgE), fungal-specific IgE
To evaluate changes in IL-33 related and 
disease biology biomarkers in the sputum of 
moderate to severe asthma participants with 
AFAD who have been treated with 
GSK3772847 compared with placebo

Difference from placebo in levels of sputum 
biomarkers including but not limited to 
interleukin (IL)-33, IL-13, IL-4, IL-5 and TNF-


Difference from placebo including but not 
limited to levels of sputum eosinophils


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5.
STUDY DESIGN
5.1.
Overall Design
This is a randomised, multicentre, double blind (sponsor open), placebo-controlled, 
stratified, parallel group study evaluating 3 doses of 10 mg/kg GSK3772847 administered 
every 4 weeks versus placebo in addition to SoC. Participants who have been diagnosed 
as having moderate to severe asthma with allergic fungal airway disease shall be enrolled 
in the study. 
Figure 1
Study Design Overview
Screening 
(28 days 
prior to V3)
GSK3772847 (IV) 10mg/kg, n=20
Follow up
Study duration (approx. 28 weeks)
Week 0
V3
Dose 1
Week 8
V6
Dose 3
Week 12
V7
No Dose
Treatment period
Placebo, n=20
Standard of Care (SoC)
Week 4
V5
Dose 2
Screening 
V1
Week 24 
V8
No Dose
Randomisation
Run-in
V2
Week 2
V4
No Dose
Run-in
(14 days 
prior to V3)
Participants who meet the eligibility criteria at Screening (Visit 1) will enter a two-week 
Run-in period during which they will undergo one 24h Holter monitoring session and 
fulfil paper Diary requirements. Participants who meet the pre-defined randomisation 
criteria (Section 6.4), will be randomised in a 1:1 ratio to one of the following treatment 
groups: 

10 mg/kg GSK3772847 administered intravenously 

Matching placebo administered intravenously 
The randomisation will be stratified based on whether a participant is taking anti-fungal 
medication or not, determined at screening.  
Both treatments will be administered on Week 0 (Day 1), Week 4 and Week 8.
Each participant will: 

Be screened;


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
Attend a run-in visit (Visit 2) and enter the run-in period, approximately 14 days 
before the first treatment visit;

Receive a total of 3 doses, each one on separate study visits (Visits 3, 5 and 6); doses 
will be every 4 weeks starting at Week 0;

Attend treatment period study visits at Week 2 (Visit 4) and Week 12 (Visit 7) but 
not receive study treatment during these visits; and

Have a follow-up visit (approximately 12 weeks after Visit 7).
Each participant will be involved in the study for approximately 28 weeks. 
At specified visits, each participant will undergo the following procedures: 

Sputum inductions at baseline (Visit 2) and end of treatment period (Visit 7). The 
sputum inductions may each be repeated once: for baseline at Visit 3 and for end of 
treatment period at an extra visit after Visit 7;

24 h Holter monitoring at Visits 2 and 3 only.
During treatment period study visits, the participant will: 

Have blood drawn, for PD and/or PK assessments;

Undergo FeNO measurement and spirometry;

Have vital signs measured; and

Complete 2 Quality of Life (QoL) questionnaires.
For participants who discontinue IP early, but have not withdrawn consent to participate 
in the study, an early withdrawal (EW) visit will be performed 4 weeks after the last dose 
of blinded study treatment. These participants should continue in the study and complete 
all assessments at the remaining protocol-defined visits until their EW visit, and complete 
the follow-up visit assessments.
5.2.
Number of Participants
Approximately 46 participants with moderate to severe asthma will be randomised such 
that approximately 40 evaluable participants complete the study, where evaluable is 
defined as subjects with at least one post-baseline measurement for both FeNO and blood 
eosinophils.
If participants prematurely discontinue the study, additional replacement participants may
be recruited and assigned to the same treatment (from Visit 1), at the discretion of the 
Sponsor in consultation with the investigator.
5.3.
Participant and Study Completion
A participant is considered to have completed the study if he/she has completed all 
phases of the study including screening, run-in, the randomised treatment phase, and the 
follow-up visit.


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The end of the study is defined as the date of the last visit (Visit 8) of the last participant 
in the study.
5.4.
Scientific Rationale for Study Design
This study will use a randomised, multi-centre, double blind (sponsor open), placebo-
controlled, parallel-group design. This is a well-established design to evaluate the 
efficacy, safety, PK and PD profile of an investigational medicinal product.
Use of a placebo arm is considered justified as all patients will be continuing on standard 
of care treatments and will also allow the absolute effect of GSK3772847 to be assessed. 
The study will be sponsor open to allow selected sponsor study team members to be 
unblinded in order to perform interim analysis of in-stream data.
The dosing duration of 8 weeks is supported by pre-clinical study data. Dosing frequency 
of GSK3772847 every 4 weeks with endpoints assessments scheduled 4 weeks post final 
dose were determined by the available target engagement pharmacodynamic findings. 
Participants will be followed up for an additional 12 weeks before a final safety 
evaluation. This follow up period will ensure that sufficient PK samples are collected to 
characterise the pharmacokinetics, pharmacodynamics, and anti-drug antibody responses 
in this patient population.
5.5.
Dose Justification
The dosing regimen of 10 mg/kg IV at Week 0 then Weeks 4 and 8 was selected based on 
the observed evidence of target suppression following single doses in healthy participants 
(CNTO7160ASH1001). In summary, administration of a single 10 mg/kg dose led to 
significant (>95%) suppression of serum free sST2 and sustained elevations of total sST2 
up to at least 28 days after dosing. Therefore, the selected regimen should deliver 
significant target suppression throughout the treatment period, including at trough, and 
allow determination of the impact of targeting this pathway on the primary endpoint 
(measured over 0-12 weeks).
Simulations of exposure were generated using a preliminary Michaelis Menten (MM) 
population PK model using the single dose data from 0.03-10 mg/kg up to 28 days. 
Safety margins were estimated by comparing the mean clinical exposures (predicted or 
observed) against the mean observations in the 3-month GLP toxicology study in 
cynomolgus monkeys (T-2013-007). Area under the curve (AUC) margins were 
calculated by comparing the predicted clinical exposures from 0-28 weeks (end of study) 
to the observed exposure from 0-92 days (13 weeks) when the main study animals were 
removed from study. Predicted exposures throughout the study and follow up period are 
significantly lower than those observed in study T-2013-007 as shown in Figure 2. 
The anticipated exposure margins of the dosing regimen of 10 mg/kg IV at Week 0 then 
Weeks 4, and 8 over the 3-month GLP toxicology study in cynomolgus monkeys (T-
2013-007) are summarised in Figure 2.


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Figure 2
Predicted clinical exposures at 10mg/kg at weeks 0, 4, and 8 using a 
preliminary MM population PK model against observed exposures in 
study CNTO7160ASH1001 (part 1 single dose) and observed 
exposures at the No Observed Adverse Effect Level (100 mg/kg 
weekly) in the 3-month GLP toxicology study in cynomolgus 
monkeys (T-2013-007)
Open Triangles: Observed mean and standard deviation of exposures through main study and 
recovery phase (post week 13) in toxicology study T-2013-007. 
Solid circles: Observed clinical exposures in part 1 of study CNTO7160ASH1001. 
Solid line and shade region: median and 95% prediction interval for clinical exposures using a 
preliminary MM population PK model.


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Table 1
Predicted clinical exposures and safety margins for study 207972 
following dosing of 10 mg/kg at weeks 0, 4, and 8.
Day 1 mean 
Cmax
(g/mL)
Exposure
margina
Week 8
mean Cmax
(g/mL)
Exposure
margina
0-28 weeks 
mean AUC
(g.day/mL)
Exposure
marginb
245.3c
10.5
304.5d
17.9
12545.3d
24.4
a.
Margins calculated against mean maximum serum concentration (Cmax) on day 1 and day 84 (last 
dose) in study T-2013-007 (2592.55 and 5444.07 μg/mL respectively).
b.
Margins calculated based on AUC (0-92 (13 weeks)) estimated using compartmental modelling of 
mean exposures in study T-2013-007 (306900 ug.day/mL).
c.
Mean observed exposures in study CNTO7160ASH1001.
d.
Predicted exposures using preliminary MM model
As an additional approach to comparing exposure margins the AUC() at steady state at 
10 mg/kg every 4 weeks was estimated based on the preliminary population PK model. 
At this regimen, the contribution of the non-linear elimination is minimal and so 
AUC(inf) can be estimated as Dose/Clearance. Clearance was estimated at 2.38 
mL/kg/day, therefore, mean predicted AUC() at steady state is 4202 µg.day/mL.
The mean AUC(day85-92) at the no observed adverse effect level (NOAEL) (100 mg/kg, 
IV, weekly) in cynomolgus monkeys was 27408 µg.day/mL (T-2013-007). In order to 
correct for weekly dosing in the cynomolgus and dosing every 4 weeks in this study, this 
figure was multiplied by 4 and results in an estimated exposure margin of 26.


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6.
STUDY POPULATION
Prospective approval of protocol deviations to recruitment and enrolment criteria, also 
known as protocol waivers or exemptions, is not permitted.
6.1.
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria 
apply:
Age
1.
Participant must be at least 18 years of age inclusive, at the time of signing the 
informed consent.
Type of Participant and Disease Characteristics
2.
Documented history of physician diagnosed moderate or severe asthma for 12 
months based on  [GINA, 2017] Guidelines and treated with inhaled corticosteroid 
(ICS) and long-acting beta-2-agonist (LABA) for at least 4 months (≥500 g/day 
fluticasone propionate or equivalent as defined in the [GINA, 2017] guidelines). 
Additional therapy: with low dose oral corticosteroid (10 mg/day prednisolone or 
equivalent), with a leukotriene receptor antagonist (LTRA), with anticholinergics, 
with anti-fungal medication is permissible.
3.
Pre-bronchodilator FEV1 35-79% of predicted value for participant inclusive
4.
FeNO 25ppb at Screening (Visit 1) 
5.
ACQ-5 score 1.5 at Screening (Visit 1)
6.
Blood eosinophils 300 cells/microliter at Screening (Visit 1). Participants with 
blood eosinophils of 250-299 cells/microliters (inclusive) at screening but with 
documented evidence of 300 cells /microliters within 5 months of screening will be 
eligible for the study.
7.
Evidence of allergic fungal airway disease: 
Fungal sensitisation to at least one of the following fungi: Aspergillus fumigatus, 
Penicillium chrysogenum (notatum) at screening measured by serum-specific IgE
test. Documented fungal sensitisation either by serum-specific IgE or skin prick test 
is also acceptable. 
A history of exacerbations (at least 1 severe exacerbation (defined as requiring a 
minimum of 3 days of high-dose oral corticosteroids [>10 mg/day prednisolone, or 
equivalent] for asthma symptoms) in the previous 12 months.
Weight
8.
Body weight within 50-150 kg (inclusive).
Sex
9.
Male and female


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a. Female participants: 
A female participant is eligible to participate if she is not pregnant (see Appendix 5), 
not breastfeeding, and at least one of the following conditions applies:
i.
Not a woman of childbearing potential (WOCBP) as defined in Appendix 5
OR
ii.
A WOCBP who agrees to follow the contraceptive guidance in Appendix 5
during the treatment period and for the duration of the follow-up period until 
the last visit at week 24 (or 16 weeks after the last dose, which is equivalent to 
5.5 half-lives).
Informed Consent
10. Capable of giving signed informed consent as described in Appendix 3 which 
includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol.
6.2.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. Historical diagnosis of cystic fibrosis
2. Concurrent respiratory diseases: Presence of a known pre-existing, clinically 
important respiratory conditions (e.g. pneumonia, pneumothorax, atelectasis
segmental or larger, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic 
bronchitis, emphysema, chronic obstructive pulmonary disease, or other respiratory 
abnormalities) other than asthma or AFAD
3. Has a history of chronic or recurrent non-pulmonary infectious disease or ongoing 
non-pulmonary infection including, but not limited to, chronic renal infection, chronic 
chest infection, recurrent urinary tract infection (eg, recurrent pyelonephritis, chronic 
non-remitting cystitis), or open, draining skin wound or an ulcer
4. Serious infection within 8 weeks of enrolment, including, but not limited to hepatitis, 
pneumonia, sepsis, or pyelonephritis; or has been hospitalised for an infection; or has 
been treated with IV antibiotics for an infection, within 8 weeks prior to the first 
administration of study drug
5. Evidence of poorly controlled chronic medical conditions other than asthma, e.g., 
patients with known, pre-existing, clinically significant endocrine, autoimmune, 
metabolic, neurological, renal, cardiovascular, gastrointestinal, hepatic, and 
haematological or any other system abnormalities that are uncontrolled with standard 
treatment.
6. Cardiovascular disease: Clinically significant organic heart disease (e.g. CAD, 
NYHA Class III/IV heart failure).
7. Participants with a diagnosis of malignancy or in the process of investigation for a 
malignancy. Participants with carcinoma that have not been in complete remission for 


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at least 5 years. Participants who have had carcinoma in situ of the cervix, squamous 
cell carcinoma and basal cell carcinoma of the skin would not be excluded based on 
the 5 year waiting period if the patient has been considered cured by treatment..
8. Eosinophilic diseases: Other conditions that could lead to elevated eosinophils such 
as hypereosinophilic syndromes. Participants with a known, pre-existing parasitic 
infestation within 6 months prior to Screening (Visit 1).
Prior/Concomitant Therapy
9. Use of the medications listed in Table 2 is not permitted within the defined time 
intervals prior to Screening (Visit 1) and throughout the study. Potential participants 
should not be washed out of their medication solely for the purpose of enrolling in the 
trial.
Table 2
Prohibited Medications
Medication
Time interval prior to Screening
Investigational drug
30 days or 5-half-lives (whichever is longer)
Biologic agents (such as monoclonal 
antibodies including marketed drugs)
130 days or 5 half-lives whichever is longer
Live or attenuated vaccines
2 weeks 
Experimental anti-inflammatory drugs 
(nonbiologics)
3 months
Oral corticosteroids (>10 mg/day prednisolone 
or equivalent)
2 weeks as short-term treatment of asthma 
exacerbation 
>4 weeks as SoC
Corticosteroids intramuscular, long acting 
depot
3 months
Immunomodulatory/suppressive agents (e.g. 
Methotrexate, troleandomycin, oral or 
parenteral gold, cyclosporin, azathioprine, 
cyclophosphamide, tacrolimus, mycophenolate 
mofetil, D-penicillamine)
3 months
Theophylline
3 months
Chemotherapy and radiotherapy
12 months
Diagnostic assessments
10. Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test 
result at screening or within 3 months prior to first dose of study treatment. 
11. A known immunodeficiency such as human immunodeficiency virus infection.
12. Hypersensitivity: significant allergies to humanised monoclonal antibodies or 
biologic or to any components of the formulation used in this study.
13. Clinically significant multiple or severe drug allergies, intolerance to topical 
corticosteroids, or severe post-treatment hypersensitivity reactions (including, but 


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not limited to, erythema multiforme major, linear immunoglobulin a dermatosis, 
toxic epidermal necrolysis, and exfoliative dermatitis).
14. Clinically significant abnormality on 12-lead ECG assessment at screening (Visit 1). 
Site investigators will be provided with ECG over-read conducted by a centralised 
independent cardiologist, to assist in evaluation of participant eligibility. For this 
study, an abnormal and clinically significant ECG that would preclude a participant 
from entering the trial is defined as a 12-lead tracing that is interpreted as, but not 
limited to, any of the findings in Table 3. 


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Table 3
Abnormal and clinically significant ECG findings

Sinus bradycardia <45 beats per minute (bpm)
*Note: Sinus bradycardia <45bpm should be confirmed by two additional readings at least 5 
minutes apart.

Sinus tachycardia 110bpm
*Note: Sinus tachycardia 110 should be confirmed by two additional readings at least 5 minutes 
apart.

Multifocal atrial tachycardia (wandering atrial pacemaker with rate >100bpm)

Evidence of Mobitz II second degree or third degree atrioventricular (AV) block

Pathological Q waves (defined as wide [>0.04 seconds] and deep [>0.4mV (4mm with 
10mm/mV setting)] or >25% of the height of the corresponding R wave, providing the R 
wave was >0.5mV [5mm with 10mm/mV setting], appearing in at least two contiguous 
leads
*Note: prior evidence (i.e., ECG obtained at least 12 months prior) of pathological Q waves that are 
unchanged are not exclusionary; and the investigator will determine if the participant is precluded 
from entering the study.

Evidence of ventricular ectopic couplets, bigeminy, trigeminy or multifocal premature 
ventricular complexes

For participants without complete right bundle branch block: QT interval corrected for heart 
rate by Fridericia’s formula (QTc[F]) 450 msec or an ECG that is unsuitable for QT 
measurements (e.g., poor defined termination of the T wave)

For participants with complete right bundle branch block: QTc(F) 480 msec or an ECG 
that is unsuitable for QT measurements (e.g., poor defined termination of the T wave)
*Note: All potentially exclusionary QT measurements should be confirmed by two additional 
readings at least 5 minutes apart.

ST-T wave abnormalities (excluding non-specific ST-T wave abnormalities)
*Note: prior evidence (i.e., ECG obtained at least 12 months prior) of ST-T waves that are 
unchanged are not exclusionary and the investigator will determine if the participant is precluded 
from entering the study.

Clinically significant conduction abnormalities (e.g., Wolff-Parkinson-White syndrome or 
bifascicular block defined as complete left bundle branch block or complete right bundle 
branch block with concomitant left fascicular block)

Clinically significant arrhythmias (e.g., atrial fibrillation with rapid ventricular response, 
ventricular tachycardia)
Other Exclusions
15. Smoking history: current smokers or former smokers with a smoking history ≥10 
pack years (pack years = number of cigarettes smoked per day / 20 * number of 
years smoked). Former smokers are defined by 6 months abstention.


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16. History of alcohol or illegal substance abuse within 2 years prior to Screening 
(Visit1).
17. Participants at risk of non-compliance, or unable to comply with the study 
procedures. Participants who are unable to follow study instructions such as visit 
schedule and paper diary completion. Participants who have known evidence of lack 
of adherence to controller medication and/or ability to follow physician’s 
recommendations. Any infirmity, disability, or geographic location that would limit 
compliance for scheduled visits.
6.3.
Run-in Exclusion Criteria
Participants meeting any of the following criteria should not enter the run-in period at 
Visit 2:
1.
Clinically significant and abnormal laboratory finding at Screening (Visit 1): 
Evidence of clinically significant abnormal laboratory tests during screening which 
are still abnormal upon repeat analysis and are not believed to be due to disease(s) 
present. Each Investigator will use his/her own discretion in determining the clinical 
significance of the abnormality.
2.
Liver function at Screening (Visit 1) 
a.
Alanine Aminotransferase (ALT) >2x upper limit of normal (ULN) and 
bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if 
bilirubin is fractionated and direct bilirubin >35 %).
b.
Current or chronic history of liver disease, or known hepatic or biliary 
abnormalities (with the exception of Gilbert's syndrome or asymptomatic 
gallstones.
3.
Asthma exacerbation: Participants with ongoing severe asthma exacerbation at the 
time of Visit 2 (defined as requiring a minimum of 3 days of high-dose oral 
corticosteroids [>10 mg/day prednisolone or equivalent] for asthma symptoms).
4.
Positive pregnancy test at Run-in if test is done at Visit 2.
5.
Ongoing infection(s) requiring systemic antibiotics
6.4.
Randomisation Inclusion Criteria
At the end of the Run-in period (Visit 3), study participants must fulfil the following 
additional criteria in order to be randomised into the study and enter the treatment period:
1.
ACQ-5 score ≥1.5 at Visit3.
2.
FeNO 25ppb at Baseline (Visit 3)
6.5.
Randomisation Exclusion Criteria
Participants meeting any of the following criteria must not be randomised to double-blind 
study medication at Visit 3:
1.
24-Hour Holter Monitoring: An abnormal and significant finding from 24-hour 
Holter monitoring at Run-in (Visit 2). Investigators will be provided with Holter 
reviews conducted by an independent cardiologist to assist in evaluation of subject 
eligibility. Specific findings that preclude subject eligibility are listed in Table 3. The 


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study investigator will determine the medical significance of any Holter 
abnormalities not listed in Table 3.
2.
Asthma exacerbation: Participants with ongoing severe asthma exacerbation at the 
time of Visit 3 (defined as requiring a minimum of 3 days of high-dose oral 
corticosteroids [>10 mg/day prednisolone or equivalent] for asthma symptoms).
3.
Severe airflow obstruction: a pre-bronchodilator FEV1 <35 % predicted of normal 
value at Visit 3. Predicted values will be based upon GLI [Quanjer, 2012] equations 
for spirometry reference values.
4.
Positive pregnancy test at Visit 3
5.
Ongoing infection(s) requiring systemic antibiotics.
6.6.
Lifestyle Restrictions
6.6.1.
Caffeine, Alcohol, and Tobacco

During each dosing session, participants will abstain from ingesting caffeine- or 
xanthine-containing products (eg, coffee, tea, cola drinks, and chocolate) for 8 hours 
before the start of dosing until after collection of the final PK and/or 
pharmacodynamic sample.

During each dosing session, participants will abstain from alcohol for 24 hours 
before the start of dosing until after collection of the final PK and/or 
pharmacodynamic sample. 

Use of tobacco or e-cigarette products will not be allowed from screening until after 
the final follow-up visit.
6.6.2.
Activity

Participants will abstain from strenuous exercise for 24 hours before each blood 
collection for clinical laboratory tests. Participants may participate in light 
recreational activities during studies (eg, watching television, reading).


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6.7.
Screening/Run-in/Randomisation Failures
A participant will be assigned a participant number at the time the informed consent is 
signed at Visit 1.
For the purposes of this study, participants who consent to participate in the clinical study 
but do not subsequently enter the study or receive study treatment will be defined as 
follows: 

Screening failures: those participants that complete at least one Screening 
(Visit 1) procedure but do not enter the run-in period. 

Run-in failures: those participants that complete at least one Visit 2 procedure 
but do not enter the double-blind study treatment period. 

Randomisation failures: those participants that complete at least one Visit 3 
procedure but do not receive study treatment. 
Any participant who completes the run-in period and then meets the randomisation 
criteria and receives the double-blind study treatment at Visit 3 is considered to have 
entered the treatment period.
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 
publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, eligibility criteria, and any 
serious adverse events (SAEs).
Rescreening is only allowed in exceptional circumstances of technical errors or at the 
Investigator’s discretion in consultation with GSK if a participant experiences an asthma 
exacerbation either at run-in or randomisation. Rescreened participants will be assigned a 
new participant number. Rescreening of subjects who screen-failed based on inclusion 
criterion 6 prior to Amendment 02 implementation may be rescreened after consultation 
with GSK.


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7.
TREATMENTS
Study treatment is defined as any investigational treatment(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol.
7.1.
Treatments Administered
Study Treatment Name:
GSK3772847
Placebo
Dosage formulation:
50mg/mL GSK377284, 15 
mM Sodium Phosphate, 
8.5% [w/v] Sucrose, and 
0.04% [w/v] Polysorbate 
20, pH 7.3.
Unit dose strength(s)/Dosage
level(s):
10 mg/kg
Commercially sourced 
sterile normal saline
Route of Administration 
IV infusion
IV infusion
Dosing instructions:
GSK3772847 for injection 
will require further 
reconstitution and dilution 
at the study site prior to 
administration:
dilution between 10 and 30 
mg/mL may be 
accomplished by using 
commercially sourced 
sterile normal saline
Packaging and Labeling
Study Treatment will be 
provided as 100mg/vial, 
white to yellow, uniform 
lyophilized cake in a 5ml 
clear glass vial with 20mm 
closure sealed by red metal 
and yellow overseal.
Each container will be 
labelled as required per 
country requirement.
Commercially sourced 
sterile normal saline


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7.1.1.
Medical Devices

Other medical devices (not manufactured by or for GSK) provided for use in this
study are 24h Holter monitor.

Instructions for the 24h Holter monitor use are provided in the Holter monitor 
manual.
7.1.2.
Rescue medication
A rescue inhaler for as needed use throughout the study will be dispensed starting at Visit 
2. At the Investigator’s discretion, more than one rescue inhalers may be dispensed at any 
one time. Short acting -2 agonist (SABA) will be sourced from local commercial stock. 
The contents of the label will be in accordance with all applicable regulatory 
requirements. The investigator should attempt to match the participant’s current 
medication or provide a suitable alternative. The use of rescue medications is allowable at 
any time during the study following randomisation. The date of rescue medication 
administration must be recorded on the rescue medication worksheet/diary card. 
7.2.
Dose Modification
There are no dose modifications planned for this protocol. 
7.3.
Method of Treatment Assignment
Participants will be assigned to study treatment in accordance with the randomisation 
schedule. The randomisation code will be generated by GSK using a validated 
computerised system. Participants will be randomised using an interactive web response 
system (IWRS). The study will use central-based randomisation to allocate treatments. 
Once a randomisation number is assigned to a participant, it cannot be reassigned to any 
other participant in the study.
Following the 2-week Run-in period and satisfaction of all eligibility criteria, participants 
will be randomised 1:1 to one of the following double-blind (sponsor open) treatments 
for the duration of the Treatment Period:

GSK3772847 (10 mg/kg) administered intravenously

Placebo administered intravenously
The duration of the Treatment Period for each participant is 12 weeks. Study treatment 
will be dispensed at the study visits summarized in the SoA (Section 2). Returned study 
treatment should not be re-dispensed to the participants. 
Each Investigator will be provided with sufficient supplies to conduct the trial. Additional 
treatment kits will be supplied as needed to the sites. Details of how to use the IWRS 
system to randomise participants and manage study treatment supplies (including
dispensing) is provided in the IWRS manual and the SRM.


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7.4.
Blinding
This will be a double blind (sponsor open) study and the following will apply:

All study staff involved in clinical assessments (which includes the investigator, 
sub-investigators, other site staff), and the participant will be blinded to the 
treatment allocated to individual participants. Selected sponsor study team 
members (and delegates if programming activities are outsourced) will be 
unblinded to perform the interim analysis. This may include the study statistician, 
study programmer (and delegates) and study pharmacokineticist; however, only 
the statistician and programmer (and delegates) will have access to individual 
participant level data. Access to unblinded data will be kept to the minimum set of 
individuals required to implement any interim analyses, but may include GSK 
management/review committees if alterations to the study conduct are required. 
Details of who were unblinded to what data and when will be included in the 
clinical study report.

The IWRS will be programmed with blind-breaking instructions. In case of an 
emergency, the investigator has the sole responsibility for determining if 
unblinding of a participant’s treatment assignment is warranted. Participant safety 
must always be the first consideration in making such a determination. If the 
investigator decides that unblinding is warranted, the investigator should make 
every effort to contact GSK prior to unblinding a participant’s treatment 
assignment unless this could delay emergency treatment of the participant. If a 
participant’s treatment assignment is unblinded GSK must be notified within 24 
hours after breaking the blind. The date and reason that the blind was broken must 
be recorded in the source documentation and Case Report Form (CRF), as 
applicable.  

In the event of unblinding by the investigator or treating physician the Medical 
monitor/GSK team should be contacted to determine whether subject withdrawal 
is required. Should a participant’s treatment assignment be unblinded and the 
Medical monitor/GSK team determine that the participant must be withdrawn 
from study treatment, the participant must be followed-up as per protocol until the 
completion of the early withdrawal (EW) assessments (see SoA in Section 2).

A participant whose treatment assignment is inadvertently unblinded (either to 
investigative staff or the participant themselves) will be permitted to remain in the 
study, although the accidental unblinding will be recorded as a protocol deviation 
and hence the participant will be subject to review as to their inclusion in 
analyses.
Participants will be randomised in a [1:1] ratio to receive study treatment. Investigators 
will remain blinded to each participant’s assigned study treatment throughout the course 
of the study. In order to maintain this blind, an otherwise uninvolved 3rd party (such as 
an unblinded pharmacist or other appropriately licensed and authorised personnel) will be 
responsible for the reconstitution and dispensation of all study treatment and will 
endeavour to ensure that there are no differences in time taken to dispense following 
randomisation.


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Unblinded monitors and in the event of a Quality Assurance audit, the auditor(s) will be 
allowed access to un-blinded study treatment records at the site(s) to verify that 
randomisation/dispensing has been done accurately.
GSK’s Global Clinical Safety and Pharmacovigilance staff may unblind the treatment 
assignment for any participant with an SAE. If the SAE requires that an expedited 
regulatory report be sent to one or more regulatory agencies, a copy of the report, 
identifying the participant’s treatment assignment, may be sent to investigators in 
accordance with local regulations and/or GSK policy.
7.5.
Preparation/Handling/Storage/Accountability
7.5.1.
Accountability
1.
The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study treatment received and any discrepancies 
are reported and resolved before use of the study treatment.
2.
Only participants enrolled in the study may receive study treatment and only 
authorised site staff may supply or administer study treatment. All study treatments 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorised site staff.
3.
The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study treatment accountability, reconciliation, and record 
maintenance (ie, receipt, reconciliation, and final disposition records).
4.
Further guidance and information for the final disposition of unused study treatment 
are provided in the Study Reference Manual. 
7.5.2.
Preparation, Storage and Handling
GSK3772847 is provided as a white to yellow, uniform lyophilized cake in a 5ml clear 
glass vial with 20mm closure sealed by red metal and yellow overseal. Each vial contains 
100 mg of a lyophilised GSK3772847. When reconstituted with 2.0 mL of water for 
injection, the final concentration of GSK3772847 is 50 mg/mL. Excipients include: 
sucrose, sodium phosphate buffer, and polysorbate 20 at a pH of 7.3. Vials contain no 
preservatives and thus are for single use. Vials must be stored 2– 8C, protected from 
light. Protection from light during preparation and administration is not required. Full 
details on specific 2to 8C storage temperature conditions, preparation and 
administration including requirements for filtration are provided in the unblinded site 
staff reference manual or study reference manual. 
Commercially available sterile normal saline will be used for dilution of study agent and 
will also serve as placebo for this study. Use of study agent sterile normal saline as 
placebo for injection provides an adequate comparator to broadly assess safety in early 
clinical development. 
GSK3772847 must be prepared by an unblinded pharmacist or other appropriately 
licensed and authorised personnel and administered according to each participant’s body 


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weight at Screening (Visit 1). A different site staff member, who will be blinded to the 
treatment assignment, will administer the study agent. Aseptic procedures must be used 
during preparation and administration of the study agent. Diluted GSK3772847 at 
volumes of 50 mL are to be administered by IV infusion over a period of at least 30 
minutes using an in-line 0.22 micron filter. At least 30 mL of commercially available 
sterile normal saline will be used to flush diluted drug from the administration set to 
ensure full study agent administration. 
Unblinded site staff will be responsible for receipt, storage, reconstitution, and labelling, 
and accountability of investigational product. 
GSK3772847 should be inspected visually for particulate matter and discoloration prior 
to administration whenever solution and container permit. If visibly opaque particles, 
discoloration, or other foreign particles are observed, the solution should not be used. 
Detailed instructions for storage conditions, dose preparation, and administration will be 
provided in the unblinded site staff reference manual or study reference manual. Required 
storage conditions and expiration date are indicated on the label. 
Under normal conditions of handling and administration, study treatment is not expected 
to pose significant safety risks to site staff.  Take adequate precautions to avoid direct eye 
or skin contact and the generation of aerosols or mists. In the case of unintentional 
occupational exposure notify the monitor, Medical Monitor and/or GSK study contact.
A Material Safety Data Sheet/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.
7.6.
Treatment Compliance

GSK3772847 or placebo will be intravenously administered to participants at the 
site.  Administration will be documented in the source documents and reported in the 
electronic case report form (eCRF).
7.7.
Concomitant Therapy
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) that the participant is taking at the time of 
enrolment or 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.
7.7.1.
Permitted Medications and Non-Drug Therapies
The following medications are allowed during the study: 


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•
ICS/LABA, SABA, LTRA and anticholinergics as defined in the inclusion criteria
(Section 6.1 criterion 2), used in a consistent dosage and frequency from 
screening and throughout the study
•
Low dose oral corticosteroids (≤10 mg prednisolone per day) are permitted as 
standard of care. This should have been started a minimum of 4 weeks prior to 
screening and should be maintained at that dose until the end of the treatment 
period (V7).
•
Anti-fungal medications (oral) are permitted if treatment was started a minimum 
of 1 month from screening and must be used in a consistent dosage and 
frequency from screening and throughout the treatment period. If discontinued 
recently, a washout of 3 months prior to screening is required. Ad hoc use 
during the treatment period is not permitted.
•
Medications for rhinitis (e.g., intranasal corticosteroids, antihistamines [including 
ocular and intranasal], cromolyn, nedocromil, nasal decongestants) are 
permitted but they are disallowed 48 hours prior to ECG measurements.
•
Azithromicin used in a consistent dosage and frequency from screening and 
throughout the study. 
•
Antibiotics for short term treatment of acute infections. Long term treatment with 
topical or ophthalmic antibiotics are permitted.
•
Decongestants: Participants may take decongestants during the study, but these 
are disallowed for 24 hours prior to ECG measurements. 
•
Topical and ophthalmic corticosteroids
•
Paracetamol or Acetaminophen, at doses of 3 grams/day
•
Hormone replacement therapy (HRT) or hormonal contraception 
A participant who requires systemic corticosteroid for the treatment of a severe 
asthma exacerbation after randomisation will be permitted to continue the study. The 
Investigator, in consultation with the medical monitor, will determine if 
discontinuation of study treatment is required (Section 8). 
Any medication, herbal therapy or vitamin which is not listed as prohibited in Section 
7.7.2 is permitted at the discretion of the investigator.
7.7.2.
Prohibited Medications and Non-drug Therapies
Use of the medications listed below is not permitted at any time during the study. Refer 
to Table 2 for the minimum time interval since discontinuation prior to screening if 
medications were used by participants before screening. 

Biologics, e.g. Mepolizumab and Omalizumab.

Potent CYP3A4 inhibitors, (e.g., ritonavir, ketoconazole, etc.)

Anticonvulsants (barbiturates, hydantoins, and carbamazepine).

Polycyclic antidepressants.

Beta-adrenergic blocking agents.

Phenothiazines.


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
Monoamine oxidase inhibitors.

Live or attenuated vaccines (and up to 6 months after the last dose of blinded 
study treatment).

Experimental anti-inflammatory drugs (non-biologics).

Intramuscular and long acting depot corticosteroids.

Methotrexate, troleandomycin, oral or parenteral gold, cyclosporin, azathioprine, 
cyclophosphamide, tacrolimus, mycophenolate mofetil, D-penicillamine.

Theophylline.

Chemotherapy and radiotherapy.
All concomitant medications may be reviewed by the Medical Monitor and it will be up 
to the discretion of the Investigator and if necessary the Medical Monitor, whether the 
medication can be continued and/or the participant can take part in the study.
7.8.
Treatment after the End of the Study
Participants will not receive any additional treatment from GSK after completion of the 
study or withdrawal of IP because other treatment options are available.
The Investigator is responsible for ensuring that consideration has been given to the post-
study care of the participant’s medical condition.


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8.
DISCONTINUATION CRITERIA
8.1.
Discontinuation of Study Treatment
Participants that permanently stop study treatment are encouraged to remain in the study. 
Participants have the right to discontinue study treatment before the end of the study. A 
participant may also be asked to discontinue study treatment at the Investigator’s 
discretion. 
Participants who withdraw from study treatment prematurely (for any reason) should, 
where possible, continue to be followed-up until the completion of the Safety Follow-up 
assessments: 

For participants who discontinue IP early, but have not withdrawn consent to 
participate in the study, an EW visit will be performed 4 weeks after the last dose 
of blinded study treatment. These participants should continue in the study and 
complete all assessments at the remaining protocol-defined visits until their EW 
visit. Participants should continue regular treatment for their asthma, as 
determined by the investigator. The follow-up visits will then be performed 12 
weeks after the EW visit for safety assessments. 

Participants who discontinue IP early and withdraw consent to participate in the 
study should complete as many assessments planned for the EW visit as possible. 
If this is not possible, the Investigator must encourage the participant to participate in as 
much of the study as they are willing (or able) to. 
A participant may be withdrawn from study treatment at any time. A reason for 
premature discontinuation of study treatment (e.g., AE, protocol deviation, Investigator 
discretion, consent withdrawn etc.) must be captured in the eCRF.
A participant must be withdrawn from study treatment if any of the following stopping 
criteria are met at any time during the study:
1. Liver Chemistry: Meets any of the protocol-defined liver chemistry 
stopping criteria.
2. QT interval corrected for heart rate (QTc): Meets any of the protocol-
defined stopping criteria.
3. Pregnancy: Positive pregnancy test.
4. A clinically significant asthma exacerbation (requiring hospitalisation).
5. Abnormal Holter of Mobitz II AVB, complete AVB, sustained or non-
sustained ventricular tachycardia (VT), paroxysmal supraventricular 
tachycardia (PSVT), new onset atrial fibrillation/flutter will be a 
withdrawal/stopping criterion. These findings on ECG (baseline [V2], V3) 
or findings of myocardial ischemia will also result in withdrawal/stopping.
6. Hypersensitivity or anaphylactic reaction


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8.1.1.
Liver Chemistry Stopping Criteria
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology.
Discontinuation of study treatment for abnormal liver tests should be considered by the 
investigator when a participant meets one of the conditions outlined in the algorithm or if 
the investigator believes that it is in the best interest of the participant.
Phase II Liver Chemistry Stopping and Increased Monitoring Algorithm
Liver Safety Required Actions and Follow up Assessments Section can be found in 
Appendix 7.
8.1.2.
QTc Stopping Criteria

The QTc is the QT interval corrected for heart rate according to Bazett’s formula 
(QTcB), Fridericia’s formula (QTcF), and/or another method, machine-read or 
manually over-read. The same QT correction formula must be used for each 
individual participant to determine eligibility for and discontinuation from the study. 
This formula may not be changed or substituted once the participant has been 
enrolled.

For example, if a participant is eligible for the protocol based on QTcB, then QTcB 
must be used for discontinuation of this individual participant as well. 

Once the QT correction formula has been chosen for a participant’s eligibility, the 
same formula must continue to be used for that participant for all QTc data being 


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collected for data analysis. Safety ECGs and other non-protocol specified ECGs are 
an exception. 

The QTc should be based on single or averaged QTc values of triplicate ECGs 
obtained over a brief (e.g., 5-10 minute) recording period.
A participant who meets the bulleted criteria based on the average of triplicate ECG 
readings will be withdrawn from study treatment: 

QTc >500 msec OR Uncorrected QT >600 msec

Change from baseline of QTc >60 msec
Note: The baseline is defined as visit 3 pre-dose. 
For participants with underlying bundle branch block, follow the discontinuation criteria 
listed below: 

Baseline QTc with Bundle Branch Block <450 msec, Discontinuation QTc with 
Bundle Branch Block >500 msec

Baseline QTc with Bundle Branch Block <450-480 msec, Discontinuation QTc 
with Bundle Branch Block 530 msec. 
See the SoA (Section 2) for data to be collected at the time of EW visit and follow-up and 
for any further evaluations that need to be completed.
8.1.3.
Rechallenge
8.1.3.1.
Study Treatment Restart or Rechallenge
Study treatment restart or rechallenge after liver chemistry stopping criteria are met by 
any participant in this study is not allowed. Additionally, if hypersensitivity or 
anaphylactic reaction occurs, infusion should be discontinued and study restart is not 
allowed.
8.2.
Withdrawal from the Study

A participant may withdraw from the study at any time at his/her own request, 
or may be withdrawn at any time at the discretion of the investigator for safety, 
behavioral, compliance or administrative reasons.

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.

Refer to the SoA (Section 2) for data to be collected at the time of early 
withdrawal (EW) and follow-up and for any further evaluations that need to be 
completed.


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8.3.
Lost to Follow Up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit:

The site must attempt to contact the participant and reschedule the missed visit 
as soon as possible and counsel the participant on the importance of maintaining 
the assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study.

Before a participant is deemed lost to follow up, the investigator or designee 
must make every effort to regain contact with the participant (where possible, 3 
telephone calls 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 with a primary reason of lost to follow-up. 


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9.
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and their timing are summarized in the SoA (Section 2). 

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 treatment.

Adherence to the study design requirements, including those specified in the SoA
(Section 2), is essential and required for study conduct.

The preferred order of assessments at each visit is: ACQ-5, AQLQ, medical review 
and vital signs, ECG, FeNO, spirometry, blood draws and treatment administration 
by infusion. The preferred post-dose order of assessments is: vital signs, ECG, 
andblood draws. 

All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening 
log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable. 

Procedures conducted as part of the participant’s routine clinical management (eg, 
blood count) and obtained before signing of ICF may be utilized for screening or 
baseline purposes provided the procedure met the protocol-specified criteria and was 
performed within the time frame defined in the SoA (Section 2).
9.1.
Efficacy Assessments
The timings of all efficacy assessments are specified in the SoA (Section 2).
9.1.1.
Blood Eosinophils
Blood samples for haematology, specifically for blood eosinophil cell count as an 
efficacy endpoint, will be taken at the specified time points indicated in the SoA (Section 
2). The differential cell counts will be blinded from V3 onwards. 
9.1.2.
Fractional Exhaled Nitric Oxide (FeNO)
FeNO will be measured using a handheld electronic device. Measurements will be 
obtained in accordance with the American Thoracic Socity (ATS)/European Respiratory 
Society (ERS) Recommendations for Standardized Procedures for the Online and Offline 
Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide
American Thoracic Society; European Respiratory Society [ATS/ERS, 2005]. All sites 
will use standardised equipment provided by a central vendor. For each observation, at 
least 2 measurements will be obtained to establish reproducibility (up to 8 measurements 
can be performed). FeNO measurements will be interpreted in accordance with the 
Official ATS Clinical Practice Guideline: Interpretation of Exhaled Nitric Oxide Levels 
(FeNO) for Clinical Applications [Dweik, 2011]. 
FeNO observations must be completed before FEV1 assessments. 


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Participants should not use their rescue medication for at least 6 hours before each FeNO 
assessment, unless essential for clinical need. Participants should also withhold LABAs, 
ICSs and OCSs for 1 dosing interval (i.e. 12 or 24 hours based on the prescribed 
dosing interval of the product) before each FeNO assessment.
Further details will be provided in the SRM and third party vendor manual. 
9.1.3.
Questionnaires
The questionnaires should be completed before any procedures are performed on the 
participant to avoid influencing the participant’s response.  To avoid biasing responses, 
the participant should not be told the results of diagnostic tests prior to completing the 
questionnaires and it is recommended that the questionnaires be administered at the same 
time of day during each visit (as applicable).  
Adequate time must be allowed to complete all items on the questionnaires; the 
questionnaires must be reviewed for completeness and, if necessary, the participant must 
be encouraged to complete any missing assessments or items.
Instructions for completing the questionnaires can be found in the SRM.
9.1.3.1.
Asthma Control Questionnaire (ACQ-5)
The ACQ-5 is a five-item questionnaire that is as a measure of a participant’s asthma 
control [Juniper, 2005].  The questions are self-completed by the participant, recalling 
over the previous 7 days, and enquire about the frequency and/or severity of symptoms 
(nocturnal awakening, activity limitation, shortness of breath and wheeze).  The response 
options for all these questions consist of a zero (no impairment/limitation) to six (total 
impairment/ limitation) scale.
The questions are equally weighted and the ACQ score is the mean of the 5 questions and 
therefore between 0 (totally controlled) and 6 (severely uncontrolled).
The ACQ-5 questionnaire shall be completed at the visits indicated in the SoA
(Section 2). 
9.1.3.2.
Asthma Quality of Life Questionnaire (AQLQ)
The AQLQ is a disease-specific, self-administered quality of life questionnaire recalling 
over the previous 14 days. It was developed to evaluate the impact of asthma treatments 
on the quality of life of asthma sufferers [Juniper, 1993; Juniper, 2005]. The AQLQ 
contains 32 items in four domains: activity limitation (11 items), symptoms (12 items), 
emotional function (five items), and environmental stimuli (four items). In addition, the 
32 items of the questionnaire are also averaged to produce one overall quality of life 
score. The response format consists of a seven-point scale where a value of 1 indicates 
‘total impairment’ and 7 indicates ‘no impairment’. 
The AQLQ questionnaire shall be completed at the visits indicated in the SoA (Section 
2). 


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9.1.4.
Spirometry
Spirometry assessments will be performed from screening through the final visit as 
indicated in the SoA (Section 2).  The following parameters will be assessed:

Forced expiratory volume in one second (FEV1)

Forced vital capacity (FVC)
At least three acceptable spirometry manoeuvres (from a maximum of 8 attempts) should 
be achieved for each spirometry assessment, in accordance with ATS/ERS standards 
[Miller, 2005]. At each visit, spirometry assessments must be performed at the same time 
of day (1 hour) as the assessment performed at Baseline (Visit 3).  
Participants should withhold use of short-acting bronchodilators for 6 hours and 
LABAs, ICSs and OCSs for 12 hours prior to each clinic visit, if possible.  Participants 
who take medications that contain once daily bronchodilators and once daily maintenance 
therapy medication should withhold use for 24 hours prior to each clinic visit.
Further details will be provided in the SRM and third party vendor manual.
9.2.
Adverse Events
The definitions of an AE or SAE can be found in Appendix 4.
The investigator and any designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study treatment or the study, 
or that caused the participant to discontinue the study treatment (see Section 8). 
9.2.1.
Time Period and Frequency for Collecting AE and SAE 
Information

All SAEs will be collected from Visit 3 until the follow-up visit at the time 
points specified in the SoA (Section 2).  At Visits 1 and 2 SAE information will 
be collected only for any SAEs considered as related to study participation. 

All AEs will be collected from Visit 3 until the follow-up visit at the time points 
specified in the SoA (Section 2).

Medical occurrences that begin before the start of study treatment but after 
obtaining informed consent will be recorded on the Medical History/Current 
Medical Conditions section of the eCRF not the AE section.

All SAEs will be recorded and reported to the sponsor or designee immediately 
and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 4. The investigator will submit any updated SAE data to the sponsor 
within 24 hours of it being available.

Investigators are not obligated to actively seek AEs or SAEs in former study 
participants. 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 


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considers the event to be reasonably related to the study treatment or study 
participation, the investigator must promptly notify the sponsor.

The method of recording, evaluating, and assessing causality of AEs and SAEs
and the procedures for completing and transmitting SAE reports are provided in 
Appendix 4.
9.2.2.
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. 
9.2.3.
Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs will be followed until the event is 
resolved, stabilized, otherwise explained, or the participant is lost to follow-up (as 
defined in Section 8.3). Further information on follow-up procedures is given in 
Appendix 4.
9.2.4.
Regulatory Reporting Requirements for SAEs

Prompt notification by the investigator to the sponsor of a SAE is essential so 
that legal obligations and ethical responsibilities towards the safety of 
participants and the safety of a study treatment under clinical investigation are 
met. 

The sponsor has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study treatment 
under clinical investigation. The sponsor will comply with country-specific 
regulatory requirements relating to safety reporting to the regulatory authority, 
Institutional Review Boards (IRB)/Independent Ethics Committees (IEC), and 
investigators.

Investigator safety reports must be prepared for suspected unexpected serious 
adverse reactions according to local regulatory requirements and sponsor policy 
and forwarded to investigators as necessary.

An investigator who receives an investigator safety report describing a SAE or 
other specific safety information eg, summary or listing of SAE) from the 
sponsor will review and then file it along with the Investigator’s Brochure and 
will notify the IRB/IEC, if appropriate according to local requirements.
9.2.5.
Cardiovascular and Death Events
For any cardiovascular events detailed in Appendix 4 and all deaths, whether or not they 
are considered SAEs, specific CV and Death sections of the eCRF will be required to be 
completed. These sections include questions regarding cardiovascular (including sudden 
cardiac death) and non-cardiovascular death. 


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The CV eCRFs are presented as queries in response to reporting of certain CV Medical 
Dictionary for Regulatory Activities (MedDRA) terms. The CV information should be 
recorded in the specific cardiovascular section of the eCRF within one week of receipt of 
a CV Event data query prompting its completion. 
The Death eCRF is provided immediately after the occurrence or outcome of death is 
reported. Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported.
9.2.6.
Pregnancy

Details of all pregnancies in female participants will be collected after the start of 
study treatment and until the follow-up visit.

If a pregnancy is reported, the investigator should inform GSK within 2 weeks of 
learning of the pregnancy and should follow the procedures outlined in Appendix 5.

Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAE.
9.3.
Treatment of Overdose
An overdose is defined as a dose greater than the total doses described above which 
results in clinical signs and symptoms. These should be recorded by the Investigator on
the AE/SAE eCRF pages. The dose of GSK3772847 considered to be an overdose has 
not been defined. There are no known antidotes and GSK does not recommend a specific 
treatment in the event of a suspected overdose. The Investigator will use clinical 
judgement in treating the symptoms of a suspected overdose.
In the event of an overdose, the investigator should:
1.
Contact the Medical Monitor immediately.
2.
Closely monitor the participant for AE/SAE and laboratory abnormalities for 16 
weeks after the last dose.
3.
Obtain a serum sample for PK analysis within 7 days from the date of the last dose of 
study treatment if requested by the Medical Monitor (determined on a case-by-case 
basis).
4.
Document the quantity of the excess dose as well as the duration of the overdosing in 
the eCRF.
Decisions regarding dose interruptions or modifications will be made by the investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the 
participant.
9.4.
Safety Assessments
Planned time points for all safety assessments are provided in the SoA (Section 2).


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9.4.1.
Physical Examinations

A complete physical examination will include, at a minimum, assessments of the 
Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. 
Height and weight will also be measured and recorded.

Investigators should pay special attention to clinical signs related to previous 
serious illnesses.
9.4.2.
Vital Signs
Vital signs should be performed at the time points specified in the SoA (Section 2) prior 
to conducting ECG and spirometry. Blood pressure (systolic and diastolic), body 
temperature and pulse rate will be measured in the supine position after approximately 5 
minutes rest. Body temperature will be collected in the participant’s source documents 
only for site use. A single set of values for blood pressure and pulse rate will be collected 
and recorded in the source documentation and eCRF.
9.4.3.
Electrocardiograms
All sites will use standardised ECG equipment provided by a centralised external vendor. 
A single 12-lead ECG and rhythm strip will be recorded after measurement of vital signs 
and before other clinical tests such as blood draws and pulmonary function tests. 
Recordings will be made at the time-points defined in the SoA (Section 2). All ECG 
measurements will be made with the participant in a supine position having rested in this 
position for approximately 5 minutes before each reading. Participants should be 
reminded to avoid caffeine or caffeinated drinks for at least 8 hours before each 12-lead 
ECG assessment. Also, decongestants are disallowed for at least 24 hours and 
antihistamines for at least 48 hours before each 12-lead ECG assessment. 
For participants who meet the QTc, protocol defined stopping criteria, triplicate ECGs 
(over a brief period of time) should be performed (Section 8.1.2). The Investigator, a 
designated sub-Investigator or other appropriately trained site personnel will be 
responsible for performing each 12-lead ECG. The Investigator must provide his/her 
dated signature on the original paper tracing, attesting to the authenticity of the ECG 
machine interpretation. 
All ECGs will be electronically transmitted to an independent cardiologist and evaluated. 
The independent cardiologist, blinded to treatment assignment, will be responsible for 
providing measurements of heart rate, QT intervals and an interpretation of all ECGs 
collected in this study. A hard copy of these results will be sent to the Investigator. The 
Investigator must provide his/her dated signature on the confirmed report, attesting to 
his/her review of the independent cardiologist’s assessment. 
Details of the cardiac monitoring procedures will be provided by the centralised 
cardiology service provider.
9.4.4.
Continuous ambulatory ECG (Holter)
Continuous ECG monitoring (Holter) assessments have been added to the protocol to 
allow for a quantitative assessment of abnormal rhythm events. Holter monitors will be 


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provided by a third party vendor to each site. The device should be connected and 
electrodes attached to the participant as per the vendor’s instructions.
9.4.5.
Clinical Safety Laboratory Assessments

Refer to Appendix 2 for the list of clinical laboratory tests to be performed and
to the SoA (Section 2) for the timing and frequency. 

The investigator must review the laboratory report, document this review, and 
record any clinically relevant changes occurring during the study in the AE 
section of the CRF. The laboratory reports must be filed with the source 
documents. Clinically significant abnormal laboratory findings are those which 
are not associated with the underlying disease, unless judged by the investigator 
to be more severe than expected for the participant's condition.

All laboratory tests with values considered clinically significantly abnormal 
during participation in the study or within 5 days after the last dose of study 
treatment 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 such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified and the sponsor 
notified.

All protocol-required laboratory assessments, as defined in Appendix 2, must be 
conducted in accordance with the laboratory manual and the SoA (Section 2).

If laboratory values from non-protocol specified laboratory assessments 
performed at the institution’s local laboratory require a change in participant 
management or are considered clinically significant by the investigator (eg, SAE 
or AE or dose modification), then the results must be recorded in the eCRF.
9.4.6.
Diary assessments
Participants will be issued with a diary card at visit 2.  Participants should complete their 
daily diary pages during the study duration to record the use of rescue (SABA)
medication, AEs and concomitant medication usage.
9.5.
Pharmacokinetics

Whole blood samples of approximately 3 mL will be collected for measurement 
of serum concentrations of GSK3772847as specified in the SoA (Section 2). The 
timing of PK samples may be altered and/or PK samples may be obtained at 
additional time points to ensure thorough PK monitoring. The actual date and 
time (24-hour clock time) of each sample will be recorded.

Samples will be used to evaluate the PK of GSK3772847. Samples collected for 
analyses of serum concentration may also be used to evaluate safety or efficacy 
aspects related to concerns arising during or after the study.

Instructions for the collection and handling of biological samples will be provided 
in the SRM.


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9.6.
Pharmacodynamics
Blood (serum) samples will be collected during this study for the purposes of measuring
free and total sST2 levels. Samples will be collected at the time points indicated in the
SoA (Section 2). The timing of the collections may be adjusted on the basis of emerging 
PK or PD data from this study or other new information in order to ensure optimal 
evaluation of the biomarker endpoints.
9.7.
Genetics
Information regarding genetic/ pharmacogenetic (PGx) research is included in
Appendix 6. The IEC/IRB and, where required, the applicable regulatory agency must 
approve the PGx and genetic assessments before these can be conducted at the site. The 
approval(s) must be in writing and will clearly specify approval of the PGx and genetic 
assessments (i.e., approval of Appendix 6).
In some cases, approval of the PGx and genetic assessments can occur after approval is 
obtained for the rest of the study. If so, then the written approval will clearly indicate 
approval of the PGx and genetic assessments is being deferred and the study, except for 
PGx and genetic assessments, can be initiated. When PGx and genetic assessments will 
not be approved, then the approval for the rest of the study will clearly indicate this and 
therefore, PGx and genetic assessments will not be conducted.
9.8.
Biomarkers
9.8.1.
Exploratory Biomarkers
Blood (serum) and induced sputum samples will be collected during this study and may 
be used for the purposes of measuring asthma biomarkers or endotypes of asthma, as well 
as response to GSK3772847. Biomarkers will include, but not be limited to, serum total 
IgE, fungal specific IgE (Aspergillus fumigatus, Penicillium chrysogenum (notatum)) as 
well as sputum cell counts (e.g. percentage eosinophils) and sputum levels of IL-33, IL-
13, IL-4, IL-5 and TNF-. Samples may also be used to identify factors that may 
influence the development of asthma and/or medically related conditions. 
Samples will be collected at the time points indicated in the SoA (Section 2). Details of 
the sputum collection and processing methodology will be provided in the SRM.
Participants should not use their rescue medication for at least 6 hours before each 
sputum sampling visit, unless essential for clinical need. Participants should also 
withhold LABAs, ICSs and OCSs for 1 dosing interval (i.e. 12 or 24 hours based on 
the prescribed dosing interval of the product) before these visits.
9.8.2.
Immunogenicity Assessments
Serum samples will be collected pre-dose and tested for the presence of antibodies that 
bind to GSK3772847, as specified in the SoA (Section 2). The actual date and time (24-
hour clock time) of each sample will be recorded.


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The presence of anti-GSK3772847 antibodies will be assessed using a tiered approach 
including a screening assay, a confirmation assay and calculation of titre.
Instructions for the collection and handling of biological samples will be provided in the 
SRM.
9.9.
Medical Resource Utilization and Health Economics
Medical Resource Utilization and Health Economics parameters are not evaluated in this 
study.


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10.
STATISTICAL CONSIDERATIONS
The primary objective of this study is to investigate the effect of treatment with 
GSK3772847 compared with placebo on blood eosinophils and FeNO levels in moderate 
to severe asthmatic participants with AFAD currently on SoC. There are no formal 
hypothesis tests associated with this objective and no formal significance tests. The 
information acquired from this study will be used to quantify the effects that 
GSK3772847 has on the selected efficacy endpoints, as measured by change in the co-
primary endpoints; change from baseline in blood eosinophils and change from baseline 
in FeNO over time.
10.1.
Sample Size Determination
To account for a 10% withdrawal rate, approximately 46 participants will be randomised 
in 1:1 ratio to active arm or placebo arm, to ensure approximately 40 will be evaluable in 
total.
The sample size is based on feasibility and no formal sample size calculation has been 
performed. 
As described below, change from baseline in blood eosinophils and change from baseline 
in FeNO will be log-transformed. 
Estimates of the variability for the ratio to baseline in blood eosinophils and the ratio to 
baseline in FeNO were obtained from [Anderson, 2012] and from studies in 
Mepolizumab in participants with severe asthma.
The half widths of the 95% confidence interval of the point estimate of the treatment ratio 
of active to placebo for the ratio to baseline in blood eosinophils and FeNO have been 
calculated and are displayed in Table 4 and Table 5.


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Table 4
Expected Half Width of 95% Confidence Interval for the ratio of 
active to placebo of ratio to baseline in blood eosinophils with an 
estimated between participant standard deviation (log-scale) of 0.9.
Sample size (per arm)
Expected Half Width of 95% 
Confidence Interval for the 
ratio of active to placebo
15
96%
20
78%
25
67%
30
59%
Assuming a standard deviation of 0.9 (log-scale), and a sample size of 20 participants per 
treatment arm, it is estimated that the lower and upper bounds of the 95% confidence 
interval for the ratio of active to placebo of ratio to baseline in blood eosinophils will be 
within approximately 78% of the ratio i.e. if the observed ratio was 1.5 then the 
confidence interval would be approximately 0.84 to 2.67.
Table 5
Expected Half Width of 95% Confidence Interval for the ratio of 
active to placebo of ratio to baseline in fractional exhaled nitric 
oxide with an estimated between participant standard deviation (log-
scale) of 0.43.
Sample size (per arm)
Expected Half Width of 95% 
Confidence Interval for the 
ratio of active to placebo
15
38%
20
32%
25
28%
30
25%
For ratio to baseline in FeNO over time, assuming a standard deviation (log-scale) of 
0.43, and a sample size of 20 participants per treatment arm it is estimated that the lower 
and upper bounds of the 95% confidence interval for the ratio of active to placebo will be 
within approximately 32% of the ratio. i.e. if the observed ratio was 1.5 the confidence 
interval would be approximately 1.14 to 1.98
A sample size of 20 participants per treatment arm will give us an adequate level of 
precision of the treatment effect differences.


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To evaluate study success criteria, data from a bivariate normal distribution will be 
simulated under different treatment effect assumptions for different sample sizes. The 
samples from the posterior probability distribution from the MCMC approximation will 
be divided into different regions exploring different treatment cut-off values. Further, the 
multivariate case will also be explored involving AQLQ or ACQ-5. The prior for the 
treatment difference for FeNO and eosinophils was elicited at a prior elicitation exercise 
with internal experts at GSK. This prior for the treatment difference includes the experts’ 
uncertainty about the size of the mean treatment effect.
10.2.
Populations for Analyses
For purposes of analysis, the following populations are defined:
Population
Description
Enrolled 
All participants who sign the ICF
Randomised
All participants who were randomised. A participant who is recorded 
as a screen or run-in failure and also randomised will be considered 
to be randomised in error provided they have not performed any 
study assessments.
Modified Intent-to-treat
All randomised participants who take at least 1 dose of study 
treatment.
Participants will be analysed according to the treatment they actually 
received
Safety
This population will be the same as the Modified Intent-to-treat 
population.
PK
All randomised participants who received at least one dose of study
medication, and for whom at least one pharmacokinetic sample was 
obtained, analysed and was measurable.


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10.3.
Statistical Analyses
10.3.1.
Efficacy Analyses
All efficacy analyses will be performed on the Intent-to-Treat population.
Endpoint
Statistical Analysis Methods
Primary
The co-primary endpoints are blood eosinophils and FeNO. Blood eosinophils and 
FeNO will be log-transformed prior to analysis. Change from baseline in log 
transformed blood eosinophils will be analysed using a mixed model repeated 
measures analysis (MMRM), where baseline is defined as Week 0. The model will 
include fixed effects of treatment group, which strata the participant was in (i.e. 
whether the participant was taking antifungals or not),  log-transformed baseline 
blood eosinophils, time as a categorical variable and a treatment by time interaction. 
Participant will be fitted as a random effect, and time as a repeated effect. A similar 
analysis will be done for change from baseline in log-transformed FeNO, except log-
transformed baseline FeNO will be used (rather than log-transformed baseline 
blood eosinophils). 
The estimated treatment ratios together with 95% CIs (back-transformed from the 
differences on the log-scale) will be presented at the end of weeks 2, 4, 8, and 12 
for each of FeNO and blood eosinophils.
To calculate the probability of success, accounting for the correlation between 
endpoints, the joint posterior probability that the true ratios for both endpoints 
simultaneously lie to the left hand side of unity will be estimated. This will be 
obtained at week 12.
Secondary
Change from baseline in ACQ-5 absolute score and AQLQ at Weeks 2, 4, 8 and 12 
will be separately analysed using a MMRM for each endpoint, where baseline is 
defined as Week 0. The model for ACQ-5 will include fixed effects of treatment 
group, which strata the participant was in (i.e. whether the participant was taking 
antifungals or not),baseline ACQ-5, time as a categorical variable and a treatment 
by time interaction. Participant will be fitted as a random effect and time as a 
repeated effect. A similar analysis will be done for Change from baseline in AQLQ 
total and domain scores at Weeks 4, 8 and 12, except baseline AQLQ (total or 
domain score) will be used instead of ACQ-5. The estimated treatment differences 
together with the 95% CIs will be presented at the end of weeks 4, 8 and 12 for 
each of ACQ-5 and AQLQ. 
Change from baseline in pre-bronchodilator FEV1 will be listed and summarised.
Analyses of responders to ACQ-5 and AQLQ will be described in the Reporting 
Analysis Plan (RAP).
Further analysis on the secondary endpoints will be described in the RAP.
Exploratory
Will be described in the reporting and analysis plan


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10.3.2.
Safety Analyses
All safety analyses will be performed on the Safety Population. 
Endpoint
Statistical Analysis Methods
Primary
There is no primary safety analysis.
Secondary
The following secondary safety endpoints will be analysed descriptively by 
treatment group:

Treatment emergent AE

Clinical Laboratory safety data 

Vital signs (blood pressure, heart rate)

12–Lead ECG monitoring

24-hour Holter monitoring

Incidence and titres of serum anti-GSK3772847 antibodies post dosing
Details will be described in the reporting and analysis plan
Exploratory
Will be described in the reporting and analysis plan 
Adverse events (AEs) will be coded using the standard GSK dictionary, MedDRA, and 
grouped by body system. The number and percentage of participants experiencing at least 
one AE of any type, AEs within each body system and AEs within each preferred term 
will be presented for each treatment group. Separate summaries will be provided for all 
AEs, drug related AEs, fatal AEs, non-fatal SAEs, adverse events of special interest and 
AEs leading to withdrawal. Deaths and SAEs, if applicable, will be documented in case 
narrative format.
10.3.3.
Pharmacokinetic Analyses
All pharmacokinetic analyses will be performed on the Pharmacokinetic Population. 
Endpoint
Statistical Analysis Methods
Primary
There is no primary pharmacokinetic analysis.
Secondary
The serum GSK3772847 levels from this study will be summarised by treatment 
and nominal time.
Further details will be described in the report and analysis plan.
10.3.4.
Pharmacodynamic Analyses
All pharmacodynamic analyses will be described in reporting and analysis plan.
10.3.5.
Other Analyses
PK, PD and biomarker exploratory analyses will be described in the reporting and 
analysis plan. Any population PK/PKPD analyses will be presented separately from the 
main clinical study report (CSR). 


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10.3.6.
Interim Analyses
An interim analysis may be conducted for internal decision making. Access to the 
unblinded interim data and the interim results will be restricted. No changes to the study 
design will be made based on the interim analysis results. Full details of the interim 
analyses including details of who will have access to the interim data and interim results 
will be provided in an interim analysis plan.
Instream review:
An iSRC (see Appendix 3) will periodically review unblinded safety data to protect and 
maintain participant safety whilst maintaining scientific validity. Members of the iSRC 
will be independent of the project. The data will include, but not necessarily be limited to 
SAEs, Holters and ECGs. Details are described in the Charter.


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11.
REFERENCES
Aburuz S, Gamble J, Heaney CG. Assessment of impairment in heatlh-related quality of 
life in patients with difficult asthma: Psychometric performance of the Asthma Quality of 
Life Questionnaire. Respirology 2007; 12:227-233.
American Thoracic Society; European Respiratory Society. ATS/ERS recommendations 
for standardized procedures for the online and offline measurement of exhaled lower 
respiratory nitric oxide and nasal nitric oxide. Am J Respir Crit Care Med 2005; 171: 
912-930.
Anderson WJ, Short PM, Williamson PA, Lipworth BJ. Inhaled Corticosteroid Dose 
Response Using Domiciliary Exhaled Nitric Oxide The FeNo Type Trial. Chest 2012; 
142: 1553–1561.
Arshad M I, Khan HA, Noel G , Piquet-Pellorce C, Samson M. Potential therapeutic 
effects of alarmin cytokine interleukin 33 or its inhibitors in various diseases. Clin 
Therapeutics 2016; 38:100-116.
Castanhinha S, Sherburn R, Walker S, Gupta A, Bossley CJ, Buckley J, et al. Pediatric 
severe asthma with fungal sensitization is mediated by steroid-resistant IL-33. J Allergy 
Clin Immunol 2015; 136: 312-322.
Chung, KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, et al. International 
ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir 
J 2014; 43:343-373.
Denning DW, O'Driscoll BR, Hogaboam CM, Bowyer P, Niven R. The link between 
fungi and severe asthma: a summary of the evidence. Eur Respir J 2006; 27:615-626.
Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, et al. An 
official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels 
(FENO) for clinical applications. Am J Respir Crit Care Med 2011; 184:602-615.
GlaxoSmithKline Document Number: 2017N316832_00;Investigator’s Brochure for 
GSK3772847 07 June 2017
GlaxoSmithKline Document Number: 2017N344518_00, Clinical Study Report for 
GSK3772847, ; 20 Sep 2017
Global Initiative for Asthma, GINA. 2017. GLOBAL STRATEGY FOR ASTHMA 
MANAGEMENT AND PREVENTION. Available from: www.ginasthma.org.
Juniper EF, Guyatt GH, Williams A, Griffith LE. Measuring quality of life in asthma. Am 
Rev Respir Dis 1993; 147:832-838.
Juniper EF, Svensson K, Mork AC, Stahl E. Measurement properties and interpretation of 
three shortened versions of the asthma control questionaire. Respir Med 2005; 99:553-
558.


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Juniper EF, Svensson K, Mork AC, Stahl E. Modification of the Asthma Quality of Life 
Questionnaire (standardised) in patients 12 years and older. Health and Quality of Life 
Outcomes 2005; 3:58.
Menzies D, Holmes L, McCumesky G, Prys-Picard C, Niven R. Aspergillus sensitization 
is associated with airflow limitation and bronchiectasis in severe asthma. Allergy 2011; 
66:679-685.
Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al.. 
Standardisation of spirometry. Eur Respir J 2005; 26:319-398.
Moore WC, Bleecker ER, Curran-Everett D, Erzurum SC, Ameredes BT, Bacharier L, et 
al. Characterization of the severe asthma phenotype by the National Heart, Lung, and
Blood Institute's Severe Asthma Research Program. J Allergy Clin Immunol 2007; 
119:405-413.
Moss RB. Treatment options in severe fungal asthma and allergic bronchopulmonary 
aspergillosis. European Respiratory Journal 2014; 1487–1500.
O'Driscoll BR, Hopkinson LC, Denning DW. Mold sensitisation is common amongst 
patients with severe asthma requiring multiple hospital admissions. BioMed Central 
Pulmonary Medicine 2005; 5:4.
Oshikawa K, Kuroiwa K, Tago K, Iwahana H, Yanagisawa K, Ohno S, et al. Elevated 
soluble ST2 protein levels in sera of patients with asthma with an acute exacerbation. Am 
J Respir Crit Care Med 2001; 164:277-281.
Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, et al. Multi-Ethnic 
Reference Values For Spirometry For The 3–95 Year Age Range: The Global Lung 
Function 2012 Equations. Eur Respir J. 2012; 40:1324–1343.
Rick EM, Woolnough K, Pashley CH, Wardlaw AJ. Allergic Fungal Airway Disease. J 
Investig Allergol Clin Immunol 2016; 26:344-354.
Smithgall MD, Comeau MR, Yoon BR, Kaufman D, Armitage R, Smith DE. IL-33 
amplifies both Th1- and Th2-type responses through its activity on human basophils, 
allergen-reactive Th2 cells, iNKT and NK cells. International Immunology 2008; 
20:1019-1030.
Tracy M, Okorie C, Foley E, Moss R. Allergic Bronchopulmonary Aspergillosis. Journal 
of Fungi 2016; 17.
Woolnough KF, Richardson M, Newby C, Craner M, Bourne M, Monteiro W, et al. The 
relationship between biomarkers of fungal allergy and lung damage in asthma. Clinical & 
Experimental Allergy 2016; 47:48-56.
Yagami A, Orihara K, Morita H, Futamura K, Hashimoto N, Matsumoto K, et al. IL-33 
mediates inflammatory responses in human lung tissue cells. J Immunol 2010; 185:5743-
5750.


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12.
APPENDICES
12.1.
Appendix 1: Abbreviations and Trademarks
Abbreviations
ABPA
Allergic bronchopulmonary aspergillosis
ACQ
Asthma Control Questionnaire
AE
Adverse Event
AFAD
Allergic fungal airway disease
ALT
Alanine Transaminase
AQLQ
Asthma Quality of Life Questionnaire
AST
Aspartate Transaminase
ATS
American Thoracic Society
AUC
Area under the curve
AV
Atrioventricular
BAL
Bronchoalveolar lavage
bpm
Beats per minute
CAD
Coronary artery disease
CPK
Creatine phosphokinase
CRS
Cytokine release syndrome
CSR
Clinical study report
CV
Cardiovascular
ECG
Electrocardiogram
(e)CRF
(Electronic) Case Report Form
ERS
European Respiratory Society
EU
European Union
EW
Early Withdrawal
FeNO
Fractional exhaled Nitric Oxide
FEV1
Forced expiratory volume in 1 second
FVC
Forced vital capacity
GCP
Good clinical practice
GINA
Global Initiative for Asthma
GLP
Good laboratory practice
GSK
GlaxoSmithKline
HBsAg
Hepatitis B surface antigen
HIV
Human immunodeficiency virus
HR
Heart rate
HRCT
High-resolution computed tomography
HRT
Hormone replacement therapy
IB
Investigator’s Brochure
ICF
Informed consent form
ICH
International Conference on Harmonization


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ICS
Inhaled corticosteroids
IEC
Independent Ethics Committee
IgE
Immunoglobulin E
IgG2
human immunoglobulin G2 sigma isotype
IL-1RL1
Interleukin-1 receptor like-1
IL-33R
Interleukin-33 receptor
INR
International normalized ratio
IP
Investigational Product
IRB
Institutional Review Board
iSRC
Internal safety review committee
IV
Intravenous
IWRS
Interactive web response system
LABA
Long-acting beta-2-agonist
LTRA
Leukotriene receptor antagonist
MedDRA
Medical Dictionary for Regulatory Activities
MM
Michaelis Menten
MMRM
Mixed model repeated measures analysis
MMRM
Mixed model repeated measures analysis
NT-proBNP
N-terminal prohormone of brain natriuretic peptide
NYHA
New York Heart Association
PD
Pharmacodynamic
PGx
Pharmacogenetic
PK
Pharmacokinetic
PSVT
Paroxysmal supraventricular tachycardia
QoL
Quality of Life
QTc
QT interval corrected for heart rate
QTcB
QT interval corrected for heart rate by Bazett’s formula
QTcF
QT interval corrected for heart rate by Fridericia’s formula
RAP
Reporting Analysis Plan
SABA
Short acting -2 agonist
SAE
Serious adverse event
SC
Subcutaneous
SoA
Schedule of activities
SoC
Standard of care
SRM
Study Reference Manual
(s) ST2
(soluble) Suppressor of tumorigenicity 2
T2
Type 2
ULN
Upper limit of normal
VT
Ventricular tachycardia
WOCBP
woman of childbearing potential


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Trademark Information
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
NONE
None


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12.2.
Appendix 2: Clinical Laboratory Tests

The tests detailed in Table 6 will be performed by the central laboratory. 

All protocol required laboratory assessments (haematology, clinical chemistry 
and urinalysis) must be conducted in accordance with the Laboratory Manual 
and the SoA (Section 2). Laboratory requisition forms must be completed and 
samples must be clearly labelled with the participant number, protocol number, 
site/centre number, and visit date. Details for the preparation and shipment of 
samples will be provided by the laboratory and are detailed in the Laboratory 
Manual. Reference for all safety parameters will be provided to the site by the 
laboratory responsible for the assessments.

All blood samples which will be taken pre-dose, will be sent to a central
laboratory for analysis (details provided in the Laboratory Manual). Standard
reference ranges will be used.

If additional non-protocol specified laboratory assessments are performed at the
institution’s local laboratory and result in a change in participant management or
are considered clinically significant by the Investigator (e.g., SAE or AE or dose
modification), the results must be recorded in the eCRF.

Refer to the Laboratory Manual for appropriate processing and handling of
samples to avoid duplicate and/or additional blood draws.

Protocol-specific requirements for inclusion or exclusion of participants are
detailed in Section 6 of the protocol.

Additional tests may be performed at any time during the study as determined
necessary by the investigator or required by local regulations.


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Table 6
Protocol-Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters
Haematology
Platelet Count
RBC Indices:
MCV
MCH
MCHC
WBC count with 
Differential:
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
These will be blinded 
from V3 onwards.
RBC Count
Haemoglobin
Haematocrit
White Cell Count
RDW
Clinical 
Chemistry1
BUN
Potassium
Aspartate 
Aminotransferase
(AST)/ Serum 
Glutamic-
Oxaloacetic 
Transaminase
Total and direct 
bilirubin
Creatinine
Sodium
ALT/ Serum 
Glutamic-Pyruvic 
Transaminase 
(SGPT)
Total Protein
Glucose 
nonfasting
Calcium
Alkaline 
phosphatase
Creatine 
phosphokinase 
(CPK)
Albumin
Phosphorus
GGT
Chloride
Carbon Dioxide
Serum IgE

Total IgE

Specific IgE to Aspergillus fumigatus and Penicillium chrysogenum
(notatum)
These will be blinded from V3 onwards.
Cardiac 
Markers

Cardiac troponin I (cTN I)

NT-proBNP
Routine 
Urinalysis

Specific gravity

pH, glucose, protein, blood, ketones, bilirubin, leukocyte, nitrite, 
urobilinogen by dipstick

Microscopic examination (if blood or protein is abnormal)
Other 
Screening 
Tests

Follicle-stimulating hormone and estradiol (as needed in women of non-
childbearing potential only)


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Laboratory 
Assessments
Parameters

Serum or urine human chorionic gonadotropin (hCG) pregnancy test (as 
needed for women of childbearing potential)2

Serology [(HIV antibody, HBsAg, and hepatitis C virus antibody)
All study-required laboratory assessments will be performed by a central 
laboratory.
NOTES :
1.
Details of liver chemistry stopping criteria and required actions and follow-up assessments 
after liver stopping or monitoring event are given in Section 8.1 and Appendix 7 All events of 
ALT 3 × upper limit of normal (ULN) and 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 as an SAE (excluding 
studies of hepatic impairment or cirrhosis).
2.
Local urine testing will be standard for the protocol unless serum testing is required by local 
regulation or IRB/IEC.
Abbreviations: RBC= Red Blood Cell Count, WBC= White Blood Cell Count, MCV= Mean 
corpuscular volume, MCH= mean corpuscular haemoglobin, MCHC= mean corpuscular 
haemoglobin concentration, RDW= Red cell distribution width, AST= Aspartate 
Aminotransferase, ALT= Alanine Aminotransferase, SGPT= Serum Glutamic- Oxaloacetic 
Transaminase, CPK= creatine phosphokinase, GGT= Gamma-glutamyltransferase, hCG= 
human chorionic gonadotropin, HIV= Human Immunodeficiency Virus
Blood eosinophils, total IgE and specific IgE from V3 only that could unblind the study 
will not be reported to investigative sites or other blinded personnel until the study has 
been unblinded.


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12.3.
Appendix 3: Study Governance Considerations
Regulatory and Ethical Considerations

This study will be conducted in accordance with the protocol and with:

Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences International Ethical Guidelines

Applicable International Conference on Harmonization (ICH) Good 
Clinical Practice (GCP) Guidelines

Applicable laws and regulations

The protocol, protocol amendments, ICF, Investigator Brochure, and other 
relevant documents (eg, advertisements) must be submitted to an IRB/IEC by 
the investigator and reviewed and approved by the IRB/IEC before the study is 
initiated. 

Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants. 

The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/EC

Notifying the IRB/IEC of SAE or other significant safety findings as 
required by IRB/IEC procedures

Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European 
regulation 536/2014 for clinical studies (if applicable), and all other 
applicable local regulations
Financial Disclosure
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study.
Informed Consent Process

The investigator or his/her representative will explain the nature of the study to 
the participant or his/her 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 


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informed consent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, Health Insurance Portability and Accountability Act 
requirements, where applicable, and the IRB/IEC or study centre. 

The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorised person obtaining the informed consent 
must also sign the ICF.

Participants must be re-consented to the most current version of the ICF(s) 
during their participation in the study. 

A copy of the ICF(s) must be provided to the participant or the participant’s 
legally authorised representative. 

Participants who are rescreened are required to sign a new ICF.
Data Protection

Participants will be assigned a unique identifier by the sponsor. Any participant 
records or datasets that are transferred to the sponsor will contain the identifier 
only; participant names or any information which would make the participant 
identifiable will not be transferred. 

The participant must be informed that his/her personal study-related data will be 
used by the sponsor in accordance with local data protection law. The level of 
disclosure must also be explained to the participant. 

The participant must be informed that his/her medical records may be examined 
by Clinical Quality Assurance auditors or other authorised personnel appointed 
by the sponsor, by appropriate IRB/IEC members, and by inspectors from
regulatory authorities.
Committees Structure
The Internal Safety Review Committee (iSRC) consists of a panel of four members: two 
senior GSK members and two medical consultants.  The members are all independent 
from this study and their remit is to periodically review specific aspects of the clinical 
trial in order to protect and enhance patient safety while maintaining the scientific 
validity of the data. 
The iSRC will meet at predefined times as defined in the iSRC charter to evaluate cardiac 
safety data for participants who receive GSK3774827.
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.

The sponsor will comply with the requirements for publication of study results. 
In accordance with standard editorial and ethical practice, the sponsor will 


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generally support publication of multicentre studies only in their entirety and not 
as individual site data. In this case, a coordinating investigator will be 
designated by mutual agreement.

Authorship will be determined by mutual agreement and in line with 
International Committee of Medical Journal Editors authorship requirements.
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 the investigator with the full summary of the study 
results.  The investigator is encouraged to share the summary results with the 
study subjects, as appropriate.

GSK will provide the investigator with the randomisation codes for their site 
only after completion of the full statistical analysis.
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 (eg, laboratory 
data). The investigator is responsible for verifying that data entries are accurate 
and correct by physically or electronically signing the eCRF. 

The investigator must maintain accurate documentation (source data) that 
supports the information entered in the eCRF. 

The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents. 

The sponsor or designee is responsible for the data management of this study 
including quality checking of the data. 

Study monitors will perform ongoing source data verification to confirm that 
data entered into the eCRF by authorized site personnel are accurate, complete, 
and verifiable from source documents; that the safety and rights of participants 
are being protected; and that the study is being conducted in accordance with the 
currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements. 

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 
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 the sponsor. No records may be 
transferred to another location or party without written notification to the 
sponsor. 


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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 can be found in the source document 
agreement (to be signed by the investigator (or delegate) at each site) .
Study and Site Closure
GSK or its 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:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines

Inadequate recruitment of participants by the investigator

Discontinuation of further study treatment development


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12.4.
Appendix 4: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting
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 treatment, whether or not considered related to the 
study treatment.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a study treatment.
Events Meeting the AE Definition 

Any abnormal laboratory test results (haematology, clinical chemistry, or urinalysis) 
or other safety assessments (eg, ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator (ie, 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 treatment administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae.

"Lack of efficacy" or "failure of expected pharmacological action" per se will not be 
reported as an AE or SAE. Such instances will be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting from 
lack of efficacy will be reported as AE or SAE if they fulfil the definition of an AE 
or SAE. 
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 


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the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.

Medical or surgical procedure (eg, 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.
Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalisation for signs/symptoms of the disease under study, 
death due to progression of disease).
A SAE is defined as any untoward medical occurrence that, at any dose:
a.
Results in death
b.
Is life-threatening
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe.
c.
Requires inpatient hospitalisation or prolongation of existing hospitalisation
In general, hospitalisation signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalisation are AE. If a 
complication prolongs hospitalisation or fulfils any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalisation” occurred or was necessary, the AE 
should be considered serious.
Hospitalisation for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE.
d.
Results in persistent 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


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f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that may 
not be immediately life-threatening or result in death or hospitalisation but 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.
Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalisation, or development of drug dependency 
or drug abuse.
Definition of Cardiovascular Events
Cardiovascular Events (CV) Definition:
Investigators will be required to fill out the specific CV event page of the eCRF 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
Recording AE and SAE
AE and SAE Recording

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory, and diagnostics reports) 
related to the event.

The investigator will then record all relevant AE/SAE information in the eCRF.

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 /AE/SAE eCRF page.

There may be instances when copies of medical records for certain cases are 


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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 treatment 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 disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study treatment 
administration will be considered and investigated.

The investigator will also consult the IB and/or Product Information, for marketed 
products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK. However, it is very 
important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to GSK.


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
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 completed eCRF.

The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information.
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 for more than 24 hours, then the site will use 
the paper SAE data collection tool (see next section).

The site will enter the SAE data into the electronic system as soon as it becomes 
available.

The investigator or medically-qualified sub-investigator must show evidence within 
the eCRF (e.g., check review box, signature, etc.) of review and verification of the 
relationship of each SAE to IP/study participation (causality) within 72 hours of SAE 
entry into the eCRF.

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 SAE coordinator by telephone.

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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SAE Reporting to GSK via Paper CRF

Facsimile transmission of the SAE paper CRF is the preferred method to transmit 
this information to 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 CRF pages 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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12.5.
Appendix 5: Contraceptive Guidance and Collection of 
Pregnancy Information
Definitions
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below)
Women in the following categories are not considered WOCBP
1. Premenarchal
2. Premenopausal female with ONE of the following:

Documented hysterectomy

Documented bilateral salpingectomy

Documented bilateral oophorectomy
Note:  Documentation can come from the site personnel’s: review of participant’s 
medical records, medical examination, or medical history interview.
3. Postmenopausal female

A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. A high follicle stimulating hormone (FSH) level in 
the postmenopausal range may be used to confirm a postmenopausal state in 
women not using hormonal contraception or HRT. However, in the absence of 
12 months of amenorrhea, a single FSH measurement is insufficient. 

Females on HRT and whose menopausal status is in doubt will be required to 
use one of the non-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.
Contraception Guidance
Female participants
Female participants of childbearing potential are eligible to participate if they agree to 
use a highly effective method of contraception consistently and correctly as described in 
Table 7. 


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Table 7
Highly Effective Contraceptive Methods
Highly Effective Contraceptive Methods That Are User Dependent a
Failure rate of <1% per year when used consistently and correctly. 
Combined (estrogen- and progestogen-containing ) hormonal contraception associated with 
inhibition of ovulationb

oral

intravaginal 

transdermal 
Progestogen-only hormonal contraception associated with inhibition of ovulationb

injectable 
Highly Effective Methods That Are User Independent 

Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulationb

Intrauterine device

Intrauterine hormone-releasing system

bilateral tubal occlusion
Vasectomized partner 
(A vasectomized partner is a highly effective contraception method provided that the partner is 
the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If 
not, an additional highly effective method of contraception should be used.)
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 drug. 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.)
NOTES: 
a.
Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for participants in clinical studies. 
b.
Hormonal contraception may be susceptible to interaction with the study drug, which may reduce the efficacy of 
the contraceptive method. In this case two highly effective methods of contraception should be utilized during the 
treatment period and for the follow-up period until the last visit at Week 24 (or 16 weeks after the last dose, which 
is equivalent to 5.5 half-lives). 
Pregnancy Testing

WOCBP should only be included after a confirmed menstrual period and a negative 
highly sensitive serum pregnancy test 

Additional pregnancy testing during the treatment period as specified in the SoA
(Section 2). 


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
Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected 

Pregnancy testing will be performed and assayed in a certified laboratory OR and 
assayed in the central laboratory OR using the test kit provided by the central 
laboratory / provided by the sponsor /approved by the sponsor and in accordance 
with instructions provided in its package insert
Collection of Pregnancy Information
Female Participants who become pregnant

Investigator will collect pregnancy information on any female participant, who 
becomes pregnant while participating in this study. 

Information will be recorded on the appropriate form and submitted to GSK within 
24 hours of learning of a participant's pregnancy. 

Participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow up information on participant and neonate, which will 
be forwarded to GSK Generally, follow-up will not be required for longer than 6 to 8 
weeks beyond the estimated delivery date.  

Any termination of pregnancy will be reported, regardless of foetal status (presence 
or absence of anomalies) or indication for procedure. 

While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy will be reported as an AE or 
SAE. 

A spontaneous abortion is always considered to be an SAE and will be reported as 
such.  

Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study treatment by the investigator, will be reported to GSK
as described in Appendix 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 will discontinue study 
treatment.


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12.6.
Appendix 6: Genetics
USE/ANALYSIS OF DNA

Genetic variation may impact a participant’s response to therapy, susceptibility, 
severity and progression of disease. Variable response to therapy may be due to 
genetic determinants that impact drug absorption, distribution, metabolism, and 
excretion; mechanism of action of the drug; disease etiology; and/or molecular 
subtype of the disease being treated. Therefore, where local regulations and IRB/IEC 
allow, a blood sample will be collected for DNA analysis

DNA samples will be used for research related to GSK3772847 or asthma and 
related diseases. They may also be used to develop tests/assays including diagnostic 
tests) related to GSK3772847 or other treatments which may regulate eosinophils, 
impact the epithelium or other study treatments including, but not limited to, 
steroids, long-acting beta-agonists, and other drugs used in the treatment of asthma, 
or for asthma and related diseases. Genetic research may consist of the analysis of 
one or more candidate genes or the analysis of genetic markers throughout the 
genome or analysis of the entire genome (as appropriate)

DNA samples may be analysed for genetic effects on response. This may include, 
but not be limited to, an investigation as to whether polymorphisms from IL33 and 
IL1RL1 gene regions associate with IL33 or soluble ST2 expression levels or 
associate with efficacy or safety responses. Additional analyses may be conducted if 
it is hypothesized that this may help further understand the clinical data.

The samples may be analysed as part of a multi-study assessment of genetic factors 
involved in the response to GSK3772847 or study treatments of this class. The 
results of genetic analyses may be reported in the clinical study report or in a 
separate study summary.

The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality. 

The samples will be retained while research on GSK3772847 (or study treatments of 
this class) or asthma continues but no longer than 15 years after the last subject last 
visit or other period as per local requirements.


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12.7.
Appendix 7: Liver Safety: Required Actions and Follow-up 
Assessments
Phase II liver chemistry stopping and increased monitoring criteria have been 
designed to assure participant safety and evaluate liver event aetiology
Phase II liver chemistry stopping criteria and required follow up assessments 
Liver Chemistry Stopping Criteria 
ALT-absolute
ALT 5xULN
ALT Increase
ALT 3xULN persists for 4 weeks
Bilirubin1, 2
ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin)
INR2
ALT 3xULN and INR>1.5, if INR measured
Cannot Monitor
ALT 3xULN 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 and Follow up Assessments 
Actions
Follow Up Assessments

Immediately discontinue study treatment 

Report the event to GSK within 24 hours

Complete the liver event CRF and complete an 
SAE data collection tool if the event also meets 
the criteria for an SAE2

Perform liver chemistry event follow up 
assessments 

Monitor the participant until liver chemistries
resolve, stabilise, or return to within baseline 
(see MONITORING below)

Do not restart/rechallenge participant with 
study treatment unless allowed per protocol and 
GSK Medical Governance approval is granted 
(see below)
If restart/rechallenge not allowed per protocol or 
not granted, permanently discontinue study 
treatment and continue participant in the study for 
any protocol specified follow up assessments 

Viral hepatitis serology4

Obtain INR and recheck with each liver 
chemistry assessment until the 
transaminases values show downward 
trend

Obtain blood sample for PK analysis 
winthin 1 week after the liver event5

Serum CPK and lactate 
dehydrogenase.

Fractionate bilirubin, if total 
bilirubin2xULN

Obtain complete blood count with 
differential to assess eosinophilia

Record the appearance or worsening of 
clinical symptoms of liver injury, or 
hypersensitivity, on the AE report form

Record use of concomitant medications 
on the concomitant medications report 


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MONITORING:
For bilirubin or INR criteria:

Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
liver event follow up assessments within 24 hrs

Monitor participants twice weekly until liver 
chemistries resolve, stabilise or return to within 
baseline 

A specialist or hepatology consultation is 
recommended
For All other criteria: 

Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
liver event follow up assessments within 24-72 
hrs 

Monitor participants weekly until liver 
chemistries resolve, stabilise or return to within 
baseline
form including acetaminophen, herbal 
remedies, other over the counter 
medications.

Record alcohol use on the liver event 
alcohol intake case report form (CRF) 
page 
For bilirubin or INR criteria:

Anti-nuclear antibody, anti-smooth 
muscle antibody, Type 1 anti-liver 
kidney microsomal antibodies, and 
quantitative total Immunoglobulin G 
or gamma globulins.

Serum acetaminophen adduct high 
performance liquid chromatography 
(HPLC) assay (quantifies potential 
acetaminophen contribution to liver 
injury in participants with definite or 
likely acetaminophen use in the 
preceding week [James, 2009]). 

Liver imaging (ultrasound, magnetic 
resonance, or computerised 
tomography) and /or liver biopsy to 
evaluate liver disease; complete Liver 
Imaging and/or Liver Biopsy CRF 
pages.
1.
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study treatment for that subject if ALT 3xULN and 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, if INR 
measured which may indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE (excluding 
studies of hepatic impairment or cirrhosis); INR measurement is not required and the 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 IgM antibody; Hepatitis B surface antigen (HbsAg) and Hepatitis B Core Antibody (IgM); 
Hepatitis C RNA; Cytomegalovirus IgM antibody;  Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, 
obtain heterophile antibody or monospot testing);  Hepatitis E IgM antibody 
5.
PK sample may not be required for participants known to be receiving placebo or non-GSK comparator 
treatments.)  Record the date/time of the PK blood sample draw and the date/time of the last dose of study 
treatment prior to 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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Phase II liver chemistry increased monitoring criteria with continued therapy
Liver Chemistry Increased Monitoring Criteria – Liver Monitoring Event
Criteria
Actions
ALT 3xULN and <5xULN and bilirubin 
<2xULN, 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 treatment   

Participant must return weekly for repeat liver 
chemistries (ALT, AST, alkaline phosphatase, 
bilirubin) 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, after 4 weeks of monitoring, ALT <3xULN and 
bilirubin <2xULN, monitor participants twice monthly 
until liver chemistries normalize or return to within 
baseline.
References
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davern TJ, Lee 
WM. Pharmacokinetics of Acetaminophen-Adduct in Adults with Acetaminophen 
Overdose and Acute Liver Failure. Drug Metab Dispos 2009; 37:1779-1784.


2017N331706_03
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94
12.8.
Appendix 8 : 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 05-FEB-2018
Overall Rationale for the Amendment: To address clarifications regarding the 
eligibility criteria, the study population, the schedule of activities and the clinical 
assessments. Also, a few typographical errors were corrected.


2017N331706_03
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95
Section # and Name
Description of Change
Brief Rationale
Section 6.2 Table 2; 
Section 7.7.2
Clarified that oral 
corticosteroids are not 
permitted as standard of care. 
Participants with severe 
asthma for whom it is felt oral 
corticosteroids are warranted 
are not eligible for this study.
Section 6.2 Table 2;
Section 7.7.1
Updated Section 7.7.1 to 
support the use of anti-fungal 
medication. Removed anti-
fungal medication from the list 
of prohibited medications in 
Table 2.  
The study is being stratified 
on the use of anti-fungal 
medication and therefore 
treatment with anti-fungal 
medication is permitted during 
the treatment period if used in 
a consistent dosage and 
frequency from screening and 
throughout the treatment 
period.
Section 3.1 Study Rationale
Clarified that the study 
population may include 
participants who have asthma 
with allergic 
bronchopulmonary 
aspergillosis (ABPA). 
The target population for this 
study is moderate to severe 
asthmatics who have allergic 
fungal airway disease (AFAD). 
AFAD is determined by 
positive IgE sensitisation to 
thermotolerant filamentous 
fungi particularly Aspergillus 
fumigatus. Therefore, this 
definition would include 
participants who have asthma 
and ABPA as ABPA is loosely 
defined by the following 
features: eosinophilia, fleeting 
lung shadows, high total IgE, 
and raised A fumigatus–
specific IgE. 
Section 1 Synopsis;
Section 4 Objectives and 
Endpoints;
Section 9.4.2 Vital Signs;
Section 10.3.2 Safety 
Analyses
Removed the body 
temperature in the objectives 
and safety analyses and 
updated Section 9 to reflect 
that body temperature will be 
collected but only available in 
source documents. 
Body temperature will be 
monitored at the site only and 
not included in any analyses.  
Section 2 Schedule of 
Activities
Updated the note as to the 
timing for obtaining informed 
consent.
Informed consent may be 
obtained prior to Screening. 


2017N331706_03
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96
Section # and Name
Description of Change
Brief Rationale
Section 2 Schedule of 
Activities
Updated the definition of the 
medical history notes.
Medical history should include 
asthma disease duration and 
exacerbation history.
Section 2 Schedule of 
Activities
Clarified the notes for sputum 
sample collection.
If a participant does not 
produce a viable baseline 
sputum sample at visit 2 or at 
visit 3, the participant will not 
need to undergo a sputum 
induction at the end of the 
treatment period. 
Section 2 Schedule of 
Activities
Changed the PK sample 
timepoint ‘post end of infusion’ 
to ‘post dose’.
Clarify the definition of the 
post dose sample such that it 
is consistent with Section 2 
notes.  
Section 2 Schedule of 
Activities
Clarified the Vital signs notes 
as to order of performance.  
Vital signs should be obtained 
prior to the 12-lead ECGs. 
Section 2 Schedule of 
Activities;
Section 9.2.1 Time Period and 
Frequency for Collecting AE 
and SAE Information
Adjusted the timing for 
collection of AEs/SAEs from 
randomisation onward and for 
collection of SAEs at V1 and 
V2. 
At Visits 1 and 2 SAE 
information will only be 
collected if considered as 
related to study participation. 
AEs and SAEs will be 
collected from randomisation 
until the end of the study. 
Section 3 Introduction;
Section 11 References
Added newly published 
internal reference and 
corrected the dates for the 
referenced Ph2 study. 
Added newly available clinical 
study report reference and 
accurate dates of the Ph2 
study with the same IP. 
Section 3.3.1 Risk 
Assessment;
Section 10.3.6 Interim 
Analyses;
Appendix 1 Abbreviations and 
Trademarks
Appendix 3 Study 
Governance Considerations
Changed independent safety 
review committee to internal 
safety review committee 
(iSRC).
Added a link to Appendix 3 in 
reference to the iSRC.
The safety review committee 
is independent of the study 
team but does have members 
who are employees of the 
sponsor. The title of the 
committee was changed to 
reflect its affiliation to the 
sponsor. The description of 
the iSRC is included in 
Appendix 3. 
Section 6.1 Inclusion Criteria;
Appendix 5 Contraceptive 
Guidance and Collection of 
Updated Inclusion criterion 
9aii and Table 7 Note b with 
regards to the contraceptive 
A WOCBP will be eligible if 
they agree to follow the 
contraceptive guidance in 


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97
Section # and Name
Description of Change
Brief Rationale
Pregnancy Information
requirements for female 
participants. 
Appendix 5 during the 
treatment period and for the 
duration of the follow-up 
period until the last visit at 
week 24 (or 16 weeks after 
the last dose, which is 
equivalent to 5.5 half-lives).
Section 6.2 Exclusion Criteria
Provided a definition for 
former smokers.
Former smokers are defined 
as smokers with greater than 
6 months abstention. 
Section 6.3 Run-in Exclusion 
Criteria;
Section 6.5 Randomisation 
Exclusion Criteria
Clarified and corrected the 
run-in and randomisation 
criteria sections. 
Removed criteria in each 
section pertaining to the 
previous visits or sections and 
corrected typographical errors 
and visit label within each 
section. 
Section 6.7 Screening/Run-
in/Randomisation Failures
Updated the circumstances 
allowed for rescreening and 
the screening number for a 
rescreened participant. 
If a participant has an asthma 
exacerbation at the time of 
run-in or randomisation, they 
may be rescreened at the 
Investigator’s discretion in 
consulation with the sponsor 
after the exacerbation has 
resolved.
Section 8.1 Discontinuation of 
Study Treatment
Clarified the stopping criteria 
for study treatment to align 
with Section 7.4 Blinding.
In the event of unblinding by 
the investigator or treating 
physician the Medical 
monitor/GSK team should be 
contacted to determine 
whether subject withdrawal is 
required.
Section 1 Synopsis
Deleted a space between 
fumigatus and the period.
Typographical error
Section 2 Schedule of 
Activities
Updated the sST2 boxes to 
match the assessments.
Formatting error
Section 3.2 Background
Corrected spelling of the term 
‘thermotolerant'
Typographical error
Section 5.2 Number of 
Participants
Corrected the spelling of 
randomised.
Typographical error


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98
Section # and Name
Description of Change
Brief Rationale
Section 6.1 Inclusion criteria
Added a parentheses after 
‘guidelines’ in inclusion 
criterion 2
Typographical error
Section 6.2 Exclusion criteria
Replaced word ‘on’ with ‘of’ in 
the exclusion criteria 9.
Typographical error
Section 6.3 Run-in Exclusion 
Criteria
Corrected the direct bilirubin 
levels to >35%.
Typographical error
Section 10.2 Populations for 
Analyses
Changed the word subject to 
participant and corrected 
randomised. 
Typographical errors
Appendix 3 Study 
Governance Considerations, 
Dissemination of Clinical 
Study Data 
Corrected the spelling of 
randomisation
Typographical error

SAP_001.pdf: 
CONFIDENTIAL
The GlaxoSmithKline group of companies
207972
1
Division
:
Worldwide Development
Information Type
:
Reporting and Analysis Plan (RAP)
Title
:
Reporting and Analysis Plan for a double blind (sponsor
open) placebo-controlled, stratified, parallel group study to 
evaluate the efficacy and safety of repeat doses of 
GSK3772847 in participants with moderate to severe asthma 
with allergic fungal airway disease (AFAD).
Compound Number 
:
GSK3772847
Effective Date 
:
24-JAN-2020
Description:

The purpose of this RAP is to describe the planned analyses and output to be
included in the Clinical Study Report for Protocol 207972 (Document Number:
2017N331706_04)

This RAP is intended to describe the Efficacy, Safety, PK, PD and Biomarker outputs
required for the study.

This RAP will be provided to the study team members to convey the content of the
Statistical Analysis Complete (SAC) deliverable.
RAP Author(s):
Author
Date
26-Nov-2019
Principal Statistician (Respiratory, Clinical Statistics)
Copyright 2020 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited.
PPD


CONFIDENTIAL
207972
2
RAP Team Review Confirmations 
(Method: E-mail)
Reviewer
Date
26-Nov-2019
Clinical Investigation Lead, Clinical Development Manager 
(Respiratory, Clinical Development)
26-Nov-2019
Programmer, Principal Programmer (Respiratory, Clinical 
Programming)
02-Dec-2019
Pharmacokinetics, Senior Director (Respiratory, Clinical 
Pharmacology Modelling and Simulation)
26-Nov-2019
Medical Monitor, Clinical Development Physician (Respiratory, 
MDC Global Clinical)
10-Dec-2019
Project Physician Lead, Director of Clinical Development 
(Respiratory, MDC Global Clinical)
26-Nov-2019
Value Evidence and Outcomes, Director Patient Centred 
Outcomes, (Respiratory, Value Evidence and Outcomes)
26-Nov-2019
Value Evidence and Outcomes, Scientist, Patient Centred 
Outcomes, (Respiratory, Value Evidence and Outcomes)
Clinical Statistics & Clinical Programming Line Approvals 
(Method: Pharma TMF eSignature)
Approver
Date
13-Jan-2020
Senior Statistics Director (Respiratory, Clinical Statistics)
24-Jan-2020
Programming Manger (Respiratory, Clinical Programming)
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


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207972
3
TABLE OF CONTENTS
PAGE
1.
INTRODUCTION......................................................................................................5
2.
SUMMARY OF KEY PROTOCOL INFORMATION ..................................................5
2.1.
Changes to the Protocol Defined Statistical Analysis Plan............................5
2.2.
Study Objective(s) and Endpoint(s)...............................................................6
2.3.
Study Design ................................................................................................8
2.4.
Statistical Analyses.......................................................................................8
3.
PLANNED ANALYSES ............................................................................................9
3.1.
Final Analyses ..............................................................................................9
4.
ANALYSIS POPULATIONS .....................................................................................9
4.1.
Analysis Populations.....................................................................................9
4.2.
Protocol Deviations.....................................................................................10
5.
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS.....................................................................................................11
5.1.
Study Treatment & Sub-group Display Descriptors.....................................11
5.2.
Baseline Definitions ....................................................................................11
5.3.
Multicentre Studies .....................................................................................12
5.4.
Examination of Covariates, Other Strata and Subgroups............................12
5.5.
Multiple Comparisons and Multiplicity .........................................................12
5.6.
Other Considerations for Data Analyses and Data Handling 
Conventions................................................................................................13
6.
STUDY POPULATION ANALYSES .......................................................................14
6.1.
Overview of Planned Study Population Analyses........................................14
6.2.
Disposition..................................................................................................14
6.3.
Medical Conditions .....................................................................................14
6.4.
Concomitant Medications............................................................................15
7.
EFFICACY ANALYSES..........................................................................................16
7.1.
Primary Efficacy Analyses ..........................................................................16
7.2.
Secondary Efficacy Analyses......................................................................16
8.
SAFETY ANALYSES .............................................................................................17
8.1.
Adverse Events Analyses ...........................................................................17
8.2.
Vital Signs, Electrocardiogram (ECG) and Holter........................................17
8.3.
Clinical Chemistry, Haematology and Cardiac Markers...............................17
8.4.
Antibodies...................................................................................................17
8.5.
Clinical Laboratory Analyses.......................................................................17
9.
PHARMACOKINETIC ANALYSES.........................................................................18
9.1.
Secondary Pharmacokinetic Analyses........................................................18
10. PHARMACODYNAMIC AND BIOMARKER ANALYSES........................................18
10.1.
Secondary Pharmacodynamic Analyses.....................................................18


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207972
4
11. REFERENCES........................................................................................................18
12. APPENDICES........................................................................................................19
12.1.
Appendix 1: Protocol Deviation Management and Definitions for Per 
Protocol Population.....................................................................................19
12.2.
Appendix 2: Schedule of Activities ..............................................................20
12.2.1.
Protocol Defined Schedule of Events...........................................20
12.3.
Appendix 3: Assessment Windows .............................................................26
12.3.1.
Definitions of Assessment Windows for Analyses........................26
12.4.
Appendix 4: Study Phases and Treatment Emergent Adverse 
Events ........................................................................................................27
12.4.1.
Study Phases ..............................................................................27
12.4.2.
Study Phases for Concomitant Medication...................................27
12.4.3.
Treatment Emergent Flag for Adverse Events .............................28
12.5.
Appendix 5: Data Display Standards & Handling Conventions....................29
12.5.1.
Reporting Process .......................................................................29
12.5.2.
Reporting Standards....................................................................29
12.6.
Appendix 6: Derived and Transformed Data ...............................................31
12.6.1.
General........................................................................................31
12.6.2.
Study Population..........................................................................31
12.6.3.
Safety ..........................................................................................31
12.7.
Appendix 7: Reporting Standards for Missing Data.....................................33
12.7.1.
Premature Withdrawals................................................................33
12.7.2.
Handling of Missing Data.............................................................33
12.7.2.1.
Handling of Missing and Partial Dates ........................33
12.8.
Appendix 8: Values of Potential Clinical Importance ...................................35
12.9.
Appendix 9: Abbreviations & Trade Marks ..................................................36
12.9.1.
Abbreviations...............................................................................36
12.9.2.
Trademarks .................................................................................37
12.10. Appendix 10: List of Data Displays..............................................................38
12.10.1. Data Display Numbering..............................................................38
12.10.2. Mock Example Shell Referencing ................................................38
12.10.3. Deliverables.................................................................................39
12.10.4. Study Population Tables..............................................................40
12.10.5. Efficacy Tables ............................................................................42
12.10.6. Safety Tables...............................................................................43
12.10.7. Pharmacokinetic Tables...............................................................45
12.10.8. Pharmacodynamic and Biomarker Tables....................................45
12.10.9. ICH Listings .................................................................................46
12.10.10.Non-ICH Listings..........................................................................49


CONFIDENTIAL
207972
5
1.
INTRODUCTION
The purpose of this reporting and analysis plan (RAP) is to describe the analyses to be 
included in the Clinical Study Report for Protocol of study 207972 (GSK Document No.: 
2017N331706_03).
Revision Chronology:
2017N331706_00
01-SEP-2017
Original
2017N331706_01
05-FEB-2018
Clarified that participants with severe asthma for whom it is 
felt oral corticosteroids are warranted are not eligible for this 
study.
Clarified the use of anti-fungal medication throughout the 
study.
Clarified the run-in and randomisation criteria sections.
Clarified the timing of contraceptive requirements for female 
participants. 
Provided a definition for former smokers.
Removed the body temperature in the objectives and safety 
analyses and updated Section 9 to reflect that body 
temperature will be collected but only available in source 
documents.
Corrected formatting and typographical errors. 
2017N331706_02
26-JUL-2018
Russia specific: To allow Russian Federation Sites to conduct 
the screening assessments over 2 separate visits.
2017N331706_03
10-OCT-2018
To include participants with severe asthma with AFAD treated 
with low dose oral corticosteroid who still demonstrate a lack 
of complete control as demonstrated by ACQ-5, FeNO and 
blood eosinophil levels. Also, a few clarifications were 
included.
2017N331706_04
10-OCT-2018
Russia specific: To include participants with severe asthma 
with AFAD treated with low dose oral corticosteroid who still 
demonstrate a lack of complete control as demonstrated by 
ACQ-5, FeNO and blood eosinophil levels. Also, a few 
clarifications were included.
2.
SUMMARY OF KEY PROTOCOL INFORMATION
2.1.
Changes to the Protocol Defined Statistical Analysis Plan
Changes from the originally planned statistical analysis specified in the protocol are 
outlined in Table 1.
Table 1
Changes to Protocol Defined Analysis Plan
Protocol
Reporting & Analysis Plan
Statistical Analysis Plan
Statistical Analysis Plan
Rationale for Changes
Primary and secondary endpoints 
to be analysed.
All endpoints to be summarised 
only.
Enrolment into the 207972 study 
was terminated early due to the 


CONFIDENTIAL
207972
6
Protocol
Reporting & Analysis Plan
Statistical Analysis Plan
Statistical Analysis Plan
Rationale for Changes
feasibility of completing the 
study in a timely manner, 
resulting in insufficient subjects 
for analysis to be performed.
An internal Safety Review 
Committee (iSRC) was to review 
safety data after the 20th
randomised subject received their 
first post-dose ECG/24hr Holter.
A potential interim analysis, end of 
treatment analysis and final SAC 
analysis was due to be performed.
No iSRC analysis and only one 
final SAC analysis to be performed.
The study was unable to recruit 
the 20 randomised subjects 
required for the iSRC prior to 
termination. 
In addition, as recruitment was 
terminated early, and would not 
inform internal decision making, 
there was no requirement to 
report at multiple timepoints to 
align with portfolio decisions.
Primary, secondary and 
exploratory endpoints to be 
reported.
Primary and secondary endpoints 
only to be reported.
As there is insufficient data to 
draw any conclusions on 
exploratory endpoints, and they 
are not required for external 
disclosure, no outputs will be 
created.
2.2.
Study Objective(s) and Endpoint(s)
Objectives
Endpoints
Primary Objectives
Primary Endpoints
To evaluate the efficacy of 3 doses of GSK3772847 
(administered every 4 weeks) compared with 
placebo in moderate to severe asthma participants 
with allergic fungal airway disease (AFAD) who are 
currently on Standard of Care (SoC)

Change from baseline (Week 0) in blood eosinophils 
over time

Change from baseline (Week 0) in fractional exhaled 
nitric oxide (FeNO) over time
Secondary Objectives
Secondary Endpoints
To evaluate the serum pharmacokinetics (PK) of 3 
doses of GSK3772847 (administered every 4 
weeks) in moderate to severe asthma participants 
with AFAD

Serum concentrations of GSK3772847
To evaluate the pharmacodynamics (PD) of 
GSK3772847 in moderate to severe asthma 
participants with AFAD

Serum levels of free and total soluble suppressor of 
tumorigenicity 2 (sST2)
To evaluate the levels and specificity of any anti-
drug antibodies formed following dosing with 
GSK3772847

Incidence and titres of serum anti- GSK3772847 
antibodies
To evaluate the health status of moderate to severe 
asthma participants with AFAD currently on SoC, 
and who are treated with GSK3772847 compared 
with placebo-treated participants

Change from baseline (Week 0) in Asthma Control 
Questionnaire -5 (ACQ-5) absolute score at Weeks 2, 4, 
8 and 12

Change from baseline (Week 0) in Asthma Quality of 
Life Questionnaire (AQLQ) total and domain scores at 
Weeks 2, 4, 8 and 12

Proportion of responders to ACQ-5. A responder to 


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207972
7
Objectives
Endpoints
ACQ-5 will be defined as a subject who has a decrease 
from baseline in ACQ-5 score of 0.5 or more at Weeks 
2, 4, 8 and 12.

Proportion of responders to AQLQ. A responder to 
AQLQ will be defined as a subject who has an increase 
from baseline in AQLQ score of 0.5 or more at Weeks 2, 
4, 8 and 12.
To evaluate the effect on lung function of
moderate to severe asthma participants with AFAD 
currently on SoC, treated with GSK3772847 
compared with placebo

Change from baseline (Week 0) in spirometry 
parameters over time including but not limited to pre-
bronchodilator Forced expiratory volume in 1 second 
(FEV1).
To evaluate the safety and tolerability of
GSK3772847 compared with placebo in
moderate to severe asthma participants with AFAD
Safety and tolerability parameters include:

Treatment emergent adverse events (AE)

Clinical Laboratory safety data

Vital signs (blood pressure, heart rate)

12–Lead Electrocardiogram (ECG) monitoring

24-hour Holter monitoring
Exploratory Objectives
Exploratory Endpoints
To evaluate changes in exploratory biomarkers in 
the blood of moderate to severe asthma participants 
with AFAD who have been treated with 
GSK3772847 compared with placebo

Change over time in levels of serum total 
Immunoglobulin E (IgE), fungal-specific IgE
To evaluate changes in IL-33 related and disease 
biology biomarkers in the sputum of moderate to 
severe asthma participants with AFAD who have 
been treated with GSK3772847 compared with 
placebo

Difference from placebo in levels of sputum biomarkers 
including but not limited to interleukin (IL)-33, IL-13, IL-
4, IL-5 and TNF- 

Difference from placebo including but not limited to 
levels of sputum eosinophils


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207972
8
2.3.
Study Design
Overview of Study Design and Key Features
Screening 
(28 days 
prior to V3)
GSK3772847 (IV) 10mg/kg, n=20
Follow up
Study duration (approx. 28 weeks)
Week 0
V3
Dose 1
Week 8
V6
Dose 3
Week 12
V7
No Dose
Treatment period
Placebo, n=20
Standard of Care (SoC)
Week 4
V5
Dose 2
Screening 
V1
Week 24 
V8
No Dose
Randomisation
Run-in
V2
Week 2
V4
No Dose
Run-in
(14 days 
prior to V3)
Design Features

The study is a double blind (sponsor open) placebo-controlled, 
stratified, parallel group study
Dosing

Participants will remain on SoC treatments for the duration of the 
treatment period.

Following run-in, they will be randomised to receive three doses of 
either GSK3772847 or Placebo intravenously (Week 0, 4, 8) on top of 
their SoC treatment.
Treatment Assignment

Participants will be randomised in a 1:1 ratio to receive three doses of 
either GSK3772847 10 mg/kg or Placebo administered intravenously 
every 4 weeks.

Randomisation will be stratified based on whether the participant is 
taking antifungal medication.
Final Analysis

The Final Analysis will take place after all participants have completed 
the study. This will be the only analysis for the study.
2.4.
Statistical Analyses
Due to the study being terminated early, there were insufficient subjects to enable the 
planned statistical analysis to be performed. As a result, all data will be summarised 
descriptively only.


CONFIDENTIAL
207972
9
3.
PLANNED ANALYSES
3.1.
Final Analyses
The final planned analyses will be performed after the completion of the following 
sequential steps:
1.
All participants have completed the study as defined in the protocol 
2.
All required database cleaning activities have been completed and database release 
has been declared by Data Management.
3.
All criteria for unblinding the randomisation codes have been met. 
4.
Randomisation codes have been distributed according to RandAll NG procedures.
5.
Database freeze (DBF) has been declared by Data Management.
4.
ANALYSIS POPULATIONS
4.1.
Analysis Populations
Population
Definition / Criteria
Analyses Evaluated
Enrolled
The All Subjects Enrolled (ASE) population will consist of all 
participants who sign the ICF.

Study population

Subjects by 
country and site ID

Age ranges

Screening/run-in 
status and reason 
for screening/run-
in failure.
Screened
The screened population will consist of all participants who 
sign the ICF, but who did not pass the screening/run-in 
criteria and therefore were not randomised. 

Reasons for 
screen/run-in 
failure
Randomised
The randomised population will consist of all participants 
who were randomised. A participant who is recorded as a 
screen or run-in failure and also randomised will be 
considered to be randomised in error provided they have not 
performed any study assessments.

No formal analysis 
will be performed 
on this population
Modified Intent-
to-Treat

The modified Intent-to-Treat (mITT) will consist of all 
randomised participants who take at least 1 dose of 
study treatment. 

Participants will be analysed according to the treatment 
they receive >=50% of the time. If the participant 
receives 50% of each treatment they will be analysed 
according to the randomised treatment.

Study population

Inclusion, 
exclusion and 
randomisation 
criteria deviations

Participant
disposition

Efficacy


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207972
10
Population
Definition / Criteria
Analyses Evaluated
Safety
This population will be the same as the Modified Intent-to-
Treat population. 

Safety
Pharmacokinetic
The PK population will consist of all randomised participants 
who received at least one dose of study medication, and for 
whom at least one pharmacokinetic sample was obtained, 
analysed and was measurable.

PK
Refer to Appendix 10: List of Data Displays which details the population used for each display.
4.2.
Protocol Deviations
Important protocol deviations (including deviations related to study inclusion/exclusion 
criteria, conduct of the trial, patient management or patient assessment) will be 
summarised and listed.
Protocol deviations will be tracked by the study team throughout the conduct of the study 
in accordance with the Protocol Deviation Management Plan [Version 2 (19-JUN-2018) 
or higher].
o Data will be reviewed prior to unblinding and freezing the database, to ensure all 
important deviations are captured and categorised on the protocol deviations 
dataset. 
o This dataset will be the basis for the summaries and listings of protocol 
deviations.
A separate summary and listing of all inclusion/exclusion criteria deviations will also be 
provided. This summary will be based on data as recorded on the inclusion/exclusion 
page of the eCRF.
Note: Inclusion and exclusion criteria deviations are always reported as important.


CONFIDENTIAL
207972
11
5.
CONSIDERATIONS FOR DATA ANALYSES AND DATA
HANDLING CONVENTIONS
5.1.
Study Treatment & Sub-group Display Descriptors
Treatment Group Descriptions
RandAll NG 
Data Displays for Reporting 
Code
Description
Description
Order [1]
G
GSK3772847 10 mg/kg
GSK3772847
2
P
Placebo
Placebo
1
NOTES:
[1] Order represents treatments being presented in TFL, as appropriate
Treatment comparisons will be displayed as follows using the descriptors as specified:

GSK3772847 vs Placebo
5.2.
Baseline Definitions
For all endpoints (except as noted in baseline definitions) the baseline value will be the 
latest pre-dose assessment with a non-missing value, including those from unscheduled 
visits. If time is not collected, Day 1 assessments are assumed to be taken prior to first 
dose and used as baseline.
Parameter
Study Assessments 
Considered as Baseline
Baseline Used in 
Data Display
Screening
Run-in
Day 1 
(Pre-Dose)
Primary Endpoints
Fractional Exhaled Nitric Oxide 
(FeNO)
X
X
Day 1
Blood Eosinophils
X
X
Day 1
Other Patient Reported Outcomes
AQLQ
X
Day 1
Asthma Control Questionnaire 
(ACQ-5) score
X
X
Day 1
Spirometry
Forced Expiratory Volume (FEV1)
X
X
Day 1
Pharmacodynamics
Free and total sST2 (serum)
X
Day 1


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Parameter
Study Assessments 
Considered as Baseline
Baseline Used in 
Data Display
Screening
Run-in
Day 1 
(Pre-Dose)
Safety
Vital Signs
X
X
X
Day 1
12-lead Electrocardiogram (ECG) 
measurements
X
X
Day 1
24 hours Holter measurements
X
X
Day 1
Clinical laboratory tests 
(haematology and chemistry)
X
X
Day 1
Immunogenicity: Anti-
GSK3772847 antibodies
X
Day 1
Biomarkers
Induced sputum biomarkers
X
X
Run-in 1
Exploratory serum markers
(including IgE and Fungal-specific 
IgE)
X
X
Day 1
NOTES:

Unless otherwise stated, the mean of replicate assessments taken on the same day will be used as the value for 
that day.
1      Baseline is taken at run-in. If the sputum taken at run-in is not viable then a sample is taken at Day 1 (Pre-Dose)
       and is used as baseline.
5.3.
Multicentre Studies
In this multicentre global study, enrolment will be presented by investigative site and 
country.
5.4.
Examination of Covariates, Other Strata and Subgroups
No analysis will be performed on this data due to low subject numbers.
5.5.
Multiple Comparisons and Multiplicity
No adjustment for multiplicity is required for this study, as no analysis will be performed.


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5.6.
Other Considerations for Data Analyses and Data Handling 
Conventions
Other considerations for data analyses and data handling conventions are outlined in the 
appendices:
Section
Component
12.3
Appendix 3: Assessment Windows
12.4
Appendix 4: Study Phases and Treatment Emergent Adverse Events
12.5
Appendix 5: Data Display Standards & Handling Conventions
12.6
Appendix 6: Derived and Transformed Data
12.7
Appendix 7: Reporting Standards for Missing Data
12.8
Appendix 8: Values of Potential Clinical Importance


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6.
STUDY POPULATION ANALYSES
6.1.
Overview of Planned Study Population Analyses
The study population summaries will be based on the modified intent to treat population 
(mITT), unless specified to be on the All Subjects Enrolled (ASE) population.
Study population summaries including subject’s disposition, protocol deviations, 
demographic and baseline characteristics, prior and concomitant medications, exposure 
and treatment compliance will be based on GSK Core Data Standards.  Details of the 
planned displays are presented in Appendix 10: List of Data Displays.
6.2.
Disposition
The study populations summary will use the All Subjects Enrolled (ASE) population and 
show the number of subjects overall who were enrolled, the number of screen failures 
and the number with each reason for screen failure. It will also show the number of 
subjects who were randomised and who were in the mITT, Safety and PK populations.
For the mITT population, two tables will be produced showing reasons for withdrawal 
from study and reasons for withdrawal from treatment. These summaries will show the 
number and percentage of subjects who completed the treatment/study, who withdrew 
prematurely and who reported each primary and sub-reason for withdrawal. 
6.3.
Medical Conditions
The number and percentage of subjects reporting each current medical condition will be 
presented. This table will include a subheading of ‘Cardiovascular Risk Factors,’ which 
will summarise the information taken from the cardiac disorders page in the eCRF.  All 
medical conditions must be summarised on this table regardless of frequency. This will 
be repeated for past medical conditions.


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6.4.
Concomitant Medications
Non-Asthma medications will be summarised by Anatomical-Therapeutic-Chemical 
(ATC) level 1 and ingredient. Asthma medications will be summarised by the latest 
version of the Respiratory Medication Class (RMC), and will be derived for each asthma 
concomitant medication. Multi-ingredient medications will be presented according to 
their combination ATC classification rather than the classifications of the ingredients. 
Asthma and non-asthma medications will be listed together. A listing of the relationship 
between ATC Level 1, ingredient and verbatim text will be produced for non-asthma 
medications only.


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7.
EFFICACY ANALYSES
Due to low subject numbers no statistical analysis will be performed.
7.1.
Primary Efficacy Analyses
7.1.1.
Endpoints and Summary Measures
Primary Endpoints
Summary Measure
Change from baseline (Week 0) in blood eosinophils over 
time
Summary statistics (raw and change from 
baseline)
Change from baseline (Week 0) in fractional exhaled 
nitric oxide over time
Summary statistics (raw and change from 
baseline)
Primary efficacy summaries will be based on the mITT population and no intercurrent 
events will be considered. 
7.2.
Secondary Efficacy Analyses
7.2.1.
Endpoint and Summary Measure 
Secondary Endpoints
Summary Measure

Change from baseline (Week 0) in spirometry parameters over time 
including but not limited to pre-bronchodilator Forced expiratory 
volume in 1 second.

Change from baseline (Week 0) in Asthma Control Questionnaire -5 
absolute score at Weeks 2, 4, 8 and 12

Change from baseline (Week 0) in Asthma Quality of Life 
Questionnaire total and domain scores at Weeks 2, 4, 8 and 12
Summary statistics (raw 
and change from 
baseline)

Proportion of responders to ACQ-5. A responder to ACQ-5 will 
be defined as a subject who has a decrease from baseline in 
ACQ-5 score of 0.5 or more at Weeks 2, 4, 8 and 12.

Proportion of responders to AQLQ. A responder to AQLQ will be 
defined as a subject who has an increase from baseline in 
AQLQ score of 0.5 or more at Weeks 2, 4, 8 and 12.
Number and percentage 
of responders
Secondary efficacy summaries will be based on the mITT population and no intercurrent 
events will be considered. 


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8.
SAFETY ANALYSES
The safety analyses will be based on the Safety population, unless otherwise specified. 
The details of the planned displays are provided in Appendix 10: List of Data Displays.
8.1.
Adverse Events Analyses
Adverse events analyses including the analysis of adverse events (AEs) and Serious 
(SAEs) will be based on GSK Core Data Standards. 
8.2.
Vital Signs, Electrocardiogram (ECG) and Holter
Summary statistics for vital signs at baseline, Weeks 0, 4, 8, 12, and 24 will be produced 
along with change from baseline summaries for each post baseline timepoint. In addition, 
the change between post-dose and pre-dose vital signs measurements will be summarised 
at weeks 0, 4 and 8.
A summary of ECG findings along with a table that shows the maximum increase in 
QTcF values post-baseline relative to baseline category will be produced.
In addition a summary of Holter interpretations will be produced for participants with at 
least 16 hours of data, however all data will be listed.
8.3.
Clinical Chemistry, Haematology and Cardiac Markers
A summary of worst case clinical chemistry results relative to the normal range post-
baseline, will be produced. Similar tables will be created for haematology and cardiac 
markers.
8.4.
Antibodies
Summaries of the incidence of and titres of anti- GSK3772847 antibodies at weeks 0*, 2, 
4*, 8*, 12 and 24.
* = Pre-dose only
8.5.
Clinical Laboratory Analyses
Laboratory evaluations including the analyses of liver function tests will be based on 
GSK Core Data Standards.


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9.
PHARMACOKINETIC ANALYSES
Due to low subject numbers no statistical analysis will be performed.
9.1.
Secondary Pharmacokinetic Analyses
Serum concentrations of GSK3772847 will be summarised by nominal time.
Pharmacokinetic summaries will be based on the Pharmacokinetic population, and no 
intercurrent events will be considered. 
10.
PHARMACODYNAMIC AND BIOMARKER ANALYSES
10.1.
Secondary Pharmacodynamic Analyses
Summary statistics of raw and percentage change from baseline in free and total soluble 
ST2 levels (serum) will be produced.
Pharmacodynamics summaries will be based on the mITT population, and no intercurrent 
events will be considered. 
11. REFERENCES
GlaxoSmithKline Document Number 2017N331706_04, Protocol Amendment 2: A 
double blind (sponsor open) placebo-controlled, stratified, parallel group study to 
evaluate the efficacy and safety of repeat doses of GSK3772847 in participants with 
moderate to severe asthma with allergic fungal airway disease (AFAD). [10/OCT/2018].
Charter for the Internal Safety Review Committee (iSRC): A double blind (sponsor open) 
placebo-controlled, stratified, parallel group study to evaluate the efficacy and safety of 
repeat doses of GSK3772847 in participants with moderate to severe asthma with allergic 
fungal airway disease (AFAD). [30/JAN/2018]
Protocol Deviation Management Plan Version 2 (19-JUN-2018) or higher.
Winthrop et al, 2015, Opportunistic infections and biologic therapies in immune-
mediated inflammatory diseases: consensus recommendations for infection reporting 
during clinical trials and postmarketing surveillance, Annals of the Rheumatoid Arthritis 
Disease, doi: 10.1136/annrheumdis-2015-207841. Epub 2015 Sep 22


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12.
APPENDICES
12.1.
Appendix 1: Protocol Deviation Management and Definitions 
for Per Protocol Population
The full list of protocol deviations collected on the eCRF is in the Protocol Deviation 
Management Plan (PDMP). Please refer to this document for current guidance. 
There is no per protocol population in this study.


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12.2.
Appendix 2: Schedule of Activities
12.2.1.
Protocol Defined Schedule of Events


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12.3.
Appendix 3: Assessment Windows
12.3.1.
Definitions of Assessment Windows for Analyses
Nominal visits will be used and no windowing will be applied for analysis.


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12.4.
Appendix 4: Study Phases and Treatment Emergent 
Adverse Events
12.4.1.
Study Phases
Assessments and events will be classified according to the time of occurrence relative to 
study treatment start date.
Study Phase
Definition
Pre-Treatment 
Date ≤Study Treatment Start Date
On-Treatment
Study Treatment Start Date < Date ≤ Study Treatment Stop Date + 28 days
Post-Treatment
Date > Study Treatment Stop Date + 28 days
Completion of study epochs will be defined as the following:
Study Phase
Definition of Completion 
Run-in 
Randomised into study and received first dose of study treatment
Treatment
Completed Week 12 visit 
Follow up
Completed 12 week follow-up period
12.4.2.
Study Phases for Concomitant Medication
Study Phase
Definition
Note: All programming should use start and end dates where available, CMSTRF 
and CMENRF are only to be used where dates are unavailable to help determine 
the correct study phase.
Pre-Treatment

Conmed Start Date < Study Treatment First Dose Date

Conmed End Date < Study Treatment First Dose Date

CMSTRF = ”BEFORE” 

Randomisation date is missing i.e. subject was not randomised
On-Treatment

Study Treatment First Dose Date <= Conmed Start Date <= Study 
Treatment Last Dose Date + 28

Study Treatment First Dose Date <= Conmed End Date <= Study Treatment 
Last Dose Date + 28

(Conmed Start Date <= Study Treatment Last Dose Date + 28) and (Conmed 
End Date >= Study Treatment First Dose Date)

(Conmed Start Date <= Study Treatment Last Dose Date + 28) and (CMENRF 
=”DURING/AFTER” or CMENRF =”AFTER” or CMSTRF = “DURING”)

(CMSTRF = ”BEFORE” or CMSTRF = ”DURING” or CMENRF 
=”DURING/AFTER”) and (Conmed End Date >= Study Treatment First Dose 
Date)

(CMSTRF = ”BEFORE” or CMSTRF =”DURING”) and (CMENRF 
=”DURING/AFTER” or CMENRF =”AFTER”) 

CMSTRF = ”DURING”

CMENRF = ”DURING/AFTER”
Post-Treatment 

Conmed Start Date > Study Treatment Last Dose Date + 28


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Study Phase
Definition
Note: All programming should use start and end dates where available, CMSTRF 
and CMENRF are only to be used where dates are unavailable to help determine 
the correct study phase.

Conmed End Date > Study Treatment Last Dose Date + 28

CMENRF = ”AFTER” 

CMENRF = ”DURING/AFTER”
All phases

Conmed start date is missing and CMSTRF is missing and conmed end 
date is missing and CMENRF is missing
NOTES: 

The duration of a single concomitant medication can extend over multiple study phases 

Please refer to Appendix 7: Reporting Standards for Missing Data for handling of missing and partial dates for 
concomitant medication. Use the rules in this table if concomitant medication date is completely missing.
12.4.3.
Treatment Emergent Flag for Adverse Events
Flag
Definition
Treatment 
Emergent
If AE onset date is on or after treatment start date & on or before treatment stop date + 
28 days. 
Study Treatment Start Date ≤ AE Start Date ≤ Study Treatment Stop Date + 28 days
NOTES: 

If the study treatment stop date is missing then the AE will be considered to be On-Treatment.


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12.5.
Appendix 5: Data Display Standards & Handling 
Conventions
12.5.1.
Reporting Process
Software

The currently supported versions of SAS software will be used.
Reporting Area
HARP Server
: uk1salx00175
HARP Compound
: /arenv/arprod/gsk3772847/mid207972/
final_01:This is where the end of study analysis will take place.
Analysis Datasets 

Analysis datasets will be created according to CDISC standards
Generation of RTF Files

RTF files will be generated for all reporting efforts
12.5.2.
Reporting Standards
General

The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated (IDSL Standards Location: https://spope.gsk.com/sites/IDSLLibrary/SitePages/Home.aspx):

4.03 to 4.23: General Principles

5.01 to 5.08: Principles Related to Data Listings

6.01 to 6.11: Principles Related to Summary Tables

7.01 to 7.13: Principles Related to Graphics 

Do not include subject level listings in the main body of the GSK Clinical Study Report. All subject level 
listings should be located in the modular appendices as ICH or non-ICH listings
Formats

GSK IDSL Statistical Principles (5.03 & 6.06.3) for decimal places (DP’s) will be adopted for reporting of 
data based on the raw data collected, unless otherwise stated.

Numeric data will be reported at the precision collected on the eCRF.

The reported precision from non eCRF sources will follow the IDSL statistical principles but may be 
adjusted to a clinically interpretable number of DP’s.
Planned and Actual Time

Reporting for tables, figures and formal statistical analyses:

Planned time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated.

The impact of any major deviation from the planned assessment times and/or scheduled visit days 
on the analyses and interpretation of the results will be assessed as appropriate.

Reporting for Data Listings: 

Planned and actual time relative to study drug dosing will be shown in listings (Refer to IDSL 
Statistical Principle 5.05.1).

Unscheduled or unplanned readings will be presented within the subject’s listings. 
Unscheduled Visits

Unscheduled visits will only be included in summary tables as part of ‘minimum/maximum post baseline’ 


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and ‘minimum/maximum change from baseline’ summary.

Unscheduled visits will not be included in figures.

All unscheduled visits will be included in listings.
Descriptive Summary Statistics
Continuous Data
Refer to IDSL Statistical Principle 6.06.1
Categorical Data
N, n, frequency, %
Graphical Displays

Refer to IDSL Statistical Principals 7.01 to 7.13.


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12.6.
Appendix 6: Derived and Transformed Data
12.6.1.
General
Multiple Measurements at One Analysis Time Point

Mean of the measurements will be calculated and used in any derivation of summary statistics but if 
listed, all data will be presented.

If there are two values within a time window (as per Section 12.3.1) the value closest to the target day 
for that window will be used. If values are the same distance from the target, then the mean will be 
taken.

Participants having both High and Low values for Normal Ranges at any post-baseline visit for safety 
parameters will be counted in both the High and Low categories of “Any visit post-baseline” row of 
related summary tables. This will also be applicable to relevant Potential Clinical Importance summary 
tables.
Study Day

Calculated as the number of days from First Dose Date:

Ref Date = Missing              → Study Day = Missing 

Ref Date < First Dose Date → Study Day = Ref Date – First Dose Date

Ref Data ≥ First Dose Date → Study Day = Ref Date – (First Dose Date) + 1    
12.6.2.
Study Population
Age
Date of birth will be set as 30-JUN-YYYY where YYYY is the year of birth taken from the CRF. For 
participants who attended a screening visit, age will be calculated at the screening visit date. 
Body Mass Index (BMI)
BMI = Weight (kg) / Height(m)2
Treatment Misallocations
To allocate treatment, the number of doses of GSK3772847 and Placebo that were given will be 
calculated, and the subject will be assigned to whichever treatment has the higher number. The only 
exception will be when both treatments were given equally, in which case the subject will be 
assigned their randomised treatment.
Extent of Exposure (Therapeutic Coverage)

IP is administered approximately every 4 weeks and each dose viewed as providing therapeutic 
coverage for 4 weeks (28 days).  

Number of days of exposure to study drug will be calculated based on the formula:  
Duration of Exposure in Days = Study Treatment Last Dose Date – (Study Treatment First Dose 
Date) + 29 

The only exception to this will be when a participant dies in which case
Duration of Exposure in Days = Death Date – (Study Treatment First Dose Date) + 1
12.6.3.
Safety
Maximum/Minimum On-Treatment Definitions for Vital Signs Data
Maximum and Minimum on-treatment: Maximum and Minimum on-treatment value over all time-points 
(including scheduled and unscheduled assessments) will be presented.


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Adverse Events
Adverse Events of Special Interest (AESI)
Systemic Allergic/Hypersensitivity and Non-allergic Reactions:

Hypersensitivity (SMQ) [narrow]

Anaphylactic reaction (SMQ) [narrow]

Angioedema (SMQ) [narrow]
Alterations in immune response (infections)
All infections and serious infections reported under the MedDRA system organ class of ‘Infections and 
Infestations’. Specific events of interest are opportunistic infections with preferred terms matching 
identified/pre-determined terms based on a published list of pathogens and/or presentations of specific 
pathogens to be considered as opportunistic infections in the setting of biologic therapy [Winthrop et al, 
2015].
Alterations in immune response (malignancies):
All neoplasms reported under the MedDRA system organ class of ‘Neoplasms, benign, malignant and 
unspecified (including cysts and polyps)’. Specific events of interest are malignancies which will be identified 
through matching of collected preferred terms with those from the following:
Sub-SMQs under the Malignancies SMQ:

Malignant tumours sub-SMQ (narrow terms)

Tumours of unspecified malignancy sub-SMQ (narrow terms)
Alterations in cardiovascular safety:
Cardiac disorders and serious cardiac disorders reported under the MedDRA system organ class of 
‘Cardiac Disorders’. Serious cardiac, vascular and thromboembolic (CVT) events, identified as all serious 
events classified under the MedDRA system organ classes of ‘Cardiac Disorders’ and of ‘Vascular 
Disorders’, and thromboembolic events identified through matching of collected preferred terms with those 
from the following:
Sub-SMQs under the Embolic and thrombotic events SMQ:

Embolic and thrombotic events, arterial sub-SMQ (narrow terms)

Embolic and thrombotic events, venous sub-SMQ (narrow terms)

Embolic and thrombotic events, vessel type unspecified and mixed arterial and venous sub-SMQ 
(narrow terms)
Sub-SMQs under the Ischaemic Heart Disease SMQ

Myocardial infarction sub-SMQ (narrow terms)

Other Ischaemic heart disease sub-SMQ (narrow terms)
Sub-SMQs under the Central Nervous System Vascular Disorders SMQ

Ischaemic central nervous system vascular conditions sub-SMQ (narrow terms)

Central nervous system vascular disorders, not specified as haemorrhagic or ischaemic sub-SMQ 
(narrow terms)

Serious ischemic adverse events, a subset of the serious CVT events identified through matching of 
collected preferred terms with those from the following:
Local Injection Site Reactions
Local injection site reactions are identifying through preferred terms which had been selected by medical 
review of the MedDRA dictionary and are provided in a separate spreadsheet.


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12.7.
Appendix 7: Reporting Standards for Missing Data
12.7.1.
Premature Withdrawals
Element
Reporting Detail
General

Subject study completion (i.e. as specified in the protocol) was defined as completing 
the 12-week treatment period and three month safety follow up.

Withdrawn participants were not replaced in the study.

All available data from participants who were withdrawn from the study will be listed 
and all available planned data will be included in summary tables and figures, unless 
otherwise specified. 
12.7.2.
Handling of Missing Data
Element
Reporting Detail
General

Missing data occurs when any requested data is not provided, leading to blank fields on 
the collection instrument:
o
These data will be indicated by the use of a “blank” in subject listing displays. 
Unless all data for a specific visit are missing in which case the data is excluded 
from the table. 
o
Answers such as “Not applicable” and “Not evaluable” are not considered to be 
missing data and should be displayed as such.
Analysis

All missing data will be handled according to estimand of interest as described within 
the main body of the RAP.
ACQ-5

If one of the five items in the ACQ-5 is missing then the response from the four 
remaining items will be interpolated (pro-rata) to gain the overall response for the 
participant.

If more than one item is missing then the ACQ-5 will be considered missing.  
AQLQ

The AQLQ contains 32 items in four domains: activity limitation (11 items), symptoms 
(12 items), emotional function (five items), and environmental stimuli (four items). For 
the overall score, there must be no more than three missing responses (and never 
more than one per domain). The symptom and activity domain scores can have up to 
one missing value per domain, but for the emotional function and environmental stimuli 
domain scores must have no missing responses.

If there are missing values at a visit (for example visit 2) then data will be imputed using 
data from both this visit and the previous study visit (for example visit 1) as shown 
below:
Visit 1 (completed data): Total score = A
Visit 2 (incomplete data): Total score = B
Visit 2 imputed score: B/A x 2
12.7.2.1.
Handling of Missing and Partial Dates
Element
Reporting Detail
General

Partial dates will be displayed as captured in subject listing displays.
Adverse 

The eCRF allows for the possibility of partial dates (i.e., only month and year) to be 


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Events
recorded for AE start and end dates; that is, the day of the month may be missing. In 
such a case, the following conventions will be applied for calculating the time to onset 
and the duration of the event:
o
Missing Start Day: First of the month will be used unless this is before the start 
date of study treatment; in this case the study treatment start date will be used and 
hence the event is considered On-treatment as per Appendix 4: Study Phases and 
Treatment Emergent Adverse Events.
o
Missing Stop Day: Last day of the month will be used, unless this is after the stop 
date of study treatment; in this case the study treatment stop date will be used.

Completely missing start or end dates will remain missing, with no imputation applied. 
Consequently, time to onset and duration of such events will be missing.
Concomitant 
Medications/
Medical 
History

Partial dates for any concomitant medications recorded in the CRF will be imputed 
using the following convention:
o
If the partial date is a start date, a '01' will be used for the day and 'Jan' will be 
used for the month
o
If the partial date is a stop date, a '28/29/30/31' will be used for the day (dependent 
on the month and year) and 'Dec' will be used for the month.

The recorded partial date will be displayed in listings.


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12.8.
Appendix 8: Values of Potential Clinical Importance
Values of potential clinical importance will not be used in this study, instead normal 
reference ranges of “Low”, “Normal” and “High” will be used.


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12.9.
Appendix 9: Abbreviations & Trade Marks
12.9.1.
Abbreviations
Abbreviation
Description
ACQ-5
Asthma Control Questionnaire
ADaM
Analysis Data Model
AE
Adverse Event
AFAD
Allergic Fungal Airway Disease
AIC
Akaike's Information Criteria
AQLQ
Asthma Quality of Life Questionnaire
ASE
All Subjects Enrolled
A&R
Analysis and Reporting 
CDISC
Clinical Data Interchange Standards Consortium
CI
Confidence Interval
CPMS
Clinical Pharmacology Modelling & Simulation
CRO
Contract Research Organisation
CS
Clinical Statistics
CSR
Clinical Study Report
CTR
Clinical Trial Register
CVb / CVw
Coefficient of Variation (Between) / Coefficient of Variation (Within)
DBF
Database Freeze
DBR
Database Release
DOB
Date of Birth
DP
Decimal Places
ECG
Electrocardiogram
eCRF
Electronic Case Record Form
EOS
Eosinophils
FeNO
Fractional Exhaled Oxide
FEV1
Forced expiratory volume in 1 second
HARP
Harmonisation of Analysis and Reporting Program
IA
Interim Analysis
ICF
Informed Consent Form
ICH
International Conference on Harmonisation
IDMC
Independent Data Monitoring Committee 
IDSL
Integrated Data Standards Library
IgE
Immunoglobulin E
IMMS
International Modules Management System
IP
Investigational Product
iSRC
Internal Safety Review Committee
ITT
Intent-To-Treat
GUI
Guidance
LOC
Last Observation Carries Forward
mITT
Modified Intent-To-Treat
MMRM
Mixed Model Repeated Measures
PCI
Potential Clinical Importance 


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Abbreviation
Description
PD
Pharmacodynamic
PDMP
Protocol Deviation Management Plan
PGx
Pharmacogenetic
PK
Pharmacokinetic
POC
Proof of Concept
PP
Per Protocol
QC
Quality Control
QTcF
Frederica’s QT Interval Corrected for Heart Rate
QTcB
Bazett’s QT Interval Corrected for Heart Rate
RAP
Reporting & Analysis Plan
RAMOS
Randomisation & Medication Ordering System 
RTF
Rich Text Format
SAC
Statistical Analysis Complete
SAE
Serious Adverse Event
SDTM
Study Data Tabulation Model
SoC
Standard of Care
SOP
Standard Operation Procedure
ST2
Suppressor of Tumorigenicity 2
TA
Therapeutic Area
TFL
Tables, Figures & Listings 
WOCBP
Woman of Child Bearing Potential
GSK
GlaxoSmithKline
12.9.2.
Trademarks
Trademarks of the GlaxoSmithKline 
Group of Companies
Trademarks not owned by the 
GlaxoSmithKline Group of Companies
None
SAS


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12.10.
Appendix 10: List of Data Displays
All displays (Tables, Figures & Listings) will use the term 'Subjects' instead of 
“Participants”.
12.10.1.
Data Display Numbering
The following numbering will be applied for RAP generated displays:
Section
Tables
Figures
Study Population
1.1 to 1.n
1.1 to 1.n
Efficacy
2.1 to 2.n
2.1 to 2.n
Safety
3.1 to 3.n
3.1 to 3.n
Pharmacokinetic
4.1 to 4.n
4.1 to 4.n
Population Pharmacokinetic (PopPK)
5.1 to 5.n
5.1 to 5.n
Pharmacodynamic and / or Biomarker
6.1 to 6.n
6.1 to 6.n
Pharmacokinetic / Pharmacodynamic
7.1 to 7.n
7.1 to 7.n
Section
Listings
ICH Listings
1 to x
Other Listings
y to z
12.10.2.
Mock Example Shell Referencing
Non IDSL specifications will be referenced as indicated and if required example mock-up 
displays provided in Appendix 10: List of Data Displays: Example Mock Shells for Data 
Displays.
Section
Figure
Table
Listing
Study Population
POP_Fn
POP_Tn
POP_Ln
Efficacy
EFF_Fn
EFF_Tn
EFF_Ln
Safety
SAFE_Fn
SAFE_Tn
SAFE_Ln
Pharmacokinetic
PK_Fn
PK_Tn
PK_Ln
Population Pharmacokinetic (PopPK)
POPPK_Fn
POPPK_Tn
POPPK_Ln
Pharmacodynamic and / or Biomarker
PD_Fn
PD_Tn
PD_Ln
Pharmacokinetic / Pharmacodynamic
PKPD_Fn
PKPD_Tn
PK/PD_Ln
NOTES: 

Non-Standard displays are indicated in the ‘IDSL /  Example Shell’ or ‘Programming Notes’ column as ‘[Non-
Standard] + Reference.’


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12.10.3.
Deliverables
Delivery
Description
SAC
Final Statistical Analysis Complete


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12.10.4.
Study Population Tables
Study Population Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Subject Disposition
1.01.
mITT
ES8 
Summary of Subject Status and Reason for Study Withdrawal
ICH E3, FDAAA, EudraCT
SAC
1.02.
mITT
SD4
Summary of Treatment Status and Reasons for Discontinuation 
of Study Treatment
ICH E3
SAC
1.03.
mITT
ES4
Summary of Subject Disposition at Each Study Epoch
ICH E3
SAC
1.04.
ASE
ES6
Summary of Screening/Run-in Status and Reasons for 
Screen/Run-in Failure
Journal Requirements
SAC
1.05.
ASE
NS1
Summary of Number of Subjects by Country and Site ID
EudraCT/Clinical Operations
SAC
1.06.
mITT
NS1
Summary of Number of Subjects by Country and Site ID
EudraCT/Clinical Operations
SAC
Protocol Deviation
1.07.
mITT
DV1
Summary of Important Protocol Deviations
ICH E3
SAC
1.08.
mITT
IE1
Summary of Inclusion/ Exclusion Deviations 
ICH E3
SAC
Population Analysed
1.09.
Enrolled
SP1
Summary of Study Populations 
IDSL. Footnote on population summary 
table that Safety and mITT populations 
are the same.
SAC
Demographic and Baseline Characteristics
1.10.
mITT
DM1 
Summary of Demographic Characteristics
ICH E3, FDAAA, EudraCT
SAC
1.11.
Enrolled
DM11
Summary of Age Ranges
EudraCT
SAC
1.12.
mITT
DM5
Summary of Race and Racial Combinations
ICH E3, FDA, FDAAA, EudraCT
SAC


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Study Population Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Prior and Concomitant Medications
1.13.
mITT
Summary of Anti-Fungal Medications at Screening
SAC
1.14.
mITT
MH4
Summary of Current Medical Conditions
ICH E3 
SAC
1.15.
mITT
MH4
Summary of Past Medical Conditions
ICH E3 
SAC
1.16.
mITT
POP_T01 
Summary of Disease Duration and Exacerbation History
SAC
1.17.
mITT
CM1
Summary of On-treatment Concomitant Medications
ICH E3
SAC
1.18.
mITT
CM1
Summary of On-treatment Asthma Concomitant Medications
ICH E3
SAC


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12.10.5.
Efficacy Tables
Efficacy: Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Primary Efficacy: Blood Eosinophils and FeNO
2.01.
mITT
EX1 
Summary of Exposure to Study Treatment
ICH E3
SAC
2.02.
mITT
Summary of Raw and Change from Baseline in Blood 
Eosinophils 
SAC
2.03.
mITT
Summary of Raw and Change from Baseline in FeNO 
SAC
Secondary Efficacy: Spirometry
2.04.
mITT
Summary of Raw and Change from Baseline in FEV1
SAC
Secondary Efficacy: Patient Reported Outcomes
2.05.
mITT
Summary of Raw and Change from Baseline in ACQ-5 Total 
Score 
SAC
2.06.
mITT
Summary of ACQ-5 Responders
SAC
2.07.
mITT
Summary of Raw and Change from Baseline in AQLQ Total 
Score
SAC
2.08.
mITT
Summary of AQLQ Responders
SAC


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12.10.6.
Safety Tables
Safety: Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Adverse Events (AEs)
3.01.
SAFF
SAFE_T01
Overview of On-treatment Adverse Events During the Study
SAC
3.02.
SAFF
AE1
Summary of All On-treatment Adverse Events by System Organ 
Class and Preferred Term
ICH E3
SAC
3.03.
SAFF
AE1
Summary of All On-treatment Serious Adverse Events by 
System Organ Class and Preferred Term
ICH E3
SAC
3.04.
SAFF
AE3
Summary of All On-treatment Adverse Events by Overall 
Frequency
ICH E3, summarise by PT
SAC
Laboratory: Chemistry 
3.05.
SAFF
LB1
Summary of Worst Case Chemistry Results Relative to Normal 
Range Post-Baseline Relative to Baseline
ICH E3
SAC
Laboratory: Hematology and Cardiac Markers
3.06.
SAFF
LB1
Summary of Worst Case Hematology and Cardiac Markers 
Results Relative to Normal Range Post-Baseline Relative to 
Baseline
ICH E3
SAC


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Safety: Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
ECG and Holter
3.07.
SAFF
EG1
Summary of ECG Findings 
IDSL
SAC
3.08.
SAFF
EG11
Summary of Maximum Increase in QTcF Values Post-Baseline 
Relative to Baseline by Category
IDSL
SAC
3.09.
SAFF
HM1
Summary of Holter Interpretations
IDSL
SAC
Vital Signs
3.10.
SAFF
VS1
Summary of Vital Signs
ICH E3
SAC
3.11.
SAFF
VS1
Summary of Change from Baseline in Vital Signs
ICH E3
SAC
3.12.
SAFF
VS1
Summary of Change from Pre-dose to Post-dose in Vital Signs
ICH E3
SAC


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12.10.7.
Pharmacokinetic Tables
Pharmacokinetic: Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Secondary: Pharmacokinetic
4.01.
PK
Summary of GSK3772847 Serum Pharmacokinetic 
Concentration-Time Data (ug/ml)
SAC
4.02.
PK
Summaries of the Incidence of and Titres of Anti-
GSK3772847 Antibodies
SAC
12.10.8.
Pharmacodynamic and Biomarker Tables
Pharmacodynamic and Biomarker: Tables
No.
Population
IDSL /
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Secondary Pharmacodynamic: Free and Total SST2
6.01.
mITT
Summary of Raw and Percentage Change from Baseline in Free 
Soluble ST2 concentration (ug/mL) (On-treatment)
SAC
6.02.
mITT
Summary of Raw and Percentage Change from Baseline in 
Total Soluble ST2 concentration (ng/mL) (On-treatment)
SAC


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12.10.9.
ICH Listings
ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Subject Disposition
1.
Screened
ES7
Listing of Reasons for Screen and Run-in Failure
Journal Guidelines
SAC
2.
mITT
ES2 / ES3
Listing of Reasons for Study Withdrawal
ICH E3
SAC
3.
mITT
SD2/SD3
Listing of Reasons for Study Treatment Discontinuation
ICH E3
SAC
4.
mITT
BL1 / BL2
Listing of Participants for Whom the Treatment Blind was Broken
ICH E3
SAC
5.
mITT
TA1 / CP_RD1x
Listing of Randomised and Actual Treatments
IDSL
SAC
Protocol Deviations
6.
mITT
DV2
Listing of Important Protocol Deviations 
ICH E3
SAC
7.
mITT
IE3 
Listing of Subjects with Inclusion/Exclusion Criteria Deviations
ICH E3
SAC
Populations Analysed
8.
mITT
SP3
Listing of Participants Excluded from Any Population
ICH E3.
SAC
Demographic and Baseline Characteristics
9.
mITT
DM2
Listing of Demographic Characteristics
ICH E3
SAC
10.
mITT
DM9 
Listing of Race
ICH E3
SAC


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ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Prior and Concomitant Medications
11.
mITT
CP_CM3
Listing of Concomitant Medications
IDSL
SAC
Exposure and Treatment Compliance
12.
mITT
EX3
Listing of Exposure Data
ICH E3
SAC
Adverse Events
13.
SAFF
AE8 
Listing of All Adverse Events
ICH E3
SAC
14.
SAFF
AE7
Listing of Subject Numbers for Individual Adverse Events
ICH E3
SAC
15.
SAFF
AE8
Listing of Adverse Events Leading to Withdrawal from Study / 
Permanent Discontinuation of Study Treatment
ICH E3
SAC
16.
SAFF
AE2
Listing of Relationship Between Adverse Event System Organ 
Classes, Preferred Terms, and Verbatim Text
IDSL
SAC
Serious and Other Significant Adverse Events
17.
SAFF
AE8
Listing of Fatal Serious Adverse Events
ICH E3
SAC
18.
SAFF
AE8
Listing of Non-Fatal Serious Adverse Events
ICH E3
SAC
19.
SAFF
AE14
Listing of Reasons for Considering as a Serious Adverse Event
ICH E3
SAC
20.
SAFF
AE8
Listing of Serious Adverse Events Leading to Withdrawal from 
Study / Permanent Discontinuation of Study Treatment
ICH E3
SAC
21.
SAFF
AE8
Listing of Adverse Events of Special Interest
ICH E3
SAC
Hepatobiliary (Liver)
22.
SAFF
MH2
Listing of Medical Conditions for Participants with Liver Stopping 
Events
IDSL
SAC
23.
SAFF
SU2
Listing of Substance Use for Participants with Liver Stopping 
Events
IDSL
SAC


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ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
All Laboratory
24.
SAFF
LB5 / LB6
Listing of All Laboratory Data for Participants with Any Value 
Outside Normal Range
ICH E3
SAC
25.
SAFF
LB14
Listing of Laboratory Data with Character Results
ICH E3
SAC
ECG
26.
SAFF
EG5
Listing of All ECG Findings for Participants with an Abnormal 
ECG Finding
IDSL
SAC
Holter
27.
SAFF
MH6
Listing of Holter R-on-T Beat Data 
IDSL
SAC
28.
SAFF
MH7
Listing of Holter {Supraventricular} {Ventricular} Event Data 
IDSL, Update title as appropriate based 
on data
SAC
29.
SAFF
MH8
Listing of Holter {Sustained} {Non-sustained} {Supraventricular} 
{Ventricular} Run
IDSL, Update title as appropriate based 
on data
SAC
30.
SAFF
MH9
Listing of Holter Atrial {Fibrillation} {Flutter} Data 
IDSL, Update title as appropriate based 
on data
SAC
31.
SAFF
MH10
Listing of Holter Abnormalities
IDSL
SAC
Vital Signs
32.
SAFF
VS4 
Listing of All Vital Signs Data 
IDSL
SAC
Primary Endpoint Data: Blood Eosinophils and FeNO
33.
mITT
Listing of Blood Eosinophils
SAC
34.
mITT
Listing of FeNO
SAC


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12.10.10. Non-ICH Listings
Non-ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Liver Events: Note only produced if there is a Liver Event
35.
SAFF
Patient Profile
Listing of Liver Events
SAC
36.
SAFF
Patient Profile
Listing of Liver Event Information for RUCAM Score
SAC
37.
SAFF
Patient Profile
Listing of Liver Biopsy
SAC
38.
SAFF
Patient Profile
Listing of Liver Imaging Details
SAC
Cardiovascular Events: Note only produced if there is a Cardiovascular Event
39.
SAFF
Patient Profile
Listing of Myocardial infarction/unstable angina
SAC
40.
SAFF
Patient Profile
Listing of Congestive heart failure
SAC
41.
SAFF
Patient Profile
Listing of Arrhythmias
SAC
42.
SAFF
Patient Profile
Listing of Valvulopathy
SAC
43.
SAFF
Patient Profile
Listing of Pulmonary hypertension
SAC
44.
SAFF
Patient Profile
Listing of Cerebrovascular events/stroke and transient ischemic 
attack
SAC
45.
SAFF
Patient Profile
Listing of Peripheral arterial thromboembolism
SAC
46.
SAFF
Patient Profile
Listing of Deep venous thrombosis/pulmonary embolism
SAC
47.
SAFF
Patient Profile
Listing of Revascularisation
SAC
48.
SAFF
Patient Profile
Listing of Deaths
SAC