Conditions: Psoriasis
Keywords: tolerability safety GSK2982772 RIP1 kinase inhibitor psoriasis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 65
Healthy volunteers: no

Brief summary:
This is the first study with GSK2982772, a receptor-interacting protein-1 (RIP1) kinase inhibitor, in subjects with active plaque-type psoriasis (PsO). The primary objective will be to investigate the safety and tolerability of repeat oral doses of GSK2982772 60 milligram (mg) twice daily (BID) for 84 days in Cohort 1 and 60 mg thrice daily (TID) for 84 days in Cohort 2. In addition, a number of experimental and clinical endpoints will be employed to obtain information on the pharmacokinetics, pharmacodynamics, and efficacy in subjects with active PsO. There will be two Cohorts of subjects. In Cohort 1 after a screening period of up to 30 days, approximately 30 subjects will be randomized to receive either GSK2982772 60 mg BID or placebo for 84 days (12 Weeks), followed by a follow-up period (28 days). In Cohort 2 after a screening period of up to 30 days, approximately 24 subjects will be randomized to receive either GSK2982772 60 mg TID or placebo for 84 days (12 Weeks), followed by a follow-up period (28 days). The total duration of participation is approximately 20 Weeks from screening to the last study visit.

Detailed description:

Arms:
arm 1: Randomized subjects will receive GSK2982772 BID (approximately 12 hours apart) via oral route for 84 days. arm 2: Randomized subjects will receive placebo BID via oral route for 84 days. arm 3: Randomized subjects will receive GSK2982772 TID (approximately 8 hours apart) via oral route for 84 days arm 4: Randomized subjects will receive placebo TID via oral route for 84 days.

Interventions: intervention 1: GSK2982772 intervention 2: Placebo
Intervention descriptions: intervention 1: GSK2982772 will be supplied as a white to almost white, round, film coated 30 mg oral tablets; two tablets to be taken in the morning and two in the evening, as directed for Cohort 1 and for Cohort 2 two tablets to be taken three times daily as directed. intervention 2: Matching placebo will be supplied as a white to almost white, round film coated tablets; two tablets to be taken in the morning and two in the evening, as directed for Cohort 1 and for Cohort 2 two tablets to be taken three times daily as directed.

Protocol document:
Prot_000.pdf: 
2015N251765_02
CONFIDENTIAL
The GlaxoSmithKline group of companies
203167
1
TITLE PAGE
Division: Worldwide Development
Information Type: Protocol Amendment
Title:
A multicentre, randomised, double-blind (sponsor-unblinded), 
placebo-controlled, repeat dose study to investigate the safety 
and tolerability, pharmacokinetics, pharmacodynamics, and 
efficacy of GSK2982772 in subjects with active plaque-type 
psoriasis
Compound Number:
GSK2982772
Development Phase:
IIA
Effective Date:
12-APR-2017
Protocol Amendment Number:  02
Author (s):
 
 
Revision Chronology
GlaxoSmithKline
Document Number
Date
Version
2015N251765_00
2016-MAR-22
Original
2015N251765_01
2016-MAY-25
Amendment No. 1
Regulatory feedback led to a requirement for additional concomitant medication 
restrictions. In addition, some administrative clarifications have been made.
2015N251765_02
2017-APR-12
Amendment No. 2
Addition of a second cohort of subjects in the study to evaluate a 60 mg three times daily 
(TID) dosing regimen.
Copyright 2017 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited.
PPD


PPD
PPD


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MEDICAL MONITOR/SPONSOR INFORMATION PAGE
Medical Monitor/SAE Contact Information: 
Role
Name
Day Time Phone Number 
and email address
After-hours 
Phone/Cell/
Pager 
Number
Fax Number
Site Address
Primary 
Medical 
Monitor 
Tel      
Email:   
Mobile:  
Mobile:  
N/A
Stockley Park 
West, 1-3 
Ironbridge 
Road, Uxbridge, 
Middlesex, 
UB11 1BT, 
United Kingdom
Secondary 
Medical 
Monitor
Mobile
Email:  
Mobile
N/A
1250 S.
Collegeville Rd.
Collegeville PA 
19426, USA
SAE 
contact  
information 
Medical 
Monitor as 
above
Sponsor Legal Registered Address: 
GlaxoSmithKline Research & Development Limited
980 Great West Road
Brentford
Middlesex, TW8 9GS
UK
In some countries, the clinical trial sponsor may be the local GlaxoSmithKline Affiliate 
Company (or designee). If applicable, the details of the alternative Sponsor and contact 
person in the territory will be provided to the relevant regulatory authority as part of the 
clinical trial application.   
PPD
PPD
PP
D
PPD
PPD
PPD
PPD
PPD
PPD
PPD


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INVESTIGATOR PROTOCOL AGREEMENT PAGE
For protocol number 203167
I confirm agreement to conduct the study in compliance with the protocol, as amended by 
this protocol amendment.
I acknowledge that I am responsible for overall study conduct. I agree to personally 
conduct or supervise the described study.
I agree to ensure that all associates, colleagues and employees assisting in the conduct of 
the study are informed about their obligations. Mechanisms are in place to ensure that site 
staff receives the appropriate information throughout the study.
Investigator Name:
Investigator Address:
Investigator Phone Number:
Investigator Signature
Date


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TABLE OF CONTENTS
PAGE
1.
PROTOCOL SYNOPSIS FOR STUDY 203167........................................................8
2.
INTRODUCTION....................................................................................................12
2.1.
Study Rationale ..........................................................................................12
2.2.
Brief Background ........................................................................................13
3.
OBJECTIVE(S) AND ENDPOINT(S) ......................................................................14
4.
STUDY DESIGN ....................................................................................................16
4.1.
Overall Design ............................................................................................16
4.2.
Treatment Arms and Duration.....................................................................16
4.2.1.
Screening ....................................................................................17
4.2.2.
Treatment Period.........................................................................17
4.2.3.
Follow-up Period..........................................................................17
4.3.
Type and Number of Subjects.....................................................................17
4.4.
Design Justification.....................................................................................18
4.5.
Dose Justification........................................................................................18
4.6.
Benefit: Risk Assessment ...........................................................................20
4.6.1.
Risk Assessment .........................................................................21
4.6.2.
Benefit Assessment.....................................................................26
4.6.3.
Overall Benefit: Risk Conclusion..................................................26
5.
SELECTION OF STUDY POPULATION AND WITHDRAWAL CRITERIA .............26
5.1.
Inclusion Criteria.........................................................................................26
5.2.
Exclusion Criteria........................................................................................28
5.3.
Screening/Baseline/Run-in Failures............................................................31
5.4.
Withdrawal/Stopping Criteria.......................................................................31
5.4.1.
Individual Safety Stopping Rules .................................................32
5.4.2.
Group Safety Stopping Rules.......................................................33
5.4.3.
Liver Chemistry Stopping Criteria ................................................33
5.4.3.1.
Study Treatment Restart or Rechallenge....................34
5.4.4.
QTc Stopping Criteria ..................................................................34
5.4.5.
Haematologic Stopping Criteria ...................................................35
5.5.
Subject and Study Completion....................................................................35
6.
STUDY TREATMENT ............................................................................................35
6.1.
Investigational Product and Other Study Treatment....................................35
6.2.
Treatment Assignment................................................................................36
6.3.
Planned Dose Adjustments.........................................................................36
6.4.
Blinding.......................................................................................................37
6.5.
Packaging and Labeling..............................................................................37
6.6.
Preparation/Handling/Storage/Accountability..............................................38
6.7.
Compliance with Study Treatment Administration.......................................38
6.8.
Treatment of Study Treatment Overdose....................................................38
6.9.
Treatment after the End of the Study ..........................................................39
6.10.
Lifestyle and/or Dietary Restrictions............................................................39
6.10.1.
Sun Exposure and Activity...........................................................39
6.11.
Concomitant Medications and Non-Drug Therapies....................................39


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6.11.1.
Permitted Medications and Non-Drug Therapies..........................39
6.11.2.
Prohibited Medications and Non-Drug Therapies.........................40
7.
STUDY ASSESSMENTS AND PROCEDURES .....................................................41
7.1.
Time and Events Table...............................................................................43
7.2.
Screening and Critical Baseline Assessments ............................................45
7.3.
Safety .........................................................................................................45
7.3.1.
Adverse Events (AE) and Serious Adverse Events (SAEs)..........45
7.3.1.1.
Time period and Frequency for collecting AE 
and SAE information...................................................45
7.3.1.2.
Method of Detecting AEs and SAEs ...........................46
7.3.1.3.
Follow-up of AEs and SAEs........................................46
7.3.1.4.
Cardiovascular and Death Events ..............................46
7.3.1.5.
Regulatory Reporting Requirements for SAEs............47
7.3.2.
Pregnancy ...................................................................................47
7.3.3.
Physical Exams ...........................................................................47
7.3.4.
Vital Signs....................................................................................48
7.3.5.
Electrocardiogram (ECG).............................................................48
7.3.6.
Clinical Safety Laboratory Assessments ......................................48
7.3.7.
Suicidal Risk Monitoring...............................................................50
7.4.
Efficacy.......................................................................................................50
7.4.1.
Patient Reported Outcomes.........................................................50
7.4.1.1.
Itch Visual Analogue Scale.........................................51
7.4.1.2.
Dermatology Life Quality Index...................................51
7.4.2.
Clinical Disease Assessments .....................................................51
7.4.2.1.
Body Surface Area (BSA)...........................................51
7.4.2.2.
Selection of Psoriasis Plaques and Plaque 
Lesion Severity Scoring (PLSS)..................................51
7.4.2.3.
Psoriasis Area Severity Index (PASI) .........................52
7.4.2.4.
Digital Photography ....................................................52
7.4.2.5.
Physician’s Global Assessment of Disease 
Activity........................................................................52
7.5.
Pharmacokinetics .......................................................................................53
7.5.1.
Blood Sample Collection..............................................................53
7.5.2.
Sample Analysis ..........................................................................53
7.5.3.
Punch Skin Biopsy for Pharmacokinetic Assay ............................53
7.5.4.
Sample Analysis ..........................................................................53
7.6.
Biomarker(s)/Pharmacodynamic Markers ...................................................53
7.6.1.
Skin Lesion Biopsy ......................................................................53
7.6.2.
Novel Pharmacodynamic Biomarkers ..........................................54
7.6.2.1.
RIP1 Target Engagement in Blood .............................54
7.6.2.2.
RIP1 Target Engagement in Tissue............................55
7.6.2.3.
RIP1 Pathway Markers in Tissue................................55
7.6.3.
Exploratory Novel Biomarkers......................................................55
7.7.
Genetics .....................................................................................................56
8.
DATA MANAGEMENT ...........................................................................................56
9.
STATISTICAL CONSIDERATIONS AND DATA ANALYSES .................................56
9.1.
Hypotheses.................................................................................................56
9.2.
Sample Size Considerations.......................................................................56
9.2.1.
Sample Size Assumptions ...........................................................56


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9.2.2.
Sample Size Sensitivity................................................................58
9.2.3.
Sample Size Re-estimation or Adjustment...................................59
9.3.
Data Analysis Considerations .....................................................................59
9.3.1.
Analysis Populations....................................................................59
9.3.2.
Interim Analysis ...........................................................................60
9.3.3.
Primary Analyses.........................................................................60
9.3.4.
Secondary Analyses ....................................................................60
9.3.5.
Other Analyses ............................................................................61
9.3.5.1.
Exploratory Analyses..................................................61
10. STUDY GOVERNANCE CONSIDERATIONS........................................................61
10.1.
Posting of Information on Publicly Available Clinical Trial Registers............61
10.2.
Regulatory and Ethical Considerations, Including the Informed 
Consent Process ........................................................................................61
10.3.
Quality Control (Study Monitoring) ..............................................................62
10.4.
Quality Assurance.......................................................................................62
10.5.
Study and Site Closure ...............................................................................63
10.6.
Records Retention......................................................................................63
10.7.
Provision of Study Results to Investigators, Posting of Information 
on Publically Available Clinical Trials Registers and Publication .................64
11. REFERENCES.......................................................................................................65
12. APPENDICES........................................................................................................67
12.1.
Appendix 1 – Abbreviations and Trademarks..............................................67
12.2.
Appendix 2: Liver Safety Required Actions and Follow up 
Assessments ..............................................................................................70
12.3.
Appendix 3 - Genetic Research ..................................................................72
12.4.
Appendix 4: Definition of and Procedures for Recording, Evaluating, 
Follow-Up and Reporting of Adverse Events...............................................75
12.4.1.
Definition of Adverse Events........................................................75
12.4.2.
Definition of Serious Adverse Events...........................................76
12.4.3.
Definition of Cardiovascular Events .............................................77
12.4.4.
Recording of AEs and SAEs ........................................................78
12.4.5.
Evaluating AEs and SAEs............................................................79
12.4.6.
Reporting of SAEs to GSK...........................................................80
12.5.
Appendix 5: Modified List of Highly Effective Methods for Avoiding 
Pregnancy in FRP and Collection of Pregnancy Information.......................81
12.5.1.
Modified List of Highly Effective Methods for Avoiding 
Pregnancy in Females of Reproductive Potential (FRP) ..............81
12.5.2.
Collection of Pregnancy Information ............................................82
12.6.
Appendix 6: Protocol Changes....................................................................84
12.6.1.
Protocol Amendment 01 ..............................................................84
12.6.2.
Protocol Amendment 2 ................................................................89


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1.
PROTOCOL SYNOPSIS FOR STUDY 203167
Rationale
This is the first study with GSK2982772, a receptor-interacting protein-1 (RIP1) kinase 
inhibitor, in subjects with active, plaque-type psoriasis. 
The primary objective will be to investigate the safety and tolerability of repeat oral doses 
of GSK2982772 (60 mg twice daily and 60 mg three times daily for 84 days). In addition 
a number of experimental and clinical endpoints will be employed to obtain information 
on the pharmacokinetics, pharmacodynamics, and efficacy in subjects with active plaque-
type psoriasis (PsO).  Although no formal hypothesis will be tested, these endpoints will 
enable a fuller understanding of the mechanism of action and potential for clinical 
efficacy of GSK2982772 in PsO, by making full use of the information obtained from 
each subject enrolled.
Objective(s)/Endpoint(s)
Objectives
Endpoints
Primary

To investigate the safety and tolerability of 
60 mg twice daily doses and 60 mg three 
times daily doses of GSK2982772 in 
subjects with active plaque-type psoriasis.

Adverse events

Clinical laboratory values (clinical chemistry, 
haematology and urinalysis)

Vital sign measurements (blood pressure, 
heart rate, respiratory rate and body 
temperature)

12-Lead ECG monitoring
Secondary

To investigate the pharmacokinetics of 
GSK2982772 in blood following 60 mg 
twice daily doses and 60 mg three times 
daily doses of GSK2982772 in subjects 
with active plaque-type psoriasis.

Pre-dose plasma concentrations of 
GSK2982772 at Days 43 (Week 6) and 85 
(Week 12).

Post-dose plasma concentrations of 
GSK2982772 on Days 1 and 43 (Week 6) 
at 1, 2, 4 and 6 hours post dose.

To investigate the effect of 60 mg twice 
daily doses and 60 mg three times daily 
doses of GSK2982772 on inflammatory 
biomarkers in skin biopsies from psoriatic 
skin lesions in subjects with active plaque-
type psoriasis.

Change from baseline in histopathological 
scoring of psoriatic lesional biopsies which 
may include, but are not limited to the 
following as data permit:  K16, 
CD3/CD11c, CD161, elastase positive 
dermal cells and epidermal thickness.  

mRNA expression of inflammatory gene 
transcripts which may include, but are not 
limited to the following as data permit:  IL-
4, IL-10, IL-17, IL-21, IL-22, IL-23, TNF and 
IFNγ on Days 1 (Week 0) and 43 (Week 6).


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Objectives
Endpoints

To investigate the effect of 60 mg twice 
daily doses and 60 mg three times daily 
doses of GSK2982772 on disease activity 
in subjects with active plaque-type 
psoriasis

Percentage change from baseline and 
actual Psoriatic Lesion Severity Sum 
(PLSS) scores in the index lesion.
Exploratory

To investigate the effect of 60 mg twice 
daily doses and 60 mg three times daily 
doses of GSK2982772 on disease activity 
in subjects with active plaque-type 
psoriasis

Change from baseline in Psoriasis Area 
Severity Index (PASI) scores.

The proportion of subjects who achieve 
PASI ≥ 50%, 75%, and 90% improvement 
from baseline score.

Change from baseline and actual
Physician Global Assessment (PGA).

The proportion of subjects who achieve 
“clear” (0) or “almost clear” (1) on (PGA).

Change from baseline in body surface area 
(BSA).

To investigate the effect of 60 mg twice 
daily doses and 60 mg three times daily 
doses of GSK2982772 on inflammatory 
biomarkers in the blood of subjects with 
active plaque-type psoriasis.

Change from baseline in blood 
inflammatory markers which may include, 
but are not limited to the following as data 
permit:  CRP, VEGF, S100A8, S100A9, IL-
17, IL-22, and TNF.

To investigate the effect of 60 mg twice 
daily doses and 60 mg three times daily 
doses of GSK2982772 on transcriptome 
profiling of both blood and skin of subjects 
with active plaque-type psoriasis.

Transcriptomic analysis of mRNA isolated 
from blood and skin at Day 1 (Week 0) and 
Day 43 (Week 6).

To investigate pathway and target 
engagement following 60 mg twice daily 
doses and 60 mg three times daily doses
of GSK2982772 in blood and skin biopsy 
tissue in subjects with active plaque-type 
psoriasis.

Pharmacology biomarker endpoints may 
include, but are not limited to the following 
Days 1 (Week 0), 43 (Week 6) and 85 
(Week 12),  as data permit:
o
Target Engagement Assay 
RiP1 (TEAR1) in blood and 
skin.
o
Total or phosphorylated RIP1, 
MLKL, and RIP3, cleaved and 
total caspase 3 and caspase 8
signatures in skin.

To investigate the concentration of 
GSK2982772 in the skin of subjects with 
active plaque-type psoriasis after 60 mg 

Pre-dose GSK2982772 concentrations in 
skin biopsies at Days 1 (Week 0) and 43 


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Objectives
Endpoints
twice daily doses and 60 mg three times 
daily doses of GSK2982772.
(Week 6), as data permit.

To investigate the effect of 60 mg twice 
daily doses and 60 mg three times daily 
doses of GSK2982772 on the patient 
reported outcomes (PROs) of subjects with 
active plaque-type psoriasis.

Change from baseline in Dermatology Life 
Quality Index (DLQI) score.

Change from baseline and actual Visual 
Analogue Scale (VAS) itch score.
Overall Design
This is a multicentre, randomised, double-blind (sponsor-unblinded), placebo-controlled, 
repeat dose study to investigate the safety and tolerability, PK, PD, and preliminary 
efficacy of GSK2982772 in subjects with active plaque-type psoriasis.  The study design 
schematic is depicted in Figure 1 below.  There will be two cohorts of subjects.  Cohort 1 
will receive either GSK2982772 60 mg or placebo orally twice daily and Cohort 2 will 
receive either GSK2982772 60 mg or placebo orally three times daily.
Figure 1
Study Overview
Cohort 1
Cohort 2
Safety assessments, PK samples in skin and blood, PASI,
PLSS, DLQI, Itch VAS, PGA assessments, Target 
engagement, inflammatory biomarkers in skin and blood


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Treatment Arms and Duration
Each subject will participate in the study for approximately 20 weeks.  This includes a 
screening period up to 30 days, an 84 day (12 week) treatment period, and a 28 day
follow-up visit after the last dose.
Subjects will attend the clinical site to be consented and if eligible for the study,
screening assessments will be completed.  Subjects will then enter the Treatment Period 
and be dosed (Day 1) within 30 days of the screening visit.
Punch skin biopsies will be performed on all subjects.  Two (2) target lesions will be 
identified (3cm x3 cm) on the trunk or extremities.  One target lesion will be used for 
lesion biopsy and the other for PLSS at baseline (pre-dose Day 1) and Day 43 (Week 6). 
A third biopsy will be performed at baseline only (pre-dose Day 1) from non-lesional 
skin.
The Post-Treatment Period is 28 days (4 weeks) long.
In Cohort 1 subjects who have completed screening assessments and are eligible will be 
randomised in a 2:1 ratio (active to placebo) to one of the following treatments:
60 mg GSK2982772 twice daily (BID) 
Placebo twice daily (BID) 
In Cohort 2 subjects who have completed screening assessments and are eligible will be 
randomised in a 3:1 ratio (active to placebo) to one of the following treatments:
60 mg GSK2982772 three times daily (TID) 
Placebo three times daily (TID) 
Type and Number of Subjects
In Cohort 1, a sufficient number of subjects will be screened so that approximately 30 
subjects with active PsO are randomised.  Additional or replacement subjects may be 
randomised (up to a maximum of 36) into the study at the discretion of the Sponsor, to 
ensure that approximately 24 evaluable subjects complete the study.
In Cohort 2, a sufficient number of subjects will be screened so that approximately 24 
subjects with active PsO are randomised.  Additional or replacement subjects may be 
randomised (up to a maximum of 32) into the study at the discretion of the Sponsor, to 
ensure that approximately 20 evaluable subjects complete the study. 
For both cohorts, a subject is considered evaluable if they have completed at least one 
post-treatment biopsy.


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Analysis
The safety and tolerability of GSK2982772 following 12 weeks of treatment will be 
based on the review and displays of adverse events, clinical laboratory values, vital sign 
measurements and 12-lead ECG monitoring.
An ongoing review of available efficacy, pharmacodynamic and mechanistic endpoints 
will be conducted during the study by a Data Review Committee (DRC), consisting of a 
limited number of GSK individuals, some of whom are also members of the GSK study 
team who are not involved in the day-to-day running of the study.  The primary purpose 
of these reviews will be to monitor target engagement, inflammatory markers and the 
index lesion PLSS for internal decision making. A data review charter will outline in 
detail the activities of this review and how the integrity of the study will be maintained.  
An interim analysis will be conducted after the completion of Cohort 1.
Comparisons between treatment groups on any changes observed will be conducted for 
the secondary endpoints if deemed appropriate, e.g. changes in the mean target 
engagement, changes in inflammatory markers and percentage change in index lesion 
PLSS will be statistically analyzed using a repeated measures mixed effects model 
(MMRM) comparing each GSK2982772 arm with placebo at each time point.  
The relationship between each of the mechanistic endpoints and also with the clinical 
endpoints may also be graphically presented and analysed using an appropriate statistical 
model identifying any trends. The model will determine whether the mechanistic effect 
significantly explains or predicts the effect on the other mechanistic or clinical endpoints 
(e.g., index lesion PLSS score).  In addition, based on the data that we observe in the 
study, probabilities of success will be determined, where the definition of success will be 
dependent on the endpoint. For example, what is the probability that we would observe a 
certain percentage change in PLSS (i.e., comparatory rate), based on the data that we 
have observed in the study.  Further details regarding the statistical analysis will be 
outlined in the Reporting and Analysis Plan (RAP).
2.
INTRODUCTION
2.1.
Study Rationale
This is the first study with GSK2982772, a receptor-interacting protein-1 (RIP1) kinase 
inhibitor, in subjects with active plaque-type psoriasis. 
The primary objective will be to investigate the safety and tolerability of repeat oral doses 
of GSK2982772 (60 mg twice daily and 60 mg three times daily for 84 days). In addition, 
a number of experimental and clinical endpoints will be employed to obtain information 
on the pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy in 
subjects with active PsO.  Although no formal hypothesis will be tested, these endpoints 
will enable a fuller understanding of the mechanism of action and potential for clinical 
efficacy of GSK2982772 in PsO.


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2.2.
Brief Background
GSK2982772 is a first-in-class, highly selective, receptor-interacting protein 1 kinase 
(RIP1) inhibitor being developed for the treatment of inflammatory disease conditions.
RIP1 is a member of the receptor-interacting Serine/Threonine kinase family containing 
an amino-terminal kinase domain, an intermediate domain and a carboxy-terminal death 
domain.  RIP1 is a key signalling node which plays an essential role in inflammation and 
cell death in response to signals including TNF family cytokines, ligands for 
TLR3/TLR4, sensors of viral infection, and interferons [Ofengeim, 2013].  Through tight 
regulation by ubiquitylation, deubiquitylation and interaction with its receptors, RIP1 has 
dual roles as a kinase and a scaffolding protein, and serves as an upstream checkpoint for 
both cell death and survival [Ofengeim, 2013]. Detailed understanding of RIP1 kinase 
function has not been fully elucidated, but it is known that RIP1 exerts it signalling 
functions through both its catalytic kinase activity and by acting as a scaffolding protein 
for signalling complexes.  Recent work has demonstrated that RIP1 catalytic kinase 
activity can regulate TNF-mediated necroptosis [Ofengeim, 2013] and noncanonical 
apoptosis [Wang, 2008, Dondelinger, 2013]. In addition, the production of certain 
inflammatory cytokines can be regulated by RIP1 kinase activity [GlaxoSmithKline 
Document Number 2014N204126_01].  In contrast, RIP1’s scaffolding function acts to 
facilitate other immune processes including TNF mediated classical apoptosis and NF-
kB-signalling [Ofengeim, 2013, Humphries, 2015].  With this, an inhibitor of RIP1
kinase activity with GSK2982772 may fill a unique niche in the treatment of 
inflammatory conditions through multiple mechanisms, including inhibition of 
inflammation-induced cell death (necroptosis and apoptosis) and inhibition of the 
production of certain pro-inflammatory cytokines.
Plaque psoriasis (PsO) is a chronic relapsing inflammatory skin disease that is 
characterized by keratinocyte hyperproliferation and epidermal hyperplasia. In 
preclinical models, blockade of NFB or apoptosis pathways results in spontaneous TNF-
dependent dermal inflammation that resembles human PsO in murine models 
[Bonnet, 2011].  In contrast to UC, overt cellular necrosis is not a histologic feature of 
PsO; however, innate immune responses to DAMPs have been reported in preclinical 
PsO models [Chen, 2013].  Like Inflammatory Bowel Disease (IBD) and other chronic 
inflammatory diseases, its pathobiology is incompletely understood.  However, a number 
of inflammatory cytokines, including TNF, IL12/23, and IL17 family members, are 
thought to play a role in the pathogenesis of PsO, as evidenced by the clinical successes 
of several biologics targeting these signalling pathways.
Standard treatment generally requires long-term use of topical therapies, followed by 
systemic immunosuppressant therapies, Psoralen and ultraviolet A (PUVA), and 
Ultraviolet B (UVB) therapies to achieve and maintain adequate disease control. Novel 
oral therapies for PsO are becoming more widely used for moderate to severe disease, but 
may be limited by efficacy (apremilast) and safety/tolerability profiles (tofacitinib). 
Biologic therapies targeting TNF or Th17/IL22/IL23 pathways have demonstrated 
significant clinical efficacy for those patients who have had inadequate response to 
standard topical, UV, and/or oral therapy, but all biologics carry risks for loss of 
response, side effects, and anti-drug antibodies.  There remains a high unmet need for 


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novel oral therapies which will achieve maximal sustained clearance of skin lesions and 
improvement in quality of life, balanced by favourable safety and tolerability profiles.
3.
OBJECTIVE(S) AND ENDPOINT(S)
Objectives
Endpoints
Primary

To investigate the safety and tolerability of
60 mg twice daily doses, and 60 mg three 
times daily doses, of GSK2982772 in 
subjects with active plaque-type psoriasis.

Adverse events

Clinical laboratory values (clinical chemistry, 
haematology and urinalysis)

Vital sign measurements (blood pressure, 
heart rate, respiratory rate and body 
temperature)

12-Lead ECG monitoring
Secondary

To investigate the pharmacokinetics of 
GSK2982772 in blood following 60 mg 
twice daily doses, and 60 mg three times 
daily doses, of GSK2982772 in subjects 
with active plaque-type psoriasis.

Pre-dose plasma concentrations of 
GSK2982772 at Days 43 (Week 6) and 85 
(Week 12).

Post-dose plasma concentrations of 
GSK2982772 on Days 1 and 43 (Week 6) 
at 1, 2, 4 and 6 hours post dose.

To investigate the effect of 60 mg twice 
daily doses, and 60 mg three times daily 
doses, of GSK2982772 on inflammatory 
biomarkers in skin biopsies from psoriatic 
skin lesions in subjects with active plaque-
type psoriasis.

Change from baseline in histopathological 
scoring of psoriatic lesional biopsies which 
may include, but are not limited to the 
following as data permit:  K16, 
CD3/CD11c, CD161, elastase positive 
dermal cells and epidermal thickness.  

mRNA expression of inflammatory gene 
transcripts which may include, but are not 
limited to the following as data permit:  IL-
4, IL-10, IL-17, IL-21, IL-22, IL-23, TNF and 
IFNγ on Days 1 (Week 0) and 43 (Week 6).

To investigate the effect of 60 mg twice 
daily doses, and 60 mg three times daily 
doses, of GSK2982772 on disease activity 
in subjects with active plaque-type 
psoriasis

Percentage change from baseline and 
actual Psoriatic Lesion Severity Sum 
(PLSS) scores in the index lesion.
Exploratory 

To investigate the effect of 60 mg twice 
daily doses, and 60 mg three times daily 
doses, of GSK2982772 on disease activity 
in subjects with active plaque-type 
psoriasis

Change from baseline in Psoriasis Area 
Severity Index (PASI) scores.

The proportion of subjects who achieve 
PASI ≥ 50%, 75%, and 90% improvement 
from baseline score.


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Objectives
Endpoints

Change from baseline and actual
Physician Global Assessment (PGA).

The proportion of subjects who achieve 
“clear” (0) or “almost clear” (1) on PGA.

Change from baseline in body surface area 
(BSA).

To investigate the effect of 60 mg twice 
daily doses, and 60 mg three times daily 
doses, of GSK2982772 on inflammatory 
biomarkers in the blood of subjects with 
active plaque-type psoriasis.

Change from baseline in blood 
inflammatory markers which may include, 
but are not limited to the following as data 
permit:  CRP, VEGF, S100A8, S100A9, IL-
17, IL-22, and TNF.

To investigate the effect of 60 mg twice 
daily doses, and 60 mg three times daily 
doses, of GSK2982772 on transcriptome 
profiling of both blood and skin of subjects 
with active plaque-type psoriasis.

Transcriptomic analysis of mRNA isolated 
from blood and skin at Day 1 (Week 0) and 
Day 43 (Week 6).

To investigate pathway and target 
engagement following 60 mg twice daily 
doses, and 60 mg three times daily doses,
of GSK2982772 in blood and skin biopsy 
tissue in subjects with active plaque-type 
psoriasis.

Pharmacology biomarker endpoints may 
include, but are not limited to the following 
Days 1 (Week 0), 43 (Week 6) and 85 
(Week 12),  as data permit:
o
Target Engagement Assay 
RIP1 (TEAR1) in blood and 
skin.
o
Total or phosphorylated RIP1, 
MLKL, and RIP3, cleaved and 
total caspase 3 and caspase 8
signatures in skin.

To investigate the concentration of 
GSK2982772 in the skin of subjects with 
active plaque-type psoriasis after 60 mg 
twice daily doses, and 60 mg three times 
daily doses of GSK2982772.

Pre-dose GSK2982772 concentrations in 
skin biopsies at Days 1 (Week 0) and 43 
(Week 6), as data permit.

To investigate the effect of 60 mg twice 
daily doses, and 60 mg three times daily 
doses, of GSK2982772 on the patient 
reported outcomes (PROs) of subjects with 
active plaque-type psoriasis.

Change from baseline in Dermatology Life 
Quality Index (DLQI) score.

Change from baseline and actual Visual 
Analogue Scale (VAS) itch score.


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4.
STUDY DESIGN
4.1.
Overall Design
This is a multicentre, randomised, double-blind (sponsor-unblinded), placebo-controlled, 
repeat dose study to investigate the safety and tolerability, PK, PD, and preliminary 
efficacy of GSK2982772 in subjects with active plaque-type psoriasis.  The study design 
schematic is depicted in Figure 2 below.  There will be two cohorts of subjects.  Cohort 1 
will receive either GSK2982772 60 mg or placebo orally twice daily and Cohort 2 will 
receive either GSK2982772 60 mg or placebo orally three times daily.
Figure 2
Study Overview
Cohort 1
Cohort 2
Safety assessments, PK samples in skin and blood, PASI,
PLSS, DLQI, Itch VAS, PGA assessments, Target 
engagement, inflammatory biomarkers in skin and blood
4.2.
Treatment Arms and Duration
It is anticipated that the total duration of participation in the study will be approximately 
20 weeks from screening to the last study visit.


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4.2.1.
Screening
Subjects will attend the clinical unit for a screening visit and if eligible and consenting 
may enter the Treatment Period of the study.
4.2.2.
Treatment Period
In Cohort 1, subjects will be randomly assigned to either GSK2982772 60mg or placebo 
orally twice daily (approximately 12 hours apart) for 84 days.  In Cohort 2 subjects will 
be randomly assigned to either GSK2982772 60 mg or placebo orally three times daily 
(approximately 8 hours apart) for 84 days.  Further guidance and information for study 
treatment and dosing are provided in the Study Reference Manual (SRM).  
Punch skin biopsies will be performed on all subjects.  Two (2) target lesions will be 
identified (3 cm by 3 cm) on the trunk or extremities.  One target lesion will be used for 
lesion biopsy and the other for PLSS at baseline (pre-dose Day 1) and Day 43 (Week 6). 
A third biopsy will be performed at baseline only (pre-dose Day 1) from non-lesional 
skin. Photographs will be taken by the investigator or designee to illustrate any visible 
changes in psoriasis target lesions during the course of the study.
During the 12 week treatment period, subjects will return to the clinical site for visits on 
Days 8, 15, 29 and 43, and then every 2 weeks thereafter until Day 85.  At specific visits, 
subjects must not take study treatment prior to their scheduled visit (see Section 7.1).  On 
Days 22, 36, 50, 64 and 78 each subject will be contacted by telephone and asked about 
their general health. Subjects will be given a diary card at each visit, in which will they 
will be instructed to record their daily study medication and concomitant medication 
administration and any adverse events while away from the clinical site.
4.2.3.
Follow-up Period
After the Treatment Period, the subject enters the Follow-up Period for 28 days, to 
complete follow-up assessments per the Time and Events table (Section 7.1).
4.3.
Type and Number of Subjects
In Cohort 1, a sufficient number of subjects will be screened so that approximately 30 
subjects with active PsO are randomised.  Additional or replacement subjects may be 
randomised (up to a maximum of 36) into the study at the discretion of the Sponsor, to 
ensure that approximately 24 evaluable subjects complete the study.
In Cohort 2, a sufficient number of subjects will be screened so that approximately 24 
subjects with active PsO are randomised.  Additional or replacement subjects may be 
randomised (up to a maximum of 32) into the study at the discretion of the Sponsor, to 
ensure that approximately 20 evaluable subjects complete the study.
For both cohorts, a subject is considered evaluable if they have completed at least one 
post-treatment biopsy.


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4.4.
Design Justification
As this is the first trial of GSK2982772 in subjects with PsO, the primary endpoint is the 
safety and tolerability of GSK2982772.  In addition, this study will include assessments 
of target engagement and downstream pathway PD effects of GSK2982772, to 
understand whether GSK2982772 is inhibiting the pathway of interest in this disease.
Skin biopsies are being taken at pre-dose on Days 1 (Week 0) and 43 (Week 6) to 
measure PK, target and pathway engagement and effects on inflammatory markers in the 
skin.  It is felt that six weeks of treatment allows adequate time to assess histological 
improvement in the skin.
The 12 week duration of treatment is based on review of previous proof of mechanism 
and proof of concept studies in PsO and is limited by the supporting 13 week toxicology 
studies. It is expected that an effective therapy should cause group level changes in the 
mechanistic parameters by the 12 week time point.  
In Cohort 1 the subjects will be randomised in a 2:1 ratio to GSK2982772 60 mg BID 
and placebo respectively.  In Cohort 2 the subjects will be randomised in a 3:1 ratio to 
GSK2982772 60 mg TID and placebo respectively. The primary objective of this study is 
safety and tolerability and assessment of this is most valuable in a placebo controlled, 
blinded study. The placebo group was deemed necessary as autoimmune diseases 
naturally fluctuate in severity.  However, the size of the placebo group has been kept to a 
minimum.  Subjects will not be allowed to continue standard of care therapy including 
topical (not permitted on biopsy areas), oral and biologic therapy.  A washout period of 
specific therapies can be found in Section 6.11.
4.5.
Dose Justification
The initial selection of the 60 mg BID dose being tested in this study is based on the 
safety, PK, and PD data from the GSK2982772 First Time in Human (FTiH) study, 
200975.  GSK2982772 administered at 60 mg BID for 14 days was well tolerated and no 
safety concerns were identified. A BID dosing regimen was initially selected over a QD 
dosing regimen due to the short half-life of GSK2982772 in humans (~2 hours).  Based 
on preliminary PK/PD modelling of ex-vivo RIP1 target engagement and GSK2982772 
concentrations from the multiple dose ascending part of Study 200975, a 60 mg BID dose 
was predicted to have on average 95% RIP1 target engagement in blood and 
approximately 90% of subjects are predicted to have >90% RIP1 target engagement in 
blood at Cmin using a novel in-house ex-vivo PD/target engagement assay based solely on 
the TNF pathway which is believed to be a key component of the RIP1 pathway.  
Assuming a skin: blood ratio of 0.4 (as observed in the rat), the average RIP1 target 
engagement in skin is predicted to be 92%.  At Cmin, 44% of subjects are predicted to 
have >90% RIP1 target engagement in the skin and 90% of subjects are predicted to have 
>80% RIP1 target engagement in the skin.
However, based on final PK/PD modelling from the full repeat dose part of the Study 
200975 (up to 120 mg BID), a 60 mg BID dose is now predicted to have on average 99% 
RIP1 target engagement in blood and approximately 90% of subjects will have >85% 
target engagement at Cmin.  In skin, assuming the same skin: blood ratio of 0.4 as noted 


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above, the average RIP target engagement at 60 mg BID in skin is predicted to be 96%.  
At Cmin, 43% of subjects are predicted to have >90% RIP1 target engagement in the skin 
and 90% of subjects are predicted to have >70% RIP1 target engagement in the skin. 
In review of this final FTiH data, it is believed that the Cmin target exposure may not be 
achieved with a 60mg BID dosing regimen.  The Cmin values at 60 mg TID are predicted 
to be approximately 3.5 fold higher than for 60 mg BID.  Therefore, a 60 mg TID cohort 
is now being proposed.
Using the final PK/PD, a 60 mg TID dose is predicted to have on average 99% RIP1 
target engagement in blood and approximately 90% of subjects will have  > 96% target 
engagement at Cmin.  In skin, the average RIP target engagement at 60 mg TID is 
predicted to be 98%.  At Cmin, 91% of subjects are predicted to have >90% RIP1 target 
engagement in the skin and 90% of subjects are predicted to have >91% RIP1 target 
engagement in the skin.
In addition, because of the short half-life, a modified release formulation is now being 
developed with the aim to provide a once daily dosing regimen.  By increasing the 
frequency of dosing to three times daily (TID) with the current immediate release 
formulation, this will more closely match the PK, safety and efficacy profile of a 
preferred once daily modified release formulation.
The safety of increasing the dose frequency to 60 mg TID is justified based on 
nonclinical safety findings to date with GSK2982772. It is anticipated that a human dose 
of 60 mg TID (180 mg/day) will produce AUC(0-24) and Cmax values of approximately 9.9 
ug.h/mL and 0.8 ug/mL, respectively, which are approximately 1/5th and 1/15th of the 
gender-averaged AUC (48.4 ug.h/mL) and Cmax (12.3 ug/mL) achieved in the 13 week 
monkey study at the no adverse effect level (NOAEL) dose of 30 mg/kg/day. Please see 
GSK2982772 IB [GlaxoSmithKline Document Number 2014N204126_01].
Up to 03 Apr 2017, a total of approximately 93 subjects across 4 clinical studies have 
been randomised to receive GSK2982772. In Study 200975, GSK2982772 administered 
up to 120 mg BID for 14 days and was well tolerated and no safety concerns were 
identified. A total of 9 subjects had received 120 mg BID in that study.  Please see 
GSK2982772 IB [GlaxoSmithKline Document Number 2014N204126_01]. In this 
current study, 203167, approximately 22 of 33 subjects have been randomised to 
GSK2982772 60 mg BID. In other Phase 2a studies in Rheumatoid Arthritis [(RA); Study 
203168] and Ulcerative Colitis [(UC); Study 202152], a total of 4 subjects have been 
randomised to GSK2982772 60 mg BID. GSK2982772 was well tolerated and no drug-
related SAEs have been reported.  There was a death of a 19 year old male subject in this 
current study due to an accidental overdose with 3,4-methylenedioxy-methamphetamine 
(MDMA) that was not considered drug related by the Principal Investigator (PI).  
The proposed 60 mg TID dose regimen is predicted to have mean Cmax (0.80 µg/mL) and 
AUC(0-24) (9.9 µg.hr/mL ) that are approximately 10% and 50% higher, respectively than 
for 60 mg BID (0.70 µg/mL and 6.6 µg.hr/mL).  This exposure is well within the 
observed Cmax and AUC(0-24) values at 120 mg BID in Study 200975.


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4.6.
Benefit: Risk Assessment
Summaries of findings from both clinical and non-clinical studies conducted with 
GSK2982772 can be found in the Investigator’s Brochure.  The following section 
outlines the risk assessment and mitigation strategy for this protocol:  


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4.6.1.
Risk Assessment
Potential Risk of 
Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Investigational Product (IP) GSK2982772
Central Nervous 
System (CNS)
effects
Non-clinical data: 
In the 4-week GLP toxicology study, CNS findings were observed in 4/12 
monkeys which were administered 100 or 300 mg/kg/day.  CNS findings 
included uncoordination, irregular gait, trembling, hunched appearance, and 
decreased activity. The clinical relevance of these findings in humans is not 
known.  The NOAEL for this study was determined at 10 mg/kg/day.
In the 13-week GLP toxicology study, there were no CNS findings observed 
in monkeys administered 10, 30 or 100 mg/kg/day.  The NOAEL for this 
study was determined at 30 mg/kg/day.
Clinical data:
A First Time in Human (FTiH) study with single ascending and multiple 
ascending dose study has been performed in 67 healthy male volunteers to 
date (see Investigators Brochure (IB) [GlaxoSmithKline Document Number 
2014N204126_01].  No drug-associated CNS adverse events were identified 
and no Serious Adverse Effects (SAEs) were reported.
Subject Selection:

Subjects with known history of significant neurologic disorders
including but not limited to progressive multiple sclerosis (MS), 
Amyotrophic lateral sclerosis (ALS), Alzheimer’s and dementia will 
be excluded.

Individuals with potentially increased susceptibility for neurologic 
effects will be excluded based on medical history at screening.
Subject Monitoring:

Subjects will be monitored for standard CNS-related adverse 
events.
Immunosuppression
The possibility of immunosuppression, including an increase in the frequency 
and/or severity of infection, may result from the intended pharmacologic 
effect of GSK2982772.  This may be enhanced in subjects taking other 
immunomodulating drugs or corticosteroids.
Clinical data:
In the FTiH study, no SAEs were reported.  One subject experienced an 
Adverse Effect (AE) herpes zoster approximately 27 days after receiving his 
last dose with GSK2982772 or placebo.  The blinded investigator determined 
this to be potentially drug-related.
Subject Selection:

Subjects with recurrent, chronic or active infections will be excluded 
from the study.

Subjects will be screened for TB, HIV, Hepatitis B and C, and 
excluded from the study if positive.

Investigators are expected to follow local and/or national guidelines 
with respect to vaccinations, including against influenza and 
pneumococcus, in subjects with PsO.


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Potential Risk of 
Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Subject Monitoring:

Subjects will be monitored for signs of infection.

See Individual Stopping Criteria for atypical or opportunistic 
infections (Section 5.4.1).
Vaccinations
There is a theoretical risk that GSK2982772 could decrease an individual’s 
immune response to vaccines or allow symptoms to develop following 
vaccination with a live vaccine when administered while on therapy.
Subject Selection:

Attenuated or live vaccines should not be administered to subjects 
from 30 days prior to the first dose of GSK2982772, during the 
study and for 5 half-lives plus 30 days (total 32 days) after
GSK2982772 is discontinued.

If indicated, non-live vaccines (e.g. inactivated influenza vaccines) 
may be administered while receiving GSK2982772 based on a 
treating physician assessment of the benefit: risk (e.g., risk of 
theoretical decreased responsiveness). 

Investigators will be expected to have followed local and/or national 
guidelines with respect to vaccinations, including against influenza 
and pneumococcus, in subjects with PsO.
Respiratory
Non-clinical data:
In the single dose Safety Cardiovascular and Respiratory Study in monkeys, 
a decrease in minute volume (MV) and respiratory rate was observed at all 
doses (10, 100, and 300 mg/kg).  These findings were noted to be reversible 
and mild in severity.  
In a 14 day repeat oral dose respiratory function study, no respiratory effects 
on respiratory function (e.g., tidal volume, minute volume or respiratory rate) 
were observed at doses of 1 or 10 mg/kg/day. See Investigator’s Brochure 
for GSK2982772 [GlaxoSmithKline Document Number 2014N204126_01].
Clinical data:
In the FTiH study, repeat doses of GSK2982772 were administered x 14 
days in 36 healthy male volunteers. Extensive respiratory monitoring with 
end-tidal CO2 (ETCO2), oxygen saturation (SpO2) and nocturnal respiratory 
Subject Monitoring:

Subjects should be monitored for standard respiratory-related 
adverse events.

Vital signs will be monitored during study visits.


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Potential Risk of 
Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
rate monitoring was performed.   No SAEs occurred, and no drug-associated 
respiratory-related adverse events were identified.
CNS/Suicidality
GSK2982772 is considered to be a CNS-active drug based on pre-clinical 
studies.
Clinical data:
In the FTiH study, there have been some reports of lethargy, abnormal 
dreams, and depressed mood.  No events of suicidal ideation or behaviour 
or changes in behaviour were reported.    
Subject selection:

Subjects with a current history of Suicidal Ideation Behaviour (SIB) 
as measured using the Columbia Suicide Severity Rating Scale (C-
SSRS) or a history of attempted suicide will be excluded from the 
study.
Subject Monitoring:

Subjects should be monitored appropriately and observed closely 
for suicidal ideation and behaviour or any other unusual changes in 
behaviour.

Baseline and treatment emergent assessment of suicidality will be 
conducted by trained site personnel using the Columbia Suicide 
Severity Rating Scale (C-SSRS) in all subjects.  See Section 7.3.7.
Reproductive 
toxicity
Non-clinical data:
In the rat embryofetal development study, was no maternal or developmental 
toxicity at doses 200 mg/kg/day.
In the rabbit embryofetal development study, GSK2982772 was administered 
at doses of 0, 10, 100, 300 or 600 mg/kg/day on gestation day 7 to 19.  No 
developmental toxicity was evident at doses up to 300 mg/kg/day.
Subject selection:

Male and female subjects of childbearing potential will be included 
in this study only if they agree to use highly effective methods of 
contraception and avoid conception for defined periods of time 
before first administration of study drug until 30 days (females) and 
90 days (males) after the last administration of study drug 
(Appendix 5).

Females of childbearing potential will undergo serum pregnancy 
test at screening and then urine pregnancy testing at regular 
intervals during the study. 

Pregnant and lactating females are not eligible for inclusion in the 
study.


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Potential Risk of 
Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Withdrawal criteria:

If a female subject should become pregnant during the study, study 
medication should be discontinued.  The subject will be followed to 
determine the outcome of the pregnancy.  Any pregnancy 
complication or elective termination of a pregnancy will be reported 
as an AE or SAE.
Drug Interaction
Non-clinical data:
In vitro studies with GSK2982772 assessing potential drug-drug interactions 
with Cytochrome P450 3A4 (CYP3A4) substrates and P-glycoprotein (Pgp) 
inhibitors were completed.  To date, formal drug interaction studies in 
humans have not been performed with GSK2982772. 
There is a low risk that GSK2982772 could be an inducer of CYP3A4 and 
therefore may lower circulating levels of concomitant medications that are 
metabolised by CYP3A4 when co administered with GSK2982772.
GSK2982772 is a Pgp substrate and therefore co administration with 
concomitant medications that are Pgp inhibitors could increase circulating 
levels of GSK2982772.
See Section 4.3.6 of GSK2982772 IB [GlaxoSmithKline Document Number 
2014N204126_01].
Subject Selections:

Subjects who are taking concomitant medications known to inhibit 
Pgp or are CYP3A4 narrow therapeutic index (NTI) substrates will 
be excluded from the study.  See Section 6.11.2 for a 
comprehensive list of medications.
Subject Monitoring:

Subjects’ concomitant medication usage will be reviewed prior to 
inclusion and monitored throughout the study.
Subjects should be monitored throughout the study for potential effects 
of interaction between GSK2982772 and other concomitant medications.
Study Procedures
Punch skin lesion
biopsies
Potential risks of the procedure include discomfort, infection or bleeding.
Subject selection:

Subjects with history of hypertrophic scarring or keloid, or known 
allergy to lidocaine or other local anaesthetics will not be included 
in the study.

Subjects with a platelet count <100x 109/L will be excluded from 
participation.


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Potential Risk of 
Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Subject management:

A local anaesthetic will be administered before each skin biopsy is 
taken (as per local practice) to reduce the risk of pain.  The biopsy 
procedure will be done only by experienced personnel to reduce 
the risk of bleeding and scarring.  Aseptic technique will be utilized 
to reduce the risk of infection.

The risk of infection, although low given the low invasiveness of the 
procedure, will be reduced by dressing the site after biopsy.  
Subjects will be advised to keep the site covered and dry for 24-48 
hours before leaving open to the air.  Subjects will be instructed as 
to the signs and symptoms of infection, and to contact site 
personnel should they develop.  This information will also be 
contained in the patient information leaflet.

Biopsy site healing will be monitored during the study as part of AE 
review.


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4.6.2.
Benefit Assessment
There are additional treatment options available for subjects who have an inadequate 
response to current therapies for PsO.  It is possible that treatment with GSK2982772 
may be effective in the treatment of PsO, as the FTiH study demonstrated that the drug 
engaged with the target and produced ex vivo PD effects in RIP1-dependent cytokines 
MIP1and MIP1[GlaxoSmithKline Document Number 2014N204126_01].  There will 
be limited direct benefit to the subject for participating in this trial.  However, subjects 
will indirectly benefit through their contribution to the process of developing new 
therapies in an area of unmet need.  
4.6.3.
Overall Benefit: Risk Conclusion
Taking into account the measures taken to minimize risk to subjects participating in this 
study, the potential risks identified in association with GSK2982772 are justified by the 
anticipated benefits that may be afforded to subjects with PsO by contributing to the 
understanding of the disease and the development of new therapies for patients with these 
conditions in the future.  
5.
SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA
Specific information regarding warnings, precautions, contraindications, adverse events, 
and other pertinent information on the GSK investigational product or other study 
treatment that may impact subject eligibility is provided in the IB [GlaxoSmithKline 
Document Number 2014N204126_01].
In addition, investigators are expected to follow local and/or national guidelines with 
respect to vaccinations, including against influenza and pneumococcus, in subjects with 
PsO.
Deviations from inclusion and exclusion criteria are not allowed because they can 
potentially jeopardize the scientific integrity of the study, regulatory acceptability or 
subject safety. Therefore, adherence to the criteria as specified in the protocol is essential.
5.1.
Inclusion Criteria
For both cohorts, a subject will be eligible for inclusion in this study only if all of the 
following criteria apply:
AGE
1. Between 18 and 75 years of age inclusive, at the time of signing the informed 
consent.


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TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY
2. Subjects that do not have any medical conditions, other than active plaque-type 
psoriasis, that in the opinion of the Investigator put the subject at unacceptable risk or 
interfere with study assessments or integrity of the data. All medical conditions must 
be stable for the duration of the study.
3. Presence of active chronic plaque-type psoriasis as determined by the Investigator for 
at least 6 months (confirmed by the subject or medical record) before first dose of 
study treatment (Day 1).  
4. Subject has psoriasis plaques involving Body Surface Area (BSA) ≥ 3% assessed at 
Screening and before dosing on Day 1.
5. Physician Global Assessment (PGA) ≥3.
6. Subject must agree to avoid prolonged exposure to natural sunlight, tanning beds or 
phototherapy devices for the duration of the study. See Section 6.11.2.
7. Subject has at least two stable plaques assessed at Screening and before dosing on
Day 1.  

Both must be of a suitable size (3 cm by 3 cm) and one in a site suitable for 
repeat biopsy, and one in a site suitable for index lesion Psoriatic Lesion 
Severity Sum (PLSS) scoring.

Both plaques must have a PLSS lesional score 2 for the induration 
component (moderate or above), ≥1 for erythema and scaling with a total 
score of 5.

The biopsy lesion must not be on the face, groin, scalp, knees, elbows, or on 
the palmar/plantar surfaces of the hands/feet, and must be shielded from 
natural light with clothing.
8. Subject is naive to any biologic therapies for PsO, OR has had previous exposure to a 
single anti-TNF biologic agent in the context of a previous clinical trial.  The anti-
TNF biologic agent must have been discontinued more than 8 weeks prior to 
screening visit (12 weeks or 5 half lives whichever is longer from first dose).
WEIGHT
9. A body mass index BMI within the range of 18.5 – 35 kg/m2 (inclusive).
SEX
10. Male and Female subjects
Males:
Male subjects with female partners of child bearing potential must comply with the 
contraception requirements in Appendix 5. 
Females: 
A female subject is eligible to participate if she is not pregnant (as confirmed by a 
negative serum human chorionic gonadotrophin (hCG) test), not lactating, and at least 
one of the following conditions applies:


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a.
Non-reproductive potential defined as:
Pre-menopausal females with one of the following:
Documented tubal ligation
Documented hysteroscopic tubal occlusion procedure with follow-up 
confirmation of bilateral tubal occlusion 
Hysterectomy
Documented Bilateral Oophorectomy

Postmenopausal defined as 12 months of spontaneous amenorrhea in 
questionable cases a blood sample with simultaneous follicle stimulating 
hormone (FSH) and estradiol levels consistent with menopause (refer to 
laboratory reference ranges for confirmatory levels).  Females on hormone 
replacement therapy (HRT) and whose menopausal status is in doubt will be 
required to use one of the highly effective contraception methods if they wish 
to continue their HRT during the study.  Otherwise, they must discontinue 
HRT to allow confirmation of post-menopausal status prior to study 
enrolment.
b.
Reproductive potential and agrees to follow one of the options listed in the Modified 
List of Highly Effective Methods for Avoiding Pregnancy in Females of 
Reproductive Potential (FRP) (see Appendix 5) from 30 days prior to the first dose of 
study medication and until 30 days after the last dose of study medication and 
completion of the follow-up visit.
The investigator is responsible for ensuring that subjects understand how to properly use 
these methods of contraception.
INFORMED CONSENT
11. Capable of giving signed informed consent as described in Section 10.2 which 
includes compliance with the requirements and restrictions listed in the consent form 
and in this protocol.
5.2.
Exclusion Criteria
For both cohorts, a subject will not be eligible for inclusion in this study if any of the 
following criteria apply:
CONCURRENT CONDITIONS/MEDICAL HISTORY (INCLUDES LIVER 
FUNCTION AND QTc INTERVAL)
1. Subjects with clinically overt concurrent psoriatic arthritis who are receiving chronic 
DMARD therapy (other than NSAIDs), as judged by the Investigator.
2. Has nonplaque forms of psoriasis (e.g. erythrodermic, guttate, or pustular), as judged 
by the Investigator.
3. Has current drug-induced psoriasis (e.g., a new onset of psoriasis or an exacerbation 


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from beta blockers, calcium channel blockers, or lithium).
4. Subject with current history of Suicidal Ideation Behaviour (SIB) as measured using 
the Columbia Suicide Severity Rating Scale (C-SSRS) or a history of attempted 
suicide.
5. An active infection, or a history of infections as follows:

Hospitalisation for treatment of infection within 60 days before first dose 
(Day 1).

Currently on any suppressive therapy for a chronic infection (such as 
pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and 
atypical mycobacteria).

Use of parenteral (IV or intramuscular) antibiotics (antibacterials, antivirals, 
antifungals, or antiparasitic agents) within 60 days before first dose.

A history of opportunistic infections within 1 year of screening (e.g. 
pneumocystis jirovecii, CMV pneumonitis, aspergillosis).  This does not 
include infections that may occur in immunocompetent individuals, such as 
fungal nail infections or vaginal candidiasis, unless it is of an unusual severity 
or recurrent nature.

Recurrent or chronic infection or other active infection that, in the opinion of 
the investigator might cause this study to be detrimental to the patient.

History of TB, irrespective of treatment status.

A positive diagnostic TB test at screening defined as a positive 
QuantiFERON-TB Gold test or T-spot test.
o
In cases where the QuantiFERON or T-spot test is indeterminate, the 
subject may have the test repeated once, but they will not be eligible 
for the study unless the second test is negative.
o
In cases where the QuantiFERON or T-spot test is positive, but a 
locally-read follow up chest X-ray, shows no evidence of current or 
previous pulmonary tuberculosis, the subject may be eligible for the 
study at the discretion of the Investigator and medical monitor.
6. QTc >450msec or QTc >480msec in subjects with bundle branch block.

The QTc is the QT interval corrected for heart rate according to either 
Bazett’s formula (QTcB), Fridericia’s formula (QTcF), or another method, 
machine or manual over read.

The specific formula that will be used to determine eligibility and 
discontinuation for an individual subject should be determined prior to 
initiation of the study. In other words, several different formulae cannot be 
used to calculate the QTc for an individual subject and then the lowest QTc 
value used to include or discontinue the subject from the trial. For purposes of 
data analysis, QTcB, QTcF, another QT correction formula, or a composite of 
available values of QTc will be used as specified in the Reporting and 
Analysis Plan (RAP). 
7. ALT >2xULN and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if 
bilirubin is fractionated and direct bilirubin <35%) at screening.
8. Current or chronic history of liver disease, or known hepatic or biliary abnormalities 
(with the exception of Gilbert’s syndrome or asymptomatic gallstones).


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9. Current or history of renal disease or estimated glomerular filtrate rate (GFR) by 
Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) <60 
mL/min/1.73 m2.
10. Hereditary or acquired immunodeficiency disorder, including immunoglobulin 
deficiency.
11. A major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem 
cell/marrow transplant.
12. A planned surgical procedure that, in the opinion of the investigator, makes the 
subject unsuitable for the study.
13. A history of malignant neoplasm within the last 5 years, except for adequately treated 
cancers of the skin (basal or squamous cell carcinoma) or carcinoma in situ of the 
uterine cervix that has been fully treated and shows no evidence of recurrence.
14. A history of hypertrophic scarring or keloid formation, or known allergy to lidocaine 
or other local anaesthetics.
CONCOMITANT MEDICATIONS
15. The subject has received treatment with the therapies listed in Section 6.11, or 
changes to those treatments, within the specified timeframe.  If in doubt, or the 
therapy is not listed please consult with the medical monitor.

Other medications (including vitamins, herbal and dietary supplements) will 
be considered on a case-by-case basis, and will be allowed if in the opinion of 
the investigator the medication will not interfere with the study procedures or 
compromise subject safety.
RELEVANT HABITS
16. History of alcohol or drug abuse that would interfere with the ability to comply with 
the study.
17. Subject intends to sunbathe or use a tanning device (sun bed or solarium) within 14 
days prior to Day 1 and until completion of the follow up visit (Day 112).
CONTRAINDICATIONS 
18. History of sensitivity to any of the study treatments, or components thereof or a 
history of drug or other allergy that, in the opinion of the investigator or Medical 
Monitor, contraindicates their participation.
19. Received a live or attenuated vaccine within 30 days of randomization OR plan to 
receive a vaccination during the study until completion of the follow-up visit.
20. The subject has participated in a clinical trial and has received an investigational 
product within 30 days or 5 half-lives, whichever is longer before the first dose of 
study medication, or plans to take part in another clinical trial at the same time as 
participating in this clinical trial. Subjects who were randomized into Cohort 1 are not 
eligible to be re-randomized into Cohort 2.


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DIAGNOSTIC ASSESSMENTS AND OTHER CRITERIA
21. Haemoglobin <11 g/dL; haematocrit <30%, white blood cell count ≤3000/mm3 (≤3.0 
x 109/L); platelet count ≤ 100,000/µL (≤100 x 109/L); absolute neutrophil count ≤1.5
x 109/L at the screening visit.
22. Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test 
result at screening or within 3 months prior to first dose of study treatment.  As 
potential for and magnitude of immunosuppression with this compound is unknown, 
subjects with presence of hepatitis B core antibody (HBcAb) should be excluded.
Subjects positive for HBsAg and/or positive for anti-HBc antibody (regardless of 
anti-HBs antibody status) are excluded.
23. A positive serology for human immunodeficiency virus (HIV) 1 or 2 at screening.
24. Where participation in the study would result in donation of blood or blood products 
in excess of 500 mL within 3 months.
25. Exposure to more than 4 investigational medicinal products within 12 months prior to 
the first dosing day.
5.3.
Screening/Baseline/Run-in Failures
Screen failures are defined as subjects who consent to participate in the clinical trial but 
are never subsequently randomized. In order to ensure transparent reporting of screen 
failure subjects, meet the Consolidated Standards of Reporting Trials (CONSORT) 
publishing requirements, and respond to queries from Regulatory authorities, a minimal 
set of screen failure information is required including Demography, Screen Failure 
details, Eligibility Criteria, and Serious Adverse Events (see Section 7.3.1.5).
Subjects who do not qualify to participate in the study due to a screening laboratory value 
or ECG abnormality can repeat the test once within the original screening time window, 
if the Investigator believes there is a reasonable possibility that the subject would be 
eligible if re-tested. 
Subjects can be re-screened only on approval of the GSK Medical Monitor and only 
once. Re-screening is allowed when a subject failed inclusion/exclusion criteria or some 
other screening condition initially, but the Investigator believes there is a reasonable 
probability that the subject would be eligible if re-screened.
5.4.
Withdrawal/Stopping Criteria
Subjects may be withdrawn from the study for any of the following reasons:

A subject may withdraw from study treatment at any time at his/her own request, 
or may be withdrawn at any time at the discretion of the investigator for safety, 
behavioural or administrative reasons.  If a subject withdraws from the study, 
he/she may request destruction of any samples taken, and the investigator must 
document this in the site study records.  The reason for withdrawal should be 
documented in the Case Report Form (CRF).


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
The Sponsor may request a subject withdraw for reasons such as significant 
protocol deviations (after discussion with the investigator).

If a subject is withdrawn from study treatment, this subject is also considered to 
be withdrawn from the study.

Study is terminated by the Sponsor.
If a subject is withdrawn, the Sponsor may decide to replace that subject and this will be 
done through the Interactive Response Technology System (IRTS).
The following actions must be taken in relation to a subject who fails to attend the clinic 
for a required study visit:

The site must attempt to contact the subject and re-schedule the missed visit as 
soon as possible. 

The site must counsel the subject on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the subject wishes to and/or should 
continue in the study. 

In cases where the subject is deemed ‘lost to follow up’, the investigator or 
designee must make every effort to regain contact with the subject (where 
possible, 3 telephone calls and if necessary a certified letter to the subject’s last 
known mailing address or local equivalent methods). These contact attempts 
should be documented in the subject’s medical record. 

Should the subject continue to be unreachable, only then will he/she be considered 
to have withdrawn from the study with a primary reason of “Lost to Follow-up”. 
If a subject chooses to withdraw from the study after dosing, the investigator must make 
every effort to complete the follow up assessments detailed in the Time and Events Table 
(Section 7.1).
5.4.1.
Individual Safety Stopping Rules
Study medication will be discontinued in the event of any of the following:

If a subject experiences a serious or severe clinically significant AE that in the 
clinical judgement of the investigator, after consultation with the medical monitor, 
there is a reasonable possibility that the AE is related to investigational product.

The subject becomes pregnant.

The subject initiates treatment with any prohibited medication for the treatment of 
PsO as listed in Section 6.11.2.

The subject develops a serious opportunistic or atypical infection.

If the liver chemistry stopping criteria (Section 5.4.3), QTc stopping criteria 
(Section 5.4.4), or haematologic stopping criteria (Section 5.4.5) are met.


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
The subject experiences any signs of suicidal ideation or behaviour (Section 
7.3.7).
5.4.2.
Group Safety Stopping Rules
In addition to the criteria specified above, AEs, SAEs, laboratory abnormalities, ECG 
abnormalities and changes in vital signs occurring across all randomised subject will be 
regularly reviewed by the Sponsor Safety Review Team (SRT) in order to ensure 
appropriate subject safety.  Any changes to the study due to safety reasons will be 
promptly communicated to the appropriate Regulatory Authorities.
5.4.3.
Liver Chemistry Stopping Criteria
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure subject safety and evaluate liver event etiology (in alignment with the FDA 
premarketing clinical liver safety guidance). 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/UCM174090.pdf


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Figure 3
Phase II Liver Chemistry Stopping and Increased Monitoring 
Algorithm
Phase II Liver Chemistry Stopping and Increased Monitoring Algorithm
Continue Study Treatment 
Discontinue Study Treatment 
Plus
Bilirubin≥2x
ULN (>35% 
direct) 
or plus
INR>1.5, if 
measured*
Possible
Hy’s Law
ALT≥3xULN
ALT≥5xULN
ALT≥3xULN
Plus
Symptoms of 
liver injury
or 
hypersensitivity
ALT≥3xULN
but able to 
monitor 
weekly for 
4 weeks
No
Yes
Yes
Yes
Yes
No
No
No
No
Yes
ALT≥3xULN
persist for
4 weeks or 
stopping 
criteria 
met
Yes
No
*INR value not applicable to subjects on anticoagulants
Yes
If subject to be monitored weekly must refer to Liver Safety Required  Actions and  Follow  up 
Assessments  section  in  the  Appendix
Must refer to Liver Safety Required Actions and Follow  up Assessments section in the Appendix
Report as an SAE if possible Hy’s Law case: ALT≥3xULN and  Bilirubin≥2xULN (>35% direct)  or 
INR>1.5, if measured*
Liver Safety Required Actions and Follow up Assessments Section can be found in 
Appendix 2.
5.4.3.1.
Study Treatment Restart or Rechallenge
Study treatment restart or rechallenge after liver chemistry stopping criteria are met by 
any subject participating in this study is not allowed.
5.4.4.
QTc Stopping Criteria
A subject who meets either of the bulleted criteria below will be withdrawn from the 
study:

QTc >500 msec or Uncorrected QT >600 msec

Change from baseline of QTc >60 msec
For patients with underlying bundle branch block, follow the discontinuation criteria 
listed below:


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Baseline QTc with Bundle Branch Block
Discontinuation QTc with Bundle 
Branch Block
<450 msec
>500 msec
450–480 msec
530 msec

The same QT correction formula must be used for each individual subject to 
determine eligibility for and discontinuation from the study.  This formula may not 
be changed or substituted once the subject has been enrolled.

For example, if a subject is eligible for the protocol based on QTcB, then QTcB must 
be used for discontinuation of this individual subject as well.

Once the QT correction formula has been chosen for a subject’s eligibility, the same 
formula must continue to be used for that subject for all QTc data being collected for 
data analysis.  Safety ECGs and other non-protocol specified ECGs are an 
exception.  

The decision to withdraw a subject will be based on an average QTc value of 
triplicate ECGs.  If an ECG demonstrates a prolonged QTc, obtain 2 more ECGs 
over a brief period (5-10 minutes), and then use the averaged QTc values of the 3 
ECGs to determine whether the subject should be discontinued from the study.
5.4.5.
Haematologic Stopping Criteria
Study treatment will be stopped for a subject if any of the following haematological 
stopping criteria is met:

Haemoglobin <9 g/dL or an absolute decrease of ≥3 g/dL from baseline (pre-
dose Day 1)

Platelets <50 × 109/L
5.5.
Subject and Study Completion
A completed subject is one who has completed all phases of the study including the 
follow-up visit.
The end of the study is defined as the last subject’s last visit.
6.
STUDY TREATMENT
6.1.
Investigational Product and Other Study Treatment
The term ‘study treatment’ is used throughout the protocol to describe any combination 
of products received by the subject as per the protocol design. Study treatment may 
therefore refer to the individual study treatments or the combination of those study 
treatments.


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Study Treatment
Product name:
GSK2982772
Placebo
Dosage form:
Tablet
Tablet
Unit dose strength(s)/Dosage 
level(s):
30 mg
NA
Route of Administration
For oral use only
For oral use only
Dosing instructions for Cohort 
1:
Take TWO tablets in the 
MORNING and TWO tablets in the 
EVENING as directed
Take TWO tablets in the 
MORNING and TWO tablets in the 
EVENING as directed
Dosing instructions for Cohort 
2:
Take TWO tablets THREE times 
daily as directed by your physician
Take TWO tablets THREE times 
daily as directed by your physician
Physical description
White to almost white, round, film 
coated tablet
White to almost white, round film 
coated tablet
Source of procurement
Study medication is supplied by 
GlaxoSmithKline
Placebo is supplied by 
GlaxoSmithKline
6.2.
Treatment Assignment
At screening, a unique Subject Number will be assigned to any subject who has at least 
one Screening procedure performed, other than informed consent.  The unique Subject 
Number will be used to identify individual subjects during the course of the study. 
Subjects who meet screening eligibility criteria will be randomised to a treatment group 
through Interactive Response Technology System (IRTS).  The IRTS will confirm the 
subject’s CRF number (Subject Number) and provide the randomisation number, where:

A randomisation number will be assigned from a randomisation schedule generated 
by Clinical Statistics, prior to the start of the study, using validated internal software.  
Once assigned, this number must not be reassigned to any other subject in the study.
The randomisation is centrally controlled by the IRTS.
In Cohort 1, subjects will take study medication every day, twice a day, approximately 12 
hours apart.   Subjects will be randomised to receive either GSK2982772 or placebo in a 
2:1 ratio. In Cohort 2, subjects will take study medication every day, three times a day, 
with approximately 8 hours between each dose.  Subjects will be randomised to receive 
either GSK2982772 or placebo in a 3:1 ratio.
Subjects will be administered the first daily dose of study medication by site staff during 
the site visit for Day 1 (week 0) and Day 43 (week 6). Subjects will self-administer all 
other doses of study medication and will record the date and time in the diary cards 
provided to them.
6.3.
Planned Dose Adjustments
No dose adjustments are allowed.


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6.4.
Blinding
This will be a double blind (sponsor unblind) study and the following will apply. 

Sponsor unblinded refers only to the Data Review Committee (DRC) consisting 
of the GSK Project Physician Lead (PPL), the study statistician, the study 
pharmacokineticist, Pattern Recognition Receptor (PRR) Discovery Performance 
Unit (DPU) Head, the Early Development Leader (EDL), the Safety Review Team 
(SRT) leader, or their designees on an ongoing basis. A physician external to the 
GSK2982772 project team may also be involved in the data review.  A data 
review charter will identify the specific GSK individuals involved; outline in 
detail the activities of this review, and how the integrity of the study will be 
maintained. The rest of the core GSK study team will remain blinded.

The investigator or treating physician may unblind a subject’s treatment 
assignment only in the case of an emergency OR in the event of a serious 
medical condition when knowledge of the study treatment is essential for the 
appropriate clinical management or welfare of the subject as judged by the 
investigator. Investigators have direct access to the subject’s individual study 
treatment.

It is preferred (but not required) that the investigator first contacts the Medical 
Monitor or appropriate GSK study personnel to discuss options before unblinding 
the subject’s treatment assignment. 

If GSK personnel are not contacted before the unblinding, the investigator must 
notify GSK as soon as possible after unblinding, but without revealing the 
treatment assignment of the unblinded subject, unless that information is 
important for the safety of subjects currently in the study. 

The date and reason for the unblinding must be fully documented in the CRF.

A subject will be withdrawn if the subject’s treatment code is unblinded by the 
investigator or treating physician. The primary reason for discontinuation (the 
event or condition which led to the unblinding) will be recorded in the CRF. 

GSK’s Global Clinical Safety and Pharmacovigilance (GCSP) staff may unblind 
the treatment assignment for any subject 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 subject’s treatment assignment, may be sent to 
investigators in accordance with local regulations and/or GSK policy.
6.5.
Packaging and Labeling
The contents of the label will be in accordance with all applicable regulatory 
requirements.


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6.6.
Preparation/Handling/Storage/Accountability
No special preparation of study treatment is required.

Only subjects enrolled in the study may receive study treatment and only 
authorized site staff may supply or administer study treatment.  All study 
treatments must be stored in a secure environmentally controlled and monitored 
(manual or automated) area in accordance with the labelled storage conditions 
with access limited to the investigator and authorized site staff. 

The investigator, institution, or the head of the medical institution (where 
applicable) is responsible for study treatment accountability, reconciliation, and 
record maintenance (i.e. receipt, reconciliation and final disposition records).  

Further guidance and information for final disposition of unused study treatment 
are provided in the SRM. 

Under normal conditions of handling and administration, study treatment is not 
expected to pose significant safety risks to site staff.  

A Material Safety Data Sheet (MSDS)/equivalent document describing 
occupational hazards and recommended handling precautions either will be 
provided to the investigator, where this is required by local laws, or is available 
upon request from GSK.
6.7.
Compliance with Study Treatment Administration
When subjects are dosed at the site, they will receive study treatment directly from the 
investigator or designee, under medical supervision.  The date and time of each dose 
administered in the clinic will be recorded in the source documents.  The dose of study 
treatment and study subject identification will be confirmed at the time of dosing by a 
member of the study site staff other than the person administering the study treatment. 
When subjects self-administer study treatment(s) at home, compliance with GSK2982772 
will be assessed through querying the subject during the site visits and documented in the 
source documents (diary cards) and CRF.  A record of the number of GSK2982772 or 
placebo tablets dispensed to and taken by each subject must be maintained and reconciled 
with study treatment and compliance records.  Treatment start and stop dates, including 
dates for treatment delays and/or dose reductions will also be recorded in the CRF.
6.8.
Treatment of Study Treatment Overdose
For this study, any dose of GSK2982772 >120 mg daily will be considered an overdose
in Cohort 1 and any dose of GSK2982772 >180 mg daily will be considered an overdose 
in Cohort 2.  GSK does not recommend specific treatment for an overdose.  The 
investigator will use clinical judgement to treat any overdose as and when they are made 
aware of this.
In the event of an overdose the investigator or treating physician should:
1. Contact the Medical Monitor immediately.


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2. Closely monitor the subject for adverse events (AEs)/serious adverse events 
(SAEs) and laboratory abnormalities until GSK2982772 can no longer be detected 
systemically (at least 2 days for GSK2982772).
3. Obtain a plasma sample for pharmacokinetic (PK) analysis if requested by the 
Medical Monitor (determined on a case-by-case basis)
4. Document the quantity of the excess dose as well as the duration of the 
overdosing in the CRF.
Decisions regarding dose interruptions or modifications will be made by the investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the subject.
6.9.
Treatment after the End of the Study
Subjects will not receive any additional treatment from GSK after completion of the 
study because other treatment options are available.
The investigator is responsible for ensuring that consideration has been given to the post-
study care of the subject’s medical condition, whether or not GSK is providing specific 
post-study treatment.
6.10.
Lifestyle and/or Dietary Restrictions

Subjects must adhere to the contraceptive requirements listed in Appendix 5.

Subjects must abstain from alcohol for 24 hours before all clinic visits.
6.10.1.
Sun Exposure and Activity
Subjects must not sunbathe or use a tanning device (sun bed or solarium) for 14 days 
prior to Day 1 until the follow up visit (Day 112).  Subjects will be advised that when 
they are outdoors they should wear protective clothing (e.g. sun hat, long sleeves) 
covering the selected target lesions for biopsy and PLSS scoring as well as use a broad 
spectrum UVA/UVB sunscreen and lip balm (SPF ≥30) on exposed areas when outdoors.
Subjects will abstain from strenuous exercise for 48 hours prior to each blood collection 
for clinical laboratory tests.  
6.11.
Concomitant Medications and Non-Drug Therapies
6.11.1.
Permitted Medications and Non-Drug Therapies
Selected medications for the treatment of PsO may be taken, with specific requirements 
listed in Table 1, and as long as they are not prohibited (Section 6.11.2).  All concomitant 
medications taken during the study will be recorded in the CRF.  The minimum 
requirement is that drug name and dates of administration are recorded.


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Table 1
Specific Requirements for Permitted Medications During the Study
Therapy
Requirement
Emollients (excluding those containing salicylic 
acid)
Omit on day of study visits until after all skin 
assessments have been performed.  May be 
used at other times.
Medicinal shampoos that contain tar and/or 
salicylic acid (but not corticosteroids)
Permitted at any time on scalp area.
6.11.2.
Prohibited Medications and Non-Drug Therapies
Table 2 lists prohibited medications for defined periods of time before and during the 
study until after the follow up visit (Day 112). 
Subjects who start prohibited medications or therapies as a treatment for PsO or other 
reasons during the study may be withdrawn from study treatment for safety reasons.  If in 
any doubt, investigators are advised to discuss medications with the medical monitor.
Table 2
Prohibited Medications
Therapy
Time period 
Biologic therapies for the treatment of chronic 
plaque-type psoriasis

Exception:  Can have only been 
exposed to one anti-TNF biologic 
previously administered in a clinical 
study setting. 
12 weeks or 5 half-lives (whichever is longer) 
prior to first dose.  Otherwise, cannot have 
been on an anti-TNF biologic treatment at any 
time during the study.
Photochemotherapy with psoralens and 
ultraviolet A (PUVA) therapy
4 weeks prior to first dose until after the follow 
up visit (Day 112).
Phototherapy (e.g., UVB or self treatment with 
tanning beds)
14 days
Topical therapies (e.g., corticosteroids, 
cyclosporine, calcineurin inhibitors, coal tar, 
vitamin A or D analog preparations, anthralin, 
calcipotrienen, retinoids, tazarotene, 
methoxsalen, trimethy psoralens).
2 weeks prior to first dose until after the follow 
up visit (Day 112).
Systemic immunomodulating medications for 
other medical conditions that are known to affect 
psoriasis, including but not limited to oral 
corticosteroids cyclosporine, methotrexate, 
cyclophosphamide, and beta-adrenergic 
blockers.
Intravenous or oral calcineurin inhibitors (e.g., 
tacrolimus).
4 weeks prior to first dose until after the follow 
up visit (Day 112).
P-glycoprotein (Pgp) inhibitors including but not 
limited to amiodarone, azithromycin, captopril, 
carvedilol, clarithromycin, conivaptan, 
cyclosporine, diltiazem, dronedarone, 
4 weeks prior to first dose until after the follow 
up visit (Day 112).


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Therapy
Time period 
erythromycin, felodipine, itraconazole, 
ketoconazole, lopinavir, ritonavir, quercetin, 
quinidine, ranolazine, ticagrelor, verapamil [FDA,
2012].
Narrow therapeutic index (NTI) CYP3A4 
substrates including but not limited to alfentanil, 
astemizole, cisapride, cyclosporine, 
dihydroergotamine, ergotamine, fentanyl, 
pimozide, quinidine, sirolimus, tacrolimus, 
terfenadine [FDA, 2012].
4 weeks prior to the first dose until after the 
follow up visit (Day 112).
Live vaccination
Vaccinations (either live, attenuated) are not 
permitted within 30 days of randomization or 
plan to receive a vaccination during the study 
until follow-up visit.  If indicated, non-live 
vaccines (e.g. inactivated influenza vaccines) 
may be administered whilst receiving 
GSK2982772 based on an assessment of the 
benefit: risk (e.g. risk of decreased 
responsiveness).  Investigators are expected to 
follow local and/or national guidelines with 
respect to vaccinations, including against 
pneumococcus and influenza, in subjects with 
PsO.
7.
STUDY ASSESSMENTS AND PROCEDURES
Protocol waivers or exemptions are not allowed with the exception of immediate safety 
concerns. Therefore, adherence to the study design requirements, including those 
specified in the Time and Events Table (Section 7.1), are essential and required for study 
conduct.
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the SRM.  The SRM will provide the site personnel with administrative and 
detailed technical information that does not impact subject safety.
This section lists the procedures and parameters of each planned study assessment.  The 
exact timing of each assessment is listed in the Time and Events Table Section 7.1.
The following points must be noted:

If assessments are scheduled for the same nominal time, THEN the assessments 
should occur in the following order:
a.
Patient Reported Outcomes (PROs)
b.
12-lead ECG
c.
vital signs


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d.
blood draws  
Note: The timing of the assessments should allow the blood draw to occur at the exact 
nominal time.

The timing and number of planned study assessments, including safety, 
pharmacokinetic, pharmacodynamic/biomarker or other 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. 

The change in timing or addition of time points for any planned study 
assessments must be documented in a Note to File which is approved by the
relevant GSK study team member and then archived in the study sponsor and 
site study files, but this will not constitute a protocol amendment. 

No more than 500 mL of blood will be collected over the duration of the study, 
including any extra assessments that may be required.

The Institutional Review Board/ Independent Ethics Committee (IRB/IEC) will 
be informed of any safety issues that require alteration of the safety monitoring 
scheme or amendment of the Informed Consent Form. 
A table defining the allowed variance in timings of assessments without being considered 
a protocol deviation will be included in the Study Reference Manual (SRM).


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7.1.
Time and Events Table
Procedures
Screening
Treatment Period
Early Withdrawal 14
Follow Up
Notes
Day 1 
Day 8 
Day 15
Day 22
Day 29
Day 36
Day 43
(week 6)
Day 50
Day 57
Day 64
Day 71
Day 78
Day 85
(week 12)
Visit windows
Screening: up to 30d before Day 1.
Treatment Period (except Day 1 & 
85): 3d. Day 1 NA; Day 85 2d.
Early Withdrawal: NA
Follow Up: 28d after last dose 3d
Screening Procedures
Screening procedures in addition to those listed below are (outpatient visit): informed consent; inclusion/ exclusion criteria; demography; medical history (includes past and 
current conditions, medication history, and family history of premature CV disease); HIV, Hep B and Hep C screen; serum pregnancy test (WCBP only).
Site Visit
X
X
X
X
X
X
X
X
X
X
X
1. Full physical exam: height/weight at 
Screening, height not required at later 
timepoints.
2. Vitals: BP, HR, RR, temperature. 
ECG triplicate at Screening only.
3. Urinalysis not required on Days 29, 
57 and 71. 
4. If urine test is positive, confirmatory 
serum test must be performed.
5. Pre-dose
6. In Cohort 1, subjects must take study 
medication twice a day approx. 12h
apart. In Cohort 2, subjects must take 
study medication three times a day 
approx. 8h apart. Exact time of dosing 
to be recorded in diary cards. On Days 
43 and 85, subjects must not take 
medication at home in the morning. 
Subjects will complete pre-dose 
assessments and then will be 
administered their morning dose of 
medication at site on Day 43 only. On 
Day 85, subjects no longer dosed.
7. Diary card checked by site staff and 
new diary card dispensed at every 
study visit.
8.  Blood samples for inflammatory 
Phone call
X
X
X
X
X
Safety Assessments
Full physical exam1
X
X
X
X
Brief physical exam
X5
X
X
X5
X
X
12-lead ECG, vital signs2
X
X5
X
X
X
X5
X
X
X
X
X
Columbia Suicide Severity 
Rating Scale (C-SSRS)
X
X5
X5
X
X
Hematology, chemistry,
urinalysis 
X
X5
X
X
X3
X5
X3
X3
X
X
X
FSH & estradiol  (if 
applicable)
X
Serum pregnancy (WCBP)
X
Urine pregnancy test 
(WCBP only)4
X5
X
X
X
X5
X
X
X
X
X
Study Treatment
Randomisation
X
Study medication6
X
X-------------------------------------------------------------------------------------------------X
Dispensing of study 
medication
X
X
X
Dispensing of diary cards7
X
X
X
X
X
X
X
PROs/ Disease Assessments


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Procedures
Screening
Treatment Period
Early Withdrawal 14
Follow Up
Notes
Day 1 
Day 8 
Day 15
Day 22
Day 29
Day 36
Day 43
(week 6)
Day 50
Day 57
Day 64
Day 71
Day 78
Day 85
(week 12)
Visit windows
Screening: up to 30d before Day 1.
Treatment Period (except Day 1 & 
85): 3d. Day 1 NA; Day 85 2d.
Early Withdrawal: NA
Follow Up: 28d after last dose 3d
Psoriatic Body Surface 
Area
X
X5
X
X
biomarkers and mRNA taken pre-dose 
on Day 1, Day 43 and Day 85. 
9. PK blood samples taken pre-dose on 
Day 43. Post-dose serial PK samples 
taken on Day 1 and Day 43 at 1, 2, 4, 
and 6 hours post-dose.
10. Pre-dose Day 1 one biopsy taken 
from non-lesional skin and two biopsies 
taken from biopsy target lesion.
11. On Day 43, two biopsies taken from 
the same target lesion that was 
selected at Day 1. Punch biopsies on 
Day 43 are to be taken pre-dose.
12. Biopsy only required at Early 
Withdrawal visit if completed at least 14 
days of treatment and prior to Day 43.
13. PGx sample collected at Day 1, 
after randomization and separate 
informed consent. If sample not 
collected at Day 1, can be collected at 
any time post-randomization. 
14. If subject withdraws early, every 
effort will be made for the subject to 
complete an Early Withdrawal visit prior 
to Follow Up. 
PASI, PGA, PLSS, Itch
X
X5
X
X
X5
X
X
X
X
DLQI
X
X5
X5
X
X
Photograph of lesions
X5
X5
X
X
Other Assessments and Procedures
Blood sample for 
inflammatory biomarkers8
X5
X5
X
X
Blood sample for mRNA 
analysis8
X5
X5
X
X
Blood sample for Target 
Engagement
X5
X5
X
X
PK blood samples9
X
X5
X
X
Skin punch biopsies for 
PK, inflammatory 
biomarkers, mRNA, target 
engagement & pathway 
engagement
X5,10
X11
X12
Pharmacogenetic sample 
(PGx)
X13
Con med review & AE/SAE 
reporting
X-------------------------------------------------------------------------------------------------------------------------X


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7.2.
Screening and Critical Baseline Assessments
After written informed consent, screening assessments will be performed as outlined in 
the Time and Events Table (Section 7.1).
The following demographic parameters will be captured: year of birth, sex, race and 
ethnicity.
Medical/medication/family history will be assessed as related to the inclusion/exclusion 
criteria listed in Section 5. 
Cardiovascular medical history/risk factors and smoking history (as detailed in the CRF) 
will be assessed at screening. 
Procedures conducted as part of the subject’s routine clinical management (e.g. blood
count) and obtained prior to signing of informed consent may be utilized for Screening or 
baseline purposes provided the procedure meets the protocol-defined criteria and has 
been performed in the timeframe of the study.
7.3.
Safety
Planned time points for all safety assessments are listed in the Time and Events Table 
(Section 7.1).  Additional time points for safety tests such as vital signs, physical exams 
and laboratory safety tests may be added during the course of the study based on newly 
available data to ensure appropriate safety monitoring.
The investigator will be responsible for determining the clinical significance of any 
results the fall outside of the laboratory normal ranges.
In line with routine pharmacovigilance, an internal GSK Safety Review Team (SRT), 
which will include 203167 study team members, will review blinded safety data, 
including clinical laboratory parameters and adverse events, at appropriate intervals 
during the period of study conduct.
7.3.1.
Adverse Events (AE) and Serious Adverse Events (SAEs)
The definitions of an AE or SAE can be found in Appendix 4.
The investigator and their designees are responsible for detecting, documenting and 
reporting events that meet the definition of an AE or SAE. 
7.3.1.1.
Time period and Frequency for collecting AE and SAE information

Any SAEs assessed as related to study participation (e.g., protocol-mandated 
procedures, invasive tests, or change in existing therapy) or related to a GSK 
product will be recorded from the time a subject consents to participate in the 
study up to and including any follow-up contact. 


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
AEs will be collected from the start of study treatment on Day 1 until the follow-
up contact (see Section 7.3.1.3), at the time points specified in the Time and 
Events Table (Section 7.1).

Medical occurrences that begin prior to the start of study treatment but after 
obtaining informed consent may be recorded on the Medical History/Current 
Medical Conditions section of the CRF.

All SAEs will be recorded and reported to GSK within 24 hours, as indicated in
Appendix 4.

Investigators are not obligated to actively seek AEs or SAEs in former study 
subjects. However, if the investigator learns of any SAE, including a death, at any 
time after a subject has been discharged from the study, and he/she considers the 
event reasonably related to the study treatment or study participation, the 
investigator must promptly notify GSK.
NOTE: The method of recording, evaluating and assessing causality of AEs and SAEs 
plus procedures for completing and transmitting SAE reports to GSK are provided in 
Appendix 4.
7.3.1.2.
Method of Detecting AEs and SAEs
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended 
and non-leading verbal questioning of the subject is the preferred method to inquire about 
AE occurrence.  Appropriate questions include:

“How are you feeling?” 

“Have you had any (other) medical problems since your last visit/contact?”

“Have you taken any new medicines, other than those provided in this study, since 
your last visit/contact?”
7.3.1.3.
Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
subject at subsequent visits/contacts.  All SAEs, and non-serious AEs of special interest 
(as defined in Section 4.6.1) will be followed until resolution, until the condition 
stabilizes, until the event is otherwise explained, or until the subject is lost to follow-up 
(as defined in Section 5.4). Further information on follow-up procedures is given in
Appendix 4.
7.3.1.4.
Cardiovascular and Death Events
For any cardiovascular events detailed in Appendix 4 and all deaths, whether or not they 
are considered SAEs, specific Cardiovascular (CV) and Death sections of the CRF will 
be required to be completed.  These sections include questions regarding cardiovascular 
(including sudden cardiac death) and non-cardiovascular death.


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The CV CRFs are presented as queries in response to reporting of certain CV MedDRA 
terms.  The CV information should be recorded in the specific cardiovascular section of 
the CRF within one week of receipt of a CV Event data query prompting its completion.
The Death CRF is provided immediately after the occurrence or outcome of death is 
reported.  Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported.
7.3.1.5.
Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to GSK of SAEs related to study treatment (even 
for non- interventional post-marketing studies) is essential so that legal obligations and 
ethical responsibilities towards the safety of subjects and the safety of a product under 
clinical investigation are met. 
GSK has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a product under clinical investigation.  GSK will 
comply with country specific regulatory requirements relating to safety reporting to the 
regulatory authority, Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) and investigators.
Investigator safety reports are prepared for suspected unexpected serious adverse 
reactions according to local regulatory requirements and GSK policy and are forwarded 
to investigators as necessary.
An investigator who receives an investigator safety report describing a SAE(s) or other 
specific safety information (e.g., summary or listing of SAEs) from GSK will file it with 
the IB and will notify the IRB/IEC, if appropriate according to local requirements.
7.3.2.
Pregnancy

Details of all pregnancies in female subjects and female partners of male subjects
will be collected after the start of dosing and until 30 days after the last dose.

If a pregnancy is reported then the investigator should inform GSK within 2 
weeks of learning of the pregnancy and should follow the procedures outlined in 
Appendix 5.
7.3.3.
Physical Exams

A complete physical examination will include, at a minimum, assessment of the 
head, eyes, ears, nose, throat, skin, thyroid, joint, lymph nodes, cardiovascular, 
respiratory, gastrointestinal and neurological systems. Height and weight will also 
be measured and recorded. 

A brief physical examination will include, at a minimum assessments of the skin,
lungs, cardiovascular system, and abdomen (liver and spleen).

Investigators should pay special attention to clinical signs related to previous 
serious illnesses.


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7.3.4.
Vital Signs

Vital signs will be measured in a supine or semi-supine position after 5 minutes 
rest and will include temperature, systolic and diastolic blood pressure, pulse rate 
and respiratory rate. 
7.3.5.
Electrocardiogram (ECG)

Triplicate ECGs will be obtained at screening and single 12-lead ECGs will be 
obtained at every other time point during the study using an ECG machine that 
automatically calculates the heart rate and measures PR, QRS, QT, and QTc (F or 
B) intervals.  Refer to Section 5.4.4 for QTc withdrawal criteria and additional 
QTc readings that may be necessary.

ECG is to be measured in a supine or semi supine position after 5 minutes rest.
7.3.6.
Clinical Safety Laboratory Assessments
All protocol required laboratory assessments, as defined in Table 3, must be conducted in 
accordance with the Laboratory Manual, and Protocol Time and Events Schedule.
Laboratory requisition forms must be completed and samples must be clearly labelled 
with the subject number, protocol number, site/centre number, and visit date. Details for 
the preparation and shipment of samples will be provided by the laboratory and are 
detailed in the laboratory manual. Reference ranges for all safety parameters will be 
provided to the site by the laboratory responsible for the assessments.
If additional non-protocol specified laboratory assessments are performed at the 
institution’s local laboratory and result in a change in subject management or are 
considered clinically significant by the investigator (e.g., SAE or AE or dose 
modification) the results must be recorded in the CRF.
Refer to the laboratory manual for appropriate processing and handling of samples to 
avoid duplicate and/or additional blood draws.
All study-required laboratory assessments will be performed by a central laboratory.
NOTE:  Local laboratory results are only required in the event that the central laboratory 
results are not available in times for either a treatment and/or response evaluation to be 
performed.  If a local sample is required it is important that the sample for central 
analysis is obtained at the same time. Additionally if the local laboratory results are used 
to make either a treatment or response evaluation, the results must be entered into the 
CRF.
Haematology, clinical chemistry, urinalysis and additional parameters to be tested are 
listed in Table 3. 


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Table 3
Protocol Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters
Haematology
Platelet Count
RBC Indices:
WBC count with Differential:
RBC Count
MCV
Neutrophils
Hemoglobin
MCH
Lymphocytes
Hematocrit
Monocytes
Eosinophils
Basophils
Clinical 
Chemistry 1
BUN
Potassium
AST (SGOT)
Total and direct 
bilirubin
Creatinine
Sodium
ALT (SGPT)
Total Protein
Glucose 2
Calcium
Alkaline 
phosphatise
Albumin
Triglycerides 2
Total 
Cholesterol2
HDL cholesterol 2
LDL cholesterol 2
Routine 
Urinalysis

Specific gravity

pH, glucose, protein, blood and ketones by dipstick

Microscopic examination (if blood or protein is abnormal)
Other 
Screening 
Tests

HIV

Hepatitis B surface antigen (HBsAg)

Hepatitis B core antibody (HBcAb)

Hepatitis C (Hep C antibody)

QuantiFeron Gold test

T-spot (if QuantiFeron is indeterminant)

FSH and estradiol (as needed in women of non-child bearing 
potential only)

Urine hCG Pregnancy test (as needed for women of child bearing 
potential) 3.  

Serum hCG (as needed for women of child bearing potential) to be 
done at screening and if urine test positive at other timepoints in 
study.

Estimated glomerular filtrate rate (eGFR) will be calculated using 
the CKD-EPIformula.
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 5.4.3 and 
Appendix 2.
2.
No fasting required.  Any abnormal result for glucose or lipids (non-fasted) may be 
repeated at the discretion of the investigator.
3.
Local urine testing will be standard for the protocol unless serum testing is required 
by local regulation or ethics committee.


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All laboratory tests with values that are considered clinically significantly abnormal 
during participation in the study should be repeated until the values return to normal or 
baseline.  If such values do not return to normal within a period judged reasonable by the 
investigator, the etiology should be identified and the sponsor notified.
7.3.7.
Suicidal Risk Monitoring
GSK2982772 is considered to be a CNS-active drug. There has been some concern that 
some CNS-active drugs may be associated with an increased risk of suicidal thinking or 
behaviour when given to some patients with PsO.  Although this drug has not been shown 
to be associated with an increased risk of suicidal thinking or behaviour when given to 
healthy volunteers, GSK considers it important to monitor for such events before or 
during clinical studies with compounds such as this.   
Families and caregivers of subjects being treated with GSK2982772 should be alerted 
about the need to monitor subjects for the emergence of unusual changes in behaviour, as 
well as the emergence of suicidal ideation and behaviour and to report such symptoms 
immediately to the study investigator.
Subjects being treated with GSK2982772 should be monitored appropriately for suicidal 
ideation and behaviour or any other unusual changes in behaviour. All subjects who 
experience signs of suicidal ideation or behaviour must immediately be discontinued 
from study medication.
At Screening and baseline (pre-dose Day 1), the ‘Baseline/Screening CSSRS’ (Columbia 
Suicide Severity Rating Scale) will be completed.  At Days 43 (week 6) and Day 85 
(week 12), the ‘Since Last Visit CSSRS’ will be completed.  GSK Version 4.1 of both 
rating scales will be used.
Subjects who answer ‘yes’ to any suicidal behaviour or ‘yes’ to suicidal ideation 
Questions 4 or 5 will be referred to their GP or appropriate psychiatric care.  The medical 
monitor will be notified.  If appropriate, an AE or SAE should be reported (see 
Section 7.3.1 - AE and SAE).  In addition, the investigator should complete a Possible 
Suicidality Related Adverse Event (PSRAE) form to collect detailed information on the 
circumstances of the reported AEs which, in the investigator’s opinion, are possibly 
suicidality-related.  These may include, but are not limited to, an event involving suicidal 
ideation, a preparatory act toward imminent suicidal behaviour, a suicide attempt, or a 
completed suicide.
7.4.
Efficacy
7.4.1.
Patient Reported Outcomes
Note: Patient Reported Outcomes questionnaires should be completed by subjects before 
any other assessments at a clinic visit.


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7.4.1.1.
Itch Visual Analogue Scale
The subject will be asked to rate the intensity of itch over the past week by marking a line 
on a 10 cm VAS with anchors “0” (no noticeable itching) to “10” (maximum itching 
sensation).
7.4.1.2.
Dermatology Life Quality Index
The DLQI [Finlay, 1994] will be used to assess quality of life.  The subject will complete 
the questionnaire to evaluate how their psoriasis has affected their life over the previous 
week before the assessment occurs.  Each question will be scored out of 0-3 or 0-2, as 
follows.
0 = Not at all
1 = A little
2 = A lot
3 = Very much
The questionnaire comprises of 10 questions (see SRM for full details). 
7.4.2.
Clinical Disease Assessments
7.4.2.1.
Body Surface Area (BSA)
The BSA affected with psoriasis will be evaluated at Screening and baseline (pre-dose 
Day 1) and on Day 85 by the investigator or suitably trained delegate.  In order to be 
eligible for the study, BSA must be 3%.  As a reference, the area of the whole palm is 
counted as 1% BSA.
7.4.2.2.
Selection of Psoriasis Plaques and Plaque Lesion Severity Scoring 
(PLSS)
Two plaques of at least 3 cm by 3 cm in area will be selected during the Screening 
period, one for clinical assessment (clinical efficacy skin lesion) and one for skin biopsy 
(punch biopsies). If at baseline on Day 1, prior to dosing, another lesion appears more 
suitable, the selected lesion can be changed. Once the lesions have been selected at 
baseline on Day 1, they must not change.
At a minimum, each plaque will have an induration score of 2 (moderate or above) and 
a score of 1 in erythema and scaling.  The PLSS is the sum of the erythema, scaling and 
plaque thickness scores.  Each lesion must have a PLSS score of 5.
Ideally, the biopsy skin lesion should be the most severe plaque of the two.
Selected lesions should be located on areas (trunk or extremities) that can be shielded to 
reduce natural exposure to UV light and should not include scalp, inguinal, genital 
lesions, or the palmar surfaces of the hands and/or feet. Preferably, symmetrical lesions 
will be chosen, but this is not an absolute requirement.


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During the study, the PLSS will be recorded for the clinical efficacy skin lesion (the 
biopsy lesion is only for biopsy).
7.4.2.3.
Psoriasis Area Severity Index (PASI)
The PASI scoring system is a widely-used standard clinical tool for assessing the severity 
of psoriasis that takes into account the overall severity of erythema (redness), thickness 
(induration), and scaling, as well as the extent of BSA affected with psoriasis 
[Fredriksson, 1978].  Erythema, induration, and scale are each graded on a 5-point scale 
(0-4), and the % BSA affected is scored on a 7-point scale (0-6) for each of the 4 
specified body regions (head, upper extremities, trunk, and lower extremities). The body 
region scores are each multiplied by a weighted factor; and the sum of the region scores 
give the overall PASI score.  Higher scores indicate more severe disease.  PASI is a static 
measurement made without reference to a previous score (see SRM for full details).
The PASI assessment will be performed by the investigator or suitably trained delegate, 
and whenever possible, the PASI assessments for an individual subject will be completed 
by the same assessor at all time points.
7.4.2.4.
Digital Photography
Photographs will be taken by the investigator or designee to illustrate any visible changes 
in psoriasis target lesions selected on Day 1.  For each subject, the investigator or 
delegate will take photographs of the same area of the body at each time point (i.e., same 
background, same illuminations, and same distance from the body).  Photographs will be 
taken of the area(s) of the body where the selected lesions are present and should be taken 
prior to performing the biopsy.  Photographs of the face will not be taken.  Photographs 
will be stored electronically, labelled, and collected centrally as explained in the Image 
Acquisition Guidelines.  Photographs will be used to document visual changes in lesions. 
Date, time and location of the photographs will be captured in the CRF.
Further details are contained in the Image Acquisition Guidelines.
7.4.2.5.
Physician’s Global Assessment of Disease Activity
The investigator or physician designee only will complete a global assessment of disease 
activity using the physician global assessment item. A 6-point scoring system will be 
used to measure the severity of psoriatic lesions over the entire body at the time of 
evaluation (see SRM for full details).
Note:

The investigator or physician designee should complete the physician’s global 
assessment independently of the subject.

Ideally, the same investigator or physician designee should perform all global 
assessments for each subject for the duration of the study.


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7.5.
Pharmacokinetics
7.5.1.
Blood Sample Collection
Blood samples for pharmacokinetic (PK) analysis of GSK2982772 will be collected at 
the time points indicated in Section 7.1, Time and Events Table.  The actual date and 
time of each blood sample collection will be recorded.  The timing of PK samples may be 
altered and/or PK samples may be obtained at additional time points to ensure thorough 
PK monitoring.  
Details of blood sample collection, processing, storage and shipping procedures are 
provided in the laboratory manual. 
7.5.2.
Sample Analysis
Plasma analysis will be performed at a bioanalytical site (to be detailed in the SRM) 
under the control of Platform Technologies and Science In vitro/ In vivo Translation
(PTS IVIVT) and Third Party Resource, GlaxoSmithKline. Concentrations of 
GSK2982772 will be determined in plasma samples using the currently approved 
bioanalytical methodology. Raw data will be archived at the bioanalytical site (detailed 
in the SRM). Once the plasma has been analyzed for GSK2982772 any remaining plasma 
may be analyzed for other compound-related material and the results reported under a 
separate PTS-IVIVT, GlaxoSmithKline protocol.
7.5.3.
Punch Skin Biopsy for Pharmacokinetic Assay
See Section 7.6.1 for more details on punch skin biopsies. A punch skin biopsy will be 
taken at baseline (pre-dose Day 1) and Day 43 (Week 6) to measure the concentration of 
GSK2982772 in the skin (taken from the outer third of the target lesion).  Information on 
processing the biopsies for the skin pharmacokinetic assay will be provided in the SRM.
Once the skin extract has been analyzed for GSK2982772, any remaining skin extract 
may be analyzed for other compound-related material and the results reported under a 
separate PTS-IVIVT, GlaxoSmithKline protocol.
7.5.4.
Sample Analysis
Skin biopsy sample analysis will be performed under the control of PTS-IVIVT, 
GlaxoSmithKline.  An exploratory analysis of concentrations of GSK2982772 in skin 
will be conducted.
7.6.
Biomarker(s)/Pharmacodynamic Markers
7.6.1.
Skin Lesion Biopsy
At baseline (pre-dose Day 1), a target lesion for biopsy will be identified (3 cm by 3 cm) 
on the trunk or extremities. The same target lesion will be used for both the baseline 
lesion biopsy and at Day 43 (Week 6) even if the lesion has cleared. Lesions on palmar 


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surfaces of the hands and feet, scalp, knees, elbows and intertriginous areas will not be 
used as the target lesion site.

Two 4-mm tissue biopsies will be taken from the outer third of the selected 
biopsy lesion at baseline (pre-dose Day 1) using standard methodology. The 
second site on the outer third of the same lesion should be at least 1.5 cm from 
the first biopsy. Local anaesthetic will be administered before each biopsy, and 
only suitably experienced personnel, trained in aseptic technique, will obtain the 
biopsies.

At baseline only (pre-dose Day 1), a total of 3 biopsies will be taken, 1 from a 
non-lesional area of skin and 2 biopsies will be taken from the target lesion site.
The target lesion biopsy will be taken from the outer third of the lesion. The 
non-lesional biopsy will be taken from an unaffected area close to the target 
lesion, and cannot include the palmar surfaces of the hands and feet, scalp, 
knees, elbows and intertriginous areas

At Day 43 (Week 6), 2 biopsies will be taken from the same target lesion as 
identified at baseline even if the lesion has cleared. As above, the biopsies will 
be taken from the outer third of the lesion. 
Biopsy tissue taken from the psoriatic skin lesions will be divided accordingly for 
pharmacokinetic, target and pathway engagement, histological and gene expression 
analyses as feasibility dictates. Histologic assessment will include measurement of 
epidermal thickness, total inflammatory infiltrates, keratin expression (e.g., K16) and 
specific cell numbers (which may include by not be limited to) CD3+T-cells, CD11c+ 
myeloid dendritic cells. mRNA may be isolated from skin biopsy tissue, as feasibility
dictates, to determine the effect of placebo and GSK2982772 on markers of inflammation 
and tissue healing (e.g., may include and not be limited to measurement of chemokines, 
cytokines, and extracellular matrix proteases). Examples of technologies that may be 
used for analysis include, but are not limited to quantitative PCR, RNAseq, microarray, 
mass cytometry (CyTOF). See SRM for full details of the division of biopsy tissues. 
The baseline nonlesional skin biopsy will be divided accordingly for histologic and gene 
expression analysis as feasibility dictates.  Histologic assessment will include 
measurement of epidermal thickness, total inflammatory infiltrates, keratin expression 
(e.g., K16) and specific cell numbers (which may include by not be limited to) CD3+T-
cells, CD11c+ myeloid dendritic cells. mRNA expression of inflammatory markers and 
tissue healing will be assessed in baseline nonlesional skin (as above) as feasibility 
dictates, using the same technologies as outlined above.  
7.6.2.
Novel Pharmacodynamic Biomarkers
7.6.2.1.
RIP1 Target Engagement in Blood
Blood samples for RIP1 target engagement will be collected at the time points indicated 
in Section 7.1 to measure levels of free and total RIP1 antibodies.


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7.6.2.2.
RIP1 Target Engagement in Tissue
Skin punch biopsy samples for RIP1 target engagement will be collected at the time 
points indicated in Section 7.1 to measure levels of free and drug-bound RIP1 protein if 
sample quantity and data allow.
7.6.2.3.
RIP1 Pathway Markers in Tissue
Skin punch biopsy samples for RIP1 pathway markers will be collected at the time points 
indicated in Section 7.1 to measure total or phosphorylated RIP1, RIP3, MLKL and 
cleaved or total caspase 3 and 8 if sample quantity and data allow.
7.6.3.
Exploratory Novel Biomarkers
With the subject’s consent, tissue, and/or blood sample(s) will be collected during this 
study and may be used for the purposes of measuring novel biomarkers to identify factors 
that may influence disease/condition for study treatment, and/or medically related 
conditions, as well as the biological and clinical responses to GSK2982772.  If relevant, 
this approach will be extended to include the identification of biomarkers associated with 
adverse events.
Samples will be collected at the time points indicated in Section 7.1.  The timing of the 
collections may be adjusted on the basis of emerging pharmacokinetic or PD data from 
this study or other new information in order to ensure optimal evaluation of the PD 
endpoints.
Novel candidate biomarkers and subsequently discovered biomarkers of the biological 
response associated with PsO and/or the action of GSK2982772 may be identified by 
application of:

Gene expression array analysis may be conducted on the blood and/or punch skin 
biopsies using microarray, and/or alternative equivalent technologies such as RNA 
sequencing, which facilitates the simultaneous measurement (and confirmation) of the 
relative abundances of thousands of RNA species resulting in a transcriptome profile 
for each skin sample.

Soluble inflammatory mediators in the blood may be assayed for cytokine and 
inflammatory mediators including, but not limited to, pro-inflammatory and anti-
inflammatory cytokines, chemokines, and acute phase proteins. 

Phosphoprotein detection in skin tissue and blood may be used to validate RIP1 
kinase pathway activation.

High dimensional CyTOF/Helios based immune profiling of peripheral blood cells 
including measurement of immune cell phenotypes, intracellular signalling events and 
key cytokines / chemokines. 
These analyses may be reported under separate protocol following the completion of the 
study. All samples will be retained for a maximum of 15 years after the last subject 
completes the trial. 


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7.7.
Genetics
In consenting subjects, a blood sample for pharmacogenetics (PGx) research will be 
drawn on Day 1 (or any time point post randomisation and prior to study completion) to 
better characterize genetic variability that may affect efficacy or safety endpoints.
Information regarding pharmacogenetic (PGx) research is included in Appendix 3.
8.
DATA MANAGEMENT

For this study subject data will be entered into GSK defined CRFs, transmitted 
electronically to GSK or designee and combined with data provided from other 
sources in a validated data system.  

Management of clinical data will be performed in accordance with applicable 
GSK standards and data cleaning procedures to ensure the integrity of the data, 
e.g., removing errors and inconsistencies in the data.

Adverse events and concomitant medications terms will be coded using MedDRA 
(Medical Dictionary for Regulatory Activities) and an internal validated 
medication dictionary, GSKDrug.  

CRFs (including queries and audit trails) will be retained by GSK, and copies will 
be sent to the investigator to maintain as the investigator copy.  Subject initials 
will not be collected or transmitted to GSK according to GSK policy.
9.
STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES
9.1.
Hypotheses
The primary objective of the study is to investigate the safety and tolerability of 
GSK2982772 60 mg BID and 60 mg TID following 12 weeks of treatment.  No formal 
statistical hypotheses will be conducted to assess this objective.
If appropriate, comparisons between the GSK2982772 arms and the placebo arm will be 
made to investigate the secondary inflammatory, mechanistic and efficacy objectives.
Trends over time will be investigated for both treatment arms along with associations 
between each of the parameters.
9.2.
Sample Size Considerations
9.2.1.
Sample Size Assumptions
The study is not powered to detect pre-defined differences.  In Cohort 1, approximately 
30 subjects and up to a maximum of 36, will be randomised into the study to either 
GSK2982772 or placebo in a 2:1 ratio to ensure that approximately 24 evaluable subjects 
complete the study.  


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In Cohort 2, approximately 24 subjects and up to a maximum of 32, will be randomised 
into the study to either GSK2982772 or placebo in a 3:1 ratio to ensure that 
approximately 20 evaluable subjects complete the study.
A subject is considered evaluable if they have completed at least one post-treatment 
biopsy.
The primary objective of the study is safety and tolerability, where there will be 20 
subjects randomised to GSK2982772 60 mg BID and 18 subjects randomised to 
GSK2982772 60 mg TID.  Using a Bayesian approach to determine the confidence 
interval around an observed safety event, we would assume a flat Beta (1, 1) prior, and if 
we were to observe one safety event in 20 then the posterior distribution would be Beta 
(2, 20), as outlined below in Figure 4.
Figure 4
One Event in 20 Subjects: Beta (2,20) Distribution
Thus, we can be 95% certain that the true probability of the safety event lies between 
0.01 and 0.24.  Similarly, if we were to observe one safety event in 18 then the posterior 


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distribution would be Beta (2, 18), thus we can be 95% certain that the true probability of 
the safety event lies between 0.01 and 0.26.  
For supportive information the properties of the secondary endpoint PLSS have also been 
considered.  Assuming a standard deviation of 25%, it is estimated that the lower and 
upper bounds of the 95% confidence interval for the difference between GSK2982772 60
mg BID (n=20) and placebo (n=10) in percentage change in index lesion PLSS will be 
within approximately 17.1% of the point estimate, and that the lower and upper bounds of 
the 95% confidence interval for the difference between GSK2982772 60 mg TID (n=18) 
and placebo (n=6) in percentage change in index lesion PLSS will be within 
approximately 17.5% of the point estimate.
9.2.2.
Sample Size Sensitivity
A sample size sensitivity analysis has been conducted on the primary endpoint to 
investigate the different safety event rates.  If the number of subjects who complete the 
12 weeks is lower than anticipated, then the true incidence rates of safety events that 
could not be ruled out (as outlined in Section 9.2.1) would change.  These changes are 
outlined in Table 4.
Table 4
Sample Size Sensitivity
GSK2982772 subjects 
completing the study
Number of a particular safety 
event observed with 
GSK2982772
Upper limit of exact 95% CI 
indicating that a true 
incidence rate of x% could 
not be ruled out
20
0
16.1%
20
1
23.8%
20
2
30.4%
18
0
17.6%
18
1
26.0%
18
2
33.1%
16
0
19.5%
16
1
28.7%
16
2
36.4%
Similarly, for supportive information a sensitivity analysis of the precision of the 
secondary endpoint percentage change in PLSS has been performed to assess the impact 
of varying variability and numbers of GSK2982772 and placebo subjects Figure 5.


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Figure 5
Sample Size Sensitivity for Percentage Change in PLSS
9.2.3.
Sample Size Re-estimation or Adjustment
No sample size re-estimation or adjustment will be conducted.
9.3.
Data Analysis Considerations
9.3.1.
Analysis Populations
All Subjects Population: The ‘All Subjects Population’ is defined as subjects who were 
screened for the study.  This population is used for the summary of selected 
accountability data.
Safety Population: The ‘Safety Population’ is defined as subjects who receive at least 
one dose of study medication. This population is used for the summary of all data 
including demography, safety, efficacy and exploratory data but excluding PK data.


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Pharmacokinetic Population: The ‘PK Population' is defined as subjects in the ‘Safety’ 
population who received an active dose and for whom a pharmacokinetic sample was 
obtained and analysed.   This population is used for the summary of PK data only.  Any 
PKPD analyses will be conducted on the Safety population such that subjects receiving 
placebo can be included.
9.3.2.
Interim Analysis
In line with routine pharmacovigilance, an internal GSK Safety Review Team (SRT) 
which will include members of the GSK2982772 project team, will review blinded safety 
data, including clinical laboratory parameters and adverse events, at appropriate intervals 
during the period of study conduct.
In both cohorts, once an appropriate number of subjects randomised to GSK2982772 
have completed Day 43 (Week 6), the PLSS data will be reviewed in an unblinded 
manner by a Data Review Committee (DRC) consisting of the GSK Project Physician 
Lead (PPL), the study statistician, the study pharmacokineticist, the PRR DPU Head, the 
Early Development Lead (EDL), the Safety Review Team (SRT) leader, or their 
designees on an ongoing basis. A physician external to the GSK2982772 project team 
may also be involved in the data review. Additional inflammatory biomarkers, clinical 
and mechanistic endpoints (e.g., target engagement) may be reviewed if available. No 
other member of the GSK core study team will be unblinded to this data. The primary 
purpose of these reviews will be to monitor PLSS changes for internal decision making 
purposes.  A data review charter will identify the specific GSK individuals involved, 
outline in detail the activities of this review and how the integrity of the study will be 
maintained.  
A formal interim analysis will be conducted after the completion of Cohort 1 and will 
only include those subjects randomised to a BID dosing regimen. The purpose of the 
interim analysis is primarily to provide the project team and key GSK stakeholders with 
an early indication of the safety and efficacy from the trial, and to facilitate decision 
making regarding the subsequent clinical development of GSK2982772.  
9.3.3.
Primary Analyses
All safety evaluations will be based on the Safety population.  Clinical interpretation will 
be based on the review and displays of adverse events, clinical laboratory values, vital 
sign measurements and 12-lead ECG monitoring.
9.3.4.
Secondary Analyses
Comparisons between treatment groups on any changes observed will be conducted for 
the secondary endpoints if deemed appropriate, e.g. changes in the mean target 
engagement, changes in inflammatory markers and percentage change in index lesion 
PLSS be statistically analyzed using a MMRM (repeated measures mixed effects model) 
comparing each GSK2982772 arm with placebo at each time point. If sufficient numbers 
of subjects are enrolled with a BSA >5% then the proportion of subjects achieving PASI 
50/75/90 at Day 85 (12 Weeks), will be statistically analysed using a Generalised 
Estimating Equations (GEE) model comparing each GSK2982772 arm with placebo at 


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each time point if appropriate. Similar analyses will be conducted for other secondary 
endpoints if deemed appropriate.
The relationship between each of the mechanistic endpoints and also with the clinical 
endpoints may also be graphically presented and analysed using an appropriate statistical 
model identifying any trends. The model will determine whether the mechanistic effect 
significantly explains or predicts the effect on the other mechanistic or clinical endpoints 
(e.g., index lesion PLSS score). This may be conducted through comparing statistical 
models incorporating different explanatory terms (i.e. mechanistic endpoints) with the 
‘null’ model (no mechanistic endpoints); or if deemed appropriate, multivariate statistical 
methods may also be applied to determine the relationship between the key endpoints. 
The consistency in the changes over time between the endpoints will also be assessed. 
In addition, based on the data that we observe in the study, probabilities of success will 
be determined, where the definition of success will be dependent on the endpoint. For 
example, what is the probability that we would observe a certain percentage change in 
PLSS (i.e., comparatory rate), based on the data that we have observed in the study.
GSK2982772 plasma concentrations will be summarised descriptively by Day and 
nominal time point by dosing regimen. 
Further details regarding the statistical analysis will be outlined in the Reporting and 
Analysis Plan (RAP).
9.3.5.
Other Analyses
9.3.5.1.
Exploratory Analyses
All exploratory endpoints will be descriptively summarized, graphically presented and 
listed appropriately.  Further details can be found in the RAP.
10.
STUDY GOVERNANCE CONSIDERATIONS
10.1.
Posting of Information on Publicly Available Clinical Trial 
Registers
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrollment of subjects begins.
10.2.
Regulatory and Ethical Considerations, Including the 
Informed Consent Process
The study will be conducted in accordance with all applicable regulatory requirements, 
and with GSK policy.
The study will also be conducted in accordance with ICH Good Clinical Practice (GCP), 
all applicable subject privacy requirements, and the guiding principles of the current 
version of the Declaration of Helsinki.  This includes, but is not limited to, the following:


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
IRB/IEC review and favorable opinion/approval of the study protocol and 
amendments as applicable

Obtaining signed informed consent

Investigator reporting requirements (e.g. reporting of AEs/SAEs/protocol 
deviations to IRB/IEC)

GSK will provide full details of the above procedures, either verbally, in writing, 
or both.

Signed informed consent must be obtained for each subject prior to participation 
in the study

The IEC/IRB, and where applicable the regulatory authority, approve the clinical 
protocol and all optional assessments, including genetic research.  

Optional assessments (including those in a separate protocol and/or under separate 
informed consent) and the clinical protocol should be concurrently submitted for 
approval unless regulation requires separate submission.  

Approval of the optional assessments may occur after approval is granted for the 
clinical protocol where required by regulatory authorities.  In this situation, 
written approval of the clinical protocol should state that approval of optional 
assessments is being deferred and the study, with the exception of the optional 
assessments, can be initiated.
10.3.
Quality Control (Study Monitoring)

In accordance with applicable regulations including GCP, and GSK procedures, 
GSK monitors will contact the site prior to the start of the study to review with the 
site staff the protocol, study requirements, and their responsibilities to satisfy 
regulatory, ethical, and GSK requirements.  

When reviewing data collection procedures, the discussion will also include 
identification, agreement and documentation of data items for which the CRF will 
serve as the source document.
GSK will monitor the study and site activity to verify that the:

Data are authentic, accurate, and complete.

Safety and rights of subjects are being protected.

Study is conducted in accordance with the currently approved protocol and any 
other study agreements, GCP, and all applicable regulatory requirements.
The investigator and the head of the medical institution (where applicable) agrees to 
allow the monitor direct access to all relevant documents
10.4.
Quality Assurance

To ensure compliance with GCP and all applicable regulatory requirements, GSK 
may conduct a quality assurance assessment and/or audit of the site records, and 


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the regulatory agencies may conduct a regulatory inspection at any time during or 
after completion of the study. 

In the event of an assessment, audit or inspection, the investigator (and institution) 
must agree to grant the advisor(s), auditor(s) and inspector(s) direct access to all 
relevant documents and to allocate their time and the time of their staff to discuss 
the conduct of the study, any findings/relevant issues and to implement any 
corrective and/or preventative actions to address any findings/issues identified.
10.5.
Study and Site Closure

Upon completion or premature discontinuation of the study, the GSK monitor will 
conduct site closure activities with the investigator or site staff, as appropriate, in 
accordance with applicable regulations including GCP, and GSK Standard 
Operating Procedures.

GSK reserves the right to temporarily suspend or prematurely discontinue this 
study at any time for reasons including, but not limited to, safety or ethical issues 
or severe non-compliance. For multicenter studies, this can occur at one or more 
or at all sites.  

If GSK determines such action is needed, GSK will discuss the reasons for taking 
such action with the investigator or the head of the medical institution (where 
applicable).  When feasible, GSK will provide advance notification to the 
investigator or the head of the medical institution, where applicable, of the 
impending action.

If the study is suspended or prematurely discontinued for safety reasons, GSK will 
promptly inform all investigators, heads of the medical institutions (where 
applicable) and/or institution(s) conducting the study. GSK will also promptly 
inform the relevant regulatory authorities of the suspension or premature 
discontinuation of the study and the reason(s) for the action.  

If required by applicable regulations, the investigator or the head of the medical 
institution (where applicable) must inform the IRB/IEC promptly and provide the 
reason for the suspension or premature discontinuation.
10.6.
Records Retention

Following closure of the study, the investigator or the head of the medical 
institution (where applicable) must maintain all site study records (except for 
those required by local regulations to be maintained elsewhere), in a safe and 
secure location.  

The records must be maintained to allow easy and timely retrieval, when needed 
(e.g., for a GSK audit or regulatory inspection) and must be available for review 
in conjunction with assessment of the facility, supporting systems, and relevant 
site staff.  

Where permitted by local laws/regulations or institutional policy, some or all of 
these records can be maintained in a format other than hard copy (e.g., microfiche, 


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scanned, electronic); however, caution needs to be exercised before such action is 
taken.  

The investigator must ensure that all reproductions are legible and are a true and 
accurate copy of the original and meet accessibility and retrieval standards, 
including re-generating a hard copy, if required.  Furthermore, the investigator 
must ensure there is an acceptable back-up of these reproductions and that an 
acceptable quality control process exists for making these reproductions.

GSK will inform the investigator of the time period for retaining these records to 
comply with all applicable regulatory requirements.  The minimum retention time 
will meet the strictest standard applicable to that site for the study, as dictated by 
any institutional requirements or local laws or regulations, GSK 
standards/procedures, and/or institutional requirements.  

The investigator must notify GSK of any changes in the archival arrangements, 
including, but not limited to, archival at an off-site facility or transfer of 
ownership of the records in the event the investigator is no longer associated with 
the site.
10.7.
Provision of Study Results to Investigators, Posting of 
Information on Publically Available Clinical Trials Registers 
and Publication
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report.  The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results at a GSK site or other mutually-
agreeable location.
GSK will also provide the investigator with the full summary of the study results.  The 
investigator is encouraged to share the summary results with the study subjects, as 
appropriate.
GSK will provide the investigator with the randomization codes for their site only after 
completion of the full statistical analysis.
The procedures and timing for public disclosure of the results summary and for 
development of a manuscript for publication will be in accordance with GSK Policy.


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11.
REFERENCES
Bonnet MC, Preukschat D, Welz P-S, van Loo G, Ermolaeva MA, Bloch W et al.  The 
adaptor protein FADD protects epidermal keratinocytes from necroptosis in vivo and 
prevents skin inflammation.  Immunity, 2011;35:572-82.
Chen H, Yu KD, Xu GZ. Association between Variant Y402H in Age-Related Macular 
Degeneration (AMD) Susceptibility Gene CFH and Treatment Response of AMD: A 
Meta-Analysis. PloS ONE 2012; 7: e42464
Gorin MB. 
Chen T, Guo Z-p, Li L, Wang L, Jia R-z, Cao N et al.  Increased HMGB1 serum levels 
and altered HMGB1 expression in patients with psoriasis vulgaris.  Archives of 
Dermatological Research, 2013;305:263-7.
Dondelinger Y, Aguileta MA, Goossens V, Dubuisson C et al.  RIPK3 contributes to 
TNFR1-mediated RIPK1 kinase-dependent apoptosis in conditions of cIAP1/2 depletion 
or TAK1 kinase inhibition.  Cell Death and Differentiation, 2013;20:1381-92.
Finlay AY, Khan GK.  Dermatology Life Quality Index (DLQI) – A simple practical 
measure for routine clinical use.  Clin Exp Dermatol, 1994;19:210-216.
Fredriksson T, Pettersson U.  Severe psoriasis – oral therapy with a new retinoid.  
Dermatologica, 1978;157(4):238-44.Finlay AY, Khan GK.  Dermatology Life Quality 
Index (DLQI) – a simple practical measure for routine clinical use.  1978;157:238-44.
GlaxoSmithKline Document Number 2014N204126_01 Investigator's Brochure 
GSK2982772
08-MAR-
2016.
Gorin MB.  Genetic insights into age-related macular degeneration: Controversies 
addressing risk, causality, and therapeutics. Mo. Aspects Med. 2012; 33:467-486.
Hatcher RA, Trussell J,  Nelson AL, Cates W Jr, Stewart F, Kowal D, Policar MS, 
editors. Contraceptive Technology. 20th edition.  Atlanta, Georgia: Ardent Media, Inc., 
2011: 50.  Table 3 2.
Humphries F, Yang S, Wang B, Moynagh P N.  RIP kinases: key decision makers in cell 
death and innate immunity.  Cell Death & Differ, 2015;22:225-236.
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davern TJ, Lee 
WM. Pharmacokinetics of Acetaminophen-Adduct in Adults with Acetaminophen 
Overdose and Acute Liver Failure. Drug Metab Dispos 2009; 37:1779-1784
Ofengeim D and Yuan J.  Regulation of RIP1 kinase signaling at the crossroads of 
inflammation and cell death.  Nature Reviews Molecular Cell Biology, 2013;14:727-36.
U.S. Department of Health and Human Services, Food and Drug Administration (FDA). 
(2012) Guidance for Industry: Drug Interaction Studies – Study Design, Data Analysis, 
Implications for Dosing, and Labeling Recommendations. Center for Drug Evaluation 
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and Research, 10903 New Hampshire Avenue, Silver Spring, MD 20993.
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/UCM292362.pdf
Wang L, Du F, Wang X. TNF-alpha induces two distinct caspase-8 activation pathways. 
Cell, 2008; 133(4):693-703.


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12.
APPENDICES
12.1.
Appendix 1 – Abbreviations and Trademarks
Abbreviations
AE
Adverse Event
ALT
Alanine aminotransferase (SGPT)
AMD
Age-related macular degeneration
AST
Aspartate aminotransferase (SGOT)
AUC
Area under concentration-time curve
BID
Twice a day
BSA
Body Surface Area
CI
Confidence Interval
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration 
equation
Cmax
Maximum observed concentration
CNS
Central nervous system
CRF 
Case Report Form
CONSORT
Consolidated Standards of Reporting Trials
CRP
C-Reactive Protein
C-SSRS
Columbia Suicide Severity Rating Scale
CV
Cardiovascular
CYP
Cytochrome P
CyTOF
Mass cytometry
DAMPs
Damage-associated molecular pattern
DRC
Data Review Committee
DLQI
Dermatology Life Quality Index
DMARD
Disease-Modifying Antirheumatic Drugs
DNA
Deoxyribose Nucleic Acid
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
EDL
Early Development Lead
ETCO2
End-tidal Carbon Dioxide
FDA
Food and Drug Administration
FRP
Females of Reproductive Potential
FSH
Follicle Stimulating Hormone
FTiH
First Time in Human
GCP
Good Clinical Practice
GEE
Generalised Estimating Equations
GFR
Glomerular Filtrate Rate
GSK
GlaxoSmithKline
HBcAb
Hepatitis B Core Antibody
HBsAg
Hepatitis B Surface Antigen
hCG
Human chorionic gonadotropin
HIV
Human Immunodeficiency Virus


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IB
Investigator Brochure
IBD
Inflammatory Bowel Disease
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IgG
Immunoglobulin gamma
IP
Investigational Product
IRB
Institutional Review Board
IRTs
Interactive Response Technology System
Kg
Kilogram
L
Litre
LDH
Lactate Dehydrogenase
MCH
Mean corpuscular haemoglobin
MDMA
3,4-methylenedioxy-methamphetamine
MedDRA
Medical Dictionary for Regulatory Activity
mg
Milligram
mL
Millilitre
MLKL
Mixed lineage kinase domain-like protein
mm
Millimeter
mmol
Millimole
MMRM
Repeated measures mixed effects model
MSDS
Material Safety Data Sheet
NF-B
Nuclear factor kappa-light-chain-enhancer of activated B 
cells
NOAEL
No Adverse Effect Level
NSAID
Non-steroidal Anti-inflammatory Drug
NTI
Narrow therapeutic index
PASI
Psoriasis Area Severity Index
PCR
Polymerase Chain Reaction
PD
Pharmacodynamic
PGA
Physician Global Assessment
P-gp
P-glycoprotein
PGx
Pharmacogenetics
PI
Principal Investigator
PK
Pharmacokinetic
PLSS 
Psoriasis Lesion Severity Score
PPL
Project Physician Lead
PRO
Patient Reported Outcome
PsO
Psoriasis
PSRAE
Possible Suicidality Related Adverse Event
PTS IVIVT
Platform Technologies and Science In vitro/In vivo 
Translation
PUVA
Psoralen and ultraviolet A
QD
Once a day
QTc
Electrocardiogram QT interval corrected for heart rate
QTcB
Electrocardiogram QT interval corrected for heart rate using 
Bazett’s formula


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QTcF
Electrocardiogram QT interval corrected for heart rate using 
Fridericia’s formula
RAP
Reporting and Analysis Plan
RBC
Red Blood Cell
RIP1
Receptor-interacting protein-1
RIP3
Receptor-interacting protein-3
RNA
Ribonucleic Acid
SAE
Serious Adverse Event
SIB
Suicidal Ideation Behaviour
SOP
Standard Operating Procedure
SPF
Sun protection factor
SpO2
Peripheral Capillary Oxygen Saturation
SRM
Study Reference Manual
SRT
Safety Review Team
TB
Tuberculosis
TEAR
Target Engagement Assay RIP1
TID
Three times daily
TLR
Toll-like receptor
TNF
Tumor necrosis factor
UK
United Kingdom
ULN
Upper Limit of Normal
UVB
Ultraviolet B
V
Volume of Distribution
VAS
Visual Analogue Scale
Trademark Information
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
NONE
QuantiFERON


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12.2.
Appendix 2: Liver Safety Required Actions and Follow up 
Assessments
Phase II liver chemistry stopping and increased monitoring criteria have been 
designed to assure subject safety and evaluate liver event etiology (in alignment with the 
FDA premarketing clinical liver safety guidance).  
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/UCM174090.pdf.
Phase II liver chemistry stopping criteria and required follow up assessments
Liver Chemistry Stopping Criteria – Liver Stopping Event
ALT-absolute
ALT 5xULN
ALT Increase
ALT 3xULN persists for 4 weeks
Bilirubin1, 2
ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin)
INR2
ALT 3xULN and INR>1.5, if INR measured
Cannot Monitor
ALT 3xULN and cannot be monitored weekly for 4 weeks
Symptomatic3
ALT  3xULN associated with symptoms (new or worsening) believed to be 
related to liver injury or hypersensitivity
Required Actions and Follow up Assessments following ANY Liver Stopping Event
Actions
Follow Up Assessments

Immediately discontinue  study treatment 

Report the event to GSK within 24 hours

Complete the liver event CRF and complete an
SAE data collection tool if the event also meets 
the criteria for an SAE2

Perform liver event follow up assessments 

Monitor the subject until liver chemistries
resolve, stabilize, or return to within baseline 
(see MONITORING below)

Do not restart/rechallenge subject with study 
treatment unless allowed per protocol and GSK 
Medical Governance approval is granted

If restart/rechallenge not allowed per protocol 
or not granted, permanently discontinue study 

Viral hepatitis serology4

Blood sample for pharmacokinetic (PK) 
analysis, obtained within 2 days after 
last dose5

Serum creatine phosphokinase (CPK) 
and lactate dehydrogenase (LDH).

Fractionate bilirubin, if total 
bilirubin2xULN

Obtain complete blood count with 
differential to assess eosinophilia

Record the appearance or worsening of 
clinical symptoms of liver injury, or 
hypersensitivity, on the AE report form

Record use of concomitant medications 


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treatment and may continue subject in the study 
for any protocol specified follow up assessments 
MONITORING:
For bilirubin or INR criteria:

Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
liver event follow up assessments within  24 hrs

Monitor subjects twice weekly until liver 
chemistries resolve, stabilize or return to within 
baseline 

A specialist or hepatology consultation is 
recommended
For All other criteria:

Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
liver event follow up assessments within  24-72 
hrs 

Monitor subjects weekly until liver chemistries 
resolve, stabilize or return to within baseline
on the concomitant medications report 
form including acetaminophen, herbal 
remedies, other over the counter 
medications.

Record alcohol use on the liver event 
alcohol intake case report form
For bilirubin or INR criteria:

Anti-nuclear antibody, anti-smooth 
muscle antibody, Type 1 anti-liver 
kidney microsomal antibodies, and 
quantitative total immunoglobulin G 
(IgG or gamma globulins).

Serum acetaminophen adduct HPLC 
assay (quantifies potential 
acetaminophen contribution to liver 
injury in subjects with definite or likely 
acetaminophen use in the preceding 
week [James, 2009]). NOTE: not 
required in China

Liver imaging (ultrasound, magnetic 
resonance, or computerised 
tomography) and /or liver biopsy to 
evaluate liver disease; complete Liver 
Imaging and/or Liver Biopsy CRF 
forms.
1.
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study treatment for that subject if ALT 3xULN and bilirubin 2xULN.
Additionally, if serum bilirubin fractionation testing is unavailable, record presence of detectable urinary 
bilirubin on dipstick, indicating direct bilirubin elevations and suggesting liver injury. 
2.
All events of ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin) or ALT 3xULN and INR>1.5, if INR 
measured which may indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE (excluding 
studies of hepatic impairment or cirrhosis); INR measurement is not required and the threshold value stated 
will not apply to subjects receiving anticoagulants
3.
New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or believed to be related to hypersensitivity (such as fever, rash or 
eosinophilia)
4.
Includes: Hepatitis A IgM antibody; Hepatitis B surface antigen and Hepatitis B Core Antibody (IgM); Hepatitis C 
RNA; Cytomegalovirus IgM antibody;  Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain 
heterophile antibody or monospot testing);  Hepatitis E IgM antibody 
5.
PK sample may not be required for subjects known to be receiving placebo or non-GSK comparator treatments.)  
Record the date/time of the PK blood sample draw and the date/time of the last dose of study treatment prior to 
blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the subject’s best 
approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot be collected in 
the time period indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are in 
the SRM.  


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12.3.
Appendix 3 - Genetic Research
Genetics – Background
Naturally occurring genetic variation may contribute to inter-individual variability in 
response to medicines, as well as an individual's risk of developing specific diseases. 
Genetic factors associated with disease characteristics may also be associated with 
response to therapy, and could help to explain some clinical study outcomes. For 
example, genetic variants associated with age-related macular degeneration (AMD) are 
reported to account for much of the risk for the condition [Gorin, 2012] with certain 
variants reported to influence treatment response [Chen, 2012]. Thus, knowledge of the 
genetic etiology of disease may better inform understanding of disease and the 
development of medicines. Additionally, genetic variability may impact the 
pharmacokinetics (absorption, distribution, metabolism, and elimination), or 
pharmacodynamics (relationship between concentration and pharmacologic effects or the 
time course of pharmacologic effects) of a specific medicine and/or clinical outcomes 
(efficacy and/or safety) observed in a clinical study.
Genetic Research Objectives and Analyses
The objectives of the genetic research are to investigate the relationship between genetic 
variants and: 

Response to medicine, including GSK2982772 or any concomitant medicines;

Psoriasis susceptibility, severity, and progression and related conditions
Genetic data may be generated while the study is underway or following completion of 
the study.  Genetic evaluations may include focused candidate gene approaches and/or 
examination of a large number of genetic variants throughout the genome (whole genome 
analyses). Genetic analyses will utilize data collected in the study and will be limited to 
understanding the objectives highlighted above.  Analyses may be performed using data 
from multiple clinical studies to investigate these research objectives.
Appropriate descriptive and/or statistical analysis methods will be used. A detailed 
description of any planned analyses will be documented in a Reporting and Analysis Plan 
(RAP) prior to initiation of the analysis. Planned analyses and results of genetic 
investigations will be reported either as part of the clinical RAP and study report, or in a 
separate genetics RAP and report, as appropriate.
Study Population
Any subject who is enrolled in the study can participate in genetic research.  Any subject 
who has received an allogeneic bone marrow transplant must be excluded from the 
genetic research.
Study Assessments and Procedures
A key component of successful genetic research is the collection of samples during 
clinical studies. Collection of samples, even when no a priori hypothesis has been 


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identified, may enable future genetic analyses to be conducted to help understand 
variability in disease and medicine response.  

A 6 ml blood sample will be taken for Deoxyribonucleic acid (DNA) extraction. 
A blood sample is collected at the baseline visit, after the subject has been 
randomized and provided informed consent for genetic research. Instructions for 
collection and shipping of the genetic sample are described in the laboratory 
manual. The DNA from the blood sample may undergo quality control analyses to 
confirm the integrity of the sample. If there are concerns regarding the quality of 
the sample, then the sample may be destroyed. The blood sample is taken on a 
single occasion unless a duplicate sample is required due to an inability to utilize 
the original sample.  
The genetic sample is labelled (or “coded”) with the same study specific number used to 
label other samples and data in the study.   This number can be traced or linked back to 
the subject by the investigator or site staff. Coded samples do not carry personal 
identifiers (such as name or social security number). 
The need to conduct PGx analysis may be identified after a study (or set of studies) of 
GSK2982772 has been completed and the study data reviewed. In some cases, the 
samples may not be studied.
Samples will be stored securely and may be kept for up to 15 years after the last subject 
completes the study, or GSK may destroy the samples sooner.  GSK or those working 
with GSK (for example, other researchers) will only use samples collected from the study 
for the purpose stated in this protocol and in the informed consent form.  Samples may be 
used as part of the development of a companion diagnostic to support the GSK medicinal 
product.
Subjects can request their sample to be destroyed at any time.
Informed Consent
Subjects who do not wish to participate in the genetic research may still participate in the 
study.  Genetic informed consent must be obtained prior to any blood being taken.
Subject Withdrawal from Study
If a subject who has consented to participate in genetic research withdraws from the 
clinical study for any reason other than being lost to follow-up, the subject will be given a 
choice of one of the following options concerning the genetic sample, if already 
collected:

Continue to participate in the genetic research in which case the genetic DNA 
sample is retained

Discontinue participation in the genetic research and destroy the genetic DNA 
sample 


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If a subject withdraws consent for genetic research or requests sample destruction for any 
reason, the investigator must complete the appropriate documentation to request sample 
destruction within the timeframe specified by GSK and maintain the documentation in 
the site study records. 
Genotype data may be generated during the study or after completion of the study and 
may be analyzed during the study or stored for future analysis. 

If a subject withdraws consent for genetic research and genotype data has not been 
analyzed, it will not be analyzed or used for future research.  

Genetic data that has been analyzed at the time of withdrawn consent will 
continue to be stored and used, as appropriate. 
Screen and Baseline Failures
If a sample for genetic research has been collected and it is determined that the subject 
does not meet the entry criteria for participation in the study, then the investigator should 
instruct the subject that their genetic sample will be destroyed. No forms are required to 
complete this process as it will be completed as part of the consent and sample 
reconciliation process.  In this instance a sample destruction form will not be available to 
include in the site files.
Provision of Study Results and Confidentiality of Subject’s Genetic Data
GSK may summarize the genetic research results in the clinical study report, or 
separately and may publish the results in scientific journals. 
GSK may share genetic research data with other scientists to further scientific 
understanding in alignment with the informed consent. GSK does not inform the subject, 
family members, insurers, or employers of individual genotyping results that are not 
known to be relevant to the subject’s medical care at the time of the study, unless 
required by law. This is due to the fact that the information generated from genetic 
studies is generally preliminary in nature, and therefore the significance and scientific 
validity of the results are undetermined.  Further, data generated in a research laboratory 
may not meet regulatory requirements for inclusion in clinical care.


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12.4.
Appendix 4: Definition of and Procedures for Recording, 
Evaluating, Follow-Up and Reporting of Adverse Events
12.4.1.
Definition of Adverse Events
Adverse Event Definition:

An AE is any untoward medical occurrence in a patient or clinical investigation 
subject, temporally associated with the use of a medicinal product, whether or not 
considered related to the medicinal product.

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 medicinal product.
Events meeting AE definition include:

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (e.g., ECGs, radiological scans, vital signs 
measurements), including those that worsen from baseline, and felt to be clinically 
significant in the medical and scientific judgement of the investigator.

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study treatment administration even 
though it may have been present prior to the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication (overdose per se will not be reported as an 
AE/SAE unless this is an intentional overdose taken with possible suicidal/self-
harming intent.  This should be reported regardless of sequelae).

"Lack of efficacy" or "failure of expected pharmacological action" per se will not be 
reported as an AE or SAE.  However, the signs and symptoms and/or clinical 
sequelae resulting from lack of efficacy will be reported if they fulfil the definition 
of an AE or SAE.
Events NOT meeting definition of an AE include:

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 subject’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the subject’s 


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Events NOT meeting definition of an AE include:
condition.

Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is an AE.

Situations where 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.
12.4.2.
Definition of Serious Adverse Events
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease, etc).
Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, 
at any dose:
a. Results in death
b. Is life-threatening
NOTE:
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
subject was at risk of death at the time of the event.  It does not refer to an event, which 
hypothetically might have caused death, if it were more severe.
c.
Requires hospitalization or prolongation of existing hospitalization
NOTE:

In general, hospitalization signifies that the subject 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 out-patient setting.  Complications that occur during hospitalization are 
AEs.  If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious.  When in doubt as to whether “hospitalization” occurred or was 
necessary, the AE should be considered serious.

Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE.
d.
Results in disability/incapacity
NOTE:

The term disability means a substantial disruption of a person’s ability to conduct 


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Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, 
at any dose:
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (e.g. sprained ankle) which may interfere or prevent everyday 
life functions but do not constitute a substantial disruption
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether 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 subject or may require medical or surgical intervention to prevent one of the 
other outcomes listed in the above definition.  These should also be considered 
serious.

Examples of such events are invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency 
or drug abuse
g.
Is associated with liver injury and impaired liver function defined as:

ALT 3xULN and total bilirubin* 2xULN (>35% direct), or

ALT 3xULN and INR** > 1.5.
* Serum bilirubin fractionation should be performed if testing is available; if unavailable, 
measure urinary bilirubin via dipstick.  If fractionation is unavailable and ALT 3xULN 
and total bilirubin 2xULN, then the event is still to be reported as an SAE.
** INR testing not required per protocol and the threshold value does not apply to 
subjects receiving anticoagulants.  If INR measurement is obtained, the value is to be 
recorded on the SAE form.
12.4.3.
Definition of Cardiovascular Events
Cardiovascular Events (CV) Definition:
Investigators will be required to fill out the specific CV event page of the CRF for the 
following AEs and SAEs:

Myocardial infarction/unstable angina

Congestive heart failure

Arrhythmias


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Cardiovascular Events (CV) Definition:

Valvulopathy

Pulmonary hypertension

Cerebrovascular events/stroke and transient ischemic attack

Peripheral arterial thromboembolism

Deep venous thrombosis/pulmonary embolism

Revascularization
12.4.4.
Recording of AEs and SAEs
AEs 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) 
relative to the event.

The investigator will then record all relevant information regarding an AE/SAE in 
the CRF

It is not acceptable for the investigator to send photocopies of the subject’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 instance, all subject identifiers, with the exception of the 
subject number, will be blinded on the copies of the medical records prior to 
submission of to GSK.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  In such cases, the diagnosis will be 
documented as the AE/SAE and not the individual signs/symptoms.

Subject-completed PRO questionnaires and the collection of AE data are 
independent components of the study.

Responses to each question in the PRO questionnaire will be treated in accordance 
with standard scoring and statistical procedures detailed by the scale’s developer.

The use of a single question from a multidimensional health survey to designate a 
cause-effect relationship to an AE is inappropriate.


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12.4.5.
Evaluating AEs and SAEs
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and will assign it to one of the following categories:

Mild:  An event that is easily tolerated by the subject, causing minimal discomfort 
and not interfering with everyday activities.

Moderate:  An event that is sufficiently discomforting to interfere with normal 
everyday activities

Severe:  An event that prevents normal everyday activities. - an AE that is assessed 
as severe will not be confused with an SAE. Severity is a category utilized for rating 
the intensity of an event; and both AEs and SAEs can be assessed as severe.

An event is defined as ‘serious’ when it meets at least one of the pre-defined 
outcomes as described in the definition of an SAE.
Assessment of Causality

The investigator is obligated to assess the relationship between study treatment and 
the occurrence of each AE/SAE.

A "reasonable possibility" is meant to convey that there are facts/evidence or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled 
out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as natural history of the underlying diseases, concomitant 
therapy, other risk factors, and the temporal relationship of the event to the study 
treatment will be considered and investigated.

The investigator will also consult the Investigator Brochure (IB) and/or Product 
Information, for marketed products, in the determination of 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 when 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 
prior to the initial transmission of the SAE data to GSK.

The investigator may change his/her opinion of causality in light of follow-up 
information, amending the SAE data collection tool accordingly.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.


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Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as may be indicated or as requested by GSK to 
elucidate as fully as possible the nature and/or causality of the AE or SAE.

The investigator is obligated to assist.  This may include additional laboratory tests 
or investigations, histopathological examinations or consultation with other health 
care professionals.

If a subject 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 the designated 
reporting time frames.
12.4.6.
Reporting of SAEs to GSK
SAE reporting to GSK via electronic data collection tool

Primary mechanism for reporting SAEs to GSK will be the electronic data collection 
tool

If the electronic system is unavailable for greater than 24 hours, the site will use the 
paper SAE data collection tool and fax it to the Medical Monitor.

Site will enter the serious adverse event data into the electronic system as soon as it 
becomes available.

The investigator will be required to confirm review of the SAE causality by ticking 
the ‘reviewed’ box at the bottom of the eCRF page within 72 hours of submission of 
the SAE.

After the study is completed at a given site, the electronic data collection tool (e.g., 
InForm system) 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 subject or receives updated data 
on a previously reported SAE after the electronic data collection tool has been taken 
off-line, the site can report this information on a paper SAE form or to the Medical 
Monitor by telephone.

Contacts for SAE receipt can be found at the beginning of this protocol on the 
Sponsor/Medical Monitor Contact Information page.


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12.5.
Appendix 5: Modified List of Highly Effective Methods for 
Avoiding Pregnancy in FRP and Collection of Pregnancy 
Information
12.5.1.
Modified List of Highly Effective Methods for Avoiding Pregnancy 
in Females of Reproductive Potential (FRP)
The list does not apply to FRP with same sex partners or for subjects who are and will 
continue to be abstinent from penile-vaginal intercourse on a long term and persistent 
basis, when this is their preferred and usual lifestyle. Periodic abstinence (e.g. calendar, 
ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable 
methods of contraception.
1. Contraceptive subdermal implant
2. Intrauterine device or intrauterine system
3. Combined estrogen and progestogen oral contraceptive [Hatcher, 2011])
4. Injectable progestogen [Hatcher, 2011]
5. Contraceptive vaginal ring [Hatcher, 2011]
6. Percutaneous contraceptive patches [Hatcher, 2011]
7. Male partner sterilization with documentation of azoospermia prior to the female 
subject's entry into the study, and this male is the sole partner for that subject 
[Hatcher, 2011]. The documentation on male sterility can come from the site 
personnel’s: review of subject’s medical records, medical examination and/or semen 
analysis, or medical history interview provided by her or her partner.
These allowed methods of contraception are only effective when used consistently, 
correctly and in accordance with the product label. The investigator is responsible for 
ensuring that subjects understand how to properly use these methods of contraception
Contraceptive requirements for male subjects with female partners of reproductive 
potential (when applicable):
Male subjects with female partners of child bearing potential must comply with the 
following contraception requirements from the time of first dose of study medication 
until 90 days after the last dose of study medication.
1.
Vasectomy with documentation of azoospermia. The documentation on male sterility 
can come from the site personnel’s: review of subject’s medical records, medical 
examination and/or semen analysis, or medical history interview.
2.
Male condom plus partner use of one of the contraceptive options below that meets 
the SOP effectiveness criteria including a <1% rate of failure per year, as stated in 
the product label:

Contraceptive subdermal implant

Intrauterine device or intrauterine system


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
Combined estrogen and progestogen oral contraceptive [Hatcher, 2011] 

Injectable progestogen [Hatcher, 2011]

Contraceptive vaginal ring [Hatcher, 2011]

Percutaneous contraceptive patches [Hatcher, 2011]
These allowed methods of contraception are only effective when used consistently, 
correctly and in accordance with the product label. The investigator is responsible for 
ensuring that subjects understand how to properly use these methods of contraception.
12.5.2.
Collection of Pregnancy Information

Investigator will collect pregnancy information on any female subject, who becomes 
pregnant while participating in this study

Information will be recorded on the appropriate form and submitted to GSK within 2 
weeks of learning of a subject's pregnancy.

Subject will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow up information on mother and infant, which will be 
forwarded to GSK.  Generally, follow-up will not be required for longer than 6 to 8 
weeks beyond the estimated delivery date. 

Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for procedure.

While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy will be reported as an AE or 
SAE.

A spontaneous abortion is always considered to be an SAE and will be reported as 
such.  

Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study treatment by the investigator, will be reported to GSK 
as described in Appendix 4. While the investigator is not obligated to actively seek 
this information in former study participants, he or she may learn of an SAE through 
spontaneous reporting.
Any female subject who becomes pregnant while participating

Will be withdrawn from the study.

Investigator will attempt to collect pregnancy information on any female partner of a 
male study subject who becomes pregnant while participating in this study.  This 
applies only to subjects who are randomized to receive study medication. 

After obtaining the necessary signed informed consent from the female partner 
directly, the investigator will record pregnancy information on the appropriate form 
and submit it to GSK within 2 weeks of learning of the partner’s pregnancy

Partner will also be followed to determine the outcome of the pregnancy.  
Information on the status of the mother and child will be forwarded to GSK. 


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
Generally, follow-up will be no longer than 6 to 8 weeks following the estimated 
delivery date.  Any termination of the pregnancy will be reported regardless of fetal 
status (presence or absence of anomalies) or indication for procedure.


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12.6.
Appendix 6: Protocol Changes
12.6.1.
Protocol Amendment 01
Where the amendment applies
This protocol amendment applies to all countries.
Summary of amendment changes and rationale
Regulatory feedback led to a requirement for additional concomitant medication 
restrictions. In addition, some administrative clarifications have been made.
List of specific changes (bold indicates text added and strikethrough indicates text 
removed)
Authors
Author (s):
 
Section 1 Protocol synopsis for study 203167
An ongoing review of available efficacy, pharmacodynamic and mechanistic endpoints 
will be conducted during the study by a Data Review Committee (DRC), consisting of a 
limited number of GSK individuals, some of whom are also members of the GSK study 
team who are not involved in the day-to-day running of the study.
Section 4.5 Dose justification
It is anticipated that a human dose of 60 mg BID will produce AUC(0-24) and Cmax values 
of approximately 9 ug.h/mL and 1 ug/mL, respectively, which are approximately 1/6th  
and 1/12th of the gender-averaged AUC (48.4 ug.h/mL) and Cmax (12.3 ug/mL) achieved 
in the 13 week monkey study at the NOAEL dose of 30 mg/kg/day.
PPD


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Section 4.6.1 Risk Assessment
Potential Risk of 
Clinical Significance
Summary of Data/Rationale for 
Risk
Mitigation Strategy
Investigational Product (IP) GSK2982772
Drug Interaction
Non-clinical data:
In vitro studies with GSK2982772 
assessing potential drug-drug 
interactions with Cytochrome P450 3A4 
(CYP3A4) substrates and P-glycoprotein
(Pgp) inhibitors were completed.  To 
date, formal drug interaction studies in 
humans have not been performed with 
GSK2982772. 
There is a low risk that GSK2982772 
could be an inducer of CYP3A4 and 
therefore may lower circulating levels of 
concomitant medications that are 
metabolised by CYP3A4 when co 
administered with GSK2982772.
GSK2982772 is a Pgp substrate and 
therefore co administration with 
concomitant medications that are Pgp 
inhibitors could increase circulating 
levels of GSK2982772.
See Section 4.3.6 of GSK2982772 IB 
[GlaxoSmithKline Document Number 
2014N204126_01].
Subject Selections:

Subjects who are taking 
concomitant medications known 
to inhibit Pgp or are CYP3A4 
narrow therapeutic index (NTI) 
substrates will be excluded from 
the study.  See Section 6.11.2 for 
a comprehensive list of 
medications.
Subject Monitoring:

Subjects’ concomitant medication 
usage will be reviewed prior to 
inclusion and monitored 
throughout the study.
Subjects should be monitored 
throughout the study for potential 
effects of interaction between 
GSK2982772 and other concomitant 
medications.
Section 6.4 Blinding
This will be a double blind (sponsor unblind) study and the following will apply. 

Sponsor unblinded refers only to the Data Review Committee (DRC) consisting 
of the GSK study physician, the study statistician, the study pharmacokineticist, 
Pattern Recognition Receptor (PRR) Discovery Performance Unit (DPU) 
Head, the Early Development Leader (EDL), the Safety Review Team (SRT) 
leader, or their designees on an ongoing basis. A physician external to the 
GSK2982772 project team may also be involved in the data review.  A data 
review charter will identify the specific GSK individuals involved; outline in 
detail the activities of this review, and how the integrity of the study will be 
maintained. The rest of the core GSK study team will remain blinded.


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Section 6.11.2 Prohibited Medications and Non-Drug Therapies
Prohibited Medications
Therapy
Time period 
P-glycoprotein (Pgp) inhibitors including 
but not limited to amiodarone, azithromycin, 
captopril, carvedilol, clarithromycin, 
conivaptan, cyclosporine, diltiazem, 
dronedarone, erythromycin, felodipine, 
itraconazole, ketoconazole, lopinavir, 
ritonavir, quercetin, quinidine, ranolazine, 
ticagrelor, verapamil [FDA, 2012].
4 weeks prior to first dose until after the 
follow up visit (Day 112).
Narrow therapeutic index (NTI) CYP3A4 
substrates including but not limited to 
alfentanil, astemizole, cisapride, 
cyclosporine, dihydroergotamine, 
ergotamine, fentanyl, pimozide, quinidine, 
sirolimus, tacrolimus, terfenadine [FDA, 
2012].
4 weeks prior to the first dose until after 
the follow up visit (Day 112).


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Section 7.1 Time and Events Table
Procedures
Screening
Treatment Period
Early Withdrawal 14
Follow Up
Notes
Day 1 
Day 8 
Day 15
Day 22
Day 29
Day 36
Day 43
(week 6)
Day 50
Day 57
Day 64
Day 71
Day 78
Day 85
(week 12)
Visit windows
Screening: up to 30d before Day 1.
Treatment Period (except Day 1 & 85): 
3d. Day 1 NA; Day 85 2d.
Early Withdrawal: NA
Follow Up: 28d after last dose 3d
Screening Procedures
Screening procedures in addition to those listed below are (outpatient visit): informed consent; inclusion/ exclusion criteria; demography; medical history (includes past and 
current conditions, medication history, and family history of premature CV disease); HIV, Hep B and Hep C screen; serum pregnancy test (WCBP only).
Site Visit
X
X
X
X
X
X
X
X
X
X
X
1. Full physical exam: height/weight at 
Screening, height not required at later 
timepoints.
2. Vitals: BP, HR, RR, temperature. 
ECG triplicate at Screening only.
3. Urinalysis not required on Days 29, 
57 and 71. 
4. If urine test is positive, confirmatory 
serum test must be performed.
5. Pre-dose
6. Subjects must take study medication 
twice a day approx. 12h apart. Exact 
time of dosing to be recorded in diary 
cards. On Days 43 and 85, subjects 
must not take medication at home in the 
morning. Subjects will complete pre-
dose assessments and then will be 
administered their morning dose of 
medication at site on Day 43 only. On 
Day 85, subjects no longer dosed.
7. Diary card checked by site staff and 
new diary card dispensed at every 
study visit.
Phone call
X
X
X
X
X
Safety Assessments
Full physical exam1
X
X
X
X
Brief physical exam
X5
X
X
X5
X
X
12-lead ECG, vital signs2
X
X5
X
X
X
X5
X
X
X
X
X
Columbia Suicide Severity 
Rating Scale (C-SSRS)
X
X5
X5
X
X
Hematology, chemistry, 
urinalysis 
X
X5
X
X
X3
X5
X3
X3
X
X
X
FSH & estradiol  (if 
applicable)
X
Serum pregnancy 
(WCBP)
X
Urine pregnancy test 
(WCBP only)4
X5
X
X
X
X5
X
X
X
X
X
Study Treatment
Randomisation
X
Study medication (twice 
daily)6
X
X-------------------------------------------------------------------------------------------------X
Dispensing of study 
medication
X
X
X
Dispensing of diary cards7
X
X
X
X
X
X
X


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Procedures
Screening
Treatment Period
Early Withdrawal 14
Follow Up
Notes
Day 1 
Day 8 
Day 15
Day 22
Day 29
Day 36
Day 43
(week 6)
Day 50
Day 57
Day 64
Day 71
Day 78
Day 85
(week 12)
Visit windows
Screening: up to 30d before Day 1.
Treatment Period (except Day 1 & 85): 
3d. Day 1 NA; Day 85 2d.
Early Withdrawal: NA
Follow Up: 28d after last dose 3d
PROs/ Disease Assessments
8.  Blood samples for inflammatory 
biomarkers and mRNA taken pre-dose
on Day 1, Day 43 and Day 85. 
9. PK blood samples taken pre-dose on 
Day 43. Post-dose serial PK samples 
taken on Day 1 and Day 43 at 1, 2, 4, 
and 6 hours post-dose.
10. Pre-dose Day 1 one biopsy taken 
from non-lesional skin and two biopsies 
taken from biopsy target lesion.
11. On Day 43, two biopsies taken from 
the same target lesion that was 
selected at Day 1. Punch biopsies on 
Day 43 are to be taken pre-dose.
12. Biopsy only required at Early 
Withdrawal visit if completed at least 14 
days of treatment and prior to Day 43.
13. PGx sample collected at Day 1, 
after randomization and separate
informed consent. If sample not 
collected at Day 1, can be collected at 
any time post-randomization. 
14. If subject withdraws early, every 
effort will be made for the subject to 
complete an Early Withdrawal visit prior 
to Follow Up. 
Psoriatic Body Surface 
Area
X
X5
X
X
PASI, PGA, PLSS, Itch
X
X5
X
X
X5
X
X
X
X
DLQI
X
X5
X5
X
X
Photograph of lesions
X5
X5
X
X
Other Assessments and Procedures
Blood sample for 
inflammatory biomarkers8
X5
X5
X
X
Blood sample for mRNA 
analysis8
X5
X5
X
X
Blood sample for Target 
Engagement
X5
X5
X
X
PK blood samples9
X
X5
X
X
Skin punch biopsies for 
PK, inflammatory 
biomarkers, mRNA, target 
engagement & pathway 
engagement
X5,10
X11
X12
Pharmacogenetic sample 
(PGx)
X13
Con med review & AE/SAE 
reporting
X-------------------------------------------------------------------------------------------------------------------------X


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Section 7.2 Screening and Critical Baseline Assessments
Cardiovascular medical history/risk factors and smoking history (as detailed in the 
CRF) will be assessed at screening. 
Section 7.3.4 Vital Signs
Vital signs will be measured in a supine or semi-supine position after 5 minutes rest and 
will include temperature, systolic and diastolic blood pressure, pulse rate and respiratory 
rate
Section 7.5.2 Sample Analysis
Plasma analysis will be performed at a bioanalytical site (to be detailed in the SRM) 
under the control of Platform Technologies and Science In vivo In vitro Technology In 
vitro/ In vivo Translation (PTS IVIVT) and Third Party Resource, GlaxoSmithKline.
Section 9.3.2 Interim Analysis
Once an appropriate number of subjects randomised to GSK2982772 have completed 
Day 43 (Week 6), the PLSS data will be reviewed in an unblinded manner by a Data 
Review Committee (DRC) consisting of the GSK study physician, the study statistician, 
the study pharmacokineticist, the PRR DPU Head, the Early Development Lead (EDL), 
the Safety Review Team (SRT) leader, or their designees on an ongoing basis.
12.6.2.
Protocol Amendment 2
Where the amendment applies
This protocol amendment applies to all countries.
Summary of amendment changes and rationale
An additional cohort of subjects is being included in the study in order to evaluate a 60
mg TID dosing regimen.  Because of the short half-life, a modified release formulation is 
now being developed in attempt to increase the Ctrough and decrease the peak to trough 
ratio using a once or twice daily dosing regimen. This is considered desirable for 
improving safety and tolerability and will aid in reduction of PK variability with the 
current IR formulation. It is believed that by increasing the frequency of dosing to three 
times daily (TID) with the current formulation, this will closely simulate the PK profile 
of a preferred modified release formulation.
List of specific changes (bold indicates text added and strikethrough indicates text 
removed)
Authors
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Medical Monitor Page
Role
Name
Day Time Phone Number and 
email address
After-hours 
Phone/Cell/
Pager Number
Fax Number
Site Address
Primary 
Medical 
Monitor 
Tel       
Email   
Mobile  
Tel: 
Mobile: 
Email:
Mobile  
 
 
Mobile:
N/A
Stockley Park 
West, 1-3 
Ironbridge 
Road, 
Uxbridge, 
Middlesex, 
UB11 1BT, 
United 
Kingdom
Pattern
Recognition
Receptor DPU,
UP4440
1250 S
Collegeville, PA
19426
Secondary 
Medical 
Monitor
Mobile:
Email 
Tel: 
Mobile: 
Email:
Mobile:
Mobile: 
1250S 
Collegeville 
Rd.
Collegeville PA 
19426, USA
Cytokine
Chemokine
DPU, GSK,
Gunnels Wood
Road,
Stevenage,
SG1 2NY, UK
SAE 
contact  
information 
Medical 
Monitor as 
above
Synopsis Rationale
The primary objective will be to investigate the safety and tolerability of repeat oral doses 
of GSK2982772 (60 mg twice daily and 60 mg three times daily for 84 days). In 
addition a number of experimental and clinical endpoints will be employed to obtain 
information on the pharmacokinetics, pharmacodynamics, and efficacy in subjects with 
active plaque-type psoriasis (PsO).  
PPD
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PPD
PPD
PPD
PPD
PPD
PPD
PPD
PP
D
PPD
PPD
PPD
PPD
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Synopsis Objectives and Endpoints
Objectives
Endpoints
Primary

To investigate the safety and tolerability of 60 
mg twice daily doses and 60 mg three times 
daily doses of GSK2982772 in subjects with 
active plaque-type psoriasis.

Adverse events

Clinical laboratory values (clinical chemistry, 
haematology and urinalysis)

Vital sign measurements (blood pressure, heart 
rate, respiratory rate and body temperature)

12-Lead ECG monitoring
Secondary

To investigate the pharmacokinetics of 
GSK2982772 in blood following 60 mg twice 
daily doses and 60 mg three times daily
doses of GSK2982772 in subjects with active 
plaque-type psoriasis.

Pre-dose plasma concentrations of 
GSK2982772 at Days 43 (Week 6) and 85 
(Week 12).

Post-dose plasma concentrations of 
GSK2982772 on Days 1 and 43 (Week 6) at 1, 
2, 4 and 6 hours post dose.

To investigate the effect of 60 mg twice daily 
doses and 60 mg three times daily doses of 
GSK2982772 on inflammatory biomarkers in 
skin biopsies from psoriatic skin lesions in 
subjects with active plaque-type psoriasis.

Change from baseline in histopathological 
scoring of psoriatic lesional biopsies which 
may include, but are not limited to the following 
as data permit:  K16, CD3/CD11c, CD161, 
elastase positive dermal cells and epidermal 
thickness.  

mRNA expression of inflammatory gene 
transcripts which may include, but are not 
limited to the following as data permit:  IL-4, IL-
10, IL-17, IL-21, IL-22, IL-23, TNF and IFNγ on 
Days 1 (Week 0) and 43 (Week 6).

To investigate the effect of 60 mg twice daily 
doses and 60 mg three times daily doses of 
GSK2982772 on disease activity in subjects 
with active plaque-type psoriasis

Percentage change from baseline and actual 
Psoriatic Lesion Severity Sum (PLSS) scores 
in the index lesion.
Exploratory

To investigate the effect of 60 mg twice daily 
doses and 60 mg three times daily doses of 
GSK2982772 on disease activity in subjects 
with active plaque-type psoriasis

Change from baseline in Psoriasis Area 
Severity Index (PASI) scores.

The proportion of subjects who achieve PASI ≥ 
50%, 75%, and 90% improvement from 
baseline score.

Change from baseline and actual Physician 
Global Assessment (PGA).

The proportion of subjects who achieve “clear” 
(0) or “almost clear” (1) on (PGA).

Change from baseline in body surface area 
(BSA).

To investigate the effect of 60 mg twice daily 

Change from baseline in blood inflammatory 


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Objectives
Endpoints
doses and 60 mg three times daily doses of 
GSK2982772 on inflammatory biomarkers in 
the blood of subjects with active plaque-type 
psoriasis.
markers which may include, but are not limited 
to the following as data permit:  CRP, VEGF, 
S100A8, S100A9, IL-17, IL-22, and TNF.

To investigate the effect of 60 mg twice daily 
doses and 60 mg three times daily doses of 
GSK2982772 on transcriptome profiling of both 
blood and skin of subjects with active plaque-
type psoriasis.

Transcriptomic analysis of mRNA isolated from 
blood and skin at Day 1 (Week 0) and Day 43 
(Week 6).

To investigate pathway and target engagement 
following 60 mg twice daily doses and 60 mg 
three times daily doses of GSK2982772 in 
blood and skin biopsy tissue in subjects with 
active plaque-type psoriasis.

Pharmacology biomarker endpoints may 
include, but are not limited to the following 
Days 1 (Week 0), 43 (Week 6) and 85 (Week 
12),  as data permit:
o
Target Engagement Assay RiP1 
(TEAR1) in blood and skin.
o
Total or phosphorylated RIP1, 
MLKL, and RIP3, cleaved and 
total caspase 3 and caspase 8 
signatures in skin.

To investigate the concentration of 
GSK2982772 in the skin of subjects with active 
plaque-type psoriasis after 60 mg twice daily 
doses and 60 mg three times daily doses of 
GSK2982772.

Pre-dose GSK2982772 concentrations in skin 
biopsies at Days 1 (Week 0) and 43 (Week 6), 
as data permit.

To investigate the effect of 60 mg twice daily
doses and 60 mg three times daily doses of 
GSK2982772 on the patient reported 
outcomes (PROs) of subjects with active 
plaque-type psoriasis.

Change from baseline in Dermatology Life 
Quality Index (DLQI) score.

Change from baseline and actual Visual 
Analogue Scale (VAS) itch score.
Synopsis Overall Design
This is a multicentre, randomised, double-blind (sponsor-unblinded), placebo-controlled, 
repeat dose study to investigate the safety and tolerability, PK, PD, and preliminary 
efficacy of GSK2982772 in subjects with active plaque-type psoriasis.  The study design 
schematic is depicted in Figure 1 below.  There will be two cohorts of subjects.  
Cohort 1 will receive either GSK2982772 60 mg or placebo orally twice daily and 
Cohort 2 will receive either GSK2982772 60 mg or placebo orally three times daily.


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Schematic added:
Cohort 2
Synopsis Treatment Arms and Duration
In Cohort 1 subjects who have completed screening assessments and are eligible will be 
randomised in a 2:1 ratio (active to placebo) to one of the following treatments:
60 mg GSK2982772 twice daily (BID) 
Placebo twice daily (BID) 
In Cohort 2 subjects who have completed screening assessments and are eligible will 
be randomised in a 3:1 ratio (active to placebo) to one of the following treatments:
60 mg GSK2982772 three times daily (TID) 
Placebo three times daily (TID) 
Synopsis Type and Number of Subjects
In Cohort 1, a sufficient number of subjects will be screened so that approximately 30 
subjects with active PsO are randomised.  Additional or replacement subjects may be 
randomised (up to a maximum of 36) into the study at the discretion of the Sponsor, to 
ensure that approximately 24 evaluable subjects complete the study.
In Cohort 2, a sufficient number of subjects will be screened so that approximately 
24 subjects with active PsO are randomised.  Additional or replacement subjects 
may be randomised (up to a maximum of 32) into the study at the discretion of the 
Sponsor, to ensure that approximately 20 evaluable subjects complete the study. 
For both cohorts, a subject is considered evaluable if they have completed at least one 
post-treatment biopsy.
Synopsis Analysis
An ongoing review of available efficacy, pharmacodynamic and mechanistic endpoints 
will be conducted during the study by a Data Review Committee (DRC), consisting of a 
limited number of GSK individuals, some of whom are also members of the GSK study 


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team who are not involved in the day-to-day running of the study.  The primary purpose 
of these reviews will be to monitor target engagement, inflammatory markers and the 
index lesion PLSS for internal decision making. A data review charter will outline in 
detail the activities of this review and how the integrity of the study will be maintained.  
An interim analysis will be conducted after the completion of Cohort 1.
Comparisons between treatment groups on any changes observed will be conducted for 
the secondary endpoints if deemed appropriate, e.g. changes in the mean target 
engagement, changes in inflammatory markers and percentage change in index lesion 
PLSS will be statistically analyzed using a repeated measures mixed effects model 
(MMRM) comparing each GSK2982772 arm with placebo at each time point.  
Section 2.1 Study Rationale
The primary objective will be to investigate the safety and tolerability of repeat oral doses 
of GSK2982772 (60 mg twice daily and 60 mg three times daily for 84 days). In 
addition, a number of experimental and clinical endpoints will be employed to obtain 
information on the pharmacokinetics (PK), pharmacodynamics (PD), and preliminary 
efficacy in subjects with active PsO
Section 3 Objectives and Endpoints
Objectives
Endpoints
Primary

To investigate the safety and tolerability of 60 
mg twice daily doses and 60 mg three times 
daily doses of GSK2982772 in subjects with 
active plaque-type psoriasis.

Adverse events

Clinical laboratory values (clinical chemistry, 
haematology and urinalysis)

Vital sign measurements (blood pressure, heart 
rate, respiratory rate and body temperature)

12-Lead ECG monitoring
Secondary

To investigate the pharmacokinetics of 
GSK2982772 in blood following 60 mg twice 
daily doses and 60 mg three times daily
doses of GSK2982772 in subjects with active 
plaque-type psoriasis.

Pre-dose plasma concentrations of 
GSK2982772 at Days 43 (Week 6) and 85 
(Week 12).

Post-dose plasma concentrations of 
GSK2982772 on Days 1 and 43 (Week 6) at 1, 
2, 4 and 6 hours post dose.

To investigate the effect of 60 mg twice daily 
doses and 60 mg three times daily doses of 
GSK2982772 on inflammatory biomarkers in 
skin biopsies from psoriatic skin lesions in 
subjects with active plaque-type psoriasis.

Change from baseline in histopathological 
scoring of psoriatic lesional biopsies which 
may include, but are not limited to the following 
as data permit:  K16, CD3/CD11c, CD161, 
elastase positive dermal cells and epidermal 
thickness.  

mRNA expression of inflammatory gene 
transcripts which may include, but are not 
limited to the following as data permit:  IL-4, IL-
10, IL-17, IL-21, IL-22, IL-23, TNF and IFNγ on 
Days 1 (Week 0) and 43 (Week 6).


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Objectives
Endpoints

To investigate the effect of 60 mg twice daily 
doses and 60 mg three times daily doses of 
GSK2982772 on disease activity in subjects 
with active plaque-type psoriasis

Percentage change from baseline and actual 
Psoriatic Lesion Severity Sum (PLSS) scores 
in the index lesion.
Exploratory

To investigate the effect of 60 mg twice daily 
doses and 60 mg three times daily doses of 
GSK2982772 on disease activity in subjects 
with active plaque-type psoriasis

Change from baseline in Psoriasis Area 
Severity Index (PASI) scores.

The proportion of subjects who achieve PASI ≥ 
50%, 75%, and 90% improvement from 
baseline score.

Change from baseline and actual Physician 
Global Assessment (PGA).

The proportion of subjects who achieve “clear” 
(0) or “almost clear” (1) on (PGA).

Change from baseline in body surface area 
(BSA).

To investigate the effect of 60 mg twice daily 
doses and 60 mg three times daily doses of 
GSK2982772 on inflammatory biomarkers in 
the blood of subjects with active plaque-type 
psoriasis.

Change from baseline in blood inflammatory 
markers which may include, but are not limited 
to the following as data permit:  CRP, VEGF, 
S100A8, S100A9, IL-17, IL-22, and TNF.

To investigate the effect of 60 mg twice daily 
doses and 60 mg three times daily doses of 
GSK2982772 on transcriptome profiling of both 
blood and skin of subjects with active plaque-
type psoriasis.

Transcriptomic analysis of mRNA isolated from 
blood and skin at Day 1 (Week 0) and Day 43 
(Week 6).

To investigate pathway and target engagement 
following 60 mg twice daily doses and 60 mg 
three times daily doses of GSK2982772 in 
blood and skin biopsy tissue in subjects with 
active plaque-type psoriasis.

Pharmacology biomarker endpoints may 
include, but are not limited to the following 
Days 1 (Week 0), 43 (Week 6) and 85 (Week 
12),  as data permit:
o
Target Engagement Assay RiP1 
(TEAR1) in blood and skin.
o
Total or phosphorylated RIP1, 
MLKL, and RIP3, cleaved and 
total caspase 3 and caspase 8 
signatures in skin.

To investigate the concentration of 
GSK2982772 in the skin of subjects with active 
plaque-type psoriasis after 60 mg twice daily 
doses and 60 mg three times daily doses of 
GSK2982772.

Pre-dose GSK2982772 concentrations in skin 
biopsies at Days 1 (Week 0) and 43 (Week 6), 
as data permit.

To investigate the effect of 60 mg twice daily
doses and 60 mg three times daily doses of 
GSK2982772 on the patient reported 

Change from baseline in Dermatology Life 
Quality Index (DLQI) score.


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Objectives
Endpoints
outcomes (PROs) of subjects with active 
plaque-type psoriasis.

Change from baseline and actual Visual 
Analogue Scale (VAS) itch score.
Section 4.1 Overall Design
This is a multicentre, randomised, double-blind (sponsor-unblinded), placebo-controlled, 
repeat dose study to investigate the safety and tolerability, PK, PD, and preliminary 
efficacy of GSK2982772 in subjects with active plaque-type psoriasis.  The study design 
schematic is depicted in Figure 2 below.  There will be two cohorts of subjects.  
Cohort 1 will receive either GSK2982772 60 mg or placebo orally twice daily and 
Cohort 2 will receive either GSK2982772 60 mg or placebo orally three times daily.
Schematic added:
Cohort 2
Section 4.2.2 Treatment Period
In Cohort 1, subjects will be randomly assigned to either GSK2982772 60mg or placebo 
orally twice daily (approximately 12 hours apart) for 84 days.  In Cohort 2 subjects will 
be randomly assigned to either GSK2982772 60 mg or placebo orally three times 
daily (approximately 8 hours apart) for 84 days.  
Section 4.3 Type and Number of Subjects
In Cohort 1, a sufficient number of subjects will be screened so that approximately 30 
subjects with active PsO are randomised.  Additional or replacement subjects may be 
randomised (up to a maximum of 36) into the study at the discretion of the Sponsor, to 
ensure that approximately 24 evaluable subjects complete the study.
In Cohort 2, a sufficient number of subjects will be screened so that approximately 
24 subjects with active PsO are randomised.  Additional or replacement subjects 
may be randomised (up to a maximum of 32) into the study at the discretion of the 
Sponsor, to ensure that approximately 20 evaluable subjects complete the study. 
For both cohorts, a subject is considered evaluable if they have completed at least one 
post-treatment biopsy


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Section 4.4 Design Justification 
In Cohort 1 the subjects will be randomised in a 2:1 ratio to GSK2982772 60mg BID 
and placebo respectively.  In Cohort 2 the subjects will be randomised in a 3:1 ratio 
to GSK2982772 60 mg TID and placebo respectively. The primary objective of this 
study is safety and tolerability and assessment of this is most valuable in a placebo 
controlled, blinded study. The placebo group was deemed necessary as autoimmune 
diseases naturally fluctuate in severity.  However, the size of the placebo group has been 
kept to a minimum.  Subjects will not be allowed to continue standard of care therapy 
including topical (not permitted on biopsy areas), oral and biologic therapy.  A washout 
period of specific therapies can be found in Section 6.11 
Section 4.5 Dose Justification 
The initial selection of the 60 mg BID dose to be being tested in this study is based on 
the safety, PK, and PD data from the GSK2982772 First Time in Human (FTiH) study, 
200975. GSK2982772 administered at 60 mg BID for 14 days was well tolerated and no 
safety concerns were identified. A BID dosing regimen was initially selected over a QD 
dosing regimen due to the short half-life of GSK2982772 in humans (~2 hours). Based on 
preliminary PK/PD modelling of ex-vivo RIP1 target engagement and GSK2982772 
concentrations from the multiple dose ascending part of Study 200975, a 60 mg BID dose 
is was predicted to have on average 95% RIP1 target engagement in blood and 
approximately 90% of subjects are predicted to have >90% RIP1 target engagement in 
blood at Cmin using a novel in-house ex-vivo PD/target engagement assay based 
solely on the TNF pathway which is believed to be a key component of the RIP1 
pathway. Assuming a skin: blood ratio of 0.4 (as observed in the rat), the average RIP1 
target engagement in skin is predicted to be 92%. At Cmin, 44% of subjects are predicted 
to have >90% RIP1 target engagement in the skin and 90% of subjects are predicted to 
have >80% RIP1 target engagement in the skin. 
However, based on final PK/PD modelling from the full repeat dose part of the 
Study 200975 (up to 120 mg BID), a 60 mg BID dose is now predicted to have on 
average 99.3% RIP1 target engagement in blood and approximately 90% of 
subjects will have  >96.3% target engagement at Cmin.  In skin, assuming the same 
skin: blood ratio of 0.4 as noted above, the average RIP target engagement at 60 mg 
TID in skin in predicted to be 96%.  At Cmin, 43% of subjects are predicted to have 
>90% RIP1 target engagement in the skin and 90% of subjects are predicted to 
have >70% RIP1 target engagement in the skin.    
In review of this final FTiH data, it is believed that the Cmin target exposure may not 
be achieved with a 60mg BID dosing regimen.  The Cmin values at 60 mg TID are 
predicted to be approximately 3.5 fold higher than for 60 mg BID.  Therefore, a 60 
mg TID cohort is now being proposed.   
 
 


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Using the final PK/PD, a 60 mg TID dose is predicted to have on average 99% RIP1 
target engagement in blood and approximately 90% of subjects will have > 96% 
target engagement at Cmin.  In skin, the average RIP target engagement at 60 mg 
TID is predicted to be 98%.  At Cmin, 91% of subjects are predicted to have >90% 
RIP1 target engagement in the skin and 90% of subjects are predicted to have 
>91% RIP1 target engagement in the skin.  
In addition, because of the short half-life, a modified release formulation is now 
being developed with the aim to provide a once daily dosing regimen.  By increasing 
the frequency of dosing to three times daily (TID) with the current immediate 
release formulation, this will more closely match the PK, safety and efficacy profile 
of a preferred once daily modified release formulation.
Therefore, it is predicted that a dose of GSK2982772 60 mg BID may be clinically 
efficacious in subjects with active PsO.
It is anticipated that a human dose of 60 mg BID will produce AUC(0-24) and Cmax 
values of approximately 9 ug.h/mL and 1 ug/mL, respectively, which are approximately 
1/6th and 1/12th of the gender-averaged AUC (48.4 ug.h/mL) and Cmax (12.3 ug/mL) 
achieved in the 13 week monkey study at the NOAEL dose of 30 mg/kg/day.
The safety of increasing the dose frequency to 60 mg TID is justified based on 
nonclinical safety findings to date with GSK2982772. It is anticipated that a human 
dose of 60 mg TID (180 mg/day) will produce AUC(0-24) and Cmax values of 
approximately 9.9 ug.h/mL and 0.8 ug/mL, respectively, which are approximately 
1/5th and 1/15th of the gender-averaged AUC (48.4 ug.h/mL) and Cmax (12.3 ug/mL) 
achieved in the 13 week monkey study at the no adverse effect level (NOAEL) dose 
of 30 mg/kg/day. Please see GSK2982772 IB [GlaxoSmithKline Document Number 
2014N204126_01].
Up to 03 Apr 2017, a total of approximately 93 subjects across 4 clinical studies have 
been randomised to receive GSK2982772. In Study 200975, GSK2982772 
administered up to 120 mg BID for 14 days and was well tolerated and no safety 
concerns were identified. A total of 9 subjects had received 120 mg BID in that 
study.  Please see GSK2982772 IB [GlaxoSmithKline Document Number 
2014N204126_01]. In this current study, 203167, approximately 22 of 33 subjects 
have been randomised to GSK2982772 60 mg BID. In other Phase 2a studies in 
Rheumatoid Arthritis [(RA); Study 203168] and Ulcerative Colitis [(UC); Study 
202152], a total of 4 subjects have been randomised to GSK2982772 60 mg BID.
GSK2982772 was well tolerated and no drug-related SAEs have been reported.  
There was a death of a 19 year old male subject in this current study due to an 
accidental overdose with 3,4-methylenedioxy-methamphetamine (MDMA) that was 
not considered drug related by the Principal Investigator (PI).
The proposed 60 mg TID dose regimen is predicted to have mean Cmax (0.80 µg/mL) 
and AUC(0-24) (9.9 µg.hr/mL ) that are approximately 10% and 50% higher, 
respectively than for 60 mg BID (0.70 µg/mL and 6.6 µg.hr/mL).  This exposure is 
well within the observed Cmax and AUC(0-24) values at 120 mg BID in Study 200975.


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Section 5.1 Inclusion Criteria
For both cohorts, a subject will be eligible for inclusion in this study only if all of the 
following criteria apply:
Section 5.2 Exclusion Criteria
For both cohorts, a subject will not be eligible for inclusion in this study only if all of 
the following criteria apply:
20.  The subject has participated in a clinical trial and has received an investigational 
product within 30 days or 5 half-lives, whichever is longer before the first dose of study 
medication, or plans to take part in another clinical trial at the same time as participating 
in this clinical trial. Subjects who were randomized into Cohort 1 are not eligible to 
be re-randomized into Cohort 2.
21.  Haemoglobin <11 g/dL; haematocrit <30%, white blood cell count ≤3000/mm3 (≤3.0 
x 109/L); or ≥14,000/mm3 (≥14 x 109/L); platelet count ≤ 100,000/µL (≤100 x 109/L); 
absolute neutrophil count ≤1.5 3 x 109/L lymphocyte count <1 x 109/L at the screening 
visit.
Section 5.3 Screening / Baseline / Run-in Failures
Subjects who do not qualify to participate in the study due to a screening laboratory value 
or ECG abnormality can repeat the test once within the original screening time window, 
if the Investigator believes there is a reasonable possibility that the subject would be 
eligible if re-tested. 
Subjects can be re-screened only on approval of the GSK Medical Monitor and only 
once. Re-screening is allowed when a subject failed inclusion/exclusion criteria or 
some other screening condition initially, but the Investigator believes there is a 
reasonable probability that the subject would be eligible if re-screened.
Section 5.4.1 Individual Safety Stopping Rules
Study medication will be discontinued in the event of any of the following:

If a subject experiences a serious or severe clinically significant AE that in the 
clinical judgement of the investigator, after consultation with the medical monitor, 
there is a reasonable possibility that the AE is related to investigational product.

The subject becomes pregnant.

The subject initiates treatment with any prohibited medication for the treatment of 
PsO as listed in Section 6.11.2.

The subject develops a serious opportunistic or atypical infection.


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
If the liver chemistry stopping criteria (Section 5.4.3), QTc stopping criteria 
(Section 5.4.4), or haematologic stopping criteria (Section 5.4.5) are met.

The subject experiences any signs of suicidal ideation or behaviour (Section 
7.3.7).
Section 5.4.5 Haematologic Stopping Criteria
Study treatment will be stopped for a subject if any of the following haematological 
stopping criteria is met:

Haemoglobin <9 g/dL or an absolute decrease of ≥3 g/dL from baseline (pre-dose 
Day 1)

Neutrophils <1 x 109/L

Lymphocytes <0.5 × 109/L

Platelets <50 × 109/L
Section 6.1 Investigation Product and Other Study Treatment
Study Treatment
Product name:
GSK2982772
Placebo
Dosage form:
Tablet
Tablet
Unit dose strength(s)/Dosage 
level(s):
30 mg
NA
Route of Administration 
For oral use only
For oral use only
Dosing instructions for Cohort 1:
Take TWO tablets in the 
MORNING and TWO tablets in the 
EVENING as directed
Take TWO tablets in the 
MORNING and TWO tablets in the 
EVENING as directed
Dosing instructions for Cohort 
2:
Take TWO tablets THREE times 
daily as directed by your 
physician
Take TWO tablets THREE times 
daily as directed by your 
physician
Physical description
White to almost white, round, film 
coated tablet
White to almost white, round film 
coated tablet
Source of procurement
Study medication is supplied by 
GlaxoSmithKline
Placebo is supplied by 
GlaxoSmithKline
Section 6.2 Treatment Assignment
In Cohort 1, subjects will take study medication every day, twice a day, approximately 
12 hours apart.   Subjects will be randomised to receive either GSK2982772 or placebo in 
a 2:1 ratio. In Cohort 2, subjects will take study medication every day, three times a 
day, with approximately 8 hours between each dose.  Subjects will be randomised to 
receive either GSK2982772 or placebo in a 3:1 ratio.
Section 6.4 Blinding
This will be a double blind (sponsor unblind) study and the following will apply. 


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Sponsor unblinded refers only to the Data Review Committee (DRC) consisting of the 
GSK study physician Project Physician Lead (PPL), the study statistician, the study 
pharmacokineticist, Pattern Recognition Receptor (PRR) Discovery Performance Unit 
(DPU) Head, the Early Development Leader (EDL), the Safety Review Team (SRT) 
leader, or their designees on an ongoing basis.
Section 6.8 Treatment of Study Treatment Overdose
For this study, any dose of GSK2982772 >120 mg daily will be considered an overdose 
in Cohort 1 and any dose of GSK2982772 >180 mg daily will be considered an 
overdose in Cohort 2.  GSK does not recommend specific treatment for an overdose.  
The investigator will use clinical judgement to treat any overdose as and when they are 
made aware of this.


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Section 7.1 Time and Events Table
Procedures
Screening
Treatment Period
Early Withdrawal 14
Follow Up
Notes
Day 1 
Day 8 
Day 15
Day 22
Day 29
Day 36
Day 43
(week 6)
Day 50
Day 57
Day 64
Day 71
Day 78
Day 85
(week 12)
Visit windows
Screening: up to 30d before Day 1.
Treatment Period (except Day 1 & 
85): 3d. Day 1 NA; Day 85 2d.
Early Withdrawal: NA
Follow Up: 28d after last dose 3d
Screening Procedures
Screening procedures in addition to those listed below are (outpatient visit): informed consent; inclusion/ exclusion criteria; demography; medical history (includes past and 
current conditions, medication history, and family history of premature CV disease); HIV, Hep B and Hep C screen; serum pregnancy test (WCBP only).
Site Visit
X
X
X
X
X
X
X
X
X
X
X
1. Full physical exam: height/weight at 
Screening, height not required at later 
timepoints.
2. Vitals: BP, HR, RR, temperature. 
ECG triplicate at Screening only.
3. Urinalysis not required on Days 29, 
57 and 71. 
4. If urine test is positive, confirmatory 
serum test must be performed.
5. Pre-dose
6. In Cohort 1, subjects must take 
study medication twice a day approx. 
12h apart.  In Cohort 2, subjects must 
take study medication three times a 
day approx. 8h apart. Exact time of 
dosing to be recorded in diary cards. 
On Days 43 and 85, subjects must not 
take medication at home in the 
morning. Subjects will complete pre-
dose assessments and then will be 
administered their morning dose of 
medication at site on Day 43 only. On 
Day 85, subjects no longer dosed.
7. Diary card checked by site staff and 
new diary card dispensed at every 
study visit.
Phone call
X
X
X
X
X
Safety Assessments
Full physical exam1
X
X
X
X
Brief physical exam
X5
X
X
X5
X
X
12-lead ECG, vital signs2
X
X5
X
X
X
X5
X
X
X
X
X
Columbia Suicide Severity 
Rating Scale (C-SSRS)
X
X5
X5
X
X
Hematology, chemistry, 
urinalysis 
X
X5
X
X
X3
X5
X3
X3
X
X
X
FSH & estradiol  (if 
applicable)
X
Serum pregnancy (WCBP)
X
Urine pregnancy test 
(WCBP only)4
X5
X
X
X
X5
X
X
X
X
X
Study Treatment
Randomisation
X
Study medication (twice 
daily)6
X
X-------------------------------------------------------------------------------------------------X
Dispensing of study 
medication
X
X
X
Dispensing of diary cards7
X
X
X
X
X
X
X


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Procedures
Screening
Treatment Period
Early Withdrawal 14
Follow Up
Notes
Day 1 
Day 8 
Day 15
Day 22
Day 29
Day 36
Day 43
(week 6)
Day 50
Day 57
Day 64
Day 71
Day 78
Day 85
(week 12)
Visit windows
Screening: up to 30d before Day 1.
Treatment Period (except Day 1 & 
85): 3d. Day 1 NA; Day 85 2d.
Early Withdrawal: NA
Follow Up: 28d after last dose 3d
PROs/ Disease Assessments
8.  Blood samples for inflammatory 
biomarkers and mRNA taken pre-dose 
on Day 1, Day 43 and Day 85. 
9. PK blood samples taken pre-dose on 
Day 43. Post-dose serial PK samples 
taken on Day 1 and Day 43 at 1, 2, 4, 
and 6 hours post-dose.
10. Pre-dose Day 1 one biopsy taken 
from non-lesional skin and two biopsies 
taken from biopsy target lesion.
11. On Day 43, two biopsies taken from 
the same target lesion that was 
selected at Day 1. Punch biopsies on 
Day 43 are to be taken pre-dose.
12. Biopsy only required at Early 
Withdrawal visit if completed at least 14 
days of treatment and prior to Day 43.
13. PGx sample collected at Day 1, 
after randomization and separate 
informed consent. If sample not 
collected at Day 1, can be collected at 
any time post-randomization. 
14. If subject withdraws early, every 
effort will be made for the subject to 
complete an Early Withdrawal visit prior 
to Follow Up. 
Psoriatic Body Surface 
Area
X
X5
X
X
PASI, PGA, PLSS, Itch
X
X5
X
X
X5
X
X
X
X
DLQI
X
X5
X5
X
X
Photograph of lesions
X5
X5
X
X
Other Assessments and Procedures
Blood sample for 
inflammatory biomarkers8
X5
X5
X
X
Blood sample for mRNA 
analysis8
X5
X5
X
X
Blood sample for Target 
Engagement
X5
X5
X
X
PK blood samples9
X
X5
X
X
Skin punch biopsies for 
PK, inflammatory 
biomarkers, mRNA, target 
engagement & pathway 
engagement
X5,10
X11
X12
Pharmacogenetic sample 
(PGx)
X13
Con med review & AE/SAE 
reporting
X-------------------------------------------------------------------------------------------------------------------------X


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Section 7.3.7 Suicidal Risk Monitoring
Subjects being treated with GSK2982772 should be monitored appropriately for suicidal 
ideation and behaviour or any other unusual changes in behaviour. Consideration should 
be given to discontinuing GSK2982772 in subjects who experience signs of suicidal 
ideation or behaviour. All subjects who experience signs of suicidal ideation or 
behaviour must immediately be discontinued from study medication.
Section 9.1 Hypotheses
The primary objective of the study is to investigate the safety and tolerability of 
GSK2982772 60 mg BID and 60 mg TID following 12 weeks of treatment.  No formal 
statistical hypotheses will be conducted to assess this objective.
Section 9.2.1 Sample Size Assumptions
The study is not powered to detect pre-defined differences.  In Cohort 1, approximately 
30 subjects and up to a maximum of 36, will be randomised into the study to either 
GSK2982772 or placebo in a 2:1 ratio to ensure that approximately 24 evaluable subjects 
complete the study.  
In Cohort 2, approximately 24 subjects and up to a maximum of 32, will be 
randomised into the study to either GSK2982772 or placebo in a 3:1 ratio to ensure 
that approximately 20 evaluable subjects complete the study.
A subject is considered evaluable if they have completed at least one post-treatment 
biopsy.
The primary objective of the study is safety and tolerability, where there will be 20 
subjects randomised to GSK2982772 60 mg BID and 18 subjects randomised to 
GSK2982772 60 mg TID.  Using a Bayesian approach to determine the confidence 
interval around an observed safety event, we would assume a flat Beta (1, 1) prior, and if 
we were to observe one safety event in 20 then the posterior distribution would be Beta 
(2, 20), as outlined below in Figure 4.
Thus, we can be 95% certain that the true probability of the safety event lies between 
0.01 and 0.24.  Similarly, if we were to observe one safety event in 18 then the 
posterior distribution would be Beta (2, 18), thus we can be 95% certain that the 
true probability of the safety event lies between 0.01 and 0.26.  
For supportive information the properties of the secondary endpoint PLSS have also been 
considered.  Assuming a standard deviation of 25%, it is estimated that the lower and 
upper bounds of the 95% confidence interval for the difference between GSK2982772 60
mg BID (n=20) and placebo (n=10) in percentage change in index lesion PLSS will be 
within approximately 20.3 17.1% of the point estimate, and that the lower and upper 
bounds of the 95% confidence interval for the difference between GSK2982772 60
mg TID (n=18) and placebo (n=6) in percentage change in index lesion PLSS will be 
within approximately 17.5% of the point estimate.


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Section 9.2.2 Sample Size Sensitivity
A sample size sensitivity analysis has been conducted on the primary endpoint to 
investigate the different safety event rates.  If the number of subjects who complete the 
12 weeks is lower than 20 in the GSK2982772 group anticipated, then the true incidence 
rates of safety events that could not be ruled out (as outlined in Section 9.2.1) would 
change.  These changes are outlined in Table 4.
Figure deleted:
Figure 5
Sample Size Sensitivity for Percentage Change in PLSS


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Figure added:
Figure 5
Sample Size Sensitivity for Percentage Change in PLSS
Section 9.3.2 Interim Analysis
In both cohorts, once an appropriate number of subjects randomised to GSK2982772 
have completed Day 43 (Week 6), the PLSS data will be reviewed in an unblinded 
manner by a Data Review Committee (DRC) consisting of the GSK study physician
Project Physician Lead (PPL), the study statistician, the study pharmacokineticist, the 
PRR DPU Head, the Early Development Lead (EDL), the Safety Review Team (SRT) 
leader, or their designees on an ongoing basis.  A physician external to the GSK2982772 
project team may also be involved in the data review. Additional inflammatory 
biomarkers, clinical and mechanistic endpoints (e.g. target engagement) may be reviewed 
if available. No other member of the GSK core study team will be unblinded to this data. 
The primary purpose of these reviews will be to monitor PLSS changes for internal 
decision making purposes.  A data review charter will identify the specific GSK 
individuals involved, outline in detail the activities of this review and how the integrity of 
the study will be maintained.  


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A formal interim analysis will be conducted after the completion of Cohort 1 and 
will only include those subjects randomised to a BID dosing regimen. The purpose 
of the interim analysis is primarily to provide the project team and key GSK 
stakeholders with an early indication of the safety and efficacy from the trial, and to 
facilitate decision making regarding the subsequent clinical development of 
GSK2982772.  
Section 9.3.4 Secondary Analyses
Comparisons between treatment groups on any changes observed will be conducted for 
the secondary endpoints if deemed appropriate, e.g. changes in the mean target 
engagement, changes in inflammatory markers and percentage change in index lesion 
PLSS be statistically analyzed using a MMRM (repeated measures mixed effects model) 
comparing each GSK2982772 arm with placebo at each time point. If sufficient numbers 
of subjects are enrolled with a BSA >5% then the proportion of subjects achieving PASI 
50/75/90 at Day 85 (12 Weeks), will be statistically analysed using a Generalised 
Estimating Equations (GEE) model comparing each GSK2982772 arm with placebo at 
each time point if appropriate. Similar analyses will be conducted for other secondary 
endpoints if deemed appropriate.
GSK2982772 plasma concentrations will be summarised descriptively by Day and 
nominal time point by dosing regimen.
Section 12.1. Appendix 1 – Abbreviations and Trademarks
MDMA
3,4-methylenedioxy-methamphetamine
PI
Principal Investigator
PPL
Project Physician Lead
TID
Three times daily

SAP_001.pdf: 
 
CONFIDENTIAL 
 
The GlaxoSmithKline group of companies 
 
203167 
 
1 
 
Division 
: Worldwide Development 
Information Type 
: Reporting and Analysis Plan (RAP) 
 
Title 
: A multicentre, randomised, double-blind (sponsor-unblinded), 
placebo-controlled, repeat dose study to investigate the safety 
and tolerability, pharmacokinetics, pharmacodynamics, and 
efficacy of GSK2982772 in subjects with active plaque-type 
psoriasis. 
Compound Number  
: GSK2982772 
Effective Date  
: 24-May-2017 
 
Description : 
• 
The purpose of this RAP is to describe the planned analyses and output to be 
included in the Clinical Study Report for Protocol 203167. 
• 
This RAP is intended to describe the safety, tolerability, PK, PD, and efficacy 
analyses required for the study.  
• 
This RAP will be provided to the study team members to convey the content of the 
Statistical Analysis Complete (SAC) deliverable. 
 
Author’s Name and Functional Area:  
 
24-MAY-2017 
Statistician (Clinical Statistics)   
 
24-MAY-2017 
Manager Statistics (Clinical Statistics) 
 
Approved by:  
 
24-MAY-2017 
Director Statistics (Clinical Statistics) 
 
Copyright 2016 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited. 
 
PPD
PPD
PPD


 
CONFIDENTIAL 
 
 
 
Clinical Study Identifier 
 
2 
 
TABLE OF CONTENTS 
PAGE 
1. 
REPORTING & ANALYSIS PLAN SYNPOSIS ......................................................... 5 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION .................................................. 7 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan ............................ 7 
2.2. 
Study Objective(s) and Endpoint(s)............................................................... 7 
2.3. 
Study Design ................................................................................................ 9 
2.4. 
Statistical Hypotheses................................................................................. 10 
3. 
PLANNED ANALYSES .......................................................................................... 10 
3.1. 
Interim Analyses ......................................................................................... 10 
3.2. 
Final Analyses ............................................................................................ 11 
4. 
ANALYSIS POPULATIONS ................................................................................... 11 
4.1. 
Protocol Deviations ..................................................................................... 11 
5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS ..................................................................................................... 13 
6. 
STUDY POPULATION ANALYSES ....................................................................... 14 
6.1. 
Overview of Planned Analyses ................................................................... 14 
7. 
PRIMARY STATISTICAL ANALYSES .................................................................... 16 
7.1. 
Safety Analyses .......................................................................................... 16 
7.1.1. 
Overview of Planned Efficacy Analyses ....................................... 16 
7.1.2. 
Overview of Clinical Laboratory Analyses .................................... 16 
7.1.3. 
Overview of Planned Other Safety Analyses ................................ 17 
8. 
SECONDARY STATISTICAL ANALYSES ............................................................. 19 
8.1. 
Plasma Pharmacokinetic Analyses ............................................................. 19 
8.1.1. 
Overview of Planned Pharmacokinetic Analyses ......................... 19 
8.1.2. 
Overview of Planned pharmacokinetic Analyses .......................... 19 
8.1.3. 
Drug Concentration Measures ..................................................... 19 
8.1.3.1. 
Statistical Analysis of Pharmacokinetic 
Parameters ................................................................. 19 
8.2. 
Pharmacodynamic/Biomarker Analyses ...................................................... 20 
8.2.1. 
Overview of Planned Analyses .................................................... 20 
8.2.2. 
Statistical Analysis of Inflammatory Biomarkers in the Skin 
Biopsy (Histopathological Scoring of Psoriatic Lesional 
Biopsies) ...................................................................................... 20 
8.2.3. 
Statistical Analysis of mRNA from Skin Biopsies: 
Transcriptomic Data ..................................................................... 21 
8.2.3.1. 
Fold Change Analysis ................................................. 21 
8.3. 
Efficacy Analyses ........................................................................................ 22 
8.3.1. 
Overview of Planned Efficacy Analyses ....................................... 22 
8.3.2. 
Statistical Analysis of Efficacy Data ............................................. 22 
9. 
OTHER STATISTICAL ANALYSES ....................................................................... 24 


 
CONFIDENTIAL 
 
 
 
Clinical Study Identifier 
 
3 
 
9.1. 
Skin Pharmacokinetic Analyses .................................................................. 24 
9.1.1. 
Overview of Planned Pharmacokinetic Analyses ......................... 24 
9.1.2. 
Overview of Planned pharmacokinetic Analyses .......................... 24 
9.1.3. 
Drug Concentration Measures ..................................................... 24 
9.1.3.1. 
Statistical Analysis of Pharmacokinetic 
Parameters ................................................................. 24 
9.2. 
Exploratory Pharmacodynamic and  Biomarker Analyses ........................... 24 
9.2.1. 
Planned Exploratory Biomarker Statistical Analyses .................... 25 
9.3. 
Exploratory Efficacy Analyses ..................................................................... 26 
9.3.1. 
Planned Exploratory Efficacy Statistical Analyses ........................ 27 
9.4. 
Exploratory Pharmacodynamic / Efficacy Analyses ..................................... 29 
10. REFERENCES ....................................................................................................... 30 
11. APPENDICES ........................................................................................................ 31 
11.1. 
Appendix 1: Time & Events ......................................................................... 32 
11.1.1. 
Protocol Defined Time & Events .................................................. 32 
11.2. 
Appendix 2: Assessment Windows ............................................................. 34 
11.2.1. 
Definitions of Assessment Windows for Analyses ........................ 34 
11.3. 
Appendix 3: Treatment States and Phases ................................................. 35 
11.3.1. 
Treatment Phases ....................................................................... 35 
11.3.2. 
Treatment States ......................................................................... 35 
11.3.2.1. Treatment States for Safety Data ............................... 35 
Treatment States for AE Data ...................................................... 35 
11.4. 
Appendix 4: Data Display Standards & Handling Conventions .................... 36 
11.4.1. 
Study Treatment & Sub-group Display Descriptors ...................... 36 
11.4.2. 
Baseline Definition & Derivations ................................................. 36 
11.4.2.1. Baseline Definitions .................................................... 36 
11.4.2.2. Derivations and Handling of Missing Baseline 
Data ........................................................................... 37 
11.4.3. 
Reporting Process & Standards ................................................... 37 
11.5. 
Appendix 5: Derived and Transformed Data ............................................... 40 
11.5.1. 
General ........................................................................................ 40 
11.5.2. 
Study Population .......................................................................... 40 
11.5.3. 
Safety .......................................................................................... 41 
11.5.4. 
Pharmacokinetic .......................................................................... 41 
11.5.5. 
Efficacy ........................................................................................ 42 
11.5.6. 
Pharmacodynamic and Biomarker ............................................... 47 
11.6. 
Appendix 6: Premature Withdrawals & Handling of Missing Data ............... 48 
11.6.1. 
Premature Withdrawals ................................................................ 48 
11.6.2. 
Handling of Missing Data ............................................................. 48 
11.6.2.1. Handling of Missing Dates .......................................... 48 
11.6.2.2. Handling of Partial Dates ............................................ 49 
11.6.2.3. Handling of Missing Data for Statistical 
Analysis ...................................................................... 49 
11.7. 
Appendix 7: Values of Potential Clinical Importance ................................... 51 
11.7.1. 
Laboratory Values ........................................................................ 51 
11.7.2. 
ECG ............................................................................................. 52 
11.7.3. 
Vital Signs .................................................................................... 52 
11.8. 
Appendix 8: Multicenter Studies .................................................................. 53 


 
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11.9. 
Appendix 9: Examination of Covariates, Subgroups & Other Strata ............ 54 
11.10. Appendix 10: Multiple Comparisons & Multiplicity ....................................... 55 
11.11. Appendix 11: Model Checking and Diagnostics for Statistical 
Analyses ..................................................................................................... 56 
11.11.1. Statistical Analysis Assumptions .................................................. 56 
11.12. Appendix 14 – Abbreviations & Trade Marks .............................................. 57 
11.12.1. Abbreviations ............................................................................... 57 
11.12.2. Trademarks ................................................................................. 58 
11.13. Appendix 15: List of Data Displays.............................................................. 59 
11.13.1. Data Display Numbering .............................................................. 59 
11.13.2. Mock Example Shell Referencing ................................................ 59 
11.13.3. Deliverable [Priority] ..................................................................... 59 
11.13.4. Study Population Tables .............................................................. 60 
11.13.5. Safety Tables ............................................................................... 61 
11.13.6. Safety Figures ............................................................................. 64 
11.13.7. Efficacy Tables ............................................................................ 65 
11.13.8. Efficacy Figures ........................................................................... 68 
11.13.9. Pharmacokinetic Tables ............................................................... 71 
11.13.10. Pharmacokinetic Figures ............................................................. 72 
11.13.11. Pharmacodynamic and / or Biomarker Tables ............................. 74 
11.13.12. Pharmacodynamic (and / or Biomarker) Figures .......................... 76 
11.13.13. Biomarker / Efficacy Figures ........................................................ 79 
11.13.14. ICH Listings ................................................................................. 80 
11.13.15. Non-ICH Listings .......................................................................... 84 
11.14. Appendix 16:  Example Mock Shells for Data Displays ............................... 87 
 


 
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1. 
REPORTING & ANALYSIS PLAN SYNPOSIS 
Overview 
Key Elements of the RAP 
Purpose 
This is the first study with GSK2982772 in subjects with active, plaque-type 
psoriasis. The purpose of this study is to evaluate the safety, tolerability, 
pharmacokinetic (PK), pharmacodynamics (PD) and preliminary efficacy of 
GSK2982772. The intention of this study is to enable a fuller understanding of the 
mechanism of action and potential for clinical efficacy of GSK2982772 in PsO. 
Protocol 
This RAP is based on protocol amendment #2 [(Dated: 12/04/2017) of study 
GSK2982772 (GSK Document No. : 2015N251765_02)] and eCRF Version 3.0 
Primary 
Objective  
To investigate the safety and tolerability of 60 mg twice daily doses and 60 mg 
three times daily doses of GSK2982772 in subjects with active plaque-type 
psoriasis.  
Primary 
Endpoint 
Safety and tolerability of GSK2982772 as assessed by clinical monitoring and 
reporting of adverse events, change in laboratory values, ECG, vital signs. 
Study 
Design 
A multicentre, randomised, double-blind (sponsor-unblinded), placebo-controlled, 
repeat dose study proof of mechanism study. 
Approximately 30 subjects with active PsO will be randomised in a 2:1 ratio to 
GSK2982772 60mg BID and placebo respectively.   
Approximately 24 subjects with active PsO will be randomised in a 3:1 ratio to 
GSK2982772 60mg TID and placebo respectively 
Planned 
Analyses 
Safety and tolerability (primary). 
Pharmacokinetic (PK), Pharmacodynamic (PD) and clinical efficacy 
(secondary/exploratory). 
Analysis 
Populations 
All subjects: all subjects screened for eligibility 
Safety population: comprised all subjects who receive one dose of study treatment 
(placebo or GSK2982772). 
PK population: comprised subjects in the ‘Safety’ population for whom a 
pharmacokinetic sample was obtained and analysed. 
Hypothesis 
The primary objective of the study is to investigate the safety and tolerability of 
GSK2982772 60mg BID and 60mg TID following 12 weeks of treatment. No 
formal statistical hypotheses will be conducted to assess this objective.  
If appropriate, comparisons between the GSK2982772 60mg BID / 60mg TID 
arms and the placebo arm will be made to investigate the secondary 
inflammatory, mechanistic and efficacy objectives. Trends over time will be 
investigated for both treatment arms along with associations between each of the 
parameters. 
Primary 
Safety: 


 
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Overview 
Key Elements of the RAP 
Analyses 
• All data will be descriptively summarised, graphically presented and listed 
appropriately according to GSK’s Integrated Data Standard Library (IDSL) 
standards. 
Secondary 
Analyses 
General: 
• All data will be descriptively summarised, graphically presented and listed 
appropriately according to GSK’s Integrated Data Standard Library (IDSL) 
standards. 
• Modelling relationships between each of the mechanistic endpoints and 
also with the clinical endpoints using appropriate statistical modelling 
techniques to identify any trends.  
• Trends over time will be investigated for all treatment arms along with   
associations between each of the key secondary and exploratory 
parameters. 
• If appropriate, formal comparisons between each GSK2982772 arm and 
placebo will be made to investigate the secondary PD, mechanistic 
endpoints and efficacy. 
Pharmacokinetic:  
• No formal statistical analyses will be conducted. 
Pharmacodynamic/biomarker:  
• Descriptive statistics and/or graphical summaries for all PD and biomarker 
endpoints by treatment and time point. 
Efficacy: 
• Descriptive statistics and/or graphical summaries of index lesion PLSS 
score by treatment and time point.  
• (Percentage) change from baseline for the index lesion PLSS score will 
be analysed using repeated measures mixed effects model (MMRM), 
where appropriate. 
 
 
 


 
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2. 
SUMMARY OF KEY PROTOCOL INFORMATION 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan 
There were no changes or deviations to the originally planned statistical analysis 
specified in the protocol amendment 2 [(Dated: 12-Apr-2017)]. 
2.2. 
Study Objective(s) and Endpoint(s) 
Objectives 
Endpoints 
Primary Objectives 
Primary Endpoints 
• To investigate the safety and 
tolerability of 60 mg twice daily and 
60 mg three times daily doses 
doses of GSK2982772  in subjects 
with active plaque-type psoriasis. 
• Adverse events 
• Clinical laboratory values (clinical chemistry, 
haematology and urinalysis) 
• Vital sign measurements (blood pressure, heart rate, 
respiratory rate and body 
• temperature) 
• 
12-Lead ECG monitoring 
Secondary Objectives 
Primary Objectives 
• To investigate the 
pharmacokinetics of GSK2982772 
in blood following 60 mg twice daily 
doses and 60 mg three times daily 
doses of GSK2982772 in subjects 
with active plaque-type psoriasis. 
• Pre-dose plasma concentrations of GSK2982772 at 
Days 43 (Week 6) and 85 (Week 12). 
• Post-dose plasma concentrations of GSK2982772 
on Days 1 and 43 (Week 6) at 1, 2, 4 and 6 hours 
post dose. 
• To investigate the effect of 60 mg 
twice daily doses and 60 mg three 
times daily doses of GSK2982772 
on inflammatory biomarkers in skin 
biopsies from psoriatic skin lesions 
in subjects with active plaque-type 
psoriasis. 
• Change from baseline in histopathological scoring of 
psoriatic lesional biopsies which may include, but are 
not limited to the following as data permit: K16, 
CD3/CD11c, CD161, elastase positive dermal cells 
and epidermal thickness. 
• mRNA expression of inflammatory gene transcripts 
which may include, but are not limited to the 
following as data permit: IL-4, IL-10, IL-17, IL-21, IL-
22, IL-23, TNF and IFNγ on Days 1 (Week 0) and 43 
(Week 6). 
• To investigate the effect of 60 mg 
twice daily doses and 60 mg three 
times daily doses of GSK2982772 
on disease activity in subjects with 
active plaque-type psoriasis. 
• Percentage change from baseline and actual 
Psoriatic Lesion Severity Sum (PLSS) scores in the 
index lesion. 
Exploratory Objectives 
Exploratory Endpoints 
• To investigate the effect of 60 mg 
twice daily doses and 60 mg three 
times daily doses of GSK2982772 
on disease activity in subjects with 
• Change from baseline in Psoriasis Area Severity 
Index (PASI) scores. 
• The proportion of subjects who achieve PASI ≥ 50%, 
75%, and 90% improvement from baseline score. 


 
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Objectives 
Endpoints 
active plaque type psoriasis 
• Change from baseline and actual Physician Global 
Assessment (PGA). 
• The proportion of subjects who achieve “clear” (0) or 
“almost clear” (1) on PGA. 
• Change from baseline in body surface area (BSA). 
• To investigate the effect of 60 mg 
twice daily doses and 60 mg three 
times daily doses of GSK2982772 
on inflammatory biomarkers in the 
blood of subjects with active 
plaque-type psoriasis. 
• Change from baseline in blood inflammatory markers 
which may include, but are not limited to the 
following as data permit: CRP, VEGF, S100A8, 
S100A9, IL-17, IL-22, and TNF. 
• To investigate the effect of 60 mg 
twice daily doses and 60 mg three 
times daily doses of GSK2982772 
on transcriptome profiling of both 
blood and skin of subjects with 
active plaque-type psoriasis. 
• Transcriptomic analysis of mRNA isolated from blood 
and skin at Day 1 (Week 0) and Day 43 (Week 6). 
• To investigate pathway and target 
engagement following 60 mg twice 
daily doses and 60 mg three times 
daily doses of GSK2982772 in 
blood and skin biopsy tissue in 
subjects with active plaque-type 
psoriasis. 
• Pharmacology biomarker endpoints may include, but 
are not limited to the following Days 1 (Week 0), 43 
(Week 6) and 85 (Week 12), as data permit: 
o Target Engagement Assay RIP1 (TEAR1) in 
blood and skin. 
o Total or phosprylated RIP1, MLKL, and RIP3, 
cleaved and total caspase 3 and caspase 8 
signatures in skin. 
• To investigate the concentration of 
GSK2982772 in the skin of 
subjects with active plaque-type 
psoriasis after 60 mg twice daily 
doses of and 60 mg three times 
daily doses GSK2982772. 
• Pre-dose GSK2982772 concentrations in skin 
biopsies at Days 1 (Week 0) and 43 (Week 6), as 
data permit. 
• To investigate the effect of 60 mg 
twice daily doses and 60 mg three 
times daily doses of GSK2982772 
on the patient reported outcomes 
(PROs) of subjects with active 
plaque-type psoriasis. 
• Change from baseline in Dermatology Life Quality 
Index (DLQI) score. 
• Change from baseline and actual Visual Analogue 
Scale (VAS) itch score. 
 


 
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2.3. 
Study Design 
Overview of Study Design and Key Features 
 
Design 
Features 
• A multicentre, randomised, double-blind (sponsor-unblinded), placebo-
controlled, repeat dose study proof of mechanism study. 
• Investigate the safety and tolerability, pharmacokinetic (PK), 
pharmacodynamic (PD) and clinical efficacy of repeat doses of 
GSK2982772.   
Dosing 
• Subjects will be screened up to 30 days before the treatment phase. 
• Approximately 30 subjects randomised in 2:1 ratio to receive GSK2982772 
60mg or placebo orally twice daily (approximately 12 hours apart) for 84 
days.  
• Approximately 24 subjects randomised in 3:1 ratio to receive GSK2982772 
60mg or placebo orally three times daily (approximately 12 hours apart) for 
84 days. 
Treatment 
Assignment 
• At screening a unique Subject Number (CRF number) is assigned. 
• Subjects who meet screening eligibility criteria and complete the Pre-
Treatment assessments will be randomised through an Interactive 
Response Technology (IRT).  
• IRT will confirm the subject’s CRF number and provide the randomisation 
number.  
• Randomisation number is generated by Clinical Statistics and will assign the 
subject to a treatment.  
• Approximately 30 subjects randomised in 2:1 ratio to receive GSK2982772 
60mg BID or placebo BID. 
• Approximately 24 subjects randomised in 3:1 ratio to receive GSK2982772 
60mg TID or placebo TID. 
Interim 
• Blinded safety, clinical and adverse event data will be reviewed at 


 
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Overview of Study Design and Key Features 
Analysis 
appropriate intervals by the GSK Safety Review Team (SRT). See SRT 
charter for further details. 
• The PLSS data will be reviewed in an unblinded manner when an 
appropriate number of subjects have completed Day 43.  See the interim 
analysis chapter for further details. 
• A formal interim analysis will be conducted after the completion of Cohort 1 
and will only include those subjects randomised to a BID dosing regimen. 
 
2.4. 
Statistical Hypotheses 
The primary objective of the study is to investigate the safety and tolerability of 
GSK2982772 60mg BID and 60mg TID following 12 weeks of treatment. No formal 
statistical hypotheses will be conducted to assess this objective. 
If appropriate, comparisons between each GSK2982772 arm and the placebo arm will be 
made to investigate the secondary inflammatory, mechanistic and efficacy objectives. 
Trends over time will be investigated for both treatment arms along with associations 
between each of the parameters. 
3. 
PLANNED ANALYSES 
3.1. 
Interim Analyses 
In line with routine pharmacovigilance, an internal GSK Safety Review Team (SRT) 
which will include members of the 203167 study team, will review blinded safety data, 
including clinical laboratory parameters and adverse events, at appropriate intervals 
during the period of study conduct. Further details are outlined in the SRT charter. 
 
In both cohorts, once an appropriate number of subjects randomised to GSK2982772 
have completed Day 43 (Week 6), the PLSS data will be reviewed in an unblinded 
manner by a Data Review Committee (DRC) consisting of the GSK Project Physician 
Lead (PPL), the study statistician, the study pharmacokineticist, the Pattern Recognition 
Receptor (PRR) Discovery Performance Unit (DPU) Head, the Early Development Lead 
(EDL), the Safety Review Team (SRT) leader, or their designees on an ongoing basis. A 
physician external to the GSK2982772 project team may also be involved in the data 
review. Additional inflammatory biomarkers, clinical and mechanistic endpoints (e.g. 
target engagement) may be reviewed if available. No other member of the GSK core 
study team will be unblinded to this data. The primary purpose of these reviews will be to 
monitor PLSS changes for internal decision making purposes. A data review charter will 
identify the specific GSK individuals involved, outline in detail the activities of this 
review and how the integrity of the study will be maintained. 
  
A formal interim analysis will be conducted after the completion of Cohort 1 and will 
only include those subjects randomised to a BID dosing regimen. The purpose of the 


 
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interim analysis is primarily to provide the project team and key GSK stakeholders with 
an early indication of the safety and efficacy from the trial, and to facilitate decision 
making regarding the subsequent clinical development of GSK2982772.   
 
 
3.2. 
Final Analyses 
The final planned primary analyses will be performed after the completion of the 
following sequential steps: 
1. All subjects have completed the study as defined in the protocol. 
2. A completed subject is one who has completed all phases of the study including the 
follow-up visit.  
3. All required database cleaning activities have been completed and final database 
release and database freeze has been declared by Data Management. 
4. All criteria for unblinding the randomisation codes have been met.  
5. Randomisation codes have been distributed according to RandAll NG procedures. 
4. 
ANALYSIS POPULATIONS 
Population 
Definition / Criteria 
Analyses Evaluated 
All subjects 
• All subjects who were screened for eligibility. 
• Selected study 
population 
Safety 
• All subjects who receive at least one dose of 
study treatment. 
• This population will be based on the treatment 
the subject actually received[1] 
• Study population 
• Safety 
• Efficacy  
• PD 
 
Pharmacokinetic 
• Subjects in the ‘Safety’ population for whom a 
pharmacokinetic sample was obtained and 
analysed. 
• PK 
NOTES :  
1. 
Any subjects who actually received both placebo and GSK2982772 due to dispensing errors will be assigned to 
GSK2982772, regardless of treatment duration 
Please refer to Appendix 13: List of Data Displays which details the population to be used for each displays being 
generated. 
 
4.1. 
Protocol Deviations 
• 
Important protocol deviations (including deviations related to study 
inclusion/exclusion criteria, conduct of the trial, patient management or patient 
assessment) will be summarised and listed. 


 
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• 
Protocol deviations will be tracked by the study team throughout the conduct of the 
study in accordance with the Protocol Deviation Management Plan. 
o Data will be reviewed prior to unblinding and freezing the database to ensure all 
important deviations and deviations which may lead to exclusion from the 
analysis are captured and categorised on the protocol deviations dataset.  
o This dataset will be the basis for the summaries and listings of protocol 
deviations. 
• 
A separate summary and listing of all inclusion/exclusion criteria deviations will also 
be provided. This summary will be based on data as recorded on the 
inclusion/exclusion page of the eCRF. 


 
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5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS 
Table 1 provides an overview of appendices within the RAP for outlining general 
considerations for data analyses and data handling conventions.  
Table 1 
Overview of Appendices 
Section Component 
11.1 
Appendix 1: Time & Events 
11.2 
Appendix 2: Assessment Windows 
11.3 
Appendix 3: Treatment States and Phases 
11.4 
Appendix 4: Data Display Standards & Handling Conventions 
11.5 
Appendix 5: Derived and Transformed Data 
11.6 
Appendix 6: Premature Withdrawals & Handling of Missing Data 
11.7 
Appendix 7: Values of Potential Clinical Importance 
11.8 
Appendix 8: Multicentre Studies 
11.9 
Appendix 9: Examination of Covariates, Subgroups & Other Strata 
11.10 
Appendix 10: Multiple Comparisons & Multiplicity 
11.11 
Appendix 11: Model Checking and Diagnostics for Statistical Analyses. 
11.13 
Appendix 12: Abbreviations & Trade Marks 
11.14 
Appendix 13: Data Displays 
11.15 
Appendix 14: Example Mock Shells for Data Displays 
 


 
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6. 
STUDY POPULATION ANALYSES 
6.1. 
Overview of Planned Analyses 
The study population analyses will be based on the “Safety” population, unless otherwise 
specified. 
Table 2 provides an overview of the planned study population analyses, with full details 
of data displays being presented in Appendix 13: List of Data Displays. 
Table 2 
Overview of Planned Study Population Analyses 
Endpoint / Parameter / Display Type 
Data Displays Generated 
Table 
Figure 
Listing 
Randomisation 
Randomisation  
 
 
Y 
Subject Disposition 
Subject Disposition 
Y 
 
 
Reasons for Screen Failure 
Y 
 
Y 
Subjects by Centre 
Y 
 
 
Reasons for Subject Withdrawal 
 
 
Y 
Subjects for Whom the Treatment Blind was Broken 
 
 
Y 
Planned and Actual Treatments 
 
 
Y 
Protocol Deviations 
Important Protocol Deviations 
Y 
 
Y 
Subjects with Inclusion/Exclusion Criteria Deviations 
 
 
Y [1] 
Populations Analysed 
Study Populations and Exclusions 
Y 
 
 
Subjects Excluded from Any Population 
 
 
Y 
Demographic and Baseline Characteristics 
Demographic Characteristics 
Y 
 
Y 
PsO baseline characteristics – BSA,disease duration , prior 
treatments, naive phototherapy, PASI score, PLSS index lesions, 
PGA, Lesion severity area and score, history of tobacco use  
Y 
 
Y 
Race and Racial Combinations 
Y 
 
Y [2] 
Prior and Concomitant Medications 
 Current/Past Medical Conditions 
Y 
 
 
Concomitant Medications 
Y 
 
Y 
Exposure and Treatment Compliance 
Exposure to Study Treatment 
Y 
 
Y 
NOTES : 
• 
Y = Yes display generated. 
[1] Listing also includes analysis population exclusions. 
[2] Listing of race. 


 
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7. 
PRIMARY STATISTICAL ANALYSES 
7.1. 
Safety Analyses 
7.1.1. 
Overview of Planned SafetyAnalyses 
The primary safety analyses will be based on the “Safety” population, unless otherwise 
specified. 
Table 3 provides an overview of the planned safety analyses, with full details of data 
displays being presented in Appendix 13: List of Data Displays. 
Table 3 
Overview of Planned Adverse Event Analyses 
Endpoint / Parameter/ Display Type 
Absolute 
Summary 
Individual 
T 
F 
L 
Adverse Events (AEs) 
All AEs by SOC  
Y 
 
Y 
Common (>=10%)  AEs by Overall Frequency 
Y 
Y [1] 
 
All AEs by Maximum Intensity/Grade by SOC (and PT) 
Y 
 
 
All Drug-Related AEs  by SOC 
Y 
 
 
Subjects & No. of Occurrences of Common Non-Serious AEs by SOC and PT 
Y 
 
 
Subject Numbers for Individual AEs 
 
 
Y 
Relationship Between AE SOCs, PT & Verbatim Text 
 
 
Y 
Serious and Other Significant AEs 
Fatal Serious AEs 
 
 
Y 
Non-Fatal Serious AEs 
 
 
Y 
Serious AEs by SOC 
Y 
 
 
Reasons for Considering as a Serious AE 
 
 
Y 
Drug-Related Serious AEs by SOC 
Y 
 
 
AEs Leading to Withdrawal from Study / Permanent Discontinuation of Study 
Treatment by Overall Frequency 
Y 
 
Y 
Subjects and Number of Occurrences of Serious, Drug-Related Serious, Fatal 
Serious, and Drug-Related Fatal Serious AEs 
Y 
 
 
Other Significant Adverse Events 
 
 
Y 
NOTES: 
• 
T = Table, F = Figures, L = Listings, Y = Yes display generated, SOC = System Organ Class, PT = Preferred 
Term. 
• 
Summary = Represents TF related to any summaries (i.e. descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual subject observed raw data.  
• 
[1] Plot of common AEs and relative risk will be generated. 
7.1.2. 
Overview of Clinical Laboratory Analyses 
The safety analyses will be based on the “Safety” population, unless otherwise specified. 


 
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Table  provides an overview of the planned analyses, with further details of data displays 
being presented in Appendix 1: List of Data Displays. 
Table 5 
Overview of Planned Clinical Laboratory Analyses 
Endpoint / Parameter/ Display Type 
Absolute 
Change from BL 
Summary Individual Summary 
Individual 
T 
F 
L 
T 
F 
L 
Chemistry 
Chemistry Results  
Y 
 
 
Y 
 
 
Emergent Chemistry Results by PCI Criteria 
Y 
 
 
 
 
 
Hematology 
Hematology Results 
Y 
 
 
Y 
 
 
Emergent Hematology Results by PCI Criteria 
Y 
 
 
 
 
 
Urinalysis 
Urine Concentration  
 
 
 
Y 
 
 
Emergent Urinalysis Dipstick Results 
Y 
 
 
 
 
 
Hepatobiliary (Liver) 
Liver Monitoring/Stopping Event Reporting 
Y 
 
 
 
 
 
Hepatobiliary Laboratory Abnormalities 
Y 
 
 
 
 
 
Medical Conditions for Subjects with Liver Stopping 
Events 
 
 
Y 
 
 
 
Substance Use for Subjects with Liver Stopping Events 
 
 
Y 
 
 
 
Scatter Plot of Maximum vs. Baseline for ALT 
 
Y 
 
 
 
 
Scatter Plot of Maximum ALT vs Maximum Total Bilirubin 
 
Y 
 
 
 
 
All Laboratory 
Laboratory Data for Subjects with Abnormalities of 
Potential Clinical Concern 
 
 
Y 
 
 
 
Laboratory Data Abnormalities of Potential Clinical 
Importance 
 
 
Y 
 
 
 
NOTES: 
• 
T = Table, F = Figures, L = Listings, Y = Yes display generated, PCI = Potential Clinical Importance 
• 
Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual subject observed raw data.  
 
7.1.3. 
Overview of Planned Other Safety Analyses 
The safety analyses will be based on the “Safety” population, unless otherwise specified. 
Table  provides an overview of the planned analyses, with further details of data displays 
being presented in Appendix 13: List of Data Displays. 


 
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Table 6 
Overview of Planned Other Safety Analyses 
Endpoint / Parameter/ Display Type 
Absolute 
Change from BL 
Summary Individual Summary 
Individual 
T 
F 
L 
T 
F 
L 
ECG 
ECG Findings  
Y 
 
 
 
 
 
Change from Baseline in ECG Values by Visit 
 
 
 
Y 
 
 
Maximum Change from Baseline in QTc Values by 
Category 
 
 
 
Y 
 
 
All ECG Values for Subjects with a Value of PCI 
 
 
Y 
 
 
 
ECG Values of PCI 
 
 
Y 
 
 
 
Abnormal ECG Findings 
 
 
Y 
 
 
 
Vital Signs 
Vital Signs by Visit 
Y 
 
 
Y 
 
 
Emergent Vital Signs Results by PCI Criteria 
Y 
 
 
 
 
 
All Vital Signs for Subjects with Values of PCI 
 
 
Y 
 
 
 
NOTES: 
• 
T = Table, F = Figures, L = Listings, Y = Yes display generated, PCI = Potential Clinical Importance 
• 
Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual subject observed raw data.  
 
 


 
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8. 
SECONDARY STATISTICAL ANALYSES 
8.1. 
Plasma Pharmacokinetic Analyses 
8.1.1. 
Overview of Planned Pharmacokinetic Analyses 
The pharmacokinetic (PK) analyses will be based on the “Pharmacokinetic” population, 
unless otherwise specified. There are no planned statistical analyses. 
GUI_51487 (4.0), effective October 2014, contains the pharmacokinetic methods to be 
used in non-compartmental analysis (NCA) and reporting of pharmacokinetic studies. 
This document should be used as a reference. 
8.1.2. 
Overview of Planned pharmacokinetic Analyses 
Table  provides an overview of the planned pharmacokinetic analyses, with further 
details of data displays being presented in Appendix 13: List of Data Displays. 
Table 8 
Overview of Planned Pharmacokinetic Analyses 
Endpoints 
Untransformed  
Log-transformed  
 
Summary 
Individual 
Summary 
Individual 
 
T 
F 
F 
L 
T 
F 
F 
L 
Pharmacokinetic  
Plasma Drug concentration  
Y 
Y[1][2] 
Y[1] 
Y 
 
 
 
 
NOTES : 
• 
T = Table, F = Figure, L = Listings, Y = Display generated. 
• 
Stats Analysis = represents TFL related to any formal statistical analyses (i.e. modelling) conducted. 
• 
Summary = represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data. 
• 
Individual = represents FL related to any displays of individual subject observed raw data.   
• 
[1]:  Linear and Semi-Log plots will be created on the same display. 
• 
[2]: Separate Mean (± SD) and Median plots will be generated. 
 
8.1.3. 
Drug Concentration Measures 
Refer to Appendix 4: Data Display Standards & Handling Conventions, Section 11.4.3 
Reporting process & standards for details on how the concentration data will be derived. 
8.1.3.1. 
Statistical Analysis of Pharmacokinetic Parameters 
No formal pharmacokinetic statistical analyses will be performed.  
 


 
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8.2. 
Pharmacodynamic/Biomarker Analyses 
The pharmacodynamic/biomarker analyses will be based on the “Safety” population, 
unless otherwise specified.  
8.2.1. 
Overview of Planned Analyses 
Table 10 provides an overview of the planned analyses, with further details of data 
displays being presented in Appendix 13: List of Data Displays. 
Table 10 
Overview of Planned Pharmacodynamic/biomarker Analyses 
Endpoint  
Absolute 
Change from Baseline 
Stats Analysis 
Summary Individual 
Stats Analysis 
Summary Individual 
T 
F 
L 
T 
F 
F 
L 
T 
F 
L 
T 
F 
F 
L 
Pharmacodynamic and Biomarkers 
Inflammatory 
biomarkers in skin 
biopsy1 
 
 
 
Y 
 
Y 
Y 
Y 
Y 
Y 
Y 
 
 
 
mRNA from skin 
biopsy2 
 
 
 
Y 
 
Y 
Y 
Y 
Y 
Y 
 
 
 
 
NOTES : 
• 
T = Table, F = Figure, L = Listing, Y = Yes display generated. 
• 
Stats Analysis = Represents TFL related to any formal statistical analyses (i.e. modelling) conducted. 
• 
Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual subject observed raw data 
• 
1: Histopathloogical Scoring of Skin biopsy may include epidermal thickness, elastase positive dermal cells, K16, 
CD3/CD11c and CD161. 
• 
2: mRNA expression of inflammatory gene transcripts including but not limited to:IL-4, IL-10, IL-17, IL-21, IL-22, IL-
23, TNF, IFNγ 
 
8.2.2. 
Statistical Analysis of Inflammatory Biomarkers in the Skin 
Biopsy (Histopathological Scoring of Psoriatic Lesional Biopsies)  
Primary Statistical Analyses 
Endpoint(s) 
• Change from baseline on log transformed inflammatory biomarkers from skin biopsy on Day 43 
pre-dose: Loge Change = Loge (Visit) – loge (Baseline) 
Model Specification 
• Endpoints will be statistically analyzed using an Analysis of Covariance (ANCOVA) model.  
• Terms fitted in the ANCOVA model will include: 
o Fixed Category                           : Treatment 
o Fixed Continuous Covariates     : Loge Baseline score 
Model Checking & Diagnostics 
Refer to Appendix 1: Model Checking and Diagnostics for Statistical Analyses. 
Presentation of results 


 
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Primary Statistical Analyses 
 Adjusted geometric means, the mean difference between each dose (test) and the placebo 
(reference) at each timepoint and associated 95% confidence interval will be constructed using 
the residual variance 
 The treatment ratios and 95% CI will be calculated by back-transforming the difference 
between the least square means and associated 95% CI 
 Percentage change from baseline at each timepoint will be calculated from the adjusted 
geometric means using the formula 100% x (exp(adj mean)- 1) 
 
8.2.3. 
Statistical Analysis of mRNA from Skin Biopsies: Transcriptomic 
Data 
8.2.3.1. 
Fold Change Analysis 
The log2 normalised copy numbers (also referred to as log2(intensity)) received from the 
normalised process will be listed and summarised appropriately. 
As the data will be log2 transformed prior to the analysis the treatment effects will be 
expressed as ratios after back transformation to the original scale. These ratios can be 
converted from treatment ratios to fold change values as follows:   
• If ratio ≥ 0 then fold change = ratio 
• If ratio <0 then fold change = -1/ratio 
Primary Statistical Analyses 
Endpoint(s) 
• Log2(intensity) mRNA expression of inflammatory gene transcripts which may include, but are 
not limited to the following as data permit:  IL-4, IL-10, IL-17, IL-21, IL-22, IL-23, TNF and IFNγ  
Model Specification 
• Endpoints will be statistically analyzed using a linear repeated measures mixed effects model.  
• Terms fitted in the linear repeated measures mixed effects model will include: 
o Fixed Category                           : Treatment, Visit, Treatment * Visit 
o Random Effect                            : Subject 
 
Model Checking & Diagnostics 
Refer to Appendix 1: Model Checking and Diagnostics for Statistical Analyses. 
Presentation of Results 
• For each probeset analysed adjusted means with corresponding 95% CI and fold changes with 
corresponding 95% CI’s can be outputted. The fold change is derived from the ratio of the 
back-transformed estimate of the difference between adjusted means. 
• Plots of LS means and 95% confidence intervals from the model will be generated for each 
treatment by time. Additionally, plots of differences and 95% confidence intervals for the 
comparison between the treatment groups will be generated. 


 
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For each comparison subsets of probesets will be identified based on an appropriate fold-
change, for example, fold changes >1.5 or <-1.5. The proportion of probesets with fold 
changes >1.5 or <-1.5 will be summarised in a frequency table. 
Exploratory graphical reporting on the back-transformed scale can include: 
• Log2 (intensity) plotted against time point separately for individual subjects, 
grouped by treatment group 
• Adjusted mean intensity and 95 CI% plotted by treatment group and time point 
8.3. 
Efficacy Analyses 
8.3.1. 
Overview of Planned Efficacy Analyses 
The secondary efficacy analyses will be based on the “Safety” population, unless 
otherwise specified. 
Table 11 provides an overview of the planned efficacy analyses, with further details of 
data displays being presented in Appendix 13: List of Data Displays. 
Table 11 
Overview of Planned Efficacy Analyses 
ENDPOINT 
Absolute 
 
% Change from Baseline 
Stats Analysis 
Summary 
Individual 
Stats Analysis 
Summary Individual 
T 
F 
L 
T 
F 
F 
L 
T 
F 
L 
T 
F 
F 
L 
Psoriatic Lesion Severity Sum (PLSS) 
PLSS 
 
 
 
Y 
Y 
Y 
Y 
Y 
Y 
Y 
Y 
 
 
Y 
NOTES : 
• 
T = Table, F = Figure, L = Listing, Y = Yes display generated. 
• 
Stats Analysis = Represents TFL related to any formal statistical analyses (i.e. modelling) conducted. 
• 
Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual subject observed raw data. 
 
 
 
8.3.2. 
Statistical Analysis of Efficacy Data 
Statistical Analyses 
Secondary Endpoint(s) 
• Percentage change from baseline (pre-dose Day 1) in PLSS score at Days 15, 29, 43 (pre-
dose), 57, 71 and 85. 
Model Specification 
• Endpoints will be statistically analyzed using a mixed models repeated measures (MMRM) 
approach.  
• Terms fitted in the MMRM model will include: 
o Fixed Category                           : Treatment, Day, Treatment*Day 


 
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Statistical Analyses 
o Fixed Continuous Covariates     : Baseline Score 
o Repeated Effect                          : Day 
Note: Other covariates maybe explored, if deemed appropriate for sensitivity analyses. 
Model Checking & Diagnostics 
• Refer to Appendix 11: Model Checking and Diagnostics for Statistical Analyses. 
Presentation of results 
• LS means and corresponding standard error of means (SEs) and 95% confidence intervals will 
be presented for each treatment by time interaction, together with estimated treatment 
differences (GSK2982772 – Placebo) and the corresponding 95% confidence intervals will be 
produced. 
• Plots of LS means and 95% confidence intervals from the model will be generated over time by 
treatment. Additionally, plots of differences and 95% confidence intervals for the comparison of 
interest will be generated over time. 
 


 
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9. 
OTHER STATISTICAL ANALYSES 
9.1. 
Skin Pharmacokinetic Analyses 
9.1.1. 
Overview of Planned Pharmacokinetic Analyses 
The pharmacokinetic (PK) analyses will be based on the “Pharmacokinetic” population, 
unless otherwise specified. There are no planned statistical analyses. 
GUI_51487 (4.0), effective October 2014, contains the pharmacokinetic methods to be 
used in non-compartmental analysis (NCA) and reporting of pharmacokinetic studies. 
This document should be used as a reference. 
9.1.2. 
Overview of Planned pharmacokinetic Analyses 
Table  provides an overview of the planned pharmacokinetic analyses, with further 
details of data displays being presented in Appendix 13: List of Data Displays. 
Table 8 
Overview of Planned Pharmacokinetic Analyses 
Endpoints 
Untransformed  
Log-transformed  
 
Summary 
Individual 
Summary 
Individual 
 
T 
F 
F 
L 
T 
F 
F 
L 
Pharmacokinetic  
Skin Drug concentration  
Y 
Y[1][2] 
Y[1] 
Y 
 
 
 
 
NOTES : 
• 
T = Table, F = Figure, L = Listings, Y = Display generated. 
• 
Stats Analysis = represents TFL related to any formal statistical analyses (i.e. modelling) conducted. 
• 
Summary = represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data. 
• 
Individual = represents FL related to any displays of individual subject observed raw data.   
• 
[1]:  Linear and Semi-Log plots will be created on the same display. 
• 
[2]: Separate Mean (± SD) and Median plots will be generated. 
 
9.1.3. 
Drug Concentration Measures 
Refer to Appendix 4: Data Display Standards & Handling Conventions, Section 11.4.3 
Reporting process & standards for details on how the concentration data will be derived. 
9.1.3.1. 
Statistical Analysis of Pharmacokinetic Parameters 
No formal pharmacokinetic statistical analyses will be performed.  
9.2. 
Exploratory Pharmacodynamic and Biomarker Analyses  
The Biomarker analyses will be based on the “Safety” population, unless otherwise 
specified. 


 
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Table 13 provides an overview of the planned Pharmacodynamic/Biomarker analyses, 
with full details of data displays being presented in Appendix 13: List of Data Displays. 
Table 13 
Overview of Planned Exploratory Biomarker Analyses 
Endpoint  
Absolute 
Change from Baseline 
Stats Analysis 
Summary Individual 
Stats Analysis 
Summary Individual 
T 
F 
L 
T 
F 
F 
L 
T 
F 
L 
T 
F 
F 
L 
Pharmacodynamic and Biomarkers 
Inflammatory 
biomarkers in blood1 
 
 
 
Y 
 
Y 
Y 
Y 
Y 
Y 
Y 
 
 
Y 
Target Engagament 
Assay RIP1 (TEAR1)2 
Y 
Y 
Y 
Y 
 
Y 
Y 
 
 
 
 
 
 
 
Pharmacology 
biomarker in skin3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood Transcptomics 
sample 4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NOTES : 
• 
T = Table, F = Figure, L = Listing, Y = Yes display generated. 
• 
Stats Analysis = Represents TFL related to any formal statistical analyses (i.e. modelling) conducted. 
• 
Summary = Represents TFL related to any summaries (descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual subject observed raw data. 
• 
1: Including, but not limited to CRP, VEGF, S100A8, IL-17, IL-22 and TNF 
• 
2: In blood and skin 
• 
3: Total or phosprylated RIP1, MLKL, and RIP3, cleaved and total caspase 8 signatures are not intended to be 
delivered as part of DBF by first intent. Any future summaries and/or analyses will be deemed post-hoc 
• 
4. Transcriptomic analysis of mRNA are not intended to be delivered as part of DBF by first intent. Any future 
summaries and/or analyses will be deemed post-hoc.  
 
Scatter plots of Skin Target Engagement and skin biomarkers for Day 43 and Day 85 will 
also be produced.   
 
If deemed appropriate, the relationship between Skin Target Engagement and the skin 
biomarkers will be explored further using multivariate statistical analyses. The 
consistency in the changes over time between the endpoints will also be assessed.  Any 
such analyses will be defined after unblinding of the data and thus deemed post-hoc. 
9.2.1. 
Planned Exploratory Biomarker Statistical Analyses 
Planned Statistical Analyses 
Endpoint(s) 
• Percentage change from baseline in blood inflammatory markers, including, but not limited to 
the following as data permits: CRP, VEGF, S100A8, IL-17, IL-22 and TNF across Days 43 
(pre-dose) and 84 (pre-dose). 
Model Specification 
• Change from baseline scores will be analysed using a mixed models repeated measures 
(MMRM) across Day 43(pre-dose) and 85. 


 
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Planned Statistical Analyses 
• Terms fitted in the MMRM model will include: 
o Fixed Category                           : Treatment, Day, Treatment*Day 
o Fixed Continuous effect              : Baseline scores 
o Repeated Effect                          : Day 
Model Checking 
• Refer to Appendix 1: Model Checking and Diagnostics for Statistical Analyses. 
Model Results Presentation 
• Adjusted means and corresponding standard error of means (SEs) and 95% confidence 
intervals will be presented for each treatment by time interaction, together with estimated 
treatment differences (GSK2982772 – Placebo) and the corresponding 95% confidence 
intervals will be produced for respective endpoints.  
• Plots of LS means and 95% confidence intervals from the model will be generated for each 
treatment by time. Additionally, plots of differences and 95% confidence intervals for the 
comparison of interest will be generated. 
 
Target Engagement  
Endpoints 
• Log Ratio = Log (free TEAR1) – log (total TEAR1) 
Model Specification 
 A mixed effect model will be fitted with treatment, period, time (i.e. planned relative time) and 
treatment * time as a fixed effect and subject as a random effect.  Baseline log ratio will be 
fitted as a continuous covariate  
 The Kenward & Roger (KR) degrees of freedom approach will be used. 
Model Checking 
 Refer to Section 11.11. 
Presentation of Results 
 Adjusted geometric means, the mean difference between each dose (test) and the placebo 
(reference) at each timepoint and associated 95% confidence interval will be constructed using 
the residual variance 
 The treatment ratios and 95% CI will be calculated by back-transforming the difference 
between the least square means and associated 95% CI 
 Percentage target engagement at each timepoint will be calculated from the adjusted geometric 
means using the formula 100% x (exp ln (v2 / v1) - 1) percentage target engagement = (100 – 
engagement ratio) * 100 
 
9.3. 
Exploratory Efficacy Analyses 
The exploratory efficacy analyses will be based on the “Safety” population, unless 
otherwise specified. 


 
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Table  14 provides an overview of the planned exploratory efficacy analyses, with further 
details of data displays being presented in Appendix 13: List of Data Displays. 
 
 
Table 14 
Overview of Planned Exploratory Efficacy Analyses 
 
9.3.1. 
Planned Exploratory Efficacy Statistical Analyses 
GEE modelling will only be performed if at least 30% response rate and Day 43 or Day 
85 for any one treatment group.  Further the proportion of subjects achieving 
PASI50/75/90 will only be performed if >50% of subjects have a BSA >5% at baseline. 
Exploratory Endpoint(s) 
• Proportion of subjects who achieve ≥ xx% improvement from baseline in PASI score at Days 
15, 29, 43 (pre-dose), 57, 71 and 85 (if sufficient number of subjects are enrolled with a >5% 
BSA). 
• Proportion of subjects who have a PGA score of ‘clear’ (0) or ‘almost clear’ (1) at Days 15,29, 
Endpoint(s)  
Absolute 
Change from Baseline 
Stats Analysis 
Summary 
Individual 
Stats Analysis 
Summary Individual 
T 
F 
L 
T 
F 
F 
L 
T 
F 
L 
T 
F 
F 
L 
Psoriasis Area Severity Index (PASI) 
PASI score  
 
 
 
Y 
Y 
Y 
Y 
Y 
Y 
Y 
Y 
 
 
Y 
PASI50, PASI75, 
PASI901 
Y 
 
Y 
Y 
 
 
Y 
 
 
 
 
 
 
 
Physician Global Assessment (PGA) 
PGA 
 
 
 
Y 
Y 
 
Y 
Y 
 
Y 
Y 
 
 
Y 
PGA (clear vs almost 
clear) 
Y 
 
Y 
Y 
 
 
Y 
 
 
 
 
 
 
 
Psoriatic Body Surface Area 
BSA 
 
 
 
Y 
Y 
Y 
Y 
Y 
Y 
Y 
Y 
 
 
Y 
Patient Reported Outcomes (PROs) 
Dermatology Life 
Quality Index (DLQI) 
 
 
 
Y 
Y 
Y 
Y 
Y 
Y 
Y 
Y 
 
 
Y 
Visual Analogue Scale 
(VAS) itch score 
 
 
 
Y 
Y 
Y 
Y 
Y 
Y 
Y 
Y 
 
 
Y 
NOTES : 
• 
T = Table, F = Figure, L = Listing, Y = Yes display generated. 
• 
Stats Analysis = Represents TFL related to any formal statistical analyses (i.e. modelling) conducted. 
• 
Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual subject observed raw data. 
 
• 
PASI 50/75/90 will only be analysed if >50% of subjects have a BSA >5% at baseline 


 
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43(pre-dose), 57, 71 and 85. 
Model Specification 
• Will be analysed using a GEE (Generalized Estimating Equations) model across Day 15, 29, 
43 (pre-dose), 57, 71 and 85. 
• Terms fitted in the GEE model will include: 
o Fixed Category                           : Treatment, Day, Treatment*Day 
o Repeated Effect                          : Day 
Presentation of results 
• Adjusted Odds Ratios and corresponding 95% confidence intervals will be generated from 
contrasts for treatment by day interactions. 
• Plots of the adjusted Odds Ratios and 95% confidence intervals from the model will be 
generated for each treatment by time. Additionally plots of differences and 95% confidence 
intervals for the comparisons of interest will be generated.  
 
Exploratory Endpoint(s) 
• Psoriasis Area Severity Index (PASI) score (if sufficient number of subjects are enrolled with a 
>5% BSA). 
• Physician Global Assessment (PGA) 
• Visual Analogue Scale (VAS) itch score. 
Model Specification 
• Change from baseline scores will be analysed using a mixed models repeated measures 
(MMRM) across Day 15, 29, 43 (pre-dose), 57, 71 and 85. 
• Terms fitted in the MMRM model will include: 
o Fixed Category                           : Treatment, Day, Treatment*Day 
o Fixed Continuous effect              : Baseline scores 
o Repeated Effect                          : Day 
Note: Other covariates maybe explored, if deemed appropriate for sensitivity analyses. 
Presentation of results 
• Adjusted means and corresponding standard error of means (SEs) and 95% confidence 
intervals will be presented for each treatment by time interaction, together with estimated 
treatment differences (GSK2982772 – Placebo) and the corresponding 95% confidence 
intervals will be produced for respective endpoints.  
• Plots of LS means and 95% confidence intervals from the model will be generated for each 
treatment by time. Additionally, plots of differences and 95% confidence intervals for the 
comparison of interest will be generated. 
 
Exploratory Endpoint(s) 
• Body Surface Area (BSA) 
Model Specification 
• Change from baseline scores will be analysed using an Analysis of Covariance (ANCOVA) 
model at Day 85.  
• Terms fitted in the ANCOVA model will include: 
o Fixed Category                           : Treatment 
o Fixed Continuous effect              : Baseline scores 


 
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Presentation of results 
• Adjusted means and corresponding standard error of means (SEs) and 95% confidence 
intervals will be presented for each treatment, together with estimated treatment differences 
(GSK2982772 – Placebo) and the corresponding 95% confidence intervals will be produced. 
• Plots of LS means and 95% confidence intervals from the model will be generated for each 
treatment. Additionally, plots of differences and 95% confidence intervals for the comparison of 
interest will be generated. 
 
Exploratory Endpoint(s) 
• Dermatology Life Quality Index (DLQI) score. 
Model Specification 
• Change from baseline scores will be analysed using a mixed models repeated measures 
(MMRM) across Day 43 (pre-dose) and 85. 
• Terms fitted in the MMRM model will include: 
o Fixed Category                           : Treatment, Day, Treatment*Day 
o Fixed Continuous effect              : Baseline scores 
o Repeated Effect                          : Day 
 
Presentation of results 
• Adjusted means and corresponding standard error of means (SEs) and 95% confidence 
intervals will be presented for each treatment by time interaction, together with estimated 
treatment differences (GSK2982772 – Placebo) and the corresponding 95% confidence 
intervals will be produced for respective endpoints.  
• Plots of LS means and 95% confidence intervals from the model will be generated for each 
treatment by time. Additionally, plots of differences and 95% confidence intervals for the 
comparison of interest will be generated. 
Model Checking 
• Refer to Appendix 1: Model Checking and Diagnostics for Statistical Analyses. 
 
9.4. 
Exploratory Pharmacodynamic / Efficacy Analyses  
If deemed appropriate, the relationship between the skin biomarkers and efficacy 
endpoints will be explored further using multivariate statistical methods and/or Bayesian 
methodology as recommended by the GSK PCPS Experimental Medicine working group. 
The consistency in the changes over time between the endpoints will also be assessed.  
Any such analyses will be defined after unblinding of the interim data and thus deemed 
post-hoc. 
 


 
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10. 
REFERENCES 
 


 
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11. 
APPENDICES 
Section 
Appendix 
RAP Section 5 : General Considerations for Data Analyses & Data Handling Conventions 
Section 11.1 
Appendix 1: Time and Events 
Section 11.2 
Appendix 2: Assessment Windows 
Section 11.3 
Appendix 3: Treatment States & Phases 
Section 11.4 
Appendix 4: Data Display Standards & Handling Conventions 
Section 11.5 
Appendix 5: Derived and Transformed Data 
Section 11.6 
Appendix 6: Premature Withdrawals & Handling of Missing Data 
Section 11.7 
Appendix 7: Values of Potential Clinical Importance 
Section 11.8 
Appendix 8: Multicentre Studies 
Section 11.9 
Appendix 9: Examination of Covariates and Subgroups 
Section 11.10 
Appendix 10: Multiple Comparisons and Multiplicity 
Section 11.11 
Appendix 11: Model Checking and Diagnostics for Statistical Analyses 
Other RAP Appendices 
Section 11.12 
Appendix 12: Abbreviations & Trade Marks 
Section 11.13 
Appendix 13: List of Data Displays 
Section 11.14 
Appendix 14: Example Mock Shells for Data Displays 
 
 


 
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11.1. 
Appendix 1: Time & Events 
11.1.1. 
Protocol Defined Time & Events 
Procedures 
Screening 
Treatment Period 
Early Withdrawal 14 
Follow Up
Notes 
Day 1  
Day 8  
Day 15 
Day 22 
Day 29 
Day 36 
Day 43 
(week 6)
Day 50 
Day 57 
Day 64 
Day 71 
Day 78 
Day 85 
(week 12)
Visit windows 
Screening: up to 30d 
before Day 1. 
Treatment Period 
(except Day 1 & 85): 
± 3d. Day 1 NA; Day 
85 ± 2d. 
Early Withdrawal: NA 
Follow Up: 28d after 
last dose ± 3d 
Screening 
Procedures 
Screening procedures in addition to those listed below are (outpatient visit): informed consent; inclusion/ 
exclusion criteria; demography; medical history (includes past and current conditions, medication history, and 
family history of premature CV disease); HIV, Hep B and Hep C screen; serum pregnancy test (WCBP only). 
Site Visit 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 1. Full physical exam: 
height/weight at 
Screening, height not 
required at later 
timepoints. 
2. Vitals: BP, HR, RR, 
temperature. ECG 
triplicate at Screening 
only. 
3. Urinalysis not required 
on Days 29, 57 and 71.  
4. If urine test is positive, 
confirmatory serum test 
must be performed. 
5. Pre-dose 
6. In Cohort 1, subjects 
must take study 
medication twice a day 
approx. 12h apart.  In 
Cohort 2, subjects must 
take study medication 
three times a day 
approx. 8h apart. Exact 
time of dosing to be 
recorded in diary cards. 
On Days 43 and 85, 
subjects must not take 
medication at home in 
the morning. Subjects 
will complete pre-dose 
assessments and then 
will be administered their 
morning dose of 
medication at site on 
Day 43 only. On Day 85, 
subjects no longer 
dosed. 
Phone call 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
Safety Assessments 
Full physical 
exam1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
Brief physical 
exam 
 
X
5 
 
X 
 
X 
 
X
5 
 
X 
 
X 
 
 
 
 
12-lead ECG, 
vital signs2 
X 
X
5 
X 
X 
 
X 
 
X
5 
 
X 
 
X 
 
X 
X 
X 
Columbia Suicide 
Severity Rating 
Scale (C-SSRS) 
X 
X
5 
 
 
 
 
 
X
5 
 
 
 
 
 
X 
X 
 
Hematology, 
chemistry, 
urinalysis  
X 
X
5 
X 
X 
 
X
3 
 
X
5 
 
X
3 
 
X3 
 
X 
X 
X 
FSH & estradiol  
(if applicable) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum 
pregnancy 
(WCBP) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy 
test (WCBP 
only)4 
 
X
5 
X 
X 
 
X 
 
X
5 
 
X 
 
X 
 
X 
X 
X 
Study Treatment 
Randomisation 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study 
medication6 
 
X X--------------------------------------------------------------------------
-----------------------X 
 
 
Dispensing of 
study medication 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
Dispensing of 
diary cards7 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
 


 
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Procedures 
Screening 
Treatment Period 
Early Withdrawal 14 
Follow Up
Notes 
Day 1  
Day 8  
Day 15 
Day 22 
Day 29 
Day 36 
Day 43 
(week 6)
Day 50 
Day 57 
Day 64 
Day 71 
Day 78 
Day 85 
(week 12)
Visit windows 
Screening: up to 30d 
before Day 1. 
Treatment Period 
(except Day 1 & 85): 
± 3d. Day 1 NA; Day 
85 ± 2d. 
Early Withdrawal: NA 
Follow Up: 28d after 
last dose ± 3d 
PROs/ Disease Assessments 
7. Diary card checked by 
site staff and new diary 
card dispensed at every 
study visit. 
8.  Blood samples for 
inflammatory biomarkers 
and mRNA taken pre-
dose on Day 1, Day 43 
and Day 85.  
9. PK blood samples 
taken pre-dose on Day 
43. Post-dose serial PK 
samples taken on Day 1 
and Day 43 at 1, 2, 4, 
and 6 hours post-dose. 
10. Pre-dose Day 1 one 
biopsy taken from non-
lesional skin and two 
biopsies taken from 
biopsy target lesion. 
11. On Day 43, two 
biopsies taken from the 
same target lesion that 
was selected at Day 1. 
Punch biopsies on Day 
43 are to be taken pre-
dose. 
12. Biopsy only required 
at Early Withdrawal visit 
if completed at least 14 
days of treatment and 
prior to Day 43. 
13. PGx sample 
collected at Day 1, after 
randomization and 
separate informed 
consent. If sample not 
collected at Day 1, can 
be collected at any time 
post-randomization.  
14. If subject withdraws 
early, every effort will be 
made for the subject to 
complete an Early 
Withdrawal visit prior to 
Follow Up.  
Psoriatic Body 
Surface Area 
X 
X
5 
 
 
 
 
 
 
 
 
 
 
 
X X  
PASI, PGA, 
PLSS, Itch 
X 
X
5 
 
X 
 
X 
 
X
5 
 
X 
 
X 
 
X X  
DLQI 
X 
X
5 
 
 
 
 
 
X
5 
 
 
 
 
 
X X  
Photograph of 
lesions 
 
X
5 
 
 
 
 
 
X
5 
 
 
 
 
 
X X  
Other Assessments and Procedures 
Blood sample for 
inflammatory 
biomarkers8 
 
X
5 
 
 
 
 
 
X
5 
 
 
 
 
 
X X 
 
Blood sample for 
mRNA analysis8 
 
X
5 
 
 
 
 
 
X
5 
 
 
 
 
 
X X 
 
Blood sample for 
Target 
Engagement 
 
X
5 
 
 
 
 
 
X
5 
 
 
 
 
 
X X 
 
PK blood 
samples9 
 
X 
 
 
 
 
 
X
5 
 
 
 
 
 
X X 
 
Skin punch 
biopsies for PK, 
inflammatory 
biomarkers, 
mRNA, target 
engagement & 
pathway 
engagement 
 
X
5,1
0 
 
 
 
 
 
X
11 
 
 
 
 
 
 X12 
 
Pharmacogenetic 
sample (PGx) 
 
X
13 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Con med review 
& AE/SAE 
reporting 
 
X---------------------------------------------------------------------------------------
----------------------------------X 


 
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11.2. 
Appendix 2: Assessment Windows 
11.2.1. 
Definitions of Assessment Windows for Analyses 
No Assessment Windows will be defined for Analysis, and summaries and analyses will 
be based on nominal visits. 


 
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11.3. 
Appendix 3: Treatment States and Phases 
11.3.1. 
Treatment Phases 
Assessments and events will be classified according to the time of occurrence relative to 
study treatment unless otherwise specified.  Treatment phases are to be included on A&R 
datasets. 
Treatment Phase 
Definition 
Pre-Treatment  
Date ≤ Study Treatment Start Date 
On-Treatment 
Study Treatment Start Date < Date ≤ Study Treatment Stop Date 
Post-Treatment 
Date > Study Treatment Stop Date  
 
11.3.2. 
Treatment States 
Assessments and events will be classified according to time of occurrence relative to the 
start and/or stop date of the study treatment. 
11.3.2.1. 
Treatment States for Safety Data 
Treatment State 
Definition 
Pre-Treatment 
Date ≤ Study Treatment Start Date 
On-Treatment 
Study Treatment Start Date < Date ≤ Study Treatment Stop Date +1 
Post-Treatment 
Date > Study Treatment Stop Date +1 
NOTES:  
• 
If the study treatment stop date is missing then the assessment will be considered to be On-Treatment 
 
Treatment States for AE Data 
Treatment State 
Definition 
AE = Pre-Treatment 
AE Start Date < Study Treatment Start Date 
AE = On-Treatment 
If AE onset date is on or after treatment start date & on or before treatment stop 
date. 
Study Treatment Start Date  ≤ AE Start Date ≤ Study Treatment Stop Date +1 
AE = Post-Treatment 
If AE onset date is after the treatment stop date. 
AE Start Date > Study Treatment Stop Date  
AE Onset Time  
Since 1st Dose 
(Days) 
If Treatment Start Date ˃  AE Onset Date:  
= AE Onset Date - Treatment Start Date 
If Treatment Start Date ≤ AE Onset Date:  
= AE Onset Date - Treatment Start Date +1 
Missing otherwise. 
AE Duration (Days)  
AE Resolution Date – AE Onset Date + 1 
AE = Drug-related 
If relationship is marked ‘YES’ on [Inform/CRF OR value is missing]. 
NOTES:  
• 
If the study treatment stop date is missing then the AE will be considered to be On-Treatment. 
 


 
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11.4. 
Appendix 4: Data Display Standards & Handling 
Conventions 
11.4.1. 
Study Treatment & Sub-group Display Descriptors 
Treatment Group Descriptions 
RandAll NG  
Data Displays for Reporting  
Code 
Description 
Description 
Order [1] 
A 
GSK2982772 60mg BID 
GSK2982772 60mg BID 
2 
C 
GSK2982772 60mg TID 
GSK2982772 60mg TID 
3 
P 
Placebo 
Placebo [2] 
1 
Q 
Placebo TID 
NOTES: 
1. 
Order represents treatments being presented in TFL, as appropriate. 
2. 
Placebo BID and Placebo TID will be combined for reporting purposes 
 
Should a subject receive the wrong medication at any point during the study in error, that 
subject will be treated as having received GSK2982772 60mg BID or GSK2982772 
60mg TID, dependent on whether Cohort 1 or Cohort 2, for the duration of the study.  
Such subjects will have a footnote on Table 1.12 and Listing 1. 
 
11.4.2. 
Baseline Definition & Derivations 
11.4.2.1. 
Baseline Definitions 
For all endpoints (expect as noted in baseline definitions) the baseline value will be the 
latest pre-dose assessment.  
Parameter 
Study Assessments Considered As Baseline 
Baseline Used in 
Data Display 
Screening 
Day 1 (Pre-Dose) 
Safety Assessments 
Vital signs1 
X 
X 
Day 1 (Pre-Dose)  
12-lead ECG2 
X 
X 
Day 1 (Pre-Dose) 
Laboratory 
(Haematology, 
clinical chemistry and 
urinalysis) 
X 
X 
Day 1 (Pre-Dose) 
Columbia Suicide 
Severity Rating 
Scale (C-SSRS) 
X 
X 
Day 1 (Pre-Dose) 
PROs/Disease Assessments  
Psoriatic Body 
X 
X 
Day 1 (Pre-Dose) 


 
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Parameter 
Study Assessments Considered As Baseline 
Baseline Used in 
Data Display 
Screening 
Day 1 (Pre-Dose) 
Surface Area 
PASI, PGA, PLSS, 
itch 
X 
X 
Day 1 (Pre-Dose) 
DLQI 
X 
X 
Day 1 (Pre-Dose) 
Other Assessments and Procedures 
Blood sample for 
inflammatory 
biomarkers 
 
X 
Day 1 (Pre-Dose) 
Blood sample for 
mRNA analysis 
 
X 
Day 1 (Pre-Dose) 
Blood sample for 
Target Engagement  
 
X 
Day 1 (Pre-Dose) 
PK blood samples 
 
X 
Day 1 (Pre-Dose) 
Skin punch biopsies 
for PK, inflammatory 
biomarkers, mRNA, 
target engagement & 
pathway 
engagement  
 
X 
Day 1 (Pre-Dose) 
NOTES : 
• 
Unless otherwise stated, the mean of replicate assessments at any given time point will be used as the value 
for that time point. 
• 
1 = Vitals: BP, HR, RR, temperature 
• 
2 = ECG triplicate at screening only  
11.4.2.2. 
Derivations and Handling of Missing Baseline Data 
Definition 
Reporting Details 
Change from Baseline 
= Post-Dose Visit Value – Baseline 
% Change from Baseline 
= 100 x [(Post-Dose Visit Value – Baseline) / Baseline] 
Maximum Change from 
Baseline 
= Calculate the change from baseline at each given timepoint  
   and determine the maximum change 
NOTES : 
• 
Unless otherwise specified, the baseline definitions specified in Section 11.4.2.1 Baseline Definitions will be 
used for derivations for endpoints / parameters and indicated on summaries and listings. 
• 
Unless otherwise stated, if baseline data is missing no derivation will be performed and will be set to missing. 
• 
The baseline definition will be footnoted on all change from baseline displays. 
 
11.4.3. 
Reporting Process & Standards 
Reporting Process 
Software 


 
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Reporting Process 
• The currently supported versions of SAS software will be used. 
Reporting Area 
HARP Server 
UK1SALX00175 
HARP Area 
arenv \ arprod \ gsk2982772 \ mid203167 \ internal_03 
arenv \ arprod \ gsk2982772 \ mid203167 \ final 
QC Spreadsheet 
arenv \ arprod \ gsk2982772 \ mid203167 \ internal_03 
arenv \ arwork \ gsk2982772 \ mid203167 \ final \ documents 
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 key outputs at the time of the IA, SAC. 
 
Reporting Standards 
General 
• The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated: 
o 4.03 to 4.23: General Principles 
o 5.01 to 5.08: Principles Related to Data Listings 
o 6.01 to 6.11: Principles Related to Summary Tables 
o 7.01 to 7.13: Principles Related to Graphics  
Formats 
• All data will be reported according to the actual treatment the subject received unless 
otherwise stated. 
• 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. 
• Numeric data will be reported at the precision collected on the eCRF. 
• The reported precision from non eCRF sources will follow the IDSL statistical principles but 
may be adjusted to a clinically interpretable number of DP’s. 
Planned and Actual Time 
• Reporting for tables, figures and formal statistical analyses : 
• Planned time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated. 
• The impact of any major deviation from the planned assessment times and/or scheduled 
visit days on the analyses and interpretation of the results will be assessed as appropriate. 
• Reporting for Data Listings:  
• Planned and actual time relative to study drug dosing will be shown in listings (Refer to 
IDSL Statistical Principle 5.05.1). 
• Unscheduled or unplanned readings will be presented within the subject’s listings.  
• Visits outside the protocol defined time-windows (i.e. recorded as protocol deviations) will 
be included in listings but omitted from figures, summaries and statistical analyses. 
Unscheduled Visits 


 
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Reporting Standards 
• Unscheduled visits will not be included in summary tables or figures, unless otherwise stated.. 
• All unscheduled visits will be listed. 
Descriptive Summary Statistics 
Continuous Data 
Refer to IDSL Statistical Principle 6.06.1 
Categorical Data 
N, n, frequency, % 
Reporting of Pharmacokinetic Concentration Data 
Descriptive 
Summary Statistics 
Refer to IDSL Statistical Principle 6.06.1 
Assign zero to NQ values (Refer to GUI_51487 for further details) 
Reporting of Pharmacokinetic Parameters 
Descriptive 
Summary Statistics 
(Log Transformed) 
N, n, geometric mean, 95% CI of geometric mean, standard deviation (SD) 
of logged data and [between and or within] geometric coefficient of variation 
(CVb/w (%)) will be reported. 
[1] CVb (%) = √ (exp(SD2) - 1) * 100 
(SD = SD of log transformed data)  
[2] CVw (%) = √ (exp(MSE) - 1) * 100  
(MSE = mean square error from mixed effect model of loge-transformed data). 
Parameters Not 
Being Log 
Transformed 
tmax, first point, last point and number of points used in the determination of 
Lambda_z. 
Summary Tables 
The following PK parameters will not be summarised: tmax, first point, last 
point and number of points used in the determination of Lambda_z. 
Listings 
Additionally, include the first point, last point and number of points used in 
the determination of lambda_z for listings. 
Graphical Displays 
• Refer to IDSL Statistical Principals 7.01 to 7.13. 
 


 
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11.5. 
Appendix 5: Derived and Transformed Data 
11.5.1. 
General 
Multiple Measurements at One Time Point 
• Mean of the measurements will be calculated and used in any derivation of summary statistics 
but if listed, all data will be presented. 
• If there are two values within a time window the value closest to the target day for that window 
will be used. If values are the same distance from the target then the mean will be taken. 
• Subjects having both High and Low values for Normal Ranges at any post-baseline visits 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 randomisation date : 
• Ref Date = Missing                       → Study Day = Missing  
• Ref Date < Randomisation Date   → Study Day = Ref Date – Randomisation Date     
• Ref Data ≥ Randomisation Date   → Study Day = Ref Date – (Randomisation Date) + 1     
 
11.5.2. 
Study Population 
Demographics 
Date of Birth  
• Only the year of birth will be captured, and therefore the date of birth is then derived as follows: 
Year of birth = YYYY → Date of birth = 30th June YYYY 
Age 
• Calculated as the integer part of (date of baseline – date of birth) 
Age = integer part (date of baseline – 30th June YYYY) 
• Birth date will be presented in listings as ‘YYYY’. 
Body Mass Index (BMI) 
• Calculated as Weight (kg) / [Height (m)2 
Race category  
• White: ‘White: Arabic/North African Heritage’ and ‘White: White/Caucasian/European Heritage’, 
or both of these, but no other category checked 
• African descent: ‘African American/African Heritage’, and no other category checked 
• Asian: ‘Asian – Central/South Asian Heritage’, ‘Asian – East Asian Heritage’, ‘Asian – Japanese 
Heritage’, and ‘Asian – South East Asian Heritage’, or any combination of these, but no other 
category checked 
• Other: Any combination that has not been categorized above (‘mixed race’) 
 
Extent of Exposure 
• Number of days of exposure to study drug will be calculated based on the formula:   


 
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Extent of Exposure 
Duration of Exposure in Days = Treatment Stop Date – (Treatment Start Date) + 1 
• Subjects who were randomized but did not report a treatment start date will be categorised as 
having zero days of exposure.  
• The cumulative dose will be based on the formula: 
Cumulative Dose = Sum of (Number of Days x Total Daily Dose) 
• If there are any treatment breaks during the study, exposure data will be adjusted accordingly. 
11.5.3. 
Safety 
ECG Parameters 
RR Interval 
• IF RR interval (msec) is not provided directly, then RR can be derived as : 
[1] If QTcB is machine read & QTcF is not provided, then : 
 
[2] If QTcF is machine read and QTcB is not provided, then:  
 
• 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 Bazett’s (QTcB) and 
Fredericia’s (QTcF) formulas will be calculated, in msec, depending on the availability of other 
measurements. 
• IF RR interval (msec) is provided then missing QTcB and/or 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 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     
 
11.5.4. 
Pharmacokinetic 
Skin Pharmacokinetic Concentrations 


 
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Skin PK Conc 
• The density of human skin tissue is 1.184 g/mL per Gastroplus V9.0. 
• The volume of solvent added to each tissue sample was 0.5 mL. 
• For actual tissue weights, please refer to the Excel spreadsheet 
Skin PK Concentration (ng/mL) 
1. 
PK Conc in Weight of Tissue Sample = SMS PK Conc in Soln (ng/mL) X [0.5 mL + (Tissue 
Weight (g) / 1.184 g/mL)]  
2. 
PK Conc in tissue  as concentration (ng/g) = PK Conc in Weight of Tissue Sample / Tissue 
Weight 
3. 
PK Conc in tissue  as concentration (ng/mL) = PK Conc in tissue  as concentration (ng/g)  
1.184 g/mL  
Example (fictitious) data: 
SMS tissue homogenate concentration = 2 ng/mL 
Tissue weight = 0.014 g 
SMS plasma concentration= 400 ng/mL 
Example Calculations: 
1. 
Convert GSK2982772 concentration in the homogenate to GSK2982772 concentration in 
the tissue sample as follows: 
2 ng/mL X [0.5 mL + (0.014 g/1.184 g/mL)] = 2ng/mL X 0.512 mL = 1.024 ng GSK2982772 in a 
0.014 g tissue sample 
2. 
Convert absolute amount of GSK2982772 in this skin tissue sample to a tissue 
concentration as follows: 
1.024 ng / 0.014 g tissue = 73.1 ng GSK2982772/g tissue = 73.1 ng/g 
3. 
Convert ng/g tissue to ng/mL tissue as follows : 
73.1 ng/g X 1.184 g/mL = 86.5 ng GSK2982772/mL tissue = 86.5 ng/mL 
4. 
Determine the ratio of GSK2982772 tissue concentration to GSK2982772 plasma 
concentration for a given patient as follows: 
86.5 ng/mL / 400 ng/mL = 0.216 
 
11.5.5. 
Efficacy 
Clinical Efficacy 
Plaque Lesional Severity Score (PLSS) and index plaque 
selection 
Two plaques will be selected at Day -1, one for clinical assessment (index plaque) and one for 
biopsy. Ideally the index plaque should be the most severe plaque. At a minimum each plaque will 
have an induration score of ≥2 (moderate or above) and a score of ≥1 in erythema and scaling, as 
detailed in the scoring list below. Each lesion must have a PLSS score of ≥5. The PLSS is the sum 
of the erythema, scaling and induration. The PLSS assessment will be performed by the same 
qualified dermatologist throughout, wherever possible and will be scored using the same scale (0-4 
point rating scale) as the PASI. 
 
 


 
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Clinical Efficacy 
Psoriasis Area Severity Index (PASI), PASI50, PASI75, PASI90 
Psoriatic lesions will be assessed using the PASI. The PASI assessment will be performed by the 
investigator or a suitably trained delegate, and whenever possible, the PASI assessments for an 
individual subject will be completed by the same assessor at all time-points.  Each area of the body 
(head, upper extremities, trunk, lower extremities) will be assessed for the following symptoms:  
erythema, induration, scaling.  A 0–4 point rating scale will be used, as follows: 
0 = No symptom 
1 = Slight 
2 = Moderate 
3 = Marked 
4 = Very Marked 
After calculating the BSA as detailed above, use the multiplier for that body region to calculate the 
area score for each region as detailed below: 
• Head 
Number of palms x 10% = % of head 
• Upper extremities 
Number of palms x 5% = % of upper extremities 
• Trunk 
Number of palms x 3.3% = % of area trunk 
• Lower extremities 
Number of palms x 2.5% = % of lower extremities 
The area of psoriatic involvement for each area of the body (head, upper extremities, trunk, lower 
extremities) will be assessed using a 0–6 point rating scale, as follows: 
0 = 0% 
1 = 0−9% 
2 = 10−29% 
3 = 30−49% 
4 = 50−69% 
5 = 70−89% 
6 = 90−100% 
Total PASI score will be calculated using the following method: 
• 
Add up the 3 intensity scores for each area of the body to give 4 subtotals (A1−A4): 
• 
A1 (head intensity score) = head redness score + head thickness score + head scaling 
score 


 
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Clinical Efficacy 
• 
A2 (upper extremities intensity score) = upper extremities redness score + upper 
extremities thickness score + upper extremities scaling score 
• 
A3 (trunk intensity score) = trunk redness score + trunk thickness score + trunk scaling 
score 
• 
A4 (lower extremities intensity score) = lower extremities redness score + lower 
extremities thickness score + lower extremities scaling score 
• 
Multiply each subtotal (A1−A4) by the body surface area represented by that region to give 4 
new subtotals (B1−B4):  
• 
B1 (head)  
= A1 x 0.1  
• 
B2 (upper extremities)  
= A2 x 0.2  
• 
B3 (trunk)  
= A3 x 0.3  
• 
B4 (lower extremities)  
= A4 x 0.4  
• 
Multiply each subtotal (B1−B4) by the area affected for that region to give 4 new subtotals 
(C1−C4): 
• 
C1 (head)  
= B1 x 1−6 
• 
C2 (upper extremities)  
= B2 x 1−6 
• 
C3 (trunk)  
= B3 x 1−6 
• 
C4 (lower extremities)  
= B4 x 1−6 
• 
Calculate the total PASI score = C1 + C2 + C3 + C4 
From the total scores, the following will be derived: change from baseline, percentage change from 
baseline, PASI50, PASI75 and PASI90 at each time point. Calculation of change from baseline and 
percentage change from baseline is described in Section 11.4.2.2. 
Where PASI50, PASI75 and PASI90 are given by: 
PASI50 
Yes: 
No: 
≥ 50% reduction in PASI total score from baseline at time point 
< 50% reduction in PASI total score from baseline at time point 
PASI75 
Yes: 
No: 
≥ 75% reduction in PASI total score from baseline at time point 
< 75% reduction in PASI total score from baseline at time point 
PASI90 
Yes: 
No: 
≥ 90% reduction in PASI total score from baseline at time point 
< 90% reduction in PASI total score from baseline at time point 
 
Physician Global Assessment (PGA) 
Psoriatic lesions will be assessed using the PGA.  The PGA assessment will be performed by the 
investigator or a suitably trained delegate, and whenever possible, the PGA assessments for an 
individual subject will be completed by the same assessor at all time-points.  A 6-point scoring 
system will be used to measure the severity of psoriatic lesions over the whole body, at the time of 
the evaluation:  
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by 
third party copyright laws and therefore have been excluded.


 
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Clinical Efficacy 
 
PGA (clear and almost clear) 
PGA is given by: 
PGA 
Clear (0): 
Almost 
Clear (1): 
No signs of psoriasis (post-inflammatory hypopigmentation or 
hyperpigmentaition could be present) 
slight elevation, scale and/or erythema 
 
Body Surface Area (BSA) 
As part of the inclusion criteria the patients Psoarisis plaques need to cover 2-10% of body surface 
area. This will be calculated based on the areas outlined as part of the PASI score (see section 
9.6.4.2). Where body surface area is calculated based on the palm method, where a patient’s  palm 
to PIP and thumb = 1%, and so: 
 
Head and Neck 
10%  (10 palms) 
Upper extremities 
20% (20 palms) 
Trunk (axillae and groin) 
30%  (30 palms) 
Lower extremities (buttocks) 
40% (40 palms) 
 
Therefore the total BSA = 100% (100 palms) 
So these proportions are applied to the absolute areas identified at Baseline to determine the 
overall body surface area, assuming that the areas are available. If only the categories are available 
(eg. 0-9%, 10-29%) then this calculation cannot be calculated. 
 
Dermatology Life Quality Index (DLQI)  
The Dermatology Life Quality Index (DLQI) is a ten-question questionnaire used to measure the 
impact of skin disease on the quality of life of an affected person. It is designed for people aged 16 
years and above.  
CCI


 
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Clinical Efficacy 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by 
third party copyright laws and therefore have been excluded.


 
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Clinical Efficacy 
 
Visual Analogue Scale (VAS) itch score 
The subject will be asked to rate the intensity of itch over the past week by marking a line on a 10 
cm VAS with anchors “0” (no noticeable itching) to “10” (maximum itching sensation). 
 
 
11.5.6. 
Pharmacodynamic and Biomarker 
TEAR 
Target Engagement 
• Ratio = free / total 
• Target Engagement = 100 – (ratio post/ratio baseline) * 100)) 
• BIOMARK dataset: 
BICATCD = TRALBP1 (total) or RALB1F (free) 
BITESTCD = CONC (Sample = Target Engagement) and CONCTSZ (Sample = Tru Culture) 
 
CCI


 
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11.6. 
Appendix 6: Premature Withdrawals & Handling of Missing 
Data 
11.6.1. 
Premature Withdrawals 
Element 
Reporting Detail 
General 
• Subject study completion (i.e. as specified in the protocol) was defined as one 
who has completed all phases of the study including the follow-up visit.  
• Withdrawn subjects may be replaced in the study at the discretion of the 
investigator. 
• All available data from subjects 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. 
 
11.6.2. 
Handling of Missing Data 
Element 
Reporting Detail 
General 
• Missing data occurs when any requested data is not provided, leading to blank 
fields on the collection instrument : 
o These data will be indicated by the use of a “blank” in subject listing 
displays. Unless all data for a specific visit are missing in which case the 
data is excluded from the table.  
o Answers such as “Not applicable” and “Not evaluable” are not considered to 
be missing data and should be displayed as such. 
Outliers 
• Any subjects excluded from the summaries and/or statistical analyses will be 
documented along with the reason for exclusion in the clinical study report. 
11.6.2.1. 
Handling of Missing Dates 
Element 
Reporting Detail 
General 
Partial dates will be displayed as captured in subject listing displays. 
Imputed dates should be stored in variables IMPSTDT (Imputed Start Date) and 
IMPENDT (Imputed End Date) 
Adverse 
Events 
• The eCRF allows for the possibility of partial dates (i.e., only month and year) to 
be recorded for AE start and end dates; that is, the day of the month may be 
missing. In such a case, the following conventions will be applied for calculating 
the time to onset and the duration of the event: 
o Missing Start Day: First of the month will be used unless this is before the 
start date of study treatment; in this case the study treatment start date will 
be used and hence the event is considered On-treatment as per Appendix : 
Treatment States and Phases. 
o Missing Stop Day: Last day of the month will be used, unless this is after the 
stop date of study treatment; in this case the study treatment stop date will 
be used. 
• Completely missing start or end dates will remain missing, with no imputation 


 
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Element 
Reporting Detail 
applied. Consequently, time to onset and duration of such events will be 
missing. 
• Start or end dates which are completely missing (i.e. no year specified) will 
remain missing, with no imputation applied. 
 
11.6.2.2. 
Handling of Partial Dates 
Element 
Reporting Detail 
Concomitant 
Medications 
• Partial dates for any concomitant medications recorded in the CRF will be 
imputed using the following convention: 
o If the partial date is a start date, a '01' will be used for the day and 'Jan' will 
be used for the month 
o If the partial date is a stop date, a '28/29/30/31' will be used for the day 
(dependent on the month and year) and 'Dec' will be used for the month. 
• The recorded partial date will be displayed in listings. 
Adverse 
Events 
• Any partial dates for adverse events will be raised to data management. If the 
full date cannot be ascertained, the following assumptions will be made: 
o If the partial date is a start date, a '01' will be used for the day and 'Jan' will 
be used for the month.  
o However, if these results in a date prior to Week 1 Day 1 and the event 
could possibly have occurred during treatment from the partial information, 
then the Week 1 Day 1 date will be assumed to be the start date.  
o The AE will then be considered to start on-treatment (worst case). 
o If the partial date is a stop date, a '28/29/30/31' will be used for the day 
(dependent on the month and year) and 'Dec' will be used for the month. 
• The recorded partial date will be displayed in listings. 
11.6.2.3. 
Handling of Missing Data for Statistical Analysis 
Element 
Reporting Detail 
PLSS 
• Actual score: The mixed models repeated measures model will be applied to the 
data in the analysis and account for missing data in the repeated measures 
analysis over time. 
• Percentage change from baseline: 
o If baseline missing: Exclude from analysis 
o If baseline not missing: The mixed models repeated measures model 
will be applied to the data in the analysis and account for missing data 
in the repeated measures analysis over time 
PASI 
• Change from baseline:  
o If baseline missing: Exclude from analysis 
o If baseline not missing: The mixed models repeated measures model 
will be applied to the data in the analysis and account for missing data 
in the repeated measures analysis over time. 
PASI50 
• If the data is missing then failure is assumed, and therefore a ‘non-response’ 


 
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Element 
Reporting Detail 
PASI75 
PASI90 
assigned to the missing data point. 
PGA  
• Actual score: The mixed models repeated measures model will be applied to the 
data in the analysis and account for missing data in the repeated measures 
analysis over time. 
• Change from baseline:  
o If baseline missing: Exclude from analysis 
o If baseline not missing: The mixed models repeated measures model 
will be applied to the data in the analysis and account for missing data 
in the repeated measures analysis over time. 
PGA (clear 
and almost) 
• If the data is missing then failure is assumed, and therefore a ‘non-response’ 
assigned to the missing data point. 
BSA 
• Change from baseline:  
o If data is missing, exclude from analysis as it is not possible to calculate 
change from baseline since BSA is measured at only two time points; 
baseline (Day 1 pre-dose) and at Day 85. 
DLQI 
• Actual score: The mixed models repeated measures model will be applied to the 
data in the analysis and account for missing data in the repeated measures 
analysis over time. 
• Change from baseline:  
o If baseline missing: Exclude from analysis 
If baseline not missing: The mixed models repeated measures model will be 
applied to the data in the analysis and account for missing data in the repeated 
measures analysis over time. 
VAS 
• Actual score: The mixed models repeated measures model will be applied to the 
data in the analysis and account for missing data in the repeated measures 
analysis over time. 
• Change from baseline:  
o If baseline missing: Exclude from analysis 
• If baseline not missing: The mixed models repeated measures model will be 
applied to the data in the analysis and account for missing data in the repeated 
measures analysis over time. 
 


 
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11.7. 
Appendix 7: Values of Potential Clinical Importance 
11.7.1. 
Laboratory Values 
Haematology 
Laboratory Parameter 
 
Units 
Category 
Clinical Concern Range 
Low Flag (< x) 
High Flag (>x) 
Hematocrit  
Ratio of 1 
Male 
 
0.54 
Female 
 
0.54 
∆ from BL 
↓0.075 
 
Hemoglobin  
g/L 
 
Male 
 
180 
Female 
 
180 
∆ from BL 
↓25 
 
Lymphocytes  
x109/ L 
 
0.8 
 
Neutrophil Count  
x109/ L 
 
1.5 
 
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) 
Albumin  
mmol/L 
 
30 
 
Calcium 
mmol/L 
 
2 
2.75 
Creatinine 
mmol/L 
∆ from BL 
 
↑ 44.2 
Glucose 
mmol/L 
 
3 
9 
Magnesium 
mmol/L 
 
0.5 
1.23 
Phosphorus 
mmol/L 
 
0.8 
1.6 
Potassium 
mmol/L 
 
3 
5.5 
Sodium 
mmol/L 
 
130 
150 
Total CO2 
mmol/L 
 
18 
32 
 
Liver Function 
Test Analyte 
Units 
Category 
Clinical Concern Range 
ALT/SGPT  
U/L 
High 
≥ 2x ULN 
AST/SGOT  
U/L 
High 
≥ 2x ULN 
AlkPhos  
U/L 
High 
≥ 2x ULN 
T Bilirubin  
µmol/L 
High 
≥ 1.5xULN 
T. Bilirubin + ALT 
µmol/L 
High 
1.5xULN T. Bilirubin 
 
+ 
U/L 
≥ 2x ULN ALT 
 
 


 
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11.7.2. 
ECG 
ECG Parameter 
Units 
Clinical Concern Range 
Lower 
Upper 
Absolute 
Absolute QTc Interval 
msec 
> 450 [1] 
 
> 450 [2] 
≤ 479 [2] 
≥ 480 [2] 
≤ 499 [2] 
≥ 500 [2] 
 
Absolute PR Interval 
msec 
< 110 [1] 
> 220 [1] 
Absolute QRS Interval 
msec 
< 75 [1] 
> 110 [1] 
Change from Baseline 
Increase from Baseline QTc 
msec 
> 60 [1] 
 
msec 
> 30  [2] 
≤ 59  [2] 
msec 
≥ 60  [2] 
 
NOTES: [Remove footnotes for RAP development] 
1. 
Represent standard ECG values of PCI for HV studies 
2. 
Represent further subdivisions of ECG values for analysis whereby the RAP team needs to decide whether these 
need to be generated in addition to standard ECG values being flagged. IF not required, then delete. 
11.7.3. 
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 
 
Vital Sign Parameter 
(Change from Baseline) 
Units 
Clinical Concern Range 
Decrease 
Increase 
Lower 
Upper 
Lower 
Upper 
Systolic Blood Pressure 
mmHg 
≥ 20 
≥ 40 
≥ 20 
≥ 40 
Diastolic Blood Pressure 
mmHg 
≥ 10 
≥ 20 
≥ 10 
≥ 20 
Heart Rate 
bpm 
≥ 15 
≥ 30 
≥ 15 
≥ 30 
NOTES: : [Remove footnotes for RAP development] 
Represent further subdivisions of BP & HR for analysis whereby the RAP team needs to decide whether these need 
to be generated in addition to standard absolute BP & HR values being flagged. IF not required, then delete. 


 
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Vital Sign Parameter 
(Change from Baseline) 
Units 
Clinical Concern Range 
Decrease 
Increase 
Lower 
Upper 
Lower 
Upper 
11.8. 
Appendix 8: Multicenter Studies 
No specific outputs will be produced by centre or highlighting the recruitment by site.  
 


 
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11.9. 
Appendix 9: Examination of Covariates, Subgroups & Other 
Strata 
No sub group analyses are to be conducted in this study. 
 
 


 
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11.10. 
Appendix 10: Multiple Comparisons & Multiplicity 
No adjustments will be made for multiplicity. 


 
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11.11. 
Appendix 11: Model Checking and Diagnostics for 
Statistical Analyses 
11.11.1. 
Statistical Analysis Assumptions 
Analysis 
• MMRM 
• For the MMRM, model assumptions will be applied, but appropriate adjustments maybe 
applied based on the data. 
• The Kenward and Roger method for approximating the denominator degrees of freedom and 
correcting for bias in the estimated variance-covariance of the fixed effects will be used. 
• An unstructured covariance structure for the R matrix will be used by specifying ‘type=UN’ on 
the REPEATED line.  
o In the event that this model fails to converge, alternative correlation structures may be 
considered such as CSH or CS.  
o Akaike's Information Criteria (AIC) will be used to assist with the selection of covariance 
structure. 
• Distributional assumptions underlying the model used for analysis will be examined by 
obtaining a normal probability plot of the residuals and a plot of the residuals versus the fitted 
values (i.e. checking the normality assumption and constant variance assumption of the model 
respectively) to gain confidence that the model assumptions are reasonable.  
• If there are any departures from the distributional assumptions, alternative models will be 
explored using appropriate transformed data. 
 


 
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11.12. 
Appendix 12 – Abbreviations & Trade Marks 
11.12.1. 
Abbreviations 
Abbreviation 
Description 
ADaM 
Analysis Data Model 
AE 
Adverse Event 
AIC 
Akaike's Information Criteria 
A&R 
Analysis and Reporting  
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence Interval 
CPMS 
Clinical Pharmacology Modelling & Simulation 
CS 
Clinical Statistics 
CSR 
Clinical Study Report 
CTR 
Clinical Trial Register 
CVb / CVw 
Coefficient of Variation (Between) / Coefficient of Variation (Within) 
DOB 
Date of Birth 
DP 
Decimal Places 
eCRF 
Electronic Case Record Form 
IA 
Interim Analysis 
ICH 
International Conference on Harmonisation 
IDMC 
Independent Data Monitoring Committee  
IDSL 
Integrated Data Standards Library 
IMMS 
International Modules Management System 
IP 
Investigational Product 
ITT 
Intent-To-Treat 
GUI 
Guidance 
LOC 
Last Observation Carries Forward 
MMRM 
Mixed Model Repeated Measures 
PCI 
Potential Clinical Importance  
PD 
Pharmacodynamic 
PDMP 
Protocol Deviation Management Plan 
PK 
Pharmacokinetic 
PP 
Per Protocol 
QC 
Quality Control 
QTcF 
Frederica’s QT Interval Corrected for Heart Rate 
QTcB 
Bazett’s QT Interval Corrected for Heart Rate 
RAP 
Reporting & Analysis Plan 
RAMOS 
Randomization & Medication Ordering System  
IA, SAC 
Statistical Analysis Complete 
SDTM 
Study Data Tabulation Model 
SOP 
Standard Operation Procedure 
TA 
Therapeutic Area 
TFL 
Tables, Figures & Listings  
GSK 
GlaxoSmithKline 


 
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11.12.2. 
Trademarks 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
ADVAIR 
 
WinNonlin 
 
 
SAS 
 
 
 
 


 
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11.13. 
Appendix 13: List of Data Displays 
11.13.1. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
1.1 to 1.n 
1.1 to 1.n 
Efficacy 
2.1 to 2.n 
2.1 to 2.n 
Safety 
3.1 to 3.n 
3.1 to 3.n 
Pharmacokinetic 
4.1 to 4.n 
4.1 to 4.n 
Pharmacodynamic and / or Biomarker 
5.1 to 5.n 
5.1 to 5.n 
Pharmacokinetic / Pharmacodynamic 
6.1 to 6.n 
6.1 to 6.n 
Section 
Listings 
ICH Listings 
1 to x 
Other Listings 
y to z 
 
11.13.2. 
Mock Example Shell Referencing 
Non IDSL specifications will be referenced as indicated and if required an example 
mock-up displays provided in Appendix [X]: Example Mock Shells for Data Displays. 
Section 
Figure 
Table 
Listing 
Study Population 
POP_Fn 
POP_Tn 
POP_Ln 
Efficacy 
EFF_Fn 
EFF_Tn 
EFF_Ln 
Safety 
SAFE_Fn 
SAFE_Tn 
SAFE_Ln 
Pharmacokinetic 
PK_Fn 
PK_Tn 
PK_Ln 
Pharmacodynamic and / or Biomarker 
PD_Fn 
PD_Tn 
PD_Ln 
Pharmacokinetic / Pharmacodynamic 
PKPD_Fn 
PKPD_Tn 
PK/PD_Ln 
NOTES:  
• 
Non-Standard displays are indicated in the ‘IDSL / TST ID / Example Shell’ or ‘Programming Notes’ column as 
‘[Non-Standard] + Reference.’ 
 
11.13.3. 
Deliverable [Priority] 
Delivery 
Description 
IA  
Interim Analysis Statistical Analysis Complete 
IA, SAC  
Final Statistical Analysis Complete 
 
 


 
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11.13.4. 
Study Population Tables 
Study Population Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition  
1.1.  
Safety 
ES1 
Summary of Subject Disposition  
ICH E3, GSK CTR, FDAAA, EudraCT 
IA, SAC 
1.2.  
All screened  
ES6 
Summary of Reasons for Screen Failure  
Journal Requirements 
IA, SAC 
1.3.  
Safety 
NS1 
Summary of Number of Subjects by Centre  
EudraCT 
IA, SAC 
Protocol Deviation  
1.4.  
Safety 
DV1 
Summary of Important Protocol Deviations  
ICH E3 
IA, SAC 
Population Analysed 
1.5.  
Safety 
SP1 
Summary of Study Populations and Exclusions 
IDSL 
IA, SAC 
Demographic and Baseline Characteristics  
1.6.  
Safety 
DM1 
Summary of Demographic Characteristics  
ICH E3, GSK CTR, FDAAA, EudraCT 
IA, SAC 
1.7.  
Safety 
DM5 
Summary of Race and Racial Combinations  
ICH E3, FDA,  GSK CTR, FDAAA, 
EudraCT 
IA, SAC 
1.8.  
Safety 
DM6 
Summary of Race and Racial Combination Details  
ICH E3, FDA 
IA, SAC 
1.9.  
Safety 
 
Summary of Psoarsis Baseline Characteristics 
Based on DM1 to include: 
Baseline BSA, Duration, Prior 
Treatment, Naive to Phototherapy, 
Baseline PASI Score, Baseline PLSS 
score, Baseline PGA, Lesion Seveirty 
(area and score), history of tobacco use 
IA, SAC 
Prior and Concomitant Medications 


 
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Study Population Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.10. 
Safety 
MH4 
Summary of Current/Past Medical Conditions 
ICH E3  
Separate summaries for Current & Past 
conditions, if collected. 
IA, SAC 
1.11. 
Safety 
CM1 
Summary of Concomitant Medications  
ICH E3 
IA, SAC 
Exposure and Treatment Compliance  
1.12. 
Safety 
EX1, EX2, 
OEX1, OEX5 
Summary of Exposure to Study Treatment 
ICH E3 
Dose and/or time on treatment, as 
applicable.  
IA, SAC 
 
11.13.5. 
Safety Tables 
Safety : Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Adverse Events (AEs) 
2.1.  
Safety 
AE5a 
Summary of All Adverse Events by System Organ Class and 
Maximum Intensity 
ICH E3 
 
IA, SAC 
2.2.  
Safety 
AE3 
Summary of Common (>10%) Adverse Events by Overall 
Frequency 
GSK CTR 
IA, SAC 
2.3.  
Safety 
AE5a 
Summary of All Drug-Related Adverse Events by System Organ 
Class and Maximum Intensity 
GSK CTR 
IA, SAC 
Serious and Other Significant Adverse Events 
2.4.  
Safety 
AE1  
Summary of Serious Adverse Events by System Organ Class 
IDSL / GSK CTR 
IA, SAC 
2.5.  
Safety 
CP_AE8a 
Listing of Fatal Adverse Events 
 
IA, SAC 


 
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Safety : Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.6.  
Safety 
AE1 
Summary of Drug-Related Serious Adverse Events by System 
Organ Class 
GSK CTR 
IA, SAC 
2.7.  
Safety 
AE3 
Summary of Adverse Events Leading to Withdrawal from Study / 
Permanent Discontinuation of Study Treatment by Overall 
Frequency 
IDSL 
IA, SAC 
2.8.  
Safety 
AE16 
Summary of Subjects and Number of Occurrences of Serious, 
Drug-Related Serious, Fatal Serious, and Drug-Related Fatal 
Serious Adverse Events 
FDAAA, EudraCT 
 
 IA, SAC 
Laboratory: Chemistry  
2.9.  
Safety 
LB1 
Summary of Clinical Chemistry Changes from Baseline  
ICH E3 
Includes Baseline values. 
Includes pre-specified parameters 
repeated in conventional units. 
 IA, SAC 
2.10. 
Safety 
LB1 
Summary of Clinical Chemistry Values 
 
IA, SAC 
2.11. 
Safety 
LB3 
Summary of Emergent Clinical Chemistry Results by Potential 
Clinical Importance Criteria   
 
IA, SAC 
Laboratory: Hematology 
2.12. 
Safety 
LB1 
Summary of Hematology Changes From Baseline 
ICH E3 
Includes baseline values. 
IA, SAC 
2.13. 
Safety 
LB1 
Summary of Hematology Values 
ICH E3 
Includes baseline values. 
IA, SAC 
2.14. 
Safety 
LB3 
Summary of Emergent Hematology Results by Potential Clinical 
Importance Criteria   
 
IA, SAC 
Laboratory: Urinalysis 


 
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Safety : Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.15. 
Safety 
LB1 
Summary of Urine Concentration Changes from Baseline 
ICH E3 
Includes Baseline values. 
IA, SAC 
Laboratory: Hepatobiliary (Liver) 
2.16. 
Safety 
LIVER1 
Summary of Liver Monitoring/Stopping Event Reporting 
IDSL 
IA, SAC 
2.17. 
Safety 
LIVER10 
Summary of Hepatobiliary Laboratory Abnormalities 
 
IA, SAC 
ECG 
2.18. 
Safety 
EG1 
Summary of ECG Findings  
IDSL 
As above for Chemistry, using ECG 
findings categories (and change from 
baseline categories, if applicable). 
IA, SAC 
2.19. 
Safety 
EG2 
Summary of Change from Baseline in ECG Values by Visit 
IDSL 
IA, SAC 
2.20. 
Safety 
CP_EG12 
Summary of Maximum Change from Baseline in QTc Values by 
Category 
IDSL 
IA, SAC 
Vital Signs 
2.21. 
Safety 
VS1 
Summary of Change From Baseline in Vital Signs by Visit 
ICH E3 
Includes Baseline values. 
IA, SAC 
2.22. 
Safety 
VS1 
Summary of Vital Signs by Visit 
 
IA, SAC 
 
 


 
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11.13.6. 
Safety Figures 
Safety : Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Adverse Events  
2.1.  
Safety 
AE10 
Plot of Common Adverse Events and Relative Risk 
IDSL 
Common defined as >10% 
IA, SAC 
Hepatobilary (Liver) 
2.2.  
Safety 
LIVER14 
Scatter Plot of Maximum vs Baseline for ALT 
 
IA, SAC 
2.3.  
Safety 
LIVER9 
Scatter Ploy for Maximum ALT va Maximum Total Bilirubin 
 
IA, SAC 
 
 


 
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11.13.7. 
Efficacy Tables 
Efficacy: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
PLSS 
3.1.  
Safety 
EFF_T3 
Summary Statistics for PLSS scores by Treatment and Visit 
 
IA, SAC 
3.2.  
Safety 
EFF_T3 
Summary Statistics for % change from baseline PLSS scores by 
Treatment and Visit 
 
IA, SAC 
3.3.  
Safety 
EFF_T4 
Summary of Statistical Analysis Results for Percentage Change 
from Baseline PLSS score  by Visit 
 
IA, SAC 
PASI 
3.4.  
Safety 
EFF_T3 
Summary Statistics for PASI scores by Treatment and Visit 
 
IA, SAC 
3.5.  
Safety 
EFF_T3 
Summary Statistics for Change from baseline PASI scores by 
Treatment and Visit 
 
IA, SAC 
3.6.  
Safety 
EFF_T4 
Summary of Statistical Analysis Results for Percentage Change 
from Baseline PASI score  by Visit 
 
IA, SAC 
3.7.  
Safety  
EFF_T2 
Frequency: Proportion of subjects improving from baseline in 
PASI Score (PASI 50. PASI 75 and PASI 90) by Treatment and 
Visit 
 
IA, SAC 
3.8.  
Safety 
EFF_T1 
GEE adjusted odds ratio and 95% CI for PASI50 by Visit  
 
IA, SAC 
3.9.  
Safety 
EFF_T1 
GEE adjusted odds ratio and 95% CI for PASI75 by Visit  
 
IA, SAC 
3.10. 
Safety 
EFF_T1 
GEE adjusted odds ratio and 95% CI for PASI90 by Visit  
 
IA, SAC 
PGA 
3.11. 
Safety 
EFF_T3 
Summary Statistics for PGA Scores by Treatment and Visit 
 
IA, SAC 
3.12. 
Safety 
EFF_T3 
Summary Statistics for change from baseline PGA Scores by 
Treatment and Visit 
 
IA, SAC 


 
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Efficacy: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.13. 
Safety 
EFF_T4 
Summary of Statistical Analysis Results for Change from 
Baseline PGA Score by Visit 
Include related estimated LSMeans and 
treatment differences. 
Footnote: 
IA, SAC 
PGA “Clear”/“Almost Clear”  
3.14. 
Safety 
EFF_T2 
Frequency: PGA score of Clear/Almost Clear by Treatment and 
Visit  
Clear/Almost is a score of 0 or 1 
IA, SAC 
3.15. 
Safety 
EFF_T1 
GEE Point Estimate and 95% CI for PGA Score of Clear / 
Almost Clear by Visit 
Footnote: 
IA, SAC 
BSA 
3.16. 
Safety 
EFF_T3 
Summary Statistics for BSA scores by Treatment and Visit 
 
IA, SAC 
3.17. 
Safety 
EFF_T3 
Summary Statistics for change from baseline BSA scores by 
Treatment and Visit 
 
IA, SAC 
3.18. 
Safety 
EFF_T4 
Summary of Statistical Analysis Results for Change from 
Baseline BSA score by Visit 
 
IA, SAC 
DLQI 
3.19. 
Safety 
EFF_T3 
Summary Statistics for DLQI scores by Treatment and Visit 
 
IA, SAC 
3.20. 
Safety 
EFF_T3 
Summary Statistics for change from baseline  DLQI scores by 
Treatment and Visit 
 
IA, SAC 
3.21. 
Safety 
EFF_T4 
Summary of Statistical Analysis Results for Change from 
Baseline DLQI score by Visit 
 
IA, SAC 
VAS Itch Score  
3.22. 
Safety 
EFF_T3 
Summary Statistics for VAS scores by Treatment and Visit 
 
IA, SAC 
3.23. 
Safety 
EFF_T3 
Summary Statistics for change from baseline VAS scores by 
Treatment and Visit 
 
IA, SAC 


 
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Efficacy: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.24. 
Safety 
EFF_T4 
Summary of Statistical Analysis Results for Change from 
Baseline VAS score by Visit 
 
IA, SAC 
 


 
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11.13.8. 
Efficacy Figures 
Efficacy: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
PLSS 
3.1.  
Safety 
FE1 
Individual PLSS scores over Time by Treatment 
Panel plot by subject, line colour to 
reflect treatment group, subjid as cell 
header 
IA, SAC 
3.2.  
Safety 
FE2 
Mean (+/-SD) PLSS Scores over Time by Treatment   
 
IA, SAC 
3.3.  
Safety 
FE2 
Point Estimates and 95% CI for Change from Baseline in PLSS 
Score over Time by Treatment  
Grey dashed ref line at y=0 
IA, SAC 
PASI 
3.4.  
Safety 
FE1 
Individual PASI Scores over Time by Treatment  
Panel plot by subject, line colour to 
reflect treatment group, subjid as cell 
header 
IA, SAC 
3.5.  
Safety 
FE2 
Mean (+/-SD) PASI Scores over Time by Treatment   
 
IA, SAC 
3.6.  
Safety 
FE2 
Point Estimates and 95% CI for Change from Baseline in PASI 
Score over Time by Treatment 
Grey dashed ref line ay y=0 
IA, SAC 
3.7.  
Safety 
FE2 
Proportion of Subjects Who Achieved PASI50 over Time by 
Treatment  
Line graph 
Treatment on the same plot 
IA, SAC 
3.8.  
Safety 
FE3 
Odds Ratio and 95% CI for Achieving PASI50 over Time by 
Treatment  
 
IA, SAC 
3.9.  
Safety 
FE2 
Proportion of Subjects Who Achieved PASI75 over Time by 
Treatment 
Line graph 
Treatment on the same plot 
IA, SAC 
3.10. 
Safety 
FE3 
Odds Ratio and 95% CI for Achieving PASI75 over Time by 
Treatment  
 
IA, SAC 
3.11. 
Safety 
FE2 
Proportion of Subjects Who Achieved PASI90 over Time by 
Treatment 
Line graph 
Treatment on the same plot 
IA, SAC 


 
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Efficacy: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.12. 
Safety 
FE3 
Odds Ratio and 95% CI for Achieving PASI90 over Time by 
Treatment  
 
IA, SAC 
PGA 
3.13. 
Safety 
FE1 
Individual PGA Scores over Time by Treatment 
Panel plot by subject, line colour to 
reflect treatment group, subjid as cell 
header 
IA, SAC 
3.14. 
Safety 
FE2 
Mean (+/-SD) PGA Scores over Time by Treatment   
 
IA, SAC 
3.15. 
Safety 
FE3 
Point Estimates and 95% CI for Change from Baseline in PGA 
Score over Time by Treatment  
Grey dashed ref line ay y=0 
IA, SAC 
PGA “Clear”/“Almost Clear” 
3.16. 
Safety 
FE2 
Proportion of Subjects Who Achieve PGA Score of Clear / 
Almost Clear over Time by Treatment 
 
IA, SAC 
3.17. 
Safety 
FE3 
Odds Ratio and 95% CI for Achieving PGA Score of Clear over 
Time by Treatment  
 
IA, SAC 
BSA 
3.18. 
Safety 
FE1 
Individual BSA Scores over Time by Treatment 
Panel plot by subject, line colour to 
reflect treatment group, subjid as cell 
header 
IA, SAC 
3.19. 
Safety 
FE2 
Mean (+/-SD) BSA Scores over Time by Treatment   
 
IA, SAC 
3.20. 
Safety 
FE3 
Point Estimates and 95% CI for Change from Baseline in BSA 
Score over Time by Treatment 
Grey dashed ref line ay y=0 
IA, SAC 
DLQI 
3.21. 
Safety 
FE1 
Individual DLQI Scores over Time by Treatment 
Panel plot by subject, line colour to 
reflect treatment group, subjid as cell 
header 
IA, SAC 


 
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Efficacy: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.22. 
Safety 
FE2  
Mean (+/-SD) DLQI Scores over Time by Treatment   
 
IA, SAC 
3.23. 
Safety 
FE3 
Point Estimates and 95% CI for Change from Baseline in DLQI 
Score over Time by Treatment 
Grey dashed ref line ay y=0 
IA, SAC 
VAS itch score 
3.24. 
Safety 
FE1 
Individual VAS itch Scores over Time by Treatment 
Panel plot by subject, line colour to 
reflect treatment group 
IA, SAC 
3.25. 
Safety 
FE2 
Mean (+/-SD) VAS itch Scores over Time by Treatment   
 
IA, SAC 
3.26. 
Safety 
FE3 
Point Estimates and 95% CI for Change from Baseline in VAS 
itch Score over Time by Treatment 
Grey dashed ref line ay y=0 
IA, SAC 
 


 
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11.13.9. 
Pharmacokinetic Tables 
Pharmacokinetic : Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
PK concentration data 
4.1.  
PK 
PKPT1 
Summary of Plasma GSK2982772 Pharmacokinetic 
Concentration-Time Data (ng/mL) 
 
IA, SAC 
4.2.  
PK 
PKPT1 
Summary of Skin GSK2982772 Pharmacokinetic Concentration-
Time Data (ng/mL) 
 
IA, SAC 
 


 
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11.13.10. Pharmacokinetic Figures 
Pharmacokinetic : Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Individual concentration plots  
4.1.  
PK 
PKCF1P 
Individual Plasma GSK2982772 Concentration-Time Plot by 
Subject (Linear and Semi-Log) 
Page by: subject 
Panel: linear and semi-log 
x-axis: actual relative time 
y-axis: PK concentration 
Legend: Visit  
IA, SAC 
Mean/median concentration plots 
4.2.  
PK 
PKCF2 
Mean (+ SD) plot: Plasma GSK2982772 concentrations (linear 
and semi-log) 
Panel: linear and semi-log 
x-axis: planned relative time 
y-axis: PK concentration 
Legend: active treatment 
IA, SAC 
4.3.  
PK 
PKCF3 
Median (range) plot: GSK2982772 Plasma concentrations 
(linear and semi-log) 
Panel: linear and semi-log 
x-axis: planned relative time 
y-axis: PK concentration 
Legend: active treatment 
IA, SAC 
Individual concentration plots  
4.4.  
PK 
PKCF1P 
Individual Skin GSK2982772 Concentration-Time Plot by 
Subject (Linear and Semi-Log) 
Page by: subject 
Panel: linear and semi-log 
x-axis: actual relative time 
y-axis: PK concentration 
Legend: Visit  
IA, SAC 
Mean/median concentration plots 
4.5.  
PK 
PKCF2 
Mean (+ SD) plot: Skin GSK2982772  concentrations (linear and 
semi-log) 
Panel: linear and semi-log 
x-axis: planned relative time 
y-axis: PK concentration 
Legend: active treatment 
IA, SAC 


 
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Pharmacokinetic : Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
4.6.  
PK 
PKCF3 
Median (range) plot: Skin GSK2982772 concentrations (linear 
and semi-log) 
Panel: linear and semi-log 
x-axis: planned relative time 
y-axis: PK concentration 
Legend: active treatment 
IA, SAC 
 


 
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11.13.11. Pharmacodynamic and / or Biomarker Tables 
Pharmacodynamic (and or Biomarker) : Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Inflammatory Biomarkers in Skin 
5.1.  
Safety 
PD1 
Summary of Histopathological Scoring in Psoriatic Lesional 
Biopsies   
By parameter / (epidermis/dermis) 
K16: 0 or 1 
IA, SAC 
5.2.  
Safety 
PD3 
Summary of Percentage Change in Histopathological Scoring in 
Psoriatic Lesional Biopsies   
 
IA, SAC 
5.3.  
Safety 
EFF_T4 
Adjusted Mean (95% CI)  Percentage Change in 
Histopathological Scoring of Psoriatic Lesional Biopsy   
Present %CVb instead of SE 
IA, SAC 
mRNA in Skin 
5.4.  
Safety 
PD2 
Summary of mRNA Expression of Inflammatory Gene 
Transcripts in Psoriatic Lesional Biopsies   
 
IA, SAC 
5.5.  
Safety 
PD_T2 
Frequency Table Summarising the Number of Probe Sets with 
Various Fold Change in Psoriatic Lesional Biopsies   
Use cut-offs 1.5 and -1.5 initially.  
Change to -1.25 and 1.5 if no one 
achieves the initial cut-offs 
IA, SAC 
5.6.  
Safety 
PD_T3 
Summary of Adjusted Mean Fold Changes in mRNA Expression 
of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies   
If Adj Mean FC lies between -1 and 1 
then do not include on table 
IA, SAC 
 Inflammatory Biomarkers in Blood 
5.7.  
Safety 
PD1 
Summary Statistics of Blood Inflammatory Biomarkers   
One page for each cell type/measure 
by visit/time and treatment 
IA, SAC 
5.8.  
Safety 
PD2 
Summary of Percentage Change in Blood Inflammatory 
Biomarkers   
One page for each cell type/measure 
by visit/time and treatment 
IA, SAC 
5.9.  
Safety 
EFF_T4 
Adjusted Mean (95% CI)  Percentage Change in Blood 
Inflammatory Biomarkers   
Present %CVb instead of SE 
IA, SAC 
Pathway and Target Engagement  


 
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Pharmacodynamic (and or Biomarker) : Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
5.10. 
Safety 
 
Summary of TEAR1 % Target Engagement in Blood 
% Target Engagement by visit/time, 
Refer to 200975/Partb_final for display 
IA, SAC 
5.11. 
Safety 
 
Adjusted Mean (95% CI) TEAR1 % Target Engagement in Blood 
Refer to 200975/Partb_final for 
display 
IA, SAC 
5.12. 
Safety 
 
Summary of TEAR1 % Target Engagement in Skin 
% Target Engagement by visit/time, 
Refer to 200975/Partb_final for 
display 
IA, SAC 
5.13. 
Safety 
 
Adjusted Mean (95% CI) TEAR1 % Target Engagement in Skin 
Refer to 200975/Partb_final for 
display 
IA, SAC 
 


 
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11.13.12. Pharmacodynamic (and / or Biomarker) Figures 
Pharmacodynamic (and or Biomarker) : Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Inflammatory Biomarkers in Skin 
5.14. 
Safety 
FE1 
Individual  Subject Profiles for Histopathological Scoring in 
Psoriatic Lesional Biopsies   
Page by biomarker and location 
(dermis/epidermis) 
Panel plot, line colours by treatment 
group, subjid as cell header 
 
IA, SAC 
5.15. 
Safety 
FE2 
Adjusted Mean (95% CI)  Percentage Change in 
Histopathological Scoring of Psoriatic Lesional Biopsy   
Reference line at y=0, grey dashed 
style 
IA, SAC 
mRNA in Skin 
5.16. 
Safety 
FE1 
Individual  Subject Profiles for mRNA Expression of 
Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies   
Panel plot, line colours by treatment 
group, subjid as cell header 
 
IA, SAC 
5.17. 
Safety 
FE4 
Adjusted Mean Intensities for for mRNA Expression of 
Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies   Y xais – log2 scale 
IA, SAC 
5.18. 
Safety 
FE5 
Adjusted Mean (95% CI) Fold Change in mRNA Expression 
of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies   
If Adj Mean FC lies between -1 and 1 
then do not include on table 
Include band from FC -1 to 1, 
transparency 0.5 
IA, SAC 
 Inflammatory Biomarkers in Blood 
5.19. 
Safety 
FE1 
Summary Statistics of Blood Inflammatory Biomarkers   
Page by biomarker 
Panel plot, line colours by treatment 
group, subjid as cell header 
 
IA, SAC 
5.20. 
Safety 
FE2 
Adjusted Mean (95% CI)  Percentage Change in Blood 
Inflammatory Biomarkers   
Reference line at y=0, grey dashed 
style 
IA, SAC 


 
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Pharmacodynamic (and or Biomarker) : Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Pathway and Target Engagement  
5.21. 
Safety 
FE1 
Individual  Subject Profiles for TEAR1  % Target Engagement in 
Blood 
Panel plot, line colours by treatment 
group, subjid as cell header 
 
IA, SAC 
5.22. 
Safety 
FE2 
Adjusted Mean (95% CI)  TEAR1  % Target Engagement in 
Blood 
 
IA, SAC 
5.23. 
Safety 
FE1 
Individual  Subject Profiles for TEAR1  % Target Engagement in 
Skin 
Panel plot, line colours by treatment 
group, subjid as cell header 
 
IA, SAC 
5.24. 
Safety 
FE2 
Adjusted Mean (95% CI)  TEAR1  % Target Engagement in Skin 
 
IA, SAC 
5.25. 
Safety 
FE6 
Scatter Plot of TEAR 1 % Target Engagement in Blood vs. 
TEAR1 % Target Engagement in Skin by Treatment Group 
X axis- TE Blood, y axis TE Skin 
Include bands for lower 10th and 90th 
percentile from PKPD, and grey dashed 
ref line at median 
60mg BID PKPD model: 
 
 
10th 
percen
tile 
Media
n 
90th 
Perce
ntile 
Blood 
85.3%    95%       98.4% 
Skin 
70.3%    88.5%    96.1
% 
IA, SAC 
Exploratory  


 
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Pharmacodynamic (and or Biomarker) : Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
5.26. 
Safety 
FE7 
Scatter Plot of TEAR1 % Target Engagement in Skin vs. 
Percentage Change in Histopathological Scoring in Psoriatic 
Lesional Biopsies   
Page by biomarker and location 
(dermis/epidermis) 
X axis – TE Skin, y axis - % Chg 
Biomarker 
Markers by treatment group 
 
IA, SAC 
5.27. 
Safety 
FE7 
Scatter Plot of TEAR1 % Target Engagement in Skin vs. Fold 
Change in mRNA Expression of Inflammatory Gene Transcripts 
in Psoriatic Lesional Biopsies   
Page by biomarker and location 
(dermis/epidermis) 
X axis – TE Skin, y axis - % Chg 
Biomarker 
Markers by treatment group 
Band for FC between -1 to 1 
IA, SAC 
 


 
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11.13.13. Biomarker / Efficacy Figures 
Pharmacodynamic (and or Biomarker) : Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
5.28. 
Safety 
FE7 
Scatter Plot of TEAR1 % Target Engagement in Skin vs. 
Percentage Change in PLSS   
Page by biomarker and location 
(dermis/epidermis) 
X axis – TE Skin, y axis - % Chg 
Biomarker 
Markers by treatment group 
Band for FC between -1 to 1 
IA, SAC 
5.29. 
Safety 
FE7 
Scatter Plot of TEAR1 % Target Engagement in Skin vs. 
Percentage Change in PASI 
Page by biomarker and location 
(dermis/epidermis) 
X axis – TE Skin, y axis - % Chg 
Biomarker 
Markers by treatment group 
Band for FC between -1 to 1 
IA, SAC 
 
 
 
 


 
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11.13.14. ICH Listings 
ICH : Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Randomisation  
1.  
Safety 
CP_TA1 
Listings of Randomised and Actual Treatments  
 
IA, SAC 
Subject Disposition 
2.  
All subjects 
ES7 
Listing of Reasons for Screen Failure 
Journal Guidelines 
IA, SAC 
3.  
Safety 
ES2  
Listing of Reasons for Study Withdrawal 
ICH E3 
IA, SAC 
4.  
Safety 
BL1 
Listing of Subjects for Whom the Treatment Blind was Broken 
ICH E3 
IA, SAC 
5.  
Safety 
TA1  
Listing of Planned and Actual Treatments 
IDSL 
IA, SAC 
Protocol Deviations 
6.  
Safety 
DV2 
Listing of Important Protocol Deviations  
ICH E3 
Listing also includes analysis 
population exclusions. 
IA, SAC 
7.  
Safety 
IE3  
Listing of Subjects with Inclusion/Exclusion Criteria Deviations 
ICH E3 
IA, SAC 
Population Analysed 
8.  
All Subjects  
SA3a 
Listing of Subjects Excluded from Any Population 
ICH E3 
e.g., subjects screened but not 
randomized, subjects randomized but 
not treated, subjects with deviations 
leading to exclusion from per protocol 
population (can be separate listing per 
population). 
IA, SAC 


 
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Demographic and Baseline Characteristics  
9.  
Safety 
DM2  
Listing of Demographic Characteristics 
ICH E3 
IA, SAC 
10.  
Safety 
DM9 
Listing of Race 
ICH E3 
IA, SAC 
Prior and Concomitant Medications 
11.  
Safety 
CP_CM3 
Listing of Concomitant Medications 
IDSL 
 
IA, SAC 
Exposure and Treatment Compliance 
12.  
Safety 
EX3  
Listing of Exposure Data 
ICH E3 
IA, SAC 
Adverse Events  
13.  
Safety 
AE8  
Listing of All Adverse Events 
ICH E3 
IA, SAC 
14.  
Safety 
AE7 
Listing of Subject Numbers for Individual Adverse Events 
ICH E3 
IA, SAC 
15.  
Safety 
AE2 
Listing of Relationship Between Adverse Event System Organ 
Classes, Preferred Terms, and Verbatim Text 
IDSL 
IA, SAC 
Serious and Other Significant Adverse Events 
16.  
Safety 
CP_AE8a  
 
Listing of Serious Adverse events 
ICH E3 
 
IA, SAC 
17.  
Safety 
SAE Reasons 
Listing of Reasons for Considering as a Serious Adverse Event 
FDA 
Note: IDSL shell in development. 
IA, SAC 
18.  
Safety 
CP_AE8  
Listing of Adverse Events Leading to Withdrawal from Study / 
Permanent Discontinuation of Study Treatment 
ICH E3 
IA, SAC 
Hepatobiliary (Liver) 
19.  
Safety 
MH2 
Listing of Medical Conditions for Subjects with Liver Stopping 
Events 
IDSL 
IA, SAC 
20.  
Safety 
SU2 
Listing of Substance Use for Subjects with Liver Stopping 
Events 
IDSL 
IA, SAC 


 
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All Laboratory 
21.  
Safety 
LB5  
Listing of Laboratory Data for Subjects with Abnormalities of 
Potential Clinical Concern 
ICH E3 
Include fasted or non-fasted. 
Include subjects that have both 
absolute and change from baseline PCI 
IA, SAC 
22.  
Safety 
LB5 / LB6 
Listing of Laboratory Data Abnormalities of Potential Clinical 
Importance 
Include fasted or non-fasted. 
IA, SAC 
ECG 
23.  
Safety 
CP_EG3 
Listing of All ECG Values for Subjects with a Value of Potential 
Clinical Importance 
IDSL 
Include absolute PCI subjects.  
Footnote: 
H=High absolute, L= Low absolute." 
IA, SAC 
24.  
Safety 
CP_EG3 
Listing of All ECG Changes for Subjects with a Value of 
Potential Clinical Importance 
IDSL 
Include change from baseline PCI 
subjects.  
Footnote: 
H=High change from baseline value, L= 
Low change from baseline value 
IA, SAC 
25.  
Safety 
CP_EG3  
Listing of ECG Values of Potential Clinical Importance 
"Include absolute PCIs.  
Footnote: 
H=High absolute, L= Low absolute." 
IA, SAC 
26.  
Safety 
CP_EG3  
Listing of ECG Changes of Potential Clinical Importance 
"Include change from baseline PCIs.  
Footnote: 
H=High change, L= Low changee." 
IA, SAC 
27.  
Safety 
CP_EG5  
Listing of Abnormal ECG Findings 
IDSL 
IA, SAC 
Vital Signs 


 
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28.  
Safety 
CP_VS4  
Listing of All Vital Signs for Subjects with Values of Potential 
Clinical Importance 
"Include both absolute and change from 
baseline PCI subjects.  
Footnote: 
H=High, L=Low 
H1=Lower Increase, H2=Upper 
Increase, L1=Lower Decrease, 
L2=Upper Decrease" 
IA, SAC 
 


 
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11.13.15. Non-ICH Listings 
Non-ICH : Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Columbia Suicide Severity Rating Scale (C-SSRS)  
29.  
Safety 
ECSSRS4 
Listing of C-SSRS suicidal Ideation and Behaviour Data 
 
IA, SAC 
30.  
Safety 
ECSSRS5 
Listing of C-SSRS Suicidal Behaviour Details 
 
IA, SAC 
Pharmacokinetic 
31.  
PK 
PKCL1X 
Listing of Blood GSK2982772 Pharmacokinetic Concentration-
Time (ng/mL) Data 
 
IA, SAC  
32.  
PK 
PKCL1X 
Listing of Skin GSK2982772 Pharmacokinetic Concentration-
Time (ng/mL) Data 
 
IA, SAC  
Pharmacodynamic  
33.  
Safety 
LS2 
Listing of Histopathological Scoring in Psoriatic Lesional 
Biopsies 
Including, but not limited to K16, 
CD3/Cd11c, CD161, elastase positive 
dermal cells and epidermal thickness.  
IA, SAC 
34.  
Safety 
LS1 
Listing of mRNA Expression of Inflammatory Gene 
Transcripts in Psoriatic Lesional Biopsies   
Including, but not limited to CRP, 
VEGF, S100A8, S100A9, IL-17, IL-22 
and TNF. 
IA, SAC 
35.  
Safety 
LS2 
Listing of Blood Inflammatory Biomarkers 
 
IA, SAC 
36.  
Safety 
 
Listings of TEAR1 % Target Engagement 
See 200975/partb_final 
IA, SAC 
37.  
Safety 
n/a 
Raw SAS Output of Statistical Analysis of Histopathological 
Scoring in Psoriatic Lesional Biopsies 
 
IA, SAC  
38.  
Safety 
n/a 
Raw SAS Output of Statistical Analysis of Inflammatory Gene 
Transcripts in Psoriatic Lesional Biopsies   
 
IA, SAC 
39.  
Safety 
n/a 
Raw SAS Output of Statistical Analysis of Blood Inflammatory 
Biomarkers 
 
IA, SAC 


 
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Non-ICH : Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
40.  
Safety 
n/a 
Raw SAS Output of Statistical Analysis of TEAR1 % Target 
Engagement 
 
IA, SAC 
Efficacy 
41.  
Safety 
LS2 
Listings of PLSS absolute and change from baseline score 
 
IA, SAC 
42.  
Safety 
LS2 
Listings of PASI absolute, change from baseline, percentage 
change from baseline, PASI50, PASI75 and PASI90 status  
 
IA, SAC 
43.  
Safety  
LS2 
Listing of PGA categories by treatment over time  
 
IA, SAC 
44.  
Safety 
LS2 
Listing of BSA absolute and change from baseline score 
 
IA, SAC 
45.  
Safety 
LS2 
Listing of DLQI Absolute and Change From Baseline Score   
IA, SAC 
46.  
Safety 
LS2 
Listings of VAS Absolute and Change From Baseline 
Score  
 
IA, SAC 
47.  
Safety 
n/a 
RAW SAS Output of Statistical Analysis Results for 
Percentage Change From Baseline PLSS  Score 
 
IA, SAC 
48.  
Safety 
n/a 
RAW SAS Output of Statistical Analysis Results for 
Change From Baseline PASI Score 
 
IA, SAC 
49.  
Safety 
n/a 
RAW SAS Output of Statistical Analysis Results for 
PASI50 Score 
 
IA, SAC 
50.  
Safety 
n/a 
RAW SAS Output of Statistical Analysis Results for 
PASI75 Score 
 
IA, SAC 
51.  
Safety 
n/a 
RAW SAS Output of Statistical Analysis Results for 
PASI90 Score 
 
IA, SAC 
52.  
Safety 
n/a 
RAW SAS Output of Statistical Analysis Results for 
Change from Baseline PGA Score 
 
IA, SAC 


 
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Non-ICH : Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
53.  
Safety 
n/a 
RAW SAS Output of Statistical Analysis Results for PGA 
Score of Clear / Almost Clear  
 
IA, SAC 
54.  
Safety 
n/a 
RAW SAS Output of Statistical Analysis Results for 
Change From Baseline BSA score 
 
IA, SAC 
55.  
Safety 
n/a 
RAW SAS Output of Statistical Analysis Results for 
Change From Baseline BSA score 
 
IA, SAC 
56.  
Safety 
n/a 
RAW SAS Output of Statistical Analysis Results for 
Change From Baseline DLQI score 
 
IA, SAC 
57.  
Safety 
n/a 
RAW SAS Output of Statistical Analysis Results for 
Change From Baseline VAS score 
 
IA, SAC 
 


 
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11.14. 
Appendix 14:  Example Mock Shells for Data Displays 


 
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88 
 
Example  
: LS1 
 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 203167 
Population 
: Safety 
 
                                                 Listing XX:  
  Listing of Absolute, Percentage Inhibition and Maximum Percentage Inhibition in qPCR Expression 
 
                                                            CT1/CT2/                            Maximum 
                                                            CTAVG/                Percentage    Percentage 
                                                            Copy                  Inhibition    Inhibition 
Gene        Treatment              Subject   Visit          Number         Value  [1]           [2] 
------------------------------------------------------------------------------------------------------------ 
XXXXGENE    GSKXXXXXX XXmg         XXXX      Screening      CT1           XX.XXX 
                                                            CT2           XX.XXX 
                                                            CTAVG         XX.XXX 
                                                            NORMALISED    XX.XXX 
 
                                             Baseline       CT1           XX.XXX 
                                                            CT2           XX.XXX 
                                                            CTAVG         XX.XXX 
                                                            NORMALISED    XX.XXX     x.xxx 
 
                                             Week X         CT1           XX.XXX 
                                                            CT2           XX.XXX 
                                                            CTAVG         XX.XXX 
                                                            NORMALISED    XX.XXX     x.xxx 
 
 
 
 
 
 
 
 


 
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Example  
: LS2 
 
 
 
 
 
 
 
 
 
 
 Page 1 of n 
Protocol 
: 203167 
Population 
: Safety 
 
                                                 Listing XX:  
Listing of Raw, Change from baseline and Percent Change in [variable} 
 
 
 
 
 
 


 
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Example EFF_T1  
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of 1 
Protocol: 203167                                                          
Population: Safety 
 
Table XX:  GEE Point Estimate and 95% CI for PASIXX by Week  
                                                                                   95% CI of 
     Comparison                            Parameter                 Odds Ratio    Odds Ratio     
     -------------------------------------------------------------------------------------------------- 
     GSK2982772 vs Placebo           PASIXX at Day 1   
 
    x.xx        (x.xx, x.xx)     
     GSK2982772 vs Placebo           PASIXX at Day 15                 x.xx        (x.xx, x.xx)     
     GSK2982772 vs Placebo           PASIXX at Day 29   
 
    x.xx        (x.xx, x.xx)         ....
 
.... .. 
.... .. 
     
 
 
 
 
 
 
 
 
 
 
 


 
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Example EFF_T2  
 
 
 
 
 
 
 
 
 
 
 
Page 1 of 1 
Protocol: 203167                                                           
Population: Safety 
 
Table XX:  Frequency Table for PASI50, PASI75 by week  
 
 
 
Parameter 
 
 
 
Visit 
 
Placebo 
 
N=x 
100mg 
 
N=x  
200mg 
 
N=x  
400mg 
 
N =x 
 
 
 
 
 
 
 
 
PASI50 
 
Day 1 
 
nn/nn 
(xx.xx) 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
 
 
Day 15 
 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
 
 
Day 29 
 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
PASI75 
 
Day 1 
 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
 
 
Day 15 
 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
 
 
Day 29 
 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
PASI90 
 
Day 1 
 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
 
 
Day 15 
 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
 
 
Day 29 
 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
nn / nn 
(xx.xx) 
 
 
... 
 
 
 
 
 
 


 
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Example EFF_T3  
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of 1 
Protocol: 203167                                                           
Population: Safety 
 
Table XX:  Summary Statistics (Mean +/- SD) for Actual and Change from Baseline [Continuous 
Parameter] by Treatment and Week  
 
 
 
Parameter 
 
 
Treatment 
 
 
N 
  
 
Visit 
 
 
n 
 
 
 Mean 
 
{95% CI 
(Lower,Upper)} 
 
 
SD 
 
 
Median 
 
 
Min. 
 
 
Max. 
 
 
 
 
 
 
 
 
 
 
 
Continuous  GSK2982772 
18 
Day 1 
18 
xxxx.xx 
(xxxx.xx,xxxx.xx) xx.xxx 
xxxx.xx 
xxxx.x 
xxxx.x 
Parameter  
 
 
Day 15 
18 
xxxx.xx 
(xxxx.xx,xxxx.xx) xx.xxx 
xxxx.xx 
xxxx.x 
xxxx.x 
 
 
 
Day 29 
18 
xxxx.xx 
(xxxx.xx,xxxx.xx) xx.xxx 
xxxx.xx 
xxxx.x 
xxxx.x 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Placebo 
6 
Day 1 
6 
xxxx.xx 
(xxxx.xx,xxxx.xx) xx.xxx 
xxxx.xx 
xxxx.x 
xxxx.x 
 
 
 
Day 15 
6 
xxxx.xx 
(xxxx.xx,xxxx.xx) xx.xxx 
xxxx.xx 
xxxx.x 
xxxx.x 
 
 
 
Day 29 
6 
xxxx.xx 
(xxxx.xx,xxxx.xx) xx.xxx 
xxxx.xx 
xxxx.x 
xxxx.x 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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Example: EFF_T4 
Protocol: 203167                                                                     Page 1 of x 
Population: Safety 
                                                 Table x.x: 
               Repeated Measures Analysis of the Change from Baseline in [Continuous Parameter] at Each Visit 
 
                                                               95% CI for   Difference    95% CI for 
                             Treatment              Standard    LS Mean      from    Difference 
                      Visit  Group       n   LSMean     Error               Placebo   (Lower,Upper) 
                   ---------------------------------------------------------------------- 
 
                    Week 1   Placebo     x    x.xx     x.xxx   (x.xx, x.xx) 
 
                             GSK2982772  x    x.xx     x.xxx                  x.xx       (x.xx, x.xx) 
                              
 
 
                    Week 2   Placebo     x    x.xx     x.xxx   (x.xx, x.xx) 
 
                             GSK2982772  x    x.xx     x.xxx   (x.xx, x.xx)   x.xx       (x.xx, x.xx) 
                              
 
 
                     ... 
 
 
 
 


 
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Repeated Measures Analysis adjusted for Baseline Score, Treatment Group, Visit and Treatment Group 
by Visit Interaction 
 
 
Example: PD_T1 
Protocol: 203167                                                                     Page 1 of x 
Population: Safety 
Listing XX:  
  Listing of Absolute, Percentage Inhibition and Maximum Percentage Inhibition in mRNA Expression 
 
                                                            CT1/CT2/                            Maximum 
                                                            CTAVG/                Percentage    Percentage 
                                                            Copy                  Inhibition    Inhibition 
Gene        Treatment              Subject   Visit          Number         Value  [1]           [2] 
------------------------------------------------------------------------------------------------------------ 
XXXXGENE    GSKXXXXXX XXmg         XXXX      Screening      CT1           XX.XXX 
                                                            CT2           XX.XXX 
                                                            CTAVG         XX.XXX 
                                                            NORMALISED    XX.XXX 
 
                                             Baseline       CT1           XX.XXX 
                                                            CT2           XX.XXX 
                                                            CTAVG         XX.XXX 
                                                            NORMALISED    XX.XXX     x.xxx 
 
                                             Week X         CT1           XX.XXX 
                                                            CT2           XX.XXX 
                                                            CTAVG         XX.XXX 
                                                            NORMALISED    XX.XXX     x.xxx 
 
 
 
 


 
CONFIDENTIAL 
 
 
 
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95 
 
 
 
 
 
 
 
 
 
 
 
 
 
Example: PD_T2 
Protocol: 203167                                                                     Page 1 of x 
Population: Safety 
Table XX.XX :  
Frequency table summarising the number of probe sets in various fold change  
                                                          Fold Change          
Probeset  Gene   Visit      N     n   Treatment           < 1.5        >1.5      
 
XXXXXX    XXXXXX Baseline  XX    XX 
Placebo            xx (xx.xx)   xx (xx.xx)    
           
 
 
   
GSKXXXXXX XXmg     xx (xx.xx)   xx (xx.xx) 
 
 
                 WEEK xx   XX    XX 
Placebo            xx (xx.xx)   xx (xx.xx)  
           
 
 
   
GSKXXXXXX XXmg     xx (xx.xx)   xx (xx.xx)  
 
 
                 WEEK xx   XX    XX 
Placebo            xx (xx.xx)   xx (xx.xx) 
           
 
 
   
GSKXXXXXX XXmg     xx (xx.xx)   xx (xx.xx)  
 
 
 
 
 
 
 
 


 
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Example: PD_T3 
Protocol: 203167                                                                     Page 1 of x 
Population: Safety 
 
                    n                     n             Fold Chg. From    Comparison to Placebo  
Treatment     Adjusted Mean         Adjusted Mean          Baseline          Fold Change      
Group             95% CI                95% CI              95% CI             95% CI         
_________________________________________________________________________________________________________
___ 
                                                                                                             
Placebo S            4                     4                                                   
D/RD (4W)        10033.48              13337.45             1.33                                             
(N=6)      (5015.87, 20070.45)   (4806.65, 37008.63)    (-1.24, 2.19)                                        
                                                                                                             
GSK 60mg BID             8118.18               6830.11            -1.19              -1.58                          
(N=4)      (3264.70, 20187.10)   (2150.27, 21695.19)    (-1.96, 1.39)      (-3.21, 1.28)                     
                                                                                                             
GSK 60mg TID            9                     9                                                     
 15mg/kg          6459.95               6471.40             1.00              -1.33                          
(N=15)     (3943.96, 10580.99)   (3139.22, 13340.56)    (-1.42, 1.43)      (-2.45, 1.39)                     
                                                                                                             
  
  
  
  
  
  
 


 
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Example: FE1                                                                               Page 1 of 1 
Protocol: 203167                                                         
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Individual [Continuous Parameter] Scores over Time by Treatment  
 


 
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Example: FE2 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of 1 
Protocol: 203167                                                            
Population: Safety 
 
 
Table X 
Mean (+/-SD) [Continuous Parameter] over Time by Treatment 
 
 
 
 


 
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Example: FE3 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of 1 
Protocol: 203167                                                            
Population: Safety 
 
 
Table X 
Treatment Difference and 95% CI of [Continuous Parameter]  
 
 
 


 
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Example: FE4 
Protocol: 203167                                                                     Page 1 of x 
Population: Safety 
 
Figure XX.XX:  
Adjusted mean probe set intensity values (95% CI) by time from xxxx 
Gene ID: XXXX 


 
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Example: FE5 
Protocol: 203167                                                                     Page 1 of x 
Population: Safety 
 
Figure XX.XX:  
Adjusted Fold Change in mRNA Expression 
Gene ID: XXXX 


 
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Example: FE6 
Protocol: 203167                                                                     Page 1 of x 
Population: Safety 
Figure XX.XX:  


 
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Plasma TE vs Skin TE  
 
 
 
Example: FE7 
Protocol: 203167                                                                     Page 1 of x 
Population: Safety 
Figure XX.XX:  
Skin TE vs Effiacy/Biomarkers 
 


 
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