Conditions: Healthy Volunteers
Keywords: Japanese, Caucasian, pharmacokinetics, pharmacodynamics, GSK2831781, lymphocyte activation gene-3
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 36
Healthy volunteers: yes

Brief summary:
This is a double-blind, placebo-controlled, randomized, parallel group, two-part study where single IV doses of GSK2831781 will be administered to healthy Japanese and Caucasian subjects in part A and SC doses will be administered to healthy Caucasian subjects in part B. GSK2831781 is a humanized, antibody-dependent cell cytotoxicity (ADCC) enhanced depleting monoclonal antibody that is specific to the lymphocyte activation gene-3 (LAG3) protein. LAG3 is a transmembrane receptor, which is upregulated on T cells following activation. The objective of the study is to assess the safety, tolerability, PK, PD and immunogenicity post administration of GSK2831781 in healthy subjects. The duration of the study is approximately 147 days for each subject enrolled. Approximately 36 subjects will be enrolled in the study, 16 subjects in Part A and 20 subjects in Part B.

Detailed description:

Arms:
arm 1: Caucasian male participants were administered a single IV infusion of 0.9% weight by volume (w/v) saline placebo. arm 2: Caucasian male participants were administered a single IV infusion of GSK2831781 at a dose of 450 milligram (mg), diluted in 0.9% w/v saline. arm 3: Japanese male participants were administered a single IV infusion of 0.9% w/v saline placebo. arm 4: Japanese male participants were administered a single IV infusion of GSK2831781 at a dose of 450 mg, diluted in 0.9% w/v saline. arm 5: Caucasian male participants were administered three SC injections of 0.9% w/v saline placebo. arm 6: Caucasian male participants were administered a single SC injection of a unit dose strength of 150 mg per milliliter (mL) of GSK2831781, diluted in 0.9% w/v saline. Participants also received 2 dummy injections of 0.9% w/v saline placebo SC to maintain the blinding. arm 7: Caucasian male participants were administered three SC injections of a unit dose strength of 150 mg per mL of GSK2831781 to achieve a dose of 450 mg.

Interventions: intervention 1: GSK2831781 intervention 2: Placebo
Intervention descriptions: intervention 1: GSK2831781 will be available as Dose-1 and Dose-2 as IV infusion or SC injection. Subjects will receive GSK2831781 Dose-1 IV diluted in 0.9% saline or GSK2831781 SC as multiples of Dose-2 SC. intervention 2: Placebo will be 0.9% saline solution which will be administered in subjects as IV infusion or SC injection.

Protocol document:
Prot_000.pdf: 
2018N393275_01
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TITLE PAGE
Protocol Title: A randomised, double-blind, placebo-controlled Phase I study of the 
safety and tolerability, pharmacokinetics, and pharmacodynamics of a single intravenous 
dose of GSK2831781 in healthy Japanese and Caucasian participants, and a single 
subcutaneous dose of GSK2831781 in healthy Caucasian participants.
Protocol Number: 207823/ amendment 01
Compound Number:
GSK2831781
Study Phase: Phase 1 
Short Title: Safety, tolerability, pharmacokinetics and pharmacodynamics of 
GSK2831781 after an intravenous dose in healthy Japanese and Caucasian participants, 
and a subcutaneous dose in healthy Caucasian participants. 
Sponsor Name and Legal Registered Address: 
GlaxoSmithKline Research & Development Limited
980 Great West Road
Brentford
Middlesex, TW8 9GS
UK
Medical Monitor Name and Contact Information can be found in the Study Reference 
Manual (SRM).
Regulatory Agency Identifying Number(s):
IND: 
139126
EudraCT:  2019-000832-25
Approval Date: 06-MAY-2019
Copyright 2019 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited.
 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document
Date
DNG Number
Amendment 1
06-MAY-2019
2018N393275_01
Original Protocol
13-Mar-2019
2018N393275_00
Amendment 1 06-MAY-2019
Overall Rationale for the Amendment: This is a protocol amendment with changes to 
the exclusion criteria, ECG assessment time points, inclusion of medical management 
guidance, clarification regarding the re-start of dosing and changes to the wording 
regarding the recording of SAEs. This amendment was made as per MHRA’s request for 
study approval. 
 
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Section # and 
Name
Description of Change
*Bolded text indicates newly added text, 
and strikethrough indicates deleted text.
Brief Rationale
2.2 Schedule 
of Activities 
Part B
The SoA was amended to include 
additional ECG monitoring post-
dose on Day 1 and Day 2 of Part 
B.
This amendment was made so that ECG 
monitoring in Part B is in line with 
monitoring in Part A of the study.
6.2 Exclusion 
Criteria #13
The following change was made: 
Absolute nNeutrophil count 
<1.5x109/L or lymphocyte counts
below the normal range
<0.8x109/L.
Participants with any grade of neutropenia 
are excluded.
6.2 Exclusion 
Criteria #14
The following change was made:
Estimated glomerular filtration rate 
(GFR) by Chronic Kidney Disease 
Epidemiology Collaboration 
equation (CKD-EPI) calculation
<60mL ≤90mL/min/1.73 m2 at 
screening.
The value has been amended to ensure a 
healthy participant population.
7.1 Study 
Intervention(s) 
Administered
GSK2831781,
 
 
The concentration of 
has been 
amended
, it was previously listed
as 
 in error.  
8.3 Role of 
Safety Review 
Team
An amendment was made to 
include the following:
If the study is halted due to 
safety concerns based on a 
decision by the SRT (or DRC; 
see 11.1.5), and a subsequent 
decision is made to restart 
dosing, this will only occur after 
competent authority 
authorization via a substantial 
amendment.
This amendment was made for clarification 
surrounding the restarting of dosing during 
the trial. 
9.1.5 Infusion-
related 
Reactions
An amendment was made to 
include guidance on medical 
management of infusion-related 
reactions (section 9.1.5), 
This provides guidance if any of the 
reactions mentioned occur in a participant 
during the study. 
 
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Section # and 
Name
Description of Change
*Bolded text indicates newly added text, 
and strikethrough indicates deleted text.
Brief Rationale
hypersensitivity reactions (section 
9.1.6) and cytokine-release 
syndrome (9.1.7).
9.2.1 Time 
Period and 
Frequency for 
Collecting AE 
and SAE 
information
An amendment was made to 
include the following:
Medical occurrences that begin 
before the start of study 
intervention but after obtaining 
informed consent will be recorded 
on the Medical History/Current 
Medical Conditions section of the 
CRF not the AE section. The 
exceptions are SAEs, which 
must be recorded in the CRF 
AE/SAE section.
This amendment clarifies the wording as 
previously it was inconsistent regarding the 
instructions for SAE recording in the trial.
 
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TABLE OF CONTENTS
PAGE
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE.....................................3
1.
PROTOCOL SUMMARY..........................................................................................9
1.1.
Synopsis.......................................................................................................9
1.2.
Schema ......................................................................................................11
2.
SCHEDULE OF ACTIVITIES (SOA).......................................................................12
2.1.
Part A: Japanese and Caucasian Participants – IV Dose............................12
2.2.
Part B: Caucasian Participants – Subcutaneous Dose................................16
3.
INTRODUCTION....................................................................................................19
3.1.
Study Rationale ..........................................................................................19
3.2.
Background ................................................................................................19
3.3.
Benefit/Risk Assessment ............................................................................20
3.3.1.
Risk Assessment .........................................................................21
3.3.2.
Benefit Assessment.....................................................................28
3.3.3.
Overall Benefit: Risk Conclusion..................................................28
4.
OBJECTIVES AND ENDPOINTS...........................................................................28
5.
STUDY DESIGN ....................................................................................................29
5.1.
Overall Design ............................................................................................29
5.2.
Number of Participants ...............................................................................29
5.3.
Intervention Groups and Duration ...............................................................30
5.3.1.
Part A ..........................................................................................30
5.3.2.
Part B ..........................................................................................30
5.4.
Participant and Study Completion...............................................................30
5.5.
Scientific Rationale for Study Design ..........................................................31
5.5.1.
Part A (Japanese ethnosensitivity)...............................................31
5.5.2.
Part B (subcutaneous PK) ...........................................................31
5.6.
Placebo control...........................................................................................32
5.7.
Justification for Dose ..................................................................................32
6.
STUDY POPULATION...........................................................................................32
6.1.
Inclusion Criteria.........................................................................................33
6.2.
Exclusion Criteria........................................................................................34
6.3.
Lifestyle Considerations..............................................................................36
6.3.1.
Alcohol Restrictions .....................................................................36
6.3.2.
Activity .........................................................................................36
6.4.
Screen Failures...........................................................................................36
7.
STUDY INTERVENTION........................................................................................36
7.1.
Study Intervention(s) Administered .............................................................37
7.2.
Preparation/Handling/Storage/Accountability..............................................38
7.3.
Method of Treatment Assignment ...............................................................38
7.4.
Blinding.......................................................................................................39
7.5.
Study Intervention Compliance ...................................................................40
7.6.
Concomitant Therapy..................................................................................40
7.7.
Dose Modification .......................................................................................40
 
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8.
DISCONTINUATION CRITERIA.............................................................................41
8.1.
Discontinuation of Study Intervention..........................................................41
8.2.
Study Stopping Criteria...............................................................................41
8.2.1.
Serious Adverse Events...............................................................41
8.2.2.
AEs of Special Interest.................................................................41
8.2.3.
Liver Chemistry Criteria ...............................................................41
8.2.4.
QTc Criteria .................................................................................42
8.3.
Role of the Safety Review Team (SRT) ......................................................42
8.4.
Participant Discontinuation/Withdrawal from the Study ...............................43
8.5.
Lost to Follow-Up........................................................................................43
9.
STUDY ASSESSMENTS AND PROCEDURES .....................................................44
9.1.
Safety Assessments ...................................................................................44
9.1.1.
Physical Examinations.................................................................44
9.1.2.
Vital Signs....................................................................................45
9.1.3.
Electrocardiograms......................................................................45
9.1.4.
Clinical Safety Laboratory Assessments ......................................45
9.1.5.
Infusion-related Reactions ...........................................................45
9.1.6.
Hypersensitivity Reactions...........................................................46
9.1.7.
Cytokine Release Syndrome........................................................47
9.1.8.
Immunosuppression and Infections..............................................47
9.1.9.
Autoimmunity...............................................................................47
9.2.
Adverse Events and Serious Adverse Events.............................................47
9.2.1.
Time Period and Frequency for Collecting AE and SAE 
Information...................................................................................48
9.2.2.
Method of Detecting AEs and SAEs.............................................48
9.2.3.
Follow-up of AEs and SAEs.........................................................48
9.2.4.
Regulatory Reporting Requirements for SAEs .............................49
9.3.
Treatment of Overdose...............................................................................49
9.4.
Pharmacokinetics .......................................................................................49
9.4.1.
Soluble LAG3 (sLAG3) ................................................................50
9.5.
Pharmacodynamics ....................................................................................50
9.6.
Genetics .....................................................................................................50
9.7.
Immunogenicity Assessments.....................................................................50
10. STATISTICAL CONSIDERATIONS........................................................................51
10.1.
Statistical Hypotheses.................................................................................51
10.2.
Sample Size Determination ........................................................................51
10.2.1.
Part A ..........................................................................................51
10.2.2.
Part B ..........................................................................................52
10.2.3.
Sample Size Sensitivity................................................................52
10.3.
Populations for Analyses ............................................................................53
10.4.
Statistical Analyses.....................................................................................53
10.4.1.
Safety Analyses...........................................................................53
10.4.2.
Pharmacokinetic Analyses...........................................................53
10.4.3.
Pharmacokinetic/Pharmacodynamic Analysis..............................54
10.4.4.
Other Analyses ............................................................................54
10.5.
Interim Analyses .........................................................................................54
11. SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS...............................................................................................56
 
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11.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations............................................................................................56
11.1.1.
Regulatory and Ethical Considerations ........................................56
11.1.2.
Financial Disclosure.....................................................................56
11.1.3.
Informed Consent Process ..........................................................57
11.1.4.
Data Protection............................................................................57
11.1.5.
Committees Structure ..................................................................57
11.1.6.
Dissemination of Clinical Study Data ...........................................58
11.1.7.
Data Quality Assurance ...............................................................58
11.1.8.
Source Documents ......................................................................59
11.1.9.
Study and Site Closure ................................................................59
11.1.10. Publication Policy.........................................................................60
11.2.
Appendix 2: Clinical Laboratory Tests.........................................................61
11.3.
Appendix 3: Adverse Events: Definitions and Procedures for
Recording, Evaluating, Follow-up, and Reporting .......................................63
11.3.1.
Definition of AE............................................................................63
11.3.2.
Definition of SAE..........................................................................64
11.3.3.
Recording and Follow-Up of AE and SAE....................................65
11.3.4.
Reporting of SAE to GSK.............................................................66
11.4.
Appendix 4: Genetics..................................................................................68
11.5.
Appendix 5: Liver Safety: Required Actions and Follow-up 
Assessments ..............................................................................................69
11.6.
Appendix 6: Abbreviations and Trademarks................................................71
11.7.
Appendix 7 : Protocol Amendment History..................................................75
12. REFERENCES.......................................................................................................76
 
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1.
PROTOCOL SUMMARY
1.1.
Synopsis
Protocol Title: A randomised, double-blind, placebo-controlled Phase I study of the 
safety and tolerability, pharmacokinetics, and pharmacodynamics of a single intravenous 
dose of GSK2831781 in healthy Japanese and Caucasian participants, and a single 
subcutaneous dose of GSK2831781 in healthy Caucasian participants.
Short Title: Safety, tolerability, pharmacokinetics and pharmacodynamics of 
GSK2831781 after an intravenous dose in healthy Japanese and Caucasian participants, 
and a subcutaneous dose in healthy Caucasian participants. 
Rationale: The purpose of this study is to evaluate the safety, tolerability, 
pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity after single 
intravenous (IV) doses of GSK2831781 administered to healthy Japanese and Caucasian 
participants, and single subcutaneous (SC) doses administered to healthy Caucasian 
participants. This information is intended to enable further studies in Japanese 
participants, and to support defining the optimal SC dose for future studies.
Objectives and Endpoints:
Exploratory endpoints can be found in Section 4, Objectives and Endpoints.
Objectives
Endpoints
Primary

To evaluate the safety and tolerability 
after single IV dosing of GSK2831781 in 
healthy Japanese and Caucasian 
participants, and SC dosing in healthy
Caucasian participants

AEs, vital signs, clinical laboratory values 
(haematology, clinical chemistry, and 
urinalysis), 12-lead electrocardiogram 
(ECG)

Local tolerability
Secondary

To evaluate the PK of GSK2831781 after 
a single IV dose in healthy Japanese and 
Caucasian participants (Part A) 

GSK2831781 PK parameters following 
single IV dose: area under the plasma 
concentration-time curve [AUC(0-t)], 
maximum observed plasma 
concentration (Cmax), time of 
occurrence of Cmax (tmax)

To evaluate the PK of GSK2831781 after 
a single SC dose in healthy Caucasian 
participants (Part B) 

GSK2831781 PK parameters following 
single SC dose: AUC(0-t), Cmax, tmax, 
bioavailability (F)

To evaluate the effect of a single IV or 
SC dose of GSK2831781 on depletion of
Lymphocyte Activation Gene-3 (LAG)3+
T cells in blood

PK/PD relationship between plasma PK 
of GSK2831781 and LAG3+ T cells in 
blood over time
 
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Objectives
Endpoints

To investigate the immunogenicity of 
single IV and SC doses of GSK2831781

Anti-drug antibody (ADAs) over time
Overall Design:
This study is a double-blind, placebo-controlled, randomised, parallel group, two-part 
study, with single IV doses administered to healthy Japanese and Caucasian participants, 
or single SC doses administered to healthy Caucasian participants.
In Part A, single IV doses of 450 mg GSK2831781 or placebo will be administered to 
healthy Japanese or Caucasian participants, with stratification by ethnicity. 
In Part B, single SC doses of 150 mg or 450 mg GSK2831781, or placebo, will be 
administered to healthy Caucasian participants.
At least one interim analysis is planned and will be conducted and reviewed by a Data 
Review Committee (DRC).
Disclosure Statement: 
This is a double-blind, parallel group safety and PK study.
Number of Participants:
Part A: A sufficient number of participants will be randomised such that 8 evaluable 
Japanese participants (6:2 GSK2831781:Placebo) and 8 evaluable Caucasian participants 
(6:2 GSK2831781:Placebo) complete Part A, at the same dose level in each stratum. A 
total of 16 evaluable participants are needed to complete part A, however up to a 
maximum of 32 participants may be enrolled if a dose reduction is needed.
Part B: A sufficient number of participants will be randomised such that 20 evaluable 
Caucasian participants (8:8:4 450 mg : 150 mg : placebo) complete Part B.  A total of 20 
evaluable participants are needed to complete Part B, however up to a maximum of 30 
participants may be enrolled if a dose reduction is needed (see Section 7.7).
Evaluable is defined as a participant who has been dosed and has safety and PK data up 
to Day 29.
Intervention Groups and Duration:
This is a two-part study. Part A is designed to investigate whether there are any 
differences due to ethnicity in safety and tolerability, or PK and PK/PD relationship in 
blood between healthy Japanese and Caucasian participants following a single IV 450 mg 
dose of GSK2831781. Participants will be randomised to GSK2831781 or placebo, with 
stratification by ethnicity. In Part A, in order to bridge from the first-time-in human study 
(GSK Study 200630), dosing episodes will initially be separated by a minimum of 
22 hours, until 3 participants in one of the strata have been dosed and monitored for a 
 
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minimum of 46 hours. Subsequently, the remaining participants in the Part A will be 
dosed, unless stopping criteria have been met.
Once the final Caucasian participant has been recruited into Part A of the study, 
recruitment to Part B may commence. Part B will explore the safety and tolerability, PK 
and PK/PD relationship in blood following a single dose of SC GSK2831781 at 150 mg 
and 450 mg dose levels, or placebo, in healthy Caucasian participants. As the 450 mg 
dose level requires 3 injections of 150 mg GSK2831781, participants randomised to the 
150 mg dose level or placebo will also receive 3 injections (using 0.9% saline placebo as 
dummy injections, where needed) to maintain the blind. In Part B, as this will be the first 
experience with SC administration in humans, the first two participants dosed will be 
randomised so that 1 participant will receive 150 mg GSK2831781 and 1 will receive 
placebo, and injection sites monitored. Since the 450 mg SC dose is delivered as 3x 150
mg injections at discrete injection sites, sentinel dosing at this dose level is not required, 
as local tolerability will have been assessed at the 150 mg dose level and systemic 
exposure at 450 mg IV in Part A. After review of sentinel safety data at 46 hours post-
dose, the remaining participants in Part B will be dosed, unless stopping criteria have 
been met.
The study duration, including screening and follow-up, is not expected to exceed 
147 days for any participant in the study.
1.2.
Schema
 
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2.
SCHEDULE OF ACTIVITIES (SOA)
2.1.
Part A: Japanese and Caucasian Participants – IV Dose
Procedure
Screeni
ng 
(up to 
28 days 
before 
Dosing)
Day -1
Day 1 (Hours)
Days 3 – 85
Follow 
Up/Early 
Withdra
wal (112 
Days 
post 
dose)3
Pre-
Dose
0 
h1
1 h
2 h 
(end of 
infusio
n)
6 h
12 h
24 h
3
2
4
2
8
15
22
29
43
57
71
85
Window 
-60 
min
±10 
min
+30 
min4
±30 
min
±30 
min
±60 
min
±1
d
±2
d
±2
d
±2
d
±3
d
±3
d
±3
d
±3
d
±7d
Informed 
Consent
X
Inclusion and 
Exclusion 
Criteria
X
X
Demography
X
Full physical 
examination 
including height 
and weight
X
X
Medical history 
(includes 
substance usage)
X
Past and Current 
Medical 
Conditions
X
 
 
 
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Procedure
Screeni
ng 
(up to 
28 days 
before 
Dosing)
Day -1
Day 1 (Hours)
Days 3 – 85
Follow 
Up/Early 
Withdra
wal (112 
Days 
post 
dose)3
Pre-
Dose
0 
h1
1 h
2 h 
(end of 
infusio
n)
6 h
12 h
24 h
3
2
4
2
8
15
22
29
43
57
71
85
Window 
-60 
min
±10 
min
+30 
min4
±30 
min
±30 
min
±60 
min
±1
d
±2
d
±2
d
±2
d
±3
d
±3
d
±3
d
±3
d
±7d
Serology (HIV, 
HBV, HCV, 
CMV, EBV, 
VZV)
X
TB screening 
(QuantiFERON 
PPD)
X
Breath Alcohol 
Screen 
X
X
Urine Drug 
Screen
X
X
Haematology & 
Clinical 
Chemistry 
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
12-Lead ECG5
X
X
X
X
X
X
Vital Signs6
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
 
 
 
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Procedure
Screeni
ng 
(up to 
28 days 
before 
Dosing)
Day -1
Day 1 (Hours)
Days 3 – 85
Follow 
Up/Early 
Withdra
wal (112 
Days 
post 
dose)3
Pre-
Dose
0 
h1
1 h
2 h 
(end of 
infusio
n)
6 h
12 h
24 h
3
2
4
2
8
15
22
29
43
57
71
85
Window 
-60 
min
±10 
min
+30 
min4
±30 
min
±30 
min
±60 
min
±1
d
±2
d
±2
d
±2
d
±3
d
±3
d
±3
d
±3
d
±7d
Randomization
X
IMP 
Administration 
<===========>
Resident in unit
<=====================================>
Local 
Tolerability
X
X
X
X
X
sLAG3 
concentrations
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PK
X
X
X7
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Immunogenicity
X
X
X
X
X
LAG3+ Cell 
Depletion and 
Immunophenoty
ping
X
X
X
X
X
X
X
X
X
X
X
Genetic Sample8
X
AE/ SAE 
Review
SAEs collected from signing of informed consent form; AEs collected continuously from time of first dose. 
Concomitant 
Medication 
Monitored from screening until the end of the final treatment period. 
 
 
 
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Procedure
Screeni
ng 
(up to 
28 days 
before 
Dosing)
Day -1
Day 1 (Hours)
Days 3 – 85
Follow 
Up/Early 
Withdra
wal (112 
Days 
post 
dose)3
Pre-
Dose
0 
h1
1 h
2 h 
(end of 
infusio
n)
6 h
12 h
24 h
3
2
4
2
8
15
22
29
43
57
71
85
Window 
-60 
min
±10 
min
+30 
min4
±30 
min
±30 
min
±60 
min
±1
d
±2
d
±2
d
±2
d
±3
d
±3
d
±3
d
±3
d
±7d
Review
Footnotes:
1.
All post dose time points are in reference to the start of infusion.
2.
Assessments at these visits should be on the scheduled day however can be at any time in the day. 
3.
Early withdrawal assessments will be the same as Follow-Up
4.
End of infusion assessment time window is +30 minutes for all assessments except for the PK sample which should be collected just before the end of the 
infusion. 
5.
ECG in triplicate at screening and single at all other time points. 
6.
Vital Signs to be taken every 30 minutes from start of infusion until completion of 2hr post dose monitoring period.
7.
PK sample at end of infusion should be collected just before the end of the infusion.
8.
The genetic sample is optional and can be taken any time after consent has been signed and the participant is randomized.
The timing and number of planned study assessments, including safety, pharmacokinetic, and pharmacodynamic 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 as the result of emerging 
pharmacokinetic/pharmacodynamic data from this study 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 Competent Authority (CA) and ethics 
committee (EC) will be informed of any safety issues that constitute a substantial amendment and require alteration of the safety
monitoring scheme or amendment of the informed consent form (ICF). The changes will be approved by the CA and the EC before 
implementation.
 
 
 
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2.2.
Part B: Caucasian Participants – Subcutaneous Dose
Procedure
Screening 
(up to 28 days 
before Dosing)
Day - 1
Day 1
Days 2-85
Follow 
Up/Early 
Withdrawal 
(112 Days 
post dose)3
Pre-Dose
0h
Post Dose1
22
32
42
62
8
11
15
18
22
29
43
57
71
85
Window 
-60
min
±1d
±2d
±2d
±2d
±2d
±2d
±3d
±3d
±3d
±3d
±7d
Informed consent
X
Inclusion and 
exclusion criteria
X
X
Demography
X
Full physical 
examination 
including height and 
weight
X
X
Medical history 
(includes substance 
usage)
X
Past and current 
medical conditions  
X
Serology (HIV, 
HBV, HCV, CMV, 
EBV, VZV)
X
TB screening
(QuantiFERON 
PPD)
X
 
 
 
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Procedure
Screening 
(up to 28 days 
before Dosing)
Day - 1
Day 1
Days 2-85
Follow 
Up/Early 
Withdrawal 
(112 Days 
post dose)3
Pre-Dose
0h
Post Dose1
22
32
42
62
8
11
15
18
22
29
43
57
71
85
Window 
-60
min
±1d
±2d
±2d
±2d
±2d
±2d
±3d
±3d
±3d
±3d
±7d
Breath Alcohol 
Screen
X
X
Urine Drug Screen 
X
X
Haematology & 
Clinical Chemistry 
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
12-Lead ECG4
X
X
X5
X
X
X
Vital Signs6
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Randomization
X
IMP Administration 
X7
Resident in Unit 
<================>
Local tolerability at 
injection sites
X
X8
X
X
X
sLAG3 
concentrations
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PK
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Immunogenicity
X
X
X
X
X
 
 
 
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Procedure
Screening 
(up to 28 days 
before Dosing)
Day - 1
Day 1
Days 2-85
Follow 
Up/Early 
Withdrawal 
(112 Days 
post dose)3
Pre-Dose
0h
Post Dose1
22
32
42
62
8
11
15
18
22
29
43
57
71
85
Window 
-60
min
±1d
±2d
±2d
±2d
±2d
±2d
±3d
±3d
±3d
±3d
±7d
LAG3+ Cell 
Depletion
X
X
X
X
X
X
X
X
X
X
Genetic Sample9
X
AE/SAE Review
SAEs collected from signing of informed consent form; AEs collected continuously from time of first dose. 
Concomitant 
medication review
Monitored from screening until the end of the final treatment period.
Footnotes: 
1.
All post dose time points are in reference to the first injection of IMP.
2.
Assessments at these visits should be on the scheduled day however can be at any time in the day. 
3.
Early withdrawal assessments will be the same as Follow-Up.
4.
ECG in triplicate at screening and single at all other time points.  
5.
ECG to be performed 6 hours post dose.
6.
Vital Signs to be taken every 30 minutes from first IMP injection until completion of 2hr post dose monitoring period.
7.
IMP administration consists of 3 syringes, all 3 syringes are to be administered as closely together as possible (preferably within 10 minutes).
8.
Post dose Local tolerability at injection sites to be reviewed at 2, 6, 12, and 24 hours post dose. 
9.
The genetic sample is optional and can be taken any time after consent has been signed and the participant is randomized. 
The timing and number of planned study assessments, including safety, pharmacokinetic, and pharmacodynamic 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 as the result of emerging 
pharmacokinetic/pharmacodynamic data from this study 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 Competent Authority (CA) and ethics 
committee (EC) will be informed of any safety issues that constitute a substantial amendment and require alteration of the safety.
 
 
 
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3.
INTRODUCTION
3.1.
Study Rationale
GSK2831781 is a humanised, Antibody-Dependent Cell Cytotoxicity (ADCC)-enhanced,
depleting monoclonal antibody that is specific to the Lymphocyte Activation Gene-3 
(LAG3) protein. LAG3 is a transmembrane receptor, which is upregulated on T cells 
following activation [Workman, 2002]. Increased expression of LAG3 on T cells has 
been observed in inflamed tissue in a range of immunoinflammatory diseases, including 
ulcerative colitis [Slevin, 2018], Crohn’s disease and psoriasis, but the number of LAG3+
cells in healthy tissues remains very low. Further, LAG3+ cell depletion in psoriasis 
showed preliminary evidence of clinical efficacy in a First Time In Humans
(FTIH)/Phase 1b trial [Ellis, 2019, and see Section 3.2 Background and GSK2831781 
Investigator Brochure (IB)]. However, as only 0.5-5% of T cells in blood and secondary 
lymphoid organs express LAG3, GSK2831781 should spare LAG3- resting memory and 
naïve T cells, as well as the majority of natural regulatory T cells responsible for normal 
immune homeostasis. By rapid and potent depletion of LAG3+ T cells in diseased tissues, 
there is the potential to achieve fast and long-lasting disease remission of T cell-driven 
immunoinflammatory diseases. Additionally, given the highly selective nature of 
depletion, there may be improved safety and tolerability compared to current standard of 
care in many of these conditions. 
The purpose of this study is to evaluate the safety, tolerability, PK, PD and 
immunogenicity after single IV doses of GSK2831781 administered to healthy Japanese 
and Caucasian participants, and single SC doses administered to healthy Caucasian 
participants. This information is intended to enable further studies in Japanese patients
with immunoinflammatory diseases, and to support defining the optimal SC dose for 
future studies.
3.2.
Background
Clinical experience with GSK2831781 to date comes from a single IV ascending dose 
Phase 1a/1b study (NCT02195349, GSK Study 200630) in healthy participants (up to 
0.15 mg/kg) and patients with active mild to moderate plaque psoriasis (0.5 – 5 mg/kg). 
No safety or tolerability concerns were identified. Proof of mechanism was achieved, 
with dose-dependent depletion of LAG3+ cells in blood and skin (psoriasis plaques), 
positive effects on psoriatic skin disease activity markers such as CD3 and pro-
inflammatory messenger RNA (mRNA) transcripts, and preliminary evidence of clinical 
efficacy in ameliorating psoriasis plaques [Ellis, 2019, and GSK2831781 IB].
GSK2831781 is currently being assessed in a Phase 2 trial (GSK Study 204869) of 
moderate-severe active ulcerative colitis (UC). This trial explores a range of IV doses for 
induction of remission (
), and a single 
 dose level 
(
, administered as two injections of 
) in clinical 
responders for maintenance of remission. Should a robust proof of concept be achieved in 
this study, efficacy in additional immunoinflammatory diseases may be explored. In 
order to include Japanese participants into the Phase 2 development programme, safety 
and tolerability, and PK at the highest dose level (450 mg IV) needs to be confirmed. 
 
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In addition, all experience with GSK2831781 to date is with IV administration. Since the 
PK has been shown to be non-linear due to target-mediated drug disposition, it is possible 
that GSK2831781 bioavailability after SC administration may be non-linear, resulting in 
an apparent dose-dependent bioavailability (see Section 5.5). As the Phase 2 study 
204869 explores only a SD level,
, the bioavailability needs to 
be characterised at both ends of the dose range at which SC GSK2831781 might be 
administered in future studies to inform on the optimal dosing strategy. 
3.3.
Benefit/Risk Assessment
More detailed information about the known and expected benefits and risks and 
reasonably expected adverse events of GSK2831781 may be found in the IB. 
 
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3.3.1.
Risk Assessment
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Refer to GSK2831781 IB for details.
Mitigation Strategy
Investigational Medicinal Product (IMP) [GSK2831781]
Neutropaenia 
Non-clinical:
In the repeat dose IV and SC studies in 
monkeys, marked decreases in absolute 
neutrophils counts were observed in animals 
given ≥30 mg/kg/week, without clinical sequelae. 
Neutropenic nadir is observed approximately 4 
weeks after start of dosing and is considered to 
be reversible based on the transient nature of 
neutropenia observed in the 26-week repeat 
dose study and the apparent strong adaptive 
response in the bone marrow of animals in the 4-
week study, both in the presence of high 
systemic GSK2831781 exposure.
Clinical:
No neutropenia, or trends towards reduced 
neutrophil counts, were observed in the FTIH 
study (200630) in healthy volunteers or patients 
with plaque psoriasis, up to a maximum single 
dose of 5 mg/kg.
Exclusion criteria for low neutrophil counts 
(<1.5x109/L) at baseline.
Neutrophil count and adverse events 
(AE)/serious adverse events (SAEs) related to 
neutropaenia will be monitored.
Haematological stopping criteria. 
Investigators should manage participants as 
clinically indicated if neutropaenia is seen.
Infection
Non-clinical:
No specific studies have been conducted in 
Appropriate exclusion criteria for history of e.g. 
tuberculosis (TB) (screening for latent infection 
 
 
 
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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Refer to GSK2831781 IB for details.
Mitigation Strategy
nonclinical species to investigate the effect of 
GSK2831781 on response to viral or bacterial 
infection.
In the 26-week study, natural killer cells were 
lower (down to 0.1X pre-study values) in 4 of the 
8 monkeys dosed at 100 mg/kg/week from 
Day 29, although levels were at or near the 
overall pre-study and control group values. 
A significant proportion of newly activated T cells 
express LAG3, and therefore T cell proliferation 
upon encounter with an infectious agent may be 
inhibited by GSK2831781 if exposure is at the 
same time. However, it has been demonstrated 
that in healthy participants only a small 
proportion of central memory T cells express 
LAG3, so there is low risk of eliminating central 
memory of anti-infectious immune response 
against future encounter.
Clinical:
No clinical concerns regarding infections were 
identified in the FTIH study (200630).
included) or other relevant chronic infectious 
disease [e.g. Hepatitis B virus (HBV) and 
Hepatitis C virus (HCV), Human 
Immunodeficiency Virus (HIV)]. In addition, 
participants with a recent infection or evidence of 
significant active infection will be excluded from 
the study.
Participants will not be allowed to receive live 
vaccines within the 4 weeks prior to Day 1 or 
during the study until the end of Follow-Up. 
Investigators are expected to follow local and/or 
national guidelines with respect to vaccinations, 
including against influenza and pneumococcus. If 
indicated, non-live vaccines may be administered 
based on a treating physician assessment of the 
benefit:risk (e.g., risk of theoretical decreased 
responsiveness).
Investigators will be advised to counsel 
participants regarding implications for foreign 
travel, including possible impact on vaccinations 
and theoretical risks associated with travel to 
areas of high endemic infection while exposed to 
GSK2831781. Prior to consenting, participants 
will be asked to consider whether any impact this 
might have on their lifestyle would affect their 
decision to participate in the study.
 
 
 
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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Refer to GSK2831781 IB for details.
Mitigation Strategy
Close monitoring of participants for infections will 
be continued up to the Follow-Up visit, and 
supportive therapy (including anti-infectives) 
provided as clinically indicated.
Infusion reaction/hypersensitivity
Non-clinical:
No evidence to date.
Clinical:
No infusion reactions or hypersensitivity to 
GSK2831781 were observed in the FTIH study 
(200630).
IMP will be administered by clinical staff at 
clinical sites with appropriate staff training and 
facilities for the emergency management of 
hypersensitivity, angioedema and anaphylaxis. 
Participants will be resident in the clinical unit for 
24 hours following start of IMP administration.
Exclusion criteria, stopping criteria and 
appropriate treatment for hypersensitivity 
reactions.
Local injection site reaction
Non-clinical:
A dose-related increase in incidence and/or 
severity of mononuclear cell perivascular 
infiltration was observed at SC injection sites of 
monkeys given 30 mg/kg/week. Partial 
recovery in females and full recovery in males at 
30 mg/kg/week was observed after 17 weeks off-
dose. Not seen with IV administration.
Clinical:
No reactions were observed following IV 
administration in the FTIH study (200630).
Participants will be resident in the clinical unit for
24 hours following start of IMP administration, 
and injection sites will be monitored. Any 
adverse reactions will be managed appropriately 
and monitored until resolution.
 
 
 
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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Refer to GSK2831781 IB for details.
Mitigation Strategy
Immunogenicity
Non-clinical:
Administration of GSK2831781 to monkeys leads 
to an ADA response which is more prevalent at 
lower doses and is associated with a reduction in 
GSK2831781 systemic exposure.
Neutralizing ADA, observed in one animal given 
100 mg/kg/week SC in the 26-Week GLP study, 
correlated with decreased GSK2831781 plasma 
concentrations and were associated with 
immune complex mediated clinical pathology 
changes and increased heart rate, which were 
transient and of minimal magnitude. 
Immunogenicity in nonclinical species is not
predictive of the potential for immunogenicity in 
humans
Clinical:
Pre-existing ADAs and post-dosing ADA have 
been identified in humans. No adverse reactions 
or alterations in PK associated with 
immunogenicity were observed in the FTIH study 
200630. 
Safety and tolerability is being assessed in 
participants (including clinical chemistry, 
haematology, AEs, hypersensitivity reactions). 
Immunogenicity and the impact, if any, on PK
and safety parameters will be monitored.
Cytokine release syndrome (CRS)
Non-clinical:
Hyper-immune activation leading to activation of 
the innate immune system is only a theoretical 
Appropriate monitoring for clinical symptoms 
associated with cytokine release such as fever, 
nausea, chills, hypotension, tachycardia, 
 
 
 
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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Refer to GSK2831781 IB for details.
Mitigation Strategy
safety concern, as there is no in vitro and in vivo
evidence of cytokine release associated with 
LAG3 and the T cell depletion mechanism. 
GSK2831781 did not induce cytokine release in 
the human in vitro assay when using a soluble or 
immobilised format or in the 4-week study in 
monkeys.
As GSK2831781 is expected to induce ADCC, 
this may lead to cytokine release due to cell 
lysis. However, a low proportion of T cells 
express LAG3, therefore the risk of this is 
expected to be lower than less targeted depleting 
mAbs.
Clinical:
No CRS was observed in the FTIH study 
200630. There were minor transient increases in 
serum Tumour Necrosis Factor (TNF)-α 
concentrations between 6-48 hours after dosing 
at all dose levels, but no dose-response 
relationship, and the magnitude of these rises 
was not clinically relevant. There were no 
meaningful changes to serum Interleukin (IL)-6, 
IL-8, Interferon (IFN)-γ or Granulocyte-colony 
stimulating factor (G-CSF).
asthenia, headache, rash, tongue and throat 
swelling, and dyspnoea, during and for an 
appropriate period after dosing. 
Participants will be resident in the clinical unit for 
24 hours following start of IMP administration.  
Participants will be informed in the Informed 
Consent Form (ICF) to seek prompt medical 
advice should symptoms indicative of CRS
occur, particularly within 72 hours of dosing. 
Initially, dosing episodes will be separated by a 
minimum of 22 hours, until at least 3 participants 
have been dosed in one of the strata. 
Study site to include facilities and staff training 
expertise for emergency care/resuscitation.
 
 
 
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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Refer to GSK2831781 IB for details.
Mitigation Strategy
Autoimmune-like reactions
Non-clinical:
A small percentage of regulatory T cells express 
LAG3. The clinical relevance of this minority 
subset of T cells in the pathogenesis of 
autoimmune reactions is unknown.
In the 4-week study minimally increased 
percentages of subpopulations of regulatory T 
cells were noted on Day 29 at 100 mg/kg/week 
IV, which was not observed in monkeys 
administered 100 mg/kg/week SC. No changes 
in regulatory T cells were observed in the 26-
week study.
Increases in anti-keyhole limpet hemocyanin 
(KLH) immunoglobulin (Ig)M and IgG responses, 
which were not adverse, were noted after each 
KLH injection (administered during Weeks 16 
and 19) in monkeys given 30 or 100 mg/kg/week 
for 26-weeks compared to responses in control 
animals, which persisted in the 30 mg/kg/week 
group at 12-weeks off-dose. Following an off-
dose period of 47 and 50 weeks administration of 
neoantigen tetanus-toxoid (TT) injection to 
animals previously administered 30 mg/kg/week, 
resulted anti-TT IgG antibody levels which were 
similar to control animals.
Exclusion criteria for uncontrolled medical 
conditions or any background medical history 
that the investigator (in consultation with the 
GSK Medical Monitor) considers would put the 
participant at unacceptable risk.
Participants will undergo regular assessment 
until GSK2831781 has been cleared and LAG3+
cells expected to replete. AEs that could be 
related to autoimmunity will be monitored.
Given the increases in anti-KLH IgM and IgG
responses observed in cynomolgus monkeys, 
there is a theoretical potential for an enhanced 
response to vaccination, which has not yet been 
evaluated in clinical studies. The implications of 
this are not known but are not considered high 
risk. Investigators will counsel participants 
regarding the possible impact on vaccination 
(both of potential reduced responsiveness and 
enhanced reaction). 
 
 
 
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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Refer to GSK2831781 IB for details.
Mitigation Strategy
Clinical:
No autoimmune phenomena were observed in 
the FTIH study 200630. In patients who received 
GSK2831781, clinical activity scores for psoriasis 
(a T cell-mediated disease) tended to improve 
over the time course of exposure to 
GSK2831781.
Reproductive Toxicity
Non-clinical:
Whereas there are no data for the drug class or 
mode of action pointing to a known pregnancy 
hazard, no animal reproduction testing has been 
conducted. Therefore, there is the potential for 
unidentified risks to the embryo-foetus or 
pregnancy. 
Doses up to 100 mg/kg/week for 26-weeks did 
not result in pathology in the reproductive organs 
of mature monkeys or effects on 
spermatogenesis staging.
Clinical:
The IMP level of monoclonal antibody (mAb) in 
human semen is expected to be too low to be of 
concern.
The study will recruit only male participants. 
There are no specific contraception requirements 
for males participating in this study.
 
 
 
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3.3.2.
Benefit Assessment
There will be no direct benefit to the healthy participants in this study. However, 
information obtained in this study will inform the conduct of future clinical studies to 
contribute to the process of developing new therapies for diseases where there is unmet 
medical need, including UC. 
3.3.3.
Overall Benefit: Risk Conclusion
Taking into account the measures to minimise risks, the potential risks of participation in 
this study of GSK2831781 are considered justified and adequately mitigated.
4.
OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary

To evaluate the safety and tolerability 
after single IV dosing of GSK2831781 in 
healthy Japanese and Caucasian 
participants, and SC dosing in healthy 
Caucasian participants

AEs, vital signs, clinical laboratory values 
(haematology, clinical chemistry, and 
urinalysis), 12-lead ECG

Local tolerability
Secondary

To evaluate the PK of GSK2831781 after 
a single IV dose in healthy Japanese and 
Caucasian participants (Part A) 

GSK2831781 PK parameters following 
single IV dose: area under the plasma 
concentration-time curve [AUC(0-t)], 
maximum observed plasma 
concentration (Cmax), time of 
occurrence of Cmax (tmax)

To evaluate the PK of GSK2831781 after 
a single SC dose in healthy Caucasian 
participants (Part B) 

GSK2831781 PK parameters following 
single SC dose: AUC(0-t), Cmax, tmax, 
bioavailability (F)

To evaluate the effect of a single IV or 
SC dose of GSK2831781 on depletion of 
LAG3+ T cells in blood

PK/PD relationship between plasma PK 
of GSK2831781 and LAG3+ T cells in 
blood over time

To investigate the immunogenicity of 
single IV and SC doses of GSK2831781

ADAs over time
Exploratory

To evaluate the concentration-time 
profiles of GSK2831781 after a single IV 
dose in healthy Japanese and 
Caucasian participants (Part A) 

GSK2831781 PK concentrations over 
time following single IV dose

To evaluate the concentration-time 
profiles of GSK2831781 after a single 

GSK2831781 PK concentrations over 
time following single SC dose
 
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Objectives
Endpoints
SC dose in healthy Caucasian 
participants (Part B) 

To evaluate the effect of a single IV or 
SC dose of GSK2831781 on soluble 
LAG3 (sLAG3) concentrations

Soluble LAG3 (sLAG3) concentrations in 
blood over time

To evaluate the effect of GSK2831781 
on regulatory T cells in blood

PK/PD relationship between plasma PK 
of GSK2831781 and regulatory T cells in 
blood over time
5.
STUDY DESIGN
5.1.
Overall Design
This study is a double-blind, placebo-controlled, randomised, parallel group, two-part 
study, with single IV doses administered to healthy Japanese and Caucasian participants, 
or SC doses administered to healthy Caucasian participants.
In Part A, single IV doses of 450 mg GSK2831781 or placebo will be administered to 
Japanese or Caucasian healthy participants, with stratification by ethnicity. 
In Part B, single SC doses of 150 mg or 450 mg GSK2831781, or placebo, will be 
administered to healthy Caucasian participants.
At least one interim analysis will be conducted during the study (see Section 10.5 for 
further details). 
In line with routine pharmacovigilance, an internal GSK Safety Review Team (SRT) 
(which will include a subset of the 207823 study team) will review blinded safety data, 
including clinical laboratory parameters and adverse events, at appropriate intervals 
during the period of study conduct.
If, following a Safety Review Team (SRT) review, it is felt that the dose level in Part A 
has to be lowered from 450 mg (see Section 7.7) then the randomisation to the new dose 
level will also be 6:2 (GSK2831781:Placebo) within both the Japanese and Caucasian 
strata.
5.2.
Number of Participants 
Part A: A sufficient number of participants will be randomised such that 8 evaluable 
Japanese participants (6:2 GSK2831781:Placebo) and 8 evaluable Caucasian participants 
(6:2 GSK2831781:Placebo) complete Part A, at the same dose level in each stratum. A 
total of 16 evaluable participants are needed to complete part A, however up to a 
maximum of 32 participants may be enrolled if a dose reduction is needed (see Section 
7.7).
 
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Part B: A sufficient number of participants will be randomised such that 20 evaluable 
Caucasian participants (8:8:4 450 mg : 150 mg : placebo) complete Part B.  A total of 20 
evaluable participants are needed to complete Part B, however up to a maximum of 30 
participants may be enrolled if a dose reduction is needed (see Section 7.7).
Evaluable is defined as a participant who has been dosed and has safety and PK data up 
to Day 29.
5.3.
Intervention Groups and Duration
5.3.1.
Part A
This is a two-part study. Part A is designed to investigate whether there are any 
differences due to ethnicity in safety and tolerability, or PK and PK/PD relationship in 
blood between healthy Japanese and Caucasian participants following a single IV 450 mg 
dose of GSK2831781. Participants will be randomised to GSK2831781 or placebo, with 
stratification by ethnicity.
The study duration, including screening and follow-up, is not expected to exceed 
147 days for any participant in the study.
5.3.2.
Part B 
Once the final Caucasian participant is recruited into Part A of the study, recruitment to 
Part B may commence. Part B will explore the safety and tolerability, PK and PK/PD 
relationship in blood following a single dose of SC GSK2831781 at 150 mg and 450 mg 
dose levels, or placebo, in healthy Caucasian participants. As the 450 mg dose level 
requires 3 injections of GSK2831781 150 mg, participants randomised to the 150 mg 
dose level or placebo will also receive 3 injections (using 0.9% saline placebo as dummy 
injections, where needed) to maintain the blind.
The study duration, including screening and follow-up, is not expected to exceed 
147 days for any participant in the study.
5.4.
Participant and Study Completion 
A participant is considered to have completed the study if he has completed all phases of 
the study including the last scheduled assessment shown in the SoA (Section 2).
The participants who withdraw from the study early should be encouraged to complete 
all visits as set out in the SoA (Section 2); however, if this is not possible at a minimum 
participants will be encouraged to complete an Early Withdrawal visit, as well as the 
Follow-Up visit approximately 16 weeks after the dose (Section 8.4) to ensure participant 
monitoring until drug wash out is achieved.
end of the study is defined as the date of the last visit of the last participant in the study.
 
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5.5.
Scientific Rationale for Study Design
5.5.1.
Part A (Japanese ethnosensitivity)
IV administration of GSK2831781 at the same dose to both healthy Japanese and 
Caucasian participants will allow for assessing the ethnic sensitivity of GSK2831781 in 
terms of safety and tolerability, PK and PD. The dose level for Part A is chosen such that 
the full PK/PD curve (i.e., from no depletion to full depletion, then to repletion) and the 
maximum exposure following a SD used in subsequent Phase 2 and potential Phase 3 
studies will be achieved (see Section 5.7). Single (rather than repeat) doses are required 
so that the repletion of LAG3+ cells in blood can be quantified. This study will be 
performed in healthy participants to ensure full pharmacological characterisation of 
GSK2831781 without confounding from disease-specific factors or other medications.
Doses of approximately 450 mg IV (5 mg/kg dose level) were administered to patients 
with psoriasis in the FTIH study (200630) and repeat IV doses of 
 are approved 
for administration to patients with ulcerative colitis in the Phase 2 study (204869). In 
Study 200630, there was no imbalance in AEs between participants receiving 
GSK2831781 or placebo, the 5 mg/kg dose was well-tolerated, and target pharmacology 
in blood had been saturated by doses of 0.5 mg/kg and above. Healthy participants were 
included in the FTIH study up to a dose level of 0.15 mg/kg IV; but thereafter 
GSK2831781 was administered to patients with active plaque psoriasis to inform on 
safety at higher doses and provide pharmacodynamic and clinical readouts in a 
population with active T cell-driven inflammation. 
In Study 200630, there were no observed differences in PK between healthy volunteers 
and psoriasis patients, nor a dose-response in relation to safety parameters. However, 
since this study will be the first experience of the 450 mg dose in healthy participants, to 
bridge from the FTIH, dosing episodes will initially be separated by a minimum of 22 
hours (in addition to the 2-hour period of IV dose administration). This will ensure that, 
at the start of the study, only one participant is dosed in a 24-hour period. Once three 
participants in one of the strata have been dosed (meaning that at least one participant has 
received active drug), there will be a further 46-hour observation period (on top of the 2-
hour dose administration interval). If no events meeting study stopping criteria have 
occurred (see Section 8), the remaining participants in Part A can then be dosed. 
5.5.2.
Part B (subcutaneous PK)
By including cohorts with SC administration in the same study, the bioavailability (and 
PK in general) of GSK2831781 by the SC route can be assessed. The FTIH study 
(200630) demonstrated that PK in healthy volunteers was not linear, with evidence of 
target-mediated drug disposition (TMDD), much of which was mediated by sLAG3. The 
regulation and source of sLAG3 is currently uncertain. TMDD due to sLAG3 was 
saturated following IV doses of GSK2831781 of 0.5 mg/kg and above, but since the 
absorption rate of drug from SC tissue will be slower than the infusion rate following an 
IV dose, it is possible that the impact of this mechanism will have a non-linear effect on 
SC bioavailability. Characterisation of 150 mg and 450 mg SC doses in the current study, 
alongside data from the 
 dose in study 204869, will determine whether the 
 
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bioavailability is non-linear at these doses via this route, and is necessary to fully inform 
the dosing strategy for later phase clinical development.
As this will be the first experience with SC administration in humans, sentinel dosing will 
be used. The first two participants dosed will be randomised so that 1 participant will 
receive 150 mg GSK2831781 and 1 will receive placebo, and injection sites monitored. 
Since the 450 mg SC dose is delivered as 3x 150 mg injections at discrete injection sites, 
sentinel dosing at this dose level is not required, as local tolerability will have been 
assessed at the 150 mg dose level and systemic exposure at 450 mg IV in Part A. After 
review of sentinel safety data at 46 hours post-dose, the remaining participants in Part B 
will be dosed, unless stopping criteria have been met (see Section 8). 
5.6.
Placebo control
This study includes placebo arms to allow for a valid evaluation of AEs attributable to 
treatment versus those independent of treatment.
5.7.
Justification for Dose 
To date, GSK2831781 has been administered as single IV doses to healthy volunteers 
(0.0003-0.15 mg/kg) and patients with mild-moderate plaque psoriasis (0.5-5 mg/kg) in 
the FTIH study 200630. In the highest dose cohort in study 200630, the average 
administered dose was 472 mg. No imbalance in adverse effects attributed to 
GSK2831781 was seen between participants receiving active treatment versus placebo in 
any of the cohorts, AEs were generally mild in nature and severity, and overall 
GSK2831781 was well-tolerated and safety considered acceptable.
At the highest dose studied in study 200630 (5 mg/kg, or on average 472 mg), near 
complete depletion of LAG3+ T cells in blood was achieved, with these T cells beginning 
to replenish by approximately Day 42, and in the majority of participants were 
approximately back to baseline by Day 85. Therefore, it is expected that a dose of 450 mg 
IV is appropriate to investigate the complete PK/PD relationship. In addition, 
IV 
is the highest dose that is tested in the global Phase 2 study (204869) in UC, and so will
provide the maximum exposure for evaluation of safety in Japanese participants prior to 
their inclusion in study 204869.
GSK2831781 exhibits non-linear PK through TMDD. In theory this could result in non-
linearity in bioavailability, and therefore two SC doses (150 mg and 450 mg) will be 
investigated in this study. These doses, in combination with the 
 dose being 
assessed for maintenance in study 204869, cover the anticipated therapeutic dose range 
for later phase development. 
6.
STUDY POPULATION
Prospective approval of protocol deviations to recruitment and enrolment criteria, also 
known as protocol waivers or exemptions, is not permitted.
 
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6.1.
Inclusion Criteria
TYPE OF PARTICIPANT
1. Participants who are overtly healthy as determined by medical evaluation 
including medical history, physical examination, laboratory tests, and 12-lead 
ECGs. A participant with a clinical abnormality or laboratory parameter(s) 
outside the reference range for the population being studied that is not specifically 
listed in the inclusion or exclusion criteria may be included if the Investigator (in 
consultation with the GSK Medical Monitor if required) agree and document that 
the finding is unlikely to introduce additional risk factors and will not interfere 
with the study procedures or interpretation.
AGE
2. Between 18 and 65 years of age inclusive, at the time of signing the informed 
consent.
WEIGHT
3. Body weight 40 kg and body mass index (BMI) ≤30 kg/m2. 
SEX
4. Male. 
INFORMED CONSENT
5. Capable of giving signed informed consent, which includes compliance with the 
requirements and restrictions listed in the ICF and in this protocol.
GEOGRAPHIC ANCESTRY
6. Japanese ancestry, defined as having been born in Japan, being descendants of 
four ethnic Japanese grandparents and two ethnic Japanese parents, holding a 
Japanese passport or identity papers, and being able to speak Japanese. 
Participants should have lived outside Japan for less than 10 years at the time of 
screening.
Caucasian ancestry, defined as Caucasian descent as evidenced by appearance and 
verbal confirmation of familial heritage (a participant has 2 Caucasian parents and 
4 Caucasian grandparents).
 
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6.2.
Exclusion Criteria
MEDICAL CONDITIONS
1. History or presence of a disease that in the opinion of the investigator constitutes a 
risk when taking the study intervention or interfering with study assessment or
interpretation of the data.
2. A medical history of severe allergic reaction, angioedema, anaphylaxis, clinically 
significant drug hypersensitivity reaction, or autoimmune or immunodeficiency 
disorder. 
3. An active infection or a history of serious infections as follows:
a.
Use of antimicrobials (antibacterials, antivirals, antifungals or antiparasitic 
agents) for an infection within 30 days before first dose. Topical treatments 
may be allowed at the Medical Monitor’s discretion.
b. A history of opportunistic infections. 
c.
Recurrent or chronic infection, or other active infection, that in the opinion of 
the Investigator might cause this study to be detrimental to the participant.
d. Symptomatic herpes zoster within 3 months prior to screening.
e.
History of TB (active or latent) irrespective of treatment status. 
f.
A positive diagnostic TB test at screening (defined as a positive 
QuantiFERON test). In cases where the QuantiFERON test is indeterminate, 
the participant may have the test repeated once and if their second test is 
negative they will be eligible. In the event a second test is also indeterminate, 
the investigator has the option to undertake PPD testing. If the PPD reaction is 
<5 mm at 48 to 72 hours, then the participant is eligible. If the reaction is 
≥5 mm, or PPD testing is not undertaken, the participant is not eligible.
4. Any planned major surgical procedure during the study.
5. A history of malignant neoplasm within the last 10 years, except for fully treated non-
metastatic basal or squamous cell cancers of the skin (within 3 years) that shows no 
evidence of recurrence.
PRIOR/CONCOMITANT THERAPY
6. Use of prescription or non-prescription drugs (including recreational drugs and herbal 
medications) within 7 days or 5 half-lives (whichever is longer) prior to dosing, 
unless in the opinion of the investigator (in consultation with the GSK Medical 
Monitor), the medication will not interfere with the study or compromise participant 
safety. Paracetamol (acetaminophen) at doses of 4 grams/day, and occasional use of
non-steroidal anti-inflammatory drugs (NSAIDs) at licensed doses, are permitted.
7. Received live vaccination within 4 weeks of Day 1, or plan to receive a live 
vaccination during the study until follow-up.
8. Previous exposure to GSK2831781, or hypersensitivity to any excipients in the 
clinical formulation of GSK2831781 (see Section 9.1.5).
9. Treatment with biologic agents (such as monoclonal antibodies) within 3 months or 5 
 
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half-lives (whichever is longer) prior to dosing.
PRIOR/CONCURRENT CLINICAL STUDY EXPERIENCE
10. Participation in a clinical trial and has received an IMP within the following time 
period prior to screening in the current study: 3 months, 5 half-lives, or twice the 
duration of the biological effect of the IMP (whichever is longer).
11. Exposure to more than 4 new chemical entities within 12 months prior to the first 
dosing day.
12. Participation in the study would result in loss of blood or blood products in excess of 
500 mL within 3 months.
DIAGNOSTIC ASSESSMENTS*
13. Neutrophil or lymphocyte counts below the normal range.
14. Estimated glomerular filtration rate (GFR) by Chronic Kidney Disease Epidemiology 
Collaboration equation (CKD-EPI) calculation ≤90 mL/min/1.73 m2 at screening.
15. Alanine transaminase (ALT) >2x upper limit of normal (ULN) and bilirubin >1.5x 
ULN (isolated bilirubin >1.5x ULN is acceptable if bilirubin is fractionated and direct 
bilirubin <35%) at screening.
16. Other clinically significant abnormalities of laboratory assessments, as judged by the 
Investigator and/or GSK Medical Monitor, that could affect the safety of the 
participant, or the interpretation of the data from the study. 
17. Presence of hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody 
(HBcAb), or positive hepatitis C antibody result at screening (NB. Participants with 
positive Hepatitis C antibody due to prior resolved disease can be enrolled only if a 
confirmatory negative Hepatitis C RNA test is obtained).
18. Positive serology for HIV at screening.
19. Positive pre-study drug/alcohol screen.
20. QTc >450 msec, based on the mean of triplicate ECGs. The QTc is the QT interval 
corrected for heart rate according to Fridericia’s formula (QTcF; preferred method), 
or another method, machine or overread.**
*Retesting in the case of potentially spurious results or sample handling errors is allowed 
during the screening period. 
**Same correction to be used throughout the study.
 
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OTHER EXCLUSIONS
21. History of regular alcohol consumption within 6 months of the study defined as an 
average weekly intake of >21 units. One unit is equivalent to 8 g of alcohol: a half-
pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
22. Unstable lifestyle factors, to the extent that in the opinion of the investigator they 
would interfere with the ability of a participant to complete the study.
6.3.
Lifestyle Considerations
6.3.1.
Alcohol Restrictions
Participants will abstain from alcohol for 24 hours prior to each visit to the clinical unit. 
Additionally, they should refrain from alcohol for 7 days after dosing. Thereafter an 
average weekly intake of <21 units alcohol is permitted.
6.3.2.
Activity
Participants will abstain from strenuous exercise for 48 hours before each visit. 
6.4.
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently randomized. 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 SAEs.
Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened once. Rescreened participants should be assigned a new participant 
number.
Individuals who pass screening but are not dosed for reasons other than screen failure 
may be rescreened and should be assigned a new participant number. 
Screening assessments that yield aberrant results (e.g., safety laboratory samples) may be 
repeated once within the screening window by the investigator based upon clinical 
judgement. Retested participants should be assigned the same participant number as for 
the initial screening. 
7.
STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol.
 
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7.1.
Study Intervention(s) Administered
Intervention Name
GSK2831781
Placebo
Type 
Biologic
N/A
Dose Formulation
GSK2831781,
 
 
Commercial saline 
solution, 0.9% (w/v)
Unit Dose Strength(s)
150 mg/mL
N/A
Dosage Level(s)
IV: 450 mg 
SC: 150 mg or 450 mg
N/A
Route(s) of 
Administration
IV infusion or SC injection
IV infusion or SC injection
IMP and NIMP
IMP
IMP
Sourcing
Provided centrally by the Sponsor or 
designee
Supplied by site
Packaging and 
Labelling
Study intervention will be provided in 
vial. Each vial will be labelled as 
required per country requirement.
N/A
[Current/Former 
Name(s) or Alias(es)]
aLAG3, anti-LAG3
N/A
GSK2831781 is a fully humanized monoclonal antibody and all formulation ingredients 
have been previously used in the clinic. 
Intravenous GSK2831781 (or placebo) will be diluted in 0.9% saline as described in the 
Study Reference Manual (SRM), and administered over a 2 hour infusion, with active 
post-dose monitoring for a further 2 hours. Participants will remain resident for a 
minimum of 24 following IMP administration.
SC GSK2831781 is administered as multiples of 150 mg injections, each provided as 
1 mL of GSK2831781 150 mg/mL. Participants randomised to the different dose levels 
will receive: 

450 mg dose level: 3x 150 mg GSK2831781.

150 mg dose level: 1x 150 mg GSK2831781 and 2x 1 mL 0.9% (w/v) saline for 
injection.

Placebo: 3x 1 mL 0.9% (w/v) saline for injection.
Each participant in Part B will therefore receive 3 injections at the dosing visit. In an 
individual participant, injections should preferably be administered into the same part of 
the body (arms, legs or abdomen, either on the left or right side or both), but should be 
separated by a minimum of 2 cm. Syringes will be labelled in a blinded fashion, and the 
location of each injection will be recorded, so that the locations of active and placebo 
injections at 150 mg dose level are traceable. This is relevant for assessment of those 
 
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participants who receive both active and placebo injections.
7.2.
Preparation/Handling/Storage/Accountability
1.
The investigator or designee must confirm appropriate temperature conditions 
have been maintained during transit for all study intervention received and any 
discrepancies are reported and resolved before use of the study intervention.
2.
Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
interventions must be stored in a secure, environmentally controlled, and 
monitored (manual or automated) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff.
3.
The investigator, institution, or the head of the medical institution (where 
applicable) is responsible for study intervention accountability, reconciliation, and 
record maintenance (i.e., receipt, reconciliation, and final disposition records).
4.
Further guidance and information for the final disposition of unused study 
intervention are provided in the Study Reference Manual.
5.
Under normal conditions of handling and administration, study intervention is not 
expected to pose significant safety risks to site staff. Take adequate precautions to 
avoid direct eye or skin contact and the generation of aerosols or mists. In the case 
of unintentional occupational exposure notify the monitor, Medical Monitor 
and/or GSK study contact.
6.
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.
7.3.
Method of Treatment Assignment
At Screening a unique Participant Number (case report form [CRF] number) will be 
assigned to any participant who has at least one Screening procedure performed, other 
than informed consent. The unique Participant Number will be used to identify individual 
participants during the study.
Participants who meet the screening eligibility criteria will be randomised to a treatment 
group through the IWRS. The IWRS will confirm the participant’s CRF number 
(Participant number) and provide the randomisation number, where:

A randomisation number will be assigned from a randomisation schedule 
generated by Biostatistics, prior to the start of the study, using validated internal 
software. Once assigned, this number must not be reassigned to any other 
participant in the study.
Therefore, the randomisation is centrally controlled by the IWRS.
 
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Part A: Participants will be assigned to either 450mg GSK2831781 IV or placebo in a 
3:1 ratio, stratified by ethnicity. The treatment codes will be:
Treatment code
Treatment Description
A
450 mg GSK2831781 IV
P
Placebo IV
Part B: Participants will be assigned to 150 mg GSK2831781 SC or 450 mg 
GSK2831781 SC or placebo in a 2:2:1 ratio. The treatment codes will be:
Treatment code
Treatment Description
B
150 mg GSK2831781 SC
C
450 mg GSK2831781 SC
Q
Placebo SC
7.4.
Blinding
This will be a double-blind study with respect to allocation of GSK2831781 or placebo to 
participants. All study staff and participants will be blinded with the exception of 
unblinded pharmacists or delegates.
The following will apply:

The IWRS will be programmed with blind-breaking instructions. In case of an 
emergency, the investigator has the sole responsibility for determining if 
unblinding of a participant’s treatment assignment is warranted. Participant safety 
must always be the first consideration in making such a determination. If a 
participant’s treatment assignment is unblinded GSK must be notified within 24 
hours after breaking the blind.

The date and reason for the unblinding must be fully documented in the CRF.

A participant may continue in the study if the participant’s treatment code is
unblinded
by
the investigator
or
treating
physician.
If the participant 
discontinues the date and primary reason for discontinuation (the event or
condition which led to the unblinding) will be recorded in the CRF.

GSK’s Safety and Medical Governance (SMG) 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.
Members of the DRC may be unblinded if individual data needs to be reviewed as part of 
the interim analysis. 
 
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7.5.
Study Intervention Compliance

GSK2831781 will be intravenously administered in Part A, and subcutaneously 
administered in Part B to participants at the site. Administration will be documented 
in the source documents and reported in the CRF.

Participants will receive study intervention 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 intervention 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 intervention.  
7.6.
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.
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. Participants will be questioned about concomitant 
medication at each study visit.
Paracetamol (acetaminophen) at doses of 4 grams/day, and occasional NSAIDs at 
licensed doses, are permitted for use. 
Otherwise, participants must abstain from taking prescription or non-prescription drugs 
(including vitamins and dietary or herbal supplements) within 7 days or 5 half-lives 
(whichever is longer) before the start of study intervention until completion of the follow-
up visit unless, in the opinion of the investigator and sponsor, the medication will not 
interfere with the study. 
Live vaccination is prohibited within 4 weeks of Day 1 until after the Follow-Up visit.
7.7.
Dose Modification
Study stopping criteria are detailed in Section 8.2. In addition, if moderate or severe AEs 
not meeting stopping criteria are consistently observed across participants in a cohort or 
strata, or if unacceptable pharmacological effects reasonably attributable to GSK2831781 
are observed, this will result in review by the SRT prior to additional participants being 
dosed. This protocol allows for dose reduction if necessary following SRT review (see 
Section 8.3).
 
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8.
DISCONTINUATION CRITERIA 
8.1.
Discontinuation of Study Intervention
This is a SD study. In rare instances, a participant in Part A may not be able to complete 
the IV infusion, or a participant in Part B may not receive all 3 injections. In such 
circumstances, if the study intervention is permanently discontinued, the participant will
be encouraged to remain in the study for the planned duration, or minimally to complete 
safety and PK assessments up to Day 29.
8.2.
Study Stopping Criteria
8.2.1.
Serious Adverse Events 
If one or more participants experience an SAE in either Part A or Part B of the study that 
can be reasonably attributed to GSK2831781, and which is not a subcutaneous injection 
site reaction, no further participants will be dosed until a full safety review has taken 
place and the study will be temporarily halted. 
If one or more participants in Part B experience an SAE due to a SC injection site 
reaction, no further participants will be dosed in Part B until a full safety review has 
taken place, although dosing in Part A may continue. 
Relevant reporting and discussion with the GSK2831781 Safety Review Team (SRT; see 
Section 8.3 for additional details), relevant GSK personnel, and with the Ethics 
Committee and Regulatory Agency will then take place. If, following the safety review, a 
decision is made to restart dosing (which may be at either the same dose or a lower dose), 
this will only occur after approval of a substantial amendment.
8.2.2.
AEs of Special Interest 
The following events of note across both Part A and Part B will result in review by the 
SRT before further participants are dosed:
A severe opportunistic or atypical infection.
Cytokine release syndrome of Common Terminology Criteria for Adverse Events 
(CTCAE) (Version 5) Grade 2.
Serum sickness of CTCAE (Version 5) Grade 2.
A neutrophil count <0.5x109/L on any occasion (confirmed on repeat testing within 
3-5 days), an absolute neutrophil count <1.0x109/L for 2 weeks, or CTCAE Grade 3 
febrile neutropaenia (neutrophil count <1.0x109/L and fever ≥38.5ºC).
8.2.3.
Liver Chemistry Criteria
Liver chemistry study stopping criteria, and individual participant increased monitoring 
criteria, have been designed to assure participant safety and evaluate liver event
aetiology.

Liver events meeting SAE criteria will be managed as detailed in Section 11.5.
 
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
Liver events characterized by an ALT ≥3x ULN but not meeting SAE criteria, if 
reasonably attributable to GSK2831781, will result in review by the SRT before 
further participants are dosed and additional assessments as detailed in Section
11.5.
8.2.4.
QTc Criteria
QTc study stopping criteria, and individual participant increased monitoring criteria, have 
been designed to assure participant safety. The same QT correction formula must be used 
for each individual participant to determine eligibility for and discontinuation from the 
study. Use of Fridericia’s formula (QTcF) is preferred in this study. The 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. Safety ECGs and other non-protocol 
specified ECGs are an exception.  
If a participant meets any of the criteria below, this will result in review by the SRT 
before further participants are dosed, as well as additional monitoring of the affected 
individual:

QTc >500 msec. 

Uncorrected QT >600 msec.

Change from baseline of QTc >60 msec.
With the exception of screening, the QTc should be based on single ECG reading. If an 
ECG demonstrates a prolonged QTc interval, then a further two ECG readings should be 
obtained over a brief recording period and the averaged QTc interval used to determine 
whether the participant meets the criteria to trigger SRT review and for individual further 
monitoring. Further monitoring will consist at minimum of triplicate ECGs one week 
later, and then follow-up until values are no longer clinically significant.  
8.3.
Role of the Safety Review Team (SRT)
An SRT will oversee the safety of participants in this study. The SRT will review blinded 
safety data at planned interims during the study, and unscheduled as required. Further 
details of the SRT are described in Section 11.1.5 and the SRT charter. 
Unscheduled SRT reviews may be triggered as described in Section 8.2, if moderate or 
severe AEs are consistently observed across participants in a cohort or strata, or if 
unacceptable pharmacological effects reasonably attributable to GSK2831781 are 
observed. Should an unscheduled SRT review of this study be required, possible 
outcomes may include:

Restart dosing at the current dose levels.

Restart dosing but reduce the dose levels in Part A and/or Part B as guided by 
emerging safety data and data on GSK2831781 plasma concentrations.

Stop dosing in the relevant part of the study (A or B) but continue with the other 
part.

Stop dosing both Part A and Part B.
 
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If the study is halted due to safety concerns based on a decision by the SRT (or DRC; see
11.1.5 ), and a subsequent decision is made to restart dosing, this will only occur after 
competent authority authorization via a substantial amendment.
8.4.
Participant Discontinuation/Withdrawal from the Study

A participant may withdraw from the study at any time at his own request or
may be withdrawn at any time at the discretion of the investigator for safety, 
behavioural, compliance or administrative reasons. This is expected to be 
uncommon.

At the time of discontinuing from the study, if possible, an early discontinuation 
visit should be conducted, as shown in the Schedule of Activities (SoA). See
Section 2 Schedule of Activities (SoA) SoA for data to be collected at the time 
of study discontinuation and follow-up and for any further evaluations that need 
to be completed.

The participant will be permanently discontinued both from the study 
intervention and from the study at that time.

If the participant withdraws consent for disclosure of future information, the 
sponsor may retain and continue to use any data collected before such a 
withdrawal of consent.

If a participant withdraws from the study, he may request destruction of any 
samples taken and not tested, and the investigator must document this in the site 
study records.
8.5.
Lost to Follow-Up
A participant will be considered lost to follow-up if he 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 will be considered to have 
withdrawn from the study. 
 
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Discontinuation of specific sites or of the study as a whole are handled as part of Section 
11.1.9.
9.
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and their timing are summarized in the SoA. 

Protocol waivers or exemptions are not allowed.

Immediate safety concerns will be managed by the investigator with discussions with 
the GSK Medical Monitor as required to determine if the participant should continue 
or discontinue study intervention.

Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct.

All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening 
log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable. 

Procedures conducted as part of the participant’s routine clinical management (e.g., 
blood count) and obtained before signing of ICF may be utilized for screening 
purposes provided the procedure met the protocol-specified criteria and was 
performed within the time frame defined in the SoA.

Include the maximum amount of blood collected from each participant over the 
duration of the study and if any repeat or unscheduled samples may be taken, as 
appropriate.

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 over 3 months.

Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples.

The actual date and time of each blood sample collection will be recorded. The 
collection, sample handling, processing, storage and shipping procedures are 
provided in the SRM or equivalent.

Drug concentration information that would unblind the study will not be reported to 
investigative sites or blinded personnel until the study has been unblinded.
9.1.
Safety Assessments
Planned time points for all safety assessments are provided in the SoA.
9.1.1.
Physical Examinations
A complete physical examination will include, at a minimum, assessments of the Skin, 
Cardiovascular, Respiratory, Gastrointestinal, Endocrine and Neurological systems. 
Height and weight will also be measured and recorded at screening.
 
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9.1.2.
Vital Signs
Vital signs (to be taken before blood collection for laboratory tests) will be measured in a 
semi-supine position after 5 minutes rest and will include temperature, systolic and 
diastolic blood pressure and pulse rate.
Blood pressure and pulse measurements will be with a completely automated device. 
Manual techniques will be used only if an automated device is not available. 
Temperature measurements should be oral or tympanic.
9.1.3.
Electrocardiograms

Triplicate (at screening) or single 12-lead ECG will be obtained in a semi-supine 
position, after 5 minutes rest, as outlined in Section 2 (SoA) using an ECG 
machine that automatically calculates the heart rate and measures PR, QRS, QT, 
and QTc intervals. The same QT correction formula must be used for each 
individual participant to determine eligibility for and discontinuation from the 
study, and this formula may not be changed or substituted once the participant has 
been screened.

Where single ECG measurements are obtained, if the QTc measurement fulfils a 
QTc withdrawal criterion an additional two QTc readings will be obtained and the 
average of these three measurements will be used. Refer to Section 8.2.4 for QTc 
withdrawal criteria and additional QTc readings that may be necessary.

Where triplicate ECGs are required, 3 individual ECG tracings should be obtained 
as closely as possible in succession, but no more than 2 minutes apart. The full set 
of triplicates should be completed in less than 4 minutes.
9.1.4.
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 
CRF. The laboratory reports must be filed with the source documents. 

All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 16 weeks after dosing 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.
9.1.5.
Infusion-related Reactions 
Symptoms and signs of an infusion reaction include tenderness, warmth, redness at the 
site of injection or along the vein, and/or itching. More severe reactions may additionally 
include pain at the site of injection, blistering or skin damage. 
 
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Management consists of discontinuing the infusion (if possible), hot or cold compresses, 
and analgesia. A plastic surgery consult should be requested if there is significant skin 
injury or symptomatic extravasation.
9.1.6.
Hypersensitivity Reactions
As GSK2831781 is a fully humanized monoclonal antibody, it is considered unlikely that 
acute allergic reactions will occur in response to exposure; however, all participants 
should be monitored carefully for evidence of allergic response. 
Participants should be instructed to report the development of rash, hives, pruritus, 
flushing, urticaria, vomiting, or other symptoms that may represent a hypersensitivity 
reaction to study intervention. It is important to recognize early signs of a 
hypersensitivity reaction and prevent progression to a severe reaction. In the case of a 
mild reaction during dosing, study intervention administration may be reinitiated (with 
appropriate pre-medication) at the discretion of the investigator. 
In the event of a suspected severe acute hypersensitivity reaction or anaphylaxis, sites 
should manage this in accordance with relevant local or national guidelines (for example, 
the Resuscitation Council (UK) Emergency Treatment of Anaphylactic Reactions 
Guidelines for Healthcare Providers (2008). In particular sites should:
Discontinue administration of study intervention (if still ongoing), and not delay 
initial treatment due to indefinite diagnosis.
Ensure adrenaline, chlorphenamine, hydrocortisone, and a resuscitation trolley are 
immediately available.
Assess the participant using the Airway, Breathing, Circulation, Disability, 
Exposure approach. In the event of a cardiac arrest, initiate cardiopulmonary 
resuscitation.
Provide adrenaline as per relevant local/national guidelines if there is any 
compromise of the participant’s airway, breathing or circulation:
Provide high concentration oxygen via a non-rebreathe mask; fluid resuscitation; 
initiate ECG monitoring and pulse oximetry; and monitor blood pressure.
Administer an appropriate antihistamine (e.g., chlorphenamine maleate 10 mg by 
slow intravenous injection, or intramuscularly).
Administer
hydrocortisone 200 mg by slow intravenous injection, or 
intramuscularly.
Acquire two blood samples should be taken for serum tryptase analysis:
o As soon as possible after the onset of symptoms, and
o Within 1-2 hours (but no later than 4 hours) from the onset of symptoms.
 
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Discuss the clinical situation with the relevant hospital medical and/or intensive 
care team, and arrange transfer to hospital for further treatment and observation as 
indicated.
9.1.7.
Cytokine Release Syndrome
Symptoms and signs of severe Cytokine Release Syndrome (CRS) may include severe 
headache, muscle pain, nausea, vomiting, diarrhoea, pyrexia, generalised erythema, 
peripheral vasoconstriction, hypotension, tachycardia and/or tachypnoea. 
If CRS is suspected, in addition to assessment for infection, sites should:
Start high flow oxygen, obtain intravenous access, and start fluid resuscitation.
Give 100 mg intravenous hydrocortisone, and consider higher doses if the 
participant is severely unwell.
Discuss the clinical situation with the relevant hospital medical and/or intensive 
care team, and arrange transfer to hospital as indicated.
Take blood for measurement of cytokine levels (including interleukin [IL]-6, IL-8, 
interferon [IFN]-γ and tumour necrosis factor [TNF]-α), and C-reactive protein 
(CRP). These should also be measured approximately every other day until 
symptoms show improvement or an alternative diagnosis is confirmed.
Treat myalgia with analgesia, and give a suitable intravenous antiemetic (e.g. 
ondansetron), if required.
9.1.8.
Immunosuppression and Infections
Participants with signs and symptoms suggestive of infection should be treated as 
clinically indicated according to medical best practice. Blood, sputum, urine, and/or stool 
cultures will be obtained as appropriate for detection and diagnosis of infection. Blood 
samples for
determination of
viral serology ± measurement of viral load 
[cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV)], as 
well as measurement of immunoglobulins, will be taken if the participant demonstrates 
clinical symptoms consistent with viral reactivation; serology samples for these viruses 
will also be tested at screening.
9.1.9.
Autoimmunity
There are a small percentage of regulatory T cells that are LAG3+ [Gagliani, 2013; 
Camisaschi, 2010], and therefore investigators should be alert for the development of 
autoimmunity. Any participant who reports symptoms suspicious for autoimmunity 
should be investigated and managed as clinically appropriate.
9.2.
Adverse Events and Serious Adverse Events
The definitions of an AE or SAE can be found in Appendix 3.
 
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The investigator and any qualified designees are responsible for detecting, documenting, 
and reporting events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study intervention or the 
study, or that caused the participant to discontinue the GSK2831781 (see Section 8).
9.2.1.
Time Period and Frequency for Collecting AE and SAE 
Information

All SAEs will be collected from consenting participants until the Follow-Up 
visit at the time point specified in the SoA (Section 2). However, any SAEs 
assessed as related to study participation (e.g. study intervention, protocol-
mandated procedures, invasive tests, or change in existing therapy) or related to 
a GSK product will be recorded from the time a participant consents to 
participate in the study.

All AEs will be collected from the start of intervention until the Follow-Up visit 
at the time points specified in the SoA (Section 2).

Medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will be recorded on the Medical History/Current 
Medical Conditions section of the CRF not the AE section. The exceptions are 
SAEs, which must be recorded in the CRF AE/SAE section.

All SAEs will be recorded and reported to the sponsor or designee immediately 
and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. 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 after the conclusion 
of the study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the 
study, and he/she considers the event to be reasonably related to the study 
intervention or study participation, the investigator must promptly notify the 
sponsor.
9.2.2.
Method of Detecting AEs and SAEs

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 3.

Care will be taken not to introduce bias when detecting AE and/or SAE. Open-
ended and non-leading verbal questioning of the participant is the preferred 
method to inquire about AE occurrence. 
9.2.3.
Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All AE/SAEs will be followed until the event is 
resolved, stabilized, otherwise explained, or the participant is lost to follow-up (as 
 
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defined in Section 8.5). Further information on follow-up procedures is given in 
Appendix 3.
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 intervention 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 intervention
under clinical investigation. The sponsor will comply with country-specific 
regulatory requirements relating to safety reporting to the regulatory authority, 
Institutional Review Boards (IRB)/Independent Ethics Committees (IEC), and 
investigators.

Investigator safety reports must be prepared for suspected unexpected serious 
adverse reactions (SUSAR) according to local regulatory requirements and 
sponsor policy and forwarded to investigators as necessary.

An investigator who receives an investigator safety report describing a SAE or 
other specific safety information e.g., summary or listing of SAE) from the 
sponsor will review and then file it along with the IB and will notify the 
IRB/IEC, if appropriate according to local requirements.
9.3.
Treatment of Overdose
For this study, any dose of GSK2831781 greater than the agreed dose level will be 
considered an overdose.
GSK does not recommend specific treatment for an overdose. 
If an overdose is identified by unblinded staff, but is less than 450 mg, this should be 
documented by the unblinded monitor (including the quantity of the overdosing), but no 
additional action need be taken.
If the total dose administered has exceeded 450 mg, investigators should: 
1. Contact the Medical Monitor immediately.
2. Closely monitor the participant for AE/SAE and laboratory abnormalities for at 
least 4 weeks from the date the overdose occurred, and thereafter as advised by 
the Medical Monitor.
3. Document the quantity of the excess dose.
9.4.
Pharmacokinetics
Blood (3 mL per time point) will be collected into K2-ethylenediaminetetraacetic acid
(EDTA) tubes and processed to obtain plasma for PK analysis of GSK2831781 at the 
time points indicated in Section 2, SoA Tables. The actual date and time (24-hour clock 
time) of each blood sample collection will be recorded. 
 
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Details of blood sample collection, processing, storage and shipping procedures are
provided in the SRM.
Drug concentration information that would unblind the study will not be reported to 
investigative sites or blinded personnel until the study has been unblinded.
9.4.1.
Soluble LAG3 (sLAG3)
Venous blood samples will be collected for measurement of sLAG3 as specified in the 
Section 2, SoA.
9.5.
Pharmacodynamics
The PD effect of GSK2831781 on LAG3+ target engagement and cell depletion will be 
determined through analysis of blood. Blood PD analysis will be undertaken through 
flow cytometry as specified in the Section 2 SoA.
More detailed immunophenotyping, including identification of regulatory T cells, may be 
carried out on samples from a subset of participants.
9.6.
Genetics
A 6 mL blood sample for DNA isolation will be collected from participants who have 
consented to participate in the genetics analysis component of the study. Participation is 
optional. Participants who do not wish to participate in the genetic research may still 
participate in the study.
In the event of DNA extraction failure, a replacement genetic blood sample may be 
requested from the participant. Signed informed consent will be required to obtain a 
replacement sample unless it was included in the original consent.
See Appendix 4, Section 11.4 for Information regarding genetic research. 
9.7.
Immunogenicity Assessments 
Antibodies to GSK2831781 will be evaluated in serum samples collected from all 
participants according to Section 2, SoA. The detection and characterization of 
antibodies to GSK2831781 will be performed using a validated assay method by or under 
the supervision of the Sponsor.
Serum samples will be assessed for the presence of ADA using a tiered approach. 
Samples will first be screened for antibodies binding to GSK2831781. Samples with 
screening result above the screening cut point will be further assayed in an assay to 
confirm the specificity of the ADA. Samples testing positive in the confirmation assay 
will be further assayed through sequential dilution in order to report a titre value. The 
titre is the reciprocal of the last dilution at which the sample tests positive in the 
screening assay. Additional analysis may be performed on samples collected to monitor 
immunogenicity to assess the presence of neutralizing antibodies to GSK2831781 and/or 
to further characterize the immunogenicity of GSK2831781.
 
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10.
STATISTICAL CONSIDERATIONS
10.1.
Statistical Hypotheses
The primary objective is to determine the safety and tolerability of single IV doses of 
GSK2831781 in healthy Japanese and Caucasian participants (Part A); or of single SC 
doses of GSK2831781 in healthy Caucasian participants (Part B). There are no formal 
hypotheses planned.
10.2.
Sample Size Determination
10.2.1.
Part A
There will be a minimum of 8 Japanese and 8 Caucasian participants in Part A. The 
participants in each ethnicity stratum will be randomised 6:2 to GSK2831781 (450 mg) 
or placebo.
If 0/6 of a particular safety event is observed among the GSK2831781 participants of an 
ethnicity stratum, then the upper limit of the exact 95% Confidence Interval indicates that 
a true incidence rate of 41.0% could not be ruled out. Using a Bayesian approach to 
determine the credible interval around an observed safety event, we will assume a flat 
Beta (1,1) prior. If in an ethnicity stratum we were to observe 1 safety event out of the 6 
participants who received GSK2831781, then the posterior distribution would be Beta 
(2,6). In that case there is a 95% certainty that the true probability of the safety event lies 
between 0.04 and 0.58.
The following between-subject coefficients of variation (CVb) for the geometric means of 
PK parameters were observed in the FTIH study 200630 following GSK2831781 IV
administration:
Study 200630
Treatment group
CVb (%)
Volunteer type
AUC (0-t)
Cmax
Healthy volunteer
0.0075 mg/kg
32.0
19.1
Healthy volunteer
0.04 mg/kg
27.3
25.6
Healthy volunteer
0.15 mg/kg
36.8
18.3
Psoriasis patient
0.5 mg/kg
34.2
23.5
Psoriasis patient
1.5 mg/kg
13.8
15.5
Psoriasis patient
5 mg/kg
24.2
22.2
The 5 mg/kg dose corresponds to an average of 472 mg; therefore, the corresponding 
CVb %’s are a good approximation for 450 mg.
Assuming a sample size of 6, it is estimated that the lower and upper bounds of the 90% 
confidence interval for the geometric means of area under the curve (AUC) and Cmax 
will be within approximately 21.7% and 19.8% of the point estimate respectively.
 
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10.2.2.
Part B
There will be a minimum of 20 participants in Part B, randomised 8:8:4 to low dose 
GSK2831781 (150 mg) or high dose GSK2831781 (450 mg) or placebo.
If 0/8 of a particular safety event is observed among the GSK2831781 participants, then
the upper limit of the exact 95% Confidence Interval indicates that a true incidence rate 
of 33.6% could not be ruled out. Using a Bayesian approach to determine the credible 
interval around an observed safety event, we will assume a flat Beta (1,1) prior. If on 
GSK2831781 we were to observe 1 safety event out of the 8 participants, then the 
posterior distribution would be Beta (2,8). In that case there is a 95% certainty that the 
true probability of the safety event lies between 0.03 and 0.48.
To date we do not have any GSK2831781 SC PK variability data available. Therefore, 
literature data was used to obtain informative priors for the absorption rate constant (ka) 
and bioavailability (F). Using these priors, and the PK/PD relationship derived from the 
data of the First Time in Humans Study 200630, a sample size of 8 participants on active 
treatment has a probability of 65% to result in a median cell depletion in blood greater 
than 90% at week 4 after dosing.
10.2.3.
Sample Size Sensitivity
A sample size sensitivity analysis was conducted to investigate different safety event 
rates. A Bayesian approach was used, specifying a flat Beta (1,1) prior. If the number of 
subjects who complete each active dose reduce, then the 95% credible interval of the true 
event rate would change:
N Dosed 
Number of a particular safety 
event observed with 
GSK2831781
95% certain that the true 
probability of the safety event 
lies between
8
2
(0.07, 0.60)
3
(0.14, 0.70)
7
0
(0.00, 0.37)
1
(0.03, 0.53)
2
(0.09, 0.65)
6
2
(0.10, 0.71)
3
(0.18, 0.82)
5
0
(0.00, 0.46)
1
(0.04, 0.64)
2
(0.12, 0.78)
4
0
(0.01, 0.52)
1
(0.05, 0.72)
2
(0.15, 0.85)
 
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10.3.
Populations for Analyses
For purposes of analysis, the following populations are defined:
Population
Description
Enrolled
All participants who sign the ICF.
Randomized
All participants who are randomised into the study and receive a 
randomisation number.
Safety
All randomized participants who receive at least 1 dose of study 
intervention. Participants will be analysed according to the intervention 
they actually received.
Pharmacokinetic
All safety participants for whom a PK sample was obtained and analysed.
10.4.
Statistical Analyses
The final analysis will be performed once all participants in Part A and in Part B have 
completed their Day 112 visit.
10.4.1.
Safety Analyses
All safety analyses will be performed on the Safety Population.
Endpoint
Statistical Analysis Methods
Primary
The primary safety analyses will be based on the “Safety” population. These 
endpoints will be presented in tabular and/or graphical format and summarised 
descriptively according to GSK's Integrated Data Standards Library standards.
10.4.2.
Pharmacokinetic Analyses
Endpoint
Statistical Analysis Methods
Secondary
The PK analyses will be based on the “Pharmacokinetic” population. Plasma 
GSK2831781 concentration-time data will be analysed by non-compartmental 
methods. Calculations will be based on the actual sampling times recorded during 
the study. From the plasma concentration-time data, the following PK parameters 
will be determined, as data permit: Cmax, tmax, AUC(0-t).
Descriptive statistics (n, arithmetic mean, standard deviation, 95% CI, minimum, 
median and maximum,) will be calculated for all pharmacokinetic parameters. In 
addition, for log e-transformed variables geometric mean, 95% confidence interval 
 
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Endpoint
Statistical Analysis Methods
and %CVb will be provided.
Ethnicity comparison (Part A): Analysis of variance (ANOVA) will be performed to 
determine the point estimate for the comparison of Japanese to Caucasian 
participants for each of the PK parameters AUC(0-t) and Cmax at each dose level 
studied, with the 90% confidence interval based on the geometric least square 
mean of Japanese:Caucasian participants.
Bioavailability Analyses (Part B): Comparative plots will be provided showing 
individual values by treatment for each of the PK parameters AUC(0-t) and Cmax.  
Plots will also be provided showing the adjusted geometric mean ratio of test to 
reference treatment for AUC(0-t) and Cmax together with 90% confidence intervals. 
ANOVA will be performed as appropriate to determine the point estimate for 
absolute bioavailability, Fabs, with 90% confidence interval based on the geometric 
least square mean of test/reference ratio. The primary statistical analysis will be 
analysis of variance of loge-transformed AUC(0-t). Fabs is defined as follows:
10.4.3.
Pharmacokinetic/Pharmacodynamic Analysis
Endpoint
Statistical Analysis Methods
Secondary
A population PK/PD analysis will be performed based on the safety population. This 
will investigate PK, sLAG3 and cell depletion data. In Part A, this analysis may
include ethnicity as a covariate.
10.4.4.
Other Analyses
For Parts A and B, the immunogenicity assessment will include the incidence (confirmed 
positive results only) and titres of anti-GSK2831781 binding antibodies at each time 
point and at any time point post baseline. 
Further details of the statistical analyses will be provided in the Reporting Analysis Plan 
(RAP).
10.5.
Interim Analyses
An interim analysis for Part A will be performed once at least 8 participants in each 
stratum have completed their Day 8 visit, and at least 6 participants in each strataum have
complete their Day 29 visit, where Safety, PK and PD data will be reviewed. The interim 
analysis will be utilised to determine if Japanese participants can be recruited into the 
 
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Phase 2 study (204869). To aid this decision, an additional interim analysis may also be 
conducted once all Part A participants complete Day 112. An appropriate committee will 
conduct the interim analysis, where details will be outlined clearly in the RAP.
A DRC will be utilised in this study to review the interim analyses data. The DRC will be
comprised of a predefined subset of study team members. No study personnel with direct 
contact with sites or site staff will be involved in the DRC (see Appendix 1, Section 
11.1.5).
 
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11.
SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS
11.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations
11.1.1.
Regulatory and Ethical Considerations

This study will be conducted in accordance with the protocol and with:

Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical 
Guidelines.

Applicable ICH (International Conference of Harmonization) Good 
Clinical Practice (GCP) Guidelines.

Applicable laws and regulations.

The protocol, protocol amendments, ICF, IB, and other relevant documents 
(e.g., advertisements) must be submitted to an IRB/IEC by the investigator and 
reviewed and approved by the IRB/IEC before the study is initiated. 

Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants. 

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.
11.1.2.
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.
 
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11.1.3.
Informed Consent Process

The investigator or his representative will explain the nature of the study to the 
participant and answer all questions regarding the study. 

Participants must be informed that their participation is voluntary. Participants 
will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, and the IRB/IEC 
or study centre. 

The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The 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. 

Participants who are rescreened are required to sign a new ICF.
11.1.4.
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 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 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.
11.1.5.
Committees Structure
Safety Review Team (SRT)
In line with routine pharmacovigilance, an internal GSK SRT, which will include a 
limited number of 207823 study team members, will review blinded safety data, 
including clinical laboratory parameters and adverse events, at appropriate intervals 
during the period of study conduct. The SRT charter outlines the roles and 
responsibilities in more detail.
Data Review Committee (DRC)
During an Interim Analysis unblinded study data may be reviewed by the DRC, and 
decisions made based on the outlined criteria included in the DRC charter. The DRC will 
be composed of a limited number of people, who may be members of the 207823 study 
 
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team, including the statistician, a senior safety representative, lead physician and the 
pharmacokineticist. No members of the study team involved in the direct day-to-day 
conduct of the study or in the acquisition of data will take part in the DRC.
11.1.6.
Dissemination of Clinical Study Data

Where required by applicable regulatory requirements, an investigator signatory 
will be identified for the approval of the CSR. The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have 
the opportunity to review the complete study results at a GSK site or other 
mutually-agreeable location.

GSK will also provide the investigator with the full summary of the study 
results. The investigator is encouraged to share the summary results with the 
study participants, as appropriate.

GSK will provide the investigator with the randomization codes for their site 
only after completion of the full statistical analysis.

The procedures and timing for public disclosure of the protocol and results 
summary and for development of a manuscript for publication for this study will 
be in accordance with GSK Policy.

GSK intends to make anonymized patient-level data from this trial available to 
external researchers for scientific analyses or to conduct further research that 
can help advance medical science or improve patient care. This helps ensure the 
data provided by trial participants are used to maximum effect in the creation of 
knowledge and understanding

A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge.
11.1.7.
Data Quality Assurance

All participant data relating to the study will be recorded on printed or electronic 
CRF unless transmitted to the sponsor or designee electronically (e.g., 
laboratory data). The investigator is responsible for verifying that data entries 
are accurate and correct by physically or electronically signing the CRF. 

The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF. 

The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents. 

Monitoring details describing strategy (e.g., risk-based initiatives in operations 
and quality such as Risk Management and Mitigation Strategies and Analytical 
Risk-Based Monitoring), methods, responsibilities and requirements, including 
handling of noncompliance issues and monitoring techniques (central, remote, 
or on-site monitoring) are provided in the Monitoring Plan.
 
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
The sponsor or designee is responsible for the data management of this study 
including quality checking of the data. 

The sponsor assumes accountability for actions delegated to other individuals 
(e.g., Contract Research Organizations).

Study monitors will perform ongoing source data verification to confirm that 
data entered into the CRF by authorized site personnel are accurate, complete, 
and verifiable from source documents; that the safety and rights of participants 
are being protected; and that the study is being conducted in accordance with the 
currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements. 

Records and documents, including signed ICF, pertaining to the conduct of this 
study must be retained by the investigator for 25 years from the issue of the final 
CSR/equivalent summary unless local regulations or institutional policies 
require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the 
sponsor. 
11.1.8.
Source Documents

Data reported on the CRF or entered in the electronic case report form (eCRF)
that are transcribed from source documents must be consistent with the source 
documents or the discrepancies must be explained. The investigator may need to 
request previous medical records or transfer records, depending on the study. 
Also, current medical records must be available.

Definition of what constitutes source data can be found in the Source Document 
Agreement. 
11.1.9.
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 intervention development.
 
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11.1.10.
Publication Policy
The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the investigator agrees to submit all manuscripts or abstracts to the sponsor 
before submission. This allows the sponsor to protect proprietary information and to 
provide comments.

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 multicentre studies only in their entirety and not 
as individual site data. In this case, a coordinating investigator will be 
designated by mutual agreement.

Authorship will be determined by mutual agreement and in line with 
International Committee of Medical Journal Editors authorship requirements.
 
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11.2.
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
Haematology
Platelet Count
RBC Indices:
Mean Corpuscular 
Volume (MCV)
Mean Corpuscular 
Haemoglobin (MCH)
%Reticulocytes
White Blood Cell (WBC)
count with Differential:
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
Red Blood Cell (RBC)
Count
Haemoglobin
Haematocrit
Clinical 
Chemistry1
Blood Urea 
Nitrogen (BUN)
Potassium
Aspartate 
Aminotransferase
(AST)/Serum 
Glutamic-
Oxaloacetic 
Transaminase
(SGOT)
Total and direct 
bilirubin
Creatinine 
Estimated 
Glomerular 
Filtration Rate 
(eGFR)
Sodium
Alanine 
Aminotransferase
(ALT/Serum 
Glutamic-Pyruvic 
Transaminase
(SGPT)
Total Protein
Glucose [non-
fasting]
Calcium
Alkaline 
phosphatase
Routine 
Urinalysis

Specific gravity

pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte 
esterase by dipstick

Microscopic examination (if blood or protein is abnormal)
Other 
Screening 
Tests

Breath alcohol screen

Urine drug screen (to include at minimum: amphetamines, barbiturates, 
cocaine, opiates, cannabinoids and benzodiazepines)

Serology: HIV antibody, HbsAg, HbcAb, HCV antibody, EBV antibody3, 
CMV antibody3, VZV antibody3

Quantiferon test for TB
 
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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 8.2.3. All events of ALT 3 × upper limit of normal (ULN) and bilirubin 2 × 
ULN (>35% direct bilirubin) or ALT 3 × ULN and international normalized ratio (INR) >1.5, if INR measured, 
which may indicate severe liver injury (possible Hy’s Law), must be reported as an SAE (excluding studies of 
hepatic impairment or cirrhosis).
2.
Local urine testing will be standard for the protocol unless serum testing is required by local regulation or IRB/IEC.
3.
To be repeated in event of possible viral reactivation.
Laboratory results that could unblind the study will not be reported to investigative sites 
or other blinded personnel until the study has been unblinded.
 
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11.3.
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting
11.3.1.
Definition of AE
AE Definition

An AE is any untoward medical occurrence in a clinical study participant, temporally 
associated with the use of a study intervention, whether or not considered related to 
the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (haematology, clinical chemistry, or urinalysis) 
or other safety assessments (e.g., ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not related 
to progression of underlying disease).

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae.
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.

Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen.
 
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11.3.2.
Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease).
A SAE is defined as any untoward medical occurrence that, at any dose:
o
Results in death
o
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.
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 fulfils any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious.
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE.
Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhoea, influenza, 
and accidental trauma (e.g. sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption.
Is a congenital anomaly/birth defect
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that may 
not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the participant or may require medical or surgical intervention to prevent 
one of the other outcomes listed in the above definition. These events should usually 
be considered serious.
Examples of such events include invasive or malignant cancers, intensive treatment 
 
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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.
11.3.3.
Recording and Follow-Up of AE and SAE
AE and SAE Recording

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory, and diagnostics reports) 
related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

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 CRF 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 sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with an SAE. Severe is a category utilized for rating 
the intensity of an event; and both AE and SAE can be assessed as severe.
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes 
as described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE.

A "reasonable possibility" of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.
 
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
The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB 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 CRF.

The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information.
11.3.4.
Reporting of SAE to GSK
SAE Reporting to GSK via Electronic Data Collection Tool

The primary mechanism for reporting SAE to GSK will be the electronic data 
collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as it becomes 
 
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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 IMP/study participation (causality) within 72 hours of 
SAE entry into the eCRF.

After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see 
next section) or to the medical monitor by telephone.

Contacts for SAE reporting can be found in the Study Reference Manual.
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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11.4.
Appendix 4: Genetics
USE/ANALYSIS OF DNA

Genetic variation may impact a participant’s response to study intervention, 
susceptibility, severity and progression of disease. Variable response to study 
intervention may be due to genetic determinants that impact drug absorption, 
distribution, metabolism, and excretion; mechanism of action of the drug; disease 
aetiology; and/or molecular subtype of the disease being treated. Therefore, where 
local regulations and IRB/IEC allow, a blood sample will be collected for DNA 
analysis.

DNA samples will be used for research related to GSK2831781 and related diseases. 
They may also be used to develop tests/assays (including diagnostic tests) related to 
GSK2831781. Genetic research may consist of the analysis of one or more candidate 
genes, or the analysis of genetic markers throughout the genome, DNA samples will 
be analysed if it is hypothesized that this may help further understand the clinical 
data. 

The samples may be analysed as part of a multi-study assessment of genetic factors 
involved in the response to GSK2831781 or study interventions of this class. The 
results of genetic analyses may be reported in the CSR 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 GSK2831781 continues but no 
longer than 15 years after the last participant last visit or other period as per local 
requirements.
 
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11.5.
Appendix 5: Liver Safety: Required Actions and Follow-up 
Assessments
Phase I liver chemistry stopping criteria and required follow up assessments
Liver Chemistry Stopping Criteria 
ALT-absolute
ALT ≥3x ULN
If ALT ≥3x ULN AND bilirubin1,2 2x ULN (>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 
Actions
Follow Up Assessments

Report the event to GSK within 24 hours

Complete the liver event CRF, and complete 
an SAE data collection tool if the event also 
meets the criteria for an SAE2

Perform liver event follow up assessments 

Monitor the participant until liver chemistries 
resolve, stabilise, or return to within baseline 
(see MONITORING below)
MONITORING:
If ALT ≥3x ULN AND bilirubin 2x ULN or INR 
>1.5

Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin and INR) and 
perform liver event follow up assessments 
within 24 hours

Monitor participant twice weekly until liver 
chemistries resolve, stabilise or return to 
within baseline

A specialist or hepatology consultation is 
recommended
If ALT ≥3x ULN AND bilirubin <2x ULN and 
INR ≤1.5:

Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin and INR) and 
perform liver event follow up assessments 

Viral hepatitis serology3

Obtain INR and recheck with each liver 
chemistry assessment until the 
transaminases values show downward 
trend

Obtain blood sample for PK analysis, as 
soon as possible, and at least within 7 
days after last dose4 

Serum creatine phosphokinase (CPK) and 
lactate dehydrogenase (LDH).

Fractionate bilirubin, if total bilirubin 2x
ULN

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 form 
including paracetamol (acetaminophen), 
herbal remedies, other over the counter 
medications.

Record alcohol use on the liver event 
alcohol intake case report form
If ALT ≥3x ULN AND bilirubin 2x ULN or 
 
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Liver Chemistry Stopping Criteria 
within 24-72 hours

Monitor participant weekly until liver 
chemistries resolve, stabilize or return to 
within baseline
INR >1.5:

Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney 
microsomal antibodies, and quantitative 
total IgG or gamma globulins.

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 intervention for that subject if ALT 3x ULN and bilirubin 2x ULN. 
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 3x ULN and bilirubin 2x ULN (>35% direct bilirubin) or ALT 3x ULN and INR >1.5, which 
may indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE (excluding studies of hepatic 
impairment or cirrhosis); the INR threshold value stated will not apply to subjects receiving anticoagulants
3.
Includes: Hepatitis A immunoglobulin (gM) antibody; HbsAg and HbcAb; Hepatitis C RNA; Cytomegalovirus IgM 
antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain heterophile antibody or 
monospot testing) and Hepatitis E IgM antibody 
4.
PK sample may not be required for participants known to be receiving placebo or non-GSK comparator 
interventions.  Record the date/time of the PK blood sample draw and the date/time of the last dose of study 
intervention prior to PK blood sample draw on the CRF. Instructions for sample handling and shipping are in the 
SRM.
 
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11.6.
Appendix 6: Abbreviations and Trademarks
ABBREVIATIONS
ADA
Anti-drug antibody
ADCC
Antibody-Dependent Cell Cytotoxicity
AE
Adverse event(s)
ALT
Alanine aminotransaminase 
ANOVA
Analysis of variance 
AST
Aspartate Aminotransferase
AUC
Area under the curve 
AUC(0-t)
Area under the plasma concentration-time curve
BUN
Blood Urea Nitrogen
DRC
Data Review Committee
EBV
Epstein-Barr Virus
ECG
Electrocardiogram
eCRF
Electronic case report form
eGFR
Estimated Glomerular Filtration Rate
CD3
Cluster of Differentiation 
CIOMS
Council for International Organizations of Medical Sciences 
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration equation 
Cmax
Maximum observed plasma concentration
CMV
Cytomegalovirus 
CONSORT
Consolidated Standards of Reporting Trials 
CRF
Case Report Form
CRP
C-reactive protein
CPK
Creatine phosphokinase 
 
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CSR
Clinical Study Report
CTCAE
Common Terminology Criteria for Adverse Events 
CVb
Coefficients of variation 
DRC
Data Review Committee
EDTA
Ethylenediaminetetraacetic acid
F
Bioavailability 
FTIH
First Time In Human
GCP
Good Clinical Practice 
G-CSF
Granulocyte-colony stimulating factor 
GFR
Glomerular Filtration Rate 
GLP
Good Laboratory Practice
GSK
GlaxoSmithKline
HBcAb
Hepatitis B core antibody 
HBsAg
Hepatitis B surface antigen 
HBV
Hepatitis B virus
HCV
Hepatitis C virus
HIPAA
Health Insurance Portability and Accountability Act 
HIV
Human Immunodeficiency Virus
IB
Investigator(‘s) Brochure
ICH
International Council of Harmonization
IEC
Independent Ethics Committees 
IFN
Interferon 
Ig
Immunoglobulin 
IL
Interleukin 
IMP
Investigational Medicinal Product
 
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INF
Interferon
INR
International normalized ratio 
IRB
Institutional Review Boards
IV
Intravenous
KLH
Keyhole Limpet Hemocyanin 
LAG3
Lymphocyte Activation Gene-3
LDH
Lactate dehydrogenase 
mAb
Monoclonal antibody 
MCH
Mean Corpuscular Haemoglobin
MCV
Mean Corpuscular Volume
mRNA
Messenger ribonucleic acid
MSDS
Material Safety Data Sheet
NIMP
Non-investigational medicinal product
NSAID
Non-steroidal anti-inflammatory drug
PD
Pharmacodynamic
PGx
Pharmacogenetics
PK
Pharmacokinetic
PPD
Purified protein derivative
QTcF
Corrected QT interval (Fridericia’s formula)
RAP
Reporting Analysis Plan 
RBC
Red Blood Cell
SAE
Serious adverse event(s)
SC
Subcutaneous
SD
Single dose
SGOT
Serum Glutamic-Oxaloacetic Transaminase
 
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SGPT
Serum Glutamic-Pyruvic Transaminase
sLAG3
Soluble LAG3
SMG
Safety and Medical Governance 
SoA
Schedule of Activities 
SRM
Study Reference Manual
SRT
Safety Review Team
SUSAR
Suspected unexpected serious adverse reactions
TB
Tuberculosis
tmax
Time of occurrence of Cmax
TMDD
Target-mediated drug disposition 
TNF
Tumour Necrosis Factor 
TT
Tetanus-toxoid
UC
Ulcerative Colitis
ULN
Upper limit of normal
VZV
Varicella zoster virus
WBC
White Blood Cell
Trademark Information
Trademarks of the GlaxoSmithKline group 
of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
NONE
None
 
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11.7.
Appendix 7 : Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC).
 
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12.
REFERENCES
Camisaschi C, Casati C, Rini F, Perego M, De Filippo A, Triebel F, et al.  LAG-3 
expression defines a subset of CD4(+) CD25(high) Foxp3(+) regulatory T cells that are 
expanded at tumor sites. J. Immunol 2010;184:6545-51.
Ellis J, Marks D, Barrett C, Hopkins T, Richards A, Fuhr R, et al. Selective depletion of 
LAG3+ cells in T-cell-driven inflammation: a randomised, double-blind, placebo-
controlled, FTIH phase I/Ib clinical trial. J Crohn’s Colitis 2019;13(S1):S336
Gagliani N, Magnani CF, Huber S, Gianolini ME, Pala M, Licona-Limon P, et al.  
Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 
cells.  Nat Med 2013;19(6):739-46.
Slevin S, Tan M, Lahiff C, Williamson K, Geremia A, Hughes S, et al. Intestinal 
expression of LAG-3 correlates with inflammatory activity and response to biological 
therapy in ulcerative colitis. J Crohn’s Colitis 2018;;12(1):S125.
Workman CJ1, Dugger KJ, Vignali DA. Cutting edge: molecular analysis of the negative 
regulatory function of lymphocyte activation gene-3. J Immunol 2002;169(10):5392-5.
 
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SAP_001.pdf: 
CONFIDENTIAL
The GlaxoSmithKline group of companies
207823
1
Division
:
Worldwide Development
Information Type
:
Reporting and Analysis Plan (RAP)
Title
:
Reporting and Analysis Plan for GSK2831781 study 207823: 
A randomised, double-blind, placebo-controlled Phase I 
study of the safety and tolerability, pharmacokinetics, and 
pharmacodynamics of a single intravenous dose of 
GSK2831781 in healthy Japanese and Caucasian participants, 
and a single subcutaneous dose of GSK2831781 in healthy 
Caucasian participants.
Compound Number 
:
GSK2831781
Effective Date 
:
01-OCT-2019
Description:

The purpose of this RAP is to describe the planned analyses and output to be 
included in the Clinical Study Report for Protocol 2018N393275_01 of study 
207823.

This RAP is intended to describe the safety, tolerability, pharmacokinetics and 
pharmacodynamics analyses required for the study.

This RAP will be provided to the study team members to convey the content of the 
Interim Analysis (IA) and Statistical Analysis Complete (SAC) deliverables.
RAP Author(s):
Approver
Date
Approval Method
Lead
27-SEP-2019
Email
Statistician (Biostatistics)
Co-author
27-SEP-2019
Email
Director (CPMS)
Copyright 2019 the GlaxoSmithKline group of companies. All rights reserved.
Unauthorised copying or use of this information is prohibited.
 
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RAP Team Review Confirmation:
Reviewer
Date
Confirmation
Method
26-SEP-2019
Email
Programming Manager (Biostatistics)
26-SEP-2019
Email
Physician Director, Discovery Medicine (CPEM)
Other RAP Team Members:
Reviewer
Date
Confirmation
Method
N/A
N/A
Global Clinical Development Manager (GCSD)
N/A
N/A
Principal Clinical Data Manager (GCDO)
N/A
N/A
Director (SMG)
N/A
N/A
Group Leader (BIB-Immunogenicity)
N/A
N/A
Immunologist (Discovery Medicine)
Clinical Statistics and Clinical Programming Line Approvals:
Approver
Date
Approval Method
30-SEP-2019
Pharma TMF 
eSignature
Statistics Director (Biostatistics)
01-OCT-2019
Pharma TMF 
eSignature
Programming Manager (Biostatistics)
 
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TABLE OF CONTENTS
PAGE
1.
INTRODUCTION......................................................................................................6
2.
SUMMARY OF KEY PROTOCOL INFORMATION ..................................................6
2.1.
Changes to the Protocol Defined Statistical Analysis Plan............................6
2.2.
Study Objectives and Endpoints ...................................................................6
2.3.
Study Design ................................................................................................7
2.4.
Statistical Analyses.....................................................................................10
3.
PLANNED ANALYSES ..........................................................................................11
3.1.
Interim Analyses .........................................................................................11
3.2.
Final Analyses ............................................................................................11
4.
ANALYSIS POPULATIONS ...................................................................................12
4.1.
Protocol Deviations.....................................................................................12
5.
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS.....................................................................................................13
5.1.
General.......................................................................................................13
5.2.
Study Treatment & Sub-group Display Descriptors.....................................13
5.3.
Baseline Definitions ....................................................................................14
5.4.
Examination of Strata..................................................................................14
5.5.
Other Considerations for Data Analyses and Data Handling 
Conventions................................................................................................14
6.
STUDY POPULATION ANALYSES .......................................................................15
7.
EFFICACY ANALYSES..........................................................................................16
8.
SAFETY ANALYSES .............................................................................................17
8.1.
Adverse Events Analyses ...........................................................................17
8.2.
Clinical Laboratory Analyses.......................................................................17
8.3.
Other Safety Analyses ................................................................................18
9.
PHARMACOKINETIC ANALYSES.........................................................................19
9.1.
Endpoint / Variables....................................................................................19
9.1.1.
Drug Concentration Measures .....................................................19
9.1.2.
Derived Pharmacokinetic Parameters..........................................19
9.2.
Summary Measure .....................................................................................19
9.3.
Population of Interest..................................................................................19
9.4.
Strategy for Intercurrent (Post-Randomization) Events ...............................19
9.5.
Statistical Analyses / Methods ....................................................................20
9.5.1.
Statistical Methodology Specification (Part A)..............................20
9.5.2.
Statistical Methodology Specification (Part B)..............................21
10. POPULATION PHARMACOKINETIC (POPPK) ANALYSES..................................22
10.1.
Statistical Analyses / Methods ....................................................................22
11. PHARMACODYNAMIC ANALYSES.......................................................................23
 
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11.1.
Secondary Pharmacodynamic Analyses.....................................................23
11.1.1.
Endpoint / Variables.....................................................................23
11.1.2.
Summary Measure ......................................................................23
11.1.3.
Population of Interest...................................................................23
11.1.4.
Strategy for Intercurrent (Post-Randomization) Events ................23
11.1.5.
Statistical Analyses / Methods .....................................................23
11.2.
Exploratory Pharmacodynamic Analyses....................................................24
11.2.1.
Endpoint / Variables.....................................................................24
11.2.2.
Summary Measure ......................................................................24
11.2.3.
Population of Interest...................................................................24
11.2.4.
Strategy for Intercurrent (Post-Randomization) Events ................24
11.2.5.
Statistical Analyses / Methods .....................................................24
12. PHARMACOKINETIC / PHARMACODYNAMIC ANALYSES .................................25
12.1.
Statistical Analyses / Methods ....................................................................25
13. IMMUNOGENICITY ANALYSES............................................................................26
13.1.
Endpoint / Variables....................................................................................26
13.2.
Summary Measure .....................................................................................26
13.3.
Population of Interest..................................................................................26
13.4.
Strategy for Intercurrent (Post-Randomization) Events ...............................26
13.5.
Statistical Analyses / Methods ....................................................................26
14. REFERENCES.......................................................................................................27
15. APPENDICES........................................................................................................28
15.1.
Appendix 1: Protocol Deviation Management .............................................28
15.2.
Appendix 2: Schedule of Activities ..............................................................29
15.2.1.
Part A: Japanese and Caucasian Participants – IV dose .............29
15.2.2.
Part B: Caucasian Participants – SC dose...................................33
15.3.
Appendix 3: Assessment Windows .............................................................36
15.3.1.
Definitions of Assessment Windows for Analyses........................36
15.4.
Appendix 4: Study Phases and Treatment Emergent Adverse 
Events ........................................................................................................37
15.4.1.
Study Phases for Parts A and B...................................................37
15.4.1.1.
Study Phases for Concomitant Medication .................37
15.4.2.
Treatment Emergent Flag for Adverse Events .............................38
15.5.
Appendix 5: Data Display Standards & Handling Conventions....................39
15.5.1.
Reporting Process .......................................................................39
15.5.2.
Reporting Standards....................................................................39
15.5.3.
Reporting Standards for Pharmacokinetic....................................40
15.6.
Appendix 6: Derived and Transformed Data ...............................................41
15.6.1.
General (Parts A and B)...............................................................41
15.6.2.
Study Population..........................................................................41
15.6.3.
Safety ..........................................................................................41
15.7.
Appendix 7: Reporting Standards for Missing Data.....................................43
15.7.1.
Premature Withdrawals................................................................43
15.7.2.
Handling of Missing Data.............................................................43
15.7.2.1.
Handling of Missing and Partial Dates ........................43
15.8.
Appendix 8: Values of Potential Clinical Importance ...................................45
15.8.1.
Laboratory Values........................................................................45
15.8.2.
ECG.............................................................................................46
 
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15.8.3.
Vital Signs....................................................................................46
15.8.4.
Urinalysis.....................................................................................46
15.9.
Appendix 9: Population Pharmacokinetic (PopPK) Analyses ......................47
15.9.1.
Population Pharmacokinetic (PopPK) Dataset 
Specification ................................................................................47
15.9.2.
Population Pharmacokinetic (PopPK) Methodology.....................47
15.10. Appendix 10: Pharmacokinetic / Pharmacodynamic Analyses ....................48
15.10.1. Pharmacokinetic / Pharmacodynamic Dataset 
Specification ................................................................................48
15.10.2. Pharmacokinetic / Pharmacodynamic Methodology.....................48
15.11. Appendix 11: Abbreviations & Trade Marks ................................................49
15.11.1. Abbreviations...............................................................................49
15.11.2. Trademarks .................................................................................51
15.12. Appendix 12: List of Data Displays..............................................................52
15.12.1. Data Display Numbering..............................................................52
15.12.2. Mock Example Shell Referencing ................................................52
15.12.3. Deliverables.................................................................................52
15.12.4. Study Population Tables..............................................................53
15.12.5. Safety Tables...............................................................................56
15.12.6. Safety Figures .............................................................................60
15.12.7. Pharmacokinetic Tables...............................................................61
15.12.8. Pharmacokinetic Figures .............................................................63
15.12.9. Pharmacokinetic Population (PopPK) Tables...............................64
15.12.10.Pharmacokinetic Population (PopPK) Figures .............................65
15.12.11.Pharmacodynamic Tables ...........................................................66
15.12.12.Pharmacodynamic Figures ..........................................................68
15.12.13.Pharmacokinetic / Pharmacodynamic Tables ..............................70
15.12.14.Pharmacokinetic / Pharmacodynamic Figures .............................71
15.12.15.ICH Listings .................................................................................72
15.12.16.Non-ICH Listings..........................................................................78
15.13. Appendix 13: Example Mock Shells for Data Displays ................................80
 
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1.
INTRODUCTION
The purpose of this reporting and analysis plan (RAP) is to describe the analyses to be 
included in the Clinical Study Report for Protocol:
Revision Chronology:
2018N393275_01
06-MAY-2019
Amendment 1
2018N393275_00
13-MAR-2019
Original
2.
SUMMARY OF KEY PROTOCOL INFORMATION
2.1.
Changes to the Protocol Defined Statistical Analysis Plan
Changes from the originally planned statistical analysis specified in the protocol are 
outlined in Table 1.
Table 1
Changes to Protocol Defined Analysis Plan
Protocol
Reporting & Analysis Plan
Statistical Analysis Plan
Statistical Analysis Plan
Rationale for Changes

Section 7.3 of the Protocol: a 
single Treatment Group B is 
defined for the active 150 mg SC 
dose.

Section 2.3 and Section 5.2
of the RAP: the active 150 
mg SC dose in Part B 
corresponds to 3 treatment 
groups, coded B1, B2 and 
B3.

As described in the RCCS 
document, the randomised 
allocation of active dose to 
syringe 1, 2 or 3 is 
performed as part of the 
main randomisation effort.
2.2.
Study Objectives and Endpoints
Objectives
Endpoints
Primary

To evaluate the safety and tolerability after 
single IV dosing of GSK2831781 in healthy 
Japanese and Caucasian participants, and 
SC dosing in healthy Caucasian participants

AEs, vital signs, clinical laboratory values 
(haematology, clinical chemistry, and 
urinalysis), 12-lead ECG

Local tolerability
Secondary

To evaluate the PK of GSK2831781 after a 
single IV dose in healthy Japanese and 
Caucasian participants (Part A) 

GSK2831781 PK parameters following single IV 
dose: area under the plasma concentration-time 
curve [AUC(0-t)], maximum observed plasma 
concentration (Cmax), time of occurrence of 
Cmax (tmax)

To evaluate the PK of GSK2831781 after a 
single SC dose in healthy Caucasian 
participants (Part B) 

GSK2831781 PK parameters following single 
SC dose: AUC(0-t), Cmax, tmax, bioavailability 
(F)
 
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Objectives
Endpoints

To evaluate the effect of a single IV or SC 
dose of GSK2831781 on depletion of LAG3+
T cells in blood

PK/PD relationship between plasma PK of 
GSK2831781 and LAG3+ T cells in blood over 
time

To investigate the immunogenicity of single IV 
and SC doses of GSK2831781

ADAs over time
Exploratory

To evaluate the concentration-time profiles of 
GSK2831781 after a single IV dose in healthy 
Japanese and Caucasian participants (Part A) 

GSK2831781 PK concentrations over time 
following single IV dose

To evaluate the concentration-time profiles of 
GSK2831781 after a single SC dose in 
healthy Caucasian participants (Part B) 

GSK2831781 PK concentrations over time 
following single SC dose

To evaluate the effect of a single IV or SC 
dose of GSK2831781 on soluble LAG3 
(sLAG3) concentrations

Soluble LAG3 (sLAG3) concentrations in blood 
over time

To evaluate the effect of GSK2831781 on 
regulatory T cells in blood

PK/PD relationship between plasma PK of 
GSK2831781 and regulatory T cells in blood 
over time
2.3.
Study Design
This study is a double-blind, placebo-controlled, randomised, parallel group, two-part 
study, with single IV doses administered to healthy Japanese and Caucasian participants, 
or SC doses administered to healthy Caucasian participants.
In Part A, single IV doses of 450 mg GSK2831781 or placebo will be administered to 
Japanese or Caucasian healthy participants, with stratification by ethnicity.
In Part B, single SC doses of 150 mg or 450 mg GSK2831781, or placebo, will be 
administered to healthy Caucasian participants.
At least one interim analysis will be conducted during the study (see Section 3.1 for 
further details).
In line with routine pharmacovigilance, an internal GSK Safety Review Team (SRT) 
(which will include a subset of the 207823 study team) will review blinded safety data, 
including clinical laboratory parameters and adverse events, at appropriate intervals 
during the period of study conduct.
 
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Study Schematic
Part A: Overview of Study Design and Key Features
Part A Design 
Features

Part A will be a single centre, parallel group, single dose part. It is designed to 
investigate whether there are any differences due to ethnicity in safety and 
tolerability, or PK and PK/PD relationship in blood between healthy Japanese and 
Caucasian participants following a single IV 450 mg dose of GSK2831781.

Separate cohorts of participants will be enrolled into Parts A and B.

Part A will consist of a single cohort of 16 healthy participants, stratified by 
ethnicity: 8 participants will be Japanese and 8 will be Caucasian. Up to a 
maximum of 32 participants may be enrolled if a dose reduction is needed.

The participants in each ethnicity stratum will be randomised in a 3:1 ratio to 
receive either 450 mg GSK2831781 IV or placebo. If a dose reduction is needed, 
the new participants in each ethnicity stratum will also be randomised in a 3:1 ratio 
to receive either GSK2831781 IV or placebo.

Part A study duration, including screening and follow-up, is not expected to exceed 
147 days for any participant.
Part A Dosing

Participants will be dosed once on day 1.

In Part A, in order to bridge from the first-time-in human study (GSK Study 
200630), dosing episodes will initially be separated by a minimum of 22 hours, 
until 3 participants in one of the strata have been dosed and monitored for a 
minimum of 46 hours. Subsequently, the remaining participants in Part A will be 
dosed, unless stopping criteria have been met.
Part A Time & 
Events

Refer to Appendix 2.
Part A 
Treatment 
Assignment

Participants will be assigned to either 450mg GSK2831781 IV or placebo in a 3:1 
ratio, stratified by ethnicity. The treatment codes will be:
Treatment code
Treatment Description
A
450 mg GSK2831781 IV
P
Placebo IV
 
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Part A: Overview of Study Design and Key Features

If a dose reduction is needed, the new participants in each ethnicity stratum will 
also be randomised in a 3:1 ratio to receive either GSK2831781 IV or placebo, 
according to the randomisation schedule.
Part A Interim 
Analysis

An interim analysis for Part A will be performed once at least 8 participants in each 
stratum have completed their Day 8 visit, and at least 6 participants in each 
stratum have completed their Day 29 visit, where Safety, PK and PD data will be 
reviewed.

See Section 3.1 for further details.
Part B: Overview of Study Design and Key Features
Part B Design 
Features

Once the final Caucasian participant is recruited into Part A of the study, 
recruitment to Part B may commence.

Part B will be a single centre, parallel group, single dose part. It is designed to 
explore the safety and tolerability, PK and PK/PD relationship in blood following a 
single dose of SC GSK2831781 at 150 mg and 450 mg dose levels, or placebo, in 
healthy Caucasian participants.

As the 450 mg dose level requires 3 injections of GSK2831781 150 mg, 
participants randomised to the 150 mg dose level or placebo will also receive 3 
injections (using 0.9% saline placebo as dummy injections, where needed) to 
maintain the blind. In the 150 mg case, the allocation of active GSK2831781 to 
one of the three syringes will be randomised.

Separate cohorts of participants will be enrolled into Parts A and B.

Part B will consist of a single cohort of 20 healthy Caucasian participants. Up to a 
maximum of 30 participants may be enrolled if a dose reduction is needed.

The participants will be randomised in a 2:2:1 ratio to receive 150 mg 
GSK2831781 SC, 450 mg GSK2831781 SC, or placebo.

The 8 planned 150 mg participants will be randomly allocated active syringe 1, 2 or 
3 in a 3:3:2 ratio.

Part B study duration, including screening and follow-up, is not expected to exceed 
147 days for any participant.
Part B Dosing

Participants will be dosed once on day 1.

In Part B, as this will be the first experience with SC administration in humans,
sentinel dosing will take place: the first two participants dosed will be randomised 
so that 1 participant will receive 150 mg GSK2831781 and 1 will receive placebo.
Part B Time & 
Events

Refer to Appendix 2.
Part B 
Treatment 
Assignment

Participants will be assigned to 150 mg GSK2831781 SC or 450 mg GSK2831781 
SC or placebo in a 2:2:1 ratio. The treatment codes will be:
Treatment code
Treatment Description
B1
150 mg GSK2831781 SC injection 1 active
B2
150 mg GSK2831781 SC injection 2 active
B3
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Part B: Overview of Study Design and Key Features
C
450 mg GSK2831781 SC
Q
Placebo SC
Part B Interim 
Analysis

No interim analyses will be performed during Part B.
2.4.
Statistical Analyses
The primary objective of this study is to determine the safety and tolerability of a single 
intravenous dose of GSK2831781 in healthy Japanese and Caucasian participants, and a 
single subcutaneous dose of GSK2831781 in healthy Caucasian participants. No formal 
hypotheses will be tested.
An estimation approach will be used to describe pharmacokinetics of GSK2831781, 
where point estimates and corresponding 90% confidence intervals will be constructed, 
unless otherwise stated.
 
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3.
PLANNED ANALYSES
3.1.
Interim Analyses
An interim analysis for Part A will be performed once at least 8 participants in each 
stratum have completed their Day 8 visit, and at least 6 participants in each stratum have 
completed their Day 29 visit, where Safety, PK and PD data will be reviewed. The 
interim analysis will be utilised to determine if Japanese participants can be recruited into 
the Phase 2 study (204869) under the existing dosing strategy.
An Interim Data Review Committee (DRC) will be utilised in this study to review the 
interim analysis data. The DRC will be composed of a limited number of people, who 
may be members of the 207823 study team, including the statistician, a senior safety 
representative, lead physician and the pharmacokineticist. A DRC Charter will contain 
the details regarding the DRC, including membership, decision rules for the interim, and 
required data integrity and data quality control.
3.2.
Final Analyses
The final planned primary analyses will be performed after the completion of the 
following sequential steps:
1.
All participants have completed the study as defined in Section 5.4 of the protocol: 
the end of the study is defined as the date of the last visit (including follow-up) of the 
last participant in the study (Parts A and B).
2.
All required database cleaning activities have been completed and final database 
release (DBR) and database freeze (DBF) have been declared by Data Management.
3.
All criteria for unblinding the randomisation codes have been met. 
4.
Randomisation codes have been distributed according to RandAll NG procedures.
 
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4.
ANALYSIS POPULATIONS
Population
Description
Analyses Evaluated
Screened
All participants who were screened for eligibility.

Study Population 
(specific only)
Randomized
All participants who are randomised into the study and receive 
a randomisation number.

Study Population 
(specific only)
Safety
All Randomized participants who receive study intervention. 
Participants will be analysed according to the intervention they 
actually received.

Study Population

Safety

PD

PK/PD
Pharmacokinetic
(PK)
All Safety participants for whom a PK sample was obtained 
and analysed.
Participants will be analysed according to the intervention they 
actually received.

PK
Refer to Appendix 12: List of Data Displays which details the population used for each display.
Note that a participant is considered evaluable if they have been dosed and have safety 
and PK data up to Day 29 (Parts A and B).
4.1.
Protocol Deviations
Important protocol deviations (including deviations related to study inclusion/exclusion 
criteria, conduct of the trial, participant management or participant assessment) will be 
summarised and listed.
Protocol deviations will be tracked by the study team throughout the conduct of the study 
in accordance with the Protocol Deviation Management Plan.
Data will be reviewed prior to unblinding and freezing the database to ensure all 
important deviations are captured and categorised on the protocol deviations 
dataset. 
This dataset will be the basis for the summaries and listings of protocol 
deviations.
A separate listing of all inclusion/exclusion criteria deviations will also be provided. This 
output will be based on data as recorded on the inclusion/exclusion page of the eCRF.
 
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5.
CONSIDERATIONS FOR DATA ANALYSES AND DATA
HANDLING CONVENTIONS
5.1.
General
Parts A and B will be reported separately, with separate outputs generated for each, 
unless stated otherwise.
5.2.
Study Treatment & Sub-group Display Descriptors
In the Tables, Listings and Figures (TLF), treatment should be presented with placebo 
first, then in order of increasing dose within each part.
Part A: Treatment Groups Descriptions
Randall NG
Data Displays for Reporting
Code
Description
Description
Order in TLF
A
450 mg GSK2831781 IV
450 mg GSK2831781 IV
2
P
Placebo IV
Placebo IV
1
Treatment comparisons will be displayed as follows using the descriptors as specified:
1. 450 mg GSK2831781 IV vs Placebo IV
A subset of Part A data displays will be presented with a combination of treatment groups 
and geographic ancestry stratification, as described in Section 5.4.
Part B: Treatment Groups Descriptions
Randall NG
Data Displays for Reporting
Code
Description
Description
Order in TLF
B1
150 mg GSK2831781 SC injection 1 
active
150 mg GSK2831781 SC injection 
1
2 (*)
B2
150 mg GSK2831781 SC injection 2 
active
150 mg GSK2831781 SC injection 
2
3 (*)
B3
150 mg GSK2831781 SC injection 3 
active
150 mg GSK2831781 SC injection 
3
4 (*)
C
450 mg GSK2831781 SC
450 mg GSK2831781 SC
5
Q
Placebo SC
Placebo SC
1
(*) Note that treatment groups B1, B2 and B3 will be combined into a single “150 mg 
GSK2831781 SC” group in most tables, figures and listings. Only a small subset of 
outputs, including listings of injection site reactions (Section 15.12 for details), will 
report B1, B2 and B3 as separate treatment groups.
Treatment comparisons will be displayed as follows using the descriptors as specified, 
where “150 mg GSK2831781 SC” includes treatment groups B1, B2 and B3:
1. 150 mg GSK2831781 SC vs Placebo SC
2. 450 mg GSK2831781 SC vs Placebo SC
 
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5.3.
Baseline Definitions

The baseline value (in both Parts A and B) will be the latest pre-dose assessment 
with a non-missing value, including those from unscheduled visits.

If time is not collected, Day 1 assessments are assumed to be taken prior to dosing
and used as baseline.

Replicate assessments at a timepoint will be averaged, and the mean value will be 
used.

Unless otherwise stated, if baseline data is missing no derivation will be 
performed and baseline will be set to missing.
5.4.
Examination of Strata
The list of strata may be used in descriptive summaries and statistical analyses. 
Additional covariates and other strata of clinical interest may also be considered.
Category
Details
Strata

Part A: stratification by geographic ancestry (Caucasian vs Japanese).

Used for ethnosensitivity comparisons.

A subset of Part A data displays will be presented with the following groups, in this 
order:
o
Placebo (Caucasian)
o
Placebo (Japanese)
o
450 mg GSK2831781 (Caucasian)
o
450 mg GSK2831781 (Japanese)
5.5.
Other Considerations for Data Analyses and Data Handling 
Conventions
Other considerations for data analyses and data handling conventions are outlined in the 
appendices:
Section
Component
15.3
Appendix 3: Assessment Windows
15.4
Appendix 4: Study Phases and Treatment Emergent Adverse Events
15.5
Appendix 5: Data Display Standards & Handling Conventions
15.6
Appendix 6: Derived and Transformed Data
15.7
Appendix 7: Reporting Standards for Missing Data
15.8
Appendix 8: Values of Potential Clinical Importance
 
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6.
STUDY POPULATION ANALYSES
The study population analyses will be based on the Safety population, unless otherwise 
specified.
Study population analyses including analyses of participant’s disposition, protocol 
deviations, demographic and baseline characteristics, prior and concomitant medications, 
and exposure and treatment compliance will be based on GSK Core Data Standards.  
Details of the planned displays are presented in Appendix 12: List of Data Displays.
 
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7.
EFFICACY ANALYSES
There are no efficacy analyses to be included in this study.
 
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8.
SAFETY ANALYSES
The safety analyses will be based on the Safety population, unless otherwise specified.
8.1.
Adverse Events Analyses
The definition of an AE is detailed in Appendix 3 of the protocol.
Analyses of AEs will include those events that are Treatment Emergent as defined in 
Section 15.4.
Adverse events analyses including the analysis of adverse events (AEs), Serious (SAEs)
and other significant AEs will be based on GSK Core Data Standards. The details of the 
planned displays are provided in Appendix 12: List of Data Displays.
8.2.
Clinical Laboratory Analyses
Laboratory evaluations including the analyses of Chemistry laboratory tests, 
Haematology laboratory tests, Urinalysis, and Liver function tests will be based on GSK 
Core Data Standards.
Clinical laboratory summaries will include all assessments post-baseline. All clinical 
laboratory assessments, including pre-baseline (i.e. screening), will be listed.
The details of the planned displays are in Appendix 12: List of Data Displays.
The laboratory assessments for each category are displayed below (Table 1 in Section 
11.2 of the protocol):
Laboratory 
Assessments
Parameters
Haematology
Platelet Count
RBC Indices:
Mean Corpuscular Volume 
(MCV)
Mean Corpuscular 
Haemoglobin (MCH)
%Reticulocytes
White Blood Cell (WBC) 
count with Differential:
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
Red Blood Cell (RBC) 
Count
Haemoglobin
Haematocrit
Clinical 
Chemistry1
Blood Urea 
Nitrogen (BUN)
Potassium
Aspartate 
Aminotransferase
(AST)/Serum 
Glutamic-
Oxaloacetic 
Transaminase
(SGOT)
Total and direct 
bilirubin
Creatinine 
Estimated 
Glomerular 
Filtration Rate 
(eGFR)
Sodium
Alanine 
Aminotransferase
(ALT/Serum 
Glutamic-Pyruvic 
Transaminase
Total Protein
 
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Laboratory 
Assessments
Parameters
(SGPT)
Glucose [non-
fasting]
Calcium
Alkaline 
phosphatase
Routine 
Urinalysis

Specific gravity

pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte 
esterase by dipstick

Microscopic examination (if blood or protein is abnormal)
Other Screening 
Tests (not to be 
reported)

Breath alcohol screen

Urine drug screen (to include at minimum: amphetamines, barbiturates, cocaine, 
opiates, cannabinoids and benzodiazepines)

Serology: HIV antibody, HbsAg, HbcAb, HCV antibody, EBV antibody3, CMV 
antibody3, VZV antibody3

Quantiferon test for TB
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 8.2.3 of the protocol. All events of ALT 3 × upper limit of normal (ULN) and 
bilirubin 2 × ULN (>35% direct bilirubin) or ALT 3 × ULN and international normalized ratio (INR) >1.5, if INR 
measured, which may indicate severe liver injury (possible Hy’s Law), must be reported as an SAE (excluding 
studies of hepatic impairment or cirrhosis).
2.
Local urine testing will be standard for the protocol unless serum testing is required by local regulation or IRB/IEC.
3.
To be repeated in event of possible viral reactivation.
Laboratory results that could unblind the study will not be reported to investigative sites 
or other blinded personnel until the study has been unblinded.
8.3.
Other Safety Analyses
The analyses of non-laboratory safety test results including ECGs and vital signs will be 
based on GSK Core Data Standards, unless otherwise specified.
The non-laboratory safety test results include:

ECGs

Vital signs

Local tolerability
The details of the planned displays are presented in Appendix 12: List of Data Displays.
 
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9.
PHARMACOKINETIC ANALYSES
9.1.
Endpoint / Variables
9.1.1.
Drug Concentration Measures
Refer to Appendix 5: Data Display Standards & Handling Conventions (Section 15.5.3
Reporting Standards for Pharmacokinetic).
9.1.2.
Derived Pharmacokinetic Parameters
Pharmacokinetic parameters will be calculated by standard non-compartmental analysis 
according to current working practices and using the currently supported version of 
WinNonlin. All calculations of non-compartmental parameters will be based on actual 
sampling times.
Pharmacokinetic parameters listed will be determined from the plasma concentration-
time data, as data permits. Additional parameters may be included as required.
Parameter
Parameter Description
AUC(0-t)

Area under the concentration-time curve from time zero to the time of last quantifiable 
concentration (C(t)).

Calculated using the linear trapezoidal rule for each incremental trapezoid and the log 
trapezoidal rule for each decremental trapezoid.
Cmax

Maximum observed concentration.

Determined directly from the concentration-time data.
tmax

Time to reach Cmax.

Determined directly from the concentration-time data.
9.2.
Summary Measure
Descriptive statistics (n, arithmetic mean, standard deviation [SD], 95% CI, minimum, 
median and maximum) will be calculated by treatment (and geographic ancestry in Part 
A) for all PK concentrations over time and for the derived PK parameters. In addition, for 
log-transformed PK parameter variables, geometric mean, 95% CI and %CVb will be 
provided.
9.3.
Population of Interest 
The primary pharmacokinetic analyses will be based on the Pharmacokinetic population, 
unless otherwise specified.
9.4.
Strategy for Intercurrent (Post-Randomization) Events
A ‘While on-study’ strategy will be implemented for intercurrent events.

Withdrawn participants may be replaced in the study. Replacement participants will 
be dosed with the planned treatment of the withdrawn participant.
 
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
All available data from participants who were withdrawn from the study will be 
analysed and listed, and all available planned data will be included in summary tables 
and figures, unless otherwise specified.

Missing and anomalous concentration data not due to intercurrent events will be 
handled according to SOP_314000.
9.5.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 12: List of Data Displays and 
will be based on GSK Data Standards and statistical principles.
Unless otherwise specified, endpoints / variables defined in Section 9.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed.
9.5.1.
Statistical Methodology Specification (Part A)
The following pharmacokinetic statistical analyses will only be performed if sufficient 
data is available (i.e. if participants have well defined plasma concentration-time 
profiles).
Ethnosensitivity (Part A)
Endpoint / Variables

AUC(0-t)

Cmax
Model Specification

Analysis of variance (ANOVA) will be performed on log-transformed data to determine the point 
estimate for the comparison of Japanese to Caucasian participants.

This analysis will be repeated for each of the PK parameters at the 450 mg dose level.

The 90% confidence interval for the mean difference of the log-transformed data will be calculated. The 
equivalent 90% confidence interval for the geometric means will be provided.
Model Checking & Diagnostics

Normality assumptions underlying the model used for analysis will be examined by obtaining a normal 
probability plot of the residuals and a plot of the residuals versus the fitted values (i.e. checking the 
normality assumption and constant variance assumption of the model, respectively) to gain confidence 
that the model assumptions are reasonable.

If there are any departures from the distributional assumptions, alternative models will be explored 
using appropriate transformed data.
Model Results Presentation

Table of:
o
Geometric means and ratio of geometric means with 90% CI.
 
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9.5.2.
Statistical Methodology Specification (Part B)
The following pharmacokinetic statistical analyses will only be performed if sufficient 
data is available (i.e. if participants have well defined plasma concentration-time
profiles).
Note that the intravenous PK data for bioavailability analyses will be taken from the 
Caucasian stratum in Part A.
Bioavailability (Part B)
Endpoint / Variables

AUC(0-t)
Model Specification

Analysis of variance (ANOVA) will be performed on log-transformed data to determine the point 
estimate for the comparison of SC and IV administration.

The resulting estimated difference is the log point estimate of the absolute bioavailability (Fabs).

This analysis will be conducted at the 450 mg dose level only.

The 90% confidence interval for the mean difference of the log-transformed data will be calculated. The 
equivalent 90% confidence interval for the geometric means will be provided.
Model Checking & Diagnostics

Normality assumptions underlying the model used for analysis will be examined by obtaining a normal 
probability plot of the residuals and a plot of the residuals versus the fitted values (i.e. checking the 
normality assumption and constant variance assumption of the model, respectively) to gain confidence 
that the model assumptions are reasonable.

If there are any departures from the distributional assumptions, alternative models will be explored 
using appropriate transformed data.
Model Results Presentation

Table of:
o
Geometric means and ratio of geometric means with 90% CI.
 
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10.
POPULATION PHARMACOKINETIC (POPPK) 
ANALYSES
The primary goal of this analysis is to characterize the population pharmacokinetics of 
GSK2831781 administered IV in Japanese and Caucasian healthy volunteers and SC in 
Caucasian healthy volunteers. The individual participant PK parameters will be estimated 
and documented for the purposes of any subsequent exposure-response (PK/PD) 
analyses. Any inter-ethnic differences in the PK will also be investigated.
10.1.
Statistical Analyses / Methods
A summary of the planned population pharmacokinetic analyses is outlined below:

A previous PopPK model developed based on the drug plasma and total serum 
sLAG3 concentrations collected during the first-time in human study 200630 (GSK 
Document Number 2017N352860_00) will be fitted to the drug plasma 
concentration-time data using the nonlinear mixed effects modelling software 
NONMEM.  

Individual post-hoc estimated PK parameters will be summarised descriptively.

To support this analysis a PopPK dataset will be generated. The details for the dataset 
specifications are provided in Appendix 9: Population Pharmacokinetic (PopPK) 
Analyses.
Detailed PopPK methodology is presented in Appendix 9: Population Pharmacokinetic 
(PopPK) Analyses.
 
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11.
PHARMACODYNAMIC ANALYSES
11.1.
Secondary Pharmacodynamic Analyses
11.1.1.
Endpoint / Variables
Parameter
Parameter Description
LAG3+

LAG3+ T cell numbers and frequencies in blood. The following cell populations will be 
reported:
o
CD4+CD45RA-J11L1+
o
CD4+CD45RA-REA351+
o
CD4-CD45RA-J11L1+
o
CD4-CD45RA-REA351+
11.1.2.
Summary Measure
Absolute value and percent change from baseline (%CFB) are of interest.
Part A: Data will be available at baseline and at day 1 (6h, 24h), 4, 8, 15, 29, 43, 57, 85 
and 112.
Part B: Data will be available at baseline and at day 2, 4, 8, 15, 29, 43, 57, 85 and 112.
11.1.3.
Population of Interest 
The secondary pharmacodynamics analyses will be based on the Safety population, 
unless otherwise specified.
11.1.4.
Strategy for Intercurrent (Post-Randomization) Events
A ‘While on-study’ strategy will be implemented for intercurrent events.

Withdrawn participants may be replaced in the study. Replacement participants will 
be dosed with the planned treatment of the withdrawn participant.

All available data from participants who were withdrawn from the study will be listed 
and all available planned data will be included in summary tables and figures, unless 
otherwise specified.
11.1.5.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 12: List of Data Displays and 
will be based on GSK Data Standards and statistical principles.
Unless otherwise specified, endpoints / variables defined in Section 11.1.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed.
 
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11.2.
Exploratory Pharmacodynamic Analyses
11.2.1.
Endpoint / Variables
Parameter
Parameter Description
sLAG3

Concentration of soluble LAG3 in blood.
Regulatory T cells

CD3+CD4+CD45RA-CD25+CD127loFoxP3+ Regulatory T cell numbers and 
frequencies in blood
11.2.2.
Summary Measure
Absolute value and percent change from baseline (%CFB) are of interest.
sLAG3:
Part A: Data will be available at baseline and at day 1 (1h, 2h, 6h, 12h, 24h), 3, 4, 8, 15, 
22, 29, 43, 57, 71, 85 and 112.
Part B: Data will be available at baseline and at day 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 43, 
57, 71, 85 and 112.
Regulatory T cells:
Part A: Data will be available at baseline and at day 4 and 112.
11.2.3.
Population of Interest 
The exploratory pharmacodynamics analyses will be based on the Safety population, 
unless otherwise specified.
11.2.4.
Strategy for Intercurrent (Post-Randomization) Events
A ‘While on-study’ strategy will be implemented for intercurrent events.

Withdrawn participants may be replaced in the study. Replacement participants will 
be dosed with the planned treatment of the withdrawn participant.

All available data from participants who were withdrawn from the study will be listed 
and all available planned data will be included in summary tables and figures, unless 
otherwise specified.
11.2.5.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 12: List of Data Displays and 
will be based on GSK Data Standards and statistical principles.
Unless otherwise specified, endpoints / variables defined in Section 11.2.1 will be
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed.
 
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12.
PHARMACOKINETIC / PHARMACODYNAMIC
ANALYSES
The primary goal of this analysis is to characterize the
pharmacokinetic
/
pharmacodynamic (PK/PD) relationship of GSK2831781 administered IV in Japanese 
and Caucasian healthy volunteers and SC in Caucasian healthy volunteers. Any inter-
ethnic differences in the PK/PD relationship will also be investigated.
12.1.
Statistical Analyses / Methods
A summary of the planned population PK/PD analyses are outlined below:

A previous PopPK/PD model developed based on the individual post hoc predicted 
PK parameters and all available cell depletion data from the first-time in human study 
200630 (GSK Document Number 2017N352860_00) will be fitted to the drug plasma 
concentration (or PK parameters) and PD data using the nonlinear mixed effects 
modelling software NONMEM.

To support this analysis a PK/PD dataset will be generated. The details for the dataset 
specifications are provided in Appendix 10: Pharmacokinetic / Pharmacodynamic 
Analyses.

Detailed PK/PD methodology is presented in Appendix 10: Pharmacokinetic / 
Pharmacodynamic Analyses.
 
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13.
IMMUNOGENICITY ANALYSES
13.1.
Endpoint / Variables
Parameter
Parameter Description
ADAs

Anti-drug antibodies over time.
13.2.
Summary Measure
Incidence and duration of anti-drug antibodies (ADA).
The GSK2831781 immunogenicity response will be summarized for the binding antibody 
assay by treatment group and timepoint. The table will include the number and proportion 
of participants in each result category for each visit. Binding confirmatory assay results 
will be categorized as Negative, Positive, or Unknown.  Positive samples in the binding 
assay are further categorized as Transient Positive (i.e. single positive response that does 
not occur at the final assessment) or Persistent Positive (i.e. positive response that occurs 
at least 2 consecutive assessments or a single result at the final assessment). Titre for 
samples confirming positive in the binding assay will be reported in listings.
Parts A and B: Data will be available at baseline and at day 29, 57, 85 and 112.
13.3.
Population of Interest 
The immunogenicity analyses will be based on the Safety population, unless otherwise 
specified.
13.4.
Strategy for Intercurrent (Post-Randomization) Events
A ‘While on-study’ strategy will be implemented for intercurrent events.

Withdrawn participants may be replaced in the study. Replacement participants will 
be dosed with the planned treatment of the withdrawn participant.

All available data from participants who were withdrawn from the study will be listed 
and all available planned data will be included in summary tables and figures, unless 
otherwise specified.
13.5.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 12: List of Data Displays and 
will be based on GSK Data Standards and statistical principles.
Unless otherwise specified, endpoints / variables defined in Section 13.1 will be
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed.
 
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14.
REFERENCES
GSK Document Number 2018N393275_01. Study ID 207823: A randomised, double-
blind, placebo-controlled Phase I study of the safety and tolerability, pharmacokinetics, 
and pharmacodynamics of a single intravenous dose of GSK2831781 in healthy Japanese 
and Caucasian participants, and a single subcutaneous dose of GSK2831781 in healthy 
Caucasian participants. 06-MAY-2019.
GSK Document Number 2017N352860_00. Study ID 200630: A randomised, double 
blind (sponsor unblinded), placebo controlled, single ascending dose study to investigate 
the safety, tolerability, pharmacokinetics, and pharmacodynamics of a IV dose of 
GSK2831781 in healthy volunteers and patients with plaque psoriasis.
 
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15.
APPENDICES
15.1.
Appendix 1: Protocol Deviation Management
Protocol deviations will be tracked by the study team throughout the conduct of the study 
in accordance with the Protocol Deviation Management Plan. Data will be reviewed prior 
to freezing the database to ensure all important deviations are captured and categorised 
on the protocol deviations dataset. This dataset will be the basis for the summaries and 
listings of protocol deviations.
 
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15.2.
Appendix 2: Schedule of Activities
15.2.1.
Part A: Japanese and Caucasian Participants – IV dose
Procedure
Screeni
ng 
(up to 
28 days 
before 
Dosing)
Day -1
Day 1 (Hours)
Days 3 – 85
Follow 
Up/Early 
Withdra
wal (112 
Days 
post 
dose)3
Pre-
Dose
0 
h1
1 h
2 h 
(end of 
infusio
n)
6 h
12 h
24 h
3
2
4
2
8
15
22
29
43
57
71
85
Window 
-60 
min
±10 
min
+30 
min4
±30 
min
±30 
min
±60 
min
±1
d
±2
d
±2
d
±2
d
±3
d
±3
d
±3
d
±3
d
±7d
Informed 
Consent
X
Inclusion and 
Exclusion 
Criteria
X
X
Demography
X
Full physical 
examination 
including height 
and weight
X
X
Medical history 
(includes 
substance usage)
X
Past and Current 
Medical 
Conditions
X
 
 
 
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Procedure
Screeni
ng 
(up to 
28 days 
before 
Dosing)
Day -1
Day 1 (Hours)
Days 3 – 85
Follow 
Up/Early 
Withdra
wal (112 
Days 
post 
dose)3
Pre-
Dose
0 
h1
1 h
2 h 
(end of 
infusio
n)
6 h
12 h
24 h
3
2
4
2
8
15
22
29
43
57
71
85
Window 
-60 
min
±10 
min
+30 
min4
±30 
min
±30 
min
±60 
min
±1
d
±2
d
±2
d
±2
d
±3
d
±3
d
±3
d
±3
d
±7d
Serology (HIV, 
HBV, HCV, 
CMV, EBV, 
VZV)
X
TB screening 
(QuantiFERON 
PPD)
X
Breath Alcohol 
Screen 
X
X
Urine Drug 
Screen
X
X
Haematology & 
Clinical 
Chemistry 
X
X
X
X
X
X
X
X
X
X
X
Urinalysis 
X
X
X
X
X
X
X
X
X
X
X
12-Lead ECG5
X
X
X
X
X
X
Vital Signs6
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
 
 
 
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Procedure
Screeni
ng 
(up to 
28 days 
before 
Dosing)
Day -1
Day 1 (Hours)
Days 3 – 85
Follow 
Up/Early 
Withdra
wal (112 
Days 
post 
dose)3
Pre-
Dose
0 
h1
1 h
2 h 
(end of 
infusio
n)
6 h
12 h
24 h
3
2
4
2
8
15
22
29
43
57
71
85
Window 
-60 
min
±10 
min
+30 
min4
±30 
min
±30 
min
±60 
min
±1
d
±2
d
±2
d
±2
d
±3
d
±3
d
±3
d
±3
d
±7d
Randomization
X
IMP 
Administration 
<===========>
Resident in unit
<=====================================>
Local 
Tolerability
X
X
X
X
X
sLAG3 
concentrations
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PK
X
X
X7
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Immunogenicity
X
X
X
X
X
LAG3+ Cell 
Depletion and 
Immunophenoty
ping
X
X
X
X
X
X
X
X
X
X
X
Genetic Sample8
X
AE/ SAE 
Review
SAEs collected from signing of informed consent form; AEs collected continuously from time of first dose. 
Concomitant 
Medication 
Monitored from screening until the end of the final treatment period. 
 
 
 
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Procedure
Screeni
ng 
(up to 
28 days 
before 
Dosing)
Day -1
Day 1 (Hours)
Days 3 – 85
Follow 
Up/Early 
Withdra
wal (112 
Days 
post 
dose)3
Pre-
Dose
0 
h1
1 h
2 h 
(end of 
infusio
n)
6 h
12 h
24 h
3
2
4
2
8
15
22
29
43
57
71
85
Window 
-60 
min
±10 
min
+30 
min4
±30 
min
±30 
min
±60 
min
±1
d
±2
d
±2
d
±2
d
±3
d
±3
d
±3
d
±3
d
±7d
Review
Footnotes:
1.
All post dose time points are in reference to the start of infusion.
2.
Assessments at these visits should be on the scheduled day however can be at any time in the day.
3.
Early withdrawal assessments will be the same as Follow-Up.
4.
End of infusion assessment time window is +30 minutes for all assessments except for the PK sample which should be collected just before the end of the 
infusion.
5.
ECG in triplicate at screening and single at all other time points.
6.
Vital Signs to be taken every 30 minutes from start of infusion until completion of 2hr post dose monitoring period.
7.
PK sample at end of infusion should be collected just before the end of the infusion.
8.
The genetic sample is optional and can be taken any time after consent has been signed and the participant is randomized.
 
 
 
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15.2.2.
Part B: Caucasian Participants – SC dose
Procedure
Screening 
(up to 28 days 
before Dosing)
Day - 1
Day 1
Days 2-85
Follow Up/Early 
Withdrawal (112 
Days post dose)3
Pre-Dose
0h
Post Dose1
22
32
42
62
8
11
15
18
22
29
43
57
71
85
Window 
-60
min
±1d
±2d
±2d
±2d
±2d
±2d
±3d
±3d
±3d
±3d
±7d
Informed consent
X
Inclusion and 
exclusion criteria
X
X
Demography
X
Full physical 
examination 
including height 
and weight
X
X
Medical history 
(includes substance 
usage)
X
Past and current 
medical conditions  
X
Serology (HIV, 
HBV, HCV, CMV, 
EBV, VZV)
X
TB screening
(QuantiFERON 
PPD)
X
 
 
 
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Procedure
Screening 
(up to 28 days 
before Dosing)
Day - 1
Day 1
Days 2-85
Follow Up/Early 
Withdrawal (112 
Days post dose)3
Pre-Dose
0h
Post Dose1
22
32
42
62
8
11
15
18
22
29
43
57
71
85
Window 
-60
min
±1d
±2d
±2d
±2d
±2d
±2d
±3d
±3d
±3d
±3d
±7d
Breath Alcohol 
Screen
X
X
Urine Drug Screen 
X
X
Haematology & 
Clinical Chemistry 
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
12-Lead ECG4
X
X
X5
X
X
X
Vital Signs6
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Randomization
X
IMP Administration 
X7
Resident in Unit 
<================>
Local tolerability at 
injection sites
X
X8
X
X
X
sLAG3 
concentrations
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PK
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Immunogenicity
X
X
X
X
X
 
 
 
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Procedure
Screening 
(up to 28 days 
before Dosing)
Day - 1
Day 1
Days 2-85
Follow Up/Early 
Withdrawal (112 
Days post dose)3
Pre-Dose
0h
Post Dose1
22
32
42
62
8
11
15
18
22
29
43
57
71
85
Window 
-60
min
±1d
±2d
±2d
±2d
±2d
±2d
±3d
±3d
±3d
±3d
±7d
LAG3+ Cell 
Depletion
X
X
X
X
X
X
X
X
X
X
Genetic Sample9
X
AE/SAE Review 
SAEs collected from signing of informed consent form; AEs collected continuously from time of first dose. 
Concomitant 
medication review
Monitored from screening until the end of the final treatment period.
Footnotes: 
1.
All post dose time points are in reference to the first injection of IMP.
2.
Assessments at these visits should be on the scheduled day however can be at any time in the day. 
3.
Early withdrawal assessments will be the same as Follow-Up.
4.
ECG in triplicate at screening and single at all other time points.  
5.
ECG to be performed 6 hours post dose.
6.
Vital Signs to be taken every 30 minutes from first IMP injection until completion of 2hr post dose monitoring period.
7.
IMP administration consists of 3 syringes, all 3 syringes are to be administered as closely together as possible (preferably within 10 minutes).
8.
Post dose Local tolerability at injection sites to be reviewed at 2, 6, 12, and 24 hours post dose. 
9.
The genetic sample is optional and can be taken any time after consent has been signed and the participant is randomized. 
 
 
 
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15.3.
Appendix 3: Assessment Windows
15.3.1.
Definitions of Assessment Windows for Analyses
No assessment windows will be defined for analyses. Summaries and analyses will be 
based on nominal visits.
 
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15.4.
Appendix 4: Study Phases and Treatment Emergent 
Adverse Events
15.4.1.
Study Phases for Parts A and B
Assessments and events will be classified according to the time of occurrence relative to 
the dose.
Study Phase
Definition
Pre-Treatment 
Date/Time ≤ Study Treatment Start Date/Time
Treatment Emergent
Date/Time > Study Treatment Start Date/Time
15.4.1.1.
Study Phases for Concomitant Medication
Study Phase
Definition
Prior
If medication end date is not missing and is prior to study treatment.
Concomitant
Any medication that is not a prior
NOTES: 

Please refer to Appendix 7: Reporting Standards for Missing Data for handling of missing and partial dates for 
concomitant medication. Use the rules in this table if concomitant medication date is completely missing.
 
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15.4.2.
Treatment Emergent Flag for Adverse Events
Adverse Events will be flagged as Treatment Emergent as described in the table in 
Section 15.4.1, where the AE Start Date/Time will be considered.
 
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15.5.
Appendix 5: Data Display Standards & Handling 
Conventions
15.5.1.
Reporting Process
Software

The currently supported versions of SAS software will be used.
Reporting Area
HARP Server
: us1salx00259
HARP Compound
Each of the following directories will be used for both Parts A and B.
: \arprod\gsk2831781\mid207823\internal_01
: \arprod\gsk2831781\mid207823\interim_01
: \arprod\gsk2831781\mid207823\final_01
Analysis Datasets 

Analysis datasets will be created according to Integrated Data Standards Library (IDSL) GSK A&R 
dataset standards.
Generation of RTF Files

RTF files will be generated for SAC.
15.5.2.
Reporting Standards
General

The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated (IDSL Standards Location: https://spope.gsk.com/sites/IDSLLibrary/SitePages/Home.aspx):

4.03 to 4.23: General Principles

5.01 to 5.08: Principles Related to Data Listings

6.01 to 6.11: Principles Related to Summary Tables

7.01 to 7.13: Principles Related to Graphics

Do not include participant level listings in the main body of the GSK Clinical Study Report. All 
participant level listings should be located in the modular appendices as ICH or non-ICH listings.
Formats

GSK IDSL Statistical Principles (5.03 & 6.06.3) for decimal places (DP’s) will be adopted for reporting of 
data based on the raw data collected, unless otherwise stated.

Numeric data will be reported at the precision collected on the eCRF.

The reported precision from non eCRF sources will follow the IDSL statistical principles but may be
adjusted to a clinically interpretable number of DP’s.
Planned and Actual Time

Reporting for tables, figures and formal statistical analyses:

Planned time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated.

The impact of any major deviation from the planned assessment times and/or scheduled visit days 
on the analyses and interpretation of the results will be assessed as appropriate.

Reporting for Data Listings:

Planned and actual time relative to study drug dosing will be shown in listings (Refer to IDSL 
Statistical Principle 5.05.1).

Unscheduled or unplanned readings will be presented within the participant’s listings.
Unscheduled Visits
 
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
Unscheduled visits will not be included in summary tables and/or figures.

All unscheduled visits will be included in listings.
Descriptive Summary Statistics
Continuous Data
Refer to IDSL Statistical Principle 6.06.1
Categorical Data
N, n, frequency, %
Graphical Displays

Refer to IDSL Statistical Principals 7.01 to 7.13.
15.5.3.
Reporting Standards for Pharmacokinetic
Pharmacokinetic Concentration Data
PC Windows Non-
Linear (WNL) File
PC WNL file (CSV format) for the non-compartmental analysis by Clinical 
Pharmacology Modelling and Simulation function will be created according to 
PKOne standards.
Note: Concentration values will be imputed as per GUI_51487.
Descriptive Summary 
Statistics, Graphical 
Displays and Listings
Refer to IDSL PK Display Standards.
Refer to IDSL Statistical Principle 6.06.1.
Note: Concentration values will be imputed as per GUI_51487 for descriptive 
summary statistics/analysis and summarized graphical displays only. 
NONMEM/Pop PK 
File
Pop-PK file (CSV format) for the POP-PK analysis by Clinical Pharmacology 
Modelling and Simulation function will be created. Dataset specification will be 
detailed in a separate document.
NONMEM/PK/PD 
File
PK/PD file (CSV format) for the PK/PD analysis by Clinical Pharmacology Modelling 
and Simulation function will be created. Dataset specification will be detailed in a 
separate document.
Pharmacokinetic Parameter Derivation
PK Parameter to be 
Derived by 
Programmer
The following PK parameters will be derived by the Programmer: None
Pharmacokinetic Parameter Data
Is NQ impacted PK 
Parameters Rule 
Being Followed
Yes, refer to SOP_314000.
Descriptive Summary 
Statistics, Graphical 
Displays and Listings
Refer to IDSL PK Display Standards.
Refer to PKOne.
 
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15.6.
Appendix 6: Derived and Transformed Data
15.6.1.
General (Parts A and B)
Multiple Measurements at One Analysis Time Point

Mean of the measurements will be calculated and used in any derivation of summary statistics but if 
listed, all data will be presented.

Participants having both High and Low values for Normal Ranges at any post-baseline visit for safety 
parameters will be counted in both the High and Low categories of “Any visit post-baseline” row of 
related summary tables. This will also be applicable to relevant Potential Clinical Importance summary 
tables.
Study Day

Calculated as the number of days from Dose Date:

Ref Date = Missing      → Study Day = Missing 

Ref Date < Dose Date → Study Day = Ref Date – Dose Date

Ref Data ≥ Dose Date → Study Day = Ref Date – Dose Date + 1
15.6.2.
Study Population
Age

Only year of birth will be collected on the CRF and birth date will be presented in listings as ‘YYYY’.

GSK standard IDSL algorithms will be used for calculating age where birth date will be imputed as ‘30th
June’ and then calculated based on the dose date.
15.6.3.
Safety
ECG Parameters
RR Interval

If RR interval (msec) is not provided directly, then RR can be derived as:
o
If QTcF is machine read, then:
o
If ECGs are manually read, the RR value preceding the measurement QT interval should 
be a collected value, then do not derive.
Corrected QT Intervals

When not entered directly in the eCRF, corrected QT intervals by Fridericia’s (QTcF) formulas will be 
calculated, in msec, depending on the availability of other measurements.

IF RR interval (msec) is provided then missing QTcF will be derived as:
Laboratory parameters

If a laboratory value which is expected to have a numeric value for summary purposes, has a non-
detectable level reported in the database, where the numeric value is missing, but typically a character 
 
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ECG Parameters
value starting with ‘<x’ or ‘>x’ (or indicated as less than x or greater than x in the comment field) is 
present, the number of significant digits in the observed values will be used to determine how much to 
add or subtract in order to impute the corresponding numeric value. 
o
Example 1: 2 Significant Digits →‘< x’ becomes x – 0.01
o
Example 2: 1 Significant Digit   →‘> x’ becomes x + 0.1
o
Example 3: 0 Significant Digits →‘< x’ becomes x – 1
 
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15.7.
Appendix 7: Reporting Standards for Missing Data
15.7.1.
Premature Withdrawals
Element
Reporting Detail
General

In both Parts A and B, participant study completion (i.e. as specified in the protocol) is
defined as having completed all phases of the study including the last scheduled 
assessment shown in the SoA (Section 15.2).

Withdrawn participants may be replaced in the study.

All available data from participants who were withdrawn from the study will be listed 
and all available data will be included in summary tables and figures, unless otherwise 
specified.

Withdrawal visits will be slotted as per Section 15.3 or will be summarised as
withdrawal visits.
15.7.2.
Handling of Missing Data
Element
Reporting Detail
General

Missing data occurs when any requested data is not provided, leading to blank fields on 
the collection instrument:
o
These data will be indicated using a “blank” in participant listing displays, unless all 
data for a specific visit are missing (in which case the data is excluded from the 
table).
o
Answers such as “Not applicable” and “Not evaluable” are not considered to be 
missing data and should be displayed as such.
15.7.2.1.
Handling of Missing and Partial Dates
Element
Reporting Detail
General

Partial dates will be displayed as captured in participant listing displays.
Adverse 
Events

In case of partial dates (i.e. day missing, only month and year present) recorded for AE 
start and end, the following conventions will be applied for calculating the time to onset 
and the duration of the event:
o
Missing Start Day: First of the month will be used unless this is before the start 
date of study treatment; in this case the study treatment start date will be used and 
hence the event is considered Treatment Emergent as per Appendix 4: Study 
Phases and Treatment Emergent Adverse Events.
o
Missing Stop Day: Last day of the month will be used, unless this is after the stop 
date of study treatment; in this case the last contact date will be used.

Completely missing start or end dates will remain missing, with no imputation applied. 
Consequently, time to onset and duration of such events will be missing.
Concomitant 
Medications/
Medical 
History

Partial dates for any concomitant medications recorded in the CRF will be imputed 
using the following convention:
o
If the partial date is a start date: '01' will be used for the day if the month is not 
missing, and '01-Jan' will be used if both month and day are missing.
o
If the partial date is a stop date: '28/29/30/31' will be used for the day if the month 
is not missing, and '31-Dec' will be used if both month and day are missing.
o
For medications recorded in the eCRF as prior medications, the earlier of this 
imputed date or the day before the treatment start date will be used. 
 
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Element
Reporting Detail

The recorded partial date will be displayed in listings.
 
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15.8.
Appendix 8: Values of Potential Clinical Importance
15.8.1.
Laboratory Values
Haematology
Laboratory Parameter
Units
Category
Clinical Concern Range
Low Flag (< x)
High Flag (> x)
Haematocrit 
Ratio of 
1
Male
0.54
∆from BL
↓ 0.075
Haemoglobin
g/L
Male
180
∆from BL
↓ 25
Lymphocytes 
x109/ L
0.8
Neutrophil Count 
x109/ L
1.5
Eosinophil Count
x109/ L
1
Platelet Count 
x109/ L
100
550
While Blood Cell Count (WBC)
x109/ L
3
20
Clinical Chemistry
Laboratory Parameter
Units
Category
Clinical Concern Range
Low Flag (< x)
High Flag (> x)
Blood urea nitrogen
mmol/L
10.5
Calcium
mmol/L
2
2.75
Creatinine
mol/L
∆from BL
↑ 26
eGFR
ml/min/1.
73m2
60
Glucose
mmol/L
3
9
Potassium
mmol/L
3
5.5
Sodium
mmol/L
130
150
Total Protein
g/L
50
85
Liver Function
Test Analyte
Units
Category
Clinical Concern Range
ALT/SGPT 
U/L
High
≥ 2 x ULN
AST/SGOT 
U/L
High
≥ 2 x ULN
AlkPhos 
U/L
High
≥ 2 x ULN
T Bilirubin 
µmol/L
High
≥ 1.5 x ULN
T. Bilirubin + ALT
µmol/L
High
≥ 1.5 x ULN T. Bilirubin
+
U/L
≥ 2 x ULN ALT
 
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15.8.2.
ECG
ECG Parameter
Units
Clinical Concern Range
Lower
Upper
Absolute
Absolute QTc Interval
msec
> 450
Absolute PR Interval
msec
< 110
> 220
Absolute QRS Interval
msec
< 75
> 110
Change from Baseline
Increase from Baseline QTc
msec
> 60
15.8.3.
Vital Signs
Vital Sign Parameter
(Absolute)
Units
Clinical Concern Range
Lower
Upper
Systolic Blood Pressure
mmHg
< 85
> 160
Diastolic Blood Pressure
mmHg
< 45
> 100
Heart Rate
bpm
< 40
> 110
Temperature
ºC
<35
≥37.5
15.8.4.
Urinalysis
Urinalysis
Test Analyte
Units
Category
Clinical Concern Range
Bilirubin
High
>1+
Glucose
High
>1+
Ketone
High
>2+
Leukocytes (dipstick)
High
>1+
Nitrite
High
Positive
Occult blood (dipstick)
High
>1+
pH
Low
<4.6
High
>8
Protein
High
>1+
RBC (microscopy)
cells/hpf
High
>3
Specific gravity
Low
<1.001
High
>1.035
Urobilinogen
mg/dL
High
>1
WBC (microscopy)
cells/hpf
High
>5
 
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15.9.
Appendix 9: Population Pharmacokinetic (PopPK) Analyses
15.9.1.
Population Pharmacokinetic (PopPK) Dataset Specification
PopPK dataset specification will be provided as a separate document.
15.9.2.
Population Pharmacokinetic (PopPK) Methodology
An exploratory graphical analysis of the drug plasma concentration-time data will be 
performed by generating the plots as presented in Appendix 12: List of Data Displays.
A previous PopPK model developed from the first time in human study 200630 (GSK 
Document Number 2017N352860_00), incorporating linear and non-linear (target 
mediated drug disposition (TMDD), Michaelis-Menten) elimination pathways, will be 
used to fit the drug plasma concentration-time data. The model will be updated 
accordingly to describe the absorption profiles after SC doses of GSK2831781. For this 
update it will be assumed that the distribution and elimination of GSK2831781 will be 
the same regardless of the route of administration (IV or SC). 
The appropriateness of the updated model will be assessed by the objective function 
value (OFV), successful convergence, covariance estimation, shrinkage, parameter 
uncertainty, standard Goodness-of-Fit (GoF) and simulation-based diagnostic plots e.g. 
Visual Predictive Check (VPC).  
The GoF plots may include, but are not limited to:
•
Population and individual predictions versus observations
•
Conditional weighted residuals versus population predictions and time
If a VPC is done, this will be based on 1000 simulations with the model and the design 
structure of the observed data (i.e. dose level and time, time of PK sampling and 
individual values of model covariates, if any). The median and the 10th and 90th will be 
compared to the observed data. Stratification by dose level and administration route of 
GSK2831781 or geographic ancestry will be used. 
The individual PK parameters will be computed from the PopPK model and will be 
summarised by treatment group and geographic ancestry.
 
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15.10.
Appendix 10: Pharmacokinetic / Pharmacodynamic 
Analyses
15.10.1.
Pharmacokinetic / Pharmacodynamic Dataset Specification
PK/PD dataset specification will be provided as a separate document.
15.10.2.
Pharmacokinetic / Pharmacodynamic Methodology
An exploratory graphical analysis of the drug effect on LAG3+ cell depletion, sLAG3 
concentrations and regulatory T cells count will be performed by generating the PD plots 
as presented in Appendix 12: List of Data Displays.
A previous indirect response model developed from all available cell depletion data from 
the first-time in human study 200630 (GSK Document Number 2017N352860_00) will 
be fitted to the current PD data using the nonlinear mixed effects modelling software 
NONMEM. Data relative to CD4+CD45RA-1B4+ cell count will be used to model T cell 
depletion.
The appropriateness of the PopPK/PD model will be assessed by the OFV, successful 
convergence, covariance estimation, shrinkage, parameter uncertainty, standard GoF and 
simulation-based diagnostic plots e.g. VPC.  
The GoF plots may include, but are not limited to:
•
Population and individual predictions versus observations
•
Conditional weighted residuals versus population predictions and time
If a VPC is done, this will be based on 1000 simulations with the model and the design 
structure of the observed data (i.e. dose level and time, time of PD sampling and 
individual values of model covariates, if any). The median and the 10th and 90th will be 
compared to the observed data. Stratification by dose level and administration route of 
GSK2831781 or geographic ancestry will be used.
 
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15.11.
Appendix 11: Abbreviations & Trade Marks
15.11.1.
Abbreviations
Abbreviation
Description
ADA
Anti-drug antibody
AE
Adverse Event
ALT
Alanine aminotransaminase
ANOVA
Analysis of variance
AST
Aspartate Aminotransferase
AUC(0-t)
Area under the plasma concentration-time curve from time zero (pre-dose) to 
last time of quantifiable concentration
A&R
Analysis and Reporting 
BUN
Blood Urea Nitrogen
CI
Confidence Interval
Cmax
Maximum observed plasma concentration
CMV
Cytomegalovirus
CPEM
Clinical Pharmacology and Experimental Medicine
CPMS
Clinical Pharmacology Modelling & Simulation
CRF
Case Record Form
CSV
Comma-separated values
CVb / CVw
Coefficient of Variation (Between) / Coefficient of Variation (Within)
DBF
Database Freeze
DBR
Database Release
DP
Decimal Places
EBV
Epstein-Barr Virus
ECG
Electrocardiogram
eCRF
Electronic Case Record Form
eGFR
Estimated Glomerular Filtration Rate
EMA
European Medicines Agency
F
Bioavailability
FDA
Food and Drug Administration
FDAAA
Food and Drug Administration Clinical Results Disclosure Requirements
GCDO
Global Clinical & Data Operations
GCSD
Global Clinical Sciences & Delivery
GoF
Goodness-of-Fit
GSK
GlaxoSmithKline
HARP
Harmonized Analysis and Reporting Process
HbcAb
Hepatitis B core antibody
HbsAg
Hepatitis B surface antigen
HCV
Hepatitis C virus
HIV
Human Immunodeficiency Virus
IA
Interim Analysis
ICH
International Conference on Harmonization
IDSL
Integrated Data Standards Library
INR
International normalized ratio
 
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Abbreviation
Description
IP
Investigational Product
IV
Intravenous
LAG3
Lymphocyte Activation Gene-3
MCH
Mean Corpuscular Hemoglobin
MCV
Mean Corpuscular Volume
NQ
Non-quantifiable
OFV
Objective Function Value
PCI
Potential Clinical Importance
PD
Pharmacodynamic
PDMP
Protocol Deviation Management Plan
PK
Pharmacokinetic
PKPD
Pharmacokinetic / Pharmacodynamic
PopPK
Population PK
QC
Quality Control
QTcF
Frederica’s QT Interval Corrected for Heart Rate
QTcB
Bazett’s QT Interval Corrected for Heart Rate
RAP
Reporting & Analysis Plan
RAMOS
Randomization & Medication Ordering System
RBC
Red Blood Cell
RC
(Interim) Review Committee
RTF
Rich Text Format
SAC
Statistical Analysis Complete
SAE
Serious Adverse Event
SC
Subcutaneous
SD
Standard Deviation
SGOT
Serum Glutamic-Oxaloacetic Transaminase
SGPT
Serum Glutamic-Pyruvic Transaminase
sLAG3
Soluble LAG3
SMG
Safety and Medical Governance
SoA
Schedule of Activities
SOP
Standard Operation Procedure
TA
Therapeutic Area
TB
Tuberculosis
TLF
Tables, Listings & Figures
tmax
Time of occurrence of Cmax
TMDD
Target Mediated Drug Disposition
ULN
Upper limit of normal
VPC
Visual Predictive Check
VZV
Varicella zoster virus
WBC
White Blood Cell
WNL
Windows Non-Linear
 
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15.11.2.
Trademarks
Trademarks of the GlaxoSmithKline 
Group of Companies
Trademarks not owned by the 
GlaxoSmithKline Group of Companies
None
NONMEM
SAS
WinNonlin
 
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15.12.
Appendix 12: List of Data Displays
15.12.1.
Data Display Numbering
The following numbering will be applied for RAP generated displays:
Section
Tables
Figures
Study Population
1.1 to 1.20
-
Safety
2.1 to 2.34
2.1 to 2.2
Pharmacokinetic
3.1 to 3.8
3.1 to 3.4
Population Pharmacokinetic (PopPK)
4.1 to 4.x*
4.1 to 4.x*
Pharmacodynamic
5.1 to 5.7
5.1 to 5.10
Pharmacokinetic / Pharmacodynamic
6.1 to 6.x*
6.1 to 6.x*
Section
Listings
ICH Listings
1 to 66
Other Listings
67 to x*
* PopPK and PK/PD displays will be generated by CPMS as needed; the number of displays is not pre-
defined.
15.12.2.
Mock Example Shell Referencing
Non IDSL specifications will be referenced as indicated and if required example mock-up 
displays provided in Appendix 13: Example Mock Shells for Data Displays.
Section
Figure
Table
Listing
Study Population
-
-
POP_Ln
Safety
SAFE_Fn
-
SAFE_Ln
Pharmacokinetic
-
PK_Tn
-
Population Pharmacokinetic (PopPK)
-
-
-
Pharmacodynamic
PD_Fn
-
PD_Ln
Pharmacokinetic / Pharmacodynamic
-
-
-
NOTES: 

Non-Standard displays are indicated in the ‘IDSL / Example Shell’ or ‘Programming Notes’ column as ‘[Non-
Standard] + Reference.’
15.12.3.
Deliverables
Delivery
Description
IA
Interim Analysis Statistical Analysis Complete
SAC
Final Statistical Analysis Complete
 
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15.12.4.
Study Population Tables
Part A
Study Population Tables (Part A)
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Subject Disposition
1.1.
Safety
ES1
Part A: Summary of Subject Disposition for the Subject 
Conclusion Record
Add footnote: Note: “Subjects” is used 
to refer to “Participants” in all data 
displays to reflect GSK display 
standards.
By treatment and geographic ancestry.
IA
SAC
1.2.
Screened
ES6
Part A: Summary of Screening Status and Reasons for Screen 
Failure
SAC
Protocol Deviation
1.3.
Safety
DV1
Part A: Summary of Important Protocol Deviations
By treatment and geographic ancestry.
Include Total column.
SAC
Population Analysed
1.4.
Screened
SP1
Part A: Summary of Study Populations
By treatment and geographic ancestry.
IA
SAC
Demographic and Baseline Characteristics
1.5.
Safety
DM1
Part A: Summary of Demographic Characteristics
By treatment and geographic ancestry.
IA
SAC
1.6.
Safety
DM5
Part A: Summary of Race and Racial Combinations
Only include race detail categories with 
>0 subjects.
By treatment.
SAC
1.7.
Randomized
DM11
Part A: Summary of Age Ranges
By treatment and geographic ancestry.
SAC
Medical Conditions
 
 
 
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Study Population Tables (Part A)
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
1.8.
Safety
MH1
Part A: Summary of Past Medical Conditions
By treatment and geographic ancestry.
SAC
1.9.
Safety
MH1
Part A: Summary of Current Medical Conditions
By treatment and geographic ancestry.
SAC
Exposure and Treatment Compliance
1.10.
Safety
EX1
Part A: Summary of Exposure to Study Treatment
By treatment and geographic ancestry.
SAC
Part B
Study Population Tables (Part B)
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Subject Disposition
1.11.
Safety
ES1
Part B: Summary of Subject Disposition for the Subject 
Conclusion Record
By treatment.
SAC
1.12.
Screened
ES6
Part B: Summary of Screening Status and Reasons for Screen 
Failure
SAC
Protocol Deviation
1.13.
Safety
DV1
Part B: Summary of Important Protocol Deviations
By treatment.
Include Total column.
SAC
Population Analysed
1.14.
Screened
SP1
Part B: Summary of Study Populations
By treatment.
SAC
Demographic and Baseline Characteristics
1.15.
Safety
DM1
Part B: Summary of Demographic Characteristics
By treatment.
SAC
 
 
 
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Study Population Tables (Part B)
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
1.16.
Safety
DM5
Part B: Summary of Race and Racial Combinations
Only include race detail categories with 
>0 subjects.
By treatment.
SAC
1.17.
Randomized
DM11
Part B: Summary of Age Ranges
By treatment.
SAC
Medical Conditions
1.18.
Safety
MH1
Part B: Summary of Past Medical Conditions
By treatment.
SAC
1.19.
Safety
MH1
Part B: Summary of Current Medical Conditions
By treatment.
SAC
Exposure and Treatment Compliance
1.20.
Safety
EX1
Part B: Summary of Exposure to Study Treatment
By treatment.
SAC
 
 
 
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15.12.5.
Safety Tables
Part A
Safety Tables (Part A)
No.
Population
IDSL /
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Adverse Events (AEs)
2.1.
Safety
AE1
Part A: Summary of All Adverse Events by System Organ Class 
and Preferred Term
IA: By geographic ancestry.
SAC: By treatment and geographic 
ancestry.
IA
SAC
2.2.
Safety
AE3
Part A: Summary of Drug-Related Adverse Events
IA: By geographic ancestry.
SAC: By treatment and geographic 
ancestry.
IA
SAC
2.3.
Safety
AE3
Part A: Summary of Non-Serious Drug-Related Adverse Events 
by Overall Frequency
By treatment and geographic ancestry.
SAC
2.4.
Safety
AE5A
Part A: Summary of All Adverse Events by Maximum Intensity 
by System Organ Class and Preferred Term
Page by treatment and geographic 
ancestry.
SAC
2.5.
Safety
AE5A
Part A: Summary of Drug-Related Adverse Events by Maximum 
Intensity by System Organ Class and Preferred Term
Page by treatment and geographic 
ancestry.
SAC
Serious and Other Significant Adverse Events
2.6.
Safety
AE16
Part A: Summary of Serious Adverse Events by System Organ 
Class and Preferred Term (Number of Subjects and 
Occurrences) 
IA: By geographic ancestry.
SAC: By treatment and geographic 
ancestry.
IA
SAC
2.7.
Safety
AE3
Part A: Summary of Serious Drug-Related Adverse Events by
Overall Frequency
IA: By geographic ancestry.
SAC: By treatment and geographic 
ancestry.
IA
SAC
2.8.
Safety
AE3
Part A: Summary of Adverse Events Leading to Permanent
Discontinuation of Study Treatment or Withdrawal from Study
By treatment and geographic ancestry.
SAC
 
 
 
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Safety Tables (Part A)
No.
Population
IDSL /
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Laboratory: Chemistry 
2.9.
Safety
LB1
Part A: Summary of Chemistry Changes from Baseline
By treatment and geographic ancestry.
SAC
Laboratory: Haematology
2.10.
Safety
LB1
Part A: Summary of Haematology Changes from Baseline
By treatment and geographic ancestry.
IA: Only include the following 
parameters: Neutrophils, Lymphocytes.
IA
SAC
Laboratory: Urinalysis
2.11.
Safety
LB1
Part A: Summary of Urine Concentration Changes from Baseline
By treatment and geographic ancestry.
SAC
Laboratory: Hepatobiliary (Liver)
2.12.
Safety
LIVER1
Part A: Summary of Liver Monitoring/Stopping Event Reporting
By treatment and geographic ancestry.
IA
SAC
2.13.
Safety
LIVER10
Part A: Summary of Hepatobiliary Laboratory Abnormalities
By treatment and geographic ancestry.
SAC
ECG
2.14.
Safety
EG1
Part A: Summary of ECG Findings 
By treatment and geographic ancestry.
SAC
2.15.
Safety
EG10
Part A: Summary of Maximum QTc Values Post-Baseline 
Relative to Baseline by Category
By treatment and geographic ancestry.
SAC
2.16.
Safety
EG2
Part A: Summary of Change from Baseline in ECG Values by 
Visit
By treatment and geographic ancestry.
SAC
Vital Signs
2.17.
Safety
VS1
Part A: Summary of Change from Baseline in Vital Signs
By treatment and geographic ancestry.
SAC
 
 
 
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Part B
Safety Tables (Part B)
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Adverse Events (AEs)
2.18.
Safety
AE1
Part B: Summary of All Adverse Events by System Organ Class 
and Preferred Term
By treatment.
SAC
2.19.
Safety
AE3
Part B: Summary of Drug-Related Adverse Events
By treatment.
SAC
2.20.
Safety
AE3
Part B: Summary of Non-Serious Drug-Related Adverse Events 
by Overall Frequency
By treatment.
SAC
2.21.
Safety
AE5A
Part B: Summary of All Adverse Events by Maximum Intensity 
by System Organ Class and Preferred Term
Page by treatment.
SAC
2.22.
Safety
AE5A
Part B: Summary of Drug-Related Adverse Events by Maximum 
Intensity by System Organ Class and Preferred Term
Page by treatment.
SAC
Serious and Other Significant Adverse Events
2.23.
Safety
AE16
Part B: Summary of Serious Adverse Events by System Organ 
Class and Preferred Term (Number of Subjects and 
Occurrences) 
By treatment.
SAC
2.24.
Safety
AE3
Part B: Summary of Serious Drug-Related Adverse Events by
Overall Frequency
By treatment.
SAC
2.25.
Safety
AE3
Part B: Summary of Adverse Events Leading to Permanent
Discontinuation of Study Treatment or Withdrawal from Study
By treatment.
SAC
Laboratory: Chemistry 
2.26.
Safety
LB1
Part B: Summary of Chemistry Changes from Baseline
By treatment.
SAC
Laboratory: Haematology
2.27.
Safety
LB1
Part B: Summary of Haematology Changes from Baseline
By treatment.
SAC
 
 
 
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Safety Tables (Part B)
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Laboratory: Urinalysis
2.28.
Safety
LB1
Part B: Summary of Urine Concentration Changes from Baseline
By treatment.
SAC
Laboratory: Hepatobiliary (Liver)
2.29.
Safety
LIVER1
Part B: Summary of Liver Monitoring/Stopping Event Reporting
By treatment.
SAC
2.30.
Safety
LIVER10
Part B: Summary of Hepatobiliary Laboratory Abnormalities
By treatment.
SAC
ECG
2.31.
Safety
EG1
Part B: Summary of ECG Findings 
By treatment.
SAC
2.32.
Safety
EG10
Part B: Summary of Maximum QTc Values Post-Baseline 
Relative to Baseline by Category
By treatment.
SAC
2.33.
Safety
EG2
Part B: Summary of Change from Baseline in ECG Values by 
Visit
By treatment.
SAC
Vital Signs
2.34.
Safety
VS1
Part B: Summary of Change from Baseline in Vital Signs
By treatment.
SAC
 
 
 
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15.12.6.
Safety Figures
Part A
Pharmacokinetic Tables (Part A)
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Laboratory: Haematology
2.1.
Safety
[Non-standard]
SAFE_F1
Part A: Individual Plots of Haematology
By treatment and geographic ancestry.
Only include the following parameters: 
Neutrophils, Lymphocytes.
IA
2.2.
Safety
[Non-standard]
SAFE_F2
Part A: Mean (SD) Plots of Haematology
By treatment and geographic ancestry.
Only include the following parameters: 
Neutrophils, Lymphocytes.
IA
 
 
 
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15.12.7.
Pharmacokinetic Tables
Part A
Pharmacokinetic Tables (Part A)
No.
Population
IDSL /
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Pharmacokinetic Concentrations
3.1.
PK
PK01
Part A: Summary of GSK2831781 Plasma Pharmacokinetic 
Concentration-Time Data
Include 95% Confidence Interval for the 
mean.
By treatment and geographic ancestry.
IA: only include data up to Day 29.
IA
SAC
Pharmacokinetic Parameters
3.2.
PK
PK03
Part A: Summary of Derived GSK2831781 Plasma 
Pharmacokinetic Parameters
Include 95% Confidence Interval for the 
mean.
By treatment and geographic ancestry.
IA
SAC
3.3.
PK
PK05
Part A: Summary of Log-Transformed Derived GSK2831781 
Plasma Pharmacokinetic Parameters
By treatment and geographic ancestry.
IA
SAC
Pharmacokinetic Statistical Analyses
3.4.
PK
[Non-standard]
PK_T1
Part A: Table of Ethnosensitivity Model Results
SAC
 
 
 
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Part B
Pharmacokinetic Tables (Part B)
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Pharmacokinetic Concentrations
3.5.
PK
PK01
Part B: Summary of GSK2831781 Plasma Pharmacokinetic 
Concentration-Time Data
Include 95% Confidence Interval for the 
mean.
By treatment.
SAC
Pharmacokinetic Parameters
3.6.
PK
PK03
Part B: Summary of Derived GSK2831781 Plasma 
Pharmacokinetic Parameters
Include 95% Confidence Interval for the 
mean.
By treatment.
SAC
3.7.
PK
PK05
Part B: Summary of Log-Transformed Derived GSK2831781 
Plasma Pharmacokinetic Parameters
By treatment.
SAC
Pharmacokinetic Statistical Analyses
3.8.
PK
[Non-standard]
PK_T1
Part B: Table of Bioavailability Model Results
SAC
 
 
 
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15.12.8.
Pharmacokinetic Figures
Part A
Pharmacokinetic Figures (Part A)
No.
Population
IDSL /
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Pharmacokinetic Concentrations
3.1.
PK
PK24
Part A: Individual GSK2831781 Plasma Concentration-Time 
Plots (Linear and Semi-log) by Treatment and Geographic 
Ancestry
By treatment and geographic ancestry.
IA: do not show subject IDs. Different 
colours and symbols for treatment and 
geographic ancestry.
IA: only include data up to Day 29.
IA
SAC
3.2.
PK
PK19
Part A: Mean (SD) GSK2831781 Plasma Concentration-Time 
Plots (Linear and Semi-log) by Treatment and Geographic 
Ancestry
By treatment and geographic ancestry.
IA: only include data up to Day 29.
IA
SAC
Part B
Pharmacokinetic Figures (Part B)
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Pharmacokinetic Concentrations
3.3.
PK
PK24
Part B: Individual GSK2831781 Plasma Concentration-Time 
Plots (Linear and Semi-log) by Treatment
By treatment.
SAC
3.4.
PK
PK19
Part B: Mean (SD) GSK2831781 Plasma Concentration-Time 
Plots (Linear and Semi-log) by Treatment
By treatment.
SAC
 
 
 
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15.12.9.
Pharmacokinetic Population (PopPK) Tables
Tables will be generated by CPMS as needed for part A & B.
 
 
 
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15.12.10. Pharmacokinetic Population (PopPK) Figures
Figures will be generated by CPMS as needed for part A & B.
 
 
 
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15.12.11. Pharmacodynamic Tables
Part A
Pharmacodynamic Tables (Part A)
No.
Population
IDSL /
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
LAG3+ T Cells
5.1.
Safety
PD1
Part A: Summary of LAG3+ T Cells in Blood by Visit
Absolute, %CFB.
By treatment and geographic ancestry.
By cell populations as defined in 11.1.1.
IA: only include data up to Day 29.
IA
SAC
Soluble LAG3
5.2.
Safety
PD1
Part A: Summary of sLAG3 in Blood by Visit
Absolute, %CFB.
By treatment and geographic ancestry.
IA: only include data up to Day 29.
IA
SAC
Regulatory T Cells
5.3.
Safety
PD1
Part A: Summary of Regulatory T Cells in Blood by Visit
Absolute, %CFB.
By treatment.
SAC
Immunogenicity
5.4.
Safety
IMM1
Part A: Summary of Positive Immunogenicity Results
SAC
 
 
 
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Part B
Pharmacodynamic Tables (Part B)
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
LAG3+ T Cells
5.5.
Safety
PD1
Part B: Summary of LAG3+ T Cells in Blood by Visit
Absolute, %CFB.
By treatment.
By cell populations as defined in 11.1.1.
SAC
Soluble LAG3
5.6.
Safety
PD1
Part B: Summary of sLAG3 in Blood by Visit
Absolute, %CFB.
By treatment.
SAC
Immunogenicity
5.7.
Safety
IMM1
Part B: Summary of Positive Immunogenicity Results
SAC
 
 
 
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15.12.12. Pharmacodynamic Figures
Part A
Pharmacodynamic Figures (Part A)
No.
Population
IDSL /
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
LAG3+ T Cells
5.1.
Safety
[Non-standard]
PD_F1
Part A: Individual Plot of LAG3+ T Cells in Blood Over Time
Absolute, %CFB.
By treatment and geographic ancestry.
Page by cell population, as defined in 
11.1.1.
IA: do not show subject IDs. Different 
colours and symbols for treatment and 
geographic ancestry.
IA: only include data up to Day 29.
IA
SAC
5.2.
Safety
[Non-standard]
PD_F2
Part A: Mean (SD) Plot of LAG3+ T Cells in Blood Over Time
Absolute, %CFB.
By treatment and geographic ancestry.
Page by cell population, as defined in 
11.1.1.
IA: only include data up to Day 29.
IA
SAC
Soluble LAG3
5.3.
Safety
[Non-standard]
PD_F1
Part A: Individual Plot of sLAG3 in Blood Over Time
Absolute, %CFB.
By treatment and geographic ancestry.
IA: do not show subject IDs. Different 
colours and symbols for treatment and 
geographic ancestry.
IA: only include data up to Day 29.
IA
SAC
5.4.
Safety
[Non-standard]
PD_F2
Part A: Mean (SD) Plot of sLAG3 in Blood Over Time
Absolute, %CFB.
By treatment and geographic ancestry.
IA: only include data up to Day 29.
IA
SAC
 
 
 
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Part B
Regulatory T Cells
5.5.
Safety
[Non-standard]
PD_F1
Part A: Individual Plot of Regulatory T Cells in Blood Over Time
Absolute, %CFB.
By treatment.
SAC
5.6.
Safety
[Non-standard]
PD_F2
Part A: Mean (SD) Plot of Regulatory T Cells in Blood Over 
Time
Absolute, %CFB.
By treatment.
SAC
Pharmacodynamic Figures (Part B)
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
LAG3+ T Cells
5.7.
Safety
[Non-standard]
PD_F1
Part B: Individual Plot of LAG3+ T Cells in Blood Over Time
Absolute, %CFB.
By treatment.
Page by cell population, as defined in 
11.1.1.
SAC
5.8.
Safety
[Non-standard]
PD_F2
Part B: Mean (SD) Plot of LAG3+ T Cells in Blood Over Time
Absolute, %CFB.
By treatment.
Page by cell population, as defined in 
11.1.1.
SAC
Soluble LAG3
5.9.
Safety
[Non-standard]
PD_F1
Part B: Individual Plot of sLAG3 in Blood Over Time
Absolute, %CFB.
By treatment.
SAC
5.10.
Safety
[Non-standard]
PD_F2
Part B: Mean (SD) Plot of sLAG3 in Blood Over Time
Absolute, %CFB.
By treatment.
SAC
 
 
 
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15.12.13. Pharmacokinetic / Pharmacodynamic Tables
Tables will be generated by CPMS as needed for part A & B.
 
 
 
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15.12.14. Pharmacokinetic / Pharmacodynamic Figures
Figures will be generated by CPMS as needed for part A & B.
 
 
 
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15.12.15. ICH Listings
Part A
ICH Listings (Part A)
No.
Population
IDSL / Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Subject Disposition
1.
Safety
ES2
Part A: Listing of Reasons for Study Withdrawal
SAC
2.
Screened
ES7
Part A: Listing of Reasons for Screen Failure
SAC
3.
Safety
SD2
Part A: Listing of Reasons for Study Treatment 
Discontinuation
SAC
4.
Safety
BL1
Part A: Listing of Subjects for Whom the Treatment Blind was 
Broken
SAC
5.
Safety
TA1
Part A: Listing of Planned and Actual Treatments
SAC
Protocol Deviations
6.
Safety
DV2
Part A: Listing of Important Protocol Deviations
SAC
7.
Safety
IE3
Part A: Listing of Subjects with Inclusion/Exclusion Criteria 
Deviations
SAC
Populations Analysed
8.
Screened
SP3
Part A: Listing of Subjects Excluded from Any Population
SAC
Demographic and Baseline Characteristics
9.
Safety
DM2
Part A: Listing of Demographic Characteristics
SAC
10.
Safety
DM9
Part A: Listing of Race
SAC
Medical Conditions and Prior/Concomitant Medications
11.
Safety
MH2
Part A: Listing of Current/Past Medical Conditions
SAC
12.
Safety
CM2
Part A: Listing of Concomitant Medications
SAC
 
 
 
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ICH Listings (Part A)
No.
Population
IDSL / Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
Exposure and Treatment Compliance
13.
Safety
EX3
Part A: Listing of Exposure Data
SAC
Adverse Events
14.
Safety
AE7
Part A: Listing of Subject Numbers for Individual Adverse 
Events
SAC
15.
Safety
AE8
Part A: Listing of All Adverse Events
IA
SAC
16.
Safety
AE2
Part A: Listing of Relationship Between Adverse Event 
System Organ Classes, Preferred Terms, and Verbatim Text
SAC
Serious and Other Significant Adverse Events
17.
Safety
AE8CPA
Part A: Listing of Serious Adverse Events (Fatal & Non-Fatal)
Include fatal and non-fatal status
SAC
18.
Safety
AE8
Part A: Listing of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment or Withdrawal from Study
SAC
19.
Safety
AE8
Part A: Listing of Other Significant Adverse Events
SAC
20.
Safety
AE14
Part A: Listing of Reasons for Considering as a Serious 
Adverse Event
SAC
Hepatobiliary (Liver)
21.
Safety
MH2
Part A: Listing of Medical Conditions for Subjects with Liver 
Stopping Events
SAC
22.
Safety
SU2
Part A: Listing of Substance Use for Subjects with Liver 
Stopping Events
SAC
23.
Safety
LIVER6
Part A: Listing of Liver Stopping Event Information for RUCAM 
Score
SAC
24.
Safety
LIVER7
Part A: Listing of Liver Biopsy Details
SAC
 
 
 
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ICH Listings (Part A)
No.
Population
IDSL / Example 
Shell
Title
Programming Notes
Deliverable 
[Priority]
25.
Safety
LIVER8
Part A: Listing of Liver Imaging Details
SAC
All Laboratory
26.
Safety
LB5
Part A: Listing of All Laboratory Data for Subjects with Any 
Value of Potential Clinical Importance
SAC
27.
Safety
LB5
Part A: Listing of Laboratory Values of Potential Clinical 
Importance
SAC
28.
Safety
LB14
Part A: Listing of Laboratory Data with Character Results
IA: Only include the following 
parameters: Neutrophils, 
Lymphocytes
IA
SAC
29.
Safety
UR2A
Part A: Listing of Urinalysis Data for Subjects with Any Value 
of Potential Clinical Importance
SAC
ECG
30.
Safety
EG3
Part A: Listing of All ECG Values for Subjects with Any Value 
of Potential Clinical Importance
SAC
31.
Safety
EG3
Part A: Listing of ECG Values of Potential Clinical Importance
SAC
32.
Safety
EG5
Part A: Listing of All ECG Findings for Subjects with an 
Abnormal ECG Finding
SAC
Vital Signs
33.
Safety
VS4
Part A: Listing of All Vital Signs for Subjects with any Value of 
Potential Clinical Importance
SAC
 
 
 
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Part B
ICH Listings (Part B)
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Subject Disposition
34.
Safety
ES2
Part B: Listing of Reasons for Study Withdrawal
SAC
35.
Screened
ES7
Part B: Listing of Reasons for Screen Failure
SAC
36.
Safety
SD2
Part B: Listing of Reasons for Study Treatment Discontinuation
SAC
37.
Safety
BL1
Part B: Listing of Subjects for Whom the Treatment Blind was 
Broken
SAC
38.
Safety
TA1
Part B: Listing of Planned and Actual Treatments
SAC
Protocol Deviations
39.
Safety
DV2
Part B: Listing of Important Protocol Deviations
SAC
40.
Safety
IE3
Part B: Listing of Subjects with Inclusion/Exclusion Criteria 
Deviations
SAC
Populations Analysed
41.
Screened
SP3
Part B: Listing of Subjects Excluded from Any Population
SAC
Demographic and Baseline Characteristics
42.
Safety
DM2
Part B: Listing of Demographic Characteristics
SAC
43.
Safety
DM9
Part B: Listing of Race
SAC
Medical Conditions and Prior/Concomitant Medications
44.
Safety
MH2
Part B: Listing of Current/Past Medical Conditions
SAC
45.
Safety
CM2
Part B: Listing of Concomitant Medications
SAC
Exposure and Treatment Compliance
46.
Safety
EX3
Part B: Listing of Exposure Data
SAC
 
 
 
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ICH Listings (Part B)
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Adverse Events
47.
Safety
AE7
Part B: Listing of Subject Numbers for Individual Adverse Events
SAC
48.
Safety
AE8
Part B: Listing of All Adverse Events
SAC
49.
Safety
AE2
Part B: Listing of Relationship Between Adverse Event System 
Organ Classes, Preferred Terms, and Verbatim Text
SAC
Serious and Other Significant Adverse Events
50.
Safety
AE8CPA
Part B: Listing of Serious Adverse Events (Fatal & Non-Fatal)
Include fatal and non-fatal status
SAC
51.
Safety
AE8
Part B: Listing of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment or Withdrawal from Study
SAC
52.
Safety
AE8
Part B: Listing of Other Significant Adverse Events
SAC
53.
Safety
AE14
Part B: Listing of Reasons for Considering as a Serious Adverse 
Event
SAC
Hepatobiliary (Liver)
54.
Safety
MH2
Part B: Listing of Medical Conditions for Subjects with Liver 
Stopping Events
SAC
55.
Safety
SU2
Part B: Listing of Substance Use for Subjects with Liver 
Stopping Events
SAC
56.
Safety
LIVER6
Part B: Listing of Liver Stopping Event Information for RUCAM 
Score
SAC
57.
Safety
LIVER7
Part B: Listing of Liver Biopsy Details
SAC
58.
Safety
LIVER8
Part B: Listing of Liver Imaging Details
SAC
All Laboratory
59.
Safety
LB5
Part B: Listing of All Laboratory Data for Subjects with Any Value
of Potential Clinical Importance
SAC
 
 
 
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ICH Listings (Part B)
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
60.
Safety
LB5
Part B: Listing of Laboratory Values of Potential Clinical 
Importance
SAC
61.
Safety
LB14
Part B: Listing of Laboratory Data with Character Results
SAC
62.
Safety
UR2A
Part B: Listing of Urinalysis Data for Subjects with Any Value of 
Potential Clinical Importance
SAC
ECG
63.
Safety
EG3
Part B: Listing of All ECG Values for Subjects with Any Value of 
Potential Clinical Importance
SAC
64.
Safety
EG3
Part B: Listing of ECG Values of Potential Clinical Importance
SAC
65.
Safety
EG5
Part B: Listing of All ECG Findings for Subjects with an 
Abnormal ECG Finding
SAC
Vital Signs
66.
Safety
VS4
Part B: Listing of All Vital Signs for Subjects with any Value of 
Potential Clinical Importance
SAC
 
 
 
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15.12.16. Non-ICH Listings
Part A
Non-ICH Listings (Part A)
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Exposure and Treatment Compliance
67.
Safety
[Non-standard]
POP_L1
Part A: Listing of Dose Dispensation Deviations
By geographic ancestry.
IA
Pharmacokinetic Data
68.
PK
PK07
Part A: Listing of GSK2831781 Plasma Pharmacokinetic 
Concentration-Time Data
SAC
69.
PK
PK13
Part A: Listing of Derived GSK2831781 Plasma Pharmacokinetic 
Parameters
SAC
Pharmacodynamic: LAG3+ T Cells
70.
Safety
[Non-standard]
PD_L1
Part A: Listing of LAG3+ T cells in Blood
SAC
Pharmacodynamic: Soluble LAG3
71.
Safety
[Non-standard]
PD_L1
Part A: Listing of sLAG3 in Blood
SAC
Pharmacodynamic: Regulatory T Cells
72.
Safety
[Non-standard]
PD_L1
Part A: Listing of Regulatory T Cells in Blood
SAC
Pharmacodynamic: Immunogenicity
73.
Safety
IMM2
Part A: Listing of Immunogenicity Results
SAC
 
 
 
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Part B
Non-ICH Listings (Part B)
No.
Population
IDSL / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Local Tolerability
74.
Safety
[Non-standard]
SAFE_L1
Part B: Listing of Injection Sites and Injection Site Reactions
SAC
Pharmacokinetic Data
75.
PK
PK07
Part B: Listing of GSK2831781 Plasma Pharmacokinetic 
Concentration-Time Data
SAC
76.
PK
PK13
Part B: Listing of Derived GSK2831781 Plasma Pharmacokinetic 
Parameters
SAC
Pharmacodynamic: LAG3+ T Cells
77.
Safety
[Non-standard]
PD_L1
Part B: Listing of LAG3+ T Cells in Blood
SAC
Pharmacodynamic: Soluble LAG3
78.
Safety
[Non-standard]
PD_L1
Part B: Listing of sLAG3 in Blood
SAC
Pharmacodynamic: Immunogenicity
79.
Safety
IMM2
Part B: Listing of Immunogenicity Results
SAC
 
 
 
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15.13.
Appendix 13: Example Mock Shells for Data Displays
Data Display Specification will be made available on Request
 
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