Conditions: Asthma
Keywords: Severe asthma Safety GSK3772847 Efficacy
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 165
Healthy volunteers: no

Brief summary:
GSK3772847, an anti-interleukin (IL)33 receptor monoclonal antibody, is a novel treatment for asthma. This is a phase 2a study which aims to evaluate efficacy, safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of GSK3772847 in subjects with moderately severe asthma. The study will be conducted in 4 phases including screening, run-in phase, treatment phase and follow-up. In treatment phase, eligible subjects will be randomized to receive either GSK3772847 or placebo administered via intravenous (IV) route every 4 weeks in addition to open-label background therapy of fluticasone propionate/ salmeterol (FP/Sal) 500/50 micrograms (mcg) twice daily. During the treatment phase, the background therapy will be switched to FP 500 mcg for 2 weeks and the dose of FP will be reduced by approximately 50 percent at every 2 weeks until complete FP discontinuation. The total duration of study will be approximately 33 weeks and approximately 165 subjects with moderately severe asthma who are maintained on high-dose of inhaled corticosteroids/ Long-Acting Beta-2-Agonists (ICS/LABA) will be randomized.

Detailed description:

Arms:
arm 1: Eligible subjects will receive GSK3772847 once every 4 weeks via IV route along with 500/50 mcg FP/Sal twice daily for first 2 weeks and dose of FP was reduced by approximately 50 percent at every 2 weeks until complete FP discontinuation. arm 2: Eligible subjects will receive placebo once every 4 weeks via IV route along with 500/50 mcg FP/Sal twice daily for first 2 weeks and dose of FP was reduced by approximately 50 percent at every 2 weeks until complete FP discontinuation.

Interventions: intervention 1: GSK3772847 intervention 2: Placebo intervention 3: Fluticasone propionate/salmeterol intervention 4: Fluticasone propionate
Intervention descriptions: intervention 1: GSK3772847 10 mg/kg will be administered as IV infusion once every 4 weeks to randomized subjects. intervention 2: Placebo sterile normal saline will be administered as IV infusion once every 4 weeks to randomized subjects. intervention 3: FP/Sal 500/50 mcg will be administered via inhalation route twice daily to all subjects. intervention 4: FP 500, 250, 100 or 50 mcg will be administered via inhalation route twice daily to all subjects.

Protocol document:
Prot_000.pdf: 
2017N311825_02
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GlaxoSmithKline group of companies
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TITLE PAGE
Protocol Title: A randomized, double-blind, parallel group, multicenter, stratified study 
evaluating the efficacy and safety of repeat doses of GSK3772847 compared with 
placebo in participants with moderately severe asthma
Protocol Number: 207597/02
Short Title: A study to evaluate the effect of GSK3772847 in patients with moderately
severe asthma.
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
 MB.BS 
Email: 
Tel: 
Regulatory Agency Identifying Number(s): IND number 134366, EudraCT number: 
2017-001072-34
Approval Date: 13-SEP-2017
Copyright 2017 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
13-SEP-2017
Amendment 1
02-JUN-2017
Original Protocol-2017N311825_00
06-MAR-2017
Amendment 2: 13-SEPTEMBER-2017
Overall Rationale for the Amendment: To add more information on the risk:benefit 
section and the study design justification sections. To address clarifications regarding the 
unblinding of treatment in case of emergency. To clarify that rechallenge is not allowed 
once the treatment discontinuation criteria are met. Also, a few typographical errors were 
corrected.
Section # and 
Name
Description of Change
Brief Rationale
Section 2 
Schedule of 
Activities
In SoA Table 2, corrected Week 
8 as Day 57, rather than Day 49.
Typographical error
Section 3.3.2 
Benefit 
Assessment
Clarified that there is no 
marketed treatment for non T2-
driven severe asthma.
To provide additional information on the 
risk:benefit assessment.
Section 3.3.2 
Benefit 
Assessment
Included more information on the 
plan for monitoring the 
participants’ asthma status.
To provide additional information on the 
risk:benefit assessment.
Section 3.3.2 
Benefit 
Assessment
Included that ICS titration design 
is recommended per GINA 
guidelines to identify the lowest 
effective dose.
To provide additional information on the 
risk:benefit assessment.
Section 5.1 Overall 
study design
Corrected the visit of the last 
blinded study treatment in the 
parentheses as Visit 9, rather 
than Visit 10. The last dose of 
blinded study treatment is Visit 9 
and not Visit 10.
Typographical error
Section 5.4 
Scientific Rationale 
for Study Design
Clarified that loss of asthma 
control as a result of ICS titration 
could be completely 
compensated by re-
establishment of the previous 
To provide additional justification on the 
selected study design.


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Section # and 
Name
Description of Change
Brief Rationale
treatment regimen with the 
participant achieving the same 
level of asthma control that 
existed prior to study entry.
Section 7.4
Blinding
Clarified that the investigator has 
the sole responsibility for
unblinding in case of emergency 
and that the investigator should 
try to contact GSK prior to 
unblinding only if this does not 
delay emergency treatment of the 
participant
To be consistent with EMA guidelines on 
treatment unblinding in case of 
emergency
Section 8.1 
Treatment 
discontinuation 
criteria
Removed the parentheses 
specifying at which visits 
abnormal ECGs would lead to 
treatment discontinuation. 
Abnormal ECGs at any visit 
would lead to treatment 
discontinuation. The visit 
numbers in the parentheses were 
included in error.
Typographical error
Section 8.1.3 
Rechallenge
Clarified that rechallenge is not 
allowed after a participant has 
met any of the treatment 
discontinuation criteria
To clarify that rechallenge is not allowed 
if any of the treatment discontinuation 
criteria are met.
Section 10.3 
Populations for 
Analysis
Removed the definition of the 
Safety population 
The modified intention to treat population
(mITT) is the same as the safety 
population.
Section 10.4 
Statistical Analyses
Clarified that the efficacy 
analyses and the safety analyses 
will be performed on the mITT 
population
The modified intention to treat population 
is the same as the safety population.
Section 11 
References
Included the reference on the 
paper by Matz J 2001 and McIvor 
RA, 1998.
To provide the reference paper on the 
updated information on loss of asthma 
control in Section 5.4.


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TABLE OF CONTENTS
PAGE
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE.....................................3
1.
SYNOPSIS...............................................................................................................8
2.
SCHEDULE OF ACTIVITIES (SOA).......................................................................13
3.
INTRODUCTION....................................................................................................19
3.1.
Study Rationale ..........................................................................................19
3.2.
Background ................................................................................................19
3.3.
Benefit/Risk Assessment ............................................................................20
3.3.1.
Risk Assessment .........................................................................21
3.3.2.
Benefit Assessment.....................................................................27
3.3.3.
Overall Benefit:Risk Conclusion...................................................28
4.
OBJECTIVES AND ENDPOINTS...........................................................................28
5.
STUDY DESIGN ....................................................................................................30
5.1.
Overall Design ............................................................................................30
5.2.
Number of Participants ...............................................................................32
5.3.
Participant and Study Completion...............................................................33
5.4.
Scientific Rationale for Study Design ..........................................................33
5.5.
Dose Justification........................................................................................34
6.
STUDY POPULATION...........................................................................................36
6.1.
Inclusion Criteria.........................................................................................36
6.2.
Exclusion Criteria........................................................................................37
6.3.
Randomization Inclusion Criteria ................................................................41
6.4.
Randomization Exclusion Criteria ...............................................................41
6.5.
Lifestyle Restrictions...................................................................................42
6.6.
Pre-Screening/Screening/Run-in/Randomization Failures ..........................42
7.
TREATMENTS.......................................................................................................43
7.1.
Treatments Administered............................................................................44
7.1.1.
Description of Albuterol/Salbutamol .............................................45
7.1.2.
DISKUS Return............................................................................45
7.2.
Dose Modification .......................................................................................46
7.3.
Method of Treatment Assignment ...............................................................46
7.4.
Blinding.......................................................................................................46
7.5.
Preparation/Handling/Storage/Accountability..............................................47
7.6.
Treatment Compliance................................................................................49
7.7.
Concomitant Therapy..................................................................................49
7.7.1.
Permitted Non-asthma Medications .............................................49
7.7.2.
Prohibited Medications and Non-Drug Therapies.........................49
7.8.
Treatment after the End of the Study ..........................................................50
8.
DISCONTINUATION CRITERIA.............................................................................50
8.1.
Discontinuation of Study Treatment ............................................................50
8.1.1.
Liver Chemistry Stopping Criteria ................................................51


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8.1.2.
QTc Stopping Criteria ..................................................................52
8.1.3.
Rechallenge.................................................................................53
8.1.3.1.
Study Treatment Restart or Rechallenge....................53
8.2.
Withdrawal from the Study..........................................................................53
8.3.
Lost to Follow Up........................................................................................54
9.
STUDY ASSESSMENTS AND PROCEDURES .....................................................54
9.1.
Efficacy Assessments.................................................................................54
9.1.1.
Questionnaires ............................................................................55
9.1.1.1.
Asthma Control Questionnaire ACQ-5........................55
9.1.1.2.
St. George’s Respiratory of Life Questionnaire 
(SGRQ) ......................................................................55
9.1.2.
Daily Diaries ................................................................................55
9.1.2.1.
Night-time Awakening, Daytime Asthma 
Symptom Questions ...................................................56
9.1.2.2.
Morning and Evening Home PEF ...............................56
9.1.2.3.
Alerts..........................................................................56
9.1.3.
Pulmonary Function Test.............................................................57
9.1.3.1.
Spirometry..................................................................57
9.1.3.2.
Reversibility................................................................57
9.1.4.
Fractional Exhaled Nitric Oxide (FeNO) .......................................58
9.1.5.
Review of Loss of Asthma Control...............................................58
9.2.
Adverse Events...........................................................................................58
9.2.1.
Time Period and Frequency for Collecting AE and SAE 
Information...................................................................................59
9.2.2.
Method of Detecting AEs and SAEs.............................................59
9.2.3.
Follow-up of AEs and SAEs.........................................................60
9.2.4.
Regulatory Reporting Requirements for SAEs .............................60
9.2.5.
Cardiovascular and Death Events................................................60
9.2.6.
Pregnancy ...................................................................................61
9.3.
Treatment of Overdose...............................................................................61
9.4.
Safety Assessments ...................................................................................61
9.4.1.
Physical Examinations.................................................................61
9.4.2.
Vital Signs....................................................................................62
9.4.3.
Electrocardiograms......................................................................62
9.4.4.
Continuous ambulatory ECG (Holter)...........................................62
9.4.5.
Clinical Safety Laboratory Assessments ......................................63
9.5.
Pharmacokinetics .......................................................................................63
9.6.
Pharmacodynamics ....................................................................................63
9.7.
Genetics .....................................................................................................64
9.8.
Biomarkers .................................................................................................64
9.8.1.
Exploratory Biomarkers................................................................64
9.8.1.1.
Sputum Sub-Study .....................................................64
9.8.2.
Immunogenicity Assessments......................................................64
9.9.
Health Economics OR Medical Resource Utilization and Health 
Economics..................................................................................................65
10. STATISTICAL CONSIDERATIONS........................................................................65
10.1.
Hypotheses.................................................................................................65
10.2.
Sample Size Determination ........................................................................65
10.3.
Populations for Analyses ............................................................................66
10.4.
Statistical Analyses.....................................................................................67


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10.4.1.
Efficacy Analyses.........................................................................67
10.4.2.
Safety Analyses...........................................................................69
10.4.3.
Pharmacokinetic Analyses...........................................................70
10.4.4.
Pharmacodynamic Analyses........................................................70
10.4.5.
Other Analyses ............................................................................70
10.4.6.
Interim Analyses ..........................................................................70
11. REFERENCES.......................................................................................................72
12. APPENDICES........................................................................................................74
12.1.
Appendix 1: Abbreviations and Trademarks................................................74
12.2.
Appendix 2: Clinical Laboratory Tests.........................................................77
12.3.
Appendix 3: Study Governance Considerations..........................................79
12.4.
Appendix 4: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .......................................83
12.5.
Appendix 5: Contraceptive Guidance and Collection of Pregnancy 
Information..................................................................................................89
12.6.
Appendix 6: Genetics..................................................................................92
12.7.
Appendix 7: Liver Safety: Required Actions and Follow-up 
Assessments ..............................................................................................93
12.8.
Appendix 8: Protocol Amendment History...................................................96


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1.
SYNOPSIS
Protocol Title: A randomized, double-blind, parallel group, multicenter, stratified study 
evaluating the efficacy and safety of repeat doses of GSK3772847 compared with 
placebo in participants with moderately severe asthma.
Short Title: A study to evaluate the effect of GSK3772847 in patients with moderately
severe asthma.
Rationale:
GSK3772847 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 (FTIH) study has completed dosing (final clinical study report is pending).
The safety information from this study is included in the investigator brochure
(GlaxoSmithKline Document Number 2017N316832_00). There are no efficacy data 
available to date. 
The present study is the first GSK sponsored study with GSK3772847. It is a Phase IIa / 
proof of concept study to investigate efficacy, safety and tolerability, pharmacokinetic 
(PK) and pharmacodynamic (PD) profiles of GSK3772847 in participants with 
moderately severe asthma. The study will use an inhaled steroid titration design in order 
to evaluate whether GSK3772847 maintains protection of asthma control. The design of 
steroid titration (oral or inhaled) in participants with asthma has been used in various 
studies with different investigational products, in which changes in the level of asthma 
control were induced by medication withdrawal. This design may not reflect real world 
fluctuations in asthma control; however, studies with the design of steroid titration have 
shown the ability to assess effects of a potential treatment on changes in asthma control
in a relatively short period of time, before further investigations are conducted in longer 
term studies.


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Objectives and Endpoints:
Objectives
Endpoints
Primary

To evaluate the efficacy of GSK3772847, compared 
with placebo, administered intravenously every 4 
weeks for 12 weeks (Week 0 – Week 12, 4 doses in 
total) in participants with moderately severe asthma.
Primary – Proportion of participants with loss of asthma 
control over Weeks 0-16 where ‘loss of asthma control’ is 
defined as at least one of the following:

Asthma Control Questionnaire (ACQ-5) score 
increase from baseline (measured at the end of Run-
in) ≥0.5 point or

Pre-bronchodilator Forced expiratory volume in 1 
second (FEV1) decrease from baseline (measured 
at the end of Run-in) >7.5 % or

Inability to titrate inhaled corticosteroid according to 
the pre-defined schedule (Section 5.1) or

A clinically significant asthma exacerbation (requiring 
oral corticosteroid [OCS] and/or hospitalisation).
Secondary

To evaluate other aspects of efficacy of 
GSK3772847 compared with placebo in participants 
with moderately severe asthma.
Other efficacy endpoints (at or by Week 16):

Proportion of participants with a ≥0.5 point. ACQ-5 
score increase from baseline.

Proportion of participants who have pre-
bronchodilator FEV1 decrease from baseline 
(measured at the end of Run-in) >7.5 %.

Proportion of participants where inhaled 
corticosteroids (ICS) cannot be titrated in 
accordance with the pre-defined schedule.

Proportion of participants who have a significant 
asthma exacerbation (requiring OCS and/or 
hospitalisation).

Time to loss of asthma control.

Proportion of participants with a clinically significant 
asthma exacerbation or inability to titrate ICS 
according to the pre-defined schedule

The incidence, mean rate, and total number per 
participant of hospitalisations or Emergency Room 
(ER) visits during the study treatment period.

Change from baseline in ACQ-5 absolute score at 
each week from Week 1 to Week 16.

Proportion of participants with ≥0.5 point ACQ-5 
score decrease from baseline (responder) at each 
week from Week 1 to Week 16.

Change from baseline in SGRQ total score at Weeks 
4, 8, 12 and 16.

Proportion of St. George’s Respiratory Questionnaire 
(SGRQ) responders (at least a 4 unit improvement 
from baseline) at Weeks 4, 8, 12 and 16.

Change from baseline in pre-bronchodilator FEV1 at 
Weeks 2, 4, 6, 8, 10, 12, 14, 16.

Change from baseline in mean morning peak 
expiratory flow (PEF) and mean evening PEF over 
each four weeks of the 16 week treatment period.

Change form baseline in mean daytime asthma 
symptom score over each four weeks of the 16 week
treatment period.


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Objectives
Endpoints

Change from baseline in rescue medication use 
(albuterol/salbutamol): mean number of inhalations 
per day over each four weeks of the 16 week 
treatment period.

Changes from baseline in night-time awakenings
due to asthma symptoms requiring rescue 
medication use over each four weeks of the16 week 
treatment period.

Change from baseline in fractional exhaled nitric 
oxide (FeNO) at each week measured.

To evaluate the safety and tolerability of 
GSK3772847, compared with placebo administered 
intravenously every 4 weeks for 12 weeks (Week 0-
12, 4 doses in total) in participants with moderately
severe asthma. 

Incidence and frequency of adverse events (AEs) 
and serious adverse events (SAEs).

Change from baseline in vital signs at weeks 1, 2, 
4, 6, 8, 10, 12, 14, 16, 20, 24 and 28.

Change between post-dose and pre-dose in vital 
signs at weeks 0, 4, 8 and 12.

Change from baseline in 12-lead electrocardiogram 
(ECG) measurements at weeks 4, 8, 12 and 16.

Change between post-dose and pre-dose in 12-
lead ECG measurements at weeks 0, 4, 8 and 12.

Change from baseline in 24 hours Holter 
measurements at weeks 4 and 12.

Change from baseline in clinical chemistry at 
weeks 2, 4, 8, 12, 16 and 28.

Change from baseline in hematology and cardiac 
markers at weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 
28. 

Incidence of and titres of anti- GSK3772847 
antibodies at weeks 2, 4, 8, 12, 16, 20, 24 and 28.

To evaluate the pharmacokinetics (PK) of 
GSK3772847 in participants with moderately severe 
asthma.

Serum concentrations of GSK3772847 at weeks 2, 
4, 8, 12, 16, 20, 24 and 28.

To evaluate the pharmacodynamics (PD) of 
GSK3772847 in participants with moderately severe 
asthma.

Free and total soluble ST2 levels in serum at 
weeks 2, 4, 8, 12, 16, 20, 24 and 28.


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Overall Design:
This is a Phase IIa, multicenter, randomized, placebo-controlled, double-blind, stratified, 
parallel group study in participants with moderately severe asthma.
There will be a 2-week Run-in period following Screening (Visit 1). Eligible participants 
will be randomized at the end of the Run-in period (Visit 2). Randomization will be 
stratified based on participants’ baseline peripheral blood eosinophil count aiming for at 
least 30% of participants with eosinophil count <150 cells /L, which is measured at 
Screening.
Number of Participants:
Approximately 300 participants with moderately severe asthma who are maintained on 
high-dose ICS/LABA will be screened to ensure 148 randomized (74 on GSK3772847, 
74 on placebo) participants and 140 evaluable participants. High-dose ICS is defined as 
fluticasone propionate 500 mcg twice daily (i.e. 1000 mcg /day) or equivalent. For the 
purpose of this study an evaluable participant is defined as a participant who completes 
the Week 16 clinic visit whilst remaining on investigational product (IP) or who 
withdraws from IP having met the primary endpoint. 
Treatment Groups and Duration:
When required, a pre-screening visit (Visit 0) can be scheduled for signing the informed 
consent, up to 2 weeks prior to Screening (Visit 1). The pre-screening visit can also occur 
on the same day as the Screening visit. Participants who meet the eligibility criteria at 
Screening (Visit 1) will withdraw their regular ICS/LABA treatment for asthma and enter 
a two-week Run-in period during which they will receive open label background therapy 
of fluticasone propionate (FP)/salmeterol (Sal) 500/50 mcg twice daily (BID). At the end 
of the Run-in period at Visit 2 (Week 0), participants who meet pre-defined 
randomization criteria will be randomized in a 1:1 ratio to enter a double-blind treatment 
period and receive the following study treatment every 4 weeks for 12 weeks (Week 0, 4, 
8 and 12) while initially remaining on the open label background therapy of FP/Sal 
500/50 mcg BID at Randomization:

GSK3772847 administered intravenously or

Placebo administered intravenously
At Visit 4, two weeks after Randomization, the open label background therapy will be 
switched from FP/Sal 500/50 mcg BID to FP 500 mcg BID for 2 weeks. Visit 4 will be 
the beginning of a six week FP titration period. Every two weeks for the next six weeks 
the dose of FP will be reduced by approximately 50 % (i.e. FP 250 mcg BID at Visit 5 for 
2 weeks, FP 100 mcg BID at Visit 6 for 2 weeks, then FP 50 mcg BID at Visit 7 for 2 
weeks) until complete discontinuation at Visit 8, provided that the participant does not 
meet any of the loss of asthma control criteria. If any of the pre-defined criteria for loss of 
asthma control are met during the Treatment period, participants will be withdrawn from 
the investigational product (IP) and should resume regular treatment for their asthma, as 
determined by the investigator. 


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An End of Treatment Phase (ETP) Visit will be performed 4 weeks after the final dose of 
the blinded study treatment is administered at Week 12. 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. 
Participants should resume regular treatment for their asthma, as determined by the 
investigator, after protocol defined study assessments are completed. Three Follow-up 
visits will be performed 4, 8, and 12 weeks (Week 20, Week 24, and Week 28) after the 
ETP/EW Visit for safety assessments.
Following randomization participants will return to the clinic at least every 2 weeks for 
scheduled FP dose titration and assessment of asthma control until the last dose of 
blinded study treatment (Visit 9). Albuterol/salbutamol will be provided for symptomatic 
relief to be used on an as needed basis from Screening through to the ETP visit. 
The maximum total duration of the study is approximately 33 weeks.


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2.
SCHEDULE OF ACTIVITIES (SOA)
Procedure
Pre-
Screen
ing1
Screen 
Run-in
Treatment Period
Follow-up Period2
(3 days)
Notes
2 days
3 days
Visit 
0
1
23
3
4
5
6
7
8
9
10
11
(ETP 
or 
EW)
12
13
14
1.Pre-screening and screening 
can occur on the same day 
2. FU period to start 4 weeks 
after ETP or EW visit.
3. Visit 2 = Day 1 (first dose of 
IP).
Week
-4~-2
-2
0
1
2
4
6
8
10
12
14
16
20
24
28
Study Day
-28~-14
-14
1
8
15
29
43
57
71
85
99
113
Informed consent 
(ICF)
X
Genetic ICF
X
ICF for sputum
X
Inclusion and 
exclusion criteria
X
Randomisation 
Criteria
X
Demography
X
Full physical exam 
including height and 
weight
X
Medical history 
(includes substance 
abuse)
X
Substances [Drugs, Alcohol, 
tobacco] and family history of 
premature CV disease]):
[including cardiovascular 
medical history]


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Procedure
Pre-
Screen
ing1
Screen 
Run-in
Treatment Period
Follow-up Period2
(3 days)
Notes
2 days
3 days
Visit 
0
1
23
3
4
5
6
7
8
9
10
11
(ETP 
or 
EW)
12
13
14
1.Pre-screening and screening 
can occur on the same day 
2. FU period to start 4 weeks 
after ETP or EW visit.
3. Visit 2 = Day 1 (first dose of 
IP).
Week
-4~-2
-2
0
1
2
4
6
8
10
12
14
16
20
24
28
Study Day
-28~-14
-14
1
8
15
29
43
57
71
85
99
113
Laboratory
Laboratory 
assessments
X1, 2
X1
X
X1
X1
X
X1
X
X1
X
X1
X1
Haematology (including 
eosinophil count) and cardiac
markers measured at all clinic 
visits.
1. Clinical chemistry (including 
liver chemistry).
2. Routine urinalysis at 
screening (Visit 1)
Pregnancy test1
X2
X3
X3
X3
X3
X
X
X
X
1. Test for women with child 
bearing potential. 
2. Serum pregnancy test at 
V0/V1.
3. Test to be performed pre-
dose during the treatment 
period.
[HIV, Hep B and Hep 
C screen]
X
A confirmatory negative 
Hepatitis C RNA test must be 
obtained, to be able to enrol 
participants with positive 
Hepatitis C antibody due to 
prior resolved disease. If test 
has been performed within 3 
months prior to first dose of 
study treatment, testing at 
screening is not required.


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Procedure
Pre-
Screen
ing1
Screen 
Run-in
Treatment Period
Follow-up Period2
(3 days)
Notes
2 days
3 days
Visit 
0
1
23
3
4
5
6
7
8
9
10
11
(ETP 
or 
EW)
12
13
14
1.Pre-screening and screening 
can occur on the same day 
2. FU period to start 4 weeks 
after ETP or EW visit.
3. Visit 2 = Day 1 (first dose of 
IP).
Week
-4~-2
-2
0
1
2
4
6
8
10
12
14
16
20
24
28
Study Day
-28~-14
-14
1
8
15
29
43
57
71
85
99
113
Genetic blood sample 
– Pre dose
X
Pharmacogenetic sample may 
be drawn any time from Visit 2 
onwards. Informed consent for 
optional substudies e.g. 
genetics must be obtained
before collecting a sample
Sputum sample 
collection
X
X
X
Pre-dose collection and in a 
sub-set of participants (~50 %) 
at selected sites; also collected 
for EW participants
PK, target 
engagement and 
immunogenicity 
assessments
X
X
X
X
X
X
X
X
X
X
See SoA Table 2 for details
Exploratory 
Biomarkers
X
X
X
Pre dose collection 
Efficacy
Spirometry 
X
X
X
X
X
X
X
X
X
X
Test to be performed pre-dose 
during the Treatment period         
Reversibility
X
FeNO
X
X
X
X
X
X
X
X
X
X
Test to be performed pre-dose
Review loss of 
asthma control 
criteria
X
X
X
X
X
X
X
X
X
It will include review of data to 
determine loss of asthma 
control. See Section 9.1.5.
Dispense eDiary
X


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Procedure
Pre-
Screen
ing1
Screen 
Run-in
Treatment Period
Follow-up Period2
(3 days)
Notes
2 days
3 days
Visit 
0
1
23
3
4
5
6
7
8
9
10
11
(ETP 
or 
EW)
12
13
14
1.Pre-screening and screening 
can occur on the same day 
2. FU period to start 4 weeks 
after ETP or EW visit.
3. Visit 2 = Day 1 (first dose of 
IP).
Week
-4~-2
-2
0
1
2
4
6
8
10
12
14
16
20
24
28
Study Day
-28~-14
-14
1
8
15
29
43
57
71
85
99
113
Collect eDiary
X
Review eDiary
X
X
X
X
X
X
X
X
X
X
Safety
12-lead ECG
X
X1
X1
X1
X1
X
1. Test to be performed pre-
dose and post-dose within 30 
mins after end of infusion.
24 hrs Holter
X
X1
X1
X1
Holter monitor needs to be 
returned to clinic at end of 24-
hour recording (i.e. the next 
day).
1. Place the Holter 30-60 mins 
prior to dosing.
Vital signs
X
X1
X
X
X1
X
X1
X
X1
X
X
X
X
X
1. Test to be performed pre-
dose prior to spirometry and 
post-dose prior the 12 –lead 
ECG.
Dispense paper 
Medical 
Problems/Medication
s Taken worksheet
X
X
X
X
X
X
X
X
X
X
X
X
X
Review paper 
Medical 
Problems/Medication
s Taken worksheet
X
X
X
X
X
X
X
X
X
X
X
X
X


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Procedure
Pre-
Screen
ing1
Screen 
Run-in
Treatment Period
Follow-up Period2
(3 days)
Notes
2 days
3 days
Visit 
0
1
23
3
4
5
6
7
8
9
10
11
(ETP 
or 
EW)
12
13
14
1.Pre-screening and screening 
can occur on the same day 
2. FU period to start 4 weeks 
after ETP or EW visit.
3. Visit 2 = Day 1 (first dose of 
IP).
Week
-4~-2
-2
0
1
2
4
6
8
10
12
14
16
20
24
28
Study Day
-28~-14
-14
1
8
15
29
43
57
71
85
99
113
AE/SAE review
X1
X1
==========================================
X
X
X
1. At V0 and V1 collect only 
SAEs considered as related to 
study participation.
Concomitant 
medication review
X
X
==========================================
X
X
X
Questionnaires
ACQ-5
X
X
After randomization, ACQ5 will 
be completed by the 
participants every 7 days. 
SGRQ
X
X
X
X
X
Study Treatment
Double blind Study 
Treatment (IP)
X
X
X
X
Patients will remain in the clinic 
for monitoring for at least 2 
hours after the end of infusion.
FP/Sal (500/50) 
dispensing
X
X
FP (mcg) dispensing
500
250
100
50
Dispense albuterol 
(as needed)
X
X
X
X
X
X
X
X
X
X
X


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SoA Table 2: Timings of PK, target engagement and immunogenicity samples
Procedure
Treatment Period 
Follow-up2
(3 days)
Notes
2 days
3 days
Visit 
21
3
4
5
6
7
8
9
10
11 
(ETP 
or EW)
12
13
14
1. Visit 2 = Day 1 
(first dose of IP). 
2. FU period to start 
4 weeks after ETP or 
EW visit.
Week
0
1
2
4
6
8
10
12
14
16
20
24
28
Study Day
1
8
15
29
43
57
71
85
99
113
Double blind 
Study 
Treatment 
(IP)
X
X
X
X
PK sample
X2
X
X
X3
X3
X1
X
X
X
X
1. Pre dose and 
post dose.
2. Post dose only.
3. Pre dose only.
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.
Free and total 
sST2
X1
X
X
X3
X3
X1
X
X
X
X
Immunogenicit
y sample
X3
X
X3
X3
X3
X
X
X
X


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3.
INTRODUCTION
3.1.
Study Rationale
GSK3772847 is a human immunoglobulin G2 sigma isotype (IgG2) antibody that binds 
Domain 1 of the cell-surface receptor 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 (FTIH) study has completed dosing (final report is pending). The safety 
information from this study is included in the investigator brochure (IB 
[GlaxoSmithKline Document Number 2017N316832_00]). There are no efficacy data 
available to date. 
The present study is the first GSK sponsored study with GSK3772847. It is a Phase IIa / 
proof of concept study to investigate efficacy, safety and tolerability, pharmacokinetic 
(PK) and pharmacodynamic (PD) profiles of GSK3772847 in participants with 
moderately severe asthma. The study will use an inhaled steroid titration design in order 
to evaluate whether GSK3772847 maintains protection of asthma control. The design of 
steroid titration (oral or inhaled) in participants with asthma has been used in various 
studies with different investigational products, in which changes in the level of asthma 
control were induced by medication withdrawal [Bel, 2014; Wenzel, 2013; Nair, 2009]. 
This design may not reflect real world fluctuations in asthma control; however, studies 
with the design of steroid titration have shown the ability to assess effects of a potential 
treatment on changes in asthma control in a relatively short period of time, before further 
investigations are conducted in longer term studies.
3.2.
Background
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]. 
Current biologic agents approved for the management of patients with severe asthma
have demonstrated efficacy for T2-driven disease (i.e., eosinophilic and/or elevated 
serum immunoglobulin E (IgE) however, there is no currently approved therapy that 
targets non-T2-driven asthma. 
GSK3772847 (formerly CNTO 7160 which was in-licensed from Janssen) is a human 
IgG2  monoclonal antibody (mAb) that binds to the extracellular domain of interleukin-
33 receptor (IL-33R) and neutralizes IL-33-mediated IL-33R signaling. 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].


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IL-33R is expressed on immune cells, such as mast cells, basophils, eosinophils, and T 
helper cell type 2 (Th2) cells and has been shown to be upregulated on macrophages, 
neutrophils, and dendritic cells. It is also expressed on non-immune cells such as 
endothelial, epithelial and smooth muscle cells and fibroblasts. IL-33 has been shown to 
be released after endothelial or epithelial cell damage during trauma, physicochemical / 
microbarometric stress or infection [Arshad, 2016]. IL-33R signalling causes downstream 
production of Type 2 cytokines. The engagement of IL-33R with its ligand IL-33 
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 via blockade of the IL-
33R 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 IV infusion (20 or 100 
mg/kg) and was found to be well-tolerated at both doses. 
Janssen (Study CNTO7160ASH1001) have conducted a Phase I randomized, double-
blind, placebo-controlled, intravenous (IV) single ascending dose study in healthy 
participants and multiple ascending dose study in participants with asthma and 
participants with atopic dermatitis. The study has completed dosing. The final clinical 
study report is still pending. There are no efficacy data available to date.
More information about the non-clinical and clinical studies is available in the
GSK3772847 IB (GlaxoSmithKline Document Number 2017N316832_00).
3.3.
Benefit/Risk Assessment
More detailed information about the known and expected benefits, risks and reasonably 
expected adverse events of GSK3772847 may be found in the IB (GlaxoSmithKline 
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 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 subcutaneous (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 CNTO7160ASH1001, 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 the 
Exclude participants with existing clinically 
significant organic heart disease (e.g. Coronary 
artery disease [CAD], New York Heart 
Association (NYHA) Class III/IV heart failure) and 
abnormal, clinically significant findings from 12-
lead 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 Section 2. 
All cardiac-related AEs will be reviewed by an 
independent safety review committee (iSRC).
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
investigational product. No specific cause was 
identified. Data on this event was reviewed by 
GSK (Internal Cardiac Safety Panel and CMO), 
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 
CNTO7160ASH1001, 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. 


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Dosing was continued as planned, and the dose 
escalated to 10 mg/kg.
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 
(SAD) has shown the most frequent adverse 
events 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 6/24 [40%] 
administered placebo).
Safety data from Part 2 of the Janssen study 
CNTO7160ASH1001 have shown the System-
organ class (SOC) with the most frequent 
adverse events reported was ’Infections and 
infestations’. The number of asthma participants 
experiencing infections and infestations was 
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. 
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 patients with ongoing or recurrent 
infections.


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
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 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
Close monitoring of infection AEs (including 
pneumonia).
Increased risk of hyper-sensitivity, 
anaphylaxis, cytokine release syndrome 
(CRS)
Therapy with other mAbs 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 
patients at doses up to 10 mg/kg (3 doses, once 
every two weeks [q2W] 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 subject will not mount an 
adequate immune response to a vaccine or even 
Non-clinical:
In the monkey 13 week toxicity study no 
GSK3772847-related changes in the T cell 
dependent B cell response (IgM or IgG) was 
observed at doses ≤ 100 mg/kg/week. This data 
is indicative that healthy monkeys were able to 
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
cause the infection the vaccine should protect 
against.
Steroid withdrawal is expected to augment a pro-
inflammatory response in the lung of the patients 
that drives the asthma phenotype.  Vaccination 
will also drive a systemic immune response to 
the pathogen antigen that runs the risk of 
causing some immunomodulation of the lung 
immune responses.  This has been best studied 
in murine models where eosinophilic lung 
inflammation has been suppressed by systemic 
toll-like receptor activation.
mount a response against the antigen challenge 
during GSK3772847 administration at doses 
where near complete inhibition of IL-33 was 
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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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. Currently available marketed biological treatments for the treatment of 
severe asthma are indicated for patients with T2-driven disease, refractory eosinophilic 
asthma, or patients with IgE-mediated asthma. There is currently no marketed treatment 
for non T2-driven severe asthma.
All study participants will receive open label salbutamol/albuterol to use as needed for 
asthma symptom relief from Screening 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, electrocardiogram (ECG), Holter 
monitoring, and clinical laboratory evaluation including liver chemistry and blood 
chemistry panel at a number of clinic visits. 
Participants will be monitored for changes in asthma control through daily use of an 
electronic Diary (eDiary) and twice-daily PEF measurements. The participants will use 
the eDiary to record asthma symptoms, rescue medication use, and nocturnal awakening 
due to asthma symptoms requiring rescue medication use. Alerts, indicative of worsening 
asthma, will be programmed into the eDiary with instructions for the participant to 
contact the investigator and send the data as soon as possible. Data will also be 
transmitted automatically within 24 hours to the centralised server. Email notifications 
will be sent to the investigator as soon as the data is transmitted to the centralized server 
allowing the investigator to contact the participants in order to discuss the participants’ 
symptoms and evaluate whether they experienced loss of asthma control. Participants’ 
health status will also be evaluated by ACQ-5 and SGRQ during the study. With this 
built-in safety monitoring and the frequent visit schedule, a participant will be withdrawn 
from study treatment due to experiencing symptomatic or spirometric changes that meet 
one of the pre-defined loss of asthma control criteria and will be started on alternative 
standard of care therapy. The aim will be to retain participants in the study post 
withdrawal of study medication to follow-up for safety.
Potential participants must be clinically stable on their asthma regimen for at least 4 
months prior to study entry. The Global Initiative for Asthma (GINA), 2016 Guidelines 
advocate attempting to discontinue LABA if possible and step-down therapy once 
adequate asthma control is met. During ICS titration, the lowest effective dose is 
determined at the dose, below which asthma control deteriorates. According to GINA
2016 Guidelines, during this process the patients’ asthma status is closely monitored and 
a clear plan is provided to the patients with instructions on how asthma symptoms should 


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be documented by the patients and the action plan that should be followed if previous 
therapy needs to be resumed. Similarly, in this study, participants will have their asthma 
status documented at study entry, their symptoms and PEF will be monitored twice daily, 
scheduled visits will be arranged and they will have clear instructions as to what actions 
to take with any increase in asthma symptoms. Furthermore, a potential benefit to the 
subjects would be the ascertainment that asthma control might be maintained on a lower 
ICS dose than that which the subject received prior to study entry, with the potential for 
fewer or less severe ICS-related adverse events.
3.3.3.
Overall Benefit:Risk Conclusion
Taking into account the measures taken 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.
4.
OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary

To evaluate the efficacy of GSK3772847, 
compared with placebo, administered 
intravenously every 4 weeks for 12 weeks 
(Week 0 – Week 12, 4 doses in total) in 
participants with moderately severe asthma.
Primary – Proportion of participants with loss of 
asthma control over Weeks 0-16 where ‘loss of 
asthma control’ is defined as at least one of the 
following:

Asthma Control Questionnaire (ACQ-5) score 
increase from baseline (measured at the end of 
Run-in) ≥0.5 point or

Pre-bronchodilator Forced expiratory volume in 
1 second (FEV1) decrease from baseline 
(measured at the end of Run-in) >7.5 % or

Inability to titrate inhaled corticosteroid 
according to the pre-defined schedule (Section 
5.1) or

A clinically significant asthma exacerbation 
(requiring oral corticosteroid [OCS] and/or 
hospitalisation).
Secondary

To evaluate other aspects of efficacy of 
GSK3772847 compared with placebo in 
participants with moderately severe asthma.
Other efficacy endpoints (at or by Week 16):

Proportion of participants with a ≥0.5 point. 
ACQ-5 score increase from baseline.

Proportion of participants who have pre-
bronchodilator FEV1 decrease from baseline 
(measured at the end of Run-in) >7.5 %.

Proportion of participants where inhaled 
corticosteroids (ICS) cannot be titrated in 
accordance with the pre-defined schedule.

Proportion of participants who have a significant 
asthma exacerbation (requiring OCS and/or 
hospitalisation).


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Objectives
Endpoints

Time to loss of asthma control.

Proportion of participants with a clinically 
significant asthma exacerbation or inability to 
titrate ICS according to the pre-defined 
schedule

The incidence, mean rate, and total number per 
participant of hospitalisations or Emergency 
Room (ER) visits during the study treatment 
period.

Change from baseline in ACQ-5 absolute score 
at each week from Week 1 to Week 16.

Proportion of participants with ≥0.5 point ACQ-5 
score decrease from baseline (responder) at 
each week from Week 1 to Week 16.

Change from baseline in SGRQ total score at 
Weeks 4, 8, 12 and 16.

Proportion of St. George’s Respiratory 
Questionnaire (SGRQ) responders (at least a 4 
unit improvement from baseline) at Weeks 4, 8, 
12 and 16.

Change from baseline in pre-bronchodilator 
FEV1 at Weeks 2, 4, 6, 8, 10, 12, 14, 16.

Change from baseline in mean morning peak 
expiratory flow (PEF) and mean evening PEF 
over each four weeks of the 16 week treatment 
period.

Change form baseline in mean daytime asthma 
symptom score over each four weeks of the 16 
week treatment period.

Change from baseline in rescue medication use 
(albuterol/salbutamol): mean number of 
inhalations per day over each four weeks of the 
16 week treatment period.

Changes from baseline in night-time 
awakenings due to asthma symptoms requiring 
rescue medication use over each four weeks of 
the16 week treatment period.

Change from baseline in fractional exhaled nitric 
oxide (FeNO) at each week measured.

To evaluate the safety and tolerability of 
GSK3772847, compared with placebo 
administered intravenously every 4 weeks for 
12 weeks (Week 0-12, 4 doses in total) in 
participants with moderately severe asthma. 

Incidence and frequency of adverse events 
(AEs) and serious adverse events (SAEs).

Change from baseline in vital signs at weeks 
1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24 and 28.

Change between post-dose and pre-dose in 
vital signs at weeks 0, 4, 8 and 12.

Change from baseline in 12-lead 
electrocardiogram (ECG) measurements at 
weeks 4, 8, 12 and 16.

Change between post-dose and pre-dose in 


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Objectives
Endpoints
12-lead ECG measurements at weeks 0, 4, 8 
and 12.

Change from baseline in 24 hours Holter 
measurements at weeks 4 and 12.

Change from baseline in clinical chemistry at 
weeks 2, 4, 8, 12, 16 and 28.

Change from baseline in hematology and 
cardiac markers at weeks 1, 2, 4, 6, 8, 10, 12, 
14, 16 and 28. 

Incidence of and titres of anti- GSK3772847 
antibodies at weeks 2, 4, 8, 12, 16, 20, 24 and 
28.

To evaluate the pharmacokinetics (PK) of 
GSK3772847 in participants with moderately
severe asthma.

Serum concentrations of GSK3772847 at 
weeks 2, 4, 8, 12, 16, 20, 24 and 28.

To evaluate the pharmacodynamics (PD) of 
GSK3772847 in participants with moderately
severe asthma.

Free and total soluble ST2 levels in serum at 
weeks 2, 4, 8, 12, 16, 20, 24 and 28.
Exploratory 

To compare the effect of GSK3772847 with 
placebo on biomarkers in serum and sputum.

Changes from baseline in induced sputum 
biomarkers (subset) at weeks 8 and 16.

Changes from baseline in exploratory serum 
markers at weeks 8 and 16.
5.
STUDY DESIGN
5.1.
Overall Design
This is a Phase IIa, multicenter, randomized, placebo-controlled, double-blind, stratified,
parallel group study.
There will be a 2-week Run-in period following Screening (Visit 1). Eligible participants 
will be randomized at the end of the Run-in period (Visit 2). Randomization will be 
stratified based on participants’ baseline peripheral blood eosinophil count aiming 
for at least 30% of participants with eosinophil count <150 cells/L, which is 
measured at Screening. In order to achieve the stratification balance, as a result of 
participants’ eosinophil count it may be necessary to withdraw participants from 
the study during the Run-in period.
When required, a pre-screening visit (Visit 0) can be scheduled up to 2 weeks prior to 
Screening (Visit 1). The pre-screening visit (Visit 0) can also occur on the same day as 
the Screening visit (Visit 1). Participants who meet the eligibility criteria at Screening 
(Visit 1) will withdraw their regular ICS/ long-acting beta-2-agonists (LABA) treatment 
for asthma and enter a two-week Run-in period during which they will receive open label 
background therapy of fluticasone propionate (FP)/salmeterol (Sal) 500/50 mcg BID. At 


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the end of the Run-in period at Visit 2 (Week 0), participants who meet pre-defined 
randomization criteria (Section 6.3) will be randomized in a 1:1 ratio to enter a double-
blinded Treatment Period and receive the following study treatment every 4 weeks for 12 
weeks (Week 0, 4, 8 and 12) while initially remaining on the open label background 
therapy of FP/Sal 500/50 mcg BID at Randomization:

GSK3772847 administered intravenously  or

Placebo administered intravenously
At Visit 4 (i.e. two weeks after Randomization) the open label background therapy will 
be switched from FP/Salmeterol 500/50 mcg BID to FP 500 mcg BID for 2 weeks. This 
will mark the beginning of the FP titration period. Every two weeks for the next six 
weeks the dose of FP will be reduced by approximately 50 % (i.e. FP 250 mcg BID at 
Visit 5 for 2 weeks, FP 100 mcg BID at Visit 6 for 2 weeks, then FP 50 mcg BID at Visit 
7 for 2 weeks) until complete FP discontinuation at Visit 8, provided that the participant 
does not meet any of the loss of asthma control criteria. If any of the pre-defined criteria 
for loss of asthma control are met during the Treatment Period, participants will be 
withdrawn from the investigational product (IP) and should resume regular treatment for 
their asthma, as determined by the investigator. 
Participants will be monitored for loss of asthma control through daily use of an eDiary 
and twice-daily PEF measurements. The participants will use the eDiary to record asthma 
symptoms, rescue medication use, and nocturnal awakenings due to asthma symptoms 
requiring rescue medication use. This information will be transmitted daily to a 
centralized server and available to the investigators. Alerts for pre-defined changes in 
PEF or asthma symptoms, indicative of worsening asthma, will be programmed into the 
eDiary with prompts to the participants to contact the investigator if any of the alert 
criteria are met (Section 9.1.2.3). Additionally, email notifications will be sent to the 
investigator, if any of the alert criteria are met, as soon as the data is transmitted to the 
centralized server. The investigator will make every effort to contact the participants in 
order to discuss the participants’ symptoms and evaluate whether they experienced loss 
of asthma control.
For participants who receive all four doses of blinded study treatment, an End of 
Treatment Period (ETP) Visit will be performed 4 weeks after the final dose of the 
blinded study treatment is administered at Week 12. Participants should resume regular 
treatment for their asthma, as determined by the investigator, after protocol defined study 
assessments are completed. Three Follow-up visits will be performed 4, 8, and 12 weeks 
(Week 20, Week 24, and Week 28) after the ETP Visit for safety assessments.
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. Participants 
should resume regular treatment for their asthma, as determined by the investigator. 
Three Follow-up visits will then be performed 4, 8, and 12 weeks after the EW visit for 
safety assessments. 


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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.   
Following randomization participants will return to the clinic at least every 2 weeks for 
scheduled FP dose titration and assessment of asthma control until the last dose of 
blinded study treatment (Visit 9).
Albuterol/salbutamol will be provided for symptomatic relief to be used on an as needed 
basis from Screening through to the ETP visit. 
The maximum total duration of the study is approximately 33 weeks.
An independent Safety Review Committee (iSRC) 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 
iSRC Charter. 
5.2.
Number of Participants
Approximately 300 participants with moderately severe asthma who are maintained on 
high-dose ICS/LABA will be screened to ensure 148 randomized (74 on GSK3772847, 
74 on placebo) participants and 140 evaluable participants. For the purpose of this study 
an evaluable participant is defined as a participant who completes the Week 16 clinic 


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visit whilst remaining on IP or who withdraws from IP having met the primary endpoint. 
High-dose ICS is defined as fluticasone propionate 500 mcg twice daily (i.e. 
1000 mcg total daily dose) or equivalent.
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 randomized treatment phase, and 
safety follow-up. 
The end of the study is defined as the date of the last scheduled procedure shown in the 
Schedule of Activities for the last participant in the trial globally.
5.4.
Scientific Rationale for Study Design
This study will use a multicenter, randomized, double-blind, parallel-group and placebo-
controlled design.  This is a well-established design to evaluate the efficacy, safety, PK 
and PD profiles of an investigational drug. The design of steroid titration (oral or inhaled) 
in participants with asthma has been used in various studies with different investigational 
products, in which changes in the level of asthma control were induced by medication 
withdrawal [Bel, 2014; Wenzel, 2013; Nair, 2009]. This design may not reflect real world 
fluctuations in asthma control, however studies with the design of steroid titration have 
shown the ability to assess effects of a potential treatment on changes in asthma control
in a relatively short period of time, before further investigations are conducted in longer 
term studies.  
In this study, the target population would be participants with moderately severe asthma 
and with an ACQ5 score ≥1 and <4 whose symptoms must have been managed on a 
stable, high dose ICS/LABA for at least 4 months prior to Screening. The use of loss of 
asthma control as a composite study endpoint and a criterion for ICS titration allows for 
the overall clinical evaluation of the participant’s asthma status taking into account both 
lung function and symptom control. Participants will also be monitored through the use 
of the eDiary. Pre-specified asthma symptom scores and participant-measured PEF that is 
inputted into the eDiary will be used as prompts for contacts between subjects and 
investigators (Section 9.1.2.3).
The FP titration period will occur during the Treatment Period of the study. The FP dose 
reduction will be assessed and managed at scheduled clinic visits. During the FP titration 
period the subjects’ FP dose will be reduced as described in Section 5.1 and the SoA, 
unless the subject meets protocol defined criteria for loss of asthma control indicating 
that it is not acceptable for the participant to further reduce ICS. Prior to each FP dose 
reduction an assessment of the participants’ asthma control should be completed and the 
decision to reduce the dose of FP will be based on: 1) the presence and severity of 
exacerbations, 2) changes in FEV1, 3) changes in the most recent ACQ-5 score, or 4) the 
ability to titrate ICS as per the pre-defined schedule, according to the investigator’s 
clinical judgment. If loss of asthma control is confirmed during the FP titration period, 
the participant will discontinue IP immediately and should resume regular treatment for 
their asthma, as determined by the investigator. A similar methodology was recently 
reported [Wenzel, 2013] and successfully allowed titration of ICS. 


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To evaluate the safety and tolerability of repeat dose of GSK3772847, a placebo arm will 
be included to allow the absolute effect of GSK3772847 to be assessed. The treatment 
duration of 12 weeks is supported by pre-clinical study data. Dosing frequency of IP 
every 4 weeks with endpoints assessments scheduled 4 weeks post final IP dose are 
determined by the available target engagement pharmacodynamic findings. Upon 
completing the 16 week Treatment Period (or after IP discontinuation), participants 
should resume regular treatment for their asthma, as determined by the investigator and 
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 taken to fully characterise the 
pharmacokinetics, pharmacodynamics, and anti-drug antibody responses in this 
population.
An inhaled short acting beta2–receptor agonist, salbutamol/albuterol will be provided to 
all participants to use as needed to relieve asthma symptoms from Screening (Visit 1) to 
end of the Treatment Period. Both safety and efficacy parameters will be assessed 
regularly in the clinic to minimise any potential risks to the participants. Participants’
safety will also be assured by having withdrawal criteria (Section 8.1) in case of loss of 
asthma control. Should a participant experience loss of asthma control, the same level of 
pre-study asthma control can be achieved following treatment/resolution of the acute 
event [Matz, 2001; McIvor, 1998]. Any event that defines loss of asthma control in this 
study should not result in an irreversible pathophysiological process that precludes the 
subject from achieving the level of asthma control that existed prior to study entry. The 
proposed study design allows the objectives of the trial to be addressed, but the same 
objectives will provide appropriate safety assessments to minimize the likelihood of 
participants experiencing an actual exacerbation.
5.5.
Dose Justification
The dosing regimen of 10 mg/kg IV at Week 0 then Weeks 4, 8 and 12 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 0-16 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 1


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Figure 1
Predicted clinical exposures at 10mg/kg at weeks 0, 4, 8 and 12 
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 
(NOAEL) (100 mg/kg weekly) in the 3-month GLP toxicology study in 
cynomolgus monkeys (T-2013-007).

Open Triangles: Observed mean and SD 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.
The anticipated exposure margins of the dosing regimen of 10 mg/kg IV at Week 0 then 
Weeks 4, 8 and 12 over the 3-month GLP toxicology study in cynomolgus monkeys (T-
2013-007) are summarised in Table 1. 


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Table 1
Predicted clinical exposures and safety margins for study 207597
following dosing of 10 mg/kg at weeks 0, 4, 8 and 12.
Day 1 mean Cmax
(µg/mL)
Exposure 
margina
Week 12 
mean Cmax 
(µg/mL)
Exposure 
margina
0-28 weeks
AUC
(µg.day/mL)
Exposure 
marginb
245.3c
10.5
313.5d
17.4
16830.2d
18.2
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.
c.
Mean observed exposures in study CNTO7160ASH1001.
d.
Predicted exposures using preliminary MM model
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:
1.
Age: At least 18 years of age at the time of signing the informed consent.
2.
Gender: Males and females. 
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:

Not a woman of childbearing potential (WOCBP) as defined in Appendix 5.
i.
OR

A WOCBP who agrees to follow one of the options listed in Appendix 5 from 
4 weeks prior to the first dose of study medication and until at least 16 weeks
after the last dose of study medication and completion of the follow-up visit.
3.
Informed consent: Capable of giving signed informed consent which includes 
compliance with the requirements and restrictions listed in the consent form and in 
this protocol.
4.
Asthma diagnosis and severity: A participant with a documented diagnosis of 
moderate-severe asthma based on Global Initiative for Asthma (GINA), 2016
Guidelines, whose asthma has been managed with regular treatment of high dose ICS 
defined as fluticasone propionate 500 mcg twice daily (i.e. 1000 mcg total daily dose) 
or equivalent, and long-acting beta-2-agonist (LABA) for at least 4 months.
Additional therapy with a leukotriene receptor antagonist (LTRA) is permissible.
5.
Reversibility: Airway reversibility of at least 12 % and 200 mL in FEV1 at 
Screening (Visit 1), or documented reversibility prior to Screening (Visit 1), or 
documented history of bronchial hyperreactivity (e.g. fall in FEV1 from baseline of 


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≥20% with standard doses of methacholine or histamine, or ≥15% with standardized 
hyperventilation, hypertonic saline or mannitol challenge) from a bronchoprovocation 
study (e.g. methacholine challenge) prior to Screening (Visit 1).
Note: If the participant does not meet the above reversibility criteria at Screening 
(Visit 1) then the reversibility assessment may be repeated once within 7 days of Visit 
1. Should the participant successfully demonstrate airway reversibility at the second 
attempt then, provided that all other eligibility criteria assessed at Screening (Visit 1) 
are met, the participant may enter the 2-week run-in period.
6.
Asthma Control Questionnaire (ACQ): ACQ-5 score ≥1 and <4 at Screening 
(Visit 1).
7.
Exacerbation history: Had at least one asthma exacerbation within 12 months prior 
to Screening that required treatment with systemic corticosteroid and/or 
hospitalization.
8.
Short-Acting Beta2-Agonists: All subjects must be able to replace their current 
SABA treatment with albuterol/salbutamol aerosol inhaler at Visit 1 for use as 
needed, per product label, for the duration of the study.
6.2.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
1. Smoking history: Current smokers or former smokers with a smoking history ≥10 
pack years. 
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.
3. Severe airflow obstruction: A pre-bronchodilator FEV1 <50 % predicted of normal 
value at Screening (Visit 1). Predicted values will be based upon Global Lung 
Function Initiative (GLI) [Quanjer, 2012] equations for spirometry reference values. 
Note: If the spirometry is deemed technically inadequate by the central reader, the 
spirometry assessment may be repeated once within 7 days of Screening (Visit 1).
4. Malignancy: 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 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.
5. Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody 
test result at Screening (Visit 1) or within 3 months prior to first dose of study 
treatment.


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NOTE: Participants with positive Hepatitis C antibody due to prior resolved disease 
can be enrolled, only if a confirmatory negative Hepatitis C Ribonucleic acid (RNA) 
test is obtained.
6. 12-lead ECG assessment at Screening (Visit 1): Site investigators will be provided 
with ECG over-read conducted by a centralized independent cardiologist, to assist in 
evaluation of subject eligibility. For this study, an abnormal and clinically significant 
ECG that would preclude a subject 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 2: 
Table 2
Abnormal and clinically significant ECG findings

Sinus bradycardia <45bpm
*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 
subject is precluded from entering the study.

Evidence of ventricular ectopic couplets, bigeminy, trigeminy or multifocal 
premature ventricular complexes.

For subjects 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 subjects 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 subject is 
precluded from entering the study.

Clinically significant conduction abnormalities (e.g., Wolff-Parkinson-White 


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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)
7.
Weight: <50 kg and >150 kg
8.
Regular use of systemic corticosteroids for conditions including asthma within 3 
months prior to Screening (Visit 1).
9.
Participants with high parasympathetic tone (e.g. trained athletes with baseline 
bradycardia) or chronic conditions associated with parasympathetic surges (e.g. 
migraines)
10. 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).
11. Cardiovascular disease: Clinically significant organic heart disease (e.g. CAD, 
NYHA Class III/IV heart failure).
12. Ongoing infections (i.e. not resolved within 7 days prior to Screening [Visit 1]) or 
recurrent infections (i.e. requiring treatment for an identical diagnosis within 3 
months) requiring systemic antibiotics. Known, pre-existing parasitic infestations 
within 6 months prior to Screening.
13. Other Concurrent Diseases/Abnormalities:  A subject must not have any clinically 
significant, uncontrolled condition, or disease state that, in the opinion of the 
investigator, would put the safety of the subject at risk through study participation or 
would confound the interpretation of the efficacy results if the condition/disease 
exacerbated during the study.
The list of additional excluded conditions/diseases includes, but is not limited to, the 
following:
Addison's disease
hypertension1 (uncontrolled)
aortic aneurysm (clinically significant)
peptic ulcer (recent or poorly controlled)
Cushing's disease
renal disease
diabetes mellitus (uncontrolled)
stroke within 3 months of Visit 1
hematological disease
thyroid disorder (uncontrolled)
hepatic disease
tuberculosis (current or untreated2)
1.
Two or more measurements with systolic pressure >160mmHg or diastolic pressure >100mmHg
2.
Subjects with a history of tuberculosis infection who have completed an appropriate course of 
antituberculosis treatment may be suitable for study entry provided that there is no clinical suspicion of 
active or recurrent disease.
14. Immunodeficiency: A known immunodeficiency such as human immunodeficiency 
virus infection.
15. Hypersensitivity: Participants with allergy or intolerance to a monoclonal antibody 
or biologic or to any components of the formulation used in this study.


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16. Alcohol and Substance abuse: Participants with a history (or suspected history) of 
alcohol misuse or substance abuse within 2 years prior to Screening (Visit 1).
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, dosing directions, study eDiary completion, or use of a standard metered 
dose inhaler. 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.
18. Participants who have previously participated in a study of GSK3772847.
19. Excluded Medications:  Use of the medications listed in Table 3 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 on enrolling in the trial.
Table 3
Prohibited Medications
Medication
Time interval prior to Visit 1
Investigational drug
One month or 5 half-lives whichever is longer
Live or attenuated vaccinesa
2 weeks (i.e. 4 weeks prior to IP administration)
Biologics, for example Mepolizumab and 
Omalizumab
130 days or 5 half-lives whichever is longer
Experimental anti-inflammatory drugs (non-
biologics)
3 months
Corticosteroids intramuscular, long acting depot 
Regular systemic corticosteroid - oral, 
parenteral, depot
3 months
Methotrexate, troleandomycin, oral gold, 
cyclosporin, azathioprine, 
3 months
Theophylline
3 months
Chemotherapy and radiotherapy
12 months
Inhaled anti-cholinergics e.g. tiotropium
1 week
a.
Vaccines containing killed bacteria or inactivated virus will be permitted
20. Affiliation with Investigator Site:  A participant will not be eligible for this study if 
he/she is an immediate family member of the participating investigator, sub-
investigator, study coordinator, or employee of the participating investigator.
21. Inability to read:  In the opinion of the investigator, any participant who is unable to 
read and/or would not be able to complete a diary card/questionnaire.  
22. Questionable validity of consent: Participants with a history of psychiatric disease, 
intellectual deficiency, poor motivation or other conditions that will limit the validity 
of informed consent to participate in the study.


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6.3.
Randomization Inclusion Criteria
At the end of the Run-in period (Visit 2), study participants must fulfil the following 
additional criteria in order to be randomized into the study and enter the treatment period:
1. Asthma Control Questionnaire (ACQ): ACQ-5 score ≥1 and <4 at Visit 2.
2. eDiary Compliance: Compliance with completion of the eDiary reporting defined as 
completion of all questions/assessments on ≥4 of the last 7 days during the run-in 
period. 
6.4.
Randomization Exclusion Criteria
Participants meeting any of the following criteria must not be randomized to double-
blind study medication 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. 12-lead ECG over-read: Evidence of clinically significant abnormal ECG findings 
(Table 2) at Screening (Visit 1).
3. 24-Hour Holter Monitoring: An abnormal and significant finding from 24-hour 
Holter monitoring at Screening (Visit 1). 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 2. The 
study investigator will determine the medical significance of any Holter abnormalities 
not listed in Table 2.
4. Liver function at Screening (Visit 1)

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 %). 

Current or chronic history of liver disease, or known hepatic or biliary 
abnormalities (with the exception of Gilbert's syndrome or asymptomatic 
gallstones.
5. Asthma exacerbation: Participants with ongoing asthma exacerbation at the time of 
Visit 2. 
Note: At the Investigator’s discretion, participants with an ongoing asthma 
exacerbation at Visit 2 may be re-screened 2 weeks after Visit 2. In such cases, the 
full screening process (i.e. all Visit 0, 1 and Visit 2 assessments) must be repeated. 


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6. Severe airflow obstruction: a pre-bronchodilator FEV1 <50 % predicted of normal 
value at Visit 2. Predicted values will be based upon GLI [Quanjer, 2012] equations 
for spirometry reference values.
7. Positive pregnancy test at Visit 0, Screening (Visit 1) or Visit 2.
8. Ongoing or recurrent infections requiring systemic antibiotics.
6.5.
Lifestyle Restrictions
No lifestyle restrictions are required for this study.
6.6.
Pre-Screening/Screening/Run-in/Randomization Failures
A participant will be assigned a participant number at the time the informed consent is 
signed at Visit 0.
The study site will be responsible for reporting pre-screen failures. The following 
information will be collected in the eCRF for participants who are pre-screen failures:

Demographic information including race, age and gender

Participant number

Serious Adverse Event information only for any SAE considered as related to 
study participation
For the purposes of this study, pre-screening failures, screening failures, run-in failures
and randomization failures will be defined as follows:

Pre-screening failures: those participants that sign the informed consent 
document but do not have a Screening (Visit 1) procedure.

Screening failures: those participants that complete at least one Screening
(Visit 1) procedure but do not enter the run-in period. 
A participant who completes Visit 1 assessments and is dispensed the study 
medication for the run-in period is considered to have entered the run-in period.

Run-in failures: those participants that enter the run-in period but do not have 
any Visit 2 procedures.

Randomization failures: those participants that complete at least one Visit 2 
procedure but do not enter the double-blind study treatment period.
Any participant who completes the run-in period and then meets the randomization 
criteria and receives the double-blind study treatment at Visit 2 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 
(CONSORT) 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).


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Rescreening is only allowed in exceptional circumstances of technical errors and with 
prior approval from the GSK study team. Participants who are excluded due to an 
ongoing asthma exacerbation at Visit 2 (Randomization exclusion criterion 5) may be 
rescreened 2 weeks after Visit 2, at the investigators discretion. Rescreened participants 
will be assigned a new participant number.
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.


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7.1.
Treatments Administered
Study Treatment 
Name:
GSK3772847
Placebo
Fluticasone 
Propionate/Salmeterol 
Fluticasone
Propionate
Dosage 
formulation:
50mg/mL 
GSK377284, 
15 mM 
Sodium 
Phosphate, 
8.5% [w/v] 
Sucrose, and 
0.04% [w/v] 
Polysorbate 
20, pH 7.3.
DISKUS– 60 doses 
per device
DISKUS– 60 
doses per device
Unit dose 
strength(s)/Dosage 
level(s):
10 mg/kg
Commercially 
sourced 
sterile normal 
saline
500/50 mcg per 
actuation
500, 250, 100 
and 50 mcg per 
actuation
Route of 
Administration 
IV infusion
IV infusion
Inhaled
Inhaled
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
Twice daily; once in 
the morning and once 
in the evening
Twice daily; once 
in the morning 
and once in the 
evening


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Study Treatment 
Name:
GSK3772847
Placebo
Fluticasone 
Propionate/Salmeterol 
Fluticasone
Propionate
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 labeled as 
required per
country 
requirement. 
Commercially 
sourced 
sterile normal 
saline will be 
sourced by 
the site
Diskus Inhaler with 60 
doses
(1 strip with 60 
blisters per strip)
Each container will be 
labeled as required 
per country 
requirement.
Diskus Inhaler 
with 60 doses
(1 strip with 60 
blisters per strip)
Each container 
will be labeled as 
required per 
country 
requirement.
7.1.1.
Description of Albuterol/Salbutamol
Albuterol/salbutamol via metered-dose inhaler (MDI) will be issued for reversibility 
testing at Screening (Visit 1). An albuterol/salbutamol MDI for as needed (prn) use 
throughout the study will be dispensed starting at Visit 1; at the Investigator’s discretion, 
more than one MDI may be dispensed at any one time. Albuterol/salbutamol will be 
sourced from local commercial stock. The contents of the label will be in accordance 
with all applicable regulatory requirements.
7.1.2.
DISKUS Return
DISKUS inhalers containing FP/Salmeterol and FP will be dispensed to a participant 
during their visit to the study clinic (as applicable). The participant must return all 
dispensed inhalers at the subsequent clinic visit. The schedule for dispensing and 
collecting FP/Sal and FP is provided in the SoA (Section 2).
All used and unused FP/Sal, FP will be returned to GSK at the end of the study to be 
available for disposal. In some instances, for sites outside the United States (US), study 
supplies will be disposed of locally either by the site, the country medical department or 


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third-party vendor. Detailed instructions for the return of the study drug can be found in 
the Study Reference Manual (SRM).
If any DISKUS inhaler fails to function properly, the participant should return to the 
clinic as soon as possible to obtain a new inhaler. The site will use the Interactive Web 
Response System (IWRS) (RAMOS NG) to obtain a new treatment pack number for the 
participant and dispense a new study treatment kit from the site’s study treatment supply 
as instructed by the IWRS. Details of the failure will be documented in the eCRF. 
Additional information on how to handle medical device incidents can be found in the 
SRM.
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 randomization
schedule. The randomization code will be generated by GSK using a validated 
computerized system. Participants will be randomized using an interactive web response 
system (IWRS) RAMOS NG. The study will use central-based randomization to allocate 
treatments. Once a randomization 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 subject to satisfying all eligibility criteria, 
participants will be randomized 1:1 to one of the following double-blind 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 16 weeks. 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 (RAMOS 
NG) to randomize participants and manage study treatment supplies (including 
dispensing) is provided in the RAMOS NG manual and SRM.
7.4.
Blinding
This will be a double-blind study and the following will apply. 

The Investigator or treating physician may unblind a participant’s treatment
assignment only in the case of an emergency OR in the event of a serious 
medical condition when knowledge of the study treatment is essential for the 
appropriate clinical management or welfare of the participant as judged by the 
Investigator. 

Investigators have direct access to the participant’s individual study treatment. 


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
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 GSK personnel are not contacted before the unblinding, the Investigator must 
notify GSK within 24 hours after unblinding, but without revealing the treatment 
assignment of the unblinded participant, unless that information is important for 
the safety of participants currently in the study. 

The date and event or condition which led to the unblinding (i.e. the primary 
reason) will be recorded in source documentation and in the eCRF. 
In the event of unblinding 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 IP, the participant must be followed-up as per 
protocol until the completion of the Safety Follow-up assessments. 
GSK’s Global Clinical Safety and Pharmacovigilance (GCSP) 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
GSK3772847 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 WFI, 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 2º – 8C, protected from light. Protection 
from light during preparation and administration is not required. Full details on specific 
2º to 8C storage temperature conditions, preparation and administration including 
requirements for filtration are provided separately. 
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 authorized personnel and administered according to each participant’s body 
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 


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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. Required storage conditions and 
expiration date are indicated on the label.
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 
authorized 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 authorized 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 or unblinded site staff reference manual.

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 (MSDS)/equivalent document describing occupational 
hazards and recommended handling precautions either will be provided to the 
investigator, where this is required by local laws, or is available upon request from 
GSK.
Precaution will be taken to avoid direct contact with the study treatment. A Material 
Safety Data Sheet (MSDS) describing occupational hazards and recommended handling 
precautions will be provided to the investigator.  In the case of unintentional occupational 
exposure notify the monitor, Medical Monitor and/or GSK study contact.


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7.6.
Treatment Compliance

FP/Sal and FP during the run-in and treatment periods will be self-administered at 
home; compliance will be assessed via dose counter during the site visits and 
documented in the source documents and eCRF. A record of the number of doses on 
the DISKUS inhaler will be recorded in the eCRF. Treatment start and stop dates, 
including dates for treatment delays and/or dose reductions will also be recorded in 
the eCRF.

The double blind IP will be intravenously administered to participants at the site.  
Administration will be documented in the source documents and reported in the 
eCRF.
7.7.
Concomitant Therapy
All asthma medications used within approximately 12 weeks prior to screening and 
during the study (including the post-treatment period) should be recorded in the eCRF.
All non-asthma medications taken during the study (after randomization including post-
treatment) and any changes to concomitant medications will be recorded in the eCRF. 
Note: Study provided FP/Sal, FP, and albuterol/salbutamol should not be recorded in the 
ConMeds page of the eCRF.
The minimum requirement is that the drug name, reason for use, dose (including unit e.g. 
mcg) and frequency, route and the dates of administration are to be recorded.
7.7.1.
Permitted Non-asthma Medications
The following medications are permitted during the study:

Medications for rhinitis (e.g., intranasal corticosteroids, antihistamines [including 
ocular and intranasal] but they are disallowed 48 hours prior to ECG 
measurements, cromolyn, nedocromil, nasal decongestants)

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.

Immunotherapy: Immunotherapy for the treatment of allergies is allowed during 
the study provided it was initiated 4 weeks prior to Visit 1 and participants remain 
in the maintenance phase for the duration of the study.

Topical and ophthalmic corticosteroids.
7.7.2.
Prohibited Medications and Non-Drug Therapies
Use of the medications listed below is not permitted during the study: 

Inhaled anti-cholinergics (e.g.tiotropium).


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
ICS/LABA other than the study-provided FP/Sal.

Inhaled Corticosteroids other than the study-provided FP.

LABA other than the salmeterol component in the study-provided FP/Sal. 

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.

Monoamine oxidase (MAO) inhibitors.

Live or attenuated vaccines (and up to 6 months after the last dose of blinded 
study treatment).

Experimental anti-inflammatory drugs (non-biologics).

Corticosteroids intramuscular, long acting depot, regular systemic (oral, 
parenteral, depot) corticosteroid.

Methotrexate, troleandomycin, oral gold, cyclosporin, azathioprine.

Theophylline.

Chemotherapy and radiotherapy.
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.
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 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. Participants should resume regular treatment for their asthma, 
as determined by the investigator. Three Follow-up visits will then be performed 
4, 8, and 12 weeks after the EW visit for safety assessments. 


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
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, lack of efficacy [including loss of 
asthma control], 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: 
1.
Liver Chemistry: Meets any of the protocol-defined liver chemistry stopping criteria.
2.
QTc: Meets any of the protocol-defined stopping criteria.
3.
Pregnancy: Positive pregnancy test.
4.
Participant meets at least one of the following criteria for ‘loss of asthma control’:

ACQ-5 score increase from baseline (measured at Visit 2) ≥0.5 point. 

Pre-bronchodilator FEV1 decrease from baseline (measured at Visit 2) >7.5 %. 

Inability to continue inhaled corticosteroid titration which is assessed and 
determined by the investigator at any time point following randomization, 
including on scheduled clinic visits.

A clinically significant asthma exacerbation (requiring OCS and/or 
hospitalization).
5.
Study treatment unblinded.
Note: In the event of unblinding the Medical monitor/GSK team should be contacted 
to determine whether subject withdrawal is required.
6.
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 or findings of myocardial ischemia will also result in withdrawal/stopping.
7.
Hypersensitivity or anaphylactic reaction
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 (in alignment with the Food 
and Drug Administration [FDA] premarketing clinical liver safety guidance). These 
protocol guidelines are in alignment with FDA premarketing clinical liver safety 
guidance: 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/UCM174090.pdf.


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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 
collected for data analysis.  Safety ECGs and other non-protocol specified ECGs are 
an exception.  


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
The QTc should be based on single or averaged QTc values of triplicate 
electrocardiograms 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
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 for data to be collected at the time of early withdrawal (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 or any of the 
individual discontinuation criteria listed in Section 8.1 of the protocol are met 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.
Note: In order to achieve the stratification balance, as a result of participants’ 
eosinophil count it may be necessary to withdraw participants from the study 
during the Run-in period.

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 for data to be collected at the time of early withdrawal (EW 
visit) 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. 
9.
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and their timing are summarized in the Schedule of Activities 
(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, is 
essential and required for study conduct.
No study related procedures may be performed until the informed consent form has 
been signed by the participant.  Selection and modification of the participant’s 
medications prior to study participation is based on the physician’s judgment according to 
sound medical practice, principles, and each participant’s needs.  A participant’s 
treatment must not be changed merely for the purpose of enabling the participant’s 
participation in the study.
9.1.
Efficacy Assessments
The timings of all efficacy assessments are specified in SoA.


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9.1.1.
Questionnaires
9.1.1.1.
Asthma Control Questionnaire ACQ-5
The ACQ-5 measures attributes of asthma control [Juniper, 1999], measured with 
questions designed to be self-completed by the participant.  Participants will complete the 
ACQ-5 with the use of an e-Diary device on a weekly basis. The ACQ-5 includes five 
questions (concerning nocturnal awakening, waking in the morning, activity limitation,
shortness of breath and wheeze) which enquire about the frequency and/or severity of 
symptoms over the previous week. The response options for all these questions consist of 
a zero (no impairment/limitation) to six (total impairment/ limitation) scale. The recall 
period is the past week. A score of <0.75 indicates well-controlled asthma and a score 
1.5 indicates poorly controlled asthma [Juniper, 2006]. A change of 0.5 in score 
suggests a clinically important change in score [Juniper, 2005].
9.1.1.2.
St. George’s Respiratory of Life Questionnaire (SGRQ)
The St. George’s Respiratory Questionnaire is a well established instrument, comprising 
50 questions designed to measure Quality of Life in patients with diseases of airway 
obstruction, measuring symptoms, impact, and activity. The questions are designed to be 
self-completed by the participant [Jones, 1992] with a recall over the past 4 weeks. 
Higher scores indicate worse health status, and a change of 4 points is considered a 
clinically relevant change [Jones, 2005].
9.1.2.
Daily Diaries
Participants will be issued with a PEF/e-Diary device at Visit 1 for twice daily use (in the 
morning upon waking and in the evening just before going to bed) throughout the study. 
The device will be provided by a third-party vendor. Information on the device and its 
use are documented in the SRM and the third-party vendor manual. Participants will be 
instructed on how to use the device in order to record results for the following in the 
eDiary each day from Visit 1 onwards:

Morning and evening peak flow (best of three).

Daytime asthma symptom score using a 5-point scale 

Inhalations of rescue medication usage over the previous 24-hours

Frequency of awakening due to asthma symptoms requiring rescue medication use

Morning and Evening use of FP/Sal and FP during the run-in and treatment periods
Section 9.1.2 describes the assessments and questionnaires recorded on the eDiary 
device, as well as the alerts that can be triggered based on recorded results. The data from 
the eDiary device will be automatically transmitted to a centralized server. The 
Investigator and designee(s) will be provided with access to the transmitted eDiary data 
via a vendor-provided portal and should review the data on an ongoing basis to check for 
the incidence of alerts as well as subject compliance with eDiary use.
Participants will also be issued with a paper Medical Problems/Medications Taken 
worksheet to record medical problems experienced and medications used during the 


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study (please refer to the SRM for further details). Participants must also use this paper 
worksheet to record all healthcare contacts that occur during their participation in the 
study. This paper worksheet will be used to assist participant recall in discussions with 
the Investigator, for site staff to then enter as appropriate in the electronic case report 
form (eCRF).
9.1.2.1.
Night-time Awakening, Daytime Asthma Symptom Questions
Every morning upon waking (from the morning after Visit 1 onwards), participants will 
answer a question on the occurrence of night-time awakenings due to asthma symptoms. 
The participant’s response to the question on the occurrence of night-time awakenings 
will be either ‘Yes’ (i.e. Did you wake up due to asthma symptoms (i.e. wheezing, 
coughing, shortness of breath, or chest tightness) or ‘No’ (i.e. they did not experience at 
least one night-time awakening due to asthma symptoms). If ‘Yes’, participants will be 
asked to respond either ‘Yes’ or ‘No’ to the question on rescue medication (i.e. when you 
woke up due to your asthma symptoms did you use any rescue bronchodilator?).
On the evening of Visit 1 (just before going to bed) and every evening there-after, 
participants will answer a question on daytime asthma symptoms. These questions will be 
answered on a 5-point scale (0 to 4) with ‘0’ representing no daytime asthma symptoms 
and ‘4’ representing very severe daytime asthma symptoms. Please describe the severity 
of your asthma symptoms (i.e. cough, wheeze, chest tightness, shortness of breath) today 
[0=no asthma symptoms, 1=mild asthma symptoms, 2= moderate asthma symptoms, 
3=severe asthma symptoms, 4= very severe asthma symptoms]. 
9.1.2.2.
Morning and Evening Home PEF
Participants will conduct PEF measurements using the PEF/eDiary device each morning 
and each evening. Three measurements for each session will be recorded by the 
participants in the eDiary. Assessments will be performed:

After completing all other eDiary assessments

Prior to albuterol/salbutamol use

Prior to FP/Sal and FP use
9.1.2.3.
Alerts
For safety the following alerts, indicative of worsening asthma, will be programmed into 
the eDiary with instructions for the participant to contact the investigator and transmit the 
data to the centralised server as soon as possible if any of the alert criteria are met. An 
alert in itself will not qualify as a clinically significant exacerbation:

Decrease in morning PEF 30% on at least two of three successive days, 
compared with Baseline (last 7 days of run-in).

A daytime symptom score of 3 for at least two of three successive days.

An increase from baseline of ≥4 puffs /day of albuterol/salbutamol use on 2 
consecutive days.


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
Awakening due to asthma symptoms requiring rescue medication use for at least 
two of three successive nights.
If any of the alert criteria are met, email notifications will be sent to the investigator as 
soon as the data is transmitted to the centralized server. The investigator will make every 
effort to contact the participants in order to discuss the participants’ symptoms and 
evaluate whether they experienced loss of asthma control.
9.1.3.
Pulmonary Function Test
Spirometry equipment and a device to measure FeNO (see Section 9.1.4) will be 
provided to all sites by a third-party vendor. Spirometry data from this study will be 
analysed by a third-party vendor. Details on performing the spirometry assessments, 
including information on the equipment provided and its use as well as specific 
instructions on performing the spirometry manoeuvres are documented in the SRM and
the third-party vendor manual.
9.1.3.1.
Spirometry
Spirometry will be performed to assess FEV1 and FVC. At least 3 spirometry 
manoeuvres (from a maximum of 8 attempts) should be achieved on each occasion that 
spirometry assessments are performed. For spirometry data collected at Screening (Visits 
1), the best spirometry effort will be selected from a measurement that meets American 
Thoracic Society (ATS)/ European Respiratory Society (ERS) guidelines and has a 
minimum of 2 efforts which are considered valid and repeatable, in accordance with the 
ATS/ERS standards [Miller, 2005]. Measurements with 3 valid but non-repeatable efforts 
will not be accepted. For spirometry data collected during the Treatment Period (Visits 2 
– 11, including EW visit), the best spirometry effort will be selected from a measurement 
that meets ATS/ERS guidelines and has a minimum of 2 efforts which are considered 
valid (not necessarily repeatable). As always, sites should continue to strive to collect at 
least 3 valid (with no more than 8) efforts, as per ATS/ERS guidelines. At each visit, 
spirometry assessments must be performed at the same time of day (2 hour) as the 
assessment performed at Visit 2 (the baseline assessment). Participants should withhold 
short-acting beta-2-agonists (SABAs) for 6 hours and LABAs for 1 dosing interval 
(i.e. 12 or 24 hours based on the prescribed dosing interval of the product) prior to the 
clinic visit, if possible.
9.1.3.2.
Reversibility
All reversibility evaluations should follow the recommendations of the ATS/ ERS Task 
force: Standardization of Lung Function Testing [Miller, 2005]. A baseline spirometry 
assessment should be performed after a washout period of at least 6 hours for short-acting 
β2- agonists and 1 dosing interval for long-acting β2-agonists (or fixed dose combinations 
of LABA and ICS).
To perform the reversibility assessment, 4 puffs of the provided salbutamol/albuterol is 
administered following completion of the baseline assessment. A spacer device may be 
used for testing, if required. A second spirometry assessment is performed within 10 to 
15 minutes after administration of the salbutamol/albuterol.


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Reversibility assessment at Screening (Visit 1) is not required if there is documented 
reversibility prior to Screening (Visit 1), or documented history of bronchial 
hyperreactivity from a bronchoprovocation study (e.g. methacholine challenge) prior to 
Screening (Visit 1).
9.1.4.
Fractional Exhaled Nitric Oxide (FeNO)
FeNO will be measured using a handheld electronic device. Measurements will be 
obtained in accordance with the ATS/ERS Recommendations for Standardized 
Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric 
Oxide and Nasal Nitric Oxide [Miller, 2005]. All sites will use standardized 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. 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 for 1 dosing interval (i.e. 12 or 24 hours based on the prescribed 
dosing interval of the product) before each FeNO assessment.
9.1.5.
Review of Loss of Asthma Control
Loss of asthma control is defined as at least one of the following: 

ACQ-5 score increase from baseline (measured at the end of Run-in) ≥0.5 point) 
or

Pre-bronchodilator FEV1 decrease from baseline (measured at the end of Run-in) 
> 7.5 % or

Inability to titrate inhaled corticosteroid according to the pre-defined schedule 
(Section 5.1) or

A clinically significant asthma exacerbation (requiring OCS and/or 
hospitalisation.
At each clinic visit, the Investigator will utilize clinical discretion and available objective 
evidence (including but not limited to eDiary data, spirometry data, the most recent 
ACQ5 scores, history of exacerbations, conmeds, AEs) to determine if the patient is 
experiencing loss of asthma control. The paper Medical Problems/Medications Taken 
worksheet must also be reviewed by the Investigator (or appropriately trained designee) 
at each visit to the study site to assist the Investigator in the identification of loss of 
asthma control. It is expected that the Investigator will indicate which criterion (criteria) 
the subject met that constituted loss of asthma control.
9.2.
Adverse Events
The definitions of an AE or SAE can be found in Appendix 4.
Asthma exacerbations or worsening of asthma should not be recorded as an AE, unless 
they meet the definition of an SAE. For the purposes of this study, asthma exacerbations 


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will be collected and recorded on the exacerbations log in the eCRF. The treatment 
details must also be recorded in the eCRF. The time period for collection of asthma 
exacerbations will begin from screening and will end after the follow-up period has been 
completed.
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 the Visit 2 until the last follow-up visit at the 
time points specified in the SoA (Section 2). At Visits 0 and 1 SAE information 
will be collected only for any SAEs considered as related to study participation.

All AEs will be collected from the signing of the ICF 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 case report form (eCRF) not the AE section.

All SAEs will be recorded and reported to the sponsor or designee within 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 
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 an AE and/or SAE. Open-ended 
and non-leading verbal questioning of the participant is the preferred method to inquire 
about AE occurrence. Appropriate questions include:

“How are you feeling?” 

“Have you had any (other) medical problems since your last visit/contact?” 

“Have you taken any new medicines, other than those provided in this study, since 
your last visit/contact?” 


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Participants will be issued with a paper Medical Problems/Medications Taken worksheet
to record any medical problems experienced and medications used during the study (See 
Section 9.1.2).
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 (SUSAR) 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 e.g. summary or listing of SAEs 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 Cardiovascular (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. 
The CV eCRFs are presented as queries in response to reporting of certain CV Medicinal 
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.


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9.2.6.
Pregnancy

Details of all pregnancies in female participants will be collected after the start of 
study treatment and until the last follow-up visit.

If a pregnancy is reported, the investigator should inform GlaxoSmithKline (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 GlaxoSmithKline 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.
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.


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9.4.2.
Vital Signs
Vital signs should be performed at the time points specified in the Schedule of Activities 
(SoA) table (Section 2) prior to conducting spirometry. Blood pressure (systolic and 
diastolic) and pulse rate will be measured in the supine position after approximately 5 
minutes rest. A single set of values 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 centralized 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 Schedule of Activities (SoA) 
table (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).
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 centralized 
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 
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.


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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 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 eCRF. The laboratory reports must be filed with the source 
documents. Clinically significant abnormal laboratory findings are those which 
are not associated with the underlying disease, unless judged by the investigator 
to be more severe than expected for the participant's condition.

All laboratory tests with values considered clinically significantly abnormal 
during participation in the study 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.

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.
9.5.
Pharmacokinetics

Whole blood samples of approximately 3 mL will be collected for measurement 
of serum concentrations of GSK3772847as specified in the SoA. 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
9.6.
Pharmacodynamics
Pharmacodynamic (PD) Biomarkers
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. The timing of the collections may be adjusted on the basis of emerging PK or PD 


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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 sputum (Section 9.8.1.1) 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, Eosinophilic Cationic Protein (ECP) and Type-2 chemokines (e.g. 
CCL13, CCL17) as well as sputum cell counts (e.g. percentage eosinophils). 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. 
9.8.1.1.
Sputum Sub-Study
At selected sites only, consenting participants who are eligible for randomisation at Visit 
2 will be entered into the Sputum sub-study. In a subset of approximately 50% of eligible 
participants, sputum samples will be collected as specified in the SoA. The participants in 
the Sputum Sub-Study will be randomised equally in the two treatment groups.
Details of the sputum collection and processing methodology will be provided in the 
SRM.
9.8.2.
Immunogenicity Assessments 
Serum samples will be collected and tested for the presence of antibodies that bind to 
GSK3772847, as specified in the SoA. The actual date and time (24-hour clock time) of 
each sample will be recorded.
The presence of anti-GSK3772847 antibodies will be assessed using a tiered approach 
including a screening assay, a confirmation assay and calculation of titre.


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Instructions for the collection and handling of biological samples will be provided in the 
SRM. 
9.9.
Health Economics OR Medical Resource Utilization and 
Health Economics
Health Economics/Medical Resource Utilization and Health Economics parameters are 
not evaluated in this study.
10.
STATISTICAL CONSIDERATIONS
10.1.
Hypotheses
The primary null hypothesis (
) for this study is that the ratio of the proportions of 
subjects with loss of asthma control from randomization to Week 16 between 
GSK3772847 and placebo is unity.
The alternative hypothesis (
) for this study is that the ratio of the proportions of 
subjects with loss of asthma control from randomization to Week 16 between 
GSK3772847 and placebo is not unity. 
The hypothesis will be tested by calculating the posterior probability that the ratio of the 
proportion of subjects with loss of asthma control on GSK3772847 compared with 
placebo is less than 1.0, 0.75, 0.5 and 0.2 (i.e. a 0%, 25%, 50% and 80% reduction) and 
supported by an estimate of the ratio with a 95% credible interval. A non-informative
prior will be used.
Although the success of the study will be assessed by calculating posterior probabilities 
of the treatment effect reaching various thresholds and not statistical significance, a 
frequentist analysis will also be performed testing the above hypothesis.
10.2.
Sample Size Determination
The study will randomize 74 participants per treatment arm with the aim of having 70 
evaluable participants per arm. For the purpose of this study an evaluable participant is 
defined as a participant who completes the Week 16 clinic visit whilst remaining on IP or 
who withdraws from IP having met the primary endpoint. See Section 10.4.1 for how 
subjects who withdraw early from IP for reasons other than loss of asthma control are 
handled in the analysis.


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In addition to testing the hypothesis in the overall population, the study will randomize a 
sufficient number of participants to evaluate trends in pre-defined subgroups (e.g. 
eosinophil strata).
The true proportion of participants that would experience a loss of asthma control on each 
treatment is unknown. However in a similar study of Dupilumab compared with placebo, 
the proportion of participants with loss of control were 6% and 44% for Dupilumab and 
placebo respectively. Table 4 gives the power to detect a statistically significant 
difference (at the two-sided 5% level) between the two treatments assuming the true 
proportion with loss of control on placebo is 44% and the true proportion with loss of 
control on active is 6%, 11%, 19% and 22% [Fleiss, 2003].
Table 4
Table of Power Achievable for Different Treatment Comparisons 
using N=70 per arm calculated using PASS
True proportion on 
Placebo
True proportion on 
GSK3772847
Reduction
Power
44%
6%
86%
> 99%
44%
11%
75%
> 99%
44%
19%
57%
90%
44%
22%
50%
80%
Assuming the true proportion with loss of control on placebo is 44%, then with 70 
evaluable participants per arm, the study will have at least 80% power to detect a 
statistically significant difference between treatments assuming the true proportion with 
loss of control on GSK3772487 is at most 22% (Table 4).
With 70 evaluable participants per arm and assuming the true proportion with loss of 
control on placebo is 44%, the smallest observed difference that would lead to rejection 
of the null hypothesis (minimum detectable effect) is 31% corresponding to a proportion 
with loss of control on GSK3772847 of 28%.
There is a single primary endpoint so no adjustments are required for multiplicity.
10.3.
Populations for Analyses
For purposes of analysis, the following populations are defined:
Population
Description
Enrolled 
All participants who sign the ICF.
Randomized
All participants who were randomized. A subject who is recorded as 
a screen or run-in failure and also randomized will be considered to 
be randomized in error provided they have not performed any study 
assessments.
Modified Intent-to-treat 
(mITT)
All randomized subjects who take at least 1 dose of study treatment. 
Participants will be analyzed according to the treatment they actually 


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Population
Description
received.
PK
All randomized subjects who received at least one dose of study 
medication, and for whom at least one pharmacokinetic sample was 
obtained, analyzed and was measurable.
10.4.
Statistical Analyses
10.4.1.
Efficacy Analyses
All efficacy analyses will be performed on the mITT Population.
Endpoint
Statistical Analysis Methods
Primary
The primary endpoint proportion of subjects with loss of asthma control will 
be analyzed using both Bayesian and Frequentist methods. A subject is 
deemed to have met the endpoint of loss of asthma control if they meet the 
criteria for any of the components of the definition of loss of asthma control.
The posterior probabilities that the ratio of the proportion of subjects with loss 
of asthma control on GSK3772847 compared with placebo is less than 1.0, 
0.75, 0.5 and 0.2 (i.e. a 0%, 25%, 50% and 80% reduction) will be calculated 
analytically assuming a non-informative prior. This will be supported by an 
estimate of the ratio with a 95% credible interval. Results will also be 
presented for the two eosinophils strata separately.
In addition, the proportion of participants with loss of asthma control will be 
analyzed using logistic regression allowing for baseline eosinophils strata. 
The odds ratio, 95% CI and p-value for the comparison of GSK3772847 with 
placebo will be presented. 
Results will also be presented for the two eosinophils strata separately by 
fitting a separate model with an additional term for eosinophil strata by 
treatment interaction. The effect of eosinophils as a continuous covariate will 
also be examined in a separate-logistic regression model.
Missing data will be handled using the following methods:
1) The loss of asthma control will be set to missing for participants who 
withdraw from IP prior to Week 16 for reasons other than loss of 
asthma control
2) A sensitivity analysis will be performed where participants who 
withdraw from IP prior to Week 16 for reasons other than loss of 
asthma control will have the endpoint set to loss of control
Secondary
The following secondary endpoints will be analyzed using the same 
statistical analysis as described for the primary endpoint:

Proportion of participants with a clinically significant asthma exacerbation 


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Endpoint
Statistical Analysis Methods
(requiring OCS and/or hospitalisation) 

Proportion of participants with Pre-bronchodilator FEV1  decrease from 
Baseline (measured at the end of Run-in) >7.5 % 

Proportion of participants with Inability to titrate inhaled corticosteroid 
according to the pre-defined schedule (Section 5.1) 

Proportion of participants with ACQ-5 score increase from Baseline 
(measured at the end of Run-in) ≥0.5 point.

Proportion of participants with a clinically significant asthma exacerbation 
or inability to titrate ICS according to the pre-defined schedule.
In these analyses, the endpoint will be set to missing for participants who 
withdraw from IP prior to Week 16 for reasons other than loss of asthma 
control.
Time to loss of asthma control will be analyzed using Kaplan-Meier analysis. 
Percentiles for time to loss of control will be presented for both treatment 
groups, along with graphical survival plots. Any early withdrawals from IP 
that did not experience loss of control will be censored. Results will be 
presented for both of the two eosinophil strata separately, and combined. 
The following endpoints will be analyzed using repeated logistic regression. 
This analysis will be repeated including an additional term for eosinophil 
strata by treatment by visit interaction to provide estimates for the two 
eosinophil strata separately:

Proportion of ACQ-5 responders (a ≥0.5 point improvement from
baseline at Week 16)

Proportion of SGRQ responders (at least a 4 unit improvement from 
baseline at Week 16
These analyzes will be performed using two different methods for handling 
missing data:
1) If endpoint at a visit is missing then the responder status is set to 
missing
2) If endpoint at a visit is missing and the endpoint is also missing at all 
subsequent visits then the responder status is set to non-responder
The odds ratio, 95% CI and p-value for the comparison of GSK3772847 with 
placebo will be presented for all models.
Mixed model repeated measures will be used to analyze the following 
endpoints. The baseline value of each endpoint will be included along with 
baseline*visit and treatment*visit interactions. Treatment differences, 95% 
confidence intervals and p-values will be presented.

Change from baseline in ACQ-5 absolute score 

Change from baseline in SGRQ total score

Change from baseline in Pre-bronchodilator FEV1

Change from baseline in FeNO
This analysis will be repeated including an additional term for eosinophil 


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Endpoint
Statistical Analysis Methods
strata by treatment by visit interaction to provide estimates for each 
eosinophil strata separately. No adjustment will be made for missing data.
Further information on how the following endpoints will be analyzed will be 
described in the report and analysis plan:

Hospitalisation or ER visit during the study treatment period

Morning and evening PEF

Daily asthma symptom score

Rescue medication use (albuterol/salbutamol): number of occasions 
per day 

Night-time awakenings due to asthma symptoms requiring rescue 
medication
Any changes to the planned analysis methods will be documented in the 
reporting and analysis plan. Details of subgroup analyses for the primary and 
secondary endpoints will be described in the reporting and analysis plan.
Exploratory
Will be described in the reporting and analysis plan
10.4.2.
Safety Analyses
All safety analyses will be performed on the mITT Population. 
Endpoint
Statistical Analysis Methods
Primary
There is no primary safety analysis.
Secondary
The following secondary safety endpoints will be analyzed descriptively by 
treatment group:

Incidence and frequency of AEs and SAEs

Vital signs

12-lead ECG

24 hours Holter

Clinical laboratory evaluation

Incidence of and titres of anti-GSK3772847 antibodies.
Details will be described in the reporting and analysis plan
Adverse events (AEs) will be coded using the standard GSK dictionary, Medical
Dictionary for Regulatory Activities (MedDRA), and grouped by body system. The
number and percentage of subjects 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


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AEs, non-fatal SAEs, adverse events of special interest (AESIs) and AEs leading to 
withdrawal.
Deaths and SAEs, if applicable, will be documented in case narrative format.
10.4.3.
Pharmacokinetic Analyses
All safety analyzes will be performed on the PK 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.
10.4.4.
Pharmacodynamic Analyses
All pharmacodynamic analysis will be described in reporting and analysis plan.
10.4.5.
Other Analyses
PK, pharmacodynamic, and biomarker exploratory analysis will be described in the 
reporting and analysis plan. Any population PK analysis and pharmacodynamic analysis
will be reported separately from the main clinical study report (CSR). Should a 
genetic/PGx analysis be performed, a separate reporting and analysis plan will be 
generated (See Appendix 6: Genetics).
10.4.6.
Interim Analyses
Formal analyses will be performed at two timepoints.
End of Treatment Phase Analysis:
This will take place after all participants have completed the Week 16 visit. The data will 
be cleaned, the treatments unblinded and all clinic visits up to and including week 16 
frozen. However, whilst no further efficacy data will be collected post week 16, due to an 
inability to lock log forms used for collection of exacerbation data, the end of treatment 
phase analysis will be considered an interim analysis for both efficacy and safety. Any 
safety data collected for participants who have completed clinic visits after Week 16 will 
also be cleaned and included in the analysis. 
There will be no modifications to dosing regimens, sample size or any other aspects of 
the trial based on this data, as all study assessments, apart from follow-up, will have 
already been completed. As such an Independent Data Monitoring Committee (IDMC) 


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will not be used, as no further investigational product will be prescribed after this 
analysis has taken place. 
Final Analysis:  
This will take place after all subjects have completed the study. Data for visits after Week 
16 as well as data collected on log pages will be cleaned and the database frozen. This 
will be the final analysis for the study. 
The Reporting and Analysis Plan will describe the planned analyses in greater detail.  
Instream review: 
An iSRC 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 
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life in patients with difficult asthma: Psychometric performance of the Asthma Quality of 
Life Questionnaire. Respirology 2007; 12:227-233. 
Arshad MI, 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; 38:100-16. 
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. 
Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, et al. Oral 
Glucocorticoid-Sparing Effect of Mepolizumab in Eosinophilic Asthma. N Engl J Med 
2014; 371:1189-1197. 
Chung KF, Wenzel SE, Brozek JC, 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. 
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. 
Fleiss, J. L., Levin, B., Paik, M.C. 2003. Statistical Methods for Rates and Proportions. 
Third Edition. John Wiley & Sons. New York. 
http://onlinelibrary.wiley.com/doi/10.1002/0471445428.ch4/pdf 
Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma 
(GINA) 2016. Available from: http://www.ginasthma.org/ 
GlaxoSmithKline Document Number 2017N316832_00 GSK3772847 Investigator's 
Brochure. Effective Date: 07-JUN-2017 
Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health 
status for chronic airflow limitation. The St. George's Respiratory Questionnaire. Am 
Rev Respir Dis 1992;145:1321-1327. 
Jones PW. St. George’s Respiratory Questionnaire: MCID. Journal of Chronic 
Obstructive Pulmonary Disease 2005;2:75-79. 
Juniper EF, Bousquet J, Abetz L, Bateman ED; GOAL Committee. Identifying 'well-
controlled' and 'not well-controlled' asthma using the Asthma Control Questionnaire. 
Respir Med 2006;100:616-621. 
Juniper EF, O'Byrne PM, Guyatt GH, Ferrie PJ, King DR. Development and validation of 
a questionnaire to measure asthma control. Eur Respir J. 1999;14(4):902-907. 


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Juniper EF, Svensson K, Mörk AC, Ståhl E. Measurement properties and interpretation of 
three shortened versions of the asthma control questionnaire. Respir Med 2005;99:553-
558.
Matz J, Emmett A, Rickard K, Kalberg C. Addition of salmeterol to low-dose fluticasone 
versus higher-dose fluticasone: An analysis of asthma exacerbations. J Allergy Clin 
Immunol 2001;107:783-89.
McIvor RA, Pizzichini E, Turner MO, Hussack P, Hargreave FE, Sears MR. Potential 
masking effects of salmeterol on airway inflammation in asthma. Am J Respir Crit Care 
Med 1998;158:924-30.
Miller MR, Crapo R, Hankinson J, Brusasco V, Burgos F, Casaburi R, et al. 
Standardization of Lung Function Testing. Eur Resp J 2005;26:153-161.
Moore WC, Bleecker ER, Curran-Everett D Erzurum SC, Ameredes BT, Bacharier L, 
Calhoun WJ, 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.
Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, et al.
Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 
2009; 360:985-93.
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 P, Stanojevic S, Cole T, Baur X., Hall G, Enright P, et al. on behalf of the ERS 
Global Lung Function Initiative. 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.
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(8):1019-1030.
Wenzel SE, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, et al. Dupilumab in 
Persistent Asthma with Elevated Eosinophil Levels. N Engl J Med. 2013;368: 2455-66.
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mediates inflammatory responses in human lung tissue cells. J Immunol. 
2010;185(10):5743-5750.


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12.
APPENDICES
12.1.
Appendix 1: Abbreviations and Trademarks
Abbreviations
ACQ
Asthma Control Questionnaire
AE
Adverse Event
AESI
Adverse Event of Special Interest
ALT
Alanine Transaminase
AST
Aspartate Transaminase
ATS
American Thoracic Society
AUC
Area Under the Curve
BID
Twice a day
BUN
Blood Urea Nitrogen
CAD
Coronary artery disease
CI
Confidence Interval
CV
Cardiovascular
Cmax
maximum serum concentration
CIOMS
Council for International Organizations of Medical Sciences
CONSORT
Consolidated Standards of Reporting Trials
COPD
Chronic Obstructive Pulmonary Disease
CPK
Serum creatine phosphokinase
CSR
Clinical Study Report
DNA
Deoxyribonucleic acid
ECG
Electrocardiogram
(e)CRF
(Electronic) Case Report Form
ER
Emergency Room
eDiary
Electronic Diary
ETP
End of Treatment Phase
ERS
European Respiratory Society
EW
Early Withdrawal
FDA
Food and Drug Administration
FeNO
Fractional Exhaled Nitric Oxide
FEV1
Forced expiratory volume in 1 second
FP
Fluticasone Propionate
FSH
Follicle Stimulating Hormone
FTIH
First Time in Human
FVC
Forced Vital Capacity
GCP
Good clinical practice
GCSP
Global Clinical Safety and Pharmacovigilance
GGT
Gamma-glutamyltransferase
GINA
Global Initiative for Asthma
GLI
Global Lung Function Initiative
GLP
Good laboratory practice
GSK
GlaxoSmithKline


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HBsAg
hepatitis B surface antigen
hCG
Human Chorionic Gonadotropin
HIPAA
Health Insurance Portability and Accountability Act
HIV
Human Immunodeficiency Virus
HPLC
High performance liquid chromatography
HR
Heart rate
HRT
Hormone Replacement Therapy
IB
Investigator’s Brochure
ICF
Informed Consent Form
ICH
International Conference on Harmonization
ICS
Inhaled Corticosteroids
IEC
Independent Ethics Committee
IgG2
human immunoglobulin G2 sigma isotype
IgG
Immunoglobulin G
IL-33R
Interleukin-33 receptor
IL-1RL1
Interleukin-1 receptor like-1
IP
Investigational Product
IRB
Institutional Review Board
iSRC
Independent Safety Review Committee
IUD
Intrauterine device
IUS
Intrauterine hormone-releasing system
IV
Intravenous
IWRS
Interactive Web Response System
Kg
Kilogram
LABA
Long-Acting Beta-2-Agonists
LTRA
Leukotriene Receptor Antagonist
mAb
monoclonal antibody
MAO
Monoamine oxidase
MedDRA
Medicinal Dictionary for Regulatory Activities
mcg (g)
Microgram
MCH
Mean corpuscular haemoglobin
MCHC
Mean corpuscular haemoglobin concentration
MCV
Mean corpuscular volume
MDI
Metered Dose Inhaler
mg
Milligram
min
Minute
mIU
Milli international units
mITT
Modified Intent-to-treat
mL
Milliliter
L
Microlitre
mm
Millimeter
mV
Millivolt
MSDS
Material Safety Data Sheet
msec
Millisecond
NOAEL
No Observed Adverse Effect Level
NT-proBNP
N-terminal prohormone of brain natriuretic peptide


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NYHA
New York Heart Association
OCS
Oral Corticosteroid
PEF
Peak Expiratory Flow
PD
Pharmacodynamic
PGx
Pharmacogenetic
PK
Pharmacokinetic
prn
As needed
PSVT
Paroxysmal supraventricular tachycardia
q2W
Every two weeks
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
RBC
Red Blood Cell
RDW
Red cell distribution width
RNA
Ribonucleic acid
SABA
Short-Acting Beta-2-Agonists
SAD
Single Ascending Dose
SAE
Serious Adverse Event
Sal
Salmeterol
SGPT
Serum Glutamic-Oxaloacetic Transaminase
SGRQ
St. George’s Respiratory Questionnaire
SRM
Study Reference Manual
ST2
Suppressor of tumorigenicity 2
sST2
Soluble ST2
ULN
Upper Limit of Normal
US
United States
VT
Ventricular Tachycardia
WBC
White Blood Cell
WOCBP
Woman of childbearing potential
w/v
Weight/volume
Trademark Information
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
DISKUS
None


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12.2.
Appendix 2: Clinical Laboratory Tests

The tests detailed in Table 5 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. 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.
Table 5
Protocol-Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters
Hematology
Platelet Count
RBC Indices:
MCV
MCH
MCHC
WBC count with Differential:
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
These will be blinded from Visit 3
onwards.
Red Blood Cell (RBC) 
Count
Hemoglobin
Hematocrit
White Cell Count
RDW
Clinical 
Chemistry1
BUN
Potassium
Aspartate 
Aminotransferase
(AST)/ Serum 
Glutamic-
Oxaloacetic 
Transaminase
(SGOT)
Total and direct 
bilirubin


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Laboratory 
Assessments
Parameters
Creatinine
Sodium
Alanine 
Aminotransferase
(ALT)/ Serum 
Glutamic-Pyruvic 
Transaminase
(SGPT)
Total Protein
Glucose 
nonfasting
Calcium
Alkaline 
phosphatase
CPK
Albumin
Phosphorus
GGT
Chloride
Carbon Dioxide
Cardiac 
Markers

Cardiac troponin I (cTn I) 

N-terminal pro-brain natriuretic peptide (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)

Serum/urine human chorionic gonadotropin (hCG) pregnancy test (as 
needed for women of childbearing potential)2

Serology (HIV antibody, hepatitis B surface antigen 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


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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 (CIOMS) International Ethical 
Guidelines

Applicable 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 authorized representative and answer all 
questions regarding the study. 


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
Participants must be informed that their participation is voluntary. Participants 
or their legally authorized representative will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study center. 

The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent 
must also sign the ICF.

Participants must be re-consented to the most current version of the ICF(s) 
during their participation in the study. 

A copy of the ICF(s) must be provided to the participant or the participant’s 
legally authorized 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 authorized personnel appointed 
by the sponsor, by appropriate IRB/IEC members, and by inspectors from 
regulatory authorities.
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 
generally support publication of multicenter studies only in their entirety and not 
as individual site data. In this case, a coordinating investigator will be 
designated by mutual agreement.

Authorship will be determined by mutual agreement and in line with 
International Committee of Medical Journal Editors authorship requirements.


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Data Quality Assurance

All participant data relating to the study will be recorded on printed or electronic 
eCRF unless transmitted to the sponsor or designee electronically (eg, laboratory 
data). The 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 
Clinical Study Report (CSR)/ equivalent summary unless local regulations or 
institutional policies require a longer retention period. No records may be 
destroyed during the retention period without the written approval of the 
sponsor. No records may be transferred to another location or party without 
written notification to the sponsor. 
Source Documents

Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site.

Data reported on the eCRF or entered in the eCRF that are transcribed from 
source documents must be consistent with the source documents or the 
discrepancies must be explained. The investigator may need to request previous 
medical records or transfer records, depending on the study. Also, current 
medical records must be available.
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.


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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 (hematology, 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 fulfill the definition of an AE 
or SAE. 

The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be 
reported as AE or SAE if they fulfill the definition of an AE or SAE. Also, "lack of 
efficacy" or "failure of expected pharmacological action" constitutes an AE or SAE.


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Events NOT Meeting the AE Definition 

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.

Medical or surgical procedure (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 (eg, hospitalization 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 hospitalization or prolongation of existing hospitalization
In general, hospitalization 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 hospitalization are AE. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious.
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE.


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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, diarrhea, influenza, 
and accidental trauma (eg, sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

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 hospitalization but may 
jeopardize the participant or may require medical or surgical intervention to prevent 
one of the other outcomes listed in the above definition. These events should usually 
be considered serious.
Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, 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


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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 
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 sufficiently 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 utilized 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.


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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 Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK. However, it is very 
important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to GSK.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-up of AE and SAE

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, 
or consultation with other health care professionals.

If a participant dies during participation in the study or during a recognized follow-
up period, the investigator will provide GSK with a copy of any post-mortem 
findings including histopathology

New or updated information will be recorded in the originally completed eCRF.

The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information.


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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 or to the
assigned SAE contact by telephone.

Contacts for SAE reporting can be found at the beginning of this protocol on the 
Sponsor/Medical Monitor Contact Information page
SAE Reporting to GSK via Paper eCRF

Facsimile transmission of the SAE paper eCRF is the preferred method to transmit 
this information to the assigned SAE contact by telephone.

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 eCRF 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 hormonal replacement therapy 
(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 enrollment.
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 6. 


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Table 6
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 ovulation

oral

intravaginal 

transdermal 
Progestogen-only hormonal contraception associated with inhibition of ovulation 

injectable 
Highly Effective Methods That Are User Independent 

Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulation

Intrauterine device (IUD)

Intrauterine hormone-releasing system (IUS)

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. 
Pregnancy Testing

WOCBP should only be included after a confirmed menstrual period and a negative 
highly sensitive serum pregnancy test 

Additional pregnancy testing should be performed during the treatment period as 
specified in the Table of Events

Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected 


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
Pregnancy testing, with a sensitivity of 5, 10, 25 mIU/mL 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 fetal 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 Deoxyribonucleic acid (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 neutrophils 
and eosinophils 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 analyzed 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 analyzed 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 and related diseases 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 etiology 
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, stabilize, 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 
pharmacokinetic (PK) analysis within 1 
week after the liver event5

Serum creatine phosphokinase (CPK) 
and lactate dehydrogenase (LDH).

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 


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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, stabilize 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, stabilize or return to within 
baseline
on the concomitant medications report 
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 
(IgG) 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]). NOTE: 
not required in China

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


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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 02-JUN-2017
Overall Rationale for the Amendment: To address clarifications regarding the aim of 
the study, the eligibility criteria, the schedule of activities, the clinical assessments, and 
the recording of lab data and adverse events. The benefit:risk section was also updated 
based on the Part 2 results from study CNTO7160ASH1001. Also, a few typographical 
errors were corrected.
Section # and 
Name
Description of Change
Brief Rationale
Protocol title;
Section 1 
Synopsis; 
Section 3.1 Study 
Rationale; 
Section 5.2 
Number of 
participants; 
Section 5.4 
Scientific Rationale 
for study design
Section 6.1 
Inclusion Criteria
Clarified that the study will recruit 
participants with moderately 
severe asthma.
Participants with severe asthma for 
whom it is felt oral corticosteroids (OCS) 
or biologics are warranted (Step 5 
Global Initiative for Asthma GINA), are 
not eligible for this study.
Section 1 
Synopsis;
Section 3.1 Study 
Rationale
Clarified that the steroid titration 
design in this study will include 
inhaled corticosteroids.
To clarify that inhaled steroids will be 
titrated. Oral steroids are not allowed in 
this study.
Section 1 
Synopsis;
Section 3.1 Study 
Rationale
Section 5.4 
Scientific Rationale
Clarified that the aim of the 
steroid titration design is not to 
induce instability and 
exacerbations but changes in the 
level of asthma control. 
The aim of the study is to assess the 
effects on changes in the level of asthma 
control and not on exacerbations.
Section 1 
Synopsis;
Section 4 
Clarified that the objective of this 
study is to evaluate the efficacy, 
safety, pharmacokinetic, 
pharmacodynamics of 
The study will recruit participants with 
moderately severe asthma. Participants 
with severe asthma for whom it is felt 
OCS or biologics are warranted (Step 5 


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Section # and 
Name
Description of Change
Brief Rationale
Objectives and 
Endpoints
GSK3772847 in participants with 
moderately severe asthma and 
not in patients with severe 
asthma.
GINA), are not eligible for this study.
Section 1 
Synopsis;
Section 4 
Objectives and 
Endpoints
Included information on when the 
change from baseline will be 
measured for the safety and 
tolerability, pharmacokinetic and 
pharmacodynamics endpoints
To clarify how these endpoints will be 
analysed and reported.
Section 2 
Schedule of 
Activities
The assessments and 
procedures have been grouped 
together under efficacy, safety, 
laboratory, and study treatment
To make the SoA easier to read and 
follow.
Section 2 
Schedule of 
Activities
Reduced the visit window for 
Visits (V) 3 and 4 to 2 days.
With the previously allowed visit window 
of 3 days for weekly visits 3 and 4, 
these visits, in theory, could occur on 
consecutive days. To avoid this, the time 
window for these visits was reduced to 
2 days.
Section 2 
Schedule of 
Activities
Removed “Review of Loss of 
asthma control criteria” line item 
“X” at Visit 2.
Sites will not be able to review any of the 
criteria for loss of asthma control at V2 
so this assessment is not required at 
Visit 2
Section 2 
Schedule of 
Activities
Corrected “Medical history 
(includes substance usage)” line 
item to “Medical history (includes 
substance abuse)”.
Information on substance abuse is 
required as part of the medical history.
Section 2 
Schedule of 
Activities
Removed “caffeine” from the 
examples of substances for 
which information on abuse is 
required as part of medical 
history.
Information on caffeine usage or abuse 
is not required. This had been included 
in the previous protocol version in error.
Section 2 
Schedule of 
Activities
Corrected Week 8 as Day 57, 
rather than Day 49.
Typographical error
Section 2 
Schedule of 
Included in line item “Laboratory 
Assessments” that clinical 
chemistry tests will be performed 
Added information on the frequency of 
clinical chemistry tests.


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Section # and 
Name
Description of Change
Brief Rationale
Activities
at study visits indicated with a 
superscript 1.
Section 2 
Schedule of 
Activities
Included in line item “Laboratory 
Assessments” that cardiac lab 
tests will be performed at every 
clinic visit.
Added information on the frequency of 
cardiac lab markers.
Section 2 
Schedule of 
Activities
Included in line item “Laboratory 
Assessments” that routine 
urinalysis will be performed at 
Screening
Added information on the frequency of 
urinalysis test.
Section 2 
Schedule of 
Activities
Included in line item “Double 
blind Study Treatment (IP)” in the 
Notes column that patients will be 
monitored for 2 hours after the 
end of infusion
Added information on the duration of 
post-dose monitoring.
Section 3.3.1 Risk 
Assessment
Included more information on the 
identified risks based on the final 
data analysis from study 
CNTO7160ASH1001.
To update the risk assessment with 
information that became available after 
the final analysis of Part 2 of study 
CNTO7160ASH1001 
Section 3.3.2 
Benefit 
Assessment
Included that there are no 
existing efficacy data from 
molecules with the same mode of 
action and that the aim of the 
study is to provide evidence of 
efficacy in eosinophilic but also in 
non-eosinophilic asthma.
To provide further information on 
risk:benefit.
Section 3.3.2 
Benefit 
Assessment
Included that the IL-33 pathway 
may be implicated in type 2 and 
non-type 2 driven disease.
To add more information on the 
anticipated benefits from this study.
Section 3.3.2 
Benefit 
Assessment
Clarified that the electronic Diary 
(eDiary), the peak expiratory flow 
(PEF) measurement and the 
programmed safety alerts will be 
used in order to monitor the 
participants’ asthma status.
To clarify the safety measures that are in 
place in order to monitor the participants 
during the study. 
Section 5.1 Overall 
Design
Section 8.2 
Clarified that participants may 
need to be withdrawn during the 
run-in period depending on their 
For this study, the aim is to randomize at 
least 30% of participants with low 
eosinophil count. Therefore, participants 


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Section # and 
Name
Description of Change
Brief Rationale
Withdrawal from 
the study
blood eosinophil count in order to 
achieve the stratification balance.
may have to be withdrawn based on 
their eosinophil count measured at 
screening.
Section 5.1 Overall 
Design
Clarified that the data from the 
eDiary and the safety alerts will 
be available to the sites and 
provided information on how 
these data should be used by the 
participants and the sites in order 
to ensure adequate monitoring of 
the participant’s asthma status.
To clarify the safety measures that are in 
place in order to monitor the participants 
during the study.
Section 6.1 
Inclusion Criteria
Inclusion criterion 5: Added 
information on the eligibility 
criteria for participants with a 
history of bronchial 
hyperreactivity from bronchial 
challenge studies.
To clarify that for participants with a 
documented history of bronchial 
challenge tests, GINA guidelines and 
values will be used in order to determine 
eligibility.
Section 6.1 
Inclusion Criteria
Inclusion criterion 8: Added the 
requirement to use the study-
provided rescue medication as 
an inclusion criterion.
All participants must use the same 
rescue medication during the study.
Section 6.1 
Inclusion criteria; 
Section 6.3 
Randomisation
inclusion criteria
Inclusion criterion 6: Reduced the 
lower limit of ACQ5 to ≥1 and 
added an upper limit of <4. 
To clarify that participants with well-
controlled symptoms or participants with 
very severe and uncontrolled symptoms 
are not eligible.
Section 6.2 
Exclusion Criteria
Exclusion criterion 3: Added that 
the predicted values used for the 
spirometry eligibility will be based 
on the Global Lung Function 
Initiative (GLI) equations.
To clarify that the predicted values for 
spirometry will be based on the GLI 
equations.
Section 6.2 
Exclusion Criteria
Exclusion Criterion 4: Added the 
years in remission required for 
eligibility and provided 
clarification on eligibility of 
participants with certain types of 
carcinomas.
To provide clarification on the eligibility 
of participants.
Section 6.2 
Exclusion Criteria
Exclusion criterion 12: Added that 
participants with known or 
To provide further clarification on this 
exclusion criterion.


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Section # and 
Name
Description of Change
Brief Rationale
parasitic infestation 6 months 
prior to visit 1 are not eligible. 
Also, provided a definition for 
ongoing and recurrent infections.
Section 6.2 
Exclusion Criteria
Exclusion criterion 19: Added that 
participants should not be 
withdrawn or washed out of their 
medication for the sole purpose 
of participating in the study.
To clarify that participants’ treatment 
should not be changed only for study 
eligibility purposes.
Section 6.2 
Exclusion Criteria 
Exclusion criterion 19: Clarified 
that systemic corticosteroids are 
oral and parenteral, depot.
To provide clarification on systemic 
corticosteroids.
Section 6.2 
Exclusion Criteria
Exclusion criterion 19: 
Highlighted that potential 
participants should not be 
washed out of their regular 
medication for the sole purpose 
on enrolling in the trial. 
The participants’ medication should not 
be altered for the sole purpose on 
participating in the trial.
Section 6.2 
Exclusion Criteria
Exclusion criterion 19: Added the 
wash-out period for inhaled 
anticholinergics. 
To clarify that inhaled anticholinergics 
are not allowed 1 week prior to 
screening visit.
Section 6.4 
Randomisation 
Exclusion Criteria
Exclusion criterion 6: Added that 
the predicted values used for the 
spirometry eligibility will be based 
on the Global Lung Function 
Initiative (GLI) equations.
To clarify that the predicted values for 
spirometry will be based on the GLI 
equations.
Section 7.1 
Treatments 
Administered;
Section 7.5 
Preparation, 
Handling, Storage, 
Accountability
Clarified that normal saline will be 
used as a diluent for dilution of 
the study treatment and as 
placebo.
To provide information on the acceptable 
diluent.
Section 7.5
Preparation, 
Handling, Storage, 
Accountability
Removed the pre-dilution 
filtration step from the description 
of the treatment preparation
This step is not required.
Section 7.7.1 
Clarified that antihistamines 
To clarify the wash-out period for 


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Section # and 
Name
Description of Change
Brief Rationale
Permitted non-
asthma 
medications
should be avoided 48 hours prior 
to electrocardiogram (ECG) 
measurements
antihistamines prior to an ECG.
Section 7.7.2 
Prohibited 
Medications and 
Drug Therapies
Included that live or attenuated 
vaccines are prohibited 6 months 
after the last dose of blinded 
study treatment. Also clarified 
that systemic corticosteroids are 
oral and parenteral, depot.
To provide further clarifications on the 
prohibited medications.
Section 9.1.2.3 
Alerts
Added that in case of an alert the 
participant will receive notification 
to send the data to the 
centralised server as soon as 
possible and that the investigator 
will receive notification as soon 
as the data is transferred to the 
centralised server.
To provide further information on the 
alert notification process.
Section 9.1.3.1 
Spirometry
Clarified that a minimum of 2 
valid and 2 repeatable efforts are 
required at V1 and a minimum of 
2 valid (not necessarily 
repeatable) efforts are required at 
V2-11.
Different quality criteria apply for 
spirometry at various visits.
Section 9.1.3.2 
Reversibility
Included that a spacer may be 
used for reversibility.
To clarify the use of a spacer for 
reversibility.
Section 9.2 
Adverse Events
Clarified that asthma 
exacerbations will not be 
captured as adverse events 
(AEs) 
To clarify the way that asthma 
exacerbations will be captured in the 
electronic Case Report Form (eCRF).
Section 9.4.3 
Electrocardiograms
Clarified that ECGs should be 
performed before any blood 
draws and lung function tests.
To clarify the order of assessments.
Section 9.4.3 
Electrocardiograms 
Added that the participants 
should refrain from caffeine-
containing products, 
antihistamines and 
decongestants for a certain 
period of time prior to an ECG.
To clarify the wash-out period of 
caffeine, antihistamines and 
decongestants prior to an ECG.


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Section # and 
Name
Description of Change
Brief Rationale
Section 9.8.1.1 
Sputum Sub-Study
Clarified that the participants in 
the sputum sub-study will be 
randomised equally in the two 
treatment groups.
To provide clarification on the 
randomization strategy for the Sputum 
Sub-Study.
Section 10.4.1 
Efficacy Analysis
Added that the posterior 
probabilities will be calculated 
assuming a non-informative prior.
To clarify the analysis method that will 
be used.
Section 11 
Reference
Included the reference on the 
paper by Quanjer et al.
To provide the reference paper on the 
predicted values for spirometry that will 
be used in this study.
Section 12.2 
Appendix 2: 
Clinical Laboratory 
Tests
Added that the white blood cell 
(WBC) count differential will be 
blinded form V3 onwards
To clarify that these lab data will be 
blinded after randomisation.
Section 12.2 
Appendix 2: 
Clinical Laboratory 
Tests
Added that cardiac markers 
measured are Troponin I and N-
terminal prohormone of brain 
natriuretic peptide (NT-proBNP).
To clarify the cardiac markers that will be 
measured.
Section 12.2 
Appendix 2: 
Clinical Laboratory 
Tests
Removed the sentence "The 
results of each test should be 
entered into the eCRF" from the 
table.
Lab results will be electronically 
transferred from the central lab vendor to 
GSK. Sites are not required to transcribe 
lab data in the eCRF.
Section 12.7 
Appendix 7: Liver 
Safety: Required 
Actions and 
Follow-up 
Assessments
Added that a PK sample should 
be obtained within 1 week after 
the liver event. 
Typographical error. This edit removes 
the wording “insert time interval 
recommended by clinical 
pharmacokinetics representative after 
last dose” that was inadvertently copied 
from the protocol template to the final 
version of the protocol.


2017N311825_01
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GlaxoSmithKline group of companies
207597
1
TITLE PAGE
Protocol Title: A randomized, double-blind, parallel group, multicenter, stratified study 
evaluating the efficacy and safety of repeat doses of GSK3772847 compared with 
placebo in participants with moderately severe asthma
Protocol Number: 207597/01
Short Title: A study to evaluate the effect of GSK3772847 in patients with moderately
severe asthma.
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
 MB.BS 
Email: 
Tel: 
Regulatory Agency Identifying Number(s): IND number 134366, EudraCT number: 
2017-001072-34
Approval Date: 02-JUN-2017
Copyright 2017 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited.
PPD
PPD
PPD


PPD
PPD
PPD


2017N311825_01
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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document
Date
Amendment 1
02-JUN-2017
Original Protocol-2017N311825_00
06-MAR-2017
Amendment 1 02-JUN-2017
Overall Rationale for the Amendment: To address clarifications regarding the aim of 
the study, the eligibility criteria, the schedule of activities, the clinical assessments, and 
the recording of lab data and adverse events. The benefit:risk section was also updated 
based on the Part 2 results from study CNTO7160ASH1001. Also, a few typographical 
errors were corrected.
Section # and 
Name
Description of Change
Brief Rationale
Protocol title;
Section 1 
Synopsis;
Section 3.1 Study 
Rationale;
Section 5.2 
Number of 
participants;
Section 5.4 
Scientific Rationale 
for study design
Section 6.1 
Inclusion Criteria
Clarified that the study will recruit 
participants with moderately 
severe asthma.
Participants with severe asthma for
whom it is felt oral corticosteroids (OCS)
or biologics are warranted (Step 5 
Global Initiative for Asthma GINA), are 
not eligible for this study.
Section 1 
Synopsis;
Section 3.1 Study 
Rationale
Clarified that the steroid titration 
design in this study will include 
inhaled corticosteroids.
To clarify that inhaled steroids will be 
titrated. Oral steroids are not allowed in 
this study.
Section 1 
Synopsis;
Section 3.1 Study 
Rationale
Section 5.4 
Scientific Rationale
Clarified that the aim of the 
steroid titration design is not to 
induce instability and 
exacerbations but changes in the 
level of asthma control. 
The aim of the study is to assess the 
effects on changes in the level of asthma 
control and not on exacerbations.


2017N311825_01
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Section # and 
Name
Description of Change
Brief Rationale
Section 1 
Synopsis;
Section 4 
Objectives and 
Endpoints
Clarified that the objective of this 
study is to evaluate the efficacy, 
safety, pharmacokinetic, 
pharmacodynamics of 
GSK3772847 in participants with 
moderately severe asthma and 
not in patients with severe 
asthma.
The study will recruit participants with 
moderately severe asthma. Participants 
with severe asthma for whom it is felt 
OCS or biologics are warranted (Step 5 
GINA), are not eligible for this study.
Section 1 
Synopsis;
Section 4 
Objectives and 
Endpoints
Included information on when the 
change from baseline will be 
measured for the safety and 
tolerability, pharmacokinetic and 
pharmacodynamics endpoints
To clarify how these endpoints will be 
analysed and reported.
Section 2 
Schedule of 
Activities
The assessments and 
procedures have been grouped 
together under efficacy, safety, 
laboratory, and study treatment
To make the SoA easier to read and 
follow.
Section 2 
Schedule of 
Activities
Reduced the visit window for 
Visits (V) 3 and 4 to 2 days.
With the previously allowed visit window 
of 3 days for weekly visits 3 and 4, 
these visits, in theory, could occur on
consecutive days. To avoid this, the time 
window for these visits was reduced to 
2 days.
Section 2 
Schedule of 
Activities
Removed “Review of Loss of 
asthma control criteria” line item 
“X” at Visit 2.
Sites will not be able to review any of the 
criteria for loss of asthma control at V2
so this assessment is not required at 
Visit 2
Section 2 
Schedule of 
Activities
Corrected “Medical history 
(includes substance usage)” line 
item to “Medical history (includes 
substance abuse)”.
Information on substance abuse is 
required as part of the medical history.
Section 2 
Schedule of 
Activities
Removed “caffeine” from the 
examples of substances for 
which information on abuse is 
required as part of medical 
history.
Information on caffeine usage or abuse 
is not required. This had been included 
in the previous protocol version in error.
Section 2 
Schedule of 
Corrected Week 8 as Day 57, 
rather than Day 49.
Typographical error


2017N311825_01
CONFIDENTIAL
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5
Section # and 
Name
Description of Change
Brief Rationale
Activities
Section 2 
Schedule of 
Activities
Included in line item “Laboratory 
Assessments” that clinical 
chemistry tests will be performed 
at study visits indicated with a 
superscript 1.
Added information on the frequency of 
clinical chemistry tests.
Section 2 
Schedule of 
Activities
Included in line item “Laboratory 
Assessments” that cardiac lab 
tests will be performed at every 
clinic visit.
Added information on the frequency of 
cardiac lab markers.
Section 2 
Schedule of 
Activities
Included in line item “Laboratory 
Assessments” that routine 
urinalysis will be performed at 
Screening
Added information on the frequency of 
urinalysis test.
Section 2 
Schedule of 
Activities
Included in line item “Double 
blind Study Treatment (IP)” in the 
Notes column that patients will be 
monitored for 2 hours after the 
end of infusion
Added information on the duration of 
post-dose monitoring.
Section 3.3.1 Risk 
Assessment
Included more information on the 
identified risks based on the final 
data analysis from study 
CNTO7160ASH1001.
To update the risk assessment with 
information that became available after 
the final analysis of Part 2 of study 
CNTO7160ASH1001 
Section 3.3.2 
Benefit 
Assessment
Included that there are no 
existing efficacy data from 
molecules with the same mode of 
action and that the aim of the 
study is to provide evidence of 
efficacy in eosinophilic but also in 
non-eosinophilic asthma.
To provide further information on 
risk:benefit.
Section 3.3.2 
Benefit 
Assessment
Included that the IL-33 pathway 
may be implicated in type 2 and 
non-type 2 driven disease.
To add more information on the 
anticipated benefits from this study.
Section 3.3.2 
Benefit 
Assessment
Clarified that the electronic Diary 
(eDiary), the peak expiratory flow 
(PEF) measurement and the 
programmed safety alerts will be 
used in order to monitor the 
To clarify the safety measures that are in 
place in order to monitor the participants
during the study. 


2017N311825_01
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Section # and 
Name
Description of Change
Brief Rationale
participants’ asthma status.
Section 5.1 Overall 
Design
Section 8.2 
Withdrawal from 
the study
Clarified that participants may 
need to be withdrawn during the 
run-in period depending on their 
blood eosinophil count in order to 
achieve the stratification balance.
For this study, the aim is to randomize at 
least 30% of participants with low 
eosinophil count. Therefore, participants 
may have to be withdrawn based on 
their eosinophil count measured at 
screening.
Section 5.1 Overall 
Design
Clarified that the data from the 
eDiary and the safety alerts will 
be available to the sites and 
provided information on how 
these data should be used by the 
participants and the sites in order 
to ensure adequate monitoring of 
the participant’s asthma status.
To clarify the safety measures that are in 
place in order to monitor the participants 
during the study.
Section 6.1 
Inclusion Criteria
Inclusion criterion 5: Added 
information on the eligibility 
criteria for participants with a 
history of bronchial 
hyperreactivity from bronchial 
challenge studies.
To clarify that for participants with a 
documented history of bronchial 
challenge tests, GINA guidelines and 
values will be used in order to determine 
eligibility.
Section 6.1 
Inclusion Criteria
Inclusion criterion 8: Added the 
requirement to use the study-
provided rescue medication as 
an inclusion criterion.
All participants must use the same 
rescue medication during the study.
Section 6.1 
Inclusion criteria; 
Section 6.3 
Randomisation 
inclusion criteria
Inclusion criterion 6: Reduced the 
lower limit of ACQ5 to ≥1 and 
added an upper limit of <4. 
To clarify that participants with well-
controlled symptoms or participants with 
very severe and uncontrolled symptoms 
are not eligible.
Section 6.2 
Exclusion Criteria
Exclusion criterion 3: Added that 
the predicted values used for the 
spirometry eligibility will be based 
on the Global Lung Function 
Initiative (GLI) equations.
To clarify that the predicted values for 
spirometry will be based on the GLI 
equations.
Section 6.2 
Exclusion Criteria
Exclusion Criterion 4: Added the 
years in remission required for 
eligibility and provided 
clarification on eligibility of 
To provide clarification on the eligibility 
of participants.


2017N311825_01
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Section # and 
Name
Description of Change
Brief Rationale
participants with certain types of 
carcinomas.
Section 6.2 
Exclusion Criteria
Exclusion criterion 12: Added that 
participants with known or 
parasitic infestation 6 months 
prior to visit 1 are not eligible.
Also, provided a definition for 
ongoing and recurrent infections.
To provide further clarification on this
exclusion criterion.
Section 6.2 
Exclusion Criteria
Exclusion criterion 19: Added that 
participants should not be 
withdrawn or washed out of their 
medication for the sole purpose 
of participating in the study.
To clarify that participants’ treatment 
should not be changed only for study 
eligibility purposes.
Section 6.2 
Exclusion Criteria 
Exclusion criterion 19: Clarified 
that systemic corticosteroids are 
oral and parenteral, depot.
To provide clarification on systemic 
corticosteroids.
Section 6.2 
Exclusion Criteria
Exclusion criterion 19: 
Highlighted that potential 
participants should not be 
washed out of their regular 
medication for the sole purpose 
on enrolling in the trial. 
The participants’ medication should not 
be altered for the sole purpose on 
participating in the trial.
Section 6.2 
Exclusion Criteria
Exclusion criterion 19: Added the 
wash-out period for inhaled 
anticholinergics. 
To clarify that inhaled anticholinergics 
are not allowed 1 week prior to 
screening visit.
Section 6.4 
Randomisation 
Exclusion Criteria
Exclusion criterion 6: Added that 
the predicted values used for the 
spirometry eligibility will be based 
on the Global Lung Function 
Initiative (GLI) equations.
To clarify that the predicted values for 
spirometry will be based on the GLI 
equations.
Section 7.1 
Treatments 
Administered;
Section 7.5 
Preparation, 
Handling, Storage, 
Accountability
Clarified that normal saline will be 
used as a diluent for dilution of 
the study treatment and as 
placebo.
To provide information on the acceptable 
diluent.
Section 7.5 
Removed the pre-dilution 
This step is not required.


2017N311825_01
CONFIDENTIAL
207597
8
Section # and 
Name
Description of Change
Brief Rationale
Preparation, 
Handling, Storage, 
Accountability
filtration step from the description 
of the treatment preparation
Section 7.7.1 
Permitted non-
asthma 
medications
Clarified that antihistamines 
should be avoided 48 hours prior 
to electrocardiogram (ECG)
measurements
To clarify the wash-out period for 
antihistamines prior to an ECG.
Section 7.7.2 
Prohibited 
Medications and 
Drug Therapies
Included that live or attenuated 
vaccines are prohibited 6 months 
after the last dose of blinded 
study treatment. Also clarified 
that systemic corticosteroids are 
oral and parenteral, depot.
To provide further clarifications on the 
prohibited medications.
Section 9.1.2.3 
Alerts
Added that in case of an alert the 
participant will receive notification 
to send the data to the 
centralised server as soon as 
possible and that the investigator 
will receive notification as soon 
as the data is transferred to the 
centralised server.
To provide further information on the 
alert notification process.
Section 9.1.3.1 
Spirometry
Clarified that a minimum of 2 
valid and 2 repeatable efforts are 
required at V1 and a minimum of 
2 valid (not necessarily 
repeatable) efforts are required at 
V2-11.
Different quality criteria apply for 
spirometry at various visits.
Section 9.1.3.2 
Reversibility
Included that a spacer may be 
used for reversibility.
To clarify the use of a spacer for 
reversibility.
Section 9.2 
Adverse Events
Clarified that asthma 
exacerbations will not be 
captured as adverse events 
(AEs)
To clarify the way that asthma 
exacerbations will be captured in the 
electronic Case Report Form (eCRF).
Section 9.4.3 
Electrocardiograms
Clarified that ECGs should be 
performed before any blood 
draws and lung function tests.
To clarify the order of assessments.
Section 9.4.3 
Electrocardiograms 
Added that the participants 
should refrain from caffeine-
To clarify the wash-out period of 
caffeine, antihistamines and 


2017N311825_01
CONFIDENTIAL
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Section # and 
Name
Description of Change
Brief Rationale
containing products, 
antihistamines and 
decongestants for a certain 
period of time prior to an ECG.
decongestants prior to an ECG.
Section 9.8.1.1 
Sputum Sub-Study
Clarified that the participants in 
the sputum sub-study will be 
randomised equally in the two 
treatment groups.
To provide clarification on the 
randomization strategy for the Sputum 
Sub-Study.
Section 10.4.1 
Efficacy Analysis
Added that the posterior 
probabilities will be calculated 
assuming a non-informative prior.
To clarify the analysis method that will 
be used.
Section 11 
Reference
Included the reference on the 
paper by Quanjer et al.
To provide the reference paper on the 
predicted values for spirometry that will 
be used in this study.
Section 12.2 
Appendix 2: 
Clinical Laboratory 
Tests
Added that the white blood cell 
(WBC) count differential will be 
blinded form V3 onwards
To clarify that these lab data will be 
blinded after randomisation.
Section 12.2 
Appendix 2: 
Clinical Laboratory 
Tests
Added that cardiac markers 
measured are Troponin I and N-
terminal prohormone of brain 
natriuretic peptide (NT-proBNP).
To clarify the cardiac markers that will be 
measured.
Section 12.2 
Appendix 2: 
Clinical Laboratory 
Tests
Removed the sentence "The 
results of each test should be 
entered into the eCRF" from the 
table.
Lab results will be electronically 
transferred from the central lab vendor to 
GSK. Sites are not required to transcribe 
lab data in the eCRF.
Section 12.7 
Appendix 7: Liver 
Safety: Required 
Actions and 
Follow-up 
Assessments
Added that a PK sample should 
be obtained within 1 week after 
the liver event. 
Typographical error. This edit removes 
the wording “insert time interval 
recommended by clinical 
pharmacokinetics representative after 
last dose” that was inadvertently copied 
from the protocol template to the final 
version of the protocol.


2017N311825_01
CONFIDENTIAL
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TABLE OF CONTENTS
PAGE
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE.....................................3
1.
SYNOPSIS.............................................................................................................13
2.
SCHEDULE OF ACTIVITIES (SOA).......................................................................18
3.
INTRODUCTION....................................................................................................24
3.1.
Study Rationale ..........................................................................................24
3.2.
Background ................................................................................................24
3.3.
Benefit/Risk Assessment ............................................................................25
3.3.1.
Risk Assessment .........................................................................26
3.3.2.
Benefit Assessment.....................................................................32
3.3.3.
Overall Benefit:Risk Conclusion...................................................32
4.
OBJECTIVES AND ENDPOINTS...........................................................................33
5.
STUDY DESIGN ....................................................................................................35
5.1.
Overall Design ............................................................................................35
5.2.
Number of Participants ...............................................................................37
5.3.
Participant and Study Completion...............................................................38
5.4.
Scientific Rationale for Study Design ..........................................................38
5.5.
Dose Justification........................................................................................39
6.
STUDY POPULATION...........................................................................................41
6.1.
Inclusion Criteria.........................................................................................41
6.2.
Exclusion Criteria........................................................................................42
6.3.
Randomization Inclusion Criteria ................................................................46
6.4.
Randomization Exclusion Criteria ...............................................................47
6.5.
Lifestyle Restrictions...................................................................................47
6.6.
Pre-Screening/Screening/Run-in/Randomization Failures ..........................48
7.
TREATMENTS.......................................................................................................48
7.1.
Treatments Administered............................................................................49
7.1.1.
Description of Albuterol/Salbutamol .............................................50
7.1.2.
DISKUS Return............................................................................50
7.2.
Dose Modification .......................................................................................51
7.3.
Method of Treatment Assignment ...............................................................51
7.4.
Blinding.......................................................................................................51
7.5.
Preparation/Handling/Storage/Accountability..............................................52
7.6.
Treatment Compliance................................................................................53
7.7.
Concomitant Therapy..................................................................................54
7.7.1.
Permitted Non-asthma Medications .............................................54
7.7.2.
Prohibited Medications and Non-Drug Therapies.........................54
7.8.
Treatment after the End of the Study ..........................................................55
8.
DISCONTINUATION CRITERIA.............................................................................55
8.1.
Discontinuation of Study Treatment ............................................................55


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8.1.1.
Liver Chemistry Stopping Criteria ................................................56
8.1.2.
QTc Stopping Criteria ..................................................................57
8.1.3.
Rechallenge.................................................................................58
8.1.3.1.
Study Treatment Restart or Rechallenge....................58
8.2.
Withdrawal from the Study..........................................................................58
8.3.
Lost to Follow Up........................................................................................58
9.
STUDY ASSESSMENTS AND PROCEDURES .....................................................59
9.1.
Efficacy Assessments.................................................................................59
9.1.1.
Questionnaires ............................................................................59
9.1.1.1.
Asthma Control Questionnaire ACQ-5........................59
9.1.1.2.
St. George’s Respiratory of Life Questionnaire 
(SGRQ) ......................................................................60
9.1.2.
Daily Diaries ................................................................................60
9.1.2.1.
Night-time Awakening, Daytime Asthma 
Symptom Questions ...................................................61
9.1.2.2.
Morning and Evening Home PEF ...............................61
9.1.2.3.
Alerts..........................................................................61
9.1.3.
Pulmonary Function Test.............................................................62
9.1.3.1.
Spirometry..................................................................62
9.1.3.2.
Reversibility................................................................62
9.1.4.
Fractional Exhaled Nitric Oxide (FeNO) .......................................63
9.1.5.
Review of Loss of Asthma Control...............................................63
9.2.
Adverse Events...........................................................................................63
9.2.1.
Time Period and Frequency for Collecting AE and SAE 
Information...................................................................................64
9.2.2.
Method of Detecting AEs and SAEs.............................................64
9.2.3.
Follow-up of AEs and SAEs.........................................................65
9.2.4.
Regulatory Reporting Requirements for SAEs .............................65
9.2.5.
Cardiovascular and Death Events................................................65
9.2.6.
Pregnancy ...................................................................................65
9.3.
Treatment of Overdose...............................................................................66
9.4.
Safety Assessments ...................................................................................66
9.4.1.
Physical Examinations.................................................................66
9.4.2.
Vital Signs....................................................................................66
9.4.3.
Electrocardiograms......................................................................67
9.4.4.
Continuous ambulatory ECG (Holter)...........................................67
9.4.5.
Clinical Safety Laboratory Assessments ......................................68
9.5.
Pharmacokinetics .......................................................................................68
9.6.
Pharmacodynamics ....................................................................................68
9.7.
Genetics .....................................................................................................69
9.8.
Biomarkers .................................................................................................69
9.8.1.
Exploratory Biomarkers................................................................69
9.8.1.1.
Sputum Sub-Study .....................................................69
9.8.2.
Immunogenicity Assessments......................................................69
9.9.
Health Economics OR Medical Resource Utilization and Health 
Economics..................................................................................................70
10. STATISTICAL CONSIDERATIONS........................................................................70
10.1.
Hypotheses.................................................................................................70
10.2.
Sample Size Determination ........................................................................70
10.3.
Populations for Analyses ............................................................................71


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10.4.
Statistical Analyses.....................................................................................72
10.4.1.
Efficacy Analyses.........................................................................72
10.4.2.
Safety Analyses...........................................................................74
10.4.3.
Pharmacokinetic Analyses...........................................................75
10.4.4.
Pharmacodynamic Analyses........................................................75
10.4.5.
Other Analyses ............................................................................75
10.4.6.
Interim Analyses ..........................................................................75
11. REFERENCES.......................................................................................................77
12. APPENDICES........................................................................................................79
12.1.
Appendix 1: Abbreviations and Trademarks................................................79
12.2.
Appendix 2: Clinical Laboratory Tests.........................................................82
12.3.
Appendix 3: Study Governance Considerations..........................................84
12.4.
Appendix 4: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .......................................88
12.5.
Appendix 5: Contraceptive Guidance and Collection of Pregnancy 
Information..................................................................................................94
12.6.
Appendix 6: Genetics..................................................................................97
12.7.
Appendix 7: Liver Safety: Required Actions and Follow-up 
Assessments ..............................................................................................98


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1.
SYNOPSIS
Protocol Title: A randomized, double-blind, parallel group, multicenter, stratified study 
evaluating the efficacy and safety of repeat doses of GSK3772847 compared with 
placebo in participants with moderately severe asthma.
Short Title: A study to evaluate the effect of GSK3772847 in patients with moderately
severe asthma.
Rationale:
GSK3772847 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 (FTIH) study has completed dosing (final clinical study report is pending).
The safety information from this study is included in the investigator brochure
(GlaxoSmithKline Document Number 2017N316832_00). There are no efficacy data 
available to date. 
The present study is the first GSK sponsored study with GSK3772847. It is a Phase IIa / 
proof of concept study to investigate efficacy, safety and tolerability, pharmacokinetic 
(PK) and pharmacodynamic (PD) profiles of GSK3772847 in participants with 
moderately severe asthma. The study will use an inhaled steroid titration design in order 
to evaluate whether GSK3772847 maintains protection of asthma control. The design of 
steroid titration (oral or inhaled) in participants with asthma has been used in various 
studies with different investigational products, in which changes in the level of asthma 
control were induced by medication withdrawal. This design may not reflect real world 
fluctuations in asthma control; however, studies with the design of steroid titration have 
shown the ability to assess effects of a potential treatment on changes in asthma control
in a relatively short period of time, before further investigations are conducted in longer 
term studies.


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Objectives and Endpoints:
Objectives
Endpoints
Primary

To evaluate the efficacy of GSK3772847, 
compared with placebo, administered 
intravenously every 4 weeks for 12 weeks (Week 
0 – Week 12, 4 doses in total) in participants with
moderately severe asthma.
Primary – Proportion of participants with loss of asthma 
control over Weeks 0-16 where ‘loss of asthma control’ 
is defined as at least one of the following:

Asthma Control Questionnaire (ACQ-5) score 
increase from baseline (measured at the end of 
Run-in) ≥0.5 point or

Pre-bronchodilator Forced expiratory volume in 1 
second (FEV1) decrease from baseline 
(measured at the end of Run-in) >7.5 % or

Inability to titrate inhaled corticosteroid according 
to the pre-defined schedule (Section 5.1) or

A clinically significant asthma exacerbation 
(requiring oral corticosteroid [OCS] and/or 
hospitalisation).
Secondary

To evaluate other aspects of efficacy of 
GSK3772847 compared with placebo in 
participants with moderately severe asthma.
Other efficacy endpoints (at or by Week 16):

Proportion of participants with a ≥0.5 point. ACQ-
5 score increase from baseline.

Proportion of participants who have pre-
bronchodilator FEV1 decrease from baseline 
(measured at the end of Run-in) >7.5 %.

Proportion of participants where inhaled 
corticosteroids (ICS) cannot be titrated in 
accordance with the pre-defined schedule.

Proportion of participants who have a significant 
asthma exacerbation (requiring OCS and/or 
hospitalisation).

Time to loss of asthma control.

Proportion of participants with a clinically 
significant asthma exacerbation or inability to 
titrate ICS according to the pre-defined schedule

The incidence, mean rate, and total number per 
participant of hospitalisations or Emergency Room 
(ER) visits during the study treatment period.

Change from baseline in ACQ-5 absolute score at 
each week from Week 1 to Week 16.

Proportion of participants with ≥0.5 point ACQ-5 
score decrease from baseline (responder) at each 
week from Week 1 to Week 16.

Change from baseline in SGRQ total score at 
Weeks 4, 8, 12 and 16.

Proportion of St. George’s Respiratory 
Questionnaire (SGRQ) responders (at least a 4 
unit improvement from baseline) at Weeks 4, 8, 
12 and 16.

Change from baseline in pre-bronchodilator FEV1 
at Weeks 2, 4, 6, 8, 10, 12, 14, 16.

Change from baseline in mean morning peak 
expiratory flow (PEF) and mean evening PEF over 
each four weeks of the 16 week treatment period.

Change form baseline in mean daytime asthma 
symptom score over each four weeks of the 16 


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Objectives
Endpoints
week treatment period.

Change from baseline in rescue medication use 
(albuterol/salbutamol): mean number of 
inhalations per day over each four weeks of the 
16 week treatment period.

Changes from baseline in night-time awakenings
due to asthma symptoms requiring rescue 
medication use over each four weeks of the16 
week treatment period.

Change from baseline in fractional exhaled nitric 
oxide (FeNO) at each week measured.

To evaluate the safety and tolerability of 
GSK3772847, compared with placebo 
administered intravenously every 4 weeks for 12 
weeks (Week 0-12, 4 doses in total) in
participants with moderately severe asthma. 

Incidence and frequency of adverse events 
(AEs) and serious adverse events (SAEs).

Change from baseline in vital signs at weeks 1, 
2, 4, 6, 8, 10, 12, 14, 16, 20, 24 and 28.

Change between post-dose and pre-dose in vital 
signs at weeks 0, 4, 8 and 12.

Change from baseline in 12-lead 
electrocardiogram (ECG) measurements at 
weeks 4, 8, 12 and 16.

Change between post-dose and pre-dose in 12-
lead ECG measurements at weeks 0, 4, 8 and 
12.

Change from baseline in 24 hours Holter 
measurements at weeks 4 and 12.

Change from baseline in clinical chemistry at 
weeks 2, 4, 8, 12, 16 and 28.

Change from baseline in hematology and cardiac 
markers at weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 
and 28. 

Incidence of and titres of anti- GSK3772847 
antibodies at weeks 2, 4, 8, 12, 16, 20, 24 and 
28.

To evaluate the pharmacokinetics (PK) of 
GSK3772847 in participants with moderately
severe asthma.

Serum concentrations of GSK3772847 at weeks 
2, 4, 8, 12, 16, 20, 24 and 28.

To evaluate the pharmacodynamics (PD) of 
GSK3772847 in participants with moderately
severe asthma.

Free and total soluble ST2 levels in serum at 
weeks 2, 4, 8, 12, 16, 20, 24 and 28.


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Overall Design:
This is a Phase IIa, multicenter, randomized, placebo-controlled, double-blind, stratified, 
parallel group study in participants with moderately severe asthma.
There will be a 2-week Run-in period following Screening (Visit 1). Eligible participants 
will be randomized at the end of the Run-in period (Visit 2). Randomization will be 
stratified based on participants’ baseline peripheral blood eosinophil count aiming for at 
least 30% of participants with eosinophil count <150 cells /L, which is measured at 
Screening.
Number of Participants:
Approximately 300 participants with moderately severe asthma who are maintained on 
high-dose ICS/LABA will be screened to ensure 148 randomized (74 on GSK3772847, 
74 on placebo) participants and 140 evaluable participants. High-dose ICS is defined as 
fluticasone propionate 500 mcg twice daily (i.e. 1000 mcg /day) or equivalent. For the 
purpose of this study an evaluable participant is defined as a participant who completes 
the Week 16 clinic visit whilst remaining on investigational product (IP) or who 
withdraws from IP having met the primary endpoint. 
Treatment Groups and Duration:
When required, a pre-screening visit (Visit 0) can be scheduled for signing the informed 
consent, up to 2 weeks prior to Screening (Visit 1). The pre-screening visit can also occur 
on the same day as the Screening visit. Participants who meet the eligibility criteria at 
Screening (Visit 1) will withdraw their regular ICS/LABA treatment for asthma and enter 
a two-week Run-in period during which they will receive open label background therapy 
of fluticasone propionate (FP)/salmeterol (Sal) 500/50 mcg twice daily (BID). At the end 
of the Run-in period at Visit 2 (Week 0), participants who meet pre-defined 
randomization criteria will be randomized in a 1:1 ratio to enter a double-blind treatment 
period and receive the following study treatment every 4 weeks for 12 weeks (Week 0, 4, 
8 and 12) while initially remaining on the open label background therapy of FP/Sal 
500/50 mcg BID at Randomization:

GSK3772847 administered intravenously or

Placebo administered intravenously
At Visit 4, two weeks after Randomization, the open label background therapy will be 
switched from FP/Sal 500/50 mcg BID to FP 500 mcg BID for 2 weeks. Visit 4 will be 
the beginning of a six week FP titration period. Every two weeks for the next six weeks 
the dose of FP will be reduced by approximately 50 % (i.e. FP 250 mcg BID at Visit 5 for 
2 weeks, FP 100 mcg BID at Visit 6 for 2 weeks, then FP 50 mcg BID at Visit 7 for 2 
weeks) until complete discontinuation at Visit 8, provided that the participant does not 
meet any of the loss of asthma control criteria. If any of the pre-defined criteria for loss of 
asthma control are met during the Treatment period, participants will be withdrawn from 
the investigational product (IP) and should resume regular treatment for their asthma, as 
determined by the investigator. 


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An End of Treatment Phase (ETP) Visit will be performed 4 weeks after the final dose of 
the blinded study treatment is administered at Week 12. 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. 
Participants should resume regular treatment for their asthma, as determined by the 
investigator, after protocol defined study assessments are completed. Three Follow-up 
visits will be performed 4, 8, and 12 weeks (Week 20, Week 24, and Week 28) after the 
ETP/EW Visit for safety assessments.
Following randomization participants will return to the clinic at least every 2 weeks for 
scheduled FP dose titration and assessment of asthma control until the last dose of 
blinded study treatment (Visit 9). Albuterol/salbutamol will be provided for symptomatic 
relief to be used on an as needed basis from Screening through to the ETP visit. 
The maximum total duration of the study is approximately 33 weeks.


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2.
SCHEDULE OF ACTIVITIES (SOA)
Procedure
Pre-
Screen
ing1
Scree
n Run-
in
Treatment Period
Follow-up Period2
(3 days)
Notes
2 days
3 days
Visit 
0
1
23
3
4
5
6
7
8
9
10
11
(ETP 
or 
EW)
12
13
14
1.Pre-screening and screening 
can occur on the same day 
2. FU period to start 4 weeks 
after ETP or EW visit.
3. Visit 2 = Day 1 (first dose of 
IP).
Week
-4~-2
-2
0
1
2
4
6
8
10
12
14
16
20
24
28
Study Day
-28~-14
-14
1
8
15
29
43
57
71
85
99
113
Informed consent 
(ICF)
X
Genetic ICF
X
ICF for sputum
X
Inclusion and 
exclusion criteria
X
Randomisation 
Criteria
X
Demography
X
Full physical exam 
including height and 
weight
X
Medical history 
(includes substance 
abuse)
X
Substances [Drugs, Alcohol, 
tobacco] and family history of 
premature CV disease]):
[including cardiovascular 
medical history]
Laboratory


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Procedure
Pre-
Screen
ing1
Scree
n Run-
in
Treatment Period
Follow-up Period2
(3 days)
Notes
2 days
3 days
Visit 
0
1
23
3
4
5
6
7
8
9
10
11
(ETP 
or 
EW)
12
13
14
1.Pre-screening and screening 
can occur on the same day 
2. FU period to start 4 weeks 
after ETP or EW visit.
3. Visit 2 = Day 1 (first dose of 
IP).
Week
-4~-2
-2
0
1
2
4
6
8
10
12
14
16
20
24
28
Study Day
-28~-14
-14
1
8
15
29
43
57
71
85
99
113
Laboratory 
assessments
X1, 2
X1
X
X1
X1
X
X1
X
X1
X
X1
X1
Haematology (including 
eosinophil count) and cardiac
markers measured at all clinic 
visits.
1. Clinical chemistry (including 
liver chemistry).
2. Routine urinalysis at 
screening (Visit 1)
Pregnancy test1
X2
X3
X3
X3
X3
X
X
X
X
1. Test for women with child 
bearing potential. 
2. Serum pregnancy test at 
V0/V1.
3. Test to be performed pre-
dose during the treatment 
period.
[HIV, Hep B and Hep 
C screen]
X
A confirmatory negative 
Hepatitis C RNA test must be 
obtained, to be able to enrol 
participants with positive 
Hepatitis C antibody due to 
prior resolved disease. If test 
has been performed within 3 
months prior to first dose of 
study treatment, testing at 
screening is not required.


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Procedure
Pre-
Screen
ing1
Scree
n Run-
in
Treatment Period
Follow-up Period2
(3 days)
Notes
2 days
3 days
Visit 
0
1
23
3
4
5
6
7
8
9
10
11
(ETP 
or 
EW)
12
13
14
1.Pre-screening and screening 
can occur on the same day 
2. FU period to start 4 weeks 
after ETP or EW visit.
3. Visit 2 = Day 1 (first dose of 
IP).
Week
-4~-2
-2
0
1
2
4
6
8
10
12
14
16
20
24
28
Study Day
-28~-14
-14
1
8
15
29
43
57
71
85
99
113
Genetic blood sample 
– Pre dose
X
Pharmacogenetic sample may 
be drawn any time from Visit 2 
onwards. Informed consent for 
optional substudies e.g. 
genetics must be obtained 
before collecting a sample
Sputum sample 
collection
X
X
X
Pre-dose collection and in a 
sub-set of participants (~50 %) 
at selected sites; also collected 
for EW participants
PK, target 
engagement and 
immunogenicity 
assessments
X
X
X
X
X
X
X
X
X
X
See SoA Table 2 for details
Exploratory 
Biomarkers
X
X
X
Pre dose collection 
Efficacy
Spirometry 
X
X
X
X
X
X
X
X
X
X
Test to be performed pre-dose 
during the Treatment period         
Reversibility
X
FeNO
X
X
X
X
X
X
X
X
X
X
Test to be performed pre-dose
Review loss of 
asthma control 
criteria
X
X
X
X
X
X
X
X
X
It will include review of data to 
determine loss of asthma 
control. See Section 9.1.5.
Dispense eDiary
X


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Procedure
Pre-
Screen
ing1
Scree
n Run-
in
Treatment Period
Follow-up Period2
(3 days)
Notes
2 days
3 days
Visit 
0
1
23
3
4
5
6
7
8
9
10
11
(ETP 
or 
EW)
12
13
14
1.Pre-screening and screening 
can occur on the same day 
2. FU period to start 4 weeks 
after ETP or EW visit.
3. Visit 2 = Day 1 (first dose of 
IP).
Week
-4~-2
-2
0
1
2
4
6
8
10
12
14
16
20
24
28
Study Day
-28~-14
-14
1
8
15
29
43
57
71
85
99
113
Collect eDiary
X
Review eDiary
X
X
X
X
X
X
X
X
X
X
Safety
12-lead ECG
X
X1
X1
X1
X1
X
1. Test to be performed pre-
dose and post-dose within 30 
mins after end of infusion.
24 hrs Holter
X
X1
X1
X1
Holter monitor needs to be 
returned to clinic at end of 24-
hour recording (i.e. the next 
day).
1. Place the Holter 30-60 mins 
prior to dosing.
Vital signs
X
X1
X
X
X1
X
X1
X
X1
X
X
X
X
X
1. Test to be performed pre-
dose prior to spirometry and 
post-dose prior the 12 –lead 
ECG.
Dispense paper 
Medical 
Problems/Medication
s Taken worksheet
X
X
X
X
X
X
X
X
X
X
X
X
X
Review paper 
Medical 
Problems/Medication
s Taken worksheet
X
X
X
X
X
X
X
X
X
X
X
X
X


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Procedure
Pre-
Screen
ing1
Scree
n Run-
in
Treatment Period
Follow-up Period2
(3 days)
Notes
2 days
3 days
Visit 
0
1
23
3
4
5
6
7
8
9
10
11
(ETP 
or 
EW)
12
13
14
1.Pre-screening and screening 
can occur on the same day 
2. FU period to start 4 weeks 
after ETP or EW visit.
3. Visit 2 = Day 1 (first dose of 
IP).
Week
-4~-2
-2
0
1
2
4
6
8
10
12
14
16
20
24
28
Study Day
-28~-14
-14
1
8
15
29
43
57
71
85
99
113
AE/SAE review
X1
X1
==========================================
X
X
X
1. At V0 and V1 collect only 
SAEs considered as related to 
study participation.
Concomitant 
medication review
X
X
==========================================
X
X
X
Questionnaires
ACQ-5
X
X
After randomization, ACQ5 will 
be completed by the 
participants every 7 days. 
SGRQ
X
X
X
X
X
Study Treatment
Double blind Study 
Treatment (IP)
X
X
X
X
Patients will remain in the clinic 
for monitoring for at least 2 
hours after the end of infusion.
FP/Sal (500/50) 
dispensing
X
X
FP (mcg) dispensing
500
250
100
50
Dispense albuterol 
(as needed)
X
X
X
X
X
X
X
X
X
X
X


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SoA Table 2: Timings of PK, target engagement and immunogenicity samples
Procedure
Treatment Period 
Follow-up2
(3 days)
Notes
2 days
3 days
Visit 
21
3
4
5
6
7
8
9
10
11 
(ETP 
or EW)
12
13
14
1. Visit 2 = Day 1 
(first dose of IP). 
2. FU period to start 
4 weeks after ETP or 
EW visit.
Week
0
1
2
4
6
8
10
12
14
16
20
24
28
Study Day
1
8
15
29
43
49
71
85
99
113
Double blind 
Study 
Treatment 
(IP)
X
X
X
X
PK sample
X2
X
X
X3
X3
X1
X
X
X
X
1. Pre dose and 
post dose.
2. Post dose only.
3. Pre dose only.
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.
Free and total 
sST2
X1
X
X
X3
X3
X1
X
X
X
X
Immunogenicit
y sample
X3
X
X3
X3
X3
X
X
X
X


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3.
INTRODUCTION
3.1.
Study Rationale
GSK3772847 is a human immunoglobulin G2 sigma isotype (IgG2) antibody that binds 
Domain 1 of the cell-surface receptor 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 (FTIH) study has completed dosing (final report is pending). The safety 
information from this study is included in the investigator brochure (IB 
[GlaxoSmithKline Document Number 2017N316832_00]). There are no efficacy data 
available to date. 
The present study is the first GSK sponsored study with GSK3772847. It is a Phase IIa / 
proof of concept study to investigate efficacy, safety and tolerability, pharmacokinetic 
(PK) and pharmacodynamic (PD) profiles of GSK3772847 in participants with 
moderately severe asthma. The study will use an inhaled steroid titration design in order 
to evaluate whether GSK3772847 maintains protection of asthma control. The design of 
steroid titration (oral or inhaled) in participants with asthma has been used in various 
studies with different investigational products, in which changes in the level of asthma 
control were induced by medication withdrawal [Bel, 2014; Wenzel, 2013; Nair, 2009]. 
This design may not reflect real world fluctuations in asthma control; however, studies 
with the design of steroid titration have shown the ability to assess effects of a potential 
treatment on changes in asthma control in a relatively short period of time, before further 
investigations are conducted in longer term studies.
3.2.
Background
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]. 
Current biologic agents approved for the management of patients with severe asthma
have demonstrated efficacy for T2-driven disease (i.e., eosinophilic and/or elevated 
serum immunoglobulin E (IgE) however, there is no currently approved therapy that 
targets non-T2-driven asthma. 
GSK3772847 (formerly CNTO 7160 which was in-licensed from Janssen) is a human 
IgG2  monoclonal antibody (mAb) that binds to the extracellular domain of interleukin-
33 receptor (IL-33R) and neutralizes IL-33-mediated IL-33R signaling. 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].


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IL-33R is expressed on immune cells, such as mast cells, basophils, eosinophils, and T 
helper cell type 2 (Th2) cells and has been shown to be upregulated on macrophages, 
neutrophils, and dendritic cells. It is also expressed on non-immune cells such as 
endothelial, epithelial and smooth muscle cells and fibroblasts. IL-33 has been shown to 
be released after endothelial or epithelial cell damage during trauma, physicochemical / 
microbarometric stress or infection [Arshad, 2016]. IL-33R signalling causes downstream 
production of Type 2 cytokines. The engagement of IL-33R with its ligand IL-33 
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 via blockade of the IL-
33R 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 IV infusion (20 or 100 
mg/kg) and was found to be well-tolerated at both doses. 
Janssen (Study CNTO7160ASH1001) have conducted a Phase I randomized, double-
blind, placebo-controlled, intravenous (IV) single ascending dose study in healthy 
participants and multiple ascending dose study in participants with asthma and 
participants with atopic dermatitis. The study has completed dosing. The final clinical 
study report is still pending. There are no efficacy data available to date.
More information about the non-clinical and clinical studies is available in the
GSK3772847 IB (GlaxoSmithKline Document Number 2017N316832_00).
3.3.
Benefit/Risk Assessment
More detailed information about the known and expected benefits, risks and reasonably 
expected adverse events of GSK3772847 may be found in the IB (GlaxoSmithKline 
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 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 subcutaneous (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 CNTO7160ASH1001, 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 
Exclude participants with existing clinically 
significant organic heart disease (e.g. Coronary 
artery disease [CAD], New York Heart 
Association (NYHA) Class III/IV heart failure) and 
abnormal, clinically significant findings from 12-
lead 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 Section 2. 
All cardiac-related AEs will be reviewed by an 
independent safety review committee (iSRC).
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
temperature. The event was considered by the 
investigator to be likely related to the 
investigational product. No specific cause was 
identified. Data on this event was reviewed by 
GSK (Internal Cardiac Safety Panel and CMO), 
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 
CNTO7160ASH1001, 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 


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
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.
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 
(SAD) has shown the most frequent adverse 
events 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 6/24 [40%] 
administered placebo).
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. 
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 


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Safety data from Part 2 of the Janssen study 
CNTO7160ASH1001 have shown the System-
organ class (SOC) with the most frequent 
adverse events 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 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
part of the post marketing pharmacovigilance 
process.
Exclude patients with ongoing or recurrent 
infections.
Close monitoring of infection AEs (including 
pneumonia).
Increased risk of hyper-sensitivity, 
anaphylaxis, cytokine release syndrome 
(CRS)
Therapy with other mAbs 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 
patients at doses up to 10 mg/kg (3 doses, once 
every two weeks [q2W] over four weeks).
Based on in vitro cytokine release data and 
safety experience in Janssen study 
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.


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
CNTO7160ASH1001 the risk of CRS is 
considered negligible.
Possible interaction with live virus or 
bacterial vaccines
As GSK3772847 is an immunomodulator, there 
is a possibility that the subject will not mount an 
adequate immune response to a vaccine or even 
cause the infection the vaccine should protect 
against.
Steroid withdrawal is expected to augment a pro-
inflammatory response in the lung of the patients 
that drives the asthma phenotype.  Vaccination 
will also drive a systemic immune response to 
the pathogen antigen that runs the risk of 
causing some immunomodulation of the lung 
immune responses.  This has been best studied 
in murine models where eosinophilic lung 
inflammation has been suppressed by systemic 
toll-like receptor activation.
Non-clinical:
In the monkey 13 week toxicity study no 
GSK3772847-related changes in the T cell 
dependent B cell response (IgM or 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 
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).
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.
Gastrointestinal disorders
Nausea
Vomiting
Clinical:
In Part 2 of Janssen study CNTO7160ASH1001, 
the incidence of gastrointestinal disorders was 
greater in participants in the GSK3772847 
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
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.
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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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 open label salbutamol/albuterol to use as needed for 
asthma symptom relief from Screening 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, electrocardiogram (ECG), Holter 
monitoring, and clinical laboratory evaluation including liver chemistry and blood 
chemistry panel at a number of clinic visits. Participants will be monitored for changes in 
asthma control through daily use of an electronic Diary (eDiary) and twice-daily PEF 
measurements. Safety alerts will be provided to the participants and the sites in case of 
worsening of asthma. Participants’ health status will also be evaluated by ACQ-5 and 
SGRQ during the study. Participants’ safety will be assured by having criteria for 
withdrawal from study medication/reinstatement of usual care 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 the measures taken 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 GSK3772847, 
compared with placebo, administered 
intravenously every 4 weeks for 12 weeks 
(Week 0 – Week 12, 4 doses in total) in 
participants with moderately severe asthma.
Primary – Proportion of participants with loss of 
asthma control over Weeks 0-16 where ‘loss of 
asthma control’ is defined as at least one of the 
following:

Asthma Control Questionnaire (ACQ-5) score 
increase from baseline (measured at the end of 
Run-in) ≥0.5 point or

Pre-bronchodilator Forced expiratory volume in 
1 second (FEV1) decrease from baseline 
(measured at the end of Run-in) >7.5 % or

Inability to titrate inhaled corticosteroid 
according to the pre-defined schedule (Section 
5.1) or

A clinically significant asthma exacerbation 
(requiring oral corticosteroid [OCS] and/or 
hospitalisation).
Secondary

To evaluate other aspects of efficacy of 
GSK3772847 compared with placebo in 
participants with moderately severe asthma.
Other efficacy endpoints (at or by Week 16):

Proportion of participants with a ≥0.5 point. 
ACQ-5 score increase from baseline.

Proportion of participants who have pre-
bronchodilator FEV1 decrease from baseline 
(measured at the end of Run-in) >7.5 %.

Proportion of participants where inhaled 
corticosteroids (ICS) cannot be titrated in 
accordance with the pre-defined schedule.

Proportion of participants who have a significant 
asthma exacerbation (requiring OCS and/or 
hospitalisation).

Time to loss of asthma control.

Proportion of participants with a clinically 
significant asthma exacerbation or inability to 
titrate ICS according to the pre-defined 
schedule

The incidence, mean rate, and total number per 
participant of hospitalisations or Emergency 
Room (ER) visits during the study treatment 
period.

Change from baseline in ACQ-5 absolute score 
at each week from Week 1 to Week 16.

Proportion of participants with ≥0.5 point ACQ-5 
score decrease from baseline (responder) at 
each week from Week 1 to Week 16.

Change from baseline in SGRQ total score at 
Weeks 4, 8, 12 and 16.

Proportion of St. George’s Respiratory 


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Objectives
Endpoints
Questionnaire (SGRQ) responders (at least a 4 
unit improvement from baseline) at Weeks 4, 8, 
12 and 16.

Change from baseline in pre-bronchodilator 
FEV1 at Weeks 2, 4, 6, 8, 10, 12, 14, 16.

Change from baseline in mean morning peak 
expiratory flow (PEF) and mean evening PEF 
over each four weeks of the 16 week treatment 
period.

Change form baseline in mean daytime asthma 
symptom score over each four weeks of the 16 
week treatment period.

Change from baseline in rescue medication use 
(albuterol/salbutamol): mean number of 
inhalations per day over each four weeks of the 
16 week treatment period.

Changes from baseline in night-time 
awakenings due to asthma symptoms requiring 
rescue medication use over each four weeks of 
the16 week treatment period.

Change from baseline in fractional exhaled nitric 
oxide (FeNO) at each week measured.

To evaluate the safety and tolerability of 
GSK3772847, compared with placebo 
administered intravenously every 4 weeks for 
12 weeks (Week 0-12, 4 doses in total) in 
participants with moderately severe asthma. 

Incidence and frequency of adverse events 
(AEs) and serious adverse events (SAEs).

Change from baseline in vital signs at weeks 
1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24 and 28.

Change between post-dose and pre-dose in 
vital signs at weeks 0, 4, 8 and 12.

Change from baseline in 12-lead 
electrocardiogram (ECG) measurements at 
weeks 4, 8, 12 and 16.

Change between post-dose and pre-dose in 
12-lead ECG measurements at weeks 0, 4, 8 
and 12.

Change from baseline in 24 hours Holter 
measurements at weeks 4 and 12.

Change from baseline in clinical chemistry at 
weeks 2, 4, 8, 12, 16 and 28.

Change from baseline in hematology and 
cardiac markers at weeks 1, 2, 4, 6, 8, 10, 12, 
14, 16 and 28. 

Incidence of and titres of anti- GSK3772847 
antibodies at weeks 2, 4, 8, 12, 16, 20, 24 and 
28.

To evaluate the pharmacokinetics (PK) of 
GSK3772847 in participants with moderately
severe asthma.

Serum concentrations of GSK3772847 at 
weeks 2, 4, 8, 12, 16, 20, 24 and 28.

To evaluate the pharmacodynamics (PD) of 
GSK3772847 in participants with moderately

Free and total soluble ST2 levels in serum at 
weeks 2, 4, 8, 12, 16, 20, 24 and 28.


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Objectives
Endpoints
severe asthma.
Exploratory 

To compare the effect of GSK3772847 with 
placebo on biomarkers in serum and sputum.

Changes from baseline in induced sputum 
biomarkers (subset) at weeks 8 and 16.

Changes from baseline in exploratory serum 
markers at weeks 8 and 16.
5.
STUDY DESIGN
5.1.
Overall Design
This is a Phase IIa, multicenter, randomized, placebo-controlled, double-blind, stratified,
parallel group study.
There will be a 2-week Run-in period following Screening (Visit 1). Eligible participants 
will be randomized at the end of the Run-in period (Visit 2). Randomization will be 
stratified based on participants’ baseline peripheral blood eosinophil count aiming 
for at least 30% of participants with eosinophil count <150 cells/L, which is 
measured at Screening. In order to achieve the stratification balance, as a result of 
participants’ eosinophil count it may be necessary to withdraw participants from 
the study during the Run-in period.
When required, a pre-screening visit (Visit 0) can be scheduled up to 2 weeks prior to 
Screening (Visit 1). The pre-screening visit (Visit 0) can also occur on the same day as 
the Screening visit (Visit 1). Participants who meet the eligibility criteria at Screening 
(Visit 1) will withdraw their regular ICS/ long-acting beta-2-agonists (LABA) treatment 
for asthma and enter a two-week Run-in period during which they will receive open label 
background therapy of fluticasone propionate (FP)/salmeterol (Sal) 500/50 mcg BID. At 
the end of the Run-in period at Visit 2 (Week 0), participants who meet pre-defined 
randomization criteria (Section 6.3) will be randomized in a 1:1 ratio to enter a double-
blinded Treatment Period and receive the following study treatment every 4 weeks for 12 
weeks (Week 0, 4, 8 and 12) while initially remaining on the open label background 
therapy of FP/Sal 500/50 mcg BID at Randomization:

GSK3772847 administered intravenously  or

Placebo administered intravenously
At Visit 4 (i.e. two weeks after Randomization) the open label background therapy will 
be switched from FP/Salmeterol 500/50 mcg BID to FP 500 mcg BID for 2 weeks. This 
will mark the beginning of the FP titration period. Every two weeks for the next six 
weeks the dose of FP will be reduced by approximately 50 % (i.e. FP 250 mcg BID at 
Visit 5 for 2 weeks, FP 100 mcg BID at Visit 6 for 2 weeks, then FP 50 mcg BID at Visit 
7 for 2 weeks) until complete FP discontinuation at Visit 8, provided that the participant 
does not meet any of the loss of asthma control criteria. If any of the pre-defined criteria 


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for loss of asthma control are met during the Treatment Period, participants will be 
withdrawn from the investigational product (IP) and should resume regular treatment for 
their asthma, as determined by the investigator. 
Participants will be monitored for loss of asthma control through daily use of an eDiary 
and twice-daily PEF measurements. The participants will use the eDiary to record asthma 
symptoms, rescue medication use, and nocturnal awakenings due to asthma symptoms 
requiring rescue medication use. This information will be transmitted daily to a 
centralized server and available to the investigators. Alerts for pre-defined changes in 
PEF or asthma symptoms, indicative of worsening asthma, will be programmed into the 
eDiary with prompts to the participants to contact the investigator if any of the alert 
criteria are met (Section 9.1.2.3). Additionally, email notifications will be sent to the 
investigator, if any of the alert criteria are met, as soon as the data is transmitted to the 
centralized server. The investigator will make every effort to contact the participants in 
order to discuss the participants’ symptoms and evaluate whether they experienced loss 
of asthma control.
For participants who receive all four doses of blinded study treatment, an End of 
Treatment Period (ETP) Visit will be performed 4 weeks after the final dose of the 
blinded study treatment is administered at Week 12. Participants should resume regular 
treatment for their asthma, as determined by the investigator, after protocol defined study 
assessments are completed. Three Follow-up visits will be performed 4, 8, and 12 weeks 
(Week 20, Week 24, and Week 28) after the ETP Visit for safety assessments.
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. Participants 
should resume regular treatment for their asthma, as determined by the investigator. 
Three Follow-up visits will then be performed 4, 8, and 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.   


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Following randomization participants will return to the clinic at least every 2 weeks for 
scheduled FP dose titration and assessment of asthma control until the last dose of 
blinded study treatment (Visit 10).
Albuterol/salbutamol will be provided for symptomatic relief to be used on an as needed 
basis from Screening through to the ETP visit. 
The maximum total duration of the study is approximately 33 weeks.
An independent Safety Review Committee (iSRC) 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 
iSRC Charter. 
5.2.
Number of Participants
Approximately 300 participants with moderately severe asthma who are maintained on 
high-dose ICS/LABA will be screened to ensure 148 randomized (74 on GSK3772847, 
74 on placebo) participants and 140 evaluable participants. For the purpose of this study 
an evaluable participant is defined as a participant who completes the Week 16 clinic 
visit whilst remaining on IP or who withdraws from IP having met the primary endpoint. 
High-dose ICS is defined as fluticasone propionate 500 mcg twice daily (i.e. 
1000 mcg total daily dose) or equivalent.


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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 randomized treatment phase, and 
safety follow-up. 
The end of the study is defined as the date of the last scheduled procedure shown in the 
Schedule of Activities for the last participant in the trial globally.
5.4.
Scientific Rationale for Study Design
This study will use a multicenter, randomized, double-blind, parallel-group and placebo-
controlled design.  This is a well-established design to evaluate the efficacy, safety, PK 
and PD profiles of an investigational drug. The design of steroid titration (oral or inhaled) 
in participants with asthma has been used in various studies with different investigational 
products, in which changes in the level of asthma control were induced by medication 
withdrawal [Bel, 2014; Wenzel, 2013; Nair, 2009]. This design may not reflect real world 
fluctuations in asthma control, however studies with the design of steroid titration have 
shown the ability to assess effects of a potential treatment on changes in asthma control
in a relatively short period of time, before further investigations are conducted in longer 
term studies.  
In this study, the target population would be participants with moderately severe asthma 
and with an ACQ5 score ≥1 and <4 whose symptoms must have been managed on a 
stable, high dose ICS/LABA for at least 4 months prior to Screening. The use of loss of 
asthma control as a composite study endpoint and a criterion for ICS titration allows for 
the overall clinical evaluation of the participant’s asthma status taking into account both 
lung function and symptom control. Participants will also be monitored through the use 
of the eDiary. Pre-specified asthma symptom scores and participant-measured PEF that is 
inputted into the eDiary will be used as prompts for contacts between subjects and 
investigators (Section 9.1.2.3).
The FP titration period will occur during the Treatment Period of the study. The FP dose 
reduction will be assessed and managed at scheduled clinic visits. During the FP titration 
period the subjects’ FP dose will be reduced as described in Section 5.1 and the SoA, 
unless the subject meets protocol defined criteria for loss of asthma control indicating 
that it is not acceptable for the participant to further reduce ICS. Prior to each FP dose 
reduction an assessment of the participants’ asthma control should be completed and the 
decision to reduce the dose of FP will be based on: 1) the presence and severity of 
exacerbations, 2) changes in FEV1, 3) changes in the most recent ACQ-5 score, or 4) the 
ability to titrate ICS as per the pre-defined schedule, according to the investigator’s 
clinical judgment. If loss of asthma control is confirmed during the FP titration period, 
the participant will discontinue IP immediately and should resume regular treatment for 
their asthma, as determined by the investigator. A similar methodology was recently 
reported [Wenzel, 2013] and successfully allowed titration of ICS. 
To evaluate the safety and tolerability of repeat dose of GSK3772847, a placebo arm will 
be included to allow the absolute effect of GSK3772847 to be assessed. The treatment 
duration of 12 weeks is supported by pre-clinical study data. Dosing frequency of IP 


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every 4 weeks with endpoints assessments scheduled 4 weeks post final IP dose are 
determined by the available target engagement pharmacodynamic findings. Upon 
completing the 16 week Treatment Period (or after IP discontinuation), participants 
should resume regular treatment for their asthma, as determined by the investigator and 
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 taken to fully characterise the 
pharmacokinetics, pharmacodynamics, and anti-drug antibody responses in this 
population.
An inhaled short acting beta2–receptor agonist, salbutamol/albuterol will be provided to 
all participants to use as needed to relieve asthma symptoms from Screening (Visit 1) to 
end of the Treatment Period. Both safety and efficacy parameters will be assessed 
regularly in the clinic to minimise any potential risks to the participants. Participants’
safety will also be assured by having withdrawal criteria (Section 8.1) in case of loss of 
asthma control.
5.5.
Dose Justification
The dosing regimen of 10 mg/kg IV at Week 0 then Weeks 4, 8 and 12 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 0-16 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 1


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Figure 1
Predicted clinical exposures at 10mg/kg at weeks 0, 4, 8 and 12 
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 
(NOAEL) (100 mg/kg weekly) in the 3-month GLP toxicology study in 
cynomolgus monkeys (T-2013-007).

Open Triangles: Observed mean and SD 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.
The anticipated exposure margins of the dosing regimen of 10 mg/kg IV at Week 0 then 
Weeks 4, 8 and 12 over the 3-month GLP toxicology study in cynomolgus monkeys (T-
2013-007) are summarised in Table 1. 


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Table 1
Predicted clinical exposures and safety margins for study 207597
following dosing of 10 mg/kg at weeks 0, 4, 8 and 12.
Day 1 mean Cmax
(µg/mL)
Exposure 
margina
Week 12 
mean Cmax 
(µg/mL)
Exposure 
margina
0-28 weeks
AUC
(µg.day/mL)
Exposure 
marginb
245.3c
10.5
313.5d
17.4
16830.2d
18.2
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.
c.
Mean observed exposures in study CNTO7160ASH1001.
d.
Predicted exposures using preliminary MM model
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:
1.
Age: At least 18 years of age at the time of signing the informed consent.
2.
Gender: Males and females. 
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:

Not a woman of childbearing potential (WOCBP) as defined in Appendix 5.
i.
OR

A WOCBP who agrees to follow one of the options listed in Appendix 5 from 
4 weeks prior to the first dose of study medication and until at least 16 weeks
after the last dose of study medication and completion of the follow-up visit.
3.
Informed consent: Capable of giving signed informed consent which includes 
compliance with the requirements and restrictions listed in the consent form and in 
this protocol.
4.
Asthma diagnosis and severity: A participant with a documented diagnosis of 
moderate-severe asthma based on Global Initiative for Asthma (GINA) 2016 
Guidelines, whose asthma has been managed with regular treatment of high dose ICS 
defined as fluticasone propionate 500 mcg twice daily (i.e. 1000 mcg total daily dose) 
or equivalent, and long-acting beta-2-agonist (LABA) for at least 4 months.
Additional therapy with a leukotriene receptor antagonist (LTRA) is permissible.
5.
Reversibility: Airway reversibility of at least 12 % and 200 mL in FEV1 at 
Screening (Visit 1), or documented reversibility prior to Screening (Visit 1), or 


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documented history of bronchial hyperreactivity (e.g. fall in FEV1 from baseline of 
≥20% with standard doses of methacholine or histamine, or ≥15% with standardized 
hyperventilation, hypertonic saline or mannitol challenge) from a bronchoprovocation 
study (e.g. methacholine challenge) prior to Screening (Visit 1).
Note: If the participant does not meet the above reversibility criteria at Screening 
(Visit 1) then the reversibility assessment may be repeated once within 7 days of Visit 
1. Should the participant successfully demonstrate airway reversibility at the second 
attempt then, provided that all other eligibility criteria assessed at Screening (Visit 1) 
are met, the participant may enter the 2-week run-in period.
6.
Asthma Control Questionnaire (ACQ): ACQ-5 score ≥1 and <4 at Screening 
(Visit 1).
7.
Exacerbation history: Had at least one asthma exacerbation within 12 months prior 
to Screening that required treatment with systemic corticosteroid and/or 
hospitalization.
8.
Short-Acting Beta2-Agonists: All subjects must be able to replace their current 
SABA treatment with albuterol/salbutamol aerosol inhaler at Visit 1 for use as 
needed, per product label, for the duration of the study.
6.2.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
1. Smoking history: Current smokers or former smokers with a smoking history ≥10 
pack years. 
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.
3. Severe airflow obstruction: A pre-bronchodilator FEV1 <50 % predicted of normal 
value at Screening (Visit 1). Predicted values will be based upon Global Lung 
Function Initiative (GLI) [Quanjer, 2012] equations for spirometry reference values. 
Note: If the spirometry is deemed technically inadequate by the central reader, the 
spirometry assessment may be repeated once within 7 days of Screening (Visit 1).
4. Malignancy: 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 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.
5. Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody 
test result at Screening (Visit 1) or within 3 months prior to first dose of study 
treatment.


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NOTE: Participants with positive Hepatitis C antibody due to prior resolved disease 
can be enrolled, only if a confirmatory negative Hepatitis C Ribonucleic acid (RNA) 
test is obtained.
6. 12-lead ECG assessment at Screening (Visit 1): Site investigators will be provided 
with ECG over-read conducted by a centralized independent cardiologist, to assist in 
evaluation of subject eligibility. For this study, an abnormal and clinically significant 
ECG that would preclude a subject 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 2: 


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Table 2
Abnormal and clinically significant ECG findings

Sinus bradycardia <45bpm
*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 
subject is precluded from entering the study.

Evidence of ventricular ectopic couplets, bigeminy, trigeminy or multifocal 
premature ventricular complexes.

For subjects 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 subjects 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 subject 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)
7.
Weight: <50 kg and >150 kg


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8.
Regular use of systemic corticosteroids for conditions including asthma within 3 
months prior to Screening (Visit 1).
9.
Participants with high parasympathetic tone (e.g. trained athletes with baseline 
bradycardia) or chronic conditions associated with parasympathetic surges (e.g. 
migraines)
10. 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).
11. Cardiovascular disease: Clinically significant organic heart disease (e.g. CAD, 
NYHA Class III/IV heart failure).
12. Ongoing infections (i.e. not resolved within 7 days prior to Screening [Visit 1]) or 
recurrent infections (i.e. requiring treatment for an identical diagnosis within 3 
months) requiring systemic antibiotics. Known, pre-existing parasitic infestations 
within 6 months prior to Screening.
13. Other Concurrent Diseases/Abnormalities:  A subject must not have any clinically 
significant, uncontrolled condition, or disease state that, in the opinion of the 
investigator, would put the safety of the subject at risk through study participation or 
would confound the interpretation of the efficacy results if the condition/disease 
exacerbated during the study.
The list of additional excluded conditions/diseases includes, but is not limited to, the 
following:
Addison's disease
hypertension1 (uncontrolled)
aortic aneurysm (clinically significant)
peptic ulcer (recent or poorly controlled)
Cushing's disease
renal disease
diabetes mellitus (uncontrolled)
stroke within 3 months of Visit 1
hematological disease
thyroid disorder (uncontrolled)
hepatic disease
tuberculosis (current or untreated2)
1.
Two or more measurements with systolic pressure >160mmHg or diastolic pressure >100mmHg
2.
Subjects with a history of tuberculosis infection who have completed an appropriate course of 
antituberculosis treatment may be suitable for study entry provided that there is no clinical suspicion of 
active or recurrent disease.
14. Immunodeficiency: A known immunodeficiency such as human immunodeficiency 
virus infection.
15. Hypersensitivity: Participants with allergy or intolerance to a monoclonal antibody 
or biologic or to any components of the formulation used in this study.
16. Alcohol and Substance abuse: Participants with a history (or suspected history) of 
alcohol misuse or substance abuse within 2 years prior to Screening (Visit 1).
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, dosing directions, study eDiary completion, or use of a standard metered 
dose inhaler. Participants who have known evidence of lack of adherence to 
controller medication and/or ability to follow physician’s recommendations.  Any 


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infirmity, disability, or geographic location that would limit compliance for scheduled 
visits.
18. Participants who have previously participated in a study of GSK3772847.
19. Excluded Medications:  Use of the medications listed in Table 3 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 on enrolling in the trial.
Table 3
Prohibited Medications
Medication
Time interval prior to Visit 1
Investigational drug
One month or 5 half-lives whichever is longer
Live or attenuated vaccinesa
2 weeks (i.e. 4 weeks prior to IP administration)
Biologics, for example Mepolizumab and 
Omalizumab
130 days or 5 half-lives whichever is longer
Experimental anti-inflammatory drugs (non-
biologics)
3 months
Corticosteroids intramuscular, long acting depot 
Regular systemic corticosteroid - oral, 
parenteral, depot
3 months
Methotrexate, troleandomycin, oral gold, 
cyclosporin, azathioprine, 
3 months
Theophylline
3 months
Chemotherapy and radiotherapy
12 months
Inhaled anti-cholinergics e.g. tiotropium
1 week
a.
Vaccines containing killed bacteria or inactivated virus will be permitted
20. Affiliation with Investigator Site:  A participant will not be eligible for this study if 
he/she is an immediate family member of the participating investigator, sub-
investigator, study coordinator, or employee of the participating investigator.
21. Inability to read:  In the opinion of the investigator, any participant who is unable to 
read and/or would not be able to complete a diary card/questionnaire.  
22. Questionable validity of consent: Participants with a history of psychiatric disease, 
intellectual deficiency, poor motivation or other conditions that will limit the validity 
of informed consent to participate in the study.
6.3.
Randomization Inclusion Criteria
At the end of the Run-in period (Visit 2), study participants must fulfil the following 
additional criteria in order to be randomized into the study and enter the treatment period:
1. Asthma Control Questionnaire (ACQ): ACQ-5 score ≥1 and <4 at Visit 2.
2. eDiary Compliance: Compliance with completion of the eDiary reporting defined as 
completion of all questions/assessments on ≥4 of the last 7 days during the run-in 
period. 


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6.4.
Randomization Exclusion Criteria
Participants meeting any of the following criteria must not be randomized to double-
blind study medication 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. 12-lead ECG over-read: Evidence of clinically significant abnormal ECG findings 
(Table 2) at Screening (Visit 1).
3. 24-Hour Holter Monitoring: An abnormal and significant finding from 24-hour 
Holter monitoring at Screening (Visit 1). 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 2. The 
study investigator will determine the medical significance of any Holter abnormalities 
not listed in Table 2.
4. Liver function at Screening (Visit 1)

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 %). 

Current or chronic history of liver disease, or known hepatic or biliary 
abnormalities (with the exception of Gilbert's syndrome or asymptomatic 
gallstones.
5. Asthma exacerbation: Participants with ongoing asthma exacerbation at the time of 
Visit 2. 
Note: At the Investigator’s discretion, participants with an ongoing asthma 
exacerbation at Visit 2 may be re-screened 2 weeks after Visit 2. In such cases, the 
full screening process (i.e. all Visit 0, 1 and Visit 2 assessments) must be repeated. 
6. Severe airflow obstruction: a pre-bronchodilator FEV1 <50 % predicted of normal 
value at Visit 2. Predicted values will be based upon GLI [Quanjer, 2012] equations 
for spirometry reference values.
7. Positive pregnancy test at Visit 0, Screening (Visit 1) or Visit 2.
8. Ongoing or recurrent infections requiring systemic antibiotics.
6.5.
Lifestyle Restrictions
No lifestyle restrictions are required for this study.


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6.6.
Pre-Screening/Screening/Run-in/Randomization Failures
A participant will be assigned a participant number at the time the informed consent is 
signed at Visit 0.
The study site will be responsible for reporting pre-screen failures. The following 
information will be collected in the eCRF for participants who are pre-screen failures:

Demographic information including race, age and gender

Participant number

Serious Adverse Event information only for any SAE considered as related to 
study participation
For the purposes of this study, pre-screening failures, screening failures, run-in failures
and randomization failures will be defined as follows:

Pre-screening failures: those participants that sign the informed consent 
document but do not have a Screening (Visit 1) procedure.

Screening failures: those participants that complete at least one Screening
(Visit 1) procedure but do not enter the run-in period. 
A participant who completes Visit 1 assessments and is dispensed the study 
medication for the run-in period is considered to have entered the run-in period.

Run-in failures: those participants that enter the run-in period but do not have 
any Visit 2 procedures.

Randomization failures: those participants that complete at least one Visit 2 
procedure but do not enter the double-blind study treatment period.
Any participant who completes the run-in period and then meets the randomization 
criteria and receives the double-blind study treatment at Visit 2 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 
(CONSORT) 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 and with 
prior approval from the GSK study team. Participants who are excluded due to an 
ongoing asthma exacerbation at Visit 2 (Randomization exclusion criterion 5) may be 
rescreened 2 weeks after Visit 2, at the investigators discretion. Rescreened participants 
will be assigned a new participant number.
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.


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7.1.
Treatments Administered
Study 
Treatment 
Name:
GSK3772847
Placebo
Fluticasone 
Propionate/Salmet
erol 
Fluticasone
Propionate
Dosage 
formulation:
50mg/mL 
GSK377284, 15 
mM Sodium 
Phosphate, 
8.5% [w/v] 
Sucrose, and 
0.04% [w/v] 
Polysorbate 20, 
pH 7.3.
DISKUS– 60 
doses per device
DISKUS– 60 doses 
per device
Unit dose 
strength(s)/Dos
age level(s):
10 mg/kg
Commercially 
sourced sterile 
normal saline
500/50 mcg per 
actuation
500, 250, 100 and 
50 mcg per 
actuation
Route of 
Administration 
IV infusion
IV infusion
Inhaled
Inhaled
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
Twice daily; once 
in the morning 
and once in the 
evening
Twice daily; once in 
the morning and 
once in the evening


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Study 
Treatment 
Name:
GSK3772847
Placebo
Fluticasone 
Propionate/Salmet
erol 
Fluticasone
Propionate
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 labeled 
as required per
country 
requirement. 
Commercially 
sourced sterile 
normal saline
will be sourced
by the site
Diskus Inhaler 
with 60 doses
(1 strip with 60 
blisters per strip)
Each container 
will be labeled as 
required per 
country 
requirement.
Diskus Inhaler with 
60 doses
(1 strip with 60 
blisters per strip)
Each container will 
be labeled as 
required per 
country 
requirement.
7.1.1.
Description of Albuterol/Salbutamol
Albuterol/salbutamol via metered-dose inhaler (MDI) will be issued for reversibility 
testing at Screening (Visit 1). An albuterol/salbutamol MDI for as needed (prn) use 
throughout the study will be dispensed starting at Visit 1; at the Investigator’s discretion, 
more than one MDI may be dispensed at any one time. Albuterol/salbutamol will be 
sourced from local commercial stock. The contents of the label will be in accordance 
with all applicable regulatory requirements.
7.1.2.
DISKUS Return
DISKUS inhalers containing FP/Salmeterol and FP will be dispensed to a participant 
during their visit to the study clinic (as applicable). The participant must return all 
dispensed inhalers at the subsequent clinic visit. The schedule for dispensing and 
collecting FP/Sal and FP is provided in the SoA (Section 2).
All used and unused FP/Sal, FP will be returned to GSK at the end of the study to be 
available for disposal. In some instances, for sites outside the United States (US), study 
supplies will be disposed of locally either by the site, the country medical department or 
third-party vendor. Detailed instructions for the return of the study drug can be found in 
the Study Reference Manual (SRM).


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If any DISKUS inhaler fails to function properly, the participant should return to the 
clinic as soon as possible to obtain a new inhaler. The site will use the Interactive Web 
Response System (IWRS) (RAMOS NG) to obtain a new treatment pack number for the 
participant and dispense a new study treatment kit from the site’s study treatment supply 
as instructed by the IWRS. Details of the failure will be documented in the eCRF. 
Additional information on how to handle medical device incidents can be found in the 
SRM.
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 randomization
schedule. The randomization code will be generated by GSK using a validated 
computerized system. Participants will be randomized using an interactive web response 
system (IWRS) RAMOS NG. The study will use central-based randomization to allocate 
treatments. Once a randomization 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 subject to satisfying all eligibility criteria, 
participants will be randomized 1:1 to one of the following double-blind 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 16 weeks. 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 (RAMOS 
NG) to randomize participants and manage study treatment supplies (including 
dispensing) is provided in the RAMOS NG manual and SRM.
7.4.
Blinding
This will be a double-blind study and the following will apply. 

The Investigator or treating physician may unblind a participant’s treatment
assignment only in the case of an emergency OR in the event of a serious 
medical condition when knowledge of the study treatment is essential for the 
appropriate clinical management or welfare of the participant as judged by the 
Investigator. 

Investigators have direct access to the participant’s individual study treatment. 

It is preferred (but not required) that the Investigator first contacts the Medical 
Monitor or appropriate GSK study personnel to discuss options before unblinding 
the participant’s treatment assignment. 


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
If GSK personnel are not contacted before the unblinding, the Investigator must 
notify GSK within 24 hours after unblinding, but without revealing the treatment 
assignment of the unblinded participant, unless that information is important for 
the safety of participants currently in the study. 

The date and event or condition which led to the unblinding (i.e. the primary 
reason) will be recorded in source documentation and in the eCRF. 
In the event of unblinding 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 IP, the participant must be followed-up as per 
protocol until the completion of the Safety Follow-up assessments. 
GSK’s Global Clinical Safety and Pharmacovigilance (GCSP) 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
GSK3772847 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 WFI, 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 2º – 8C, protected from light. Protection 
from light during preparation and administration is not required. Full details on specific 
2º to 8C storage temperature conditions, preparation and administration including 
requirements for filtration are provided separately. 
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 authorized personnel and administered according to each participant’s body 
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.


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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. Required storage conditions and 
expiration date are indicated on the label.
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 
authorized 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 authorized 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 or unblinded site staff reference manual.

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 (MSDS)/equivalent document describing occupational 
hazards and recommended handling precautions either will be provided to the 
investigator, where this is required by local laws, or is available upon request from 
GSK.
Precaution will be taken to avoid direct contact with the study treatment. A Material 
Safety Data Sheet (MSDS) describing occupational hazards and recommended handling 
precautions will be provided to the investigator.  In the case of unintentional occupational 
exposure notify the monitor, Medical Monitor and/or GSK study contact.
7.6.
Treatment Compliance

FP/Sal and FP during the run-in and treatment periods will be self-administered at 
home; compliance will be assessed via dose counter during the site visits and 
documented in the source documents and eCRF. A record of the number of doses on 
the DISKUS inhaler will be recorded in the eCRF. Treatment start and stop dates, 
including dates for treatment delays and/or dose reductions will also be recorded in 
the eCRF.


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
The double blind IP will be intravenously administered to participants at the site.  
Administration will be documented in the source documents and reported in the 
eCRF.
7.7.
Concomitant Therapy
All asthma medications used within approximately 12 weeks prior to screening and 
during the study (including the post-treatment period) should be recorded in the eCRF.
All non-asthma medications taken during the study (after randomization including post-
treatment) and any changes to concomitant medications will be recorded in the eCRF. 
Note: Study provided FP/Sal, FP, and albuterol/salbutamol should not be recorded in the 
ConMeds page of the eCRF.
The minimum requirement is that the drug name, reason for use, dose (including unit e.g. 
mcg) and frequency, route and the dates of administration are to be recorded.
7.7.1.
Permitted Non-asthma Medications
The following medications are permitted during the study:

Medications for rhinitis (e.g., intranasal corticosteroids, antihistamines [including 
ocular and intranasal] but they are disallowed 48 hours prior to ECG 
measurements, cromolyn, nedocromil, nasal decongestants)

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.

Immunotherapy: Immunotherapy for the treatment of allergies is allowed during 
the study provided it was initiated 4 weeks prior to Visit 1 and participants remain 
in the maintenance phase for the duration of the study.

Topical and ophthalmic corticosteroids.
7.7.2.
Prohibited Medications and Non-Drug Therapies
Use of the medications listed below is not permitted during the study: 

Inhaled anti-cholinergics (e.g.tiotropium).

ICS/LABA other than the study-provided FP/Sal.

Inhaled Corticosteroids other than the study-provided FP.

LABA other than the salmeterol component in the study-provided FP/Sal. 

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 (MAO) inhibitors.

Live or attenuated vaccines (and up to 6 months after the last dose of blinded 
study treatment).

Experimental anti-inflammatory drugs (non-biologics).

Corticosteroids intramuscular, long acting depot, regular systemic (oral, 
parenteral, depot) corticosteroid.

Methotrexate, troleandomycin, oral gold, cyclosporin, azathioprine.

Theophylline.

Chemotherapy and radiotherapy.
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.
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 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. Participants should resume regular treatment for their asthma, 
as determined by the investigator. Three Follow-up visits will then be performed 
4, 8, and 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, lack of efficacy [including loss of 
asthma control], protocol deviation, Investigator discretion, consent withdrawn etc.) must 
be captured in the eCRF.


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A participant must be withdrawn from study treatment if any of the following stopping 
criteria are met: 
1.
Liver Chemistry: Meets any of the protocol-defined liver chemistry stopping criteria.
2.
QTc: Meets any of the protocol-defined stopping criteria.
3.
Pregnancy: Positive pregnancy test.
4.
Participant meets at least one of the following criteria for ‘loss of asthma control’:

ACQ-5 score increase from baseline (measured at Visit 2) ≥0.5 point. 

Pre-bronchodilator FEV1 decrease from baseline (measured at Visit 2) >7.5 %. 

Inability to continue inhaled corticosteroid titration which is assessed and 
determined by the investigator at any time point following randomization, 
including on scheduled clinic visits.

A clinically significant asthma exacerbation (requiring OCS and/or 
hospitalization).
5.
Study treatment unblinded.
Note: In the event of unblinding the Medical monitor/GSK team should be contacted 
to determine whether subject withdrawal is required.
6.
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, V4, V6) or findings of myocardial ischemia will also result in 
withdrawal/stopping.
7.
Hypersensitivity or anaphylactic reaction
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 (in alignment with the Food 
and Drug Administration [FDA] premarketing clinical liver safety guidance). These 
protocol guidelines are in alignment with FDA premarketing clinical liver safety 
guidance: 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/UCM174090.pdf.
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.


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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 
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 
electrocardiograms obtained over a brief (e.g., 5-10 minute) recording period.  


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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
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 for data to be collected at the time of early withdrawal (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.
Note: In order to achieve the stratification balance, as a result of participants’ 
eosinophil count it may be necessary to withdraw participants from the study 
during the Run-in period.

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 for data to be collected at the time of early withdrawal (EW 
visit) and follow-up and for any further evaluations that need to be completed.
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. 


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The following actions must be taken if a participant fails to return to the clinic for a 
required study visit:

The site must attempt to contact the participant and reschedule the missed visit 
as soon as possible and counsel the participant on the importance of maintaining 
the assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study.

Before a participant is deemed lost to follow up, the investigator or designee 
must make every effort to regain contact with the participant (where possible, 3 
telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record.

Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study with a primary reason of lost to follow-up. 
9.
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and their timing are summarized in the Schedule of Activities 
(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, is 
essential and required for study conduct.
No study related procedures may be performed until the informed consent form has 
been signed by the participant.  Selection and modification of the participant’s 
medications prior to study participation is based on the physician’s judgment according to 
sound medical practice, principles, and each participant’s needs.  A participant’s 
treatment must not be changed merely for the purpose of enabling the participant’s 
participation in the study.
9.1.
Efficacy Assessments
The timings of all efficacy assessments are specified in SoA.
9.1.1.
Questionnaires
9.1.1.1.
Asthma Control Questionnaire ACQ-5
The ACQ-5 measures attributes of asthma control [Juniper, 1999], measured with 
questions designed to be self-completed by the participant.  Participants will complete the 
ACQ-5 with the use of an e-Diary device on a weekly basis. The ACQ-5 includes five 
questions (concerning nocturnal awakening, waking in the morning, activity limitation, 
shortness of breath and wheeze) which enquire about the frequency and/or severity of 


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symptoms over the previous week. The response options for all these questions consist of 
a zero (no impairment/limitation) to six (total impairment/ limitation) scale. The recall 
period is the past week. A score of <0.75 indicates well-controlled asthma and a score 
1.5 indicates poorly controlled asthma [Juniper, 2006]. A change of 0.5 in score 
suggests a clinically important change in score [Juniper, 2005].
9.1.1.2.
St. George’s Respiratory of Life Questionnaire (SGRQ)
The St. George’s Respiratory Questionnaire is a well established instrument, comprising 
50 questions designed to measure Quality of Life in patients with diseases of airway 
obstruction, measuring symptoms, impact, and activity. The questions are designed to be 
self-completed by the participant [Jones, 1992] with a recall over the past 4 weeks. 
Higher scores indicate worse health status, and a change of 4 points is considered a 
clinically relevant change [Jones, 2005].
9.1.2.
Daily Diaries
Participants will be issued with a PEF/e-Diary device at Visit 1 for twice daily use (in the 
morning upon waking and in the evening just before going to bed) throughout the study. 
The device will be provided by a third-party vendor. Information on the device and its 
use are documented in the SRM and the third-party vendor manual. Participants will be 
instructed on how to use the device in order to record results for the following in the 
eDiary each day from Visit 1 onwards:

Morning and evening peak flow (best of three).

Daytime asthma symptom score using a 5-point scale 

Inhalations of rescue medication usage over the previous 24-hours

Frequency of awakening due to asthma symptoms requiring rescue medication use

Morning and Evening use of FP/Sal and FP during the run-in and treatment periods
Section 9.1.2 describes the assessments and questionnaires recorded on the eDiary 
device, as well as the alerts that can be triggered based on recorded results. The data from 
the eDiary device will be automatically transmitted to a centralized server. The 
Investigator and designee(s) will be provided with access to the transmitted eDiary data 
via a vendor-provided portal and should review the data on an ongoing basis to check for 
the incidence of alerts as well as subject compliance with eDiary use.
Participants will also be issued with a paper Medical Problems/Medications Taken 
worksheet to record medical problems experienced and medications used during the 
study (please refer to the SRM for further details). Participants must also use this paper 
worksheet to record all healthcare contacts that occur during their participation in the 
study. This paper worksheet will be used to assist participant recall in discussions with 
the Investigator, for site staff to then enter as appropriate in the electronic case report 
form (eCRF).


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9.1.2.1.
Night-time Awakening, Daytime Asthma Symptom Questions
Every morning upon waking (from the morning after Visit 1 onwards), participants will 
answer a question on the occurrence of night-time awakenings due to asthma symptoms. 
The participant’s response to the question on the occurrence of night-time awakenings 
will be either ‘Yes’ (i.e. Did you wake up due to asthma symptoms (i.e. wheezing, 
coughing, shortness of breath, or chest tightness) or ‘No’ (i.e. they did not experience at 
least one night-time awakening due to asthma symptoms). If ‘Yes’, participants will be 
asked to respond either ‘Yes’ or ‘No’ to the question on rescue medication (i.e. when you 
woke up due to your asthma symptoms did you use any rescue bronchodilator?).
On the evening of Visit 1 (just before going to bed) and every evening there-after, 
participants will answer a question on daytime asthma symptoms. These questions will be 
answered on a 5-point scale (0 to 4) with ‘0’ representing no daytime asthma symptoms 
and ‘4’ representing very severe daytime asthma symptoms. Please describe the severity 
of your asthma symptoms (i.e. cough, wheeze, chest tightness, shortness of breath) today 
[0=no asthma symptoms, 1=mild asthma symptoms, 2= moderate asthma symptoms, 
3=severe asthma symptoms, 4= very severe asthma symptoms]. 
9.1.2.2.
Morning and Evening Home PEF
Participants will conduct PEF measurements using the PEF/eDiary device each morning 
and each evening. Three measurements for each session will be recorded by the 
participants in the eDiary. Assessments will be performed:

After completing all other eDiary assessments

Prior to albuterol/salbutamol use

Prior to FP/Sal and FP use
9.1.2.3.
Alerts
For safety the following alerts, indicative of worsening asthma, will be programmed into 
the eDiary with instructions for the participant to contact the investigator and transmit the 
data to the centralised server as soon as possible if any of the alert criteria are met. An 
alert in itself will not qualify as a clinically significant exacerbation:

Decrease in morning PEF 30% on at least two of three successive days, 
compared with Baseline (last 7 days of run-in).

A daytime symptom score of 3 for at least two of three successive days.

An increase from baseline of ≥4 puffs /day of albuterol/salbutamol use on 2 
consecutive days.

Awakening due to asthma symptoms requiring rescue medication use for at least 
two of three successive nights.
If any of the alert criteria are met, email notifications will be sent to the investigator as 
soon as the data is transmitted to the centralized server. The investigator will make every 
effort to contact the participants in order to discuss the participants’ symptoms and 
evaluate whether they experienced loss of asthma control.


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9.1.3.
Pulmonary Function Test
Spirometry equipment and a device to measure FeNO (see Section 9.1.4) will be 
provided to all sites by a third-party vendor. Spirometry data from this study will be 
analysed by a third-party vendor. Details on performing the spirometry assessments, 
including information on the equipment provided and its use as well as specific 
instructions on performing the spirometry manoeuvres are documented in the SRM and
the third-party vendor manual.
9.1.3.1.
Spirometry
Spirometry will be performed to assess FEV1 and FVC. At least 3 spirometry 
manoeuvres (from a maximum of 8 attempts) should be achieved on each occasion that 
spirometry assessments are performed. For spirometry data collected at Screening (Visits 
1), the best spirometry effort will be selected from a measurement that meets American 
Thoracic Society (ATS)/ European Respiratory Society (ERS) guidelines and has a 
minimum of 2 efforts which are considered valid and repeatable, in accordance with the 
ATS/ERS standards [Miller, 2005]. Measurements with 3 valid but non-repeatable efforts 
will not be accepted. For spirometry data collected during the Treatment Period (Visits 2 
– 11, including EW visit), the best spirometry effort will be selected from a measurement 
that meets ATS/ERS guidelines and has a minimum of 2 efforts which are considered 
valid (not necessarily repeatable). As always, sites should continue to strive to collect at 
least 3 valid (with no more than 8) efforts, as per ATS/ERS guidelines. At each visit, 
spirometry assessments must be performed at the same time of day (2 hour) as the 
assessment performed at Visit 2 (the baseline assessment). Participants should withhold 
short-acting beta-2-agonists (SABAs) for 6 hours and LABAs for 1 dosing interval 
(i.e. 12 or 24 hours based on the prescribed dosing interval of the product) prior to the 
clinic visit, if possible.
9.1.3.2.
Reversibility
All reversibility evaluations should follow the recommendations of the ATS/ ERS Task 
force: Standardization of Lung Function Testing [Miller, 2005]. A baseline spirometry 
assessment should be performed after a washout period of at least 6 hours for short-acting 
β2- agonists and 1 dosing interval for long-acting β2-agonists (or fixed dose combinations 
of LABA and ICS).
To perform the reversibility assessment, 4 puffs of the provided salbutamol/albuterol is 
administered following completion of the baseline assessment. A spacer device may be 
used for testing, if required. A second spirometry assessment is performed within 10 to 
15 minutes after administration of the salbutamol/albuterol.
Reversibility assessment at Screening (Visit 1) is not required if there is documented 
reversibility prior to Screening (Visit 1), or documented history of bronchial 
hyperreactivity from a bronchoprovocation study (e.g. methacholine challenge) prior to 
Screening (Visit 1).


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9.1.4.
Fractional Exhaled Nitric Oxide (FeNO)
FeNO will be measured using a handheld electronic device. Measurements will be 
obtained in accordance with the ATS/ERS Recommendations for Standardized 
Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric 
Oxide and Nasal Nitric Oxide [Miller, 2005]. All sites will use standardized 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. 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 for 1 dosing interval (i.e. 12 or 24 hours based on the prescribed 
dosing interval of the product) before each FeNO assessment.
9.1.5.
Review of Loss of Asthma Control
Loss of asthma control is defined as at least one of the following: 

ACQ-5 score increase from baseline (measured at the end of Run-in) ≥0.5 point) 
or

Pre-bronchodilator FEV1 decrease from baseline (measured at the end of Run-in) 
> 7.5 % or

Inability to titrate inhaled corticosteroid according to the pre-defined schedule 
(Section 5.1) or

A clinically significant asthma exacerbation (requiring OCS and/or 
hospitalisation.
At each clinic visit, the Investigator will utilize clinical discretion and available objective 
evidence (including but not limited to eDiary data, spirometry data, the most recent 
ACQ5 scores, history of exacerbations, conmeds, AEs) to determine if the patient is 
experiencing loss of asthma control. The paper Medical Problems/Medications Taken 
worksheet must also be reviewed by the Investigator (or appropriately trained designee) 
at each visit to the study site to assist the Investigator in the identification of loss of 
asthma control. It is expected that the Investigator will indicate which criterion (criteria) 
the subject met that constituted loss of asthma control.
9.2.
Adverse Events
The definitions of an AE or SAE can be found in Appendix 4.
Asthma exacerbations or worsening of asthma should not be recorded as an AE, unless 
they meet the definition of an SAE. For the purposes of this study, asthma exacerbations 
will be collected and recorded on the exacerbations log in the eCRF. The treatment 
details must also be recorded in the eCRF. The time period for collection of asthma 
exacerbations will begin from screening and will end after the follow-up period has been 
completed.


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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 the Visit 2 until the last follow-up visit at the 
time points specified in the SoA (Section 2). At Visits 0 and 1 SAE information 
will be collected only for any SAEs considered as related to study participation.

All AEs will be collected from the signing of the ICF 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 case report form (eCRF) not the AE section.

All SAEs will be recorded and reported to the sponsor or designee within 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 
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 an AE and/or SAE. Open-ended 
and non-leading verbal questioning of the participant is the preferred method to inquire 
about AE occurrence. Appropriate questions include:

“How are you feeling?” 

“Have you had any (other) medical problems since your last visit/contact?” 

“Have you taken any new medicines, other than those provided in this study, since 
your last visit/contact?” 
Participants will be issued with a paper Medical Problems/Medications Taken worksheet
to record any medical problems experienced and medications used during the study (See 
Section 9.1.2).


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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 (SUSAR) 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 e.g. summary or listing of SAEs 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 Cardiovascular (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. 
The CV eCRFs are presented as queries in response to reporting of certain CV Medicinal 
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 last follow-up visit.


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
If a pregnancy is reported, the investigator should inform GlaxoSmithKline (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 GlaxoSmithKline 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.
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 Schedule of Activities 
(SoA) table (Section 2) prior to conducting spirometry. Blood pressure (systolic and 


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diastolic) and pulse rate will be measured in the supine position after approximately 5 
minutes rest. A single set of values 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 centralized 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 Schedule of Activities (SoA) 
table (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).
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 centralized 
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 
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.


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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 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 eCRF. The laboratory reports must be filed with the source 
documents. Clinically significant abnormal laboratory findings are those which 
are not associated with the underlying disease, unless judged by the investigator 
to be more severe than expected for the participant's condition.

All laboratory tests with values considered clinically significantly abnormal 
during participation in the study 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.

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.
9.5.
Pharmacokinetics

Whole blood samples of approximately 3 mL will be collected for measurement 
of serum concentrations of GSK3772847as specified in the SoA. 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
9.6.
Pharmacodynamics
Pharmacodynamic (PD) Biomarkers
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. The timing of the collections may be adjusted on the basis of emerging PK or PD 


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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 sputum (Section 9.8.1.1) 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, Eosinophilic Cationic Protein (ECP) and Type-2 chemokines (e.g. 
CCL13, CCL17) as well as sputum cell counts (e.g. percentage eosinophils). 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. 
9.8.1.1.
Sputum Sub-Study
At selected sites only, consenting participants who are eligible for randomisation at Visit 
2 will be entered into the Sputum sub-study. In a subset of approximately 50% of eligible 
participants, sputum samples will be collected as specified in the SoA. The participants in 
the Sputum Sub-Study will be randomised equally in the two treatment groups.
Details of the sputum collection and processing methodology will be provided in the 
SRM.
9.8.2.
Immunogenicity Assessments 
Serum samples will be collected and tested for the presence of antibodies that bind to 
GSK3772847, as specified in the SoA. The actual date and time (24-hour clock time) of 
each sample will be recorded.
The presence of anti-GSK3772847 antibodies will be assessed using a tiered approach 
including a screening assay, a confirmation assay and calculation of titre.


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Instructions for the collection and handling of biological samples will be provided in the 
SRM. 
9.9.
Health Economics OR Medical Resource Utilization and 
Health Economics
Health Economics/Medical Resource Utilization and Health Economics parameters are 
not evaluated in this study.
10.
STATISTICAL CONSIDERATIONS
10.1.
Hypotheses
The primary null hypothesis (
) for this study is that the ratio of the proportions of 
subjects with loss of asthma control from randomization to Week 16 between 
GSK3772847 and placebo is unity.
The alternative hypothesis (
) for this study is that the ratio of the proportions of 
subjects with loss of asthma control from randomization to Week 16 between 
GSK3772847 and placebo is not unity. 
The hypothesis will be tested by calculating the posterior probability that the ratio of the 
proportion of subjects with loss of asthma control on GSK3772847 compared with 
placebo is less than 1.0, 0.75, 0.5 and 0.2 (i.e. a 0%, 25%, 50% and 80% reduction) and 
supported by an estimate of the ratio with a 95% credible interval. A non-informative 
prior will be used.
Although the success of the study will be assessed by calculating posterior probabilities 
of the treatment effect reaching various thresholds and not statistical significance, a 
frequentist analysis will also be performed testing the above hypothesis.
10.2.
Sample Size Determination
The study will randomize 74 participants per treatment arm with the aim of having 70 
evaluable participants per arm. For the purpose of this study an evaluable participant is 
defined as a participant who completes the Week 16 clinic visit whilst remaining on IP or 
who withdraws from IP having met the primary endpoint. See Section 10.4.1 for how 
subjects who withdraw early from IP for reasons other than loss of asthma control are 
handled in the analysis.


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In addition to testing the hypothesis in the overall population, the study will randomize a 
sufficient number of participants to evaluate trends in pre-defined subgroups (e.g. 
eosinophil strata).
The true proportion of participants that would experience a loss of asthma control on each 
treatment is unknown. However in a similar study of Dupilumab compared with placebo, 
the proportion of participants with loss of control were 6% and 44% for Dupilumab and 
placebo respectively. Table 4 gives the power to detect a statistically significant 
difference (at the two-sided 5% level) between the two treatments assuming the true 
proportion with loss of control on placebo is 44% and the true proportion with loss of 
control on active is 6%, 11%, 19% and 22% [Fleiss, 2003].
Table 4
Table of Power Achievable for Different Treatment Comparisons 
using N=70 per arm calculated using PASS
True proportion on 
Placebo
True proportion on 
GSK3772847
Reduction
Power
44%
6%
86%
> 99%
44%
11%
75%
> 99%
44%
19%
57%
90%
44%
22%
50%
80%
Assuming the true proportion with loss of control on placebo is 44%, then with 70 
evaluable participants per arm, the study will have at least 80% power to detect a 
statistically significant difference between treatments assuming the true proportion with 
loss of control on GSK3772487 is at most 22% (Table 4).
With 70 evaluable participants per arm and assuming the true proportion with loss of 
control on placebo is 44%, the smallest observed difference that would lead to rejection 
of the null hypothesis (minimum detectable effect) is 31% corresponding to a proportion 
with loss of control on GSK3772847 of 28%.
There is a single primary endpoint so no adjustments are required for multiplicity.
10.3.
Populations for Analyses
For purposes of analysis, the following populations are defined:
Population
Description
Enrolled 
All participants who sign the ICF.
Randomized
All participants who were randomized. A subject who is recorded as 
a screen or run-in failure and also randomized will be considered to 
be randomized in error provided they have not performed any study 
assessments.
Modified Intent-to-treat 
All randomized subjects who take at least 1 dose of study treatment. 
Participants will be analyzed according to the treatment they actually 


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Population
Description
(ITT)
received.
Safety
This population will be the same as the Modified Intent-to-treat 
population.
PK
All randomized subjects who received at least one dose of study 
medication, and for whom at least one pharmacokinetic sample was 
obtained, analyzed and was measurable.
10.4.
Statistical Analyses
10.4.1.
Efficacy Analyses
Endpoint
Statistical Analysis Methods
Primary
The primary endpoint proportion of subjects with loss of asthma control will 
be analyzed using both Bayesian and Frequentist methods. A subject is 
deemed to have met the endpoint of loss of asthma control if they meet the 
criteria for any of the components of the definition of loss of asthma control.
The posterior probabilities that the ratio of the proportion of subjects with loss 
of asthma control on GSK3772847 compared with placebo is less than 1.0, 
0.75, 0.5 and 0.2 (i.e. a 0%, 25%, 50% and 80% reduction) will be calculated 
analytically assuming a non-informative prior. This will be supported by an 
estimate of the ratio with a 95% credible interval. Results will also be 
presented for the two eosinophils strata separately.
In addition, the proportion of participants with loss of asthma control will be 
analyzed using logistic regression allowing for baseline eosinophils strata. 
The odds ratio, 95% CI and p-value for the comparison of GSK3772847 with 
placebo will be presented. 
Results will also be presented for the two eosinophils strata separately by 
fitting a separate model with an additional term for eosinophil strata by 
treatment interaction. The effect of eosinophils as a continuous covariate will 
also be examined in a separate-logistic regression model.
Missing data will be handled using the following methods:
1) The loss of asthma control will be set to missing for participants who 
withdraw from IP prior to Week 16 for reasons other than loss of 
asthma control
2) A sensitivity analysis will be performed where participants who 
withdraw from IP prior to Week 16 for reasons other than loss of 
asthma control will have the endpoint set to loss of control


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Endpoint
Statistical Analysis Methods
Secondary
The following secondary endpoints will be analyzed using the same 
statistical analysis as described for the primary endpoint:

Proportion of participants with a clinically significant asthma exacerbation 
(requiring OCS and/or hospitalisation) 

Proportion of participants with Pre-bronchodilator FEV1  decrease from 
Baseline (measured at the end of Run-in) >7.5 % 

Proportion of participants with Inability to titrate inhaled corticosteroid 
according to the pre-defined schedule (Section 5.1) 

Proportion of participants with ACQ-5 score increase from Baseline 
(measured at the end of Run-in) ≥0.5 point.

Proportion of participants with a clinically significant asthma exacerbation 
or inability to titrate ICS according to the pre-defined schedule.
In these analyses, the endpoint will be set to missing for participants who 
withdraw from IP prior to Week 16 for reasons other than loss of asthma 
control.
Time to loss of asthma control will be analyzed using Kaplan-Meier analysis. 
Percentiles for time to loss of control will be presented for both treatment 
groups, along with graphical survival plots. Any early withdrawals from IP 
that did not experience loss of control will be censored. Results will be 
presented for both of the two eosinophil strata separately, and combined. 
The following endpoints will be analyzed using repeated logistic regression. 
This analysis will be repeated including an additional term for eosinophil 
strata by treatment by visit interaction to provide estimates for the two 
eosinophil strata separately:

Proportion of ACQ-5 responders (a ≥0.5 point improvement from 
baseline at Week 16)

Proportion of SGRQ responders (at least a 4 unit improvement from 
baseline at Week 16
These analyzes will be performed using two different methods for handling 
missing data:
1) If endpoint at a visit is missing then the responder status is set to 
missing
2) If endpoint at a visit is missing and the endpoint is also missing at all 
subsequent visits then the responder status is set to non-responder
The odds ratio, 95% CI and p-value for the comparison of GSK3772847 with 
placebo will be presented for all models.
Mixed model repeated measures will be used to analyze the following 
endpoints. The baseline value of each endpoint will be included along with 
baseline*visit and treatment*visit interactions. Treatment differences, 95% 
confidence intervals and p-values will be presented.

Change from baseline in ACQ-5 absolute score 

Change from baseline in SGRQ total score


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Endpoint
Statistical Analysis Methods

Change from baseline in Pre-bronchodilator FEV1

Change from baseline in FeNO
This analysis will be repeated including an additional term for eosinophil 
strata by treatment by visit interaction to provide estimates for each 
eosinophil strata separately. No adjustment will be made for missing data.
Further information on how the following endpoints will be analyzed will be 
described in the report and analysis plan:

Hospitalisation or ER visit during the study treatment period

Morning and evening PEF

Daily asthma symptom score

Rescue medication use (albuterol/salbutamol): number of occasions 
per day 

Night-time awakenings due to asthma symptoms requiring rescue 
medication
Any changes to the planned analysis methods will be documented in the 
reporting and analysis plan. Details of subgroup analyses for the primary and 
secondary endpoints will be described in the reporting and analysis plan.
Exploratory
Will be described in the reporting and analysis plan
10.4.2.
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 analyzed descriptively by 
treatment group:

Incidence and frequency of AEs and SAEs

Vital signs

12-lead ECG

24 hours Holter

Clinical laboratory evaluation

Incidence of and titres of anti-GSK3772847 antibodies.
Details will be described in the reporting and analysis plan
Adverse events (AEs) will be coded using the standard GSK dictionary, Medical
Dictionary for Regulatory Activities (MedDRA), and grouped by body system. The
number and percentage of subjects experiencing at least one AE of any type, AEs within


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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 (AESIs) and AEs leading to 
withdrawal.
Deaths and SAEs, if applicable, will be documented in case narrative format.
10.4.3.
Pharmacokinetic Analyses
All safety analyzes will be performed on the PK 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.
10.4.4.
Pharmacodynamic Analyses
All pharmacodynamic analysis will be described in reporting and analysis plan.
10.4.5.
Other Analyses
PK, pharmacodynamic, and biomarker exploratory analysis will be described in the 
reporting and analysis plan. Any population PK analysis and pharmacodynamic analysis
will be reported separately from the main clinical study report (CSR). Should a 
genetic/PGx analysis be performed, a separate reporting and analysis plan will be 
generated (See Appendix 6: Genetics).
10.4.6.
Interim Analyses
Formal analyses will be performed at two timepoints.
End of Treatment Phase Analysis:
This will take place after all participants have completed the Week 16 visit. The data will 
be cleaned, the treatments unblinded and all clinic visits up to and including week 16 
frozen. However, whilst no further efficacy data will be collected post week 16, due to an 
inability to lock log forms used for collection of exacerbation data, the end of treatment 
phase analysis will be considered an interim analysis for both efficacy and safety. Any 
safety data collected for participants who have completed clinic visits after Week 16 will 
also be cleaned and included in the analysis. 
There will be no modifications to dosing regimens, sample size or any other aspects of 
the trial based on this data, as all study assessments, apart from follow-up, will have 


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already been completed. As such an Independent Data Monitoring Committee (IDMC) 
will not be used, as no further investigational product will be prescribed after this 
analysis has taken place.
Final Analysis:
This will take place after all subjects have completed the study. Data for visits after Week 
16 as well as data collected on log pages will be cleaned and the database frozen. This 
will be the final analysis for the study.
The Reporting and Analysis Plan will describe the planned analyses in greater detail. 
Instream review:
An iSRC 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.
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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.
Fleiss, J. L., Levin, B., Paik, M.C. 2003. Statistical Methods for Rates and Proportions. 
Third Edition. John Wiley & Sons. New York. 
http://onlinelibrary.wiley.com/doi/10.1002/0471445428.ch4/pdf
GlaxoSmithKline Document Number 2017N316832_00 GSK3772847 Investigator's 
Brochure.
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status for chronic airflow limitation. The St. George's Respiratory Questionnaire. Am 
Rev Respir Dis 1992;145:1321-1327.
Jones PW. St. George’s Respiratory Questionnaire: MCID. Journal of Chronic 
Obstructive Pulmonary Disease 2005;2:75-79.
Juniper EF, Bousquet J, Abetz L, Bateman ED; GOAL Committee. Identifying 'well-
controlled' and 'not well-controlled' asthma using the Asthma Control Questionnaire. 
Respir Med 2006;100:616-621.
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a questionnaire to measure asthma control. Eur Respir J. 1999;14(4):902-907.


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three shortened versions of the asthma control questionnaire. Respir Med 2005;99:553-
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Standardization of Lung Function Testing. Eur Resp J 2005;26:153-161.
Moore WC, Bleecker ER, Curran-Everett D Erzurum SC, Ameredes BT, Bacharier L, 
Calhoun WJ, 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.
Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, et al.
Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 
2009; 360:985-93.
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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 P, Stanojevic S, Cole T, Baur X., Hall G, Enright P, et al. on behalf of the ERS 
Global Lung Function Initiative. 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.
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, 
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Persistent Asthma with Elevated Eosinophil Levels. N Engl J Med. 2013;368: 2455-66.
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12.
APPENDICES
12.1.
Appendix 1: Abbreviations and Trademarks
Abbreviations
ACQ
Asthma Control Questionnaire
AE
Adverse Event
AESI
Adverse Event of Special Interest
ALT
Alanine Transaminase
AST
Aspartate Transaminase
ATS
American Thoracic Society
AUC
Area Under the Curve
BID
Twice a day
BUN
Blood Urea Nitrogen
CAD
Coronary artery disease
CI
Confidence Interval
CV
Cardiovascular
Cmax
maximum serum concentration
CIOMS
Council for International Organizations of Medical Sciences
CONSORT
Consolidated Standards of Reporting Trials
COPD
Chronic Obstructive Pulmonary Disease
CPK
Serum creatine phosphokinase
CSR
Clinical Study Report
DNA
Deoxyribonucleic acid
ECG
Electrocardiogram
(e)CRF
(Electronic) Case Report Form
ER
Emergency Room
eDiary
Electronic Diary
ETP
End of Treatment Phase
ERS
European Respiratory Society
EW
Early Withdrawal
FDA
Food and Drug Administration
FeNO
Fractional Exhaled Nitric Oxide
FEV1
Forced expiratory volume in 1 second
FP
Fluticasone Propionate
FSH
Follicle Stimulating Hormone
FTIH
First Time in Human
FVC
Forced Vital Capacity
GCP
Good clinical practice
GCSP
Global Clinical Safety and Pharmacovigilance
GGT
Gamma-glutamyltransferase
GINA
Global Initiative for Asthma
GLI
Global Lung Function Initiative
GLP
Good laboratory practice
GSK
GlaxoSmithKline


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HBsAg
hepatitis B surface antigen
hCG
Human Chorionic Gonadotropin
HIPAA
Health Insurance Portability and Accountability Act
HIV
Human Immunodeficiency Virus
HPLC
High performance liquid chromatography
HR
Heart rate
HRT
Hormone Replacement Therapy
IB
Investigator’s Brochure
ICF
Informed Consent Form
ICH
International Conference on Harmonization
ICS
Inhaled Corticosteroids
IEC
Independent Ethics Committee
IgG2
human immunoglobulin G2 sigma isotype
IgG
Immunoglobulin G
IL-33R
Interleukin-33 receptor
IL-1RL1
Interleukin-1 receptor like-1
IP
Investigational Product
IRB
Institutional Review Board
iSRC
Independent Safety Review Committee
IUD
Intrauterine device
IUS
Intrauterine hormone-releasing system
IV
Intravenous
IWRS
Interactive Web Response System
ITT
Intent to Treat
Kg
Kilogram
LABA
Long-Acting Beta-2-Agonists
LTRA
Leukotriene Receptor Antagonist
mAb
monoclonal antibody
MAO
Monoamine oxidase
MedDRA
Medicinal Dictionary for Regulatory Activities
mcg (g)
Microgram
MCH
Mean corpuscular haemoglobin
MCHC
Mean corpuscular haemoglobin concentration
MCV
Mean corpuscular volume
MDI
Metered Dose Inhaler
mg
Milligram
min
Minute
mIU
Milli international units
mL
Milliliter
L
Microlitre
mm
Millimeter
mV
Millivolt
MSDS
Material Safety Data Sheet
msec
Millisecond
NOAEL
No Observed Adverse Effect Level
NT-proBNP
N-terminal prohormone of brain natriuretic peptide


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NYHA
New York Heart Association
OCS
Oral Corticosteroid
PEF
Peak Expiratory Flow
PD
Pharmacodynamic
PGx
Pharmacogenetic
PK
Pharmacokinetic
prn
As needed
PSVT
Paroxysmal supraventricular tachycardia
q2W
Every two weeks
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
RBC
Red Blood Cell
RDW
Red cell distribution width
RNA
Ribonucleic acid
SABA
Short-Acting Beta-2-Agonists
SAD
Single Ascending Dose
SAE
Serious Adverse Event
Sal
Salmeterol
SGPT
Serum Glutamic-Oxaloacetic Transaminase
SGRQ
St. George’s Respiratory Questionnaire
SRM
Study Reference Manual
ST2
Suppressor of tumorigenicity 2
sST2
Soluble ST2
ULN
Upper Limit of Normal
US
United States
VT
Ventricular Tachycardia
WBC
White Blood Cell
WOCBP
Woman of childbearing potential
w/v
Weight/volume
Trademark Information
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
DISKUS
None


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12.2.
Appendix 2: Clinical Laboratory Tests

The tests detailed in Table 5 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. 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.
Table 5
Protocol-Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters
Hematology
Platelet Count
RBC Indices:
MCV
MCH
MCHC
WBC count with Differential:
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
These will be blinded from Visit 3
onwards.
Red Blood Cell (RBC) 
Count
Hemoglobin
Hematocrit
White Cell Count
RDW
Clinical 
Chemistry1
BUN
Potassium
Aspartate 
Aminotransferase
(AST)/ Serum 
Glutamic-
Oxaloacetic 
Transaminase
(SGOT)
Total and direct 
bilirubin


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Laboratory 
Assessments
Parameters
Creatinine
Sodium
Alanine 
Aminotransferase
(ALT)/ Serum 
Glutamic-Pyruvic 
Transaminase
(SGPT)
Total Protein
Glucose 
nonfasting
Calcium
Alkaline 
phosphatase
CPK
Albumin
Phosphorus
GGT
Chloride
Carbon Dioxide
Cardiac 
Markers

Cardiac troponin I (cTn I) 

N-terminal pro-brain natriuretic peptide (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)

Serum/urine human chorionic gonadotropin (hCG) pregnancy test (as 
needed for women of childbearing potential)2

Serology (HIV antibody, hepatitis B surface antigen 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


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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 (CIOMS) International Ethical 
Guidelines

Applicable 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 authorized representative and answer all 
questions regarding the study. 


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
Participants must be informed that their participation is voluntary. Participants 
or their legally authorized representative will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study center. 

The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent 
must also sign the ICF.

Participants must be re-consented to the most current version of the ICF(s) 
during their participation in the study. 

A copy of the ICF(s) must be provided to the participant or the participant’s 
legally authorized 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 authorized personnel appointed 
by the sponsor, by appropriate IRB/IEC members, and by inspectors from 
regulatory authorities.
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 
generally support publication of multicenter studies only in their entirety and not 
as individual site data. In this case, a coordinating investigator will be 
designated by mutual agreement.

Authorship will be determined by mutual agreement and in line with 
International Committee of Medical Journal Editors authorship requirements.


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Data Quality Assurance

All participant data relating to the study will be recorded on printed or electronic 
eCRF unless transmitted to the sponsor or designee electronically (eg, laboratory 
data). The 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 
Clinical Study Report (CSR)/ equivalent summary unless local regulations or 
institutional policies require a longer retention period. No records may be 
destroyed during the retention period without the written approval of the 
sponsor. No records may be transferred to another location or party without 
written notification to the sponsor. 
Source Documents

Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site.

Data reported on the eCRF or entered in the eCRF that are transcribed from 
source documents must be consistent with the source documents or the 
discrepancies must be explained. The investigator may need to request previous 
medical records or transfer records, depending on the study. Also, current 
medical records must be available.
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.


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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 (hematology, 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 fulfill the definition of an AE 
or SAE. 

The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be 
reported as AE or SAE if they fulfill the definition of an AE or SAE. Also, "lack of 
efficacy" or "failure of expected pharmacological action" constitutes an AE or SAE.


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Events NOT Meeting the AE Definition 

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.

Medical or surgical procedure (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 (eg, hospitalization 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 hospitalization or prolongation of existing hospitalization
In general, hospitalization 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 hospitalization are AE. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious.
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE.


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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, diarrhea, influenza, 
and accidental trauma (eg, sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

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 hospitalization but may 
jeopardize the participant or may require medical or surgical intervention to prevent 
one of the other outcomes listed in the above definition. These events should usually 
be considered serious.
Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, 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


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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 
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 sufficiently 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 utilized 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.


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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 Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK. However, it is very 
important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to GSK.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-up of AE and SAE

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, 
or consultation with other health care professionals.

If a participant dies during participation in the study or during a recognized follow-
up period, the investigator will provide GSK with a copy of any post-mortem 
findings including histopathology

New or updated information will be recorded in the originally completed eCRF.

The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information.


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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 or to the
assigned SAE contact by telephone.

Contacts for SAE reporting can be found at the beginning of this protocol on the 
Sponsor/Medical Monitor Contact Information page
SAE Reporting to GSK via Paper eCRF

Facsimile transmission of the SAE paper eCRF is the preferred method to transmit 
this information to the assigned SAE contact by telephone.

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 eCRF 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 hormonal replacement therapy 
(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 enrollment.
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 6. 


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Table 6
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 ovulation 

oral

intravaginal 

transdermal 
Progestogen-only hormonal contraception associated with inhibition of ovulation 

injectable 
Highly Effective Methods That Are User Independent 

Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulation

Intrauterine device (IUD)

Intrauterine hormone-releasing system (IUS)

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. 
Pregnancy Testing

WOCBP should only be included after a confirmed menstrual period and a negative 
highly sensitive serum pregnancy test 

Additional pregnancy testing should be performed during the treatment period as 
specified in the Table of Events

Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected 


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
Pregnancy testing, with a sensitivity of 5, 10, 25 mIU/mL 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 fetal 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 Deoxyribonucleic acid (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 neutrophils 
and eosinophils 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 analyzed 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 analyzed 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 and related diseases 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 etiology 
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, stabilize, 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 
pharmacokinetic (PK) analysis within 1 
week after the liver event5

Serum creatine phosphokinase (CPK) 
and lactate dehydrogenase (LDH).

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 


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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, stabilize 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, stabilize or return to within 
baseline
on the concomitant medications report 
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 
(IgG) 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]). NOTE: 
not required in China

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


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TITLE PAGE
Protocol Title: A randomized, double-blind, parallel group, multicenter, stratified study 
evaluating the efficacy and safety of repeat doses of GSK3772847 compared with 
placebo in participants with severe asthma.
Protocol Number: 207597
Short Title: A study to evaluate the effect of GSK3772847 in patients with severe 
asthma.
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
 MB.BS 
Email: 
Tel: 
Regulatory Agency Identifying Number(s): IND number 134366, EudraCT number: 
2017-001072-34
Approval Date: 06-FEB-2017
Copyright 2017 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited.
PPD
PPD
PPD


PPD
PPD
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TABLE OF CONTENTS
PAGE
1.
SYNOPSIS...............................................................................................................6
2.
SCHEDULE OF ACTIVITIES (SOA).......................................................................11
3.
INTRODUCTION....................................................................................................17
3.1.
Study Rationale ..........................................................................................17
3.2.
Background ................................................................................................17
3.3.
Benefit/Risk Assessment ............................................................................18
3.3.1.
Risk Assessment .........................................................................19
3.3.2.
Benefit Assessment.....................................................................24
3.3.3.
Overall Benefit:Risk Conclusion...................................................24
4.
OBJECTIVES AND ENDPOINTS...........................................................................24
5.
STUDY DESIGN ....................................................................................................26
5.1.
Overall Design ............................................................................................26
5.2.
Number of Participants ...............................................................................28
5.3.
Participant and Study Completion...............................................................29
5.4.
Scientific Rationale for Study Design ..........................................................29
5.5.
Dose Justification........................................................................................30
6.
STUDY POPULATION...........................................................................................32
6.1.
Inclusion Criteria.........................................................................................32
6.2.
Exclusion Criteria........................................................................................33
6.3.
Randomization Inclusion Criteria ................................................................36
6.4.
Randomization Exclusion Criteria ...............................................................36
6.5.
Lifestyle Restrictions...................................................................................37
6.6.
Pre-Screening/Screening/Run-in/Randomization Failures ..........................37
7.
TREATMENTS.......................................................................................................38
7.1.
Treatments Administered............................................................................39
7.1.1.
Description of Albuterol/Salbutamol .............................................40
7.1.2.
DISKUS Return............................................................................40
7.2.
Dose Modification .......................................................................................41
7.3.
Method of Treatment Assignment ...............................................................41
7.4.
Blinding.......................................................................................................41
7.5.
Preparation/Handling/Storage/Accountability..............................................42
7.6.
Treatment Compliance................................................................................43
7.7.
Concomitant Therapy..................................................................................44
7.7.1.
Permitted Non-asthma Medications .............................................44
7.7.2.
Prohibited Medications and Non-Drug Therapies.........................44
7.8.
Treatment after the End of the Study ..........................................................45
8.
DISCONTINUATION CRITERIA.............................................................................45
8.1.
Discontinuation of Study Treatment ............................................................45
8.1.1.
Liver Chemistry Stopping Criteria ................................................46
8.1.2.
QTc Stopping Criteria ..................................................................47
8.1.3.
Rechallenge.................................................................................48
8.1.3.1.
Study Treatment Restart or Rechallenge....................48


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8.2.
Withdrawal from the Study..........................................................................48
8.3.
Lost to Follow Up........................................................................................48
9.
STUDY ASSESSMENTS AND PROCEDURES .....................................................49
9.1.
Efficacy Assessments.................................................................................49
9.1.1.
Questionnaires ............................................................................49
9.1.1.1.
Asthma Control Questionnaire ACQ-5........................49
9.1.1.2.
St. George’s Respiratory of Life Questionnaire 
(SGRQ) ......................................................................50
9.1.2.
Daily Diaries ................................................................................50
9.1.2.1.
Night-time Awakening, Daytime Asthma 
Symptom Questions ...................................................50
9.1.2.2.
Morning and Evening Home PEF ...............................51
9.1.2.3.
Alerts..........................................................................51
9.1.3.
Pulmonary Function Test.............................................................51
9.1.3.1.
Spirometry..................................................................52
9.1.3.2.
Reversibility................................................................52
9.1.4.
Fractional Exhaled Nitric Oxide (FeNO) .......................................52
9.1.5.
Review of Loss of Asthma Control...............................................53
9.2.
Adverse Events...........................................................................................53
9.2.1.
Time Period and Frequency for Collecting AE and SAE 
Information...................................................................................53
9.2.2.
Method of Detecting AEs and SAEs.............................................54
9.2.3.
Follow-up of AEs and SAEs.........................................................54
9.2.4.
Regulatory Reporting Requirements for SAEs .............................54
9.2.5.
Cardiovascular and Death Events................................................55
9.2.6.
Pregnancy ...................................................................................55
9.3.
Treatment of Overdose...............................................................................55
9.4.
Safety Assessments ...................................................................................56
9.4.1.
Physical Examinations.................................................................56
9.4.2.
Vital Signs....................................................................................56
9.4.3.
Electrocardiograms......................................................................56
9.4.4.
Continuous ambulatory ECG (Holter)...........................................57
9.4.5.
Clinical Safety Laboratory Assessments ......................................58
9.5.
Pharmacokinetics .......................................................................................58
9.6.
Pharmacodynamics ....................................................................................58
9.7.
Genetics .....................................................................................................59
9.8.
Biomarkers .................................................................................................59
9.8.1.
Exploratory Biomarkers................................................................59
9.8.1.1.
Sputum Sub-Study .....................................................59
9.8.2.
Immunogenicity Assessments......................................................59
9.9.
Health Economics OR Medical Resource Utilization and Health 
Economics..................................................................................................60
10. STATISTICAL CONSIDERATIONS........................................................................60
10.1.
Hypotheses.................................................................................................60
10.2.
Sample Size Determination ........................................................................60
10.3.
Populations for Analyses ............................................................................61
10.4.
Statistical Analyses.....................................................................................62
10.4.1.
Efficacy Analyses.........................................................................62
10.4.2.
Safety Analyses...........................................................................64
10.4.3.
Pharmacokinetic Analyses...........................................................65


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10.4.4.
Pharmacodynamic Analyses........................................................65
10.4.5.
Other Analyses ............................................................................65
10.4.6.
Interim Analyses ..........................................................................65
11. REFERENCES.......................................................................................................67
12. APPENDICES........................................................................................................69
12.1.
Appendix 1: Abbreviations and Trademarks................................................69
12.2.
Appendix 2: Clinical Laboratory Tests.........................................................72
12.3.
Appendix 3: Study Governance Considerations..........................................74
12.4.
Appendix 4: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .......................................78
12.5.
Appendix 5: Contraceptive Guidance and Collection of Pregnancy 
Information..................................................................................................84
12.6.
Appendix 6: Genetics..................................................................................87
12.7.
Appendix 7: Liver Safety: Required Actions and Follow-up 
Assessments ..............................................................................................88


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1.
SYNOPSIS
Protocol Title: A randomized, double-blind, parallel group, multicenter, stratified study 
evaluating the efficacy and safety of repeat doses of GSK3772847 compared with 
placebo in participants with severe asthma.
Short Title: A study to evaluate the effect of GSK3772847 in patients with severe 
asthma.
Rationale:
GSK3772847 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 (FTIH) study has completed dosing (final clinical study report is 
pending).The safety information from this study is included in the investigator brochure.
There are no efficacy data available to date. 
The present study is the first GSK sponsored study with GSK3772847. It is a Phase IIa 
study to investigate efficacy, safety and tolerability, pharmacokinetic (PK) and 
pharmacodynamic (PD) profiles of GSK3772847 in participants with severe asthma. The 
study will use a steroid titration design in order to induce instability and evaluate whether 
GSK3772847 maintains protection of asthma control. The design of steroid titration (oral 
or inhaled) in participants with asthma has been used in various studies with different 
investigational products, in which exacerbations were induced by medication withdrawal. 
This design may not reflect real world exacerbations; however studies with the design of 
steroid titration have shown the ability to assess effects of a potential treatment on 
exacerbations in a relatively short period of time, before further investigations are 
conducted in longer term studies.


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Objectives and Endpoints:
Objectives
Endpoints
Primary

To evaluate the efficacy of GSK3772847, 
compared with placebo, administered 
intravenously every 4 weeks for 12 weeks 
(Week 0 – Week 12, 4 doses in total) in 
participants with severe asthma.
Primary – Proportion of participants with loss of 
asthma control  over Weeks 0-16 where ‘loss of 
asthma control’ is defined as at least one of the 
following:

A clinically significant asthma exacerbation 
(requiring oral corticosteroid [OCS] and/or 
hospitalisation) or

Pre-bronchodilator Forced expiratory volume 
in 1 second (FEV1) decrease from baseline 
(measured at the end of Run-in) >7.5 % or

Inability to titrate inhaled corticosteroid 
according to the pre-defined schedule
(Section 5.1) or

Asthma Control Questionnaire (ACQ-5) score 
increase from baseline (measured at the end 
of Run-in) ≥0.5 point.
Secondary

To evaluate other aspects of efficacy of 
GSK3772847 compared with placebo in 
participants with severe asthma.
Other efficacy endpoints (at or  by Week 16):

Proportion of participants who have a 
significant asthma exacerbation (requiring 
OCS and/or hospitalisation).

Proportion of participants who have pre-
bronchodilator FEV1 decrease from baseline 
(measured at the end of Run-in) >7.5 %.

Proportion of participants where inhaled 
corticosteroids (ICS) cannot be titrated in 
accordance with the pre-defined schedule.

Proportion of participants with a ≥0.5 point. 
ACQ-5 score increase from baseline.

Time to loss of asthma control.

Proportion of participants with a clinically 
significant asthma exacerbation or inability to 
titrate ICS according to the pre-defined 
schedule

The incidence, mean rate, and total number 
per participant of hospitalisations or 
Emergency Room (ER) visits during the study 
treatment period.

Change from baseline in ACQ-5 absolute 
score at each week from Week 1 to Week 16.

Proportion of participants with ≥0.5 point 
ACQ-5 score decrease from baseline 
(responder) at each week from Week 1 to 
Week 16.

Change from baseline in SGRQ total score at 
Weeks 4, 8, 12 and 16.

Proportion of St. George’s Respiratory 


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Objectives
Endpoints
Questionnaire (SGRQ) responders (at least a 
4 unit improvement from baseline) at Weeks 
4, 8, 12 and 16.

Change from baseline in pre-bronchodilator 
FEV1 at Weeks 2, 4, 6, 8, 10, 12, 14, 16.

Change from baseline in mean morning peak 
expiratory flow (PEF) and mean evening PEF 
over each four weeks of the 16 week 
treatment period.

Change form baseline in mean daytime
asthma symptom score over each four weeks 
of the 16 week treatment period.

Change from baseline in rescue medication 
use (albuterol/salbutamol): mean number of 
inhalations per day over each four weeks of
the 16 week treatment period.

Changes from baseline in night-time 
awakenings due to asthma symptoms 
requiring rescue medication use over each 
four weeks of the16 week treatment period.

Change from baseline in fractional exhaled 
nitric oxide (FeNO) at each week measured.

To evaluate the safety and tolerability of 
GSK3772847, compared with placebo 
administered intravenously every 4 weeks
for 12 weeks (Week 0-12, 4 doses in total) in 
participants with severe asthma.

Incidence and frequency of adverse events 
(AEs) and serious adverse events (SAEs).

Change from baseline in vital signs.

Change between post-dose and pre-dose in 
vital signs.

Change from baseline in 12-lead 
electrocardiogram (ECG) measurements.

Change between post-dose and pre-dose in 
12-lead ECG measurements

Change from baseline in 24 hours Holter 
measurements.

Change from baseline in clinical laboratory 
tests (haematology and chemistry).

Incidence of and titres of anti- GSK3772847 
antibodies.

To evaluate the pharmacokinetics (PK) of 
GSK3772847 in participants with severe 
asthma.

Serum concentrations of GSK3772847.

To evaluate the pharmacodynamics (PD) of 
GSK3772847 in participants with severe 
asthma.

Free and total soluble ST2 levels in serum.


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Overall Design:
This is a Phase IIa, multicenter, randomized, placebo-controlled, double-blind, stratified,
parallel group study in participants with severe asthma.
There will be a 2-week Run-in period following Screening (Visit 1). Eligible participants 
will be randomized at the end of the Run-in period (Visit 2). Randomization will be 
stratified based on participants’ baseline peripheral blood eosinophil count aiming for at 
least 30% of participants with eosinophil count <150 cells /L, which is measured at 
Screening.
Number of Participants:
Approximately 300 participants with severe asthma who are maintained on high-dose 
ICS/LABA will be screened to ensure 148 randomized (74 on GSK3772847, 74 on 
placebo) participants and 140 evaluable participants. For the purpose of this study an 
evaluable participant is defined as a participant who completes the Week 16 clinic visit 
whilst remaining on investigational product (IP) or who withdraws from IP having met 
the primary endpoint. High-dose ICS is defined as fluticasone propionate 500 mcg twice 
daily (i.e. 1000 mcg /day) or equivalent.
Treatment Groups and Duration:
When required, a pre-screening visit (Visit 0) can be scheduled for signing the informed 
consent, up to 2 weeks prior to Screening (Visit 1). The pre-screening visit can also occur 
on the same day as the Screening visit. Participants who meet the eligibility criteria at 
Screening (Visit 1) will withdraw their regular ICS/LABA treatment for asthma and enter 
a two-week Run-in period during which they will receive open label background therapy 
of fluticasone propionate (FP)/salmeterol (Sal) 500/50 mcg twice daily (BID). At the end 
of the Run-in period at Visit 2 (Week 0), participants who meet pre-defined 
randomization criteria will be randomized in a 1:1 ratio to enter a double-blind treatment 
period and receive the following study treatment every 4 weeks for 12 weeks (Week 0, 4, 
8 and 12) while initially remaining on the open label background therapy of FP/Sal 
500/50 mcg BID at Randomization:

GSK3772847 administered intravenously or

Placebo administered intravenously
At Visit 4, two weeks after Randomization, the open label background therapy will be 
switched from FP/Sal 500/50 mcg BID to FP 500 mcg BID for 2 weeks. Visit 4 will be 
the beginning of a six week FP titration period. Every two weeks for the next six weeks
the dose of FP will be reduced by approximately 50 % (i.e. FP 250 mcg BID at Visit 5 for 
2 weeks, FP 100 mcg BID at Visit 6 for 2 weeks, then FP 50 mcg BID at Visit 7 for 2 
weeks) until complete discontinuation at Visit 8, provided that the participant does not 
meet any of the loss of asthma control criteria. If any of the pre-defined criteria for loss of 
asthma control are met during the Treatment period, participants will be withdrawn from 
the investigational product (IP) and should resume regular treatment for their asthma, as 
determined by the investigator. 


2017N311825_00
An End of Treatment Phase (
the blinded study treatment is
IP early, but have not withdra
(EW) visit will be performed
Participants should resume re
investigator, after protocol de
visits will be performed 4, 8, 
ETP/EW Visit for safety asse
Following randomization par
scheduled FP dose titration an
blinded study treatment (Visi
relief to be used on an as nee
The maximum total duration 
CONFIDENTIAL
10
(ETP) Visit will be performed 4 weeks after the 
s administered at Week 12. For participants who
awn consent to participate in the study, an Early 
d 4 weeks after the last dose of blinded study trea
egular treatment for their asthma, as determined 
efined study assessments are completed. Three F
and 12 weeks (Week 20, Week 24, and Week 2
essments.
rticipants will return to the clinic at least every 2
nd assessment of asthma control until the last do
it 9). Albuterol/salbutamol will be provided for s
ded basis from Screening through to the ETP vi
of the study is approximately 33 weeks.
207597
final dose of 
o discontinue 
Withdrawal 
atment.
by the 
Follow-up 
28) after the 
2 weeks for 
ose of 
symptomatic 
sit. 


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2.
SCHEDULE OF ACTIVITIES (SOA)
Procedure
Pre-
Screen
ing1
Scree
n Run-
in
Treatment Period (Visit window 3 days)
Follow-up Period2
(3 days)
Notes
Visit 
0
1
23
3
4
5
6
7
8
9
10
11
(ETP 
or 
EW)
12
13
14
1.Pre-screening and screening 
can occur on the same day 
2. FU period to start 4 weeks 
after ETP or EW visit.
3. Visit 2 = Day 1 (first dose of 
IP).
Week
-4~-2
-2
0
1
2
4
6
8
10
12
14
16
20
24
28
Study Day
-28~-14
-14
1
8
15
29
43
49
71
85
99
113
Informed consent
(ICF)
X
Genetic ICF
X
ICF for sputum
X
Inclusion and 
exclusion criteria
X
Demography
X
Full physical exam 
including height and 
weight
X
Medical history 
(includes substance 
usage)
X
Substances [Drugs, Alcohol, 
tobacco and caffeine] and 
family history of premature CV 
disease]): [including 
cardiovascular medical history]
Laboratory 
assessments
X1
X1
X
X1
X1
X
X1
X
X1
X
X1
X1
Haematology (including 
eosinophil count) measured at 
all clinic visits.
1. Include liver chemistries.


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Procedure
Pre-
Screen
ing1
Scree
n Run-
in
Treatment Period (Visit window 3 days)
Follow-up Period2
(3 days)
Notes
Visit 
0
1
23
3
4
5
6
7
8
9
10
11
(ETP 
or 
EW)
12
13
14
1.Pre-screening and screening 
can occur on the same day 
2. FU period to start 4 weeks 
after ETP or EW visit.
3. Visit 2 = Day 1 (first dose of 
IP).
Week
-4~-2
-2
0
1
2
4
6
8
10
12
14
16
20
24
28
Study Day
-28~-14
-14
1
8
15
29
43
49
71
85
99
113
Pregnancy test1
X2
X3
X3
X3
X3
X
X
X
X
1. Test for women with child 
bearing potential. 
2. Serum pregnancy test at 
V0/V1.
3. Test to be performed pre-
dose during the treatment 
period.
[HIV, Hep B and Hep 
C screen]
X
A confirmatory negative 
Hepatitis C RNA test must be 
obtained, to be able to enrol 
participants with positive 
Hepatitis C antibody due to 
prior resolved disease. If test 
has been performed within 3 
months prior to first dose of 
study treatment, testing at
screening is not required.
Randomization 
Criteria
X
Spirometry 
X
X
X
X
X
X
X
X
X
X
Test to be performed pre-dose 
during the Treatment period         
Reversibility
X
12-lead ECG
X
X1
X1
X1
X1
X
1. Test to be performed pre-
dose and post-dose within 30 
mins after end of infusion.


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Procedure
Pre-
Screen
ing1
Scree
n Run-
in
Treatment Period (Visit window 3 days)
Follow-up Period2
(3 days)
Notes
Visit 
0
1
23
3
4
5
6
7
8
9
10
11
(ETP 
or 
EW)
12
13
14
1.Pre-screening and screening 
can occur on the same day 
2. FU period to start 4 weeks 
after ETP or EW visit.
3. Visit 2 = Day 1 (first dose of 
IP).
Week
-4~-2
-2
0
1
2
4
6
8
10
12
14
16
20
24
28
Study Day
-28~-14
-14
1
8
15
29
43
49
71
85
99
113
24 hrs Holter
X
X1
X1
X1
Holter monitor needs to be 
returned to clinic at end of 24-
hour recording (i.e. the next 
day).
1. Place the Holter 30-60 mins 
prior to dosing.
Vital signs
X
X1
X
X
X1
X
X1
X
X1
X
X
X
X
X
1. Test to be performed pre-
dose prior to spirometry and 
post-dose prior the 12 –lead 
ECG.
Double blind Study 
Treatment (IP)
X
X
X
X
FP/Sal (500/50) 
dispensing
X
X
FP (mcg) dispensing
500
250
100
50
Genetic blood sample 
– Pre dose
X
Pharmacogenetic sample may 
be drawn any time from Visit 2 
onwards. Informed consent for 
optional substudies 
e.g.genetics must be obtained 
before collecting a sample
ACQ-5
X
X
After randomization, ACQ5 will 
be completed by the 
participants every 7 days. 
SGRQ
X
X
X
X
X


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Procedure
Pre-
Screen
ing1
Scree
n Run-
in
Treatment Period (Visit window 3 days)
Follow-up Period2
(3 days)
Notes
Visit 
0
1
23
3
4
5
6
7
8
9
10
11
(ETP 
or 
EW)
12
13
14
1.Pre-screening and screening 
can occur on the same day 
2. FU period to start 4 weeks 
after ETP or EW visit.
3. Visit 2 = Day 1 (first dose of 
IP).
Week
-4~-2
-2
0
1
2
4
6
8
10
12
14
16
20
24
28
Study Day
-28~-14
-14
1
8
15
29
43
49
71
85
99
113
Review loss of 
asthma control 
criteria
X
X
X
X
X
X
X
X
X
X
It will include review of data to 
determine loss of asthma 
control. See Section 9.1.5.
Sputum sample 
collection
X
X
X
Pre-dose collection and in a 
sub-set of participants (~50 %) 
at selected sites; also collected 
for EW participants
PK, target 
engagement and 
immunogenicity 
assessments
X
X
X
X
X
X
X
X
X
X
See SoA Table 2 for details
FeNO
X
X
X
X
X
X
X
X
X
X
Test to be performed pre-dose
Exploratory 
Biomarkers
X
X
X
Pre dose collection 
Dispense eDiary
X
Collect eDiary
X
Review eDiary
X
X
X
X
X
X
X
X
X
X
Dispense paper 
Medical 
Problems/Medication
s Taken worksheet
X
X
X
X
X
X
X
X
X
X
X
X
X
Review paper 
Medical 
Problems/Medication
s Taken worksheet
X
X
X
X
X
X
X
X
X
X
X
X
X


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Procedure
Pre-
Screen
ing1
Scree
n Run-
in
Treatment Period (Visit window 3 days)
Follow-up Period2
(3 days)
Notes
Visit 
0
1
23
3
4
5
6
7
8
9
10
11
(ETP 
or 
EW)
12
13
14
1.Pre-screening and screening 
can occur on the same day 
2. FU period to start 4 weeks 
after ETP or EW visit.
3. Visit 2 = Day 1 (first dose of 
IP).
Week
-4~-2
-2
0
1
2
4
6
8
10
12
14
16
20
24
28
Study Day
-28~-14
-14
1
8
15
29
43
49
71
85
99
113
Dispense albuterol 
(as needed)
X
X
X
X
X
X
X
X
X
X
X
AE/SAE review
X1
X1
==========================================
X
X
X
1. At V0 and V1 collect only 
SAEs considered as related to 
study participation.
Concomitant 
medication review
X
X
==========================================
X
X
X


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SoA Table 2: Timings of PK, target engagement and immunogenicity samples
Procedure
Treatment Period (Visit window 3 days)
Follow-up2
(3 days)
Notes
Visit 
21
3
4
5
6
7
8
9
10
11 
(ETP 
or EW)
12
13
14
1. Visit 2 = Day 1 
(first dose of IP). 
2. FU period to start 
4 weeks after ETP or 
EW visit.
Week
0
1
2
4
6
8
10
12
14
16
20
24
28
Study Day
1
8
15
29
43
49
71
85
99
113
Double blind 
Study 
Treatment 
(IP)
X
X
X
X
PK sample
X2
X
X
X3
X3
X1
X
X
X
X
1. Pre dose and 
post dose.
2. Post dose only.
3. Pre dose only.
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.
Free and total 
sST2
X1
X
X
X3
X3
X1
X
X
X
X
Immunogenicit
y sample
X3
X
X3
X3
X3
X
X
X
X


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3.
INTRODUCTION
3.1.
Study Rationale
GSK3772847 is a human immunoglobulin G2 sigma isotype (IgG2) antibody that binds 
Domain 1 of the cell-surface receptor 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 (FTIH) study has completed dosing (final report is pending). The safety 
information from this study is included in the investigator brochure. There are no efficacy 
data available to date. 
The present study is the first GSK sponsored study with GSK3772847. It is a Phase IIa 
study to investigate efficacy, safety and tolerability, pharmacokinetic (PK) and 
pharmacodynamic (PD) profiles of GSK3772847 in participants with severe asthma. The 
study will use a steroid titration design in order to induce instability and evaluate whether 
GSK3772847 maintains protection of asthma control. The design of steroid titration (oral 
or inhaled) in participants with asthma has been used in various studies with different 
investigational products, in which exacerbations were induced by medication withdrawal 
[Bel, 2014; Wenzel, 2013; Nair, 2009]. This design may not reflect real world 
exacerbations; however studies with the design of steroid titration have shown the ability 
to assess effects of a potential treatment on exacerbations in a relatively short period of 
time, before further investigations are conducted in longer term studies.
3.2.
Background
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].
Current biologic agents approved for the management of patients with severe asthma
have demonstrated efficacy for T2-driven disease (i.e., eosinophilic and/or elevated 
serum immunoglobulin E (IgE) however, there is no currently approved therapy that 
targets non-T2-driven asthma.
GSK3772847 (formerly CNTO 7160 which was in-licensed from Janssen) is a human 
IgG2monoclonal antibody (mAb) that binds to the extracellular domain of interleukin-
33 receptor (IL-33R) and neutralizes IL-33-mediated IL-33R signaling. 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 immune cells, such as mast cells, basophils, eosinophils, and T 
helper cell type 2 (Th2) cells and has been shown to be upregulated on macrophages, 


2017N311825_00
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neutrophils, and dendritic cells. It is also expressed on non-immune cells such as 
endothelial, epithelial and smooth muscle cells and fibroblasts. IL-33 has been shown to 
be released after endothelial or epithelial cell damage during trauma, physicochemical / 
microbarometric stress or infection [Arshad, 2016]. IL-33R signalling causes downstream 
production of Type 2 cytokines. The engagement of IL-33R with its ligand IL-33 
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 via blockade of the IL-
33R 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 IV infusion (20 or 100 
mg/kg) and was found to be well-tolerated at both doses. 
Janssen (Study CNTO7160ASH1001) have conducted a Phase I randomized, double-
blind, placebo-controlled, intravenous (IV) single ascending dose study in healthy 
participants  and multiple ascending dose study in participants with asthma and 
participants with atopic dermatitis. The study has completed dosing. The final clinical 
study report is still pending. There are no efficacy data available to date.
More information about the non-clinical and clinical studies is available in the
GSK3772847 Investigator’s Brochure (IB).
3.3.
Benefit/Risk Assessment
More detailed information about the known and expected benefits, risks and reasonably 
expected adverse events of GSK3772847 may be found in the Investigator’s Brochure.


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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 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 subcutaneous (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 was 
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 
Exclude participants with existing clinically 
significant organic heart disease (e.g. Coronary 
artery disease [CAD], New York Heart 
Association (NYHA) Class III/IV heart failure) and 
abnormal, clinically significant findings from 12-
lead 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 Section 2. 
All cardiac-related AEs will be reviewed by an 
independent safety review committee (iSRC).
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
temperature. The event was considered by the 
investigator to be likely related to IP. No specific 
cause was identified. Data on this event was 
reviewed by GSK (Internal Cardiac Safety Panel 
and CMO), and was not considered to impact 
further clinical development.
In Part 2 of the Janssen study CNTO
7160ASH1001, there were three reports of non-
sustained ventricular tachycardia. Of these 
reports, one participant received placebo and 
two received GSK3772847 at 3 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). 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
In Part 2, abnormal Holter findings of 2nd
degree AV block were observed in two 
participants at 10 mg/kg. Following review, 
an independent electrophysiologist stated
that these Holter findings were not evidence 
of “malignant conduction disease”. The 
Janssen Safety Management team advised 
that one subject should not receive the final 
scheduled dose; the 2nd subject had received 
the final dose by the time of review by the 
Safety Management team. Following 
unblinding it was noted that one participant 
received GSK3772847 whilst the other 
participant had received placebo. 
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 
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 
(SAD) has shown the most frequent adverse 
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. 
EU Regulatory guidance on development of 
asthma drugs request that agents that interact 
with the immune system should be investigated 


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
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.
events 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 6/24 [40%] 
administered placebo).
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 patients with ongoing or recurrent 
infections.
Close monitoring of infection AEs (including 
pneumonia).
Increased risk of hyper-sensitivity, 
anaphylaxis, cytokine release syndrome 
(CRS)
Therapy with other mAbs 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
patients at doses up to 10 mg/kg (3 doses, q2W 
over four weeks).
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 


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Based on in vitro cytokine release data and 
safety experience in Janssen study 
CNTO7160ASH1001 the risk of CRS is 
considered negligible.
administered in the clinic.
Possible interaction with live virus or 
bacterial vaccines
As GSK3772847 is an immunomodulator, there 
is a possibility that the subject will not mount an 
adequate vaccine response or even cause the 
infection the vaccine should protect against.
Non-clinical:
In the monkey 13 week toxicity study no 
GSK3772847-related changes in the T cell 
dependent B cell response (IgM or 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 
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, q2W 
over four weeks).
In the study, subjects should not be vaccinated 
with live or attenuated vaccines within 4 weeks 
prior to receiving IP or during the study. However 
vaccines containing killed bacteria or inactivated 
virus will be permitted.


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3.3.2.
Benefit Assessment
Efficacy of GSK3772847 has not yet been demonstrated. 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.
All study participants will receive open label salbutamol/albuterol to use as needed for 
asthma symptom relief from Screening 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, electrocardiogram (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 SGRQ during the study. Participants’ safety will also be assured 
by having criteria for withdrawal from study medication/reinstatement of usual care 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 the measures taken to minimize the risk to the participants 
participating in the study, the overall benefit:risk is considered to be positive. 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.
4.
OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary

To evaluate the efficacy of GSK3772847, 
compared with placebo, administered 
intravenously every 4 weeks for 12 weeks 
(Week 0 – Week 12, 4 doses in total) in 
participants with severe asthma.
Primary – Proportion of participants with loss of 
asthma control  over Weeks 0-16 where ‘loss of 
asthma control’ is defined as at least one of the 
following:

A clinically significant asthma exacerbation 
(requiring oral corticosteroid [OCS] and/or 
hospitalisation) or

Pre-bronchodilator Forced expiratory volume in 
1 second (FEV1) decrease from baseline 
(measured at the end of Run-in) >7.5 % or

Inability to titrate inhaled corticosteroid 
according to the pre-defined schedule (Section 
5.1) or

Asthma Control Questionnaire (ACQ-5) score 
increase from baseline (measured at the end of 
Run-in) ≥0.5 point.
Secondary

To evaluate other aspects of efficacy of 
GSK3772847 compared with placebo in 
Other efficacy endpoints (at or  by Week 16):

Proportion of participants who have a significant 
asthma exacerbation (requiring OCS and/or 


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Objectives
Endpoints
participants with severe asthma.
hospitalisation).

Proportion of participants who have pre-
bronchodilator FEV1 decrease from baseline 
(measured at the end of Run-in) >7.5 %.

Proportion of participants where inhaled 
corticosteroids (ICS) cannot be titrated in 
accordance with the pre-defined schedule.

Proportion of participants with a ≥0.5 point. 
ACQ-5 score increase from baseline.

Time to loss of asthma control.

Proportion of participants with a clinically 
significant asthma exacerbation or inability to 
titrate ICS according to the pre-defined 
schedule

The incidence, mean rate, and total number per 
participant of hospitalisations or Emergency 
Room (ER) visits during the study treatment 
period.

Change from baseline in ACQ-5 absolute score 
at each week from Week 1 to Week 16.

Proportion of participants with ≥0.5 point ACQ-5 
score decrease from baseline (responder) at 
each week from Week 1 to Week 16.

Change from baseline in SGRQ total score at 
Weeks 4, 8, 12 and 16.

Proportion of St. George’s Respiratory 
Questionnaire (SGRQ) responders (at least a 4 
unit improvement from baseline) at Weeks 4, 8, 
12 and 16.

Change from baseline in pre-bronchodilator 
FEV1 at Weeks 2, 4, 6, 8, 10, 12, 14, 16.

Change from baseline in mean morning peak 
expiratory flow (PEF) and mean evening PEF 
over each four weeks of the 16 week treatment 
period.

Change form baseline in mean daytime asthma 
symptom score over each four weeks of the 16 
week treatment period.

Change from baseline in rescue medication use 
(albuterol/salbutamol): mean number of 
inhalations per day over each four weeks of the 
16 week treatment period.

Changes from baseline in night-time 
awakenings due to asthma symptoms requiring 
rescue medication use over each four weeks of 
the16 week treatment period.

Change from baseline in fractional exhaled nitric 
oxide (FeNO) at each week measured.

To evaluate the safety and tolerability of 
GSK3772847, compared with placebo 

Incidence and frequency of adverse events 
(AEs) and serious adverse events (SAEs).


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Objectives
Endpoints
administered intravenously every 4 weeks for 
12 weeks (Week 0-12, 4 doses in total) in 
participants with severe asthma. 

Change from baseline in vital signs.

Change between post-dose and pre-dose in 
vital signs.

Change from baseline in 12-lead 
electrocardiogram (ECG) measurements.

Change between post-dose and pre-dose in 
12-lead ECG measurements

Change from baseline in 24 hours Holter 
measurements.

Change from baseline in clinical laboratory 
tests (haematology and chemistry).

Incidence of and titres of anti- GSK3772847 
antibodies.

To evaluate the pharmacokinetics (PK) of 
GSK3772847 in participants with severe 
asthma.

Serum concentrations of GSK3772847.

To evaluate the pharmacodynamics (PD) of 
GSK3772847 in participants with severe 
asthma.

Free and total soluble ST2 levels in serum.
Exploratory 

To compare the effect of GSK3772847 with 
placebo on biomarkers in serum and sputum.

Changes from baseline in induced sputum 
biomarkers (subset).

Changes from baseline in exploratory serum 
markers.
5.
STUDY DESIGN
5.1.
Overall Design
This is a Phase IIa, multicenter, randomized, placebo-controlled, double-blind, stratified,
parallel group study.
There will be a 2-week Run-in period following Screening (Visit 1). Eligible participants 
will be randomized at the end of the Run-in period (Visit 2). Randomization will be 
stratified based on participants’ baseline peripheral blood eosinophil count aiming 
for at least 30% of participants with eosinophil count <150 cells/L, which is 
measured at Screening.
When required, a pre-screening visit (Visit 0) can be scheduled up to 2 weeks prior to 
Screening (Visit 1). The pre-screening visit (Visit 0) can also occur on the same day as 
the Screening visit (Visit 1). Participants who meet the eligibility criteria at Screening 
(Visit 1) will withdraw their regular ICS/ long-acting beta-2-agonists (LABA) treatment 
for asthma and enter a two-week Run-in period during which they will receive open label 
background therapy of fluticasone propionate (FP)/salmeterol (Sal) 500/50 mcg BID. At 
the end of the Run-in period at Visit 2 (Week 0), participants who meet pre-defined 


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randomization criteria (Section 6.3) will be randomized in a 1:1 ratio to enter a double-
blinded Treatment Period and receive the following study treatment every 4 weeks for 12 
weeks (Week 0, 4, 8 and 12) while initially remaining on the open label background 
therapy of FP/Sal 500/50 mcg BID at Randomization:

GSK3772847 administered intravenously  or

Placebo administered intravenously
At Visit 4 (i.e. two weeks after Randomization) the open label background therapy will 
be switched from FP/Salmeterol 500/50 mcg BID to FP 500 mcg BID for 2 weeks. This
will mark the beginning of the FP titration period. Every two weeks for the next six 
weeks the dose of FP will be reduced by approximately 50 % (i.e. FP 250 mcg BID at 
Visit 5 for 2 weeks, FP 100 mcg BID at Visit 6 for 2 weeks, then FP 50 mcg BID at Visit 
7 for 2 weeks) until complete FP discontinuation at Visit 8, provided that the participant
does not meet any of the loss of asthma control criteria. If any of the pre-defined criteria 
for loss of asthma control are met during the Treatment Period, participants will be 
withdrawn from the investigational product (IP) and should resume regular treatment for 
their asthma, as determined by the investigator. 
For participants who receive all four doses of blinded study treatment, an End of 
Treatment Period (ETP) Visit will be performed 4 weeks after the final dose of the 
blinded study treatment is administered at Week 12. Participants should resume regular 
treatment for their asthma, as determined by the investigator, after protocol defined study 
assessments are completed. Three Follow-up visits will be performed 4, 8, and 12 weeks 
(Week 20, Week 24, and Week 28) after the ETP Visit for safety assessments.
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. Participants 
should resume regular treatment for their asthma, as determined by the investigator.
Three Follow-up visits will then be performed 4, 8, and 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.  


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Following randomization par
scheduled FP dose titration an
blinded study treatment (Visi
Albuterol/salbutamol will be 
basis from Screening through
The maximum total duration 
An independent Safety Revie
safety data to protect and mai
validity. Members of the iSR
but not necessarily be limited
iSRC Charter. 
5.2.
Number of Pa
Approximately 300 participan
high-dose ICS/LABA will be
74 on placebo) participants an
an evaluable participant is de
visit whilst remaining on IP o
High-dose ICS is defined as
1000 mcg total daily dose) o
CONFIDENTIAL
28
rticipants will return to the clinic at least every 2
nd assessment of asthma control until the last do
it 10).
provided for symptomatic relief to be used on a
h to the ETP visit. 
of the study is approximately 33 weeks.
ew Committee (iSRC) will periodically review u
intain participant safety whilst maintaining scien
RC will be independent of the project. The data w
d to SAEs, Holters, and ECGs. Details are descri
articipants
nts with severe persistent asthma who are maint
e screened to ensure 148 randomized (74 on GSK
and 140 evaluable participants. For the purpose o
efined as a participant who completes the Week 
or who withdraws from IP having met the primar
s fluticasone propionate 500 mcg twice daily (
or equivalent.
207597
2 weeks for 
ose of 
an as needed 
unblinded
ntific 
will include, 
ibed in the 
ained on 
K3772847, 
of this study 
16 clinic 
ry endpoint.
(i.e. 


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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 randomized treatment phase, and 
safety follow-up.
Distinguish between the end of the study (EU definition) and study completion (US CT 
Registry definition: Final date on which data was or is expected to be collected) if they 
are not the same. 
The end of the study is defined as the date of the last scheduled procedure shown in the 
Schedule of Activities for the last participant in the trial globally.
5.4.
Scientific Rationale for Study Design
This study will use a multicenter, randomized, double-blind, parallel-group and placebo-
controlled design.  This is a well-established design to evaluate the efficacy, safety, PK 
and PD profiles of an investigational drug. The design of steroid titration (oral or inhaled) 
in participants with asthma has been used in various studies with different investigational 
products, in which exacerbations were induced by medication withdrawal [Bel, 2014; 
Wenzel, 2013; Nair, 2009]. This design may not reflect real world exacerbations, 
however studies with the design of steroid titration have shown the ability to assess 
effects of a potential treatment on exacerbations in a relatively short period of time, 
before further investigations are conducted in longer term studies.  
In this study, the target population would be participants with severe asthma and with an 
ACQ5 ≥1.5 whose symptoms must have been managed on a stable, high dose ICS/LABA 
for at least 4 months prior to Screening. The use of loss of asthma control as a composite 
study endpoint and a criterion for ICS titration allows for the overall clinical evaluation 
of the participant’s asthma status taking into account both lung function and symptom 
control. Participants will also be monitored through the use of the eDiary. Pre-specified 
asthma symptom scores and participant-measured PEF that is inputted into the eDiary 
will be used as prompts for contacts between subjects and investigators (Section 9.1.2.3).
The FP titration period will occur during the Treatment Period of the study. The FP dose 
reduction will be assessed and managed at scheduled clinic visits. During the FP titration 
period the subjects’ FP dose will be reduced as described in Section 5.1 and the SoA, 
unless the subject meets protocol defined criteria for loss of asthma control indicating 
that it is not acceptable for the participant to further reduce ICS. Prior to each FP dose
reduction an assessment of the participants’ asthma control should be completed and the
decision to reduce the dose of FP will be based on: 1) the presence and severity of 
exacerbations, 2) changes in FEV1, 3) changes in the most recent ACQ-5 score, or 4) the 
ability to titrate ICS as per the pre-defined schedule, according to the investigator’s 
clinical judgment. If loss of control is confirmed during the FP titration period, the 
participant will discontinue IP immediately and should resume regular treatment for their
asthma, as determined by the investigator. A similar methodology was recently reported 
[Wenzel, 2013] and successfully allowed titration of ICS. 


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To evaluate the safety and tolerability of repeat dose of GSK3772847, a placebo arm will 
be included to allow the absolute effect of GSK3772847 to be assessed. The treatment 
duration of 12 weeks is supported by pre-clinical study data. Dosing frequency of IP 
every 4 weeks with endpoints assessments scheduled 4 weeks post final IP dose are 
determined by the available target engagement pharmacodynamic findings. Upon 
completing the 16 week Treatment Period (or after IP discontinuation), participants
should resume regular treatment for their asthma, as determined by the investigator and 
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 taken to fully characterise the 
pharmacokinetics, pharmacodynamics, and anti-drug antibody responses in this 
population.
An inhaled short acting beta2–receptor agonist, salbutamol/albuterol will be provided to 
all participants to use as needed to relieve asthma symptoms from Screening (Visit 1) to 
end of the Treatment Period. Both safety and efficacy parameters will be assessed 
regularly in the clinic to minimise any potential risks to the participants. Participants’
safety will also be assured by having withdrawal criteria (Section 8.1) in case of loss of 
asthma control.
5.5.
Dose Justification
The dosing regimen of 10 mg/kg IV at Week 0 then Weeks 4, 8 and 12 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 0-16 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 1


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Figure 1
Predicted clinical exposures at 10mg/kg at weeks 0, 4, 8 and 12 
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 
(NOAEL) (100 mg/kg weekly) in the 3-month GLP toxicology study in 
cynomolgus monkeys (T-2013-007).

Open Triangles: Observed mean and SD 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.
The anticipated exposure margins of the dosing regimen of 10 mg/kg IV at Week 0 then 
Weeks 4, 8 and 12 over the 3-month GLP toxicology study in cynomolgus monkeys (T-
2013-007) are summarised in Table 1. 


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Table 1
Predicted clinical exposures and safety margins for study 207597
following dosing of 10 mg/kg at weeks 0, 4, 8 and 12.
Day 1 mean Cmax
(µg/mL)
Exposure 
margina
Week 12 
mean Cmax 
(µg/mL)
Exposure 
margina
0-28 weeks
AUC
(µg.day/mL)
Exposure 
marginb
245.3c
10.5
313.5d
17.4
16830.2d
18.2
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.
c.
Mean observed exposures in study CNTO7160ASH1001.
d.
Predicted exposures using preliminary MM model
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:
1. Age: At least 18 years of age at the time of signing the informed consent.
2. Gender: Males and females. 
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:

Not a woman of childbearing potential (WOCBP) as defined in Appendix 5.
OR

A WOCBP who agrees to follow one of the options listed in Appendix 5 from 
4 weeks prior to the first dose of study medication and until at least 16 weeks
after the last dose of study medication and completion of the follow-up visit.
3. Informed consent: Capable of giving signed informed consent which includes 
compliance with the requirements and restrictions listed in the consent form and in 
this protocol.
4. Asthma diagnosis and severity: A participant with a documented diagnosis of 
severe asthma based on Global Initiative for Asthma (GINA) 2016 Guidelines, whose 
asthma has been managed with regular treatment of  high dose ICS defined as 
fluticasone propionate 500 mcg twice daily (i.e. 1000 mcg total daily dose) or 
equivalent, and long-acting beta-2-agonist (LABA) for at least 4 months. Additional 
therapy with a leukotriene receptor antagonist (LTRA) is permissible.
5. Reversibility: Airway reversibility of at least 12 % and 200 mL in FEV1 at 
Screening (Visit 1), or documented reversibility prior to Screening (Visit 1), or 


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documented history of bronchial hyperreactivity from a bronchoprovocation study 
(e.g. methacholine challenge) prior to Screening (Visit 1).
Note: If the participant does not meet the above reversibility criteria at Screening
(Visit 1) then the reversibility assessment may be repeated once within 7 days of Visit 
1. Should the participant successfully demonstrate airway reversibility at the second 
attempt then, provided that all other eligibility criteria assessed at Screening (Visit 1)
are met, the participant may enter the 2 week run-in period.
6. Asthma Control Questionnaire (ACQ): ACQ-5 score ≥1.5 at Screening (Visit 1).
7. Exacerbation history: Had at least one asthma exacerbation within 12 months prior 
to Screening that required treatment with systemic corticosteroid and/or 
hospitalization.
6.2.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
1. Smoking history: Current smokers or former smokers with a smoking history ≥10 
pack years. 
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.
3. Severe airflow obstruction: A pre-bronchodilator FEV1 <50 % predicted of normal 
value at Screening (Visit 1).
Note: If the spirometry is deemed technically inadequate by the central reader, the 
spirometry assessment may be repeated once within 7 days of Screening (Visit 1).
4. Malignancy: Participants with a diagnosis of malignancy or in the process of 
investigation for a malignancy.
5. Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody 
test result at Screening (Visit 1) or within 3 months prior to first dose of study 
treatment.
NOTE: Participants with positive Hepatitis C antibody due to prior resolved disease 
can be enrolled, only if a confirmatory negative Hepatitis C Ribonucleic acid (RNA)
test is obtained.
6. 12-lead ECG assessment at Screening (Visit 1): Site investigators will be provided 
with ECG over-read conducted by a centralized independent cardiologist, to assist in 
evaluation of subject eligibility. For this study, an abnormal and clinically significant 
ECG that would preclude a subject 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 2:


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Table 2
Abnormal and clinically significant ECG findings

Sinus bradycardia <45bpm
*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 
subject is precluded from entering the study.

Evidence of ventricular ectopic couplets, bigeminy, trigeminy or multifocal 
premature ventricular complexes.

For subjects 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 subjects 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 subject 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)
7. Weight: <50 kg and >150 kg


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8. Regular use of systemic corticosteroids for conditions including asthma within 3 
months prior to Screening (Visit 1).
9. Participants with high parasympathetic tone (e.g. trained athletes with baseline 
bradycardia) or chronic conditions associated with parasympathetic surges (e.g. 
migraines)
10. 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).
11. Cardiovascular disease: Clinically significant organic heart disease (e.g. CAD, 
NYHA Class III/IV heart failure).
12. Ongoing or recurrent infections requiring systemic antibiotics.
13. Other Concurrent Diseases/Abnormalities:  A subject must not have any clinically 
significant, uncontrolled condition, or disease state that, in the opinion of the 
investigator, would put the safety of the subject at risk through study participation or 
would confound the interpretation of the efficacy results if the condition/disease 
exacerbated during the study.
The list of additional excluded conditions/diseases includes, but is not limited to, the 
following:
Addison's disease
hypertension1 (uncontrolled)
aortic aneurysm (clinically significant)
peptic ulcer (recent or poorly controlled)
Cushing's disease
renal disease
diabetes mellitus (uncontrolled)
stroke within 3 months of Visit 1
hematological disease
thyroid disorder (uncontrolled)
hepatic disease
tuberculosis (current or untreated2)
1.
Two or more measurements with systolic pressure >160mmHg or diastolic pressure >100mmHg
2.
Subjects with a history of tuberculosis infection who have completed an appropriate course of 
antituberculosis treatment may be suitable for study entry provided that there is no clinical suspicion of 
active or recurrent disease.
14. Immunodeficiency: A known immunodeficiency such as human immunodeficiency 
virus infection.
15. Hypersensitivity: Participants with allergy or intolerance to a monoclonal antibody 
or biologic or to any components of the formulation used in this study.
16. Alcohol and Substance abuse: Participants with a history (or suspected history) of 
alcohol misuse or substance abuse within 2 years prior to Screening (Visit 1).
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, dosing directions, study electronic diary (eDiary) completion, or use of a 
standard metered dose inhaler. 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.
18. Participants who have previously participated in a study of GSK3772847.


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19. Excluded Medications:  Use of the medications listed in Table 3 is not permitted 
within the defined time intervals prior to Screening (Visit 1) and throughout the 
study.
Table 3
Prohibited Medications
Medication
Time interval prior to Visit 1
Investigational drug
One month or 5 half-lives whichever is longer
Live or attenuated vaccinesa
2 weeks (i.e. 4 weeks prior to IP administration)
Biologics, for example Mepolizumab and 
Omalizumab
130 days or 5 half-lives whichever is longer
Experimental  anti-inflammatory drugs (non-
biologics)
3 months
Corticosteroids intramuscular, long acting depot 
Regular systemic corticosteroid
3 months
Methotrexate, troleandomycin, oral gold, 
cyclosporin, azathioprine, 
3 months
Theophylline
3 months
Chemotherapy and radiotherapy
12 months
a.
Vaccines containing killed bacteria or inactivated virus will be permitted
20. Affiliation with Investigator Site:  A participant will not be eligible for this study if 
he/she is an immediate family member of the participating investigator, sub-
investigator, study coordinator, or employee of the participating investigator.
21. Inability to read:  In the opinion of the investigator, any participant who is unable to 
read and/or would not be able to complete a diary card/questionnaire.  
22. Questionable validity of consent: Participants with a history of psychiatric disease, 
intellectual deficiency, poor motivation or other conditions that will limit the validity 
of informed consent to participate in the study.
6.3.
Randomization Inclusion Criteria
At the end of the Run-in period (Visit 2), study participants must fulfil the following 
additional criteria in order to be randomized into the study and enter the treatment period:
1. Asthma Control Questionnaire (ACQ): ACQ-5 score ≥1.5 at Visit 2.
2. eDiary Compliance: Compliance with completion of the Daily eDiary reporting 
defined as completion of all questions/assessments on ≥4 of the last 7 days during the 
run-in period.
6.4.
Randomization Exclusion Criteria
Participants meeting any of the following criteria must not be randomized to double-
blind study medication at Visit 2:


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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. 12-lead ECG over-read: Evidence of clinically significant abnormal ECG findings 
(Table 2) at Screening (Visit 1).
3. 24-Hour Holter Monitoring: An abnormal and significant finding from 24-hour 
Holter monitoring at Screening (Visit 1). 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 2. The 
study investigator will determine the medical significance of any Holter abnormalities 
not listed in Table 2.
4. Liver function at Screening (Visit 1)

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 %). 

Current or chronic history of liver disease, or known hepatic or biliary 
abnormalities (with the exception of Gilbert's syndrome or asymptomatic 
gallstones.
5. Asthma exacerbation: Participants with ongoing asthma exacerbation at the time of 
Visit 2.
Note: At the Investigator’s discretion, participants with an ongoing asthma 
exacerbation at Visit 2 may be re-screened 2 weeks after Visit 2. In such cases, the 
full screening process (i.e. all Visit 0, 1 and Visit 2 assessments) must be repeated.
6. Severe airflow obstruction: a pre-bronchodilator FEV1 <50 % predicted of normal 
value at Visit 2.
7. Positive pregnancy test at Visit 0, Screening (Visit 1) or Visit 2.
8. Ongoing or recurrent infections requiring systemic antibiotics.
6.5.
Lifestyle Restrictions
No lifestyle restrictions are required for this study.
6.6.
Pre-Screening/Screening/Run-in/Randomization Failures
A participant will be assigned a participant number at the time the informed consent is 
signed at Visit 0.
The study site will be responsible for reporting pre-screen failures. The following 
information will be collected in the eCRF for participants who are pre-screen failures:


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
Demographic information including race, age and gender

Participant number

Serious Adverse Event information only for any SAE considered as related to 
study participation
For the purposes of this study, pre-screening failures, screening failures, run-in failures
and randomization failures will be defined as follows:

Pre-screening failures: those participants that sign the informed consent 
document but do not have a Screening (Visit 1) procedure.

Screening failures: those participants that complete at least one Screening
(Visit 1) procedure but do not enter the run-in period. 
A participant who completes Visit 1 assessments and is dispensed the study 
medication for the run-in period is considered to have entered the run-in period.

Run-in failures: those participants that enter the run-in period but do not have 
any Visit 2 procedures.

Randomization failures: those participants that complete at least one Visit 2 
procedure but do not enter the double-blind study treatment period.
Any participant who completes the run-in period and then meets the randomization 
criteria and receives the double-blind study treatment at Visit 2 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 
(CONSORT) 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 and with 
prior approval from the GSK study team.. Participants who are excluded due to an 
ongoing asthma exacerbation at Visit 2 (Randomization exclusion criterion 5) may be 
rescreened 2 weeks after Visit 2, at the investigators discretion. Rescreened participants 
will be assigned a new participant number.
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.


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7.1.
Treatments Administered
Study 
Treatment 
Name:
GSK3772847
Placebo
Fluticasone 
Propionate/Salmet
erol 
Fluticasone 
Propionate
Dosage 
formulation:
50mg/mL
GSK377284, 15 
mM Sodium 
Phosphate, 
8.5% [w/v] 
Sucrose, and 
0.04% [w/v] 
Polysorbate 20, 
pH 7.3.
DISKUS– 60 
doses per device
DISKUS– 60 doses 
per device
Unit dose 
strength(s)/Dos
age level(s):
10 mg/kg
Commercially 
sourced sterile 
diluent
500/50 mcg per 
actuation
500, 250, 100 and 
50 mcg per 
actuation
Route of 
Administration 
IV infusion
IV infusion
Inhaled
Inhaled
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 
diluent
Twice daily; once 
in the morning 
and once in the 
evening
Twice daily; once in 
the morning and 
once in the evening


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Study 
Treatment 
Name:
GSK3772847
Placebo
Fluticasone 
Propionate/Salmet
erol 
Fluticasone 
Propionate
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 labeled 
as required per 
country 
requirement. 
Commercially 
sourced sterile 
diluent will be 
sourced by the 
site
Diskus Inhaler 
with 60 doses
(1 strip with 60 
blisters per strip)
Each container 
will be labeled as 
required per 
country 
requirement.
Diskus Inhaler with 
60 doses
(1 strip with 60 
blisters per strip)
Each container will 
be labeled as 
required per 
country 
requirement.
7.1.1.
Description of Albuterol/Salbutamol
Albuterol/salbutamol via metered-dose inhaler (MDI) will be issued for reversibility 
testing at Screening (Visit 1). An albuterol/salbutamol MDI for as needed (prn) use 
throughout the study will be dispensed starting at Visit 1; at the Investigator’s discretion, 
more than one MDI may be dispensed at any one time. Albuterol/salbutamol will be 
sourced from local commercial stock. The contents of the label will be in accordance 
with all applicable regulatory requirements.
7.1.2.
DISKUS Return
DISKUS inhalers containing FP/Salmeterol and FP will be dispensed to a participant 
during their visit to the study clinic (as applicable). The participant must return all 
dispensed inhalers at the subsequent clinic visit. The schedule for dispensing and 
collecting FP/Sal and FP is provided in the SoA (Section 2).
All used and unused FP/Sal, FP will be returned to GSK at the end of the study to be 
available for disposal. In some instances for sites outside the United States (US), study 
supplies will be disposed of locally either by the site, the country medical department or 
third-party vendor. Detailed instructions for the return of the study drug can be found in 
the Study Reference Manual (SRM).


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If any DISKUS inhaler fails to function properly, the participant should return to the 
clinic as soon as possible to obtain a new inhaler. The site will use the Interactive Web 
Response System (IWRS) (RAMOS NG) to obtain a new treatment pack number for the 
participant and dispense a new study treatment kit from the site’s study treatment supply 
as instructed by the IWRS. Details of the failure will be documented in the eCRF. 
Additional information on how to handle medical device incidents can be found in the 
SRM.
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 randomization
schedule. The randomization code will be generated by GSK using a validated 
computerized system. Participants will be randomized using an interactive web response 
system (IWRS) RAMOS NG. The study will use central-based randomization to allocate 
treatments. Once a randomization 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 subject to satisfying all eligibility criteria, 
participants will be randomized 1:1 to one of the following double-blind 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 16 weeks. 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 (RAMOS 
NG) to randomize participants and manage study treatment supplies (including 
dispensing) is provided in the RAMOS NG manual and SRM.
7.4.
Blinding
This will be a double-blind study and the following will apply. 

The Investigator or treating physician may unblind a participant’s treatment 
assignment only in the case of an emergency OR in the event of a serious 
medical condition when knowledge of the study treatment is essential for the 
appropriate clinical management or welfare of the participant as judged by the 
Investigator. 

Investigators have direct access to the participant’s individual study treatment. 

It is preferred (but not required) that the Investigator first contacts the Medical 
Monitor or appropriate GSK study personnel to discuss options before unblinding 
the participant’s treatment assignment. 


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
If GSK personnel are not contacted before the unblinding, the Investigator must 
notify GSK within 24 hours after unblinding, but without revealing the treatment 
assignment of the unblinded participant, unless that information is important for 
the safety of participants currently in the study. 

The date and event or condition which led to the unblinding (i.e. the primary 
reason) will be recorded in source documentation and in the eCRF. 
In the event of unblinding 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 IP, the participant must be followed-up as per 
protocol until the completion of the Safety Follow-up assessments.
GSK’s Global Clinical Safety and Pharmacovigilance (GCSP) 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
GSK3772847 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 WFI, 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 2º – 8C, protected from light. Protection 
from light during preparation and administration is not required. Full details on specific 
2º to 8C storage temperature conditions, preparation and administration including 
requirements for filtration are provided separately. 
Commercially available diluent will be used for dilution of study agent and will also 
serve as placebo for this study. Use of study agent diluent 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 authorized personnel and administered according to each participant’s body 
weight at Screening (Visit 2). 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. GSK3772847 must be filtered 
with a 0.22 micron filter before being diluted in sterile commercially available diluent. 
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 diluent 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.


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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. Required storage conditions and 
expiration date are indicated on the label.
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 
authorized 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 authorized 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 or unblinded site staff reference manual.

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 (MSDS)/equivalent document describing occupational 
hazards and recommended handling precautions either will be provided to the 
investigator, where this is required by local laws, or is available upon request from 
GSK.
Precaution will be taken to avoid direct contact with the study treatment. A Material 
Safety Data Sheet (MSDS) describing occupational hazards and recommended handling 
precautions will be provided to the investigator.  In the case of unintentional occupational 
exposure notify the monitor, Medical Monitor and/or GSK study contact.
7.6.
Treatment Compliance

FP/Sal and FP during the run-in and treatment periods will be self-administered at 
home; compliance will be assessed via dose counter during the site visits and 
documented in the source documents and eCRF. A record of the number of doses on 
the DISKUS inhaler will be recorded in the eCRF. Treatment start and stop dates, 
including dates for treatment delays and/or dose reductions will also be recorded in 
the eCRF.


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
The double blind IP will be intravenously administered to participants at the site.  
Administration will be documented in the source documents and reported in the 
eCRF.
7.7.
Concomitant Therapy
All asthma medications used within approximately 12 weeks prior to screening and 
during the study (including the post-treatment period) should be recorded in the eCRF.
All non-asthma medications taken during the study (after randomization including post-
treatment) and any changes to concomitant medications will be recorded in the eCRF. 
Note: Study provided FP/Sal, FP, and albuterol/salbutamol should not be recorded in the 
ConMeds page of the eCRF.
The minimum requirement is that the drug name, reason for use, dose (including unit e.g. 
mcg) and frequency, route and the dates of administration are to be recorded.
7.7.1.
Permitted Non-asthma Medications
The following medications are permitted during the study:

Medications for rhinitis (e.g., intranasal corticosteroids, antihistamines [including 
ocular and intranasal], cromolyn, nedocromil, nasal decongestants)

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.

Immunotherapy: Immunotherapy for the treatment of allergies is allowed during 
the study provided it was initiated 4 weeks prior to Visit 1 and participants remain 
in the maintenance phase for the duration of the study.

Topical and ophthalmic corticosteroids.
7.7.2.
Prohibited Medications and Non-Drug Therapies
Use of the medications listed below is not permitted during the study: 

Inhaled anti-cholinergics (e.g.tiotropium).

ICS/LABA other than the study-provided FP/Sal .

Inhaled Corticosteroids other than the study-provided FP.

LABA other than the salmeterol component in the study-provided FP/Sal.

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.

Monoamine oxidase (MAO) inhibitors.


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
Live or attenuated vaccines.

Experimental anti-inflammatory drugs (non-biologics).

Corticosteroids intramuscular, long acting depot regular systemic corticosteroid.

Methotrexate, troleandomycin, oral gold, cyclosporin, azathioprine.

Theophylline.

Chemotherapy and radiotherapy.
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.
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 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. Participants should resume regular treatment 
for their asthma, as determined by the investigator. Three Follow-up visits will 
then be performed 4, 8, and 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, lack of efficacy [including loss of 
asthma control], 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: 


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1. Liver Chemistry: Meets any of the protocol-defined liver chemistry stopping criteria.
2. QTc: Meets any of the protocol-defined stopping criteria.
3. Pregnancy: Positive pregnancy test.
4. Participant meets at least one of the following criteria for ‘loss of asthma control’:

A clinically significant asthma exacerbation (requiring OCS and/or 
hospitalization).

Pre-bronchodilator FEV1 decrease from baseline (measured at Visit 2) >7.5 %.

Inability to continue inhaled corticosteroid titration which is assessed and 
determined by the investigator at any time point following randomization, 
including on scheduled clinic visits.

ACQ-5 score increase from baseline (measured at Visit 2) ≥0.5 point
5. Study treatment unblinded.
Note: In the event of unblinding the Medical monitor/GSK team should be contacted 
to determine whether subject withdrawal is required.
6. 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, V4, V6) or findings of myocardial ischemia will also result in 
withdrawal/stopping.
7. Hypersensitivity or anaphylactic reaction
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 (in alignment with the Food 
and Drug Administration [FDA] premarketing clinical liver safety guidance). These 
protocol guidelines are in alignment with FDA premarketing clinical liver safety 
guidance:
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/UCM174090.pdf.
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.


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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 
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 
electrocardiograms obtained over a brief (e.g., 5-10 minute) recording period.  


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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
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 for data to be collected at the time of early withdrawal (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 for data to be collected at the time of early withdrawal (EW 
visit) and follow-up and for any further evaluations that need to be completed.
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:


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
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. 
9.
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and their timing are summarized in the Schedule of Activities
(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, is 
essential and required for study conduct.
No study related procedures may be performed until the informed consent form has 
been signed by the participant.  Selection and modification of the participant’s 
medications prior to study participation is based on the physician’s judgment according to 
sound medical practice, principles, and each participant’s needs.  A participant’s 
treatment must not be changed merely for the purpose of enabling the participant’s 
participation in the study.
9.1.
Efficacy Assessments
The timings of all efficacy assessments are specified in SoA.
9.1.1.
Questionnaires
9.1.1.1.
Asthma Control Questionnaire ACQ-5
The ACQ-5 measures attributes of asthma control [Juniper, 1999], measured with 
questions designed to be self-completed by the participant.  Participants will complete the 
ACQ-5 with the use of an e-Diary device on a weekly basis. The ACQ-5 includes five 
questions (concerning nocturnal awakening, waking in the morning, activity limitation, 
shortness of breath and wheeze) which enquire about the frequency and/or severity of 
symptoms over the previous week. The response options for all these questions consist of 
a zero (no impairment/limitation) to six (total impairment/ limitation) scale. The recall 


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period is the past week. A score of <0.75 indicates well-controlled asthma and a score 
1.5 indicates poorly controlled asthma [Juniper, 2006]. A change of 0.5 in score 
suggests a clinically important change in score [Juniper, 2005].
9.1.1.2.
St. George’s Respiratory of Life Questionnaire (SGRQ)
The St. George’s Respiratory Questionnaire is a well established instrument, comprising 
50 questions designed to measure Quality of Life in patients with diseases of airway 
obstruction, measuring symptoms, impact, and activity. The questions are designed to be 
self-completed by the participant [Jones, 1992] with a recall over the past 4 weeks.
Higher scores indicate worse health status, and a change of 4 points is considered a 
clinically relevant change [Jones, 2005].
9.1.2.
Daily Diaries
Participants will be issued with a PEF/e-Diary device at Visit 1 for twice daily use (in the 
morning upon waking and in the evening just before going to bed) throughout the study. 
The device will be provided by a third-party vendor. Information on the device and its 
use are documented in the SRM and the third-party vendor manual. Participants will be 
instructed on how to use the device in order to record results for the following in the 
eDiary each day from Visit 1 onwards:

Morning and evening peak flow (best of three).

Daytime asthma symptom score using a 5-point scale 

Inhalations of rescue medication usage over the previous 24-hours

Frequency of awakening due to asthma symptoms requiring rescue medication use

Morning and Evening use of FP/Sal and FP during the run-in and treatment periods
Section 9.1.2 describes the assessments and questionnaires recorded on the eDiary 
device, as well as the alerts that can be triggered based on recorded results. The data from 
the eDiary device will be automatically transmitted to a centralized server. The 
Investigator and designee(s) will be provided with access to the transmitted eDiary data 
via a vendor-provided portal and should review the data on an ongoing basis to check for 
the incidence of alerts as well as subject compliance with eDiary use.
Participants will also be issued with a paper Medical Problems/Medications Taken 
worksheet to record medical problems experienced and medications used during the 
study (please refer to the SRM for further details). Participants must also use this paper 
worksheet to record all healthcare contacts that occur during their participation in the 
study. This paper worksheet will be used to assist participant recall in discussions with 
the Investigator, for site staff to then enter as appropriate in the electronic case report 
form (eCRF).
9.1.2.1.
Night-time Awakening, Daytime Asthma Symptom Questions
Every morning upon waking (from the morning after Visit 1 onwards), participants will 
answer a question on the occurrence of night-time awakenings due to asthma symptoms. 
The participant’s response to the question on the occurrence of night-time awakenings 


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will be either ‘Yes’ (i.e. Did you wake up due to asthma symptoms (i.e. wheezing, 
coughing, shortness of breath, or chest tightness) or ‘No’ (i.e. they did not experience at 
least one night-time awakening due to asthma symptoms). If ‘Yes’, participants will be 
asked to respond either ‘Yes’ or ‘No’ to the question on rescue medication (i.e. when you 
woke up due to your asthma symptoms did you use any rescue bronchodilator?).
On the evening of Visit 1 (just before going to bed) and every evening there-after, 
participants will answer a question on daytime asthma symptoms. These questions will be 
answered on a 5-point scale (0 to 4) with ‘0’ representing no daytime asthma symptoms 
and ‘4’ representing very severe daytime asthma symptoms. Please describe the severity 
of your asthma symptoms (i.e. cough, wheeze, chest tightness, shortness of breath) today 
[0=no asthma symptoms, 1=mild asthma symptoms, 2= moderate asthma symptoms, 
3=severe asthma symptoms, 4= very severe asthma symptoms]. 
9.1.2.2.
Morning and Evening Home PEF
Participants will conduct PEF measurements using the PEF/eDiary device each morning 
and each evening. Three measurements for each session will be recorded by the 
participants in the eDiary. Assessments will be performed:

After completing all other eDiary assessments

Prior to albuterol/salbutamol use

Prior to FP/Sal and FP use
9.1.2.3.
Alerts
For safety the following alerts, indicative of worsening asthma, will be programmed into 
the eDiary with instructions for the participant to contact the investigator if any of the 
alert criteria are met. An alert in itself will not qualify as a clinically significant 
exacerbation:

Decrease in morning PEF 30% on at least two of three successive days, 
compared with Baseline (last 7 days of run-in).

A symptom score of 3 for at least two of three successive days.

An increase from baseline of ≥4 puffs /day of albuterol/salbutamol use on 2 
consecutive days.

Awakening due to asthma symptoms requiring rescue medication use for at least 
two of three successive nights.
9.1.3.
Pulmonary Function Test
Spirometry equipment and a device to measure FeNO (see Section 9.1.4) will be 
provided to all sites by a third-party vendor. Spirometry data from this study will be 
analysed by a third-party vendor. Details on performing the spirometry assessments, 
including information on the equipment provided and its use as well as specific 


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instructions on performing the spirometry manoeuvres are documented in the SRM and
the third-party vendor manual.
9.1.3.1.
Spirometry
Spirometry will be performed to assess FEV1 and FVC. At least 3 spirometry 
manoeuvres (from a maximum of 8 attempts) should be achieved on each occasion that 
spirometry assessments are performed. The best spirometry effort will be selected from a 
measurement that meets American Thoracic Society (ATS)/ European Respiratory 
Society (ERS) guidelines and has a minimum of 2 efforts which are considered valid and
repeatable, in accordance with the ATS/ERS standards [Miller, 2005]. At each visit, 
spirometry assessments must be performed at the same time of day (2 hour) as the 
assessment performed at Visit 2 (the baseline assessment). Participants should withhold 
short-acting beta-2-agonists (SABAs) for 6 hours and LABAs for 1 dosing interval 
(i.e. 12 or 24 hours based on the prescribed dosing interval of the product) prior to the 
clinic visit, if possible.
9.1.3.2.
Reversibility
All reversibility evaluations should follow the recommendations of the ATS/European 
Respiratory Society (ERS) Task force: Standardization of Lung Function Testing [Miller,
2005]. A baseline spirometry assessment should be performed after a washout period of 
at least 6 hours for short-acting β2- agonists and 1 dosing interval for long-acting β2-
agonists (or fixed dose combinations of LABA and ICS).
To perform the reversibility assessment, 4 puffs of the provided salbutamol/albuterol is 
administered following completion of the baseline assessment. A second spirometry 
assessment is performed within 10 to 15 minutes after administration of the 
salbutamol/albuterol.
Reversibility assessment at Screening (Visit 1) is not required if there is documented 
reversibility prior to Screening (Visit 1), or documented history of bronchial 
hyperreactivity from a bronchoprovocation study (e.g. methacholine challenge) prior to 
Screening (Visit 1).
9.1.4.
Fractional Exhaled Nitric Oxide (FeNO)
FeNO will be measured using a handheld electronic device. Measurements will be 
obtained in accordance with the ATS/ERS Recommendations for Standardized 
Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric 
Oxide and Nasal Nitric Oxide [Miller, 2005]. All sites will use standardized 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. Participants should not use their rescue medication for at least 6 hours 
before each FeNO assessment, unless essential for clinical need. Participants should also 


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withhold LABAs for 1 dosing interval (i.e. 12 or 24 hours based on the prescribed 
dosing interval of the product) before each FeNO assessment.
9.1.5.
Review of Loss of Asthma Control
Loss of asthma control is defined as at least one of the following: 

A clinically significant asthma exacerbation (requiring OCS and/or 
hospitalisation) or

Pre-bronchodilator FEV1 decrease from baseline (measured at the end of Run-in) 
> 7.5 % or

Inability to titrate inhaled corticosteroid according to the pre-defined schedule 
(Section 5.1) or

ACQ-5 score increase from baseline (measured at the end of Run-in) ≥0.5 point.
At each clinic visit, the Investigator will utilize clinical discretion and available objective 
evidence (including but not limited to eDiary data, spirometry data, the most recent 
ACQ5 scores, history of exacerbations, conmeds, AEs) to determine if the patient is 
experiencing loss of asthma control. The paper Medical Problems/Medications Taken 
worksheet must also be reviewed by the Investigator (or appropriately trained designee) 
at each visit to the study site to assist the Investigator in the identification of loss of 
asthma control. It is expected that the Investigator will indicate which criterion (criteria) 
the subject met that constituted loss of asthma control.
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 the Visit 2 until the last follow-up visit at the 
time points specified in the SoA (Section 2). At Visits 0 and 1 SAE information 
will be collected only for any SAEs considered as related to study participation.

All AEs will be collected from the signing of the ICF 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 case report form (eCRF) not the AE section.

All SAEs will be recorded and reported to the sponsor or designee within 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.


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
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 
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 an AE and/or SAE. Open-ended 
and non-leading verbal questioning of the participant is the preferred method to inquire 
about AE occurrence. Appropriate questions include:

“How are you feeling?” 

“Have you had any (other) medical problems since your last visit/contact?” 

“Have you taken any new medicines, other than those provided in this study, since 
your last visit/contact?” 
Participants will be issued with a paper Medical Problems/Medications Taken worksheet
to record any medical problems experienced and medications used during the study (See 
Section 9.1.2).
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 (SUSAR) according to local regulatory requirements and 
sponsor policy and forwarded to investigators as necessary.


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
An investigator who receives an investigator safety report describing a SAE or 
other specific safety information e.g. summary or listing of SAEs from the 
sponsor will review and then file it along with the 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 Cardiovascular (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. 
The CV eCRFs are presented as queries in response to reporting of certain CV Medicinal 
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 last follow-up visit.

If a pregnancy is reported, the investigator should inform GlaxoSmithKline (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 GlaxoSmithKline 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.


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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.
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 Schedule of Activities 
(SoA) table (Section 2) prior to conducting spirometry. Blood pressure (systolic and 
diastolic) and pulse rate will be measured in the supine position after approximately 5 
minutes rest. A single set of values 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 centralized external vendor. 
A single 12-lead ECG and rhythm strip will be recorded after measurement of vital signs. 
Recordings will be made at the time-points defined in the Schedule of Activities (SoA) 
table (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.
For participants who meet the QTc, protocol defined stopping criteria, triplicate ECGs 
(over a brief period of time) should be performed (Section 8).
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 


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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 centralized 
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 
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.


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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 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 eCRF. The laboratory reports must be filed with the source 
documents. Clinically significant abnormal laboratory findings are those which 
are not associated with the underlying disease, unless judged by the investigator 
to be more severe than expected for the participant's condition.

All laboratory tests with values considered clinically significantly abnormal 
during participation in the study 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.

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.
9.5.
Pharmacokinetics

Whole blood samples of approximately 3 mL will be collected for measurement 
of serum concentrations of GSK3772847as specified in the SoA. 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
9.6.
Pharmacodynamics
Pharmacodynamic (PD) Biomarkers
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. The timing of the collections may be adjusted on the basis of emerging PK or PD 


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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 sputum (Section 9.8.1.1) 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,  Eosinophilic Cationic Protein (ECP) and Type-2 chemokines (e.g. 
CCL13, CCL17) as well as sputum cell counts (e.g. percentage eosinophils). 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.
9.8.1.1.
Sputum Sub-Study
At selected sites only, consenting participants who are randomized at Visit 2 will be 
entered into the Sputum sub-study. In a subset of approximately 50% of eligible 
participants sputum samples will be collated as specified in the SoA.
Details of the sputum collection and processing methodology will be provided in the 
SRM.
9.8.2.
Immunogenicity Assessments 
Serum samples will be collected and tested for the presence of antibodies that bind to 
GSK3772847, as specified in the SoA. The actual date and time (24-hour clock time) of 
each sample will be recorded.
The presence of anti-GSK3772847 antibodies will be assessed using a tiered approach 
including a screening assay, a confirmation assay and calculation of titre.


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Instructions for the collection and handling of biological samples will be provided in the 
SRM. 
9.9.
Health Economics OR Medical Resource Utilization and 
Health Economics
Health Economics/Medical Resource Utilization and Health Economics parameters are 
not evaluated in this study.
10.
STATISTICAL CONSIDERATIONS
10.1.
Hypotheses
The primary null hypothesis () for this study is that the ratio of the proportions of 
subjects with loss of asthma control from randomization to Week 16 between 
GSK3772847 and placebo is unity.
: 	
		 ℎ 	 	 ℎ 		   16 	 3772847
	
		 ℎ 	 	 ℎ 		    16 	 #	
= 1 
The alternative hypothesis (%) for this study is that the ratio of the proportions of 
subjects with loss of asthma control from randomization to Week 16 between 
GSK3772847 and placebo is not unity. 
%: 	
		 ℎ 	 	 ℎ 		   16 	 3772847
	
		 ℎ 	 	 ℎ 		    16 	 #	
≠1 
The hypothesis will be tested by calculating the posterior probability that the ratio of the 
proportion of subjects with loss of asthma control on GSK3772847 compared with 
placebo is less than 1.0, 0.75, 0.5 and 0.2 (i.e. a 0%, 25%, 50% and 80% reduction) and 
supported by an estimate of the ratio with a 95% credible interval. A non-informative 
prior will be used.
Although the success of the study will be assessed by calculating posterior probabilities 
of the treatment effect reaching various thresholds and not statistical significance, a 
frequentist analysis will also be performed testing the above hypothesis.
10.2.
Sample Size Determination
The study will randomize 74 participants per treatment arm with the aim of having 70 
evaluable participants per arm. For the purpose of this study an evaluable participant is 
defined as a participant who completes the Week 16 clinic visit whilst remaining on IP or 
who withdraws from IP having met the primary endpoint. See Section 10.4.1 for how 
subjects who withdraw early from IP for reasons other than loss of asthma control are 
handled in the analysis.


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In addition to testing the hypothesis in the overall population, the study will randomize a 
sufficient number of participants to evaluate trends in pre-defined subgroups (e.g. 
eosinophil strata).
The true proportion of participants that would experience a loss of asthma control on each 
treatment is unknown. However in a similar study of Dupilumab compared with placebo, 
the proportion of participants with loss of control were 6% and 44% for Dupilumab and 
placebo respectively. Table 4 gives the power to detect a statistically significant 
difference (at the two-sided 5% level) between the two treatments assuming the true 
proportion with loss of control on placebo is 44% and the true proportion with loss of 
control on active is 6%, 11%, 19% and 22% [Fleiss, 2003].
Table 4
Table of Power Achievable for Different Treatment Comparisons 
using N=70 per arm calculated using PASS
True proportion on 
Placebo
True proportion on 
GSK3772847
Reduction
Power
44%
6%
86%
> 99%
44%
11%
75%
> 99%
44%
19%
57%
90%
44%
22%
50%
80%
Assuming the true proportion with loss of control on placebo is 44%, then with 70 
evaluable participants per arm, the study will have at least 80% power to detect a 
statistically significant difference between treatments assuming the true proportion with 
loss of control on GSK3772487 is at most 22% (Table 4).
With 70 evaluable participants per arm and assuming the true proportion with loss of 
control on placebo is 44%, the smallest observed difference that would lead to rejection 
of the null hypothesis (minimum detectable effect) is 31% corresponding to a proportion 
with loss of control on GSK3772847 of 28%.
There is a single primary endpoint so no adjustments are required for multiplicity.
10.3.
Populations for Analyses
For purposes of analysis, the following populations are defined:
Population
Description
Enrolled 
All participants who sign the ICF.
Randomized
All participants who were randomized. A subject who is recorded as 
a screen or run-in failure and also randomized will be considered to 
be randomized in error provided they have not performed any study 
assessments.
Modified Intent-to-treat 
All randomized subjects who take at least 1 dose of study treatment. 
Participants will be analyzed according to the treatment they actually 


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Population
Description
(ITT)
received.
Safety
This population will be the same as the Modified Intent-to-treat 
population.
PK
All randomized subjects who received at least one dose of study 
medication, and for whom at least one pharmacokinetic sample was 
obtained, analyzed and was measurable.
10.4.
Statistical Analyses
10.4.1.
Efficacy Analyses
Endpoint
Statistical Analysis Methods
Primary
The primary endpoint proportion of subjects with loss of asthma control will 
be analyzed using both Bayesian and Frequentist methods. A subject is 
deemed to have met the endpoint of loss of asthma control if they meet the 
criteria for any of the components of the definition of loss of asthma control.
The posterior probabilities that the ratio of the proportion of subjects with loss 
of asthma control on GSK3772847 compared with placebo is less than 1.0, 
0.75, 0.5 and 0.2 (i.e. a 0%, 25%, 50% and 80% reduction) will  be 
calculated analytically using a normal approximation for the logarithm of the 
ratio of proportions. This will be supported by an estimate of the ratio with a 
95% credible interval. Results will also be presented for the two eosinophils 
strata separately.
In addition, the proportion of participants with loss of asthma control will be 
analyzed using logistic regression allowing for baseline eosinophils strata. 
The odds ratio, 95% CI and p-value for the comparison of GSK3772847 with 
placebo will be presented. 
Results will also be presented for the two eosinophils strata separately by 
fitting a separate model with an additional term for eosinophil strata by 
treatment interaction. The effect of eosinophils as a continuous covariate will 
also be examined in a separate-logistic regression model.
Missing data will be handled using the following methods:
1) The loss of asthma control will be set to missing for participants who 
withdraw from IP prior to Week 16 for reasons other than loss of 
asthma control
2) A sensitivity analysis will be performed where participants who 
withdraw from IP prior to Week 16 for reasons other than loss of 
asthma control will have the endpoint set to loss of control


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Endpoint
Statistical Analysis Methods
Secondary
The following secondary endpoints will be analyzed using the same 
statistical analysis as described for the primary endpoint:

Proportion of participants with a clinically significant asthma exacerbation 
(requiring OCS and/or hospitalisation) 

Proportion of participants with Pre-bronchodilator FEV1  decrease from 
Baseline (measured at the end of Run-in) >7.5 % 

Proportion of participants with Inability to titrate inhaled corticosteroid 
according to the pre-defined schedule (Section 5.1) 

Proportion of participants with ACQ-5 score increase from Baseline 
(measured at the end of Run-in) ≥0.5 point.

Proportion of participants with a clinically significant asthma exacerbation 
or inability to titrate ICS according to the pre-defined schedule.
In these analyses, the endpoint will be set to missing for participants who 
withdraw from IP prior to Week 16 for reasons other than loss of asthma 
control.
Time to loss of asthma control will be analyzed using Kaplan-Meier analysis. 
Percentiles for time to loss of control will be presented for both treatment 
groups, along with graphical survival plots. Any early withdrawals from IP
that did not experience loss of control will be censored. Results will be 
presented for both of the two eosinophil strata separately, and combined. 
The following endpoints will be analyzed using repeated logistic regression. 
This analysis will be repeated including an additional term for eosinophil 
strata by treatment by visit interaction to provide estimates for the two 
eosinophil strata separately:

Proportion of ACQ-5 responders (a ≥0.5 point improvement from 
baseline at Week 16)

Proportion of SGRQ responders (at least a 4 unit improvement from 
baseline at Week 16
These analyzes will be performed using two different methods for handling 
missing data:
1) If endpoint at a visit is missing then the responder status is set to 
missing
2) If endpoint at a visit is missing and the endpoint is also missing at all 
subsequent visits then the responder status is set to non-responder
The odds ratio, 95% CI and p-value for the comparison of GSK3772847 with 
placebo will be presented for all models.
Mixed model repeated measures will be used to analyze the following 
endpoints. The baseline value of each endpoint will be included along with 
baseline*visit and treatment*visit interactions. Treatment differences, 95% 
confidence intervals and p-values will be presented.

Change from baseline in ACQ-5 absolute score 

Change from baseline in SGRQ total score


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Endpoint
Statistical Analysis Methods

Change from baseline in Pre-bronchodilator FEV1

Change from baseline in FeNO
This analysis will be repeated including an additional term for eosinophil 
strata by treatment by visit interaction to provide estimates for each 
eosinophil strata separately. No adjustment will be made for missing data.
Further information on how the following endpoints will be analyzed will be 
described in the report and analysis plan:

Hospitalisation or ER visit during the study treatment period

Morning and evening PEF

Daily asthma symptom score

Rescue medication use (albuterol/salbutamol): number of occasions 
per day 

Night-time awakenings due to asthma symptoms requiring rescue 
medication
Any changes to the planned analysis methods will be documented in the 
reporting and analysis plan. Details of subgroup analyses for the primary and 
secondary endpoints will be described in the reporting and analysis plan.
Exploratory
Will be described in the reporting and analysis plan
10.4.2.
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 analyzed descriptively by 
treatment group:

Incidence and frequency of AEs and SAEs

Vital signs

12-lead ECG

24 hours Holter

Clinical laboratory evaluation

Incidence of and titres of anti-GSK3772847 antibodies.
Details will be described in the reporting and analysis plan
Adverse events (AEs) will be coded using the standard GSK dictionary, Medical
Dictionary for Regulatory Activities (MedDRA), and grouped by body system. The
number and percentage of subjects experiencing at least one AE of any type, AEs within


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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 (AESIs) and AEs leading to 
withdrawal.
Deaths and SAEs, if applicable, will be documented in case narrative format.
10.4.3.
Pharmacokinetic Analyses
All safety analyzes will be performed on the PK 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.
10.4.4.
Pharmacodynamic Analyses
All pharmacodynamic analysis will be described in reporting and analysis plan.
10.4.5.
Other Analyses
PK, pharmacodynamic, and biomarker exploratory analysis will be described in the 
reporting and analysis plan. Any population PK analysis and pharmacodynamic analysis
will be reported separately from the main clinical study report (CSR). Should a 
genetic/PGx analysis be performed, a separate reporting and analysis plan will be 
generated (See Appendix 6: Genetics).
10.4.6.
Interim Analyses
Formal analyses will be performed at two timepoints.
End of Treatment Phase Analysis:
This will take place after all participants have completed the Week 16 visit. The data will 
be cleaned, the treatments unblinded and all clinic visits up to and including week 16 
frozen.However, whilst no further efficacy data will be collected post week 16, due to an 
inability to lock log forms used for collection of exacerbation data, the end of treatment 
phase analysis will be considered an interim analysis for both efficacy and safety. Any 
safety data collected for participants who have completed clinic visits after Week 16 will 
also be cleaned and included in the analysis. 
There will be no modifications to dosing regimens, sample size or any other aspects of 
the trial based on this data, as all study assessments, apart from follow-up, will have 


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already been completed. As such an Independent Data Monitoring Committee (IDMC) 
will not be used, as no further investigational product will be prescribed after this 
analysis has taken place.
Final Analysis:
This will take place after all subjects have completed the study. Data for visits after Week 
16 as well as data collected on log pages will be cleaned and the database frozen. This 
will be the final analysis for the study.
The Reporting and Analysis Plan will describe the planned analyses in greater detail.
Instream review:
An iSRC 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.
Arshad MI, Khan HA, Noel G, Piquet-Pellorce C, Samson M. Potential therapeutic 
effects of alarmin cytokine interleukin 33 or its inhibitors in various diseases. Clin 
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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.
Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, et al. Oral 
Glucocorticoid-Sparing Effect of Mepolizumab in Eosinophilic Asthma. N Engl J Med 
2014; 371:1189-1197.
Chung KF, Wenzel SE, Brozek JC, 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.
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.
Fleiss, J. L., Levin, B., Paik, M.C. 2003. Statistical Methods for Rates and Proportions. 
Third Edition. John Wiley & Sons. New York. 
http://onlinelibrary.wiley.com/doi/10.1002/0471445428.ch4/pdf
Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health 
status for chronic airflow limitation. The St. George's Respiratory Questionnaire. Am 
Rev Respir Dis 1992;145:1321-1327.
Jones PW. St. George’s Respiratory Questionnaire: MCID. Journal of Chronic 
Obstructive Pulmonary Disease 2005;2:75-79.
Juniper EF, Bousquet J, Abetz L, Bateman ED; GOAL Committee. Identifying 'well-
controlled' and 'not well-controlled' asthma using the Asthma Control Questionnaire. 
Respir Med 2006;100:616-621.
Juniper EF, O'Byrne PM, Guyatt GH, Ferrie PJ, King DR. Development and validation of 
a questionnaire to measure asthma control. Eur Respir J. 1999;14(4):902-907.
Juniper EF, Svensson K, Mörk AC, Ståhl E. Measurement properties and interpretation of 
three shortened versions of the asthma control questionnaire. Respir Med 2005;99:553-
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Miller MR, Crapo R, Hankinson J, Brusasco V, Burgos F, Casaburi R, et al.
Standardization of Lung Function Testing. Eur Resp J 2005;26:153-161.
Moore WC, Bleecker ER, Curran-Everett D Erzurum SC, Ameredes BT, Bacharier L, 
Calhoun WJ, 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.
Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, et al.
Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 
2009; 360:985-93.
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.
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(8):1019-1030.
Wenzel SE, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, et al. Dupilumab in 
Persistent Asthma with Elevated Eosinophil Levels. N Engl J Med. 2013;368: 2455-66.
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(10):5743-5750.


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12.
APPENDICES
12.1.
Appendix 1: Abbreviations and Trademarks
Abbreviations
ACQ
Asthma Control Questionnaire
AE
Adverse Event
AESI
Adverse Event of Special Interest
ALT
Alanine Transaminase
AST
Aspartate Transaminase
ATS
American Thoracic Society
AUC
Area Under the Curve
BID
Twice a day
BUN
Blood Urea Nitrogen
CAD
Coronary artery disease
CI
Confidence Interval
CV
Cardiovascular
Cmax
maximum serum concentration
CIOMS
Council for International Organizations of Medical Sciences
CONSORT
Consolidated Standards of Reporting Trials
COPD
Chronic Obstructive Pulmonary Disease
CPK
Serum creatine phosphokinase
CSR
Clinical Study Report
DNA
Deoxyribonucleic acid
ECG
Electrocardiogram
(e)CRF
(Electronic) Case Report Form
ER
Emergency Room
eDiary
Electronic Diary
ETP
End of Treatment Phase
ERS
European Respiratory Society
EW
Early Withdrawal
FDA
Food and Drug Administration
FeNO
Fractional Exhaled Nitric Oxide
FEV1
Forced expiratory volume in 1 second
FP
Fluticasone Propionate
FSH
Follicle Stimulating Hormone
FTIH
First Time in Human
FVC
Forced Vital Capacity
GCP
Good clinical practice
GCSP
Global Clinical Safety and Pharmacovigilance
GGT
Gamma-glutamyltransferase
GINA
Global Initiative for Asthma
GLP
Good laboratory practice
GSK
GlaxoSmithKline
HBsAg
hepatitis B surface antigen


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hCG
Human Chorionic Gonadotropin
HIPAA
Health Insurance Portability and Accountability Act
HIV
Human Immunodeficiency Virus
HPLC
High performance liquid chromatography
HR
Heart rate
HRT
Hormone Replacement Therapy
IB
Investigator’s Brochure
ICF
Informed Consent Form
ICH
International Conference on Harmonization
ICS
Inhaled Corticosteroids
IEC
Independent Ethics Committee
IgG2
human immunoglobulin G2 sigma isotype
IgG
Immunoglobulin G
IL-33R
Interleukin-33 receptor
IL-1RL1
Interleukin-1 receptor like-1
IP
Investigational Product
IRB
Institutional Review Board
iSRC
Independent Safety Review Committee
IUD
Intrauterine device
IUS
Intrauterine hormone-releasing system
IV
Intravenous
IWRS
Interactive Web Response System
ITT
Intent to Treat
Kg
Kilogram
LABA
Long-Acting Beta-2-Agonists
LTRA
Leukotriene Receptor Antagonist
mAb
monoclonal antibody
MAO
Monoamine oxidase
MedDRA
Medicinal Dictionary for Regulatory Activities
mcg (g)
Microgram
MCH
Mean corpuscular haemoglobin
MCHC
Mean corpuscular haemoglobin concentration
MCV
Mean corpuscular volume
MDI
Metered Dose Inhaler
mg
Milligram
min
Minute
mIU
Milli international units
mL
Milliliter
L
Microlitre
mm
Millimeter
mV
Millivolt
MSDS
Material Safety Data Sheet
msec
Millisecond
NOAEL
No Observed Adverse Effect Level
NT-proBNP
N-terminal prohormone of brain natriuretic peptide
NYHA
New York Heart Association


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OCS
Oral Corticosteroid
PEF
Peak Expiratory Flow
PD
Pharmacodynamic
PGx
Pharmacogenetic
PK
Pharmacokinetic
prn
As needed
PSVT
Paroxysmal supraventricular tachycardia
q2W
Every two weeks
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
RBC
Red Blood Cell
RDW
Red cell distribution width
RNA
Ribonucleic acid
SABA
Short-Acting Beta-2-Agonists
SAD
Single Ascending Dose
SAE
Serious Adverse Event
Sal
Salmeterol
SGPT
Serum Glutamic-Oxaloacetic Transaminase
SGRQ
St. George’s Respiratory Questionnaire
SRM
Study Reference Manual
ST2
Suppressor of tumorigenicity 2
sST2
Soluble ST2
ULN
Upper Limit of Normal
US
United States
VT
Ventricular Tachycardia
WBC
White Blood Cell
WOCBP
Woman of childbearing potential
w/v
Weight/volume
Trademark Information
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
DISKUS
None


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12.2.
Appendix 2: Clinical Laboratory Tests

The tests detailed in Table 5 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. 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.
Table 5
Protocol-Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters
Hematology
Platelet Count
RBC Indices:
MCV
MCH
MCHC
WBC count with 
Differential:
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
Red Blood Cell (RBC)
Count
Hemoglobin
Hematocrit
White Cell Count
RDW
Clinical 
Chemistry1
BUN
Potassium
Aspartate 
Aminotransferase
(AST)/ Serum 
Glutamic-
Oxaloacetic 
Transaminase
(SGOT)
Total and direct 
bilirubin


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Laboratory 
Assessments
Parameters
Creatinine
Sodium
Alanine 
Aminotransferase
(ALT)/ Serum 
Glutamic-Pyruvic 
Transaminase
(SGPT)
Total Protein
Glucose 
nonfasting
Calcium
Alkaline 
phosphatase
CPK
Albumin
Phosphorus
GGT
Chloride
Carbon Dioxide
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)

Serum/urine human chorionic gonadotropin (hCG) pregnancy test (as 
needed for women of childbearing potential)2

Serology (HIV antibody, hepatitis B surface antigen HBsAg, and hepatitis C 
virus antibody) 

“All study-required laboratory assessments will be performed by a 
central laboratory
The results of each test must be entered into the eCRF.
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


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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 (CIOMS) International Ethical 
Guidelines

Applicable 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 authorized representative and answer all 
questions regarding the study. 


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
Participants must be informed that their participation is voluntary. Participants 
or their legally authorized representative will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study center. 

The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent 
must also sign the ICF.

Participants must be re-consented to the most current version of the ICF(s) 
during their participation in the study. 

A copy of the ICF(s) must be provided to the participant or the participant’s 
legally authorized 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 authorized personnel appointed 
by the sponsor, by appropriate IRB/IEC members, and by inspectors from 
regulatory authorities.
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 
generally support publication of multicenter studies only in their entirety and not 
as individual site data. In this case, a coordinating investigator will be 
designated by mutual agreement.

Authorship will be determined by mutual agreement and in line with 
International Committee of Medical Journal Editors authorship requirements.


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Data Quality Assurance

All participant data relating to the study will be recorded on printed or electronic 
eCRF unless transmitted to the sponsor or designee electronically (eg, laboratory 
data). The 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 
Clinical Study Report (CSR)/ equivalent summary unless local regulations or 
institutional policies require a longer retention period. No records may be 
destroyed during the retention period without the written approval of the 
sponsor. No records may be transferred to another location or party without 
written notification to the sponsor. 
Source Documents

Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site.

Data reported on the eCRF or entered in the eCRF that are transcribed from 
source documents must be consistent with the source documents or the 
discrepancies must be explained. The investigator may need to request previous 
medical records or transfer records, depending on the study. Also, current 
medical records must be available.
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.


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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 (hematology, 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 fulfill the definition of an AE 
or SAE. 

The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be 
reported as AE or SAE if they fulfill the definition of an AE or SAE. Also, "lack of 
efficacy" or "failure of expected pharmacological action" constitutes an AE or SAE.
Events NOT Meeting the AE Definition 

Any clinically significant abnormal laboratory findings or other abnormal safety 


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assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.

Medical or surgical procedure (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 (eg, hospitalization 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 hospitalization or prolongation of existing hospitalization
In general, hospitalization 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 hospitalization are AE. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious.
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE.
d.
Results in persistent 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, diarrhea, influenza, 


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and accidental trauma (eg, sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

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 hospitalization but may 
jeopardize the participant or may require medical or surgical intervention to prevent 
one of the other outcomes listed in the above definition. These events should usually 
be considered serious.
Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, 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.


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
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 
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 sufficiently 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 utilized 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 Investigator’s Brochure (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 


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minimal information to include in the initial report to GSK. However, it is very 
important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to GSK.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-up of AE and SAE

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, 
or consultation with other health care professionals.

If a participant dies during participation in the study or during a recognized follow-
up period, the investigator will provide GSK with a copy of any 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 or to the


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assigned SAE contact by telephone.

Contacts for SAE reporting can be found at the beginning of this protocol on the 
Sponsor/Medical Monitor Contact Information page
SAE Reporting to GSK via Paper eCRF

Facsimile transmission of the SAE paper eCRF is the preferred method to transmit 
this information to the assigned SAE contact by telephone.

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 eCRF 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 hormonal replacement therapy 
(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 enrollment.
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 6. 


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Table 6
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 ovulation 

oral

intravaginal 

transdermal 
Progestogen-only hormonal contraception associated with inhibition of ovulation 

injectable 
Highly Effective Methods That Are User Independent 

Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulation

Intrauterine device (IUD)

Intrauterine hormone-releasing system (IUS)

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. 
Pregnancy Testing

WOCBP should only be included after a confirmed menstrual period and a negative 
highly sensitive serum pregnancy test 

Additional pregnancy testing should be performed during the treatment period as 
specified in the Table of Events

Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected 


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
Pregnancy testing, with a sensitivity of 5, 10, 25 mIU/mL 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 fetal 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 Deoxyribonucleic acid (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 neutrophils 
and eosinophils 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 analyzed 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 analyzed 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 and related diseases 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 etiology 
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, stabilize, 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 
pharmacokinetic (PK) analysis, insert 
time interval recommended by clinical 
pharmacokinetics representative after 
last dose5

Serum creatine phosphokinase (CPK) 
and lactate dehydrogenase (LDH).

Fractionate bilirubin, if total 
bilirubin2xULN

Obtain complete blood count with 
differential to assess eosinophilia

Record the appearance or worsening of 


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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, stabilize 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, stabilize or return to within 
baseline
clinical symptoms of liver injury, or 
hypersensitivity, on the AE report form

Record use of concomitant medications 
on the concomitant medications report 
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 
(IgG) 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]). NOTE: 
not required in China

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 


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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.  
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

SAP_001.pdf: 
CONFIDENTIAL
The GlaxoSmithKline group of companies
207597
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Division
:
Worldwide Development
Information Type
:
Reporting and Analysis Plan (RAP)
Title
:
Reporting and Analysis Plan for a randomised, double-blind, 
parallel group, multicenter, stratified study evaluating the 
efficacy and safety of repeat doses of GSK3772847 
compared with placebo in participants with moderately 
severe asthma
Compound Number 
:
GSK3772847
Effective Date 
:
27-MAR-2019
Description:

The purpose of this RAP is to describe the planned analyses and output to be 
included in the Clinical Study Report for Protocol 2017N311825_02.

This RAP is intended to describe the Efficacy, Safety, PK, PD and Biomarker
analyses required for the study. 

This RAP will be provided to the study team members to convey the content of the 
End of Treatment Phase (ETP) and Statistical Analysis Complete (SAC) deliverable.

This study does have an internal safety review committee (iSRC) and all details of 
iSRC deliverable are documented in a separate iSRC RAP.
Author’s Name and Functional Area: 
Approver
Date
20-MAR-2019
Principal Statistician (Respiratory, Clinical Statistics)
Copyright 2019 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited.
PPD


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The GlaxoSmithKline group of companies
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RAP Team Review Confirmations 
(Method: E-mail)
Reviewer
Date
20-MAR-2019
Clinical Investigation Lead (Respiratory, HUP Clinical 
Development)
22-MAR-2019
Principal Programmer (Respiratory, Clinical Programming)
25-MAR-2019
Clinical Development Physician (Respiratory, MDC Global 
Clinical)
22-MAR-2019
Scientist (Respiratory, Patient Centred Outcomes, Value 
Evidence and Outcomes)
20-MAR-2019
Director (Respiratory, Value Evidence and Outcomes)
22-MAR-2019
Senior Director (Respiratory, Clinical Pharmacology Modelling 
and Simulation)
26-MAR-2019
Director of Clinical Development (Respiratory, MDC Global 
Clinical)
25-MAR-2019
Senior Scientific Director (Respiratory, RD AI DPU Head)
Clinical Statistics & Clinical Programming Line Approvals 
(Method: Pharma TMF eSignature)
Approver
Date
27-MAR-2019
Senior Statistics Director (Respiratory, Clinical Statistics)
27-MAR-2019
Programming Manager (Respiratory, Clinical Programming)
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


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TABLE OF CONTENTS
PAGE
1.
INTRODUCTION......................................................................................................6
2.
SUMMARY OF KEY PROTOCOL INFORMATION ..................................................7
2.1.
Changes to the Protocol Defined Statistical Analysis Plan............................7
2.2.
RAP Amendments ......................................................................................10
2.3.
Study Objective(s) and Endpoint(s).............................................................11
2.4.
Study Design ..............................................................................................14
2.5.
Statistical Hypotheses.................................................................................15
2.6.
Sample Size Calculations ...........................................................................15
3.
PLANNED ANALYSES ..........................................................................................16
3.1.
End of Treatment Phase Analyses..............................................................16
3.2.
Final Analyses ............................................................................................16
4.
ANALYSIS POPULATIONS ...................................................................................17
4.1.
Protocol Deviations.....................................................................................18
5.
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS.....................................................................................................19
5.1.
Study Treatment & Sub-group Display Descriptors.....................................19
5.2.
Baseline Definitions ....................................................................................20
5.3.
Multicentre Studies .....................................................................................21
5.4.
Examination of Covariates, Other Strata and Subgroups............................22
5.4.1.
Covariates and Other Strata ........................................................22
5.5.
Multiple Comparisons and Multiplicity .........................................................22
5.6.
Other Considerations for Data Analyses and Data Handling 
Conventions................................................................................................22
6.
STUDY POPULATION ANALYSES .......................................................................23
6.1.
Overview of Planned Study Population Analyses........................................23
6.2.
Disposition..................................................................................................23
6.3.
Medical Conditions .....................................................................................23
6.4.
Concomitant Medications............................................................................23
7.
EFFICACY ANALYSES..........................................................................................24
7.1.
Primary Efficacy Analyses ..........................................................................24
7.1.1.
Endpoint ......................................................................................24
7.1.2.
Summary Measure ......................................................................24
7.1.3.
Population of Interest...................................................................24
7.1.4.
Strategy for Intercurrent (Post-Randomisation) Events ................24
7.1.5.
Statistical Analyses / Methods .....................................................25
7.1.5.1.
Statistical Methodology Specification..........................25
7.2.
Secondary Efficacy Analyses......................................................................29
7.2.1.
Endpoint and Summary Measure.................................................29
7.2.2.
Population of Interest...................................................................30
7.2.3.
Strategy for Intercurrent (Post-Randomisation) Events ................30
7.2.4.
Statistical Analyses / Methods .....................................................31
7.2.4.1.
Statistical Methodology Specification..........................31


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8.
SAFETY ANALYSES .............................................................................................36
8.1.
Adverse Events Analyses ...........................................................................36
8.2.
Adverse Events of Special Interest Analyses..............................................36
8.3.
Vital Signs, Electrocardiogram (ECG) and Holter........................................36
8.4.
Clinical Chemistry, Haematology and Cardiac Markers...............................36
8.5.
Antibodies...................................................................................................37
8.6.
Clinical Laboratory Analyses.......................................................................37
9.
PHARMACOKINETIC ANALYSES.........................................................................37
9.1.
Secondary Pharmacokinetic Analyses........................................................37
9.1.1.
Endpoint / Variables.....................................................................37
9.1.2.
Population of Interest...................................................................37
9.1.3.
Strategy for Intercurrent (Post-Randomisation) Events ................37
9.1.4.
Statistical Analyses / Methods .....................................................37
10. PHARMACODYNAMIC AND BIOMARKER ANALYSES........................................38
10.1.
Secondary Pharmacodynamic Analyses.....................................................38
10.1.1.
Endpoint / Variables.....................................................................38
10.1.2.
Summary Measure ......................................................................38
10.1.3.
Population of Interest...................................................................38
10.1.4.
Strategy for Intercurrent (Post-Randomisation) Events ................38
10.1.5.
Statistical Analyses / Methods .....................................................38
10.2.
Exploratory Biomarker Analyses .................................................................40
10.2.1.
Endpoint / Variables.....................................................................40
10.2.2.
Summary Measure ......................................................................40
10.2.3.
Population of Interest...................................................................40
10.2.4.
Strategy for Intercurrent (Post-Randomisation) Events........................40
10.2.5.
Statistical Analyses / Methods .....................................................40
11. REFERENCES.......................................................................................................41
12. APPENDICES........................................................................................................42
12.1.
Appendix 1: Protocol Deviation Management .............................................42
12.2.
Appendix 2: Schedule of Activities ..............................................................43
12.2.1.
Protocol Defined Schedule of Events...........................................43
12.3.
Appendix 3: Assessment Windows .............................................................49
12.3.1.
Definitions of Assessment Windows for Analyses........................49
12.4.
Appendix 4: Study Phases and Treatment Emergent Adverse 
Events ........................................................................................................50
12.4.1.
Study Phases ..............................................................................50
12.4.1.1.
Study Phases for Concomitant Medication .................51
12.4.2.
Treatment Emergent Flag for Adverse Events .............................51
12.5.
Appendix 5: Data Display Standards & Handling Conventions....................52
12.5.1.
Reporting Process .......................................................................52
12.5.2.
Reporting Standards....................................................................52
12.6.
Appendix 6: Derived and Transformed Data ...............................................54
12.6.1.
General........................................................................................54
12.6.2.
Study Population..........................................................................54
12.6.3.
Efficacy........................................................................................56
12.6.4.
Safety ..........................................................................................57
12.7.
Appendix 7: Reporting Standards for Missing Data.....................................59
12.7.1.
Premature Withdrawals................................................................59


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12.7.2.
Handling of Missing Data.............................................................59
12.7.2.1.
Handling of Missing and Partial Dates ........................60
12.8.
Appendix 8: Values of Potential Clinical Importance ...................................61
12.9.
Appendix 9: Abbreviations & Trade Marks ..................................................62
12.9.1.
Abbreviations...............................................................................62
12.9.2.
Trademarks .................................................................................63
12.10. Appendix 10: List of Data Displays..............................................................64
12.10.1. Data Display Numbering..............................................................64
12.10.2. Mock Example Shell Referencing ................................................64
12.10.3. Deliverables.................................................................................64
12.10.4. Study Population Tables..............................................................65
12.10.5. Efficacy Tables ............................................................................67
12.10.6. Efficacy Figures ...........................................................................70
12.10.7. Safety Tables...............................................................................73
12.10.8. Pharmacokinetic Tables...............................................................77
12.10.9. Pharmacodynamic and Biomarker Tables....................................78
12.10.10.Pharmacokinetic Figures .............................................................79
12.10.11.Pharmacodynamic and Biomarker Figures ..................................80
12.10.12.ICH Listings .................................................................................81
12.10.13.Non-ICH Listings..........................................................................85
12.11. Appendix 11: Example Mock Shells for Data Displays ................................88


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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 207597:
Protocol Revision Chronology:
2017N311825_00
2017-MAR-06
Original
2017N311825_01
2017-JUN-02
To address clarifications regarding the aim of the study, the 
eligibility criteria, the schedule of activities, the clinical 
assessments, and the recording of lab data and adverse 
events. The benefit: risk section was also updated based on 
the Part 2 results from study CNTO7160ASH1001. Also, a few 
typographical errors were corrected.
2017N311825_02
2017-SEP-13
To add more information on the risk: benefit section and the 
study design justification sections. To address clarifications 
regarding the unblinding of treatment in case of emergency. 
To clarify that rechallenge is not allowed once the treatment 
discontinuation criteria are met. Also, a few typographical 
errors were corrected.


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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
Modified Intent to Treat population.
Modified Intent to Treat (Loss of 
Control), Modified Intent to Treat 
and Safety excluding GCP non-
compliant subjects populations.
The Modified Intent to Treat 
(Loss of Control) was added to 
account for the intercurrent 
event when participants receive 
the wrong study treatment. 
Whilst the data from GCP non-
compliant participants should 
not be used in the efficacy 
analysis, the participants were 
dosed with GSK3772847 or 
Placebo so all safety data (AEs, 
SAEs, ECGs etc.) should be 
reported.
Section 10.4.1 of the protocol 
describes a sensitivity analysis 
where data is analysed as missing 
and worst case (loss of control) for 
participants who withdraw from the 
study for reasons other than loss of 
asthma control.
A primary and secondary 
estimand have been defined to 
capture where data is analysed 
as missing and worst case (loss 
of control) for various 
intercurrent events where 
participants withdraw from the 
study for reasons other than 
loss of asthma control.
The protocol was approved 
before the ICH E9 addendum on 
estimands. The RAP is 
performing the same planned 
analysis as detailed in the 
Protocol however the 
terminology has been updated 
in accordance with ICH E9.  
Statistical analysis would be 
performed for each screening 
eosinophil strata separately.
Bayesian analysis will include 
screening eosinophil strata as a 
covariate instead of performing 
split analysis models. 
In addition, an exploratory 
analysis using fractional 
polynomials was added to 
examine the relationship 
between loss of control and 
screening eosinophils
(continuous), IgE and FeNO.
Bayesian analysis will now 
include the same covariates as 
the frequentist analysis.
By modelling eosinophils as a 
continuous endpoint, it will 
provide more information on the 
impact of varying screening 
eosinophil levels on the 
treatment effect. It will also 
provide additional information 
on the role of IgE and FeNO on 
loss of asthma control.


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Protocol
Reporting & Analysis Plan
Statistical Analysis Plan
Statistical Analysis Plan
Rationale for Changes
Mixed model repeated measures will 
be used to analyse the following
endpoints. The baseline value of 
each endpoint will be included along 
with baseline*visit and treatment*visit 
interactions. Treatment differences, 
95% confidence intervals and p-
values will be presented.

Change from baseline in ACQ-5 
absolute score

Change from baseline in SGRQ 
total score

Change from baseline in Pre-
bronchodilator FEV1

Change from baseline in FeNO
FEV1 and FeNO will only be 
analysed up until Week 4 (down 
titration of ICS), all data post 
Week 4 will be summarised 
descriptively only. 
In addition, an exploratory 
analysis using fractional 
polynomials was added to 
examine the relationship 
between FEV1 at Week 4 with
screening eosinophils 
(continuous), IgE and FeNO.
Continuous ACQ-5 and SGRQ 
will only be summarised and will 
not be analysed.
FEV1 and FeNO are impacted 
by ICS, so including change 
from baseline post-down 
titration of ICS would be 
confounding change due to 
study treatment with change 
due to ICS. To better explore 
the data prior to down titration, 
the fractional polynomial 
analysis has been added to 
examine the relationship 
between FEV1 at Week 4 with
screening eosinophils 
(continuous), IgE and FeNO.
FEV1, FeNO, ACQ-5 and 
SGRQ analysed using an 
MMRM would be assuming that 
data is missing at random. In 
fact, participants could have 
withdrawn due to loss of asthma 
control which is related to study 
treatment, so the analysis 
assumptions would not have 
been valid.
Secondary endpoints listed as:

Serum concentrations of 
GSK3772847 at weeks 2, 4, 8, 
12, 16, 20, 24 and 28.

Free and total soluble ST2 levels 
at weeks 2, 4, 8, 12, 16, 20, 24 
and 28.
Secondary endpoints listed as:

Serum concentrations of 
GSK3772847 by nominal 
time.

Free and total soluble ST2 
levels in serum by nominal 
time.
Endpoint updated to use 
nominal time so that all data 
collected is summarised. 
Proportion of participants with loss of 
asthma control assessed over 
Weeks 0-16 only.
Proportion of participants with 
loss of asthma control assessed
over Weeks 0-16 and over 
Weeks 0-6.
An additional endpoint 
assessing loss of control 
between Weeks 0 and 6 was 
added to help support the time 
to loss of asthma control 
analysis.
The posterior probabilities that the 
ratio of the proportion of subjects 
with loss of asthma control on 
GSK3772847 compared with placebo 
is less than 1.0, 0.75, 0.5 and 0.2 
(i.e. more than a 0%, 25%, 50% and 
80% reduction) will be produced.
The posterior probabilities that 
the ratio of the proportion of 
subjects with loss of asthma 
control on GSK3772847 
compared with placebo is less 
than 1.0, 0.75, 0.7, 0.5 and 0.2 
(i.e. more than a 0%, 25%, 30%, 
50% and 80% reduction), and 
greater than 0.6 (i.e. less than a 
40% reduction) will be 
produced.
The additional posterior 
probabilities of the ratio of the 
proportion of subjects with loss 
of asthma control on 
GSK3772847 compared with 
placebo being <0.70 (more than 
a 30% reduction) and >0.60 
(less that a 40% reduction) were 
added to assist internal decision 
making.


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Protocol
Reporting & Analysis Plan
Statistical Analysis Plan
Statistical Analysis Plan
Rationale for Changes
Endpoints included:

Proportion of participants with a 
≥0.5 point ACQ-5 score 
increase from baseline.

Proportion of participants who 
have pre-bronchodilator FEV1 
decrease from baseline 
(measured at the end of Run-in) 
>7.5 %.

Proportion of participants where 
inhaled corticosteroids (ICS) 
cannot be titrated in accordance 
with the pre-defined schedule.

Proportion of participants who 
have a significant asthma 
exacerbation (requiring OCS 
and/or hospitalisation).

Proportion of participants with a 
clinically significant asthma 
exacerbation or inability to titrate 
ICS according to the pre-defined 
schedule

Proportion of participants with 
≥0.5 point ACQ-5 score 
decrease from baseline 
(responder) at each week from 
Week 1 to Week 16.

Proportion of St. George’s 
Respiratory Questionnaire 
(SGRQ) responders (at least a 4 
unit improvement from baseline) 
at Weeks 4, 8, 12 and 16.
Endpoints to be summarised 
and not analysed.
Due to participants being 
withdrawn after they reach one 
component of loss of control, 
there is no information available 
for the other components/ ACQ-
5 /SGRQ after this date. As a 
result the numbers of the 
subjects who have useable data 
are very small, and any 
estimates will be biased, so 
informative decisions can’t be 
made. The data must still be 
summarised to comply with 
disclosure rules for pre-specified 
secondary endpoints.
The minimum detectable effect for
the sample size calculations is 
reported as 31% corresponding to a 
proportion
with loss of control on GSK3772847 
of 28%.
The minimum detectable effect 
for the sample size calculations 
is reported as 36% 
corresponding to a proportion
with loss of control on 
GSK3772847 of 28%.
A typographical error in the 
protocol which meant that 
minimum detectable effect was 
incorrectly reported as 31%, this 
has been corrected in the RAP.


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2.2.
RAP Amendments 
Revision chronology: 
RAP Section
Amendment Details
Reporting and Analysis Plan_207597_Final_V01 [20-DEC-2018]
Reporting and Analysis Plan_207597_Amendment_Final_V01
Analysis of components of 
loss of asthma control and 
responder analysis

Analysis of components of loss of asthma control and responder analysis 
were removed as explained in Section 2.1.
Bayesian Analysis 

Additional information provided on the Bayesian logistic regression 
including starting values, set seeds and thinning options.

The posterior probabilities of the ratio of the proportion of subjects with 
loss of asthma control on GSK3772847 compared with placebo being 
<0.70 (more than a 30% reduction) and >0.40 (less that a 40% reduction) 
were added to assist internal decision making.
Repeated Measures 
Analysis

Information on the variance-covariance matrix and use of the OM option 
added. 
Treatment Discontinuation 
Date

Derivation added for treatment discontinuation date
Sample Size 

A typographical error in the protocol which meant that minimum 
detectable effect was incorrectly reported as 31%, this has been 
corrected in the RAP amendment.
Tables, Listings and 
Figures

Minor clarification/typographical errors in output titles and associated
RAP text were added.


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2.3.
Study Objective(s) and Endpoint(s)
Objectives
Endpoints
Primary

To evaluate the efficacy of GSK3772847, 
compared with placebo, administered 
intravenously every 4 weeks for 12 
weeks (Week 0 – Week 12, 4 doses in 
total) in participants with moderately 
severe asthma.
Primary – Proportion of participants with loss of 
asthma control over Weeks 0-16 where ‘loss of 
asthma control’ is defined as at least one of the 
following:

Asthma Control Questionnaire (ACQ-5) score 
increase from baseline (measured at the end 
of Run-in) ≥ 0.5 point or

Pre-bronchodilator Forced expiratory volume 
in 1 second (FEV1) decrease from baseline 
(measured at the end of Run-in) >7.5 % or

Inability to titrate inhaled corticosteroid 
according to the pre-defined schedule or 

A clinically significant asthma exacerbation 
(requiring oral corticosteroid [OCS] and/or 
hospitalisation).
Secondary

To evaluate other aspects of efficacy of 
GSK3772847 compared with placebo in 
participants with moderately severe asthma.
Other efficacy endpoints (at or by Week 16):

Proportion of participants with a ≥0.5 point 
ACQ-5 score increase from baseline.

Proportion of participants who have pre-
bronchodilator FEV1 decrease from baseline 
(measured at the end of Run-in) >7.5 %.

Proportion of participants where inhaled 
corticosteroids (ICS) cannot be titrated in 
accordance with the pre-defined schedule.

Proportion of participants who have a 
significant asthma exacerbation (requiring 
OCS and/or hospitalisation).

Proportion of participants with loss of asthma 
control over Weeks 0-6 

Time to loss of asthma control.

Proportion of participants with a clinically 
significant asthma exacerbation or inability to 
titrate ICS according to the pre-defined 
schedule

The incidence, mean rate, and total number 
per participant of hospitalisations or 
Emergency Room (ER) visits during the study 
treatment period.

Change from baseline in ACQ-5 absolute 
score at each week from Week 1 to Week 16.

Proportion of participants with ≥0.5 point 
ACQ-5 score decrease from baseline 
(responder) at each week from Week 1 to 


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Objectives
Endpoints
Week 16.

Change from baseline in SGRQ total score at 
Weeks 4, 8, 12 and 16.

Proportion of St. George’s Respiratory 
Questionnaire (SGRQ) responders (at least a 
4 unit improvement from baseline) at Weeks 
4, 8, 12 and 16.

Change from baseline in pre-bronchodilator 
FEV1 at Weeks 2, 4, 6, 8, 10, 12, 14, 16.

Change from baseline in mean morning peak 
expiratory flow (PEF) and mean evening PEF 
over each four weeks of the 16 week 
treatment period.

Change from baseline in mean daytime 
asthma symptom score over each four weeks 
of the 16 week treatment period.

Change from baseline in rescue medication 
use (albuterol/salbutamol): mean number of 
inhalations per day over each four weeks of 
the 16 week treatment period.

Changes from baseline in night-time 
awakenings due to asthma symptoms 
requiring rescue medication use over each 
four weeks of the16 week treatment period.

Change from baseline in fractional exhaled 
nitric oxide (FeNO) at each week measured.

To evaluate the safety and tolerability of 
GSK3772847, compared with placebo 
administered intravenously every 4 weeks 
for 12 weeks (Week 0-12, 4 doses in total) in 
participants with moderately severe asthma. 

Incidence and frequency of adverse events 
(AEs) and serious adverse events (SAEs).

Change from baseline in vital signs at weeks 
1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24 and 28.

Change between post-dose and pre-dose in 
vital signs at weeks 0, 4, 8 and 12.

Change from baseline in 12-lead 
electrocardiogram (ECG) measurements at 
weeks 4, 8, 12 and 16.

Change between post-dose and pre-dose in 
12-lead ECG measurements at weeks 0, 4, 
8 and 12.

Change from baseline in 24 hours Holter 
measurements at weeks 4 and 12. 

Change from baseline in clinical chemistry 
at weeks 2, 4, 8, 12, 16 and 28.

Change from baseline in haematology and 
cardiac markers at weeks 1, 2, 4, 6, 8, 10, 
12, 14, 16 and 28.

Incidence of and titres of anti- GSK3772847 
antibodies at weeks 2, 4, 8, 12, 16, 20, 24 
and 28.


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Objectives
Endpoints

To evaluate the pharmacokinetics (PK) of 
GSK3772847 in participants with moderately 
severe asthma.

Serum concentrations of GSK3772847 by 
nominal time.

To evaluate the pharmacodynamics (PD) of 
GSK3772847 in participants with moderately 
severe asthma.

Free and total soluble ST2 levels in serum 
by nominal time.
Exploratory 

To compare the effect of GSK3772847 with 
placebo on biomarkers in serum and 
sputum.

Changes from baseline in induced 
sputum biomarkers (subset) at weeks 8 
and 16.

Changes from baseline in exploratory 
serum markers at weeks 8 and 16.


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2.4.
Study Design
Overview of Study Design and Key Features
Design 
Features

The study is a Phase IIa, multicenter, randomised, placebo-controlled, double-
blind, stratified, parallel group study.
Dosing

Participants will have a two-week Run-in period in which they take a 
background therapy of fluticasone propionate (FP)/salmeterol 500/50 mcg 
BID.

Following run-in they will be randomised to receive four doses of either 
GSK3772847 or Placebo intravenously (Week 0, 4, 8 and 12) whilst initially 
still receiving background FP/Salmeterol 500/50 mcg BID.

At Week 2 background therapy will be changed to FP 500 mcg BID only. This 
will then be reduced by approximately 50 % every two weeks until complete 
FP discontinuation at Week 10.
Treatment 
Assignment

Participants will be randomised in a 1:1 ratio to receive four doses of either 
GSK3772847 or Placebo administered intravenously every 4 weeks.

Randomisation will be stratified based on participants’ baseline peripheral 
blood eosinophil count which is measured at screening (<150 cells/µL, >=150 
cells/µL), Randomisation will also be stratified according to whether 
participants consent to the sputum sub study.


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Overview of Study Design and Key Features
Interim 
Analysis

The End of Treatment Phase Analysis will take place after all subjects have 
completed the week 16 visit, and will be considered an interim analysis for 
both efficacy and safety. There will be no modifications to dosing regimens, 
sample size or any other aspects of the trial based on this data, as all study 
assessments, apart from follow-up, will have already been completed.
2.5.
Statistical Hypotheses
The primary null hypothesis (
) for this study is that the ratio of the proportions of 
subjects with loss of asthma control from randomisation to Week 16 between 
GSK3772847 and placebo is unity.
The alternative hypothesis (
) for this study is that the ratio of the proportions of 
subjects with loss of asthma control from randomisation to Week 16 between 
GSK3772847 and placebo is not unity. 
2.6.
Sample Size Calculations
With 70 evaluable participants per arm and assuming the true proportion with loss of
control on placebo is 44%, the smallest observed difference that would lead to rejection
of the null hypothesis (minimum detectable effect) is 36% corresponding to a proportion
with loss of control on GSK3772847 of 28%.
As detailed in Section 2.1, there was a typographical error in the protocol which meant 
that minimum detectable effect was incorrectly reported as 31%, this has been corrected 
above. 


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3.
PLANNED ANALYSES
3.1.
End of Treatment Phase Analyses
The End of Treatment Phase Analysis will be performed after the completion of the 
following sequential steps:
1.
All subjects have completed the Week 16 visit or the Early Withdrawal visit
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.
Due to an inability to lock log forms used for collection of exacerbation data, the end of 
treatment phase analysis will be considered an interim analysis for both efficacy and 
safety. Any safety data collected for participants who have completed clinic visits after 
Week 16 will also be cleaned and included in the analysis. 
All participants will have completed the active treatment phase of the study by the time 
of the interim, so no modifications will be made to the study as a result of the End of 
Treatment Phase Analysis. The Final Analysis is intended to be an analysis of safety data 
collected in the Post-treatment Follow-Up phase.
The sponsor will be unblinded to the results of the analysis. 
3.2.
Final Analyses
The final planned primary analyses will be performed after the completion of the 
following sequential steps:

All subjects have completed the study. 

All required database cleaning activities for data after Week 16/ Early Withdrawal
as well as data collected on log pages have been completed.

Final database release and database freeze has been declared by Data 
Management.
No unblinding will take place as part of the final analysis as all participants will have 
already been unblinded during the End of Treatment Phase Analysis. 


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4.
ANALYSIS POPULATIONS
Some participants are being excluded from the efficacy analyses due to a failure at their 
site to follow GCP. As these participants received GSK3772847 or placebo during their 
period of participation, all safety data will be reported.
Population
Definition / Criteria
Analyses Evaluated
Enrolled

The All Subjects Enrolled (ASE) population 
will consist of all participants who sign the 
ICF.
Study population
Reason for withdrawal 
prior to randomisation
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 excluding 
GCP non-
compliant 
subjects (Loss of 
Control)

The Modified Intent-to-Treat excluding GCP 
non-compliant subjects (Loss of Control)
(mITT_LoC) will consist of all randomised 
participants who take at least 1 dose of study 
treatment, excluding participants where an 
investigation by GSK has shown that good 
clinical practice has not been followed. Any 
participants excluded from this population will 
be identified as protocol deviations and listed 
in a separate output. 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. For loss of asthma control,
participants will be analysed according to the 
treatment they were receiving at the time of 
loss of control. 
Efficacy (loss of 
control)
Modified Intent-to-
Treat excluding 
GCP non-
compliant 
subjects 

The Modified Intent-to-Treat excluding GCP 
non-compliant subjects (mITT) population will 
consist of all randomised participants who 
take at least 1 dose of study treatment, 
excluding participants where an investigation 
by GSK has shown that good clinical practice 
has not been followed. Any participants 
excluded from this population will be identified 
as protocol deviations and listed in a separate 
output. Participants will be analysed 
according to the treatment they receive 
Efficacy (all except loss 
of control)


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Population
Definition / Criteria
Analyses Evaluated
>=50% of the time. If the participant receives 
50% of each treatment they will be analysed 
according to the randomised treatment.
Safety including 
GCP non-
compliant 
subjects

The Safety (SAFF_ALL) population will 
consist of all randomised participants who 
take at least 1 dose of study treatment. 
Participant 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
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
NOTES : 
1.
Please refer to Appendix 10: List of Data Displays which details the population to be used for each display being
generated.
2.
If a participant is inadvertently given both study treatments they will be analysed according to the treatment that 
they received the more frequently. 
4.1.
Protocol Deviations
All 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 [21-Aug-2017 (Version 1) 
or later].
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. 
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.


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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:

Order represents treatments being presented in TFL, as appropriate.
Treatment comparisons will be displayed as follows using the descriptors as specified:

GSK3772847 vs Placebo
There were four strata used for the randomisation depending on the participants baseline 
blood eosinophil count and whether they consented to the sputum sub-study:

Sputum sub-study and screening blood eosinophils < 150 cells/µL

Sputum sub-study and screening blood eosinophils >=150 cells/µL

Not sputum sub-study and screening blood eosinophils < 150 cells/µL

Not sputum sub-study and screening blood eosinophils >=150 cells/µL
Displays will be presented by combining data across all four strata to give the overall 
estimate of GSK3772847 versus placebo. 
Sputum sub-study will not be accounted for within the statistical analysis as the sputum 
sub-study strata was for monitoring recruitment only.
An additional exploratory analysis using fractional polynomials has been added to further 
investigate the relationship between loss of control and screening eosinophils and 
summary statistics on eosinophils will also be provided. 


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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. 
Parameter
Study Assessments 
Considered As Baseline
Baseline Used in 
Data Display
Pre-
Screening
Screen 
Run-in
Day 1 
(Pre-Dose)
Loss of Asthma Control
Pre-bronchodilator Forced 
expiratory volume in 1 second 
(FEV1)
X
X
Day 1
Asthma Control Questionnaire 
(ACQ-5) score
X
X
Day 1
Other Patient Reported Outcomes
St. George’s Respiratory 
Questionnaire (SGRQ)
X
Day 1
Peak Expiratory Flow (PEF)
Mean morning peak expiratory 
flow (PEF)
X
X
Run-in [1]
Mean evening peak expiratory 
flow (PEF)
X
X
Run-in [1]
Fractional Exhaled Nitric Oxide (FeNO)
Fractional Exhaled Nitric Oxide 
(FeNO)
X
Day 1
Symptom Scores
Mean daytime asthma symptom 
score
X
X
Run-in [1]
Night-time awakenings due to 
asthma symptoms requiring 
rescue medication
X
X
Run-in [1]


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Parameter
Study Assessments 
Considered As Baseline
Baseline Used in 
Data Display
Pre-
Screening
Screen 
Run-in
Day 1 
(Pre-Dose)
Rescue Medication
Rescue medication use
X
X
Run-in [1]
Mean number of inhalations per 
day over each four weeks
X
X
Run-in [1]
Safety
Vital Signs
X
X
Day 1
12-lead Electrocardiogram (ECG) 
measurements
X
X
Day 1
24 hours Holter measurements
X
Screen/Run in
Clinical laboratory tests 
(haematology and chemistry)
X
X
Day 1
Biomarkers
Induced sputum biomarkers
X
Day 1
Serum biomarkers
X
Day 1
Exploratory serum markers
X
Day 1
NOTES :

Unless otherwise stated, the mean of replicate assessments at any given time point will be used as the value for
that time point.

[1] Mean over the last 7 days of the run-in period prior to V2.  Participants must have at least 4 full days of data 
(morning and evening) in the last 7 days of run-in to be eligible.
5.3.
Multicentre Studies
In this multicentre global study, enrolment will be presented by investigative site, 
country, and regions.
Region
Countries
North America
United States, Canada
Latin America
Mexico 
Eastern Europe
Ukraine, Russian Federation
Oceania
Australia


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5.4.
Examination of Covariates, Other Strata and Subgroups
5.4.1.
Covariates and Other Strata
The list of covariates and other strata may be used in descriptive summaries and 
statistical analyses, some of which may also be used for subgroup analyses. Additional 
covariates and other strata of clinical interest may also be considered.
5.5.
Multiple Comparisons and Multiplicity
As there is a single primary treatment comparison, no adjustment is required for primary 
comparisons. No adjustments will be made for multiplicity for other endpoints.
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
Category
Covariates 
Screening eosinophils
At randomisation participants are stratified according to their 
screening peripheral blood eosinophil count. Screening 
eosinophils will be included in both primary and secondary 
analysis as a categorical variable (<150 cells/µL, >=150 
cells/µL). 
If the analysis models are unable to converge due to low 
number of participants with screening blood eosinophils <150 
cells/µL, then screening eosinophil will be re-categorised 
according to a cut point of 300 cells/µL instead i.e. <300 
cells/µL and >=300 cells/µL


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6.
STUDY POPULATION ANALYSES
6.1.
Overview of Planned Study Population Analyses
The study population analyses will be based on the Safety Population including GCP 
non-compliant subjects population (SAFF_ALL), unless specified to be on the All
Subjects Enrolled (ASE) population.
Study population analyses including analyses of subject’s disposition, protocol 
deviations, demographic and baseline characteristics, prior and concomitant medications, 
and 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 population 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 modified Intent-to-treat (Loss of 
Control), modified Intent-to-treat, Safety including GCP non-compliant subjects, and PK
populations.
For the Safety including GCP non-compliant subjects, reasons for withdrawal summary 
will show the number and percentage of subjects who completed the study, who 
withdrew prematurely from the study 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 Disorders,’ 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.
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 separately. 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
7.1.
Primary Efficacy Analyses
7.1.1.
Endpoint 

Proportion of participants with loss of asthma control over Weeks 0-16

Proportion of participants with loss of asthma control over Weeks 0-6 (Secondary)
7.1.2.
Summary Measure
Bayesian Method (Primary): The posterior median and 95% credible interval. In addition, 
the posterior probabilities that the ratio of the proportion of subjects with loss of asthma 
control on GSK3772847 compared with placebo is less than 1.0, 0.75, 0.7, 0.5 and 0.2 
(i.e. more than a 0%, 25%, 30%, 50% and 80% reduction), and greater than 0.6 (i.e. less 
than a 40% reduction).
Frequentist Method (Supportive): Odds Ratio. The odds of having experienced loss of 
asthma control on GSK3772847 compared to the odds of having experienced loss of 
asthma control on placebo.
7.1.3.
Population of Interest 
The primary efficacy analyses will be based on the modified Intent to Treat (Loss of 
Control) population, unless otherwise specified.
7.1.4.
Strategy for Intercurrent (Post-Randomisation) Events
Intercurrent Event
Primary Estimand
Secondary Estimand
Study treatment 
discontinuation due to an 
AE/SAE
Excluded from analysis
Set as loss of asthma control (i.e. worst case 
scenario).
Death 
Excluded from analysis
Set as loss of asthma control (i.e. worst case 
scenario).
Prohibited/ Concomitant 
medications that could 
impact patients’ asthma 
control 
Use data as is.
Set as loss of asthma control (i.e. worst case 
scenario).
Non-compliance with 
FP/SAL, FP or study titration
Use data as is.
Set as loss of asthma control (i.e. worst case 
scenario).
Missing data *
Excluded from analysis
Set as loss of asthma control (i.e. worst case 
scenario).
Notes:

* Missing data is not an intercurrent event, however missing values will be imputed according to 
the estimand under investigation.


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
If the intercurrent event occurs after loss of asthma control then all information on loss of asthma 
control will be used. 

Prohibited/ concomitant medications will be identified as protocol deviations within the prohibited/ 
concomitant medications category and will have text that start with “LoAC”

Non-compliance FP/SAL, FP or study titration will be identified as compliance <80%, compliance 
≥ 120% or protocol deviations within the other deviations related to wrong study 
treatment/administration/dose sub-category and will have text that starts with “TIT”
If any of the following intercurrent events occurs, then all data will be accepted:

Pregnancy
Accidental unblinding 
Whilst it’s possible that site staff were unable to administer study drug as they were
unable to find a suitable vein, the team felt this would not be caused by the randomised 
study treatment and the visit would be rescheduled. Therefore, if this occurs all data will 
be accepted and treated as any other out of window assessment. 
7.1.5.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 10: List of Data Displays and 
will be based on GSK data standards and statistical principles.
Unless otherwise specified, endpoints / variables defined in Section 7.1.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and
listed.
7.1.5.1.
Statistical Methodology Specification
Endpoint / Variables

Proportion of participants with loss of asthma control over Weeks 0-16

Proportion of participants with loss of asthma control over Weeks 0-6 (Secondary)
Model Specification

The primary endpoint proportion of subjects with loss of asthma control will be analysed for the 
Modified Intent-to-Treat excluding GCP non-compliant subjects (Loss of Control) population 
using both Bayesian (primary) and Frequentist (supportive) methods.
Bayesian Method (Primary):

A logistic regression model within proc MCMC will be used to generate the posterior 
distribution of the ratio of GSK/Placebo. 

The analysis model will include categorical variables for treatment and screening eosinophil 
strata, with each coefficient (including the intercept) having a non-informative
normal(mean=0,var=1x106) prior.

Odds ratios generated from the model will be back-transform to produce the probability of 
experiencing loss of asthma control on both GSK3772847 and Placebo. From these estimates 
the ratio of loss of asthma control on GSK/Placebo will be calculated within the proc MCMC 
call. 


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
Three Markov chain Monte Carlo (MCMC) chains will be run, with all parameters in the model 
being assessed for convergence. This is done to ensure that the results are not sensitive to the 
initial values selected. The chain with the lowest deviance information criteria (DIC) will be 
used for the analysis output. Each chain will have 100,000 simulations, with a thinning of 10 
and a burn-in of 500, in order to generate 10,000 samples per chain. This may be adjusted if 
the chains fail to converge. The starting seeds and initial values for all three chains are given 
below:
Set Seed
Starting Value
Chain 1
2075971
-2
Chain 2
2075972
0
Chain 3
2075973
2

The posterior probabilities that the ratio of the proportion of subjects with loss of asthma control 
on GSK3772847 compared with placebo is less than 1.0, 0.75, 0.7, 0.5 and 0.2 (i.e. more than 
a 0%, 25%, 30%, 50% and 80% reduction), and greater than 0.6 (i.e. less than a 40% 
reduction) will be calculated, along with the estimated median ratio and associated 95% 
credible interval. The 95% credible interval will use the highest posterior density where 
possible, and if this isn’t possible then the 2.5% and 97.5% credible intervals will be reported.

In addition to summary tables a plot of the cumulative probabilities from the posterior 
distribution for the ratio of the proportion of subjects with loss of asthma control on 
GSK3772847 compared with placebo will be generated.

This analysis will be repeated for loss of asthma control between Weeks 0 and 6.
Frequentist Method (Supportive):

The proportion of participants with loss of asthma control will be analysed using logistic
regression allowing for screening eosinophils strata. It will include fixed effects terms for 
treatment and screening eosinophil strata. 
Fractional Polynomials (Exploratory Analysis for Loss of Control Over Weeks 0-16):

Screening blood eosinophil count will be transformed using a first order fractional polynomial 
term, and then a second order fractional polynomial term which will be included in the model as 
a continuous covariate. A treatment group by transformed eosinophil covariate interaction will 
also be included in the model to allow the magnitude of the treatment difference to differ by 
screening eosinophil count.

The impact of extreme observations are a well-known problem with fraction polynomial 
modelling. To address this a two-step transformation to “pull-in” extremes and shift the origin
away from zero will be used (Royston and Sauerbrei, 2007). The formula to achieve this is 
given below:


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where 
with: 
As recommended we shall use 
and 
.

All models (first and second order) will be evaluated and the best fitting model will be selected 
based on the Akaike information criterion (AIC). 

The selected best fitting model will be used to predict the probability of loss of control by 
treatment arm along with the corresponding predicted odds ratio by screening eosinophil 
count. This model will include the observed margins (OM) option which will use the analysis 
dataset. 

The fit of the model to the raw data will be assessed visually by overlaying a plot of the 
treatment estimates and differences estimated in groups defined by quartiles of screening 
eosinophil counts. Estimates will be plotted against the mean eosinophil count within each
subgroup.

The role of baseline immunoglobulin E (IgE) and baseline FeNO (separately) on the 
effectiveness of GSK3772847 with respect to loss of asthma control will be investigated in a 
similar way.
Model Checking & Diagnostics
Bayesian Method (Primary):

The Markov chain standard error (MCSE) should be compared to the standard deviation of the 
distribution (SD) to make sure that MCSE/SD ≤ 0.01 for all parameters in the mode.

The Geweke diagnostic test will be used to check whether the mean estimates have converged 
by comparing means from the early and later part of the Markov chain using a z-score t-test. 
Large absolute values of the z-score statistic indicate rejection of the null hypothesis of no 
difference between the mean estimates obtained from the early and latter parts of the chain.

Gelman & Rubin diagnostic checks should be used to assess if the Markov chains have mixed. 

Visual checks on diagnostic plots will be performed to assess:


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o
Has the Markov chain settled down? 
o
Are sufficient simulations being run? 
o
Is there sufficient burn-in? 
o
Is the effective sample size large enough? 
Frequentist Method (Supportive):

None.
Model Results Presentation
Bayesian Method (Primary):

The proportions of participants experience loss of asthma control on GSK3772847, Placebo 
and the ratio of GSK3772847/Placebo will be presented along with their 95% credible interval.
Frequentist Method (Supportive):

The proportion of participants experiencing loss of asthma control on GSK3772847, Placebo 
and the odds ratio will be presented along with the 95% confidence intervals and p-value. This
will be presented for all participants combined.
Fractional Polynomials (Exploratory Analysis):

A plot of the relationship between the probability of experiencing loss of control on each 
treatment as well as the odds ratio versus continuous eosinophils will be produced.


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7.2.
Secondary Efficacy Analyses
7.2.1.
Endpoint and Summary Measure
Endpoint
Summary Measure
Individual Components of Loss of Asthma 
Control:

Proportion of participants with a ≥0.5 point. 
ACQ-5 score increase from baseline.

Proportion of participants who have pre-
bronchodilator FEV1 decrease from 
baseline (measured at the end of Run-in) 
>7.5 %.

Proportion of participants where inhaled 
corticosteroids (ICS) cannot be titrated in 
accordance with the pre-defined schedule.

Proportion of participants who have a 
significant asthma exacerbation (requiring 
OCS and/or hospitalisation).

Proportion of participants with a clinically 
significant asthma exacerbation or inability 
to titrate ICS according to the pre-defined 
schedule
Number and percentage of participants
experiencing each component of loss of 
asthma control (summary statistics only).
Time to loss of asthma control.
Mean, median, lower and upper quartiles of
time to loss of asthma control, along with 
probability of experiencing loss of asthma 
control at each dosing visit.
The incidence, mean rate, and total number 
per participant of Asthma Related 
hospitalisations or Emergency Room (ER) 
visits during the study treatment period.
Summary statistics and study treatment 
exposure (no statistical analysis required).
Responders:

Proportion of participants with ≥0.5 point 
ACQ-5 score decrease from baseline 
(responder) at each week from Week 1 to 
Week 16.

Proportion of St. George’s Respiratory 
Questionnaire (SGRQ) responders (at 
least a 4 unit improvement from baseline) 
at Weeks 4, 8, 12 and 16.
Number and percentage of participants
(summary statistics only)
Change from Baseline Analysis:

Change from baseline in pre-
bronchodilator FEV1 

Change from baseline in fractional exhaled 
nitric oxide (FeNO) 
Mean change from baseline (summary 
statistics only)


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Endpoint
Summary Measure
Change from Baseline:

Change from baseline in ACQ-5 absolute 
score at each week from Week 1 to Week 
16.

Change from baseline in SGRQ total score 
at Weeks 4, 8, 12 and 16.
Mean change from baseline (summary 
statistics only)

Change from baseline in mean morning 
peak expiratory flow (PEF) and mean 
evening PEF for each four week period of 
the overall 16 week treatment period.

Change from baseline in mean daytime 
asthma symptom score over each four 
weeks of the 16 week treatment period.

Changes from baseline in night-time 
awakenings due to asthma symptoms 
requiring rescue medication use over each 
four weeks of the 16 week treatment 
period.

Change from baseline in rescue 
medication use (albuterol/salbutamol): 
mean number of inhalations per day over 
each four weeks of the 16 week treatment 
period.
Change from baseline (summary statistics 
only)
7.2.2.
Population of Interest 
The secondary efficacy analyses will be based on the modified Intent to Treat population, 
unless otherwise specified.
7.2.3.
Strategy for Intercurrent (Post-Randomisation) Events
For the analysis of time to loss of asthma control, both primary and secondary estimands 
(Section 7.1.4) will be examined. It is important to assess both estimands as data is 
missing after withdrawal or loss of asthma control. This could produce biased estimates, 
as loss of control and therefore missing data is related to study treatment, and so the 
secondary estimand where missing data is set as non-responders must also be considered.
For all other endpoints, only the primary estimand will be examined. This estimand uses 
all data as collected, except for data collected after the date of loss of asthma control or 
early withdrawal from study treatment. 
Once participants experience loss of asthma control and/or withdraw from study 
treatment they immediately restart their standard of care medication (ICS/LABA). As a 


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result, any data collected past this point will have been impacted by the standard of care 
medications and any estimates produced biased by the additional use of ICS/LABA. For 
this reason, data post withdrawal from study treatment is not included in the on-treatment 
efficacy analysis. 
7.2.4.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 10: List of Data Displays and 
will be based on GSK data standards and statistical principles.
Unless otherwise specified, endpoints / variables defined in Section 7.2.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed.
7.2.4.1.
Statistical Methodology Specification
Endpoint / Variables

Time to loss of asthma control.
Strategy for Intercurrent (Post-Randomisation) Events

Both primary and secondary estimands (Section 7.1.4) will be examined. It is important to 
assess both estimands as data is missing after withdrawal or loss of asthma control. This could 
produce biased estimates, as loss of control and therefore missing data is related to study 
treatment, and so the secondary estimand where missing data is set as non-responders must 
also be considered.
Model Specification

Time to loss of asthma control will be analysed on the Modified Intent-to-Treat excluding GCP 
non-compliant subjects (Loss of Control) population using Kaplan-Meier analysis (Proc lifetest).
Within the Kaplan Meier plot participants will either be counted as an event or they will be 
censored.

A log rank test will be performed to test for difference between the time to loss of asthma 
control on Placebo compared with GSK3772847
Primary Estimand:

Events: Participants who experience loss of asthma control during the study

Censoring: Participants who discontinue investigational product for reasons other than loss of 
asthma control will be censored at the date of early withdrawal from study treatment.
Participants who successfully complete the 16 week treatment period will be censored at 113 
days (16 weeks + 1 day). 
Secondary Estimand:

Events: Participants who experience loss of asthma control during the study or who 
discontinue investigational product for reasons other than loss of asthma control (date of event 
will be set to date of early withdrawal from study treatment). 

Censoring: Participants who successfully complete the 16 week treatment period will be 
censored at 113 days (16 weeks + 1 day). 


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Time to event/censoring = Date of event/censoring– Treatment start date + 1. If participants 
experience multiple reasons for loss of control then the earliest date will be used as described in 
Section 0.
Model Checking & Diagnostics

None
Model Results Presentation

Kaplan-Meier plots of the probability of a participant experiencing loss of asthma control by 
treatment will be produced.

In addition, a summary table will be produced showing the probability of experiencing loss of 
asthma control by 4, 8, 12 and 16 weeks along with the median, upper and lower quartiles of 
time to loss of asthma control on both treatment arms (this will be NA if <50% of participants on 
a treatment lose control).
Endpoint / Variables

Change from baseline in pre-bronchodilator FEV1 at Weeks 2, 4, 6, 8, 10, 12, 14, 16.
Strategy for Intercurrent (Post-Randomisation) Events
Primary estimand only.
Model Specification
Only data until Week 4 (down titration of ICS) will be analysed, all data post Week 4 will be 
summarised descriptively only. 
Data up to and include Week 4 (down titration of ICS):
A repeated measures model with terms for baseline FEV1, treatment, visit and screening eosinophil 
strata. The model will also include baseline FEV1 by visit, visit by treatment and screening 
eosinophil strata by visit interactions.
Model Structure:

The variance-covariance matrix will be assumed unstructured.

Kenward Roger (KR) method will be used for calculating degrees of freedom. If the analysis 
does not run using the KR method then the residual method will be used instead. 

An observed margins (OM) dataset will be used to derive the LS means using coefficients 
which are based on the subjects used in the analysis. This is a dataset with a row for every 
subject-visit combination that contains all of the covariates. The OM will be at the average 
baseline FEV1.
FEV1 at Weeks 4 Only - Fractional Polynomials (Exploratory Analysis):

Screening blood eosinophil count will be transformed using a first order fractional polynomial 
term, and then a second order fractional polynomial term which will be included in the model as 
a continuous covariate. A treatment group by transformed eosinophil covariate interaction will 
also be included in the model to allow the magnitude of the treatment difference to differ by 


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screening eosinophil count.

The impact of extreme observations are a well-known problem with fraction polynomial 
modelling. To address this a two-step transformation to “pull-in” extremes and shift the origin 
away from zero will be used (Royston and Sauerbrei, 2007). The formula to achieve this is 
given below:
where 
with: 
As recommended we shall use 
and 
.

All models (first and second order) will be evaluated and the best fitting model will be selected 
based on the AIC. 

The selected best fitting model will be used to predict FEV1 by treatment arm along with the 
corresponding predicted difference in FEV1 by screening eosinophil count. This model will 
include the OM option which will use the analysis dataset. 

The fit of the model to the raw data will be assessed visually by overlaying a plot of the 
treatment estimates and differences estimated in groups defined by quartiles of screening 
eosinophil counts. Estimates will be plotted against the mean eosinophil count within each 
subgroup.
Model Checking & Diagnostics

Distributional assumptions underlying the model used for analysis will be examined by 


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obtaining a normal probability plot of the residuals and a plot of the residuals versus the fitted 
values (i.e. checking the normality assumption and constant variance assumption of the model 
respectively) to gain confidence that the model assumptions are reasonable.
Model Results Presentation

The estimates of the mean and difference for each treatment group from the model will be 
produced, along with 95% confidence intervals and p-values for treatment comparisons.
Endpoint / Variables

Change from baseline in fractional exhaled nitric oxide (FeNO).

Change from baseline in blood eosinophils
Strategy for Intercurrent (Post-Randomisation) Events
Primary estimand only.
Model Specification
Only data until Week 4 (down titration of ICS) will be analysed, all data post Week 4 will be 
summarised descriptively only. Both FeNO and eosinophils have the ratio of post-baseline values 
to baseline values log transformed prior to analysis. For FeNO where multiple measurements can 
be taken at a visit, the data will be log transformed (using the natural logarithm (ln) hereby referred 
to as log) and the average log transformed value used as the visit value. 
FeNO Analysis Model:
A repeated measures model with terms for log(baseline FeNO), treatment, visit, screening 
eosinophil strata and interaction terms for log(baseline FeNO) by visit, treatment by visit and 
screening eosinophil strata by visit.
Eosinophil Analysis Model:
A repeated measures model with terms log(baseline eosinophils), treatment, visit and interaction 
terms for log(baseline eosinophils) by visit and treatment by visit.
Model Structure:

The variance-covariance matrix will be assumed unstructured.

Kenward Roger (KR) method will be used for calculating degrees of freedom. If the analysis 
does not run using the KR method then the residual method will be used instead. 

An observed margins (OM) dataset will be used to derive the LS means using coefficients 
which are based on the subjects used in the analysis. This is a dataset with a row for every 
subject-visit combination that contains all of the covariates. The OM will be at the average 
logarithm of baseline FeNO or average logarithm of baseline eosinophils dependent on the 
model.
Due to a large amount of FeNO data being outside the normal range, further analysis of FeNO may 
be explored. 
Model Checking & Diagnostics

Distributional assumptions underlying the model used for analysis will be examined by 
obtaining a normal probability plot of the residuals and a plot of the residuals versus the fitted 
values (i.e. checking the normality assumption and constant variance assumption of the model 


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respectively) to gain confidence that the model assumptions are reasonable.
Model Results Presentation

The estimated treatment ratios together with 95% CIs (back-transformed from the differences 
on the log-scale) will be produced for each treatment group along with the treatment 
comparisons and p-values.

In addition the percentage change from baseline will also be presented where this is calculated 
as:
% change from baseline = (ratio-1)*100
The following endpoints will be summarised descriptively only. No analysis will be 
performed and all data will be reported as collected excluding data after which 
participants had reached loss of asthma control/withdrawn early from study treatment and 
restarted their standard of care medication (Primary Estimand only), using the modified 
Intent to Treat population:

Change from baseline in ACQ-5 absolute score at each week from Week 1 to Week 
16.

Participants with ≥0.5 point ACQ-5 score decrease from baseline (responder) at each 
week from Week 1 to Week 16.

Change from baseline in SGRQ total score at Weeks 4, 8, 12 and 16.

St. George’s Respiratory Questionnaire (SGRQ) responders (at least a 4 unit 
improvement from baseline) at Weeks 4, 8, 12 and 16.

Change from baseline in mean morning peak expiratory flow (PEF) and mean 
evening PEF over each four weeks of the 16 week treatment period. Note: Each PEF 
is taken in triplicate with the maximum value being used.

Change from baseline in mean daytime asthma symptom score over each four weeks 
of the 16 week treatment period.

Changes from baseline in night-time awakenings due to asthma symptoms requiring 
rescue medication use over each four weeks of the16 week treatment period. Note: 
This is the change from baseline in the average number of nights a participant woke 
up at least once and had to use their rescue medication.

Change from baseline in rescue medication use (albuterol/salbutamol): mean number 
of inhalations per day over each four weeks of the 16 week treatment period.


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8.
SAFETY ANALYSES
The safety analyses will be based on the Safety including GCP non-compliant subjects 
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), Serious (SAEs)
and Adverse Events of Special Interest (AESIs) will be based on GSK Core Data 
Standards. 
8.2.
Adverse Events of Special Interest Analyses
A comprehensive list of MedDRA terms based on clinical review will be used to identify 
each type of event. Changes to the MedDRA dictionary may occur between the start of 
the study and the time of reporting and/or emerging data from on-going studies may 
highlight additional adverse events of special interest, therefore the list of terms to be 
used for each event of interest and the specific events of interest will be based on the 
safety review team (SRT) agreements in place at the time of reporting.
8.3.
Vital Signs, Electrocardiogram (ECG) and Holter
Summary statistics for vital signs at baseline, weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24 
and 28 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, 8 and 12.
Similar 12-lead electrocardiogram (ECG) measurements at baseline, weeks 4, 8, 12 and 
16 will be produced along with change from baseline summaries for each post baseline 
timepoint, and changes between post-dose and pre-dose in 12-lead ECG measurements at 
weeks 0, 4, 8 and 12.
24 hour Holter measurements collected at baseline, weeks 0, 4 and 12 will be summarised 
along with change from baseline at weeks 0, 4 and 12. Only participants with at least 
16hrs worth of data will be included in any tables however all data will be listed.
8.4.
Clinical Chemistry, Haematology and Cardiac Markers
Summaries of clinical chemistry results at baseline, weeks 2, 4, 8, 12, 16 and 28 along 
with change from baseline for all post-baseline measurements will be produced.
Similarly, haematology and cardiac markers at baseline, weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 
and 28 along with change from baseline for all post-baseline measurements will also be 
produced. 


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8.5.
Antibodies
Summaries of the incidence of and titres of anti- GSK3772847 antibodies at weeks 0*, 2, 
4*, 8*, 12*, 16, 20, 24 and 28.
* = Pre-dose only
8.6.
Clinical Laboratory Analyses
Laboratory evaluations including the analyses of liver function tests will be based on 
GSK Core Data Standards.
9.
PHARMACOKINETIC ANALYSES
Due to the time required to analyse PK samples, no PK outputs will be included in the 
end of treatment phases analysis.
9.1.
Secondary Pharmacokinetic Analyses
9.1.1.
Endpoint / Variables
Serum concentrations of GSK3772847 by nominal time.
9.1.2.
Population of Interest 
The secondary pharmacokinetic analyses will be based on the Pharmacokinetic
population, unless otherwise specified.
9.1.3.
Strategy for Intercurrent (Post-Randomisation) Events
Not applicable.
9.1.4.
Statistical Analyses / Methods

No statistical analysis will be performed. 

Serum concentration will be summarised descriptively with summary figures being 
produced.

Scatter plots of trough serum concentration vs FeNO, trough serum concentration vs 
blood eosinophils, and trough serum concentration vs IgE at Week 4 only will also be 
produced.


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10.
PHARMACODYNAMIC AND BIOMARKER ANALYSES
10.1.
Secondary Pharmacodynamic Analyses
10.1.1.
Endpoint / Variables
Free and total soluble ST2 levels in serum
10.1.2.
Summary Measure
Free soluble ST2: Summary statistics and percentage change from baseline 
Total soluble ST2: Summary statistics and percentage change from baseline 
Only pre-dose trough sST2 will be used for analysis. Post-dose trough sST2 will be 
summarised only.
10.1.3.
Population of Interest 
The secondary pharmacodynamics analyses will be based on the modified Intent to Treat
population, unless otherwise specified.
10.1.4.
Strategy for Intercurrent (Post-Randomisation) Events
Not applicable.
10.1.5.
Statistical Analyses / Methods
Endpoint / Variables

Percentage change from baseline in free sST2 (On-treatment)

Percentage change from baseline in free sST2 (Post-treatment)

Percentage change from baseline in total sST2 (On-treatment)

Percentage change from baseline in total sST2 (Post-treatment)
Strategy for Intercurrent (Post-Randomisation) Events
No intercurrent events are considered for this endpoint. All data will be used as collected. 
Model Specification

The ratio of post-baseline sST2 values to baseline sST2 values will be log transformed prior to 
analysis. Note: Log(post baseline sST2 /baseline sST2) is equivalent to log(post baseline 
sST2) – log(baseline sST2).

A repeated measures model with terms for treatment, visit, visit by treatment, the logarithm of 
baseline sST2, the logarithm of baseline sST2 by visit and screening eosinophil strata will be 
fitted.
Model Structure:

The variance-covariance matrix will be assumed unstructured.

Kenward Roger (KR) method will be used for calculating degrees of freedom. If the analysis 
does not run using the KR method then the residual method will be used instead. 


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
An observed margins (OM) dataset will be used to derive the LS means using coefficients 
which are based on the subjects used in the analysis. This is a dataset with a row for every 
subject-visit combination that contains all of the covariates. The OM will be at the average 
baseline of free sST2 (either On-treatment or Post-treatment according to the model).
Model Checking & Diagnostics

Distributional assumptions underlying the model used for analysis will be examined by 
obtaining a normal probability plot of the residuals and a plot of the residuals versus the fitted 
values (i.e. checking the normality assumption and constant variance assumption of the model 
respectively) to gain confidence that the model assumptions are reasonable.
Model Results Presentation

The estimated treatment ratios together with 95% CIs (back-transformed from the differences 
on the log-scale).
Fractional Polynomials (Exploratory Analysis)
The role of free sST2 on the effectiveness of GSK3772847 with respect to loss of asthma 
control will be investigated, using the modified intent to treat (loss of control) population. 
The number of participants experiencing loss of control will be predicted at each level of 
baseline free sST2 based on a model including a free sST2 main effect term and an 
interaction with treatment term. 
Baseline free sST2 will be transformed using a first order fractional polynomial term, and 
then a second order fractional polynomial term which will be included in the model as a 
continuous covariate. A treatment group by transformed free sST2 covariate interaction 
will also be included in the model to allow the magnitude of the treatment difference to 
differ by baseline free sST2. 
The impact of extreme observations are a well-known problem with fraction polynomial 
modelling. To address this a two-step transformation to “pull-in” extremes and shift the 
origin away from zero will be used (Royston and Sauerbrei, 2007). The formula to 
achieve this is given below:
where 
with: 


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As recommended we shall use 
and 
.
All models (first and second order) will be evaluated and the best fitting model will be 
selected based on the AIC. 
The selected best fitting model will be used to predict the probability of loss of control by 
treatment arm along with the corresponding predicted odds ratio by baseline free sST2. 
This model will include the OM option which will use the analysis dataset. 
The fit of the model to the raw data will be assessed visually by overlaying a plot of the 
treatment estimates and differences estimated in groups defined by quartiles of baseline 
free sST2 counts. Estimates will be plotted against the mean baseline free sST2 count 
within each subgroup.
10.2.
Exploratory Biomarker Analyses
10.2.1.
Endpoint / Variables

Changes from baseline in induced sputum biomarkers (subset) at weeks 8 and 16.

Changes from baseline in exploratory serum markers at weeks 8 and 16.
10.2.2.
Summary Measure
Change from baseline
10.2.3.
Population of Interest 
The exploratory biomarker analyses will be based on the modified Intent to Treat 
population, unless otherwise specified.
10.2.4.
Strategy for Intercurrent (Post-Randomisation) Events
Not applicable.
10.2.5.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 10: List of Data Displays and 
will be based on GSK Data Standards and statistical principles.
Induced sputum biomarkers and exploratory serum markers at weeks 8 and 16 will be 
summarised using descriptive statistics, including the geometric mean and CV as well as 
listed.
No statistical analysis will be performed on this data.


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11.
REFERENCES
Charter for the Internal Safety Review Commitee (iSRC), Protocol 207597 Title:  A 
randomised, double-blind, parallel group, multicenter, stratified study assessing the 
efficacy and safety of repeat doses of GSK3772847 compared with placebo in 
participants with severe asthma, 26 June 2017
GlaxoSmithKline Document Number 2017N311825_02, Protocol: A randomised, 
double-blind, parallel group, multicenter, stratified study evaluating the efficacy and 
safety of repeat doses of GSK3772847 compared with placebo in participants with 
moderately severe asthma, 13 September 2017
Internal Safety Review Commitee (iSRC) Reporting and Analysis Plan for a randomised, 
double-blind, parallel group, multicenter, stratified study evaluating the efficacy and 
safety of repeat doses of GSK3772847 compared with placebo in participants with 
moderately severe asthma, 20 July 2018
Protocol Deviation Management Plan (PDMP), Version 01, 21 August 2017
Royston and Sauerbrei, Improving the robustness of fractional polynomial models by 
preliminary covariate transformation: A pragmatic approach, Computational Statistics & 
Data Analysis , Volume 51, Issue 9, 15 May 2007, Pages 4240-4253
doi.org/10.1016/j.csda.2006.05.006
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
The full list of protocol deviations collected on the eCRF is in the 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 for all data 
except efficacy
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
Study Phase for efficacy
Definition
Pre-treatment 
Date ≤ Study Treatment Start Date
On-treatment
Study Treatment Start Date < Date ≤ Date of discontinuation from study 
treatment
Or if the participant did not discontinue early from study treatment
Study Treatment Start Date < Date ≤ Study Treatment Stop Date + 28 days
Post-treatment
Date > Study Treatment Stop Date + 28 days
Once participants withdraw from study treatment they immediately restart their standard 
of care medication (ICS/LABA). As a result, any data collected past this point will have 
been impacted by the standard of care medications and any estimates produced biased by 
the additional use of ICS/LABA. For this reason, data post withdrawal from study 
treatment is not included in the on-treatment efficacy analysis. 
The post treatment definition is the same for efficacy and safety analysis.
Completion of study epoch’s 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 16 visit or withdrew from treatment phase due to loss of asthma 
control
Follow up
Completed 12 week follow-up period


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12.4.1.1.
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

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
1.
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.
12.4.2.
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/mid207597/
Additional information of reporting areas:
data_look_01
This is where the blinded dry run will take place.
final_01: 
This is where the end of treatment phase analysis will take place.
final_02:
This is where the end of study analysis will take place.
Details of the reporting efforts used for the iSRC analysis are detailed in the separate iSRC RAP.
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.


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
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 not be included in summary tables and/or 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.

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. 
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 
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. For pre-screen 
failures, age will be calculated at the pre-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.
Early Withdrawal from Study Treatment Date
The eCRF captures the study treatment start and end, however this is the physical time and date of the 
infusion. The date of early withdrawal from study treatment is not captured and should therefore be 
calculated as follows:

If the participant withdrew from treatment due to loss of asthma control then the date of early 
withdrawal from study treatment is set to the date of loss of asthma control. 

If the participant withdrew due to an AE/SAE/Death then withdrawal date is set to the AE/SAE
onset date (all deaths should be reported as serious adverse events)

If the participant withdrew from study treatment (for a reason other than those above) during the 
first 10 weeks of the study i.e. during the down titration of the background medications, then the 
FP/SAL or FP discontinuation date should be used as the date of withdrawal from study treatment.

For participants who withdraw from study treatment (for a reason other than those above) between 
Week 10 and Week 16, there is no information on when they withdrew as they are no longer taking 
background medications. The date of early withdrawal from study treatment should therefore be set 
to the maximum of date of last dose of FP and date of last dose +1. This is because no more 
information is available other than the fact that they had not lost control prior to completing the 
down titration or prior to receiving their final dose of IP. 
PPD


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Treatment Compliance for Fluticasone Propionate (FP) and Salmeterol (SAL)

Treatment compliance will be calculated based on the formula:  
Treatment Compliance = Number of Actual Doses / (Planned Treatment Duration in Days * 
Frequency)*100

Frequency is 2 for BID and 1 for QD. Treatment compliance could be greater than 100% if there are 
events of overdose. Cumulative compliance (since Day 1) by each background therapy will be 
calculated.

Planned Treatment Duration is defined according to the schedule of activities.

Compliance will be summarized by the following categories:
<80%, 
≥ 80% to < 95%, 
≥95% to <105%,
≥ 105% to <120% and
≥120%
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 


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12.6.3.
Efficacy
Loss of Asthma Control
Multiple Loss of Asthma Control

If a participant reaches loss of control for multiple reasons then all reasons will be reported. For any 
time to loss of asthma control analysis, the time of the earliest component of loss of control will be used. 
Date of Loss of Asthma Control
Date of loss of control will be taken from the loss of control log page.
Diary Data
The vendor data captures the date on which the subject completes the diary (actual date of collection) rather 
than the date to which the questions relate. For example, in the morning diary subjects are asked ‘Did you 
wake up due to asthma symptoms’ and ‘when you woke up due to your asthma symptoms did you use any 
rescue bronchodilator?’ In the evening diaries subjects answer a question on daytime asthma symptoms 
and record the number of puffs of rescue medication used during the day. This means that the morning 
diary date in the raw data refers to the events during the previous night and that the evening diary relates to 
the events during the day time.
In order to ensure that correct observations are assigned to each four-week time period, measurements 
recorded in the morning diary will have 1 day removed in the analysis dataset to ensure that the date 
reflects the time period that the information related to. This adjustment is not required for evening diary as 
these are collected in the evening of the day to which they relate. Questions which this affects are those 
where the timepoint reference is MORNING:

Was evening dose taken?

Did you wake up due to asthma symptoms? 

When you woke up due to your asthma symptoms did you use any rescue bronchodilator?

Number of puffs – night time
PEF assessments will not have the adjustment made as these reflect the PEF as assessed (so the PEF 
recorded in the morning diary is the PEF at that time). 


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12.6.4.
Safety
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, 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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Rate of Events per 1000 Treatment Years
Rate of events per 1000 treatment years will be calculated using:
Rate = number of events * 1000 / total treatment exposure in years
where subjects can contribute more than one event.  
This is equivalent to: 
Rate = number of events * 1000 / (number of subjects in treatment group * mean treatment exposure in 
years).
Maximum/Minimum Definitions for Vital Signs Data
Maximum and Minimum: Maximum and Minimum post-randomisation value over all time-points (including
scheduled and unscheduled assessments) will be presented.
FEV1
Absolute Reversibility
Absolute reversibility (mL) = (post-bronchodilator FEV1 – pre-bronchodilator FEV1)
Percent Reversibility
Definition of Percentage Reversibility as a percentage of predicted FEV1 = ((post-bronchodilator FEV1– pre-
bronchodilator FEV1) / predicted FEV1) x 100%
Definition of Percentage Reversibility as a percentage of pre-bronchodilator FEV1 = ((post-bronchodilator 
FEV1– pre-bronchodilator FEV1) / pre-bronchodilator FEV1) x 100%


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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 either 
completing the 16 week treatment period and three month safety follow up, or 
withdrawing from the treatment period early due to loss of asthma control and 
completing the three month safety follow up period. 

Withdrawn participants were not replaced in the study, unless the participants were 
withdrawn due to sites failing to comply with GCP.

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.

Withdrawal visits will be slotted as per Appendix 3: Assessment Windows or will be 
summarised as withdrawal visits.
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

If one of the five items in the ACQ 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 will be considered missing.  
SGRQ
The SGRQ questionnaire has three components; symptoms, activity and impact.
Symptoms

The Symptoms component will tolerate a maximum of 2 missed items. The weight for 
the missed item is subtracted from the total possible weight for the Symptoms 
component (662.5) and from the Total weight (3989.4)
Activity

The Activity component will tolerate a maximum of 4 missed items. The weight for the 
missed item is subtracted from the total possible weight for the Activity component 
(1209.1) and from the Total weight (3989.4)
Impacts

The Impacts component will tolerate a maximum of 6 missed items. The weight for the 
missed item is subtracted from the total possible weight for the Impacts component 
(2117.8) and from the Total weight (3989.4)
If any component has more missing items then mentioned above then the SGRQ will be 
considered missing.


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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 
Events

The eCRF allows for the possibility of partial dates (i.e., only month and year) to be 
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
ADaM
Analysis Data Model
AE
Adverse Event
A&R
Analysis and Reporting 
CDISC
Clinical Data Interchange Standards Consortium
CI
Confidence Interval
CS
Clinical Statistics
CSR
Clinical Study Report
CVb / CVw
Coefficient of Variation (Between) / Coefficient of Variation (Within)
DBF
Database Freeze
DBR
Database Release
DOB
Date of Birth
DP
Decimal Places
eCRF
Electronic Case Record Form
EMA
European Medicines Agency
FDA
Food and Drug Administration
FDAAA
Food and Drug Administration Clinical Results Disclosure Requirements
GSK
GlaxoSmithKline
IA
Interim Analysis
ICH
International Conference on Harmonization
IDSL
Integrated Data Standards Library
IgE
Immunoglobulin E 
IMMS
International Modules Management System
IP
Investigational Product
mIT
Modified Intent-to-Treat excluding GCP non-compliant subjects
mITT_LoC
Modified Intent-to-Treat excluding GCP non-compliant subjects (Loss of 
Control)
MMRM
Mixed Model Repeated Measures
PCI
Potential Clinical Importance 
PD
Pharmacodynamic
PDMP
Protocol Deviation Management Plan
PK
Pharmacokinetic
QC
Quality Control
QTcF
Frederica’s QT Interval Corrected for Heart Rate
RAP
Reporting & Analysis Plan
RAMOS
Randomisation & Medication Ordering System 
SAC
Statistical Analysis Complete
SAFF_ALL
Safety including site including GCP non-compliant subjects
SDTM
Study Data Tabulation Model
SOP
Standard Operation Procedure
TA
Therapeutic Area
TFL
Tables, Figures & Listings 


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12.9.2.
Trademarks
Trademarks of the GlaxoSmithKline 
Group of Companies
Trademarks not owned by the 
GlaxoSmithKline Group of Companies
None
NONMEM
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
Pharmacodynamic or Biomarker
6.1 to 6.n
6.1 to 6.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 11: 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
Pharmacodynamic or Biomarker
PD_Fn
PD_Tn
PD_Ln
NOTES: 

Non-Standard displays are indicated in the ‘IDSL /  Example Shell’ or ‘Programming Notes’ column as ‘[Non-
Standard] + Reference.’
12.10.3.
Deliverables
Delivery [Priority] [1]
Description
ETP [1]
End of Treatment Phase Statistical Analysis Complete
SAC [1]
Final Statistical Analysis Complete
NOTES: 
1.
Indicates priority (i.e. order) in which displays will be generated for the reporting effort


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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
1.1.
SAFF_ALL
ES8 
Summary of Subject Status and Reason for Study Withdrawal
ICH E3, FDAAA, EudraCT
ETP, SAC
1.2.
SAFF_ALL
SD4
Summary of Treatment Status and Reasons for Discontinuation 
of Study Treatment
ICH E3
ETP, SAC
1.3.
SAFF_ALL
ES4
Summary of Subject Disposition at Each Study Epoch
ICH E3
ETP, SAC
1.4.
ASE
ES6
Summary of Screening/Run-in Status and Reasons for 
Screen/Run-in Failure
Journal Requirements
ETP, SAC
1.5.
Enrolled
NS1
Summary of Number of Subjects by Country and Site ID
EudraCT/Clinical Operations
ETP, SAC
1.6.
SAFF_ALL
NS1
Summary of Number of Subjects by Country and Site ID
EudraCT/Clinical Operations
ETP, SAC
Protocol Deviation
1.7.
SAFF_ALL
DV1
Summary of Important Protocol Deviations
ICH E3
ETP, SAC
1.8.
SAFF_ALL
IE1
Summary of Inclusion/ Exclusion Deviations 
ICH E3
ETP, SAC
Population Analysed
1.9.
Enrolled
SP1
Summary of Study Populations 
IDSL
ETP, SAC
Demographic and Baseline Characteristics
1.10.
SAFF_ALL
DM1 
Summary of Demographic Characteristics
ICH E3, FDAAA, EudraCT
ETP, SAC
1.11.
Enrolled
DM11
Summary of Age Ranges
EudraCT
ETP, SAC
1.12.
SAFF_ALL
DM5
Summary of Race and Racial Combinations
ICH E3, FDA, FDAAA, EudraCT
ETP, SAC
Prior and Concomitant Medications
1.13.
SAFF_ALL
MH4
Summary of Current Medical Conditions
ICH E3 
ETP, SAC


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Study Population Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
1.14.
SAFF_ALL
MH4
Summary of Past Medical Conditions
ICH E3 
ETP, SAC
1.15.
SAFF_ALL
SP07
Summary of Family History of Cardiovascular Disorders at 
Screening
ETP, SAC
1.16.
SAFF_ALL
POP_T01
Summary of Disease Duration and Exacerbation History
ETP, SAC
1.17.
SAFF_ALL
SU1
Summary of Smoking History at Screening
ETP, SAC
1.18.
SAFF_ALL
CM1
Summary of Pre-treatment Non-Asthma Concomitant 
Medications
ICH E3
ETP, SAC
1.19.
SAFF_ALL
CM1
Summary of On-treatment Non-Asthma Concomitant 
Medications
ICH E3
ETP, SAC
1.20.
SAFF_ALL
CM1
Summary of Post-treatment Non-Asthma Concomitant 
Medications
ICH E3
ETP, SAC
1.21.
SAFF_ALL
CM1
Summary of On-treatment Asthma Concomitant Medications
ICH E3
ETP, SAC
1.22.
SAFF_ALL
CM1
Summary of Post-treatment Asthma Concomitant Medications
ICH E3
ETP, SAC
Pre-treatment Lung Function
1.23.
SAFF_ALL
POP_T02
Summary of Screening Lung Function
Include Pre- and Post- albuterol 
(salbutamol) FEV1, FVC, FEV1/FVC and 
% Predicted Normal and post-BD at 
screening %predicted. Include overall 
and by treatment group.
ETP, SAC
1.24.
SAFF_ALL
POP_T03
Summary of Baseline Lung Function
FEV1, FVC, FEV1/FVC and % Predicted 
Normal. Include overall and by 
treatment group.
ETP, SAC
Exposure and Treatment Compliance
1.25.
SAFF_ALL
EX1
Summary of Exposure and Compliance to Background Therapy 
(FP and SAL)
ICH E3
ETP, SAC


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12.10.5.
Efficacy Tables
Efficacy: Tables
No.
Population
IDSL /  
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Exposure
2.1.
SAFF_ALL
EX1 
Summary of Exposure to Study Treatment
ICH E3
ETP, SAC
Primary Endpoint: Loss of Asthma Control Weeks 0-16
2.2.
mITT_LoC
EFF_T01
Summary of Loss of Asthma Control 
Include overall loss of control, each 
component and the combination of 
exacerbation or inability to titrate.
ETP, SAC
2.3.
mITT_LoC
EFF_T02
Summary of On-treatment Intercurrent Events 
ETP, SAC
2.4.
mITT_LoC
EFF_T03
Bayesian Analysis of Loss of Asthma Control Over Weeks 0-16 
(Primary Estimand)
ETP, SAC
2.5.
mITT_LoC
EFF_T04
Frequentist Analysis of Loss of Asthma Control Over Weeks 0-
16 (Primary Estimand)
ETP, SAC
2.6.
mITT_LoC
EFF_T03
Bayesian Analysis of Loss of Asthma Control Over Weeks 0-16 
(Secondary Estimand)
ETP, SAC
2.7.
mITT_LoC
EFF_T04
Frequentist Analysis of Loss of Asthma Control Over Weeks 0-
16 (Secondary Estimand)
ETP, SAC
Secondary Endpoint: Loss of Asthma Control Weeks 0-6
2.8.
mITT_LoC
EFF_T03 
Bayesian Analysis of Loss of Asthma Control Over Weeks 0-6 
(Primary Estimand)
ETP, SAC
2.9.
mITT_LoC
EFF_T04
Frequentist Analysis of Loss of Asthma Control Over Weeks 0-6 
(Primary Estimand)
ETP, SAC
2.10.
mITT_LoC
EFF_T03
Bayesian Analysis of Loss of Asthma Control Over Weeks 0-6 
(Secondary Estimand)
ETP, SAC


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Efficacy: Tables
No.
Population
IDSL /  
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
2.11.
mITT_LoC
EFF_T04
Frequentist Analysis of Loss of Asthma Control Over Weeks 0-6 
(Secondary Estimand)
ETP, SAC
Secondary Endpoints: Time to Loss of Asthma Control
2.12.
mITT_LoC
EFF_T05
Summary and Analysis of Time to Loss of Asthma Control 
(Primary Estimand)
ETP, SAC
2.13.
mITT_LoC
EFF_T05
Summary and Analysis of Time to Loss of Asthma Control 
(Secondary Estimand)
ETP, SAC
Secondary Endpoints: Hospitalisation and Emergency Room Visits
2.14.
mITT
EFF_T06
Summary and Rate of Asthma-Related On-treatment 
Hospitalisations and Emergency Room Visits (Primary 
Estimand)
ETP, SAC
Secondary Endpoint: ACQ-5 and SGRQ
2.15.
mITT
EFF_T07
Summary of Raw and Change from Baseline in ACQ-5 Total 
Score (Primary Estimand)
ETP, SAC
2.16.
mITT
EFF_T07
Summary of ACQ-5 Responders (Primary Estimand)
ETP, SAC
2.17.
mITT
EFF_T07 
Summary of Raw and Change from Baseline in SGRQ Total 
Score (Primary Estimand)
ETP, SAC
2.18.
mITT
EFF_T07
Summary of SGRQ-Responders (Primary Estimand)
ETP, SAC
Secondary Endpoint: FEV1 and PEF
2.19.
mITT
EFF_T07
Summary of Raw and Change from Baseline FEV1 (Primary 
Estimand)
ETP, SAC
2.20.
mITT
EFF_T08
Analysis of Change from Baseline in FEV1 up to Week 4(Primary 
Estimand)
ETP, SAC


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Efficacy: Tables
No.
Population
IDSL /  
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
2.21.
mITT
EFF_T07
Summary of Raw and Change from Baseline Fractional 
Exhaled Nitric Oxide (FeNO) (Primary Estimand)
ETP, SAC
2.22.
mITT
EFF_T08 
Analysis of Change from Baseline in Fractional Exhaled Nitric 
Oxide (FeNO) up to Week 4 (Primary Estimand)
ETP, SAC
Secondary Endpoint: Exacerbations
2.23.
mITT
EFF_T09
Summary of On-treatment Asthma Exacerbations 
ETP, SAC
Secondary Endpoint: Eosinophils
2.24.
mITT
EFF_T07
Summary of Raw and Change from Baseline in Eosinophils 
(Primary Estimand)
ETP, SAC
2.25.
mITT
EFF_T08
Analysis of Eosinophils up to Week 4 (Primary Estimand)
ETP, SAC
Secondary Endpoint: PEF, Daytime Symptom Score, Night-time Symptom Score and Rescue Medication 
2.26.
mITT
EFF_T010
Summary of Raw and Change from Baseline in Mean Morning 
Peak Expiratory Flow (PEF) 
ETP, SAC
2.27.
mITT
EFF_T010
Summary of Raw and Change from Baseline in Mean Evening 
Peak Expiratory Flow (PEF)  
ETP, SAC
2.28.
mITT
EFF_T010
Summary of Raw and Change from Baseline in Mean Daytime 
Asthma Symptom Score
ETP, SAC
2.29.
mITT
EFF_T010
Summary of Raw and Change from Baseline in Night-Time
Awakenings Due to Asthma Symptoms
ETP, SAC
2.30.
mITT
EFF_T010
Summary of Raw and Change from Baseline in Mean Rescue 
Medication use (Albuterol/Salbutamol)
ETP, SAC


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12.10.6.
Efficacy Figures
Efficacy: Figures
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Primary Endpoint: Loss of Asthma Control
2.1.
mITT_LoC
Plot of Loss of Asthma Control Over Weeks 0-16 (Primary 
Estimand)
Include overall and components of loss 
on control
ETP, SAC
2.2.
mITT_LoC
Plot of Loss of Asthma Control Over Weeks 0-16 (Secondary 
Estimand)
Include overall and components of loss 
on control
ETP, SAC
2.3.
mITT_LoC
Cumulative Density Plot of the Posterior Distribution for Loss of 
Asthma Control Over Weeks 0-16 (Primary Estimand)
ETP, SAC
2.4.
mITT_LoC
Cumulative Density Plot of the Posterior Distribution for Loss of 
Asthma Control Over Weeks 0-16 (Secondary Estimand)
ETP, SAC
2.5.
mITT_LoC
Plot of Loss of Asthma Control Over Weeks 0-6 (Primary 
Estimand)
Include overall and components of loss 
on control
ETP, SAC
2.6.
mITT_LoC
Plot of Loss of Asthma Control Over Weeks 0-6 (Secondary 
Estimand)
Include overall and components of loss 
on control
ETP, SAC
2.7.
mITT_LoC
Cumulative Density Plot of the Posterior Distribution for Loss of 
Asthma Control Over Weeks 0-6 (Primary Estimand)
ETP, SAC
2.8.
mITT_LoC
Cumulative Density Plot of the Posterior Distribution for Loss of 
Asthma Control Over Weeks 0-6 (Secondary Estimand)
ETP, SAC
Secondary Endpoint: Time to Loss of Control
2.9.
mITT_LoC
Kaplan-Meir Plot of Time to Loss of Asthma Control (Primary 
Estimand)
ETP, SAC
2.10.
mITT_LoC
Kaplan-Meir Plot of Time to Loss of Asthma Control (Secondary 
Estimand)
ETP, SAC


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Efficacy: Figures
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Secondary Endpoint: Secondary Analysis of Loss of Asthma Control
2.11.
mITT_LoC
Cumulative Density Plot of Eosinophils
ETP, SAC
2.12.
mITT_LoC
Loss of Control Over Weeks 0-16 vs Eosinophils by Treatment –
Fractional Polynomial Model (Primary Estimand)
ETP, SAC
2.13.
mITT_LoC
Loss of Control Over Weeks 0-16 vs Eosinophils – Fractional 
Polynomial Treatment Difference (Primary Estimand)
ETP, SAC
2.14.
mITT_LoC
Loss of Control Over Weeks 0-16 vs Eosinophils by Treatment –
Fractional Polynomial Model (Secondary Estimand)
ETP, SAC
2.15.
mITT_LoC
Loss of Control Over Weeks 0-16 vs Eosinophils – Fractional 
Polynomial Treatment Difference (Secondary Estimand)
ETP, SAC
2.16.
mITT_LoC
Loss of Control Over Weeks 0-6 vs Eosinophils by Treatment –
Fractional Polynomial Model (Primary Estimand)
ETP, SAC
2.17.
mITT_LoC
Loss of Control Over Weeks 0-6 vs Eosinophils – Fractional 
Polynomial Treatment Difference (Primary Estimand)
ETP, SAC
2.18.
mITT_LoC
Loss of Control Over Weeks 0-6 vs Eosinophils by Treatment –
Fractional Polynomial Model (Secondary Estimand)
ETP, SAC
2.19.
mITT_LoC
Loss of Control Over Weeks 0-6 vs Eosinophils – Fractional 
Polynomial Treatment Difference (Secondary Estimand)
ETP, SAC
2.20.
mITT_LoC
Loss of Control Over Weeks 0-16 vs IgE by Treatment -
Fractional Polynomial Model (Primary Estimand)
ETP, SAC
2.21.
mITT_LoC
Loss of Control Over Weeks 0-16 vs IgE – Fractional Polynomial 
Treatment Difference (Primary Estimand)
ETP, SAC
2.22.
mITT_LoC
Loss of Control Over Weeks 0-16 vs IgE by Treatment –
Fractional Polynomial Model (Secondary Estimand)
ETP, SAC


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Efficacy: Figures
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
2.23.
mITT_LoC
Loss of Control Over Weeks 0-16 vs IgE – Fractional Polynomial 
Treatment Difference (Secondary Estimand)
ETP, SAC
2.24.
mITT_LoC
Loss of Control Over Weeks 0-16 vs FeNO by Treatment –
Fractional Polynomial Model (Primary Estimand)
ETP, SAC
2.25.
mITT_LoC
Loss of Control Over Weeks 0-16 vs FeNO – Fractional 
Polynomial Treatment Difference (Primary Estimand)
ETP, SAC
2.26.
mITT_LoC
Loss of Control Over Weeks 0-16 vs FeNO by Treatment –
Fractional Polynomial Model (Secondary Estimand)
ETP, SAC
2.27.
mITT_LoC
Loss of Control Over Weeks 0-16 vs FeNO – Fractional 
Polynomial Treatment Difference (Secondary Estimand)
ETP, SAC
Secondary Endpoint: Exploratory Analysis of FEV1
2.28.
mITT
FEV1 at Week 4 vs Eosinophils by Treatment – Fractional 
Polynomial Model
ETP, SAC
2.29.
mITT
FEV1 at Week 4 vs Eosinophils – Fractional Polynomial 
Treatment Difference
ETP, SAC
2.30.
mITT
FEV1 at Week 4 vs IgE by Treatment – Fractional Polynomial 
Model
ETP, SAC
2.31.
mITT
FEV1 at Week 4 vs IgE – Fractional Polynomial Treatment 
Difference
ETP, SAC
2.32.
mITT
FEV1 at Week 4 vs FeNO by Treatment – Fractional Polynomial 
Model
ETP, SAC
2.33.
mITT
FEV1 at Week 4 vs FeNO – Fractional Polynomial Treatment 
Difference
ETP, SAC


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12.10.7.
Safety Tables
Safety: Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Adverse Events (AEs)
3.1.
SAFF_ALL
SAFE_T01
Overview of On-treatment Adverse Events During the Study
ETP, SAC
3.2.
SAFF_ALL
AE1
Summary of All On-treatment Adverse Events by System Organ 
Class and Preferred Term
ICH E3
ETP, SAC
3.3.
SAFF_ALL
AE1
Summary of All Post-treatment Adverse Events by System 
Organ Class and Preferred Term
ICH E3
ETP, SAC
3.4.
SAFF_ALL
AE1
Summary of All On-treatment Adverse Events Leading to 
Permanent Discontinuation of Study Treatment by System 
Organ Class and Preferred Term
ICH E3
ETP, SAC
3.5.
SAFF_ALL
AE1
Summary of All On-treatment Adverse Events Leading to 
Withdrawal from Study by System Organ Class and Preferred 
Term
ICH E3
ETP, SAC
3.6.
SAFF_ALL
AE1
Summary of All On-treatment Fatal Adverse Events by System 
Organ Class and Preferred Term
ICH E3
ETP, SAC
3.7.
SAFF_ALL
AE3
Summary of All On-treatment Common (>=3%) Adverse Events 
by Overall Frequency
ICH E3
ETP, SAC
3.8.
SAFF_ALL
AE1 
Summary of All On-treatment Drug-Related Adverse Events by 
System Organ Class and Preferred Term
ICH E3
ETP, SAC
3.9.
SAFF_ALL
AE15
Summary of All On-treatment Common (>=3%) Non-serious
Adverse Events by System Organ Class and Preferred Term 
(Number of Participant and Occurrences)
FDAAA, EudraCT
ETP, SAC
3.10.
SAFF_ALL
AE1
Summary of All Pre-treatment Serious Adverse Events by 
System Organ Class and Preferred Term
ETP, SAC


CONFIDENTIAL
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74
Safety: Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
3.11.
SAFF_ALL
AE1
Summary of All On-treatment Serious Adverse Events by 
System Organ Class and Preferred Term
ICH E3
ETP, SAC
3.12.
SAFF_ALL
AE1
Summary of All Post-treatment Serious Adverse Events by 
System Organ Class and Preferred Term
ICH E3
ETP, SAC
3.13.
SAFF_ALL
AE16
Summary of All On-treatment Serious Adverse Events by 
System Organ Class and Preferred Term (Number of 
Participants and Occurrences)
FDAAA, EudraCT
ETP, SAC
3.14.
SAFF_ALL
AE1
Summary of All On-treatment Serious Adverse Events Leading 
to Permanent Discontinuation of Study Treatment by System 
Organ Class and Preferred Term 
IDSL
ETP, SAC
3.15.
SAFF_ALL
AE1
Summary of All On-treatment Serious Adverse Events Leading 
to Withdrawal from Study by System Organ Class and Preferred 
Term 
IDSL
ETP, SAC
Adverse Events of Special Interest (AESIs)
3.16.
SAFF_ALL
AE1
Summary of On-treatment Adverse Events of Special Interest
IDSL
ETP, SAC
3.17.
SAFF_ALL
AE1
Summary of On-treatment Serious Adverse Events of Special 
Interest
IDSL
ETP, SAC
3.18.
SAFF_ALL
AE1
Summary of Post-treatment Adverse Events of Special Interest
IDSL
ETP, SAC
3.19.
SAFF_ALL
AE1
Summary of Post-treatment Serious Adverse Events of Special 
Interest
IDSL
ETP, SAC
Mexico Specific Tables
3.20.
SAFF_ALL
Summary of Suspected Investigational Product Adverse 
Reaction (Mexican Participants Only)
ETP, SAC
3.21.
SAFF_ALL
Summary of Suspected Investigational Product Adverse 
Reaction (Non-Mexican Participants)
ETP, SAC


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Safety: Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Laboratory: Chemistry 
3.22.
SAFF_ALL
LB1
Summary of Clinical Chemistry
ICH E3
ETP, SAC
3.23.
SAFF_ALL
LB1
Summary of Change from Baseline in Clinical Chemistry
ICH E3
ETP, SAC
3.24.
SAFF_ALL
LB16
Summary of Worst Case Chemistry Results Relative to Normal 
Range Post-Baseline Relative to Baseline
ICH E3
ETP, SAC
Laboratory: Hematology and Cardiac Markers
3.25.
SAFF_ALL
LB1
Summary of Hematology and Cardiac Markers 
ICH E3
ETP, SAC
3.26.
SAFF_ALL
LB1
Summary of Changes from Baseline in Hematology and Cardiac 
Markers
ICH E3
ETP, SAC
3.27.
SAFF_ALL
LB16
Summary of Worst Case Hematology and Cardiac Markers 
Results Relative to Normal Range Post-Baseline Relative to 
Baseline
ICH E3
ETP, SAC
Laboratory: Hepatobiliary (Liver)
3.28.
SAFF_ALL
LIVER1
Summary of Liver Monitoring/Stopping Event Reporting
IDSL
ETP, SAC
3.29.
SAFF_ALL
LIVER10
Summary of Hepatobiliary Laboratory Abnormalities
IDSL
ETP, SAC
ECG
3.30.
SAFF_ALL
Summary of Antihistamine, Decongestant and Caffeine Use 
Prior to ECG assessments
ETP, SAC
3.31.
SAFF_ALL
EG1
Summary of ECG Findings 
IDSL
ETP, SAC
3.32.
SAFF_ALL
EG2
Summary of ECG Values by Visit
IDSL
ETP, SAC


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Safety: Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
3.33.
SAFF_ALL
EG2
Summary of Change from Baseline in ECG Values by Visit
IDSL
ETP, SAC
3.34.
SAFF_ALL
EG10
Summary of Maximum QTcF Values Post-Baseline Relative to 
Baseline by Category
IDSL
ETP, SAC
3.35.
SAFF_ALL
EG11
Summary of Maximum Increase in QTcF Values Post-Baseline 
Relative to Baseline by Category
IDSL
ETP, SAC
Holter
3.36.
SAFF_ALL
HM1
Summary of Holter Interpretations
IDSL
ETP, SAC
3.37.
SAFF_ALL
HM2
Summary of Holter Abnormalities
IDSL
ETP, SAC
3.38.
SAFF_ALL
HM3
Summary of Holter Values
IDSL
ETP, SAC
3.39.
SAFF_ALL
HM3
Summary of Change from Baseline in Holter Values
IDSL
ETP, SAC
3.40.
SAFF_ALL
HM4
Summary of Subjects with R-on-T Beats
IDSL
ETP, SAC
Vital Signs
3.41.
SAFF_ALL
VS1
Summary of Vital Signs
ICH E3
ETP, SAC
3.42.
SAFF_ALL
VS1
Summary of Change from Baseline in Vital Signs
ICH E3
ETP, SAC
3.43.
SAFF_ALL
VS1
Summary of Change from Pre-dose to Post-dose in Vital Signs
ICH E3
ETP, SAC


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12.10.8.
Pharmacokinetic Tables
Pharmacokinetic: Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Secondary: Pharmacokinetic
4.1.
PK
Summary of PK Serum Concentrations of GSK3772847
SAC only
4.2.
PK
Summary of Incidence and Titres of Anti-GSK3772847 
Antibodies
SAC only


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12.10.9.
Pharmacodynamic and Biomarker Tables
Pharmacodynamic and Biomarker: Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Secondary: Pharmacodynamic
6.1.
mITT
Summary of Raw and Percentage Change from Baseline in Free 
Soluble ST2 concentration (ug/L) (On-treatment)
Pre and Post dose.
ETP, SAC
6.2.
mITT
Analysis of Percentage Change from Baseline in Free Soluble 
ST2 concentration (ug/mL) (On-treatment)
Pre dose only. 
ETP, SAC
6.3.
mITT
Summary of Raw and Percentage Change from Baseline in Free 
soluble ST2 concentration (ug/L) (Post-treatment)
ETP, SAC
6.4.
mITT
Analysis of Percentage Change from Baseline in Free soluble 
ST2 concentration (ug/mL) (Post-treatment)
ETP, SAC
6.5.
mITT
Summary of Raw and Percentage Change from Baseline in 
Total Soluble ST2 concentration (ug/L) (On-treatment)
Pre and Post dose.
ETP, SAC
6.6.
mITT
Analysis of Percentage Change from Baseline in Total Soluble 
ST2 concentration (ug/L) (On-treatment)
Pre dose only. 
ETP, SAC
6.7.
mITT
Summary of Raw and Percentage Change from Baseline in 
Total Soluble ST2 concentration (ug/L) (Post-treatment)
ETP, SAC
6.8.
mITT
Analysis of Percentage Change from Baseline in Total Soluble 
ST2 concentration (ug/L) (Post-treatment)
ETP, SAC
Exploratory: Biomarkers
6.9.
mITT
Summary and Change from Baseline in Induced Sputum 
Biomarkers (subset) at Weeks 8 and 16
Include geometric mean and %CV
ETP, SAC
6.10.
mITT
Summary and Change from Baseline in Exploratory Serum 
Markers at Weeks 8 and 16
Include geometric mean and %CV
ETP, SAC


CONFIDENTIAL
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79
12.10.10. Pharmacokinetic Figures
Pharmacokinetic: Figures
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Secondary: Pharmacokinetic
6.1.
PK
Plot of Serum Concentrations of GSK3772847 over Time
ETP, SAC
6.2.
PK
Pre-dose Trough Concentration of GSK3772847 vs Eosinophils 
at Week 4
ETP, SAC
6.3.
PK
Pre-dose Trough Concentration of GSK3772847 vs FeNO at 
Week 4
ETP, SAC
6.4.
PK
Pre-dose Trough Concentration of GSK3772847 vs IgE at Week 
4
ETP, SAC


CONFIDENTIAL
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80
12.10.11. Pharmacodynamic and Biomarker Figures
Pharmacodynamic: Figures
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Secondary: Pharmacodynamic
6.5.
mITT
Plot of Percentage Change from Baseline in Free Soluble ST2 
levels (On-treatment)
ETP, SAC
6.6.
mITT
Plot of Percentage Change from Baseline in Free soluble ST2 
levels (Post-treatment)
ETP, SAC
6.7.
mITT
Plot of Percentage Change from Baseline in Total Soluble ST2 
levels (On-treatment)
ETP, SAC
6.8.
mITT
Plot of Percentage 
Change from Baseline in Total Soluble ST2 levels (Post-
treatment)
ETP, SAC
6.9.
mITT_LoC
Loss of Control Over Weeks 0-16 vs Free soluble ST2 by 
Treatment – Fractional Polynomial Model (Primary Estimand)
ETP, SAC
6.10.
mITT_LoC
Loss of Control Over Weeks 0-16 vs Free soluble ST2 
Treatment Difference – Fractional Polynomial (Primary 
Estimand)
ETP, SAC
6.11.
mITT_LoC
Loss of Control Over Weeks 0-16 vs Free soluble ST2 by 
Treatment – Fractional Polynomial Model (Secondary Estimand)
ETP, SAC
6.12.
mITT_LoC
Loss of Control Over Weeks 0-16 vs Free soluble ST2 
Treatment Difference – Fractional Polynomial (Secondary 
Estimand)
ETP, SAC


CONFIDENTIAL
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81
12.10.12. 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
ETP, SAC
2.
SAFF_ALL
ES2 / ES3
Listing of Reasons for Study Withdrawal
ICH E3
ETP, SAC
3.
SAFF_ALL
SD2/SD3
Listing of Reasons for Study Treatment Discontinuation
ICH E3
ETP, SAC
4.
SAFF_ALL
BL1 / BL2
Listing of Participants for Whom the Treatment Blind was Broken
ICH E3
ETP, SAC
5.
SAFF_ALL
TA1 / CP_RD1x
Listing of Planned and Actual Treatments
IDSL
ETP, SAC
Protocol Deviations
6.
SAFF_ALL
DV2
Listing of Important Protocol Deviations 
ICH E3
ETP, SAC
7.
SAFF_ALL
IE3 
Listing of Subjects with Inclusion/Exclusion Criteria Deviations
ICH E3
ETP, SAC
Populations Analysed
8.
SAFF_ALL
Listing of Participants Excluded from Any Population (GCP non 
compliance)
ICH E3.
ETP, SAC
Demographic and Baseline Characteristics
9.
SAFF_ALL
DM2
Listing of Demographic Characteristics
ICH E3
ETP, SAC
10.
SAFF_ALL
DM9 
Listing of Race
ICH E3
ETP, SAC


CONFIDENTIAL
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82
ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Prior and Concomitant Medications
11.
SAFF_ALL
CP_CM3
Listing of Concomitant Medications
IDSL
ETP, SAC
Exposure and Treatment Compliance
12.
SAFF_ALL
EX3
Listing of Exposure Data
ICH E3
ETP, SAC
Adverse Events
13.
SAFF_ALL
AE8 
Listing of All Adverse Events
ICH E3
ETP, SAC
14.
SAFF_ALL
AE7
Listing of Subject Numbers for Individual Adverse Events
ICH E3
ETP, SAC
15.
SAFF_ALL
AE8
Listing of Adverse Events Leading to Withdrawal from Study / 
Permanent Discontinuation of Study Treatment
ICH E3
ETP, SAC
16.
SAFF_ALL
AE2
Listing of Relationship Between Adverse Event System Organ 
Classes, Preferred Terms, and Verbatim Text
IDSL
ETP, SAC
Serious and Other Significant Adverse Events
17.
SAFF_ALL
AE8
Listing of Fatal Serious Adverse Events
ICH E3
ETP, SAC
18.
SAFF_ALL
AE8
Listing of Non-Fatal Serious Adverse Events
ICH E3
ETP, SAC
19.
SAFF_ALL
AE14
Listing of Reasons for Considering as a Serious Adverse Event
ICH E3
ETP, SAC
20.
SAFF_ALL
AE8
Listing of Serious Adverse Events Leading to Withdrawal from 
Study / Permanent Discontinuation of Study Treatment
ICH E3
ETP, SAC
21.
SAFF_ALL
AE8
Listing of Adverse Events of Special Interest
ICH E3
ETP, SAC


CONFIDENTIAL
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83
ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Hepatobiliary (Liver)
22.
SAFF_ALL
MH2
Listing of Medical Conditions for Participants with Liver Stopping 
Events
IDSL
ETP, SAC
23.
SAFF_ALL
SU2
Listing of Substance Use for Participants with Liver Stopping 
Events
IDSL
ETP, SAC
All Laboratory
24.
SAFF_ALL
LB5 / LB6
Listing of All Laboratory Data for Participants with Any Value 
Outside Normal Range
ICH E3
ETP, SAC
25.
SAFF_ALL
LB14
Listing of Laboratory Data with Character Results
ICH E3
ETP, SAC
ECG
26.
SAFF_ALL
EG5
Listing of All ECG Findings for Participants with an Abnormal 
ECG Finding
IDSL
ETP, SAC
27.
SAFF_ALL
EG5 
Listing of Abnormal ECG Findings
IDSL
ETP, SAC
Holter
28.
SAFF_ALL
MH6
Listing of Holter R-on-T Beat Data 
IDSL
ETP, SAC
29.
SAFF_ALL
MH7
Listing of Holter {Supraventricular} {Ventricular} Event Data 
IDSL, Update title as appropriate based 
on data
ETP, SAC
30.
SAFF_ALL
MH8
Listing of Holter {Sustained} {Non-sustained} {Supraventricular} 
{Ventricular} Run
IDSL, Update title as appropriate based 
on data
ETP, SAC
31.
SAFF_ALL
MH9
Listing of Holter Atrial {Fibrillation} {Flutter} Data 
IDSL, Update title as appropriate based 
on data
ETP, SAC
32.
SAFF_ALL
MH10
Listing of Holter Abnormalities
IDSL
ETP, SAC


CONFIDENTIAL
207597
84
ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Vital Signs
33.
SAFF_ALL
VS4 
Listing of All Vital Signs Data 
IDSL
ETP, SAC
Primary Analysis Data: Loss of Asthma Control and Intercurrent Events
34.
mITT_LoC
Listing of Loss of Asthma Control
Include all reasons for loss of control 
and time to loss of asthma control
ETP, SAC
35.
mITT_LoC
Listing of Intercurrent Events
Include treatment subject was analysed 
as taking and treatment at time of loss 
of control
ETP, SAC


CONFIDENTIAL
207597
85
12.10.13. Non-ICH Listings
Non-ICH: Listings
No.
Population
IDSL / Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Study Population
36.
SAFF_ALL
SP2
Listing of the Follow-up Contact
ETP, SAC
37.
SAFF_ALL
TA1
Listing of Treatment Misallocations
Change Centre ID to Investigator ID: xxxxxx and also 
Investigator at Centre: xxxxxx 
ETP, SAC
38.
SAFF_ALL
SP4
Listing of Overall Percentage Treatment 
Compliance
ETP, SAC
Secondary Efficacy
39.
mITT
Listing of Eosinophils
Include randomisation and analysis strata
ETP, SAC
40.
mITT
SP10
Listing of Lung Function Results at Screening
ETP, SAC
41.
mITT
SP10
Listing of Lung Function Results post-Screening
ETP, SAC
42.
mITT
S3
Listing of Asthma Exacerbations 
Include a column for severity 
ETP, SAC
43.
mITT
Listing of Asthma Control Questionnaire (ACQ-5) 
ETP, SAC
44.
mITT
Listing of St George’s Respiratory Questionnaire 
(SGRQ)
ETP, SAC
45.
mITT
Listing of Peak Exploratory Flow (PEF)
ETP, SAC
46.
mITT
Listing of Fractional Exhaled Nitric Oxide (FeNO)
ETP, SAC
47.
mITT
Listing of Daytime and Night-time Asthma 
Symptoms
ETP, SAC
48.
mITT
Listing of Rescue Medication Use
ETP, SAC
49.
mITT
Listing of Hospitalisations and Emergency Room 
Visits
ETP, SAC
50.
PK
Listing of Serum GSK3772847 Concentration
SAC Only


CONFIDENTIAL
207597
86
Non-ICH: Listings
No.
Population
IDSL / Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
51.
mITT
List of Free and Total Soluble ST2 
Concentrations
Adverse Events
52.
SAFF_ALL
Listing of Clinical Chemistry
ETP, SAC
53.
SAFF_ALL
Listing of Haematology and Cardiac Markers
ETP, SAC
54.
SAFF_ALL
Listing of Anti-GSK3772847 Antibodies
ETP, SAC
55.
SAFF_ALL
ESI8
Listing of AE Terms of Special Interest 
IDSL
ETP, SAC
Exploratory Biomarker
56.
mITT
Listing of Induced Sputum and Exploratory 
Serum Biomarkers
ETP, SAC
Medical History
57.
SAFF_ALL
MH2
Listing of Medical Conditions at Screening
ETP, SAC
58.
SAFF_ALL
SP5
Listing of Family History of Cardiovascular 
Disorders
ETP, SAC
59.
SAFF_ALL
SP6
Listing of Asthma History
ETP, SAC
60.
SAFF_ALL
SP7
Listing of Smoking History and Smoking Status
ETP, SAC
61.
SAFF_ALL
CM6
Relationship between ATC Level 1, Ingredient 
and Verbatim Text
ETP, SAC
Liver Events: Note only produced if there is a Liver Event
62.
SAFF_ALL
LIVER5
Listing of Liver Events
ETP, SAC
63.
SAFF_ALL
LIVER6
Listing of Liver Event Information for RUCAM 
Score
ETP, SAC
64.
SAFF_ALL
LIVER7
Listing of Liver Biopsy
ETP, SAC


CONFIDENTIAL
207597
87
Non-ICH: Listings
No.
Population
IDSL / Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
65.
SAFF_ALL
LIVER8
Listing of Liver Imaging Details
ETP, SAC
Cardiovascular Events: Note only produced if there is a Cardiovascular Event
66.
SAFF_ALL
Patient Profile
Listing of Myocardial infarction/unstable angina
ETP, SAC
67.
SAFF_ALL
Patient Profile
Listing of Congestive heart failure
ETP, SAC
68.
SAFF_ALL
Patient Profile
Listing of Arrhythmias
ETP, SAC
69.
SAFF_ALL
Patient Profile
Listing of Valvulopathy
ETP, SAC
70.
SAFF_ALL
Patient Profile
Listing of Pulmonary hypertension
ETP, SAC
71.
SAFF_ALL
Patient Profile
Listing of Cerebrovascular events/stroke and 
transient ischemic attack
72.
SAFF_ALL
Patient Profile
Listing of Peripheral arterial thromboembolism
73.
SAFF_ALL
Patient Profile
Listing of Deep venous thrombosis/pulmonary 
embolism
74.
SAFF_ALL
Patient Profile
Listing of Revascularisation
75.
SAFF_ALL
Patient Profile
Listing of Deaths


CONFIDENTIAL
207597
88
12.11.
Appendix 11: Example Mock Shells for Data Displays
Data Display Specification will be made available on Request.


CONFIDENTIAL
The GlaxoSmithKline group of companies
207597
1
Division
:
Worldwide Development
Information Type
:
Reporting and Analysis Plan (RAP)
Title
:
GSK3772847
Compound Number 
:
Reporting and Analysis Plan for a randomised, double-blind, 
parallel group, multicenter, stratified study evaluating the 
efficacy and safety of repeat doses of GSK3772847 
compared with placebo in participants with moderately 
severe asthma.
Effective Date 
:
20-DEC-2018
Description:

The purpose of this RAP is to describe the planned analyses and output to be 
included in the Clinical Study Report for Protocol 2017N311825_02.

This RAP is intended to describe the Efficacy, Safety, PK, PD and Biomarker
analyses required for the study. 

This RAP will be provided to the study team members to convey the content of the 
End of Treatment Phase (ETP) and Statistical Analysis Complete (SAC) deliverable.

This study does have an internal safety review committee (iSRC) and all details of 
iSRC deliverable are documented in a separate iSRC RAP.
Author’s Name and Functional Area: 
Approver
Date
27-NOV-2018
Principal Statistician (Respiratory, Clinical Statistics)
Copyright 2018 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited.
PPD


CONFIDENTIAL
The GlaxoSmithKline group of companies
207597
2
RAP Team Review Confirmations 
(Method: E-mail)
Reviewer
Date
27-NOV-2018
Clinical Investigation Lead (Respiratory, HUP Clinical 
Development)
27-NOV-2018
Principal Programmer (Respiratory, Clinical Programming)
27-NOV-2018
Clinical Development Physician (Respiratory, MDC Global 
Clinical)
19-DEC-2018
Scientist (Respiratory, Value Evidence and Outcomes)
29-NOV-2018
Director (Respiratory, Value Evidence and Outcomes)
27-NOV-2018
Senior Director (Respiratory, Clinical Pharmacology Modelling 
and Simulation)
18-DEC-2018
Director of Clinical Development (Respiratory, MDC Global 
Clinical)
18-DEC-2018
Senior Scientific Director (Respiratory, RD AI DPU Head)
Clinical Statistics & Clinical Programming Line Approvals 
(Method: Pharma TMF eSignature)
Approver
Date
20-DEC-2018
Senior Statistics Director (Respiratory, Clinical Statistics)
20-DEC-2018
Programming Manger (Respiratory, Clinical Programming)
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


CONFIDENTIAL
207597
3
TABLE OF CONTENTS
PAGE
1.
INTRODUCTION......................................................................................................6
2.
SUMMARY OF KEY PROTOCOL INFORMATION ..................................................6
2.1.
Changes to the Protocol Defined Statistical Analysis Plan............................6
2.2.
Study Objective(s) and Endpoint(s)...............................................................9
2.3.
Study Design ..............................................................................................12
2.4.
Statistical Hypotheses.................................................................................13
3.
PLANNED ANALYSES ..........................................................................................13
3.1.
End of Treatment Phase Analyses..............................................................13
3.2.
Final Analyses ............................................................................................14
4.
ANALYSIS POPULATIONS ...................................................................................14
4.1.
Protocol Deviations.....................................................................................16
5.
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS.....................................................................................................16
5.1.
Study Treatment & Sub-group Display Descriptors.....................................16
5.2.
Baseline Definitions ....................................................................................17
5.3.
Multicentre Studies .....................................................................................18
5.4.
Examination of Covariates, Other Strata and Subgroups............................19
5.4.1.
Covariates and Other Strata ........................................................19
5.5.
Multiple Comparisons and Multiplicity .........................................................19
5.6.
Other Considerations for Data Analyses and Data Handling 
Conventions................................................................................................19
6.
STUDY POPULATION ANALYSES .......................................................................20
6.1.
Overview of Planned Study Population Analyses........................................20
6.2.
Disposition..................................................................................................20
6.3.
Medical Conditions .....................................................................................20
6.4.
Concomitant Medications............................................................................20
7.
EFFICACY ANALYSES..........................................................................................21
7.1.
Primary Efficacy Analyses ..........................................................................21
7.1.1.
Endpoint ......................................................................................21
7.1.2.
Summary Measure ......................................................................21
7.1.3.
Population of Interest...................................................................21
7.1.4.
Strategy for Intercurrent (Post-Randomisation) Events ................21
7.1.5.
Statistical Analyses / Methods .....................................................22
7.1.5.1.
Statistical Methodology Specification..........................22
7.2.
Secondary Efficacy Analyses......................................................................25
7.2.1.
Endpoint and Summary Measure.................................................25
7.2.2.
Population of Interest...................................................................26
7.2.3.
Strategy for Intercurrent (Post-Randomisation) Events ................26
7.2.4.
Statistical Analyses / Methods .....................................................27
7.2.4.1.
Statistical Methodology Specification..........................27
8.
SAFETY ANALYSES .............................................................................................30


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8.1.
Adverse Events Analyses ...........................................................................31
8.2.
Adverse Events of Special Interest Analyses..............................................31
8.3.
Vital Signs, Electrocardiogram (ECG) and Holter........................................31
8.4.
Clinical Chemistry, Haematology and Cardiac Markers...............................31
8.5.
Antibodies...................................................................................................31
8.6.
Clinical Laboratory Analyses.......................................................................32
9.
PHARMACOKINETIC ANALYSES.........................................................................32
9.1.
Secondary Pharmacokinetic Analyses........................................................32
9.1.1.
Endpoint / Variables.....................................................................32
9.1.2.
Population of Interest...................................................................32
9.1.3.
Strategy for Intercurrent (Post-Randomisation) Events ................32
9.1.4.
Statistical Analyses / Methods .....................................................32
10. PHARMACODYNAMIC AND BIOMARKER ANALYSES........................................32
10.1.
Secondary Pharmacodynamic Analyses.....................................................32
10.1.1.
Endpoint / Variables.....................................................................32
10.1.2.
Summary Measure ......................................................................32
10.1.3.
Population of Interest...................................................................33
10.1.4.
Strategy for Intercurrent (Post-Randomisation) Events ................33
10.1.5.
Statistical Analyses / Methods .....................................................33
10.2.
Exploratory Biomarker Analyses .................................................................34
10.2.1.
Endpoint / Variables.....................................................................34
10.2.2.
Summary Measure ......................................................................34
10.2.3.
Population of Interest...................................................................34
10.2.4.
Strategy for Intercurrent (Post-Randomisation) Events........................35
10.2.5.
Statistical Analyses / Methods .....................................................35
11. REFERENCES.......................................................................................................36
12. APPENDICES........................................................................................................37
12.1.
Appendix 1: Protocol Deviation Management .............................................37
12.2.
Appendix 2: Schedule of Activities ..............................................................38
12.2.1.
Protocol Defined Schedule of Events...........................................38
12.3.
Appendix 3: Assessment Windows .............................................................44
12.3.1.
Definitions of Assessment Windows for Analyses........................44
12.4.
Appendix 4: Study Phases and Treatment Emergent Adverse 
Events ........................................................................................................45
12.4.1.
Study Phases ..............................................................................45
12.4.1.1.
Study Phases for Concomitant Medication .................45
12.4.2.
Treatment Emergent Flag for Adverse Events .............................46
12.5.
Appendix 5: Data Display Standards & Handling Conventions....................47
12.5.1.
Reporting Process .......................................................................47
12.5.2.
Reporting Standards....................................................................47
12.6.
Appendix 6: Derived and Transformed Data ...............................................49
12.6.1.
General........................................................................................49
12.6.2.
Study Population..........................................................................49
12.6.3.
Efficacy........................................................................................50
12.6.4.
Safety ..........................................................................................51
12.7.
Appendix 7: Reporting Standards for Missing Data.....................................53
12.7.1.
Premature Withdrawals................................................................53
12.7.2.
Handling of Missing Data.............................................................54


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12.7.2.1.
Handling of Missing and Partial Dates ........................54
12.8.
Appendix 8: Values of Potential Clinical Importance ...................................56
12.9.
Appendix 9: Abbreviations & Trade Marks ..................................................57
12.9.1.
Abbreviations...............................................................................57
12.9.2.
Trademarks .................................................................................58
12.10. Appendix 10: List of Data Displays..............................................................59
12.10.1. Data Display Numbering..............................................................59
12.10.2. Mock Example Shell Referencing ................................................59
12.10.3. Deliverables.................................................................................59
12.10.4. Study Population Tables..............................................................60
12.10.5. Efficacy Tables ............................................................................62
12.10.6. Efficacy Figures ...........................................................................66
12.10.7. Safety Tables...............................................................................68
12.10.8. Pharmacokinetic Tables...............................................................73
12.10.9. Pharmacodynamic and Biomarker Tables....................................74
12.10.10.Pharmacokinetic Figures .............................................................75
12.10.11.Pharmacodynamic and Biomarker Figures ..................................76
12.10.12.ICH Listings .................................................................................77
12.10.13.Non-ICH Listings..........................................................................81
12.11. Appendix 11: Example Mock Shells for Data Displays ................................84


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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 207597:
Protocol Revision Chronology:
2017N311825_00
2017-MAR-06
Original
2017N311825_01
2017-JUN-02
To address clarifications regarding the aim of the study, the 
eligibility criteria, the schedule of activities, the clinical 
assessments, and the recording of lab data and adverse 
events. The benefit: risk section was also updated based on 
the Part 2 results from study CNTO7160ASH1001. Also, a few 
typographical errors were corrected.
2017N311825_02
2017-SEP-13
To add more information on the risk: benefit section and the 
study design justification sections. To address clarifications 
regarding the unblinding of treatment in case of emergency. 
To clarify that rechallenge is not allowed once the treatment 
discontinuation criteria are met. Also, a few typographical 
errors were corrected.
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
Modified Intent to Treat population.
Modified Intent to Treat (Loss of 
Control), Modified Intent to Treat 
and Safety excluding GCP non-
compliant subjects populations.
The Modified Intent to Treat 
(Loss of Control) was added to 
account for the intercurrent 
event when participants receive 
the wrong study treatment. 
Whilst the data from GCP non-
compliant participants should 
not be used in the efficacy 
analysis, the participants were 
dosed with GSK3772847 or 
Placebo so all safety data (AEs, 
SAEs, ECGs etc.) should be 
reported.
Section 10.4.1 of the protocol 
describes a sensitivity analysis 
A primary and secondary 
estimand have been defined to 
The protocol was approved 
before the ICH E9 addendum on 


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Protocol
Reporting & Analysis Plan
Statistical Analysis Plan
Statistical Analysis Plan
Rationale for Changes
where data is analysed as missing 
and worst case (loss of control) for 
participants who withdraw from the 
study for reasons other than loss of 
asthma control.
capture where data is analysed 
as missing and worst case (loss 
of control) for various 
intercurrent events where 
participants withdraw from the 
study for reasons other than 
loss of asthma control.
estimands. The RAP is 
performing the same planned 
analysis as detailed in the 
Protocol however the 
terminology has been updated 
in accordance with ICH E9.  
Statistical analysis would be 
performed for each screening 
eosinophil strata separately.
Bayesian analysis will include 
screening eosinophil strata as a 
covariate instead of performing 
split analysis models. 
In addition, an exploratory 
analysis using fractional 
polynomials was added to 
examine the relationship 
between loss of control and 
screening eosinophils
(continuous), IgE and FeNO.
Bayesian analysis will now 
include the same covariates as 
the frequentist analysis.
By modelling eosinophils as a 
continuous endpoint, it will 
provide more information on the 
impact of varying screening 
eosinophil levels on the 
treatment effect. It will also 
provide additional information 
on the role of IgE and FeNO on 
loss of asthma control.
Mixed model repeated measures will 
be used to analyse the following
endpoints. The baseline value of 
each endpoint will be included along 
with baseline*visit and treatment*visit 
interactions. Treatment differences, 
95% confidence intervals and p-
values will be presented.

Change from baseline in ACQ-5 
absolute score

Change from baseline in SGRQ 
total score

Change from baseline in Pre-
bronchodilator FEV1

Change from baseline in FeNO
FEV1 and FeNO will only be 
analysed up until Week 4 (down 
titration of ICS), all data post 
Week 4 will be summarised 
descriptively only. 
In addition, an exploratory 
analysis using fractional 
polynomials was added to 
examine the relationship 
between FEV1 at Week 4 with
screening eosinophils 
(continuous), IgE and FeNO.
Continuous ACQ-5 and SGRQ 
will only be summarised and will 
not be analysed.
Responder analysis will still be 
performed. This will not impact 
any of the responder analysis in 
the primary or secondary 
endpoints. 
FEV1 and FeNO are impacted 
by ICS, so including change 
from baseline post-down 
titration of ICS would be 
confounding change due to 
study treatment with change 
due to ICS. To better explore 
the data prior to down titration, 
the fractional polynomial 
analysis has been added to 
examine the relationship 
between FEV1 at Week 4 with
screening eosinophils 
(continuous), IgE and FeNO.
FEV1, FeNO, ACQ-5 and 
SGRQ analysed using an 
MMRM would be assuming that 
data is missing at random. In 
fact, participants could have 
withdrawn due to loss of asthma 
control which is related to study 
treatment, so the analysis 
assumptions would not have 
been valid.
Secondary endpoints listed as:

Serum concentrations of 
GSK3772847 at weeks 2, 4, 8, 
12, 16, 20, 24 and 28.

Free and total soluble ST2 levels 
Secondary endpoints listed as:

Serum concentrations of 
GSK3772847 by nominal 
time.

Free and total soluble ST2 
Endpoint updated to use 
nominal time so that all data 
collected is summarised. 


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Protocol
Reporting & Analysis Plan
Statistical Analysis Plan
Statistical Analysis Plan
Rationale for Changes
at weeks 2, 4, 8, 12, 16, 20, 24 
and 28.
levels in serum by nominal 
time.
Proportion of participants with loss of 
asthma control assessed over 
Weeks 0-16 only.
Proportion of participants with 
loss of asthma control assessed
over Weeks 0-16 and over 
Weeks 0-6.
An additional endpoint 
assessing loss of control 
between Weeks 0 and 6 was 
added to help support the time 
to loss of asthma control 
analysis.


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2.2.
Study Objective(s) and Endpoint(s)
Objectives
Endpoints
Primary

To evaluate the efficacy of GSK3772847, 
compared with placebo, administered 
intravenously every 4 weeks for 12 
weeks (Week 0 – Week 12, 4 doses in 
total) in participants with moderately 
severe asthma.
Primary – Proportion of participants with loss of 
asthma control over Weeks 0-16 where ‘loss of 
asthma control’ is defined as at least one of the 
following:

Asthma Control Questionnaire (ACQ-5) 
score increase from baseline (measured 
at the end of Run-in) ≥ 0.5 point or

Pre-bronchodilator Forced expiratory 
volume in 1 second (FEV1) decrease 
from baseline (measured at the end of 
Run-in) >7.5 % or

Inability to titrate inhaled corticosteroid 
according to the pre-defined schedule or 

A clinically significant asthma 
exacerbation (requiring oral 
corticosteroid [OCS] and/or 
hospitalisation).
Secondary

To evaluate other aspects of efficacy of 
GSK3772847 compared with placebo in 
participants with moderately severe asthma.
Other efficacy endpoints (at or by Week 16):

Proportion of participants with a ≥0.5 
point. ACQ-5 score increase from 
baseline.

Proportion of participants who have pre-
bronchodilator FEV1 decrease from 
baseline (measured at the end of Run-in) 
>7.5 %.

Proportion of participants where inhaled 
corticosteroids (ICS) cannot be titrated in 
accordance with the pre-defined 
schedule.

Proportion of participants who have a 
significant asthma exacerbation 
(requiring OCS and/or hospitalisation).

Proportion of participants with loss of 
asthma control over Weeks 0-6 

Time to loss of asthma control.

Proportion of participants with a clinically 
significant asthma exacerbation or 
inability to titrate ICS according to the 
pre-defined schedule

The incidence, mean rate, and total 
number per participant of hospitalisations 
or Emergency Room (ER) visits during 
the study treatment period.


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Objectives
Endpoints

Change from baseline in ACQ-5 absolute 
score at each week from Week 1 to 
Week 16.

Proportion of participants with ≥0.5 point 
ACQ-5 score decrease from baseline 
(responder) at each week from Week 1 
to Week 16.

Change from baseline in SGRQ total 
score at Weeks 4, 8, 12 and 16.

Proportion of St. George’s Respiratory 
Questionnaire (SGRQ) responders (at 
least a 4 unit improvement from 
baseline) at Weeks 4, 8, 12 and 16.

Change from baseline in pre-
bronchodilator FEV1 at Weeks 2, 4, 6, 8, 
10, 12, 14, 16.

Change from baseline in mean morning 
peak expiratory flow (PEF) and mean 
evening PEF over each four weeks of the 
16 week treatment period.

Change from baseline in mean daytime 
asthma symptom score over each four 
weeks of the 16 week treatment period.

Change from baseline in rescue 
medication use (albuterol/salbutamol): 
mean number of inhalations per day over 
each four weeks of the 16 week 
treatment period.

Changes from baseline in night-time 
awakenings due to asthma symptoms 
requiring rescue medication use over 
each four weeks of the16 week treatment 
period.

Change from baseline in fractional 
exhaled nitric oxide (FeNO) at each 
week measured.

To evaluate the safety and tolerability of 
GSK3772847, compared with placebo 
administered intravenously every 4 weeks 
for 12 weeks (Week 0-12, 4 doses in total) in 
participants with moderately severe asthma. 

Incidence and frequency of adverse events 
(AEs) and serious adverse events (SAEs).

Change from baseline in vital signs at weeks 
1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24 and 28.

Change between post-dose and pre-dose in 
vital signs at weeks 0, 4, 8 and 12.

Change from baseline in 12-lead 
electrocardiogram (ECG) measurements at 
weeks 4, 8, 12 and 16.

Change between post-dose and pre-dose in 
12-lead ECG measurements at weeks 0, 4, 
8 and 12.

Change from baseline in 24 hours Holter 


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Objectives
Endpoints
measurements at weeks 4 and 12. 

Change from baseline in clinical chemistry 
at weeks 2, 4, 8, 12, 16 and 28.

Change from baseline in haematology and 
cardiac markers at weeks 1, 2, 4, 6, 8, 10, 
12, 14, 16 and 28.

Incidence of and titres of anti- GSK3772847 
antibodies at weeks 2, 4, 8, 12, 16, 20, 24 
and 28.

To evaluate the pharmacokinetics (PK) of 
GSK3772847 in participants with moderately 
severe asthma.

Serum concentrations of GSK3772847 by 
nominal time.

To evaluate the pharmacodynamics (PD) of 
GSK3772847 in participants with moderately 
severe asthma.

Free and total soluble ST2 levels in serum 
by nominal time.
Exploratory 

To compare the effect of GSK3772847 with 
placebo on biomarkers in serum and 
sputum.

Changes from baseline in induced 
sputum biomarkers (subset) at weeks 8 
and 16.

Changes from baseline in exploratory 
serum markers at weeks 8 and 16.


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2.3.
Study Design
Overview of Study Design and Key Features
Design 
Features

The study is a Phase IIa, multicenter, randomised, placebo-controlled, double-
blind, stratified, parallel group study.
Dosing

Participants will have a two-week Run-in period in which they take a 
background therapy of fluticasone propionate (FP)/salmeterol 500/50 mcg 
BID.

Following run-in they will be randomised to receive four doses of either 
GSK3772847 or Placebo intravenously (Week 0, 4, 8 and 12) whilst initially 
still receiving background FP/Salmeterol 500/50 mcg BID.

At Week 2 background therapy will be changed to FP 500 mcg BID only. This 
will then be reduced by approximately 50 % every two weeks until complete 
FP discontinuation at Week 10.
Treatment 
Assignment

Participants will be randomised in a 1:1 ratio to receive four doses of either 
GSK3772847 or Placebo administered intravenously every 4 weeks.

Randomisation will be stratified based on participants’ baseline peripheral 
blood eosinophil count which is measured at screening (<150 cells/µL, >=150 
cells/µL), Randomisation will also be stratified according to whether 
participants consent to the sputum sub study.


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Overview of Study Design and Key Features
Interim 
Analysis

The End of Treatment Phase Analysis will take place after all subjects have 
completed the week 16 visit, and will be considered an interim analysis for 
both efficacy and safety. There will be no modifications to dosing regimens, 
sample size or any other aspects of the trial based on this data, as all study 
assessments, apart from follow-up, will have already been completed.
2.4.
Statistical Hypotheses
The primary null hypothesis (
) for this study is that the ratio of the proportions of 
subjects with loss of asthma control from randomisation to Week 16 between 
GSK3772847 and placebo is unity.
The alternative hypothesis (
) for this study is that the ratio of the proportions of 
subjects with loss of asthma control from randomisation to Week 16 between 
GSK3772847 and placebo is not unity. 
3.
PLANNED ANALYSES
3.1.
End of Treatment Phase Analyses
The End of Treatment Phase Analysis will be performed after the completion of the 
following sequential steps:
1.
All subjects have completed the Week 16 visit or the Early Withdrawal visit
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.
Due to an inability to lock log forms used for collection of exacerbation data, the end of 
treatment phase analysis will be considered an interim analysis for both efficacy and 
safety. Any safety data collected for participants who have completed clinic visits after 
Week 16 will also be cleaned and included in the analysis. 


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All participants will have completed the active treatment phase of the study by the time 
of the interim, so no modifications will be made to the study as a result of the End of 
Treatment Phase Analysis. The Final Analysis is intended to be an analysis of safety data 
collected in the Post-Treatment Follow-Up phase.
The sponsor will be unblinded to the results of the analysis. 
3.2.
Final Analyses
The final planned primary analyses will be performed after the completion of the 
following sequential steps:

All subjects have completed the study. 

All required database cleaning activities for data after Week 16/ Early Withdrawal
as well as data collected on log pages have been completed.

Final database release and database freeze has been declared by Data 
Management.
No unblinding will take place as part of the final analysis as all participants will have 
already been unblinded during the End of Treatment Phase Analysis. 
4.
ANALYSIS POPULATIONS
Some participants are being excluded from the efficacy analyses due to a failure at their 
site to follow GCP. As these participants received GSK3772847 or placebo during their 
period of participation, all safety data will be reported.
Population
Definition / Criteria
Analyses Evaluated
Enrolled

The All Subjects Enrolled (ASE) population 
will consist of all participants who sign the 
ICF.
Study population
Reason for withdrawal 
prior to randomisation
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 excluding 
GCP non-
compliant 
subjects (Loss of 
Control)

The Modified Intent-to-Treat excluding GCP 
non-compliant subjects (Loss of Control)
(mITT_LoC) will consist of all randomised 
participants who take at least 1 dose of study 
treatment, excluding participants where an 
investigation by GSK has shown that good
clinical practice has not been followed. Any 
participants excluded from this population will 
Efficacy (loss of 
control)


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Population
Definition / Criteria
Analyses Evaluated
be identified as protocol deviations and listed 
in a separate output. 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. For loss of asthma control,
participants will be analysed according to the 
treatment they were receiving at the time of 
loss of control. 
Modified Intent-to-
Treat excluding 
GCP non-
compliant 
subjects 

The Modified Intent-to-Treat excluding GCP 
non-compliant subjects (mITT) population will 
consist of all randomised participants who 
take at least 1 dose of study treatment, 
excluding participants where an investigation 
by GSK has shown that good clinical practice 
has not been followed. Any participants 
excluded from this population will be identified 
as protocol deviations and listed in a separate 
output. 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.
Efficacy (all except loss 
of control)
Safety including 
GCP non-
compliant 
subjects

The Safety (SAFF_ALL) population will 
consist of all randomised participants who 
take at least 1 dose of study treatment. 
Participant 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
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
NOTES : 
1.
Please refer to Appendix 10: List of Data Displays which details the population to be used for each display being
generated.
2.
If a participant is inadvertently given both study treatments they will be analysed according to the treatment that 
they received the more frequently. 


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4.1.
Protocol Deviations
All 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 [21-Aug-2017 (Version 1) 
or later].
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. 
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.
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:

Order represents treatments being presented in TFL, as appropriate.
Treatment comparisons will be displayed as follows using the descriptors as specified:

GSK3772847 vs Placebo
There were four strata used for the randomisation depending on the participants baseline 
blood eosinophil count and whether they consented to the sputum sub-study:

Sputum sub-study and baseline blood eosinophils < 150 cells/µL

Sputum sub-study and baseline blood eosinophils >=150 cells/µL

Not sputum sub-study and baseline blood eosinophils < 150 cells/µL

Not sputum sub-study and baseline blood eosinophils >=150 cells/µL


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Displays will be presented by combining data across all four strata to give the overall 
estimate of GSK3772847 versus placebo. 
Sputum sub-study will not be accounted for within the statistical analysis as the sputum 
sub-study strata was for monitoring recruitment only.
An additional exploratory analysis using fractional polynomials has been added to further 
investigate the relationship between loss of control and screening eosinophils and 
summary statistics on eosinophils will also be provided. 
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. 
Parameter
Study Assessments 
Considered As Baseline
Baseline Used in 
Data Display
Pre-
Screening
Screen 
Run-in
Day 1 
(Pre-Dose)
Loss of Asthma Control
Pre-bronchodilator Forced 
expiratory volume in 1 second 
(FEV1)
X
X
Day 1
Asthma Control Questionnaire 
(ACQ-5) score
X
X
Day 1
Other Patient Reported Outcomes
St. George’s Respiratory 
Questionnaire (SGRQ)
X
Day 1
Peak Expiratory Flow (PEF)
Mean morning peak expiratory 
flow (PEF)
X
X
Run-in [1]
Mean evening peak expiratory 
flow (PEF)
X
X
Run-in [1]
Fractional Exhaled Nitric Oxide (FeNO)
Fractional Exhaled Nitric Oxide 
(FeNO)
X
Day 1
Symptom Scores
Mean daytime asthma symptom 
score
X
X
Run-in [1]
Night-time awakenings due to 
asthma symptoms requiring 
rescue medication
X
X
Run-in [1]


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Parameter
Study Assessments 
Considered As Baseline
Baseline Used in 
Data Display
Pre-
Screening
Screen 
Run-in
Day 1 
(Pre-Dose)
Rescue Medication
Rescue medication use
X
X
Run-in [1]
Mean number of inhalations per 
day over each four weeks
X
X
Run-in [1]
Safety
Vital Signs
X
X
Day 1
12-lead Electrocardiogram (ECG) 
measurements
X
X
Day 1
24 hours Holter measurements
X
Screen/Run in
Clinical laboratory tests 
(haematology and chemistry)
X
X
Day 1
Biomarkers
Induced sputum biomarkers
X
Day 1
Serum biomarkers
X
Day 1
Exploratory serum markers
X
Day 1
NOTES :

Unless otherwise stated, the mean of replicate assessments at any given time point will be used as the value for 
that time point.

[1] Mean over the last 7 days of the run-in period prior to V2.  Participants must have at least 4 full days of data 
(morning and evening) in the last 7 days of run-in to be eligible.
5.3.
Multicentre Studies
In this multicentre global study, enrolment will be presented by investigative site, 
country, and regions.
Region
Countries
North America
United States, Canada
Latin America
Mexico 
Eastern Europe
Ukraine, Russian Federation
Oceania
Australia


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5.4.
Examination of Covariates, Other Strata and Subgroups
5.4.1.
Covariates and Other Strata
The list of covariates and other strata may be used in descriptive summaries and 
statistical analyses, some of which may also be used for subgroup analyses. Additional 
covariates and other strata of clinical interest may also be considered.
5.5.
Multiple Comparisons and Multiplicity
As there is a single primary treatment comparison, no adjustment is required for primary 
comparisons. No adjustments will be made for multiplicity for other endpoints.
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
Category
Covariates 
Screening eosinophils
At randomisation participants are stratified according to their 
baseline peripheral blood eosinophil. Screening eosinophils will 
be included in both primary and secondary analysis as a 
categorical variable (<150 cells/µL, >=150 cells/µL). An 
additional exploratory analysis of the primary endpoint using 
continuous eosinophils will also be examined. 
If the analysis models are unable to converge due to low 
number of participants with baseline blood eosinophils <150 
cells/µL, then screening eosinophil will be re-categorised 
according to a cut point of 300 cells/µL instead i.e. <300 
cells/µL and >=300 cells/µL


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6.
STUDY POPULATION ANALYSES
6.1.
Overview of Planned Study Population Analyses
The study population analyses will be based on the Safety Population including GCP 
non-compliant subjects population (SAFF_ALL), unless specified to be on the All 
Subjects Enrolled (ASE) population.
Study population analyses including analyses of subject’s disposition, protocol 
deviations, demographic and baseline characteristics, prior and concomitant medications, 
and 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 population 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 modified Intent-to-treat (Loss of 
Control), modified Intent-to-treat, Safety including GCP non-compliant subjects, and PK
populations.
For the Safety including GCP non-compliant subjects, reasons for withdrawal summary 
will show the number and percentage of subjects who completed the study, who 
withdrew prematurely from the study 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.
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 separately. 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
7.1.
Primary Efficacy Analyses
7.1.1.
Endpoint 

Proportion of participants with loss of asthma control over Weeks 0-16

Proportion of participants with loss of asthma control over Weeks 0-6 (Secondary)
7.1.2.
Summary Measure
Bayesian Method (Primary): The posterior probabilities that the ratio of the proportion of 
subjects with loss of asthma control on GSK3772847 compared with placebo is less than 
1.0, 0.75, 0.5 and 0.2 (i.e. a 0%, 25%, 50% and 80% reduction).
Frequentist Method (Supportive): Odds Ratio. The odds of having experienced loss of 
asthma control on GSK3772847 compared to the odds of having experienced loss of 
asthma control on placebo.
7.1.3.
Population of Interest 
The primary efficacy analyses will be based on the modified Intent to Treat (Loss of 
Control) population, unless otherwise specified.
7.1.4.
Strategy for Intercurrent (Post-Randomisation) Events
Intercurrent Event
Primary Estimand
Secondary Estimand
Treatment discontinuation due 
to AE/SAE (not related to loss 
of asthma control)
Set to missing.
If the AE/SAE was deemed related to IP 
then set as an event (i.e. worst case 
scenario).
If the AE/SAE was not deemed related to IP 
then set to missing.
Death 
Set to missing.
If the death was deemed related to IP then 
set as an event (i.e. worst case scenario).
If the death was not deemed related to IP
then set to missing.
Prohibited/ Concomitant 
medications that could impact 
patients’ asthma control 
Use data as is.
Set as an event (i.e. worst case scenario).
Non-compliance with FP/SAL, 
FP or study titration
Use data as is.
Set as an event (i.e. worst case scenario).
Continuation in the study after 
LOC criteria met
Use information from first 
loss of asthma control. 
Use information from first loss of asthma 
control.
Note:

Identification of whether an event (AE/SAE/Death) is considered related to IP will be identified 


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using the investigator tick box collected on the eCRF.

If the intercurrent event occurs after loss of asthma control then all information on loss of asthma 
control will be used. 

Prohibited/ concomitant medications will be identified as protocol deviations within the prohibited/ 
concomitant medications category and will have text that start with “LoAC”

Non-compliance FP/SAL, FP or study titration will be identified as compliance <80%, compliance 
≥ 120% or not changing from FP/SAL or FP doses according to the predetermined schedule.
If any of the following intercurrent events occurs, then all data will be accepted:

Pregnancy
Accidental unblinding 
Whilst it’s possible that site staff were unable to administer study drug as they were
unable to find a suitable vein, the team felt this would not be caused by the randomised 
study treatment and the visit would be rescheduled. Therefore, if this occurs all data will 
be accepted and treated as any other out of window assessment. 
7.1.5.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 10: List of Data Displays and 
will be based on GSK data standards and statistical principles.
Unless otherwise specified, endpoints / variables defined in Section 7.1.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and
listed.
7.1.5.1.
Statistical Methodology Specification
Endpoint / Variables

Proportion of participants with loss of asthma control over Weeks 0-16

Proportion of participants with loss of asthma control over Weeks 0-6 (Secondary)
Model Specification

The primary endpoint proportion of subjects with loss of asthma control will be analysed for the 
Modified Intent-to-Treat excluding GCP non-compliant subjects (Loss of Control) population 
using both Bayesian (primary) and Frequentist (supportive) methods.
Bayesian Method (Primary):

Proc MCMC will be used in order to gain the posterior distribution of the study data combined 
with a non-information beta(1,1) prior, and screening eosinophil strata included as a covariate. 
Note: This prior is equivalent to one event on both GSK3772847 and Placebo treatment arms.

Three MCMC chains should be run, with all parameters in the model being assessed for 
convergence. Each chain will have 10,000 simulations (using a burn-in of 500) and will start 
with a set seed of 207597 to enable comparison between the main and qc.

The posterior probabilities that the ratio of the proportion of subjects with loss of asthma control 
on GSK3772847 compared with placebo is less than 1.0, 0.75, 0.5 and 0.2 (i.e. a 0%, 25%, 
50% and 80% reduction) will be calculated along with the estimated ratio and associated 95% 


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credible interval. The 95% credible interval will use the highest posterior density where 
possible, and if this isn’t possible then the 2.5% and 97.5% credible intervals will be reported.

The posterior median and standard deviation will also be reported together with a 95% credible 
interval.

In addition to summary tables a plot of the posterior distribution for the ratio of the proportion of 
subjects with loss of asthma control on GSK3772847 compared with placebo, along with the 
proportion of subjects with loss of asthma control on GSK3772847 and placebo separately will 
be generated.

This analysis will be repeated for loss of asthma control between Weeks 0 and 6.
Frequentist Method (Supportive):

The proportion of participants with loss of asthma control will be analysed using logistic 
regression allowing for screening eosinophils strata. It will include fixed effects terms for 
treatment and screening eosinophil strata. 
Fractional Polynomials (Exploratory Analysis for Loss of Control Over Weeks 0-16):

Screening blood eosinophil count will be transformed using a fractional polynomial term which 
will be included in the model as a continuous covariate. A treatment group by eosinophil 
covariate interaction will also be included in the model to allow the magnitude of the interaction 
(but not the order of the fractional polynomial transformation) to differ with each treatment 
group). The best fitting model will be selected based on likelihood. The selected best fitting 
model will be plotted as continuous eosinophil count versus loss of asthma control in each 
treatment arm. The fit of the model to the raw data will be assessed visually.

The role of baseline IgE and baseline FeNO (separately) on the effectiveness of GSK3772847 
with respect to loss of asthma control will be investigated in a similar way.
Model Checking & Diagnostics
Bayesian Method (Primary):

The Markov chain standard error (MCSE) should be compared to the standard deviation of the 
distribution (SD) to make sure that MCSE/SD ≤ 0.01 for all parameters in the mode.

The Geweke diagnostic test will be used to check whether the mean estimates have converged 
by comparing means from the early and later part of the Markov chain using a z-score t-test. 
Large absolute values of the z-score statistic indicate rejection of the null hypothesis of no 
difference between the mean estimates obtained from the early and latter parts of the chain.

Gelman & Rubin diagnostic checks should be used to assess if the Markov chains have mixed. 

Visual checks on diagnostic plots will be performed to assess:
o
Has the Markov chain settled down? 
o
Are sufficient simulations being run? 
o
Is there sufficient burn-in? 
o
Is the effective sample size large enough? 
Frequentist Method (Supportive):

None.
Model Results Presentation
Bayesian Method (Primary):


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
The proportions of participants experience loss of asthma control on GSK3772847, Placebo 
and the ratio of GSK3882747/Placebo will be presented along with their 95% credible interval
for all participants combined.
Frequentist Method (Supportive):

The odds of experiencing loss of asthma control on GSK3772947, Placebo and the odds ratio
will be presented along with the 95% confidence intervals and p-value. This will be presented 
for all participants combined.
Fractional Polynomials (Exploratory Analysis):

A plot of the relationship between the probability of experiencing loss of control on each 
treatment as well as the odds ratio versus continuous eosinophils will be produced.


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7.2.
Secondary Efficacy Analyses
7.2.1.
Endpoint and Summary Measure
Endpoint
Summary Measure
Individual Components of Loss of Asthma 
Control:

Proportion of participants with a ≥0.5 
point. ACQ-5 score increase from 
baseline.

Proportion of participants who have 
pre-bronchodilator FEV1 decrease 
from baseline (measured at the end of 
Run-in) >7.5 %.

Proportion of participants where 
inhaled corticosteroids (ICS) cannot be 
titrated in accordance with the pre-
defined schedule.

Proportion of participants who have a 
significant asthma exacerbation 
(requiring OCS and/or hospitalisation).

Proportion of participants with a 
clinically significant asthma 
exacerbation or inability to titrate ICS 
according to the pre-defined schedule
Frequentist Method (Supportive): Odds Ratio. 
For each endpoint listed, the odds of having 
experienced loss of asthma control on 
GSK3772847 compared to the odds of having 
experienced loss of asthma control on placebo
will be produced.
Time to loss of asthma control.
Median and lower and upper quartiles (only 
calculable if>= 50%, 25%, 75% subjects lose 
control for each treatment respectively) for
time to loss of asthma control
The incidence, mean rate, and total number 
per participant of hospitalisations or 
Emergency Room (ER) visits during the study 
treatment period.
Summary statistics and study treatment 
exposure (no statistical analysis required).
Responder Analysis:

Proportion of participants with ≥0.5 
point ACQ-5 score decrease from 
baseline (responder) at each week 
from Week 1 to Week 16.

Proportion of St. George’s Respiratory 
Questionnaire (SGRQ) responders (at 
least a 4 unit improvement from 
baseline) at Weeks 4, 8, 12 and 16.
Odds Ratio. The odds of being a responder on 
GSK3772847 compared to the odds of being a 
responder on placebo.
Change from Baseline Analysis:

Change from baseline in pre-
bronchodilator FEV1 at Weeks 2, 4, 6, 
8, 10, 12, 14, 16.

Change from baseline in fractional 
Mean change from baseline


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Endpoint
Summary Measure
exhaled nitric oxide (FeNO) at each 
week measured.
Change from Baseline Analysis:

Change from baseline in ACQ-5 
absolute score at each week from 
Week 1 to Week 16.

Change from baseline in SGRQ total 
score at Weeks 4, 8, 12 and 16.
Mean change from baseline

Change from baseline in mean 
morning peak expiratory flow (PEF) 
and mean evening PEF for each four
week period of the overall 16 week 
treatment period.

Change from baseline in mean 
daytime asthma symptom score over 
each four weeks of the 16 week 
treatment period.

Changes from baseline in night-time 
awakenings due to asthma symptoms 
requiring rescue medication use over 
each four weeks of the 16 week 
treatment period.

Change from baseline in rescue 
medication use (albuterol/salbutamol): 
mean number of inhalations per day 
over each four weeks of the 16 week 
treatment period.
Change from baseline (summary statistics 
only)
7.2.2.
Population of Interest 
The secondary efficacy analyses will be based on the modified Intent to Treat population, 
unless otherwise specified.
7.2.3.
Strategy for Intercurrent (Post-Randomisation) Events
For components of Loss of Asthma Control see Section 7.1.4.
For SGRQ and ACQ Responders primary and secondary estimands as table below:
Intercurrent Event
Primary Estimand
Secondary Estimand
Treatment discontinuation due 
to AE/SAE (not related to loss 
of asthma control)
Set to missing.
If the AE/SAE was deemed related to IP 
then set as non-responder.
If the AE/SAE was not deemed related to IP 
then set to missing.


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Intercurrent Event
Primary Estimand
Secondary Estimand
Death 
Set to missing.
If the death was deemed related to IP then 
set as non-responder.
If the death was not deemed related to IP 
then set to missing.
Prohibited/ Concomitant 
medications that could impact 
patients’ asthma control 
Use data as is.
Set as non-responder.
Non-compliance with FP/SAL, 
FP or study titration
Use data as is.
Set as non-responder.
Note:

Identification of whether an event (AE/SAE/Death) is considered related to IP will be identified 
using the investigator tick box collected on the eCRF.

If the intercurrent event occurs after loss of asthma control then all information on loss of asthma 
control will be used. 

Prohibited/ concomitant medications will be identified as protocol deviations within the prohibited/ 
concomitant medications category and will have text that start with “LoAC”

Non-compliance FP/SAL, FP or study titration will be identified as compliance <80%, compliance 
≥ 120% or not changing from FP/SAL or FP doses according to the predetermined schedule.
7.2.4.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 10: List of Data Displays and 
will be based on GSK data standards and statistical principles.
Unless otherwise specified, endpoints / variables defined in Section 7.2.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed.
7.2.4.1.
Statistical Methodology Specification
Endpoint / Variables

Proportion of participants with a ≥0.5 point. ACQ-5 score increase from baseline.

Proportion of participants who have pre-bronchodilator FEV1 decrease from baseline 
(measured at the end of Run-in) >7.5 %.

Proportion of participants where inhaled corticosteroids (ICS) cannot be titrated in accordance 
with the pre-defined schedule.

Proportion of participants who have a significant asthma exacerbation (requiring OCS and/or 
hospitalisation).

Proportion of participants with a clinically significant asthma exacerbation or inability to titrate 
ICS according to the pre-defined schedule
Strategy for Intercurrent (Post-Randomisation) Events
Both primary and secondary estimands (Section 7.1.4) will be examined. It is important to assess 
both estimands as data is set to missing after withdrawal or loss of asthma control. This could 
produce biased estimands, as loss of control and therefore missing data is related to study 
treatment, and so the secondary estimand where missing data is set as non-responders must also 
be considered.


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Model Specification

See Section 7.1.5.1.
Model Checking & Diagnostics

See Section 7.1.5.1
Model Results Presentation

See Section 7.1.5.1
Endpoint / Variables

Proportion of participants with ≥0.5 point ACQ-5 score decrease from baseline 
(responder) at each week from Week 1 to Week 16.

Proportion of St. George’s Respiratory Questionnaire (SGRQ) responders (at least a 4 unit 
improvement from baseline) at Weeks 4, 8, 12 and 16.
Strategy for Intercurrent (Post-Randomisation) Events
Both primary and secondary estimands (Section 7.2.3) will be examined. It is important to assess 
both estimands as data is missing after withdrawal or loss of asthma control. This could produce 
biased estimands, as loss of control and therefore missing data is related to study treatment, and 
so the secondary estimand where missing data is set as non-responders must also be considered.
Model Specification

The proportion of participants who were responders will be analysed using logistic regression 
allowing for screening eosinophils strata.

A responder on ACQ-5 is defined as participants with a ≥0.5 point decrease from baseline 
whilst a responder on SGRQ is defined as a ≥4 point decrease from baseline.

This endpoint will be analysed using logistic regression. Treatment, eosinophil strata will be 
fixed effects.
Model Checking & Diagnostics

None
Model Results Presentation

The odds of being a responder (as defined above) on GSK3772947, Placebo and the odds 
ratio will be presented along with the 95% confidence intervals and p-value.
Endpoint / Variables

Time to loss of asthma control.
Strategy for Intercurrent (Post-Randomisation) Events

Both primary and secondary estimands (Section 7.1.4) will be examined. It is important to 
assess both estimands as data is missing after withdrawal or loss of asthma control. This 
could produce biased estimands, as loss of control and therefore missing data is related to 
study treatment, and so the secondary estimand where missing data is set as non-
responders must also be considered.
Model Specification

Time to loss of asthma control will be analysed on the Modified Intent-to-Treat excluding GCP 


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non-compliant subjects (Loss of Control) population using Kaplan-Meier analysis (Proc lifetest).
Within the Kaplan Meier plot participants will either be counted as an event or they will be 
censored.
Events:

Participants who experience loss of asthma control during the study.
Censoring:

Participants who discontinue investigational product for reasons other than loss of asthma 
control.

Participants who successfully complete the 16 week treatment period will be censored at 113 
days (16 weeks + 1 day). 
Time to loss of asthma control = Date of loss of asthma control – Treatment start date + 1. If 
participants experience multiple reasons for loss of control then the earliest date will be used as 
described in Section 12.6.3.
Model Checking & Diagnostics

None
Model Results Presentation

Kaplan-Meier plots of the probability of a participant experiencing loss of asthma control by 
treatment will be produced.

In addition, a summary table will be produced showing the probability of experiencing loss of 
asthma control after 4, 8, 12 and 16 weeks along with the median time (this will be NA if <50% 
of participants on a treatment lose control) to loss of asthma control on both treatment arms.
Endpoint / Variables

Change from baseline in pre-bronchodilator FEV1 at Weeks 2, 4, 6, 8, 10, 12, 14, 16.

Change from baseline in fractional exhaled nitric oxide (FeNO) at each week measured.

Change from baseline in blood eosinophils
Strategy for Intercurrent (Post-Randomisation) Events
No intercurrent events are considered for this endpoint. All data will be used as collected. 
Model Specification
Only data until Week 4 (down titration of ICS) will be analysed, all data post Week 4 will be 
summarised descriptively only. 
Data up to and include Week 4 (down titration of ICS):
A repeated measures model with terms for treatment, visit, visit by treatment and screening 
eosinophil strata will be included along with the screening eosinophil strata*visit and treatment*visit 
interactions.  
FEV1 at Weeks 4 Only - Fractional Polynomials (Exploratory Analysis):

Screening blood eosinophil count will be transformed using a fractional polynomial term which 
will be included in the model as a continuous covariate. A treatment group by eosinophil 


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covariate interaction will also be included in the model to allow the magnitude of the interaction 
(but not the order of the fractional polynomial transformation) to differ with each treatment 
group). The best fitting model will be selected based on likelihood. The selected best fitting 
model will be plotted as continuous eosinophil count versus loss of asthma control in each 
treatment arm. The fit of the model to the raw data will be assessed visually.

The role of baseline IgE and baseline FeNO (separately) on the effectiveness of GSK3772847 
with respect to FEV1 at Weeks 4 will be investigated in a similar way.
Model Checking & Diagnostics

Distributional assumptions underlying the model used for analysis will be examined by 
obtaining a normal probability plot of the residuals and a plot of the residuals versus the fitted 
values (i.e. checking the normality assumption and constant variance assumption of the model 
respectively) to gain confidence that the model assumptions are reasonable.
Model Results Presentation

The estimates of the mean and difference for each treatment group from the model will be 
produced, along with 95% confidence intervals and p-values for treatment comparisons.
The following endpoints will be summarised descriptively only. No analysis will be 
performed and all data will be reported as collected (no intercurrent events will be 
considered) using the modified Intent to Treat population:

Change from baseline in ACQ-5 absolute score at each week from Week 1 to 
Week 16.

Change from baseline in SGRQ total score at Weeks 4, 8, 12 and 16.

Change from baseline in mean morning peak expiratory flow (PEF) and mean 
evening PEF over each four weeks of the 16 week treatment period.

Change from baseline in mean daytime asthma symptom score over each four 
weeks of the 16 week treatment period.

Changes from baseline in night-time awakenings due to asthma symptoms 
requiring rescue medication use over each four weeks of the16 week treatment 
period.

Change from baseline in rescue medication use (albuterol/salbutamol): mean 
number of inhalations per day over each four weeks of the 16 week treatment 
period.
8.
SAFETY ANALYSES
The safety analyses will be based on the Safety including GCP non-compliant subjects 
population, unless otherwise specified. The details of the planned displays are provided in 
Appendix 10: List of Data Displays.


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8.1.
Adverse Events Analyses
Adverse events analyses including the analysis of adverse events (AEs), Serious (SAEs)
and other significant AEs will be based on GSK Core Data Standards. 
8.2.
Adverse Events of Special Interest Analyses
A comprehensive list of MedDRA terms based on clinical review will be used to identify 
each type of event. Changes to the MedDRA dictionary may occur between the start of 
the study and the time of reporting and/or emerging data from on-going studies may 
highlight additional adverse events of special interest, therefore the list of terms to be 
used for each event of interest and the specific events of interest will be based on the 
safety review team (SRT) agreements in place at the time of reporting.
8.3.
Vital Signs, Electrocardiogram (ECG) and Holter
Summary statistics for vital signs at baseline, weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24 
and 28 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, 8 and 12.
Similar 12-lead electrocardiogram (ECG) measurements at baseline, weeks 4, 8, 12 and 
16 will be produced along with change from baseline summaries for each post baseline 
timepoint, and changes between post-dose and pre-dose in 12-lead ECG measurements at 
weeks 0, 4, 8 and 12.
24 hour Holter measurements collected at baseline, weeks 4 and 12 will be summarised 
along with change from baseline at weeks 4 and 12. Only participants with at least 16hrs 
worth of data will be included in any tables however all data will be listed.
8.4.
Clinical Chemistry, Haematology and Cardiac Markers
Summaries of clinical chemistry results at baseline, weeks 2, 4, 8, 12, 16 and 28 along 
with change from baseline for all post-baseline measurements will be produced.
Similarly, haematology and cardiac markers at baseline, weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 
and 28 along with change from baseline for all post-baseline measurements will also be 
produced. 
8.5.
Antibodies
Summaries of the incidence of and titres of anti- GSK3772847 antibodies at weeks 0*, 2, 
4*, 8*, 12*, 16, 20, 24 and 26.
* = Pre-dose only


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8.6.
Clinical Laboratory Analyses
Laboratory evaluations including the analyses of liver function tests will be based on 
GSK Core Data Standards.
9.
PHARMACOKINETIC ANALYSES
Due to the time required to analyse PK samples, no PK outputs will be included in the 
end of treatment phases analysis.
9.1.
Secondary Pharmacokinetic Analyses
9.1.1.
Endpoint / Variables
Serum concentrations of GSK3772847 by nominal time.
9.1.2.
Population of Interest 
The secondary pharmacokinetic analyses will be based on the Pharmacokinetic
population, unless otherwise specified.
9.1.3.
Strategy for Intercurrent (Post-Randomisation) Events
Not applicable.
9.1.4.
Statistical Analyses / Methods

No statistical analysis will be performed. 

Serum concentration will be summarised descriptively with summary figures being 
produced.

Scatter plots of trough serum concentration vs FeNO, trough serum concentration vs 
blood eosinophils, and trough serum concentration vs IgE at Week 4 only will also be 
produced.
10.
PHARMACODYNAMIC AND BIOMARKER ANALYSES
10.1.
Secondary Pharmacodynamic Analyses
10.1.1.
Endpoint / Variables
Free and total soluble ST2 levels in serum
10.1.2.
Summary Measure
Free soluble ST2: Summary statistics and percentage change from baseline 
Total soluble ST2: Summary statistics and change from baseline 


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Only pre-dose trough sST2 will be used for analysis. Post-dose trough sST2 will be 
summarised only.
10.1.3.
Population of Interest 
The secondary pharmacodynamics analyses will be based on the modified Intent to Treat
population, unless otherwise specified.
10.1.4.
Strategy for Intercurrent (Post-Randomisation) Events
Not applicable.
10.1.5.
Statistical Analyses / Methods
Endpoint / Variables

Percentage change from baseline in free sST2 (On-treatment)

Percentage change from baseline in free sST2 (Post-treatment)
Strategy for Intercurrent (Post-Randomisation) Events
No intercurrent events are considered for this endpoint. All data will be used as collected. 
Model Specification

The ratio of post-baseline sST2 values to baseline sST2 values will be log transformed prior to 
analysis. Note: Log(post baseline sST2 /baseline sST2) is equivalent to log(post baseline 
sST2) – log(baseline sST2).

A repeated measures model with terms for treatment, visit, visit by treatment, the logarithm of 
baseline sST2, the logarithm of baseline sST2 by visit and screening eosinophil strata will be 
fitted.
Model Checking & Diagnostics

Distributional assumptions underlying the model used for analysis will be examined by 
obtaining a normal probability plot of the residuals and a plot of the residuals versus the fitted 
values (i.e. checking the normality assumption and constant variance assumption of the model 
respectively) to gain confidence that the model assumptions are reasonable.
Model Results Presentation

The estimated treatment ratios together with 95% CIs (back-transformed from the differences 
on the log-scale).
Endpoint / Variables

Change from baseline in free sST2 (On-treatment)

Change from baseline in free sST2 (Post-treatment)
Strategy for Intercurrent (Post-Randomisation) Events
No intercurrent events are considered for this endpoint. All data will be used as collected. 
Model Specification

A repeated measures model with terms for treatment, visit, visit by treatment, baseline sST2, 
baseline sST2 by visit and screening eosinophil strata will be fitted.


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Model Checking & Diagnostics

Distributional assumptions underlying the model used for analysis will be examined by 
obtaining a normal probability plot of the residuals and a plot of the residuals versus the fitted 
values (i.e. checking the normality assumption and constant variance assumption of the model 
respectively) to gain confidence that the model assumptions are reasonable.
Model Results Presentation

The estimates of the mean and difference for each treatment group from the model will be 
produced, along with 95% confidence intervals and p-values for treatment comparisons.
Fractional Polynomials (Exploratory Analysis)
The role of free sST2 on the effectiveness of GSK3772847 with respect to loss of asthma 
control will be investigated, using the modified intent to treat population. The number of 
participants experiencing loss of control will be predicted at each level of baseline free 
sST2 based on a model including a free sST2 main effect term and an interaction with 
treatment term. 
Baseline free sST2 will be transformed using a fractional polynomial term which will be 
included in the model as a continuous covariate. A treatment group by free sST2 
covariate interaction will also be included in the model to allow the magnitude of the 
interaction (but not the order of the fractional polynomial transformation) to differ with 
each treatment group. The best fitting model will be selected based on likelihood. The 
selected best fitting model will be plotted as continuous free sST2 versus loss of asthma 
control in each treatment arm. The fit of the model to the raw data will be assessed 
visually.
10.2.
Exploratory Biomarker Analyses
10.2.1.
Endpoint / Variables

Changes from baseline in induced sputum biomarkers (subset) at weeks 8 and 16.

Changes from baseline in exploratory serum markers at weeks 8 and 16.
10.2.2.
Summary Measure
Change from baseline
10.2.3.
Population of Interest 
The exploratory biomarker analyses will be based on the modified Intent to Treat 
population, unless otherwise specified.


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10.2.4.
Strategy for Intercurrent (Post-Randomisation) Events
Not applicable.
10.2.5.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 10: List of Data Displays and 
will be based on GSK Data Standards and statistical principles.
Induced sputum biomarkers and exploratory serum markers at weeks 8 and 16 will be 
summarised using descriptive statistics, including the geometric mean and CV as well as 
listed.
No statistical analysis will be performed on this data.


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11.
REFERENCES
Charter for the Internal Safety Review Commitee (iSRC), Protocol 207597 Title:  A 
randomised, double-blind, parallel group, multicenter, stratified study assessing the 
efficacy and safety of repeat doses of GSK3772847 compared with placebo in 
participants with severe asthma, 26 June 2017
GlaxoSmithKline Document Number 2017N311825_02, Protocol: A randomised, 
double-blind, parallel group, multicenter, stratified study evaluating the efficacy and 
safety of repeat doses of GSK3772847 compared with placebo in participants with 
moderately severe asthma, 13 September 2017
Internal Safety Review Commitee (iSRC) Reporting and Analysis Plan for a randomised, 
double-blind, parallel group, multicenter, stratified study evaluating the efficacy and 
safety of repeat doses of GSK3772847 compared with placebo in participants with 
moderately severe asthma, 20 July 2018
Protocol Deviation Management Plan (PDMP), Version 01, 21 August 2017
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
The full list of protocol deviations collected on the eCRF is in the 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 epoch’s 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 16 visit or withdrew from treatment phase due to loss of asthma 
control
Follow up
Completed 12 week follow-up period
12.4.1.1.
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”


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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.
Post-Treatment 

Conmed Start Date > Study Treatment Last Dose Date + 28

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.
12.4.2.
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/mid207597/
Additional information of reporting areas:
data_look_01
This is where the blinded dry run will take place.
final_01: 
This is where the end of treatment phase analysis will take place.
final_02:
This is where the end of study analysis will take place.
Details of the reporting efforts used for the iSRC analysis are detailed in the separate iSRC RAP.
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


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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 not be included in summary tables and/or 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. 
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 
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. For 
pre-screen failures, age will be calculated at the pre-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.
Treatment Compliance for Fluticasone Propionate (FP) and Salmeterol (SAL)

Treatment compliance will be calculated based on the formula:  
Treatment Compliance = Number of Actual Doses / (Planned Treatment Duration in Days * 
Frequency)*100

Frequency is 2 for BID and 1 for QD. Treatment compliance could be greater than 100% if there are 
events of overdose. Cumulative compliance (since Day 1) by each background therapy will be 
calculated.

Planned Treatment Duration is defined according to the schedule of activities.

Compliance will be summarized by the following categories:
<80%, 
≥ 80% to < 95%, 
≥95% to <105%,
≥ 105% to <120% and
≥120%
PPD


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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.
Efficacy
Loss of Asthma Control
Multiple Loss of Asthma Control

If a participant reaches loss of control for multiple reasons then all reasons will be reported. For any 
time to loss of asthma control analysis, the time of the earliest component of loss of control will be used. 
Time of Loss of Asthma Control
Time to loss of control will be taken from the loss of control log page.


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12.6.4.
Safety
Adverse Events
Adverse Events of Special Interest (AESI)
Systemic Allergic/Hypersensitivity and Non-allergic Reactions:
Systemic allergic/hypersensitivity and non-allergic reactions are identifying through preferred terms which 
had been selected by medical review of the MedDRA dictionary and are provided in a separate 
spreadsheet.
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, 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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Rate of Events per 1000 Treatment Years
Rate of events per 1000 treatment years will be calculated using:
Rate = number of events * 1000 / total treatment exposure in years
where subjects can contribute more than one event.  
This is equivalent to: 
Rate = number of events * 1000 / (number of subjects in treatment group * mean treatment exposure in 
years).
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.
FEV1
Absolute Reversibility
Absolute reversibility (mL) = (post-bronchodilator FEV1 – pre-bronchodilator FEV1)
Percent Reversibility
Definition of Percentage Reversibility as a percentage of predicted FEV1 = ((post-bronchodilator FEV1– pre-
bronchodilator FEV1) / predicted FEV1) x 100%
Definition of Percentage Reversibility as a percentage of pre-bronchodilator FEV1 = ((post-bronchodilator 
FEV1– pre-bronchodilator FEV1) / pre-bronchodilator FEV1) x 100%


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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 either 
completing the 16 week treatment period and three month safety follow up, or 
withdrawing from the treatment period early due to loss of asthma control and 
completing the three month safety follow up period. 

Withdrawn participants were not replaced in the study, unless the participants were 
withdrawn due to sites failing to comply with GCP.

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.

Withdrawal visits will be slotted as per Appendix 3: Assessment Windows or will be 
summarised as withdrawal visits.


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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

If one of the five items in the ACQ 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 will be considered missing.  
SGRQ
The SGRQ questionnaire has three components; symptoms, activity and impact.
Symptoms

The Symptoms component will tolerate a maximum of 2 missed items. The weight for 
the missed item is subtracted from the total possible weight for the Symptoms 
component (662.5) and from the Total weight (3989.4)
Activity

The Activity component will tolerate a maximum of 4 missed items. The weight for the 
missed item is subtracted from the total possible weight for the Activity component 
(1209.1) and from the Total weight (3989.4)
Impacts

The Impacts component will tolerate a maximum of 6 missed items. The weight for the 
missed item is subtracted from the total possible weight for the Impacts component 
(2117.8) and from the Total weight (3989.4)
If any component has more missing items then mentioned above then the SGRQ will be 
considered missing.
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 
Events

The eCRF allows for the possibility of partial dates (i.e., only month and year) to be 
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.


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Element
Reporting Detail
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
ADaM
Analysis Data Model
AE
Adverse Event
A&R
Analysis and Reporting 
CDISC
Clinical Data Interchange Standards Consortium
CI
Confidence Interval
CS
Clinical Statistics
CSR
Clinical Study Report
CVb / CVw
Coefficient of Variation (Between) / Coefficient of Variation (Within)
DBF
Database Freeze
DBR
Database Release
DOB
Date of Birth
DP
Decimal Places
eCRF
Electronic Case Record Form
EMA
European Medicines Agency
FDA
Food and Drug Administration
FDAAA
Food and Drug Administration Clinical Results Disclosure Requirements
GSK
GlaxoSmithKline
IA
Interim Analysis
ICH
International Conference on Harmonization
IDSL
Integrated Data Standards Library
IMMS
International Modules Management System
IP
Investigational Product
mIT
Modified Intent-to-Treat excluding GCP non-compliant subjects
mITT_LoC
Modified Intent-to-Treat excluding GCP non-compliant subjects (Loss of 
Control)
MMRM
Mixed Model Repeated Measures
PCI
Potential Clinical Importance 
PD
Pharmacodynamic
PDMP
Protocol Deviation Management Plan
PK
Pharmacokinetic
QC
Quality Control
QTcF
Frederica’s QT Interval Corrected for Heart Rate
RAP
Reporting & Analysis Plan
RAMOS
Randomisation & Medication Ordering System 
SAC
Statistical Analysis Complete
SAFF_ALL
Safety including site including GCP non-compliant subjects
SDTM
Study Data Tabulation Model
SOP
Standard Operation Procedure
TA
Therapeutic Area
TFL
Tables, Figures & Listings 


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12.9.2.
Trademarks
Trademarks of the GlaxoSmithKline 
Group of Companies
Trademarks not owned by the 
GlaxoSmithKline Group of 
Companies
None
NONMEM
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
Pharmacodynamic or Biomarker
6.1 to 6.n
6.1 to 6.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 11: 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
Pharmacodynamic or Biomarker
PD_Fn
PD_Tn
PD_Ln
NOTES: 

Non-Standard displays are indicated in the ‘IDSL /  Example Shell’ or ‘Programming Notes’ column as ‘[Non-
Standard] + Reference.’
12.10.3.
Deliverables
Delivery [Priority] [1]
Description
ETP [1]
End of Treatment Phase Statistical Analysis Complete
SAC [1]
Final Statistical Analysis Complete
NOTES: 
1.
Indicates priority (i.e. order) in which displays will be generated for the reporting effort


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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
1.1.
SAFF_ALL
ES8 
Summary of Subject Status and Reason for Study Withdrawal
ICH E3, FDAAA, EudraCT
ETP, SAC
1.2.
SAFF_ALL
SD4
Summary of Treatment Status and Reasons for Discontinuation 
of Study Treatment
ICH E3
ETP, SAC
1.3.
SAFF_ALL
ES4
Summary of Subject Disposition at Each Study Epoch
ICH E3
ETP, SAC
1.4.
ASE
ES6
Summary of Screening/Run-in Status and Reasons for 
Screen/Run-in Failure
Journal Requirements
ETP, SAC
1.5.
Enrolled
NS1
Summary of Number of Subjects by Country and Site ID
EudraCT/Clinical Operations
ETP, SAC
1.6.
SAFF_ALL
NS1
Summary of Number of Subjects by Country and Site ID
EudraCT/Clinical Operations
ETP, SAC
Protocol Deviation
1.7.
SAFF_ALL
DV1
Summary of Important Protocol Deviations
ICH E3
ETP, SAC
1.8.
SAFF_ALL
IE1
Summary of Inclusion/ Exclusion Deviations 
ICH E3
ETP, SAC
Population Analysed
1.9.
Enrolled
SP1
Summary of Study Populations 
IDSL
ETP, SAC
Demographic and Baseline Characteristics
1.10.
SAFF_ALL
DM1 
Summary of Demographic Characteristics
ICH E3, FDAAA, EudraCT
ETP, SAC
1.11.
Enrolled
DM11
Summary of Age Ranges
EudraCT
ETP, SAC
1.12.
SAFF_ALL
DM5
Summary of Race and Racial Combinations
ICH E3, FDA, FDAAA, EudraCT
ETP, SAC
Prior and Concomitant Medications
1.13.
SAFF_ALL
MH4
Summary of Current Medical Conditions
ICH E3 
ETP, SAC


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Study Population Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
1.14.
SAFF_ALL
MH4
Summary of Past Medical Conditions
ICH E3 
ETP, SAC
1.15.
SAFF_ALL
SP07
Summary of Family History of Cardiovascular Risk Factors at 
Screening
ETP, SAC
1.16.
SAFF_ALL
POP_T01
Summary of Disease Duration and Exacerbation History
ETP, SAC
1.17.
SAFF_ALL
SU1
Summary of Smoking History at Screening
ETP, SAC
1.18.
SAFF_ALL
CM1
Summary of Pre-Treatment Concomitant Medications
ICH E3
ETP, SAC
1.19.
SAFF_ALL
CM1
Summary of On-Treatment Concomitant Medications
ICH E3
ETP, SAC
1.20.
SAFF_ALL
CM1
Summary of Post-Treatment Concomitant Medications
ICH E3
ETP, SAC
1.21.
SAFF_ALL
CM1
Summary of On-Treatment Asthma Concomitant Medications
ICH E3
ETP, SAC
1.22.
SAFF_ALL
CM1
Summary of Post-Treatment Asthma Concomitant Medications
ICH E3
ETP, SAC
Pre-Treatment Lung Function
1.23.
SAFF_ALL
POP_T02
Summary of Screening Lung Function
Include Pre- and Post- albuterol 
(salbutamol) FEV1, FVC, FEV1/FVC and 
% Predicted Normal and post-BD at 
screening %predicted. Include overall 
and by treatment group.
ETP, SAC
1.24.
SAFF_ALL
POP_T03
Summary of Baseline Lung Function
FEV1, FVC, FEV1/FVC and % Predicted 
Normal. Include overall and by 
treatment group.
ETP, SAC
Exposure and Treatment Compliance
1.25.
SAFF_ALL
EX1
Summary of Exposure and Compliance to Background Therapy 
(FP and SAL)
ICH E3
ETP, SAC


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12.10.5.
Efficacy Tables
Efficacy: Tables
No.
Population
IDSL /  
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Exposure
2.1.
SAFF_ALL
EX1 
Summary of Exposure to Study Treatment
ICH E3
ETP, SAC
Primary Endpoint: Loss of Asthma Control Weeks 0-16
2.2.
mITT_LoC
EFF_T01
Summary of Loss of Asthma Control 
Include overall loss of control, each 
component and the combination of 
exacerbation or inability to titrate.
ETP, SAC
2.3.
mITT_LoC
EFF_T02
Summary of Intercurrent Events 
ETP, SAC
2.4.
mITT_LoC
EFF_T03
Bayesian Analysis of Loss of Asthma Control Over Weeks 0-16 
(Primary Estimand)
ETP, SAC
2.5.
mITT_LoC
EFF_T04
Frequentist Analysis of Loss of Asthma Control Over Weeks 0-
16 (Primary Estimand)
ETP, SAC
2.6.
mITT_LoC
EFF_T03
Bayesian Analysis of Loss of Asthma Control Over Weeks 0-16 
(Secondary Estimand)
ETP, SAC
2.7.
mITT_LoC
EFF_T04
Frequentist Analysis of Loss of Asthma Control Over Weeks 0-
16 (Secondary Estimand)
ETP, SAC
Secondary Endpoint: Loss of Asthma Control Weeks 0-6
2.8.
mITT_LoC
EFF_T03 
Bayesian Analysis of Loss of Asthma Control Over Weeks 0-6 
(Primary Estimand)
ETP, SAC
2.9.
mITT_LoC
EFF_T04
Frequentist Analysis of Loss of Asthma Control Over Weeks 0-6 
(Primary Estimand)
ETP, SAC
2.10.
mITT_LoC
EFF_T03
Bayesian Analysis of Loss of Asthma Control Over Weeks 0-6 
(Secondary Estimand)
ETP, SAC


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Efficacy: Tables
No.
Population
IDSL /  
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
2.11.
mITT_LoC
EFF_T04
Frequentist Analysis of Loss of Asthma Control Over Weeks 0-6 
(Secondary Estimand)
ETP, SAC
Secondary Endpoints: Components of Loss of Asthma Control
2.12.
mITT_LoC
EFF_T03
Analysis of Proportion of Subjects with an ACQ increase from 
Baseline >= 0.5 (Primary Estimand)
ETP, SAC
2.13.
mITT_LoC
EFF_T03
Analysis of Proportion of Subjects with an ACQ increase from 
Baseline >= 0.5 (Secondary Estimand)
ETP, SAC
2.14.
mITT_LoC
EFF_T03
Analysis of Proportion of Subjects with an FEV1 decrease from 
Baseline > 7.5% (Primary Estimand)
ETP, SAC
2.15.
mITT_LoC
EFF_T03
Analysis of Proportion of Subjects with an FEV1 decrease from 
Baseline > 7.5% (Secondary Estimand)
ETP, SAC
2.16.
mITT_LoC
EFF_T03
Analysis of Proportion of Subjects with an Inability to Titrate 
According to the Pre-Defined Schedule (Primary Estimand)
ETP, SAC
2.17.
mITT_LoC
EFF_T03
Analysis of Proportion of Subjects with an Inability to Titrate 
According to the Pre-Defined Schedule (Secondary Estimand)
ETP, SAC
2.18.
mITT_LoC
EFF_T03
Analysis of Proportion of Subjects with a Significant Asthma 
Exacerbation (Primary Estimand)
ETP, SAC
2.19.
mITT_LoC
EFF_T03
Analysis of Proportion of Subjects with a Significant Asthma 
Exacerbation (Secondary Estimand)
ETP, SAC
2.20.
mITT_LoC
EFF_T03
Analysis of Proportion of Subjects with a Significant Asthma 
Exacerbation or Inability to Titrate According to the Pre-Defined 
Schedule (Primary Estimand)
ETP, SAC
2.21.
mITT_LoC
EFF_T03
Analysis of Proportion of Subjects with a Significant Asthma 
Exacerbation or Inability to Titrate According to the Pre-Defined 
Schedule (Secondary Estimand)
ETP, SAC


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Efficacy: Tables
No.
Population
IDSL /  
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Secondary Endpoints: Time to Loss of Asthma Control
2.22.
mITT_LoC
EFF_T05
Summary and Analysis of Time to Loss of Asthma Control 
(Primary Estimand)
ETP, SAC
2.23.
mITT_LoC
EFF_T05
Summary and Analysis of Time to Loss of Asthma Control 
(Secondary Estimand)
ETP, SAC
Secondary Endpoints: Hospitalisation and Emergency Room Visits
2.24.
mITT
EFF_T06
Summary and Rate of Asthma-Related On-Treatment 
Hospitalisations and Emergency Room Visits (Primary 
Estimand)
ETP, SAC
Secondary Endpoint: ACQ-5
2.25.
mITT
EFF_T07
Summary of Raw and Change from Baseline in ACQ-5 Total 
Score (Primary Estimand)
ETP, SAC
2.26.
mITT
EFF_T04
Analysis of Proportion of Subjects with an ACQ-5 Total Score 
increase from Baseline >= 0.5 (Primary Estimand)
ETP, SAC
2.27.
mITT
EFF_T04
Analysis of Proportion of Subjects with an ACQ-5 Total Score 
increase from Baseline >= 0.5 (Secondary Estimand)
ETP, SAC
Secondary Endpoint: SGRQ
2.28.
mITT
EFF_T07 
Summary of Raw and Change from Baseline in SGRQ Total 
Score (Primary Estimand)
ETP, SAC
2.29.
mITT
EFF_T04
Analysis of Proportion of Subjects with an SGRQ Total Score 
increase from Baseline >= 4 (Primary Estimand)
ETP, SAC
2.30.
mITT
EFF_T04
Analysis of Proportion of Subjects with an SGRQ Total Score 
decrease from Baseline >= 4 (Secondary Estimand)
ETP, SAC


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Efficacy: Tables
No.
Population
IDSL /  
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Secondary Endpoint: FEV1 and PEF
2.31.
mITT
EFF_T07
Summary of Raw and Change from Baseline FEV1 (Primary 
Estimand)
ETP, SAC
2.32.
mITT
EFF_T08
Analysis of Change from Baseline in FEV1 up to Week 4(Primary 
Estimand)
ETP, SAC
2.33.
mITT
EFF_T07
Summary of Raw and Change from Baseline Fractional 
Exhaled Nitric Oxide (FeNO) (Primary Estimand)
ETP, SAC
2.34.
mITT
EFF_T08 
Analysis of Change from Baseline in Fractional Exhaled Nitric 
Oxide (FeNO) up to Week 4 (Primary Estimand)
ETP, SAC
Secondary Endpoint: Exacerbations
2.35.
mITT
EFF_T09
Summary of On-Treatment Asthma Exacerbations 
ETP, SAC
Secondary Endpoint: Eosinophils
2.36.
mITT
EFF_T07
Summary of Raw and Change from Baseline in Eosinophils 
(Primary Estimand)
ETP, SAC
2.37.
mITT
EFF_T08
Analysis of Eosinophils (Primary Estimand)
ETP, SAC
Secondary Endpoint: PEF, Daytime Symptom Score, Night-time Symptom Score and Rescue Medication 
2.38.
mITT
EFF_T010
Summary of Raw and Change from Baseline in Mean Morning 
Peak Expiratory Flow (PEF) 
ETP, SAC
2.39.
mITT
EFF_T010
Summary of Raw and Change from Baseline in Mean Evening 
Peak Expiratory Flow (PEF)  
ETP, SAC
2.40.
mITT
EFF_T010
Summary of Raw and Change from Baseline in Mean Daytime 
Asthma Symptom Score
ETP, SAC
2.41.
mITT
EFF_T010
Summary of Raw and Change from Baseline in Night-Time
Awakenings Due to Asthma Symptoms
ETP, SAC


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Efficacy: Tables
No.
Population
IDSL /  
Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
2.42.
mITT
EFF_T010
Summary of Raw and Change from Baseline in Mean Rescue 
Medication use (Albuterol/Salbutamol)
ETP, SAC
12.10.6.
Efficacy Figures
Efficacy: Figures
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Primary Endpoint: Loss of Asthma Control 
2.1
mITT_LoC
Plot of Loss of Asthma Control (Primary Estimand)
Include Show overall and components 
of loss on control
ETP, SAC
2.2
mITT_LoC
Plot of Loss of Asthma Control (Secondary Estimand)
Include Show overall and components 
of loss on control
ETP, SAC
Secondary Endpoint: Time to Loss of Control
2.1.
mITT_LoC
Kaplan-Meir Plot of Time to Loss of Asthma Control (Primary 
Estimand)
ETP, SAC
2.2.
mITT_LoC
Kaplan-Meir Plot of Time to Loss of Asthma Control (Secondary 
Estimand)
ETP, SAC
Secondary Endpoint: Eosinophils
2.3.
mITT_LoC
Cumulative Density Plot of Eosinophils
ETP, SAC
2.4.
mITT_LoC
Loss of Control Over Weeks 0-16 vs Eosinophils by Treatment –
Fractional Polynomial Model (Primary Estimand)
ETP, SAC
2.5.
mITT_LoC
Loss of Control Over Weeks 0-16 vs Eosinophils – Fractional 
Polynomial Treatment Difference (Primary Estimand)
ETP, SAC
2.6.
mITT_LoC
Loss of Control Over Weeks 0-16 vs Eosinophils by Treatment –
Fractional Polynomial Model (Secondary Estimand)
ETP, SAC


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Efficacy: Figures
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
2.7.
mITT_LoC
Loss of Control Over Weeks 0-16 vs Eosinophils – Fractional 
Polynomial Treatment Difference (Secondary Estimand)
ETP, SAC
2.8.
mITT_LoC
Loss of Control Over Weeks 0-6 vs Eosinophils by Treatment –
Fractional Polynomial Model (Primary Estimand)
ETP, SAC
2.9.
mITT_LoC
Loss of Control Over Weeks 0-6 vs Eosinophils – Fractional 
Polynomial Treatment Difference (Primary Estimand)
ETP, SAC
2.10.
mITT_LoC
Loss of Control Over Weeks 0-6 vs Eosinophils by Treatment –
Fractional Polynomial Model (Secondary Estimand)
ETP, SAC
2.11.
mITT_LoC
Loss of Control Over Weeks 0-6 vs Eosinophils – Fractional 
Polynomial Treatment Difference (Secondary Estimand)
ETP, SAC
Secondary Endpoints: IgE and FeNO Over Weeks 0-16
2.12.
mITT_LoC
Loss of Control Over Weeks 0-16 vs IgE by Treatment -
Fractional Polynomial Model (Primary Estimand)
ETP, SAC
2.13.
mITT_LoC
Loss of Control Over Weeks 0-16 vs IgE – Fractional Polynomial 
Treatment Difference (Primary Estimand)
ETP, SAC
2.14.
mITT_LoC
Loss of Control Over Weeks 0-16 vs IgE by Treatment –
Fractional Polynomial Model (Secondary Estimand)
ETP, SAC
2.15.
mITT_LoC
Loss of Control Over Weeks 0-16 vs IgE – Fractional Polynomial 
Treatment Difference (Secondary Estimand)
ETP, SAC
2.16.
mITT_LoC
Loss of Control Over Weeks 0-16 vs FeNO by Treatment –
Fractional Polynomial Model (Primary Estimand)
ETP, SAC
2.17.
mITT_LoC
Loss of Control Over Weeks 0-16 vs FeNO – Fractional 
Polynomial Treatment Difference (Primary Estimand)
ETP, SAC
2.18.
mITT_LoC
Loss of Control Over Weeks 0-16 vs FeNO by Treatment –
Fractional Polynomial Model (Secondary Estimand)
ETP, SAC


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Efficacy: Figures
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
2.19.
mITT_LoC
Loss of Control Over Weeks 0-16 vs FeNO – Fractional 
Polynomial Treatment Difference (Secondary Estimand)
ETP, SAC
2.20.
mITT
FEV1 at Week 4 vs Eosinophils by Treatment – Fractional 
Polynomial Model
ETP, SAC
2.21.
mITT
FEV1 at Week vs Eosinophils – Fractional Polynomial Treatment 
Difference
ETP, SAC
2.22.
mITT
FEV1 at Week 4 vs IgE by Treatment – Fractional Polynomial 
Model
ETP, SAC
2.23.
mITT
FEV1 at Week vs IgE – Fractional Polynomial Treatment 
Difference
ETP, SAC
2.24.
mITT
FEV1 at Week 4 vs FeNO by Treatment – Fractional Polynomial 
Model
ETP, SAC
2.25.
mITT
FEV1 at Week vs FeNO – Fractional Polynomial Treatment 
Difference
ETP, SAC
12.10.7.
Safety Tables
Safety: Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Adverse Events (AEs)
3.1.
SAFF_ALL
SAFE_T01
Overview of On-treatment Adverse Events During the Study
ETP, SAC
3.2.
SAFF_ALL
AE1
Summary of All Pre-treatment Adverse Events by System Organ 
Class and Preferred Term
ETP, SAC


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Safety: Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
3.3.
SAFF_ALL
AE1
Summary of All On-treatment Adverse Events by System Organ 
Class and Preferred Term
ICH E3
ETP, SAC
3.4.
SAFF_ALL
AE1
Summary of All Post-treatment Adverse Events by System 
Organ Class and Preferred Term
ICH E3
ETP, SAC
3.5.
SAFF_ALL
AE1
Summary of All On-treatment Adverse Events Leading to 
Permanent Discontinuation of Study Treatment by System 
Organ Class and Preferred Term
ICH E3
ETP, SAC
3.6.
SAFF_ALL
AE1
Summary of All On-treatment Adverse Events Leading to 
Withdrawal from Study by System Organ Class and Preferred 
Term
ICH E3
ETP, SAC
3.7.
SAFF_ALL
AE1
Summary of All On-treatment Fatal Adverse Events by System 
Organ Class and Preferred Term
ICH E3
ETP, SAC
3.8.
SAFF_ALL
AE3
Summary of All On-treatment Common (>=3%) Adverse Events 
by Overall Frequency
ICH E3
ETP, SAC
3.9.
SAFF_ALL
AE1 
Summary of All On-treatment Drug-Related Adverse Events by 
System Organ Class and Preferred Term
ICH E3
ETP, SAC
3.10.
SAFF_ALL
AE15
Summary of All On-treatment Common (>=3%) Non-serious 
Adverse Events by System Organ Class and Preferred Term 
(Number of Participant and Occurrences)
FDAAA, EudraCT
ETP, SAC
3.11.
SAFF_ALL
AE1
Summary of All Pre-treatment Serious Adverse Events by 
System Organ Class and Preferred Term
ETP, SAC
3.12.
SAFF_ALL
AE1
Summary of All On-treatment Serious Adverse Events by 
System Organ Class and Preferred Term
ICH E3
ETP, SAC
3.13.
SAFF_ALL
AE1
Summary of All Post-treatment Serious Adverse Events by 
System Organ Class and Preferred Term
ICH E3
ETP, SAC


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Safety: Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
3.14.
SAFF_ALL
AE16
Summary of All On-treatment Serious Adverse Events by 
System Organ Class and Preferred Term (Number of 
Participants and Occurrences)
FDAAA, EudraCT
ETP, SAC
3.15.
SAFF_ALL
AE1
Summary of All On-treatment Serious Adverse Events Leading 
to Permanent Discontinuation of Study Treatment by System 
Organ Class and Preferred Term 
IDSL
ETP, SAC
3.16.
SAFF_ALL
AE1
Summary of All On-treatment Serious Adverse Events Leading 
to Withdrawal from Study by System Organ Class and Preferred 
Term 
IDSL
ETP, SAC
Adverse Events of Special Interest (AESIs)
3.17.
SAFF_ALL
AE1
Summary of On-treatment Adverse Events of Special Interest
IDSL
ETP, SAC
3.18.
SAFF_ALL
AE1
Summary of On-treatment Serious Adverse Events of Special 
Interest
IDSL
ETP, SAC
3.19.
SAFF_ALL
AE1
Summary of Post-treatment Adverse Events of Special Interest
IDSL
ETP, SAC
3.20.
SAFF_ALL
AE1
Summary of Post-treatment Serious Adverse Events of Special 
Interest
IDSL
ETP, SAC
Mexico Specific Tables
3.21.
SAFF_ALL
Summary of Suspected Investigational Product Adverse 
Reaction (Mexican Participants Only)
ETP, SAC
3.22.
SAFF_ALL
Summary of Suspected Investigational Product Adverse 
Reaction (Non-Mexican Participants)
ETP, SAC
Laboratory: Chemistry 
3.23.
SAFF_ALL
LB1
Summary of Clinical Chemistry
ICH E3
ETP, SAC
3.24.
SAFF_ALL
LB1
Summary of Change from Baseline in Clinical Chemistry
ICH E3
ETP, SAC


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Safety: Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
3.25.
SAFF_ALL
LB16
Summary of Worst Case Chemistry Results Relative to Normal 
Range Post-Baseline Relative to Baseline
ICH E3
ETP, SAC
Laboratory: Hematology and Cardiac Markers
3.26.
SAFF_ALL
LB1
Summary of Hematology and Cardiac Markers 
ICH E3
ETP, SAC
3.27.
SAFF_ALL
LB1
Summary of Changes from Baseline in Hematology and Cardiac 
Markers
ICH E3
ETP, SAC
3.28.
SAFF_ALL
LB16
Summary of Worst Case Hematology and Cardiac Markers 
Results Relative to Normal Range Post-Baseline Relative to 
Baseline
ICH E3
ETP, SAC
Laboratory: Hepatobiliary (Liver)
3.29.
SAFF_ALL
LIVER1
Summary of Liver Monitoring/Stopping Event Reporting
IDSL
ETP, SAC
3.30.
SAFF_ALL
LIVER10
Summary of Hepatobiliary Laboratory Abnormalities
IDSL
ETP, SAC
ECG
3.31.
SAFF_ALL
Summary of Antihistamine, Decongestant and Caffeine Use 
Prior to ECG assessments
ETP, SAC
3.32.
SAFF_ALL
EG1
Summary of ECG Findings 
IDSL
ETP, SAC
3.33.
SAFF_ALL
EG2
Summary of ECG Values by Visit
IDSL
ETP, SAC
3.34.
SAFF_ALL
EG2
Summary of Change from Baseline in ECG Values by Visit
IDSL
ETP, SAC
3.35.
SAFF_ALL
EG10
Summary of Maximum QTcF Values Post-Baseline Relative to 
Baseline by Category
IDSL
ETP, SAC


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Safety: Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
3.36.
SAFF_ALL
EG11
Summary of Maximum Increase in QTcF Values Post-Baseline 
Relative to Baseline by Category
IDSL
ETP, SAC
Holter
3.37.
SAFF_ALL
HM1
Summary of Holter Interpretations
IDSL
ETP, SAC
3.38.
SAFF_ALL
HM2
Summary of Holter Abnormalities
IDSL
ETP, SAC
3.39.
SAFF_ALL
HM3
Summary of Holter Values
IDSL
ETP, SAC
3.40.
SAFF_ALL
HM3
Summary of Change from Baseline in Holter Values
IDSL
ETP, SAC
3.41.
SAFF_ALL
HM4
Summary of Subjects with R-on-T Beats
IDSL
ETP, SAC
Vital Signs
3.42.
SAFF_ALL
VS1
Summary of Vital Signs
ICH E3
ETP, SAC
3.43.
SAFF_ALL
VS1
Summary of Change from Baseline in Vital Signs
ICH E3
ETP, SAC
3.44.
SAFF_ALL
VS1
Summary of Change from Pre-dose to Post-dose in Vital Signs
ICH E3
ETP, SAC


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12.10.8.
Pharmacokinetic Tables
Pharmacokinetic: Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Secondary: Pharmacokinetic
4.1.
PK
Summary of PK Serum Concentrations
SAC only


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12.10.9.
Pharmacodynamic and Biomarker Tables
Pharmacodynamic and Biomarker: Tables
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Secondary: Pharmacodynamic
6.1.
mITT
Summary of Raw and Percentage Change from Baseline in Free 
Soluble ST2 concentration (ng/mL) (On-treatment)
Pre and Post dose.
ETP, SAC
6.2.
mITT
Analysis of Percentage Change from Baseline in Free Soluble 
ST2 concentration (ng/mL) (On-treatment)
Pre dose only. 
ETP, SAC
6.3.
mITT
Summary of Raw and Percentage Change from Baseline in Free 
soluble ST2 concentration (ng/mL) (Post-treatment)
ETP, SAC
6.4.
mITT
Analysis of Percentage Change from Baseline in Free soluble 
ST2 concentration (ng/mL) (Post-treatment)
ETP, SAC
6.5.
mITT
Summary of Raw and Change from Baseline in Total Soluble 
ST2 concentration (ng/mL) (On-treatment)
Pre and Post dose.
ETP, SAC
6.6.
mITT
Analysis of Change from Baseline in Total Soluble ST2 
concentration (ng/mL) (On-treatment)
Pre dose only. 
ETP, SAC
6.7.
mITT
Summary of Raw and Change from Baseline in Total Soluble 
ST2 concentration (ng/mL) (Post-treatment)
ETP, SAC
6.8.
mITT
Analysis of Change from Baseline in Total Soluble ST2 
concentration (ng/mL) (Post-treatment)
ETP, SAC
Exploratory: Biomarkers
6.9.
mITT
Summary and Change from Baseline in Induced Sputum 
Biomarkers (subset) at Weeks 8 and 16
Include geometric mean and %CV
ETP, SAC
6.10.
mITT
Summary and Change from Baseline in Exploratory Serum 
Markers at Weeks 8 and 16
Include geometric mean and %CV
ETP, SAC


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12.10.10. Pharmacokinetic Figures
Pharmacokinetic: Figures
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Secondary: Pharmacokinetic
6.1.
PK
Plot of Serum Concentrations
ETP, SAC
6.2.
PK
Pre-dose Trough Concentration vs Eosinophils at Week 4
ETP, SAC
6.3.
PK
Pre-dose Trough Concentration vs FeNO at Week 4
ETP, SAC
6.4.
PK
Pre-dose Trough Concentration vs IgE at Week 4
ETP, SAC


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12.10.11. Pharmacodynamic and Biomarker Figures
Pharmacokinetic: Figures
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Secondary: Pharmacokinetic
6.5.
mITT
Plot of Percentage Change from Baseline in Free Soluble ST2 
levels (On-treatment)
ETP, SAC
6.6.
mITT
Plot of Percentage Change from Baseline in Free soluble ST2 
levels (Post-treatment)
ETP, SAC
6.7.
mITT
Plot of Change from Baseline in Total Soluble ST2 levels (On-
treatment)
ETP, SAC
6.8.
mITT
Plot of Change from Baseline in Total Soluble ST2 levels (Post-
treatment)
ETP, SAC
6.9.
mITT_LoC
Loss of Control vs Free soluble ST2 by Treatment – Fractional 
Polynomial Model (Primary Estimand)
ETP, SAC
6.10.
mITT_LoC
Loss of Control vs Free soluble ST2 Treatment Difference –
Fractional Polynomial (Primary Estimand)
ETP, SAC
6.11.
mITT_LoC
Loss of Control vs Free soluble ST2 by Treatment – Fractional 
Polynomial Model (Secondary Estimand)
ETP, SAC
6.12.
mITT_LoC
Loss of Control vs Free soluble ST2 Treatment Difference –
Fractional Polynomial (Secondary Estimand)
ETP, SAC


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12.10.12. 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
ETP, SAC
2.
SAFF_ALL
ES2 / ES3
Listing of Reasons for Study Withdrawal
ICH E3
ETP, SAC
3.
SAFF_ALL
SD2/SD3
Listing of Reasons for Study Treatment Discontinuation
ICH E3
ETP, SAC
4.
SAFF_ALL
BL1 / BL2
Listing of Participants for Whom the Treatment Blind was Broken
ICH E3
ETP, SAC
5.
SAFF_ALL
TA1 / CP_RD1x
Listing of Planned and Actual Treatments
IDSL
ETP, SAC
Protocol Deviations
6.
SAFF_ALL
DV2
Listing of Important Protocol Deviations 
ICH E3
ETP, SAC
7.
SAFF_ALL
IE3 
Listing of Subjects with Inclusion/Exclusion Criteria Deviations
ICH E3
ETP, SAC
8.
SAFF_ALL
Listing of Subjects excluded for GCP non-compliance
Populations Analysed
9.
SAFF_ALL
SP3
Listing of Participants Excluded from Any Population
ICH E3.
ETP, SAC
Demographic and Baseline Characteristics
10.
SAFF_ALL
DM2
Listing of Demographic Characteristics
ICH E3
ETP, SAC
11.
SAFF_ALL
DM9 
Listing of Race
ICH E3
ETP, SAC


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ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Prior and Concomitant Medications
12.
SAFF_ALL
CP_CM3
Listing of Concomitant Medications
IDSL
ETP, SAC
Exposure and Treatment Compliance
13.
SAFF_ALL
EX3
Listing of Exposure Data
ICH E3
ETP, SAC
Adverse Events
14.
SAFF_ALL
AE8 
Listing of All Adverse Events
ICH E3
ETP, SAC
15.
SAFF_ALL
AE7
Listing of Subject Numbers for Individual Adverse Events
ICH E3
ETP, SAC
16.
SAFF_ALL
AE8
Listing of Adverse Events Leading to Withdrawal from Study / 
Permanent Discontinuation of Study Treatment
ICH E3
ETP, SAC
17.
SAFF_ALL
AE2
Listing of Relationship Between Adverse Event System Organ 
Classes, Preferred Terms, and Verbatim Text
IDSL
ETP, SAC
Serious and Other Significant Adverse Events
18.
SAFF_ALL
AE8
Listing of Fatal Serious Adverse Events
ICH E3
ETP, SAC
19.
SAFF_ALL
AE8
Listing of Non-Fatal Serious Adverse Events
ICH E3
ETP, SAC
20.
SAFF_ALL
AE14
Listing of Reasons for Considering as a Serious Adverse Event
ICH E3
ETP, SAC
21.
SAFF_ALL
AE8
Listing of Serious Adverse Events Leading to Withdrawal from 
Study / Permanent Discontinuation of Study Treatment
ICH E3
ETP, SAC
22.
SAFF_ALL
AE8
Listing of Other Significant Adverse Events
ICH E3
ETP, SAC


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ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Hepatobiliary (Liver)
23.
SAFF_ALL
MH2
Listing of Medical Conditions for Participants with Liver Stopping 
Events
IDSL
ETP, SAC
24.
SAFF_ALL
SU2
Listing of Substance Use for Participants with Liver Stopping 
Events
IDSL
ETP, SAC
All Laboratory
25.
SAFF_ALL
LB5 / LB6
Listing of All Laboratory Data for Participants with Any Value 
Outside Normal Range
ICH E3
ETP, SAC
26.
SAFF_ALL
LB14
Listing of Laboratory Data with Character Results
ICH E3
ETP, SAC
ECG
27.
SAFF_ALL
EG5
Listing of All ECG Findings for Participants with an Abnormal 
ECG Finding
IDSL
ETP, SAC
28.
SAFF_ALL
EG5 
Listing of Abnormal ECG Findings
IDSL
ETP, SAC
Holter
29.
SAFF_ALL
MH6
Listing of Holter R-on-T Beat Data 
IDSL
ETP, SAC
30.
SAFF_ALL
MH7
Listing of Holter {Supraventricular} {Ventricular} Event Data 
IDSL, Update title as appropriate based 
on data
ETP, SAC
31.
SAFF_ALL
MH8
Listing of Holter {Sustained} {Non-sustained} {Supraventricular} 
{Ventricular} Run
IDSL, Update title as appropriate based 
on data
ETP, SAC
32.
SAFF_ALL
MH9
Listing of Holter Atrial {Fibrillation} {Flutter} Data 
IDSL, Update title as appropriate based 
on data
ETP, SAC
33.
SAFF_ALL
MH10
Listing of Holter Abnormalities
IDSL
ETP, SAC


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ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Vital Signs
34.
SAFF_ALL
VS4 
Listing of All Vital Signs Data 
IDSL
ETP, SAC
Primary Analysis Data: Loss of Asthma Control and Intercurrent Events
35.
mITT_LoC
Listing of Loss of Asthma Control
Include all reasons for loss of control 
and time to loss of asthma control
ETP, SAC
36.
mITT_LoC
Listing of Intercurrent Events
Include treatment subject was analysed 
as taking and treatment at time of loss 
of control
ETP, SAC


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12.10.13. Non-ICH Listings
Non-ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Study Population
37.
SAFF_ALL
SP2
Listing of the Follow-up Contact
ETP, SAC
38.
SAFF_ALL
TA1
Listing of Treatment Misallocations
Change Centre ID to Investigator 
ID: xxxxxx and also Investigator at 
Centre: xxxxxx 
ETP, SAC
39.
SAFF_ALL
SP4
Listing of Overall Percentage Treatment Compliance
ETP, SAC
Secondary Efficacy
40.
mITT
Listing of Eosinophils
Include randomisation and analysis 
strata
ETP, SAC
41.
mITT
SP10
Listing of Lung Function Results including FEV1
ETP, SAC
42.
mITT
S3
Listing of Asthma Exacerbations 
Include a column for severity 
ETP, SAC
43.
mITT
Listing of Asthma Control Questionnaire (ACQ-5) 
ETP, SAC
44.
mITT
Listing of St George’s Respiratory Questionnaire (SGRQ)
ETP, SAC
45.
mITT
Listing of Peak Exploratory Flow (PEF)
ETP, SAC
46.
mITT
Listing of Fractional Exhaled Nitric Oxide (FeNO)
ETP, SAC
47.
mITT
Listing of Daytime and Night-time Asthma Symptoms
ETP, SAC
48.
mITT
Listing of Rescue Medication Use
ETP, SAC
49.
mITT
Listing of Hospitalisations and Emergency Room Visits
ETP, SAC
50.
PK
Listing of Serum Concentration 
SAC Only
51.
PD
List of Free and Total Soluble ST2 Levels


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Non-ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Adverse Events
52.
SAFF_ALL
Listing of Clinical Chemistry
ETP, SAC
53.
SAFF_ALL
Listing of Haematology and Cardiac Markers
ETP, SAC
54.
SAFF_ALL
Listing of Anti-GSK3772847 Antibodies
ETP, SAC
55.
SAFF_ALL
ESI8
Listing of AE Terms of Special Interest 
IDSL
ETP, SAC
Exploratory Biomarker
56.
mITT
Listing of Induced Sputum and Exploratory Serum Biomarkers
ETP, SAC
Medical History
mITT
57.
SAFF_ALL
MH2
Listing of Medical Conditions at Screening
ETP, SAC
58.
SAFF_ALL
SP5
Listing of Family History of Cardiovascular Risk Factors
ETP, SAC
59.
SAFF_ALL
SP6
Listing of Asthma History
ETP, SAC
60.
SAFF_ALL
SP7
Listing of Smoking History and Smoking Status
ETP, SAC
61.
SAFF_ALL
CM6
Relationship between ATC Level 1, Ingredient and Verbatim 
Text for Bone Mineral Density and Other Medications
ETP, SAC
Liver Events: Note only produced if there is a Liver Event
62.
SAFF_ALL
VS4
Listing of Liver Events
ETP, SAC
63.
SAFF_ALL
VS4
Listing of Liver Event Information for RUCAM Score
ETP, SAC
64.
SAFF_ALL
VS4
Listing of Liver Biopsy
ETP, SAC
65.
SAFF_ALL
VS4
Listing of Liver Imaging Details
ETP, SAC
Cardiovascular Events: Note only produced if there is a Cardiovascular Event
66.
SAFF_ALL
VS4
Listing of Myocardial infarction/unstable angina
ETP, SAC
67.
SAFF_ALL
VS4
Listing of Congestive heart failure
ETP, SAC


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Non-ICH: Listings
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
68.
SAFF_ALL
VS4
Listing of Arrhythmias
ETP, SAC
69.
SAFF_ALL
VS4
Listing of Valvulopathy
ETP, SAC
70.
SAFF_ALL
VS4
Listing of Pulmonary hypertension
ETP, SAC
71.
SAFF_ALL
VS4
Listing of Cerebrovascular events/stroke and transient ischemic 
attack
72.
SAFF_ALL
VS4
Listing of Peripheral arterial thromboembolism
73.
SAFF_ALL
VS4
Listing of Deep venous thrombosis/pulmonary embolism
74.
SAFF_ALL
VS4
Listing of Revascularisation
75.
SAFF_ALL
VS4
Listing of Deaths


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12.11.
Appendix 11: Example Mock Shells for Data Displays
Available upon request