Conditions: Dermatitis, Atopic
Keywords: Eczema activity severity index GSK1070806
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 34
Healthy volunteers: no

Brief summary:
This study will evaluate efficacy and safety of GSK1070806 in moderate to severe atopic dermatitis (AtD) participants.

Detailed description:

Arms:
arm 1: Participants received a single dose of 2 mg/kg GSK1070806 as intravenous infusion on Day 1. arm 2: Participants received Placebo as intravenous infusion on Day 1. arm 3: Participants received a single dose of 2 mg/kg GSK1070806 as intravenous infusion on Day 1. arm 4: Participants received Placebo as intravenous infusion on Day 1.

Interventions: intervention 1: GSK1070806 intervention 2: Placebo
Intervention descriptions: intervention 1: GSK1070806 will be administered intervention 2: Placebo will be administered

Protocol document:
Prot_000.pdf: 
 
 
                                                  Protocol Amendment  
 
Study ID:  215253 
 
Official Title of Study: A Phase Ib, Randomized, Double-Blind, Parallel Group, Placebo- 
                                       Controlled Study of the Clinical Effect, Safety and Tolerability of              
                                       a Single Intravenous Infusion of GSK1070806 in   Moderate to 
                                       Severe Atopic Dermatitis Patients 
 
NCT ID: NCT04975438 
 
Date of Document: 06-Jun-2022 
 
 


TMF-14679521 
CONFIDENTIAL 
GlaxoSmithKline group of companies 
 
215253 
 
1 
Clinical Study Protocol template V15 dated 21-Dec-2020 
TITLE PAGES 
Protocol Title: A Phase Ib, Randomized, Double-Blind, Parallel Group, Placebo-
Controlled Study of the Clinical Effect, Safety and Tolerability of a Single Intravenous 
Infusion of GSK1070806 in Moderate to Severe Atopic Dermatitis Patients.  
 
Protocol Number: 215253/Amendment 2 
Compound Number 
or Name: 
GSK1070806 
 
Brief Title:  
Clinical Effect, Safety and Tolerability of GSK1070806 in Atopic Dermatitis. 
Study Phase: Phase Ib:  
Sponsor Name and Legal Registered Address:  
Nicolas Wisniacki VP, Head of Discovery Medicine 
GlaxoSmithKline Research & Development Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
 
Medical Monitor Name and Contact Information will be provided separately 
Manufacturer: GSK  
Regulatory Agency Identifying Number(s):  
IND: 156168 
Approval Date: 06 Jun 2022 
 
 
Copyright 2022 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited. 
 


TMF-14679521 
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Clinical Study Protocol template V15 dated 21-Dec-2020 
DOCUMENT HISTORY 
Document 
Date 
Document Identifier 
Amendment 2 
06 Jun 2022 
TMF-14679521 
Amendment 1 
25-FEB-2022 
TMF-14357132 
Original Protocol 
20-JUN-2021 
TMF-13833595 
 
Amendment 2 06 Jun 2022 
This amendment is considered to be substantial based on the criteria set forth in Article 
10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union. 
Overall Rationale for Amendment 2:  
To permit (following consultation with the Medical Monitor), the screening of potential 
participants whose occasional recreational use of marijuana or medical use of marijuana 
will not likely impact the study. 
 
Section # and Name 
Description of Change 
Brief Rationale 
Section 5.2: Exclusion 
Criteria (No. 30) 
 
Substance abuse:  
ORIGINAL: Active 
substance abuse or a 
history of substance abuse 
within 6 months prior to 
the initial Screening visit. 
REVISED: Active substance 
abuse or a history of 
substance abuse (in the 
opinion of the Principal 
Investigator) within 6 
months prior to the initial 
Screening visit. Note that 
documented medical use 
of marijuana or occasional 
recreational use of 
marijuana may be 
permitted subject to a 
priori agreement with the 
Medical Monitor. 
When either the use of 
medical marijuana or the 
occasional recreational use 
of marijuana would be 
judged to not confound 
safety, efficacy or study 
compliance, then subject 
to a prior agreement with 
the Medical Monitor, such 
potential participants may 
progress to the Initial 
Screening Visit. 


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Clinical Study Protocol template V15 dated 21-Dec-2020 
Section # and Name 
Description of Change 
Brief Rationale 
Section 5.1: Inclusion 
Criteria (No. 13) 
Sequential numbering: 
Inclusion criteria No. 15 
amended to Inclusion 
Criteria No. 13 
Erroneous numbering 
 
 


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Clinical Study Protocol template V15 dated 21-Dec-2020 
TABLE OF CONTENTS 
PAGE 
TITLE PAGES ................................................................................................................. 1 
TABLE OF CONTENTS .................................................................................................. 4 
1. 
PROTOCOL SUMMARY .......................................................................................... 7 
1.1. 
Synopsis ....................................................................................................... 7 
1.2. 
Schema ........................................................................................................ 9 
1.3. 
Schedule of Activities (SoA) ........................................................................ 10 
1.3.1. 
Screening Period ......................................................................... 10 
1.3.2. 
Treatment / Follow-Up Period ...................................................... 11 
2. 
INTRODUCTION .................................................................................................... 12 
2.1. 
Study Rationale .......................................................................................... 12 
2.2. 
Background ................................................................................................ 13 
2.3. 
Benefit : Risk Assessment .......................................................................... 14 
2.3.1. 
Risk Assessment ......................................................................... 15 
2.3.2. 
Benefit Assessment ..................................................................... 22 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 22 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 22 
4. 
STUDY DESIGN .................................................................................................... 24 
4.1. 
Overall Design ............................................................................................ 24 
4.2. 
Scientific Rationale for Study Design .......................................................... 26 
4.2.1. 
Participant Input into Design ........................................................ 29 
4.3. 
Justification for Dose .................................................................................. 29 
4.4. 
End of Study Definition ............................................................................... 29 
5. 
STUDY POPULATION ........................................................................................... 30 
5.1. 
Inclusion Criteria ......................................................................................... 30 
5.2. 
Exclusion Criteria ........................................................................................ 32 
5.3. 
Lifestyle Considerations .............................................................................. 35 
5.3.1. 
COVID-19 related restrictions ...................................................... 35 
5.3.2. 
Meals and Dietary Restrictions .................................................... 35 
5.3.3. 
Caffeine, Alcohol, and Tobacco ................................................... 35 
5.3.4. 
Activity ......................................................................................... 36 
5.4. 
Screen Failures........................................................................................... 36 
5.4.1. 
Re-screening ............................................................................... 36 
5.4.2. 
Re-testing of Clinical Laboratory Values during Screening ........... 36 
5.5. 
Criteria for Temporarily Delaying ................................................................ 36 
6. 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY .............................. 37 
6.1. 
Study Intervention(s) Administered ............................................................. 37 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 38 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................... 39 
6.3.1. 
Controlled Early Access to Unblinded PK and PKPD Data .......... 39 
6.4. 
Study Intervention Compliance ................................................................... 40 
6.5. 
Dose Modification ....................................................................................... 40 
6.6. 
Continued Access to Study Intervention after the End of the Study ............ 40 


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2 1 5 2 5 3  
5  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V 1 5  d at e d 2 1 -D e c -2 0 2 0  
6. 7.  
Tr e at m e nt of O v er d o s e  ............................................................................... 4 0  
6. 8.  
C o n c o mit a nt T h er a p y .................................................................................. 4 0  
6. 8. 1.  
P er mitt e d C o n c o mit a nt T h er a pi e s  ................................................ 4 1  
6. 8. 2.  
Pr o hi bit e d M e di c ati o n s  ................................................................. 4 1  
7.  
DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L  ..................................................................... 4 1  
7. 1.  
Di s c o nti n u ati o n of St u d y I nt er v e nti o n  .......................................................... 4 1  
7. 1. 1.  
A d v er s e E v e nt Crit eri a  ................................................................. 4 2  
7. 1. 2.  
Li v er C h e mi str y Crit eri a  ............................................................... 4 2  
7. 1. 3.  
Q T c Crit eri a  ................................................................................. 4 2  
7. 1. 4.  
Ot h er Crit eri a  ............................................................................... 4 3  
7. 1. 5.  
St u d y S af et y St o p pi n g Crit eri a  ..................................................... 4 3  
7. 2.  
P arti ci p a nt Di s c o nti n u ati o n/ Wit h dr a w al fr o m t h e St u d y  ............................... 4 3  
7. 3.  
L o st t o F oll o w U p  ........................................................................................ 4 4  
8.  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  ..................................................... 4 5  
8. 1.  
Effi c a c y A s s e s s m e nt s  ................................................................................. 4 5  
8. 1. 1.  
E c z e m a Ar e a a n d S e v erit y I n d e x ( E A SI) ...................................... 4 5  
8. 1. 2.  
I n v e sti g at or Gl o b al A s s e s s m e nt (I G A) ......................................... 4 5  
8. 2.  
P ati e nt R e p ort e d O ut c o m e s ( P R O s)  ........................................................... 4 6  
8. 2. 1.  
P e a k Pr uriti s N u m eri c al R ati n g S c al e ( P P -N R S)  .......................... 4 6  
8. 2. 2.  
D er m at ol o g y Lif e Q u alit y I n d e x ( D L QI)  ........................................ 4 6  
8. 2. 3.  
T h e P ati e nt -R e p ort e d O ut c o m e s M e a s ur e m e nt 
I nf or m ati o n S y st e m ( P R O MI S) Sl e e p Di st ur b a n c e ....................... 4 7  
8. 2. 4.  
T h e F u n cti o n al A s s e s s m e nt of C hr o ni c Ill n e s s T h er a p y - 
F ati g u e ( F A CI T -F ati g u e)  .............................................................. 4 7  
8. 2. 5.  
T h e Bri ef F ati g u e I n v e nt or y ( B FI) -It e m 3 ...................................... 4 7  
8. 3.  
S af et y A s s e s s m e nt s  ................................................................................... 4 7  
8. 3. 1.  
P h y si c al E x a mi n ati o n s  ................................................................. 4 8  
8. 3. 2.  
Vit al Si g n s  .................................................................................... 4 8  
8. 3. 3.  
El e ctr o c ar di o gr a m s  ...................................................................... 4 8  
8. 3. 4.  
Cli ni c al S af et y L a b or at or y A s s e s s m e nt s  ...................................... 4 8  
8. 3. 5.  
Pr e g n a n c y T e sti n g  ....................................................................... 4 9  
8. 4.  
A d v er s e E v e nt s ( A E s), S eri o u s A d v er s e E v e nt s ( S A E s) a n d Ot h er 
S af et y R e p orti n g  ......................................................................................... 4 9  
8. 4. 1.  
Ti m e P eri o d a n d Fr e q u e n c y f or C oll e cti n g A E a n d S A E 
I nf or m ati o n ................................................................................... 5 0  
8. 4. 2.  
M et h o d of D et e cti n g A E s a n d S A E s  ............................................. 5 0  
8. 4. 3.  
F oll o w -u p of A E s a n d S A E s  ......................................................... 5 0  
8. 4. 4.  
R e g ul at or y R e p orti n g R e q uir e m e nt s f or S A E s  ............................. 5 0  
8. 4. 5.  
Pr e g n a n c y  ................................................................................... 5 2  
8. 4. 6.  
C ar di o v a s c ul ar a n d D e at h E v e nt s  ................................................ 5 2  
8. 6.  
G e n eti c s a n d/ or P h ar m a c o g e n o mi c s  .......................................................... 5 3  
8. 8.  
I m m u n o g e ni cit y A s s e s s m e nt s ..................................................................... 5 5  
C CI
C CI


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2 1 5 2 5 3  
6  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V 1 5  d at e d 2 1 -D e c -2 0 2 0  
8. 9.  
H e alt h E c o n o mi c s  ....................................................................................... 5 6  
9.  
S T A TI S TI C A L C O N SI D E R A TI O N S  ........................................................................ 5 6  
9. 1.  
St ati sti c al H y p ot h e s e s ................................................................................. 5 6  
9. 2.  
S a m pl e Si z e D et er mi n ati o n  ........................................................................ 5 6  
9. 3.  
A n al y si s S et s  .............................................................................................. 5 8  
9. 4.  
St ati sti c al A n al y s e s  ..................................................................................... 5 8  
9. 4. 1.  
G e n er al C o n si d er ati o n s  ............................................................... 5 8  
9. 4. 2.  
Pri m ar y E n d p oi nt( s)  ..................................................................... 5 9  
9. 4. 3.  
S e c o n d ar y E n d p oi nt( s)  ................................................................ 5 9  
9. 4. 5.  
Ot h er A n al y si s  ............................................................................. 6 0  
9. 5.  
I nt eri m A n al y si s .......................................................................................... 6 1  
9. 5. 1.  
R o uti n e p h ar m a c o vi gil a n c e  .......................................................... 6 1  
9. 5. 2.  
Pl a n n e d U n bli n d e d I nt eri m A n al y s e s  ........................................... 6 1  
1 0.  S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L  
C O N SI D E R A TI O N S  ............................................................................................... 6 2  
1 0. 1.  A p p e n di x 1: R e g ul at or y, Et hi c al, a n d St u d y O v er si g ht 
C o n si d er ati o n s  ............................................................................................ 6 2  
1 0. 1. 1.  
R e g ul at or y a n d Et hi c al C o n si d er ati o n s  ........................................ 6 2  
1 0 . 1. 2. 
Fi n a n ci al Di s cl o s ur e  ..................................................................... 6 3  
1 0. 1. 3.  
I nf or m e d C o n s e nt Pr o c e s s .......................................................... 6 3  
1 0. 1. 4.  
D at a Pr ot e cti o n  ............................................................................ 6 4  
1 0. 1 . 5. 
C o m mitt e e s Str u ct ur e  .................................................................. 6 4  
1 0. 1. 6.  
Di s s e mi n ati o n of Cli ni c al St u d y D at a  ........................................... 6 4  
1 0. 1. 7.  
D at a Q u alit y A s s ur a n c e  ............................................................... 6 5  
1 0. 1. 8.  
S o ur c e D o c u m e nt s  ...................................................................... 6 6  
1 0. 1 . 9. 
St u d y a n d Sit e St art a n d Cl o s ur e  ................................................. 6 6  
1 0. 1. 1 0.  P u bli c ati o n P oli c y  ......................................................................... 6 7  
1 0. 2.  A p p e n di x 2: Cli ni c al L a b or at or y T e st s  ......................................................... 6 8  
1 0. 3.  A p p e n di x 3: A E s a n d S A E s: D efi niti o n s a n d Pr o c e d ur e s f or 
R e c or di n g, E v al u ati n g, F oll o w -u p, a n d R e p orti n g  ....................................... 7 0  
1 0. 3. 1.  
D efi niti o n of A E  ............................................................................ 7 0  
1 0. 3. 2.  
D efi niti o n of S A E  .......................................................................... 7 2  
1 0. 3. 3.  
D efi niti o n of C ar di o v a s c ul ar E v e nt s  ............................................. 7 3  
1 0. 3. 4.  
R e c or di n g a n d F oll o w -U p of A E a n d S A E  .................................... 7 3  
1 0. 3. 5.  
R e p orti n g of S A E t o G S K  ............................................................. 7 5  
1 0. 4.  A p p e n di x 4: C o ntr a c e pti v e a n d B arri er G ui d a n c e  ....................................... 7 7  
1 0. 4. 1.  
D efi niti o n s:  ................................................................................... 7 7  
1 0. 4. 2.  
C o ntr a c e pti o n G ui d a n c e:  ............................................................. 7 8  
1 0. 5.  A p p e n di x 5: G e n eti c s  .................................................................................. 8 0  
1 0. 6.  A p p e n di x 6: Li v er S af et y: R e q uir e d A cti o n s a n d F oll o w -u p 
A s s e s s m e nt s.  ............................................................................................. 8 1  
1 0. 7.  A p p e n di x 7: A b br e vi ati o n s a n d Tr a d e m ar k s  ................................................ 8 3  
1 0. 8.  A p p e n di x 8: Pr ot o c ol A m e n d m e nt Hi st or y  ................................................... 8 7  
1 1.  R E F E R E N C E S  ....................................................................................................... 9 0  
 
C CI


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Clinical Study Protocol template V15 dated 21-Dec-2020 
1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A Phase Ib, Randomized, Double-Blind, Parallel Group, Placebo-
Controlled Study of the Clinical Effect, Safety and Tolerability of a Single Intravenous 
Infusion of GSK1070806 in Moderate to Severe Atopic Dermatitis Patients. 
Brief Title: Clinical Effect, Safety and Tolerability of GSK1070806 in Atopic Dermatitis. 
Rationale: Interleukin-18 (IL-18) is a pleiotropic cytokine with potential to amplify 
pathways important in Atopic Dermatitis (AtD) and for which increased IL-18 levels 
correlate with disease severity. GSK1070806 is a potent anti-IL-18 monoclonal antibody 
that is being developed for the treatment of AtD. 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
To compare the clinical effect of a 
single intravenous (IV) infusion of 
2 mg/kg GSK1070806 versus 
placebo in moderate to severe 
Atopic Dermatitis in the Biologic 
Naïve (BN) population (Group 1). 
Percent change from baseline (PCFB) in the 
Eczema Area and Severity Index (EASI) at Week 
12. 
Secondary 
To further compare the clinical 
effect (GSK1070806 versus 
placebo) in the BN population 
(Group 1). 
• 
Change from baseline (CFB) in the EASI at 
Week 12. 
• 
EASI 50/75/90 defined as ≥ 50/75/90% 
reduction in the EASI from Baseline at Week 
12. 
• 
Investigator Global Assessment (IGA) score 
of 0 or 1 at Week 12. 
To estimate the clinical effect of 
GSK1070806 in the dupilumab 
inadequate responder (Dupi-IR) 
population (Group 2). 
• 
PCFB in the EASI at Week 12. 
To assess safety and tolerability 
(GSK1070806 versus placebo) in 
the combined AtD population 
(Groups 1 and 2). 
• Incidence of serious adverse events (SAEs) 
and adverse events (AEs). 
• Incidence of clinically important findings in: 
o vital signs 
o electrocardiogram 
o laboratory: haematology, clinical 
chemistry and urinalysis. 


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Clinical Study Protocol template V15 dated 21-Dec-2020 
Objectives 
Endpoints 
To assess anti-drug antibody 
(ADA) formation in the AtD 
population (Groups 1 and 2 
combined) 
Incidence of ADAs. 
Overall Design: 
A multi-centre, 12-week, randomized, double-blind, parallel-group, placebo-controlled 
study of GSK1070806 to investigate efficacy and safety in moderate-to-severe AtD 
participants. 
Brief Summary: 
The study will assess the impact of GSK1070806 in two groups of patients with moderate-
to-severe AtD: 
• Group 1: Patients naïve to biologic treatment (and who have failed topical 
therapies). 
• Group 2: Patients who have not adequately responded (or have been intolerant) to 
dupilumab (Dupixent). 
All participants must wash out topical therapies (corticosteroids, calcineurin inhibitors, 
phosphodiesterase (PDEIV) inhibitors) for at least 7 days prior to dosing on Day 1. 
All participants are required to undergo Coronavirus strain 19 (COVID-19) testing prior to 
dosing and at the End of Study. 
Changes in the clinical signs of AtD as well as changes in disease biomarkers in blood and 
in skin (via serial biopsies and tape stripping) are to be assessed as well as patient reported 
outcomes (itch, sleep disturbance, fatigue), pharmacokinetics and anti-drug antibodies. 
The primary completion is at Week (Wk) 12 and the End of Study Visit is at Wk 24. 
Nine outpatient visits are scheduled: Screening (1), Treatment Period (6), Follow-Up 
Period (2). Skin biopsies and tape strips will be collected on Day 1 (prior to dosing), Wks 
4 and 12. 
Number of Participants: 
Approximately 64 patients are expected to be screened to achieve approximately 48 
randomly assigned participants. 


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Clinical Study Protocol template V15 dated 21-Dec-2020 
Intervention Groups and Duration: 
A single 2 mg/kg one-hour IV infusion of either GSK1070806 or placebo is to be 
administered as follows: 
• Group 1: N = 30.  20 participants will receive GSK1070806, 10 will receive 
placebo. 
• Group 2: N = 18. 15 participants will receive GSK1070806, 3 will receive 
placebo. 
The study duration for an individual participant is not expected to exceed 28 weeks 
(Screening 4 is weeks; Treatment Period is 12 weeks; Follow-Up Period is 12 weeks). 
Data Monitoring/ Other Committee:  An internal safety review team will review 
blinded safety data. A data review committee may conduct an interim analysis(es) on 
unblinded data. 
1.2. 
Schema 
 


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1 0  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V 1 5  d at e d 2 1 -D e c -2 0 2 0  
1. 3.  
S c h e d ul e of A cti viti e s ( S o A)  
1. 3. 1.  
S cr e e ni n g P eri o d  
 
 
P R O C E D U R E
S C R E E NI N G P E RI O D
U p t o D a y - 2 8
N O T E S:     Pl e as e als o r ef er t o A p p e n dix 2.                Scr e e ni n g m a y b e 
p erf or m e d acr oss o n e or m or e visits if n e e d e d.                                   
I nf or m e d C o ns e nt
X
I ncl usi o n/ Excl usi o n Crit eri a
X
D e m o gr a p h y
X
P h ysic al Ex a mi n ati o n ( F ull)
X
H ei g ht a n d W ei g ht
X
M e dic al/ m e dic ati o n/ dr u g/ alc o h ol hist or y
X
Alc o h ol Scr e e n
X
As p er st a n d ar d l oc al pr actic e.
Uri n e Dr u g Scr e e n
X
HI V, H e p atitis B a n d C.
X
C O VI D- 1 9 ( S A R S- C o V- 2) T est
X
EI T H E R  a d oc u m e nt e d ( R e g ul at or y A p pr o v e d) n e g ativ e t est wit hi n 
t w o d a ys of I niti al Scr e e n O R  t est p erf or m e d at I niti al Scr e e n
T B Scr e e ni n g ( Q u a nti F E R O N)
X
Pr e g n a ncy T est (s er u m, W O C B P) or 
F S H/ O estr a di ol (s er u m, W O N C B P)
X
W O C B P m ust h a v e c o nfir m e d m e nstr u ati o n wit hi n 2 8 d a ys of 
a ntici p at e d d osi n g o n D a y 1 a n d c o nti n u e t o r et ur n a n e g ativ e 
pr e g n a ncy t est u p t o a n d i ncl u di n g pri or t o d osi n g o n D a y 1.
1 2-l e a d E C G
Tri plic at e
Vit al Si g ns
X
H a e m at ol o gy, Cli nic al C h e mistr y
X
S e e A p p e n dix 2.
Uri n alysis
X
S e e A p p e n dix 2.
Cli nic al Ass ess m e nts ( Scr e e ni n g E A SI, I G A)
X
I nc Crit eri u m N o. 1
I d e ntif y t ar g et l esi o n
X
S T O P T C S / T CI /t o pic al P D EI Vi
D a y - 7 o n w ar ds
I nc. Crit. N o. 9 - P artici p a nt m ust S T O P T o pic als at D a y - 7
S T A R T a p plic ati o n of bl a n d e m olli e nt
D a y - 7 o n w ar ds
P P- N R S (itc h)
D a y - 7 o n w ar ds
R ec or d d aily
D a y - 7 o n w ar ds
R ec or d d aily
S A E ass ess m e nt
X
Fr o m si g ni n g  t h e I nf or m e d C o ns e nt F or m
C CI


T M F -1 4 6 7 9 5 2 1  
C O N FI D E N TI A L  
 
 
2 1 5 2 5 3  
 
1 1  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V 1 5  d at e d 2 1 -D e c -2 0 2 0  
1. 3. 2.  
Tr e at m e nt / F oll o w -U p P eri o d  
 
P R O C E D U R E
N O T E S: a ) Pri m ar y E n d p oi nt = D a y 8 5 ( W k 1 2). b)  E n d of St u d y = D a y 1 6 9 ( W k 2 4)
1
2
4
8
a1 2
1 6
b 2 4
D A Y
1
8
1 5 2 9 5 7
8 5
1 1 3
1 6 9
Disc h ar g e fr o m cli nic al u nit
X
Disc h ar g e n ot  s o o n er t h a n 2 h o urs p ost-e n d  of i nf usi o n.
I ncl usi o n/ Excl usi o n Crit eri a
X 1
1) R e-c h eck cli nic al st at us b ef or e d osi n g o n D a y 1.
Alc o h ol Scr e e n
X
M et h o d p er st a n d ar d l oc al pr actic e ( e. g. uri n e alc o h ol d u e t o C O VI D )
P h ysic al Ex a mi n ati o n ( F ull 1 / Bri ef)
( X) 1
X
X
X
X
X
X
X 1
X
X 1
1) F ull.
1 2-l e a d E C G
( X) 1
X
X
X
X
1) Tri plic at e R e a di n gs.  O n D a y 1: pr e- d os e, t h e n 3 0 a n d 6 0 mi ns p ost- st art  of i nf usi o n.
Vit al Si g ns
( X) 1
X
X
X
X
X
X
X
X
X
1) D osi n g D a y 1: pr e- d os e, 3 0 mi ns, 1,   1. 5 a n d 2  hrs p ost- e n d  of i nf usi o n.
Pr e g n a ncy T est
( X)
X
X
X
X
X
X
Hi g h s e nsiti vity uri n e pr e g n a ncy t est ( or s er u m t esti n g if r e q uir e d b y l oc al r e g ul ati o ns)
H a e m at ol o gy, Cli nic al C h e mistr y
( X)
X
X
X
X
X
X
X
X
X
S e e A p p e n dix 2.
Uri n al ysis
( X)
X
X
X
X
X
S e e A p p e n dix 2.
C O VI D- 1 9 ( S A R S- C o V- 2)
( X1)
X
X 3
X
1 ) N E G A TI V E R E S UL T m ust  b e o bt ai n e d pri or t o d osi n g. 2)   A d h oc t est i n c as e of 
s y m pt o ms. 3)  If n ec ess ar y ( at i n v esti g at or's discr eti o n).
E A SI
( X)
X
X
X
X
X
X
X
X
I G A
( X)
X
X
X
X
X
X
X
X
P P- N R S (itc h)
X
X
- Sl e e p Dist ur b a nc e 8 b
( X)
X
X
F A CI T- F ati g u e ( 1 3 it e ms)
( X)
X
X
X
X
DL QI: D er m at ol o gy Lif e Q u ality I n d ex
( X)
X
X
R a n d o miz ati o n & D O SI N G  (I V i nf.)
X
S ki n Bi o ps y (L esi o n a n d N o n-L esi o n al)
( X)1
X
X
1) N o n-L esi o n al Bi o ps y o bt ai n e d o nl y o n D a y 1.      R N As e q a n d I H C ( S ecti o n 8. 7. 4)
S ki n T a p estri p pi n g
( X)
X
X
R N As e q a n d Pr ot e o mics ( S ecti o n 8. 7. 5)
P h ar m ac o ki n etics ( P K)
( X)1
X
X
X
X
X
X
X
X
X
T ar g et E n g a g e m e nt ( T E)
( X)
X
X
X
X
X
X
X
X
X
S er u m Bi o m ar k ers (i ncl pr ot e o mics)
( X)
X
X
X
X
X 1
1) If wit h dr a w al occ urs e arli er t h a n D a y 8 5. ( S ecti o n 8. 7. 2.)  
W h ol e Bl o o d: R N A S e q u e nci n g 
( X)
X
X
P A X g e n e t u b es - ( S ecti o n 8. 7. 3.)
I m m u n o g e nicity
( X)
X
X
X
X
X
X
( S ecti o n 8. 8.)
P Gx
X
P Gx is o pti o n al ( S ecti o n 8. 6.)
S A E a n d A E 
X
X
S A Es r ec or d e d t hr o u g h o ut.  A Es r ec or d e d fr o m st art of I V i nf usi o n.
C o nc o mit a nt M e dic ati o ns
X
X
F oll o w- U p
N ot e: ( X) br ack ets d e n ot e t h e B as eli n e Ass ess m e nt.
<-------------------------------------------- >
<-------------------------------------------- >
W e e kly
Bi- w e e kly
W e e kly
Bi- w e e kly
W e e kly
Bi- w e e kly
 1)  D a y 1 P K  s a m pl es: pri or t o i nf usi o n,  i m m e di at ely at t h e e n d of i nf usi o n a n d t h e n 2 
h o urs p ost - e n d of i nf usi o n.  T E ass ess m e nt is c o m pris e d of at l e ast, b ut n ot li mit e d t o, 
T ot al IL- 1 8.  ( S ecti o n 8. 7. 1.)                                                                                                                                             
N ot e: O n D a y 1, all acti viti es a n d bl o o d s a m pl es ar e t o b e ac q uir e d pri or t o d osi n g , u nl ess st at e d ot h er wis e.
<------------------- D aily-------------------- >
Visit Wi n d o ws:  D a ys 8 t o 2 9 ( ± 1),     D a ys 5 7 t o 1 1 3 ( ± 2),    D a y 1 6 9 ( ± 3).
W e e kly:  e n d of W ks 1, 2, 3, 4.                                                                                                                    
Bi- W e e kly: e v er y t w o w e e ks, st arti n g at t h e e n d of W k 6.                                                                                                                                            
<--------------- D aily---------------- >
<------------- X 2-------------- >
U ns c h
e d ul e d 
Visit
E n d of W E E K
T R E A T M E N T P eri o d
E arl y 
wit h dr
a w
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2. 
INTRODUCTION 
GSK1070806 is a potent anti-interleukin-18 (IL-18) monoclonal antibody that is being 
developed for the treatment of Atopic Dermatitis (AtD) [see Investigator Brochure (IB), 
[GSK Document Number WM2009/00047/07]. 
2.1. 
Study Rationale  
Atopic Dermatitis 
Atopic dermatitis is a chronic relapsing inflammatory skin disease characterized by 
eczematous lesions and intense pruritus [Weidinger, 2016, Simpson, 2016a], and is 
associated with skin barrier dysfunction and immune dysregulation. Intense pruritus results 
in sleep deprivation, signs of anxiety and depression, impaired quality of life and reduced 
productivity [reviewed Yosipovitch, 2019]. 
AtD is a heterogeneous disease with primary T-helper cell (TH)2/TH22-skewing and 
variable TH1/TH17 contribution [Glickman, 2020]. Changes in the  transcriptional profile 
of AtD have been observed with a number of experimental / approved therapies that have 
also shown clinical efficacy including cyclosporin [Khattri, 2014], topical corticosteroids 
[Brunner, 2016], Janus kinase inhibitors [Pavel, 2019], phosphodiesterase 4 inhibitor 
[Bissonnette, 2019] dupilumab [Beck, 2014], ustekinumab [Khattri, 2017] and 
fezakinumab [Brunner, 2019]. The AtD skin proteome shows an inflammatory and 
vascular-endothelial signature (even in non-lesional skin), emphasizing the need for early 
treatment [Pavel, 2019]. 
Prevalence and Economic Burden 
Population-based estimates place adult prevalence between 2.1 - 4.4% across countries 
[Barbarot, 2018]. Severity is consistent worldwide with mild, moderate and severe at 
~60%, ~29%, and 11%, respectively [Fuxench, 2019]. 
In the United States (U.S.) three recent studies report that AtD occurs in approximately 7-
8% adults [Silverberg, 2015, Barbarot, 2018, Sacottte, 2018, Fuxench, 2019].  
From a 2004 study investigating the burden of skin disease in the United States, it was 
estimated that total annual burden of AtD (direct, indirect and costs due to quality of 
life) was $4.2 billion, equating to approximately $5.4 billion in 2016 [Adamson, 2017].  
Treatment(s) and Unmet Medical Need 
Dupilumab (Dupixent, see Summary of Product Characteristics, 2021] is a fully human 
monoclonal antibody directed against the IL-4 receptor α subunit and is licenced for use in 
moderate-severe AtD when topical prescription therapies have failed. Clinical trials of 
dupilumab in adults and adolescent populations with moderate to severe AtD have 
demonstrated significant improvement in clinical outcomes: for example, in two pivotal 
studies, SOLO 1 and SOLO 2, a 75% improvement in the eczema activity severity index, 
(EASI-75) was achieved in approximately 50% patients (versus placebo, 15%) with 
approximately 37% patients achieving an investigator global assessment (IGA) score of  
0/1 (clear/nearly clear skin), as compared to placebo (10% IGA 0/1). Other important 
measures including itch, quality of life and symptoms of anxiety and depression also 


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showed meaningful clinical improvement [Beck, 2014; Thaci, 2015; Simpson, 2016b; 
Blauvelt, 2017; de Bruin-Weller, 2018; Cork, 2020; Simpson, 2020a]. 
Although it was recently reported that the Investigator Global Assessment (IGA) 0/1 end 
point signiﬁcantly under estimated dupilumab’s treatment effects [Silverberg, 2019], the 
post-hoc analyses using other validated clinical endpoints suggest that there still remains 
an unmet medical need. Therefore, alternative therapies continue to be explored for patients 
who must discontinue dupilumab (or any other therapy) due to limited or slow-onset 
efficacy or adverse reactions. Indeed, there exists an opportunity to explore a broader 
approach and for which relatively infrequent dosing may also be possible, such as an anti-
IL-18 mAb (GSK1070806). 
2.2. 
Background 
Rationale for a potential role of IL-18 in Atopic Dermatitis 
Interleukin-18 (IL-18) is a pleiotropic cytokine which acts as a modulator of the innate 
and adaptive immune response in a context dependent manner with potential to amplify 
pathways important in AtD [Saikiran, 2013, Lee, 2015]. Increased IL-18 levels were 
observed in the skin and plasma of patients with AtD and correlated with disease severity 
[Inoue, 2011]. In preclinical models, overexpression of IL-18 induces skin inflammation, 
while neutralisation of IL-18 can prevent development of an AtD-like phenotype 
suggesting that IL-18 may have potential in clinical disease [Antonopoulos, 2008; Röse, 
2012; Plitz, 2003; Kawase, 2003; Ricardo-Gonzalez, 2018; Chen, 2020; Konishi, 2002; 
Terada, 2006]. Polymorphisms in the IL-18 gene locus are associated with higher 
circulating IL-18 levels and increased incidence of AtD. Collectively, these data suggest 
that IL-18 may play a key role in the pathophysiology of AtD which warrants clinical 
evaluation. 
GSK1070806 and prior clinical studies 
GSK1070806 is a highly potent anti-IL-18 monoclonal immunoglobulin G1 (IgG1) 
antibody which was previously explored in a first time in human (FTIH) and in exploratory 
studies in Type 2 Diabetes and Delayed Graft Function following renal transplantation 
[Mistry, 2014; McKie, 2016;Wlodek, 2021]. One additional early phase clinical study was 
also conducted in Crohn’s Disease but results have not yet been reported [see IB “Previous 
Human Experience” and Appendix “Tabulated List of Clinical Studies” for details, GSK 
Document Number WM2009/00047/07]. 
Study 215253 in Atopic Dermatitis: 
This translational medicine study (215253) will test the impact of GSK1070806 in two 
groups of patients with moderate-severe AtD. Group 1 participants are those who have 
failed topical therapies and remain naïve to both biologic therapies (e.g. dupilumab) and to 
inhibitors of the Janus kinase pathway (JAKi); the biologic naïve (BN) population. The 
primary efficacy endpoint of Group 1 is percent change from baseline in the eczema area 
and severity index (PCFB EASI [Hanifin, 2001]) at Wk 12. 
Given that the range of biological processes impacted by IL-18 is considerably broader 
than those impacted by IL-4/IL-13, there is the potential that GSK1070806 may provide 


T M F -1 4 6 7 9 5 2 1  
C O N FI D E N TI A L  
 
 
2 1 5 2 5 3  
 
1 4  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V 1 5  d at e d 2 1 -D e c -2 0 2 0  
i m pr o ve d be nefit c o m pare d t o d u pil u ma b  i n s o me patie nts. T heref ore, t he st u d y will 
a d dress efficac y i n patie nts w h ose disease was n ot pre vi o usl y c o ntr olle d b y d u pil u ma b  
(“ d u pil u ma b i na de q uat e res p o n der” D u pi-I R p o p ul ati o n, Gr o u p 2).  
2. 3.  
B e n efit  : Ri s k A s s e s s m e nt  
T he st u d y be n efit  : ris k assess me nt is base d u p o n  c o nsi derati o ns of  t he mec ha nis m of 
acti o n of bl oc ki n g I L-1 8 (a m o d ulat or of t he i m m u ne res p o nse), data fr o m t he o ne m o nt h 
c y n o m ol g us m o n ke y t o xic ol o g y st u d y a n d o n pri or cli nical e x perie nce f oll o wi n g si n gl e 
( u p t o 1 0 m g/ k g G S K 1 0 7 0 8 0 6) a n d t w o d oses ( 5 m g/ k g) of G S K 1 0 7 0 8 0 6, see I B, [ G S K 
D oc u me nt N u m ber W M 2 0 0 9/ 0 0 0 4 7/ 0 7 ]. 
M ore detaile d i nf or mati o n a b o ut t he p ote ntial b e n efits a n d ris ks of G S K 1 0 7 0 8 0 6  ma y be 
f o u n d i n t he I n vesti gat or’s Br oc h ure. 
 
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2.3.1. 
Risk Assessment 
Potential Risk of Clinical Significance 
 
Summary of Data/Rationale for Risk 
 
Mitigation Strategy 
 
Study Intervention(s) GSK1070806 
Increased susceptibility to infection 
 
IL-18 plays a role in host defence against 
microbial pathogens. Therefore, there is a 
theoretical risk that blocking of IL-18 
signalling by GSK1070806 may increase a 
patient’s susceptibility to bacterial and viral 
infections.  
Cynomolgus monkeys can be 
asymptomatic carriers of Shigella flexneri. 
Clinical signs of Shigella flexneri were first 
noted in a monkey administered vehicle 
control (0 mg/kg) and later in monkeys 
who received GSK1070806 at doses (3, 30 
and 300mg/kg) in the 4-week repeat dose 
study.  With the exception of 1 female in 
the top (300mg/kg) dose group, all animals 
responded to intramuscular antibiotic 
(Baytril) treatment prior to necropsy. 
In clinical studies, there was no apparent 
increase noted in infections, immune 
system disorders, or haematologic 
abnormalities in human participants dosed 
up to 10mg/kg. 
Appropriate exclusion criteria are included 
in the protocol (Section 5.2) to exclude 
patients with high risk of acute, recurrent 
and chronic infections 
Appropriate stopping criteria are included 
in the protocol (Section 7.1.1) with reviews 
of SAEs and severe AEs should they occur. 
 
 


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Potential Risk of Clinical Significance 
 
Summary of Data/Rationale for Risk 
 
Mitigation Strategy 
 
Infusion related and immune mediated side 
effects. 
 
No intravenous infusion-related or injection 
site reactions were noted in the monkey IV 
4-week repeat dose study and in human 
clinical studies. 
Participants will be monitored closely in a 
clinical unit for clinical signs of infusion-
related and immune-mediated side effects 
for 2 hours post-end of IV infusion. 
Patients will be informed of the potential 
for and symptoms of a late drug infusion 
reaction and on what to do (and this will 
also be detailed in the informed consent 
form [ICF]). 
Training for delegated staff on how to 
manage / available facilities will have been 
performed and documented. 
Immunogenicity 
No anti-drug antibodies (ADAs) were 
detected following 4 weekly 
administrations at doses up to 300 
mg/kg/week, or following the 8-week 
treatment free period, in cynomolgus 
monkeys. 
To date, 3 human participants had 
confirmed ADAs post dosing (1mg/kg), 
with relatively low titres. In 2 of 3 
participants the ADA titre were transient 
(positive at one time point) and were 
therefore not considered to be of major 
clinical significance. The third participant 
Monitoring of ADAs is included in the 
protocol.  


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Potential Risk of Clinical Significance 
 
Summary of Data/Rationale for Risk 
 
Mitigation Strategy 
 
had confirmed low titre ADA from Day 14 
to Day 213 post dose, but these did not 
result in any clinical sequelae. To date, 
there is no evidence that ADAs affected the 
safety or pharmacokinetic profile of 
GSK1070806. 
Effects on blood pressure 
There was no apparent change in blood 
pressure in a single 300 mg/kg dose non-
clinical safety pharmacology study and a 4-
week toxicology study in monkeys (300 
mg/kg administered weekly for 4 weeks). 
In the FTIH clinical study (A18110040), no 
apparent change was observed in any mean 
value for any vital sign parameters (systolic 
and diastolic blood pressure, heart or 
respiration rate and body temperature) 
following administration of placebo or 
GSK1070806 at any dose level.  
Following administration of 3 mg/kg in 
obese participants, there was one AE report 
of transient elevated heart rate and blood 
pressure values associated with an episode 
of supraventricular tachycardia that was 
noted on Holter monitoring. The 
investigator considered this AE to be 
unrelated to GSK1070806 
Vital signs are routinely monitored in the 
study. 
 


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Potential Risk of Clinical Significance 
 
Summary of Data/Rationale for Risk 
 
Mitigation Strategy 
 
In Study A18116378 AEs of hypertension 
were reported in Type 2 Diabetic Mellitus 
patients following GSK1070806 
administration (2/13 (15%) participants at 
0.25 mg/kg; 3/12 (25%) participants at 5 
mg/kg), but not placebo. A detailed review 
of blood pressure did not suggest an overall 
trend, although there were some individuals 
with variations in blood pressure.  
Effects on pregnancy 
A reproductive toxicology study has not 
been conducted. 
GSK1070806 is not considered genotoxic. 
Elevated levels of IL-18 in placentas of 
blood samples from women with 
preeclampsia have been observed. 
Non-clinical modelling suggested that the 
likely transferable drug concentration for 
sperm to female via the vaginal tract is 
negligible.  
Women who are pregnant, lactating or are 
planning on becoming pregnant during the 
study are excluded. (please refer to Section 
5.2 for male and female contraception). 
WOCBP require the use of highly effective 
contraceptive methods and are to be 
monitored for pregnancy and withdrawn 
from selected study procedures in case of 
pregnancy (excepting continued safety 
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Potential Risk of Clinical Significance 
 
Summary of Data/Rationale for Risk 
 
Mitigation Strategy 
 
Study Procedures  
Skin biopsy 
Complications of skin biopsy are 
uncommon but may include bleeding, 
infection, and scarring. 
 
Biopsies are to be performed under a local 
anaesthetic to reduce any discomfort. The 
small risk of infection after biopsy will be 
minimised by cleaning of the site before 
biopsy and the addition of a steri-
strip/suture if required (or similar). 
Participants are instructed to visually 
inspect skin biopsy sites and are informed 
on the signs of inflammation/infection to 
watch for and to contact the investigator 
with any concerns. 
 
Skin tape stripping 
Repeated tape stripping may cause mild 
discomfort. 
 
Participants are to be instructed to apply a 
bland emollient (if appropriate) following 
the procedure. 
Risk associated with attending an 
investigative site during the Coronavirus 
strain 19 (COVID-19) Pandemic 
 
The current COVID-19 (Severe acute 
respiratory syndrome-Coronavirus-2 
[SARS-CoV-2]) pandemic may pose a 
challenge to the integrity of the trial, 
protection of participants’ rights, safety and 
wellbeing and the safety of clinical trial 
staff. Therefore, risk mitigation strategies 
have been introduced and will be evaluated 
on an ongoing basis per each country. The 
Participant Selection: If it is deemed 
appropriate at a local level, participants will 
be counselled regarding the importance of 
infection control measures such as hand 
washing, reducing inter-personal contacts 
as much as possible and of potential 
COVID 19 symptoms. Site trial staff in 
direct contact and/or within 1 m distance of 
study participants will receive additional 


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Potential Risk of Clinical Significance 
 
Summary of Data/Rationale for Risk 
 
Mitigation Strategy 
 
study will be halted if the dynamics of the 
SARSCoV-2 outbreak change in such a 
way that the safety of the trial participants 
and clinical trial staff or integrity of the 
data collected cannot be guaranteed.  
protection via the use of Personal 
Protective Equipment (PPE) and 
disinfectants. 
Participant monitoring: If it is deemed 
appropriate at a local level, prospective 
AtD participants will be contacted by sites 
to check on COVID-19-related symptoms 
prior to being pre-screened (SARSCoV-2 
test) and prior to consenting. Consented 
participants may also be contacted (if it is 
deemed appropriate at a local level) prior to 
each scheduled visit. 
Participants will be screened prior to 
dosing on Day 1 and tested at the End of 
Study Visit (or at early withdrawal) as per 
protocol (see Section 1.3). 
Protection of Trial Integrity: Adherence 
to the protocol and investigative site 
procedures will go towards protecting the 
integrity of the data collected during this 
clinical trial, as well as the participants’ 
data protection rights. 
COVID-19 Contingency Plan: Any 
participant presenting with COVID-19-
related symptoms (2) and having a positive 


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Summary of Data/Rationale for Risk 
 
Mitigation Strategy 
 
SARS-CoV-2 test (3) may continue in the 
study (or may be temporarily suspended 
during recovery) if the investigator judges 
this to be possible (e.g. if the participant is 
able to adhere to local management 
guidance).  If a participant needs to be 
excluded from (further) participation in the 
trial s/he will receive follow-up medical 
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2.3.2. 
Benefit Assessment 
AtD participants may experience benefit in improved symptoms and clinical presentation 
following a single administered dose of GSK1070806. By enrolling in this study, 
participants will be contributing to the process of developing a new medicine to address 
the unmet need for patients intolerant or unresponsive to currently available treatments. 
2.3.3. 
Overall Benefit: Risk Conclusion 
There remains an unmet medical need for effective treatment of AtD in patients who 
inadequately responded to topical SoC. 
 
Considering the measures taken to minimise the potential risks of GSK1070806, the 
potential for clinical benefit outweighs the potential risks of testing GSK1070806 in 
study participants. 
3. 
OBJECTIVES AND ENDPOINTS  
 
Objectives 
Endpoints 
Primary 
To compare the clinical effect of a 
single intravenous (IV) infusion of 
2 mg/kg of GSK1070806 versus 
placebo in moderate to severe 
Atopic Dermatitis in the Biologic 
Naïve (BN) population (Group 1). 
Percent change from baseline (PCFB) in the 
Eczema Area and Severity Index (EASI) at Week 
12 (Section 8.1.1). 
Secondary 
To further compare the clinical 
effect (GSK1070806 versus 
placebo) in the BN population 
(Group 1). 
• 
Change from Baseline (CFB) in the EASI at 
Week 12. 
• 
EASI 50/75/90 defined as ≥ 50/75/90% 
reduction in the EASI from Baseline at Week 
12. 
• 
Investigator Global Assessment (IGA) score 
of 0 or 1 at Week 12. 
To estimate the clinical effect of 
GSK1070806 in the dupilumab 
inadequate responder (Dupi-IR) 
population (Group 2). 
• 
PCFB in the EASI at Week 12. 
To assess safety and tolerability 
(GSK1070806 versus placebo) in 
the combined AtD population 
(Groups 1 and 2). 
• Incidence of serious adverse events (SAEs) 
and adverse events (AEs). 
• Incidence of clinically important (1) findings 
in: 


T M F -1 4 6 7 9 5 2 1  
C O N FI D E N TI A L  
 
 
2 1 5 2 5 3  
 
2 3  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V 1 5  d at e d 2 1 -D e c -2 0 2 0  
O bjecti ves  
E n d p oi nts  
o  vital si g ns 
o  electr ocar di o gra m  
o  la b orat or y: hae mat ol o g y, cli nical 
c he mistr y a n d uri nal ysis.  ( Secti o n 8. 3 ) 
T o assess a nti -dr u g a nti b o d y 
( A D A) f or mati o n i n t he c o m bi ne d  
At D p o p ulati o n  (Gr o u ps 1 a n d 2 ) 
I n ci de nce of A D As ( Secti o n 8. 8 ) 
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Objectives 
Endpoints 
1) Absolute or change in important clinical findings are defined in the statistical 
analysis plan (SAP) for each relevant safety endpoint. 
 
4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a multi-centre, 12-week, randomized, double-blind, parallel group, placebo-
controlled study of GSK1070806 administered as a single 2 mg/kg IV and will investigate 
the efficacy and safety in moderate-severe AtD participants. See the Study Schematic 
(Section 1.2) and the Schedule of Activities (Section 1.3). 
Study Populations and Randomisation 
Group 1 - BN: for whom disease was not adequately controlled by topical treatments. 
Approximately 40 BN patients may need to be consented for screening to provide 30 
randomized. Thirty BN participants will receive GSK1070806 or placebo in a 2:1 ratio 
(20 and 10 participants, respectively). 
Group 2 - Dupi-IRs: patients whose disease was not adequately controlled following at 
least 16 weeks of dupilumab treatment (please refer to inclusion and exclusion criteria) or 
who could not tolerate dupilumab. Approximately 24 Dupi-IR patients may need to be 
consented for screening to provide 18 randomized. Eighteen Dupi-IR participants will 
receive GSK1070806 or placebo in a 5:1 ratio (15 and 3 participants, respectively). 
Primary Efficacy Endpoint 
The primary efficacy endpoint is percent change from baseline in the eczema area and 
severity index (PCFB EASI [Hanifin, 2001]) at Wk 12 in participants of Group 1. 
Study Duration 
Groups 1 and 2 will be conducted in parallel. 
The overall study duration for an individual participant is not expected to exceed 28 
weeks (Screening is 4 weeks; Treatment Period is 12 weeks; Follow-Up Period is 12 
weeks). 
The End of Study (Wk 24, Day 169) allows for continued safety monitoring beyond the 
Wk 12 primary endpoint in this new disease population (AtD), for which GSK1070806 has 
not yet been tested. 


T M F -1 4 6 7 9 5 2 1  
C O N FI D E N TI A L  
 
 
2 1 5 2 5 3  
 
2 5  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V 1 5  d at e d 2 1 -D e c -2 0 2 0  
Tre at me nt a n d  F oll o w -U p Peri o d s Scree ni n g Peri o d  
•  T he Scree ni n g Peri o d is 2 8 da ys.  
•  All partici pa nts m ust st o p usi n g t o pical treat me nts (c ortic oster oi ds, calci ne uri n 
i n hi bit ors or P h os p h o diesterase 4 [ P D EIV] i n hi bit ors) f or at least 7 da ys (starti n g 
o n Da y -7) pri or t o d osi n g o n Da y 1.  
•  Partici pa nts s h o ul d a p pl y bla n d t o pical e m ollie nt at least o nce fr o m at least Da y -7 
( u ntil at least W k 1 2). 
•  Partici pa nts m ust rec or d itc h ( P P -N R S) a n d fati g ue ( brief fati g u e i n v e nt or y,
ite m 3) dail y starti n g o n Da y -7 (see S o A Secti o n 1. 3 ). 
 
F oll o wi n g t he e n d of t he si n gle i ntra v e n o us i nf usi o n of st u d y tr eat me nt, partici pa nts are 
t o be m o nit ore d f or at least a t w o-h o ur peri o d b ef ore disc har ge fr o m t he cli nical u nit.  
T he Treat me nt a n d F oll o w -U p Peri o ds are b ot h 1 2 w eeks i n d urati o n. T he partici pa nt will 
be i nstr ucte d t o ma ke c o ntact wit h t he site at a n y ti me i n case of a n y c o ncer n . Partici pa nts 
w h o wit h dra w fr o m t he st u d y m ust  be e nc o ura ge d t o c o m plete t he assess m e nts liste d f or 
t he Wit h dra wal Visit. 
S afet y Re vie w Te a m ( S R T)  
I n li ne wit h r o uti ne p har mac o vi gila n ce, a n i nter nal G S K safet y re vi e w tea m ( S R T , see 
Secti o n 1 0. 1. 5 ) will ha v e o versi g ht of a n y e mer gi n g safet y d ata relate d t o G S K 1 0 7 0 8 0 6 
a n d will re vie w bli n de d  s afet y data at a p pr o priate i nter vals. 
St atistic al A n al yses  
•  T he pri mar y a n al ysis will be perf or m e d w he n all partici pa nts i n Gr o u p 1  h a ve 
reac h e d W k 1 2 (or ha v e wit h dra w n fr o m t he st u d y pri or t o W k 1 2 ).  
•  I nteri m a nal yses ma y b e perf or me d i n G r o u ps 1 a n d 2, a n d will be o versee n b y a Data 
Re vie w C o m mittee ( D R C,  Secti o n 1 0. 1. 5 ):  
o  Gr o u p  1: O ne u n bli n de d efficac y i nteri m a n al ysis ma y b e perf or me d w h e n 
a p pr o xi matel y 5 0 % partici pa nts i n Gr o u p 1 ha ve c o m plete d W k 1 2 (or ha v e 
wit h dra w n  pri or t o W k 1 2, see  Secti o n 9. 5. 2 ). T he s t u d y ma y be ter mi nate d 
f oll o wi n g t he i nteri m a n al ysis. A d diti o nal u n bli n de d i nteri m a nal yses ma y be 
perf or me d t o s u p p ort i nter nal decisi o ns a n d will ha ve n o i m pact o n t he 
c o n d uct of t he  st u d y. 
o  Gr o u p 2: O ne u n bli n de d efficac y i nteri m a n al ysis ma y b e perf or me d w h e n 
a p pr o xi matel y 3 0 partici pa nts i n Gr o u p 1  ha ve b ee n ra n d o mize d ( Secti o n 
9. 5. 2 ). Gr o u p 2  recr uit me nt ma y be t er mi nate d f oll o wi n g t he i nteri m a n al ysis. 
A d diti o nal u n bli n de d i nteri m a nal yses ma y b e perf or me d t o s u p p ort i nter nal 
decisi o ns a n d will ha ve n o i m pact o n t he c o n d uct of t he st u d y.  
•  A n e n d of st u d y a nal ysis will be perf or me d w he n t he last  partici pa nt last visit ( L P L V) 
has bee n ac hie ve d.   
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4.2. 
Scientific Rationale for Study Design 
Randomized, double-blind, placebo-controlled design 
GSK1070806 is an experimental drug which has not previously been studied in the AtD 
population. The inclusion of a placebo arm in Groups 1 and 2 will ensure blinding of any 
attribution of treatment to potential safety signals whilst also providing control data for 
the comparison of efficacy and biomarkers. 
Rationale for Two Study Populations 
Participants are to be grouped on the basis of their prior treatment: either Group 1 - biologic 
naïve (BN) and having failed topical therapies, or Group 2 - whether having specifically 
demonstrated an inadequate response to dupilumab (Dupi-IR).  
• Group 1: Participants with moderate to severe AtD who have not responded adequately 
to topical treatments (after 4 weeks treatment with either TCS or TCI within the last 6 
months) may usually, at this stage, be considered for an approved therapy (if available) 
e.g. Dupixent, or JAKis, or be considered for clinical trials. 
Potential BN participants must not have ever been treated for AtD with either 
dupilumab, other experimental biological treatments, or JAKi(s), owing to the potential 
for an overlapping mechanism of action with GSK1070806 
Studying GSK1070806 in the BN population will enable evaluation of preliminary 
efficacy in moderate-severe AtD and will allow indirect comparison with historical 
data. 
• Group 2: Although approximately 50% AtD patients receiving dupilumab (Dupixent, 
an anti-interleukin-4 receptor [IL-4R] mAb) achieve EASI75, there remains a 
significant unmet need.  Since the range of biological processes impacted by IL-18 is 
broader than those impacted by IL-4/IL-13, there is the potential that GSK1070806 
may provide benefit to those patients who were not adequately controlled by 
dupilumab. Therefore, it is of particular interest to additionally select/include a small 
group of Dupi-IRs to broaden the investigation.  
Given the putative difference in efficacy between the two study populations (as a 
consequence of prior treatment with dupilumab), the clinical endpoints for these 
populations are to be analysed separately (see Section 9). 
Washout of prior therapy during Screening. 
All participants must meet all clinical criteria at the point of randomization (for subsequent 
dosing on Day 1) following at least a 7-day washout of TCS (starting from Day -7).  
Duration of Treatment / Follow-Up Period 
The duration of the Treatment Period is 12 weeks (see both this Section 4.2 “Efficacy 
Endpoints” and Justification for Dose: Section 4.3). 
 


T M F -1 4 6 7 9 5 2 1  
C O N FI D E N TI A L  
 
 
2 1 5 2 5 3  
 
2 7  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V 1 5  d at e d 2 1 -D e c -2 0 2 0  
T he d urati o n of t he F oll o w -U p Peri o d is base d u p o n t he  o bser ve d h alf -life of  G S K 1 0 7 0 8 0 6 
i n healt h y v ol u nteers, w hic h was 3 1 da ys at 1 m g/ k g a n d 3 8 da ys at 3 m g/ k g  [I n vesti gat or’s 
Br oc h ure: G S K D oc u me nt N u m ber  W M 2 0 0 9/ 0 0 0 4 7/ 0 7 ]. F oll o wi n g patie nts f or 2 4 weeks 
after a d mi nistrati o n of 
G S K 1 0 7 0 8 0 6 all o ws safet y 
m o nit ori n g t o c o nti n ue f or 
a p pr o xi matel y 5 half -li ves i n t his ne w disease p o p ulati o n (see J ustificati o n f or D ose, 
Secti o n  4. 3 ). 
R a n d o mi z ati o n R ati o  
Gr o u p 1  (B N ): partici p a nts will be ra n d o mize d i n a 2: 1 rati o t o i ncrease t he o verall c ha nce 
of partici pa nts recei vi n g G S K 1 0 7 0 8 0 6 o ver place b o.  T o s u p ple me nt t he n u m ber of 
partici pa nts i n t he place b o ar m, hist orical data were us e d a n d a r o b ust meta -a nal ytic 
pre dicti ve ( M A P) pri or was c o nstr ucte d wit h a n effecti ve sa m ple siz e of 1 4  partici pa nts 
(e x pecte d l ocal-i nf or mati o n-rati o [E LI R ] met h o d [Ne ue nsc h wa n der , 2 0 2 0 ]).  
Gr o u p 2  ( D u pi-I R): p arti ci pa nts will be ra n d o mize d i n a 5: 1 rati o. T he cli nical effect i n 
t his gr o u p will n ot be c o m pare d a gai nst place b o (see Secti o n 9 ) b ut a s mall place b o ar m 
has bee n i ncl u de d t o mai ntai n t he st u d y bli n d.  
Effi c a c y E n d p oi nt s   
T he pri mar y e n d p oi nt is P C F B i n t he E A SI at W k 1 2 i n t he B N p o p ulati o n  (Gr o u p 1 ). 
E A SI (s ee Secti o n  8. 1. 1 ) is a prece d e nte d c o m p osite cli nical e n d p oi nt f or use i n earl y 
cli nical trials of m o derate t o se vere At D [ Ha nifi n , 2 0 0 1 ]. T he ma g nit u de of efficac y 
( meas ure d as P C F B a n d C F B E A SI) o bs er ve d as cli nicall y m ea ni n gf ul was e vi de nt b y 1 2 
w eeks after a d mi nistrati o n of b ot h mar k ete d pr o d ucts ( Crisa b or ole [ Bi ss o n nette, 2 0 1 9], 
D u pi x e nt [ Bec k , 2 0 1 4] a n d of P hase II/III e x peri me ntal dr u gs, U pa d aciti ni b [G utt ma n -
Yass k y , 2 0 2 0] a n d A br o citi ni b [Si m ps o n , 2 0 2 0 b] a n d will all o w f or i n direct c o m paris o n 
t o ot her t hera pies. 
Si milarl y, t he I G A res p o nse is a n esta blis he d F o o d a n d Dr u g A d mi nistrati o n ( F D A ) 
re g ulat or y e n d p oi nt. Cli nical sc ores will be meas ure d t hr o u g h o ut t o e ns ure preli mi nar y  
assess me nt  of t he o nset , e xte nt a n d d urati o n of cli nical res p o nse . 
P ati e nt R e p ort e d O ut c o m e s ( P R O s)  
Nearl y t w o‐t hir ds ( 6 2· 9 %) of m o derate t o se vere At D patie nts re p ort itc hi n g f or at least 1 2 
h eac h da y, wit h 6 0· 5 % of patie nts rati n g t heir itc h as eit her se vere or u n beara ble (Si m ps o n , 
2 0 1 6c). Re d uci n g t he itc h – scratc h c ycle is a n i m p orta nt treat me nt g oal a n d f or ms a ke y 
as pect of re d uci n g o v erall disease se v erit y. T he P P -N R S is a rec o g nize d cli nical i nstr u me nt 
f or itc h i n At D (re vie we d Y osi p o vitc h , 2 0 1 9 ). T hree a d diti o nal P R O i nstr u me nts ha ve bee n 
i ntr o d uce d t o c ollect q ualitati ve a n d mea ni n gf ul data o n slee p dist ur ba nce
Slee p 
Dis t ur ba nce, Lei , 2 0 2 0) a n d 
 [Te n na nt , 2 0 1 9 ] a n d 
[Me n d oza , 
1 9 9 9 ]). T he der mat ol o g y life q ualit y i n de x ( D L QI) c o vers t he i m pact of At D o n ge n eral 
as pects of dail y li vi n g  [Fi nla y , 1 9 9 4],  see d etails i n Secti o n 8. 2 . 
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2 8  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V 1 5  d at e d 2 1 -D e c -2 0 2 0  
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T M F -1 4 6 7 9 5 2 1  
C O N FI D E N TI A L  
 
 
2 1 5 2 5 3  
 
2 9  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V 1 5  d at e d 2 1 -D e c -2 0 2 0  
4. 2. 1.  
P arti ci p a nt I n p ut i nt o D e si g n  
Fee d b ac k o n st u d y desi g n o btai ne d d uri n g i nter vi e w wit h o ne patie nt bas e d i n U S hel d o n 
2 2 -0 4 -0 2 1. Base d o n t he patie nt fee d b ac k fr o m t he i nter vie w, t he n u m ber of bi o psies was  
decrease d fr o m 5 t o 4 .  
4. 3.  
J u stifi c ati o n f or D o s e  
A si n gle 2 m g/ k g d ose G S K 1 0 7 0 8 0 6 a d mi nistere d via i ntra ve n o us i nf usi o n is pr o p ose d f or 
St u d y 2 1 5 2 5 3.  
T he pre dict e d e x p os ures of G S K 1 0 7 0 8 0 6 ( C ma x a n d A U C; 0. 0 5 m g/ m L a n d 2 7. 2 
m g. h/ m L, res pecti vel y) after a si n gle d ose of 2 m g/ k g are 3 7 6 a n d 6 5 f ol d bel o w t h e 
N O A E L t hres h ol ds ( C ma x a n d 
wee kl y 
A U C; 1 8. 8 
m g/ m L a n d 1 7 7 5 
m g. h/ m L, 
res pecti vel y) fr o m t he 1 m o nt h c y n o m ol g us m o n ke y st u d y ( 4 wee kl y 3 0 0 m g/ k g d oses).  
T he safet y, t olera bilit y a n d P K of G S K 1 0 7 0 8 0 6 ha ve  bee n e val uat e d i n h u ma n s after 
a d mi nistrati o n of a si n gle escalati n g d ose ( d os e le vel ra n gi n g fr o m 0. 0 0 8  m g / k g u p t o 1 0  
m g / k g) a n d after t w o d oses a d mi nistere d 2 8 da ys a part ( d ose le vels st u die d: 0. 2 5  m g / k g or 
5  m g / k g). I n all cli nical st u dies t o date, G S K 1 0 7 0 8 0 6 was well t olerate d o ver at least 2 1 0 
da ys  (see I n vesti gat or Br oc h ure [ G S K D oc u me nt N u m ber W M 2 0 0 9/ 0 0 0 4 7/ 0 7 ]). 
A  mec ha nistic P K P D m o del base d o n b ot h precli nical affi nit y data a n d t he o bser ve d 
cli nical P K a n d P D  data s u g gests t hat a si n gle 2 m g/ k g d ose G S K 1 0 7 0 8 0 6 a d mi nistere d 
via i ntra ve n o us i nf usio n is a ntici pate d t o pr o vi d e > 9 0 % re d ucti o n i n plas ma free I L-1 8 
le vels i n at least 9 0 % of partici pa nts f or at least 1 2 weeks : t his e xte nt a n d d urati o n of 
i n hi biti o n is j u d ge d t o be s ufficie nt t o pr o vi de a r o b ust assess me nt of t h e p ote ntial of 
G S K 1 0 7 0 8 0 6 t o treat At D . 
G S K 1 0 7 0 8 0 6 has a ter mi nal half -life ra n gi n g fr o m 3 1 t o 3 8  da ys  after si n gl e d ose  
a d mi nistrati o n  of 1 or 3  m g / k g. T heref ore, it is e x pecte d t hat after a si n gle d ose of 2  
m g / k g, dr u g le vels at t he E n d of St u d y ( Da y 1 6 9) will be re d uce d  3 2 -f ol d (2 5) as 
c o m pare d t o t he C Ma x  at t he e n d of i nf usi o n.  Alt h o u g h t he c o nce ntr ati o n of G S K 1 0 7 0 8 0 6 
at Da y 1 6 9 is pre dict e d t o be > 1 0, 0 0 0 f ol d bel o w t he N O A E L t hr es h ol d, t he e xte n de d 
p har mac o d y n a mic effect o bser ve d i n pr e vi o us st u dies s u g gest t hat circ ulati n g 
G S K 1 0 7 0 8 0 6 at t his ti me ma y still retai n s o me p h ar mac ol o gical acti vit y. H o we ver,  in 
pre vi o us cli nical st u dies, G S K 1 0 7 0 8 0 6 was well t olerate d o ver at least 2 1 0 da ys after 
d osi n g w he n c o m pare d t o place b o at d oses u p t o 1 0 m g/ k g, s o safet y m o nit ori n g f or a 2 4 -
w eek peri o d i n t his st u d y is a p pr o priate . 
4. 4.  
E n d of St u d y D efi niti o n  
T he E n d of S t u d y is defi ne d as t he date of t he last visit of t he last partici pa nt acc or di n g t o 
t he Sc he d ule of A cti vities.  
A partici pa nt is c o nsi dere d t o ha ve c o m plete d t h e st u d y if he/s he has  c o m plete d t he last 
sc he d ule d pr o ce d ure s h o w n i n t he Sc he d ule of Acti vities. 
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5. 
STUDY POPULATION 
Inclusion Criteria Numbers 4 and 5 and Exclusion Criterion Number 21 distinguish the two 
study populations. 
Prospective approval of protocol deviations to recruitment and enrolment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria 
TYPE OF PARTICIPANT AND DISEASE CHARACTERISTICS 
1. Moderate to severe atopic dermatitis (confirmed by a dermatologist) according to the 
Hannifin and Rajka criteria or Eichenfield revised criteria [Eichenfield, 2014; 
Hanifin, 1980]. 
2. Onset of AtD symptoms occurring at least 6 months prior to Screening, with stable 
disease for at least 1 month prior to Screening. 
3. The participant should meet the following criteria at the initial Screen and 
immediately prior to trial drug infusion on Day 1 (Baseline): 
a. EASI ≥16  
b. IGA score ≥3. 
4. Group 1 - Biologic Naïve: Topical First Line Treatment: Documented recent history 
(within 6 months before Screening) of: 
a. either an inadequate response (IR) to out-patient treatment with at least one 
topical treatment (intermittent TCS, TCI), topical PDEIV inhibitor 
(Crisaborole). 
b. or that topical treatments were otherwise not recommended. 
5. Group 2 – Dupi-IRs: Documented history of an inadequate response (IR) to 
dupilumab:  
a. either following at least 16 weeks of treatment according to the Investigator’s 
judgement 
b. or intolerant to dupilumab owing to adverse events. 
6. Willing to discontinue topical corticosteroids, topical calcineurin inhibitors or topical 
PDEIV inhibitors from at least 7 days (starting Day -7) prior to trial drug infusion on 
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7. Stable use of topical emollient e.g. use of an additive-free, bland emollient for at 
least 7 days (starting Day -7) prior to dosing on Day 1 and be willing to continue a 
stable regimen for at least 12 weeks after dosing). 
8. Willing to contribute three serial 4.5 mm punch biopsies of lesional skin and a set of 
tape strips at Baseline, Wk 4 and Wk 12. Willing to contribute one 4.5 mm punch 
biopsy of non-lesional skin at Baseline. 
9. If receiving concomitant medications for any reason, the participant should try to 
stay on a stable regimen throughout the entire study.  
AGE 
10. Between 18 and 75 years of age inclusive, at the time of signing the informed 
consent.  
 
WEIGHT 
11. Body mass index (BMI) within the range 18 - 39.9 kg/m2 (inclusive). 
 
SEX and CONTRACEPTIVE/BARRIER REQUIREMENTS  
12. Sex and Contraceptive /Barrier requirements for males and females 
a. Male Participants: 
Male participants are eligible to participate.  
b. Female Participants:  
• A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and one of the following conditions applies: 
o Is a woman of non-childbearing potential (WONCBP) as defined in Section 
10.4, Contraception and Barrier Guidance. 
OR 
o Is a woman of childbearing potential WOCBP and using an acceptable 
contraceptive method as described in Section 10.4 during the study period. 
The investigator should evaluate the potential for contraceptive method 
failure (e.g., noncompliance, recently initiated in relationship to the first 
dose of study intervention. 
• A WOCBP must have a negative highly sensitive serum pregnancy test result 
(as required by local regulations) at the initial Screening visit and a negative 
urine pregnancy test result immediately prior to dosing on Day 1: see Section 
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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 Section 8.3.5. 
• 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 
13. Capable of giving signed informed consent as described in Section 10.1 which 
includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol. 
5.2. 
Exclusion Criteria 
Medical Conditions 
1. Skin Morbidity: other than atopic dermatitis, the presence of a significant skin 
morbidity that will influence the Investigator’s ability to assess the severity of the 
disease (e.g. psoriasis, confirmed or suspected cutaneous T-cell lymphoma, 
autoimmune bullous disease, fixed drug reaction and Stevens Johnson Syndrome).  
2. Major Diseases/Conditions: Participants with any uncontrolled medical conditions, 
other than Atopic Dermatitis, that in the opinion of the investigator puts the 
participant at unacceptable risk or will likely interfere with study assessments or data 
integrity. Other medical conditions should be stable at the time of screening and be 
expected to remain stable for the duration of the study. 
3. Malignancy: solid or hematological malignancy or a history of malignancy (in the 
past 5 years), except for treated/cured basal cell or squamous cell in situ skin 
carcinomas, cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the 
cervix. 
4. Infection: 
• An acute infection within 2 weeks of dosing on Day 1. 
• history of, or currently being treated for, a clinically significant recurrent or 
chronic infection/s (except very minor localised infections, for example tinea 
pedis). 
• hospitalized for treatment of infection (anti-bacterials, anti-virals, anti-fungals 
or anti-parasitic agents) within 30 days of dosing on Day 1. 
5. Known varicella, herpes zoster, or other severe viral infection within 6 weeks of 
anticipated dosing on Day 1. Or history of recurrent herpes reactivation in the past 2 
years. 
6. COVID-19 (SARS CoV-2): 
• 
Has had COVID-19 infection within 4 weeks of the initial Screening visit. 


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• 
Positive test obtained at initial Screening. 
• 
Signs and symptoms suggestive of COVID-19 (i.e. fever, cough, etc) within 
14 days of initial Screening. 
• 
Known COVID-19-positive contacts within 14 days of initial Screening, at 
any time during the Screening Period, or within 14 days of dosing on Day 1.  
7. Tuberculosis (TB): Evidence of active or latent TB as documented by medical 
history, examination, and TB testing with a positive QuantiFERON test at initial 
Screening visit. 
NOTE:  In cases where the QuantiFERON 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. In cases where the QuantiFERON test is positive, the participant should be 
followed up as per standard of care. 
8. Drug Allergy or hypersensitivity: history of clinically significant multiple or 
severe drug allergies or severe post-treatment hypersensitivity reactions (including, 
but not limited to, erythema multiforme major, linear immunoglobulin A (IgA) 
dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis).  
9. Sensitivity to any of the study interventions, or components/excipients thereof, in 
the opinion of the Principal Investigator (or following consultation with the GSK 
Medical Monitor), contraindicates participation in the study. 
10. Hepatic: current or chronic history of liver disease, or known hepatic or biliary 
abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 
a. Alanine transaminase (ALT) >2x upper limit of normal (ULN). 
b. Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if 
bilirubin is fractionated and direct bilirubin <35%). 
11. Cardiology assessment/co-morbidity defined as: corrected Q (QTc) >450 msec (480 
msec for those with Bundle Branch Block). Either QTcb (Bazett) or QTcf 
(Fridericia), machine or manual overread, may be used. The QT correction formula 
used to determine exclusion and discontinuation should be the same throughout the 
trial. The QTc should be based on a single value (derived from the average of 
triplicate readings) of ECG obtained over a brief recording period. 
12. A participant with either a clinical abnormality or a laboratory parameter(s) 
outside of the reference range (or both) that is not specifically listed in the inclusion 
or exclusion criteria may only be included if the Investigator, in consultation with 
the GSK Medical Monitor, agrees and documents that the finding is unlikely to 
introduce additional risk factors that will not interfere with the study procedures or 
interpretation. 
 
PRIOR / CONCOMITANT THERAPY 
Any patients that are receiving medication(s) detailed in this Section will not be eligible 
for randomisation into the trial. 
 
13. Surgery: major surgery (as per investigator’s judgement) within 3 months prior to 
dosing on Day 1. 


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14. Phototherapy: treatment with phototherapy (narrow band ultraviolet B [NBUVB], 
ultraviolet B [UVB], ultraviolet A1 [UVA1], psoralen + ultraviolet A [PUVA]), 
within 4 weeks of dosing on Day 1. 
15. Sun/tanning: prolonged sun exposure or use of tanning booths (which may 
confound interpretation of study data) within 2 weeks before Initial Screening. 
16. Bleach bath: three or more bleach baths during any week within 4 weeks of the 
initial Screening visit. 
17. Medical Devices: treatment of AtD with a medical device (eg, Atopiclair, MimyX, 
Epicerum, Cerave, etc) within 1 week of the initial Screening visit. 
18. Vaccines: participant has received a live, attenuated or recombinant vaccine within 
8 weeks of anticipated dosing (Day 1), or will require vaccination within 24 weeks 
following dosing.  Note that, the recombinant adenovirus vector vaccines against 
COVID-19 (both human and non-human primate in type) are permitted (refer to the 
study reference manual, SRM). 
19. Systemic corticosteroids: treatment within 30 days of dosing on Day 1. Note that, 
intra-articular steroids are permitted. 
20. Topical corticosteroids: treatment within 7 days of dosing on Day 1. 
21. Biologic agents: treatment with biologic agents (investigational and marketed 
monoclonal antibodies) within 12 weeks or 5 pharmacokinetic half-lives (whichever 
is longer) prior dosing on Day 1. 
22. JAK inhibitors: treatment with JAK inhibitors (e.g. baricitinib, upadacitinib) within 
4 weeks or 5 half-lives (whichever is longer) prior to dosing on Day 1. 
23. Other systemic treatments: mycophenolate mofetil, azathioprine, methotrexate, or 
calcineurin inhibitors within 4 weeks of Screening.  
Prior / Concurrent Clinical Study Experience 
24. Blood / product loss: participation in this study would result in loss of blood or 
blood products in excess of 500 mL within 3 months. 
25. Investigational drug: use of any investigational drug within 30 days prior to the 
initial Screening visit, or 5 pharmacokinetic half-lives, or twice the duration of the 
biological effect (if known), whichever is longer. 
Diagnostic assessments 
26. Hepatitis B: patients will be excluded with any evidence of acute or chronic 
infection, or if interpretation of their results is unclear at the initial Screening 
visit.This includes: 
a. Hepatitis B surface antigen (HbsAg) + 
b. Anti-hepatitis B core (HBc) + 
Note that, it is permissible to enrol patients who are anti-HBs+, only when 
this is attributable to vaccination and there is no history of previous infection. 


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Note that, if the serology test results remain unclear, a confirmatory hepatitis 
B (HB) deoxyribonucleic acid (DNA) + test may be performed. 
27. Hepatitis C: patients will be excluded if there is any evidence of past or current 
hepatitis C infection at the initial Screening visit (hepatitis C antibody [quantitative 
immunoassay, qIA], hepatitis C radio immunoblot assay [RIBA or PCR]). NOTE: 
Participants with positive Hepatitis C antibody due to prior resolved disease may be 
enrolled, only if a confirmatory negative Hepatitis C RNA (PCR) test is obtained. 
28. HIV: Positive human immunodeficiency virus (HIV) antibody test (obtained at the 
initial Screening visit) or known to have a historically positive HIV test. 
Other Exclusions 
29. Alcohol: Regular alcohol consumption within 6 months prior to the initial 
Screening visit defined as an average weekly intake of >14 units for males and >14 
units for females.  
One unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 
mL) of wine or 1 (25 mL) measure of spirits.  
30. Substance abuse: Active substance abuse or a history of substance abuse (in the 
opinion of the Principal Investigator) within 6 months prior to the initial Screening 
visit. Note that documented medical use of marijuana or occasional recreational use 
of marijuana may be permitted subject to a priori agreement with the Medical 
Monitor. 
31. Compliance: is unlikely to comply with scheduled study visits based on 
investigator judgment; has a history of a psychiatric disorder or condition that may 
compromise communication with the investigator. 
5.3. 
Lifestyle Considerations 
5.3.1. 
COVID-19 related restrictions 
Participants will be required to adhere to the measures and procedures outlined locally at 
each of the investigative sites to reduce the risk of COVID-19 infections among trial 
participants and clinical site staff. 
5.3.2. 
Meals and Dietary Restrictions 
Not appropriate 
5.3.3. 
Caffeine, Alcohol, and Tobacco 
• There are no restrictions on ingesting caffeine- or xanthine-containing products (e.g., 
coffee, tea, cola drinks, and chocolate). 
• Participants must abstain from alcohol for 24 hours before all scheduled visits.  
• Participants who use tobacco products will be instructed that smoking will not be 
permitted while they are in the clinical unit. 


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5.3.4. 
Activity 
Participants will abstain from strenuous exercise for 24 hours before 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/entered in the study. 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 
serious adverse events (SAEs). 
5.4.1. 
Re-screening 
Participants who do not meet the eligibility criteria for this study may be rescreened once. 
Re-screened participants should be assigned a new participant number. 
5.4.2. 
Re-testing of Clinical Laboratory Values during Screening 
If a participant fails any of the laboratory criteria (e.g. variability around the threshold 
limit of a normal value, or spurious result), the test may be repeated once 
within the screening period. If the participant fails the laboratory criteria for a second 
time they will be considered a screen failure. 
 
If a blood sample needs to be repeated due to sample handling problems, breakage or 
sample integrity, this is not considered a re-testing. Further details regarding the 
procedure for re-testing may be found in the SRM.  
5.5. 
Criteria for Temporarily Delaying  
Not applicable  


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6. 
STUDY INTERVENTION(S) AND CONCOMITANT 
THERAPY 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol. 
6.1. 
Study Intervention(s) Administered 
ARM Name 
Active 
Placebo 
Intervention 
Name 
GSK1070806 Injection, 100 mg/mL 
0.9% sodium chloride injection 
Dosage Form 
Solution for infusion 
Solution for infusion 
Unit Dose 
Strength(s) 
100 mg/mL with 100 mg (1 mL) 
withdrawable per vial. 
Variable volume 
Dosage Level(s) 
2 mg/kg - once (Groups 1 and 2) 
The appropriate volume of 0.9% 
sodium chloride injection will be 
infused (IV) in the same manner as 
the corresponding active cohort 
Route of 
Administration 
IV infusion (Groups 1 and 2) 
IV infusion (Groups 1 and 2) 
Dosing 
Instructions 
1 hour IV infusion. 
Dilute into 100 mL sterile IV infusion 
bag 0.9% Sodium Chloride (for 
details, see Pharmacy Manual) 
1 hour IV infusion. 
Manufacturer/ 
Source of 
Procurement 
 
Provided centrally by the Sponsor 
 
Provided locally by the trial site 
Packaging and 
Labelling 
 
Study Intervention will be provided 
in vials. Each vial will be labelled as 
required per country requirement. 
N/A 


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6.2. 
Preparation/Handling/Storage/Accountability 
For the required dose, the IP will be diluted in 0.9% sodium chloride injection and 
administered through IV infusion. Description of the methods and materials required for 
preparation and handling of GSK1070806 dosing solutions are detailed in the Pharmacy 
Manual. 
Study treatment must be dispensed or administered according to procedures described 
herein and in the SRM and Pharmacy Manual.  
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 
Under normal conditions of handling and administration, study intervention is not 
expected to pose significant safety risks to site staff.  Take adequate precautions to avoid 
direct eye or skin contact and the generation of aerosols or mists. In the case of 
unintentional occupational exposure notify the monitor, Medical Monitor and/or GSK 
study contact. 
Precaution will be taken to avoid direct contact with the study intervention. A Material 
Safety Data Sheet (MSDS)/equivalent document describing occupational hazards and 
recommended handling precautions either will be provided to the investigator, where this 
is required by local laws, or is available upon request from GSK. In the case of 
unintentional occupational exposure notify the monitor, Medical Monitor and/or GSK 
study contact. 
 


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6.3. 
Measures to Minimize Bias: Randomization and Blinding 
Blinded study with unblinded 
site pharmacist who is 
dispensing intervention 
All participants will be centrally randomized using an 
Interactive Voice/Web Response System 
(IVRS/IWRS): RAMOS-NG.  
Before the study is initiated, the telephone number and 
call-in directions for the IVRS and/or the log in 
information and directions for the IWRS will be 
provided to each site. 
Participants will be randomized in a 2:1 ratio (Group 1 
Biologic Naïve versus placebo) or 5:1 ratio (Group 2 
Dupi-IR) to receive study intervention. 
Investigators will remain blind to each participant’s 
assigned study intervention. 
In order to maintain the blind, an otherwise 
uninvolved 3rd party will be responsible for the 
dispensing of study intervention and will endeavour to 
ensure that there are no differences in the preparation 
time following randomization. 
Unblinded monitors, and in the event of a Quality 
Assurance audit, the auditor(s) will be permitted 
access to un-blinded study intervention records at the 
site(s) to verify that randomization/dispensing has 
been done accurately. 
 
A participant may continue in the study if that participant’s intervention assignment is 
unblinded. 
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. 
6.3.1. 
Controlled Early Access to Unblinded PK and PKPD Data 
Designated independent representative(s) may be unblinded for performing population 
PK and PKPD dataset preparation and draft PK and PKPD model development at one or 
more time points throughout the trial using scrambled (random reassignment of subject 
identification numbers) PK and PKPD unblinded datasets. 


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6.4. 
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.   
6.5. 
Dose Modification 
Not applicable  
6.6. 
Continued Access to Study Intervention after the End of the 
Study 
Not applicable 
6.7. 
Treatment of Overdose 
For this study, any dose of GSK1070806 greater than 2 mg/kg 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 to discuss details (actual dose administered) 
and next steps. 
• 
 Monitor the participant for any AE/SAE and clinical laboratory parameters for 24 
weeks (until End of Study) following dosing. 
• 
Document the quantity of the excess dose in the case report form (CRF). 
6.8. 
Concomitant Therapy 
The Medical Monitor should be contacted if there are any questions regarding prior, 
concomitant (including rescue) or non-permitted therapies. 
Documenting therapies: Any medication or vaccine (including over-the-counter or 
prescription medicines, recreational drugs, vitamins, and/or herbal supplements) or other 
specific categories of interest (topical therapies for AtD) 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 


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6.8.1. 
Permitted Concomitant Therapies 
Patients are to be instructed to apply topical non-medicated emollient at least once daily 
from Day -7 until at least Day 85. 
The following concomitant therapies are permitted under the conditions described. 
• Paracetamol/Acetaminophen, at doses of  2 grams/day at any time during the 
study. 
• Oral anti-histamines (at the approved dose) at any time during the study. 
• Intra-articular steroids (at the approved dose) at any time during the study. 
• COVID-19 vaccines: see SRM for updated list of vaccines permitted per each 
country. 
• Other concomitant medication may be considered on a case-by-case basis by the 
investigator (and in consultation with the Medical Monitor if required).  
 
6.8.2. 
Prohibited Medications 
Medications prohibited between Screening and Wk 12 are as follows owing to their 
potential to confound safety (and efficacy) assessments. 
• Topical corticosteroids, topical calcineurin inhibitors, topical PDE4 inhibitors  
• Oral immunosuppressants 
• IV corticosteroids or biological immunosuppressants 
• Phototherapy 
If a participant requires a prohibited medication to address an urgent clinical need (e.g. 
extremely active disease, see Section 7.1.4) this should be recorded as a protocol deviation. 
The protocol deviation may affect the evaluability of the participant and should be 
discussed with the Medical Monitor in advance, if possible. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
The study stopping criteria are based upon the mechanism of action of blocking IL-18 (a 
modulator of the immune response), the one month cynomolgus monkey toxicology study 
finding(s) and on prior clinical experience following single (up to 10 mg/kg GSK1070806) 
and two doses (up to 5 mg/kg) GSK1070806, see IB, [GSK Document Number 
WM2009/00047/07]. 
7.1. 
Discontinuation of Study Intervention 
As this is a single dose study, discontinuation of study intervention is not applicable. This 
section describes additional monitoring or participant management that should be 
implemented if specific safety-related criteria are fulfilled. Unless otherwise specified, 
participants experiencing any of these criteria should continue in the study. 


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7.1.1. 
Adverse Event Criteria 
• 
A participant develops a serious or severe opportunistic or atypical infection.  
• 
The participant experiences a serious or severe adverse reaction following study 
investigational product administration, meeting Grade 3 or 4 of the Common 
Terminology Criteria for Adverse Events (CTCAE) criteria, irrespective of causality. 
Full CTCAE descriptions and grades can be found in the accompanying SRM or the U.S 
Department of Health and Human Services, CTCAE, Version 5.0 (2017). 
Study assessments may be missed if it is determined by the investigator that it is not in the 
best interests of the participant to attend scheduled study visits prior to resolution of the 
adverse event. Once resolved, participants should complete remaining study assessments 
according to the SoA 
7.1.2. 
Liver Chemistry Criteria 
Since participants will receive a single dose of study medication, there are no liver specific 
stopping criteria as such and the participant may continue in the study according to the 
SoA. In the event of liver parameters deviating from the thresholds described in Section 
10.6, follow the instructions in that section. 
Liver chemistry increased monitoring criteria have been designed to assure participant 
safety and evaluate liver event etiology (in alignment with the FDA premarketing clinical 
liver safety guidance). 
fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM
174090.pdf. 
7.1.3. 
QTc Criteria 
The same QT correction formula (either Bazett’s formula [QTcB] or Fridericia’s formula 
[QTcF]) must be used for all QTc data being collected for each individual participant to 
determine eligibility for the study. This formula must not be changed or substituted once 
the participant has been enrolled. 
 
If an abnormal (prolonged) QTc is observed post-dose, obtain 2 more ECGs over a brief 
period, and then use the averaged QTc value of the triplicate ECGs to determine whether 
the participant meets these criteria: 
• QTc >500 msec OR uncorrected QT >600 
msec. 
• Change from baseline of QTc >60 msec. 
The Investigator should assess the participant for clinical consequences and potential 
causes (including concomitant medications and electrolytes). Appropriate follow-up 
should be determined by the Investigator according to their assessment and in some cases 
might include referral to an emergency facility or cardiology for further evaluation. 
 
The investigator or qualified designee will determine if the participant may continue in the 
study according to the SoA, and if any change in participant management is needed.  


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The review of the ECG printed at the time of collection must be documented. Any new 
clinically relevant finding should be reported as an AE. 
7.1.4. 
Other Criteria 
• 
Prohibited Medications: If the participant initiates and continues a prohibited 
medication (see Section 6.8.2) owing to a considerable worsening of AtD, s/he must 
be withdrawn from the study. Considerable worsening of AtD is defined as an increase 
in EASI of ≥25% from Baseline at 2 consecutive visits between Wks 4 and 12, 
according to the clinical judgement of the investigator.  
• 
Surgery: the participant requires surgery prior to Wk 12. 
• 
Pregnancy: the participant should be withdrawn from the study. 
7.1.5. 
Study Safety Stopping Criteria 
Blinded AEs, SAEs, laboratory abnormalities, ECG abnormalities, and changes in vital 
signs occurring across all randomised participants will be regularly reviewed by the SRT 
to ensure appropriate participant safety. 
The study may be paused or terminated if there are emergent safety findings that require 
further investigation or invalidate the positive benefit-risk assessment. Any changes to the 
study due to safety reasons will be promptly communicated to the appropriate Regulatory 
Authorities. The study may re-start only following approval of a substantial amendment by 
the regulatory agencies as well as the local ethics committees. 
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, 
behavioural, or compliance reasons.  
• Since participants will receive a single dose of study medication on Day 1, 
withdrawal following dosing will constitute declining to participate in study 
activities. Participants should be encouraged to remain in the study and complete 
the planned visits and assessments for the purposes of continued safety monitoring, 
if possible. 
• The Investigator must determine the primary reason for early withdrawal. 
Withdrawal due to an AE (according to the definition of an adverse event) should 
be distinguished from withdrawal due to an insufficient efficacy response.  
• In the event of an early withdrawal participants should be encouraged to complete 
at least the Early Withdrawal visit as soon as feasible. Participants should be 
encouraged to complete any/all remaining scheduled visits for the purposes of 
safety monitoring including the End of Study Visit (approximately 24 weeks after 
dosing) to mitigate safety risks associated with administration of a long-acting, 
novel immunosuppressive. The investigator should aim to follow up participants 
until all AEs and SAEs have resolved. 


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• 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.  
• Site personnel, or an independent third party, will attempt to collect the vital status 
of the participant within legal and ethical boundaries for all participants 
randomized, including those who did not get study intervention. Public sources may 
be searched for vital status information. If vital status is determined as deceased, 
this will be documented and the participant will not be considered lost to follow-
up. Sponsor personnel will not be involved in any attempts to collect vital status 
information. 
Discontinuation of specific sites or of the study as a whole are handled as part of Appendix 
1. 


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8. 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarized in the SoA.  
• 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 may continue in the study.  
• Adherence to the study design requirements, including those specified in the SoA, 
is essential and required for study conduct. 
• All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening 
log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable.  
• Procedures conducted as part of the participant’s routine clinical management (e.g., 
blood count) and obtained before signing of ICF may be utilized for screening or 
baseline purposes provided the procedure met the protocol-specified criteria and 
was performed within the time frame defined in the SoA. 
• Safety/Laboratory/analyte results that could unblind the study will not be reported 
to investigative sites or other blinded personnel until the study has been unblinded. 
• 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. 
Eczema Area and Severity Index (EASI) 
EASI [Hanifin, 2001] is an internationally used classification of atopic dermatitis severity 
and is recommended for use by Harmonising Outcome Measures for Eczema, an 
international group for standardizing clinical trial outcomes in atopic dermatitis. 
EASI is an investigator-assessed measure that is used to assess the extent (area) and 
severity of atopic dermatitis.  The range of the scale is 0-72, with a higher score indicating 
greater severity. 
Please refer to the SRM for details on scoring the EASI. 
8.1.2. 
Investigator Global Assessment (IGA) 
Investigator's Global Assessment (IGA) for Atopic Dermatitis is a measure of overall 
disease severity at the time of assessment and is the established FDA regulatory endpoint. 
It is measured on the following scale: 
0: Clear (No inflammatory signs of atopic dermatitis) 
1: Almost Clear (Just perceptible erythema and just perceptible papulation/infiltration) 


T M F -1 4 6 7 9 5 2 1  
C O N FI D E N TI A L  
 
 
2 1 5 2 5 3  
 
4 6  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V 1 5  d at e d 2 1 -D e c -2 0 2 0  
2: Mil d Disease ( Mil d er yt he ma a n d mil d pa p ulati o n/i nfiltrati o n)  
3: M o derate Dise ase ( M o derate er yt he ma a n d m o d erate pa p ulati o n/i nfiltrati o n)  
4: Se vere Diseas e ( Se vere er yt he ma a n d se vere pa p ulati o n/i nfiltrati o n wit h or wit h o ut 
o ozi n g/cr usti n g) . 
Please refer t o t he S R M f or detail s o n sc ori n g t he I G A. 
8. 2.  
P ati e nt R e p ort e d O ut c o m e s ( P R O s)  
Refer t o Secti o n 1. 3  f or t he sc he d uli n g of P R Os. 
8. 2. 1.  
P e a k Pr uriti s N u m eri c al R ati n g S c al e ( P P -N R S)  
Pr urit us (itc h) is a patie nt re p orte d m eas ure (i n t he past 2 4 h o urs) of itc h i nte nsit y assessi n g 
w orst itc h usi n g a n 1 1 -p oi nt scale (fr o m 0 t o 1 0), wit h 0 bei n g n o itc h a n d 1 0 bei n g t he 
w orst i ma gi na bl e itc h [ Y osi p o vitc h , 2 0 1 9].  
Partici pa nts c o m plete t he assess me n t o nce d ail y at a p pr o xi matel y t he sa me ti me eac h 
da y , a n d are as k e d t he f oll o wi n g q uesti o n i n t heir l ocal la n g ua ge: " O n a scal e of 0 t o 1 0, 
wit h 0 bei n g 
a n d 1 0 bei n g 
 h o w w o ul d y o u rate y o ur itc h 
at t he w orst m o me nt d uri n g  t he pre vi o us 2 4 h o urs ?" 
8. 2. 2.  
D er m at ol o g y Lif e Q u alit y I n d e x ( D L QI)  
T he D L QI is a 1 0 -ite m q uesti o n naire [Fi nla y , 1 9 9 4] t hat as ks partici pa nts t o e val uate t he 
de gree t hat t heir s ki n disease h as affecte d t h eir q ualit y of life i n t he last w eek i n t he 
f oll o wi n g 6 as p ects: 
•  
s y m pt o ms a n d feeli n gs, 
•  
dail y acti vities,  
•  
leis ure,  
•  
w or k or sc h o ol a cti vities,  
•  
pers o nal rel ati o ns hi ps a n d  
•  
treat me nt relat e d feeli n gs.  
Partici pa nts a ns wer t h e 1 0 q uesti o ns o n a scale fr o m 0 
t o 3
  
T he D L QI is calc ulate d b y s u m mi n g t he sc ores of t he 1 0 q uesti o ns, ra n gi n g fr o m 0 t o 3 0 
wit h hi g her s c ores i n dicati n g m or e i m paire d q ualit y of life. A s c ore of 0 or 1 mea ns t hat 
t he disease has n o effect at all. 
Partici pa nts will be re q uire d t o rec or d t h eir D L QI sc ores w eekl y u p t o W k 4 a n d t he n bi -
wee kl y f or t h e re mai n d er of t he st u d y  (refer t o Secti o n 1. 3 , S o A).  
C CI
C CI
C CI
C CI


T M F -1 4 6 7 9 5 2 1  
C O N FI D E N TI A L  
 
 
2 1 5 2 5 3  
 
4 7  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V 1 5  d at e d 2 1 -D e c -2 0 2 0  
8. 3.  
S af et y A s s e s s m e n t s 
Pla n ne d ti me p oi nts f or all safet y assess me nts are pr o vi de d i n t he S o A.  T he p artici pa nt will 
be e nc o ura ge d t o  c o nt act t he site at all ti mes i n case of a n y a d v erse e ve nt.  
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI


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8.3.1. 
Physical Examinations 
• A complete physical examination will include, at a minimum, assessments of the Skin, 
Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. Height 
(baseline only) and weight will also be measured and recorded. 
• A brief physical examination will include, at a minimum, assessments of the skin, 
lungs, cardiovascular system, and abdomen (liver and spleen). 
• Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
8.3.2. 
Vital Signs 
• Temperature, pulse rate, and blood pressure are to be assessed. 
• Blood pressure and pulse measurements are to be assessed in semi-supine position with 
a completely automated device. Manual techniques are only appropriate if an 
automated device is not available. 
• Blood pressure and pulse measurements should be preceded by at least 5 minutes of 
rest for the participant in a quiet setting without distractions (e.g., television, cell 
phones). 
Vital signs (to be taken before blood collection for laboratory tests) will consist of 1 
pulse and 3 blood pressure measurements (3 consecutive blood pressure readings at 
intervals of at least 1 minute). The average of the 3 blood pressure readings will be 
recorded. 
8.3.3. 
Electrocardiograms 
• Triplicate or Single 12-lead ECG 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 corrected QTc intervals. Refer to Section 7.1.3 for 
QTc criteria and additional QTc readings that may be necessary. 
• At each time point at which triplicate ECG are required, 3 individual ECG tracings 
should be obtained as closely as possible in succession, but no more than 2 minutes 
apart. 
8.3.4. 
Clinical Safety Laboratory Assessments 
• See Appendix 2 for the list of clinical laboratory tests to be performed and to the 
SoA for the timing and frequency. 
• The investigator must review the laboratory report, document this review, and 
record any clinically significant changes occurring during the study as an AE. The 
laboratory reports must be filed with the source documents.  
• Abnormal laboratory findings associated with the underlying disease are not 
considered clinically significant, unless judged by the investigator to be more 
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• All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 24 weeks after the last dose of study intervention 
should be repeated until the values return to normal or baseline or are no longer 
considered significantly abnormal by the investigator or medical monitor.  
o If clinically significant/any 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 tests, as defined in Section 8.3, must be conducted 
in accordance with the laboratory manual and the SoA (Section 1.3). 
• If laboratory values from non-protocol specified laboratory tests performed at the 
institution’s local laboratory require a change in participant management or are 
considered clinically significant by the investigator (e.g., SAE or AE or dose 
modification), then the results must be recorded. 
8.3.5. 
Pregnancy Testing 
• Refer to Section 5.1 Inclusion Criteria for pregnancy testing entry criteria. 
• Pregnancy testing (urine or serum as required by local regulations) should be 
conducted at monthly intervals during study intervention period. 
• Pregnancy testing (urine or serum as required by local regulations) should be 
conducted at the end of relevant systemic exposure 
• 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. 
8.4. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and 
Other Safety Reporting 
The definitions of adverse events (AE) or serious adverse events (SAEs) can be found in 
Section 10.3. 
The definitions of unsolicited and solicited adverse events can be found in Section 10.3. 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant's legally authorized representative). 
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 all (see Section 7).  
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 10.3. 


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8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information 
• All SAEs will be collected from the signing of the informed consent form (ICF)  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 study 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 as Medical History/Current Medical Conditions not 
as AEs. 
• 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 information on 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. 
8.4.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AE and/or SAE. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrence.  
8.4.3. 
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 
(Section 10.3). 
8.4.4. 
Regulatory Reporting Requirements for SAEs 
• Prompt notification by the investigator to the sponsor of an 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. 
• An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (e.g., summary or listing of SAEs) from the sponsor will 


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review and then file it along with the Investigator Brochure and will notify the 
IRB/IEC, if appropriate according to local requirements. 
• Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 


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8. 4. 5.  
P r e g n a n c y 
•  D etails of all pre g na n cies i n fe male partici pa nts will be c ollecte d after t he start of st u d y 
i nter ve nti o n a n d u ntil ti me peri o d f or re p orti n g pre g na n cies s h o ul d ali g n wit h t he ti me 
peri o d f or p ost -i nter ve nti o n c o ntrace pti o n deter mi ne d i n Secti o n 5. 1 . 
•  If a pre g n a nc y is re p ort e d, t he i n vesti gat or will rec or d pre g na nc y i nf or mati o n o n t he 
a p pr o priate f or m a n d s u b mit it t o  G S K wit hi n 2 4 h o urs  of lear ni n g of t he  pr e g na nc y. 
W hile pre g n a nc y itself is n ot c o nsi dere d t o be a n A E or S A E, a n y pre g na nc y 
c o m plicati o n or electi ve ter mi nati o n of a pre g n a nc y f or me dical reas o ns will be 
re p orte d as a n A E or S A E. 
•  A b n or mal pre g na n c y o utc o mes (e. g., s p o nta ne o us a b orti o n, fetal dea t h, still birt h, 
c o n ge nital a n o malies, ect o pic pre g na nc y) are c o nsi dere d S A Es a n d will be re p orte d as 
s uc h. 
•  T he partici pa nt will be f oll o we d t o deter mi ne t he o utc o me of t he pre g na nc y. T he 
i n vesti gat or will c ollect f oll o w-u p i nf or mati o n o n t he partici pa nt a n d t he n e o nate a n d 
t he i nf or mati o n will be f or war de d t o t he s p o ns or. 
•  A n y p ost -st u d y pre g na n c y-rel ate d S A E c o nsi dere d reas o n a bl y relate d t o t he st u d y 
i nter ve nti o n b y t he i n vesti gat or will be re p ort e d t o t he s p o ns or as descri be d i n Secti o n 
8. 4. 4 . W hile t he i n vesti gat or is n ot o bli gate d t o acti vel y see k t his i nf or mati o n i n f or mer 
st u d y partici p a nts, he or s he ma y l ear n of a n S A E t hr o u g h s p o nta n e o us re p orti n g. 
•  A n y p artici pa nt w h o b ec o mes pre g na nt d uri n g  t h e st u d y will be wit h dr a w n fr o m t he 
st u d y. 
8. 4. 6.  
C ar di o v a s c ul ar a n d D e at h E v e nt s  
F or a n y car di o vasc ul ar e ve nts det aile d i n  S ecti o n  1 0. 3  a n d all d eat hs, s pecific 
Car di o vasc ular ( C V) a n d Deat h secti o ns of t he C R F will be re q uire d t o be c o m plete d. 
T hese secti o ns i ncl u de q uesti o ns re gar di n g car di o vasc ular (i ncl u di n g s u d de n car diac  
deat h) a n d n o n -car di o vas c ular deat h.  
T he C V C R Fs are prese nte d as q u eries i n res p o nse t o re p orti n g of certai n C V Me d D R A 
ter ms. T he C V i nf or mati o n s h o ul d be rec or de d i n t he s pecific car di o vas c ul ar secti o n of t he 
C R F wit hi n o ne w eek of recei pt of a C V E ve n t dat a q uer y pr o m pti n g its c o m pleti o n.   
T he Deat h C R F is pr o vi de d i m me diatel y aft er t he occ urre nce or o utc o me of deat h is 
re p orte d. I nitial a n d f oll o w-u p re p orts re gar di n g d eat h m ust be c o m plete d wit hi n  o ne w ee k 
of w he n t he d eat h is re p orte d.  
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8. 6.  
G e n eti c s a n d/ or P h ar m a c o g e n o mi c s  
A 6 m L bl o o d sa m ple f or D N A is olati o n will be c ollecte d fr o m partici p a nts w h o ha ve 
c o nse nte d t o partici pate i n t he ge n etics a nal ysis c o m p o ne nt of t he st u d y. Partici pati o n is 
o pti o nal. Partici pa nts w h o d o n ot wis h t o partici pate i n t he ge n etic res earc h ma y still 
partici pate i n t he st u d y.  
I n t he e v e nt of D N A e xtracti o n fail ure, a re place me nt ge netic bl o o d sa m ple ma y be 
re q ueste d fr o m t he p arti ci pa nt. Si g ne d i nf or me d c o nse nt will be re q uir e d t o o btai n a 
re place me nt sa m ple u nless it was i ncl u de d i n t he ori gi nal c o ns e nt. 
See Secti o n 1 0. 5 . Ge netics a n d P har mac o ge n o mics f or I nf or mati o n re gar di n g ge n etic 
researc h. D etails o n pr ocesses f or c ollecti o n a n d s hi p me nt a n d destr ucti o n of t hese sa m ples 
ca n be f o u n d i n t he S R M.  
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8. 8.  
I m m u n o g e ni cit y A s s e s s m e nt s 
A nti b o dies t o G S K 1 0 7 0 8 0 6 will be e val uate d i n ser u m sa m ples c ollecte d fr o m all 
partici pa nts acc or di n g t o t he S o A. A d diti o nall y, ser u m sa m ples are t o  be c ollecte d at t he 
fi nal visit fr o m partici pa nts w h o disc o nti n ue d st u d y i nter ve nti o n or were wit h dra w n fr o m 
t he st u d y. T hes e sa m ples will be teste d b y t he s p o ns or or s p o ns or's desi g nee. 
Ser u m sa m ples will be s cree n e d f or a nti b o dies bi n di n g t o G S K 1 0 7 0 8 0 6 a n d t he titer of 
c o nfir me d p ositi ve s a m ples will be re p orte d. Ot h er a n al yses ma y be p erf or me d t o verif y 
t he sta bilit y of a nti b o dies t o G S K 1 0 7 0 8 0 6 a n d/ or f urt her c haracterize t he i m m u n o ge nicit y 
of G S K 1 0 7 0 8 0 6.  
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The detection and characterization of antibodies to GSK1070806 will be performed using 
a validated assay method by or under the supervision of the sponsor. All samples collected 
for detection of antibodies to study intervention will also be evaluated for GSK1070806 
serum concentration to enable interpretation of the antibody data. Antibodies may be 
further characterized and/or evaluated for their ability to neutralize the activity of the study 
intervention(s). Samples may be stored for a maximum of 15 years (or according to local 
regulations) following the last participant’s last visit for the study at a facility selected by 
the sponsor to enable further analysis of immune responses to GSK1070806. 
8.9. 
Health Economics 
Health economic parameters are not evaluated in this study. 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
There are no formal hypotheses to be tested. 
9.2. 
Sample Size Determination 
Approximately 64 patients may need to be screened to obtain 48 randomized participants 
(approximately 30 and 18 participants in Groups 1 and 2, respectively). 
Participants who have withdrawn from the study, may be replaced at the discretion of the 
sponsor. 
The sample sizes for Groups 1 and 2 are selected to support preliminary assessment of the 
clinical effect, based on PCFB in the EASI for Groups 1 and 2.  
Operating characteristics of some criteria of interest for the both groups of the study have 
been calculated and presented below. 
Group 1: 
Based on 30 participants (20 administered GSK1070806 and 10 administered placebo), the 
probability of different criteria of interest are given in the table below.  
A Bayesian linear regression was used, assuming that the PCFB in the EASI follows a 
Normal distribution. The priors were as follows: 
• Placebo arm: a robust meta-analytic predictive (MAP) prior was constructed based 
on placebo PCFB in the EASI reported in recent clinical trials in AtD. The resulting 
mixture prior has 28.5% weight on a Normal (-31.56, SD=5.67), 21.5% weight on 
a Normal (-31.21, SD=11.00) and 50% weight on a Normal (-30, SD = 50), with an 
effective sample size of 14 participants (expected local-information-ratio (ELIR) 
method (Neuenschwander, 2020)) assuming a between-participant SD = 50. 
• GSK1070806 arm: a vague Normal prior was used, with mean = -30 and SD = 50, 
corresponding to an effective sample size (ELIR method) of 1 participant assuming 
a between-participant SD = 50. 


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Operating characteristics are provided below. A true PCFB in the EASI of -30% in the 
placebo arm was assumed, based on recent clinical trials in AtD. Various true PCFBs in 
the EASI for the GSK1070806 arm at Wk 12 were assumed, giving various true treatment 
differences. A between-participant SD of 50% was assumed for both GSK1070806 and 
Placebo arms.  
Criteria 
True treatment difference 
-40% 
-25% 
-15% 
0% 
Observing a >75% posterior 
probability that the true difference 
from placebo is <-15% 
82.6% 
43.9% 
18.4% 
2.5% 
Observing a >75% posterior 
probability that the true difference 
from placebo is <-7.5% 
92.8%  
66.6%  
37.7% 
7.8% 
Observing a >97.5% posterior 
probability that the true difference 
from placebo is < 0% 
68.8% 
30.3% 
10.9% 
1.0% 
Group 2: 
There are no planned statistical analyses comparing GSK1070806 versus placebo. The 
analysis will be conducted on PCFB in the EASI in the GSK1070806 arm. 
Based on 15 participants on GSK1070806, the operating characteristics are given below. 
A vague Normal prior was used, with mean = 0 and SD = 1×106, corresponding to an 
effective sample size (ELIR method) of 0 participant assuming a between-participant 
SD=50.  
Criteria 
True PCFB in the EASI in GSK1070806 
-70% 
-55% 
-45% 
-30% 
Observing a >50% posterior 
probability that the true 
PCFB in EASI is <-45% 
97.4% 
78.1%  
50.0%  
12.3% 
Observing a >50% posterior 
probability that the true 
PCFB in EASI is <-37.5% 
99.4%  
91.2%  
71.9%  
28.1% 
Observing a >50% posterior 
probability that the true 
PCFB in EASI is <-30% 
99.9%  
97.4%  
87.7%  
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9.3. 
Analysis Sets 
For the purposes of analysis, the following analysis sets are defined: 
Participant Analysis Set 
Description 
Screened 
All participants who signed the ICF and are screened for 
eligibility. 
Enrolled 
All participants in the Screened analysis set who entered the 
study. 
Randomized 
All participants in the Enrolled analysis set who are randomly 
assigned to study intervention in the study. 
Safety 
All participants in the Randomized analysis set who received the 
study intervention. 
 
Participants will be analyzed according to the intervention they 
actually received. 
PK 
All participants in the Safety analysis set who had at least 1 non-
missing PK assessment (Non-quantifiable values will be 
considered as non-missing values). 
 
Participants will be analyzed according to the intervention they 
actually received. 
9.4. 
Statistical Analyses 
The SAP will be finalized prior to unblinding of the study and 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. 
General Considerations 
9.4.1.1. 
Bayesian inference 
The main statistical analyses will be carried out in the Bayesian framework. Weakly 
informative priors may be used. In that case, a sensitivity analysis using vague priors will 
also be carried out. 
The following summaries of the posterior distribution will be reported: posterior median, 
95% equal tailed credible interval, posterior probabilities of the true treatment effect 
being greater/lower than pre-specified thresholds.  
9.4.1.2. 
Baseline definition 
The 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 used as baseline. 
If baseline data is missing, no derivation will be performed, and baseline will be set to 
missing. 


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9.4.1.3. 
Statistical methods 
The following statistical models will be used for the main analysis of the primary and 
secondary endpoints: 
- 
Bayesian repeated measures model for longitudinal continuous endpoints. 
- 
Bayesian logistic regression for binary endpoints at Wk 12. 
When needed, the underlying assumptions of the models will be assessed visually. 
Covariates such as baseline value may be added and will be stated in the SAP. 
9.4.1.4. 
Site pooling 
Data from all participating sites will be pooled prior to analysis. It is anticipated that 
participant accrual will be spread thinly across sites and summaries of data by site would 
unlikely be informative and will not, therefore, be provided. 
9.4.2. 
Primary Endpoint(s) 
The primary endpoint is the PCFB in the EASI at Wk 12 in Group 1. The population-
level summary is the treatment difference (GSK1070806 – placebo) in PCFB in the EASI 
scores at Wk 12. 
The analysis will be based on the Safety analysis set. Participants will be analysed 
according to the treatment they received. 
A Bayesian repeated measures model will be used, including study treatment, visit, study 
treatment-by-visit interactions, baseline EASI value, baseline-by-visit interactions and 
subject-level repeated measures.  
Priors defined in Section 9.2 will be used for the analyses. For the MAP prior, details of 
the included studies will be documented in the SAP. An inverse Wishart prior will be 
used for the within-subject unstructured covariance. Other options may be investigated to 
determine an appropriate covariance structure in case of issues. 
A Bayesian repeated measures analysis will be conducted under the missing-at-random 
assumption.  
Further details on any sensitivity estimators used to assess the primary objective will be 
provided in the SAP. 
9.4.3. 
Secondary Endpoint(s) 
9.4.3.1. 
Safety Endpoints 
No formal statistical testing will be performed on safety data. 
All safety evaluations will be based on the Safety analysis set and will be reported for group 
1 and 2 together. 
Clinical interpretation will be based upon review and displays of adverse events, laboratory 
values and vital signs. The principal consideration in this evaluation will be the 


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i n vesti gat or-re p ort e d relati o ns hi ps of a d verse e ve nts or t he cli nical i m p ort a nt fi n di n gs i n 
la b orat or y tests t o st u d y treat me nt (refer t o t he S A P).  
T he i m m u n o ge nicit y of 
G S K 1 0 7 0 8 0 6 
will be base d o n t he P K a nal ysis set a n d 
c haracteriz e d wit h s u m mar y statistics of i nci de nce, i.e. t he n u m ber of partici pa nts wit h 
a nti-dr u g a nti b o dies b y tr eat me nt o ver ti me.  
9. 4. 3. 2.  
Effi c a c y E n d p oi nt s  
T he sec o n d ar y e n d p oi nts i n G r o u p 1 are:  
•  C F B i n t he E A SI at 
W k 1 2. T he p o p ulati o n -le vel s u m mar y is t he treat me nt 
differe n ce ( G S K 1 0 7 0 8 0 6 –  Place b o) i n C F B i n t he E A SI at W k 1 2. A Ba yesia n 
re peate d meas ur es m o del will be use d.  
•  E A SI 5 0/ 7 5/ 9 0 defi ne d as ≥ 5 0/ 7 5/ 9 0 % re d u cti o n i n t he E A SI fr o m Baseli n e at W k 
1 2. T he p o p ulati o n -le vel s u m mar y is t he tr eat m e nt differe nce ( G S K 1 0 7 0 8 0 6 –  
Place b o) i n pr o p orti o n of partici pa nts ac hie vi n g E A SI 5 0/ 7 5/ 9 0 % re d ucti o n fr o m 
baseli ne  at W k 1 2 . A Ba yesia n l o gistic re gressi o n a nal ysis will be use d.  
•  I G A sc ore of 0 or 1 at W k 1 2. T he p o p ulati o n -le vel s u m mar y is t he treat me nt 
differe n ce ( G S K 1 0 7 0 8 0 6 –  Place b o) i n pr o p orti o n of partici pa nts ac hie vi n g I G A 
sc ore 0 or 1 at W k 1 2 . A Ba yesi a n l o gistic re gressi o n a nal ysis will be use d.  
T he sec o n d ar y e n d p oi nt i n G r o u p 2 is: 
•  P C F B i n t he E A SI at W k 1 2. T he p o p ulati o n -le vel s u m mar y is t he mea n P C F B i n 
t he E A SI i n G S K 1 0 7 0 8 0 6 ar m at W k 1 2.  A Ba yesia n re peate d meas ures m o del 
w ill be use d. 
T he a nal yses of t he sec o n dar y e n d p oi nts will be b ase d o n t he Safet y a nal ysis set. Details 
of t he a nal yses f or t hese e n d p oi nts will be d oc u me nte d i n t he S A P. 
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9.5. 
Interim Analysis 
9.5.1. 
Routine pharmacovigilance 
In line with routine pharmacovigilance, the internal GSK107086 SRT will review blinded 
safety data at appropriate intervals during the study. Data reviewed will include but not 
necessarily be limited to clinical laboratory parameters, vital signs and adverse events. 
The GSK107086 SRT will include members of the study team. 
9.5.2. 
Planned Unblinded Interim Analyses 
Interim analyses for Groups 1 and 2 may be carried out and will be conducted by a DRC, 
(see Section 10.1.5). The composition and conduct of the DRC are described in the DRC 
Charter.  
All interim analyses will be based on unblinded data and outputs will be prepared by the 
sponsor study statistics and programming team and the clinical pharmacology modelling 
and simulation team (as required). The randomisation schedules and unblinded datasets 
will be stored on internal restricted drives. The GSK study team, with the exception of 
the statistics and programming and also Clinical Pharmacology and Modelling 
Simulation (CPMS) teams, will not have access to an unblinded copy of the 
randomisation schedule during the course of the trial. 
Interim Analyses for Group 1: 
Group 1 unblinded individual data and data aggregated by treatment group may be 
reviewed when approximatively 50% participants in Group 1 have completed Wk 12 (or 
have withdrawn prior to Wk 12). A potential outcome of the interim analysis might be to 
stop the study (Group 1 and Group 2). 
Additional Group 1 unblinded individual data and data aggregated by treatment group 
may be reviewed during the conduct of the study. The purpose will be only for internal 
decisions and will have no impact on the study conduct. Recruitment will continue while 
the interim analyses are being conducted, except in the case of a safety concern. 
Interim Analysis for Group 2: 
Group 2 unblinded individual data and data aggregated by treatment group may be 
reviewed when approximatively 30 participants in Group 1 have been randomized, 
although it could be done earlier. The potential outcome of this interim analysis is to stop 
recruitment to Group 2. Additional reviews of Group 2 unblinded data by treatment group 
may be carried out during the conduct of the study. The purpose will be only for internal 
decisions and will have no impact on the study conduct. Recruitment will continue while 
the interim analysis is being conducted, except in the case of a safety concern. 


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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 on Harmonisation of Technical 
Requirements for Registration of Pharmaceuticals for Human Use (ICH) 
Good Clinical Practice (GCP) Guidelines 
▪ Applicable laws and regulations 
• The protocol, protocol amendments, ICF, IB,, and other relevant documents (e.g., 
advertisements) must be submitted to an IRB/IEC by the investigator and 
reviewed and approved by the IRB/IEC before the study is initiated.  
• Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants.  
• Protocols and any substantial amendments to the protocol will require health 
authority approval prior to initiation 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), ), European Medical Device Regulation 2017/745 for clinical 
device research (if applicable), and all other applicable local regulations 


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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. 
10.1.3. 
Informed Consent Process 
• The investigator or his/her representative will explain the nature of the study to 
the participant or their 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 their 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 GSK1070806 or about the study disease; publish the results of these research 
efforts; work with government agencies or insurers to have GSK1070806 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 signature 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. 


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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 
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 
Safety Review Team (SRT): Participant safety will be continuously monitored by an 
internal SRT, which includes safety signal detection at any time during the study. Blinded 
data will be reviewed. The SRT will include a subset of the 215253 study team and will 
operate to a charter. 
Data Review Committee (DRC): The study will utilise a DRC to conduct the Interim 
Analyses described in Section 9.5. Full details of the decisions to be made, membership 
of the committee and how study integrity will be maintained will be documented in the 
DRC Charter. Details of the DRC Charter (and statistical analysis plan, SAP) will outline 
the decision-making criteria. The DRC membership will be comprised of a predefined 
subset of project team members and senior GSK stakeholders to ensure that persons with 
the appropriate expertise and knowledge conduct and interpret interim reviews of data. 
No one external to the DRC will see unblinded study data. No study personnel with direct 
contact with sites or site staff will be involved in the DRC. Further details of how the 
DRC will ensure data integrity and appropriate quality control of data prior to decision 
making are also included. 
The DRC will also conduct any unplanned interim analyses that become necessary during 
the study. These analyses will be documented through an amendment of the DRC charter 
and, if necessary, a protocol amendment. 
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. 


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• GSK will also provide all investigators who participated in the study with a 
summary of the study results and will inform the investigators what treatment 
their patients’ received.  The investigator(s) is/are encouraged to share the 
summary results with the study participants, as appropriate. 
• Under the framework of the SHARE initiative, GSK intends to make anonymized 
participant-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. 
Requests for access may be made through www.clinicalstudydatarequest.com. 
• 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. 
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.  
• Guidance on completion of CRFs will be provided in the CRF completion 
guidelines. 
• Quality tolerance limits (QTLs) will be pre-defined in the Quality Tolerance 
Limits Report to identify systematic issues that can impact participant safety 
and/or reliability of study 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 including definition of study critical data 
items and processes (e.g., risk-based initiatives in operations and quality such as 
Risk Management and Mitigation Strategies and Analytical Risk-Based 
Monitoring), methods, responsibilities and requirements, including handling of 
noncompliance issues and monitoring techniques (central, remote, or on-site 
monitoring) are provided in the Monitoring Plan. 


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• The sponsor or designee is responsible for the data management of this study 
including quality checking of the data. Detailed information about study data 
collection and management process including systems used can be found in the 
study Data Management Plan. 
• The sponsor assumes accountability for actions delegated to other individuals 
(e.g., Contract Research Organizations). 
• 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 Pharmacology Study Report (CPSR)/ 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’s site. 
• Data reported on the CRF or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents or the discrepancies 
must be explained. The investigator may need to request previous medical records 
or transfer records, depending on the study. Also, current medical records must be 
available. 
• Definition of what constitutes source data and its origin can be found in the SRM. 
• The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF. 
• 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.  
10.1.9. 
Study and Site Start and Closure 
First Act of Recruitment 
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. 
Study/Site Termination 
GSK or 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 


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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: 
For study termination: 
• Discontinuation of further study intervention development 
For site termination: 
• 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 or no recruitment of participants (evaluated after a reasonable amount 
of time) by the investigator 
• 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 subject 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 1 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. Additionally, if the local laboratory results are used 
to make either a study intervention decision or response evaluation, the results must be 
recorded. 
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. 
Table 1 
Protocol-Required Safety Laboratory Tests 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count  
RBC Indices: 
Mean Corpuscular 
Volume (MCV) 
Mean Corpuscular 
Hemoglobin (MCH) 
%Reticulocytes 
Absolute reticulocyte 
count 
White Blood Cell (WBC) 
count with Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Red Blood Cell (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 
Transaminase 
(SGPT) 
Total Protein 
and albumin. 
 
 
Corrected 
calcium 
Alkaline 
phosphatase2 
 


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Laboratory 
Assessments 
Parameters 
Routine 
Urinalysis 
• Specific gravity 
• pH, glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase, 
by dipstick 
• Microscopic examination (if blood or protein is abnormal) 
Pregnancy 
testing 
• Highly sensitive serum or urine human chorionic gonadotropin (hCG) 
pregnancy test (as needed for women of childbearing potential)3 
Other 
Screening 
Tests 
• Follicle stimulating hormone (FSH) and estradiol (as needed in women of 
non-childbearing potential only) 
• Alcohol and urine drug screen (to include at minimum: amphetamines, 
barbiturates, cocaine, opiates, cannabinoids and benzodiazepines)] 
• Serology [(HIV antibody, hepatitis B surface antigen [HBsAg], hepatitis B 
core antigen antibody and hepatitis C virus antibody)  
• QuantiFERON-TB Gold / QuantiFERON-TB Gold PLUS 
• COVID-19.  
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 7.1.2 and Section 10.6. All events of ALT 5 × upper limit of normal 
(ULN) or ALT ≥3 x ULN for 4 weeks and total 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 to GSK in an expedited manner (excluding studies of hepatic impairment or cirrhosis). 
2. 
If alkaline phosphatase is elevated, consider fractionating. 
3. 
Serum testing at the initial screening visit and at baseline (pre-dosing). Local urine testing at other timepoints. 
 


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10.3. 
Appendix 3: AEs and SAEs: 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. 
 
Definition of Unsolicited and Solicited AE 
• An unsolicited adverse event is an adverse event that was not solicited using a 
Participant Diary and that is communicated by a participant/participant’s 
parent(s)/legally acting representative (LAR)(s) who has signed the informed 
consent. Unsolicited AEs include serious and non-serious AEs. 
• Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses 
requiring a hospitalisation, or emergency room visit, or visit to/by a health care 
provider). The participants/ participant’s parent(s)/LAR(s) will be instructed to 
contact the site as soon as possible to report medically attended event(s), as well as 
any events that, though not medically attended, are of participant/ parental /LAR’s 
concern. Detailed information about reported unsolicited AEs will be collected by 
qualified site personnel and documented in the participant’s records. 
• Unsolicited AEs that are not medically attended nor perceived as a concern by 
participant/participant’s parent(s)/LAR(s) will be collected during interview with 
the participants/participant’s parent(s)/LAR(s) and by review of available medical 
records at the next visit. 
• Solicited AEs are predefined local at the injection site and systemic events for 
which the participant is specifically questioned, and which are noted by the 
participant in their diary.  
 
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). 


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Events Meeting the AE Definition 
• 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 intervention- intervention 
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 an AE or SAE if they fulfil the definition of an 
AE or SAE.  
 
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. 
 


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10.3.2. 
Definition of SAE 
An SAE is defined as any serious adverse event that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
• In general, hospitalization signifies that the participant has been admitted 
(usually involving at least an overnight stay) at the hospital or emergency ward 
for observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AE. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered 
serious. 
• Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
d. Results in persistent or significant disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. 
• This definition is not intended to include experiences of relatively minor 
medical significance such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (e.g. sprained ankle) which may 
interfere with or prevent everyday life functions but do not constitute a 
substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Is a suspected transmission of any infectious agent via an authorised medicinal 
product 
g. Other situations: 
• Possible Hy’s Law case: ALT≥3xULN AND total bilirubin ≥2xULN (>35% 
direct bilirubin) or international normalized ratio (INR) >1.5 must be reported 
as SAE 
• Medical or scientific judgment should be exercised by the investigator in 
deciding whether SAE reporting is appropriate in other situations such as 
significant medical events that 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. 


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o Examples of such events include invasive or malignant cancers, 
intensive treatment for allergic bronchospasm, blood dyscrasias,  
convulsions, or development of intervention dependency or intervention 
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 
 
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. 
• 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 required form. 
• 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. 


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Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories:  
• Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities. 
• Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities. 
• Severe: An event that prevents normal everyday activities. An AE that is assessed 
as severe should not be confused with an SAE. Severe is a category utilized for 
rating the intensity of an event; and both AE and SAE can be assessed as severe. 
• An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes 
as described in the definition of an SAE, NOT when it is rated as severe. 
 
Assessment of Causality 
The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. 
• A "reasonable possibility" of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
• 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. 
 


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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 submitted 
documents. 
• 
The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
 
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) to report the event within 24 hours. 
• The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data. 
• If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see 
next section) or to the contacts for SAE reporting by telephone. 
• 
Contacts for SAE reporting can be found in the SRM. 
 


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SAE Reporting to GSK via Paper Data Collection Tool 
• Facsimile transmission of the SAE paper data collection tool is the preferred 
method to transmit this information to the contacts for SAE reporting. 
• In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service. 
• Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE data collection tool within the designated reporting time 
frames. 
• 
Contacts for SAE reporting can be found in the Study Reference Manual. 
 


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10.4. 
Appendix 4: Contraceptive and Barrier Guidance  
10.4.1. 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
Women in the following categories are considered WOCBP (fertile): 
1. Following menarche 
2. From the time of menarche until becoming post-menopausal unless permanently 
sterile (see below) 
Notes: 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
o A high 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.  
o 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. 
• Permanent sterilization methods (for the purpose of this study) include: 
o Documented hysterectomy 
o Documented bilateral salpingectomy 
o Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (e.g., Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), 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. 
 
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. 
Woman of Nonchildbearing Potential (WONCBP) 
Women in the following categories are considered WONCBP: 


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1. Premenopausal female with permanent infertility due to one of the following (for the 
purpose of this study): 
a) Documented hysterectomy 
b) Documented bilateral salpingectomy 
c) Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (e.g., Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), 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. 
2. Postmenopausal female 
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
o A high 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. 
o Females on HRT and whose menopausal status is in doubt must discontinue 
HRT to allow confirmation of postmenopausal status before study enrolment. 
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 
• Azoospermic partner (vasectomized or due to a medical cause) 
Azoospermia 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. 
Note: documentation of azoospermia for a male participant can come from the site 
personnel’s review of the participant’s medical records, medical examination, or medical 
history interview. 


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Highly Effective Methodsb 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 
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 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. 
 
Notes: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception. 
Male condom and female condom should not be used together (due to risk of failure from friction) 


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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 GSK1070806 or atopic dermatitis 
and related diseases. They may also be used to develop tests/assays including 
diagnostic tests) related to GSK1070806 and/or atopic dermatitis. 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 GSK1070806 or study interventions of this class. The 
results of genetic analyses may be reported in the clinical study report or in a separate 
study summary. 
• The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality.  
• The samples will be retained while research on GSK1070806 (or study interventions 
of this class) or atopic dermatitis 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. 
Liver chemistry stopping and increased monitoring criteria have been designed to assure 
participant safety and evaluate liver event etiology.  
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 
participant in the study for any protocol 
specified follow-up assessments  
MONITORING: 
For bilirubin or INR criteria:  
• 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 
• 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 


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Liver Chemistry Stopping 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 
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 
be collected in the time period indicated above, do not obtain a PK sample. Instructions for sample handling and 
shipping are in the SRM.  


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10.7. 
Appendix 7: Abbreviations and Trademarks 
Abbreviations 
µg/mL 
Micrograms per millilitre 
μg*day/mL 
Micrograms day per millilitre 
ADA 
Anti-Drug Antibodies 
AE 
Adverse Event 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
AtD 
Atopic dermatitis 
AUC 
Area Under the Curve 
AUC(0-t) 
Area under the plasma concentration time curve from zero 
to time t 
AUC(0-∞) 
Area under the plasma concentration time curve from zero 
to infinity 
AUC(0-tau) 
Area under the plasma concentration time curve overthe 
dosing interval 
BCG 
Bacillus Calmette-Guerin 
BFI 
Brief Fatigue Inventory (Item -3) 
BL 
Baseline 
BMI 
Body Mass Index 
BN 
Biologic Näive 
BUN 
Blood urea nitrogen 
CFB 
Change from baseline 
CFR 
Code of Federal Regulation 
CI 
Confidence Interval 
CIN 
Cervical intraepithelial neoplasia 
CIOMS 
Council for International Organizations of Medical 
Sciences 
CL 
Clearance 
Cmax 
Maximum observed plasma concentration 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID-19 
Coronavirus strain 19 
CRF 
Case Report Form 
CPSR 
Clinical pharmacology study report 
CPMS 
Clinical Pharmacology Modelling and Simulation 
CV 
Cardiovascular 
DLQI 
Dermatology Life Quality Index 
DNA 
De-oxyribonucleic acid 
DRC 
Data review committee 
Dupi-IR 
Dupilumab-Inadequate Responder 
EASI 
Eczema Activity and Severity Index 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
ELIR 
Expected local-information-ratio 


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ePRO 
Electronic Patient Reported Outcome 
eDiary 
Electronic diary 
EoS 
End of Study 
FACIT-F 
Functional Assessment of Chronic Illness Therapy- 
Fatigue  
FDA 
Food and Drug Agency 
FPFV 
First Participant First Visit 
FTIH 
First time in human 
FSH 
Follicle Stimulating Hormone 
GCP 
Good Clinical Practice 
GCSP 
Global Clinical Safety and Pharmacovigilance 
GSK 
GlaxoSmithKline 
GSVA 
 
h 
Hours 
HBsAg 
Hepatitis B Surface Antigen positive 
HBcAb 
Hepatitis B core antibody  
hCG 
Human chorionic gonadotropin 
HepC 
Hepatitis C 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human Immunodeficiency Virus 
HRT 
Hormone Replacement Therapy 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council on Harmonisation of Technical 
Requirements for Registration of Pharmaceuticals for 
Human Use 
IEC 
Independent Ethics Committee 
IgA 
Immunoglobulin A 
IGA 
Investigator Global Assessment 
IL-18 
Interleukin-18 
IP 
Investigational Product 
IRB 
Institutional Review Board 
IV 
Intravenous 
IVRS 
Interactive voice response system 
IWRS 
Interactive Web Recognition System 
JAKi(s) 
Janus Activated Kinase inhibitor(s) 
Kdeg 
Degradation rate 
kg 
Kilogram 
kg/m2 
Kilograms per square meter 
LAR 
Legally Acting Representative 
LLQ 
Lower Limit of Quantification 
LPLV 
Last Participant Last Visit 
mAb 
Monoclonal Antibody 
MABEL 
Minimum Anticipated Biological Effect Level 
MCH 
Mean Corpuscular Hemoglobin 
MCV 
Mean Corpuscular Volume 


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MedDRA 
Medical dictionary for regulatory activities 
mg 
Milligram 
mg/day 
Milligrams per day 
mg/kg 
Milligrams per kilogram 
mg/kg/week 
Milligrams per kilogram per week 
MIA 
Monosodium iodoacetate 
min 
Minutes 
mL 
Millilitre 
mm 
Millimetre 
MM 
Medical Monitor 
MSDS 
Material Safety Data Sheet 
msec 
Millisecond 
NOAEL 
No Observed Adverse Effect Level 
NRS 
Numerical Rating Scale 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamics 
PDE4 
Phosphodiesterase 4 
pH 
Potential Hydrogen 
PK 
Pharmacokinetics 
PK/PD 
Pharmacokinetic/Pharmacodynamic 
PGx 
Pharmacogenetics 
PPE 
Personal protective equipment 
PP-NRS 
Peak Pruritis – Numerical Rating Scale 
PR 
PR cardiac wave interval 
PROMIS 
Patient-Reported Outcomes Measurement Information 
System -Sleep Disturbance 
PRO 
Patient reported outcome 
PTS 
Platform Technology and Science 
PUVA 
Psoralen + ultraviolet A 
qIA 
Quantitative Immunoassay 
QRS 
QRS cardiac wave interval 
QTc 
Corrected QT 
QTcB 
Corrected QT using Bazett’s formula 
QTcF 
Corrected QT using Fridericia’s formula 
QTL 
Quality Tolerance Limit 
RBC 
Red Blood cell count 
RIBA 
Radio immunoblot assay 
RNA 
Ribonucleic acid 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
Severe acute respiratory syndrome– Coronavirus-2 
SD 
Standard Deviation 
SGOT 
Serum Glutamic-Oxaloacetic Transaminase 
SGPT 
Serum Glutamic-Pyruvic Transaminase 
SMG 
Safety and Medical Governance 
SoA 
Schedule of Activities 


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SRM 
Study Reference Manual 
SRT 
Safety Review Team 
SUSAR 
Suspected unexpected serious adverse reactions 
T2DM 
Type 2 Diabetes Mellitus 
TB 
Mycobacterium tuberculosis 
TCI 
Topical calcineurin inhibitor 
TCS 
Topical corticosteroid 
TE 
Target engagement 
TH 
T helper (cell) 
Tmax 
Time to Cmax 
t½ 
Apparent terminal phase half-life 
ULN 
Upper limit of normal 
UVA1 
Ultraviolet A1 
UVB 
Ultraviolet B 
Vss 
Volume of distribution 
WBC 
Whole Blood Count 
Wk(s) 
Week(s) 
WONCBP 
Women Of Non Childbearing Potential 
WOCBP 
Women Of Childbearing Potential 
w/v 
Weight by volume 
 
Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
RAMOS NG 
 
Atopiclair 
 
 
Cerave 
 
 
Dupixent 
 
 
Epicerum 
 
 
MedDRA 
 
 
MimyX 
 
 
PaxGene 
 
 
QuantiFERON 


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10.8. 
Appendix 8: Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC). 
Summary of Previous Amendments 
Amendment 1 25-Feb-2022 
This amendment is considered to be substantial based on the criteria set forth in Article 
10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union. 
Overall Rationale for Amendment 1:  
To state that participants who have contracted COVID-19 during the study do not 
necessarily need to be immediately excluded. 
In addition to the changes tabulated below, minor edits/corrections have also been made 
throughout to provide refinement and clarification. 
Section # and Name 
Description of Change 
Brief Rationale 
Section 2.3.1: Risk 
Assessment (Procedural 
Risk) - Risk associated with 
attending an investigative 
site during the Coronavirus 
strain 19 (COVID-19) 
Pandemic 
 
Three changes: 
Participant monitoring: 
COVID test at Wk 12 (was 
removed to ensure 
consistency with the intent 
described in SoA). 
 
 
 
COVID-19 Contingency 
Plan: 
ORIGINAL: Any participant 
presenting with COVID-19-
related symptoms and/or 
having a positive SARS-
CoV-2 test will be excluded 
from (further) 
participation in the trial 
and will receive follow-up 
medical attention as per 
local procedure. 
REVISED: Any participant 
presenting with COVID-19-
 
(1) As per the Schedule of 
Activities: Participants 
need only have a 
mandated COVID test at 
Screening, prior to dosing 
(from Day -4 to Day 1), and 
at the End of Study Visit at 
Week 24 (or at early 
withdrawal).  
(2) A confirmed positive 
SARS-CoV-2 test is also 
required (as evidence of 
COVID-19 infection) In 
addition to initially 
presenting with COVID-19-
related symptoms. 
(3) Given there have been 
changes to circumstance 
and management options 
since start of the COVID 
pandemic, participants 
who have presented with 
COVID-19 and have a 


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Section # and Name 
Description of Change 
Brief Rationale 
related symptoms (2) and 
having a positive SARS-
CoV-2 test (3) may 
continue in the study (or 
may be temporarily 
suspended during 
recovery) if the 
investigator judges this to 
be possible (e.g. if the 
participant is able to 
adhere to local 
management guidance).  If 
a participant needs to be 
excluded from (further) 
participation in the trial 
s/he will receive follow-up 
medical attention as per 
local procedure. 
SARS-CoV-2 positive test,  
do not necessarily need to 
be immediately excluded 
from the study. The 
Investigator will judge 
whether the participant 
will be able to continue or 
not.  There is a return to 
the emphasis of continued 
monitoring within-study.  
Note that Study 215253 
administers only a single 
dose of this long-acting, 
novel immunosuppressive 
and so it is important to 
ensure continued safety 
monitoring (see Section 
7.2). 
Section 6.3.1. Controlled 
Early Access to Unblinded 
PK and PKPD Data 
ADDED New Subsection 
6.3.1. Controlled Early 
Access to Unblinded PK 
and PKPD Data 
Designated independent 
representative(s) may be 
unblinded for performing 
population PK and PKPD 
dataset preparation and 
draft PK and PKPD model 
development at one or 
more time 
points throughout the trial 
using scrambled (random 
reassignment of subject 
identification numbers) PK 
and PKPD unblinded 
datasets. 
To allow controlled early 
access to unblinded PK and 
PKPD data 
Section 9.4. Statistical 
Analyses 
The SAP will be finalized 
prior to unblinding of the 
study prior to first 
participant first visit (FPFV) 
The SAP will be finalized 
before any unblinding of 
the study (this change 
neither compromises study 
conduct nor data 
integrity). 


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Section # and Name 
Description of Change 
Brief Rationale 
Section 9.5.2. Planned 
Unblinded Interim Analysis 
Added: Group 1 unblinded 
individual data and data 
aggregated by treatment 
group may be reviewed 
when approximatively 50% 
participants in Group 1 
have been completed Wk 
12 (or have withdrawn 
prior to Wk 12). 
Added: Group 2 unblinded 
individual data and data 
aggregated by treatment 
group… 
To also enable unblinded 
individual data to be 
reviewed at the interim 
analysis. Study integrity 
will be maintained by using 
dummy participant IDs. 
 


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11. 
REFERENCES 
Adamson AS. The Economics Burden of Atopic Dermatitis. Adv Exp Med Biol. 
2017;1027:79-92.  
Antonopoulos C, Marie Cumberbatch, John B. Mee, Rebecca J. Dearman, Xiao-Qing 
Wei, Foo Y. Liew, Ian Kimber and Richard W. Groves. IL-18 is a key proximal mediator 
of contact hypersensitivity and allergen-induced Langerhans cell migration in murine 
epidermis. Journal of Leucocyte Biology. 2008; 83:361-367. 
Barbarot S, Auziere S, Gadkari A, Girolomoni G, Puig L, Simpson EL et al. 
Epidemiology of atopic dermatitis in adults: Results from an international survey. 
Allergy. 2018 Jun;73(6):1284-1293. 
Beck LA, Thac¸i D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-
severe atopic dermatitis. N Engl J Med. 2014;371(2):130-139. 
Bissonnette R. Pavel A.B. Diaz A. Werth J.L. Zang C. Vranic I. et al. Crisaborole and 
atopic dermatitis skin biomarkers: an intrapatient randomized trial. J Allergy Clin 
Immunol. 2019 144: 1274-1289. 
Blauvelt A, de Bruin-Weller M, Gooderham M, et al. Long-term management of 
moderate-to-severe atopic dermatitis with dupilumab and concomitant topical 
corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, 
placebo-controlled, phase 3 trial. Lancet. 2017;389(10086):2287-2303. 
Brunner P.M. Khattri S. Garcet S. Finney R. Oliva M. Dutt R. et al. A mild topical 
steroid leads to progressive anti-inflammatory effects in the skin of patients with 
moderate-to-severe atopic dermatitis. J Allergy Clin Immunol. 2016; 138: 169-178. 
Brunner P.M. Pavel A.B. Khattri S. Leonard A. Malik K. Rose S. et al. Baseline IL-22 
expression in patients with atopic dermatitis stratifies tissue responses to fezakinumab. J 
Allergy Clin Immunol. 2019; 143: 142-154. 
Chen JL, Niu XL, Gao YL, Ma L, Gao XH, Chen HD and Qi RQ. IL‑18 knockout 
alleviates atopic dermatitis‑like skin lesions induced by MC903 in a mouse model. Int J 
Mol Med, 2020, 46: 880-888. 
Cork MJ, Thac¸i D, Eichenfield L, et al. Dupilumab in adolescents with uncontrolled 
moderate-to-severe atopic dermatitis: results from a phase IIa open-label and subsequent 
phase III open-label extension trial. Br J Dermatol. 2020;182(1):85-96. 
de Bruin-Weller, M, Thac¸i D, Smith CH, et al. Dupilumab with concomitant topical 
corticosteroid treatment in adults with atopic dermatitis with an inadequate response or 
intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo-
controlled, randomized phase III clinical trial (LIBERTY AD CAFE´ ). Br J Dermatol. 
2018;178(5):1083-1101. 


TMF-14679521 
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Dupilumab: Summary of Product Characteristics. European Medicines Agency. 
Published 21 Jan 2021. https://www.ema.europa.eu/en/medicines/human/EPAR/dupixent. 
Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, Hanifin JM, Simpson EL. 
Guidelines of care for the management of atopic dermatitis. J Am Acad Dermatol. 2014 
Feb; 70(2): 338–351. 
Finlay AY and Khan GK. Dermatology Life Quality Index (DLQI) -a simple practical 
measure for routine clinical use. Clin Exp Dermatol 1994 May;19(3):210-6. 
Fuxench ZCC, Block JK, Boguniewicz M, Boyle J, Fonacier L, Gelfand JM et al. Atopic 
Dermatitis in America Study: A Cross-Sectional Study Examining the Prevalence and 
Disease Burden of Atopic Dermatitis in the US Adult Population. J Invest Dermatol  
Actions. 2019 Mar;139(3):583-590. 
GlaxoSmithKline Document Number WM2009/00047/07: Investigator Brochure 
GSK1070806: Effective date: JUL 2021. 
Glickman JW, Dubin C, Han J, Dahabreh D, Garcet S, Krueger JG et al. 2020.  
Comparing cutaneous molecular improvement with different treatments in atopic 
dermatitis patients. JACI April 1285 – 1288. 
Guttman-Yassky E, Thac D, Pangan AL, Chih-ho Hong H, Papp KA, Reich K. 
Upadacitinib in adults with moderate to severe atopic dermatitis: 16-week results from a 
randomized, placebo-controlled trial. J Allergy Clin Immunol 2020;145:877-84. 
Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol. 
1980; 60: 44-47.  
Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The eczema area 
and severity index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator 
Group. Exp Dermatol 2001;10:11-8. 
He H, Bissonnette R, Wu J, Diaz A, Saint-Cyr Proulx E, Maari C, Jack C, et al. Tape 
strips detect distinct immune and barrier profiles in atopic dermatitis and psoriasis J 
Allergy Clin Immunol. 2021 Jan;147(1):199-212. 
Inoue Y,  Aihara M,  Kirino M, , et al.. Interleukin‐18 is elevated in the horny layer in 
patients with atopic dermatitis and is associated with Staphylococcus aureus colonization. 
Br J Dermatol. 2011;164(3):560-567. 
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. 
Kawase Y, Hoshino T, Yokota K, Kuzuhara, A,Kirii Y, Nishiwaki E et al. Exacerbated 
and prolonged allergic and non-allergic inflammatory cutaneous reaction in mice with 
targeted interleukin-18 expression in the skin; J Invest Dermatol, 2003 Sep;121(3):502-9. 


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92 
Clinical Study Protocol template V15 dated 21-Dec-2020 
Khattri S. Brunner P.M. Garcet S. Finney R. Cohen S.R. Oliva M. et al. Efficacy and 
safety of ustekinumab treatment in adults with moderate-to-severe atopic dermatitis. Exp 
Dermatol. 2017; 26: 28-35. 
Khattri S. Shemer A. Rozenblit M. Dhingra N. Czarnowicki T. Finney R. et al. 
Cyclosporine in patients with atopic dermatitis modulates activated inflammatory 
pathways and reverses epidermal pathology. J Allergy Clin Immunol. 2014; 133: 1626-
1634. 
Konishi H, Tsutsui H, Murakami T, Yumikura-Futatsugi S, Yamanaka K-i, Tanaka M et 
al. IL-18 contributes to the spontaneous development of atopic dermatitis-like 
inflammatory skin lesion independently of IgE/stat6 under specific pathogen-free 
conditions. PNAS, 2002. 99 (17) 11340-11345. 
Lee JH, Cho DH, Park HJ. IL-18 and Cutaneous Inflammatory Diseases; Int J Mol Sci. 
2015 Dec 9;16(12):29357-69. 
Lei DK, Yousaf M, Janmohamed SR, Vakharia PP, Chopra R, Sacotte R et al.    
Validation of Patient-Reported Outcomes Information System Sleep Disturbance and 
Sleep-Related Impairment in adults with atopic dermatitis. Br J Dermatol. 2020 
Nov;183(5):875-882. 
McKie EA, Reid JL, Mistry PC, DeWall SL, Abberley L, Ambery PD, Gil-Extremera B. 
2016  A Study to Investigate the Efficacy and Safety of an Anti-Interleukin-18 
Monoclonal Antibody in the Treatment of Type 2 Diabetes Mellitus. PLOS One. 
Mendoza TR, Wang SX, Cleeland CS, Morrissey M, Johnson BA, Wendt JK, Huber SL. 
The rapid assessment of fatigue severity in cancer patients. Use of the brief fatigue 
inventory. Cancer 1999; 85:1186–96. 
Mistry P, Reid J, Pouliquen I et al. Safety, tolerability, pharmacokinetics, and 
pharmacodynamics of single-dose anti-interleukin-18 mAb GSK1070806 in healthy and 
obese subjects. Int J Clin Pharmacol Ther . 2014 Oct;52(10):867-79. 
Montan 2018.  General Population Norms for the Functional Assessment of Chronic 
Illness Therapy (FACIT)-Fatigue Scale - ScienceDirect. 
Neuenschwander B, Weber S, Schmidli H, O'Hagan A. Predictively consistent prior 
effective sample sizes. Biometrics. 2020 Jun; 76(2):578-587. 
Pavel AB, Song T, Kim HJ, Del Duca E, Krueger JG, Dubin C. et al. Oral Janus 
kinase/SYK inhibition (ASN002) suppresses inflammation and improves epidermal 
barrier markers in patients with atopic dermatitis. J Allergy Clin Immunol. 2019; 144: 
1011-1024. 
Pavel AB, Zhou L, Diaz A, Ungar B, Dan J, He H et al. The proteomic skin profile of 
moderate-to-severe atopic dermatitis patients shows an inflammatory signature, J Am 
Acad Dermatol. 2020 Mar; 82(3):690-699. 


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Clinical Study Protocol template V15 dated 21-Dec-2020 
Plitz T, Saint-Mézard P, Satho M, Herren S, Waltzinger C, de Carvalho Bittencourt M, 
Kosco-Vilbois MH and Chvatchko Y; IL-18 Binding Protein Protects Against Contact 
Hypersensitivity; J Immunol August 1, 2003, 171 (3) 1164-1171; 
Ricardo-Gonzalez RR, Van Dyken SJ, Schneider C, Lee J, Nussbaum JC, Liang H-E et 
al. Tissue signals imprint ILC2 identity with anticipatory function. Nat Immunol. 2018 
October; 19(10): 1093–1099. 
Röse L, Schneider C, Stock C, Zollner TM and Döcke W‐D. (2012), Extended DNFB‐
induced contact hypersensitivity models display characteristics of chronic inflammatory 
dermatoses. Experimental Dermatology, 21: 25-31. 
Sacottte R and Silverberg JI. Epidemiology of adult atopic dermatitis: Clinics in 
Dermatology. 2018; 36: 595-605. 
Saikiran KS, Hagglof T, Karlsson, MCI. IL‑18 in inflammatory and autoimmune disease; 
Cell. Mol. Life Sci. (2013) 70:4795–4808. 
Silverberg JI, Garg NI, Paller AS, et al. Sleep disturbances in adults with eczema are 
associated with impaired overall health: A US population-based study: J Invest Dermatol 
2015; 135: 56-66. 
Silverberg JI, Simpson EL, Ardeleanu M. Dupilumab provides important clinical beneﬁts 
to patients with atopic dermatitis who do not achieve clear or almost clear skin according 
to the Investigator’s Global Assessment: a pooled analysis of data from two phase III 
trials. Br J Dermatol. 2019;181:80-87. 
Simpson EL, Bieber T, Eckert L et al Patient burden of moderate to severe atopic 
dermatitis (AD): insights from a phase 2b clinical trial of dupilumab in adults. J Am Acad 
Dermatol 2016a; 74:491–8. 
Simpson EL, Bieber T, Guttman-Yassky E, et al. Two phase 3 trials of dupilumab versus 
placebo in atopic dermatitis. N Engl J Med. 2016b; 375(24): 2335-2348. 
Simpson EL, Gadkari A, Worm M, Soong W, Blauvelt A, Eckert L et al. Dupilumab 
therapy provides clinically meaningful improvement in patient-reported outcomes 
(PROs): a phase IIb, randomized, placebo-controlled, clinical trial in adult patients with 
moderate to severe atopic dermatitis (AD). J AmAcadDermatol. 2016c;75(3):506-515. 
Simpson EL, Paller AS, Siegfried EC, et al. Efficacy and safety of dupilumab in 
adolescents with uncontrolled moderate to severe atopic dermatitis: a phase 3 randomized 
clinical trial. JAMA Dermatol. 2020a;156(1):44-56.  
Simpson EL, Sinclair R, Forman S, Wollenberg A, Aschoff R, Cork M, Efficacy and 
safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis 
(JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 
trial. Lancet. 2020(b) Jul 25;396(10246):255-266.  


TMF-14679521 
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215253 
 
94 
Clinical Study Protocol template V15 dated 21-Dec-2020 
Tennant KF. The FACIT Fatigue Scale (Version 4) 2019. Hartford Institute for Geriatric 
Nursing (hign.org). Issue #30 of General Assessment Series. 
Terada M, Tsutsui H, Imai Y, Yasuda K, Mizutani H, Yamanishi K, et al. Contribution of 
IL-18 to atopic-dermatitis-like skin inflammation induced by Staphylococcus aureus 
product in mice, PNAS, Jun 2006, 103 (23) 8816-8821.  
Thaci D, Simpson EL, Beck LA, et al. Efficacy and safety of dupilumab in adults with 
moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a 
randomised, placebo-controlled, dose-ranging phase 2b trial. Lancet. 2015; 
387(10013):40-52. 
Thijs JL, Strickland I, Bruijnzeel-Koomen CAFM,  Nierkens S, Giovannone B, 
Csomor E, et al. Moving toward endotypes in atopic dermatitis: Identification of patient 
clusters based on serum biomarker analysis J Allergy Clin Immunol 2017;140:730-7. 
Weidinger S, Novak N. Atopic dermatitis. Lancet. 2016; 387(10023):1109-1122.  
Wlodek E, Kirkpatrick RB, Andrews S, Noble R, Schroyer R, Scott R. A pilot study 
evaluating GSK1070806 inhibition of interleukin-18 in renal transplant delayed graft 
function. PLOS One. March 8, 2021.  
Yosipovitch G, Reaney M, Mastey V, Eckert L, Abbé A, Nelson L. Peak Pruritus 
Numerical Rating Scale: psychometric validation and responder definition for assessing 
itch in moderate‐to‐severe atopic dermatitis. Br J Dermatol. 2019 Oct; 181(4): 761–769. 


Si g nat ure Pa ge f or  2 1 5 2 5 3 T M F- 1 4 6 7 9 5 2 1 v 1. 0
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Reas o n f or si g ni n g: A p pr o ve d
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Date of si g nat ure: 0 6-J u n- 2 0 2 2 1 0: 3 6: 1 9 G M T + 0 0 0 0
P P D

SAP_001.pdf: 
  
Study ID:  215253 
 
Official Title of Study: A Phase Ib, Randomized, Double-Blind, Parallel Group, Placebo- 
                                       Controlled Study of the Clinical Effect, Safety and Tolerability of              
                                       a Single Intravenous Infusion of GSK1070806 in   Moderate to 
                                       Severe Atopic Dermatitis Patients 
 
NCT ID: NCT04975438 
 
Date of Document: 15-Mar-2022 
 
 
 
                         
                      Statistical Analysis Plan 


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Information Type: 
Statistical Analysis Plan (SAP) 
 
TITLE PAGE 
Protocol Title: 
A Phase Ib, Randomized, Double-Blind, Parallel Group, 
Placebo-Controlled Study of the Clinical Effect, Safety and 
Tolerability of a Single Intravenous Infusion of GSK1070806 
in Moderate to Severe Atopic Dermatitis Patients. 
 
 
Study Number: 
215253  
Compound Number: GSK1070806 
Abbreviated Title: 
Clinical Effect, Safety and Tolerability of GSK1070806 in 
Atopic Dermatitis. 
 
 
 
Sponsor Name: GlaxoSmithKline Research & Development Limited  
Regulatory Agency Identifier Number(s)  
 
Registry 
 
ID 
Clintrials.gov 
NCT04975438 
 
 
 
Copyright 2022 the GlaxoSmithKline group of companies. All rights reserved. 
Unauthorised copying or use of this information is prohibited. 
 


C O N FI D E N TI A L  
 
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T A B L E O F C O N T E N T S  
P A G E  
1.  
I N T R O D U C TI O N ...................................................................................................... 5  
1. 1.  
O bj e cti v e s, E sti m a n d s a n d E n d p oi nt s  ........................................................... 5  
1. 2.  
St u d y D e si g n  ................................................................................................ 7  
2.  
S T A TI S TI C A L H Y P O T H E S E S  ................................................................................. 9  
2. 1.  
M ulti pli cit y A dj u st m e nt  .................................................................................. 9  
3.  
A N A L Y SI S S E T S  ................................................................................................... 1 0  
4.  
S T A TI S TI C A L A N A L Y S E S  ..................................................................................... 1 0  
4. 1.  
G e n er al C o n si d er ati o n s  .............................................................................. 1 0  
4. 1. 1.  
B a y e si a n i nf er e n c e  ...................................................................... 1 1  
4. 1. 2.  
B a s eli n e D efi niti o n  ....................................................................... 1 1  
4. 2.  
Pri m ar y E n d p oi nt A n al y s e s  ......................................................................... 1 2  
4. 2. 1.  
D efi niti o n of P er c e nt c h a n g e fr o m b a s eli n e i n t h e E A SI  ............... 1 2  
4. 2. 2.  
M ai n a n al yti c al a p pr o a c h  ............................................................. 1 2  
4. 2. 3.  
S e n siti vit y a n al y s e s  ..................................................................... 1 3  
4. 2. 4.  
A d diti o n al e sti m a n d s  .................................................................... 1 3  
4. 3.  
S e c o n d ar y E n d p oi nt s A n al y s e s  .................................................................. 1 4  
4. 3. 1.  
Cli ni c al s e c o n d ar y e n d p oi nt s  ....................................................... 1 4  
4. 3. 2.  
I m m u n o g e ni citi y ........................................................................... 1 6  
4. 5.  
S af et y A n al y s e s  .......................................................................................... 2 3  
4. 5. 1.  
E xt e nt of E x p o s ur e  ...................................................................... 2 3  
4. 5. 2.  
A d v er s e E v e nt s ............................................................................ 2 3  
4. 5. 3.  
A d diti o n al S af et y A s s e s s m e nt s  .................................................... 2 4  
4. 6.  
Ot h er A n al y s e s  ........................................................................................... 2 6  
4. 6. 1.  
S u b gr o u p a n al y s e s  ...................................................................... 2 6  
4. 7.  
I nt eri m A n al y s e s ......................................................................................... 2 6  
4. 8.  
C h a n g e s t o Pr ot o c ol D efi n e d A n al y s e s  ....................................................... 2 6  
5.  
S A M P L E SI Z E D E T E R MI N A TI O N  ......................................................................... 2 6  
6.  
S U P P O R TI N G D O C U M E N T A TI O N  ....................................................................... 2 8  
6. 1.  
A p p e n di x 1 St u d y P o p ul ati o n A n al y s e s  ....................................................... 2 8  
6. 1. 1.  
P arti ci p a nt Di s p o siti o n  ................................................................. 2 8  
6. 1. 2.  
D e m o gr a p hi c a n d B a s eli n e C h ar a ct eri sti c s  .................................. 2 8  
6. 1. 3.  
Pr ot o c ol D e vi ati o n s  ...................................................................... 2 9  
6. 1. 4.  
Pri or a n d C o n c o mit a nt M e di c ati o n s  ............................................. 2 9  
6. 1. 5.  
St u d y I nt er v e nti o n C o m pli a n c e  .................................................... 2 9  
6. 1. 6.  
A d diti o n al A n al y s e s D u e t o t h e C O VI D -1 9 P a n d e mi c  .................. 2 9  
6. 2.  
A p p e n di x 2 D at a D eri v ati o n s R ul e  .............................................................. 3 0  
6. 2. 1.  
Crit eri a f or P ot e nti al Cli ni c al I m p ort a n c e  ...................................... 3 0  
C CI


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6.2.2. 
Study Period ................................................................................ 32 
6.2.3. 
Study Day and Reference Dates .................................................. 33 
6.2.4. 
Assessment Window ................................................................... 33 
6.2.5. 
Multiple measurements at One Analysis Time Point .................... 33 
6.2.6. 
Handling of Partial Dates ............................................................. 33 
6.2.7. 
Early PK Access Key Activities .................................................... 34 
7. 
ABBREVIATIONS .................................................................................................. 36 
8. 
REFERENCES ....................................................................................................... 38 
 


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Version history 
SAP 
Version 
Approval 
Date 
Protocol 
Version (Date) 
on which SAP 
is Based 
Change 
Rationale 
SAP 
Original 
version 
15 Mar 
2022 
Protocol 
Amendment 1 
(25 Feb 2022) 
Not Applicable 
Original version 
 


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1. 
INTRODUCTION 
The purpose of this SAP is to describe the planned analyses to be included in the Clinical 
Pharmacology Study Report (CPSR) for Study 215253. Details of the planned interim 
analysis, as well as the final analyses, are provided. 
1.1. 
Objectives, Estimands and Endpoints 
Objectives 
Endpoints 
Primary 
 
• To compare the clinical effect of a 
single intravenous (IV) infusion of 2 
mg/kg of GSK1070806 versus placebo 
in moderate to severe Atopic 
Dermatitis in the Biologic Naïve (BN) 
population (Group 1). 
• 
Percent change from baseline 
(PCFB) in the Eczema Area and 
Severity Index (EASI) at Week 12  
Secondary 
 
• To further compare the clinical effect 
(GSK1070806 versus placebo) in the 
BN population (Group 1). 
• Change from Baseline (CFB) in the 
EASI at Week 12. 
• EASI 50/75/90 defined as ≥ 
50/75/90% reduction in the EASI 
from Baseline at Week 12. 
• 
Investigator Global Assessment 
(IGA) score of 0 or 1 at Week 12. 
• To estimate the clinical effect of 
GSK1070806 in the dupilumab 
inadequate responder (Dupi-IR) 
population (Group 2). 
• 
PCFB in the EASI at Week 12. 
• To assess safety and tolerability 
(GSK1070806 versus placebo) in the 
combined AtD population (Groups 1 
and 2). 
• Incidence of serious adverse events 
(SAEs) and adverse events (AEs). 
• Incidence of clinically important 
findings in: 
• Vital signs 
• Electrocardiogram 
• Laboratory: haematology, clinical 
chemistry and urinalysis. 
• To assess anti-drug antibody (ADA) 
formation in the combined AtD 
population (Groups 1 and 2). 
• Incidence of ADAs  


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O bjecti ves  
E n d p oi nts  
 
Pri m ar y esti m a n d  
T he pri mar y cli nic al q uesti o n of i nterest is: W hat is t he treat me nt effect o n Ecze ma Area 
a n d Se verit y I n de x ( E A SI)  after 1 2 wee ks of treat me nt wit h a si n gle i ntra v e n o us (I V) 
i nf usio n of 2  m g/ k g G S K 1 0 7 0 8 0 6 vers us  place b o i n  Bi ol o gic Naï ve  p artici p a nts ( Gr o u p 
1) wit h  m o derate t o se v ere At o pic Der m atitis  i n t he a bse nce of use of Resc ue T hera p y . 
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The primary estimand is described by the following attributes: 
o Population: Biologic Naïve (BN) participants with moderate to severe Atopic 
Dermatitis. 
o Treatment condition: A single 2 mg/kg one-hour IV infusion of either 
GSK1070806 or placebo at Day 1. 
o Variable / endpoint: Percent change from Baseline to Week 12 in the EASI. 
o Summary measure: Difference (GSK1070806 - placebo) in mean percent change 
from baseline in EASI at Week 12. 
o Intercurrent events: Use of Rescue Therapy. It will be handled with a hypothetical 
strategy, i.e. values after use of Rescue Therapy will be set to missing.  
 
Rescue Therapy is defined in this document as the use of any prohibited medication 
(as defined in the protocol section 6.8.2) that is considered as an important protocol 
deviation. 
Rationale for estimand: The study is designed to evaluate the treatment effect attributable 
to GSK1070806. It is important that this effect is not confounded by the effect of other 
treatments. Therefore, for participants who use any Rescue Therapy, a hypothetical 
strategy will be used in order to estimate the treatment effect in the absence of use of 
Rescue Therapy.  
1.2. 
Study Design 
Overview of Study Design and Key Features 
Design 
Features 
• 
Multi-centre, randomized, double-blind, parallel group, placebo-
controlled study of GSK1070806 administered as a single 2 mg/kg 
IV infusion to investigate the efficacy and safety in moderate-severe 
AtD participants. The primary efficacy endpoint will be measured at 
Week 12. 


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Overview of Study Design and Key Features 
• 
The overall study duration for an individual participant is not 
expected to exceed 28 weeks (Screening is 4 weeks; Treatment 
Period is 12 weeks; Follow-Up Period is 12 weeks). The End of 
Study (Week 24, Day 169) would allow for continued safety 
monitoring beyond the Week 12 primary endpoint. 
• 
The study will assess the impact of GSK1070806 in two groups of 
patients with moderate-to-severe AtD. Groups 1 and 2 will be 
conducted in parallel. 
• 
Group 1: Patients naïve to biologic treatment (and who have 
failed topical therapies). 
• 
Group 2: Patients who have not adequately responded (or have 
been intolerant) to dupilumab (Dupixent). 
 
Study 
interventio
n 
• 
All participants must meet all clinical criteria at the point of 
randomization (for subsequent dosing on Day 1) and must stop using 
topical treatments (corticosteroids, calcineurin inhibitors or 
Phosphodiesterase 4 [PDEIV] inhibitors) for at least 7 days (starting 
on Day -7) prior to dosing on Day 1. 
• 
GSK1070806 and placebo are double blinded. Participants will 
receive either GSK1070806 or placebo on Day 1.  
Study 
interventio
n 
Assignment 
• 
Approximately 64 patients are expected to be screened to achieve 
approximately 48 randomly assigned participants.  
• 
Group 1: N = 30.  20 participants will receive GSK1070806, 10 
will receive placebo in a 2:1 ratio. Approximately 40 BN 
patients may need to be consented for screening to provide 30 
randomized. 
• 
Group 2: N = 18. 15 participants will receive GSK1070806, 3 
will receive placebo in a 5:1 ratio. Approximately 24 Dupi-IR 
patients may need to be consented for screening to provide 18 
randomized. 
Interim 
Analysis 
The details of the planned analysis and timing will be documented in the 
Interim Charter. Refer to Section 4.7 for details. 
Analyses 
• 
Primary completion analysis: when the last participant in Group 1 
completes the Week 12 visit or withdraws from the study prior to 
Week 12. 


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Overview of Study Design and Key Features 
• 
Final analysis: when the last participant completes the Week 24 visit 
or withdraws from the study prior to Week 24 
 
2. 
STATISTICAL HYPOTHESES  
There is no formal hypothesis to be tested. 
2.1. 
Multiplicity Adjustment 
There will be no adjustment for multiplicity. 


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3. 
ANALYSIS SETS 
For the purposes of analysis, the following analysis sets are defined: 
Analysis Set 
Definition / Criteria 
Analyses Evaluated 
Screened  
• All participants who signed the ICF and are screened for 
eligibility. 
• Study Population 
Enrolled 
• 
All participants in the Screened analysis set who entered 
the study. 
• Study Population 
Randomised 
• All participants in the Enrolled analysis set who were 
randomly assigned to study intervention in the study. 
• 
Participants will be analysed according to the intervention 
they were randomized to receive. 
• Study Population 
Safety 
• All participants in the Randomized analysis set who 
received the study intervention. 
• 
Participants will be analysed according to the intervention 
they actually received. 
• Efficacy 
• Safety 
• Biomarker 
• PROs 
Pharmacokinetic 
(PK) 
• All participants in the Safety analysis set who had at least 
1 non-missing PK assessment (Non-quantifiable [NQ] 
values will be considered as non-missing values). 
• 
Participants will be analysed according to the intervention 
they actually received. 
• PK 
COVID-19  
• All participants in Safety analysis set who had confirmed 
COVID-19 diagnosis.  
• Safety 
 
 
The term “Analysis Set” will be referred to as “Population” in the displays.  
4. 
STATISTICAL ANALYSES 
4.1. 
General Considerations 
Unless otherwise specified, the Enrolled or Randomized Analysis Sets will be used for all 
Study Population analyses (detailed in the Output and Programming Specification 
(OPS)), the Safety Analysis Set will be used for all Efficacy, Safety, Biomarker, and PRO 
analyses, and PK Analysis Set will be used for PK analyses. 
In the case of wrong group (i.e., Group 1 vs Group 2) assignment at the time of 
randomization, the analyses will be performed based on the actual group per data 
collected in the CRF. 
Unless otherwise specified, summary tables will provide the following descriptive 
statistics as a minimum:  
• Continuous data: n, mean, standard deviation, minimum and maximum.  
• Continuous data (log-normally distributed): n, geometric mean, %CVb, minimum, 
maximum  
• Categorical data: number and percentage of participants in each category. 


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4.1.1. 
Bayesian inference 
The main statistical analyses will be carried out in the Bayesian framework. Models will 
be fitted by Monte Carlo Markov Chain (MCMC) simulations.  
Prior distributions are given in the analysis sections below and will be reported in the 
Clinical Pharmacology Study Report (CPSR).  
Posterior distributions for each arm and for the treatment difference between arms will be 
summarized using posterior median, 95% equal-tailed credible intervals (CrI), and 
posterior probabilities of the true treatment difference being greater than pre-specified 
thresholds. 
The inference will be carried out as follows: 
- 
2 chains will be run, with different (over-dispersed) initial values in order to 
assess convergence. Posterior summaries will use only 1 chain. 
- 
A minimum burn-in period of 1,000 MCMC samples (for each chain) will be 
used.  
- 
A minimum of 10,000 MCMC samples (for each chain) will be run to generate 
samples of the posterior distribution.  
- 
A thinning sample may be used to improve convergence. If k is the thinning ratio, 
the number of MCMC samples will be minimum k ×10,000. 
To assess convergence (MCMC), the following will be used: 
- 
Ratio of Monte Carlo error /posterior SD should be as small as to ensure that only 
a fraction of the posterior variability is due to simulation error.  
The final MCMC samples will be such that this ratio for the key parameters in the 
model is ≤ 0.01. 
• Gelman & Rubin diagnostic is based on the ratio of the pooled variance across the 
chains over the overall within-chain variance. Values close to 1 indicate that each 
of the subsets of MCMC samples is close to the target posterior distribution. 
A cut-off of 1.1 will be used. 
• Diagnostic plots and visual inspection 
o Trace plots (the distribution of points should not change as the chain 
progresses and the posterior mean and variance are relatively constant) 
o Autocorrelation plots (provide information on how slow or fast the Markov 
chain converges) 
All the diagnostic outputs and alternative models fitted (where applicable) will be stored 
in the refdata folder in HARP (production) in the relevant reporting efforts. 
4.1.2. 
Baseline Definition 
For all endpoints the baseline value will be the latest pre-dose assessment with a non-
missing value, including those from unscheduled visits, unless otherwise stated. If time is 


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n ot c ollecte d, Da y 1 assess me nts are ass u me d t o b e ta ke n pri or t o first d ose a n d use d as 
baseli ne.  
If baseli ne d ata is missi n g n o deri vati o n will be perf or me d a n d bas eli ne will be set t o 
missi n g.  
F or P P -N R S  a n d 
It e m 3 baseli ne, t he baseli n e sc ore will be a vera ge d fr o m dail y 
val ues fr o m Da y -7 t o Da y -1, if  ≥ 4 ( o ut of 7) da ys are n ot missi n g. If o nl y ≤ 3 da ys ( o ut 
of 7) are a vaila bl e, baseli ne is set t o missi n g.  
F or s ki n p u nc h bi o ps y, t h ere is a Lesi o nal Baseli ne a n d a N o n -lesi o n al Bas eli ne.  
 
4. 2.  
Pri m ar y E n d p oi nt  A n al y s e s  
4. 2. 1.  
D efi niti o n of P er c e nt c h a n g e fr o m b a s eli n e i n t h e E A SI  
T he pri mar y e n d p oi nt is t he Perce nt c ha n ge fr o m b aseli ne  i n t he E A SI at Wee k 1 2 i n 
Gr o u p 1, a n d t he esti ma n d is descri be d i n S ecti o n 1. 1 . 
4. 2. 2.  
M ai n a n al yti c al a p pr o a c h  
T he a nal ysis will be carri e d o ut f or Gr o u p 1 o nl y, usi n g data u p t o Wee k 1 2.  
T he a nal ysis will be base d o n t he Safet y a nal ysis s et . Partici pa nts will be a n al yse d 
acc or di n g t o t he tr eat me nt t he y recei v e d.   
E A SI s c ores c ollecte d aft er use of Res c ue T h era p y will be set t o missi n g.  
Missi n g o bser vati o ns will be ass u me d t o be Missi n g at Ra n d o m ( M A R), i.e. ass u me t hat 
t he missi n g part, gi ve n t h e hist or y, will be li ke t he data o bser ve d i n t he a bse nce of Resc u e 
T hera p y . 
E n d p oi nt( s)  
•  P erc e nt C h an g e fr o m B aseli n e i n th e E A SI at W eek 12 ( Gr o u p 1) ( Hy pot h etic al Strat e gy, r o bust 
M A P Pri or)  
A n al y sis M et h o d  
B ay esi an r e pe ate d m eas ures m o d el  
M o d el S p e cific ati o n  
O utc o m e  
P erc e nt ch a n g e fr o m bas eli n e i n t h e E A SI  
Pr e dict ors  
•  
B as eli ne E A SI scor e (c onti n uous)  
•  
Tr e at m e nt (c at eg oric al, r efer enc e: plac e bo)  
•  
Visit (cat e g oric al, w e eks 2, 4, 8, 1 2, r ef ere nc e: W e ek 1 2) 
•  
Tr e at m e nt*visit i nter acti o n (cate g oric al)  
•  
B as eli ne E A SI*visit i nter acti o n (c o nti nu o us)  
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Baseline EASI score will be centered around its observed mean prior to inclusion 
in the model 
Prior distributions for 
parameters associated 
to the predictors 
• 
Placebo at Week 12: robust MAP prior: mixture prior has 28.5% weight on a 
Normal (-31.56, SD=5.67), 21.5% weight on a Normal (-31.21, SD=11.00) and 
50% weight on a Normal (-30, SD = 50) 
• 
GSK1070806 at Week 12: vague prior Normal(-30, SD=50) 
• 
All other parameters: vague priors Normal(0, SD = 106) 
Prior distribution for 
residual covariance 
matrix 
• 
Σ: unstructured residual covariance matrix of dimension 4×4 ~ Inverse Wishart 
(J, S), with J = number of visits (degree of freedom), S = identity matrix 
 
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 4.1.1 
Results Presentation 
• Adjusted posterior median, and 95% CrI for each treatment by timepoint interaction (table). 
• Posterior median treatment differences (GSK1070806 – placebo) and associated 95% CrI for 
each timepoint (table and figure). 
• Probabilities that the true treatment difference (GSK1070806 – placebo) at each visit is < 0%, -
15%, -25%, and -40% (table), e.g., Prob(GSK1070806 – placebo < -15%) 
• Outputs will include results for earlier timepoints in addition to the objective specified timepoint 
of Week 12. 
 
For the PCFB in the EASI at Week 12 in the placebo arm, data from 16 previous trials in 
AtD were included to derive an informative prior using a meta-analytic predictive (MAP) 
method [Schmidli, 2014]. A vague mixture component was added to allow for prior-data 
conflicts. 
Data were extracted from the following publications: [Beck, 2014], [Bissonnette, 2019], 
[Gooderham, 2019], [Guttman-Yassky, 2019], [Guttman-Yassky, 2020a], [Guttman-
Yassky, 2020b], [Ruzicka, 2017], [Simpson, 2016], [Simpson, 2018], [Simpson,2019], 
[Simpson, 2020], [Thaçi, 2016]. 
4.2.3. 
Sensitivity analyses 
As a sensitivity analysis, a vague prior of Normal (-30, SD=50) will be applied instead of 
the robust MAP prior for placebo at Week 12.  
4.2.4. 
Additional estimands 
An additional estimand for the primary endpoint is defined: the intercurrent event of the 
use of Rescue Therapy will be handled with the treatment policy strategy: data collected 
after use of Rescue Therapy will be included in the statistical analysis. 


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Missing data assumption will be MAR, i.e., given the history of a subject, the part that is 
missing will be distributed similarly as those that are still in the study at that time, 
whether they have taken Rescue Therapy or not. 
The same statistical approach as described in Section 4.2.2 will be used. 
Primary endpoint additional analysis due to COVID-19 
For the primary endpoint, if >= 6 participants in Group 1 have confirmed COVID-19 up 
to Week 12, then an additional analysis whereby the intercurrent event of the onset of 
COVID-19 (confirmed diagnosis only) will be handled with the hypothetical strategy 
may be conducted. 
EASI scores collected after the onset of COVID-19 (confirmed diagnosis only) will be 
set to missing. 
Missing observations will be assumed to be Missing at Random (MAR), i.e. assume that 
the missing part, given the history, will be like the data observed in the absence of 
COVID-19. 
For the use of Rescue Thearpy, the same method (hypthetical stratgey) as in the primary 
analysis will be used.  
4.3. 
Secondary Endpoints Analyses 
For Safety analysis please refer to Section 4.5. 
4.3.1. 
Clinical secondary endpoints 
4.3.1.1. 
Definition of clinical endpoints 
The secondary endpoints for Group 1 are:  
• Change from baseline in the EASI at Week 12.  
• EASI 50/75/90 responses at Week 12, EASI 50/75/90 response is defined as ≥ 
50/75/90% reduction in the EASI from Baseline.  
• IGA score of 0 ('clear’) or 1 ('almost clear’) response at Week 12.  
The secondary endpoint for Group 2 is: 
• 
Percent change from baseline in the EASI at Week 12.  
4.3.1.2. 
Main analytical approach 
The analyses of the secondary endpoints will be based on the Safety analysis set. 
Participants will be analysed according to the treatment they received. 


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Group 1 – continuous endpoints 
The approach is the same as that used for the primary endpoint (Section 4.2.2), including 
up to Week 12 visit. Vague prior of Normal(0, SD=106) will be used for all parameters 
associated to the predictors. EASI scores will be set to missing after Rescue Therapy. 
Missing data will be assumed to be MAR. 
Group 1 – binary endpoints 
Bayesian logistic regression will be used.  
Responses collected after use of Rescue Theapy will be set to non-responders.  
Missing responses will be imputed as non-reponders. 
Binary Endpoints 
• EASI50, EASI75, and EASI90 responses at Week 12 
• IGA score of 0 or 1 response at Week 12  
Analysis Method 
Bayesian Logistic Regression 
Model Specification 
Outcome 
yi = Ryi = response (0/1) for participant i at Week 12 
Predictors 
• 
Treatment (categorical) 
• 
Baseline score (continuous) 
 
Baseline score will be centered around its observed mean prior to inclusion in the 
model 
Model 
yi ~ Ber(pi) 
logit(pi) = (Treatment=Placebo)×β1 + (Treatment=GSK)×β2 + (Baseline  score)×β3 
Prior distributions for 
coefficients (β) 
β = parameters associated to predictors 
• 
β1 ,  β2: vague prior such that logit-1(βk) ~ Beta(1/3, 1/3) 
• 
β3βk: vague prior N(0, SD=106) 
Model Checking & Diagnostics 
See Section 4.1.1 
Results Presentation 
• Adjusted posterior median and 95% CrI of true response rate for each treatment group, using 
the back-transformation of the logit (table). 
• Posterior median and 95% CrI for the true difference in proportion of responders (GSK1070806 
– placebo) (table) 


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•  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 t h a n 0  an d  1 0 %.  
•  O ut p uts will i ncl u d e r es ults for e arli er ti m e p oints i n a dditi o n t o t he o bjectiv e sp ecifi ed ti me p oint 
of W e ek 1 2. 
 
Gr o u p 2 –  c o nti n u o us e n d p oi nt  
T he P C F B i n t he E A SI i n Gr o u p 2 i n t he G S K 1 0 7 0 8 0 6  ar m will be a nal ys e d usi n g a 
si m plifie d versi o n of t he a p pr oac h us e d f or t h e pri mar y e n d p oi nt ( S ecti o n 4. 2. 2 ) wit h 
o nl y o ne tr eat me nt ar m . E A SI s c ores will be set t o missi n g after Res c ue T hera p y . 
Missi n g val ues are ass u me d t o be Missi n g at Ra n d o m ( M A R). Va g ue pri or s of N or mal ( 0, 
S D = 1 0 6) will be use d  f or t he para met ers ass oci ate d t o t he pre dict ors. 
4. 3. 1. 3.  
S e n siti vit y a n al y s e s  
N o se nsiti vit y a nal yses are pla n ne d f or sec o n dar y efficac y e n d p oi nts. 
4. 3. 1. 4.  
S u p pl e m e nt ar y a n al y s e s  
Data c ollecte d aft er use of Resc ue T h era p y  ma y b e use d.  
4. 3. 2.  
I m m u n o g e ni citi y 
T he i m m u n o ge nicit y a n al yses will be base d o n t he S afet y a nal ysis set a n d will be re p orte d 
f or gr o u ps 1 a n d 2 c o m bi ne d . 
T he i m m u n o ge nicit y of G S K 1 0 7 0 8 0 6  will be c haract erize d wit h s u m mar y st atistics of 
i nci de nce, i. e. t he n u m ber of partici pa nts wit h a nti-dr u g a nti b o dies b y treat me nt o ver ti me. 
I m m u n o ge nicit y t esti n g i n v ol ves a s cree ni n g assa y a n d a c o nfir mati o n ass a y t hat t o get her 
pr o d uce 3 res ults:  
•  Scree ni n g ass a y res ult ( p ositi ve / ne gati ve)  
•  C o nfir mat or y assa y res ult ( p ositi ve / ne gati ve) if p ositi ve res ult i n t he scree ni n g 
assa y 
•  Titre res ult ( n u meri c) if p ositi ve res ult i n t he c o nfir mati o n assa y . 
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C O N FI D E N TI A L  
 
 
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rs 
 
, 
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4. 5.  
S af et y A n al y s e s  
T he safet y a nal yses will be base d o n t he Safet y A nal ysis Set  a n d re p orte d f or gr o u ps 1 
a n d 2 c o m bi ne d . Partici p a nts will be a nal yse d acc or di n g t o t he treat me nt t he y recei ve d. 
N o f or mal statistical testi n g will be perf or me d o n Safet y d ata.  
4. 5. 1.  
E xt e nt of E x p o s ur e  
A listi n g of e x p os ure t o st u d y treat me nt will be pr o d uce d.  
4. 5. 2.  
A d v er s e E v e nt s  
A d verse e ve nt ( A E) a n al ys es i ncl u di n g t he a nal y sis of A Es, Seri o us A Es ( S A Es) a n d 
ot her si g nifica nt A Es will be base d o n G S K C ore Data Sta n dar ds. S u m mar y ta bles will 
i ncl u de t he n u m ber of partici pa nts wit h t he A E, t he perce nta ge of partici p a nts wit h t he 
A E. T he defi niti o ns of A E s or S A Es will be detail e d i n O P S.   
A n A E is c o nsi dere d st u d y i nter ve nti o n e mer ge nt if t he A E o nset date is o n or after st u d y 
i nter ve nti o n start date.  
All A E s u m maries will be base d o n st u d y i nter ve nti o n e mer ge nt e ve nts u nl ess ot her wise 
s pecifie d.  
S A E s u m maries will be base d o n  all S A Es re p orte d re gar dl ess of w het h er t he y m eet t he 
defi niti o n of st u d y i nter ve nti o n e mer ge nt or n ot.  
All A E a n d S A E s u m maries will be prese nte d b y S yste m Or ga n Class (S O C ) & Preferre d 
Ter m (P T ) u nless ot her wise s pecifie d. A d verse e v e nts will be c o de d usi n g t he sta n dar d 
Me dical Dicti o nar y f or R e g ul at or y Affairs ( Me d D R A dicti o nar y).  
S u m mar y ta bles will be pr o d uce d  f or t he f oll o wi n g cate g ories:  
1.  A d verse e ve nts b y s yste m or ga n class a n d preferre d te r m a n d ma xi m u m i nte nsit y 
2.  Dr u g -relate d a d v erse e ve nts b y s yste m or ga n class a n d preferre d ter m a n d 
ma xi m u m i nte nsit y  
3.  Seri o us a d verse e ve nts b y s yste m or ga n class a n d preferre d t er m ( n u m ber of 
s u bjects a n d occ urre n ces) 
4.  C o m m o n ( > = 0 %) a d v ers e e ve nts b y o verall  fre q u e nc y 
5.  C o m m o n ( > = 0 %) n o n -s eri o us a d verse e ve nts b y s yste m or ga n class a n d preferre d 
ter m ( n u m ber of s u bjects a n d occ urre n ces) 
6.  Seri o us a d verse e ve nts b y s yste m or ga n class a n d preferre d t er m a n d ma xi m u m 
i nte nsit y 
7.  N o n -seri o us dr u g-relat e d a d verse e ve nts b y o verall fre q ue n c y  
8.  Seri o us fatal a n d n o n -fat al dr u g-rel ate d a d v erse e ve nts b y o v erall fre q ue n c y 
 
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4.5.2.1. 
Adverse Events of Special Interest 
There are no adverse events of special interest identified for this study. 
4.5.2.2. 
COVID-19 Assessment and COVID-19 AEs 
COVID-19 assessments for participants with COVID-19 AEs will be summarized. 
4.5.2.3. 
Impact of COVID-19 Pandemic on Safety Results 
The impact of the COVID-19 pandemic on the safety results will be assessed, if any. 
Adverse Events 
A listing of COVID-19 related AEs (SMQ related to COVID to flag all preferred terms 
related to COVID-19) will be produced.  
If >= 10 participants (groups 1 and 2 combined) have confirmed COVID-19, the 
following tables will be created: 
1. Adverse Events by System Organ Class and Preferred Term and Maximum 
Intensity (AEs before the onset of COVID-19 vs. AEs on and after the onset of 
COVID-19; Safety Analysis Set) 
2. Adverse Events by System Organ Class and Preferred Term and Maximum 
Intensity (AEs on and after the onset of COVID-19; COVID-19 Analysis Set) 
3. Serious adverse events by system organ class and preferred term and maximum 
intensity (SAEs before the onset of COVID-19 vs. SAEs on and after the onset of 
COVID-19; Safety Analysis Set) 
4. Serious adverse events by system organ class and preferred term and maximum 
intensity (SAEs on and after the onset of COVID-19; COVID-19 Analysis Set) 
 
4.5.3. 
Additional Safety Assessments 
4.5.3.1. 
Laboratory Data 
Separate summary tables for haematology, and chemistry laboratory tests as well as urine 
concentration parameters will be produced. Liver function laboratory 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 (see 
Section 6.2.1) 
• For categorical urinalysis parameters 
 


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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. 
 
4.5.3.2. 
Vital Signs  
A summary table of change from baseline in vital signs will be produced, including systolic 
blood pressure (SBP), diastolic blood pressure (DBP), heart rate, and temperature. 
Shift tables of worst-case results relative to PCI criteria post-baseline relative to baseline 
will be provided for SBP, DBP and heart rate (see Section 6.2.1). 
 
4.5.3.3. 
ECG 
For all ECG analyses, baseline is taken to be the mean of the triplicate values collected 
pre-dose Day 1. The following summaries will be provided: 
1. Summary of Maximum QTc Values Post-Baseline Relative to Baseline by Category 
2. Summary of Maximum Increase in QTc Values Post-Baseline Relative to Baseline by 
Category 
3. 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. 
4. Summary of change from baseline in ECG values. In the case of triplicate ECG 
measurements, summaries will use the average of the triplicate. 
 
The QTc data analysis will use the values based on Fridericia formula. For analysis 
purposes, if QTcF is not available, it will be derived from QTcB.   
 
Shift tables will be provided for QTcF and will be used to detect any clinically important 
changes: 
- 
Maximum QTc values post-baseline relative to baseline by category defined as 
o To ≤450msec or No Change 
o Any increase > 450 msec 


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o Increase to >450 to <=480 
o Increase to >480 to <=500 
o Increase to >500 msec 
- 
Maximum increase in QTc values post-baseline relative to baseline by category 
defined as:   
o Increase of ≤ 30 msec 
o Increase between 31 and 60 msec 
o Increase > 60 msec 
4.6. 
Other Analyses 
4.6.1. 
Subgroup analyses 
There are no planned subgroup analyses for any of the endpoints. 
4.7. 
Interim Analyses 
The details of the planned analysis and timing will be documented in the Interim Analysis 
Charter. 
The decision criteria will be based on predictive probabilities of achieving two decision 
criteria (at the end of the study) defined in the interim charter, based on the interim data. 
The prediction of the future data will be based on the posterior distribution of the 
parameters at interim. The latter will be estimated using the same statistical analysis as 
described in Section 4.2.2. 
4.8. 
Changes to Protocol Defined Analyses 
There is no change or deviation to the originally planned statistical analysis specified in 
protocol amendment #1 (Dated: 25-FEB-2022). 
5. 
SAMPLE SIZE DETERMINATION 
Approximately 64 patients may need to be screened to obtain 48 randomized participants 
(approximately 30 and 18 participants in Groups 1 and 2, respectively). Participants who 
have withdrawn from the study, may be replaced at the discretion of the sponsor. 
The sample sizes for Groups 1 and 2 are selected to support preliminary assessment of the 
clinical effect, based on PCFB in the EASI for Groups 1 and 2.  
Operating characteristics of some criteria of interest for the both groups of the study have 
been calculated and presented below. 


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Group 1: 
Based on 30 participants (20 administered GSK1070806 and 10 administered placebo), the 
probability of different criteria of interest are given in the table below.  
A Bayesian linear regression was used, assuming that the PCFB in the EASI follows a 
Normal distribution. The priors were as follows: 
• Placebo arm: a robust meta-analytic predictive (MAP) prior was constructed based 
on placebo PCFB in the EASI reported in recent clinical trials in AtD. The resulting 
mixture prior has 28.5% weight on a Normal (-31.56, SD=5.67), 21.5% weight on 
a Normal (-31.21, SD=11.00) and 50% weight on a Normal (-30, SD = 50), with an 
effective sample size of 14 participants (expected local-information-ratio (ELIR) 
method (Neuenschwander, 2020)) assuming a between-participant SD = 50. 
• GSK1070806 arm: a vague Normal prior was used, with mean = -30 and SD = 50, 
corresponding to an effective sample size (ELIR method) of 1 participant assuming 
a between-participant SD = 50. 
Operating characteristics are provided below. A true PCFB in the EASI of -30% in the 
placebo arm was assumed, based on recent clinical trials in AtD. Various true PCFBs in 
the EASI for the GSK1070806 arm at Week 12 were assumed, giving various true 
treatment differences. A between-participant SD of 50% was assumed for both 
GSK1070806 and Placebo arms.  
Criteria 
True treatment difference 
-40% 
-25% 
-15% 
0% 
Observing a >75% posterior 
probability that the true difference 
from placebo is <-15% 
82.6% 
43.9% 
18.4% 
2.5% 
Observing a >75% posterior 
probability that the true difference 
from placebo is <-7.5% 
92.8%  
66.6%  
37.7% 
7.8% 
Observing a >97.5% posterior 
probability that the true difference 
from placebo is < 0% 
68.8% 
30.3% 
10.9% 
1.0% 
 
Group 2: 
There are no planned statistical analyses comparing GSK1070806 versus placebo. The 
analysis will be conducted on PCFB in the EASI in the GSK1070806 arm. 
Based on 15 participants on GSK1070806, the operating characteristics are given below. 
A vague Normal prior was used, with mean = 0 and SD = 1×106, corresponding to an 
effective sample size (ELIR method) of 0 participant assuming a between-participant 
SD=50.  


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Criteria 
True PCFB in the EASI in GSK1070806 
-70% 
-55% 
-45% 
-30% 
Observing a >50% posterior 
probability that the true 
PCFB in EASI is <-45% 
97.4% 
78.1%  
50.0%  
12.3% 
Observing a >50% posterior 
probability that the true 
PCFB in EASI is <-37.5% 
99.4%  
91.2%  
71.9%  
28.1% 
Observing a >50% posterior 
probability that the true 
PCFB in EASI is <-30% 
99.9%  
97.4%  
87.7%  
50.0% 
 
6. 
SUPPORTING DOCUMENTATION 
6.1. 
Appendix 1 Study Population Analyses 
Unless otherwise specified, the study population analyses will be based on the 
Randomised or Enrolled Analysis Set. A summary of the number of participants in each 
of the participant level analysis set will be provided. 
Study population analyses including analyses of participant’s disposition, protocol 
deviations, demographic and baseline characteristics, prior and concomitant medications 
will be based on GSK Core Data Standards.  Details of planned displays are presented in 
OPS. 
6.1.1. 
Participant Disposition 
A summary of the number and percentage of participants who completed the study as 
well as those who prematurely withdrew from the study will be provided. Reasons for 
study withdrawal will be summarized. A participant is considered to have completed the 
study if they have completed all planned study assessments including the follow-up visit.  
 
Rescreening of screen failures is allowed as per protocol. Rescreened participants will be 
summarized under their latest participant number. 
6.1.2. 
Demographic and Baseline Characteristics 
The demographic characteristics including age, gender, race, ethnicity, height, weight, 
and BMI will be summarized. 
A summary of atopic dermatitis history and characteristics will be provided. The 
summary will include baseline EASI score (continuous), baseline IGA score 
(categorical), and duration since diagnosis. 
 
Past medical conditions and current medical conditions as of screening will be 
summarized separately.  


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6.1.3. 
Protocol Deviations 
Important protocol deviations (including deviations related to study inclusion/exclusion 
criteria, conduct of the trial, patient management or patient assessment, prohibited 
medication) will be summarized. 
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: 
o Data will be reviewed prior to unblinding and freezing the database to ensure all 
important deviations (where possible without knowing the study intervention 
details) are captured and categorised in the protocol deviations dataset.  
o This dataset will be the basis for the summaries of important protocol deviations. 
 
6.1.4. 
Prior and Concomitant Medications 
Concomitant medications will be coded using both the GSK Drug and WHO Drug 
dictionaries. However, the summary will be based on GSK Drug dictionary only.  
The summary of concomitant medications will be provided by Anatomical Therapeutic 
Chemical (ATC) classification Level 1 and ingredient, i.e. multi-ingredient medications 
will be summarized for each individual ingredient rather than a combination of 
ingredients.  
Pre-intervention, Treatment, and Follow up concomitant medications are defined in OPS. 
A summary of prohibited medications and Rescue Therapy will be produced by 
ingredient. 
The incidence of use of prohibited medications and Rescue Therapy will be summarised, 
overall and by topical and non-topical groups.  Cumulative proportion of participants 
receiving prohibited medications / Rescue Therapy during the treatment period will be 
plotted.  
 
6.1.5. 
Study Intervention Compliance 
Not applicable for this study.  
 
6.1.6. 
Additional Analyses Due to the COVID-19 Pandemic 
A participant is defined as having a suspected, probable or confirmed COVID-19 
infection during the study if the answer is “Confirmed”, “Probable” or “Suspected” to the 
case diagnosis question from the COVID-19 coronavirus infection assessment eCRF.  


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Summary of COVID-19 Assessments for Subjects with COVID-19 Adverse Events and a 
Listing of Visits impacted by COVID-19 Pandemic will be provided.  
6.2. 
Appendix 2 Data Derivations Rule 
6.2.1. 
Criteria for Potential Clinical Importance 
6.2.1.1. 
Laboratory Values 
Haematology 
Laboratory Parameter 
 
Units 
Category 
Potential Clinical Importance 
Low Flag (< x) 
High Flag (>x) 
Hematocrit  
Ratio of 
1 
Male 
<0.1 
>0.54 
Female 
<0.1 
>0.54 
∆ from 
BL 
>0.075 change 
from baseline 
 
Haemoglobin  
g/L 
 
Male 
<100 
>185 
Female 
<100 
>165 
∆ from 
BL 
>25 change 
from baseline 
 
 
 
 
 
 
Lymphocytes  
x109/ L 
 
0.8 
 
Neutrophil Count  
x109/ L 
 
1.5 
 
Platelet Count  
x109/ L 
 
<100 
>999 
While Blood Cell Count 
(WBC) 
x109/ L 
 
<2 
 
 
Clinical Chemistry 
Laboratory Parameter 
Units 
Potential Clinical Importance 
Low Flag (< x) 
High Flag 
(>x) 
Albumin  
g/L 
35 - 52 
<30 
 
Corrected Calcium 
µmol/L 
 
 
 
-Ages 18-59 years 
 
2.15 - 2.5 
<1.5 
>3.25 
-Ages 60-90 years 
 
2.2 - 2.55 
<1.5 
>3.25 
Creatinine 
µmol/L 
 
 
 
-Male ≥18 yrs 
µmol/L 
59 - 103 
 
Change from 
baseline 
>44.2 
-Female ≥18 yrs 
µmol/L 
45 - 84 
 
Change from 
baseline 
>44.2 


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Clinical Chemistry 
Laboratory Parameter 
Units 
Potential Clinical Importance 
Low Flag (< x) 
High Flag 
(>x) 
Potassium 
mmol/L 
3.5 – 5.1 
<3.0 
>6.5 
Sodium 
mmol/L 
136 - 145 
<130 
>160 
Blood Urea Nitrogen (BUN) 
mg/dl 
 
 
>40 
 
Liver Function 
Laboratory Parameter 
Units 
Category 
Potential Clinical Importance 
ALT/SGPT  
U/L 
High 
≥ 3x ULN 
AST/SGOT  
U/L 
High 
≥ 3x ULN 
Alkaline Phosphatase  
U/L 
High 
≥ 2x ULN 
Total Bilirubin  
µmol/L 
High 
≥ 2x ULN 
Direct Bilirubin 
 
 
>35% 
 
 
Urinalysis 
A participant is considered to have urinalysis results of PCI, if there is an increase in 
Protein or an increase in Occult Blood results during the study, or if microscopy is 
performed. 
 
6.2.1.2. 
ECG 
ECG Parameter 
Units 
Potential Clinical Importance 
Lower Limit 
Upper Limit 
Absolute 
Absolute QTc(F) Interval 
msec 
> 450 
≤ 480 
> 480 
≤ 500 
> 500 
 
Absolute PR Interval 
msec 
< 110  
> 220  
Absolute QRS Interval 
msec 
< 75  
> 110 
Change from Baseline 
Increase from Baseline QTc(F) 
msec 
> 30 
≤ 60  
> 60 
 
 


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6.2.1.3. 
Vital Signs 
Vital Sign Parameter 
(Absolute) 
Units 
Potential Clinical Importance 
Low Flag 
High Flag 
Systolic Blood Pressure 
mmHg 
< 85 
> 160 
Diastolic Blood Pressure 
mmHg 
< 45 
> 100 
Heart Rate 
bpm 
< 40 
> 110 
 
 
 
 
Temperature 
°C 
≤ 35.5 
> 38.0 
 
Vital Sign Parameter 
(Change from Baseline) 
Units 
Potential Clinical Importance 
Decrease from Baseline 
Increase from Baseline 
Lower Limit 
Upper Limit 
Lower Limit 
Upper Limit 
Systolic Blood Pressure 
mmHg 
≥ 20 
< 40 
≥ 20 
< 40 
≥ 40 
 
≥ 40 
 
Diastolic Blood Pressure 
mmHg 
≥ 10 
< 20 
≥ 10 
< 20 
≥ 20 
 
≥ 20 
 
Heart Rate 
bpm 
≥ 15 
< 30 
≥ 15 
< 30 
≥ 30 
 
≥ 30 
 
 
Note: For a Parameter, separate rows denote categories of PCI. For example, for Systolic 
Blood Pressure, an Increase from Baseline of >= 20 mmHg to < 40 mmHg falls into a 
lower increase PCI category, and an Increase from Baseline of >=40 mmHg falls into a 
higher increase PCI category. 
 
6.2.2. 
Study Period 
Assessments and events will be classified according to the time of occurrence relative to 
the study intervention period.  
Pre-Intervention is defined as time prior to the first dose of study intervention. 
Treatment period is defined as time from first dose to and including Week 12 visit. If 
time of assessment or study intervention is not collected, the following assessment on the 
first dose date will be assumed to be taken prior to the first dose and therefore considered 
pre-intervention: ECG, Lab, and vital signs, and first dose date is considered on-
intervention for AE and concomitant medication. 
Follow up is defined as any time post on-intervention window, i.e. ≥Week 12 visit + 1 
day. 


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6.2.3. 
Study Day and Reference Dates 
The safety reference date is the study intervention start date and will be used to calculate 
study day for safety measures.  
The efficacy reference date is the study intervention start date and will be used to 
calculate study day for efficacy measures and baseline characteristics, as well as efficacy 
durations.  
The study day is calculated as below: 
• Assessment Date = Missing              → Study Day = Missing  
• Assessment Date < Reference Date → Study Day = Assessment Date – Ref Date 
• Assessment Data ≥ Reference Date → Study Day = Assessment Date – Ref Date 
+ 1     
6.2.4. 
Assessment Window  
Unscheduled and Early Withdrawal visits will not be remapped. Data from these visits 
will not be used in summary tables (except for endpoints using any post-baseline data) 
but will be presented in any relevant listings.  
6.2.5. 
Multiple measurements at One Analysis Time Point 
When triplicate ECG assessments are taken, mean of the measurement will be calculated 
first and summary statistics will be based on the calculated mean. This will apply to both 
screening, baseline, and post baseline assessments. 
6.2.6. 
Handling of Partial Dates 
Element 
Reporting Detail 
General 
• 
Partial dates will be displayed as captured in participant listing displays.   
• 
However, where necessary, display macros may impute dates as temporary 
variables for sorting data in listings only. In addition, partial dates may be 
imputed for ‘slotting’ data to study phases or for specific analysis purposes as 
outlined below. 
• 
Imputed partial dates will not be used to derive study day, time to onset or 
duration (e.g., time to onset or duration of adverse events), or elapsed time 
variables (e.g., time since diagnosis). In addition, imputed dates are not used 
for deriving the last contact date in overall survival analysis dataset. 
Concomitant 
Medications/
Medical 
History 
• 
Partial dates for any concomitant medications recorded in the CRF will be 
imputed using the following convention: 
 
Missing start 
day 
If study intervention start date is missing (i.e. 
participant did not start study intervention), then set 
start date = 1st of month. 
Else if study intervention start date is not missing: 


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Element 
Reporting Detail 
o If month and year of start date = month and 
year of study intervention start date, then 
▪ 
If stop date contains a full date and stop 
date is earlier than study intervention 
start date, then set start date= 1st of 
month. 
▪ 
Else set start date = study intervention 
start date. 
Else set start date = 1st of month. 
Missing start 
day and month 
If study intervention start date is missing (i.e. 
participant did not start study intervention), then set 
start date = January 1. 
Else if study intervention start date is not missing: 
o If year of start date = year of study intervention 
start date, then 
▪ 
If stop date contains a full date and stop 
date is earlier than study intervention 
start date, then set start date = January 
1. 
▪ 
Else set start date = study. intervention 
start date.       
Else set start date = January 1. 
Missing end day 
A '28/29/30/31' will be used for the day (dependent on 
the month and year).  
Missing end day 
and month 
A '31' will be used for the day and 'Dec' will be used for 
the month. 
Completely 
missing start/end 
date 
No imputation 
 
6.2.7. 
Early PK Access Key Activities 
Designated independent representative(s) may be unblinded for performing population 
PK and PKPD dataset preparation and draft PK and PKPD model development at one or 


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more time points throughout the trial using scrambled (random reassignment of subject 
identification numbers) PK and PKPD unblinded datasets. 


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7. 
ABBREVIATIONS  
Abbreviations 
 
AtD 
Atopic Dermatitis 
BN 
Biologic Naive 
CFB 
Change from Baseline 
CPSR 
Clinical Pharmacology Study Report 
DLQI 
Dermatology Life Quality Index 
Dupi-IR 
dupilumab inadequate responder 
EASI 
Eczema area and severity index 
GSVA 
gene set variation analysis 
IGA 
Investigator Global Assessment 
MAP 
Meta-analytic predictive prior 
MAR 
Missing at Random 
MCMC   
Monte Carlo Markov Chain 
OPS 
Output and Programming Specification 
PCFB 
Percent Change from Baseline 
PP-NRS 
Peak Pruritis numerical rating scale 
PRO 
Patient reported outcomes 
TCS 
Topical corticosteroid 
 
TRADEMARKS 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
NA 
 
Dupixent  


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Olink 
 
 


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8. 
REFERENCES 
Beck, L. A., Thaçi, D., Hamilton, J. D., Graham, N. M., Bieber, T., Rocklin, R., Ming, J. 
E., Ren, H., Kao, R., Simpson, E., Ardeleanu, M., Weinstein, S. P., Pirozzi, G., Guttman-
Yassky, E., Suárez-Fariñas, M., Hager, M. D., Stahl, N., Yancopoulos, G. D., & Radin, 
A. R. (2014). Dupilumab treatment in adults with moderate-to-severe atopic 
dermatitis. The New England journal of medicine, 371(2), 130–139.  
Bissonnette, R., Maari, C., Forman, S., Bhatia, N., Lee, M., Fowler, J., Tyring, S., 
Pariser, D., Sofen, H., Dhawan, S., Zook, M., Zammit, D. J., Usansky, H., Denis, L., Rao, 
N., Song, T., Pavel, A. B., & Guttman-Yassky, E. (2019). The oral Janus kinase/spleen 
tyrosine kinase inhibitor ASN002 demonstrates efficacy and improves associated 
systemic inflammation in patients with moderate-to-severe atopic dermatitis: results from 
a randomized double-blind placebo-controlled study. The British journal of 
dermatology, 181(4), 733–742.  
Gooderham, M. J., Forman, S. B., Bissonnette, R., Beebe, J. S., Zhang, W., Banfield, C., 
Zhu, L., Papacharalambous, J., Vincent, M. S., & Peeva, E. (2019). Efficacy and Safety 
of Oral Janus Kinase 1 Inhibitor Abrocitinib for Patients With Atopic Dermatitis: A 
Phase 2 Randomized Clinical Trial. JAMA dermatology, 155(12), 1371–1379.  
Guttman-Yassky, E., Pavel, A. B., Zhou, L., Estrada, Y. D., Zhang, N., Xu, H., Peng, X., 
Wen, H. C., Govas, P., Gudi, G., Ca, V., Fang, H., Salhi, Y., Back, J., Reddy, V., 
Bissonnette, R., Maari, C., Grossman, F., & Wolff, G. (2019). GBR 830, an anti-OX40, 
improves skin gene signatures and clinical scores in patients with atopic dermatitis. The 
Journal of allergy and clinical immunology, 144(2), 482–493.e7. 
Guttman-Yassky, E., Thaçi, D., Pangan, A. L., Hong, H. C., Papp, K. A., Reich, K., 
Beck, L. A., Mohamed, M. F., Othman, A. A., Anderson, J. K., Gu, Y., Teixeira, H. D., 
& Silverberg, J. I. (2020a). Upadacitinib in adults with moderate to severe atopic 
dermatitis: 16-week results from a randomized, placebo-controlled trial. The Journal of 
allergy and clinical immunology, 145(3), 877–884.  
Guttman-Yassky, E., Blauvelt, A., Eichenfield, L. F., Paller, A. S., Armstrong, A. W., 
Drew, J., Gopalan, R., & Simpson, E. L. (2020b). Efficacy and Safety of Lebrikizumab, a 
High-Affinity Interleukin 13 Inhibitor, in Adults With Moderate to Severe Atopic 
Dermatitis: A Phase 2b Randomized Clinical Trial. JAMA dermatology, 156(4), 411–420.  
Ruzicka, T., Hanifin, J. M., Furue, M., Pulka, G., Mlynarczyk, I., Wollenberg, A., Galus, 
R., Etoh, T., Mihara, R., Yoshida, H., Stewart, J., Kabashima, K., & XCIMA Study 
Group (2017). Anti-Interleukin-31 Receptor A Antibody for Atopic Dermatitis. The New 
England journal of medicine, 376(9), 826–835. 
Schmidli, H., Gsteiger, S., Roychoudhury, S., O'Hagan, A., Spiegelhalter, D., & 
Neuenschwander, B. (2014). Robust meta‐analytic‐predictive priors in clinical trials with 
historical control information. Biometrics, 70(4), 1023-1032. 
Neuenschwander B, Weber S, Schmidli H, O'Hagan A. Predictively consistent prior 
effective sample sizes. Biometrics. 2020 Jun; 76(2):578-587. 


CONFIDENTIAL 
 
 
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Page 39 of 39 
 
 
Simpson, E. L., Bieber, T., Guttman-Yassky, E., Beck, L. A., Blauvelt, A., Cork, M. J., 
Silverberg, J. I., Deleuran, M., Kataoka, Y., Lacour, J. P., Kingo, K., Worm, M., Poulin, 
Y., Wollenberg, A., Soo, Y., Graham, N. M., Pirozzi, G., Akinlade, B., Staudinger, H., 
Mastey, V., … SOLO 1 and SOLO 2 Investigators (2016). Two Phase 3 Trials of 
Dupilumab versus Placebo in Atopic Dermatitis. The New England journal of 
medicine, 375(24), 2335–2348.  
Simpson, E. L., Flohr, C., Eichenfield, L. F., Bieber, T., Sofen, H., Taïeb, A., Owen, R., 
Putnam, W., Castro, M., DeBusk, K., Lin, C. Y., Voulgari, A., Yen, K., & Omachi, T. A. 
(2018). Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in 
adults with moderate-to-severe atopic dermatitis inadequately controlled by topical 
corticosteroids: A randomized, placebo-controlled phase II trial (TREBLE). Journal of 
the American Academy of Dermatology, 78(5), 863–871.e11.  
Simpson, E. L., Imafuku, S., Poulin, Y., Ungar, B., Zhou, L., Malik, K., Wen, H. C., Xu, 
H., Estrada, Y. D., Peng, X., Chen, M., Shah, N., Suarez-Farinas, M., Pavel, A. B., 
Nograles, K., & Guttman-Yassky, E. (2019). A Phase 2 Randomized Trial of Apremilast 
in Patients with Atopic Dermatitis. The Journal of investigative dermatology, 139(5), 
1063–1072. 
Simpson, E. L., Lacour, J. P., Spelman, L., Galimberti, R., Eichenfield, L. F., 
Bissonnette, R., King, B. A., Thyssen, J. P., Silverberg, J. I., Bieber, T., Kabashima, K., 
Tsunemi, Y., Costanzo, A., Guttman-Yassky, E., Beck, L. A., Janes, J. M., DeLozier, A. 
M., Gamalo, M., Brinker, D. R., Cardillo, T., … Reich, K. (2020). Baricitinib in patients 
with moderate-to-severe atopic dermatitis and inadequate response to topical 
corticosteroids: results from two randomized monotherapy phase III trials. The British 
journal of dermatology, 183(2), 242–255.  
Thaçi, D., Simpson, E. L., Beck, L. A., Bieber, T., Blauvelt, A., Papp, K., Soong, W., 
Worm, M., Szepietowski, J. C., Sofen, H., Kawashima, M., Wu, R., Weinstein, S. P., 
Graham, N. M., Pirozzi, G., Teper, A., Sutherland, E. R., Mastey, V., Stahl, N., 
Yancopoulos, G. D., … Ardeleanu, M. (2016). Efficacy and safety of dupilumab in adults 
with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a 
randomised, placebo-controlled, dose-ranging phase 2b trial. Lancet (London, 
England), 387(10013), 40–52.