Clinical trial NCT04316585
Conditions: Psoriasis
Keywords: Plaque Psoriasis Modified Release GSK2982772 Skin Biopsy
Sponsor: GlaxoSmithKline
Start date: 2020-09-28; Completion date: 2021-10-12
Enrollment: 29 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Plaque psoriasis is a chronic relapsing inflammatory skin disease that is characterized by keratinocyte hyper-proliferation and epidermal hyperplasia. Standard treatment for psoriasis generally requires long-term use of topical therapies, psoralen and ultraviolet A (PUVA), ultraviolet B (UVB) and/or systemic immunosuppressant therapies to achieve and maintain adequate disease control. This is a multicenter, randomized, double-blind study conducted in participants with moderate to severe plaque psoriasis. The study will evaluate the efficacy, safety, pharmacokinetic and pharmacodynamics profile of 960 milligram (mg) GSK2982772 administered as a once daily modified release (MR) formulation. Participants will be randomized in a 2:1 ratio to receive either 960 mg GSK2982772 or placebo for 12 weeks. The duration of the study, including Screening and follow-up, will be approximately 21 weeks for each participant.

Detailed description:

Arms: arm 1: Participants will receive GSK2982772 960 mg oral tablets once daily for 12 weeks. arm 2: Participants will receive GSK2982772 matching placebo oral tablets once daily for 12 weeks.
Interventions: intervention 1: GSK2982772 intervention 2: Placebo
Intervention descriptions: intervention 1: GSK2982772 will be available as MR tablet at a unit dose strength of 480 mg. intervention 2: GSK2982772 matching placebo tablets will be administered via the oral route.

Protocol documents:
Prot_000.pdf: 
 
 
 
 
Protocol 
 
Study ID:  208022 
 
Official Title of Study: A multicentre, randomised, double-blind, placebo-controlled 
study to evaluate the efficacy and safety of GSK2982772 in participants with moderate to 
severe plaque psoriasis 
 
NCT ID: NCT04316585 
 
EudraCT: 2020-006008-18 
 
Date of Document: 06-JAN-2021 
 
 


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TITLE PAGE
Protocol Title: A multicentre, randomised, double-blind, placebo-controlled study to 
evaluate the efficacy and safety of GSK2982772 in participants with moderate to severe 
plaque psoriasis
Protocol Number: 208022/ 03
Compound Number
or Name:
GSK2982772
Short Title: A study to evaluate the benefit and safety of GSK2982772 in moderate to 
severe psoriasis patients
Study Phase: Phase 1b/2a
Sponsor Name and Legal Registered Address: 
GlaxoSmithKline Research & Development Limited
980 Great West Road
Brentford
Middlesex, TW8 9GS
UK
Regulatory Agency Identifying Number(s): EudraCT Number 2020-006008-18
Approval Date: 06-JAN-2021
Copyright 2021 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited.


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SPONSOR SIGNATORY:
Protocol Title: A multicentre, randomised, double-blind, placebo-controlled study to 
evaluate the efficacy and safety of GSK2982772 in participants with moderate to severe 
plaque psoriasis
Protocol Number: 208022 / Amendment 03
Compound Number
or Name:
GSK2982772
Nicolas Wisniacki
VP, Discover Medicine and Research CPEM
Date
The signed page is a separate document.
Medical Monitor Name and Contact Information can be found in the Study 
Reference Manual


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document
Date
DNG Number
Amendment 03
06-JAN-2021
2019N420902_03
Amendment 02
14-JUL-2020
2019N420902_02
Amendment 01
09-APR-2020
2019N420902_01
Original Protocol
07-JAN-2020
2019N420902_00
Amendment 03 06-JAN-2021
Overall Rationale for the Amendment: To update the skin biopsy sample collection 
strategy to aid with study recruitment and clarify some operational aspects of COVID-19 
testing.
Section # and Name
Description of Change
Brief Rationale
Section 1.1 Objectives 
and Endpoints
Section 3 Objectives 
and Endpoints
Section 4.2 Scientific 
Rationale for Study 
Design
Section 9.1 Statistical 
Hypotheses
Section 9.2 Sample 
Size Determination
Clarification on description of binary endpoints so 
they relate to an individual's response
Deletion of pharmacokinetics objective related to 
investigating trough skin concentrations of 
GSK2982772
Clarification
Updated based 
on revised skin 
biopsy 
collection 
strategy
Section 1.3 Schedule 
of Activities
Updated to clarify requirement and options for 
COVID-19 testing. Also updated to reflect revised 
skin biopsy collection strategy
Updates made 
to aid study 
recruitment
Section 4.1 Overall 
Design
Updated to reflect revised skin biopsy collection 
strategy
Update made to 
aid study 
recruitment
Section 6.2 Measures 
to Minimize Bias: 
Randomization and 
Blinding
Updated to allow off-site dosing at Weeks 2, 4 and 8 
in order to avoid an overdose, and provide 
instructions on follow-up with the study participant
Operational 
Update


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Section # and Name
Description of Change
Brief Rationale
Section 6.3 Study 
Intervention 
Compliance
Section 6.4 
Concomitant Therapy
Clarified wording to define stable usage of allowed 
medications.
Clarification
Section 8.5 
Pharmacokinetics
Removal of Section 8.5.3 and Section 8.5.4 related 
to skin PK. 
Updated based 
on revised skin 
biopsy 
collection 
strategy
Section 8.8 
Biomarkers
Updated to remove reference to target engagement 
using skin biopsies.
Updated based 
on revised skin 
biopsy 
collection 
strategy
Section 9.1 
Statistical Hypotheses
Clarified language to reflect objective of estimating 
efficacy response (removal of reference to 
hypothesis testing).
Clarification
Section 9.3 
Populations for 
Analyses
Added COVID-19 population and description to 
table.
Updated to 
reflect new 
analysis 
population to be 
used for a 
subset COVID 
outputs
Section 9.4 Statistical 
Analyses
Added minor clarification to Bayesian analysis. 
Removal of reference to CPMS model in SAP.
Clarification


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TABLE OF CONTENTS
PAGE
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE.....................................3
1.
PROTOCOL SUMMARY..........................................................................................8
1.1.
Synopsis.......................................................................................................8
1.2.
Schema ......................................................................................................11
1.3.
Schedule of Activities (SoA)........................................................................12
2.
INTRODUCTION....................................................................................................17
2.1.
Study Rationale ..........................................................................................17
2.2.
Background ................................................................................................17
2.3.
Benefit/Risk Assessment ............................................................................18
2.3.1.
Risk Assessment .........................................................................19
2.3.2.
Benefit Assessment.....................................................................27
2.3.3.
Overall Benefit: Risk Conclusion..................................................27
3.
OBJECTIVES AND ENDPOINTS...........................................................................27
4.
STUDY DESIGN ....................................................................................................29
4.1.
Overall Design ............................................................................................29
4.2.
Scientific Rationale for Study Design ..........................................................30
4.3.
Justification for Dose ..................................................................................31
4.4.
End of Study Definition ...............................................................................32
5.
STUDY POPULATION...........................................................................................32
5.1.
Inclusion Criteria.........................................................................................32
5.2.
Exclusion Criteria........................................................................................34
5.3.
Lifestyle Considerations..............................................................................38
5.3.1.
Meals and Dietary Restrictions ....................................................38
5.3.2.
Alcohol Consumption...................................................................38
5.3.3.
Sun Exposure and Activity...........................................................38
5.4.
Screen Failures...........................................................................................38
6.
STUDY INTERVENTION........................................................................................38
6.1.
Preparation/Handling/Storage/Accountability..............................................39
6.2.
Measures to Minimize Bias: Randomisation and Blinding ...........................40
6.3.
Study Intervention Compliance ...................................................................41
6.4.
Concomitant Therapy..................................................................................42
6.4.1.
Prohibited Medicines ...................................................................42
6.5.
Dose Modification .......................................................................................44
6.6.
Intervention after the End of the Study........................................................44
7.
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL.....................................................................45
7.1.
Discontinuation of Study Intervention..........................................................45
7.1.1.
Liver Chemistry Stopping Criteria ................................................45
7.1.2.
QTc Stopping Criteria ..................................................................46
7.1.3.
Rechallenge.................................................................................46
7.1.3.1.
Study Intervention Restart or Rechallenge after 
liver stopping criteria met............................................46


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7.2.
Participant Discontinuation/Withdrawal from the Study ...............................46
7.3.
Lost to Follow-up ........................................................................................47
8.
STUDY ASSESSMENTS AND PROCEDURES .....................................................47
8.1.
Efficacy Assessments.................................................................................48
8.1.1.
Clinical Disease Assessments .....................................................48
8.1.1.1.
Psoriasis Area Severity Index (PASI) .........................48
8.1.1.2.
Psoriasis body Surface Area (BSA)............................48
8.1.1.3.
Static Investigator’s Global Assessment of 
Disease Activity (sIGA)...............................................48
8.2.
Safety Assessments ...................................................................................49
8.2.1.
Physical Examinations.................................................................49
8.2.2.
Vital Signs....................................................................................49
8.2.3.
Electrocardiograms......................................................................49
8.2.4.
Clinical Safety Laboratory Assessments ......................................49
8.2.5.
Suicidal Ideation and Behaviour Risk Monitoring .........................50
8.3.
Adverse Events and Serious Adverse Events.............................................51
8.3.1.
Time Period and Frequency for Collecting AE and SAE 
Information...................................................................................51
8.3.2.
Method of Detecting AEs and SAEs.............................................51
8.3.3.
Follow-up of AEs and SAEs.........................................................52
8.3.4.
Regulatory Reporting Requirements for SAEs .............................52
8.3.5.
Pregnancy ...................................................................................52
8.3.6.
Cardiovascular and Death Events................................................52
8.4.
Treatment of Overdose...............................................................................53
8.5.
Pharmacokinetics .......................................................................................53
8.5.1.
Blood Sample Collection..............................................................53
8.5.2.
Plasma Sample Analysis .............................................................53
8.6.
Pharmacodynamics ....................................................................................54
8.7.
Genetics .....................................................................................................54
8.8.
Biomarkers .................................................................................................54
8.8.1.
Skin Biopsy..................................................................................55
8.8.2.
RNA Transcriptome Research .....................................................55
8.8.3.
RNA Expression Research of a Subset of RNA Species..............56
8.8.4.
Proteome Research.....................................................................56
8.8.5.
Metabolome Research.................................................................56
8.9.
Medical Resource Utilization and Health Economics ..................................56
9.
STATISTICAL CONSIDERATIONS........................................................................57
9.1.
Statistical Hypotheses.................................................................................57
9.2.
Sample Size Determination ........................................................................57
9.3.
Populations for Analyses ............................................................................58
9.4.
Statistical Analyses.....................................................................................58
9.4.1.
Primary Analyses.........................................................................58
9.4.2.
Secondary Analyses ....................................................................59
9.4.2.1.
Pharmacokinetic Analysis...........................................59
9.4.2.2.
Pharmacokinetic/Pharmacodynamic Analysis.............59
9.5.
Interim Analyses .........................................................................................60
9.6.
Data Review Committee (DRC) ..................................................................60
10. SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS...............................................................................................61


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10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations............................................................................................61
10.1.1.
Regulatory and Ethical Considerations ........................................61
10.1.2.
Financial Disclosure.....................................................................61
10.1.3.
Informed Consent Process ..........................................................62
10.1.4.
Data Protection............................................................................62
10.1.5.
Committees Structure ..................................................................63
10.1.6.
Dissemination of Clinical Study Data ...........................................63
10.1.7.
Data Quality Assurance ...............................................................63
10.1.8.
Source Documents ......................................................................64
10.1.9.
Study and Site Start and Closure.................................................65
10.1.10. Publication Policy.........................................................................65
10.2.
Appendix 2: Clinical Laboratory Tests.........................................................66
10.3.
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .......................................68
10.3.1.
Definition of AE............................................................................68
10.3.2.
Definition of SAE..........................................................................69
10.3.3.
Definition of Cardiovascular Events .............................................70
10.3.4.
Recording and Follow-Up of AE and SAE....................................71
10.3.5.
Reporting of SAE to GSK.............................................................73
10.4.
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information..................................................................................................74
10.4.1.
Definitions....................................................................................74
10.4.2.
Contraception Guidance ..............................................................75
10.4.3.
Collection of Pregnancy Information: ...........................................76
10.5.
Appendix 5: Genetics..................................................................................77
10.6.
Appendix 6: Liver Safety: Required Actions and Follow-up 
Assessments ..............................................................................................78
10.7.
Appendix 7: COVID-19 Appendix................................................................81
10.8.
Appendix 8: Abbreviations and Trademarks................................................83
10.9.
Appendix 9: Protocol Amendment History...................................................87
11. REFERENCES.......................................................................................................92


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1.
PROTOCOL SUMMARY
1.1.
Synopsis
Protocol Title: A multicentre, randomised, double-blind, placebo-controlled study to 
evaluate the efficacy and safety of GSK2982772 in participants with moderate to severe 
plaque psoriasis
Short Title: A study to evaluate the benefit and safety of GSK2982772 in moderate to 
severe psoriasis patients
Rationale: GSK2982772 is a first-in-class, highly selective, receptor-interacting protein 
1 kinase (RIP1) inhibitor being developed for the treatment of psoriasis. RIP1 is a key 
signalling node which plays an essential role in inflammation and cell death in response 
to signals including tumour-necrosis factor (TNF) family cytokines, ligands for toll-like 
receptor (TLR)-3 and TLR4, sensors of viral infection and interferons. To date, 
approximately 303 participants have been exposed to active treatment (IR formulation) of 
GSK2982772 at doses that ranged up to 960 mg, including healthy volunteers and three 
patient populations (mild to moderate plaque psoriasis, moderate to severe rheumatoid 
arthritis and moderate to severe ulcerative colitis).
Plaque psoriasis is a chronic relapsing inflammatory skin disease that is characterized by 
keratinocyte hyperproliferation and epidermal hyperplasia. Standard treatment for 
psoriasis generally requires long-term use of topical therapies, psoralen and ultraviolet A 
(PUVA), ultraviolet B (UVB) and/or systemic immunosuppressant therapies to achieve 
and maintain adequate disease control.  
In the last decade, biological therapies targeting TNF or Th17/ interleukin
(IL)12/IL22/IL23 pathways have demonstrated significant clinical efficacy for those 
patients who had inadequate response to standard topical, UV, and/or oral therapy. 
However, biologic therapies have several limitations: high cost, risk for loss of response, 
side effects, development of anti-drug antibodies (ADAs) and require parenteral 
administration, which can limit patient acceptability and treatment compliance. In 
addition, apremilast (Otezla), a PDE4 inhibitor, has been recently approved as an oral 
psoriasis treatment but its efficacy is modest in moderate to severe patients. 
GSK2982772 may fill a niche in the treatment of plaque psoriasis.  


2 0 1 9 N 4 2 0 9 0 2 _ 0 3
C O N FI D E N TI A L
2 0 8 0 2 2
9
O bjecti ves a n d E n d p oi nts :
O bjecti ves
E n d p oi nts
Pri mar y

T o d et er mi n e t h e effic acy of G S K 2 9 8 2 7 7 2 
9 6 0 m g m o difi e d r el e as e ( M R ) o nc e d aily (Q D )
f or 1 2 w e eks, c o m p ar e d wit h pl ac e b o in 
p artici p a nts wit h m o d er at e to s ev er e pl a q u e
ps ori asis.

P A SI 7 5 r es p o ns e ( ac hi ev i n g≥7 5 % 
i m pr ov e m e nt fr o m B as eli n e i n P A SI sc or e ) at 
W e ek 1 2.
Sec o n dar y

T o f urt h er ev al u at e t h e effic acy of
G S K 2 9 8 2 7 7 2 9 6 0 m g M R Q D f or 1 2 w e eks,
c o m p ar e d wit h pl ac e b o i n p artici p a nts wit h 
m o d er at e t o s ev er e pl a q u e ps ori asis . 
F urt h er P A SI p ar a m et ers:

P A SI 5 0, P A SI 9 0 a n d P A SI 1 0 0 r es p o ns e 
(ac hi ev i n g≥5 0 % , ≥9 0 % a n d 1 0 0 %
i m pr ov e m e nt fr o m B as eli n e i n P A SI sc or e ,
r es p ectiv ely) at W e ek 1 2.

C h a n g e fr o m B as eli n e P A SI sc or es at W e e k
1 2 .
St atic I nv esti g at or ’s Gl o b al Ass ess m e nt(sI G A):

sI G A r es p o ns e ( ac hi evi n g a sIG A sc or e of 
 ( 0) or 
 ( 1)) at W e ek 1 2.
Ps ori asis B o dy S urf ac e Ar e a ( B S A):

C h a n g e fr o m B as eli n e i n ps ori atic B S A at 
W e ek 1 2.
S af ety

T o ev al u at e t h e s af ety a n d t ol er a bility of 
G S K 2 9 8 2 7 7 2 9 6 0 m g M R Q D f or 1 2 w e eks, 
c o m p ar e d wit h pl ac e b o i n p artici p a nts wit h 
m o d er at e t o s ev er e pl a q u e ps ori asis.

A dv ers e ev e nts ( A Es)

Cli nic al l a b or at ory v al u es (cli nic al c h e mistry, 
h a e m at ol o gy a n d uri n alysis)

Vit al si g n m e as ur e m e nts ( bl o o d pr ess ur e, 
h e art r at e, r es pir at ory r at e a n d b o dy 
t e m p er at ur e)

1 2 -L e a d el ectr oc ar di o gr a m (E C G ) m o nit ori n g

C ol u m bi a S uici d e S ev erity R ati n g Sc al e ( C-
S S R S )
C CI
C CI
C CI
C CI


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Objectives
Endpoints
Pharmacokinetics

To assess trough plasma concentrations of 
GSK2982772 960 mg MR QD for 12 weeks, 
in participants with moderate to severe 
plaque psoriasis.

Trough plasma concentrations of 
GSK2982772 at Weeks 2, 4, 8, 12.
Additional exploratory endpoints are included to further investigate the clinical effect of 
GSK2982772, and the effect of GSK2982772 on pathways in the skin and blood and 
target engagement in blood.
Overall Design: This is a multi-centre, randomised, double-blind, placebo-controlled 
study in participants with moderate to severe psoriasis. The study is designed to assess 
the efficacy and safety of GSK2982772 administered as a QD MR oral tablet. 
Participants will receive 960 mg of GSK2982772 or placebo for 12 weeks. In addition, 
blood and skin biopsy samples will be collected to explore the pharmacokinetics, target
engagement in blood, and pharmacodynamic effects in blood and in the skin. 
An interim futility analysis will be conducted when at least six participants receiving 
GSK2982772 have completed the Week 12 visit or discontinued study treatment. 
Disclosure Statement: This is a randomized, double-blind, placebo-controlled trial. 
Number of Participants: Approximately 32 participants will be screened to achieve 21
randomly enrolled to either GSK2982772 or placebo in a 2:1 allocation ratio. 
Replacement participants may be randomised (up to approximately 6) into the study at 
the discretion of the Sponsor, to ensure that approximately 21 have completed the Week 
4 visit.
Note: "Enrolled" means a participant's, or their legally acceptable representative’s, 
agreement to participate in a clinical study following completion of the informed consent 
process. Potential participants who are screened for the purpose of determining eligibility 
for the study, but do not participate in the study, are not considered enrolled, unless 
otherwise specified by the protocol. 
Intervention Groups and Duration: Following Screening and successful completion of 
Baseline measurements, participants will be centrally randomised and will receive study 
intervention administered as oral tablets once daily for 12 weeks. Participants will be 
randomised (2:1) to receive 960 mg GSK2982772 or placebo as shown in study 
schematic in Section 1.2.   
The duration of the study, including Screening and follow-up, is not expected to exceed 
21 weeks for each participant.
Participants will receive their first dose on Day 1 at the investigational site.  On defined 
visit days, participants will administer study intervention after completion of their pre-


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dose assessments.  On all other days, participants will self-administer study intervention
at home.
A completed participant is one who has completed all planned study assessments 
including the follow-up visit.
The end of the study is defined as the last participant’s last visit.
Data Monitoring or Other Committee: Yes
1.2.
Schema
Up to Day -35
Double Blind Treatment Period
(12 Weeks)
+28 days after 
final dose
Week 2
(D15)
Week 8
(D57)
Week 4
(D29)
Screening
Follow-Up
Week 0
(Day 1)
Week 12
(Day 85)
Washout 
Period
GSK2982772 960mg Oral Tablet (n = 14)
Placebo Oral Tablet (n = 7)
Primary Endpoint
PASI75 At W12
Randomization


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1.3.
Schedule of Activities (SoA)
This section lists the procedures and parameters of each planned study assessment. 
Screening Visit 
Procedures
Screening (up to -35 days)
Informed Consent1
X
Inclusion/Exclusion Criteria Review
X
Demography
X
Medical History2
X
QuantiFERON-TB Gold Plus Test3
X
HIV, Hep B and Hep C Screen4
X
Pregnancy Test5
X
FSH & Oestradiol6
X
Safety Assessments
Full Physical Exam7
X
12-lead ECG8
X
Vital Signs9
X
COVID-19 test (SARS-CoV-2)10
X
Columbia Suicide Severity Rating Scale (C-SSRS)
X
Clinical Laboratory 
(Haematology, Chemistry and Urinalysis)
X
Concomitant Medication Review
X
SAE - commencing from time of informed consent
X
Register Visit in Randomization and Medication Ordering System New Generation
(RAMOS NG)
X
Severity of Disease
Psoriasis Area and Severity Index (PASI)
X
Psoriatic Body Surface Area (BSA)
X
Static Investigator Global Assessment of Psoriasis Severity (sIGA)
X
Footnotes:
1.
Includes study specific consent (which must be obtained before Screening activities commence) and a separate 
optional consent for Pharmacogenetics (PGx) (which may be collected at any time before PGx sample 
collection).
2.
Includes past and current conditions, medication history, and family history of premature CV disease.
3.
In cases where the QuantiFERON-TB Gold Plus test is indeterminate, the participant may have the test repeated 
once, but they will not be eligible for the study unless the second test is negative or they have a negative 
tuberculin skin test.
4.
If hepatitis C antibody is positive, a hepatitis C Ribonucleic Acid Polymerase Chain Reaction (RNA PCR) assay 
will be performed on a fresh sample to confirm the result.
5.
For women of child-bearing potential only: Serum pregnancy test must be performed at Screening.
6.
For women whose postmenopausal status is in doubt only. Refer to Appendix 4. 
7.
Includes height at Screening visit.
8.
Triplicate ECGs will be taken at Screening and at Day 1 (Baseline). At all other specified time points single ECGs 
are acceptable.  However, if QTc prolongation is detected triplicate ECGs will be performed. Fridericia’s formula 
(QTcF) must be used for the QTc correction.
9.
Blood pressure (systolic and diastolic), heart rate, respiratory rate and temperature to be assessed, as well as 
COVID-19 symptoms check.


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10. This test should be performed at the screening visit and will be analysed by the central laboratory. If the 
screening visit is more than 14 days before the Week 0 (Day 1) visit, the test must be repeated, The 2nd COVID 
test may be run by the central laboratory (7-9 days before the Day 1 visit), done at a local testing facility (test 
must be performed within 9 days of Day 1, with documented results prior to dosing), or via completion of a 
COVID point of care test at the site (within 9 days of or on Day 1).


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Treatment Period 
Procedures
Treatment Period
Follow-up
Early Withdrawal
Week 0
Week 2
Week 4
Week 8
Week 12
Week 16
(Day 1)
Baseline
(Day 15)
(Day 29)
(Day 57)
(Day 85)
(Day 113)
N/A
3D
3D
3D
3D
7D
NA
Inclusion/Exclusion Criteria Review1
X3
Pregnancy Test2,3
X
X
X
X
X
X
Safety Assessments
Full Physical Exam
X
X
Brief Physical Exam3
X
X
X
X
X
12-lead ECG3, 4
X
X
X
X
X
X
X
Vital Signs3, 5
X
X
X
X
X
X
X
Columbia Suicide Severity Rating Scale (C-SSRS) 3
X
X
X
X
X
X
X
Clinical Laboratory3
(Haematology, Chemistry and Urinalysis)
X
X
X6
X6
X
X
X
Fasting Lipids, Glucose and Insulin3, 7
X
X
X
Concomitant Medication Review
continuous throughout study 
AE/SAE Review
continuous throughout study
Study Treatment
Randomisation
X
Study Treatment8
----------------------------------------------------------------------------------------------------
Dispense Study Treatment
X
X
X
X
Collect Study Treatment
X
X
X
X
X
Assess Study Treatment Compliance
X
X
X
X
X
Register Visit in RAMOS NG
X
X
X
X
X
X
X
Clinical Outcomes Assessments
Psoriasis Area and Severity Index (PASI) 3
X
X
X
X
X
X
X
Psoriatic Body Surface Area (BSA) 3
X
X
X
X
X
X
X


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Procedures
Treatment Period
Follow-up
Early Withdrawal
Week 0
Week 2
Week 4
Week 8
Week 12
Week 16
(Day 1)
Baseline
(Day 15)
(Day 29)
(Day 57)
(Day 85)
(Day 113)
N/A
3D
3D
3D
3D
7D
NA
Static Investigator Global Assessment of Psoriasis 
Severity (sIGA) 3
X
X
X
X
X
X
X
Other Assessments and Procedures
PK Blood Sample3
X
X
X
X
X
Pharmacogenetic (PGx) Sample
X9
Skin Biopsy Sample3,10
X
X11
X
X12
PD / Biomarker Blood Samples3
X
X
X
X
Footnotes:
1.
All inclusion/exclusion criteria will be reviewed on Day 1 (Baseline) prior to randomization. In addition, physical exam (brief), ECG, vital signs, C-SSRS, and disease severity 
criteria (PASI, BSA and sIGA) will be re-assessed. 
2.
For women of child-bearing potential only: Serum pregnancy test must be performed at Screening.  At all other visits other than Week 2, a urine pregnancy test will be performed.  
If a urine test result is positive or ambiguous, a confirmatory serum test must be performed.
3.
Perform pre-dose during treatment period (NB excludes Week 12/Day 85 visit as Day 84 is the last day of dosing).
4.
Triplicate ECGs will be taken at Screening and on Day 1 (Baseline).  At all other specified time points single ECGs are acceptable.  However, if QTc prolongation is detected 
triplicate ECGs should be performed. Fridericia’s formula (QTcF) must be used for the QTc correction.
5.
Blood pressure (systolic and diastolic), heart rate, respiratory rate and temperature to be assessed at all time points, as well as COVID-19 symptoms check.
6.
Urinalysis not required on Days 29 and 57.
7.
Blood samples will be taken after overnight fast for fasting lipid, glucose and insulin analysis.
8.
Following Day 1, participants will take study medication at home. At the Week 2, 4, and 8 visits, the dose should not be taken before the clinic visit. Instead, the dose should be 
taken either on site, after  all pre-dose study assessments have been completed (preferred), or after the visit (at home) if the timing of the on-site dosing would result in the dose 
being less than 20 hours after the last dose (i.e. overdose). There is no dose administered at Week 12/Day 85.
9.
PGx sample collected at Day 1, after randomization and if the participant provides additional, optional informed consent.  If sample is not collected at Day 1, it can be collected at
any time post-randomization.
10. Mandatory skin biopsy samples will be collected from all participants: one non-lesional and one lesional biopsy will be collected on Day 1 (Baseline) before 1st dose of study 
medication. One additional lesional biopsy sample from the same plaque will be collected pre-dose at Week 12/Day 85.
11. One optional lesional skin biopsy sample will also be collected at Week 4/Day 29 from consenting participants only. A separate consent must be obtained.


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12. Collection of 1 lesional skin biopsy sample required at Early Withdrawal visit if study withdrawal occurs prior to Week 12 and if the participant has completed at least 14 days of 
treatment. If biopsy has already been obtained within the last 14 days, then another biopsy will not be collected.

The timing and number of planned study assessments, including safety, pharmacokinetic, pharmacodynamic/biomarker assessments
may be altered during the course of the study based on newly available data (e.g., to obtain data closer to the time of peak plasma 
concentrations) to ensure appropriate monitoring. 

Any changes in the timing or addition of time points for any planned study assessments as the result of emerging 
pharmacokinetic/pharmacodynamic data from this study must be documented and approved by the relevant study team member and 
then archived in the sponsor and site study files but will not constitute a protocol amendment. The Competent Authority (CA) and 
ethics committee (EC) will be informed of any safety issues that constitute a substantial amendment and require alteration of the 
safety monitoring scheme or amendment of the informed consent form (ICF). The changes will be approved by the CA and the EC 
before implementation.


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2.
INTRODUCTION
GSK2982772 is a first-in-class, highly selective, receptor-interacting protein 1 kinase 
(RIP1) inhibitor being developed for the treatment of psoriasis.
2.1.
Study Rationale
This is a Phase 1b/2a study in participants with moderate to severe plaque psoriasis. The 
study is designed to assess the efficacy, safety, pharmacokinetic (PK), and 
pharmacodynamic (PD) profiles of 960 mg GSK2982772 administered as a once daily 
modified release (MR) formulation.
This is the second study performed in participants with plaque psoriasis. 
The first study (203167) was an experimental medicine (EM) study designed to 
understand the mechanism of action and potential for clinical efficacy of GSK2982772 in 
participants with mild to moderate plaque psoriasis. GSK2982772 was administered as 
60 mg BID and 60 mg TID of an immediate release (IR) tablet formulation.  Both dose 
levels were shown to be well tolerated.  A small reduction in Psoriatic Lesion Severity 
Sum (PLSS) and improvement in Psoriatic Area and Severity Index (PASI) was observed 
for the BID versus placebo cohort but not for the TID cohort versus placebo. This is 
believed to be due to the unexpectedly large response observed in the placebo TID 
treatment group. In addition, a reduction in histopathological markers (epidermal 
thickness, cluster of differentiation 3 (CD3)+ T-Cells, CD11+ myeloid dendritic cells) in 
both cohorts in comparison to placebo was observed.  Exposure-response relationship (E-
R) analyses of the combined BID and TID regimens showed an improved PLSS score 
with increasing tertiles of GSK2982772 trough plasma concentrations and participants 
with highest GSK2982772 skin concentrations tended to have better PLSS score. Based 
on the observed E-R, it is hypothesised that 60 mg BID/TID dosing regimens did not 
provide sufficient exposure to achieve clinically relevant efficacy. In the current study, a
once daily dose of 960 mg MR provides ~15-fold higher trough plasma concentrations
than was achieved with the 60 mg TID IR regimen in study 203167.  This magnitude of 
increase should result in a significant shift in the pharmacological response, and hence 
efficacy response, thereby determining proof of concept for receptor-interacting 
serine/threonine-protein kinase 1 (RIPK1) inhibition in moderate to severe psoriasis.  
A detailed description of the chemistry, pharmacology, efficacy, and safety of 
GSK2982772 can be found in the Investigator’s Brochure (IB).
2.2.
Background
RIP1 is a key signalling node which plays an essential role in inflammation and cell death 
in response to signals including tumour-necrosis factor (TNF) family cytokines, ligands 
for toll-like receptor (TLR)-3 and TLR4, sensors of viral infection and interferons.  
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].  


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In addition, the production of certain inflammatory cytokines can be regulated by RIP1 
kinase activity. In contrast, RIP1’s scaffolding function acts to facilitate other immune 
processes including TNF mediated classical apoptosis and NFB- signalling [Griffiths, 
2017; Humphries, 2015] 
Plaque psoriasis is a chronic relapsing inflammatory skin disease that is characterized by 
keratinocyte hyperproliferation and epidermal hyperplasia. Psoriasis is considered a T 
helper type 1 and 17 (Th1 and Th17)-mediated disease, with the interleukin 23 (IL-
23)/Th17 cell axis playing a crucial role. Keratinocyte activation following a trauma or 
infection results in plasmacytoid dendritic cell activation to produce type I interferons 
(IFN). Type I IFNs then activate myeloid dendritic cells, leading to release of IL-23 and 
IL-12, which then activate Th17, Th1 and Th22 cells to produce an abundance of pro-
inflammatory cytokines (e.g. IL-17, IL-22, IFNγ and TNF) leading to an amplification of 
the inflammation [Lowes, 2014].
Standard treatment for psoriasis generally requires long-term use of topical therapies, 
psoralen and ultraviolet A (PUVA), ultraviolet B (UVB) and/or systemic 
immunosuppressant therapies to achieve and maintain adequate disease control.  
In the last decade, biological therapies targeting TNF or Th17/IL22/IL23 pathways have 
demonstrated significant clinical efficacy for those patients who had inadequate response 
to standard topical, UV, and/or oral therapy. However, biologic therapies have several 
limitations: high cost, risk for loss of response, side effects, development of anti-drug 
antibodies (ADAs) and require parenteral administration, which can limit patient 
acceptability and treatment compliance.
Although apremilast, a phosphodiesterase-4 inhibitor (PDE4) inhibitor, has been 
approved as an oral psoriasis treatment, its efficacy is modest in patients with moderate to
severe plaque psoriasis [Otezla drug label, 2019]. There remains a high unmet need for 
novel oral therapies that can achieve maximal sustained clearance of skin lesions and 
improvement in quality of life, balanced by favourable safety and tolerability profiles.  
Furthermore, an effective oral therapy could prevent transition to the use of biologic 
therapy, provide an option for patients to come off biologics or allow patients to have 
greater flexibility with dose modulation.
GSK2982772, an inhibitor of RIP1 kinase activity, may address this unmet need in the 
treatment of plaque psoriasis.  To date, approximately 303 participants have been 
exposed to active treatment (IR formulation) of GSK2982772 at doses that ranged up to 
960 mg, including healthy volunteers and three patient populations (mild to moderate 
plaque psoriasis, moderate to severe rheumatoid arthritis and moderate to severe 
ulcerative colitis). GSK2982772 will now be investigated in patients with moderate to 
severe psoriasis.
2.3.
Benefit/Risk Assessment
More detailed information about the known and expected benefits and risks and 
reasonably expected adverse events (AEs) of GSK2982772 may be found in the IB.


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2.3.1.
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 initial 4-week nonclinical toxicology studies, 
neurological-related events (uncoordinated 
movement, irregular gait, trembling, hunched 
appearance and decreased activity) were 
observed in some rats and monkeys. In 13-
week nonclinical toxicology studies, no 
neurological-related events were observed in 
rats or monkeys.
In the 39-week good laboratory practice (GLP)
toxicology study, there were no CNS findings 
observed in monkeys administered 6, 20 or 
60 mg/kg/day. 
Clinical data:
No drug-associated CNS adverse events
reported in clinical studies. 
Participant Selection:

Participants 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.
Participant Monitoring:

Participants will be monitored for 
standard CNS-related AEs.
CNS suicidality
GSK2982772 is considered to be a CNS-active 
drug based on pre-clinical studies.
Clinical data:
Participant selection:

Participants with a current history of 
Suicidal Ideation Behaviour (SIB) as 
measured using the Columbia Suicide 
Severity Rating Scale (C-SSRS) or a 


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
To date in the GSK2982772 clinical programme, 
there have been some reports of lethargy, 
abnormal dreams, and depressed mood. 
In the Phase IIa psoriasis study (201367), one 
serious adverse event (SAE) of accidental 
overdose with ecstasy/
methylenedioxymethamphetamine (MDMA) was 
reported in a participant who received 
GSK2982772 60 mg BID. There was no 
evidence to suggest that this was a suicide
attempt. Also, in this study, there was a 
participant who received GSK2982772 60 mg 
BID, who reported suicidal ideation at the Day 
43 visit via C-SSRS. The participant reported 
that he had these thoughts on and off prior to 
joining the study and did not plan to take action 
on these feelings. No further suicidal ideation 
was reported by this participant. 
In the open-label modified release formulation 
study in healthy participants (205017), a 
completed suicide (by hanging) was reported 28 
days after a single dose of GSK2982772. This 
individual had a prior undisclosed suicide 
attempt. Given the short half-life of 
GSK2982772, there is no temporal relationship 
history of attempted suicide will be 
excluded from the study.
Participant Monitoring:

Participants 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 (C-SSRS in all participants. 

Any participant in the study who 
experiences signs of suicidal ideation or 
behaviour must immediately be 
discontinued from study medication. 


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
to support a causal relationship between the 
completed suicide and GSK2982772. 
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 participants taking other
immunomodulating drugs or corticosteroids.
Clinical data:
In the first time in human (FTiH) study, no SAEs 
were reported. One participant experienced an
AE herpes zoster approximately 27 days after 
receiving his last dose with GSK2982772. The 
blinded Investigator determined
this to be potentially drug-related.
In the Psoriasis study (203167), one participant 
receiving GSK2982772 experienced an AE of 
herpes zoster on study Day 9. The blinded 
Investigator considered the AE to be of 
moderate severity and not related to study drug. 
AEs of genital herpes and oral herpes (one 
participant each) were reported in participants 
who received GSK2982772 60 mg TID in the 
Phase II Rheumatoid Arthritis (RA) study 
(203168).
Participant Selection:

Participants with recurrent, chronic or 
active infections will be excluded from 
the study. Participants will be screened 
for tuberculosis (TB), human
immunodeficiency Virus (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 participants with Psoriasis.
Participant monitoring

After administration of GSK2982772, 
participants will be monitored carefully 
for signs of infection and asked to 
report any signs of infection for 
investigation.  


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
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.
Participant Selection:

Attenuated or live vaccines should not 
be administered to participants 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 participants with Psoriasis.
Respiratory effects
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 
Participant Monitoring:

Participants should be monitored for 
standard respiratory-related AEs.

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
function (e.g., tidal volume, minute volume or 
respiratory rate) were observed at doses of 1 or 
10 mg/kg/day. 
Clinical data:
No respiratory SAEs were reported, nor were 
there any drug associated respiratory related 
AEs identified in the clinical programme to date. 
Drug interaction
In vitro studies investigating the induction and/or 
inhibition properties of GSK2982772 with 
cytochromes P450 (CYP) and uridine 
glucoronyltransferase (UGT) enzymes, as well 
as p-glycoprotein (Pgp), breast cancer 
resistance protein (BCRP) and some uptake 
transporters have been completed.  
There is a moderate risk that GSK2982772 
could be an inducer of CYP3A4 and may lower 
circulating levels of concomitant medications 
that are metabolized by CYP3A4 (e.g. oral 
contraceptives) when co-administered with 
GSK2982772. 
GSK2982772 is a Pgp substrate and co-
administration of GSK2982772 with concomitant 
medications that are Pgp inhibitors could 
increase the circulating levels of GSK2982772. 
Participant selection:

Participants who are taking concomitant 
medications known to inhibit Pgp or are 
CYP3A4 narrow therapeutic index (NTI) 
substrates will be excluded from the 
study. 

Participants (WOCBP) who are taking 
oral contraceptives will be asked to use 
an additional non-hormonal form of 
contraception.
Participant monitoring:

Concomitant medication usage will be 
reviewed and monitored prior to 
inclusion and during study duration. 

Clinical laboratory results (e.g. liver 
function tests) will be routinely 
monitored throughout the study


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
There is a low risk that GSK2982772 could be a 
perpetrator of organic anion transporter 3 
(OAT3) substrate. However, methotrexate
(MTX) (OAT3 substrate) exposures in 
participants in study 203168 were monitored 
before and after GSK2982772 treatment (60 mg 
BID or TID) and showed no discernible change. 
There is a moderate risk that GSK2982772 
could be an inhibitor of CYP3A4 and may 
increase circulating levels of concomitant 
medications that are metabolized by CYP3A4 
when co-administered with GSK2982772. 
Reproductive toxicity
Non-clinical data:

The no observed adverse effect level 
(NOAEL) for female fertility and early 
embryonic development and for 
reproductive performance and male-
mediated developmental toxicity in rats 
and for embryofetal development in 
rabbits was considered to be 
200 mg/kg/day.  Based on the findings 
in pre-and postnatal development and 
embryofetal development studies in 
rats, the NOAEL for maternal F0 
reproductive function and pre- and 
postnatal development of the F1 
offspring is 100 mg/kg/day; although the 
Participant selection:

Male and female participants 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 2 days 
after the last administration of study 
drug (Appendix 4).

Females of childbearing potential will 
undergo serum pregnancy test at 
Screening and then urine pregnancy 
testing monthly during the study.


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
NOAEL from the embryofetal 
development study was 10 mg/kg/day 
due to decreased fetal weights, 
decreased pup weights were not 
observed at 100 mg/kg/day in the pre-
and postnatal development. In the rat, 
at higher doses (>200 mg/kg/day) that 
were toxic to the female (decreased 
body weight and food consumption 
and/or clinical signs), decreased 
corpora lutea, implantations, litter size 
and increased post-implantation loss 
were observed in the female fertility 
study, decreased fetal/uterus weight in 
the embryo-fetal development rat study 
and decreased pup viability and pup
weight in the pre-and postnatal 
development study. 

Pregnant and lactating females are not 
eligible for inclusion in the study.
Withdrawal criteria:

If a female participant, or female partner 
of a male participant, should become 
pregnant during the study, study
medication should be discontinued. The 
participant 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 (Section 
10.4)
Study Procedures
Punch skin lesion biopsies
Potential risks of the procedure include 
discomfort, infection or bleeding.
Participant selection:

Participants with history of hypertrophic or 
keloid scarring, or known allergy to 
lidocaine or other local anaesthetics will not 
be included in the study.

Participants 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
Participant 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.

Participants will be advised to keep the site 
covered and dry for 24-48 hours before 
leaving open to the air. Participants 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.


2 0 1 9 N 4 2 0 9 0 2 _ 0 3
C O N FI D E N TI A L
2 0 8 0 2 2
2 7
2. 3. 2.
B e n efit A s s e s s m e nt
T here are a d diti o nal treat me nt o pti o ns a vaila ble f or partici pa nts w h o ha ve a n i na de q uate 
res po nse t o c urre nt t hera pies f or ps oriasis .  It is p ossi ble t hat treat me nt wit h G S K 2 9 8 2 7 7 2 
ma y  be effecti ve i n t he treat me nt of ps oriasis , as t he F Ti H st u d y de m o nstrate d t hat t he 
dr u g e n ga ge d wit h t he tar get a n d pr o d uce d ex viv o P D effects i n RI P 1 -de pe n de nt 
c yt o ki nes macr o p ha ge i nfla m mat or y  pr otei n 1 al p ha (MI P 1 ) a n d macr o p ha ge 
i nfla m mat or y pr otei n 1 beta (MI P 1 ).  There ma y be li mite d direct be nefit t o t he 
partici pa nt f or ta ki n g part i n t his trial.  H o we ver, partici pa nts will i n directl y  be nefit
t hr o u g h t heir c o ntri b uti o n t o t he pr ocess of de vel o pi n g ne w t hera pies i n a n area of u n met 
nee d.  
2. 3. 3.
O v er all B e n efit: Ri s k C o n cl u si o n
Ta ki n g i nt o acc o u nt t he meas ures ta ke n t o mi ni mize ris k t o partici pa nts partici pati n g i n 
t his st u d y, t he p ote ntial ris ks i de ntifie d i n ass ociati o n wit h G S K 2 9 8 2 7 7 2 are j ustifie d b y 
t he a ntici pate d be nefits t hat ma y be aff or de d t o partici pa nt s wit h ps orias is b y  c o ntri b uti n g 
t o t he u n dersta n di n g of t he disease a n d t he de vel o p me nt of ne w t hera pies f or patie nts
wit h t hese c o n diti o ns i n t he f ut ure.  
3.
O B J E C TI V E S A N D E N D P OI N T S
O bjecti ves
E n d p oi nts
Pri mar y

T o d et er mi n e t h e effic acy of G S K 2 9 8 2 7 7 2 9 6 0 
m g m o difi e d r el e as e (M R ) o nc e d aily ( Q D ) f or 
1 2 w e eks, c o m p ar e d wit h pl ac e b o i n 
p artici p a nts wit h m o d er at e t o s ev er e pl a q u e 
ps ori asis.

P A SI 7 5 r es p o ns e (ac hi ev i n g≥7 5 % 
i m pr ov e m e nt fr o m B as eli n e i n P A SI sc or e ) at 
W e ek 1 2.
Sec o n dar y

T o f urt h er ev al u at e t h e effic acy of
G S K 2 9 8 2 7 7 2 9 6 0 m g M R Q D f or 1 2 w e eks,
c o m p ar e d wit h pl ac e b o i n p artici p a nts wit h 
m o d er at e t o s ev er e pl a q u e ps ori asis . 
F urt h er P A SI p ar a m et ers:

P A SI 5 0 , P A SI 9 0 a n d P A SI 1 0 0 r es p o ns e 
(ac hi ev i n g≥5 0 % , ≥9 0 % a n d 1 0 0 %
i m pr ov e m e nt fr o m B as eli n e i n P A SI sc or e,
r es p ectiv ely) at W e ek 1 2.

C h a n g e fr o m B as eli n e P A SI sc or es at W e ek
1 2 .
St atic I nv esti g at or’s Gl o b al Ass ess m e nt(sI G A):

sI G A r es p o ns e ( ac hi evi n g a sIG A sc or e of 
( 0) or  
 ( 1)) at W e ek 1 2.
Ps ori asis B o dy S urf ac e Ar e a ( B S A):

C h a n g e fr o m B as eli n e i n ps ori atic B S A at 
W e ek 1 2.
Safet y

T o ev al u at e t h e s af ety a n d t ol er a bility of 
G S K 2 9 8 2 7 7 2 9 6 0 m g M R Q D f or 1 2 w e eks, 

A dv ers e ev e nts
C CI
C CI
C CI
C CI


2 0 1 9 N 4 2 0 9 0 2 _ 0 3
C O N FI D E N TI A L
2 0 8 0 2 2
2 8
O bjecti ves
E n d p oi nts
c o m p ar e d wit h pl ac e b o i n p artici p a nts wit h 
m o d er at e t o s ev er e pl a q u e ps ori asis.

Cli nic al l a b or at ory v al u es (cli nic al c h e mistry, 
h a e m at ol o gy a n d uri n alysis)

Vit al si g n m e as ur e m e nts ( bl o o d pr ess ur e, 
h e art r at e, r es pir at ory r at e a n d b o dy 
t e m p er at ur e)

1 2 -L e a d el ectr oc ar di o gr a m (E C G ) m o nit ori n g

C ol u m bi a S uici d e S ev erity R ati n g Sc al e ( C-
S S R S )
P har mac o ki netics

T o ass ess tr o u g h pl as m a c o nc e ntr ati o ns of 
G S K 2 9 8 2 7 7 2 9 6 0 m g M R Q D f or 1 2 w e eks, i n 
p artici p a nts wit h m o d er at e t o s ev er e pl a q u e 
ps ori asis.

Tr o u g h pl as m a c o nc e ntr ati o ns of 
G S K 2 9 8 2 7 7 2 at W e eks 2, 4, 8, 1 2.
E x pl orat or y

T o i nv esti g at et h e effic acy of G S K 2 9 8 2 7 7 2 , 
9 6 0 m g M R Q D ov er ti m e , c o m p ar e d wit h 
pl ac e b o i n p artici p a nts wit h m o d er at e t o 
s ev er e pl a q u e ps ori asis. 
A d diti o n al P A SI p ar a m et ers:

P A SI 7 5 r es p o ns e ( ac hi evi n g e ≥7 5 % 
i m pr ov e m e nt fr o m B as eli n e i n P A SI sc or e)at 
W e eks 2, 4, a n d 8.

P A SI 5 0, P A SI 9 0 a n d P A SI 1 0 0 r es p o ns e 
(ac hi ev i n g≥5 0 % , ≥9 0 % a n d 1 0 0 %
i m pr ov e m e nt fr o m B as eli n e i n P A SI sc or e
r es p ectiv ely) at W e eks 2, 4, a n d 8.

C h a n g e fr o m B as eli n e P A SI sc or es at W e eks 
2, 4, 8.
St atic I nv esti g at or’s Gl o b al Ass ess m e nt(sI G A):

sI G A r es p o ns e ( ac hi evi n g a sIG A sc or e of 
 ( 0) or 
 ( 1)) at W e eks 2, 4, 
a n d 8.

sIG A sc or e c at e g ory at W e eks 2, 4, 8, 1 2.
B o dy S urf ac e Ar e a ( B S A):

C h a n g e fr o m B as eli n e i n B S A at W e eks 2, 4, 
a n d 8.

T o i nv esti g at e eff ect of G S K 2 9 8 2 7 7 2 9 6 0 m g 
M R Q D f or 1 2 w e eks, o n p at h w ay a n d t ar g et
e n g a g e m e nt, tr a nscri pt o mic pr ofili n g, 
i nfl a m m at ory, a n d m et a b olic bi o m ark ers i n t h e 
ski n a n d bl o o d of p artici p a nts wit h m o d er at e 
t o s ev er e pl a q u e -ty p e ps ori asis.
P h ar m ac ol o gy bi o m ark er e n d p oi nts:

T ar g et E n g a g e m e nt Ass ay RI P 1 ( T E A R 1) i n 
bl o o d at W e eks 0, 4, a n d 1 2 .
Tr a nscri pt o mic pr ofili n g:

Tr a nscri pt o mic a n alysis, i ncl u di n g b ut n ot 
li mit e d t o ri b o n ucl eic aci d s e q u e nci n g (R N A -
s e q), of m ess e n g er ri b o n ucl eic aci d (m R N A )
is ol at e d fr o m ski n at W e eks 0, 4, a n d 1 2 , wit h 
C CI
C CI
C CI
C CI


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Objectives
Endpoints
any changes in specific inflammatory gene 
transcript levels (e.g. IL-4, IL-10, IL-17, IL-21,
IL-22, TNF and IFNγ) possibly being 
evaluated.
Inflammatory and Keratinocyte biomarkers:

Change from Baseline in histopathological
scoring of psoriatic lesional biopsies, which
may include, but are not limited to the
following at Weeks 0, 4, and 12: epidermal 
thickness, keratin 16 (K16), antigen KI-67 
(Ki67), CD3, cluster of differentiation 11c
(CD11c).

Change from Baseline in inflammatory protein 
markers in blood which may include but are 
not limited to the following at Weeks 0, 4, and 
12: IL-17, chemokine ligand 20 (CCL20), IL-
6, IL-8, IL-4, C-X-C motif chemokine 10
(CXCL10).
Metabolic biomarkers

Change from Baseline in metabolic markers in 
fasting blood which may include but are not 
limited to the following at Weeks 0, 4, and 12:
homeostatic model assessment of insulin 
resistance (HOMA) (glucose and insulin), 
glycated hemoglobin (HbA1c), lipid panel.
4.
STUDY DESIGN
4.1.
Overall Design
This is a multicentre, randomised, double-blind (sponsor-unblinded), placebo-controlled,
repeat dose study to investigate the efficacy, safety and tolerability, PK and PD and of 
GSK2982772 960 mg MR QD in participants with active plaque-type moderate to severe 
psoriasis.
Each participant will participate in the study for no more than 21 weeks. This includes a
Screening period up to 35 days, an 84 day (12 week) treatment period, and a 28 day
follow-up period after the last dose.
Participants will attend the clinical site to be consented and, if eligible for the study,
Screening assessments will be completed. Participants who have completed Screening 
assessments and are eligible will be randomized in a 2:1 ratio (active to placebo) to one 
of the following treatments and be dosed (Day 1) within 35 days of the Screening visit:

960 mg GSK2982772 QD


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
Placebo QD
Punch skin biopsies will be performed on all participants: 1 non-lesional and 1 lesional 
biopsys will be collected at Baseline (predose). At Week 12 (D85), 1 lesional biopsy
from the same plaque will be collectedat . An additional, optional lesional biopsy may 
also be collected at Week 4 (D29).
An interim analysis is planned to occur when at least six participants on GSK2982772 
have completed the Week 12 visit or discontinued study treatment to aid internal decision 
making around subsequent GSK2982772 trials. The study may be stopped for futility if 
the probability of a positive outcome at the end of the trial is low based on the data 
available at the interim. The data will be reviewed by an internal Data Review 
Committee. The details of the planned analyses, data to be reviewed, Data Review 
Committee (DRC) membership and results dissemination will be given in an interim 
analysis charter.
The Post-Treatment Period is 28 days (4 weeks) long.
4.2.
Scientific Rationale for Study Design
This study has been designed to evaluate the efficacy, safety, PK, and PD profiles of 
GSK2982772 in participants with moderate to severe plaque psoriasis.
Efficacy Endpoints
The PASI score is a clinician reported outcome which provides a single score combining 
the assessment of skin lesions (redness, thickness and scaling), weighted by the body 
surface area involvement in four anatomical regions (head, trunk, arms and legs).  It is 
widely agreed that a 75% improvement in PASI (PASI75) is a clinically relevant 
endpoint for patients with moderate to severe plaque psoriasis. PASI75 has been used 
extensively in clinical trials and formed the basis for regulatory drug approvals.
The primary endpoint used to evaluate the efficacy of GSK2982772 in this study is the 
PASI75 response at Week 12 relative to Baseline. Week 12 was chosen since it 
represents the timepoint of near maximal response for previous psoriasis medicines in 
development [Checchio, 2017]. Additional PASI endpoints (e.g. PASI50, PASI90, 
PASI100 and PASI score) will be collected to support the secondary objectives of this 
study.  Additional secondary efficacy endpoints incorporated in this study include the 
static sIGA and an assessment of BSA affected by psoriasis.
Patient Population
This study will evaluate GSK2982772 in participants with moderate to severe plaque 
psoriasis, defined as PASI (≥12), sIGA (≥3) and psoriasis BSA (≥10%).  The moderate to 
severe population is considered optimal for demonstrating the efficacy and safety of 
GSK2982772 and reflects the population in which a potential new oral treatment may be 
utilised in the treatment of plaque psoriasis.


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Placebo Rationale
The study includes a placebo arm to maintain the integrity of the study, preventing 
inflation of PASI75 scores which has been seen in some psoriasis (PsO) studies without 
placebo control [Griffiths, 2017]. Placebo use is minimized with a randomization ratio of 
2:1.
Biomarker Rationale
Downstream pharmacology will be evaluated using a panel of histologic, transcriptomic, 
and proteomic endpoints including some in the RIP1 pathway. The disease biomarker 
strategy includes both site of action biomarkers assessed in skin biopsies as well as 
systemic inflammation biomarkers in blood for evidence of change with therapeutic 
intervention. Keratinocyte hyperproliferation and immune infiltrate will be evaluated by 
immunohistochemistry. Pharmacodynamic effect on other inflammation pathways will be 
evaluated using transcriptomic and proteomic analysis.  Impact on metabolism will also 
be evaluated by measuring metabolic related endpoints.  These measurements will allow 
for understanding of the mechanism of action of the drug.
4.3.
Justification for Dose
In the study of participants with mild to moderate plaque psoriasis (203167), the 
magnitude of change in PLSS score was small with a treatment difference vs placebo of 
~15% at Day 43.  Since the E-R assessment showed an improved PLSS score with 
increasing tertiles of GSK2982772 trough plasma concentrations and participants with 
highest GSK2982772 skin concentration tended to have better PLSS score [GSK 
Document Number 2018N363258_01, it is hypothesised that 60 mg BID/TID dosing 
regimens did not provide sufficient exposure to achieve clinically relevant efficacy. In the 
current study, a once daily dose of 960 mg MR provides ~15-fold higher trough plasma 
concentrations than was achieved with the 60 mg TID IR regimen in the previous 203167 
study.  This magnitude of increase should result in a significant shift in the 
pharmacological response, and hence efficacy response, thereby determining proof of 
concept for RIPK1 inhibition in moderate to severe psoriasis. 
The MR formulation (DiffCORE™) was developed to provide a once daily dosing 
regimen for GSK2982772 (study 209261).  The MR dose of 960 mg (to be administered 
as 2 x 480 mg QD) was selected based on a balance of maximising GSK2982772 trough 
concentrations and staying within previously explored human GSK2982772 systemic 
exposure levels.
In study 209261, MR doses of 120, 240, 480 and 960 mg were evaluated.  The systemic 
exposure to GSK2982772 was approximately linear over the dose range 240 to 960 mg 
(2x480 mg MR tablets). The bioavailability of the MR formulation in the fasted state
relative to the IR formulation was approximately 60%.  For the MR dose of 960 mg, the 
predicted steady-state geometric mean area under the concentration-time curve from 0 to 
24 h (AUC[0-24]) and maximum concentration (Cmax) values are 29.9 µg.h/mL and 
1.75 µg/mL when administered in the fasted state and 40.2 µgh/mL and 3.80 µg/mL
when administered with a high fat meal.  These values are within the observed geometric 
mean AUC(0-24) (48.5 ng.h/mL) and Cmax (6.3 ug/mL) values observed for the 240 mg IR 


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TID dose in study 205184.  In the 39 week monkey toxicology study the AUC(0-24) and 
Cmax at the NOAEL (60 mg/kg/day) were 182 µg.h/mL and 23.2 µg/mL, respectively, 
resulting in approximate 4.6-fold and 5-fold safety margins for AUC(0-24) and Cmax
compared to the highest predicted exposures following administration of 960 mg with a 
high-fat meal.
4.4.
End of Study Definition
A participant is considered to have completed the study if he/she has completed all 
phases of the study including the last visit.
The end of the study is defined as the date of the last visit of the last participant in the 
study.
5.
STUDY POPULATION
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1.
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria 
apply:
Age
Between 18 and 75 years of age inclusive, at the time of signing the informed 
consent.


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Type of Participant and Disease Characteristics
Diagnosis of plaque psoriasis for at least 6 months before Screening visit.
Evidence of moderate to severe psoriasis, at Screening and Baseline before the first 
dose of study treatment, with:
o
PASI score ≥12, AND
o
Psoriasis plaques involving BSA ≥10%, AND
o
sIGA ≥3
Candidate for systemic therapy or phototherapy (includes naïve or previously 
treated), in the opinion of the Investigator.
Agrees to avoid any prolonged exposure to natural or artificial sources of ultraviolet 
(UV) radiation (e.g. sunlight, tanning beds or phototherapy) from 28 days before Day 
1 until the follow-up visit, which may potentially impact the participant’s psoriasis in 
the opinion of the Investigator (see Section 5.3.3).
Weight
Body mass index (BMI) within the range of 18.5 to 40.0 kg/m2 (inclusive).
Sex
Male and Female participants:
Preclinical data has not identified risk of clinically relevant genotoxicity, however there 
is demonstrated/suspected risk of teratogenicity/fetotoxicity. Accordingly, the following 
contraceptive advice must be adhered to for male and female participants.
Contraceptive use by men or women should be consistent with local regulations 
regarding the methods of contraception for those participating in clinical studies.
a.
Male Participants:
Male participants are eligible to participate if they agree to the following during the 
intervention period and for at least 2 days (i.e. 5 terminal half-lives of GSK2982772) 
after the last dose of study intervention:

Refrain from donating sperm
Plus either:

Be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long term and persistent basis) and agree to remain abstinent 
OR

Must agree to use contraception/barrier as detailed below


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o
Agree to use a male condom and will also be advised of the benefit for 
a female partner to use a highly effective method of contraception as a 
condom may break or leak when having sexual intercourse with a 
woman of childbearing potential (WOCBP) who is not currently 
pregnant
b. Female Participants: 

A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and at least one of the following conditions applies:
o
Is not a WOCBP 
OR
Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate 
of <1% per year), preferably with low user dependency, as described in Appendix 4,
during the intervention period and for at least 28 days (i.e. until resolution of potential 
drug interaction with combined hormonal contraceptives) after the last dose of study 
intervention. The Investigator should evaluate the effectiveness of the contraceptive 
method in relationship to the first dose of study intervention.
o
A WOCBP must have a negative highly sensitive pregnancy test (urine or serum 
as required by local regulations) within 24 hours before the first dose of study 
intervention.
o
If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a 
serum pregnancy test is required. In such cases, the participant must be excluded 
from participation if the serum pregnancy result is positive.

Additional requirements for pregnancy testing during and after study intervention are 
located in Appendix 2.

The Investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy.
Informed Consent
Capable of giving signed informed consent as described in Appendix 1 which 
includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol.
5.2.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:


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Medical Conditions
1. Non-plaque forms of psoriasis (e.g. erythrodermic, guttate, or pustular), in the opinion 
of the Investigator.
2. Drug-induced psoriasis (e.g. a new onset of psoriasis or an exacerbation from beta 
blockers, calcium channel blockers, lithium or anti-TNF therapies).
3. Diagnosis of psoriatic arthritis, uveitis, inflammatory bowel disease, or other 
immune-mediated conditions that are commonly associated with psoriasis for which a 
participant requires current systemic (oral, subcutanous [SC], or intravenous [IV]) 
(including corticosteroids and biologics) immunosuppressant medical treatment. 
4. Current SIB as measured using the C-SSRS or a history of attempted suicide at 
Screening and before first dose of study treatment.
5. Active infection, or a history of infections as follows:

Hospitalisation for treatment of infection within 60 days before Day 1.

Current use of any suppressive therapy for a chronic infection (such as 
pneumocystis jirovecii, cytomegalovirus, herpes simplex virus, herpes zoster 
virus and atypical mycobacteria).

Use of parenteral (IV or intramuscular) antibiotics (antibacterials, antivirals, 
antifungals, or antiparasitic agents) within 60 days before Day 1.

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.

History of recurrent, chronic or other active infection that in the opinion of the 
Investigator may put the participant at unacceptable risk or interfere/confound 
the integrity of study data.

Positive test for SARS-CoV-2 at screening or interaction with known COVID-
19 positive contacts within 14 days prior to Day 1.

History of latent or active TB, irrespective of treatment status.

A positive diagnostic TB test at Screening defined as a positive 
QuantiFERON-TB Gold plus test.
Please note: In cases where the QuantiFERON-TB Gold Plus test is 
indeterminate, the participant may have the test repeated once, but they will 
not be eligible for the study unless the second test is negative, or they have a 
negative tuberculin skin test (defined as skin induration <5 mm at 49 to 72 
hours, regardless of Bacillus Calmette-Guerin or other vaccination history). 
There must be no other clinical evidence of TB on physical examination of the 
participant at Screening.
6. Current or history of liver disease, known hepatic or biliary abnormalities (with the 
exception of Gilbert’s syndrome or asymptomatic gallstones).
7. Current or history of renal disease.


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8. Significant unstable or uncontrolled cardiovascular disease including uncontrolled 
hypertension.
Hereditary or acquired immunodeficiency disorder, including immunoglobulin 
deficiency.
History of major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic 
stem cell/marrow transplant.
Planned surgical procedure that makes the participant unsuitable for the study, in the 
opinion of the Investigator.
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 after 
at least 12 months following treatment.
History of significant progressive neurologic disorders including, but not limited to,
progressive MS, ALS, Alzheimer’s and dementia.
History of a medical condition other than plaque psoriasis, or other considerations,
which may confound interpretation of efficacy or safety study data, or put the 
participant at unacceptable risk, in the opinion of the Investigator.  
Prior/Concomitant Therapy
History of lack of primary response to anti-TNF biologic therapies (either approved 
or experimental) at approved doses (or at the doses received if experimental 
therapies) after at least 3 months of therapy.
Participant has previous exposure to 3 or more biologic therapies of any mechanism 
of action.
Treatment with the prohibited therapies listed in Section 6.4.1, or changes to those 
treatments, within the specified timeframe.  If in doubt, or the therapy is not listed 
please consult with the medical monitor.
o
Other medications (including vitamins, herbal and dietary supplements) will 
be considered on a case-by-case basis and will be allowed if the medication 
will not interfere with the study procedures or compromise participant safety, 
in the opinion of the Investigator.
Prior/Concurrent Clinical Study Experience
Participation in a clinical trial and has received an investigational product within 30 
days or 5 half-lives whichever is longer (or 12 weeks for biologic therapies), 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.
Exposure to more than four investigational products within 12 months prior to the 
first dosing day.


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Diagnostic assessments
Average QT Duration Corrected for Heart Rate (QTc) >450 msec or QTc>480 msec 
in participants with bundle branch block at Screening and before first dose of study 
treatment.
NOTES: 

The QTc is the QT interval corrected for heart rate according to Fridericia’s 
formula (QTcF). It is either machine-read or manually over-read.
Alanine transferase (ALT) >2 × upper limit of normal (ULN)
Bilirubin >1.5 × ULN at Screening (isolated bilirubin >1.5 × ULN is acceptable if 
bilirubin is fractionated and direct bilirubin <35%)
Estimated glomerular filtration rate (GFR) by Chronic Kidney Disease Epidemiology 
Collaboration equation (CKD-EPI) <60 mL/min/1.73 m2
Haemoglobin <10 g/dL; haematocrit <30 %, white blood cell count ≤3000 /mm3 
(≤3.0 x 109/L); platelet count ≤ 100,000 /µL (≤ 00 x 109/L); absolute neutrophil 
count ≤1500 /mm (≤1.5 x 109/L).
Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody 
(HBcAb).
Presence of hepatitis C antibody at Screening. Participants with positive Hepatitis C 
antibody due to prior resolved disease can be enrolled, only if a confirmatory 
negative hepatitis C RNA test is obtained.
Positive serology for HIV 1 or 2.
Where participation in the study would result in donation of blood or blood products 
in excess of 500 mL within 3 months.
Other Exclusions
History of alcohol or drug abuse, that would interfere with the ability to comply with 
the study or interfere with interpretation of the study, in the opinion of the 
Investigator.
History of sensitivity to any of the study treatments, or components thereof, or a 
history of drug or other allergy that contraindicates their participation (including 
lidocaine or other local anaesthetic), in the opinion of the Investigator or Medical 
Monitor.
History of receiving a live or attenuated vaccine within 30 days of randomization OR 
plan to receive a live or attenuated vaccination during the study until completion of 
the follow-up visit.
History of hypertrophic or keloid scarring.


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5.3.
Lifestyle Considerations
Participants must adhere to the contraceptive requirements listed in Appendix 4.
5.3.1.
Meals and Dietary Restrictions
There are no meal or dietary restrictions except on the Day 1, 29 and 85 visits when 
participants should fast overnight prior to these visits.
5.3.2.
Alcohol Consumption
Participants must abstain from alcohol for 24 hours before all study visits.
5.3.3.
Sun Exposure and Activity
Participants must not sunbathe or use a tanning device (sun bed or solarium) for 28 days
prior to Day 1 until the follow-up visit (Day 113). Participants will be advised that when
they are outdoors they must wear protective clothing (e.g. sun hat, long sleeves) as well 
as use a broad spectrum UVA/UVB sunscreen and lip balm (sun protection factor [SPF]
≥30) on exposed areas.
Participants will abstain from strenuous exercise for 48 hours prior to each blood 
collection for clinical laboratory tests.
5.4.
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently randomized. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes 
demography, screen failure details, eligibility criteria, any protocol deviations and any 
SAEs.
Retesting in case of spurious results or sample handling error at Screening is allowed.
Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened once if there is reasonable possibility that the individual would be 
eligible, in the opinion of the Investigator. Participants should be assigned a new 
participant number.
6.
STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s) to be administered to a 
study participant according to the study protocol.


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ARM Name
GSK2982772
Placebo
Type 
Drug
Drug
Dose Formulation
Tablet
Tablet
Unit Dose Strength(s)
480 mg
NA
Dosage Level(s)
960 mg QD
NA
Route of Administration
Oral
Oral
Use
Experimental
Placebo- comparator
IMP and NIMP
IMP
IMP
Sourcing
Provided centrally by the 
Sponsor 
Provided centrally by the 
Sponsor 
Packaging and Labeling
Study Intervention will be 
provided in bottles. Each 
bottle will be labeled as 
required per country 
requirement.
Study Intervention will be 
provided in bottles. Each 
bottle will be labeled as 
required per country 
requirement.
6.1.
Preparation/Handling/Storage/Accountability
The Investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study intervention received and any 
discrepancies are reported and resolved before use of the study intervention.
Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions with 
access limited to the Investigator and authorized site staff.
The Investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (i.e., receipt, reconciliation, and final disposition records).
Further guidance and information for the final disposition of unused study 
intervention are provided in the Study Reference Manual (SRM).

Under normal conditions of handling and administration, study intervention 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 


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provided to the Investigator, where this is required by local laws, or is available 
upon request from GSK.
6.2.
Measures to Minimize Bias: Randomisation and Blinding
Randomisation
At Screening, a unique Participant Number will be assigned to any participant who has at 
least one Screening procedure performed, other than informed consent. The unique 
Participant Number will be used to identify individual participants during the course of 
the study.
Participants who meet Screening eligibility criteria will be randomised to a treatment 
group through an Interactive Web Response System (IWRS). Before the study is 
initiated, the log in information & directions for the IWRS will be provided to each site. 
The IWRS will confirm the participant’s case report form (CRF) number (Participant
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 participant in the study.
The randomisation is centrally controlled by the IWRS.
Participants will be randomised to receive either GSK2982772 or placebo in a 2:1 ratio.
The randomisation will be stratified by prior biologic use.Participants will take study 
medication every day, once a day for 12 weeks, at approximately the same time each day.
Participants will be administered the first daily dose of study medication by site staff 
during the site visit for Day 1 (Week 0). At subsequent visits, the dose should be taken 
either on site (preferred) after the pre-dose assessments, or after the visit at home only if 
the participant dosing at site would result in a treatment overdose (refer to Section 8.4). 
Participants will self-administer all other doses of study medication and will record the 
date and time in the diary cards provided to them. Returned study intervention should not 
be re-dispensed to the participants.
See the SRM for further details.
Blinding
This will be a double-blind study. 
Access to participant-level unblinded data will be restricted to the GSK Biostatistics and 
CPMS members of the study team for the purpose of conducting analyses for the planned 
interim analysis. Summary-level data will be shared with the internal DRC at the interim 
analysis, membership of which will be listed in a data review charter. Results of the 
interim will not be shared outside of this committee, only the decision and its 


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implications will be communicated to the study team to minimise bias to the remainder of 
the trial.
All other members of the GSK study team will remain blinded throughout the study.
The IWRS will be programmed with blind-breaking instructions. In case of an 
emergency, the investigator has the sole responsibility for determining if unblinding of a 
participants’ intervention assignment is warranted.  Participant safety must always be the 
first consideration in making such a determination. If the Investigator decides that 
unblinding is warranted, the Investigator should make every effort to contact GSK prior 
to unblinding a participant’s intervention assignment unless this could delay emergency 
intervention of the participant.  If a participant’s intervention assignment is unblinded, 
GSK must be notified within 24 hours after breaking the blind. The date and reason that 
the blind was broken must be recorded in the source documentation and case report form 
as appropriate.
GSK’s Global Clinical Safety and Pharmacovigilance (GCSP) staff may unblind the 
intervention assignment for any participant with an SAE. If the SAE requires that an 
expedited regulatory report be sent to one or more regulatory agencies, a copy of the 
report, identifying the participant’s intervention assignment, may be sent to Investigators 
in accordance with local regulations and/or GSK policy.
6.3.
Study Intervention Compliance

When participants are dosed at the site, they will receive study intervention directly 
from the Investigator or designee, under medical supervision.  The date and time of 
each dose administered in the clinic will be recorded in the source documents.  The 
dose of study intervention and study participant identification will be confirmed at 
the time of dosing by a member of the study site staff other than the person 
administering the study intervention.  

If participants are not dosed at the site at the Week 2 (Day 15), Week 4 (Day 29)
and/or Week 8 (Day 57) visit(s), the time the dose is taken on those visit days must 
be confirmed by the site staff through follow-up with the participant, and time and 
date of dose information will be recorded in the CRF.

When participants self-administer study intervention(s) at home, compliance with 
study treatment will be assessed by reviewing the information from the returned 
diary cards at the study visits, and documenting compliance in the source documents 
and CRF.  

A record of the number of study treatment tablets dispensed to and taken by each 
participant must be maintained and reconciled with study intervention and 
compliance records. Intervention start and stop dates, including dates for intervention
delays, will also be recorded in the CRF.


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6.4.
Concomitant Therapy
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements or other specific categories of interest) that the
participant is receiving at the time of enrolment or receives during the study must be 
recorded along with:

reason for use

dates of administration including start and end dates

dosage information including dose and frequency
Any allowable medication should be stably maintained prior to enrolment to the study. 
Usage should be approximately stable and consistent throughout the study intervention 
and follow-up. The Medical Monitor should be contacted if there are any questions 
regarding concomitant or prior therapy.
Selected medications for the treatment of psoriasis may be taken, with specific 
requirements listed in Table 1, and as long as they are not prohibited (Section 6.4.1).
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.
Low or least potent (Class 6 or 7) topical 
corticosteroids1

Only on palms, soles, face, and 
intertriginous areas

Hydrocortisone 1% and 
hydrocortisone acetate 1% are the 
only topical corticosteroids permitted

Omit on day of study visits until after 
all skin assessments have been 
performed.
Medicinal shampoos that contain tar 
and/or salicylic acid (but not 
corticosteroids)

Permitted at any time on scalp area.
1. Usage should be approximately stable for 14 days prior to dosing.
6.4.1.
Prohibited Medicines
Participants must abstain from taking prescription or non-prescription drugs (including 
vitamins and dietary or herbal supplements) within 7 days (or 14 days if the drug is a 


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potential enzyme inducer) or 5 half-lives (whichever is longer) before the start of study 
intervention until completion of the follow-up visit, unless the medication will not 
interfere with the study, in the opinion of the Investigator and sponsor. 
Table 2 lists prohibited medications for defined periods of time before and during the 
study until after the follow-up visit (Day 113). 
Participants 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
Prohibited Therapy
Washout Period
(from before D1 until 
follow-up)
Biologic Agents 
(including but not limited to: adalimumab, etanercept, 
infliximab, certolizumab, ustekinumab, guselkumab, 
ixekizumab, secukinumab, risankizumab)
4 weeks for etanercept; 
8 weeks for infliximab; 
12 weeks or 5 half-lives 
(whichever is longer) 
for other biologics
Oral retinoids
(including but not limited to: acitretin or isotretinoin)
12 weeks
Systemic immunosuppressive or immunomodulating agents.
(including but not limited to: cyclosporin, interferon, 
methotrexate, apremilast)
8 weeks
Systemic corticosteroids or adrenocorticotropic hormone 
(ACTH) analogs
4 weeks
Phototherapy
(PUVA, UVB or self-treatment with tanning bed)
4 weeks
Topical Treatments
(including but not limited to: corticosteroids [low potency 
corticosteroids permitted for certain areas, see permitted 
medications], immunomodulators, anthralin [dithranol], 
Vitamin D derivatives, retinoids, or coal tar [used on the 
body])
2 weeks


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Prohibited Therapy
Washout Period
(from before D1 until 
follow-up)
Live or attenuated Vaccinations

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 
participants with PsO.
30 days for live or 
attenuated vaccinations
Pgp Inhibitors
(including but not limited to: amiodarone, azithromycin, 
clarithromycin, conivaptan, erythromycin, felodipine, 
itraconazole [FDA, 2012])
4 weeks
Narrow therapeutic index (NTI) CYP3A4 substrates.
(including but not limited to: alfentanil, astemizole, 
cisapride, fentanyl, pimozide, quinidine, sirolimus, 
terfenadine [FDA, 2012])
4 weeks
Sensitive substrates of CYP2B6 
(including but not limited to: bupropion)
4 weeks
Sensitive substrates of CYP2C8
(including but not limited to: repaglinide)
4 weeks
OAT3 inhibitors 
(including but not limited to: probenecid, teriflunomide)
4 weeks
Paracetamol/acetaminophen, at licensed doses, is permitted for use. Other concomitant 
medication may be considered on a case by case basis by the Investigator, in consultation 
with the medical monitor if required.
6.5.
Dose Modification
No dose modifications will be allowed. 
6.6.
Intervention after the End of the Study
There will be no intervention offered at the end of the study.


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7.
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL
7.1.
Discontinuation of Study Intervention
In rare instances, it may be necessary for a participant to permanently discontinue 
(definitive discontinuation) study intervention. If study intervention is definitively 
discontinued, the participant will remain in the study to be evaluated for efficacy and 
safety, unless consent is withdrawn. See the SoA (Section 1.3) for data to be collected at 
the time of discontinuation of study intervention and follow-up and for any further 
evaluations that need to be completed.
7.1.1.
Liver Chemistry Stopping Criteria
Liver chemistry stopping, and increased monitoring criteria have been designed to assure 
participant safety and evaluate liver event etiology.
Discontinuation of study intervention for abnormal liver tests is required when:

a participant meets one of the conditions outlined in the algorithm

when in the presence of abnormal liver chemistries not meeting protocol-specified 
stopping rules, the Investigator believes study intervention discontinuation is in 
the best interest of the participant. 
Phase 2 Liver Chemistry Stopping and Increased Monitoring Algorithm


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Abbreviations: ALT = alanine transaminase; INR = international normalized ratio; 
SAE = serious adverse event; ULN = upper limit of normal.
7.1.2.
QTc Stopping Criteria
A participant with an average triplicate measurement meeting either of the bulleted 
criteria below will be withdrawn from the study:

QTc >500 msec or uncorrected QT >600 msec

Change from Baseline (Day 1 pre-dose) of QTc >60 msec
For participants with underlying bundle branch block, follow the discontinuation criteria 
below:
Day 1 pre-dose QTc with bundle branch block
Discontinuation QTc with bundle branch 
block
<450 msec
>500 msec
450-480 msec
≥530 msec

The Fridericia’s QT correction formula must be used for each individual participant
to determine eligibility for and discontinuation from the study.  

The QTc should be based on the average of triplicate ECG readings obtained over a 
brief (e.g., 5-10 minute) recording period at Screening and at Day 1 (Baseline).  At 
all other specified time points single ECGs are acceptable.  However, if QTc 
prolongation (as defined in the same way as the withdrawal criteria) is detected,
triplicate ECGs will be performed and the QTc must be based on the average of 
triplicated ECG readings.
7.1.3.
Rechallenge
7.1.3.1.
Study Intervention Restart or Rechallenge after liver stopping criteria 
met
Study intervention restart or rechallenge after liver chemistry stopping criteria are met by 
any participant in this study is not allowed.
7.2.
Participant Discontinuation/Withdrawal from the Study

A participant may withdraw from the study at any time at his/her own request or
may be withdrawn at any time at the discretion of the Investigator for safety, 
behavioral, compliance or administrative reasons. This is expected to be 
uncommon.

A participant may be withdrawn from the study at any time if deemed to be 
demonstrating suspected, probable or confirmed COVID-19 infection. Specific 
details are in the SRM.

At the time of discontinuing from the study, if possible, an early discontinuation 
visit should be conducted, as shown in the SoA (Section 1.3). See SoA (Section 


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1.3) for data to be collected at the time of study discontinuation and follow-up 
and for any further evaluations that need to be completed.

If the participant withdraws consent for disclosure of future information, the 
sponsor may retain and continue to use any data collected before such a 
withdrawal of consent.

If a participant withdraws from the study, he/she may request destruction of any 
samples taken and not tested, and the Investigator must document this in the site 
study records.
7.3.
Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit:

The site must attempt to contact the participant and reschedule the missed visit 
as soon as possible and counsel the participant on the importance of maintaining 
the assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study.

Before a participant is deemed lost to follow-up, the Investigator or designee 
must make every effort to regain contact with the participant (where possible, 3 
telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record.

Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study. 
Discontinuation of specific sites or of the study as a whole are handled as part of 
Appendix 1.
8.
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and their timing are summarized in the SoA (Section 1.3). 

Protocol waivers or exemptions are not allowed.

Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or 
discontinue study intervention.

Adherence to the study design requirements, including those specified in the SoA
(Section 1.3), is essential and required for study conduct.

All Screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The Investigator will maintain a Screening 
log to record details of all participants screened and to confirm eligibility or record 
reasons for Screening failure, as applicable. 


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
Procedures conducted as part of the participant’s routine clinical management (e.g., 
blood count) and obtained before signing of ICF may be utilized for Screening or 
Baseline purposes provided the procedure met the protocol-specified criteria and was 
performed within the time frame defined in the SoA (Section 1.3).

The maximum amount of blood collected from each participant over the 
duration of the study, including any extra assessments that may be required, will 
not exceed 500 mL.

Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples.
8.1.
Efficacy Assessments
8.1.1.
Clinical Disease Assessments
8.1.1.1.
Psoriasis Area Severity Index (PASI)
Psoriatic lesions will be assessed using the PASI scoring system [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 participant should be 
completed by the same assessor at all time points.
8.1.1.2.
Psoriasis body Surface Area (BSA)
The BSA affected with psoriasis will be evaluated at all study visits by the Investigator or 
suitably trained delegate. In order to be eligible for the study, BSA must be ≥10%. As a 
reference, the area of the whole palm is counted as 1% BSA.
8.1.1.3.
Static Investigator’s Global Assessment of Disease Activity (sIGA)
The Investigator or physician designee only will complete a global assessment of disease 
activity using the physician global assessment item. A 5-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 Investigator’s global
assessment independently of the participant.

Ideally, the same Investigator or physician designee should perform all global 
assessments for each participant for the duration of the study.


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8.2.
Safety Assessments
Blinded safety data will be reviewed by the safety review team (SRT) details of which 
can be found in the SRT charter.
Planned time points for all safety assessments are provided in the SoA (Section 1.3).
8.2.1.
Physical Examinations

A complete physical examination will include, at a minimum, assessments 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. Height will be measured at the screening visit 
only.

A brief physical examination will include, at a minimum, weight and 
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 or that could be related to infection (e.g. COVID-19).

At each visit, the participant should be asked whether they have had COVID-19 
symptoms, or exposure to anyone with COVID-19 positive test in the past 14 
days. These symptoms include, but are not limited to, a high temperature and 
dry cough. Guidance on how to manage participants who develop COVID-19 
symptoms during the study are described in the SRM. Participants with exposure 
to anyone with COVID-19 infection should not be included in the study until 14 
days after the last exposure.
8.2.2.
Vital Signs

Vital signs will be measured in a semi-supine position after 5 minutes rest and 
will include temperature, systolic and diastolic blood pressure, pulse and 
respiratory rate. 
8.2.3.
Electrocardiograms

Triplicate and single 12-lead ECGs will be obtained as outlined in the SoA (see 
Section 1.3) using an ECG machine that automatically calculates the heart rate 
and measures PR, QRS, QT, and QTc intervals. Refer to Section 7 for QTc 
withdrawal criteria and additional QTc readings that may be necessary.

At each time point at which triplicate ECG are required (Screening and Day 1 
[Baseline]), 3 individual ECG tracings should be obtained as closely as possible 
in succession, but no more than 2 minutes apart. The full set of triplicates should 
be completed over a brief (e.g., 5-10 minutes) recording period.
8.2.4.
Clinical Safety Laboratory Assessments

Refer to Appendix 2 for the list of clinical laboratory tests to be performed andto 
the SoA (Section 1.3) for the timing and frequency. 


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
The Investigator must review the laboratory report, document this review, and 
record any clinically relevant changes occurring during the study in the AE 
section of the CRF. The laboratory reports must be filed with the source 
documents. Clinically significant abnormal laboratory findings are those which 
are not associated with the underlying disease, unless judged by the Investigator
to be more severe than expected for the participant's condition.

All laboratory tests with values considered clinically significantly abnormal 
during participation in the study should be repeated until the values return to 
normal or Baseline or are no longer considered significantly abnormal by the 
Investigator or medical monitor. 

If such values do not return to normal/Baseline within a period of time judged 
reasonable by the Investigator, the etiology should be identified and the sponsor 
notified.

All protocol-required laboratory assessments, as defined in Appendix 2, must be 
conducted in accordance with the laboratory manual and the SoA (Section 1.3).
8.2.5.
Suicidal Ideation and Behaviour 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 participants being treated with GSK2982772 should be alerted
regarding the need to monitor participants 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.
Participants being treated with GSK2982772 must be monitored appropriately for 
suicidal ideation and behaviour or any other unusual changes in behaviour. Participants 
that experience signs of suicidal ideation or behavior must be withdrawn from study
treatment.
At Screening, the ‘Baseline/Screening C-SSRS’ will be completed. At each subsequent 
study visit, the ‘Since Last Visit C-SSRS’ will be completed. GSK Version 4.1 of both
rating scales will be used.
Participants who answer ‘yes’ to any suicidal behaviour or ‘yes’ to suicidal ideation
Questions 4 or 5 will be referred to their general practitioner (GP) or appropriate 
psychiatric care. The medical monitor will be notified. If appropriate, an AE or SAE must
be reported (see Section 8.3- AE and SAE). In addition, the Investigator must 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 


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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.
8.3.
Adverse Events and Serious Adverse Events
The definitions of an AE or SAE can be found in Appendix 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant's legally authorized representative) to the site staff.
The Investigator and any qualified designees are responsible for detecting, documenting, 
and reporting events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study intervention or the 
study, or that caused the participant to discontinue the study (see Section 7).
8.3.1.
Time Period and Frequency for Collecting AE and SAE 
Information

All SAEs will be collected from the signing of the informed consent until the 
follow-up visit at the time points specified in the SoA (Section 1.3).

All AEs will be collected from the start of intervention until the follow-up visit
at the time points specified in the SoA (Section 1.3).

Medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will be recorded on the Medical History/Current 
Medical Conditions section of the CRF not the AE section.

All SAEs will be recorded and reported to the sponsor or designee immediately 
and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. The Investigator will submit any updated SAE data to the sponsor 
within 24 hours of it being available.

Investigators are not obligated to actively seek AEs or SAEs after the conclusion 
of the study participation. However, if the Investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the 
study, and he/she considers the event to be reasonably related to the study 
intervention or study participation, the Investigator must promptly notify the 
sponsor.
8.3.2.
Method of Detecting AEs and SAEs

The method of recording, evaluating, and assessing causality of AEs and SAEs 
and the procedures for completing and transmitting SAE reports are provided in 
Appendix 3.

Care will be taken not to introduce bias when detecting AE and/or SAE. Open-
ended and non-leading verbal questioning of the participant is the preferred 
method to inquire about AE occurrence. 


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8.3.3.
Follow-up of AEs and SAEs
After the initial AE/SAE report, the Investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs will be followed until the event is 
resolved, stabilized, otherwise explained, or the participant is lost to follow-up (as 
defined in Section 7.3). Further information on follow-up procedures is given in 
Appendix 3.
8.3.4.
Regulatory Reporting Requirements for SAEs

Prompt notification by the Investigator to the sponsor of a SAE is essential so 
that legal obligations and ethical responsibilities towards the safety of 
participants and the safety of a study intervention under clinical investigation are 
met. 

The sponsor has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study intervention
under clinical investigation. The sponsor will comply with country-specific 
regulatory requirements relating to safety reporting to the regulatory authority, 
Institutional Review Boards (IRB)/Independent Ethics Committees (IEC), and 
Investigators.

For all studies except those utilizing medical devices Investigator safety reports 
must be prepared for suspected unexpected serious adverse reactions (SUSAR) 
according to local regulatory requirements and sponsor policy and forwarded to 
Investigators as necessary.

An Investigator who receives an Investigator safety report describing a SAE or 
other specific safety information e.g., summary or listing of SAEs) from the 
sponsor will review and then file it along with the IB and will notify the 
IRB/IEC, if appropriate according to local requirements.
8.3.5.
Pregnancy

Details of all pregnancies in female participants and, if indicated, female partners of 
male participants will be collected after the start of study intervention and until 30 
days after the last dose.

If a pregnancy is reported, the Investigator must inform GSK within 24 hours of
learning of the pregnancy and must follow the procedures outlined in Appendix 4.

Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAE.
8.3.6.
Cardiovascular and Death Events
For any cardiovascular events detailed in Appendix 3 and all deaths, whether or not they 
are considered SAEs, specific Cardiovascular (CV) and Death sections of the CRF will 


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be required to be completed. These sections include questions regarding cardiovascular 
(including sudden cardiac death) and non-cardiovascular death. 
The CV CRFs are presented as queries in response to reporting of certain CV medical 
dictionary for regulatory activities (MedDRA) terms. The CV information should be 
recorded in the specific cardiovascular section of the CRF within one week of receipt of a 
CV Event data query prompting its completion.
The Death 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.
8.4.
Treatment of Overdose
For this study, any dose of GSK2982772 greater than 960 mg within a 20-hour time 
period will be considered an overdose.
GSK does not recommend specific treatment for an overdose.
In the event of an overdose, the Investigator/treating physician should:
Contact the Medical Monitor immediately.
Closely monitor the participant for AE/SAE and laboratory abnormalities until 
GSK2982772 can no longer be detected systemically (at least 2 days).
Obtain a plasma sample for PK analysis within 1 day from the date of the last dose of 
study intervention if requested by the Medical Monitor in conjunction with clinical 
pharmacologist (determined on a case-by-case basis).
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 
participant.
8.5.
Pharmacokinetics
8.5.1.
Blood Sample Collection
Blood samples for PK analysis of GSK2982772 will be collected prior to dosing at the 
time points indicated in SoA, Section 1.3. The actual date and time (24-hour clock) of
each blood sample collection will be recorded. Details of blood sample collection, 
processing, storage and shipping procedures are provided in the SRM.
8.5.2.
Plasma Sample Analysis
Plasma analysis will be performed at a bioanalytical site (to be detailed in the SRM) 
under the control of In vitro/ In vivo Translation (IVIVT), GlaxoSmithKline (GSK). 
Concentrations of GSK2982772 will be determined in plasma samples using the currently 


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approved bioanalytical methodology. Raw data will be archived at the bioanalytical site 
(detailed in the SRM). Once the plasma has been analysed for GSK2982772 any 
remaining plasma may be analysed for other compound-related material and the results 
reported under a separate IVIVT, GlaxoSmithKline protocol.
8.6.
Pharmacodynamics
Pharmacodynamic parameters are being evaluated in this study using biomarkers as 
detailed in Section 8.8.
8.7.
Genetics
A 6 mL blood sample for deoxyribonucleic acid (DNA) isolation will be collected from 
participants who have consented to participate in the genetics analysis component of the 
study. Participation is optional. Participants who do not wish to participate in the genetic 
research may still participate in the study.
In the event of DNA extraction failure, a replacement genetic blood sample may be 
requested from the participant. Signed informed consent will be required to obtain a 
replacement sample unless it was included in the original consent.
See Appendix 5 for Information regarding genetic research. Details on processes for 
collection and shipment and destruction of these samples can be found in the Q2 
Solutions laboratory manual and the Study Reference Manual.
8.8.
Biomarkers
Collection of samples for biomarker research is part of this study. The following samples 
for biomarker research are required and will be collected from all participants in this 
study as specified in the SoA (Section 1.3):

Blood (target engagement, proteomic, and metabolic analyses)

Skin biopsies (histology and transcriptomic analyses)


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Biomarkers will be analysed in samples taken at visits described in the SoA (Section 1.3),
to evaluate the effect of GSK2982772 as below:

Target engagement – TEAR1 assay (target engagement assay RIP1) in blood 
samples.

Transcriptome – see Section 8.8.2 transcriptomic analysis of mRNA, including 
but not limited to RNA-seq, isolated from skin biopsy samples. Also, if 
transcriptomic data dictate, mRNA expression of inflammatory gene transcripts
in the skin biopsies which may include, but are not limited to IL-4, IL-10, IL-17, 
IL-21, IL-22, TNF and IFNsee Section 8.8.3

Disease and inflammatory biomarkers – histopathological scoring including, but 
not limited to, epidermal thickness, K16, Ki67, CD3 and CD11c, in skin biopsy 
samples. Protein markers in blood samples which may include but are not 
limited to IL-17, CCL20, IL-6, IL-8, IL-4, CXCL10, see Section 8.8.4.

Metabolic biomarkers – HOMA, HbA1c and lipid panel may be analysed in 
blood, see Section 8.8.5.
8.8.1.
Skin Biopsy 
All biopsies will be 4 mm punch biopsies and will be taken using standard methodology 
only by suitable experienced personnel, trained in aseptic technique.
At Baseline (pre-dose Day 1), a target lesion for biopsy will be identified (3 cm2) on the 
trunk or extremities. The same target lesion will be used for all subsequent 
timepoints. Lesions on palmar surfaces of the hands and feet, scalp, knees, elbows and 
intertriginous areas will not be used as the target lesion site. At Baseline only, a non-
lesion biopsy will be taken from an unaffected area close to the target lesion.
Lesional biopsies will be taken from the outer third of the selected biopsy lesion at 
timepoints defined in the SoA (Section 1.3). The sites on the outer third of the same 
lesion should be at least 1.5 cm from each other.
Biopsy tissue taken from the psoriatic skin lesions will be divided for histological and 
gene expression (summarised in Section 8.8).
Details of biopsy processing will be in the SRM.
8.8.2.
RNA Transcriptome Research
Transcriptome studies will be conducted using RNA-seq, and/or alternative equivalent 
technologies, which facilitates the simultaneous measurement of the relative abundances 
of thousands of ribonucleic acid (RNA) species resulting in a transcriptome profile for 
each skin sample. This will enable the evaluation of changes in transcriptome profiles 
that may correlate with biological response relating to psoriasis and medically related 
conditions or the action of GSK2982772.
The same samples may also be used to confirm findings by application of alternative 
technologies.


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8.8.3.
RNA Expression Research of a Subset of RNA Species 
RNA expression studies may be conducted using quantitative reverse transcriptase 
polymerase chain reaction (RT-qPCR), and/or alternative equivalent technologies, which 
can facilitate the simultaneous measurement of the relative abundances of RNA species 
resulting in a RNA expression profile for each skin sample. The RNAs assayed may be 
those involved with the pathogenesis of psoriasis; the absorption, distribution, 
metabolism, or excretion of GSK2982772; or in the participant’s response to 
GSK2982772. In addition, continuing research may identify other proteins or regulatory 
RNAs that may be involved in the response to GSK2982772 or the pathogenesis of 
psoriasis. The RNAs that code for these proteins and/or regulatory RNAs may also be 
studied. This will enable the evaluation of changes in RNA expression profiles that may 
correlate with biological response relating to psoriasis and medically related conditions or 
the action of GSK2982772.
8.8.4.
Proteome Research
Plasma proteome studies may be performed by 2-D gel separation, and/or peptide mass 
mapping, or an alternative equivalent procedure. Proprietary algorithms and standard 
statistical techniques, such as analysis of variance (ANOVA) and analysis of covariance 
(ANCOVA), will be used to identify individual proteins exhibiting statistically 
significantly different changes in their levels between samples and/or between groups of 
samples. These differentially expressed proteins will be identified by mass spectrometry 
or equivalent technology. This will enable the evaluation of changes in proteome profiles 
that may correlate with biological response relating to psoriasis and medically related 
conditions or the action of GSK2982772.
The samples may also be used to confirm findings by application of alternative 
technologies.
8.8.5.
Metabolome Research 
Blood plasma and/or serum metabolome studies will be performed by nuclear magnetic 
resonance (NMR), mass spectrometry (MS), liquid chromatography – mass spectrometry 
(LC-MS), gas chromatography – mass spectrometry (GC MS), and/or Fourier transform 
mass spectrometry (FTMS), and equivalent methods. This may include analysis of 
identified or uncharacterized metabolites and lipids that are known to be or emerge in the 
future as important in the pathogenesis of psoriasis or a related medical condition, the 
participant’s response to GSK2982772, or AE.
8.9.
Medical Resource Utilization and Health Economics
Medical Resource Utilization and Health Economics parameters are not evaluated in this 
study.


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9.
STATISTICAL CONSIDERATIONS
9.1.
Statistical Hypotheses
The primary objective of this study is to determine the efficacy of GSK2982772 960 mg 
MR QD compared with placebo following 12 weeks of treatment, this will be assessed 
using the estimates of PASI75 response at Week 12.
There will be no adjustment for multiplicity.
9.2.
Sample Size Determination
Approximately 32 participants will be screened to achieve 21 randomly enrolled to either 
GSK2982772 or placebo in a 2:1 allocation ratio. Replacement participants may be 
randomised (up to approximately 6) into the study at the discretion of the Sponsor, to 
ensure that approximately 21 have completed the Week 4 visit.
The primary efficacy endpoint is PASI75 response (achieving ≥75% improvement from 
Baseline in PASI score)at Week 12. The sample size is based on the difference in PASI75 
response rates between GSK2982772 960 mg and placebo. 
At Week 12, the expected PASI75 response rate on placebo is approximately 7%. This value 
represents typical responses seen in this indication [Papp, 2018; Checchio, 2017]. 
The study will leverage historical placebo data to reduce the uncertainty in the placebo 
response rate and thus improve operating characteristics of the trial. The historical placebo
data will be combined with the trial data via a Bayesian analysis. 
With a sample size of 21 participants there is approximately 99% probability of achieving 
a >97.5% posterior probability that the true treatment difference over placebo >0%, based 
on an assumed placebo response of 7% and an assumed true treatment difference of 55% 
and incorporating informative historical placebo data into the analysis. For the placebo 
arm an informative Beta (3.5, 46.5) distribution with an effective sample size of 50 
participants was used. For the active arm a vague Beta (1/3, 1/3) prior is used.
An equivalent power calculation, assuming placebo response of 7% and using a two-sided 
significance level of 0.05, the proposed sample size of 21 participants gives >90% power to 
detect a 55% difference in PASI75 response rates between GSK2982772 960 mg versus 
placebo at Week 12 using a Newcombe score test [Newcombe, 1998] (assuming no 
historical data is borrowed).
No sample size re-estimation is planned for this study. 
Note: "Enrolled" means a participant's, or their legally acceptable representative’s, 
agreement to participate in a clinical study following completion of the informed consent 
process. Potential participants who are screened for the purpose of determining eligibility 
for the study, but do not participate in the study, are not considered enrolled, unless 
otherwise specified by the protocol. 


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9.3.
Populations for Analyses
The following populations are defined:
Population
Description
Screened 
All participants who were screened for eligibility.
Enrolled
All participants who signed the ICF, passed screening and were 
eligible for randomisation (regardless of whether the participant 
went on to be randomised).
Randomised
All participants who were randomly assigned to study intervention 
in the study. Participant must have signed ICF and passed 
screening. 
Data will be reported according to the randomised study 
intervention.
Intent to Treat (ITT)
All randomised participants who received at least one dose of 
study treatment. Data will be reported according to the 
randomised study intervention.
Safety
All randomized participants who receive at least 1 dose of any 
study treatment. Data will be reported according to the actual 
study intervention received.
COVID-19
All participants in the Safety set who had a confirmed, probable or 
suspected COVID-19 case diagnosis.
9.4.
Statistical Analyses
The statistical analysis plan (SAP) will be finalized prior to the first unblinded data look
(interim analysis) and it will include a more technical and detailed description of the 
statistical analyses described in this section. This section is a summary of the planned 
statistical analyses of the most important endpoints including primary and key secondary 
endpoints.
9.4.1.
Primary Analyses
Efficacy analyses will be based on the ITT population unless stated otherwise in the SAP. 
The primary analysis will assess the difference in PASI75 response rates between 
GSK2982772 960 mg and placebo at Week 12. A Bayesian logistic regression analysis of 
the difference in PASI75 response rates at Week 12 will be conducted to calculate 
posterior probabilities that the true effect of GSK2982772 relative to placebo is greater 
than a range values of interest. 
An informative prior will be used for the placebo arm to leverage relevant historical 
placebo data into the analysis. It is expected that this prior will be a Beta (3.5, 46.5)


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distribution, giving the historical data an effective sample size of 50 participants. Further
emerging placebo data may be incorporated into the prior distribution for the placebo arm 
prior to breaking the study blind. A non-informative prior will be used for the PASI75 
response rate on GSK2982772. 
Participants who discontinue early or have missing PASI data at any visit will be treated 
as PASI75 non-responders at that time point (regardless of their response at previous 
visits). Sensitivity analyses will be conducted to investigate the impact of this approach to 
handling missing data.
9.4.2.
Secondary Analyses
Secondary analyses will be based on the ITT population unless stated otherwise in the 
SAP.
The proportion of participants achieving additional PASI responder endpoints of interest 
(PASI50/90/100) will be summarised by treatment arm and visit.
Differences between treatment groups and associated confidence intervals at each visit 
will be presented. Newcombe score confidence intervals will be calculated.
Change from Baseline in both PASI score and BSA over time will be analysed using a 
mixed model repeated measures (MMRM) approach to account for the repeated visits per 
participant. Log transformations will be applied if appropriate. Summary statistics by 
treatment and visit will also be provided.
The sIGA scores will be summarised as categorical data with the proportion of 
participants achieving each result being presented by treatment group and visit. 
A population analysis will be implemented to describe the PASI score (change from 
baseline and absolute) versus time course (up to Week 12) using a longitudinal model in 
order to predict the PASI Score at Week 16 (additional time point of interest for 
comparison to competitors)The model structure will be dependent on the emerging data.
.
9.4.2.1.
Pharmacokinetic Analysis
GSK2982772 plasma concentrations will be summarised descriptively by visit.
9.4.2.2.
Pharmacokinetic/Pharmacodynamic Analysis
Exploratory plots will be presented for individual and/or pooled plasma concentration 
versus change from Baseline and/or absolute PASI score.  If data permit, potential 
association between systemic exposure of GSK2982772 and PASI score may be studied
using linear or non-linear models, as appropriate.  Exposure-response may also be 
evaluated for other efficacy or PD biomarkers.


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9.5.
Interim Analyses
An interim analysis is planned to occur when at least six participants on GSK2982772 
have completed the Week 12 visit or discontinued study treatment to aid internal decision
making around subsequent GSK2982772 trials. The study may be stopped for futility if 
the probability of a positive outcome at the end of the trial is low based on the data 
available at the interim. There is no plan to stop the trial early based on positive efficacy 
data. 
The data will be reviewed by an internal DRC. The committee will include the study 
statistician, the study pharmacokineticist and a limited number of GSK individuals. The 
charter will identify the specific individuals to form part of the DRC, as well as detail the
data to be reviewed, planned analyses, guidelines for the decision rules to be followed
and a dissemination plan for interim decisions.
The interim will focus on efficacy data including, but not limited to, PASI response rates 
and change in PASI score from Baseline.
The SAP and data review charter will describe the planned interim analyses in greater 
detail.
Safety monitoring of blinded data will be conducted by the internal GSK Safety Review 
Team (SRT) at regular intervals throughout the study, see Section 8.2.
9.6.
Data Review Committee (DRC)
An internal DRC will review data from the Interim Analysis as detailed in Section 9.5.


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10.
SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations
10.1.1.
Regulatory and Ethical Considerations

This study will be conducted in accordance with the protocol and with:

Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical 
Guidelines

Applicable International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical 
Practice (GCP) Guidelines

Applicable laws and regulations

The protocol, protocol amendments, ICF, Investigator’s Brochure, and other 
relevant documents (e.g., advertisements) must be submitted to an IRB/IEC by 
the Investigator and reviewed and approved by the IRB/IEC before the study is 
initiated. 

Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants. 

The Investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/EC

Notifying the IRB/IEC of SAE or other significant safety findings as 
required by IRB/IEC procedures

Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 code of federal regulations (CFR), ICH guidelines, the 
IRB/IEC, European regulation 536/2014 for clinical studies (if applicable), 
and all other applicable local regulations
10.1.2.
Financial Disclosure
Investigators and sub-Investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study.


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10.1.3.
Informed Consent Process

The Investigator or his/her representative will explain the nature of the study to 
the participant or his/her legally authorized representative and answer all 
questions regarding the study. 

Participants must be informed that their participation is voluntary. Participants 
or their legally authorized representative will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study center. 

The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent 
must also sign the ICF.

Participants must be re-consented to the most current version of the ICF(s) 
during their participation in the study. 

A copy of the ICF(s) must be provided to the participant or the participant’s 
legally authorized representative. 
Participants who are rescreened are required to sign a new ICF.
GSK (alone or working with others) may use participant’s coded study data and samples 
and other information to carry out this study; understand the results of this study; learn 
more about GSK2982772 or about the study disease; publish the results of these research 
efforts; work with government agencies or insurers to have GSK2982772 approved for 
medical use or approved for payment coverage.
The ICF contains a separate section that addresses the use of participant data and 
remaining samples for optional further research. The Investigator or authorised designee 
will inform each participant of the possibility of further research not related to the 
study/disease. Participants will be told that they are free to refuse to participate and may 
withdraw their consent at any time and for any reason during the storage period. A 
separate tick box will be required to document a participant's agreement to allow any 
participant data and/or remaining leftover samples to be used for further research not 
related to the study/disease. Participants who decline further research will tick the 
corresponding “No” box.
10.1.4.
Data Protection

Participants will be assigned a unique identifier by the sponsor. Any participant 
records or datasets that are transferred to the sponsor will contain the identifier 
only; participant names or any information which would make the participant 
identifiable will not be transferred. 

The participant must be informed that his/her personal study-related data will be 
used by the sponsor in accordance with local data protection law. The level of 


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disclosure must also be explained to the participant who will be required to give 
consent for their data to be used as described in the informed consent. 

The participant must be informed that his/her medical records may be examined 
by Clinical Quality Assurance auditors or other authorized personnel appointed 
by the sponsor, by appropriate IRB/IEC members, and by inspectors from 
regulatory authorities.
10.1.5.
Committees Structure
GSK will have a DRC to review data at the interim analysis and a SRT to review ongoing 
blinded safety data, refer to Section 9.5 for more details. 
10.1.6.
Dissemination of Clinical Study Data

Where required by applicable regulatory requirements, an Investigator signatory 
will be identified for the approval of the clinical study report.  The Investigator
will be provided reasonable access to statistical tables, figures, and relevant 
reports and will have the opportunity to review the complete study results at a 
GSK site or other mutually-agreeable location.

GSK will also provide the Investigator with the full summary of the study 
results.  The Investigator is encouraged to share the summary results with the 
study participants, as appropriate.

GSK will provide the Investigator with the randomization codes for their site 
only after completion of the full statistical analysis.

The procedures and timing for public disclosure of the protocol and results 
summary and for development of a manuscript for publication for this study will 
be in accordance with GSK Policy.

GSK intends to make anonymized patient-level data from this trial available to 
external researchers for scientific analyses or to conduct further research that 
can help advance medical science or improve patient care. This helps ensure the 
data provided by trial participants are used to maximum effect in the creation of 
knowledge and understanding

A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge.
10.1.7.
Data Quality Assurance

All participant data relating to the study will be recorded on printed or electronic 
CRF unless transmitted to the sponsor or designee electronically (e.g., 
laboratory data). The Investigator is responsible for verifying that data entries 
are accurate and correct by physically or electronically signing the CRF. 

The Investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF. 

Quality tolerance limits (QTLs) will be pre-defined in the QTL plan to identify 
systematic issues that can impact participant safety and/or reliability of study 


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results. These pre-defined parameters will be monitored during and at the end of 
the study and all deviations from the QTLs and remedial actions taken will be 
summarized in the clinical study report.

The Investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents. 

Monitoring details describing strategy (e.g., risk-based initiatives in operations 
and quality such as Risk Management and Mitigation Strategies and Analytical 
Risk-Based Monitoring), methods, responsibilities and requirements, including 
handling of noncompliance issues and monitoring techniques (central, remote, 
or on-site monitoring) are provided in the Monitoring Plan.

The sponsor or designee is responsible for the data management of this study 
including quality checking of the data. 

The sponsor assumes accountability for actions delegated to other individuals 
(e.g., Contract Research Organizations).

Study monitors will perform ongoing source data verification to confirm that 
data entered into the CRF by authorized site personnel are accurate, complete, 
and verifiable from source documents; that the safety and rights of participants 
are being protected; and that the study is being conducted in accordance with the 
currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements. 

Records and documents, including signed ICF, pertaining to the conduct of this 
study must be retained by the Investigator for 25 years from the issue of the final 
Clinical Study Report (CSR)/ equivalent summary unless local regulations or 
institutional policies require a longer retention period. No records may be 
destroyed during the retention period without the written approval of the 
sponsor. No records may be transferred to another location or party without 
written notification to the sponsor. 
10.1.8.
Source Documents

Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator site.

Data reported on the CRF or entered in the electronic case report form (eCRF)
that are transcribed from source documents must be consistent with the source 
documents or the discrepancies must be explained. The Investigator may need to 
request previous medical records or transfer records, depending on the study. 
Also, current medical records must be available.

Definition of what constitutes source data can be found in the SRM


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10.1.9.
Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the first site open and will be the study start date.
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The Investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or Investigator may include 
but are not limited to:

Failure of the Investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines

Inadequate recruitment of participants by the Investigator

Discontinuation of further study intervention development
If the study is prematurely terminated or suspended, the sponsor shall promptly inform 
the Investigators, the IECs/IRBs, the regulatory authorities, and any contract research 
organization(s) used in the study of the reason for termination or suspension, as specified 
by the applicable regulatory requirements. The Investigator shall promptly inform the 
participant and should assure appropriate participant therapy and/or follow-up.
10.1.10.
Publication Policy

The results of this study may be published or presented at scientific meetings. If 
this is foreseen, the Investigator agrees to submit all manuscripts or abstracts to 
the sponsor before submission. This allows the sponsor to protect proprietary 
information and to provide comments.

The sponsor will comply with the requirements for publication of study results. 
In accordance with standard editorial and ethical practice, the sponsor will 
generally support publication of multicenter studies only in their entirety and not 
as individual site data. In this case, a coordinating Investigator will be 
designated by mutual agreement.

Authorship will be determined by mutual agreement and in line with 
International Committee of Medical Journal Editors authorship requirements.


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10.2.
Appendix 2: Clinical Laboratory Tests

The tests detailed in Table 3 will be performed by the central laboratory. 

Local laboratory results are only required in the event that the central laboratory 
results are not available in time for either study intervention administration 
and/or response evaluation. If a local sample is required, it is important that the 
sample for central analysis is obtained at the same time.

Protocol-specific requirements for inclusion or exclusion of participants are 
detailed in Section 5 of the protocol.

Additional tests may be performed at any time during the study as determined 
necessary by the Investigator or required by local regulations.

Pregnancy Testing 

Refer to Section 5.1 Inclusion Criteria for Screening pregnancy criteria.

Pregnancy testing will be conducted as appropriate per Section 1.3 Schedule 
of Activities.

Additional serum or urine pregnancy tests may be performed, as determined 
necessary by the Investigator or required by local regulation, to establish the 
absence of pregnancy at any time during the participant's participation in the 
study.
Table 3
Protocol-Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters
Hematology
Platelet Count
Red blood cell (RBC)
Indices:
Mean corpuscular 
volume (MCV)
Mean corpuscular 
hemoglobin (MCH)
White blood cell 
(WBC) count with 
Differential:
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
RBC Count
Hemoglobin
Hematocrit
Clinical Chemistry1
Blood urea 
nitrogen (BUN)
Potassium
Aspartate 
Aminotransferase
(AST)/ Serum 
Glutamic-
Oxaloacetic 
Transaminase
(SGOT)
Total and direct 
bilirubin
Creatinine
Sodium
Alanine 
Aminotransferase
(ALT)/ Serum 
Glutamic-Pyruvic 
Total Protein


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Laboratory 
Assessments
Parameters
Transaminase
(SGPT)
Glucose2
Calcium
Alkaline 
phosphatase
Albumin
Triglycerides2
Total 
cholesterol2
High Density 
Lipoproteins
(HDL)
cholesterol2
Low Density 
Lipoproteins
(LDL)
cholesterol2
Glycated 
haemoglobin 
(HbA1c)
Insulin2
Routine Urinalysis

Specific gravity

pH, glucose, protein, blood, ketones by dipstick

Microscopic examination (if blood or protein is abnormal)
Other Screening 
Tests

COVID-19 (SARS-CoV-2)

HIV

Hepatitis B surface antigen (HBsAg)

Hepatitis B core antibody (HBcAb)

Hepatitis C (Hep C antibody) (and hepatitis C RNA in participants with 
positive Hepatitis C antibody due to prior resolved)

QuantiFERON-TB Gold Plus test

Tuberculin skin test (if QuantiFERON-TB Gold Plus test is 
indeterminant)

Follicle-stimulating Hormone (FSH) and estradiol (as needed in 
women of non-child bearing potential only)

Serum human chorionic gonadotropin (hCG - as needed for women of 
child bearing potential) to be done at Screening and if urine test 
positive or ambiguous at other timepoints in study.
Estimated glomerular filtrate rate (eGFR) will be calculated using the 
chronic kidney disease epidemiology collaboration (CKD-EPI) formula.
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 7.1 and Appendix 6. All events of ALT 3 ×ULN and bilirubin 2 × 
ULN (>35% direct bilirubin) or ALT 3 × ULN and international normalized ratio (INR) >1.5, if INR measured, 
which may indicate severe liver injury (possible Hy’s Law), must be reported as an SAE (excluding studies of 
hepatic impairment or cirrhosis).
2.
Overnight fasting required. Any abnormal result for glucose or lipids may be repeated at the discretion of the 
Investigator.


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10.3.
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting
10.3.1.
Definition of AE
AE Definition

An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study intervention, whether or not 
considered related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (e.g., ECG, radiological scans, vital signs 
measurements), including those that worsen from Baseline, considered clinically 
significant in the medical and scientific judgment of the Investigator (i.e., not 
related to progression of underlying disease).

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae.

"Lack of efficacy" or "failure of expected pharmacological action" per se will not 
be reported as an AE or SAE. Such instances will be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting 
from lack of efficacy will be reported as AE or SAE if they fulfill the definition of 
an AE or SAE. 


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Events NOT Meeting the AE Definition 

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by 
the Investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.

Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen.
10.3.2.
Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease).
A SAE is defined as any untoward medical occurrence that, at any dose:
o
Results in death
o
Is life-threatening
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe.
Requires inpatient hospitalization or prolongation of existing hospitalization

In general, hospitalization signifies that the participant has been detained 
(usually involving at least an overnight stay) at the hospital or emergency ward 
for observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AE. If a complication prolongs hospitalization or 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.
Results in persistent or significant disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.


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
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 with or 
prevent everyday life functions but do not constitute a substantial disruption.
Is a congenital anomaly/birth defect
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious.

Examples of such events include invasive or malignant cancers, intensive 
treatment 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.
10.3.3.
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

Valvulopathy

Pulmonary hypertension

Cerebrovascular events/stroke and transient ischemic attack

Peripheral arterial thromboembolism

Deep venous thrombosis/pulmonary embolism

Revascularization


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10.3.4.
Recording and Follow-Up of AE and SAE
AE and SAE Recording

When an AE/SAE occurs, it is the responsibility of the Investigator to review all 
documentation (e.g. hospital progress notes, laboratory, and diagnostics reports) 
related to the event.

The Investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the Investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the GSK /AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to GSK.

The Investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The Investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 

Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed 
as severe should not be confused with an SAE. Severe is a category utilized for 
rating the intensity of an event; and both AE and SAE can be assessed as severe.
An event is defined as ‘serious’ when it meets at least 1 of the predefined 
outcomes as described in the definition of an SAE, NOT when it is rated as severe.
Other measures to evaluate AE and SAE may be utilized (e.g. National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI-CTCAE).  
Assessment of Causality

The Investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE.

A "reasonable possibility" of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.


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


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10.3.5.
Reporting of SAE to GSK
SAE Reporting to GSK via Electronic Data Collection Tool

The primary mechanism for reporting SAE to GSK will be the electronic data 
collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as it becomes 
available.

The Investigator or medically-qualified sub-investigator must show evidence 
within the eCRF (e.g., check review box, signature, etc.) of review and verification 
of the relationship of each SAE to IP/study participation (causality) within 72 
hours of SAE entry into the eCRF.

After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives 
updated data on a previously reported SAE after the electronic data collection tool 
has been taken off-line, then the site can report this information on a paper SAE 
form (see next section).

Contacts for SAE reporting can be found in the SRM.
SAE Reporting to GSK via Paper CRF

Email transmission of the scanned SAE paper CRF is the preferred method to 
transmit this information to GSK.

GSK Contacts and instructions for paper SAE reporting can be found in the Study 
Reference Manual.


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10.4.
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information
10.4.1.
Definitions
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below).
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation should 
be considered.
Women in the following categories are not considered WOCBP
Premenarchal
Premenopausal female with 1 of the following:

Documented hysterectomy

Documented bilateral salpingectomy

Documented bilateral oophorectomy
For individuals with permanent infertility due to an alternate medical cause other 
than the above, (e.g., mullerian agenesis, androgen insensitivity), Investigator
discretion should be applied to determining study entry.
Note: Documentation can come from the site personnel’s: review of the 
participant’s medical records, medical examination, or medical history interview.
Postmenopausal female

A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. 

A high follicle stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not 
using hormonal contraception or hormonal replacement therapy (HRT). 
However, in the absence of 12 months of amenorrhea, confirmation with 
more than one FSH measurement is required. 

Females on HRT and whose menopausal status is in doubt will be required to 
use one of the non-estrogen hormonal highly effective contraception methods 
if they wish to continue their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before 
study enrolment.


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10.4.2.
Contraception Guidance

CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE:

Highly Effective Methodsb That Have Low User Dependency Failure rate of <1% per 
year when used consistently and correctly.

Implantable progestogen-only hormone contraception associated with inhibition of 
ovulationc

Intrauterine device (IUD)

Intrauterine hormone-releasing system (IUS)c

Bilateral tubal occlusion

Vasectomized partner

Note: Vasectomized partner is a highly effective contraceptive method provided that 
the partner is the sole sexual partner of the woman of childbearing potential and the 
absence of sperm has been confirmed. If not, an additional highly effective method of 
contraception should be used. Spermatogenesis cycle is approximately 90 days.

Highly Effective Methods b That Are User Dependent Failure rate of <1% per year when 
used consistently and correctly.

Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationc

oral

intravaginal

transdermal

injectable

Progestogen-only hormone contraception associated with inhibition of ovulationc

oral

injectable

Sexual abstinence

Note: Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with 
the study intervention. The reliability of sexual abstinence needs to be evaluated in 
relation to the duration of the study and the preferred and usual lifestyle of the 
participant
a.
Contraceptive use by men or women should will be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies.
b.
Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those 
when used consistently and correctly.
c.
,Male condoms must be used in addition to hormonal contraception. If locally required, in accordance with 
Clinical Trial Facilitation Group (CTFG) guidelines, acceptable contraceptive methods are limited to those 
which inhibit ovulation as the primary mode of action.
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception. Male 
condom and female condom should not be used together (due to risk of failure with friction)


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10.4.3.
Collection of Pregnancy Information:
Male participants with partners who become pregnant

Investigator will attempt to collect pregnancy information on any male participant’s 
female partner of a male study participant who becomes pregnant while participating 
in this study. This applies only to male participants who receive GSK2982772.

After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the Investigator will record pregnancy information on the 
appropriate form and submit it to GSK within 24 hours of learning of the partner’s 
pregnancy. 

The female partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to GSK.

Generally, follow-up will be no longer than 6 to 8 weeks following the estimated
delivery date. Any termination of the pregnancy will be reported regardless of fetal 
status (presence or absence of anomalies) or indication for procedure. 
Female Participants who become pregnant

Investigator will collect pregnancy information on any female participant, who 
becomes pregnant while participating in this study. 

The initial information will be recorded on the appropriate form and submitted to 
GSK within 24 hours of learning of a participant's pregnancy. 

Participant will be followed to determine the outcome of the pregnancy. The 
Investigator will collect follow-up information on participant and neonate, which 
will be forwarded to GSK. Generally, follow-up will not be required for longer than 
6 to 8 weeks beyond the estimated delivery date.  

Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for procedure. 

While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE. 

A spontaneous abortion (occurring at < 22 weeks gestational age) or still birth 
(occurring at > 22 weeks gestational age) 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 intervention by the Investigator, will be reported to 
GSK as described in Appendix 3. While the Investigator is not obligated to actively 
seek this information in former study participants, he or she may learn of an SAE 
through spontaneous reporting. 
Any female participant who becomes pregnant while participating  

will discontinue study intervention or be withdrawn from the study.


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10.5.
Appendix 5: Genetics
USE/ANALYSIS OF DNA

Genetic variation may impact a participant’s response to study intervention, 
susceptibility, severity and progression of disease. Variable response to study 
intervention may be due to genetic determinants that impact drug absorption, 
distribution, metabolism, and excretion; mechanism of action of the drug; disease 
etiology; and/or molecular subtype of the disease being treated. Therefore, where 
local regulations and IRB/IEC allow, a blood sample will be collected for DNA 
analysis

DNA samples will be used for research related to GSK2982772 (or study 
interventions of this drug class), and psoriasis (or immune-inflammatory and related 
diseases). They may also be used to develop tests/assays including diagnostic tests
related to GSK2982772 (or study interventions of this drug class), and psoriasis (or 
immune-inflammatory and related diseases). Genetic research may consist of the 
analysis of one or more candidate genes or the analysis of genetic markers 
throughout the genome as appropriate.

Additional analyses of DNA samples may be conducted if it is hypothesized that this 
may help further understand the clinical data. 

The samples may be analyzed as part of a multi-study assessment of genetic factors 
involved in the response to GSK2982772 (or study interventions of this class), and 
psoriasis (or immune-inflammatory and related diseases). The results of genetic 
analyses may be reported in the clinical study report or in a separate study summary.

The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality. 

The samples will be retained while research on GSK2982772 in psoriasis (or study 
interventions of this drug or drug class in immune-inflammatory and related 
diseases) continues but no longer than 15 years after the last participant last visit or 
other period as per local requirements.


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10.6.
Appendix 6: Liver Safety: Required Actions and Follow-up 
Assessments
Phase 2 liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology.
Phase 2 liver chemistry stopping criteria and required follow-up assessments
Liver Chemistry Stopping Criteria 
ALT-absolute
ALT 5xULN
ALT Increase
ALT 3xULN persists for 4 weeks
Bilirubin1, 2
ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin)
INR2
ALT 3xULN and INR>1.5
Cannot 
Monitor
ALT 3xULN and cannot be monitored weekly for 4 weeks
Symptomatic3
ALT 3xULN associated with symptoms (new or worsening) believed to be 
related to liver injury or hypersensitivity
Required Actions and Follow-up Assessments 
Actions
Follow-up Assessments

Immediately discontinue study intervention 

Report the event to GSK within 24 hours

Complete the liver event CRF and complete 
an SAE data collection tool if the event also 
meets the criteria for an SAE2

Perform liver chemistry event follow-up
assessments 

Monitor the participant until liver chemistries
resolve, stabilize, or return to within Baseline 
(see MONITORING below)

Do not restart/rechallenge participant with 
study intervention unless allowed per 
protocol and GSK Medical Governance 
approval is granted (see below).

If restart/rechallenge not allowed per 
protocol or not granted, permanently 
discontinue study intervention and continue 

Viral hepatitis serology4

Obtain INR and recheck with each liver 
chemistry assessment until the 
transaminases values show downward 
trend

Obtain blood sample for 
pharmacokinetic (PK) analysis, with 
timing to be guided by clinical 
pharmacokinetics representative on a 
case by case basis, 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


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participant 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 INR) and 
perform liver event follow-up assessments 
within 24 hours

Monitor participant 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 INR) and 
perform liver event follow-up assessments 
within 24-72 hours 

Monitor participant weekly until liver 
chemistries resolve, stabilize or return to 
within Baseline

Record the appearance or worsening of 
clinical symptoms of liver injury, or 
hypersensitivity, on the AE report form

Record use of concomitant medications 
on the concomitant medications report 
form including acetaminophen, herbal 
remedies, other over the counter 
medications.

Record alcohol use on the liver event 
alcohol intake case report form (CRF) 
page 
For bilirubin or INR criteria:

Anti-nuclear antibody, anti-smooth 
muscle antibody, Type 1 anti-liver kidney 
microsomal antibodies, and quantitative 
total immunoglobulin G (IgG) or gamma 
globulins.

Serum acetaminophen adduct high 
performance liquid chromatography 
(HPLC) assay (quantifies potential 
acetaminophen contribution to liver 
injury in participants with definite or likely 
acetaminophen use in the preceding 
week [James, 2009]). 

Liver imaging (ultrasound, magnetic 
resonance, or computerised 
tomography) and /or liver biopsy to 
evaluate liver disease; complete Liver 
Imaging and/or Liver Biopsy CRF pages.
1.
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study intervention for that participant if ALT 3xULN and bilirubin 2xULN. 
Additionally, if serum bilirubin fractionation testing is unavailable, record presence of detectable urinary 
bilirubin on dipstick, indicating direct bilirubin elevations and suggesting liver injury. 
2.
All events of ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin) or ALT 3xULN and INR>1.5, which 
may indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE (excluding studies of 
hepatic impairment or cirrhosis); the INR threshold value stated will not apply to participants receiving 
anticoagulants
3.
New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or believed to be related to hypersensitivity (such as fever, rash or 
eosinophilia)
4.
Includes: Hepatitis A Immunoglobulin M (IgM) antibody; HbsAg and HBcAb; Hepatitis CRNA; Cytomegalovirus 
IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain heterophile antibody or 
monospot testing); Hepatitis E IgM antibody 
5.
PK sample may not be required for participants known to be receiving placebo or non-GSK comparator 
interventions. Record the date/time of the PK blood sample draw and the date/time of the last dose of study 
intervention prior to pk blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the 
participant’s best approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot 


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be collected in the time period indicated above, do not obtain a PK sample. Instructions for sample handling and 
shipping are in the SRM.
Reference
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, et al. 
Pharmacokinetics of Acetaminophen-Adduct in Adults with Acetaminophen Overdose 
and Acute Liver Failure. Drug Metab Dispos 2009; 37:1779-1784.


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10.7.
Appendix 7: COVID-19 Appendix
COVID-19 pandemic may impact the conduct of clinical studies. Challenges may arise 
from quarantines, site closures, travel limitations, interruptions to the supply chain for the 
investigational product or other considerations if site personnel or study participants 
become infected with COVID-19. These challenges may lead to difficulties in meeting 
protocol-specified procedures, including administering or using the investigational 
product or adhering to protocol-mandated visits and laboratory/diagnostic testing.
This protocol appendix outlines measures that may be applicable for any site impacted by 
the COVID-19 pandemic. The purpose of the appendix is to provide information on the 
measures to be taken to protect participants’ safety, welfare and rights, and promote data 
integrity.
These measures will remain in place until until study completion.
STUDY PROCUDURES DURING COVID-19 PANDEMIC
During the special circumstances caused by the COVID-19 pandemic, you should 
consider specific public health guidance, the impact of any travel restrictions 
implemented by local/regional health authorities and local institutions, and individual 
benefit /risk when making enrollment and treatment decisions for trial participants.
Guidance on how to deal with participants who develop COVID-19 symptoms during the 
study are described in the SRM.
As outlined in Section 8, protocol waivers or exemptions are not allowed and every effort 
should be made to adhere to protocol-specified assessments for participants on study 
intervention, including follow up. However, when not possible, for the duration of these 
special circumstances, the following measures may be implemented for enrolled 
participants. 

Clinical investigators should document in site files and in participant notes as 
appropriate how restrictions related to COVID-19 led to the changes in study 
conduct and duration of those changes and indicate which trial participants were 
impacted and how those trial participants were impacted (as per the current local 
COVID-19 related regulatory guidance).
Missing protocol required data/visits due to COVID-19 should be noted in participant 
notes, captured in the eCRF and recorded as a COVID-19 protocol deviation.
Protocol Defined Procedures/Visits:

The protocol defined interval for the collection of samples during the follow-up 
visit (see Section 1.3 Schedule of Activities), may be extended up to a maximum 
length of 14 days. 
Study Interventions:

If allowed by country regulation/ethics, then study intervention (including rescue 
study medication and ancillary supplies related to IMP administration) can be 
shipped direct-to-patient (DTP) from the investigational site to the participant’s 
home address. The process for this shipment must be agreed with GSK who will 


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provide the relevant documentation and links to courier sites required to ensure 
shipments are adequately temperature controlled (if required) throughout 
transportation.

The Principal Investigator assumes Good Clinical Practice (GCP) responsibilities for 
IMP handling and the medical control for dispensing to patients. Site Staff should 
document the dispensing in the Dispensing/Accountability Logs adding a comment 
that this was a DTP dispensing.

Compliance with study intervention administration will be verified through 
observation by study staff or trained home healthcare professionals. 

In some cases, trial participants who no longer have access to investigational product 
or the investigational site may need additional safety monitoring (e.g., on withdrawal 
of an active investigational treatment).
Data Management/Monitoring:

Diary cards may be transmitted from and to the investigator by electronic mail and or 
conventional mail. If copies/scans of completed diaries are sent to the investigator by 
electronic mail, the participant should be instructed to maintain the original 
documents and to return them to the site when a visit to the site will be allowed.

If a situation arises where on-site monitoring is no longer permitted, GSK will 
consider remote Source Data Verification/Source Document Review (SDV/SDR) 
where permitted by the clinical site/institution. Remote SDV/SDR will be proposed 
to study sites to meet a participant and/or critical quality need, e.g., to assess 
participant safety or to ensure data integrity. In case of remote SDV/SDR, GSK will 
work with the site to ensure participant privacy.

eCRF/CRF Final or Interim Sign off Process: The Principal Investigator (PI) is 
responsible for ensuring that the data within the eCRF casebook and any other data 
sources utilized during the study for each study participant is complete and 
consistent with source documents throughout the study (ICH GCP 4.9.1 4.9.2). The 
PI may sign/re-sign the eCRF from any computer/location by accessing InForm (or 
other eDC platform) using his/her unique eCRF log-in credentials. The PI may 
delegate this activity to another medically qualified and trained sub-investigator and 
this must be documented on the Delegation of Responsibilities (DoR) Log. It is 
recommended that the PI identifies a sub-investigator as a back-up for eCRF 
signatures. The sub-investigator must be appropriately trained on the protocol and 
eCRF requirements (with training documented), and the DoR log updated 
accordingly.

Essential Document Sign Off Process: If an investigator is unable to print and sign 
essential documents such as Protocol /Amendment signature page then Email 
approval can be accepted by replying to the relevant email that is sent by GSK.


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10.8.
Appendix 8: Abbreviations and Trademarks
Abbreviations
µg
Microgram
ACTH
Adrenocorticotropic Hormone
ADA
Anti-drug Antibody
AE
Adverse Event
ALS
Amyotrophic Lateral Sclerosis
ALT
Alanine Transaminase
ANCOVA
Analysis of covariance
ANOVA
Analysis of variance
AST
Aspartate Aminotransferase
AUC[0-24]
Area Under Concentration-Time Curve from 0 to 24 h
BCRP
Breast Cancer Resistance Protein
BID
Twice Daily
BMI
Body mass index
BSA
Body Surface Area
BUN
Blood urea nitrogen
CCL20
Chemokine Ligand 20
CD3
Cluster of Differentiation 3
CD11c
Cluster of Differentiation 11c
CFR
Code of Federal Regulations
CIOMS
Council for International Organizations of Medical Sciences
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
Cmax
Maximum Concentration
CNS
Central Nervous System
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
Coronovirus Disease 2019
CPK
Serum Creatine Phosphokinase
CRF
Case Report Form
CSR
Clinical Study Report
C-SSRS
Columbia Suicide Severity Rating Scale
CTFG
Clinical Trial Facilitation Group
CV
Cardiovascular
CXCL10
C-X-C Motif Chemokine 10
CYP
Cytochromes P450
DNA
Deoxyribonucleic Acid
DRC
Data Review Committee
DTP
Direct to Patient
ECG
Electrocardiogram 
eCRF
Electronic Case Report Form
eGFR
Estimated glomerular filtrate rate
EM
Experimental Medicine
E-R
Exposure Response Relationship
FDA
Food and Drug Administration


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FSH
Follicle-stimulating Hormone
FTiH
First Time in Human
FTMS
Fourier Transform Mass Spectrometry 
GC MS
Gas Chromatography Mass Spectrometry
GCP
Good Clinical Practice
GCSP
Global Clinical Safety and Pharmacovigilance
GFR
Glomerular Filtration Rate
GLP
Good Laboratory Practice
GP
General Practitioner
GSK
GlaxoSmithKline
HBcAb
Hepatitis B Core Antibody
HBsAg
Hepatitis B Surface Antigen
hCG
Human Chorionic Gonadotropin
HDL
High Density Lipoproteins
HIPAA
Health Insurance Portability and Accountability Act
HIV
Human Immunodeficiency Virus
HOMA
Homeostatic Model Assessment of Insulin Resistance
HPLC
High performance liquid chromatography
hr
Hour(s)
HRT
Hormone Replacement Therapy
IB
Investigator’s Brochure
ICF
Informed Consent Form
ICH 
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use
IEC
Independent Ethics Committee
IFN
Interferon
IFNγ
Interferon Gamma
IgG
Immunoglobulin G
IgM
Immunoglobulin M
IL
Interleukin
INR
International Normalized Ratio
IP
Investigational Product
IR
Immediate Release
IRB
Institutional Review Board
ITT
Intent to Treat
IUD
Intrauterine Device
IUS
Intrauterine Hormone-Releasing System
IV
Intravenous 
IVIVT
In vitro/ In vivo Translation
IWRS
Interactive Web Response System
K16
Keratin 16
kg
Kilogram
kg/m2
Kilogram per meter square
Ki67
Antigen KI-67
LAM
Lactational Amenorrhoea Method
LC-MS
Liquid Chromatography – Mass Spectrometry


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LDH
Lactate Dehydrogenase
LDL
Low Density Lipoproteins
MCH
Mean corpuscular hemoglobin
MCV
Mean corpuscular volume
MDMA
Methylenedioxymethamphetamine
MedDRA
Medical Dictionary for Regulatory Activities
mg
Milligrams
mL
Millilitre
mm
Millimetre
MIP1
Macrophage inflammatory protein 1 alpha
MIP1
Macrophage inflammatory protein 1 beta
MMRM
Mixed Model Repeated Measures
MR
Modified Release
mRNA
Messenger Ribonucleic Acid
MS
Multiple Sclerosis
MS
Mass Spectrometry
MSDS
Material Safety Data Sheet
msec
Milliseconds
MTX
Methotrexate
MV
Minute Volume
NOAEL
No Observed Adverse Effect Level
NMR
Nuclear Magnetic Resonance
NTI
Narrow Therapeutic Index
OAT3
Organic Anion Transporter 3
PASI
Psoriasis Area and Severity Index
PD
Pharmacodynamics
PDE4
Phosphodiesterase-4 inhibitor
Pgp
P-glycoprotein
PGx
Pharmacogenetics
PI
Principle Investigator
PK
Pharmacokinetics
PLSS
Psoriatic Lesion Severity Sum
PsO
Psoriasis
PSRAE
Possible Suicidality Related Adverse Event
PUVA
Psoralen and Ultraviolet A
QD
Once Daily
QTc
QT Duration Corrected for Heart Rate
QTcF
QT Duration Corrected for Heart Rate by Fridericia’s Formula
QTL
Quality Tolerance Limit
RA
Rheumatoid Arthritis
RAMOS NG
Randomization and Medication Ordering System New Generation
RBC
Red Blood Cell
RIP1
Receptor-Interacting Protein 1
RIPK1
Receptor-interacting serine/threonine-protein kinase 1
RNA
Ribonucleic acid
RNA-seq
Ribonucleic Acid sequencing


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RNA PCR
Ribonucleic Acid Polymerase Chain Reaction
RT-qPCR
Reverse Transcriptase Quantitative Polymerase Chain Reaction
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SARS-CoV-2
Severe Acute Respiratory Syndrome-Related Coronavirus 2
SIB
Suicidal Ideation Behavior
sIGA
Static Investigator’s Global Assessment of Disease Activity
SC
Subcutanous
SDR
Source Document Review
SDV
Source Data Verification
SGOT
Serum Glutamic-Oxaloacetic Transaminase
SGPT
Serum Glutamic-Pyruvic Transaminase
SoA
Schedule of Activities
SPF
Sun Protection Factor
SRM
Study Reference Manual
SRT
Safety Review Team
SUSAR
Suspected unexpected serious adverse reactions
TB
Tuberculosis
TEAR1
Target Engagement Assay RIP1
TH1
T Helper Type 1
TH17
T Helper Type 17
TH22
T Helper Type 22
TID
Three Times a Day
TLR
Toll-like Receptor
TNF
Tumor-Necrosis Factor
UGT
Uridine Glucoronyltransferase
ULN
Upper Limit of Normal
UV
Ultraviolet
UVB
Ultraviolet B
WBC
White Blood Cells
WOCBP
Women of Child Bearing Potential
Trademark Information
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
DiffCORE
Otezla
RAMOS NG
QuantiFERON-TB Gold PLUS


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10.9.
Appendix 9: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC).
Amendment [02]: (14-JUL-2020)
Overall Rationale for the Amendment: To include additional safety monitoring for 
participants in the study in response to the COVID-19 pandemic.
Section # and Name
Description of Change
Brief Rationale
Section 1.1 Study 
Synopsis
Section 9.2 Sample Size 
Determination
Revised the allowable number of replacement 
participants to be randomised (from up to 
approximately 3 to up to approximately 6) to 
ensure that approximately 21 have completed 
the Week 4 visit.
Amended due 
to anticipated 
impact of 
COVID 
pandemic on 
participant 
retention
Section 1.3 Schedule of 
Activities
Updated to add COVID-19 testing and 
monitoring of COVID-19 signs and symptoms.
Additional 
safety 
monitoring
Section 5.2 Exclusion 
Criteria
Added exclusion criteria to exclude study 
participants who have a positive test for SARS-
CoV-2 at screening or interaction with known 
COVID-19 positive contacts within 14 days prior 
to Day 1.
In addition, expanded exclusion criteria to 
exclude study participants that may have any 
other considerations (not just medical 
conditions) that, in the opinion of the 
Investigator, would put the participant at 
unacceptable risk.
Additional 
safety 
monitoring


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Section # and Name
Description of Change
Brief Rationale
Section 7.2 Participation 
Discontinuation/Withdrawal 
from the Study
Added new information to include that a
participant may be withdrawn from the study at 
any time if deemed to be demonstrating 
suspected, probable or confirmed COVID-19 
infection. 
Additional 
safety 
monitoring
Section 8.2.1 Physical 
Examination
Added text to remind Investigators to pay 
special attention to clinical signs related to 
previous serious illnesses or that could be 
related to infection (e.g. COVID-19).
Additional 
safety 
monitoring
Section 8.2.5 Suicidal 
Ideation and Behavior Risk 
Monitoring
Correction to clarify that the
‘Baseline/Screening’ version of the C-SSRS 
questionnaire is used at the Screening visit, and 
the ‘Since Last Visit’ version of the C-SSRS 
questionnaire is used at the Week 0/Day 1 visit.
Correction
Section 10.2 Clinical 
Laboratory Tests
COVID-19 (SARS-CoV-2) test added to list of 
Other Screening Tests.
Additional 
safety 
monitoring
Section 10.7 Appendix 7
Added to provide information on the measures 
to be taken to protect participants’ safety, 
welfare and rights, and promote data integrity.
To outline 
measures that 
may be 
applicable for 
any site 
impacted by the 
COVID-19 
pandemic. 
Section 10.8 Abbreviations 
and Trademarks
Updated accordingly with new terminology.
Administrative 
Update
Amendment [01]: (09-APR-2020)
Overall Rationale for the Amendment: To address a request from Health Canada for 
clarification of contraception requirements and the QTc formula to be used in the study. 
In addition, some administrative corrections have been made to the protocol.


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Section # and Name
Description of Change
Brief Rationale
Section 1.1 Synopsis
Brand name for apremilast added.
Grammatical corrections made.
Wording updated to indicate that the interim futility 
analysis will be conducted when at least six 
participants receiving GSK2982772 have completed 
the Week 12 visit or discontinued study 
treatment. 
Clarification
Correction
Clarification
Section 1.3 Schedule 
of Activities (SoA)
Footnotes updated to indicate that Day 85 is a non-
dosing day.
Text added to describe the circumstances in which 
biopsies would not be required at the Early 
Withdrawal visit.
Text added to indicate that Fridericia’s formula 
(QTcF) must be used for QTc correction.
Clarification
Clarification
Restricted 
protocol to use 
of Fridericia’s 
formula only in 
response to 
Health Canada 
feedback.


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Section # and Name
Description of Change
Brief Rationale
Section 4.1 Overall 
Design
Correction to duration of treatment period.
Wording updated to indicate that the interim futility 
analysis will be conducted when at least six 
participants receiving GSK2982772 have completed 
the Week 12 visit or discontinued study 
treatment. 
Correction
Clarification
Section 5.1 Inclusion 
Criteria
The Female Participants Decision Tree has been 
removed from inclusion criterion 7 and replaced with 
text to improve clarity for the justification of 
contraceptive use in this study.
Clarification
Section 5.2 Exclusion 
Criteria
Section 7.1.2
QTc Stopping Criteria
The option to use Bazett’s formula for QTc has 
been removed.
In response to 
Health Canada 
feedback, 
restricted 
protocol to use 
of Fridericia’s 
formula only.
Section 2.2 
Background
Section 2.3 
Benefit/Risk 
Assessment
Section 3 Objectives 
and Endpoints
Section 4.3 
Justification of Dose
Section 5.3.1 Meal 
and Dietary 
Restrictions
Section 6.3 Study 
Intervention 
Compliance
Section 8.8 
Biomarkers
Minor typographical errors have been corrected.
Corrections


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Section # and Name
Description of Change
Brief Rationale
Section 6.2 Measures 
to Minimise Bias: 
Randomisation and 
Blinding
Addition of text to make clear that randomisation will 
be stratified by prior biologic use.
Clarification
Section 8.2.1 Physical
Examinations
Addition of text to indicate that height is measured 
at screening only.
Clarification
Section 8.2.3 
Electrocardiograms
Approximate time to complete triplicate ECG 
readings has been updated.
To align with 
information in 
Section 7.1.2
Section 9.3 Population 
for Analysis
Addition of the definition of randomised population 
and clarification of other populations.
Clarification
Section 9.5 Interim 
Analyses
Wording updated to indicate that the interim futility 
analysis will be conducted when at least six 
participants receiving GSK2982772 have completed 
the Week 12 visit or discontinued study 
treatment.
Clarification
Section 10.1.7 Data 
Quality Assurance
Language added to indicate that quality tolerance 
limits have been pre-defined for the study.
Confirmation 
that Quality 
Tolerance 
Limits have 
been defined, to 
comply with ICH 
E6 R2 
guidelines.
Section 10.2 Clinical 
Laboratory Tests
Pregnancy testing language has been updated to 
align with the Schedule of Activities (SoA).
Clarification
Section 10.7 
Abbrevations and 
Trademarks
Otezla has been added to Trademark Information 
table.
Clarification


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11.
REFERENCES
Checchio T, Ahadieh S, Gupta P, Mandema J, Puig L, Wolk R et al. Quantitative 
Evaluations of Time-Course and Treatment Effects of Systemic Agents for Psoriasis: A 
Model-Based Meta-Analysis. Clin Pharmacol Ther. 2017;102(6):1006-1016.
Fredriksson T, Pettersson U. Severe psoriasis – oral therapy with a new retinoid. 
Dermatologica. 1978;157(4):238-44. 
GlaxoSmithKline Document Number 2018N363258_01 Study ID 203167. 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 participants with active plaque-type psoriasis. Report Date 15-Jan-
2019.
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/UCM292362.pdf
Griffiths C, Thaçi D, Gerdes S, Arenberger P, Pulka G, Kingo K et al. The EGALITY 
study: a confirmatory, randomized, double-blind study comparing the efficacy, safety and 
immunogenicity of GP2015, a proposed etanercept biosimilar, vs. the originator product 
in patients with moderate-to-severe chronic plaque-type psoriasis. Br J Dermatol. 2017; 
176(4):928-938. Br J Dermatol. 2017;176(4):928-938.
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. 
Lowes MA, Suárez-Fariñas M, Krueger JG. Immunology of psoriasis. Annu Rev 
Immunol. 2014;32:227-55. 
Morgan P, Van Der Graaf PH, Arrowsmith J, Feltner DE, Drummond KS, Wegner CD, 
et al. Can the flow of medicines be improved? Fundamental pharmacokinetic and 
pharmacological principles toward improving Phase II survival. Drug Discov. Today. 
2012;17:419-424.
Newcombe RG. Two-sided confidence intervals for the single proportion: comparison of 
seven methods. Stat Med. 1998;17:857-872. 
Ofengeim D, Yuan J. Regulation of RIP1 kinase signaling at the crossroads of 
inflammation and cell death. Nat Rev Mol Cell Biol. 2013;14:727-736. 
Otezla drug label information. Accessed Oct 22, 2019. 
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3acf6751-827d-11e2-9e96-
0800200c9a66. 
Papp K, Gordon K, Thaçi D, Morita A, Gooderham M, Foley P, et al. Phase 2 Trial of 
Selective Tyrosine Kinase 2 Inhibition in Psoriasis. N Engl J Med. 2018;379:1313-21.
U.S. Department of Health and Human Services, Food and Drug Administration (FDA). 
Guidance for Industry: Drug Interaction Studies – Study Design, Data Analysis, 


2019N420902_03
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93
Implications for Dosing, and Labeling Recommendations. Center for Drug Evaluation 
and Research, 10903 New Hampshire Avenue, Silver Spring, MD 20993; 2012.

SAP_001.pdf: 
 
 
 
 
Statistical Analysis Plan 
 
Study ID:  208022 
 
Official Title of Study: A multicentre, randomised, double-blind, placebo-controlled 
study to evaluate the efficacy and safety of GSK2982772 in participants with moderate to 
severe plaque psoriasis 
 
NCT ID: NCT04316585 
 
EudraCT: 2020-006008-18 
 
Date of Document: 28-JUN-2021 
 
 


 
C O N FI D E N TI A L  
T h e Gl a x o S mit h Kli n e gr o u p of c o m p a ni e s  
 
2 0 8 0 2 2  
 
 
1  
 
Di v isi o n 
: W orl d wi de De vel o p me nt  
I nf or m ati o n T y pe 
: Statistical A nal ysis Pla n ( S A P)  
Title P a ge  
Pr ot oc ol Title: A m ultic e ntre, ra n d o mise d, d o u ble-bli n d, place b o -c o ntr oll e d st u d y t o 
e val uate t he effic ac y a n d safet y of G S K 2 9 8 2 7 7 2 i n partici pa nts wit h m o derate t o se vere 
pla q ue ps oriasis   
Pr ot oc ol N u m ber: 2 0 8 0 2 2  
C o m p o u n d N u m ber: G S K 2 9 8 2 7 7 2  
S h ort Title: A st u d y t o  e val uate t he be n efit a n d safet y of G S K 2 9 8 2 7 7 2 i n m o derate t o 
se vere ps oriasis patie nts 
Effecti ve D ate: Refer t o D oc u me nt Date  
 
S p o ns or N a me: Gla x o S mit h Kli ne Researc h & De vel o p me nt Li mite d  
Re g ul at or y A ge nc y I de ntifier N u m ber(s)  
Re gistr y  
I D 
Cli ntri als. g ov  
N C T 0 4 3 1 6 5 8 5  
S A P  A ut h or(s):  
A ut h or  
D ate  
2 5 -M A Y -2 0 2 1  
Pri nci pal Statisticia n , Bi ostatistics  
 Cli nical P har m ac ol o g y 
M o delli n g a n d Si m ulati o n  
2 5 -M A Y -2 0 2 1  
 
C o p yri g ht 2 0 2 1 t he Gla x o S mit h Kli ne gr o u p of c o m pa nies. All ri g hts r eser ve d.  
U na ut h orise d  c o p yi n g or use of t his i nf or mati o n is pr o hi bite d.  
 
P P D
P P D
P P D


 
C O N FI D E N TI A L  
T h e Gl a x o S mit h Kli n e gr o u p of c o m p a ni e s  
 
2 0 8 0 2 2  
 
 
2  
 
S A P  Te a m Re vie w C o nfir m ati o ns  ( E-m ail C o nfir m ati o n) : 
Re vie w er  
D ate of E -m ail 
C o nfir m ati o n  
E D L, E arl y D e vel o p me nt Lea ders  
1 4 -J U N-2 0 2 1  
, Cli nical P har mac ol o g y M o delli n g a n d 
Si m ulati o n  
0 8 -J U N-2 0 2 1  
, Disc o ver y M e dici ne 
0 7 -J U N-2 0 2 1  
Pri nci pal Pr o gra m mer, Cli nical Pr o gra m mi n g  
0 7 -J U N-2 0 2 1  
, Cli nical P har m ac ol o g y M o delli n g a n d 
Si m ulati o n  
1 4 -J U N-2 0 2 1  
 S E R M  
2 6 -M A Y -2 0 2 1  
S A P Bi os t atistics Li ne A p pr o v al (Vee v a V a ult  T M F e Si g n at ure) : 
A p pr o ver  
 
 Bi ost atistics 
 
 
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D


 
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208022 
 
3 
 
TABLE OF CONTENTS 
PAGE 
1. 
INTRODUCTION ...................................................................................................... 7 
1.1. 
Changes to the Protocol Defined Statistical Analysis Plan ............................ 7 
1.2. 
Objectives, Endpoints and Estimands ........................................................... 8 
1.2.1. 
Objectives and Endpoints .............................................................. 8 
1.2.2. 
Estimands .................................................................................... 10 
1.3. 
Study Design .............................................................................................. 10 
2. 
STATISTICAL HYPOTHESES / SUCCESS CRITERIA .......................................... 10 
3. 
SAMPLE SIZE DETERMINATION ......................................................................... 11 
4. 
ANALYSIS SETS ................................................................................................... 11 
4.1. 
Protocol Deviations ..................................................................................... 12 
4.1.1. 
Definitions for Per Protocol Analysis Set ...................................... 13 
5. 
STATISTICAL ANALYSES ..................................................................................... 13 
5.1. 
General Considerations .............................................................................. 13 
5.1.1. 
Bayesian Analysis ........................................................................ 14 
5.1.2. 
Baseline Definition ....................................................................... 14 
5.1.3. 
Multicenter Studies ...................................................................... 15 
5.2. 
Primary Endpoint(s) Analyses ..................................................................... 15 
5.2.1. 
Definition of endpoint(s) ............................................................... 15 
5.2.2. 
Main analytical approach ............................................................. 15 
5.2.3. 
Sensitivity analyses ..................................................................... 17 
5.2.4. 
Supplementary analyses .............................................................. 17 
5.2.5. 
Subgroup analyses ...................................................................... 17 
5.3. 
Secondary Endpoint(s) Analyses ................................................................ 17 
5.3.1. 
Definition of endpoint(s) ............................................................... 17 
5.3.2. 
Main analytical approach ............................................................. 18 
5.3.3. 
Sensitivity analyses ..................................................................... 21 
5.3.4. 
Supplementary analyses .............................................................. 21 
5.3.5. 
Subgroup analyses ...................................................................... 21 
5.4. 
Safety Analyses .......................................................................................... 21 
5.4.1. 
Extent of Exposure ...................................................................... 21 
5.4.2. 
Adverse Events............................................................................ 21 
5.4.2.1. 
Adverse Events of Special Interest ............................. 22 
5.4.3. 
Laboratory Data ........................................................................... 23 
5.4.4. 
Vitals Signs .................................................................................. 23 
5.4.5. 
ECG ............................................................................................. 23 
5.4.6. 
C-SSRS ....................................................................................... 24 
5.5. 
Pharmacokinetic ......................................................................................... 24 
5.5.1. 
Pharmacokinetic/Pharmacodynamic ............................................ 25 
5.6. 
Exploratory Endpoint(s) Analyses ............................................................... 25 
5.6.1. 
Pharmacodynamic ....................................................................... 25 
5.7. 
Other Analyses ........................................................................................... 27 
5.8. 
Interim Analyses ......................................................................................... 27 
6. 
SUPPORTING DOCUMENTATION ....................................................................... 28 
6.1. 
Appendix 1 Abbreviations and Trademarks ................................................. 28 


 
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208022 
 
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6.1.1. 
List of Abbreviations .................................................................... 28 
6.1.2. 
Trademarks ................................................................................. 29 
7. 
REFERENCES ....................................................................................................... 30 
 


 
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208022 
 
5 
 
Version history 
This Statistical Analysis Plan (SAP) for study 208022 is based on the protocol dated 06-
JAN-2021.  
 
Table 1 
SAP Version History Summary 
SAP 
Version 
Approval 
Date 
Protocol 
Version 
(Date) on 
which SAP is 
Based 
Change 
Rationale 
1 
27MAR2020 
1 
(07JAN2020) 
Not Applicable 
Original version 
2 
 
3 
(06JAN2021) 
Clarification that 
statistical 
analyses will use 
a Bayesian 
approach and 
expected 
covariates 
updated. 
Increased consistency in 
results being reported 
from the trial, given the 
primary analysis is using 
a Bayesian approach. 
Updated model text to 
include all expected 
covariates. 
 
 
 
Sensitivity 
analysis for 
binary missing 
data updated. 
Since the time of 
writing, the impact of 
COVID-19, and 
therefore the chance of 
dropouts unrelated to 
trial activities, has 
increased. To assess 
this, the team have 
decided to include 
imputing missing PASI 
response with the 
response at the previous 
timepoint (LOCF 
approach) as a 
sensitivity to NRI. 
 
 
 
Clarification of 
endpoint and 
hypothesis text  
Updated text to match 
current protocol 
wording. 
 
 
 
Addition of 
COVID and 
COVID population 
added to reflect internal 


 
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6 
 
SAP 
Version 
Approval 
Date 
Protocol 
Version 
(Date) on 
which SAP is 
Based 
Change 
Rationale 
Modified ITT 
analysis 
populations 
standards for reporting 
COVID data. 
Modified ITT included 
to assess efficacy on 
participants who have 
completed Week 4 
assessment (first 
timepoint of interest) as 
a supplementary 
population for efficacy 
assessments. 
 
 
 
Placebo prior 
Clarification on the prior 
distribution to be used in 
primary analysis.  
 
 
 
Revision of 
planned analyses 
of skin biopsy 
data for PK and 
target 
engagement 
Skin biopsy to be 
collected for PK and 
target engagement 
assays is no longer 
required under Protocol 
Amendment 3. The 
planned MMRM 
analysis of skin target 
engagement is not 
required but may be 
conducted if sufficient 
data available.  


 
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7 
 
1. 
INTRODUCTION 
The purpose of this SAP is to describe the planned analyses to be included in the Clinical 
Study Report (CSR) for Study 208022. Details of the planned interim analysis are also 
provided. 
Additional exploratory analyses of inflammatory, metabolic and transcriptomic markers; 
data handling conventions and the specification of data displays will be provided in the 
Output and Programming Specification (OPS) document. 
 
1.1. 
Changes to the Protocol Defined Statistical Analysis Plan 
There are no changes to the originally planned statistical analysis specified in the 
protocol. 
 


 
C O N FI D E N TI A L  
 
 
2 0 8 0 2 2  
8  
 
1. 2.  
O bj e cti v e s , E n d p oi nt s  a n d E sti m a n d s  
1. 2. 1.  
O bj e cti v e s a n d E n d p oi nt s  
O bjecti ves  
E n d p oi nts  
Pri mar y  
•  
T o d et er mi n e t he effic acy of G S K 2 9 8 2 7 7 2 
9 6 0 m g m o difi e d r el e as e ( M R) o nc e daily 
( Q D) f or 1 2 w e eks, c o m par e d wit h pl ac e b o 
i n p artici p ants with m o der at e to s ev ere 
pl a q u e ps oriasis. 
•  
P A SI 7 5 r es p o ns e ( ac hi evi n g ≥7 5 % i mpr ov e m e nt 
fr o m B as eli n e i n P A SI sc or e) at W e ek 1 2. 
 
Sec o n dar y  
•  
T o f urt h er ev al uat e t he effic acy of 
G S K 2 9 8 2 7 72 9 6 0 m g M R Q D f or 1 2 
we eks, c o m p are d wit h pl ace bo i n 
p articip a nts wit h mo d er at e t o sev er e 
pl a q u e ps oriasis.  
 
 
F urt h er P A SI p ar a m et ers:  
•  
P A SI 5 0, P A SI 9 0 a n d P A SI 1 0 0 r es p o ns e 
( ac hi evi n g ≥50 %, ≥9 0 % an d 10 0 % i mpr ov e m e nt 
fr o m B as eli n e i n P A SI sc or e, res p ectiv ely) at 
W e ek 1 2.  
•  
C h a n g e fr o m B as eli n e P A SI sc or es at W e ek 1 2.  
St atic I nv esti g at or’s Gl o bal Ass ess m e nt (sI G A):  
•  
sI G A r es p o nse ( achi evi n g a sI G A sc ore of  
 
( 0) or
( 1)) at W eek 1 2. 
Ps o ri asis B o dy S urf ac e Ar e a ( B S A): 
•  
C h a n g e fr o m B as eli n e i n psoriatic B S A at W eek 
1 2. 
Safet y  
•  
T o ev alu at e th e s afety an d t oler a bility of 
G S K 2 9 8 2 7 72 9 6 0 m g M R Q D f or 1 2 
we eks, c o m p are d wit h pl ace bo i n 
p articip a nts wit h mo d er at e t o sev er e 
pl a q u e ps oriasis. 
•  
A dv ers e ev e nts  
•  
Cli nic al l ab or at ory v al u es (cli nic al ch e mistry, 
h a e m at ol o gy a n d uri n alysis)  
•  
Vit al si g n me as ure m e nts ( blo od pr essur e, h eart 
r at e, r es pir at ory r at e an d b o dy t e m p er atur e) 
•  
1 2 -L e a d el ectroc ar di o gr a m ( E C G) m o nitori n g  
•  
C ol u m bi a S uici d e S ev erity R ati n g Sc al e ( C -
S S R S)  
P har mac o ki netics  
•  
T o assess tr o u g h pl as m a c o nce ntr ati o ns of 
G S K 2 9 8 2 7 72 9 6 0 m g M R Q D f or 1 2 
we eks, in p artici pa nts with m od er at e t o 
s ev er e pl a qu e psori asis. 
•  
Tr o u g h plas ma c o nc e ntr ati o ns of G S K 2 9 8 27 7 2 at 
W e eks 2, 4, 8, 1 2.  
E x pl orat or y  
•  
T o i nv esti gat e t h e effic acy of 
G S K 2 9 8 2 7 72, 9 6 0 m g M R Q D ov er ti m e, 
A d diti o nal P A SI p ar a m et ers:  
C CI
C CI


 
C O N FI D E N TI A L  
 
 
2 0 8 0 2 2  
9  
 
O bjecti ves  
E n d p oi nts  
c o m p are d wit h pl ace b o i n p artici p a nts wit h 
m o d er at e t o s ev er e pl a q ue psori asis.  
 
 
•  
P A SI 7 5 r es p o ns e ( ac hi evi n g ≥7 5 % i mpr ov e m e nt 
fr o m B as eli n e i n P A SI sc or e) at W e eks 2, 4, a n d 
8.  
•  
P A SI 5 0, P A SI 9 0 a n d P A SI 1 0 0 r es p o ns e 
( ac hi evi n g ≥50 %, ≥9 0 % an d 10 0 % i mpr ov e m e nt 
fr o m B as eli n e i n P A SI sc or e res p ectiv ely) at 
W e eks 2, 4, a nd 8.   
•  
C h a n g e fr o m B as eli n e P A SI sc or es at W e eks 2, 
4, 8. 
St atic I nv esti g at or’s Gl o bal Ass ess m e nt (s I G A): 
•  
sI G A r es p o nse ( achi evi n g a sI G A sc ore of 
( 0) or
( 1)) at W eeks 2, 4, a n d 8.  
•  
sI G A sc or e c at e g ory at We eks 2, 4, 8, 12. 
B o dy S urf ace Ar e a ( B S A):  
•  
C h a n g e fr o m B as eli n e i n B S A at W e eks 2, 4, a n d 
8. 
•  
T o i nv esti gat e effect of G S K 2 98 2 7 7 2 9 60 
m g M R Q D for 1 2 w e eks, on pat h w ay a n d 
t ar g et e n ga g e me nt, tr a nscri pto mic pr ofili n g, 
i nfl a m m at ory, a n d m et ab olic bio m ark ers i n 
t h e ski n a nd bl oo d of partici p ants wit h 
m o d er at e t o s ev er e pl a q ue -ty pe ps oriasis. 
P h ar m ac ol o gy bi o m ark er e n dp oi nts:  
•  
T ar g et E n g a ge m e nt Ass ay RI P 1 ( T E A R 1) i n  
bl o o d at W e eks 0, 4, a n d 1 2.  
 
Tr a nscri pt o mic profili n g:  
•  
Tr a nscri pt o mic an alysis, i ncl udi n g b ut n ot li mit e d 
t o ri b o n ucl eic aci d s e q u encin g ( R N A-s e q), of 
m esse n g er rib o n ucl eic aci d ( m R N A) is ol at e d 
fr o m ski n at W e eks 0, 4, a n d 12 , wit h a ny 
c h a n g es i n s p ecific i nfl a m m atory g e n e tr a nscri pt 
l ev els ( e. g. I L-4, I L -1 0, I L -17, IL -2 1, I L -2 2, T N F 
a n d I F Nγ) p ossi bly b ei n g ev alu at e d. 
I nfl a m m at ory a n d K er ati n ocyt e bi o m ark ers: 
•  
C h a n g e fr o m B as eli n e i n hist op at h ol ogic al  
sc ori ng of psori atic l esio n al bio psi es, w hic h  m ay 
i ncl ud e, b ut ar e n ot li mit e d t o th e f ollo wi n g at 
W e eks 0, 4, a nd 1 2 : e pi d er m al t hickn ess, k erati n 
1 6 ( K 1 6),  a nti g e n KI -67 ( Ki 6 7), C D 3, cl uster of 
diff er e nti ati on 1 1c ( C D 1 1c).  
•  
C h a n g e fr o m B as eli n e i n i nfl a m m at ory pr ot ei n  
m ark ers i n bl o o d w hic h m ay i ncl u d e b ut ar e n ot 
li mite d t o th e f oll o wi n g at W e eks 0, 4, a n d 1 2 :  
I L-1 7, c he m oki n e li g an d 2 0 ( C C L 2 0), I L -6, I L -8, 
I L-4, C -X -C m otif c h e moki ne 10  (C X C L 1 0).  
M et a b olic bi o mark ers  
•  
C h a n g e fr o m B as eli n e i n m et ab olic m arkers in 
f asti n g bl o od w hich m ay i ncl u de b ut ar e n ot 
li mite d t o th e f oll o wi n g at W e eks 0, 4, a n d 1 2 : 
C CI
C CI


 
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Objectives 
Endpoints 
homeostatic model assessment of insulin 
resistance (HOMA) (glucose and insulin), 
glycated hemoglobin (HbA1c), lipid panel. 
Derivations of key primary and secondary endpoints (PASI, sIGA, BSA) will be given in 
the accompanying OPS document to this SAP. No rounding will be performed on PASI 
percentage change values when deriving PASI responder variables. 
 
1.2.2. 
Estimands 
Estimands were not incorporated into the protocol for this study. The missing data 
handling rules are outlined in analysis sections. 
 
1.3. 
Study Design 
Overview of Study Design and Key Features 
Design 
Features 
• Phase 1b/2a, multicentre, randomised, double-blind, placebo-
controlled, parallel, repeat dose study of GSK2982772 in 
participants with active plaque-type moderate to severe psoriasis. 
• The maximum total duration for each participant in the study will be 
21 weeks: 
• Screening period of up to 35 days 
• Treatment period of 12 weeks (84 days) 
• Follow-up period for up to 28 days after last dose 
 
Study 
intervention 
• Participants will receive either GSK2982772 960mg MR QD or 
placebo for 12 weeks (84 days). 
• No dose modifications or adjustments are permitted per protocol. 
Study 
intervention 
Assignment 
• Participants will be randomised to receive either GSK2982772 or 
placebo in a 2:1 ratio. 
• Randomisation will be stratified by prior biologic use. 
Interim 
Analysis 
• One interim analysis is planned to occur when at least six 
GSK2982772 participants complete the Week 12 visit or withdraw 
from study treatment. 
 
2. 
STATISTICAL HYPOTHESES / SUCCESS CRITERIA 
The primary objective of this study is to estimate the efficacy of GSK2982772 960 mg 
MR QD compared with placebo following 12 weeks of treatment, this will be assessed 
using the estimates of PASI75 response at Week 12. 


 
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There will be no adjustment for multiplicity. 
 
3. 
SAMPLE SIZE DETERMINATION 
Approximately 32 participants will be screened to achieve 21 participants randomly 
enrolled to either GSK2982772 or placebo in a 2:1 allocation ratio. Replacement 
participants may be randomised (up to approximately 6) into the study at the discretion of 
the Sponsor, to ensure that approximately 21 have completed the Week 4 visit. 
 
The primary efficacy endpoint is PASI75 response (achieving ≥75% improvement from 
Baseline in PASI score) at Week 12.  
With a sample size of 21 participants there is approximately 99% probability of achieving 
a posterior probability of at least 97.5 that the true treatment difference over placebo is 
greater than zero. This is based on an assumed placebo response of 7%, an assumed true 
treatment difference of 55% and incorporating informative historical placebo data into 
the analysis. For the placebo arm an informative Beta (3.5, 46.5) distribution is assumed, 
with an effective sample size of 50 participants. For the active arm a vague Beta (1/3, 
1/3) prior is used. 
 
No sample size re-estimation is planned for this study. 
 
4. 
ANALYSIS SETS 
Analysis Set 
Definition / Criteria 
Analyses Evaluated 
Screened  
• All participants who were screened 
for eligibility 
• Study Population 
Enrolled 
• All participants who signed the ICF, 
passed screening and were eligible 
for randomisation (regardless of 
whether the participant went on to 
be randomised). 
• Note screening failures (who never 
passed screening even if rescreened) 
and participants screened but never 
enrolled into the study (Reserve, 
Not Used) are excluded from the 
Enrolled analysis set as they did not 
enter the study. 
 
• Study Population 
Randomised 
 
• 
All participants who were randomly 
assigned to study intervention in the 
study. 
• 
Participant must have signed ICF 
and passed Screening.  
• Study Population 


 
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Analysis Set 
Definition / Criteria 
Analyses Evaluated 
• Data will be reported according to 
the randomised study intervention. 
Intent to Treat 
(ITT) 
• 
All participants who were 
randomised to study intervention in 
the study and who received at least 
one dose of study intervention. 
• Data will be reported according to 
the randomised study intervention. 
 
• Efficacy 
Modified Intent 
to Treat (ITT) 
• 
All participants in the ITT 
population who completed at least 
the Week 4 assessment. 
• Data will be reported according to 
the randomised study intervention. 
• Efficacy 
Safety 
• All participants in the enrolled 
population who received at least 
one dose of study intervention. 
• Data will be reported according to 
the actual study intervention 
received. 
• Safety 
• PD 
COVID-19  
• All participants in the Safety 
set who had a confirmed, probable 
or suspected COVID-19 case 
diagnosis.  
• COVID outputs 
Pharmacokinetic 
(PK) 
• All participants in the Safety 
population who had at least one 
non-missing PK assessment (Non-
quantifiable [NQ] values will be 
considered as non-missing values). 
• Data will be reported according to 
the actual study intervention 
received. 
• PK 
Actual treatments are defined as follows: If a participant randomised to the placebo arm 
receives any amount of GSK2982772 he or she will be included in the corresponding 
active treatment arm. 
 
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.  
Protocol deviations will be tracked by the study team throughout the conduct of the 
study. These protocol deviations will be reviewed to identify those considered as 
important as follows: 


 
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o Data will be reviewed prior to unblinding and freezing the database to ensure all 
important deviations are captured and categorised in the protocol deviations 
system independent dataset (DV1).  
o This dataset will be the basis for the summaries of important protocol deviations. 
 
Data will be reviewed prior to unblinding and freezing the database to ensure all 
deviations are captured and categorised in the protocol deviations A&R dataset.  
 
4.1.1. 
Definitions for Per Protocol Analysis Set 
 This study will not include a Per Protocol analysis set. 
5. 
STATISTICAL ANALYSES 
5.1. 
General Considerations 
Unless otherwise specified, the Enrolled or Randomised Analysis Sets will be used for all 
Study Population analyses (detailed in the OPS), the Intent to Treat Set will be used for 
all Efficacy analyses, PK Set will be used for PK analyses and Safety Analysis Set will 
be used for all safety and PD analyses, COVID specific outputs as well as a subset of 
safety analyses will be produced using the COVID population. 
In the case of wrong stratification assigned at the time of randomization, the analyses will 
be performed based on the data collected in the electronic case record form (eCRF), not 
the assigned stratum at randomization. 
Credible intervals (CrI) will be equal-tailed and use 95% level unless otherwise specified.  
Unless otherwise specified, summary tables will provide the following descriptive 
statistics as a minimum: 
• Continuous data (normally distributed):  
n, mean, standard deviation (SD), median, minimum and maximum. 
 
• Continuous data (log-normally distributed):  
n, geometric mean, SD on the log scale (SD (log)), median, minimum and 
maximum. 
 
• Categorical data: 
number and percentage of participants in each category. 
 
Figures of average responses to primary and secondary endpoints for each treatment 
group over time will be produced including a suitable measure of uncertainty. Adjusted 
(posterior) values will be used where available.  
 


 
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5.1.1. 
Bayesian Analysis 
The analyses will be conducted in the Bayesian framework. Models will be fitted by 
MCMC simulations and informative priors may be used. In that case, a sensitivity 
analysis using vague priors will also be carried out. Prior distributions are given in the 
analysis sections below and will be reported in the CSR. Posterior values will be 
calculated by weighting categorical coefficients level according to the proportions 
observed in the data and taking the mean value of continuous covariates. 
For continuous endpoints, posterior distributions for each arm will be summarized using: 
posterior mean, SD, 95% CrI, as well as posterior mean and 95% CrI for the difference 
between arms. Medians may be used in place of medians for skewed posterior 
distributions. 
For categorical endpoints, posterior distributions for each arm will be summarized using: 
posterior median response rate and 95% CrI, as well as posterior median difference in 
response rates and odds ratios and associated 95% CrIs.  
Posterior probabilities of being greater than thresholds of interest may also be presented. 
Any additional requirements for a particular analysis are given alongside the analysis 
description.  
 
Bayesian Model Checking & Diagnostics 
• A minimum burn-in period of 5,000 MCMC samples will be used. 
• A minimum of 10,000 MCMC samples will be run to generate samples of the posterior 
distribution. 
• Convergence will be assessed using visual inspection of trace plots and autocorrelation 
plots, the ratio of the Monte Carlo Standard Error (MCSE) to the SD of the posterior 
distribution (ratio should be <0.01). 
• If the model is not deemed to have converged the following actions will be taken in the order 
described below: 
o Increasing the number of MCMC samples and/or the thinning will be explored. The 
blocking of the parameters will be considered. 
 
 
5.1.2. 
Baseline Definition 
Baseline value will be the latest pre-dose assessment with a non-missing value, including 
those from unscheduled visits. If time is not collected, Day 1 assessments are assumed to 
be taken prior to first dose and will be used as baseline. 
Screening values may be used if Day 1 data is unavailable for efficacy and safety 
endpoints. Otherwise, if not Screening data available, baseline will be set to missing. 
 


 
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5.1.3. 
Multicenter Studies 
Due to the small sample size, the number of participants per site will be small. It is 
anticipated that analyses by centre would unlikely be informative and will not, therefore, 
be provided. 
 
5.2. 
Primary Endpoint(s) Analyses 
5.2.1. 
Definition of endpoint(s) 
The primary endpoint for this study: 
• PASI75 response at Week 12 (Day 85), where PASI75 response is defined as a 
reduction in PASI score from baseline of at least 75%. 
 
5.2.2. 
Main analytical approach 
The primary analysis will be produced for the ITT population. 
The summary measure of interest is the difference in PASI75 response rates at Week 12 
(Day 85) between GSK2982772 and placebo. Missing values will be imputed as non-
responders. 
 
The primary endpoint will be analysed using a Bayesian logistic regression model, details 
given in Table 2. Summary statistics will be provided for the posterior distribution of the 
true difference in PASI75 response rate (GSK2982772 vs placebo) as well as posterior 
probabilities for a range of thresholds.  
 
A non-informative prior will be used for the PASI75 response rate on GSK2982772 and 
covariates.  
 
An informative prior will be used for the placebo response rate of the form: 90% weight 
on Be(5.39, 69) and 10% on Be(1/3,1/3). The prior was derived from historical data from 
similar clinical trials using meta-analytic predictive prior (MAP) approach, the effective 
sample size is approximately 63 [Schmidli, 2014].  
 
In the event that the placebo prior is different from what is presented here, this will be 
documented in the CSR.  
 


 
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Table 2 
Statistical Analysis of Primary Endpoint 
Endpoint(s) 
• PASI75 response at Week 12 (Day 85) 
Analysis Method 
Bayesian Logistic Regression (using informative prior) 
Model Specification 
Outcome 
yi = Response (0/1) for participant i 
Predictors 
• 
Treatment (categorical) 
• 
Prior Biologic Use (categorical) 
• 
Baseline PASI score (continuous) 
 
Unless stated otherwise the predictors (not including study treatment) will be 
centered around their estimated mean prior to inclusion in the model 
Model 
yi ~ Ber(pi) 
logit(pi) = (Treatment=Placebo)×β1 + (Treatment=GSK)×β2 + (Prior Biologic 
Use*)×β4 + (Baseline PASI score*)×β5 
Prior distributions for 
coefficients (β) 
β = fixed effect parameters associated to predictors 
• 
β1: informative prior such that logit-1(β1) ~ mixture of Betas* 
• 
β2: non-informative prior such that logit-1(β2) ~ Beta(1/3, 1/3) 
• 
Other βk: non-informative priors of N(0, SD=100) 
*Expected prior is a mixture of Be(5.39, 69) and Be(1/3,1/3), weighted to 90% and 
10% respectively. Final prior will be reported in the CSR. 
Model Checking & Diagnostics 
See Section 5.1.1 
Results Presentation 
• Posterior medians and 95% CrI of true response rate for each treatment group. 
•  Posterior medians and 95% CrI for the true difference in proportion of responders 
(GSK2982772 – placebo) and odds ratios of GSK2982772 to placebo. 
• Probabilities that the true treatment difference is greater than a range of values of interest 
(e.g. 0%, 20%, 45%, 55%). See OPS outputs list for details. 
• Probabilities that the true response rate on active is greater than a range of values of 
interest (e.g. 0%, 30%, 55%). See OPS outputs list for details. 
Interim Analysis 
The interim analysis will estimate the predictive probability of meeting various decision criteria 
including: 
- 
>55% probability that true difference in PASI75 response (GSK2982772 – Placebo) above 
45% 
- 
>97.5% probability that true difference in PASI75 response (GSK2982772 – Placebo) above 
0% 
 


 
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Predictive probabilities will be calculated via simulation assuming a total sample size of 21 (14:7 
for GSK2982772:Placebo). 
The parameter posterior distributions from the Bayesian logistic regression analysis of interim 
data will be used to simulate predicted PASI75 responses for remaining trial subjects. For 
participants yet to be enrolled, average covariate values will be assumed.  
The predicted data will be combined with the observed interim data and the Bayesian logistic 
model applied to assess the decision criteria. This process will be repeated for each run of the 
MCMC procedure. The proportion of times the decision criteria is met will be the predicted 
probability. 
 
 
5.2.3. 
Sensitivity analyses 
Where informative priors have been used, a sensitivity analysis using vague priors (no 
historical borrowing) will also be produced.  
Additional sensitivity analyses to assess the impact the missing data handling for binary 
data may be produced, such as using a LOCF approach to missing data.  
 
5.2.4. 
Supplementary analyses 
A supplementary analysis where the primary analysis is repeated using the Modified ITT 
population may be produced to assess the treatment effect in subjects able to complete at 
least 4 weeks of treatment. A frequency table of PASI response using this population 
would also be produced. 
Off-treatment PASI data, collected following treatment discontinuation prior to Week 12, 
may be used for additional supplementary analyses if available. 
 
5.2.5. 
Subgroup analyses 
No formal subgroup analysis is planned.  Descriptive statistics in the form of a frequency 
table of PASI75 response by prior biologic use will be produced. 
 
5.3. 
Secondary Endpoint(s) Analyses 
5.3.1. 
Definition of endpoint(s) 
The secondary efficacy endpoints are: 


 
C O N FI D E N TI A L  
 
 
2 0 8 0 2 2  
1 8  
 
C ate g oric al e n d p oi nts  
•  
P A SI 5 0, P A SI 9 0 a n d P A SI 1 0 0 res p o nse at Wee k 1 2  ( Da y 8 5), w here P A SIX  
res p o nse is defi n e d as a re d ucti o n i n P A SI sc ore fr o m baseli ne of at least X % . 
•  
sI G A res p o ns e at W ee k 1 2 ( Da y 8 5), d efi ne d as 
( 0) or
( 1). 
C o nti n u o us e n d p oi nts  
•  
C ha n ge fr o m Baseli ne i n P A SI sc ores at Wee k 1 2  ( Da y 8 5) 
•  
C ha n ge fr o m Baseli ne i n ps oriatic B S A at Wee k 1 2  ( Da y 8 5). 
 
5. 3. 2.  
M ai n a n al yti c al a p pr o a c h  
C ate g oric al e n d p oi nts  
T he pr o p orti o n of partici pa nts ac hie vi n g a d diti o nal P A SI res p o n d er e n d p oi nts of i nterest 
( P A SI 5 0/ 9 0/ 1 0 0) will be s u m marise d b y tr eat me nt ar m a n d visit. Missi n g v al ues will be 
i m p ute d as n o n -res p o n ders. Cre di ble i nter vals f or res p o nse rates will be i ncl u de d ( usi n g 
Be( 1/ 3, 1/ 3) pri or f or all treat me nt ar ms a n d visits).  
 
T he sI G A sc ores will be s u m marise d as cat e g orical data wit h t he  pr o p orti o n of 
partici pa nts ac hie vi n g eac h sI G A sc ore bei n g pres e nte d b y treat me nt gr o u p a n d visit. T he 
pr o p orti o n of sI G A 
( 0) or
 ( 1) will als o be prese nt e d, wit h m issi n g 
val ues i m p ute d as n o n -res p o n ders. Cre di ble i nter vals f or res p o ns e rat es will be i ncl u de d 
( usi n g Be( 1/ 3, 1/ 3) pri or f or all treat me nt ar ms a n d visits). 
 
Li ne pl ots of pr o p orti o n of res p o n ders ( wit h 9 5 % CrI ) o ver ti me b y tr eat me nt gr o u p will 
be pr o d uce d f or b ot h P A SI a n d sI G A res p o n der e n d p oi nt s. 
 
A Ba yesia n l o gistic r e gressi o n a p pr oac h will be us e d t o assess res p o ns e rates at Wee k 1 2 , 
details  gi ve n  i n T a ble 3 . 
 
 
C o nti n u o us e n d p oi nts  
B ot h sec o n d ar y a n d e x pl orat or y o bjecti ves of B S A a n d P A SI s c ore will be i n vesti gate d 
usi n g t he sa me Ba yesia n  re peat e d meas ures m o del ( M M R M) anal ysis.  
S u m mar y statistics  b y tr eat me nt a n d visit will be pr o vi de d f or c h a n ge fr o m baseli ne i n 
b ot h P A SI sc ore a n d B S A. A s u m mar y of perce nt a ge c h a n ge i n P A SI will als o be 
pr o vi de d.  
C CI
C CI
C CI
C CI


 
C O N FI D E N TI A L  
 
 
2 0 8 0 2 2  
1 9  
 
 A Ba yesia n M M R M a p pr oac h will be use d t o acc o u nt f or t he re p eate d visits ( details 
gi ve n i n Ta bl e 4 ). T his a p pr oac h ass u m es missi n g val ues are M A R.  
Li ne pl ots of p osteri or mea ns ( S D ) fr o m t he M M R M a nal ysis o ver ti me b y treat me nt 
gr o u p  will be pr o vi de d . 
T a bl e 3  
St ati sti c al A n al y si s of C at e g ori c al S e c o n d ar y E n d p oi nt( s)  
E n d p oi nt( s)  
•  Pr o p orti on of P A SI 5 0, P A SI9 0 a n d P A SI1 00 r es po n ders at W e ek 1 2 ( D ay 8 5)  
•  Pr o p orti on of sI G A  
( 0) or 
( 1) at W eek 1 2 ( D ay 8 5) 
A n al y sis M et h o d  
B ay esi an L o gistic R egr essi o n  
M o d el S p e cific ati o n  
O utc o m e  
y i = R esp o nse ( 0/ 1) f or p artici pa nt i 
Pr e dict ors  
•  
Tr e at m e nt (c at eg oric al)  
•  
Pri or Bi ol o gic Use (c ate g oric al)  
•  
B as eli ne  sc or e (sI G A t o be tr eat e d as c o nti n u o us) 
 
U nl ess st at e d ot h er wis e t h e pre dict ors ( n ot i ncl u di ng st udy tre at m e nt) will be 
c e nt er e d ar o u n d t h eir esti m at ed m e a n pri or t o i ncl usi o n in t he m o d el  
M o d el  
y i ~ B er( p i) 
l o git( pi) = ( Tr e at m e nt = Pl ac e bo) ×β 1 + ( Tr e at m e nt = G S K) × β 2 + ( Pri or Bi ol o gic 
Us e *)× β 4 + ( B as eli n e P A SI scor e*)× β 5 
P ri or distri b utio ns for 
c o effici e nts (β ) 
β = fix ed eff ect p ar a m et ers ass oci at e d t o pr e dict ors  
•  
β 1 & β 2: n o n -i nf or m ativ e pri or suc h t h at l o git-1( βk) ~ B et a( 1/ 3, 1/ 3)  
•  
Ot h er β k: n on -i nf or m ativ e priors of N( 0, S D = 1 0 0)  
 
M o d el C h e c ki n g & Dia g n o sti c s  
S e e S ecti on 5. 1. 1  
R e s ult s Pre se nt ati o n  
•  P ost eri or m edi a ns a n d 9 5 % CrI of tr ue r es po ns e r at e f or e ac h tre at m ent gr ou p.  
•   P ost eri or m edi a ns a nd 9 5 % CrI f or t h e tr ue differ e nce i n pr o porti o n of r esp on d ers 
( G S K 2 98 277 2 –  plac e bo)  an d o d ds r ati os of G S K 2 98 27 7 2 t o pl ac e bo.  
•  Pr o b abiliti es t h at t h e tr ue tre at m e nt differ e nce is gr eat er a r a n ge of v al ues of i nt er est ( e. g. 0 , 
2 0, 4 0 ). Se e O P S o utp uts list f or det ails.  
 
 
 
C CI
C CI


 
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Table 4 
Statistical Analysis of Continuous Secondary Endpoint(s) 
Endpoint(s) 
• Change from Baseline PASI scores at Week 12 (Day 85) 
• Change from Baseline in psoriatic BSA at Week 12 (Day 85) 
Analysis Method 
Bayesian GLMM with natural link (MMRM equivalent) 
Model Specification 
Outcome 
yi = vector of change from baseline for participant i 
 
Predictors 
• 
Treatment (categorical) 
• 
Visit (categorical) 
• 
Treatment*visit (categorical) 
• 
Prior Biologic Use (categorical) 
• 
Baseline (continuous) 
• 
Baseline*visit (continuous) 
 
Unless stated otherwise the predictors (not including study treatment or visit) 
will be centered around their estimated mean prior to inclusion in the model 
Model 
𝒚𝑖 ~ 𝑀𝑉𝑁𝑜𝑟𝑚𝑎𝑙(𝝁𝑖,  𝚺 ) 
𝝁𝑖=  𝑋𝑖 𝜷  
 
Prior distributions for 
coefficients (β) 
β = fixed effect parameters associated to predictors 
• 
βk : non-informative prior of N(0, SD=100) 
Prior distributions for 
random effects (b) 
• 
Σ ~ Inverse Wishart (J, S), with J = number of visits (degree of freedom), S 
= identity matrix 
 
Note: If convergence issues occur, an alternative covariance matrix structure 
may be used, for example a compound symmetric structure, to help improve 
convergence.  
Model Checking & Diagnostics 
See Section 5.1.1 
 
Results Presentation 
• Posterior mean, SD and 95% CrI will be presented for each treatment by timepoint 
interaction. 
• Posterior mean treatment differences (GSK2982772 – placebo) and associated 95% CrI will 
be produced for each timepoint. 
• Probabilities that the true treatment difference at each visit is greater a range of values of 
interest (e.g. 0, 100) may be provided. See OPS outputs list for details. 
• Outputs produced will include results for earlier timepoints in addition to the objective 
specified timepoint of Week 12 (Day 85). 
 


 
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5.3.3. 
Sensitivity analyses 
No sensitivity analyses are planned for secondary efficacy endpoints. 
 
5.3.4. 
Supplementary analyses 
No supplementary analyses are planned for secondary efficacy endpoints. 
 
5.3.5. 
 Subgroup analyses 
No subgroup analyses are planned for secondary efficacy endpoints. 
5.4. 
Safety Analyses 
Displays will be based on GSK Core Data Standards. No formal statistical testing will be 
performed on Safety data. 
5.4.1. 
Extent of Exposure 
Descriptive summaries of exposure data will be provided, including the average dose 
taken, duration of exposure and cumulative actual dose. Study intervention compliance 
will be reported in exposure listings and will be defined in the OPS. 
The following definitions will be used for exposure: 
• Duration of exposure (days) is defined as time between first and last dose dates 
(last dose-first dose +1).  
• Cumulative actual dose (mg) is defined as the total actual dose received (mg) 
during the 12-week treatment period (total number of active tablets taken x 
480mg). 
• The average daily dose (mg) taken is defined as the cumulative actual dose 
divided by the duration of exposure.  
 
Cumulative actual dose will be determined from the number of tablets in dispensed and 
returned bottles.  
5.4.2. 
Adverse Events 
Adverse event (AE) analyses including the analysis of AEs, Serious AEs (SAEs) and 
other significant AEs will be based on GSK Core Data Standards.   


 
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Summary tables will include the number of participants with the AE, the percentage of 
participants with the AE. The following AE categories will be provided: 
• AE 
- 
Any AEs 
- 
Common* non-serious AEs 
- 
AEs related to study intervention 
- 
AEs leading to permanent discontinuation of study intervention 
 
• SAE 
- 
Any SAEs 
- 
SAEs related to study intervention 
- 
Fatal SAEs 
*For disclosure purposes, common is defined as AEs occurring in at least 5% of any treatment arm. Due to 
the small sample size of this study this table will include all non-serious AEs.  
A summary of number and percentage of participants with any adverse events by 
maximum intensity will be produced. The AE summaries will be sorted by System Organ 
Class (SOC) and Preferred term (PT) in descending order. The summary will use the 
following algorithms for counting the participant: 
• 
Preferred term row: Participants experiencing the same AE preferred term several 
times with different severities will only be counted once with the maximum severity. 
• 
Any event row: Each participant with at least one adverse event will be counted 
only once at the maximum severity no matter how many events they have. 
A study intervention-related AE is defined as an AE for which the investigator classifies 
the possible relationship to study intervention as “Yes”.  Similarly, a study intervention-
related SAE is defined as an SAE for which the investigator classifies the relationship to 
study intervention as “Yes”. A worst-case scenario approach will be taken to handle 
missing relatedness data, i.e. the summary table will include events with the relationship 
to study intervention as ‘Yes’ or missing.  
Adverse events will be coded using the standard Medical Dictionary for Regulatory 
Affairs (MedDRA dictionary). 
Summaries tables may be omitted if the number of events is sufficiently low. 
 
5.4.2.1. 
Adverse Events of Special Interest 
There are no adverse events of special interest identified for this study. 
 


 
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5.4.3. 
Laboratory Data 
Separate summary tables for haematology and chemistry laboratory tests as well as urine 
concentration parameters will be produced. Liver function laboratory tests and lipid tests 
will be included with chemistry lab tests. Change from baseline in laboratory parameters 
will be presented for continuous variables, with a summary of baseline values included in 
the tables.  
Shift tables of worst-case results post-baseline relative to baseline will be provided for 
the following tests: 
• For lab tests with associated Potential Clinical Importance (PCI) criteria 
(criteria are listed in the OPS) 
• For categorical urinalysis parameters 
 
Only post-baseline data will be included in these tables. If a participant moves to both a 
low and a high clinical concern range during the treatment period, then the participant is 
counted in both categories.  
Summaries of hepatobiliary laboratory events including possible Hy’s law cases will be 
provided in addition to what has been described above. Possible Hy’s law cases are 
defined as any elevated alanine aminotransferase (ALT) ≥3 × upper limit of normal 
(ULN) and total bilirubin ≥2 × ULN (>35% direct bilirubin) or ALT ≥3 × ULN and 
international normalized ratio (INR) >1.5.  Total bilirubin ≥2×ULN can be within 28 
days following the ALT elevation and if direct bilirubin is available on the same day, it 
must be ≥ 35% of total bilirubin. The summary will be produced for worst-case post-
baseline only. 
An e-DISH plot of maximum post-baseline total bilirubin versus maximum post-baseline 
ALT will be created. 
 
5.4.4. 
Vitals Signs 
A summary of change from baseline vital sign values will be provided by visit and 
treatment group, including systolic blood pressure, diastolic blood pressure, heart rate, 
respiratory rate, weight, BMI and temperature. 
Blood pressure and heart rate values will be categorized into clinical concern ranges 
(listed in the OPS).  
 
5.4.5. 
ECG 
For all ECG analyses, baseline is taken to be the mean of the triplicated values collected 
pre-dose Day 1. The following summaries will be provided by visit: 


 
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• Summary of ECG findings (the clinical significance and interpretation of each 
planned ECG). In the case of triplicate ECG measurements, results will be 
presented separately by measurement number. 
• Summary of change from baseline in ECG values. In the case of triplicate ECG 
measurements, summaries will use the average of the triplicate, listings will 
present all individual measurements. 
 
The clinical concern ranges for ECG parameters are defined in the OPS. The absolute and 
change from baseline ECG values will be rounded to the nearest integer before being 
categorized according to the clinical concern ranges.  
The following summaries of participants 
• A summary of QTcF absolute values will display the number and percentage of 
participants with a post-baseline increase to a value within each clinical concern 
range for the worst-case post-baseline only.  
• A summary of change from baseline QTcF values will display the number and 
percentage of participants with a change within each range for the worst-case 
post-baseline. Participants with missing baseline values will be excluded from this 
summary. 
 
5.4.6. 
C-SSRS 
A summary of C-SSRS data may be produced if there are multiple cases (>3) of suicidal 
ideation or behaviour, otherwise the data will be listed only. 
5.5. 
Pharmacokinetic 
Pharmacokinetic analyses will be conducted using the PK population.  
Pharmacokinetic blood samples will be collected pre-dose at Week 2 (Day 15), 4 (Day 
29), 8 (Day 57) and 12 (Day 85) visits to measure trough plasma concentrations of 
GSK2982772. Skin biopsies will be taken pre-dose at Week 4 (Day 29) and Week 12 
(Day 85) to measure trough concentrations of GSK2982772 in the skin.  
Summaries of trough plasma and skin GSK2982772 concentrations by visit will be 
produced as well as for PK predicted target engagement (the formula for this derivation is 
provided in the OPS). 
Line plots of individual participant trough plasma and skin concentrations by visit will be 
produced as well as a plot for the treatment group average by visit.  
Scatter plot of trough skin concentration versus trough plasma concentration at Week 4 
(Day 29) and Week 12 (Day 85) will be produced.    


 
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5.5.1. 
Pharmacokinetic/Pharmacodynamic 
The relationship between trough concentration of GSK2982772 and target engagement in 
both plasma/blood and skin (data permitting) will be investigated graphically using 
scatter plots. 
Exploratory plots may be presented for individual and/or pooled plasma concentration 
versus change from baseline and/or absolute PASI score.  
A population analysis will be implemented by CPMS to describe the PASI score (change 
from baseline and absolute) versus time course (up to Week 12) using a longitudinal 
model in order to predict the PASI score and the derived PASI75 at Week 16 (additional 
time point of interest for comparison to competitors). The model structure will be 
dependent on the emerging data. 
If data permit, potential relationship between trough concentration of GSK2982772 and 
PASI score will be studied. PASI scores (change from baseline and absolute) over time 
(up to Week 12 (Day 85)) will be modelled in order to predict the PASI score at Week 16 
using a non-linear mixed effect approach. Exposure-response may also be evaluated for 
other efficacy or PD biomarkers. This work will be conducted by the GSK DMPK group 
and will not form part of the CSR delivery. 
 
5.6. 
Exploratory Endpoint(s) Analyses 
5.6.1. 
Pharmacodynamic 
Pharmacodynamic analysis will be conducted on the Safety population.  
Target engagement of RIP1 kinase is defined as the percentage reduction of Free/Total 
relative to baseline. Target engagement in both blood and skin will be summarized by 
treatment group and visit.  
Line plots of both individual and average target engagement by treatment group will be 
presented over time for both skin and blood. Boxplots of the target engagement data by 
visit and treatment may also be produced. 
A Bayesian MMRM analysis of the log difference in ratio of free to total RIP1 will be 
used to analyse target engagement in the blood and skin over time (details given in Table 
5).  
Following the implementation of Protocol Amendment 3, skin biopsies to be used to 
assess target engagement in the skin are not required. The MMRM analysis of skin target 
engagement outlined above may not be produced if only limited skin data is available. 
 


 
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Table 5 
Statistical Analysis of Continuous Exploratory Endpoint(s) 
Endpoint(s) 
• Log(Ratio) – Baseline log(Ratio) in the blood at Week 12 (Day 85) 
• Log(Ratio) – Baseline log(Ratio) in the skin at Week 12 (Day 85). 
 
Where Ratio = Free RIPK1/Total RIPK1 
Analysis method 
Bayesian GLMM with natural link (MMRM equivalent) 
Model Specification 
Outcome 
yi = vector of change from baseline for participant i 
 
Predictors 
• 
Treatment (categorical) 
• 
Visit (categorical) 
• 
Treatment*visit (categorical) 
• 
Prior Biologic Use (categorical) 
• 
Baseline (on log scale) (continuous) 
• 
Baseline (on log scale)*visit (continuous) 
 
Unless stated otherwise the predictors (not including study treatment or visit) will 
be centered around their estimated mean prior to inclusion in the model 
Model 
𝒚𝑖 ~ 𝑀𝑉𝑁𝑜𝑟𝑚𝑎𝑙(𝝁𝑖, 𝚺) 
𝝁𝑖=  𝑋𝑖 𝜷 
 
Prior distributions for 
coefficients (β) 
β = fixed effect parameters associated to predictors 
βk : non-informative prior of N(0, SD=100) 
Prior distributions for 
random effects (b) 
Σ ~ Inverse Wishart (J, S), with J = number of visits (degree of freedom), S = 
identity matrix 
Note: If convergence issues occur, an alternative covariance matrix structure 
may be used, for example a compound symmetric structure, to help improve 
convergence. 
Model Checking & Diagnostics 
See Section 5.1.1 
 
Results Presentation 
• Adjusted ratios to baseline and 95% CrI will be derived using the following transformation: 
exp(posterior mean) for each treatment group 
• Percentage target engagement will be calculated using the formula: (1 – Adjusted 
ratio)*100%. 
• Ratios to placebo and 95% CrI will be calculated by back-transforming (exp()) the difference 
in posterior means and associated 95% CrI. This will be used to derive the percentage 
reduction in Free/ Total for GSK2982772 compared to placebo. 
• Summary tables and figures produced will include results for earlier timepoints in addition to 
Week 12 (Day 85). 
 


 
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5.7. 
Other Analyses 
Additional analyses will be conducted on exploratory biomarkers including: proteomic 
and metabolic biomarkers in the blood, histopathological markers in the skin and 
transcriptomic RNA-seq data in the skin. Details of these analyses are given in the OPS. 
 
5.8. 
Interim Analyses  
An interim analysis (IA) is planned to occur when at least six participants on 
GSK2982772 have completed the Week 12 (Day 85) visit or withdrawn from study 
treatment. The purpose of the IA is for internal decision making about future 
GSK2982772 trials and assess futility. The study may be stopped for futility if the 
probability of a positive outcome at the end of the trial is low based on the data available 
at the IA. The trial cannot be stopped early based on positive efficacy data.  
Predictive probabilities will be calculated via simulation. The parameter posterior 
distributions from the Bayesian logistic regression analysis of interim data will be used to 
repeatedly simulate PASI75 response for remaining trial subjects. The predicted data will 
be combined with interim data to assess end of study criteria and calculate the proportion 
of times the decision criteria are met.  
The data will be reviewed by an internal Data Review Committee. The committee will 
include the study statistician, the study pharmacokineticist and a limited number of GSK 
staff. A DRC charter will identify the specific staff to form part of the DRC, as well as 
detail the data to be reviewed, planned analyses, guidelines for the decision rules to be 
followed and a dissemination plan for interim decisions. 
A subset of the outputs for the end of study will be produced for the IA. These will focus 
on efficacy data including, but not limited to: 
• Summaries of PASI response data and change from baseline in PASI score by 
treatment and visit as outlined in Section 5.3.2 (Modified ITT population).  
• Bayesian analysis of PASI75 response at Week 12 (Day 85) as outlined in Section 
5.2.2 (Modified ITT population). 
• Summaries of PK data and predicted target engagement as outlined in Section 5.5 
(PK population). 
• Summary of longitudinal model used to predict PASI score and the derived 
PASI75 at Week 16, outlined in Section 5.5.1, (conducted by CPMS on the ITT 
population).  
• Summaries of disposition and psoriatic baseline characteristics (Randomised 
population). 
 
Safety monitoring of blinded data will be conducted by the internal GSK Safety Review 
Team (SRT) at regular intervals throughout the study, see Section 8.2 of Protocol. 


 
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6. 
SUPPORTING DOCUMENTATION 
6.1. 
Appendix 1 Abbreviations and Trademarks 
6.1.1. 
List of Abbreviations 
Abbreviation 
Description 
AE 
Adverse Event 
A&R 
Analysis and Reporting  
BSA 
Psoriasis body Surface Area 
CI 
Confidence Interval 
CrI 
Credible Interval 
CSR 
Clinical Study Report 
C-SSRS 
Columbia Suicide Severity Rating Scale 
DRC 
Data review committee 
eCRF 
Electronic Case Record Form 
GSK 
GlaxoSmithKline 
IA 
Interim Analysis 
ITT 
Intent-To-Treat 
LS Mean 
Least Squares Mean (or marginal mean) 
MAR 
Missing At Random 
MMRM 
Mixed Model Repeated Measures 
MR 
Modified Release 
OPS 
Output and Programming Specification  
PASI 
Psoriasis Area Severity Index 
PCI 
Potential Clinical Importance  
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
PT 
Preferred Term 
QD 
Once Daily 
QTcB 
Bazett’s QT Interval Corrected for Heart Rate 
QTcF 
Frederica’s QT Interval Corrected for Heart Rate 
RNA-seq 
Ribonucleic Acid Sequencing 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SE 
Standard Error 
sIGA 
Static Investigator’s Global Assessment of Disease Activity 
SOC 
System Organ Class 
TEAR1 
Target Engagement Assay RIP1 
TMF 
Trial Master File 
ULN 
Upper Limit of Normal 
 


 
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6.1.2. 
Trademarks 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
None 
 
None 
 
 


 
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7. 
REFERENCES 
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Krishnaswami S, Tallman A, Kaur M, Ito Ket al. Quantitative Evaluations of Time-
Course and Treatment Effects of Systemic Agents for Psoriasis: A Model-Based Meta- 
Analysis. Clin Pharmacol Ther. 2017; 102(6):1006-1016. 
Papp K, Gordon K, Thaçi D, Morita A, Gooderham M, Foley P, Girgis IG, Kundu S, 
Banerjee Set al. Phase 2 Trial of Selective Tyrosine Kinase 2 Inhibition in Psoriasis. N 
Engl J Med. 2018; 379:1313-21. 
Schmidli H, Gsteiger S, Roychoudhury S, O'Hagan A, Spiegelhalter D, Neuenschwander 
B. Robust meta-analytic-predictive priors in clinical trials with historical control 
information. Biometrics. 2014; 70(4): 1023-32.