A Study of Single Doses to Evaluate the Safety, Tolerability, Pharmacokinetics and Target Engagement of Nebulised GSK3008348 in Idiopathic Pulmonary Fibrosis Patients, Using Positron Emission Tomography (PET) Imaging
Phase: PHASE1
Conditions: Idiopathic Pulmonary Fibrosis
Sponsor: GlaxoSmithKline

2016N291965_02
CONFIDENTIAL
GlaxoSmithKline group of companies
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TITLE PAGE
Protocol Title: A study of single doses to evaluate the safety, tolerability, 
pharmacokinetics and target engagement of nebulised GSK3008348 in idiopathic 
pulmonary fibrosis patients, using positron emission tomography (PET) imaging
Protocol Number: 204715
Protocol Amendment Number: 02
Short Title: Single doses of GSK3008348 in IPF patients using PET imaging
Compound Number:
GSK3008348
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: Please refer to the Study Reference 
Manual
Regulatory Agency Identifying Number(s): 2016-003674-41
Approval Date: 24-JAN-2018
Copyright 2018 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited.

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P R O T O C O L A M E N D M E N T S U M M A R Y O F C H A N G E S T A B L E 
D O C U M E N T HI S T O R Y 
D o c u m e nt
 D at e
 
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0 5- D ec- 2 0 1 7 
 
A me n d me nt 0 2 2 4- J A N- 2 0 1 8 
O ver all R ati o n ale f or t he A me n d me nt:  
T o c orrect t he descri pti o n of t he pri mar y e n d p oi nt a n d pr o vi de f urt her g ui da nce o n t he 
f oll o w u p visit a n d l u n g f u ncti o n re q uire me nts. Ot her t y p o gra p hical err ors ha ve als o bee n 
c orrecte d. 
Secti o n # a n d 
Na me 
Descri pti o n of C ha n ge 
Brief Rati o nale 
Secti o n 1  
S y n o psis: 
O bjecti ves a n d 
E n d p oi nts 
T he w or di n g ‘a n d bl o o d’ has bee n 
re m o ve d fr o m t he pri mar y e n d p oi nt 
pertai ni n g t o t he v ol u me of 
distri b uti o n ( V T ) 
T o pr o vi de clarit y a n d 
c orrect t he defi niti o n of 
t he pri mar y e n d p oi nt 
pertai ni n g t o t he v ol u me 
of distri b uti o n ( V T ).  T he 
V T is ge nerate d usi n g a 
ki netic m o del t hat 
i ncl u des a bl o o d 
c o m part me nt a n d is 
t heref ore i m plicitl y 
c orrecte d f or bl o o d 
v ol u me 
Secti o n 1 
S y n o psis: 
Treat me nt 
Gr o u p a n d 
F oll o w u p 
A d diti o nal w or di n g has bee n i ncl u de d 
i n t he f oll o w u p secti o n f or 
partici pa nts w h o w it h dra w fr o m t he 
st u d y pri or t o t he fi nal d ose 
T o pr o vi de f urt her 
g ui da nce f or partici pa nts 
wit h dra wi n g fr o m t he 
st u d y pri or t o t he fi nal 
d ose 
Secti o n 2 
Sc he d ule of 
Acti vities 
( S o A) 
T he re q uire me nt t o meas ure hei g ht at 
t he f oll o w u p visit has bee n re m o ve d 
A s u bsta ntial c ha n ge i n 
hei g ht is n ot e x pecte d t o 
be o bser ve d o ver a s h ort 
ti me peri o d 
Secti o n 4 
O bjecti ves a n d 
T he w or di n g ‘a n d bl o o d’ has bee n 
re m o ve d fr o m t he pri mar y e n d p oi nt 
T he v ol u me of distri b uti o n 
( VT ) is ge nerate d usi n g a 

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Section # and 
Name 
Description of Change 
Brief Rationale 
Endpoints  
Section 10.3.1 
Pharmacodynamic 
Analyses 
 
pertaining to the volume of 
distribution (VT) 
kinetic model that 
includes a blood 
compartment and is 
therefore implicitly 
corrected for blood 
volume 
Section 4 
Objectives and 
Endpoints: 
Exploratory 
The wording ‘with and without 
correction’ has been added and the 
wording ‘corrected’ has been 
removed to describe the standardised 
uptake values [SUV] and VT, for air 
and/or blood volume) 
To correct and provide 
clarity on the standardised 
uptake value (SUV) which 
cannot be readily 
corrected for blood 
volume 
Section 5.2 
Number of 
Participants 
Additional wording on the number of 
participants required to be dosed and 
considered complete when PET data 
at 30min post dose has been collected 
To provide clarity on the 
numbers of participants 
required to meet the 
primary endpoint of: 
Changes in the uptake of 
[18F]-FBA-A20FMDV2 in 
the whole lung at 
approximately 30 min 
post-dose compared to 
pre-dose, as measured by 
PET 
Section 6.4 
Screen Failures 
Re-screened participants should be 
assigned a new participant number 
The following has been removed from 
Section 6.4: 
Rescreened participants should be 
assigned the same participant number 
as for the initial screening 
 
Correction to the protocol 
Section 9.4 Safety 
Assessments 
New wording inserted in Section 
9.4.6 Lung Function Tests 
To provide guidance on 
lung function tests which 
was previously omitted 
from the protocol 
 

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TABLE OF CONTENTS
PAGE
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE.....................................3
1.
SYNOPSIS...............................................................................................................8
2.
SCHEDULE OF ACTIVITIES (SOA).......................................................................11
3.
INTRODUCTION....................................................................................................14
3.1.
Study Rationale ..........................................................................................14
3.2.
Background ................................................................................................14
3.3.
Benefit/Risk Assessment ............................................................................15
3.3.1.
Risk Assessment .........................................................................16
3.3.2.
Benefit Assessment.....................................................................20
3.3.3.
Overall Benefit:Risk Conclusion...................................................20
4.
OBJECTIVES AND ENDPOINTS...........................................................................20
5.
STUDY DESIGN ....................................................................................................21
5.1.
Overall Design ............................................................................................21
5.1.1.
Cohort 1.......................................................................................21
5.1.2.
Cohort 2.......................................................................................22
5.1.3.
Changes to Cohorts 1 or 2...........................................................23
5.2.
Number of Participants ...............................................................................24
5.3.
Participant and Study Completion...............................................................24
5.4.
Scientific Rationale for Study Design ..........................................................24
5.5.
Dose Justification........................................................................................25
6.
STUDY POPULATION...........................................................................................26
6.1.
Inclusion Criteria.........................................................................................26
6.2.
Exclusion Criteria........................................................................................27
6.3.
Lifestyle Restrictions...................................................................................28
6.3.1.
Meals and Dietary Restrictions ....................................................28
6.3.2.
Caffeine, Alcohol, and Tobacco ...................................................28
6.3.3.
Activity .........................................................................................28
6.4.
Screen Failures...........................................................................................29
7.
TREATMENTS.......................................................................................................29
7.1.
Treatments Administered............................................................................29
7.2.
Dose Modification .......................................................................................30
7.3.
Method of Treatment Assignment ...............................................................30
7.4.
Blinding.......................................................................................................30
7.5.
Preparation/Handling/Storage/Accountability..............................................31
7.6.
Treatment Compliance................................................................................32
7.7.
Concomitant Therapy..................................................................................32
7.8.
Treatment after the End of the Study ..........................................................32
8.
DISCONTINUATION CRITERIA.............................................................................33
8.1.
Discontinuation of Study Treatment ............................................................33
8.1.1.
Liver Chemistry Stopping Criteria ................................................33
8.1.2.
QTc Stopping Criteria ..................................................................33

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8.1.3.
Individual Adverse Event Stopping Criteria ..................................34
8.2.
Withdrawal from the Study..........................................................................34
8.3.
Lost to Follow Up........................................................................................35
9.
STUDY ASSESSMENTS AND PROCEDURES .....................................................35
9.1.
Efficacy Assessments.................................................................................36
9.2.
Adverse Events...........................................................................................36
9.2.1.
Time Period and Frequency for Collecting AE and SAE 
Information...................................................................................36
9.2.2.
Method of Detecting AEs and SAEs.............................................36
9.2.3.
Follow-up of AEs and SAEs.........................................................37
9.2.4.
Regulatory Reporting Requirements for SAEs .............................37
9.2.5.
Cardiovascular and Death Events................................................37
9.2.6.
Pregnancy ...................................................................................37
9.3.
Treatment of Overdose...............................................................................38
9.4.
Safety Assessments ...................................................................................38
9.4.1.
Physical Examinations.................................................................38
9.4.2.
Vital Signs....................................................................................38
9.4.3.
Peripheral capillary oxygen saturation .........................................39
9.4.4.
Electrocardiograms......................................................................39
9.4.5.
Clinical Safety Laboratory Assessments ......................................39
9.5.
Pharmacokinetics .......................................................................................40
9.6.
Positron Emission Tomography (PET)........................................................40
9.7.
Genetics .....................................................................................................41
9.8.
Biomarkers .................................................................................................41
9.9.
Immunogenicity Assessments.....................................................................42
9.10.
Health Economics OR Medical Resource Utilization and Health 
Economics..................................................................................................42
10. STATISTICAL CONSIDERATIONS........................................................................42
10.1.
Sample Size Determination ........................................................................42
10.2.
Populations for Analyses ............................................................................43
10.3.
Statistical Analyses.....................................................................................43
10.3.1.
Pharmacodynamic Analyses........................................................43
10.3.2.
Safety Analyses...........................................................................44
10.3.3.
Pharmacokinetic analyses ...........................................................44
10.3.4.
Other Analyses ............................................................................44
10.3.5.
Interim Analyses ..........................................................................44
10.3.5.1.
Interim Analysis for Futility..........................................44
10.3.5.2.
Interim Analysis for Sample Size Re-estimation .........45
11. REFERENCES.......................................................................................................46
12. APPENDICES........................................................................................................48
12.1.
Appendix 1: Abbreviations and Trademarks................................................48
12.2.
Appendix 2: Clinical Laboratory Tests.........................................................51
12.3.
Appendix 3: Study Governance Considerations..........................................52
12.4.
Appendix 4: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .......................................56
12.5.
Appendix 5: Contraceptive Guidance and Collection of Pregnancy 
Information..................................................................................................61
12.6.
Appendix 6: Genetics..................................................................................65

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12.7.
Appendix 7: Liver Safety: Required Actions and Follow-up 
Assessments ..............................................................................................66
12.8.
Appendix 8: Radiation Dose Risk Assessment ...........................................68
12.9.
Appendix 9:  Assessment of the Potential Immunogenicity Risk for 
[18F]-FBA-A20FMDV2 .................................................................................69
12.10. Appendix 10:  Diagram Summarising the Study Decision Making ...............72
12.11. Appendix 11:  Areas Endemic to Foot and Mouth Disease .........................73
12.12. Appendix 12: Protocol Amendment History.................................................74

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1.
SYNOPSIS
Protocol Title: A study of single doses to evaluate the safety, tolerability, 
pharmacokinetics and target engagement of nebulised GSK3008348 in idiopathic 
pulmonary fibrosis patients, using positron emission tomography (PET) imaging
Short Title: Single doses of GSK3008348 in IPF patients using PET imaging
Rationale:  GSK3008348 is a potent and selective inhibitor of the integrin receptor αvβ6, 
and is being developed as a treatment for idiopathic pulmonary fibrosis (IPF).  It has been 
shown to engage αvβ6 integrin and inhibit downstream fibrogenic mechanisms in mouse 
and human lung cells and tissue.  The first-time-in-human study (GSK Document 
Number 2014N201929_01, Study 200262) showed that single nebulised doses of 
1−3,000 µg GSK3008348 in healthy volunteers were well tolerated, with 
pharmacokinetic (PK) exposures within the defined limits set by the protocol.  The 
proposed study is intended to evaluate the safety, tolerability and pharmacokinetics of the 
molecule in patients with IPF not currently treated with pirfenidone or nintedanib, and 
obtain preliminary information on target engagement to support progression to repeat 
dose and proof of mechanism studies.  Target engagement will be measured by positron 
emission tomography (PET) using a radiolabelled αvβ6-specific ligand, [18F]-FBA-
A20FMDV2 (GSK2634673).    
Objectives and Endpoints:
Objective
Endpoint
Primary

To evaluate target engagement in the lung 
after single nebulised doses of 
GSK3008348 in IPF patients

Changes in the uptake of [18F]-FBA-
A20FMDV2 in the whole lung (assessed as 
the volume of distribution [VT], not corrected 
for air volume) at approximately 30 min 
post-dose compared to pre-dose, as 
measured by PET

To evaluate the safety and tolerability of 
single nebulised doses of GSK3008348 in 
IPF patients

Adverse events (AE), clinical laboratory 
values, vital signs, electrocardiogram 
(ECG), and pulmonary function tests
Secondary

To evaluate the pharmacokinetic profile of 
single nebulised doses of GSK3008348 in 
IPF patients

Derived pharmacokinetic parameters for 
GSK3008348 including, but not limited to, 
area under the plasma drug concentration 
versus time curve (AUC(0-t), AUC(0-∞)), 
maximum observed plasma drug 
concentration (Cmax), time to maximum 
observed plasma drug concentration (Tmax), 

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Objective
Endpoint
and terminal half-life (T1/2) following single 
nebulised doses, where data allow

To evaluate duration of target engagement 
after single nebulised doses of 
GSK3008348 in IPF patients

Changes in the uptake of [18F]-FBA-
A20FMDV2 in the lung (assessed as the 
VT) up to 28 h post-dose compared to pre-
dose, as measured by PET
Overall Design:
This is a multi-centre, 2-cohort, study of single doses to investigate the safety, 
tolerability, PK and target engagement of nebulised GSK3008348, in patients with IPF. 
Hospital-based clinical units will recruit and enrol participants; PET imaging will be done 
at a specialist imaging unit.  All participants will be screened up to 30 days before their 
first dose, will have 2 planned dosing periods, and will have a follow-up visit at 7–14 
days post-last dose.  
Cohort 1 will be a randomised, double-blind (sponsor unblind), placebo-controlled group 
of 7 participants, randomised 5:2 to receive 1,000 µg GSK3008348 or placebo.  Safety 
and tolerability will be assessed in dosing period 1, and PET scans in dosing period 2 will 
be used to assess target engagement of GSK3008348.  
After completion of Cohort 1, safety, PET and PK data will be reviewed. 
Cohort 2 is optional, and will be designed to further explore the safety and to provide 
additional information on the target engagement profile of GSK3008348, such that each 
participant has up to 3 PET scans and 2 planned doses of GSK3008348.  
Refer to Figure 1 for a schematic illustrating the study design.
Figure 1
Study Schematic

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Number of Participants:
It is anticipated that up to 21 participants will be randomized. 
Treatment Groups and Duration:
Cohort 1
Cohort 2
Screening
Within 30 days of the first dose.
Dosing 
Period 1
After pre-dose assessments at the 
clinical unit, participants will be 
admitted to the clinical unit the day of 
dosing (Day 1), stay overnight and be 
discharged after 24 h post-dose safety 
and PK assessments (Day 2). 
After pre-dose assessments at the 
clinical unit, participants will attend the 
clinical unit for dosing (Day 1) and stay 
for at least 8 h post-dose for safety and 
PK assessments.  Participants will return 
on Day 2 for 24 h post-dose safety and 
PK assessments.
Washout 
Period
At least 7 days and no more than 28 days between doses.  
Baseline 
PET scan
At least 7 days after the first dose, and no more than 14 days before the first 
post-dose PET.
Dosing 
Period 2
Participants will have pre-dose 
assessments at the clinical unit.  They 
will attend the imaging unit for dosing 
and a 30 min post-dose PET scan, and 
stay for at least 4 h post-dose.  
Participants will return to the imaging 
unit on Day 2 for a 24 h PET scan, and 
safety and PK assessments.
Participants will have pre-dose 
assessments at the clinical unit.  They 
will attend the clinical or imaging unit for 
dosing and will stay for at least 4 h post-
dose.  Participants will have up to 2 
post-dose PET scans on Days 1 or 2, at 
times to be determined after review of 
Cohort 1 data.
Follow-up
At least 7 days and no more than 14 days after the final dose.  If warranted, 
additional follow-up visits may be scheduled.
If a participant withdraws from the study prior to the final dose, the follow up visit 
should occur within 14 days of withdrawal unless a separate timepoint is agreed by 
the principal investigator and medical monitor
Study 
Duration
Up to 62 days
Treatment 
Arms
Participants will receive a single nebulised dose of GSK3008348 or placebo during 
each of 2 planned dosing periods. 
Participants will receive up to 3 microdose administrations of [18F]-FBA-A20FMDV2 
for the PET scanning.  The maximum amount of radioactivity injected during each 
PET scan will be 150 MBq and maximum mass of [18F]-FBA-A20FMDV2 
administered across the 3 administrations will be 100 µg.

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2.
SCHEDULE OF ACTIVITIES (SOA)
Procedure
Screening
Dosing period 1
Wash-
out
(7-28 
days 
between 
doses)
Dosing
period 2
Follow-
up
(7-14 
days 
post-final 
dose)
Comments
Day ≤-30
Day –11
Day 1
Day 2
Baseline
PET2
Day –11
Day 12
Day 22
1. Visit may take place on Day -1 or on Day 1 before dosing.
2. Visits will take place at imaging unit; all other visits will take 
place at clinical units. 
Informed consent
x
Inclusion and exclusion criteria
x
Demography
x
Medical history 
x
Past and current medical 
conditions  
x
x
Full physical exam including 
height and weight
x
x3
3. Height not required at follow up visit
Brief medical exam
x
x
X4
x
x4
x4
4. Pre-PET scan, per imaging site SOPs; timing may change in 
Cohort 2 depending on PET timing. 
Pregnancy test 
x
x
x5
x5
x5
Pregnancy tests in females, when required, in serum or urine, 
as per site SOPs. 
5. Pre-PET scan; time points may change in Cohort 2 
depending on PET timing.
Hepatitis B and Hepatitis C 
screen 
x
Laboratory assessments 
(include liver chemistries) 
x
x
x6
x
x6
x
6. 24 h post-dose 
12-lead ECG
x
x
x7
x8
x
x9
x8
x
7. 30 min and 2, 4 and 8 h post-dose
8. 24 h post-dose (pre-PET scan in Dosing period 2)
9. Post-PET scan and before leaving imaging unit 
Timings may change in Cohort 2. Vital signs include blood 
pressure, heart rate, respiration rate and temperature.
Vital signs
x
x
x7
x8
x
x9
x8
x
Oxygen saturation monitoring
x
Continuous monitoring from pre-dose to 4 h post-dose. 
Lung function tests (FEV1,FVC)
x
x
x10
x11
x
x
10.
1 h post-dose
11. 24 h post-dose

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Procedure
Screening
Dosing period 1
Wash-
out
(7-28 
days 
between 
doses)
Dosing
period 2
Follow-
up
(7-14 
days 
post-final 
dose)
Comments
Day ≤-30
Day –11
Day 1
Day 2
Baseline
PET2
Day –11
Day 12
Day 22
1. Visit may take place on Day -1 or on Day 1 before dosing.
2. Visits will take place at imaging unit; all other visits will take 
place at clinical units. 
DLCO 
x
x
x12
12. 24 h post-dose.
Randomisation
x
GSK3008348 dosing
x
x
All post-dose time points are relative to start of nebulisation
PK blood sample
x
x
x
x
In Dosing period 1, pre-dose, and at 15 and 30 min, 1, 2, 4, 8, 
12, 18 and 24 h after the start of nebulisation.  In Dosing period 
2, pre-dose; on Day 1 at 15 and 30 min, 2 and 4 h post-dose; 
and on Day 2 on arrival and discharge from imaging unit.  
Time points may change in Cohort 2. 
PK urine collection
x
Spot urine sample to be taken from pre-dose void. Total urine 
collection from pre-dose to 8 h post-dose. 
Biomarker blood sample
x13
x14
13. Samples at pre-dose, and at 2 and 8 h post-dose. 
14. Sample at 24 h post-dose.
PET ligand administration & 
PET scan
x15
x16
x17
15. At least 7 days post-first dose, and no more than 14 days 
before next PET scan. 
16. Approx. 30 min (between 20–60 min) post-dose.
17. Approx. 24 h (between 14−28 h) post-dose.  
Timing of post-dose PET scans may change in Cohort 2; 
participants will have a max of 3 PET scans in total.
HRCT
x
Immunogenicity blood sample
x18
x
18. Pre-PET scan.
Genetic sample
x
AE/SAE & CV event review
x
x
x
x
x
x
x
x
Concomitant medication review
x
x
x
x
x
x
x
x
x
ECG: Electrocardiogram, DLCO: Diffusing capacity of the lungs for carbon monoxide, FEV1: Forced expiratory volume in 1 second, FCV: Forced vital capacity, PET: Positron emission 
tomography, HRCT: High resolution computed tomography, AE: Adverse event, SAE : Serious adverse event, CV: Cardiovascular, PK: Pharmacokinetics

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
The timing and number of planned study assessments, including safety, 
pharmacokinetic, imaging, immunogenicity and biomarker assessments may be 
altered during the course of the study based on newly available data (e.g., to 
obtain data closer to the time of peak plasma concentrations) to ensure 
appropriate monitoring. 

Any changes in the timing or addition of time points for any planned study 
assessments must be documented and approved by the relevant study team 
member and then archived in the sponsor and site study files, but will not 
constitute a protocol amendment. The ethics committee will be informed of any 
safety issues that require alteration of the safety monitoring scheme or 
amendment of the information and consent form (ICF).

Acceptable time deviation windows are listed in the Study Reference Manual 
(SRM). 

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3.
INTRODUCTION
3.1.
Study Rationale
GSK3008348 is a potent and selective inhibitor of the integrin receptor αvβ6, and is 
being developed as a treatment for idiopathic pulmonary fibrosis (IPF).  It has been 
shown to engage αvβ6 integrin and inhibit downstream fibrogenic mechanisms in mouse 
and human lung cells and tissue.  The first-time-in-human study (GSK Document 
Number 2014N201929_01 Study 200262) showed that single nebulised doses of 
1−3,000 µg GSK3008348 in healthy volunteers were well tolerated, with 
pharmacokinetic (PK) exposures within the defined limits set by the protocol.  The 
proposed study is intended to evaluate the safety, tolerability and PK of the molecule in 
patients with IPF not currently treated with pirfenidone or nintedanib, and obtain 
preliminary information on target engagement to support progression to repeat dose and 
proof of mechanism studies.  Target engagement will be measured by positron emission 
tomography (PET) using a radiolabelled αvβ6-specific ligand, [18F]-FBA-A20FMDV2 
(GSK2634673).    
3.2.
Background
IPF is a form of chronic fibrosing interstitial pneumonia, limited to the lung and 
associated with the histological appearance of usual interstitial pneumonia (UIP) on 
surgical lung biopsy.  The aetiology of IPF is unknown; it progresses in a relentless and 
often insidious manner that may be difficult to detect using parameters such as 
symptomatology, chest radiographic findings, or spirometry alone. Spontaneous 
remissions do not occur, and mean survival ranges from 2 to 4 years (5-year survival 
range, 30 to 50%). 
In the United Kingdom, data from general practice shows that the 12 month prevalence is 
15−18/100,000 person and an incidence of about 5/100,000 person-years.  Approximately 
2,000 new cases of IPF are diagnosed each year in England and Wales
[Navaratnam, 2013]. 
No therapy has been demonstrated to reverse the progression of IPF and it remains a 
major indication for lung transplantation. Two oral therapies are currently marketed for 
IPF, pirfenidone (Roche), the mechanism of action for which is incompletely understood
and nintedanib (Boehringer Ingelheim), a kinase inhibitor. Both of these treatments 
demonstrate a reduction in the rate of decline in lung function (forced vital capacity 
[FVC]) over one year [King, 2014; Richeldi, 2014]. Pirfenidone is associated with 
phototoxicity, and both agents have significant gastrointestinal effects.  In a real-world 
study, treatment with pirfenidone led to discontinuation in approximately one third of 
patients due to adverse events [Hughes, 2016].
The association of transforming growth factor (TGF)activity with fibrosis has been 
established in many disease settings. TGFis secreted in an inactive form, and requires 
activation post-translationally.  Substantial evidence suggests that the v6 integrin 
performs a key TGFactivation function at sites of damaged epithelium [Margadant, 
2010].  Activation of TGFby v6 has been shown to play an important role in lung 

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fibrosis: 6 knockout mice are resistant to bleomycin-induced pulmonary fibrosis 
[Munger, 1999] and treatment with an αvβ6 neutralising antibody ameliorates bleomycin 
[Horan, 2008] and radiation-induced pulmonary fibrosis [Puthawala, 2008].
Immunohistochemistry of lung biopsy has shown that αvβ6 is significantly increased in 
the fibrotic areas of the lungs of IPF patients [Horan, 2008].  Expression levels of αvβ6 in 
IPF lungs predict mortality, with highest expression levels in IPF patients who progress 
rapidly [Saini, 2013]. In addition, animal models of pulmonary fibrosis have shown that 
the expression of αvβ6 correlates with the severity of the fibrotic response, and blockade 
of this target reduces the fibrosis [Horan, 2008; Puthawala, 2008]. Inhibition of v6 is 
considered to be advantageous over direct TGFinhibition because v6 expression is 
highly regulated and localised to damaged epithelial sites. Thus, inhibition of integrin-
mediated TGFactivation should minimise the risk of potential side effects caused by 
direct TGFinhibition, e.g. pro-inflammatory responses. 
GSK3008348 is being progressed as a twice-daily small molecule anti-fibrotic medicine,
to be delivered to IPF patients’ lungs by nebulisation. On reaching the peripheral areas of 
the lung, where the fibrosis occurs, GSK3008348 will bind to v6 on the damaged 
epithelium.  Our non-clinical work indicates that binding leads to internalisation of the 
integrin, inhibiting v6-mediated activation of TGFβ. The ability of TGFβ to promote 
collagen production by activated myofibroblasts is thereby limited.  It is hypothesised 
that GSK3008348 will slow or stop the progression of fibrosis, with the potential to 
provide significant benefit to patients in terms of reduction, avoidance or delay of 
symptoms, disability and death.
A 20 amino acid peptide (A20FMDV2), derived from the foot and mouth disease virus
(FMDV2), has been synthesised and shown to bind selectively to v6 (KD =0.22nM). 
The radiolabelled peptide, [18F]-FBA-A20FMDV2, will be used in this study to quantify 
levels of v6 expression and GSK3008348 receptor engagement in the lungs of IPF 
patients.  A single photon emission computed tomography (SPECT) analogue, 
[111In]-FBA-A20FMDV2, has been shown non-clinically to bind specifically to αvβ6 in 
the lungs of mice [John, 2013] and similar results have been obtained using the PET 
ligand in rats [internal GSK data on file].  [18F]-FBA-A20FMDV2 has also been 
administered to humans and shown to provide a signal that allows the distinction between 
IPF patients and healthy participants (GSK Document Number 2013N163906_00 Study 
RES116235). 
3.3.
Benefit/Risk Assessment
Information on the key potential risk associated with GSK3008348 and the strategies to 
mitigate this risk are detailed below in Section 3.3.1.  Further details about the potential 
risks and expected benefits of GSK3008348 may be found in the Investigator’s Brochure
(IB).

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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) [GSK3008348]
Potential local irritancy
Non-clinical:
Upper respiratory tract irritancy was observed in the 4-week 
inhalation toxicity studies in rats and dogs. Principal changes 
included epiglottic cartilage necrosis, regeneration/ 
remodelling at 5850 and 12000 µg/kg/day in rats; and soft 
palate or laryngeal ulcerations in dogs at 3070 and 
8710 µg/kg/day. No Observed Adverse Effect Levels
(NOAELs) were identified at the lowest doses tested (1420 
and 899 µg/kg/day in rats and dogs, respectively).
Lower respiratory tract irritancy was also observed in the 4-
week inhalation toxicity study in dogs. Adverse mixed 
inflammation and alveolar macrophage aggregates were 
observed at 3070 and 8710 µg/kg/day. These findings were 
also present in some animals from the lowest dose tested 
(899 µg/kg/day – the NOAEL), including control. Changes in 
local draining lymph nodes of GSK3008348-treated dogs were 
considered to be a non-adverse secondary response to the 
pulmonary inflammation. 
Non-adverse alveolar macrophage aggregates were seen at a 
low incidence in the lungs of all treated groups and also in 
control males in the 4-week inhalation study in rats. A minor 
test article-related effect could not be entirely discounted in 
female rats. 
In this planned first-time-in-patient study, IPF patients 
will only receive single doses. 
Appropriate inclusion/exclusion criteria (e.g., exclusion 
for current upper or lower respiratory tract infection) will 
be implemented in clinical protocols.
Potential adverse events associated with irritancy (e.g., 
sore throat, cough, dyspnoea, wheezing) are readily 
monitored, and will be monitored during the study. 
Interpretation of these AEs may be compromised in IPF 
patients where cough or dyspnoea may be symptoms 
of their respiratory diseases. Therefore patients’ 
baseline symptoms will be recorded as part of the 
current conditions assessment, and physical 
measurements including respiratory rate and oxygen 
saturation monitoring reviewed, to aid interpretation of 
any new symptoms. It is anticipated that symptoms 
secondary to irritancy will be more acute in nature, 
which will help distinguish from chronic symptoms due 
to IPF.
Symptoms of clinical concern may be investigated 
further in collaboration with an Ear, Nose and Throat

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Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Clinical:
No symptoms or other clinical findings indicative of upper 
respiratory tract irritancy were observed in the first-time–in-
human study 200262 in healthy volunteers following single 
doses up to 3,000 µg.
(ENT) specialist.
Study Procedures
Participants exposed to 
ionising radiation as a 
consequence of patient’s 
participation in this study. 
The ionising radiation exposure comes from the administered 
radioligand, a high resolution CT (HRCT) for anatomical 
localization and low dose CT scans performed in order to 
correct the PET data for tissue attenuation.  The maximum 
effective dose of ionising radiation that participants in this 
study may be exposed to is 20.9 mSv.  This is equivalent to 
approximately 9 times the average yearly exposure (2.3 mSv) 
from natural background radiation in the United Kingdom.
The additional risk of developing a fatal malignancy as a result 
of these exposures has been estimated as approximately 1 in 
1,000 for an adult in normal health. The reduced life 
expectancy of IPF patients will result in a lower risk for these 
individuals.
Within the UK the guidance set out by International 
Commission on Radiological Protection (ICRP) 62 is generally 
followed in setting research study dose constraints. The level 
of risk may therefore be assumed to broadly fall within the 
ICRP 62 intermediate Category IIb, where the benefit should 
be more directly aimed at the cure or prevention of disease.
The study has been designed to keep the radiation 
dose as low as reasonably practicable whilst obtaining 
images of sufficient quality to meet the objectives.
Male participants < 50 years and female participants 
< 55 years will not be eligible.
To avoid recruitment of radiation worker or serial study 
volunteers, participants who have been exposed to 
ionising radiation in excess of 10mSv above 
background over the previous 3 year period as a result 
of occupational exposure to radiation or as a result of 
research studies are excluded.  Clinically justified 
(therapeutic or diagnostic) exposures are not included 
in the exposure calculation.  Participants are asked 
about any occupational exposure or previous 
participation in research studies at screening so that 
dose estimates can be obtained where necessary.
The study will exclude women of childbearing potential.
The maximal dose of ionising radiation that participants 

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Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
in this study may be exposed to is outlined in 
Appendix 8. 
Potential risk of 
immunogenicity related to 
A20FMDV2
There is a low theoretical risk that [18F]-FBA-A20FMDV2 may 
be immunogenic in humans. This could potentially lead to 
reduced signal in PET scans from neutralising anti-drug 
antibodies. There is also potential for anaphylactic and other 
immune mediated reactions. Neither of these phenomena has 
been observed in previous administrations of [18F]-FBA-
A20FMDV2 to humans (ongoing GSK Study RES116235).
[Of note, assay for measurement of antibodies to [18F]-FBA-
A20FMDV2 produced positive results in two participants in 
study RES116235. One healthy participant was positive pre-
and post-dosing, and one IPF participant was positive after the 
first scan and negative after the second scan. No clinical 
effects were attributed to effects of antibodies.]
Exclusion of participants with prior exposure to farm 
animals that may harbour FMDV2.
Exclusion of participants from countries where FMDV2 
is endemic.
Short period between repeat PET scans.
Collection of serum samples for measurement of 
antibodies to [18F]-FBA-A20FMDV2.
PET scans performed in an imaging unit with 
immediate access to emergency measures. 
Refer to Appendix 9 for more detail on the 
immunogenicity risk assessment and mitigation.
Potential bystander exposure 
to GSK3008348
Unintended inhalation of GSK3008348 (irritant potential).  
Since clear NOAELs were established in the nonclinical 
toxicity studies (with adequate safety margins) and the 
concentration in the room will be significantly less than direct 
exposure to GSK3008348, the risk for irritancy for bystanders 
is considered to be low.
No events in bystanders were reported in the study in healthy 
volunteers following single doses up to 3,000 µg.
Appropriate precautions will be taken to minimise 
bystander exposure in the study. Nebulised drug 
should not be administered in a confined and/or 
unventilated space. 

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Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Ensuring sufficient medical 
oversight for safety 
monitoring and transport 
between sites
In dosing period 2 of Cohort 1, the doses will be administered 
to participants in the imaging unit, so that the PET can be 
carried out at approximately 30 minutes post-dose.  However, 
in Cohort 2, there is the option to administer those doses in 
the hospital clinical unit, if required for logistical or safety 
reasons.  In that case, participants would be transported after 
dosing to the imaging site for the PET scans.
In both Cohorts 1 and 2, the first dosing period will be 
conducted in a hospital-based clinical unit, under the 
supervision of a chest physician, with immediate 
access to facilities for the treatment of medical 
emergencies, facilities for stabilizing individuals in an 
acute emergency and ready availability of Intensive 
Care Unit facilities. Following Principal Investigator (PI) 
and GSK medical monitor review of the individual 
safety and tolerability data from the completed first 
dosing period, the patient will continue to the baseline 
PET visit and second dosing period. In the second 
dosing period, the same dose will be administered by 
clinical staff in the imaging unit, alongside an 
appropriately trained research nurse.
If in Cohort 2 doses are to be administered in the 
clinical unit before transporting participants to the 
imaging unit in dosing period 2, patients will be 
observed for at least 4 hours post-dose before being 
transported to the imaging unit.

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3.3.2.
Benefit Assessment
Participants will receive single doses of GSK3008348, which is being developed as a 
treatment for IPF.  It is not anticipated that this single dose study will provide any clinical 
benefit to participants.  The results will inform the evaluation of GSK3008348 as a 
treatment for IPF, so participants may contribute to the process of developing new 
therapies for IPF and related conditions.  Participants will be monitored throughout the 
study for any worsening of IPF symptoms or decline in general health.
3.3.3.
Overall Benefit:Risk Conclusion
Taking into account the measures taken to minimize risk to participants participating in 
this study, the potential risks identified in association with single doses of GSK3008348 
and with study procedures are justified by the anticipated benefits from active treatment
that may be afforded to patients in the future, in developing GSK3008348 as a new 
therapy for IPF.
4.
OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary

To evaluate target engagement in the 
lung after single nebulised doses of 
GSK3008348 in IPF patients 

Changes in the uptake of [18F]-FBA-
A20FMDV2 in the whole lung (assessed as 
the volume of distribution [VT], not 
corrected for air volume) at approximately 
30 min post-dose compared to pre-dose, 
as measured by PET 

To evaluate the safety and tolerability of 
single nebulised doses of GSK3008348 
in IPF patients

Adverse events (AE), clinical laboratory 
values, vital signs, electrocardiogram 
(ECG), and pulmonary function tests 
Secondary

To evaluate the pharmacokinetic profile 
of single nebulised doses of 
GSK3008348 in IPF patients 

Derived pharmacokinetic parameters for 
GSK3008348 including, but not limited to, 
area under the plasma drug concentration 
versus time curve (AUC(0-t), AUC(0-∞)), 
maximum observed plasma drug 
concentration (Cmax), time to maximum 
observed plasma drug concentration 
(Tmax), and terminal half-life (T1/2) following 
single nebulised doses, where data allow 

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Objectives
Endpoints

To evaluate duration of target 
engagement after single nebulised 
doses of GSK3008348 in IPF patients

Changes in the uptake of [18F]-FBA-
A20FMDV2 in the lung (assessed as the 
VT) up to 28 h post-dose compared to 
pre-dose, as measured by PET
Exploratory

To explore the pharmacodynamic 
effects of single nebulised doses of 
GSK3008348 in IPF patients using 
additional PET analyses techniques

Changes in the uptake of [18F]-FBA-
A20FMDV2 in the whole lung (assessed 
using standardised uptake values [SUV]
and VT, with and without correction for air 
and/or blood volume) at various time points 
post-dose compared to pre-dose, as 
measured by PET

To explore the spatial distribution of the 
effects of single nebulised doses of 
GSK3008348 in IPF patients and to 
compare it to the spatial distribution of 
disease  

Qualitative assessment of the distribution of 
the uptake of [18F]-FBA-A20FMDV2 in the 
lungs post-dose compared to pre-dose, as 
measured by PET and compared to the 
spatial distribution of disease as indicated 
by HRCT

To explore pharmacodynamic effects of 
GSK3008348 in blood 

Exploratory pharmacodynamic biomarkers 
of the αvβ6/TGFβ mechanism which may 
include but are not limited to: mRNA, 
microRNA and proteins in blood

To explore potential biomarkers of IPF 
disease and/or treatment response

Exploratory biomarkers in blood
5.
STUDY DESIGN
5.1.
Overall Design
This is a multi-centre, 2-cohort, study of single doses to investigate the safety, 
tolerability, PK and target engagement of nebulised GSK3008348, in patients with IPF. 
Hospital-based clinical units will recruit and enrol participants; the PET imaging will be 
done at a specialist imaging unit.  
Participants will be screened up to 30 days before their first dose, and will have a 
follow-up visit at 7–14 days post-last dose.  
Refer to Figure 1 for a schematic illustrating the study design.
5.1.1.
Cohort 1
Cohort 1 will be a randomised, double-blind (sponsor unblind), placebo-controlled group 
of 7 participants, randomised 5:2 to receive 1,000 µg GSK3008348 or placebo.  All 
participants will have 2 planned dosing periods, and receive the same dose in each period.  

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Dosing period 1 aims to assess safety and tolerability, and dosing period 2 aims to assess 
target engagement using PET imaging. 
In dosing period 1, participants will be admitted to the clinical unit on the morning of 
Day 1 for pre-dose health assessments and a pharmacogenetic sample; these assessments 
may also take place on Day –1.  On Day 1, they will remain in the clinical unit overnight, 
to enable safety assessments to be carried out for at least 24 h after receiving their 
nebulised dose.  PK and exploratory biomarker samples will also be taken.  Participants 
will then be discharged from the clinical unit. 
There will be a washout of between 7 and 28 days between doses in periods 1 and 2.  
Participants will attend the imaging unit for a baseline PET scan and a high resolution 
computerised tomography (HRCT) scan, at least 7 days after their first dose, and a 
maximum of 14 days before their first post-dose PET scan in dosing period 2.  
In dosing period 2, participants will first attend the clinical unit for pre-dose health 
assessments, on Day 1 or Day −1.  If they pass the health assessments, participants will 
attend the imaging unit for dosing and a PET scan starting approximately 30 min post-
dose (i.e., post the start of nebulisation).  Participants will remain in the imaging unit for 
safety observation for at least 4 h post-dose on Day 1, and then return on Day 2 for a PET 
scan at approximately 24 h post-dose (post the start of nebulisation).  Safety assessments 
and PK sampling will be done throughout those visits.  
Cohort 1 will be considered complete when PET data at 30 min post-dose has been 
collected from 7 participants.  After completion of Cohort 1, blinded safety and PK data 
will be reviewed by a data review team, consisting of the investigators, medical monitor, 
statistician, clinical pharmacokineticist, pharmacovigilance representative, and clinical 
study team members, as appropriate.  The statistician will also perform an unblinded 
review of the PET data. 
5.1.2.
Cohort 2
Cohort 2 is optional, and will proceed only if there is evidence of target engagement at 
30 min post-dose in Cohort 1.  It will be designed to further explore the safety and to 
provide additional information on the target engagement profile of GSK3008348.  
Decisions on whether to proceed with Cohort 2, and on the most informative design for 
Cohort 2, will be based on Cohort 1 data.  Cohort 2 data may be reviewed in-stream and 
the design of Cohort 2 adjusted to maximise the value of the data obtained.  Cohort 2 will 
be designed such that each participant will have up to 3 PET scans and 2 planned doses 
of GSK3008348, and within the logistical limitations of dosing, safety monitoring, PET 
ligand radiochemistry and PET scanning.  For example: 

If there is no evidence of target engagement at 30 min post-dose in Cohort 1, then 
Cohort 2 will not go ahead. 

If the variability in PET measurements is higher than anticipated, participants in 
Cohort 2 may follow the same dosing and scanning regime as in Cohort 1, to 
increase the sample size.

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
If significant target engagement is observed at 30 min in Cohort 1, but there is no 
evidence of target engagement at 14−28 h, then Cohort 2 may explore time points 
between 30 min and 28 h after a 1,000 µg dose. 

If significant target engagement is observed at 30 min and at 14−28 h, then Cohort 2 
may explore target engagement at time points between 30 min and 28 h after a dose 
lower than 1,000 µg.
A decision-making flowchart is shown in Appendix 10.
Cohort 2 may be open-label, in which case up to 10 participants may receive single doses 
of GSK3008348 in an open-label manner.  If Cohort 1 data suggests that including a 
placebo control would be beneficial, for example for safety reasons, Cohort 2 will be 
carried out in a double-blind (sponsor unblind) fashion, with up to 14 participants 
randomised 5:2 to receive GSK3008348 or placebo. 
The dose level will be 1,000 µg or lower, and may be changed at any time depending on 
previous or emerging data. Participants may receive a lower dose in dosing period 2 
compared to dosing period 1.  The length of post-dose safety monitoring in the clinic will 
be decided based on previous or emerging data, but participants will be monitored for at 
least 8 h post-first dose.  
Participants will have 2 planned dosing periods, both on an outpatient basis, with an 
additional visit for baseline imaging, as follows.

Dosing period 1:  participants will have pre-dose health assessments and a 
pharmacogenetics sample at the clinical unit on the morning of Day 1.  They will 
remain in the clinical unit for at least 8 h after receiving their nebulised dose for 
safety observations, and then return to the clinical unit on Day 2.  Safety assessments 
will be done, and PK and exploratory biomarker samples taken.  

Baseline PET scan and HRCT scan at least 7 days after the first dose, and a maximum 
of 14 days before the first post-dose PET scan. 

Dosing period 2:  participants will attend the clinical unit for health assessments 
before dosing, on Day 1 or Day −1.  If participants pass the health assessments, they 
will attend the imaging unit, have their dose administered, and have up to 2 post-dose 
PET scans.  Alternatively, dosing may take place at the clinical unit before the patient 
is transferred to the imaging unit for their PET scan, depending on the PET scan 
timing; however, the participant must be observed for at least 4 h post-dose without 
changing location.  The timing of the post-dose PET scans will be determined based 
on emerging study data.  Doses will be separated by a washout of between 7 and 
28 days. 
5.1.3.
Changes to Cohorts 1 or 2
Participants in Cohorts 1 and 2 will have 2 planned dosing periods.  However, if a PET 
scan cannot be performed (e.g. because of technical issues, PET ligand synthesis 
radiochemistry failure, or because the participant cannot be scanned for safety reasons), 
participants may repeat the visit or dosing period, and repeat procedures in order to 

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obtain a full dataset for each endpoint.  Participants may be administered an additional 
dose of GSK3008348 after a 7-day washout, such that they receive a maximum of 
3 single doses in total during the study.  Participants will not, however, be administered 
an additional dose of [18F]-FBA-A20FMDV2; they will receive a maximum of 3 doses of 
the radiotracer during the study.  
If a participant experiences unexpected and/or potentially serious side effects after their
first or second dose, they will be referred to the clinical site investigator for assessment 
and ongoing care. That may include admission to a clinical bed, if deemed appropriate 
by the investigator, as per routine clinical practice. 
5.2.
Number of Participants
It is anticipated that up to 21 participants will be randomised, as follows. 

Cohort 1 – 7 participants will be randomised. (7 participants will be randomised, 
dosed and considered complete when PET data at 30 min post-dose has been 
collected)

Cohort 2 – up to 10 participants may be randomised if an open-label design is chosen; 
or up to 14 participants may be randomised if a double-blind design is chosen. 
Refer to Section 10.2 for definitions of participants who will be considered evaluable and 
therefore included in the analyses. 
If participants prematurely discontinue the study, additional replacement participants may
be recruited and randomised to the same treatment at the discretion of the Sponsor in 
consultation with the investigator.  Replacement participants will start the study at dosing 
period 1, in order to establish tolerability of the study medication before entering the PET 
scanning dosing period. 
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 the baseline PET scan, at least 1 post-dose PET scan, and 
the last follow-up visit.  
The end of the study is defined as the date of the last visit of the last participant in the 
study.
5.4.
Scientific Rationale for Study Design

Cohort 1 includes a placebo control to allow assessment of safety and tolerability, as 
reporting of adverse events in patients receiving placebo will facilitate the 
differentiation between ‘disease’ and ‘intervention’ adverse events.   

Cohort 1 will be conducted in a double-blind (sponsor unblind) fashion. Safety and 
PK data reviews will be conducted without treatment group assignment or subject 
numbers, so that the investigators and data review team remain blinded. The 

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statistician will perform an unblinded review of PET data as part of the pre-planned 
interim analysis, to allow appropriate decision-making.  The sponsor (including the 
medical monitor) may also undertake separate in-stream review of unblinded data to 
help determine the most appropriate response to emerging data.  

The number of patients to be enrolled in Cohort 1 (7 participants) is based on the 
probability of detecting a change in vβ6 internalisation at approximately 30 min
post-dose compared to pre-dose of 6% or greater, as measured by the uptake of [18F]-
FBA-A20FMDV2 in the lungs reported as the volume of distribution [VT]. This
predetermined change is equivalent to approximately half the difference in [18F]-
FBA-A20FMDV2 PET signal observed between healthy volunteers and IPF patients 
in a previous study RES116235. If GSK3008348 cannot achieve that reduction in 
vβ6-associated PET signal and the endpoint variability is as expected, then the study 
will end.

The design for Cohort 2 will be defined following completion of Cohort 1, to ensure 
the most informative doses of GSK3008348 are selected and the PET scans are timed 
appropriately.  Cohort 2 data may be reviewed in-stream and the design of Cohort 2 
adjusted to maximise the value of the data obtained.  The aim is to assess target 
engagement while exposing the smallest possible number of patients to ionising 
radiation from the PET procedure.
5.5.
Dose Justification
The first-time-in-human study 200262 showed that single nebulised doses of 1–3,000 μg 
GSK3008348 were well tolerated in healthy participants, with PK exposures within the 
defined limits set by the protocol.
The 1,000 μg dose was selected for this study as the preliminary geometric mean Cmax
and AUC(inf) observed in healthy volunteers in study 200262 provided 22- and 11-fold 
margins, respectively, over the systemic exposures observed in the most sensitive 
preclinical species (Day 1 exposures from the Rat 1 month good laboratory practice
[GLP] study at the 12000 µg/kg/day dose level; the no effect level for systemic toxicity). 
Additionally, the 1,000 μg dose maintains adequate safety coverage over the NOAEL 
based on the deposited lung dose (36-fold over the rat and 26-fold over the dog, 1 month 
GLP toxicity studies).  The proposed dose therefore allows significant safety margins in 
the event that systemic exposure is greater in IPF patients than in healthy volunteers.
In addition, the observed PK in study 200262 demonstrated peak systemic unbound 
concentrations significantly in excess of the in vitro Kd for GSK3008348. Given that 
GSK3008348 is inhaled, it is reasonable to assume that lung tissue exposures were at 
least as high as those observed in plasma and so are expected to engage with vβ6 to a 
significant extent.

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6.
STUDY POPULATION
Prospective approval of protocol deviations to recruitment and enrolment criteria, also 
known as protocol waivers or exemptions, is not permitted.
6.1.
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria 
apply:
Age
1.
Male participants aged ≥ 50 years, and female participants aged ≥55 years, at the 
time of signing the informed consent.
Type of Participant and Disease Characteristics
2.
Diagnosis of definite or probable IPF as determined by a responsible and 
experienced chest physician and based on established criteria defined by the 
American Thoracic Society/European Respiratory Society Internationale 
Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias 
[Raghu, 2011]. 
3.
Ambulant and capable of attending outpatient visits. 
4.
FVC > 50 % predicted and DLCO > 40 % predicted. 
Weight
5.
Body weight 45 kg and body mass index (BMI) within the range 18.0–35.0 kg/m2
(inclusive).
Sex
6.
Male and female
a. Male participants:
A male participant must agree to use contraception as detailed in Appendix 5 of this
protocol during the study and for at least 90 days after the follow-up visit, and refrain 
from donating sperm during this period.
b. Female participants: 
A female participant is eligible to participate if she is not pregnant, not breastfeeding, 
and not a woman of childbearing potential (WOCBP) as defined in Appendix 5. 
Informed Consent
7.
Capable of giving signed informed consent as described in Appendix 3 which
includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol.

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6.2.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1.
ALT and bilirubin > 1.5x upper limit of normal (ULN; isolated bilirubin > 1.5x ULN 
is acceptable if bilirubin is fractionated and direct bilirubin < 35%).
2.
Current or chronic history of liver disease, or known hepatic or biliary abnormalities 
(with the exception of Gilbert's syndrome or asymptomatic gallstones). 
3.
QTc > 450 msec, or QTc > 480 msec in participants with Bundle Branch Block. 
4.
Current IPF exacerbation, or upper or lower respiratory tract infection on admission 
to the clinical unit.
5.
History of or suffers from claustrophobia, or unable to lie flat and still on their back 
for up to 2 h in the PET scanner.
6.
Extent of emphysema greater than the extent of fibrotic change on HRCT scan, 
based on investigator judgement.
7.
Forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) 
ratio < 0.70 at screening (post-bronchodilator). 
8.
History of sensitivity to the study treatment, or components thereof, or a history of 
drug or other allergy that, in the opinion of the investigators or Medical Monitor, 
contraindicates their participation. 
9.
Any current oro-pharygneal disease or disorders as judged by the investigator. 
Prior/Concomitant Therapy
10. Currently taking pirfenidone or nintedanib, or received pirfenidone or nintedanib 
within 30 days of the first dose of study treatment.
11. Taken, within 7 days or 5 half-lives (whichever is longer) before the first dose of 
study treatment, organic anion transporter (OAT) substrates with a narrow 
therapeutic index (eg methotrexate and tenofovir), vitamins, or dietary or herbal 
supplements, unless in the opinion of the investigator and sponsor the supplement 
will not interfere with the study medication. 
12. Long-term continuous home oxygen therapy (use of oxygen that is only intermittent 
and for symptom relief is acceptable). 
Prior/Concurrent Clinical Study Experience
13. Participation in a clinical trial and receipt of an investigational medicinal product 
within the following time period before the first dose in the current study:  30 days, 
5 half-lives or twice the duration of the biological effect of the investigational 
product (whichever is longer).
14. Exposure to more than 4 new investigational medicinal products within 12 months 
before the first dose. 

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Diagnostic assessments
15. Presence of Hepatitis B surface antigen (HBsAg) at screening, or positive 
Hepatitis C antibody test result at screening or within 3 months before the first dose 
of study treatment (Note:  participants with a positive Hepatitis C antibody test 
because of previous, resolved disease can be enrolled if a confirmatory negative 
Hepatitis C RNA test is obtained). 
16. Previous or current exposure to animals that may harbour FMDV2.
17. Previous long term (≥ 3 months) residence in a country where FMDV2 is endemic 
(such as certain areas of Africa, Asia and South America, see Appendix 11). 
18. Where participation in the study would result in loss of blood or blood products in 
excess of 500 mL within 56 days
19. History of drug or alcohol abuse that in the opinion of the investigator affects their 
participation in the study 
Other Exclusions
20. Exposure to ionising radiation in excess of 10 mSv above background over the 
previous 3 year period as a result of occupational exposure or previous participation 
in research studies.  Clinically justified (therapeutic or diagnostic) exposures are not 
included in the exposure calculation.
6.3.
Lifestyle Restrictions
6.3.1.
Meals and Dietary Restrictions

During each dosing session, participants will be fasted for 4 hours before dosing. 
Water will be allowed.  The time of the first meal after dosing will be recorded. 
6.3.2.
Caffeine, Alcohol, and Tobacco

During each dosing period, participants will abstain from ingesting caffeine- or 
xanthine-containing products (eg, coffee, tea, cola drinks, and chocolate) for at least 
12 hours before the start of dosing until after collection of the final PK sample in that 
period.

During each dosing period, participants will abstain from alcohol for 24 hours before 
the start of dosing until after collection of the final PK sample in that period. 

Participants who use tobacco products will be instructed that use of nicotine-
containing products will not be permitted while they are in the clinical or imaging 
units. Nicotine patches are allowed.
6.3.3.
Activity

Participants will abstain from strenuous exercise for 72 hours before each blood
collection for clinical laboratory tests. Participants may participate in light 
recreational activities during studies (eg, watching television, reading).

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6.4.
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently randomized due to failure to meet inclusion/exclusion criteria.
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).
Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened.  Rescreened participants should 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.
7.1.
Treatments Administered
Study Treatment 
Name:
GSK3008348
Placebo
[18F]-FBA-A20FMDV2
Dosage formulation:
Solution for 
nebulisation
Solution for 
nebulisation 
Intravenous (IV)
Formulation 
description:
Formulated at 
250 µg/ml with 5% 
mannitol, citric acid, 
sodium citrate and 
water for injection
5% mannitol, citric 
acid, sodium citrate 
and water for injection
Formulated in 0.9% 
saline
Unit dose 
strength(s)/Dosage 
level(s):
1,000 µg
N/A
Up to 150 MBq of [18F]-
FBA-A20FMDV2 per 
administration; 
≤100 µg total of [18F]-
FBA-A20FMDV2 per 
participant
Route of 
Administration 
Inhaled via 
nebulisation
Inhaled via 
nebulisation
IV
Dosing instructions:
4mL administered by 
nebulisation
4mL administered by 
nebulisation
Intravenous bolus over 
about 30 seconds

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Study Treatment 
Name:
GSK3008348
Placebo
[18F]-FBA-A20FMDV2
Physical 
description:
Clear colourless to 
pale yellow coloured 
solution in a 5mL vial 
with 20mm stopper 
and aluminium seal
Clear colourless to 
pale yellow coloured 
solution in a 5mL vial 
with 20mm stopper 
and aluminium seal
IV infusion, 20 mL
Storage conditions:
Refer to SRM
Refer to SRM
N/A
Device:
European Conformity 
mark (CE) marked 
nebuliser
CE marked nebuliser
N/A
7.2.
Dose Modification
The proposed dose for Cohorts 1 and 2 is 1,000 µg GSK3008348. The dose may be 
decreased in Cohort 2 at any time, depending on previous or emerging data.  The decision 
will be made by the data review team based on available preliminary safety, tolerability, 
PK and PET data obtained from preceding participants. The dose will not be increased 
above 1,000 µg. 
7.3.
Method of Treatment Assignment
Participants will be randomised to a subject number in accordance with the randomisation 
schedule generated by GSK Clinical Statistics before the study start, using validated 
internal software (RANDALL NG).  Each participant in Cohort 1 will be randomised 5:2 
to receive either GSK3008348 or placebo.  Participants in Cohort 2 will receive 
GSK3008348 in an open-label manner, unless it is decided that a placebo control would 
be beneficial, in which case participants will be randomised 5:2 to receive either 
GSK3008348 or placebo. 
All participants will be centrally randomised using an Interactive Voice/Web Response 
System (IVRS/IWRS).  Before the study is initiated, the telephone number or log in 
information and directions will be provided to each site.  
Study treatment for both dosing periods will be dispensed by appropriately trained 
pharmacy staff. 
Returned study treatment should not be re-dispensed to the participants. 
7.4.
Blinding
Cohort 1 will be double-blind (sponsor unblind).  Cohort 2 may be open-label, or may be 
double-blind (sponsor unblind) if required.  For double-blind cohorts, the following will 
apply.

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An unblinded monitor, if required, and in the event of a Quality Assurance audit, the 
auditors, will be allowed access to unblinded study treatment records at the sites to verify 
that randomisation and dispensing has been done accurately. 
The IVRS/IWRS will be programmed with blind-breaking instructions.  The blind may 
be broken by the investigator or treating physician in the case of an emergency, or if, in 
the opinion of the investigator, it is in the participant’s best interest for the investigator to 
know the study treatment assignment.  The investigator is encouraged to discuss with the 
GSK Medical Monitor or appropriate GSK study personnel before the blind is broken.  If 
GSK is not notified before the blind is broken, they must be notified as soon as possible 
after breaking the blind.  The date and reason that the blind was broken must be recorded 
in the source documentation and electronic case report form (eCRF), as applicable. 
A participant may continue in the study if their treatment assignment is unblinded, at the 
discretion of the Medical Monitor.  If a participant is withdrawn after their treatment code 
is unblinded by the investigator or treating physician, the primary reason for 
discontinuation (the event or condition which led to the unblinding) will be recorded in 
the eCRF.
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.
For an open-label cohort, all participants will be randomised to active study treatment. 
7.5.
Preparation/Handling/Storage/Accountability

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.

Only participants enrolled in the study may receive study treatment and only 
authorised site staff may supply or administer study treatment.  All study treatments 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labelled storage conditions with access 
limited to the investigator and authorised site staff.

The investigator is responsible for study treatment accountability, reconciliation, and 
record maintenance (ie, receipt, reconciliation, and final disposition records).

Further guidance and information for the final disposition of unused study treatment 
are provided in the Study Reference Manual (SRM). 

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.

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
A Material Safety Data Sheet (MSDS)/equivalent document describing occupational 
hazards and recommended handling precautions either will be provided to the 
investigator, where this is required by local laws, or is available upon request from 
GSK.
7.6.
Treatment Compliance
Participants will be dosed at the sites, and will receive study treatment directly from the 
investigator or designee, under medical supervision.  The date and time of each dose 
administered in the clinic will be recorded in the source documents.  The dose of study 
treatment and study participant identification will be confirmed at the time of dosing by a 
member of the study site staff other than the person administering the study treatment. 
7.7.
Concomitant Therapy
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) that the participant is receiving at the time of 
enrolment or receives during the study must be recorded along with:

reason for use

dates of administration including start and end dates

dosage information including dose and frequency
Participants must not be taking pirfenidone or nintedanib, or must abstain from taking 
pirfenidone or nintedanib within 30 days before their first dose of study treatment until 
completion of the follow-up visit. 
There is an unknown risk of interaction with OAT substrates with a narrow therapeutic 
index (eg methotrexate and tenofovir).  Therefore, participants must abstain from taking 
these agents within 7 days or 5 half-lives (whichever is longer) before their first dose of 
study treatment until completion of the follow-up visit. Participants must also abstain 
from taking vitamins and dietary or herbal supplements for the same period, unless, in the 
opinion of the investigator and sponsor, the supplement will not interfere with the study 
medication. 
Other concomitant medication, including paracetamol at doses of 4 grams/day, is
permitted for use any time during the study.  The Medical Monitor should be contacted if 
there are any questions regarding concomitant or prior therapy.
7.8.
Treatment after the End of the Study
Participants will not receive any additional treatment from GSK after completion of the 
study.  The investigators are responsible for ensuring that consideration has been given to 
the post-study care of the participant’s medical condition. 

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8.
DISCONTINUATION CRITERIA
8.1.
Discontinuation of Study Treatment
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.
Phase I Liver Chemistry Stopping Criteria – Liver Stopping Event Algorithm
Continue Study Treatment 
Discontinue Study Treatment 
*INR value not applicable to subjects on anticoagulants 
ALT ≥3xULN 
No
Yes
Must refer to Liver Safety Required Actions and Follow up Assessments  section in the Appendix
Report as an SAE if possible Hy’s Law case: ALT≥3xULN and  Bilirubin≥2xULN (>35% direct)  or 
INR>1.5, if measured*
Liver Safety Required Actions and Follow up Assessments Section can be found in 
Appendix 7.  
8.1.2.
QTc Stopping Criteria
A participant who meets either of the bulleted criteria below will be withdrawn from the 
study:

QTc > 500 msec OR Uncorrected QT > 600 msec

Change from baseline of QTc > 60 msec

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For patients with underlying bundle branch block, follow the discontinuation criteria 
listed below:
Baseline QTc with Bundle Branch Block
Discontinuation QTc with Bundle 
Branch Block
< 450 msec
> 500 msec
450 – 480 msec
≥ 530 msec

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 QTcF, then 
QTcF 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 averaged QTc values of triplicate electrocardiograms 
obtained over a brief (e.g., 5-10 minute) recording period.  
8.1.3.
Individual Adverse Event Stopping Criteria
A participant will be withdrawn from the study if they experience:
1. An SAE that is at least possibly related to the study treatment 
2. An IPF exacerbation, upper or lower respiratory tract infection or other systemic 
infection
3. A clinically significant change in a laboratory value or vital sign
4. Failure to recover from an adverse event
A participant can be discontinued from therapy if the investigator decides that the patient 
should be withdrawn. 
Participants who are withdrawn will complete the follow-up visit, as described in the 
SoA.
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, 
behavioural, 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.

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
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 follow-up for 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:

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 SoA. All post-dose time 
points are relevant to the start of nebulisation. 

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.

All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening 
log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable. 

Procedures conducted as part of the participant’s routine clinical management (eg, 
blood count) and obtained before signing of ICF may be utilized for screening or 
baseline purposes provided the procedure met the protocol-specified criteria and was
performed within the time frame defined in the SoA.

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
The maximum amount of blood collected from each participant over the duration of 
the study, including any extra assessments that may be required, will not exceed 
500 mL. 

Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples.
9.1.
Efficacy Assessments
Not applicable. 
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 (see Section 8). 
9.2.1.
Time Period and Frequency for Collecting AE and SAE 
Information

All SAEs will be collected from the first dose of study treatment until the follow-up 
visit at the time points specified in the SoA (Section 2).

All AEs will be collected from the first dose of study treatment until the follow-up 
visit at the time points specified in the SoA (Section 2).

Medical occurrences that begin before the first dose of study treatment but after 
obtaining informed consent will be recorded on the Medical History/Current Medical 
Conditions section of the eCRF not the AE section.

All SAEs will be recorded and reported to the sponsor or designee 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 AE and/or SAE. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrence. 

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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 eg, summary or listing of SAE) from the sponsor will 
review and then file it along with the Investigator’s Brochure and will notify the 
IRB/IEC, if appropriate according to local requirements.
9.2.5.
Cardiovascular and Death Events
For any cardiovascular events 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 Medical 
dictionary for regulatory activities (MedDRA) terms. The CV information should be 
recorded in the specific cardiovascular section of the CRF within one week of receipt of a 
CV Event data query prompting its completion. 
The Death 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 and, if indicated, female partners of 
male participants will be collected after the start of study treatment and until the 
follow-up visit.

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
If a pregnancy is reported, the investigator should inform GSK within 24 hours 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
For this study, any dose of GSK3008348 greater than 1,000 µg within a 24-hour time 
period will be considered an overdose.
GSK does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator should:
21. Contact the Medical Monitor immediately.
22. Closely monitor the participant for AE/SAE and laboratory abnormalities until 
GSK3008348 can no longer be detected systemically (at least 2 days).
23. Obtain a plasma sample for PK analysis within 2 days from the date of the last dose 
of study treatment if requested by the Medical Monitor (determined on a case-by-
case basis).
24. 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, and the 
oropharynx. Height and weight will also be measured and recorded.

A brief physical examination will include, at a minimum, assessments of the skin, 
lungs, oropharynx, cardiovascular system, and abdomen (liver and spleen).

Investigators should pay special attention to clinical signs related to previous serious 
illnesses.
9.4.2.
Vital Signs

Single readings of temperature, heart rate, respiratory rate, and blood pressure will be 
assessed.

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
Blood pressure and heart rate measurements will be assessed with a completely 
automated device. Manual techniques will be used only if an automated device is not 
available.

Vital signs will be measured in a semi-supine position after 5 minutes rest. 
9.4.3.
Peripheral capillary oxygen saturation

Peripheral capillary oxygen saturation (SpO2) levels will be continuously monitored 
with a completely automated device. 
9.4.4.
Electrocardiograms

Triplicate 12-lead ECG will be obtained and recorded in the eCRF as outlined in the 
SoA using an ECG machine that automatically calculates the heart rate and measures 
PR, QRS, QT, and QTcF intervals. Refer to Section 8.1.2 for QTc withdrawal 
criteria and additional QTc readings that may be necessary.
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 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 aetiology should be identified and the sponsor 
notified.

All protocol-required laboratory assessments, as defined in Appendix 2, must be 
conducted in accordance with the SRM 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.
9.4.6 Lung Function Tests

Spirometry measurements will be obtained using standard spirometry equipment 
available at sites, to include FEV1 and FVC.

DLCO will be measured according to local procedures.

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
For calculating % predicted FEV1, FVC and DLCO, the Quanjer 2012 
calculation is to be used.

All subjects will have spirometry and DLCO performed at Screening to assess 
eligibility and at time points as described in the time and events table.

Participants must perform 3 acceptable blows, all within 5% of each other. The 
difference between the highest FEV1 and the second highest should be within 
150 mL. A maximum of 8 attempts can be made for each time point.

Only the highest FEV1 and FVC measurements should be recorded. 

At each time point, measurements of FEV1 and FVC should be compared to 
baseline. Any clinically significant decreases in either measurements compared 
to baseline, as judged by the investigator, will be recorded as an AE.
9.5.
Pharmacokinetics

Whole blood samples of approximately 2 mL will be collected for measurement of 
plasma concentrations of GSK3008348 as specified in the SoA.  A maximum of 
5 additional samples may be collected at additional time points during the study if 
warranted and agreed upon between the investigator and the sponsor. Instructions for 
the collection and handling of biological samples will be provided in the SRM.  The 
actual date and time (24 hour clock time) of each sample will be recorded.

Samples will be used to evaluate the PK of GSK3008348.  Samples collected for 
analyses of GSK3008348 plasma concentration may also be used to evaluate safety or 
efficacy aspects related to concerns arising during or after the study.

Genetic analyses will not be performed on these plasma samples.  Participant 
confidentiality will be maintained. 

Once the plasma has been analyzed for GSK3008348, any remaining plasma may be 
analysed for other compound-related metabolites and the results reported under a 
separate protocol.

Urine samples will be analysed qualitatively for drug-related components and the 
results reported under a separate Platform Technology and Science-Product 
Development and Supply, GlaxoSmithKline study.
Drug concentration information that would unblind the study will not be reported to 
investigative sites or blinded personnel until the study has been unblinded.
9.6.
Positron Emission Tomography (PET)
Before each PET scan, participants will have a low dose CT scan to provide data to 
enable correction of the PET data for tissue attenuation.  [18F]-FBA-A20FMVD2 will 
then be injected into a cubital or forearm vein through an intravenous cannula, and 
emission data acquired for up to 90 minutes.  One rest period will be permitted during the 
scan, if required. 

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An additional venous cannula in a cubital or forearm vein will be used to collect blood 
samples throughout the PET scan for quantification of the total and unmetabolised [18F]-
FBA-A20FMDV2-related radioactivity in whole blood and plasma.  The data will be 
used to derive an input function for the analysis of emission PET data.  The cannula may 
be flushed with saline to keep it patent, if required; HepSal will not be used.  At the end 
of the scanning day, the cannula will be removed.  
At the baseline visit only, an HRCT scan will also be performed for anatomical 
localisation.
In the event of a problem that prevents the PET scan going ahead after the study 
treatment has been administered, such as a quality control failure of the synthesised 
tracer, the scan may be rescheduled.  An additional dose of study treatment may be 
administered to the participant if required, at the discretion of the investigator and GSK 
Medical Monitor, as described in Section 5.1.3.
9.7.
Genetics
A 6 mL blood sample for deoxyribonucleic acid (DNA) isolation will be collected from 
participants who have consented to participate in the genetics analysis component of the 
study. Participation is optional. Participants who do not wish to participate in the genetic 
research may still participate in the study.
In the event of DNA extraction failure, a replacement genetic blood sample may be 
requested from the participant. Signed informed consent will be required to obtain a 
replacement sample unless it was included in the original consent.
See Appendix 6 for information regarding genetic research. Details on processes for 
collection and shipment and destruction of these samples can be found in the SRM.
9.8.
Biomarkers
Blood samples will be collected during this study and may be used for the purposes of
measuring novel biomarkers to identify factors that may influence IPF, and/or medically
related conditions, as well as the biological and clinical responses to GSK3008348. If
relevant, this approach will be extended to include the identification of biomarkers
associated with adverse events.  These analyses are exploratory in nature, and will be 
reported separately from the results of the clinical trial. 
Samples will be collected at the timepoints indicated in the SoA. The actual date and
time of each blood sample collection will be recorded. The timing of the collections may
be adjusted on the basis of emerging PK or pharmacodynamic (PD) data from this study 
or other new information in order to ensure optimal evaluation of the endpoints.
Novel candidate biomarkers and subsequently discovered biomarkers of the biological
response associated with IPF or medically related conditions and/or the action of study
treatment may be identified by the potential application of: 

Ribonucleic acid (RNA) transcriptome analysis of blood samples.

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
Measurement of the levels of a subset of RNA species in blood.

Proteome analysis in plasma and blood samples.

Measurement of the levels of a subset of proteins in plasma and blood samples 
which may include but are not limited to chemokine (C-C  motif) ligand 18 
(CCL18) [Prasse, 2009] and collagen degradation biomarkers [Jenkins, 2015].
Samples may be used for research to develop methods, assays, prognostics and/or 
companion diagnostics related to αvβ6, IPF disease processes, pathways associated with 
IPF and/or mechanism of action of GSK3008348.
All samples will be retained for a maximum of 15 years after the last participant
completes the trial.
9.9.
Immunogenicity Assessments
Serum samples will be analysed for the presence of anti-[18F]-FBA-A20FMDV2 
antibodies. Approximately 7 mL of blood will be collected into serum separator (SST) 
tubes (no anti-coagulant) at the timepoints indicated SoA. 
9.10.
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.
Sample Size Determination
This study is designed to assess the level of receptor engagement as measured by the 
effect of nebulised GSK3008348 on the v6-associated PET signal (VT). The PET data 
from the 5 participants in Cohort 1 receiving GSK3008348 will be used.  This sample 
size has been chosen based on considerations given to: a) the probability of declaring a 
successful study for reductions in v6-associated PET signal deemed to be 
representative of the expected receptor engagement activity, and b) the within-subject 
variability of the PET signal.
The chosen study success criteria is defined as Prob (θ < 0 | Study Data, Prior (θ)) ≥80%, 
where θ is the unknown true logarithm of the ratio of v6-associated PET signal post-
dose / pre-dose in patients receiving GSK3008348, and the prior distribution for θ is non-
informative. Assuming the within-subject standard deviation is as previously observed in 
study RES116235 (within-subject standard deviation following two PET scans was 
estimated to be 0.15, 95% CI [0.099, 0.34]), consideration was given to the probability of 
achieving the study success criteria for a range of true reductions in v6-associated PET 
signal with GSK3008348. In addition, the minimum detectable effect (MDE), i.e., the 
minimum observed reduction in v6-associated PET signal leading to the success 

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criteria being achieved, was also derived. In particular, if the true reduction in v6-
associated PET signal is 14% then there is 86% probability of achieving the above 
success criteria, and the MDE is a 6.2% reduction in v6-associated PET signal. 
10.2.
Populations for Analyses
For purposes of analysis, the following populations are defined:
Population
Description
All participants
All participants who are screened and for whom a record exists on 
the study database.
Enrolled 
All participants who are screened and enrolled into the study.
Intent-To-Treat (ITT)
All randomised participants who receive at least one dose of study 
treatment. This population will be based on the treatment they 
actually received. 
Per-Protocol
All participants in the ITT population who comply with the protocol 
and that have at least one evaluable PET measurement post 
baseline. 
Pharmacokinetic
All participants in the ITT population receiving active dose for whom 
a pharmacokinetic sample was obtained and analysed. 
10.3.
Statistical Analyses
10.3.1.
Pharmacodynamic Analyses
Endpoint
Statistical Analysis Methods
Volume of 
distribution [VT] in 
whole lung, not 
corrected for air 
volume
The logarithm of the v6-associated PET signal as measured by VT
will be analysed assuming that it follows a normal distribution. The 
mean or median signal level pre- and post-dose, as appropriate 
depending on the posterior distribution, along with the median 
difference post-dose – pre-dose, will be estimated and the 
corresponding 95% credible intervals will be produced. The posterior 
probability that the true difference in the logarithm of v6-associated 
PET signal post-dose vs pre-dose is less than 0 will be calculated. 
Non-informative priors will be used for all the parameters in the 
statistical model.
Secondary
Will be described in the reporting and analysis plan (RAP)
Exploratory
Will be described in the RAP

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10.3.2.
Safety Analyses
All safety analyses will be performed on the ITT Population. Safety data will be 
presented in tabular and/or graphical format and summarised descriptively according to 
GSK’s Integrated Data Standards Library (IDSL) standards.
10.3.3.
Pharmacokinetic analyses
Plasma concentration-time data of GSK3008348 will be displayed in listings, summary 
tables and/or graphically.  Summary data will use nominal/planned sample times, listings 
will display planned and actual times.  Plasma concentration-time data may be used to 
derive PK parameters (such as AUC and Cmax) using standard non-compartmental 
analysis according to current working practices and using Phoenix WNL, or other 
currently validated software.  All calculations of non-compartmental parameters will be 
based on actual sampling times.
Additionally, plasma concentration-time data may be used to derive population PK 
parameters/models using NONMEM or other currently validated software.  Any 
population PK analysis will be presented separately from the main clinical study report 
(CSR).
Statistical analyses of the PK parameter data will be the responsibility of Clinical 
Statistics, GlaxoSmithKline.
10.3.4.
Other Analyses
Exploratory PD and biomarker analyses will be described in the RAP, and will be 
presented separately from the main CSR. 
10.3.5.
Interim Analyses
An interim analysis will be performed for futility or sample size re-estimation based on 
the variability of the PET signal (VT) and the level of receptor engagement at the end of 
Cohort 1 and prior to the start of Cohort 2. The PET data from the 5 participants in 
Cohort 1 receiving GSK3008348 will be used. The logarithm of the v6-associated PET 
signal as measured by VT will be analysed assuming that it follows a normal distribution. 
10.3.5.1.
Interim Analysis for Futility
Assuming that the variability is as anticipated, if the posterior probability Prob (θ < 0 | 
Study Data, Prior (θ)) < 80%, where θ is the unknown true logarithm of the ratio of 
v6-associated PET signal post-dose / pre-dose in patients receiving 1,000 µg
GSK3008348 in Cohort 1, and the prior distribution for θ is non-informative, then the 
study will stop for futility. If the study is stopped at the end of Cohort 1, then Cohort 2 
will not proceed.

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10.3.5.2.
Interim Analysis for Sample Size Re-estimation
If the variability in VT is higher than expected, then sample size re-estimation will be 
performed and additional participants receiving 1,000 µg GSK3008348 will be recruited 
into Cohort 2. Sample size re-estimation will be primarily based on the posterior 
predictive distribution of the data given the information collected at the interim, and the 
predictive probability of end-of-study success. This probability will be calculated for a 
range of sample sizes up to a maximum of 10 additional participants receiving 1,000 µg 
GSK3008348 in Cohort 2.
Further details of the interim analysis will be provided in the RAP.

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11.
REFERENCES
GSK Document Number 2013N163906_00 Study RES116235. Validation and Dosimetry 
Study of [18F]-FBA-A20FMDV2 PET Ligand for αvβ6 in Healthy Subjects and in the 
Lungs of Idiopathic Pulmonary Fibrosis (iPF) Subjects (PETAL study). Protocol Date 18-
Oct-2013. 
GSK Document Number 2014N201929_01 Study 200262.  A FTIH study with 
GSK3008348 in healthy volunteers and patients with Idiopathic Pulmonary Fibrosis. 
Protocol Date 29-Sep-2015.
Horan G.S, Wood S.,, Ona V., Li D.J., Lukashev M.E., Weinreb P.H. et al. Partial 
inhibition of integrin αvβ6 prevents pulmonary fibrosis without exacerbating 
inflammation. Am. J. Respir. Crit. Care Med. 2008;177:56-65. 
Hughes, G., Toellner, H., Morris, H., Leonard, C., Chaudhuri, N.  Real World 
Experiences:  Pirfenidone and Nintedanib are Effects and Well Tolerated Treatments for 
Idiopathic Pulmonary Fibrosis.  J. Clin. Med.  2016;5:78. 
Jenkins R.G., Simpson J.K., Saini G., Bentley J.H., Russell A.M., Braybrooke R. et al. 
Longitudinal change in collagen degradation biomarkers in idiopathic pulmonar fibrosis: 
an analysis from the prospective, multicentre PROFILE study. The Lancet Respirator 
Medicine. 2015;3:462-472. 
John A.E, Luckett J.C., Tatler A.L., Awais R.O., Desai A. et al. Preclinical SPECT/CT 
imaging of αvβ6 integrins for molecular statification of idiopathic pulmonary fibrosis. J. 
Nucl. Med. 2013;54:2146-2152. 
King T, Bradford W., Castro-Bernardini S., Fagan E., Glaspole I., Glassberg M., et al. 
Effect of design modifications on trial outcomes in idiopathic pulmonary fibrosis (IPF): 
Analysis of data from ASCEND and CAPACITY (CAP). Eur. Respir. J. 2014;44. 
Margadant C, Sonnenberg A.. Integrin-TGF-B crosslink in fibrosis, cancer and wound 
healing. EMBO Rep. 2010;11:97-105. 
Munger J.S., Huang X., Kawakatsu H., Griffiths M.J., Dalton S.L., Wu J., et al. The 
integrin αvβ6 binds and activates latent TGFβ: A mechanism for regulating pulmonary 
inflammation and fibrosis. Cell. 1999;96:319-328. 
Navaratnam V.,. Fogarty AW., Glendening R., McKeever T. and Hubbard RB. The 
increasing secondary care burden of idiopathic pulmonary fibrosis: Hospital admission 
trends in England from 1998 to 2010. Chest. 2013;143:1078-1084. 
Prasse A., Probst C., Bargagli E., Zissel G., Toews G.B., Flaherty K.R., et al. Serum CC-
Chemokine Ligand 18 Concentration Predicts Outcome Idiopathic Pulmonary Fibrosis. 
Am J Respir Crit Care Med. 2009;179:717-723. 

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Puthawala K., Hadjiangelis N., Jacoby S.C., Bayongan E., Zhao Z., Yang Z., et al. 
Inhibition of integrin avb6, an activator of latent transforming growth factor-β, prevents 
radiation-induced lung fibrosis. Am. J. Respir. Crit. Care Med. 2008;177:82-90. 
Raghu G., Collard H.R., Egan J.J., Martinez F.J., Behr J., Brown K.K., et al. An Official 
ATS/ERS/JRS/ALAT Statement: Idiopathic Pulonary Fibrosis: Evidence-based 
Guidelines for Diagnosis and Management. Am. J. Respir. Crit Care Med. 2011;183:788-
824. 
Richeldi L., Du Bois R.M., Raghu G., Azuma A., Brown K.K., Costabel U., et al. 
Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. New Engl. Med. 
2014;370:2071-2082. 
Saini G., J. Porte, W. Wallace, P. Weinreb, S. Violette T. McKeever and G. Jenkins. 
Imunophenotyping in VATS Lung Biopsy Predicts Prognosis in Idiopathic Pulmonary 
Fibrosis (IPF). 2013:75.

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12.
APPENDICES
12.1.
Appendix 1: Abbreviations and Trademarks
AE
Adverse Event
ALT
Alanine Transaminase
AST
Aspartate Transaminase
AUC
Area under the plasma drug concentration versus time curve
AUC(0-t)
Area under the plasma concentration-time curve from zero
(0) hours to time (t)
AUC(0-∞)
Area under the plasma concentration-time curve from zero
(0) hours to infinity (∞)
BMI
Body Mass Index
CCL18
Chemokine (C-C  motif) ligand 18
CE
European Conformity mark 
Cmax
Maximum observed plasma drug concentration
CL
Clearance 
CONSORT
Consolidated Standards of Reporting Trials
CPK
Creatinine Phosphokinase
CSR
Clinical Study Report 
CT
Computed Tomography
CV
Cardiovascular 
DLCO
Diffusing capacity of the lungs for carbon monoxide
DNA
Deoxyribonucleic acid 
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
ENT
Ear, Nose and Throat
FDA
Food and Drug Administration 
FEV1
Forced Expiratory Volume
FMDV2
Food and Mouth Disease Virus
FSH
Follicle Stimulating Hormone
FVC
Forced Vital Capacity
GCP
Good Clinical Practice
GCSP
Global Clinical Safety & Pharmacovigilance
GLP
Good Laboratory Practice
GSK
GlaxoSmithKline
HRCT
High-Resolution Computed Tomography
IB
Investigator Brochure
ICF
Information and consent form 
ICH
International Conference on Harmonisation 
ICRP
International Commission on Radiological Protection
IDSL
Integrated Data Standards Library
IEC
Independent Ethics Committee
IP
Investigational Product
IPF
Idiopathic Pulmonary Fibrosis
IRB
Institutional Review Board

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ITT
Intent-To-Treat 
IVRS/IWRS
Interactive Voice/Web Response System 
MCH
Mean Cell Haemoglobin
MCV
Mean Cell Volume
MDE
Minimum detectable effect 
MedDRA
Medical Dictionary for Regulatory Activities
mL
Milliliter
mm
Millimeter
MM
Medical Monitor
MSDS
Material Safety Data Sheet
mSV
Millisievert
NOAEL
No Observed Adverse Effect Level
OAT
Organic anion transporter
PD
Pharmacodynamic
PET
Positron Emission Tomography
PI
Principal Investigator
PK
Pharmacokinetics
QTc
Corrected QT Interval
QTcF
QT duration corrected for heart rate by Fridericia’s formula
RAP
Reporting and Analysis Plan
RBC
Red Blood Cells
RNA
Ribonucleic Acid
SAE
Serious Adverse Event
SoA
Schedule of Assessments 
SPECT
Single Photon Emission Computed Tomography
SpO2
Peripheral Capillary Oxygen Saturation
SRM
Study Reference Manual
SST
Serum-separator Tube
SUSAR
Suspected Unexpected Serious Adverse Reaction 
SUV
Standardised Uptake Volume
T1/2
Terminal half-life
TGFβ
Transforming Growth Factor Beta
Tmax
Time to maximum concentration
UIP
Usual Interstitial Pneumonia
ULN
Upper Limit of Normal
V
Volume of Distribution (of GSK3008348) 
VT
Volume of Distribution (of PET radioligand) 
WBC
White Blood Cells
WOCBP
Women of childbearing potential

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Trademark Information
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
NONE
HepSal
MedDRA
NONMEM
Phoenix WNL
RANDALL NG

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12.2.
Appendix 2: Clinical Laboratory Tests

The tests detailed in Table 1 will be performed by the local laboratory. 

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 1
Protocol-Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters
Hematology
Platelet Count
RBC Indices:
MCV
MCH
WBC count with Differential:
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
RBC Count
Hemoglobin
Hematocrit
Clinical 
Chemistry1
BUN
Potassium
Total and direct 
bilirubin
Total Protein
Creatinine
Sodium
CPK
Albumin
Glucose 
(non-fasting)
Calcium
Alkaline 
phosphatase
Gamma glutamyl 
transferase 
(gamma GT) 
Aspartate aminotransferase
(AST)
Alanine aminotransferase
(ALT)
Routine 
Urinalysis

Specific gravity

pH, glucose, protein, blood and ketones by dipstick

If blood or protein is abnormal, a mid-stream urine sample will be collected 
for further urinalysis, to include microscopy, culture and sensitivities 
Other 
Screening 
Tests

Follicle-stimulating hormone and estradiol (as needed in women of non-
childbearing potential only)

Serum or urine human chorionic gonadotropin (hCG) pregnancy test (as 
needed)2

Serology (hepatitis B surface antigen [HBsAg], and hepatitis C virus 
antibody; hepatitis C RNA test, if required after a positive antibody test) 
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 8.1.1 and Appendix 7. All events of ALT 3 × 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.

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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 substantial 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. 
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.
Dissemination of Clinical Study Data

Where required by applicable regulatory requirements, an investigator signatory 
will be identified for the approval of the clinical study report.  The investigator 

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will be provided reasonable access to statistical tables, figures, and relevant 
reports and will have the opportunity to review the complete study results at a 
GSK site or other mutually-agreeable location.

GSK will also provide the investigator with the full summary of the study 
results.  The investigator is encouraged to share the summary results with the 
study participants, as appropriate.

GSK will provide the investigator with the randomisation codes for their site 
only after completion of the full statistical analysis.

The procedures and timing for public disclosure of the results summary and for 
development of a manuscript for publication will be in accordance with GSK 
Policy. 
Data Quality Assurance

All participant data relating to the study will be recorded in the 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 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 after study completion 
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 entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained. 

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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.
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.
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 

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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, 
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 

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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.
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 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 study treatment (causality) within 72 hours of SAE entry 
into the eCRF. 

After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see 
next section) or to the medical monitor by telephone.

Contacts for SAE reporting can be found in the SRM.
SAE Reporting to GSK via Paper CRF

Facsimile transmission of the SAE paper CRF is the preferred method to transmit 
this information to the medical monitor.

In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by overnight 
mail or courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time frames.

Contacts for SAE reporting can be found in the SRM.

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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
25. Premenarchal
26. 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.
27. 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
Male participants
Male participants with female partners of child-bearing potential are eligible to 
participate if they agree to ONE of the following during the protocol-defined time frame 
in Section 6.1: 

Are abstinent from penile-vaginal intercourse as their usual and preferred 
lifestyle (abstinent on a long term and persistent basis) and agree to remain 
abstinent 

Agree to use a male condom plus an additional method of contraception with a 
failure rate of <1% per year as described in Table 2 when having penile-vaginal 
intercourse with a woman of childbearing potential 

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Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-
vaginal intercourse or use a male condom during each episode of penile penetration 
during the protocol-defined time frame.
Men must refrain from donating sperm for duration of study and for 90 days after study 
completion.
Female participants
Female participants of childbearing potential are not eligible to participate. 
Table 2
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 treatment. 
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. 

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Pregnancy Testing

Women should only be included after a negative highly sensitive urine or serum 
pregnancy test 

Additional pregnancy testing will be performed before each PET scan, as required 
locally 
Collection of Pregnancy Information
Male participants with partners who become pregnant

Investigator will attempt to collect pregnancy information on any male participant’s 
female partner of a male study participant who becomes pregnant while participating 
in this study. This applies only to participants who receive study treatment.

After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the investigator will record pregnancy information on the 
appropriate form and submit it to GSK within 24 hours of learning of the partner’s 
pregnancy. 

Partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to GSK

Generally, follow-up will be no longer than 6 to 8 weeks following the estimated
delivery date. Any termination of the pregnancy will be reported regardless of fetal 
status (presence or absence of anomalies) or indication for procedure. 
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 

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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 be withdrawn 
from the study. 

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12.6.
Appendix 6: Genetics
USE/ANALYSIS OF DNA

Genetic variation may impact a participant’s response to therapy, susceptibility, 
severity and progression of disease. Variable response to therapy may be due to 
genetic determinants that impact drug absorption, distribution, metabolism, and 
excretion; mechanism of action of the drug; disease etiology; and/or molecular 
subtype of the disease being treated. Therefore, where local regulations and IRB/IEC 
allow, a blood sample will be collected for DNA analysis

DNA samples will be used for research related to GSK3008348 or IPF and related 
diseases. They may also be used to develop tests/assays including diagnostic tests) 
related to GSK3008348 (or study treatments of this drug class), and IPF. 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 will be analyzed 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 GSK3008348 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 GSK3008348 (or study treatments of 
this class) or IPF continues but no longer than 15 years after the last visit of the last 
subject, or other period as per local requirements.

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12.7.
Appendix 7: Liver Safety: Required Actions and Follow-up
Assessments
Phase I liver chemistry stopping criteria have been designed to assure participant safety 
and to evaluate liver event etiology (in alignment with the FDA premarketing clinical 
liver safety guidance). 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/UCM174090.pdf.
Phase I liver chemistry stopping criteria and required follow up assessments
Liver Chemistry Stopping Criteria – Liver Stopping Event
ALT-absolute
ALT ≥ 3xULN
If ALT ≥ 3xULN AND bilirubin1,2 2xULN (>35% direct bilirubin) or  INR >1.5, 
Report as an SAE.
See additional Actions and Follow Up Assessments listed below
Required Actions and Follow up Assessments following Liver Stopping Event
Actions
Follow Up Assessments

Report the event to GSK within 24 hours

Complete the liver event eCRF, and complete an 
SAE data collection tool if the event also meets 
the criteria for an SAE2

Perform liver event follow up assessments 

Monitor the participant until liver chemistries 
resolve, stabilise, or return to within baseline (see 
MONITORING below)
MONITORING:
If ALT ≥ 3xULN AND bilirubin 2xULN or 
INR > 1.5: 

Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform liver 
event follow up assessments within  24 hrs

Monitor participants twice weekly until liver 
chemistries resolve, stabilise or return to within 
baseline

A specialist or hepatology consultation is 
recommended

Viral hepatitis serology3

Blood sample for pharmacokinetic 
(PK) analysis, obtained as soon as 
possible after the event, and within 
36 h of last dose4

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 on the concomitant 
medications report formincluding 
acetaminophen, herbal remedies, 
other over the counter medications.

Record alcohol use on the liver event 

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If ALT ≥3xULN AND bilirubin < 2xULN and 
INR ≤1.5:

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
alcohol intake case report form
If ALT ≥3xULN AND bilirubin 2xULN 
or INR >1.5:

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 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 
forms.
1.
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study treatment for that participant 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 
(excludingstudies of hepatic impairment or cirrhosis); INR measurement is not required and the threshold value
stated will not apply to participants receiving anticoagulants
3.
Includes: Hepatitis A IgM antibody; Hepatitis B surface antigen and Hepatitis B Core Antibody (IgM); Hepatitis 
CRNA; Cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain 
heterophile antibody or monospot testing);  Hepatitis E IgM antibody 
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: Radiation Dose Risk Assessment
Participants will be exposed to an additional dose of ionising radiation as a consequence 
of their participation in this study. The ionising radiation exposure from PET and CT 
scanning comes from three sources. A proportion of the radiation exposure comes from 
the administered radioligand ([18F]-FBA-A20FMDV2). The remaining radiation dose 
comes from an HRCT for anatomical localisation (performed once only during the study) 
and low dose CT scans performed in order to correct the PET data for tissue attenuation. 
If the participant needs to be removed from the scanner and repositioned during the PET 
scan than a second low dose CT scan may be performed. The doses chosen for this study 
aim to deliver a minimal radiation exposure, compatible with a good quality PET and CT 
signal. 
Each participant will have up to three PET-CT scans. The effective dose for each 
radioligand administration will be 3.3 mSv based on a conversion factor of 
21.7 Sv/MBq determined from study RES116235 and a maximum administered activity 
of 150 MBq. A low-dose attenuation CT scan of the lung results in an effective dose of 
1.2 mSv. If the participant leaves the scanner during the scan and is repositioned, the CT 
scan will be repeated which would result in a further effective dose of 1.2 mSv. In 
addition, each participant will have one HRCT scan, resulting in an effective dose of 
3.8 mSv. The total effective dose to each participant will therefore be up to 3 x (3.3 + 2.4) 
+ 3.8 = 20.9 mSv. All of this exposure is over and above standard practice.
The total maximum effective dose of 20.9 mSv in this study is equivalent to 
approximately 9 times the average yearly exposure (2.3 mSv) from natural background 
radiation in the United Kingdom. The additional risk of developing a fatal malignancy as 
a result of these exposures has been estimated as approximately 1 in 1,000 for an adult in 
normal health. The reduced life expectancy of IPF patients will result in a lower risk for 
these individuals.
Within the UK the guidance set out by ICRP 62 is generally followed in setting research 
study dose constraints. The level of risk may therefore be assumed to broadly fall within 
the ICRP 62 intermediate Category IIb, where the benefit should be more directly aimed 
at the cure or prevention of disease. 

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12.9.
Appendix 9: Assessment of the Potential Immunogenicity 
Risk for [18F]-FBA-A20FMDV2
Immunogenicity is a potential risk for exogenous peptides.  However, we consider the 
risk to be low under the current circumstances where the peptide is synthetic and is not 
administered repeatedly for clinical benefit, but is used as an imaging tracer. 
This potential risk may come from two sources: 
g.
pre-existing antibodies that may arise from prior exposure to the intact virus
h.
induction of a de novo immune response by exposure to the peptide
The risk assessment and management strategy is summarised in Table 3.
Table 3
Summary of the assessment of the immunogenicity risk for [18F]-
FBA-A20FMDV2 in the PETAL Study
Potential risk
Relevant factors and 
comments
Assessment of risk
Risk mitigation /management
Risk level 
Potential risk for pre-
existing antibodies
Previous exposure to 
FMDV may have 
elicited an immune 
response in certain 
individuals that may 
recognise the peptide
FMD is notifiable in 
the UK and the last 
outbreak was in 2007
FMD is endemic in 
certain areas of 
Africa, Asia and 
South America
Participants with prior exposure 
to farm animals are excluded 
from the study. 
Participants resident in 
endemic countries are 
excluded from the study.
Low
Potential risk for 
induction of a de 
novo immune 
response
Route of 
administration
[18F]-FBA-
A20FMDV2 will be 
administered 
intravenously. 
This route is less immunogenic 
than the subcutaneous route. 
Two participants in a previous 
study developed anti-peptide 
antibodies to this tracer but 
neither experienced any clinical 
event.
Low
Number and 
frequency of dosing
[18F]-FBA-
A20FMDV2 will be 
administered 2 or 3 
times to patients with 
IPF 
The 3 doses will be 
administered a maximum of 4  
weeks apart, reducing the 
potential for immune response 
maturation 
Low
Cross-reacting 
antibodies to [18F]-
FBA-A20FMDV2
Anti-[18F]-FBA-
A20FMDV2 
antibodies may 
cross-react with non-
redundant 
endogenous proteins 
and give rise to 
adverse events
Humans are likely to be 
tolerant to sequences 
containing RGD
Development of anti- [18F]-
FBA-A20FMDV2 antibodies 
would require breaking 
tolerance
Low
Physico-chemical 
properties of [18F]-
FBA-A20FMDV2
An effective 
immunogen must 
contain T cell 
epitopes presented in 
the presence of 
adjuvant
[18F]-FBA-A20FMDV2 is 
chemically synthesised and 
there is no elevated concern 
for contaminating host cell 
products with adjuvant 
properties.  
Low

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Potential risk
Relevant factors and 
comments
Assessment of risk
Risk mitigation /management
Risk level 
GSK2634673F is 
predicted to contain 
two sequences that 
have binding capacity 
for MHC class II
Aggregation of the peptide is 
minimal
Clinical relevance of in silico
predictions is uncertain, 
however a relevant T cell 
epitope cannot be excluded
In the absence of adjuvant a 
productive immune response is 
very unlikely
Risk mitigation measures
Clinical management
Although the risk of immunogenicity is low, some immune responses can progress to 
hypersensitivity reactions, such as IgE-mediated allergic reactions (anaphylaxis).  The 
impact of such a very rare event would be high. In order to manage this potential risk the 
following measures are in place at the site:

Crash trolleys are available on site

Suitably trained staff are available throughout the study

SOPs have been developed and are current at the site

Direct access to resuscitation teams and intensive care facilities are available 
immediately 
Assay to measure anti-peptide antibodies
Immunogenicity assessment will be performed for serum samples collected as per the 
SoA. Results will be analysed when the study is completed and will be correlated with 
any clinical or imaging observations.
Conclusions
Currently, the evidence suggests that the immunogenicity risk of [18F]-FBA-A20FMDV2, 
a synthetic 20 amino acid peptide, is predicted to be low. Mitigation strategies are 
incorporated into the protocol as described in the table above (such as exclusion of prior 
exposure to FMDV, short period between the 3 doses). In the unlikely event that 
anaphylaxis occurs, appropriate clinical management procedures are available 
immediately.

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References
Francis, M. J.,  Fry, C. M., Rowlands, D.J., Brown, F., Bittle, J. L. , Houghten, R. A. , 
and Lerner R. A. Immunological Priming with Synthetic Peptides of Foot-and-Mouth 
Disease Virus. J. gen. Virol. 1985: 66; 2347-2354
Schellekens H. Immunogenicity of Therapeutic Proteins: Clinical Implications and Future 
Prospects. Clinical Therapeutics 2002: 24; 1720-40

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12.10.
Appendix 10:  Diagram Summarising the Study Decision 
Making
The data from the 30 min post-dose PET scan will be used to make decisions on the 
design of Cohort 2, assuming Cohort 1 safety data supports proceeding to Cohort 2.  
Figure 2 below illustrates the decision making for the study. 
Figure 2
Diagram illustrating study decision making

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12.11.
Appendix 11: Areas Endemic to Foot and Mouth Disease
Figure 3
Global Distribution of Foot and Mouth Disease
Figure 3 shows the geographical distribution of 7 pools of foot and mouth disease viruses 
(FMDV).  Serotype O FMDV is the most widely distributed serotype.  Countries which 
are normally free of the disease (North America, Europe, Russia, Australia and most of 
South America), and are therefore not included in any of the pools shown above, are 
marked in light yellow. 
Reference
Jamal, S. M. & Belsham, G. J. Foot-and-mouth disease: Past, present and future. 
Veterinary Research 44, (2013) 

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12.12.
Appendix 12: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC).
Amendment 01
Overall Rationale for the Amendment: As part of their review of the clinical trial 
authorisation, the Medicines and Healthcare products Regulatory Agency (MHRA) 
requested a clarification to the emergency unblinding instructions in the protocol. 
Section # 
and Name
Description of Change
Brief Rationale
7.4 Blinding
Clarified that the investigator may break the 
blind for a participant in an emergency, or if it 
is in the participant’s best interest for the 
investigator to know the study treatment 
assignment, whether or not an antidote is 
available, and that the responsibility lies with 
the investigator. The investigator is 
encouraged to discuss with GSK personnel 
before breaking the blind, but if not, may 
inform GSK after the event. 
As requested by the MHRA.