Clinical trial NCT03485365
Conditions: Pain, Inflammatory
Keywords: Pain Osteoarthritis of the knee Target engagement GSK3858279 Pharmacokinetics Sequential
Sponsor: GlaxoSmithKline
Start date: 2018-05-17; Completion date: 2022-09-12
Enrollment: 97 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This study is the first administration of GSK3858279 in humans and will be conducted in two parts: Part A will consist of a single ascending dose escalation design to evaluate safety, tolerability, PK, TE and immunogenicity of either a single intravenous (IV) or a single subcutaneous (SC) dose. Approximately 48 healthy participants will be enrolled in 6 cohorts and randomized to 3:1 ratio (GSK3858279 or placebo). Part B will evaluate safety, tolerability, efficacy (pain), PK, TE and immunogenicity after repeat SC dosing. Approximately 50 OA participants will be randomized in a parallel group design to receive either GSK3858279 or placebo in a 1:1 ratio.

Detailed description:

Arms: arm 1: Eligible participants will receive GSK3858279 via IV route. arm 2: Eligible participants will receive GSK3858279 via IV route. arm 3: Eligible participants will receive GSK3858279 via IV route. arm 4: Eligible participants will receive GSK3858279 via IV route. arm 5: Eligible participants will receive GSK3858279 via IV route. arm 6: Eligible participants will receive GSK3858279 via SC route. arm 7: Eligible participants will receive placebo matching to GSK3858279 via SC or IV route. arm 8: Eligible participants will receive GSK3858279 via SC route. arm 9: Eligible participants will receive placebo matching to GSK3858279 via SC route.
Interventions: intervention 1: GSK3858279 IV intervention 2: GSK3858279 SC intervention 3: Placebo matching to GSK3858279 (SC or IV) intervention 4: Placebo matching to GSK3858279 (SC)
Intervention descriptions: intervention 1: GSK3858279 will be available as solution for injection to be administered via IV route. intervention 2: GSK3858279 will be available as solution for injection to be administered via SC route. intervention 3: Placebo will be available as sodium chloride solution to be administered via SC or IV route. intervention 4: Placebo will be available as sodium chloride solution to be administered via SC route.

Protocol documents:
Prot_000.pdf: 
 
 
 
 
Protocol Amendment 07 
 
Study ID: 207804 
 
Official Title of Study: A two-part phase I randomized, double-blind, placebo-controlled study to 
evaluate safety, tolerability, pharmacokinetics and target engagement of single 
intravenous and subcutaneous doses of GSK3858279 in healthy participants and to 
evaluate the efficacy of repeat subcutaneous doses in participants with osteoarthritis of 
the knee. 
 
NCT Number: NCT03485365  
 
Date of Document: 09-FEB-2022 
  
 


TMF-14447953 
CONFIDENTIAL 
 
GlaxoSmithKline group of companies 
 
207804 
Protocol Amd 7 
 
1 
 
TITLE PAGE 
Protocol Title: A two-part phase I randomized, double-blind, placebo-controlled study to 
evaluate safety, tolerability, pharmacokinetics and target engagement of single 
intravenous and subcutaneous doses of GSK3858279 in healthy participants and to 
evaluate the efficacy of repeat subcutaneous doses in participants with osteoarthritis of 
the knee. 
Protocol Number: 207804 /Amendment 7 
Compound 
Number: 
GSK3858279 
Study Phase: Phase I/Ib 
Short Title: GSK3858279 vs PBO, Ph1/1b, two-part, SD, safety, tolerability, 
pharmacokinetics, and target engagement study in HV and RD in participants with OA 
Sponsor Name and Legal Registered Address:  
GlaxoSmithKline Research & Development Limited 
980 Great West Road  
Brentford 
Middlesex, TW8 9GS 
UK 
Medical Monitor Name and Contact Information can be found in the Study Reference 
Manual 
Regulatory Agency Identifying Number(s): EUDRACT 2017-004809-41 
Approval Date: 09-FEB-2022 
 
 
 
 
 
 
Copyright 2022 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited. 
 


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S P O N S O R SI G N A T O R Y  
Pr ot oc ol Title:  A t w o -part p hase I ra n d o mize d, d o u ble -bli n d, place b o -c o ntr olle d st u d y t o 
e val uate safet y, t olera bilit y, p har m ac o ki netics a n d tar get e n ga ge me nt of si n gle 
i ntra ve n o us a n d s u bc uta n e o us d oses of G S K 3 8 5 8 27 9 i n healt h y p artici pa nts a n d t o 
e val uate t he effic ac y of re peat s u bc uta n e o us d oses i n partici pa nts wit h oste oart hritis of 
t he k nee. 
Pr ot oc ol N u m ber : 2 0 7 8 0 4 / A me n d me nt 7  
C o m p o u n d 
N u m ber:  
G S K 3 8 5 8 2 7 9  
 
 
 
 
 
Vice Presi de nt, H ea d of Disc o ver y Me di ci ne, Cli nical 
P har mac ol o g y a n d E x peri me ntal Me dici ne, 
I m m u n oi nfla m mati o n T h era p y Area 
 
D ate  
 
T he si g ne d p a ge is a se p ar ate d oc u m e nt.  
 
Me dic al M o nit or N a me a n d C o nt act I nf or m ati o n  ca n be f o u n d St u d y Refere nce 
Ma n ua l 
P P D


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3  
 
P R O T O C O L A M E N D M E N T S U M M A R Y O F C H A N G E S T A B L E  
D O C U M E N T HI S T O R Y  
D o c u m e nt  
D at e  
D N G N u m b er  
A m e n d m ent 7  
0 9 -F E B 2 0 2 2  
T M F -1 4 4 4 79 5 3  
A m e n d m ent 6  
1 2 -N O V -2 0 2 1  
T M F -1 1 8 3 42 3 7  
A m e n d m ent 5  
0 7 -S E P -2 0 2 0  
2 0 1 7 N 3 4 2 0 35 _ 0 5  
A m e n d m ent 4  
1 4 -N O V -2 0 1 9  
2 0 1 7 N 3 4 2 0 35 _ 0 4  
A m e n d m ent 3  
1 8 -J U L-2 0 1 9  
2 0 1 7 N 3 4 2 0 35 _ 0 3  
A m e n d m ent 2  
2 1 -N O V -2 0 1 8  
2 0 1 7 N 3 4 2 0 35 _ 0 2  
A m e n d m ent 1  
1 0 -A P R -2 0 1 8  
2 0 1 7 N 3 4 2 0 35 _ 0 1  
Ori gi nal Pr ot oc ol  
0 2 -F E B -2 0 1 8  
2 0 1 7 N 3 4 2 0 35 _ 0 0  
A me n d me nt 7 : 0 9 -F E B -2 0 2 2  
T his a me n d me nt is c o nsi dere d t o be  n o n -s u bsta ntial base d o n t he criteria s et f ort h i n  
Article 1 0(a) of Directi ve 2 0 0 1/ 2 0/ E C of t he E ur o pea n Parlia me nt a n d t h e C o u ncil of t he  
E ur o pea n U ni o n b eca us e it neit her si g nifica ntl y i m pacts t he safet y or p h ysical/ me ntal 
i nte grit y of partici pa nts n or t he scie ntific val u e of t he st u d y. 
O ver all R ati o n al e f or A me n d me nt 7  
T o clarif y t hat 1) P K a n d T E  sa m ples will be ta ke n at pre -d ose D a y 3 6, 2 0-3 6 hrs p ost -
d ose o n D a y 3 6 a n d pre -d ose o n D a y 4 3; 2 ) A d diti o nal I nteri m a nal ys es m a y b e 
c o n d ucte d 3)  Clarificati o n of re -s cree ni n g pr oce d ure 4 ) Mi n or e dits t hr o u g h o ut t o 
pr o vi de clarifi cati o n . 
Secti o n # a n d N a me  
Descri pti o n of C h a n ge  
Brief R ati o n ale  
Secti o n 5. 4. 1 Re -scree ni n g 
Clarificati o n of re -
scree ni n g pr oce d ure f or 
partici pa nts w h o scree n fail 
beca use of a n o n -m e dical 
reas o n 
T o clarif y t hat partici pa nts 
ma y b e re -scree ne d m or e 
t ha n o nce f or n o n-me dical 
reas o ns f oll o wi n g 
disc ussi o ns wit h me dical 
m o nit or e. g. recei vi n g a 
c o vi d b o oster at s h ort 
n otice  
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4 
 
Section # and Name 
Description of Change 
Brief Rationale 
Section 9.4.5. Interim 
Analyses and  
Section 1.1 Synopsis 
Potential additional interim 
analyses may occur during 
the study 
Additional interim analyses 
may occur to allow 
interactions with regulatory 
agencies and/or help 
inform internal decision 
making 
Throughout 
Minor edits throughout the 
document for consistency  
For consistency and clarity 
 
 
 


TMF-14447953 
CONFIDENTIAL 
 
 
 
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Protocol Amd 7 
 
5 
 
TABLE OF CONTENTS 
PAGE 
TITLE PAGE ................................................................................................................... 1 
SPONSOR SIGNATORY ................................................................................................ 2 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 3 
1. 
PROTOCOL SUMMARY .......................................................................................... 9 
1.1. 
Synopsis ....................................................................................................... 9 
1.2. 
Schema ...................................................................................................... 12 
1.3. 
Schedule of Activities (SoA) ........................................................................ 17 
1.3.1. 
Screening .................................................................................... 18 
1.3.2. 
Part A Cohorts Without Blister: 0.1 and 0.3 mg/kg IV ................... 19 
1.3.3. 
Part A Cohorts With Blister: 1 mg/kg IV ....................................... 20 
1.3.4. 
Part A Cohorts With Blister: 3 and 10 mg/kg IV and SC ............... 21 
1.3.5. 
Part B .......................................................................................... 22 
2. 
INTRODUCTION .................................................................................................... 23 
2.1. 
Study Rationale .......................................................................................... 23 
2.2. 
Background ................................................................................................ 23 
2.3. 
Benefit/Risk Assessment ............................................................................ 24 
2.3.1. 
Risk Assessment ......................................................................... 25 
2.3.2. 
Benefit Assessment ..................................................................... 31 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 31 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 31 
4. 
STUDY DESIGN .................................................................................................... 33 
4.1. 
Overall Design ............................................................................................ 33 
4.1.1. 
Treatment Groups and Duration .................................................. 34 
4.2. 
Number of Participants ............................................................................... 35 
4.3. 
Scientific Rationale for Study Design .......................................................... 36 
4.4. 
Justification for Dose .................................................................................. 38 
4.4.1. 
Part A .......................................................................................... 38 
4.4.2. 
Part B .......................................................................................... 39 
4.5. 
End of Study Definition ............................................................................... 40 
5. 
STUDY POPULATION ........................................................................................... 40 
5.1. 
Inclusion Criteria ......................................................................................... 40 
5.2. 
Exclusion Criteria ........................................................................................ 43 
5.3. 
Lifestyle Considerations .............................................................................. 49 
5.3.1. 
COVID-19 related restrictions ...................................................... 49 
5.3.2. 
Meals and Dietary Restrictions .................................................... 49 
5.3.3. 
Caffeine, Alcohol, and Tobacco ................................................... 49 
5.3.4. 
Physical Activity ........................................................................... 50 
5.4. 
Screen Failures........................................................................................... 50 
5.4.1. 
Re-screening ............................................................................... 50 
5.4.2. 
Re-testing of Clinical Laboratory Values during Screening ........... 50 
6. 
STUDY INTERVENTION ........................................................................................ 51 


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6  
 
6. 1.  
St u d y I nt er v e nti o n( s) A d mi ni st er e d  ............................................................. 5 1  
6. 2.  
Pr e p ar ati o n/ H a n dli n g/ St or a g e/ A c c o u nt a bilit y  .............................................. 5 2  
6. 3.  
M e a s ur e s t o Mi ni mi z e Bi a s: R a n d o mi z ati o n a n d Bli n di n g  ........................... 5 3  
6. 3. 1.  
R a n d o mi z ati o n  ............................................................................. 5 3  
6. 3. 2.  
Bli n di n g  ........................................................................................ 5 4  
6. 4.  
St u d y I nt er v e nti o n C o m pli a n c e  ................................................................... 5 5  
6. 5.  
C o n c o mit a nt T h er a p y .................................................................................. 5 5  
6. 5. 1.  
P er mitt e d T h er a pi e s  .................................................................... 5 5  
6. 5. 2.  
R e s c u e M e di c ati o n ( P art B)  ......................................................... 5 6  
6. 6.  
Pr o hi bit e d M e di c ati o n s  ................................................................................ 5 6  
6. 7.  
D o s e M o difi c ati o n  ....................................................................................... 5 6  
6. 8.  
I nt erv e nti o n aft er t h e E n d of t h e St u d y  ........................................................ 5 7  
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  ..................................................................... 5 7  
7. 1.  
St u d y st o p pi n g crit eri a  ................................................................................ 5 7  
7. 2.  
Di s c o nti n u ati o n of St u d y I nt er v e nti o n  .......................................................... 5 7  
7. 2. 1.  
Li v er C h e mi str y St o p pi n g Crit eri a  ................................................ 5 8  
7. 2. 2.  
Q T c St o p pi n g Crit eri a  .................................................................. 5 8  
7. 2. 3.  
D o s e A dj u st m e nt P h ar m a c o ki n eti c Crit eri a  .................................. 5 9  
7. 2. 4.  
T e m p or ar y Di s c o nti n u ati o n  .......................................................... 5 9  
7. 3.  
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  ............................... 5 9  
7. 4.  
L o st t o F oll o w U p  ........................................................................................ 5 9  
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  ..................................................... 6 0  
8. 1.  
S af et y A s s e s s m e nt s  ................................................................................... 6 1  
8. 1. 1.  
P h y si c al E x a mi n ati o n s  ................................................................. 6 1  
8. 1. 2.  
Vit al Si g n s  .................................................................................... 6 1  
8. 1. 3.  
El e ctr o c ar di o gr a m s  ...................................................................... 6 1  
8. 1. 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  ...................................... 6 2  
8. 1. 5.  
E c h o c ar di o gr a m ........................................................................... 6 2  
8. 1. 6.  
S ki n R e a cti o n s  ............................................................................. 6 2  
8. 2.  
P h ar m a c o ki n eti c s  ....................................................................................... 6 3  
8. 2. 1.  
Bl o o d S a m pl e C oll e cti o n f or P h ar m a c o ki n eti c s  ............................ 6 3  
8. 2. 2.  
P h ar m a c o ki n eti c S a m pl e A n al y si s  ............................................... 6 3  
8. 3.  
Effi c a c y A s s e s s m e nt s  ................................................................................. 6 3  
8. 3. 1.  
P ati e nt R e p ort e d O ut c o m e s  ......................................................... 6 3  
8. 3. 2.  
D ail y p ai n s c or e s  ......................................................................... 6 3  
8. 3. 3.  
W O M A C o st e o art hriti s i n d e x  ........................................................ 6 4  
8. 3. 4.  
P ati e nt a n d p h y si ci a n gl o b al a s s e s s m e nt s of di s e a s e 
..................................................................... 6 4  
8. 3. 5.  
P ai n D E T E C T Q u e sti o n n air e  ........................................................ 6 4  
8. 3. 6.  
P arti ci p a nt F e e d b a c k Q u e sti o n n air e  ............................................ 6 4  
8. 3. 7.  
J oi nt X -r a y ................................................................................... 6 5  
8. 4.  
P h ar m a c o d y n a mi c s/ Bi o m ar k er s  ................................................................. 6 5  
8. 4. 1.  
T ar g et E n g a g e m e nt  ..................................................................... 6 5  
8. 4. 4.  
S u cti o n bli st er  .............................................................................. 6 6  
8. 4. 5.  
Bl o o d S a m pl e f or e x vi v o str u ct ur al a n al y si s of 
G S K 3 8 5 8 2 7 9  ............................................................................... 6 6  
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8. 5.  
I m m u n o g e ni cit y A s s e s s m e nt s ..................................................................... 6 7  
8. 6.  
A d v er s e E v e nt s ........................................................................................... 6 7  
8. 6. 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 ................................................................................... 6 7  
8. 6. 2.  
M et h o d of D et e cti n g A E s a n d S A E s  ............................................. 6 8  
8. 6. 3.  
F oll o w -u p of A E s a n d S A E s  ......................................................... 6 8  
8. 6. 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  ............................. 6 8  
8. 6. 5.  
C ar di o v a s c ul ar a n d D e at h E v e nt s –  P art B o nl y ........................... 6 9  
8. 6. 6.  
Pr e g n a n c y  ................................................................................... 6 9  
8. 7.  
Tr e at m e nt of O v er d o s e  ............................................................................... 6 9  
8. 9.  
H e alt h E c o n o mi c s O R M e di c al R e s o ur c e Utili z ati o n a n d H e alt h 
E c o n o mi c s  .................................................................................................. 7 0  
9.  
S T A TI S TI C A L C O N SI D E R A TI O N S  ........................................................................ 7 0  
9. 1.  
H y p ot h e s e s  ................................................................................................. 7 0  
9. 2.  
S a m pl e Si z e D et er mi n ati o n  ........................................................................ 7 1  
9. 2. 1.  
S a m pl e Si z e A s s u m pti o n s  ........................................................... 7 1  
9. 2. 2.  
S a m pl e Si z e S e n siti vit y  ................................................................ 7 1  
9. 3.  
P o p ul ati o n s f or A n al y s e s  ............................................................................ 7 4  
9. 4.  
St ati sti c al A n al y s e s  ..................................................................................... 7 4  
9. 4. 1.  
E ffi c a c y A n al y s e s ......................................................................... 7 4  
9. 4. 2.  
S af et y A n al y s e s  ........................................................................... 7 5  
9. 4. 3.  
P h ar m a c o ki n eti c s A n al y s e s  ......................................................... 7 5  
9. 4. 5.  
I nt eri m A n al y s e s .......................................................................... 7 6  
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  ............................................................................................... 7 8  
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  ............................................................................................ 7 8  
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  ........................................ 7 8  
1 0. 1. 2.  
Fi n a n ci al Di s cl o s ur e  ..................................................................... 7 8  
1 0. 1. 3.  
I nf or m e d C o n s e nt Pr o c e s s .......................................................... 7 9  
1 0. 1. 4.  
D at a Pr ot e cti o n  ............................................................................ 7 9  
1 0. 1. 5.  
C o m mitt e e s Str u ct ur e  .................................................................. 8 0  
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  ........................................... 8 0  
1 0. 1. 7.  
D at a Q u alit y A s s ur a n c e  ............................................................... 8 1  
1 0 . 1. 8. 
S o ur c e D o c u m e nt s  ...................................................................... 8 1  
1 0. 1. 9.  
St u d y a n d Sit e Cl o s ur e  ................................................................ 8 2  
1 0. 1. 1 0.  P u bli c ati o n P oli c y  ......................................................................... 8 2  
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  ......................................................... 8 3  
1 0. 3.  A p p e n di x 3: A d v er s e E v e nt 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  ....................................... 8 5  
1 0. 3. 1.  
D efi niti o n of A E  ............................................................................ 8 5  
1 0. 3. 2.  
D efi niti o n of S A E  .......................................................................... 8 6  
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 –  P art B o nl y  ........................ 8 7  
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  .................................... 8 8  
1 0. 3. 5.  
R e p orti n g of S A E t o G S K  ............................................................. 8 9  
1 0. 4.  A p p e n di x  4: C o ntr a c e pti v e G ui d a n c e a n d C oll e cti o n of Pr e g n a n c y 
I nf or m ati o n .................................................................................................. 9 1  
1 0. 4. 1.  
D efi niti o n s:  ................................................................................... 9 1  
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1 0. 4. 2.  
C o ntr a c e pti o n g ui d a n c e f or f e m al e p art n er s of m al e s w h o 
ar e i n t h e st u d y a : .......................................................................... 9 2  
1 0. 6.  A p p e n di x 6 a: 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  .............................................................................................. 9 5  
1 0. 7.  A p p e n di x 6 b: H e alt h y V ol u nt e er a n d P ati e nt P h a s e I St u di e s Li v er 
St o p pi n g E v e nt Al g orit h m  ........................................................................... 9 7  
1 0. 8.  A p p e n di x  7: Effi c a c y A s s e s s m e nt s  ............................................................. 9 8  
1 0. 8. 1.  
A v er a g e P ai n N R S  ....................................................................... 9 8  
1 0. 8. 2.  
W or st P ai n N R S  ........................................................................... 9 8  
1 0. 9.  A p p e n di x 8: A b br e vi ati o n s a n d Tr a d e m ar k s  .............................................. 1 0 0  
1 0. 1 0.  A p p e n di x 9: Pr ot o c ol A m e n d m e nt Hi st or y  ................................................. 1 0 4  
1 0. 1 0. 1.  A m e n d m e nt 1 1 0 -A P R -2 0 1 8  ...................................................... 1 0 4  
1 0. 1 0. 2.  A m e n d m e nt 2 2 1 -N O V -2 0 1 8 ...................................................... 1 0 4  
1 0. 1 0. 3.  A m e n d m e nt 3 1 8 -J U L -2 0 1 9  ....................................................... 1 0 6  
1 0. 1 0. 4.  A m e n d m e nt 4 1 4 -N O V -2 0 1 9 ...................................................... 1 1 5  
1 0. 1 0. 5.  A m e n d m e nt 5: 0 7 -S E P -2 0 2 0  ..................................................... 1 1 6  
1 0. 1 0. 6.  A m e n d m e nt 6: 1 2 -N o v -2 0 2 1  ...................................................... 1 2 3  
1 1.  R E F E R E N C E S  ..................................................................................................... 1 2 5  
 
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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A two-part phase I randomized, double blind, placebo-controlled study to 
evaluate safety, tolerability, pharmacokinetics and target engagement of single 
intravenous and subcutaneous doses of GSK3858279 in healthy participants and to 
evaluate the efficacy of repeat subcutaneous doses in participants with osteoarthritis of 
the knee. 
Short Title: GSK3858279 vs PBO, Phase 1/1b, two-part, SD, safety, tolerability, 
pharmacokinetics and target engagement study in HV and RD in participants with OA 
Rationale: 
This study is the first administration of GSK3858279 to humans. The purpose of this 
study is two-fold: 
Part A, to evaluate the safety, tolerability, pharmacokinetics (PK) and target 
engagement (TE) of either a single intravenous (IV) or a single subcutaneous (SC) 
dose of GSK3858279 in healthy males and females of non-reproductive potential. 
Target engagement in the skin, which is a surrogate for tight tissue compartment, will 
be assessed via suction blister procedure in certain cohorts. The intention is to provide 
sufficient confidence in the safety and tolerability of the molecule as well as target 
engagement to inform progression to the following part of the study. 
Part B, to evaluate the safety, tolerability, efficacy, PK, TE and immunogenicity of 
repeat SC dosing of GSK3858279 in participants with osteoarthritis (OA) of the knee. 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
Parts A and B 
To evaluate the safety and tolerability of 
escalating doses of GSK3858279 
following single IV, single SC dosing in 
healthy participants and repeat SC dosing 
in OA participants. 
 
• 
Adverse Events (AE) and Serious 
Adverse Events (SAE).  
• 
Clinical laboratory measurements, 
12-lead electrocardiograms (ECG) 
and vital signs. 
Part B 
To assess changes in pain in participants 
with OA of the knee following repeat SC 
dosing. 
 
Change from baseline in average knee 
pain intensity, at Week 8. 
Change from baseline in worst knee pain 
intensity at Week 8. 


T M F -1 4 4 4 7 9 5 3  
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
1 0  
 
O bj e cti ve s  
E n d p oi nt s  
S e c o n d ary   
T o descri be t he p h ar mac o ki netics ( P K) of 
G S K 3 8 5 8 2 7 9 f oll o wi n g si n gle I V, si n gle 
S C i n healt h y p artici pa nts a n d re peat S C 
d osi n g i n O A partici pa nts.  
T o e val uate t he  t ar get e n ga ge me nt of 
C C L 1 7 b y G S K 3 8 5 8 2 7 9 f oll o wi n g si n gle 
I V, si n gle S C d osi n g i n h ealt h y 
partici pa nts a n d re peat S C d osi n g  i n O A 
partici pa nts . 
 
O ver all Desi g n:  
T his st u d y will be a ra n d o mize d, d o u ble -bli n d, place b o -c o ntr olle d, t w o -p art trial. After 
c o m pleti n g scree ni n g pr oce d ures s u ccessf ull y, p artici pa nts will be ra n d o mise d t o eit her 
G S K 3 8 5 8 2 7 9 or place b o o n Da y 1 j ust pri or t o d osi n g.  
Part A will be a si n gl e as ce n di n g d ose es calati o n st u d y t o e val u ate t he safet y, t olera bilit y, 
P K, a n d tar get e n ga ge me nt of G S K 3 8 5 8 2 7 9  i n healt h y partici pa nt s. Si n gle I V d oses a n d 
a si n gle S C d ose will be i n vesti gate d i n s e parate c o h orts of partici pa nts.  
Part B will i n vesti gat e t he safet y, t olera bilit y, effi cac y ( pai n), P K , an d T E a n d 
i m m u n o ge nicit y i n bl o o d of partici pa nts wit h O A of t he k nee after re p eat S C  d osi n g of 
G S K 3 8 5 8 2 7 9 or place b o.  C O VI D -1 9 scree ni n g , m o nit ori n g  a n d t he miti gati o n s trate gies 
are i nc or p orate d. 
Discl os ure St ate me nt : T his is a se q ue ntial gr o u p  ( Part A) a n d p arallel gr o u p ( Part B) 
treat me nt st u d y wit h u p t o 7 ar ms t hat is partici pa nt a n d i n vesti gat or bli n de d.  
N u m ber of P artici p a nts:  
I n Part A, a ma xi m u m of 8 partici pa nts will be ra n d o ml y assi g ne d t o st u d y i nter ve nti o n  
or place b o  wit hi n eac h c o h ort s uc h t hat a p pr o x i matel y 5 e val ua ble partici p a nts c o m plete 
t he c o h ort. 
I n Part B ap pr o xi matel y  5 0 (a mi ni m u m of 2 0 u p t o a ma xi m u m of 8 0) partici pa nts will 
be ra n d o ml y assi g ne d t o st u d y i nter ve nti o n or place b o i n a 1: 1 rati o.  
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An interim analysis will occur once approximately 20 participants have completed the 
Week 4 assessment. A second interim analysis and an unblinded sample size re-
estimation may occur prior to enrolling the 50th participant, where the sample size could 
be decreased to a minimum of 20 or increased to a maximum of 80 participants. g 
Additional interim analyses may occur in order to inform internal decision making 
Intervention Groups and Duration: 
In Part A, the total duration of the study (from signing of the informed consent until final 
follow-up) for each participant will vary between 113 and 168 days depending on the 
cohort, including a screening period of a maximum of 28 days for all cohorts.  
Following successful screening, each participant will receive a single dose of study 
intervention (GSK3858279 or placebo), either IV or SC. The planned dosing schedule is 
described in the body of the protocol, although dose levels are subject to change 
depending on emerging study data. The maximum dose that may be administered in the 
study will be 10 mg/kg, both for IV and SC cohorts.  
In Part A, the decision to proceed to the next dose level of GSK3858279 will be made by 
the Dose Escalation Committee (DEC). The dose escalation decision will be based on 
safety, tolerability and preliminary PK and TE data obtained in all participants at that 
dose level (through 15 days post dose). The actual dose level to be administered may be 
adjusted based on safety, tolerability and preliminary PK and TE data at previous dose 
levels; these dose adjustments may involve either an increase or a decrease in the planned 
dose, but will not exceed PK criteria, and the maximum dose administered in this study 
will not exceed 10 mg/kg.  Planned dose levels may also be repeated.  
Although the decision to progress one or two IV single dose levels in Part B was to be 
based on total CCL17 data, following the review of Part A blinded data, it was decided to 
amend the protocol for subcutaneous administration of repeated doses based on PK and 
TE data. 
In Part B, the total duration of the study (from signing of the informed consent until final 
follow-up) for each participant will be up to 182/183 days (inclusive of a screening 
period of a maximum of 42 days).  
Following successful screening, each participant will receive weekly SC doses of either 
GSK3858279 or placebo in a 1:1 ratio for 8 weeks. 
Dose escalation committee: Yes (Part A). A Safety Review Committee is employed in 
Part B. 


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1.2. 
Schema 
Figure 1 
Study Design Schematic 
 
 


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Figure 2 
Part A Cohorts Without Blister: 0.1 and 0.3 mg/kg IV 
 
D: day; IV: intravenous; SOA: schedule of assessments. 


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Figure 3 
Part A Cohorts With Blister: 1 mg/kg IV  
 
D: day; IV: intravenous; SOA: schedule of assessments. 


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Figure 4 
Part A Cohorts With Blister: 3 and 10 mg/kg IV and SC 
 
D: day; IV: intravenous; SC: subcutaneous; SOA: schedule of assessments 


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Figure 5 
Part B Visit Schematic 
 


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1.3. 
Schedule of Activities (SoA) 
• 
The timing and number of planned study assessments, including safety, pharmacokinetic, pharmacodynamic/biomarker or 
efficacy assessments may be altered during the course of the study based on newly available data (e.g., to obtain data closer to 
the time of peak plasma concentrations) to ensure appropriate monitoring.  
• 
Any changes in the timing or addition of time points for any planned study assessments must be documented and approved by 
the relevant study team member and then archived in the sponsor and site study files, but will not constitute a protocol 
amendment. The IRB/IEC will be informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the informed consent form (ICF). 
• 
The visit windows permitted are also specified in the Study Reference Manual (SRM). 


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1.3.1. 
Screening 
 
 


T M F -1 4 4 4 7 9 5 3  
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
1 9  
 
1. 3. 2.  
P art A C o h ort s Wit h o ut Bli st er: 0. 1 a n d 0. 3 m g/ k g I V  
 
N ot es
Pr oc e d ur e
– 1
1
2
3
8
1 5 2 2 2 9 4 3 5 7 8 5 1 1 3
All o w e d visit wi n d o ws ar e d et ail e d i n t h e S R M
O ut- p ati e nt visit
X
X
X
X
X
X
X 1
X 2
X
1 Fi n al f oll o w- u p visit f or 0. 1 m g/ k g c o h ort
2 Fi n al f oll o w- u p visit f or 0. 3 m g/ k g c o h ort
A d missi o n i n cli ni c al u nit
X
Disc h ar g e fr o m cli ni c al u nit
X
I ncl usi o n a n d e x cl usi o n crit eri a
X
Bri ef p h ysi c al e x a mi n ati o n
X
X
X
X
X
X
X
X
X
X
X
X
X
Al c o h ol a n d t o b acc o scr e e ns
X
As p er st a n d ar d l oc al pr acti c e
Uri n e dr u g scr e e n
X
C ar di ac t el e m etry
T el e m etry fr o m at l e ast 1 2 hrs b ef or e d osi n g u ntil 1 2 hrs p ost 
d os e. O ut p ut t o b e r e vi e w e d f or a b n or m aliti es pri or t o d osi n g o n 
D a y 1.
1 2-l e a d E C G
Tri pli c at e
X 1
X
X
X
X
X
X
X
X
X
X
X
O n d a y - 1 a n d d a y 1 E C Gs m a y b e g e n er at e d fr o m t el e m etry                                    
1 O n D a y 1, pr e d os e t h e n e v ery 3 0 mi ns d uri n g i nf usi o n (i. e. 3 0 
mi ns a n d 6 0 mi ns aft er st art of i nf usi o n) a n d t h e n 1 hr p ost e n d of 
i nf usi o n.
Vit al si g ns
X
X 1
X
X
X
X
X
X
X
X
X
X
X
1 O n D a y 1, pr e d os e t h e n e v ery 1 5 mi ns d uri n g i nf usi o n (i. e. 1 5, 
3 0, 4 5 a n d 6 0 mi ns p ost t h e st art of i nf usi o n) a n d t h e n 3 0 mi ns, 1, 
2 a n d 4 hr p ost e n d of i nf usi o n.
H a e m at ol o g y, cli ni c al c h e mistry, uri n al ysis
X
2 4 hr 
p ost 
d os e
4 8 hr 
p ost 
d os e
X
X
X
X
X
X
X
X
X
W ei g ht
X
 W ei g ht t o b e us e d t o c al c ul at e t h e st u d y tr e at m e nt d os e.
R a n d o miz ati o n
Pr e-
d os e
P K bl o o d s a m pl e
X
2 4 hr 
p ost 
d os e
4 8 hr 
p ost 
d os e
X
X
X
X
X
X
X
X
X
D 1 s a m pl es t o b e t a k e n at pr e- d os e, 2 hr, 4 hr, 8 hr, a n d 1 2 hr p ost 
d os e
St u d y tr e at m e nt d osi n g
X
A E ass ess m e nt
X
S A E ass ess m e nt
X
C o nc o mit a nt m e di c ati o n r e vi e w
X
D a y
E arl y 
wit h dr a w al
X
<-------------------------------------------------- >
<-------------------------------------------------------------------- >
<--------------------------------------------------------------------- >
C CI


T M F -1 4 4 4 7 9 5 3  
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
2 0  
 
1. 3. 3.  
P art A C o h ort s Wit h  Bli st er: 1 m g/ k g I V  
 
N ot es
Pr oc e d ur e
– 1
1
2
3
7
8
1 5 2 2 2 9 4 2 4 3 5 7 8 5 1 1 3
All o w e d visit wi n d o ws ar e d et ail e d i n t h e S R M
O ut- p ati e nt visit
X
X
X
X
X
X
X
A d missi o n i n cli ni c al u nit
X
X
X
Disc h ar g e fr o m cli ni c al u nit
X
X
X
I ncl usi o n a n d e x cl usi o n crit eri a
X
Bri ef p h ysi c al e x a mi n ati o n
X
X
X
X
X
X
X
X
X
X
X
X
X
Al c o h ol a n d t o b acc o scr e e ns
X
As p er st a n d ar d l oc al pr acti c e
Uri n e dr u g scr e e n
X
C ar di ac t el e m etry
T el e m etry fr o m at l e ast 1 2 hrs b ef or e d osi n g u ntil 1 2 hrs p ost 
d os e. R e vi e w f or a b n or m aliti es pri or t o d osi n g o n D a y 1.
1 2-l e a d E C G
Tri pli c at e
X 1
X
X
X
X
X
X
X
X
X
X
X
O n D a y - 1 a n d D a y 1 E C Gs m a y b e g e n er at e d fr o m t el e m etry                              
1 O n D a y 1, pr e d os e t h e n e v er y 3 0 mi ns d uri n g i nf usi o n (i. e. 3 0 
mi ns a n d 6 0 mi ns aft er st art of i nf usi o n) a n d t h e n 1 hr p ost e n d of 
i nf usi o n.
Vit al si g ns
X
X 1
X
X
X
X
X
X
X
X
X
X
X
1 O n D a y 1, pr e d os e t h e n e v er y 1 5 mi ns d uri n g i nf usi o n (i. e. 1 5, 
3 0, 4 5 a n d 6 0 mi ns p ost t h e st art of i nf usi o n) a n d t h e n 3 0 mi ns, 1, 
2 a n d 4 hr p ost e n d of i nf usi o n.
H a e m at ol o g y, cli ni c al c h e mistry, uri n al ysis
X
2 4 hr
4 8 hr
X
X
X
X
X
X
X
X
X
W ei g ht
X
 W ei g ht t o b e us e d t o c al c ul at e t h e st u d y tr e at m e nt d os e.
R a n d o miz ati o n
Pr e-
d os e
St u d y tr e at m e nt d osi n g
X
A E ass ess m e nt
X
S A E ass ess m e nt
X
C o nc o mit a nt m e di c ati o n r e vi e w
X
D a y
E arl y 
wit h dr a w al
<-------------------------------------------------- >
<-------------------------------------------------------------------- >
<--------------------------------------------------------------------- >
X
C CI


T M F -1 4 4 4 7 9 5 3  
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
2 1  
 
1. 3. 4.  
P art A C o h ort s Wit h Bli st er: 3 a n d 1 0 m g/ k g I V a n d S C  
 
N ot es
Pr oc e d ur e
– 1
1
2
3
7
8
1 5
2 2
2 8
2 9
4 3
5 7
8 5
1 1 3
1 4 1
All o w e d visit wi n d o ws ar e d et ail e d i n t h e S R M
O ut- p ati e nt visit
X
X
X
X
X
X 1
X 2
X
1  Fi n al f oll o w- u p visit f or 3 m g/ k g I V c o h ort                               
2  Fi n al f oll o w- u p visit f or 1 0 m g/ k g I V a n d S C c o h orts 
A d missi o n i n cli ni c al u nit
X
X
X
Disc h ar g e fr o m cli ni c al u nit
X
X
X
I ncl usi o n a n d e x cl usi o n crit eri a
X
Bri ef p h ysi c al e x a mi n ati o n
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Al c o h ol a n d t o b acc o scr e e ns
X
As p er st a n d ar d l oc al pr acti c e
Uri n e dr u g scr e e n
X
C ar di ac t el e m etr y
T el e m etr y fr o m at l e ast 1 2 hrs b ef or e d osi n g u ntil 1 2 hrs p ost d os e. 
R e vi e w f or a b n or m aliti es pri or t o d osi n g o n D a y 1.
1 2-l e a d E C G
Tri pli c at e
X 1, 2
X
X
X
X
X
X
X
X
X
X
X
X
X
O n D a y - 1 a n d D a y 1 E C Gs m a y b e g e n er at e d fr o m t el e m etr y                              
1  O n D a y 1, pr e d os e t h e n e v er y 3 0 mi ns d uri n g i nf usi o n (i. e. 3 0 mi ns a n d 
6 0 mi ns aft er st art of i nf usi o n) a n d t h e n 1 hr p ost e n d of i nf usi o n.   2  O n 
D a y 1, pr e d os e  t h e n 1 hr p ost i nj e cti o n.
Vit al si g ns
X
X 1, 2
X
X
X
X
X
X
X
X
X
X
X
X
X
1  O n D a y 1, pr e d os e t h e n e v er y 1 5 mi ns d uri n g i nf usi o n (i. e. 1 5, 3 0, 4 5 
a n d 6 0 mi ns p ost t h e st art of i nf usi o n) a n d t h e n 3 0 mi ns, 1, 2 a n d 4 hr p ost 
e n d of i nf usi o n.  2  O n D a y 1, pr e d os e  t h e n 1 hr p ost i nj e cti o n.
H a e m at ol o g y, cli ni c al c h e mistr y, uri n al ysis
X
2 4 hr 
p. d.
2 4 hr 
p. d.
X
X
X
X
X
X
X
X
X
X
X
W ei g ht
X
 W ei g ht t o b e us e d t o c al c ul at e t h e st u d y tr e at m e nt d os e.
R a n d o mi z ati o n
Pr e-
d os e
I n d ucti o n of blist er
X
X
X
As pir ati o n of blist er fl ui d
X
X
X
As pir ati o n 2 1 h o urs ( +/- 3 h o urs) aft er i n d ucti o n of blist er.
St u d y tr e at m e nt d osi n g
X
A E ass ess m e nt
X
S A E ass ess m e nt
X
C o nc o mit a nt m e di c ati o n r e vi e w
X
<--------------------------------------------------------------------- >
D a y
E arl y 
wit h dr a w al
X
<-------------------------------------------------- >
<-------------------------------------------------------------------- >
C CI


T M F -1 4 4 4 7 9 5 3  
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
2 2  
 
1. 3. 5.  
P art B  
 
 
C CI
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2. 
INTRODUCTION 
2.1. 
Study Rationale 
This study is the first administration of GSK3858279 to humans for which the purpose is 
two-fold: 
Part A: to evaluate the safety, tolerability, pharmacokinetics (PK) and target engagement 
(TE) of either a single intravenous (IV) or a single subcutaneous (SC) dose of 
GSK3858279 in healthy males and females of non-reproductive potential. Target 
engagement in the skin, which is a surrogate for tight tissue compartment, will be 
assessed via suction blister procedure in certain cohorts [see Schedule of Activities (SoA, 
Section 1.3) and Section 4.3]. The intention is to provide sufficient confidence in the 
safety and tolerability of the molecule as well as target engagement to inform progression 
to the following part of the study. 
Part B: to evaluate the safety, tolerability, efficacy, PK, target engagement and 
immunogenicity of repeat SC dosing of GSK3858279 in participants with osteoarthritis 
(OA) of the knee. 
2.2. 
Background 
CCL17, previously known as thymus and activation regulated chemokine (TARC), is a 
member of the CC-family of chemokines that binds and signals through the G-protein 
coupled CC-chemokine receptor, CCR4 [Imai, 1996; Imai, 1997].  CCL17 is produced by 
numerous immune and non-immune cell types.  CCR4 is predominantly expressed on 
Th2 cells but is also present on other immune cell types. 
GSK3858279 is a high affinity (Kd<1pM), human immunoglobulin G2σ (IgG2σ) (Fc-
silenced), first-in-class, monoclonal antibody (mAb), binding specifically to the 
chemokine CCL17.  It functionally inhibits CCL17 from binding to the chemokine 
receptor CCR4, to prevent downstream consequences of CCR4 signalling. 
OA is a debilitating degenerative disease of the large and small joints and the most 
common form of adult arthritis in the developed world.  Alleviating the chronic pain of 
OA is a major unmet need as current therapies such as non-steroidal anti-inflammatory 
drugs (NSAIDs) or opioids have significant side effects that prevent their effective use in 
this population [Thakur, 2014]. OA is a disease of the whole joint and underlining pain 
mechanisms are poorly understood [Malfait, 2013]. 
The rationale for CCL17 neutralisation in OA pain has been generated in vivo 
preclinically in inflammatory and arthritis models. CCL17 has been recently identified as 
a peripheral mediator of inflammatory pain. Intraplantar injection of recombinant CCL17 
resulted in pain in mice [Achuthan, 2013], whilst therapeutic dosing with an anti-CCL17 
surrogate mAb inhibited established inflammatory pain [GSK Document Number 
2017N327494_00]. Absence of CCL17 ameliorated inflammatory pain in various murine 
arthritis models [Lee, 2018]. In addition to effects on pain, CCL17 can itself induce 
arthritis and a lack of CCL17 also protected joints from disease, as evidenced by reduced 
bone erosion and proteoglycan loss [Achuthan, 2013]. CCL17 was the 6th most 


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upregulated gene in a chemically-induced, monosodium iodoacetate (MIA) murine 
arthritis model of chronic joint pain [Dawes, 2013]. 
CCL17 evokes excitatory effects in mixed neonatal dorsal root ganglia cultures [Oh, 
2001]. A relationship has been established between CCL17 and the pain-mediator nerve 
growth factor (NGF). CCL17-overexpressing mice showed significantly higher serum 
NGF levels and increased numbers of NGF+ lymphocytes in wounded tissue than wild-
type mice [Kato, 2011]. It was also shown that CCL17 could induce NGF production in a 
mouse T cell hybridoma [Kato, 2011]. 
Thus, blockade of CCL17 with the mAb GSK3858279 offers the potential to alleviate 
OA associated chronic pain.  There is no literature on CCL17 circulating levels in OA 
patients.   
2.3. 
Benefit/Risk Assessment 
More detailed information about the potential benefits, known potential  risks and 
adverse events of GSK3858279 may be found in the Investigator’s Brochure (IB) [GSK 
Document Number RPS-CLIN-004032]. 
The risk assessment of GSK3858279 is based on the pre-clinical studies conducted to 
date and a blinded review of a partial data set from Part A of this first time in human 
(FTIH) study [GSK Document Number 2020N429762_00], for which summaries can be 
found in the IB [GSK Document Number RPS-CLIN-004032]. Details of these risks, and 
the proposed strategy to mitigate/monitor these risks are detailed in Section 2.3.1 
In this study, safety will be monitored closely both by subjective reporting and by 
objective means, i.e. serial assessments of vital signs, clinical laboratory information, AE 
and cardiac monitoring.  The study will be run in clinical units which have immediate 
access to hospital facilities for the treatment of medical emergencies.  Participants will be 
monitored in the clinic as specified in the Schedule of Activities (see Section 1.3.5) and 
will only be discharged from the unit if the investigator deems it safe to do so. 
 


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2.3.1. 
Risk Assessment 
Potential Risk of  
Clinical Significance 
 
Summary of Data/Rationale for Risk 
 
 
Mitigation Strategy 
 
 
Risks of Investigational Product (IP) GSK3858279 
Risk of infection 
 
The intended pharmacologic effect of GSK3858279 may result in 
an increase in the frequency and/or severity of infection, as a 
result of changes in immune cell trafficking.  
Non-Clinical 
No specific studies have been conducted in nonclinical species to 
investigate the effect of GSK3858279 on response to viral or 
bacterial infection.  
CCL17 has an important role in early responses against skin-
invading pathogens e.g. CCL17 controls filarial larval entry by 
limiting mast cell-dependent vascular permeability. Mice 
deficient for CCL17 had an up to 4-fold higher worm burden 
compared to controls by day 10 of infection with murine filaria 
Litomosoides sigmodontis (Specht, 2011). Anti-CCL17 has been 
shown to be protective in a mouse model of invasive aspergillosis 
[Carpenter, 2005] suggesting decreased infection risk. The role of 
CCL17 in systemic anti-pathogen responses is unclear.  
Clinical 
During this FTIH study in healthy participants (Part A), there was no 
report of an infection related SAE. 
Participant Selection:  
Participants with active infections or a history of recent or recurrent 
infections will not be allowed to enter the study – see Section 5.2 
Participant monitoring: 
Participants will be monitored for infection 
Participants will be instructed in the informed consent form as to the 
signs and symptoms of infection, and to contact site personnel 
should they develop.   
 
Hypersensitivity, 
including injection 
site or 
infusion reactions:   
The administration of any recombinant protein has the potential 
to induce local or systemic immunologic reactions, for example, 
acute allergic reactions (type I) and immune complex disease 
associated with the formation of anti-drug antibodies (ADA) 
(type III). 
Non-Clinical 
In the 13-week study, administration of GSK3858279 by weekly 
IV infusion at 100 mg/kg, resulted in infusion reactions after 
Participant Selection:  
Participants with a history of sensitivity to the study medication, or 
a history of any drug or other allergy that in the opinion of the 
investigator contraindicates their participation, will not be permitted 
to enter the study. Participants with renal disorders will be also 
excluded. See Section 5.2   
 
 


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Mitigation Strategy 
 
 
dosing on Days 22 and 29, in one female cynomolgous monkey 
which was successfully managed in subsequent administrations 
by pre-treating with anti-histamine.   
 
In the 26-week study, there were inflammatory vascular changes 
in multiple organs and mesangioproliferative glomerulopathy in 
the kidney which is consistent with ICD following the formation 
of ADA. Nonspecific injection site reactions caused by the 
subcutaneous dosing route were also noted in some monkeys, 
which was exacerbated by the immune complex deposition in one 
male. These findings were considered non-adverse. 
 
Animals studies are not predictive for ADA-mediated adverse 
reactions in humans, including infusion reactions, 
hypersensitivity reactions or anaphylaxis [Kronenberg, 2017], 
especially for human proteins such as GSK3858279. In addition, 
given that GSK3858279 binds a soluble ligand (CCL17) and is 
Fc disabled, GSK3858279 is not expected to mediate effector 
functions of antibody dependent cell mediated cytotoxicity or 
complement dependent cytotoxicity. 
 
Clinical 
During this FTIH study in healthy participants (Part A), there was 
neither a report of hypersensitivity, nor injection site reaction, nor 
a clinically significant change in urinalysis. 
Participant monitoring: 
• 
Part A participants will remain in an inpatient facility for 48 
hours post dosing to allow adequate monitoring by trained site 
personnel. Emergency resuscitation facilities will also be 
available.  
• 
Part B participants will be monitored for a minimum of 2 hours 
post dosing. 
• 
Participants will be instructed in the informed consent form 
(ICF) as to the signs and symptoms of hypersensitivity 
reactions and be instructed to seek immediate clinical care 
should they develop. 
 
Immunogenicity 
 
 
Monoclonal antibodies may induce ADAs, which have the 
potential to induce adverse reactions (mentioned above) or affect 
the PK and pharmacodynamics (PD) properties of the drug.  
GSK3858279 is a human antibody, with a lower potential for 
ADA formation than a chimeric antibody.  
 
 
Participant monitoring: 
Samples will be drawn at baseline and at regular intervals to test for 
immunogenicity, and participants will be monitored for any 
evidence of adverse reaction as detailed in the hypersensitivity 
section of this table. 
Clinical laboratory safety assessments are included in the study. 
Urine microscopy and laboratory quantification of proteinuria will 


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Non-Clinical 
In the nonclinical studies a significant number of monkeys 
treated with GSK3858279 had confirmed ADA, but mostly the 
presence of ADA did not affect the systemic exposure or PK 
parameters for GSK3858279; however, there was no impact on 
clinical observations apart from the animal which had findings 
consistent with an infusion-related reaction and on the chronic 
toxicology study, vascular changes consistent with ICD were 
seen (mentioned above).  In general, the incidence and titre of 
ADA in nonclinical studies are not predictive of human. 
Clinical 
The FTIH study in healthy participants showed there was low 
incidence of ADA, low titre, no pattern of increasing incidence of 
ADAs following single ascending dose (SAD) of GSK3858279 
(or placebo) and no apparent difference between 3 mg/kg IV vs. 3 
mg/kg SC. 
be investigated following unexplained dipstick proteinuria or 
haematuria. 
 
 
Vaccination reactions 
 
There is a theoretical risk that GSK3858279 could decrease an 
individual’s immune response to vaccines administered while on 
therapy or to allow symptoms to develop following the 
administration of live vaccines.  
 
Monkeys dosed with GSK3858279 for 13 weeks did not 
demonstrate modulation of the immune system as assessed by T-
cell Dependent Antibody Response (TDAR), an assessment of 
humoral immunity, or of peripheral blood lymphocyte 
populations as assessed by flow cytometry. 
Participant selection and non-permitted medications: 
Attenuated live should not be administered to participants from 30 
days prior to the first dose of study drug and for five half-lives after  
dosing. If indicated, non-live vaccines (e.g. inactivated influenza 
vaccines) may be administered whilst receiving study drug based on 
an assessment of the benefit:risk (e.g. risk of decreased 
responsiveness). See Section 5.2  
 
Cardiac risks 
Non-Clinical 
In the 4-week study, review of the heart data (Electrocardiogram 
[ECG], blood pressure, heart rate, organ weights and 
histopathology), in monkeys at doses up to 100 mg/kg/week IV 
Participant Exclusion 
Participants with a history of cardiac disease or cardiac 
abnormalities that in the opinion of the investigator would 
compromise cardiac safety will be excluded from the study.  
 


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and 30 mg/kg/week SC to n=2/sex/group, did not identify any 
changes compared to controls. 
In the 13-week study, higher heart weights were noted compared 
to controls, without any histopathological or functional (ECG, 
blood pressure, heart rate) correlate. The heavier heart weights 
were not dose related and generally did not show a consistent 
pattern of increased absolute weights, relative to body weight or 
brain weight. Refer to IB [GSK Document Number RPS-CLIN-
004032] for further details.   
In the 26-week study, a thorough evaluation to investigate the 
potential for cardiotoxicity which included ECG, echocardiogram 
(ECHO), telemetry (blood pressure, heart rate), serum cardiac 
troponin I, N-terminal proBNP, heart weight and histopathology, 
did not identify any treatment-related effects on the heart 
following doses up to 100 mg/kg/week SC. Therefore, the 
potential effect on heart weights noted in the 13-week study was 
not reproducible following 26 weeks chronic dosing and is not 
considered to be clinically significant. GSK3858279 did not bind 
to human heart in the tissue cross-reactivity studies and there is 
no known pharmacological mechanism following administration 
of an anti-CCL17 that would lead to an increase in heart weight.  
Clinical 
During this FTIH study in healthy participants (Part A), none of 
the abnormal findings in the ECG parameters were judged to be 
clinically significant.   
Investigations during screening include ECG, Echocardiogram and 
cardiac troponin T and NT-proBNP. Troponin T and NT-proBNP 
will be monitored after dosing. See Section 5.2  
 
In addition, telemetry was performed in FTIH study (207804) in 
healthy participants. 
Bleeding risk 
 
CCR4, the receptor for CCL17 is expressed on platelets and both 
CCL17 and CCL22 activate platelets in vitro. A potential risk of 
impaired platelet activation and blood clotting exists with CCL17 
antagonism although at this stage this is theoretical; there are 2 
conflicting reports describing the ability of anti-CCR4 antibodies, 
to either block CCL17/CCL22- mediated platelet aggregation ex 
vivo [Gear, 2001] or to not block platelet function in vitro/ex vivo 
Participant exclusion 
• 
Participants with a previous or current history of bleeding 
diathesis will be excluded see Section 5.2  
• 
Use of anti-coagulants or anti-platelet agents will be prohibited. 


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assays [Hagemann, 2014]. Clinical data with direct inhibitors of 
CCR4, such as mogamulizumab (approved in Japan for treatment 
T cell lymphoma), are not associated with increased bleeding 
risk.  
Non-Clinical 
Although platelet function has not been specifically assessed 
preclinically; no effects on platelet counts or clotting times were 
observed in the monkey studies. Neither were there reports of 
excessive bruising nor difficulties in clotting after blood 
sampling. 
 
Clinical 
There were no reports of any bleeding events during the FTIH 
study in healthy volunteers. 
• 
In addition, use of NSAIDs will be prohibited in healthy 
participants.  
Skin reactions 
Cutaneous adverse clinical effects have been observed in patients 
with T-cell lymphomas treated with mogamulizumab (anti-CCR4 
antibody) including Stevens-Johnson syndrome. This may reflect 
depletion of immune regulating cells called “Regulatory T cells” 
within the skin compartment predisposing to cutaneous 
inflammatory or autoimmune responses. Given that GSK3858279 
will only block CCL17, the alternative ligand, CCL22, should 
offer redundancy to maintain T cell migration. Relevant to this, 
CCL22 is highly expressed in skin blister fluid [Bouma, 2017]. 
Participant exclusion and monitoring 
• 
Participants with a history of drug induced skin reactions and 
Steven’s Johnsons Syndrome will be excluded; see Section 5.2  
• 
Clinically significant skin reactions will be reviewed by a 
dermatologist and if appropriate a skin biopsy will be requested 
for histological analysis.  
 
Study Procedures  
Risk associated with  
blister induction  
procedure 
(Part A only) 
Possible risks of this procedure may include discomfort during 
the application of the negative pressure, skin infection after 
drawing the blister and hyperpigmentation of the skin at the 
blister induction site.  
Participants with keloids or a history of keloids will be excluded 
from Part A; see Section 5.2  


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Risk associated with 
attending an 
investigative site 
during the COVID-
19 Pandemic 
For Part B, the current COVID-19 (SARS-CoV-2) pandemic may 
pose a challenge to 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.   Part B will be halted if the dynamics of the SARS-
CoV-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. 
 
CCL17 (and CCL22) are ligands for the CCR4 receptor. The 
CCR4 receptor is predominantly expressed on Th2 cells but is 
also present on some Th1 cells (Kara, 2014). CCL17 is thus more 
likely to be involved in extracellular infections (e.g. parasitic, 
extracellular bacteria and fungi), rather than intracellular 
infections (e.g. viral such as COVID-19) although we cannot rule 
out a role for CCL17 in viral infection. 
Participant Selection:  
OA participants may fall into a higher risk category for 
complications of COVID-19 (caused by the SARS-CoV-2 virus). 
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 protection via the use of Personal 
Protective Equipment (PPE) and disinfectants. 
 
Participant monitoring: 
Prospective OA participants will be contacted by sites to check on 
COVID-19-related symptoms prior to being pre-screened (SARS-
CoV-2 PCR test) and prior to consenting. Consented participants 
will also be contacted prior to each scheduled visit. Participants will 
be screened and monitored periodically throughout the Treatment 
Period and at the End of Study Visit (or at early withdrawal) as per 
protocol (see Section 1.3.5). 
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 
and/or having a positive SARS-CoV-2 PCR will be excluded from 
(further) participation in the trial and will receive follow-up medical 
attention as per local procedure. 


T M F -1 4 4 4 7 9 5 3  
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
3 1  
 
2. 3. 2.  
B e n efit A s s e s s m e nt  
•  T here will be n o dir ect b e nefit t o t he healt h y partici pa nts i n t his trial.  
•  O A partici pa nts  ma y e x perie nce be nefit i n ter ms of relief of k nee p ai n. N ot e t hat  
partici pa nts  will be all o w e d t o use paracet a m ol as a nal gesic resc ue m e dicati o n t o hel p 
ma na ge t heir p ai n a n d disc o mf ort ass ociate d wit h O A.  
•  B y e nr olli n g i n t his st u d y, partici pa nts will be c o ntri b uti n g t o t he pr ocess of 
de vel o pi n g n e w a n al gesi c me dicati o ns, a si g nifica nt area of u n met nee d f or patie nts 
int olera nt or u nres p o nsi v e t o oral N S AI D  tr eat me nts.  
2. 3. 3.  
O v er all B e n efit:  Ri s k C o n cl u si o n  
Ta ki n g i nt o acc o u nt t he meas ures pr o p os e d t o mi ni mize t he ris k t o st u d y p artici pa nts  
(i ncl u di n g C O VI D-1 9 [ S A R S-C o V -2] testi n g at scree ni n g, a n d s parse testi n g d uri n g t he 
st u d y), t he p ote ntial ris ks i de ntifie d wit h G S K 3 8 5 8 2 7 9 fr o m 1) pre -cli nical st u dies, 2) t he 
re vie w of s afet y i n Part A of t his cli nical st u d y [see Secti o n 5 of I B] a nd 3 ) t h ose 
ass ociate d wit h st u d y pr oce d ures , are c o nsi dere d mi ni mal a n d j ustifie d f or pr o gressi o n t o 
Part B.  
3.  
O B J E C TI V E S A N D E N D P O I N T S 
O bj e cti ve s  
E n d p oi nt s  
Pri m ary   
P arts A a n d B  
T o e val uate t he s afet y a n d t olera bilit y of 
escalati n g d oses of G S K 3 8 5 8 2 7 9 
f oll o wi n g si n gle I V, si n gle S C d osi n g i n 
healt h y p artici pa nts a n d re peat S C d osi n g 
i n O A partici pa nts. 
 
A d verse E v e nts ( A E) a n d Seri o us A d verse 
E ve nts ( S A E).  
Cli nical la b orat or y meas ure me nts,  1 2 -lea d 
E C G a n d vital si g ns.  
P art B  
T o assess c ha n ges i n pai n i n partici pa nts 
wit h O A of t he k nee f oll o wi n g re peat S C 
d osi n g.  
 
C ha n ge fr o m bas eli ne i n a vera ge k nee 
pai n i nte nsit y, at Wee k 8.  
C ha n ge fr o m bas eli ne i n w orst k nee pai n 
i nte nsit y at Wee k 8  . 
S e c o n d ary  
T o descri be t he p h ar mac o ki netics ( P K ) of 
G S K 3 8 5 8 2 7 9 f oll o wi n g si n gle I V , si n gle 
S C i n healt h y p artici pa nts a n d  re peat S C 
d osi n g  i n O A partici pa nts.  
C CI


T M F -1 4 4 4 7 9 5 3  
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
3 2  
 
O bj e cti ve s  
E n d p oi nt s  
T o e val uate t he t ar get e n ga ge me nt ( T E) of 
C C L 1 7 b y G S K 3 8 5 8 2 7 9 f oll o wi n g si n gle 
I V, si n gle S C d osi n g i n h ealt h y 
partici pa nts a n d re peat S C d osi n g i n O A 
partici pa nts.  
 
C CI
C CI
C CI


T M F -1 4 4 4 7 9 5 3  
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
3 3  
 
4.  
S T U D Y D E SI G N  
4. 1.  
O v er all D e si g n  
T his st u d y is a ra n d o mize d, d o u ble -bli n d, place b o -c o ntr olle d, t w o -part trial. A st u d y 
dia gra m is i ncl u de d i n Fi g ure 1 . 
Part A is a si n gle asce n di n g d ose escal ati o n st u d y t o e val uate t he safet y, t olera bilit y, P K, 
a n d tar get e n ga ge me nt of G S K 3 8 5 8 2 7 9  i n healt h y partici pa nt s. Si n gle I V d oses a n d a 
si n gle S C d ose will be i n vesti gate d i n s e parate c o h orts of partici pa nts. Tar get e n ga ge m e nt 
( C C L 1 7) will be ass esse d b ot h i n bl o o d
(see Secti o n 4. 3  a n d S o A , Secti o n 1. 3 ). 
U p t o fi ve si n gle asce n di n g I V d oses of G S K 3 8 5 8 2 7 9 will be i n vesti gate d. A si n gle S C 
d ose of G S K 3 8 5 8 2 7 9 will als o be assesse d t o deter mi ne bi oa vaila bilit y, as f ut ure st u dies 
as well as t he tar get pr o d uct will  li kel y i n v ol ve S C a d mi nistrati o n.  
A D ose Escalati o n C o m mittee ( D E C) will re vie w at least 1 5 da ys of safet y a n d P K data 
pri or t o pr o gressi o n t o t he ne xt d ose le vel (see St u d y Rati o nale Secti o n 4. 3 ). T he decisi o n 
t o pr o gress t he S C c o h ort will be base d u p o n u n dersta n di n g t he P K a n d T E data fr o m 
s o me I V c o h orts. T h e decisi o n t o pr o gress t o Part B d osi n g  i n O A partici pa nts will be 
base d o n t he safet y , P K  a n d T E data f oll o wi n g si n gle I V a n d si n gle S C ad mi nistrati o ns i n 
healt h y p artici pa nts . 
I n Part A, se nti nel partici pa nts will be use d i n eac h d osi n g c o h ort: t w o partici pa nts will 
be d ose d first, o ne will b e ra n d o mise d t o G S K 3 8 5 8 2 7 9 a n d o ne t o place b o. 4 8 -h o ur p ost 
C CI
C CI
C CI


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dose safety data from the sentinel participants will be reviewed by the investigator and 
the remainder of the cohort will then be dosed if deemed safe to do so. The dose level 
investigated in Part B will not exceed the highest dose tested in Part A. 
Part B will investigate the safety, tolerability, efficacy (pain), PK, TE and 
immunogenicity of weekly SC dosing for 8 weeks of GSK3858279 or placebo (in a 1:1 
ratio) in participants with OA of the knee.  
Given the global COVID-19 pandemic, all participants are to be screened and monitored 
throughout and mitigation steps are incorporated. Sites are to contact participants prior to 
each clinic visit to check for COVID-related symptoms. Participants consenting to Part B 
will either have a documented negative SARS-CoV-2 PCR approved test within two days 
of initial screening OR have a test performed at the time of initial screening. A second 
mandatory negative COVID test is required before 1st dose of study drug.  Mandatory 
testing will be conducted at the end of the Treatment Period and at the End of Study Visit 
(for details see Section 8.1.4 and Section 10.2).  Recommended optional SARS-CoV-2 
PCR tests are to be obtained ideally four days before the 3rd and 6th dose such that a 
result is available prior to dosing on those dosing visits.  In the event that GSK’s 
Guidance on COVID-19 changes, GSK will consult Principal Investigators and a joint 
decision on how to modify the approach to COVID testing may be taken. The decision 
would be judged on whether this change would constitute a substantial amendment to the 
protocol (and requiring submission to the Regulatory Authority(ies) and Ethics 
Committee(s) or whether documentation via a formal File Note would suffice. 
Safety review: Part B will incorporate an early review of safety, PK, TE and ADA data 
following administration of repeat doses in OA participants. Close in-stream safety 
monitoring (AEs, clinical laboratory, vital signs, cardiac monitoring) and a review of PK 
and TE is intended for the first 8 participants (4 randomized to active treatment) with a 
detailed review when the 8th participant reaches Day 29. 
A Safety Review Team (SRT) is employed for Part B and operates in accordance with the 
SRT Charter, with country oversight described in the study-specific Safety Management 
Plan (SMP). 
Part B incorporates an interim analysis (see Section 9.4.5) of clinical efficacy, safety, 
tolerability, PK and TE which will occur once approximately 20 participants have 
completed the Week 4 assessment.  
4.1.1. 
Treatment Groups and Duration 
The total duration of the study (from signing of the informed consent until final follow-
up) for each participant will vary between cohorts (see Table 1). The screening period 
will be of a maximum of 28 days for all cohorts in Part A and a maximum of 42 days in 
Part B. Final follow-up visits will be scheduled to occur when approximately 5 half-lives 
of GSK3858279 have elapsed after dosing. Follow-up visits are scheduled earlier for the 
lowest dose group where PK parameters are expected to be below the lower limit of 
quantification (LLQ), and are extended by an additional 4 weeks for the top dose cohort 
where extended pharmacology may be observed (see Table 1 and Schedule of Activities 
[SoA, Section 1.3]). 


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In Part A, each participant will receive a single dose of study intervention (GSK3858279 
or placebo), either IV or SC. The planned dosing schedule is described in Table 1, 
although dose levels are subject to change depending on emerging study data. The 
maximum dose (level) that may be administered in the study will be 10 mg/kg, both for 
IV and SC cohorts. See Section 4.4 for further details. 
In Part B, each participant will receive SC injections weekly for 8 weeks.  
Table 1 
Dosing schedule and study duration 
Part 
Cohort 
Dose of 
GSK3858279 
Follow up 
(days post 
dosing) 
Maximum study 
duration 
including 
screening (days) 
Part A 
Cohort 1 IV 
Up to 0.1 mg/kg 
84 
112 
Cohort 2 IV 
Up to 0.3 mg/kg 
112 
140 
Cohort 3 IV 
Up to 1 mg/kg 
112 
140 
Cohort 4 IV 
Up to 3 mg/kg 
112 
140 
Cohort 5 IV 
Up to 10 mg/kg 
140 
168 
Cohort 6 SC 
Between 1 and 3 
mg/kg (max 240 mg) 
140 
168 
Part B 
Cohort 7 SC 
240 mg 
56 (Treatment) 
84(Follow Up) 
 182/183 
4.2. 
Number of Participants 
In Part A, approximately 48 healthy male and female participants (36 randomised to 
GSK3858279, 12 randomised to placebo) will be enrolled in the study across a maximum 
of six cohorts (up to five cohorts for IV dosing and one cohort for SC dosing). In each 
cohort, eight participants will be enrolled, and will be randomised in a 3:1 ratio to 
GSK3858279: placebo (six will receive GSK3858279 and two will receive placebo). Five 
evaluable participants are required per cohort, where a participant is considered evaluable 
if they complete both the screening period and all their planned visits. 
In Part B, approximately 50 (a minimum of 20 up to a maximum of 80) participants with 
OA will be enrolled and will be randomised to receive either GSK3858279 or placebo in 
a 1:1 ratio A sample-size re-estimation may be performed, and the sample size may be 
decreased or increased up to a maximum of 80 participants.  
For Part A, if participants prematurely discontinue the study, additional participants may 
be enrolled as replacements (and assigned to the same intervention) at the discretion of 
the Sponsor in consultation with the investigator.  
For Part B, if randomised participants prematurely discontinue the study prior to dosing, 
additional participants may be enrolled as replacements (and assigned to the same 
intervention) following Sponsor approval. 
 


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4.3. 
Scientific Rationale for Study Design 
Study population 
Part A of this study is the first time GSK3858279 will be given to humans. A healthy 
population is believed to be appropriate to explore the safety and tolerability of 
GSK3858279 in a population not currently receiving concomitant therapeutic treatments 
and whose immune function is not compromised. In the absence of reproductive toxicity 
data, the study population will be restricted to male participants and females of non-
reproductive potential. 
Part B of this study will investigate the effects of GSK3858279 on pain. In the absence of 
human experimental pain models that are CCL17 dependent or accurately predict 
analgesic effect in OA, and of biomarkers for pain, proof of mechanism is best achieved 
by assessing clinical endpoints in an OA patient population. Knee OA pain participants 
will be enrolled because of the high prevalence of the condition and well-established 
clinical endpoints for pain. 
The heightened relative risk of increasing age and BMI to COVID-19 susceptibility and 
poorer outcomes has been considered [Williamson, 2020]. Inclusion of participants 
between 40 to 75 years (inclusive) and with a BMI within the range 19-34.9 kg/m2 
(inclusive) will continue to be permitted in this study because these parameters are 
inherently associated to and therefore largely cover the OA population. All participants 
are to be screened and monitored throughout for COVID-19, and mitigation steps have 
been incorporated. 
Control and blinding 
As the primary objectives of the study are safety and tolerability of single IV and SC 
doses (Part A) and repeat SC doses of GSK3858279 (Part B), use of a placebo 
comparator is required for assessment of the safety profile. A placebo arm will also act as 
a true negative control for target engagement and pain assessments. 
To ensure unbiased outcomes, a double-blind approach is preferable. 
Part A data will be reviewed blinded by the Investigator and unblinded, if required, by 
the GlaxoSmithKline (GSK) members of the DEC (GSK Clinical Investigational Lead, 
GSK medical monitor, GSK Safety and Medical Governance (SMG) representative, GSK 
pharmacokineticist and GSK statistician). Further details are included in the Dose 
Escalation Plan (DEP). Part B safety monitoring will be undertaken in a blinded manner 
by the Sponsor SRT, as described in Appendix 1 Section 10.1.5. The Study Medical 
Monitor will also regularly review AEs and clinical laboratory tests for individual 
participants during the conduct of the study to ensure individual participant monitoring 
(according to the SMP). 
 
 
 


T M F -1 4 4 4 7 9 5 3  
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
3 7  
 
Se nti nel d osi n g a n d d ose esc al ati o n   
T his st u d y is t he first ti me G S K 3 8 5 8 2 7 9 will be a d mi nistere d t o h u ma ns. T o e ns ure 
a de q uate s afet y preca uti o ns, se q ue ntial d osi n g a n d d ose escal ati o n pr ocesses  will be 
i m ple me nte d i n Part A. 
O nce ei g ht partici pa nts p er eac h c o h ort ha ve c o m plete d t he Da y 1 5 visit, t he D E C will 
re vie w all a v aila ble safet y a n d P K data. I n case of earl y dr o p-o uts, a mi ni m u m of 6 
partici pa nts c o m pleti n g t he Da y 1 5 visit will be re q ui re d f or d ose escalati o n data re vie w. 
If safet y d ata is satisfact or y (see St u d y st o p pi n g criteria i n Secti o n 7. 1 ), a n d t he ne xt d ose 
le vel is a ntici pate d n ot t o e x cee d P K st o p pi n g criteria ( mea n A U C = 2 1 9 0 μ g. da y/ m L a n d 
mea n C ma x = 8 9 5 μ g/ m L , bas e d o n 4-f ol d mar gi n a gai nst t he n o o bser ve d a d verse effect  
le vel (N O A E L ) fr o m t he 3-m o nt h t o xic ol o gical st u d y), a d ose es calati o n t o t he ne xt 
pla n ne d d ose ma y occ ur a n d t he sec o n d c o h ort ma y be e nr olle d. D os es ma y be a dj uste d 
base d o n e mer ge nt data, a n d i n a n y cas e, will n ot e xcee d t he ma xi m u m pla n ne d d ose i n 
t his st u d y 1 0 m g/ k g. T he sa me pr ocess will be i m ple me nte d i n s u bse q ue nt c o h orts.  
U p o n re vie w of data fr o m t he 1 m g/ k g I V c o h ort, t he D E C ma y d eci de t o tri g ger t he S C 
c o h ort as well as t he 3 m g/ k g I V c o h ort, if data are satisfact or y.  
I n Part A, t o miti gate a ris k of a d verse reacti o ns, s e q ue ntial d osi n g will be i m ple me nte d 
per eac h c o h ort . T w o partici pa nts will recei ve st u d y i nter ve nti o n first ( o ne o n acti ve, o ne 
o n place b o) a n d will be m o nit ore d i n t he cli nical u nit f or a p pr o xi matel y 4 8 h o urs, w hic h 
is dee me d a de q u ate t o o bser ve a n y ac ute a d verse reacti o n. If n o a d verse reacti o n 
precl u des f urt her d osi n g, s u bse q ue nt partici pa nts ma y t he n be d ose d. All p artici pa nts will 
re mai n i n t he cli nical u nit f or a p pr o xi matel y 4 8 h o urs after d osi n g t o u n der g o re q uire d 
st u d y pr oce d ures, as per t he Sc he d ule of Acti vities .  
 
Pr o g ress i o n i nt o P a rt B 
O nce ei g ht partici pa nts i n t he hi g hest d ose c o h ort i n Part  A ha ve c o m plete d t he Da y  1 5 
visit, t he D E C will re vie w all a vaila ble safet y, tar get e n ga ge m e nt (i.e , free a n d t otal 
C C L 1 7 le vels) i n ser u m a n d P K data a n d d eci de w het her t o pr o cee d wit h Part B of t he 
st u d y. I n case of earl y dr o p-o uts, a mi ni m u m of 6 partici pa nts c o m pleti n g t he Da y 1 5 
C CI


T M F -1 4 4 4 7 9 5 3  
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
3 8  
 
visit will be re q uire d f or d ose escal ati o n data re vi e w. Part B will be tri g gere d if t he 
Alt h o u g h t he d ecisi o n t o pr o gress o ne or t w o I V si n gl e d ose le vels i n Part B was 
pla n ne d t o be base d o n t otal C C L 1 7 d ata, f oll o wi n g t he re vie w of Part A bli n de d P K a n d 
T E data, it was deci de d t o a me n d t he pr ot oc ol f or s u bc uta ne o us a d mi nistrati o n of 
re peat e d d oses bas e d o n P K a n d T E  data.  
4. 4.  
J u stifi c ati o n f or D o s e  
4. 4. 1.  
P art A  
D ose le vels f or Part A w ere  sel ecte d o n t he b asis of P K/ P D pre dicti o ns a n d precli nical 
data, w hic h are s u m maris e d i n  Ta ble 2 . Please refer t o t he I B f or f urt her det ails. 
A tar get me diate d dr u g dis p ositi o n m o del ( T M D D) has bee n d e vel o pe d t o c haract erise 
t he a C C L 1 7 P K a n d c he m o ki ne ki netics o bser ve d pre-cli nicall y, an d t he m o del 
para meters were all o metricall y scale d t o a 7 0  k g h u ma n [ C P 2 0 1 5 P K -0 0 2 , 2 0 1 6 ]. T he 
esti mate d c he m o ki ne de gra dati o n rat e ( K de g = 5 8 5. 6/ da y) i m plies  a c he m o ki ne half -life of 
a p pr o xi matel y 2 mi n utes, c o nsi dera bl y s h orter t ha n t he 2 0 -3 0 mi n utes e x pecte d. 
H o we ver, t he esti mate d d e gra dati o n rate ( K de g) is deri ve d b y t he ass u m pti o n of l o w 
le vels of ser u m C C L 1 7 i n e q uili bri u m wit h e xtra cell ular c o m p o ne nt, h e nce hi g h 
acc u m ulati o n of t otal (as o bser ve d i n c y n o m ol g us m o n ke y) is e x plai ne d b y l o w C C L 1 7 
le vel a n d e xtre mel y hi g h t ur n o ver. A n alter nati ve h y p ot hesis is t o ass u me a l o wer 
de gra dati o n rate a n d a m uc h lar ger e xtra -cell ular c o m p o ne nt o utsi de plas ma. A n 
alter nati ve m o del ass u mi n g a differe nt c he m o ki ne de gra dati o n rate wit h a 1 0-mi n ute half -
life has bee n als o de vel o pe d. T here are n o differe nces i n t he esti mate d P K pr ofiles f or 
G S K 3 8 5 8 2 7 9. T he l o wer c he m o ki ne de gra dati o n rate als o res ults i n a l o n ger ret ur n t o 
baseli ne f or t he free c h e m o ki ne pr ofiles a n d s ustai ne d tar get e n ga ge m e nt o ver a l o n ger 
peri o d. Pre dicti o ns a n d s afet y mar gi ns are s u m marize d i n Ta ble 2 . 
T he ‘ Mi ni mal A ntici pate d Bi ol o gical Effect Le v el’ ( M A B E L), as p er G ui d eli ne o n 
Strate gies t o I d e ntif y a n d Miti gate Ris ks f or First -I n-H u ma n Cli nical Trials wit h 
I n v esti gati o nal Me dici nal Pr o d ucts [C H M P , 2 0 1 7] was use d t o defi ne t he starti n g d ose 
a n d is defi ne d as t he d os e le vel pre di cte d t o res ult i n a ma xi m u m i n hi biti o n i n plas ma i n 
t he 3 0-5 0 % ra n ge. A d os e of 0. 1 m g/ k g was desi g nate d t he M A B E L  d ose as t he 
ma xi m u m pre dicte d P D i n hi biti o n was 5 6 %, acc or di n g t o h u ma n P K/ P D pre dicti o ns.  
Acc or di n g t o t his m o del, t he hi g hest pla n n e d d ose 1 0  m g/ k g I V is e x pecte d t o pr o vi de a 
ma xi m u m tar get e n ga ge me nt of 9 9 % wit h half of t his le vel bei n g rec o v ere d afte r 
9. 5  da ys, a n d a ret ur n t o baseli ne ar o u n d t hr ee wee ks p ost d ose. E ve n at t his hi g hest 
si m ulate d d ose, hi g h tar get e n ga ge m e nt was n ot mai ntai ne d o ver a 2 8-da y p eri o d.  
C CI
C CI
C CI


T M F -1 4 4 4 7 9 5 3  
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
3 9  
 
T he c y n o m ol g us m o n k e y st u d y, use d i n t he n o n -cli nical assess me nt of G S K 3 8 5 8 2 7 9 
p har mac ol o g y a n d t o xic ol o g y, has pr o vi d e d reas o na ble ass ura n ce t hat t here are n o u n d u e 
or u nf ores ee n ris ks f or t he first a d mi nistrati o n of G S K 3 8 5 8 2 7 9 t o h u ma ns, at t he d ose 
le vels pr o p ose d i n t his st u d y. T he hi g h est pre dicte d e x p os ures after I V a d mi nistrati o n 
( C ma x 2 1 3 μ g/ m L, A U C( 0 - ∞) = 1 4 6 0 μ g * da y/ m L) are al m ost 6 f ol d bel o w t he N O A E L 
( C ma x 3 5 8 0 µ g/ m L, A U C Da y 8 5 -9 2 8 7 6 0 μ g. da y/ m L) fr o m t he 3 m o nt h t o xic ol o g y st u d y.  
T a bl e 2  
G S K 3 8 5 8 2 7 9 D o s e s, Pr e di ct e d E x p o s ur e s a n d S af et y M ar gi n  
D os e ( m g/k g)  Pr e dict ed P K a nd P K/ P D i nhi biti o n  
S af ety M ar gi n  
M ax C C L 1 7 
i n hi biti o na ( %) 
C max 
[µ g/ m L]  
A U C  
[µ g *day/ m L]  
C max  
A U C  
0. 1 (I V) 
5 6 
2. 1 3 
1 7. 8 
1 6 8 0x 
4 9 4x 
0. 3 (I V) 
8 6 
6. 3 9 
5 2. 3 
5 6 1x 
1 6 7x 
1 (I V) 
9 6 
2 1. 3 
1 6 8 
1 6 8x 
5 2x 
3 (I V) 
9 8 
6 3. 8 
4 7 7 
5 6x 
1 8x 
1 0 (I V) 
9 9 
2 1 3 
1 4 6 0 
1 7x 
6x 
1 ( S C) 
6 6 
8. 2 4 
1 4 0 
3 7x 
1 2x 
3 ( S C)  
8 7 
2 2. 0 
4 0 2 
1 4x 
4x 
a.  
 Av er a g e T E i n t h e first 1 2 h o urs  
C m ax = m axi m u m pl as m a G S K 3 8 5 8 2 7 9 c o nc e ntr ati o n, A U C = ar e a u n d er c o nc e ntr ati o n -ti m e c urv e. 
A d ose le vel bet w ee n 1 t o 3 m g/ k g S C is a ntici pate d t o be p har mac ol o gicall y rel e va nt 
a n d will pr o vi de a preli mi nar y assess me nt of G S K 3 8 5 8 2 7 9 bi oa vaila bilit y after S C 
a d mi nistrati o n.  
4. 4. 2.  
P art B  
T he  d ose t o be a d mi nistere d i n Part B was re vise d ( pr ot oc ol a me n dme nt 3) acc or di n g t o 
t he act ual P K a n d T E ( % re d ucti o n fr o m bas eli ne i n free C C L 1 7 le vels) d at a o btai ne d 
fr o m Part A [G S K  D oc u me nt N u m ber  2 0 1 9 N 3 9 7 7 8 7 _ 0 0 ].  H o we ver, re -a nal ysis of t he 
c o nce ntr ati o n of G S K 3 8 5 8 2 7 9 i n Part A sa m ples usi n g a n i m pr o ve d a nal ytical met h o d 
[see G S K D oc u me nt N u m ber R P S -C LI N -0 0 4 0 3 2 ] has le d t o a f urt her pr ot oc ol 
a me n d me nt ( n u m ber 5). T he data fr o m Part A a n d t he rec o m me n d ati o n of t he d ose 
re gi me n f or Part B are s u m marise d here. 
C CI


T M F -1 4 4 4 7 9 5 3  
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
4 0  
 
4. 5.  
E n d of S t u d y D efi niti o n 
A partici pa nt is c o nsi dere d t o ha ve c o m plet e d t he st u d y if he/s he h as c o m plete d all 
p hases of t he st u d y i ncl u di n g t he fi nal f oll o w -u p visit.  
T he e n d of t he st u d y is d efi ne d as t he d ate of t he l ast visit of t he last partici pa nt i n t he 
st u d y. 
5.  
S T U D Y P O P U L A TI O N  
Pr os pecti ve a p pr o val of pr ot oc ol de vi ati o ns t o recr uit me nt a n d e nr ol me nt criteria, als o 
k n o w n as pr ot oc ol wai v ers or e x e m pti o ns, is n ot per mitte d.  
5. 1.  
I n cl u si o n Crit eri a 
Partici pa nts are eli gi ble t o be i ncl u de d i n t he st u d y o nl y if all of t he  f oll o wi n g criteria 
a p pl y:  
P art A  
A G E  
1.  Bet wee n 1 8 a n d 6 5 years of a ge i ncl usi ve, at t he ti me of si g ni n g t he i nf or me d 
c o nse nt.  
T Y P E O F P A R TI CI P A N T A N D DI S E A S E C H A R A C T E RI S TI C S   
2.  Partici pa nt s w h o are o v ertl y healt h y as d eter mi ne d b y me dical e val u ati o n i ncl u di n g 
me dical hist or y, p h ysic al e x a mi nati o n, la b orat or y tests, a n d car diac m o nit ori n g.  
 
W EI G H T  
3.  B o d y wei g ht wit hi n t he ra n ge 5 0 –  1 0 0 k g a n d b o d y mass i n de x ( B MI) wit hi n t he 
ra n ge 1 8-3 2 k g/ m 2 (i ncl usi ve). 
 
S E X  
4.  Male or fe m ale partici pa nt:  
a. Male partici pa nts:  
Male partici pa nts are eli gi ble t o partici pate if t he y a gree t o t he f oll o wi n g f or at least 
2 8  wee ks after t he d os e of st u d y i nter ve nti o n :  
•  
Refrai n fr o m d o n ati n g s p er m  
P L U S eit her:  
C CI


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• 
Be abstinent from heterosexual intercourse as their preferred and usual 
lifestyle (abstinent on a long term and persistent basis) and agree to remain 
abstinent  
OR 
• 
Must agree to use contraception/barrier as detailed below  
o Agree to use a male condom  
o and should also be advised of the benefit for a female partner to use 
a highly effective method of contraception (see Section 10.4; 
Appendix 4) as a condom may break or leak when having sexual 
intercourse with a woman of childbearing potential who is not 
currently pregnant 
b. Female participants:  
A female participant is eligible to participate if she is of non-reproductive potential as 
defined in Appendix 4. 
 
 
INFORMED CONSENT 
5. Capable of giving signed informed consent which includes compliance with the 
requirements and restrictions listed in the ICF and in this protocol. 
 
Part B 
AGE 
6. Between 40 and 75 years of age inclusive, at the time of signing the informed 
consent. 
TYPE OF PARTICIPANT AND DISEASE CHARACTERISTICS  
7. OA of the index knee as defined by symptoms for ≥6 months with a clinical 
diagnosis of OA as per American College of Rheumatology (ACR) clinical 
diagnosis criteria 
8. Average of daily pain score ≥4 and ≤9 by the 11-point NRS (0-10) in index knee 
over 7 days prior to dosing (Day-7 to Day-1). Data should be recorded on at least 5 
of 7 occasions by the participant to obtain a valid baseline value. 
9. Kellgren and Lawrence (KL) score ≥2 on X-ray obtained during screening 
(Kellgren, 1957). In addition, for participants with bilateral Knee OA, the index 
knee is determined at baseline as the patient reported most painful knee over the 4 
weeks prior to baseline.  
10. A history of insufficient pain relief from, or inability to tolerate, or contraindication 
to, oral NSAIDs. 


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11. Participant must be willing and able to understand and participate in all scheduled 
evaluations and to complete all required tests and procedures including the use of 
patient diaries. This will be judged by the Investigator during the screening period. 
WEIGHT 
12. BMI within the range 19-34.9 kg/m2 (inclusive) 
SEX 
13. Male or female participant: 
a. Male participants: 
Male participants are eligible to participate if they agree to the following for at least 
28 weeks after the dose of study intervention: 
• 
Refrain from donating sperm 
PLUS either: 
• 
Be abstinent from heterosexual or homosexual intercourse as their preferred 
and usual lifestyle (abstinent on a long term and persistent basis) and agree to 
remain abstinent  
or 
• 
Must agree to use contraception/barrier as detailed below  
o Agree to use a male condom   
o and should also be advised of the benefit for a female partner to use 
a highly effective method of contraception (see Appendix 4) as a 
condom may break or leak when having sexual intercourse with a 
woman of childbearing potential who is not currently pregnant 
b. Female participants:  
A female participant is eligible to participate if she is of non-reproductive potential 
as defined in Appendix 4. 
 
INFORMED CONSENT 
14. Capable of giving signed informed consent which includes compliance with the 
requirements and restrictions listed in the ICF and in this protocol. 


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5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
PART A 
MEDICAL CONDITIONS 
1. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, 
endocrine, haematological, or neurological disorders capable of significantly 
altering the absorption, metabolism, or elimination of drugs; constituting a risk 
when taking the study intervention; or interfering with the interpretation of data.  
2. Personal or family history of cardiomyopathy. 
3. Abnormal blood pressure at screening as determined by the investigator. 
4. History of symptomatic herpes zoster  
5. Evidence of active or latent tuberculosis (TB) as documented by medical history, 
examination, and TB testing with a positive (not indeterminate) QuantiFERON test. 
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. If a locally-read follow up chest x-ray 
shows no evidence of current or previous pulmonary tuberculosis, the participant may 
be eligible for the study at the discretion of the Investigator and GSK Medical Monitor. 
6. Significant allergies to humanized monoclonal antibodies as per principal 
investigator’s and GSK medical monitor’s judgements.  
7. History or evidence of clinically significant multiple or severe drug allergies, 
intolerance to topical corticosteroids, 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) 
8. Lymphoma, leukaemia, or any malignancy except for basal cell or squamous 
epithelial carcinomas of the skin that have been resected with no evidence of 
metastatic disease for 3 years. 
9. Alanine transaminase (ALT) >1.5x upper limit of normal (ULN)  
10. Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is 
fractionated and direct bilirubin <35%).  
11. Current or chronic history of liver disease, or known hepatic or biliary 
abnormalities (with the exception of Gilbert's syndrome or asymptomatic 
gallstones) 
12. Corrected QT (QTc) >450 msec  


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NOTES: 
• 
The QTc is the QT interval corrected for heart rate according to Bazett’s 
formula (QTcB), Fridericia’s formula (QTcF), and/or another method, 
machine-read or manually over-read. 
• 
The specific formula that will be used to determine eligibility and 
discontinuation for an individual participant should be determined prior to 
initiation of the study. In other words, several different formulae cannot be 
used to calculate the QTc for an individual participant and then the lowest 
QTc value used to include or discontinue the participant from the trial. 
• 
For purposes of data analysis, QTcB, QTcF, another QT correction formula, 
or a composite of available values of QTc will be used as specified in the 
Reporting and Analysis Plan (RAP). 
13. History of Stevens Johnson Syndrome 
14. Known immunodeficiency 
15. Participants with a chronic infection (e.g., osteomyelitis), who have been receiving 
treatment within three months prior to dosing or individuals with an active 
infection. 
16. Previous or current history of bleeding diathesis 
17. Previous history of hypertrophic or keloid scarring 
 
PRIOR/CONCOMITANT THERAPY 
18. Intended use of over-the-counter or prescription medication including herbal 
medications within 7 days prior to dosing until final follow-up visit.   
19. Live vaccine(s) or plans to receive such vaccines within 1 month of screening until 
final follow-up visit. 
20. Treatment with biologic agents (such as monoclonal antibodies including marketed 
drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing 
21. Treatment with antiplatelet or anticoagulant agents within 7 days of dosing 
22. Major surgery (as per investigator’s judgement) within 3 months prior to dosing.  
 
PRIOR/CONCURRENT CLINICAL STUDY EXPERIENCE 
23. Participation in the study would result in loss of blood or blood products in excess 
of 500 mL within 3 months. 
24. Exposure to more than 4 new chemical entities within 12 months prior to the first 
dosing day. 
25. Current enrolment or past participation in any other clinical study involving an 
investigational study intervention or any other type of medical research within the 


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last 30 days, 5 half-lives or twice the duration of the biological product before 
dosing day in the current study. 
 
DIAGNOSTIC ASSESSMENTS 
26. Presence of Hepatitis B surface antigen (HBsAg) at screening. 
27. Presence of the Hepatitis B core antibody (HBcAb) at screening. 
28. Positive Hepatitis C antibody test result at screening. 
NOTE: Participants with positive Hepatitis C antibody due to prior resolved 
disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is 
obtained 
29. Positive Hepatitis C RNA test result at screening or within 3 months prior to first 
dose of study intervention 
NOTE: Test is optional and participants with negative Hepatitis C antibody test are 
not required to also undergo Hepatitis C RNA testing. 
30. Abnormal clinically significant echocardiogram at screening, as assessed by the 
investigator. 
31. Cardiac troponin levels out of normal range at screening. 
32. Positive pre-study drug/alcohol screen 
33. Positive human immunodeficiency virus (HIV) antibody test 
 
OTHER EXCLUSIONS 
34. Regular alcohol consumption within 6 months prior to the study defined as:  
• 
an average weekly intake of >21 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.  
35. Smokerlyzer levels indicative of smoking or history or regular use of tobacco- or 
nicotine-containing products within 6 months prior to screening. 
36. Regular use of known drugs of abuse.  
37. Sensitivity to any of the study interventions, or components thereof, or drug or 
other allergy that, in the opinion of the investigator or medical monitor, 
contraindicates participation in the study. 
 


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Part B 
MEDICAL CONDITIONS 
Diagnosis of one or more of the following, as per medical records: 
38. Significant pain in any joint other than the index knee or any referred pain that 
would impact ability to assess pain in the index knee as per investigator’s 
judgement (Pain in other locations should be less than pain in target knee). 
39. Current inflammatory arthritis such as rheumatoid arthritis, autoimmune disorder 
affecting joints, seronegative spondyloarthritis, gout or pseudogout in any joint 
(defined as acute episodic attacks of swollen, painful joint in a patient with X-Ray 
chondrocalcinosis or calcium pyrophosphate dihydrate [CPPD] crystals). Note: 
asymptomatic CPPD crystals on X-ray are not an exclusion  
40. History of gout or pseudogout in any large joint. 
41. History or evidence of infectious arthritis, Paget’s disease, ochronosis, Wilson’s 
disease, primary osteochondromatosis, osteonecrosis, avascular necrosis and other 
causes of significant joint disease osteoarthritis as determined by the investigator 
42. History of fibromyalgia 
43. Current immunodeficiency diseases 
44. Current osteoporosis with symptomatic vertebral or hip fractures 
45. Current regional pain syndromes caused by lumbar or cervical compressions with 
radiculopathy 
46. History of significant medical illness in the opinion of the investigator would 
interfere with the study procedures and / or assessments 
47. Symptomatic herpes zoster within 3 months prior to screening 
48. Evidence of active or latent TB as documented by medical history, examination 
and TB testing: either a positive tuberculin skin test (TST; defined as a skin 
induration >5 mm at 48 to 72 hours, regardless of Bacillus Calmette-Guerin (BCG) 
or other vaccination history) or a positive (not indeterminate) QuantiFERON test.  
NOTES:  
• The choice to perform a TST or a QuantiFERON test will be made by the 
investigator according to local licensing and standard of care. The 
QuantiFERON test can only be used in countries where it is licensed, and 
the use of this test is dependent on previous treatment(s). This test may not 
be suitable if previous treatment(s) produced significant 
immunosuppression. 
• In cases where the QuantiFERON or T-spot 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 or T-spot test is positive, the participant should 
be followed up as per standard of care. If a locally-read follow up chest x-
ray shows no evidence of current or previous pulmonary tuberculosis, the 


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participant may be eligible for the study at the discretion of the Investigator 
and GSK Medical Monitor. 
 
49. History of significant allergies to humanized monoclonal antibodies  
50. History or evidence of clinically significant multiple or severe drug allergies, 
intolerance to topical corticosteroids, or severe post-treatment hypersensitivity 
reactions (including, but not limited to, erythema multiforme major, linear IgA 
dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis 
51. History of malignancy within the last 5 years, except for basal cell or squamous 
epithelial carcinomas of the skin that have been resected with no evidence of 
metastatic disease for 3 years. 
52. Breast cancer within the past 10 years. 
53. ALT >1.5x ULN  
54. Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is 
fractionated and direct bilirubin <35%) 
55. Current or chronic history of liver disease or known hepatic or biliary abnormalities 
(with the exception of Gilbert's syndrome or asymptomatic gallstones). 
56. QTc >450 msec or QTc >480 msec in participants with bundle branch block 
NOTES:  
• The QTc is the QT interval corrected for heart rate according to Bazett’s 
formula (QTcB), Fridericia’s formula (QTcF), and/or another method. It is 
either machine-read or manually over-read. 
• The specific formula used to determine eligibility and discontinuation for an 
individual participant should be determined prior to initiation of the study. In 
other words, several different formulas cannot be used to calculate the QTc for 
an individual participant and then the lowest QTc value used to include or 
discontinue the participant from the trial. 
57. History of primary cardiomyopathy and any major cardiac or vascular event within 
the last 6 months, including and not limited to myocardial infarction, unstable 
angina, cerebrovascular event, peripheral arterial or venous thrombosis. 
58. Current or history of renal disease, or estimated creatinine clearance 
<60 mL/min/1.73m2 or serum creatinine >1.5xULN or urine albumin:creatinine 
ratio of >300mg/g at screening 
59. Planned surgical procedure over the duration of the study 
60. Previous or current history of bleeding diathesis, excessive bleeding or coagulation 
disorders. 
61. History of Stevens Johnson Syndrome 
62. Participants with active, recurrent or chronic infection (e.g., osteomyelitis), who 
have been receiving treatment within three months prior to dosing or individuals 
with an active infection. 


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63. History of significant trauma or surgery to a knee, hip or shoulder within the last 6 
months. 
64. Radiographic evidence of sub-chondral fractures or radiographic abnormalities not 
consistent with osteoarthritis of the index knee at screening.  
PRIOR/CONCOMITANT THERAPY 
65. Attenuated live vaccine(s) (with the exception of recombinant non-human primate 
adenoviral vector vaccines) within 30 days prior to dosing or plans to receive such 
vaccines during the study. 
66. Treatment with biologic agents (such as monoclonal antibodies including marketed 
drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing. 
67. Intra-articular therapy within 3 months prior to signing the informed consent. 
68. Immunosuppressants, including corticosteroids (parenteral within 3 months of 
screening; oral within 1 month of screening). 
69. Unable or unwilling to discontinue all pain medication including topical analgesic 
or adjunctive treatment as per Section 6.5 and Section 6.6. 
70. Major surgery (as per investigator’s judgement) within 3 months prior to dosing. 
PRIOR/CONCURRENT CLINICAL STUDY EXPERIENCE 
71. Participation in the study would result in loss of blood or blood products in excess 
of 500 mL within 56 days. 
72. Exposure to more than 4 new chemical entities within 12 months prior to the 
dosing day. 
73. Current enrolment or past participation in a clinical study of an investigational drug 
intervention within the last 3 months or 5 half-lives (whichever is longer) of 
signing consent. 
DIAGNOSTIC ASSESSMENTS 
74. Positive HIV antibody test. 
75. Presence of HBsAg at screening. 
76. Presence of HBcAb at screening 
77. Positive Hepatitis C antibody test result. 
78. NOTE: Participants with positive Hepatitis C antibody due to prior resolved 
disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is 
obtained 
79. Positive Hepatitis C RNA test result at screening or within 3 months prior to first 
dose of study intervention 
80. NOTE: Test is optional and participants with negative Hepatitis C antibody test are 
not required to also undergo Hepatitis C RNA testing. 
81. Positive coronavirus (COVID-19: SARS-CoV-2 PCR test of a combined throat and 
nasopharyngeal swab). 


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82. Clinically significant abnormal echocardiogram at screening, as assessed by the 
investigator. 
83. Cardiac troponin or NT-proBNP levels out of normal range at screening. 
84. A positive pre-study drug/alcohol screen at screening 
OTHER EXCLUSIONS 
85. Regular alcohol consumption within 6 months prior to signing the informed 
consent 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. 
86. Regular use of known drugs of abuse 
87. Sensitivity to any of the study interventions, or components thereof, or drug or 
other allergy that, in the opinion of the investigator or medical monitor, 
contraindicates participation in the study. 
 
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. Measures and procedures are encouraged whenever 
possible and will at least be to effect social distancing (at least 1 metre apart) during the 
clinical trial and to wear a face cover during visits to the clinical unit.  
5.3.2. 
Meals and Dietary Restrictions 
Not applicable 
5.3.3. 
Caffeine, Alcohol, and Tobacco 
For Part A:  
• 
During each dosing session, participants will abstain from ingesting caffeine- or 
xanthine-containing products (e.g., coffee, tea, cola drinks, and chocolate) for 
24 hours before any clinic visit until discharge at each visit. 
• 
Participants will abstain from alcohol for 24 hours before any clinic visit until 
discharge at each visit  
• 
Participants who use tobacco products will be instructed that use of nicotine-
containing products (including nicotine patches and other delivery devices such as 
vaporizers) will not be permitted while they are in the clinical unit.  


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For Part B: 
• 
Participants will abstain from alcohol for 24 hours before any clinic visit until 
discharge at each visit  
• 
Participants who use tobacco products will be instructed that use of nicotine-
containing products (including nicotine patches and other delivery devices such as 
vaporizers) will not be permitted while they are in the clinical unit.  
5.3.4. 
Physical Activity 
• 
Participants will abstain from strenuous exercise for 24 hours before each blood 
collection for clinical laboratory tests. Participants should maintain stable levels of 
physical activity throughout the duration of screening, treatment and follow up.  
• 
Participants may continue a regimen of therapeutic exercise, provided it has been 
stable for at least 4 weeks prior to enrolment.  No new therapeutic regiments should 
be implemented during the study.  Physical therapy or therapeutic massage should 
not be initiated during this study 
• 
Heat or ice therapy can be used during the study, except 2 hours prior to eDiary 
assessments and 24 hours prior to a clinic visit 
 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently randomized. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes 
demography, screen failure details, eligibility criteria, and any SAEs. 
5.4.1. 
Re-screening  
Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened once. Individuals who screen fail due to running out of time in the 
screening window due to non-medical reasons e.g. for a short notice covid booster 
vaccine may be rescreened more than once following discussion with the medical 
monitor.  Rescreened participants should be assigned a new participant number. 
Participants who have tested positive for COVID-19 will not be re-screened. 
5.4.2. 
Re-testing of Clinical Laboratory Values during Screening 
If a participant fails any of the laboratory criteria, 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 Study Reference Manual (SRM). 


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6. 
STUDY INTERVENTION 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol. 
6.1. 
Study Intervention(s) Administered 
Study intervention is defined as any product received by the participant as per the study 
protocol. Study intervention may therefore refer to GSK3858279 or placebo. 
Table 3 
 Study interventions 
Product name: 
GSK3858279 
Diluent/Placebo 
Formulation description: 
GSK3858279 is 
formulated in 0.79 mg/mL 
sodium acetate, 50 mg/mL 
sorbitol, 0.4 mg/mL 
polysorbate 20, glacial 
acetic acid 0.28 mg/mL, 
water for injection, pH 5.0. 
GSK3858279 contains no 
preservative. 
Normal Saline (0.9% 
sodium chloride) 
Dosage form: 
Solution for injection 
Solution for injection 
Unit dose level: 
50 mg/mL. Each vial has 
an extractable volume of 
3.0 mL (150 mg per vial). 
0.9% w/v sodium chloride, 
placebo level variable. 
Route of administration 
and duration: 
IV or SC 
IV or SC 
Dosing instructions: 
IV cohorts 1-5:  
GSK3858279 will be 
infused over up to 1 hour. 
GSK3858279 can be 
diluted in normal saline 
prior to administration. 
SC Cohorts 6 (Part A)1 and 
7 (Part B)2 
The appropriate volume of 
GSK3858279 will be 
injected using a syringe at 
The appropriate volume of 
normal saline will be 
infused (IV) or injected 
(SC) in the same manner as 
the corresponding active 
cohort. 


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no more than 1.2 mL per 
injection.  
Physical description: 
The drug product is a 
brown to yellow solution 
stored in 5 mL glass vials 
with a 20 mm rubber 
stopper and a grey-brown 
20 mm Flip-top aluminium 
overseal. 
Commercial presentation 
Manufacturer/source of 
procurement: 
Study medication is 
supplied by GSK. 
0.9% w/v sodium chloride 
is sourced locally by the 
site. 
1) Part A: As a maximum of 4 SC injections will be administered for feasibility reasons, the 
maximum dose that will be administered to participants weighing >80 kg will be 240 mg.  
2) For Part B, all participants are to receive a weekly dose of 240 mg SC (4 x 1.2 mL injections) 
irrespective of weight. 
The doses of GSK3858279 for injection will be prepared at the clinical site by an 
unblinded pharmacist from the stock solution provided (see Table 3). 
6.2. 
Preparation/Handling/Storage/Accountability 
• The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study intervention received and any 
discrepancies are reported and resolved before use of the study intervention. 
Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study interventions 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labeled storage conditions with access limited to 
the investigator and authorized site staff. 
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records). 
Further guidance and information for the final disposition of unused study intervention 
are provided in the SRM.  
• 
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. 
• 
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. 


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6.3. 
Measures to Minimize Bias: Randomization and Blinding 
6.3.1. 
Randomization  
At Screening a unique Participant Number (case report form [CRF] number) will be 
assigned to any participant who has at least one Screening procedure performed, other 
than informed consent. The unique Participant Number will be used to identify individual 
participants during the course of the study. 
Participants who meet the screening eligibility criteria will be randomised to a treatment 
group through RAMOS NG. The randomisation is centrally controlled by RAMOS NG. 
RAMOS NG will confirm the participants CRF number (Participant number) and provide 
the randomisation number, where: 
• A randomisation number will be assigned from a randomisation schedule 
generated by Clinical Statistics, prior to the start of the study, using validated 
internal software. Once assigned, this number must not be reassigned to any other 
participant in the study. 
Part A 
Within each cohort, participants will be assigned to either GSK3858279 or placebo in a 
3:1 ratio, where the intervention codes are as follows: 
Intervention code 
Intervention Description 
A 
0.1 mg/kg IV GSK3858279  
B 
0.3 mg/kg IV GSK3858279  
C 
1 mg/kg IV GSK3858279  
D 
3 mg/kg IV GSK3858279 
E 
10 mg/kg IV GSK3858279 
F 
SC GSK3858279 
P 
Placebo  
 
Part B 
Participants will be assigned to either GSK3858279 or placebo; where the GSK3858279 
dose level to be studied in Part B will be dependent on the Part A data. The 
randomisation ratio will be 1:1 for GSK3858279: placebo. 
  
Intervention code 
Intervention Description 
G 
240 mg SC GSK3858279  
P 
Placebo  
 


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6.3.2. 
Blinding  
This will be a double-blind study with respect to allocation of GSK3858279 or placebo to 
participants and the following will apply. 
• The investigator or treating physician may unblind a participant’s intervention 
assignment only in the case of an emergency OR in the event of a serious 
medical condition when knowledge of the study intervention is essential for the 
appropriate clinical management or welfare of the participant as judged by the 
investigator. 
• 
The interactive voice response system (IVRS)/ interactive web recognition system 
(IWRS) will be programmed with blind-breaking instructions. In case of an 
emergency, the investigator has the sole responsibility for determining if 
unblinding of a participant’s intervention assignment is warranted. Participant 
safety must always be the first consideration in making such a determination. If 
the investigator decides that unblinding is warranted, the investigator should make 
every effort to contact GSK prior to unblinding a participant’s intervention 
assignment unless this could delay emergency treatment of the participant. If a 
participant’s intervention assignment is unblinded GSK must be notified within 
24 hours after breaking the blind. The date and reason that the blind was broken 
must be recorded in the source documentation and CRF, as applicable. 
• If GSK personnel are not contacted before the unblinding, the investigator must 
notify GSK as soon as possible after unblinding, but without revealing the 
intervention assignment of the unblinded participant, unless that information is 
important for the safety of participants currently in the study. 
• The date and reason for the unblinding must be fully documented in the CRF 
• A participant will be withdrawn if the participant’s intervention code is unblinded 
by the investigator or treating physician. The primary reason for discontinuation 
(the event or condition which led to the unblinding) will be recorded in the CRF. 
The participant will be followed up for safety monitoring if treatment was received. 
• GSK’s SMG 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. 
• GSK DEC members may review unblinded safety data from Part A on an as 
required basis and at the dose escalation meetings, where no-one outside of this 
committee will be unblinded to the study data. Further details of how this will be 
managed are included in the DEP. 
• Members of the study Interim Data Review Committee (IDRC) and senior GSK 
leadership may also review unblinded data from Part B at Interim Analyses as 
described in Section 9.4.5. 
• There will be an unblinded site pharmacist to prepare the study intervention; 
however, they will not have contact with study participants. 


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6.4. 
Study Intervention Compliance 
• 
When the individual dose for a participant is prepared from a bulk supply, the 
preparation of the dose will be confirmed by a second member of the study site staff.  
• 
Participants will receive study intervention at the clinical unit directly from the 
investigator or designee, under medical supervision, via IV or SC route depending on 
the cohort the participant is enrolled into.  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. 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) that the participant receives during the study must 
be recorded along with: 
• 
reason for use 
• 
dates of administration including start and end dates 
• 
dosage information including dose and frequency 
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
Participants will be provided with a diary card to record usage of any medications 
between visits 
6.5.1. 
Permitted Therapies 
In Part A, participants must abstain from taking prescription or non-prescription drugs 
(including vitamins and dietary or herbal supplements) within 7 days (or 14 days if the 
drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the start 
of study intervention until completion of the follow-up visit, unless, in the opinion of the 
investigator and sponsor, the medication will not interfere with the study. 
In Part B, the following medications are permitted if they were used at a stable dose for at 
least 30 days prior to screening: 
• Antidepressant medication including selective Serotonin reuptake inhibitors 
(SSRI) and Serotonin Noradrenaline reuptake inhibitors (SNRI)   
• Nutraceuticals (eg Glucosamine or Chondroitin) 
• Aspirin for cardiovascular indications at a maximum dose of 300 mg/day 
 


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6.5.2. 
Rescue Medication (Part B) 
In Part B, Paracetamol/Acetaminophen, at doses of ≤3 grams/day, is permitted for use as 
rescue medication any time during the study except 24 h before a clinical visit. The study 
site will supply rescue medication. 
6.6. 
Prohibited Medications 
The following are prohibited from Day -7 until Day 71. A washout period is required 
prior to Day -7, consisting of 3 days or 5 half-lives, whichever is longer. Refer to 
Figure 5. 
• All pain medications including anti-neuropathic agents (e.g. Gabapentin and 
Pregabalin), opioids, NSAIDs, topical analgesics 
• Adjunctive therapies 
The following are prohibited throughout the entire duration of the study: 
• Attenuated live vaccine(s)  
• Biologic agents (monoclonal antibodies, therapeutic proteins) 
• Antiplatelet or anticoagulant agents 
• Immunosuppressants 
• Systemic Corticosteroids 
• Intra-articular therapy of the index joint 
 
6.7. 
Dose Modification 
Part A: The decision to proceed to the next dose level of GSK3858279 will be made by 
the DEC. The dose escalation decision will be based on safety, tolerability and 
preliminary PK data obtained in all participants at that dose level (through 15 days post 
dose). The actual doses to be administered may be adjusted based on safety, tolerability 
and preliminary PK data at previous dose levels; these dose adjustments may involve 
either an increase or a decrease in the planned dose, but will not exceed PK criteria (See 
Section 4.4 and Section 7.2.3), and the maximum dose administered in this study will not 
exceed the maximum planned dose of 10 mg/kg.  Planned dose levels may also be 
repeated. 
The Principal Investigator and the GSK Medical Monitor will review the following and 
dosing will be halted and progression to the next higher dose level stopped if: 
• 
One (1) or more participants experience a serious adverse event which has a 
reasonable possibility of being causally related to study drug. 
• 
Two (2) or more participants experience a severe or clinically significant non-serious 
adverse event (based upon investigator judgment) which has a reasonable possibility 
of relation to study drug. Three (3) or more participants in a cohort experience the 
same adverse event of moderate severity which has a reasonable possibility of 
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Part B: Please see Dose Adjustment Pharmacokinetic Criteria (Section 7.2.3). 
6.8. 
Intervention after the End of the Study 
GSK will not provide treatment after the end of the study. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Study stopping criteria 
Recruitment will be halted by the sponsor if any of the following occur in participants 
receiving GSK3858279: 
Part A 
• One participant experiences an SAE that is considered to be related to 
GSK3858279 
• One participant experiences a significant clinical or laboratory abnormality that 
may plausibly relate to GSK3858279 (according to the clinical judgement of the 
investigator)  
• Two participants present with unexpected and clinically significant muco-
cutaneous bleeding (according to the clinical judgement of the investigator).  
Recruitment may be resumed after appropriate positive review of safety findings by the 
Principal Investigator, Medical Monitor and DEC, and following approval to restart the 
study from the regulatory agencies and ethics committees. 
Part B 
• Two participants experience a SAE that is considered related to GSK3858279. 
Please also refer to the next Section 8.5 (Adverse Events), Appendix 3 (Adverse 
Events) and the study-specific Safety Management Plan. 
• Two participants experience the same significant clinical or significant laboratory 
abnormality that may plausibly relate to GSK3858279 (according to the clinical 
judgement of the investigator)  
• Two participants present with unexplained and clinically significant muco-
cutaneous bleeding (according to the clinical judgement of the investigator and 
medical monitor) that is considered causally related to GSK3858279.  
Recruitment may be resumed after appropriate positive review of safety findings by the 
Principal Investigators, Medical Monitor and SRT, and following approval to restart the 
study from the regulatory agencies and ethics committees. 
7.2. 
Discontinuation of Study Intervention 
Not applicable for Part A.  


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In Part B, a participant will be permanently withdrawn from study treatment if any of the 
following symptoms or abnormalities occur, and an investigation will be carried out as 
described below.  After withdrawal of treatment (under these conditions), where possible 
participants should complete the Early Withdrawal visit and be followed up for safety 
monitoring. 
 
Study medications will be discontinued, and the participant withdrawn from the study in 
the event of any of the following: 
• A serious infection (including COVID-19) 
• Pregnancy 
• Severe or serious hypersensitivity reactions, including anaphylaxis 
• If the liver chemistry stopping criteria (Section 7.2.1) or QTc stopping criteria 
(Section 7.2.2) are met. 
• Other serious or severe adverse events, at the discretion of the Investigator, after 
consultation with the GSK Medical Monitor. 
Clinically significant deterioration of index knee pain or requiring recurrent rescue 
medication beyond the level permitted, at the discretion of the investigator, after 
consultation with the GSK Medical Monitor. 
7.2.1. 
Liver Chemistry Stopping Criteria 
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology.  
The Liver Safety Required Actions and Follow up Assessments Section and, Liver 
Stopping Event algorithm can be found in Appendix 6a and Appendix 6b, respectively 
respectively. 
7.2.2. 
QTc Stopping Criteria 
The QTc should be based on a single (initial reading in Part A) or the average of triplicate 
(Part B) ECG readings obtained over a brief (e.g., 5-10 minute) recording period. See the 
SoA (Section 1.3) for data to be collected at the time of intervention discontinuation and 
follow-up and for any further evaluations that need to be completed. 
A participant who meets the below QTc stopping criteria (based on the average of 
triplicate ECG readings) will be withdrawn from study intervention: 
QTc >500 msec OR Uncorrected QT >600 msec 
• 
For trial eligibility and discontinuation, ideally the same QT correction formula will 
be used for all participants within a single trial.  However, GSK does recognize that 
because multiple sites from different countries may participate in a single trial, this 
may not always be possible since QT correction formulae pre-programmed by 
different manufacturers within ECG machines tend to vary.  In these situations, the 
same QT correction formula must be used throughout the trial for an individual 
participant 


T M F -1 4 4 4 7 9 5 3  
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
5 9  
 
7. 2. 3.  
D o s e A dj u st m e nt P h ar m a c o ki n eti c Crit eri a  
T he f oll o wi n g criteri a will a p pl y.  
7. 2. 4.  
T e m p or ar y Di s c o nti n u ati o n  
N ot a p plica ble  f or Part A.  
F or Part B , if a p artici pa nt  e x perie nces a cli nicall y si g nifica nt A E t h at t he i n vesti gat or 
belie ves ma y be p ossi bl y, pr o ba bl y or defi nitel y  relate d t o i n vesti gati o nal pr o d uct (I P) 
a n d c o ul d p ote ntiall y b e e x acer bate d b y t h e ne xt d ose, t he i n vesti gat or ma y dela y I P 
d osi n g b y wit h h ol di n g o ne d ose  a n d s h o ul d c o ntact t he Me dical M o nit or. 
7. 3.  
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 
•  
A partici pa nt ma y wit h dr a w fr o m t he st u d y at a n y ti me at his/ her o w n re q uest or 
ma y b e wit h dra w n at a n y ti me at t he discreti o n of t he i n vesti gat or f or  safet y, 
be ha vi o ural , c o m plia n ce or a d mi nistrati ve reas o ns. 
•  
If t he partici p a nt wit h dra ws c o nse nt f or discl os ur e of f ut ure i nf or mati o n, t he 
s p o ns or ma y retai n a n d c o nti n ue t o use a n y d ata c ollecte d bef ore s uc h a 
wit h dra wal of c o nse nt.  
•  
If a partici pa nt wit h dra ws fr o m t he st u d y, h e/s he ma y re q uest destr u cti o n of a n y 
sa m ples ta ke n a n d n ot teste d, a n d t he i n vesti gat or m ust d oc u me nt t his i n t he site 
st u d y rec or ds. 
•  
At t he ti me of st u d y disc o nti n uati o n,  t he partici pa nt s h o ul d u n der g o t he 
assess me nts f or earl y wit h dra wal s h o w n i n t he S O A . 
 
7. 4.  
L o st t o F oll o w U p  
A partici pa nt  will be c o nsi dere d l ost t o f oll o w -u p if he or s he re peate dl y fails t o ret ur n f or 
sc he d ule d visits a n d is u na ble t o be c o ntacte d b y t he st u d y site.  
C CI


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The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• 
The site must attempt to contact the participant and reschedule the missed visit 
as soon as possible and counsel the participant on the importance of maintaining 
the assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study. 
• 
Before a participant is deemed lost to follow up, the investigator or designee 
must make every effort to regain contact with the participant (where possible, 3 
telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record. 
• 
Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study with a primary reason of lost to follow-up.  
 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
After providing informed consent, participants will undergo screening assessments. After 
a successful Screening Period of up to 28 days (for Part A) during which screening 
assessments will be performed (screening assessments may be carried out over multiple 
days), participants will be admitted to the clinical unit on the day prior to dosing. On Day 
1 they will receive a single IV or single SC dose of GSK3858279 or placebo then remain 
in house under supervision until discharged on Day 3. Participants will then return for 
outpatient visits and a follow up visit. The number of visits and the duration of the follow 
up period will depend on the dose level that the participant received. Details of the visits 
and follow up duration can be seen in the Treatment Groups and Duration section. There 
is a degree of flexibility around certain visits to facilitate scheduling. A visits schematic 
is included in Figure 1.  
For Part B the maximum Screening Period will be up to 42 days (screening assessments 
may be carried out on multiple days) refer to Section 4.1.1 and Figure 5 for SC treatment 
frequency and out-patient visits. 
• 
Study procedures and their timing are summarized in the SoA (Section 1.3).  
• 
Protocol waivers or exemptions are not allowed  
• 
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or 
discontinue study intervention. 
• 
Adherence to the study design requirements, including those specified in the SoA 
(Section 1.3), is essential and required for study conduct. 
• 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening 
log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable.  


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• 
Procedures conducted as part of the participant’s routine clinical management (eg, 
blood count) and obtained before signing of ICF may be utilized for screening or 
baseline purposes provided the procedure met the protocol-specified criteria and was 
performed within the time frame defined in the SoA (Section 1.3). 
• 
The maximum amount of blood collected from each participant over the duration of 
the study, including any extra assessments that may be required, will not exceed 500 
mL. 
• 
Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples. 
8.1. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.1.1. 
Physical Examinations 
• 
A full physical examination will include, at a minimum, assessments of the 
Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. 
Height and weight will also be measured and recorded. 
• 
A brief physical examination will include, at a minimum, assessments of the 
skin, lungs, cardiovascular system, and abdomen (liver and spleen). 
• 
Investigators should pay special attention to clinical signs related to previous 
serious illnesses. 
8.1.2. 
Vital Signs 
• 
Temperature, pulse rate, and blood pressure will be assessed following the sites 
local procedure. 
• 
Blood pressure and pulse measurements will be assessed in a semi-supine 
position with a completely automated device. Manual techniques will be used 
only 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 (eg, 
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 will be recorded at intervals of at least 1 minute). The average of the 3 
blood pressure readings will be recorded on the CRF. 
8.1.3. 
Electrocardiograms 
• 
Continuous cardiac telemetry will be performed as per the SoA (Section 
1.3).  Full disclosures will be reviewed in detail and the review maintained as 
part of the participant’s source documents. 


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• 
Triplicate or single 12-lead ECG will be obtained as outlined in the SoA 
(Section 1.3) using an ECG machine that automatically calculates the heart rate 
and measures PR, QRS, QT, and QTc intervals. Refer to Section 7.2.2  for QTc 
withdrawal 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. The full set of triplicates should be completed in less than 
10 minutes. 
• 
ECGs may be generated from telemetry. 
8.1.4. 
Clinical Safety Laboratory Assessments 
• 
Refer to Appendix 2 for the list of clinical laboratory tests to be performed and 
to the SoA (Section 1.3). for the timing and frequency.  
• 
The investigator must review the laboratory report, document this review, and 
record any clinically relevant changes occurring during the study in the AE 
section of the CRF. The laboratory reports must be filed with the source 
documents. Clinically significant abnormal laboratory findings are those which 
are not associated with the underlying disease, unless judged by the investigator 
to be more severe than expected for the participant's condition. 
• 
All laboratory tests, with values considered clinically significantly abnormal 
during participation in the study 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.  
• 
If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the aetiology should be identified, and the 
sponsor notified. 
• 
All protocol-required laboratory assessments, as defined in Appendix 2 must be 
conducted in accordance with the laboratory manual and the SoA (Section 1.3).  
8.1.5. 
Echocardiogram 
A transthoracic echocardiogram will be performed at screening and repeated if clinically 
significant changes are observed at any time during the study treatment. Images will be 
obtained in standard views, the time to acquire images should not exceed approximately 
45 minutes. 
8.1.6. 
Skin Reactions  
Skin reactions will be recorded as AEs. The investigator will assess any skin reactions for 
their clinical significance and clinically significant skin reactions (as per investigator’s 
judgement) will be reviewed by a dermatologist and if appropriate a skin biopsy will be 
requested for histological analysis. Further technical details will be provided in the SRM. 


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8. 2.  
P h ar m a c o ki n eti c s  
8. 2. 1.  
Bl o o d S a m pl e C oll e cti o n f or P h ar m a c o ki n eti c s 
Bl o o d sa m ples f or P K a n al ysis of G S K 3 8 5 8 2 7 9 will be c ollecte d at t he ti me p oi nts 
i n dicate d i n S o A  (Secti o n 1. 3 ). T he act ual date a n d ti me of eac h bl o o d sa m ple c ollecti o n 
will be rec or de d. T he ti mi n g of P K sa m ples ma y b e altere d a n d/ or P K sa m ples ma y b e 
o btai ne d at a d diti o nal ti me p oi nts t o e ns ure t h or o u g h P K m o nit ori n g. Bl o o d sa m ples of 
a p pr o xi matel y 3 m L f or P K a nal ysis of G S K 3 8 5 8 2 7 9 will be c ollecte d. Eac h P K sa m ple 
s h o ul d be c ollecte d as cl ose as p ossi ble t o t he pla n ne d ti me relati ve t o t he d ose (i.e., ti me 
zer o) a d mi nistere d t o t he partici pa nt o n P K da ys. T he act ual d ate a n d ti me of eac h bl o o d 
sa m ple c ollecti o n will be rec or ded.  
Details o n P K bl o o d sa m ple c ollecti o n i ncl u di n g pr ocessi n g, st ora ge, a n d s hi p pi n g 
pr oce d ures will be pr o vi de d i n t he S R M.  
Sa m ples ma y be retai n e d f or a ma xi m u m of 1 5 years after t he last partici pa nt c o m pletes 
t he st u d y. 
 
8. 2. 2.  
P h ar m a c o ki n eti c S a m pl e A n al y si s  
Ser u m
a nal ysis will be perf or me d u n der t he c o ntr ol of  I n Vitr o/I n Vi v o 
Tec h n ol o gies/ Bi oa n al ysis I m m u n o ge nicit y a n d Bi o mar kers (I VI V T/ BI B) , t he details of 
w hic h will be i ncl u de d i n t he S R M  a n d C L W as a p pr o priate . C o nce ntrati o ns of 
G S K 3 8 5 8 2 7 9 will be deter mi ne d i n ser u m sa m ples usi n g t he c urre ntl y a p pr o ve d 
bi oa nal ytical met h o d ol o g y. T he bi o a nal ytical site will be detaile d i n t he rel e va nt sa m ple 
pr ocessi n g d oc u me nts ( e. g. S R M, C L W) a n d ra w data will be arc hi ve d i n t he G S K R & D 
G L P arc hi ves.  Dr u g c o nce ntrati o n i nf or mati o n t hat ma y u n bli n d t he st u d y will n ot be 
re p orte d t o i n vesti gati ve sites or bli n de d pers o n nel u ntil t he st u d y has b ee n u n bli n de d. 
8. 3.  
Effi c a c y A s s e s s m e nt s  
Efficac y assess me nts will be c o n d ucte d i n Part B o f t he st u d y o nl y. 
8. 3. 1.  
P ati e nt R e p ort e d O ut c o m e s  
All patie nt re p orte d o utc o mes ( P R Os) s h o ul d be a d mi nistere d bef ore a n y la b orat or y 
assess men ts an d  ot her pr oce d ures  or c o ns ultati o ns t o a v oi d i nfl ue nci n g t h e partici pa nts ’ 
p erce pti o n of O A pai n.   
8. 3. 2.  
D ail y p ai n s c or e s   
Partici pa nts will rec or d pai n sc ores dail y (e ve ni n g ti me) i n a di gital t o ol f or t he 7 
c o nsec uti ve da ys prece di n g d osi n g ( d uri n g scree ni n g) a n d t he n dail y fr o m Da y 1 t o Da y 
8 4  (1 2  wee ks). T he y will assess, o ver t he p ast 2 4 h o urs, b ot h:  
- 
a vera ge k nee pai n i nte nsit y i n i n de x k nee 
- 
w orst k nee pai n i nte nsit y  i n i n de x k nee 
C CI


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6 4  
 
usi n g t he N R S, sc ori n g p ai n o n a n 1 1 -p oi nt scale ( 0 -1 0), wit h 0 = 
, a n d 1 0 =
 Partici pa nts  will be i nstr ucte d t o c o m plete t he pai n N R S 
matel y t he s a me ti me eac h da y. Partici pa nts will als o rec or d a n y 
resc ue p araceta m ol/aceta mi n o p he n f or k nee O A o ver t he past 2 4 h o n a di gital t o ol. 
8. 3. 3.  
W O M A C o st e o art hriti s i n d e x  
W O M A C I n de x 3. 1 will be c o m plete d b y partici pa nts o n pa per q uesti o n naires at ti me 
p oi nts s pecifie d i n t he S O A  (Bella m y , 1 9 8 8). T h e q uesti o n naire c o vers pai n, stiff ness a n d 
f u ncti o n relate d t o oste o art hritis i n t he i n de x k nee o ver t he past 7 da ys. Partici pa nts will 
res p o n d t o eac h q uesti o n usi n g a n 1 1-p oi nt N R S ( 0 -1 0), wit h 0 = n o 
T he y will be re q uire d 
t o ta ke at least 5 mi n utes t o c o m plete t he q uesti o n naire.  
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.
C CI


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8. 3. 7.  
J oi nt X -r a y 
X -ra y of t he k nee  wi ll be perf or me d at S cree ni n g f or eli gi bilit y a n d t he ra di o gra p hs are t o 
be rea d ce ntr all y b y t h e i ma gi n g C R O i n or der t o mi ni mise varia bilit y of t he rea d. T he 
k nee ra di o gra p hs will be e val uate d f or e x cl usi o n criteria ( Secti o n 5. 2 ) a n d eli gi bilit y t o 
c o nfir m a K ell gre n La wre nce  sc ore ≥2  (see i ncl usi o n criteri u m Secti o n 5. 1 ). Refer t o t he 
S R M f or details.  
8. 4.  
P h ar m a c o d y n a mi c s/ Bi o m ar k er s  
Bl o o d sa m ples  ( Parts A a n d B) a n d
will be c ollecte d fr o m 
partici pa nts i n t his st u d y t o i n vesti gate tar get e n ga ge m e nt a n d 
 ass o ciate d wit h p har mac od y n a mic effects.  
A n y s a m ples c ollecte d d uri n g t his st u d y ma y be use d t o e val uate n o v el bi o mar kers 
relate d t o t he pat h ol o g y of O A or t o i de ntif y fact ors t hat i nfl ue nce t he cli nical res p o nses 
a n d o utc o mes t o d osi n g wit h G S K 3 8 5 8 2 7 9. T his a p pr oac h m a y als o be  e xte n de d t o 
i ncl u de t he i de ntificati o n of bi o mar kers ass ociate d wit h A Es.  
T he ti mi n g of sa m ple c ollecti o ns ma y b e a dj uste d base d o n e mer gi n g P K data or ot her 
ne w i nf or mati o n fr o m t his st u d y t o e ns ure o pti mal e val uati o n of tar get e n ga ge m e nt. 
Details of t h e pr ocessi n g, st ora ge a n d s hi p pi n g pr oce d ures f or all sa m ples are pr o vi de d i n 
t he S R M. 
S a m ples ma y be retai n e d f or a ma xi m u m of 1 5 years after t he last partici pa nt c o m pletes 
t he st u d y. 
8. 4. 1.  
T ar g et E n g a g e m e nt  
Ser u m sa m ples  will be c ollecte d  f or t he e val uati o n of t he free a n d t otal c o nce ntrati o ns of 
C C L 1 7.  C C L 1 7 ca n be d etecte d i n cir c ulati o n a n d is t he bi ol o gical tar get f or 
G S K 3 8 5 8 2 7 9. T he i nte nti o n is t o e xa mi ne t he c orrelati o n bet wee n free a n d t otal C C L 1 7 
a n d t he effect of a d mi nistrati o n of G S K 3 8 5 8 2 7 9 o n t he free le vels of C C L 1 7 i n t he 
circ ulati o n.  
C CI
C CI
C CI
C CI


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C CI


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8. 5.  
I m m u n o g e ni cit y A s s e s s m e nt s 
Ser u m sa m ples will be c ollecte d  fr o m all treate d partici pa nts at pre-d ose a n d vari o us ti me 
p oi nts p ost -d osi n g. T he was h o ut sa m ples will be c ollecte d at t he f oll o w -u p visit t o 
mi ni mise i nterfere nce of circ ulati n g dr u g i n t he a nti b o d y assess me nts, see S o A ( Secti o n 
1. 3. 5 ). Testi n g will be perf or me d usi n g t he t y pical tiere d a p pr oac h i n v ol vi n g scree ni n g, 
c o nfir mati o n a n d titrati o n assa ys [ E M E A , 2 0 1 7; F D A , 2 0 1 4], perf or me d b y I VI V T, G S K. 
If sera c o ntai n p ote ntial a nti-G S K 3 8 5 8 2 7 9 a nti b o dies, t he y will be c o nfir me d b y 
i m m u ne-c o m petiti o n usi n g e x cess dr u g, f oll o we d b y a titrati o n ass a y.  
F or eac h partici pa nt, i m m u n o ge nicit y res ults, i ncl u di n g t he i nci de nce a n d titres, will be 
re p orte d. 
8. 6.  
A d v er s e E v e nt s  
T he defi niti o ns of a n A E or S A E ca n be f o u n d i n A p pe n di x 3 . 
C o ns ult t he Safet y Ma n a ge m e nt Pla n (S M P : a f or mal versi o n -c o ntr olle d d oc u me nt ). T he 
S M P descri bes a n d ser ves t o e ns ure G S K’s o verall acc o u nta bilit y b y ma xi mizi n g 
tra ns pare n c y o n i n di vi d ual r oles a n d res p o nsi bilities f or i nitial a n d f oll o w u p of safet y 
re p orti ng a n d of t he o n w ar d re p orti n g res p o nsi bilities t o re g ul at or y a ge n cies, et hics 
c o m mittees  a n d in vesti gat ors.  
T he i n vesti gat or a n d a n y desi g nees are res p o nsi ble f or detecti n g, d o c u me nti n g, a n d 
re p orti n g e ve nts t hat meet t he defi niti o n of a n A E or S A E a n d re m ai n res p o nsi ble f or 
f oll o wi n g u p A Es t hat are seri o us, c o nsi dere d relate d t o t he st u d y i nter ve nti o n or t he 
st u d y, or t hat c a use d t he partici pa nt t o disc o nti n ue t he st u d y (see Secti o n 7 ).  
8. 6. 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  
•  
All S A Es will be c ollecte d fr o m t he start of st u d y i nter ve nti o n u ntil t he f oll o w-
u p visit  at t he ti me p oi nts s pecifie d i n t h e S o A  ( Secti o n 1. 3 ).  H o we v er, a n y 
S A Es assesse d as r elate d t o st u d y partici pati o n ( e. g., st u d y i nter ve nti o n, 
pr ot oc ol -ma n date d pr oce d ures, i n vasi ve  tests, or c ha n ge i n e xisti n g t hera p y) or 
relate d t o a G S K pr o d uct will be rec or de d fr o m t h e ti me a partici pa nt c o nse nts t o 
partici pate i n t he st u d y.   
•  
All A Es will be c ollecte d fr o m t he d ose of st u d y i nter ve nti o n u ntil t he f oll o w -u p 
visit ( Secti o n 1. 3 ). 
C CI
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• 
Medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will be recorded on the Medical History/Current 
Medical Conditions section of the CRF (not the AE section). 
• 
All SAEs will be recorded and reported to the sponsor or designee immediately 
and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. The investigator will submit any updated SAE data to the sponsor 
within 24 hours of it being available. 
• 
Investigators are not obligated to actively seek AEs or SAEs in former study 
participants. However, if the investigator learns of any SAE, including a death, 
at any time after a participant has been discharged from the study, and he/she 
considers the event to be reasonably related to the study intervention or study 
participation, the investigator must promptly notify the sponsor. 
8.6.2. 
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.  
• 
Participants will be provided with a diary card to collect any changes in health 
between clinic visits. 
• 
The method of recording, evaluating, and assessing causality of AEs and SAEs 
and the procedures for completing and transmitting SAE reports are provided in 
Appendix 3. 
8.6.3. 
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 7.4). Further information on follow-up procedures is given in 
Appendix 3. 
8.6.4. 
Regulatory Reporting Requirements for SAEs 
• 
Prompt notification by the investigator to the sponsor of a SAE is essential so 
that legal obligations and ethical responsibilities towards the safety of 
participants and the safety of a study intervention under clinical investigation are 
met.  
• 
The sponsor has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study intervention 
under clinical investigation. The sponsor will comply with country-specific 
regulatory requirements relating to safety reporting to the regulatory authority, 
Institutional Review Boards (IRB)/Independent Ethics Committees (IEC), and 
investigators. 


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• 
Investigator safety reports must be prepared for suspected unexpected serious 
adverse reactions (SUSAR) according to local regulatory requirements and 
sponsor policy and forwarded to investigators as necessary. 
• 
An investigator who receives an investigator safety report describing a SAE or 
other specific safety information e.g., summary or listing of SAE from the 
sponsor will review and then file it along with the Investigator’s Brochure and 
will notify the IRB/IEC, if appropriate according to local requirements. 
8.6.5. 
Cardiovascular and Death Events – Part B only 
For any cardiovascular events detailed in Appendix 3 and all deaths, whether or not they 
are considered SAEs, specific Cardiovascular (CV) and Death sections of the CRF will 
be required to be completed.  These sections include questions regarding cardiovascular 
(including sudden cardiac death) and non-cardiovascular death.  
The CV CRFs are presented as queries in response to reporting of certain CV medical 
dictionary for regulatory activities (MedDRA) terms.  The CV information should be 
recorded in the specific cardiovascular section of the CRF within one week of receipt of a 
CV Event data query prompting its completion.   
The Death CRF is provided immediately after the occurrence or outcome of death is 
reported. Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported. 
8.6.6. 
Pregnancy 
• 
The Sponsor will make an effort to collect pregnancy details in female partners of 
male participants after the dose of study intervention and until 28 weeks after the 
dose. 
• 
If a pregnancy is reported, the investigator should inform GSK within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in Appendix 4. 
• 
Abnormal pregnancy outcomes (e.g. spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAE. 
8.7. 
Treatment of Overdose 
For this study, any dose of GSK3858279 greater than the scheduled dose will be 
considered an overdose. 
In the event of an overdose, the investigator should: 
• Contact the Medical Monitor immediately. 
• Closely monitor the participant for AE/SAE and laboratory abnormalities until the 
study intervention can no longer be detected systemically (at least 5 half-lives but not 
less than 90 days). Document the quantity of the excess dose as well as the duration 
of the overdosing in the CRF. 


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Decisi o ns re gar di n g d ose i nterr u pti o ns or m o dificati o ns will be ma de b y t h e i n vesti gat or 
i n c o ns ultati o n wit h t he Me dical M o nit or base d o n t he cli nical e val uati o n of t he 
partici pa nt.  
8. 9.  
H e alt h E c o n o mi c s O R M e di c al R e s o ur c e Utili z ati o n a n d 
H e alt h E c o n o mi c s  
Healt h Ec o n o mics/ Me dic al Res o urce Utilizati o n a n d Healt h Ec o n o mics  para meters a re 
n ot e val uate d i n t his st u d y.  
9.  
S T A TI S TI C A L C O N SI D E R A TI O N S  
9. 1.  
H y p ot h e s e s  
Part A: As t he pri mar y o bjecti ve of t he st u d y is safet y, t h ere are n o f or mal h y p ot hes es t o 
be e val uat e d. A n assess m e nt of d ose pr o p orti o nalit y will be c o n d u cte d f or selecte d 
p har mac o ki ne tic e n d p oi nts (i.e. C ma x, a n d area u n der t he ser u m c o nce ntrati o n -ti me 
c ur ve fr o m zer o t o ti me t [A U C( 0 -t)] or t o i nfi nit y [A U C ( 0-∞] ) f oll o wi n g si n gle I V d ose. 
Part B: A c o m paris o n bet wee n G S K 3 8 5 8 2 7 9 a n d Place b o will be ma de o n t he pai n 
n u merical r ati n g scale. A n assess me nt of t he pr o b a bilit y of s uccess will als o be ma de 
c o m pari n g G S K 3 8 5 8 2 7 9 t o place b o wit h res p ect t o t he ke y pai n e n d p oi nts.  
C CI
C CI


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9.2. 
Sample Size Determination 
9.2.1. 
Sample Size Assumptions 
In Part A, at each dose level studied there will be six participants randomised to each of 
the GSK3858279 treatment groups. For each dose level, there will also be two 
participants receiving placebo. The sample size is based on feasibility and will be 
conducted at one centre. 
The primary objective of the study is safety, where the number of safety events would be 
of interest, for example the number who experience a particular adverse event. At each 
dose level six participants will receive GSK3858279. If 0/6 of a particular safety event in 
the GSK3858279 group is observed, using a Bayesian approach to determine the credible 
interval around an observed safety event, we would assume a flat Beta (1,1) prior, and if 
we were to observe 1 safety event in 6 then the posterior distribution would be Beta (2, 
6), where we can be 95% certain that the true probability of the safety event lies between 
0.04 and 0.58. 
A key secondary objective for the study is to determine the pharmacokinetics of the 
GSK3858279. However, there have been no studies conducted to date within an 
appropriate population to assess pharmacokinetic precision estimates with six participants 
per treatment group. 
In Part B, approximately 50 participants (minimum of 20 to a maximum of 80) will be 
randomised in a 1:1 ratio to receive GSK3858279 or placebo. A positive conclusion will 
be declared if, given the data, there is at least 90% probability that the difference vs 
placebo is better than 0. A negative conclusion will be declared if, given the data, there is 
at least 85% probability that the difference vs placebo is worse than -1.0. 
For the primary comparison, assuming a change from baseline in participant’s assessment 
of pain score of -1.5 on placebo, and a standard deviation (SD) of 1.8 (Study 
NCT02683785 and Lane, 2010), with 50 participants, if the true treatment difference is 0 
between the two treatments 82% of trials will be declared negative. If the true treatment 
difference is 1 then 75% of trials will be declared positive. Under these assumptions, the 
least significant difference between GSK3858279 and placebo would be -0.85. 
If the estimated SD during the trial differs from 1.8, then the sample size may be 
decreased or increased up to a maximum of 80 total participants to ensure robust 
conclusions can be drawn. 
9.2.2. 
Sample Size Sensitivity 
Part A 
A sample size sensitivity analysis has been conducted on the primary endpoint, to 
investigate different safety event rates.  If the number of participants who completed each 
active dose reduces, then the true incidence rates of safety events that could not be ruled 
out would change.  These changes are outlined below: 


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N 
Completing 
Cohort 
Number of a particular 
safety event observed with 
GSK3858279 
Upper limit of exact 95%CI indicating 
that a true incidence rate of x% could 
not be ruled out 
6 
2 
71% 
3 
82% 
5 
0 
46% 
1 
64% 
2 
78% 
4 
0 
52% 
1 
72% 
2 
85% 
 
Part B 
A sample size sensitivity analysis has been conducted on the primary endpoint in Part B, 
to investigate a decrease or an increase in SD, current design and prediction highlighted: 
 
N per Arm 
SD 
Proportion of 
trials correctly 
deemed 
negative if true 
treatment 
difference is 0 
Proportion of 
trials correctly 
deemed 
negative if true 
treatment 
difference is -1 
Least 
Significant 
Difference 
14 
1.4 
80% 
73% 
-0.87 
1.8 
67% 
57% 
-1.12 
2 
61% 
52% 
-1.24 
2.2 
57% 
47% 
-1.37 
2.4 
53% 
43% 
-1.49 
22 
1.4 
91% 
86% 
-0.69 
1.8 
79% 
71% 
-0.91 
2 
73% 
65% 
-1.00 
2.2 
68% 
59% 
-1.11 
2.4 
64% 
54% 
-1.21 
25 
1.4 
93% 
89% 
-0.65 
1.8 
82% 
75% 
-0.85 
2 
77% 
69% 
-0.94 
2.2 
72% 
63% 
-1.04 
2.4 
67% 
58% 
-1.13 
32 
1.4 
97% 
94% 
-0.58 
1.8 
88% 
83% 
-0.75 
2 
83% 
76% 
-0.83 
2.2 
78% 
70% 
-0.91 


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N per Arm 
SD 
Proportion of 
trials correctly 
deemed 
negative if true 
treatment 
difference is 0 
Proportion of 
trials correctly 
deemed 
negative if true 
treatment 
difference is -1 
Least 
Significant 
Difference 
2.4 
74% 
65% 
-1.00 
40 
1.4 
98% 
97% 
-0.51 
1.8 
90% 
85% 
-0.67 
2 
88% 
83% 
-0.74 
2.2 
84% 
77% 
-0.82 
2.4 
80% 
72% 
-0.89 
 
A sample size of up to 14 per arm (28 total) could be used to maintain the acceptable 
operating characteristics SD of up to 1.4, and thus provide similar operating 
characteristics as a trial of 50 participants with and SD of 1.8. 
A sample size of up to 40 per arm (80 total) could be used to maintain the acceptable 
operating characteristics SD of up to 2.4, and thus provide similar operating 
characteristics as a trial of 50 participants with and SD of 1.8. 
If the SD is 1.8 then a total of 22 (44 total) per arm completing Week 8 would still 
provide acceptable operating characteristics. 


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9.3. 
Populations for Analyses 
For purposes of analysis, the following populations are defined, additional analyses 
populations may be defined in the Reporting and Analyses Plan: 
Population 
Description 
Safety 
• All randomized participants who received at least one dose of 
study treatment. 
• This population will be based on the treatment the participant 
received.  
Intent-to-Treat (ITT) 
• All randomized participants who received at least one dose of 
study treatment. 
• This population will be based on the treatment the participant 
was randomized to. 
• Any participants who receives a treatment randomization 
number will be considered to have been randomized. 
Pharmacokinetic (PK) 
• All participants in the Safety population who had at least 1 
non-missing serum PK assessment.  
• This population will be based on the treatment the participant 
received.  
• Note: Non-quantifiable [NQ] values will be considered as 
non-missing values   
Per Protocol 
• All participants in the ITT population who comply with the 
protocol. 
• Protocol deviations that would exclude participants from the 
PP population are defined in reporting and analyses plan. 
Fully treated 
• All participants in the Safety population who received at least 
80% of planned study treatment. 
• This population will be identified by review of protocol 
deviations 
9.4. 
Statistical Analyses 
Parts A and B will be reported separately in the outputs. 
9.4.1. 
Efficacy Analyses 
All efficacy analyses will be performed on the ITT population. 


T M F -1 4 4 4 7 9 5 3  
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
7 5  
 
E n d p oi nt  
St ati sti c al A n al ysi s M et h o d s  
Pri m ary  
T h e p ai n sc or es will b e list ed f or eac h p articip ant a n d i nt erv e nti on a n d 
s u m m ariz e d d escri ptively by i nt erv e nti o n. A Bay esi an re p eat e d m e asur es 
m o d el usi ng a n on -i nf or mativ e prior will b e fitte d t o th e pai n c ha n ge fr o m 
b as eli ne d a t a a n d  pr ob a bilities of succ ess will b e d et er mi n e d a n d pr es e nt e d at 
e ac h ti m e p oi nt.  
Ex pl or atory  
Will b e d escri b ed i n th e r eporti n g a n d a nalysis pl a n  
9. 4. 2.  
S af et y A n al y s e s  
All safet y a nal yses will be perf or me d o n t he Safet y P o p ulati o n.  
E n d p oi nt  
St ati sti c al A n al ysi s M et h o d s  
Pri m ary  
Will b e pr es e nt e d i n ta b ul ar a n d/or gr ap hic al for mat an d s u m m aris e d 
d escri ptiv ely accor di n g t o G S K's Int e gr at ed D ata Sta ndar ds Li br ary sta nd ar ds.  
9. 4. 3.  
P h ar m a c o ki n eti c s A n al y s e s  
All P K a nal ys es will be perf or me d o n t h e P har mac o ki netic P o p ulati o n.  
E n d p oi nt  
St ati sti c al A n al ysi s M et h o d s  
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T M F -1 4 4 4 7 9 5 3  
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
7 6  
 
E n d p oi nt  
St ati sti c al A n al ysi s M et h o d s  
9. 4. 5.  
I nt eri m A n al y s e s 
P art A:  N o f or mal i nteri m statistical a nal yses are pla n n e d. H o we v er, d ose escalati o n 
meeti n gs will occ ur at a rele va nt ti me p oi nt after eac h d ose le vel; i ncl u di n g bet wee n Parts 
A a n d B.  
T he decisi o n t o pr ocee d t o t he ne xt c o h ort, a n d ne xt d ose stre n gt h t o be st u die d, will be 
ma de b y t he D E C base d o n assess me nt o f safet y a n d ser u m G S K 3 8 5 8 2 7 9 
p har mac o ki netic d ata o bt ai ne d i n all partici pa nts at t he pri or d ose le vel. I n di vi d ual safet y 
data ( A Es , la b orat or y safet y tests, E C Gs a n d vital si g ns) will be re vie we d. I n a d diti o n, 
u n -bli n de d preli mi nar y P D data ma y be re vie w e d b y t he D E C d uri n g t he st u d y; w here t he 
G S K bi ol o g y lea d will j oi n t he D E C i n t hese disc ussi o ns. O nce s ufficie nt s afet y, P K a n d 
tar get e n ga ge me nt data is c ollecte d fr o m t he t o p I V d ose a n d S C c o h orts, a data re vie w 
will ta ke place a n d a decisi o n t o pr oce e d wit h Part B of t he st u d y ma y be m a de. F urt her 
details are i ncl u de d i n t he D E P.  
U n bli n de d data fr o m Part A ma y b e re p orte d o ut i n f ull f oll o wi n g t he last s u bject last 
visit i n t his part of t he st u d y a n d pri or t o t he c o n cl usi o n of Part B.  
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Part B: An interim analysis will occur once approximately 20 participants have 
completed the Week 4 assessment. A second interim analysis and an unblinded sample 
size re-estimation may occur prior to enrolling the 50th participant, where the sample size 
could be decreased to a minimum of 20 or increased to a maximum of 80 participants. 
Additional interim analyses may occur in order to inform internal decision making. Full 
details of all interim analyses will be prospectively outlined in the interim analyses 
charter. 
At the interim analyses, treatment group level, efficacy, safety, PK, TE, rescue 
medication and ADA data may be reviewed by a list of people included in the IA charter, 
including the Project Leader and Independent Internal Review Board and internal 
governance boards as required. Individual participant data may be reviewed at the request 
of the project leader, but subject identification numbers will be removed to maintain the 
blind.    
If there are interactions with regulatory agencies, any interim data presented will be at the 
treatment group level unless individual participant data is requested. Unblinded safety 
information may be presented at an individual level 
Dependent on the results observed, the study could be stopped for futility, based on pre-
specified futility criteria defined in the IA charter, or via the sample size re-estimation 
which may result in the sample size being decreased or increased.  
The Reporting and Analysis Plan will describe the planned statistical analyses performed 
at the interim analyses in greater detail. 


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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, Investigator Brochure, and other 
relevant documents (e.g., advertisements) must be submitted to an IRB/IEC by 
the investigator and reviewed and approved by the IRB/IEC before the study is 
initiated.  
• 
Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants.  
• 
The investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/EC 
• Notifying the IRB/IEC of SAE or other significant safety findings as 
required by IRB/IEC procedures 
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 Code of Federal Regulation (CFR), ICH guidelines, the 
IRB/IEC, European regulation 536/2014 for clinical studies (if applicable), 
and all other applicable local regulations 
10.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 


T M F -1 4 4 4 7 9 5 3  
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
7 9  
 
1 0. 1. 3.  
I nf or m e d C o n s e nt Pr o c e s s 
•  
T he i n vesti gat or or his/ her re prese nt ati ve will e x plai n t he nat ure of t h e st u d y t o 
t he partici pa nt or his/ her le gall y a ut h orize d re pres e ntati ve a n d a ns w er all 
q uesti o ns re gar di n g t he st u d y.  
•  
Partici pa nts m ust be i nf or me d t hat t heir partici p ati o n is v ol u ntar y. Partici pa nts 
or t heir le gall y a ut h orize d re pres e ntati ve will be re q uire d t o si g n a state me nt of 
i nf or me d c o nse nt t hat meets t he re q uire m e nts of 2 1 C F R 5 0, l ocal re g ulati o ns, 
I C H g ui deli nes, Healt h I ns ura nce P ort a bilit y a n d Acc o u nta bilit y Act ( HI P A A) 
re q uire me nts, w h ere a p plica ble, a n d t he I R B/I E C or st u d y ce ntre .  
•  
T he me dical r ec or d m ust i ncl u de a state me nt t hat writte n i nf or me d c o ns e nt was 
o btai ne d bef ore t he partici pa nt was e nr olle d i n t he st u d y a n d t he date t he writte n 
c o nse nt was o btai ne d. T h e a ut h orize d pers o n o btai ni n g t he i nf or m e d c o nse nt 
m ust als o si g n t he I C F.  
•  
Partici pa nts m ust be re -c o nse nte d t o t he m ost c urre nt versi o n of t he I C F(s) 
d uri n g t heir p artici pati o n i n t he st u d y.  
•  
A c o p y of t he I C F(s) m ust be pr o vi de d t o t he partici pa nt or t he partici pa nt’s 
le gall y a ut h orize d re pres e ntati ve.  
•  
Partici pa nts w h o are rescree ne d a re re q uir e d t o si g n a ne w I C F. 
 
1 0. 1. 4.  
D at a Pr ot e cti o n  
•  
Partici pa nts will be assi g ne d a u ni q ue i de ntifier b y t he s p o ns or. A n y partici pa nt 
rec or ds or datasets t hat are tra nsferre d t o t he s p o ns or will c o ntai n t he i de ntifier 
o nl y; partici pa nt n a mes or a n y i nf or mati o n w hic h w o ul d ma ke t he partici p a nt 
i de ntifia ble will n ot be tra nsferre d.  
•  
T he partici pa nt m ust be i nf or me d  t hat his/ her pers o nal st u d y-relate d d ata will be 
use d b y t h e s p o ns or i n acc or da nce wit h l ocal dat a pr otecti o n la w. T he l e vel of 
discl os ure m ust als o be e x plai ne d t o t he partici pa nt.  
•  
T he partici pa nt m ust be i nf or me d t hat his/ her me dical rec or ds ma y be e x a mi ne d 
b y Cli nical Q ualit y Ass ura nce a u dit ors or ot her a ut h orize d pers o n nel a p p oi nte d 
b y t he s p o ns or, b y a p pr o priate I R B/I E C me m b ers, a n d b y i ns p ect ors fr o m 
re g ulat or y a ut h orities. 
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10.1.5. 
Committees Structure 
Oversight of safety for Part A: The DEC will make the decision to proceed to the next 
dose level of GSK3858279 at the end of each cohort; along with assessing the interim 
analysis data for Part B of the study. For details of the information to be considered as 
part of this decision-making process see the DEP. 
Safety and PK stopping criteria will be strictly applied.  Details of these criteria can be 
found in Section 7.2. There will be an open and closed part to the dose escalation 
meeting. At the beginning of the meeting blinded data will be discussed in an open 
forum with the investigator in attendance. If required, the data will then be reviewed in 
an unblinded fashion by the unblinded members of the DEC. These unblinded members 
include the Medical Monitor, GSK SMG representative, GSK statistician and GSK 
pharmacokineticist. A DEP will be written outlining in detail how the study team will 
ensure data integrity used in dose selection decisions by performing clinical data review 
and appropriate quality control of data prior to making dose selection decisions, as well 
as outlining the responsibilities of the investigators and site staff for reporting safety 
data, participation during dose escalation meetings, and confirmation that the data used 
for dose escalation are accurate and complete. 
Oversight of safety for Part B will be provided by a sponsor SRT. The SRT will conduct 
in-stream review of blinded safety data including AE, SAEs, vital signs and laboratory 
data at appropriate intervals during the study. The membership of the SRT will include 
the GSK Medical Monitor, GSK Statistician and a GSK Safety and Medical Governance 
representative or appropriate designees. 
 
The SRT may decide to alter the study conduct at any time to ensure participant safety 
and any such changes to study conduct for safety reasons will be promptly communicated 
to the appropriate Regulatory Authorities and IRB/IEC. Additional detail regarding the 
composition and actions of the SRT will be included in the SRT charter. 
10.1.6. 
Dissemination of Clinical Study Data 
• 
Where required by applicable regulatory requirements, an investigator signatory 
will be identified for the approval of the clinical study report. The investigator 
will be provided reasonable access to statistical tables, figures, and relevant 
reports and will have the opportunity to review the complete study results at a 
GSK site or other mutually-agreeable location. 
• 
GSK will also provide the investigator with the full summary of the study 
results. The investigator is encouraged to share the summary results with the 
study participant, as appropriate. 
• 
GSK will provide the investigator with the randomization codes for their site 
only after completion of the full statistical analysis. 
• 
The procedures and timing for public disclosure of the protocol and results 
summary and for development of a manuscript for publication for this study will 
be in accordance with GSK Policy. 


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• 
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.  
• 
The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF.  
• 
The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents.  
• 
Monitoring details describing strategy (e.g., risk-based initiatives in operations 
and quality such as Risk Management and Mitigation Strategies and Analytical 
Risk-Based Monitoring), methods, responsibilities and requirements, including 
handling of noncompliance issues and monitoring techniques (central, remote, 
or on-site monitoring) are provided in the Monitoring Plan. 
• 
The sponsor or designee is responsible for the data management of this study 
including quality checking of the data.  
• 
The sponsor assumes accountability for actions delegated to other individuals 
(e.g., Contract Research Organizations). 
• 
Study monitors will perform ongoing source data verification to confirm that 
data entered into the CRF by authorized site personnel are accurate, complete, 
and verifiable from source documents; that the safety and rights of participants 
are being protected; and that the study is being conducted in accordance with the 
currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements.  
• 
Records and documents, including signed ICF, pertaining to the conduct of this 
study must be retained by the investigator for 25 years from the issue of the final 
Clinical Study Report (CSR)/ equivalent summary unless local regulations or 
institutional policies require a longer retention period. No records may be 
destroyed during the retention period without the written approval of the 
sponsor. No records may be transferred to another location or party without 
written notification to the sponsor.  
10.1.8. 
Source Documents 
• 
Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 


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• 
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 can be found in a study specific 
source document agreement. 
10.1.9. 
Study and Site Closure 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
• 
Inadequate recruitment of participants by the investigator 
• 
Discontinuation of further study intervention development 
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 4 will be performed by the local laboratory in Part A 
and the central laboratory in Part B. Alcohol, Tobacco screens and COVID-19 
tests will be performed as per standard local practice in Part B.  
• 
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 4 
Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Haematology 
Platelet Count  
RBC Indices: 
MCV 
MCH 
%Reticulocytes 
WBC count with Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC Count 
Hemoglobin 
Hematocrit 
Clinical 
Chemistry1,2,3,4 
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 
Glucose (non-
fasting) 
Calcium 
Alkaline 
phosphatase 
2Cardiac 
troponin T 
3NT-proBNP 
Routine 
Urinalysis 
• Specific gravity 
• pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, 
leukocyte esterase by dipstick 
• Microscopic examination and laboratory quantification of proteinuria (if 
blood or protein is abnormal on dipstick) 
• Part B: Alcohol 
Breath 
• Part A: Alcohol (breathalyzer) 


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Laboratory 
Assessments 
Parameters 
Combined 
throat and 
nasopharyngeal 
swab 
• COVID-19 (SARS-CoV2) (see SRM for further details) 
Other 
Screening 
Tests 
Blood (serum) 
• Follicle-stimulating hormone and estradiol (as needed in women of non-
childbearing potential only) 
• Serology (TB test, HIV antibody, HBsAg, HBcAb and hepatitis C virus 
antibody)  
• QuantiFERON test  
• Complement protein C3 and C4 
Urine 
• Urine drug screen to include at minimum: amphetamines, barbiturates, 
cocaine, opiates, cannabinoids and benzodiazepines. 
• Urine albumin-creatinine ratio (UACR) 
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 7.2.1 and Appendix 6a and Appendix 6b All events of ALT ≥3 × upper 
limit of normal (ULN) and bilirubin ≥2 × ULN (>35% direct bilirubin) or ALT ≥3 × ULN and international 
normalized ratio (INR) >1.5, if INR measured, which may indicate severe liver injury (possible Hy’s Law), must 
be reported as an SAE (excluding studies of hepatic impairment or cirrhosis). 
2. 
Troponin T using high sensitivity test. 
3. 
NT-proBNP (N-terminal pro B-type natriuretic peptide) at -Screening and Day 57 visit only.  
 
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. 
 
 


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


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


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Results in persistent disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
• 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhoea, 
influenza, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
Is a congenital anomaly/birth defect 
Other situations: 
• 
Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 
10.3.3. 
Definition of Cardiovascular Events – Part B only 
Cardiovascular Events (CV) Definition: 
Investigators will be required to fill out the specific CV event page of the CRF for the 
following AEs and SAEs: 
• 
Myocardial infarction/unstable angina 
• 
Congestive heart failure 
• 
Arrhythmias 
• 
Valvulopathy 
• 
Pulmonary hypertension 
• 
Cerebrovascular events/stroke and transient ischemic attack 
• 
Peripheral arterial thromboembolism 
• 
Deep venous thrombosis/pulmonary embolism 
• 
Revascularization 


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10.3.4. 
Recording and Follow-Up of AE and SAE 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory, and diagnostics reports) 
related to the event. 
• 
The investigator will then record all relevant AE/SAE information in the CRF. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the GSK /AE/SAE CRF page. 
• 
There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to GSK. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories:  
• 
Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities. 
• 
Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities. 
• 
Severe: An event that prevents normal everyday activities. An AE that is assessed 
as severe should not be confused with an SAE. Severe is a category utilized for 
rating the intensity of an event; and both AE and SAE can be assessed as severe. 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe. 
 
Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE. 
• 
A "reasonable possibility" of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
• 
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• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• 
The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment. 
• 
For each AE/SAE, the investigator must document in the medical notes that 
he/she has reviewed the AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK. However, it is very 
important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to GSK. 
• 
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of AE and SAE 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK 
to elucidate the nature and/or causality of the AE or SAE as fully as possible. This 
may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals. 
• 
If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide GSK with a copy of any post-
mortem findings including histopathology. 
• 
New or updated information will be recorded in the originally completed CRF. 
• 
The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
10.3.5. 
Reporting of SAE to GSK 
SAE Reporting to GSK via Electronic Data Collection Tool 
• 
The primary mechanism for reporting SAE to GSK will be the electronic data 
collection tool. 
• 
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours. 
• 
The site will enter the SAE data into the electronic system as soon as it becomes 
available. 


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


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


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Males must use the male condom and should be advised of the benefit for a female 
partner to use a highly effective method of contraception as outlined in Section 10.4.2. 
10.4.2. 
Contraception guidance for female partners of males who are in 
the studya: 
• 
Highly Effective Methodsb That Have Low User Dependency  
• 
Implantable progestogen-only hormone contraception associated with inhibition of 
ovulationc 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS)c 
• 
Bilateral tubal occlusion 
• 
Vasectomized partner 
• 
Note: Vasectomized partner is a highly effective contraceptive method provided that 
the partner is the sole sexual partner of the woman of childbearing potential and the 
absence of sperm has been confirmed. If not, an additional highly effective method of 
contraception should be used. Spermatogenesis cycle is approximately 90 days. 
• 
Highly Effective Methodsb That Are User Dependent  
• 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationc 
• 
oral 
• 
intravaginal 
• 
transdermal 
• 
injectable 
• 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
• 
oral 
• 
injectable 
• 
Sexual abstinence 
• 
Note: Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with 
the study intervention. The reliability of sexual abstinence needs to be evaluated in 
relation to the duration of the study and the preferred and usual lifestyle of the 
participant 
b. 
 should be consistent with local regulations 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 and female partners of study male participants advised of the benefit to use 
hormonal contraception in addition If locally required, in accordance with Clinical Trial Facilitation Group 
(CTFG) guidelines, acceptable contraceptive methods are limited to those which inhibit ovulation as the 
primary mode of action. 
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception for this 
study. Male condom and female condom should not be used together (due to risk of failure with friction) 


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10.4.3. 
Collection of Pregnancy Information: 
Male participants with partners who become pregnant 
• 
Investigator will attempt to collect pregnancy information on any male participant’s 
female partner who becomes pregnant while participating in this study. This applies 
only to male participants who receive study intervention. 
• 
After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the investigator will record pregnancy information on the 
appropriate form and submit it to GSK within 24 hours of learning of the partner’s 
pregnancy.  
• 
The female partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to GSK. 
• 
Generally, follow-up will be no longer than 6 to 8 weeks following the estimated 
delivery date. Any termination of the pregnancy will be reported regardless of foetal 
status (presence or absence of anomalies) or indication for procedure.  


T M F -1 4 4 4 7 9 5 3  
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
9 4  
 
C CI


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10.6. 
Appendix 6a: Liver Safety: Required Actions and Follow-up 
Assessments  
Phase I liver chemistry stopping criteria have been designed to assure participant safety 
and to evaluate liver event etiology.  
Phase I liver chemistry stopping criteria and required follow up assessments  
Liver Chemistry Stopping Criteria – Liver Stopping Event 
 
ALT-absolute 
 
ALT≥3xULN 
If ALT≥3xULN AND bilirubin1,2 ≥ 2xULN (>35% direct bilirubin) OR INR 
>1.5, Report as an SAE. 
See additional Actions and Follow Up Assessments listed below 
Required Actions and Follow up Assessments  
Actions 
Follow Up Assessments 
• Immediately discontinue study intervention (Part 
B only) 
• Report the event to GSK within 24 hours 
• Complete the liver event case report form 
(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, stabilise, or return to within baseline 
(see MONITORING below) 
• Do not restart or rechallenge participant with 
study intervention (Part B only) 
MONITORING: 
If ALT≥3xULN AND bilirubin ≥ 2xULN or INR 
>1.5:  
• Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
liver event follow up assessments within 24 hrs 
• Monitor participants twice weekly until liver 
chemistries resolve, stabilise or return to within 
baseline 
• Viral hepatitis serology3 
• Obtain INR and recheck with each 
liver chemistry assessment until the 
transaminases values show 
downward trend 
• Obtain blood sample for 
pharmacokinetic (PK) analysis, as 
soon as possible, and at least within 
7 days4 
• 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 case 
report form (CRF) 
• Record use of concomitant 
medications on the concomitant 
medications CRF page including 
acetaminophen, herbal remedies, 
other over the counter medications. 


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• A specialist or hepatology consultation is 
recommended 
If ALT≥3xULN AND bilirubin < 2xULN and INR 
≤1.5:  
• Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
liver event follow up assessments within 24-72 
hrs  
• Monitor participants weekly until liver 
chemistries resolve, stabilize or return to within 
baseline 
• Record alcohol use on the liver event 
alcohol intake CRF page 
If ALT≥3xULN AND bilirubin ≥ 2xULN 
or INR >1.5: 
• Anti-nuclear antibody, anti-smooth 
muscle antibody, Type 1 anti-liver 
kidney microsomal antibodies, and 
quantitative total immunoglobulin G 
(IgG) or gamma globulins. 
• Serum acetaminophen adduct 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]). 
NOTE: not required in China  
• Liver imaging (ultrasound, magnetic 
resonance, or computerised 
tomography) and /or liver biopsy to 
evaluate liver disease; complete Liver 
Imaging and/or Liver Biopsy CRF 
forms. 
1. Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study 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, if INR 
measured, which may indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE (excluding 
studies of hepatic impairment or cirrhosis); INR measurement is not required and the threshold value stated will 
not apply to participants receiving anticoagulants. 
3. Includes: Hepatitis A IgM antibody; Hepatitis B surface antigen (HbsAg) and Hepatitis B Core Antibody (IgM); 
Hepatitis CRNA; Cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, 
obtain heterophile antibody or monospot testing); Hepatitis E IgM antibody.  
4. PK sample may not be required for participants known to be receiving placebo or non-GSK comparator 
interventions.)  Record the date/time of the PK blood sample draw and the date/time of the last dose of study 
intervention prior to 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, do not obtain a PK 
sample. If a liver event occurs following dose on Day 50 and a PK sample cannot be collected in the time period 
indicated above, a PK sample should be taken within 84 days post-dose. Instructions for sample handling and 
shipping are in the SRM 
 
References 
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davern TJ, Lee 
WM. Pharmacokinetics of Acetaminophen-Adduct in Adults with Acetaminophen 
Overdose and Acute Liver Failure. Drug Metab Dispos 2009; 37:1779-1784. 


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10.7. 
Appendix 6b: Healthy Volunteer and Patient Phase I Studies 
Liver Stopping Event Algorithm 
 
Refer to Appendix 6a for required Liver Safety Actions and Follow up Assessments  
 
 


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1 0. 8.  
A p p e n di x  7: Effi c a c y A s s e s s m e nt s  
1 0. 8. 1.  
A v er a g e P ai n N R S  
 
 
 
 
 
 
1 0. 8. 2.  
W or st P ai n N R S  
 
 
 
 
 
 
W orst  P ai n S e v erit y ( P ai n N R S)  
 
Pl e as e r at e y o ur k n e e  p ai n b y s el ecti n g t h e o n e n u m b er t h at b est d escri b es y o ur  
k n e e  p ai n at its w orst  i n t h e l ast 2 4 h o urs: 
 
0    1    2    3    4    5    6    7    8    9    1 0  
N o                              P ai n as b a d as  
P ai n                              y o u c a n i m a gi n e  
A v er a g e P ai n S e v erit y ( P ai n N R S)  
 
Pl e as e r at e y o ur k n e e  p ai n b y s el ecti n g t h e o n e n u m b er t h at b est d escri b es y o ur  
k n e e  p ai n o n a v er a g e  i n t h e l ast 2 4 h o urs: 
 
0    1    2    3    4    5    6    7    8    9    1 0  
N o                              P ai n as b a d as  
P ai n                              y o u c a n i m a gi n e  
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y t hir d 
p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.


T M F -1 4 4 4 7 9 5 3  
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
9 9  
 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y t hir d p art y 
c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.


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10.9. 
Appendix 8: Abbreviations and Trademarks 
Abbreviations 
µg/mL 
Micrograms per millilitre 
μg*day/mL 
Micrograms day per millilitre 
ACR 
American College of Rheumatology 
ADA 
Anti-Drug Antibodies 
AE 
Adverse Event 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
AUC 
Area Under the Curve 
AUC(0-t) 
Area under the serum concentration-time curve from zero 
to time t 
AUC(0-∞) 
Area under the serum concentration-time curve from zero 
to infinity 
AUC(0-tau) 
Area under the serum concentration-time curve over the 
dosing interval 
BCG 
Bacillus Calmette-Guerin 
BL 
Baseline 
BMI 
Body Mass Index 
BNP 
N-terminal pro B-type natriuretic peptide 
BUN 
Blood urea nitrogen 
CFR 
Code of Federal Regulation 
CI 
Confidence Interval 
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 
CPPD 
Calcium pyrophosphate dihydrate 
CRF 
Case Report Form 
CSR 
Clinical study report 
CV 
Cardiovascular 
DEC 
Dose Escalation Committee 
DEP 
Dose Escalation Plan 
DNA 
Desoxyribonucleic acid 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram 
eCRF 
Electronic Case Report Form 
eDiary 
Electronic diary 
FTIH 
First time in human 
FSH 
Follicle Stimulating Hormone 
GCP 
Good Clinical Practice 
GSK 
GlaxoSmithKline 


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h 
Hours 
HBsAg 
Hepatitis B Surface Antigen positive 
HBcAb 
Hepatitis B core antibody  
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 
IDRC 
Interim Data Review Committee 
IEC 
Independent Ethics Committee 
IgA 
Immunoglobulin A 
IgG2 
Immunoglobulin G2 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
IV 
Intravenous 
IVRS 
Interactive voice response system 
IWRS 
Interactive Web Recognition System 
Kdeg 
Degradation rate 
KL 
Kellgren and Lawrence 
kg 
Kilogram 
kg/m2 
Kilograms per square meter 
LLQ 
Lower Limit of Quantification 
mAb 
Monoclonal Antibody 
MABEL 
Minimum Anticipated Biological Effect Level 
MCH 
Mean Corpuscular Hemoglobin 
MCV 
Mean Corpuscular Volume 
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 
MSDS 
Material Safety Data Sheet 
msec 
Millisecond 
NGF 
Nerve Growth Factor 
NOAEL 
No Observed Adverse Effect Level 
NRS 
Numerical Rating Scale 
NSAIDs 
Non-steroidal anti-inflammatory drugs 
OA 
Osteoarthritis 


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1 0 2  
 
P D  
P har mac o d y na mics  
p H  
P ote ntial H y dr o ge n  
P K  
P har mac o ki netics  
P G x  
P har mac o ge n etics  
P R O  
Patie nt  re p orte d o utc o me 
P T S  
Platf or m Tec h n ol o g y a n d Scie nce  
Q Tc  
C orrecte d Q T  
Q Tc B  
C orrecte d Q T usi n g Bazett’s f or m ula  
Q Tc F  
C orrecte d Q T usi n g Fri d ericia’s f or m ula  
R A  
R he u mat oi d Art hritis  
R A P  
Re p orti n g a n d A nal ysis Pla n  
R B C  
Re d Bl o o d cell c o u nt  
R N A  
Ri b o n ucleic aci d  
S A D  
Si n gle asce n di n g d os e  
S A E  
Seri o us A d verse E v e nt  
S A R S -C o V -2  
Se vere ac ute res pirat or y s y n dr o me –  C or o na vir us -2  
S C  
S u bc uta ne o us  
S D  
Sta n dar d De viati o n  
S G O T  
Ser u m Gl uta mic -O xal oacetic Tra nsa mi nase  
S G P T  
Ser u m  Gl uta mic -P yr u vi c Tra nsa mi nase  
S M G  
Safet y a n d Me dical G o ver na nce  
S M P  
Safet y M a na ge me nt Pla n  
S N RI  
Ser ot o ni n N ora dre nali ne re u pta ke i n hi bit ors  
S o A  
Sc he d ule o f Acti vities  
S R M  
St u d y R efere nce Ma n ual  
S R T  
Safet y R e vie w Tea m  
S S RI  
Ser ot o nic s pecific re u pta ke i n hi bit ors 
S U S A R  
S us pecte d u ne x pecte d seri o us a d verse reacti o ns  
T A R C  
T h y m us a n d acti vati o n re g ulate d c he m o ki ne  
T B  
Myc o b act eri u m t u berc ul osis  
T D A R  
T -cell De p e n de nt A nti b o d y Res p o nse  
T E  
Tar get e n ga ge me nt  
tma x  
Ti me t o C ma x  
T M D D  
Tar get Me diat e d  Dr u g Dis p ositi o n  
T S T  
T u berc uli n s ki n test  
t ½ 
A p pare nt ter mi nal p hase half -life 
U L N  
U p per li mit of n or mal  
Vss  
V ol u me of distri b uti o n  
W B C  
W h ole Bl o o d C o u nt  
W O M A C  
Wester n O ntari o & M c M aster U ni versities Oste oart hritis 
i n de x 
W N C P  
W o me n Of N o n C hil d beari n g P ote ntial  
W O C B P  
W o me n Of C hil d beari n g P ote ntial  
w/ v  
Wei g ht b y v ol u me  
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103 
 
Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
RAMOS NG 
 
MedDRA 
 
 
QuantiFERON 
 
 
WOMAC 


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C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
1 0 4  
 
1 0. 1 0.  
A p p e n di x 9 : Pr ot o c ol A m e n d m e nt Hi st or y 
T he Pr ot oc ol A me n d me nt S u m mar y of C ha n ges T a ble f or t he c urre nt a me n d me nt is 
l ocate d directl y b ef ore t he Ta ble of C o nte nts ( T O C). 
1 0. 1 0. 1.  
A m e n d m e nt 1 1 0 -A P R -2 0 1 8  
O ver all R ati o n ale f or t he A me n d me nt:  T his is a n a me n d me nt i n res p o ns e t o M H R A 
fee d bac k.  C orrecti o n of C ma x val ue at t he hi g hest pre dicte d e x p os ure after 1 0 m g/ k g I V 
a d mi nistrati o n a n d a d diti o n of d ose st o p pi n g p h ar mac o ki netic criteria.  
S e cti o n # a n d 
N a m e  
D e s cri pti o n of C h a n g e  
Bri ef R ati o n al e 
S ecti o n  
4.3 
Sci e ntific 
R ati o n ale  
f or 
St u dy Desi g n  
S ecti o n  
4.4 
J ustific ati o n 
of 
D os e  
S ecti o n  
7. 2.3 
D os e 
St o p pi ng 
P h ar mac oki netic 
Crit eri a  
 A d de d par a gr ap h on D os e St o ppi n g 
P h ar mac oki netic Crit eria  
F or cl arity S ecti on 7.2. 3 w as a d de d  
 
1 0. 1 0. 2.  
A m e n d m e nt 2 2 1 -N O V -2 0 1 8  
O ver all R ati o n ale f or t he A me n d me nt:  T o a d dress t he p oi nts raise d b y b ot h t he P a ul-
E hrlic h -I nstit ute ( P-E -I l etter date d 2 8-S E P -2 0 0 1 8) a n d t he U K Ce ntral Et hics C o m mittee 
(letter date d 1 2-S E P -2 0 1 8): pri nci pall y t o clarif y t he c o n d uct of s afet y ma na ge me nt.  
I n c or p orati o n of n o n-s u bsta ntial c ha n ges ( pre vi o usl y ca pt ure d i n File N otes ( details 
bel o w).  
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C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
1 0 5  
 
S e cti o n # a n d 
N a m e  
D e s cri pti o n of C h a n g e  
Bri ef R ati o n al e  
S ecti o n  
8.5 
A dv ers e Ev e nts 
a n d A p pe ndix 3  
R ef er e nce t o t h e st u dy s p ecific 
S af ety M a na ge m e nt Pl an ( S M P) h as 
b e en i ncl u d e d.  
P EI’s r eq u est to d efi ne, wit hi n t h e b o dy 
of th e pr ot ocol, th e pr oc ess es for 
pr o m pt  
co m m u nic atio n  
of 
S A Es/ S U S A Rs  
an d  
r a pi d 
i mpl e m e nt ati on 
of 
c orrectiv e 
a nd 
pr ev e ntive acti o ns bet w e en Sp o nsor, 
all st u dy sites a n d i nvesti g ators.  
T a bl e  
1. 3.1 
Sc h e dul e  
of 
Ass ess m e nts 
( Scr e e ni n g) 
A d diti on  
of  
Tb -Scr e e ni n g 
( Q u a nti F E R O N test) a n d F S H a n d 
estr a di ol 
(i n 
w o m en 
of 
n on -
c hil d b eari n g p ot e nti al). 
P EI’s r e q uest t o i ncl ud e th e scr e e ni n g 
ass ess m e nts i n th e 
Sch e dul e of 
Ass ess m e nts.  
S ecti o n  
7.1 
St u dy st o p pi ng 
crit eri a 
R e m ov al of d u plic ati o n of “s erio us.”  
S ec o nd b ull et m o difi ed: “ O n e pati e nt 
ex p eri e nces a “si g nific a nt” cli nic al or 
l a b or atory a bn or malilty. 
R e cr uit m e nt will be h alte d by th e 
s p o nsor ( a n d m ay be r esu m e d aft er 
a p pr opriat e p ositiv e r evi e w of saf ety 
fi n di n gs a nd foll o wi n g a ppr ov al fr o m 
t h e r e g ulat ory a ge nci es a n d ethics 
c o m mitt e es t o r est art.  If d ee m e d 
a p pr opriat e t h e I nfor me d Co ns ent m ay 
b e r evis e d. 
Fi g ur e 2, Fi gur e 
3 an d Fi gur e 4 
a n d Sc he d ule of 
Ass ess m e nts  
W e ekly ( 7 -d ay) visit arra n g e m ent 
c orrect e d fr o m D ays 1 1 2 an d 14 0 t o 
D ays 1 13 a n d 1 4 1, r es pectiv ely.  
C orr ect e d t o e nsur e c o nsist e ncy i n 
sc h e duli n g, dat a coll ecti on, a nalysis 
a n d r ep orti ng ( Fil e  N ot e 4 -O C T - 2 0 1 8).  
S ecti o n 4. 1 a nd 
Fi g ur e 1  
R e m ov al of t h e i nt er de p end e ncy of 
ex ec utin g  
C oh ort  
7  
(sin gl e 
i ntr av e no us dos e i n osteo art hritis 
p ati ents, 
Part 
B) 
i m m e di at ely 
f oll o wi n g  
Co h ort  
6  
(sin gl e 
s u bc uta ne o us 
d ose i n 
h ealt hy 
s u bj ects, P art A).  
It is lo gic al t o exec ute C oh ort 7 (sin gl e 
i ntr av e no us 
d ose i n 
ost e o arthritis 
p ati ents, P art B) foll o wi n g t h e r evi e w of 
t h e s af ety a n d tol er a bility of a si ngl e 
i ntr av e no us 
dos e 
ad mi nist er e d to  
h e althy  s u bjects i n Co h ort 5 ( P art A). 
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Section # and 
Name 
Description of Change 
Brief Rationale 
Figure 1 
Removal of the interdependency of 
executing Cohort 6 (subcutaneous 
dosing) immediately after Cohort 3 
(intravenous dosing). 
Cohort 6 (subcutaneous dosing) is not 
required to run in parallel with Cohorts 
4 or 5 and does not inform the decision 
to progress to Part B which is an 
intravenous dosing cohort. Therefore, 
the 
interdependency 
has 
been 
removed (File Note 3-OCT-2018). 
Section 
1.3.4 
Schedule 
of 
Activities 
Introduced 
New 
Schedule 
of 
Activities (Table 1.3.4) for Cohorts 4 
– 6 to move the induction blister 
forward from Days 42/43 to Days 
28/29. 
PK exposure (observed in Cohort 3) 
was lower than anticipated so the 
induction blister was no longer 
optimally 
placed 
for 
subsequent 
Cohorts 4 – 6 (File Note 3-OCT-2018). 
Section 
1.3.4 
Schedule 
of 
Activities 
Correct Side Note for Cohort 6 
subcutaneous: to “2 Cohort 6 Day 1 
Vital Signs at Pre-Dose and 1 hour 
post injection.” 
Time points for safety evaluation 
across a 2 hour infusion need to be 
adjusted for subcutaneous injection 
(File Note 9-MAY 2018). 
Section 
1.3.4 
Schedule 
of 
Activities 
Correct Side Note for Cohort 6 
subcutaneous: “2 Cohort 6 Day 1 
ECG at Pre-Dose and 1 hour post 
injection.” 
Time points for safety evaluation 
across a 2 hour infusion need to be 
adjusted for subcutaneous injection 
(File Note 9-MAY 2018). 
Section 
1.3.4 
Schedule 
of 
Activities 
Correct Side Note to “final follow-up 
visit for 1 and 3 mg/kg IV cohorts.” 
Incorrect dose level used (File Note 3-
APR-2018). 
Section 
1.3.2 
Schedule 
of 
Activities 
Remove the requirement for immune 
phenotyping of circulating cells. 
Immune cell phenotyping in blood is 
only required for comparison with 
immune cells in blister fluid (File Note 
3-APR-2018). 
 
10.10.3. 
Amendment 3 18-JUL-2019 
Overall Rationale for the Amendment: To adjust the design of Part B from a single 
intravenous dose to repeat weekly subcutaneous injections over a period of 8 weeks to 
provide adequate exposure to test the effect on pain in participants with OA of the knee. 
Areas of the protocol impacted are: Dose regimen; Treatment Period; Follow-Up Period; 
Safety Review; Safety Mitigation and Monitoring; Participant Numbers and Interim 
Analysis; Individual Participant and Study Stopping Rules. 


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Pr ot o c ol A m d 7  
 
1 0 7  
 
Ot her areas a dj uste d are: Patie nt P o p ulati o n; Patie nt Gl o bal Assess me nt of Disease 
Acti vit y, Resc u e a n d Pr o hi bite d Me dicati o ns; Pai n D E T E C T; Partici pa nt Fee d bac k 
Q uesti o n naire.  
Mi n or c ha n ges a n d c orrecti o ns are ma de t hr o u g h o ut t o pr o vi de refi ne me nt a n d 
clarificati o n.  
M AI N S e cti o n # a n d N a m e  
 
D e s cri pti o n of C h a n g e  
Bri ef R ati o n al e  
S ecti o n 4.4  
J ustific ati o n f or D ose 
 
D os e r e gi men: fr o m a si n gle 
i ntr av e no us d os e (t w o d os e 
l ev els) t o r e pe at w e ekly 
s u bc uta ne o us inj ecti on of 2 4 0 
m g ( 4 i nj ecti ons).  
D uri n g d ose escal ati on of Part 
A, a r evie w of 
p h ar mac oki netic ( P K) a n d 
t ar g et e ng a ge m e nt ( T E) d ata, 
i n dic at ed a muc h fast er 
cl e ar a nc e of G S K3 8 58 27 9 
t h a n w as origi nally pr e dicted.  
R e p e at w e ekly su bc ut a ne ous 
( S C) d osi n g is r eq uire d t o 
pr ovi d e a d eq uat e ex pos ur e t o 
t est th e p ot e nti al to eff ect p ai n 
i n p articip ants wit h O A of the 
k n e e. 
S ecti o n 3  
O bj ectiv es a n d E nd p oints  
A dj ust ed th e pri m ary o bj ectiv e 
of P art B for ass ess m ent of 
effic acy foll o wi n g r ep e at dosi n g  
 
I ncl u d e d r escu e m edic ati on as 
a c o m p on ent of t h e effic acy 
e n dp oi nt.  
B ot h saf ety an d effic acy ar e 
ev al u at e d.  
 
 
R esc u e m edic ati on is a 
c o m p o ne nt of th e effic acy 
e n dp oi nt.  
 
S ecti o n 4.1. 1  
Tr e at m e nt Gr o u ps a nd 
D ur ati o n  
 
Tr e at m e nt P erio d: fr o m a si n gl e 
d os e t o 8 w e eks of tre at m ent  
T h e s eco n dary 
o bj ectiv e/e nd p oint (c h an ge 
fr o m b as eli ne i n av er a ge 
w e ekly D aily P ai n N R S) w as 
s et at 8 w eeks t o pr ovi de 
c o nfi de nc e of a cli nic ally 
m e a ni n gf ul tr eat m e nt eff ect vs 
pl ac e bo.   
T w o a d ditio n al visits  ( Day 36 
a n d Day 5 0) ar e i ntro d uce d 
i nt o th e sc h e dul e ( dosi n g 
d ays). 
D ay 2 is r e plac e d by D ay 4  t o 
o pti miz e ph ar mac oki netic 
s a m pli n g. 
S ecti o n 4.1. 1  
Tr e at m e nt Gr o u ps a nd 
D ur ati o n  
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2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
1 0 8  
 
M AI N S e cti o n # a n d N a m e  
 
D e s cri pti o n of C h a n g e  
Bri ef R ati o n al e  
 
S ecti o n 4.1  
Ov er all D esi g n  
 
P art B  S afety r evi e w ( 8 
p articip a nts): Cl os e i n str e a m 
m o nit orin g of s af ety ( A Es, 
cli nic al l a b or atory, vit al si gns 
a n d car di ac m onit orin g) P K a n d 
A D As f or th e first 8 p articip ants 
( 4 r a n do miz e d to activ e 
tr e at m e nt) wit h a d etail e d 
r evi e w w h e n t h e 8t h p articipa nt  
r e ac h es Day 2 9. 
A r evi e w of s afety, P K a n d 
A D As will b e c o n d uct e d i n a 
s m all n u m b er of particip a nts 
f oll o wi n g r ep e at dosi n g. 
S ecti o n 4.2  
N u m b er of P artici p ants  
 
 
 
 
 
 
 
 
 
 
 
P art B P articip ant N u m bers:ar e 
i ncr e as e d fr o m 15 or 20 ( o ne or 
t w o si n gl e d ose l ev els, 
r es p ectiv ely) t o a ppr oxi m ately 
5 0 p articip a nts will b e 
r a n d o mis e d t o rec eiv e eit h er 
r e p e at d oses of G S K 3 85 827 9 
or pl ac e b o i n a 1: 1 r ati o.  
 
 
 
5 0 p articip a nts ar e suffici ent 
t o i nv esti g ate effic acy of 
G S K 38 5 82 79 wit h  r esp ect to 
c h a ng es i n p ai n v ers us 
pl ac e bo at W e ek 8 b as e d o n 
t h e ass u m pti ons list e d i n 
S ecti o n 9.2.  
 
F or t h e sec o nd ary co m p aris o n 
( ass u mi n g a ch an g e fr o m 
b as eli ne i n p articip a nt’s 
ass ess m e nt of p ai n scor e of -
1. 5 o n pl ac e bo, a n d a S D of 
1. 8, t h e l e ast si g nific ant 
diff er e nce b et w ee n 
G S K 38 5 82 79 a n d plac e bo 
w o ul d be  
-0. 8 5.  
S ecti o n 9  
St atistic al C onsi d er ati o ns  
 
 
S ecti o n 9.4. 5  
I nt eri m A nalys es 
S ecti o n 9 h as b e en a dj ust ed.  
 
 
 
P art B Int eri m An alysis: W he n 
2 0 p articip a nts hav e c o mpl et e d 
t h e e n d of W eek 4 ass ess me nt.  
Alt er ati on of t h e st udy d esi gn 
h as r es ulte d in a dj ust ed 
st atistic al c onsi d er atio ns. 
 
F or f utility. A r evie w of P K, T E 
a n d A D A will als o be 
c o n duct e d. 
A bli n de d sa m pl e siz e r e -
esti m ati o n m ay als o occ ur 
prior t o e nr ollin g th e fi n al 
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Brief Rationale 
participant, where the sample 
size may also be increased to 
a maximum of 80 participants 
(if the expected SD is greater 
than 1.8 or in the case of high 
dropout). 
If the sample size is increased 
a second interim analysis may 
occur, the timing and size of 
which will be determined 
during the sample size re-
estimation. 
Section 7.  Discontinuation 
of Study Intervention and 
Participant Discontinuation / 
Withdrawal. 
 
Section 7.1 Study Stopping 
Criteria 
 
 
 
 
Section 7.2 Discontinuation 
of Study Intervention 
Section 7.2.1 Liver 
Chemistry Stopping Criteria  
Section 7.2.3 Dose 
Adjustment Pharmacokinetic 
Criteria 
Section 7.2.4 Temporary 
Discontinuation 
Section 7.5 Participant and 
Study Completion 
Introduction of Section 7 New 
Text to set out the study rules 
accordingly for the adjustment 
from a single to repeat dose 
regimen. 
Study Stopping Criteria: 
Adjusted from one to two 
participants. 
 
 
 
 
New Text 
 
New Text 
 
New Text 
 
New Text 
 
New Text 
Individual participant 
monitoring and withdrawal 
rules, and study stopping 
rules are inherent of a repeat 
dose study design. 
The study stopping criteria for 
the Part A FTIH healthy 
volunteer are adjusted for Part 
B Osteoarthritis patient study 
(phase Ib) in light of the 
satisfactory blinded safety 
profile in Part A (no SAE in 47 
subjects,) and to take into 
account the increased cohort 
size and study duration. 
Section 5.1 
Inclusion Criteria 
Replaced “body weight 50 -100 
kg” with “BMI 19 – 39 kg/m2” 
 
Introduced: History of 
insufficient pain relief from, or 
inability to tolerate, or 
contraindication to, oral 
NSAIDs. 
 
 
Introduced: X-ray at Screening. 
 
Given the likely maturity of the 
intended study population, 
BMI was considered a better 
means of defining such a 
population. 
The patient population was 
updated to focus on those 
with significant unmet medical 
need i.e. unresponsive to 
NSAIDs 
Additional requirement for an 
X-ray (objective measure) of 


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Description of Change  
Brief Rationale 
 
the index knee to confirm 
Osteoarthritis using a Kellgren 
and Lawrence (KL) score of 
≥2 at study entry and replaces 
“symptomatic mild to 
moderate pain” because pain 
is a subjective and variable 
measure.  Screening period is 
extended (from 28 to 42 days) 
to accommodate X-ray 
assessment. 
Section 5.2  
Exclusion Criteria 
Patient Population: Introduced 
or Modified Exclusion Criteria 
 
 
Added UACR parameter to the 
existing renal exclusion criteria. 
The period within which 500 mL 
blood may be acquired was 
reduced from 3 months to 56 
days. 
To exclude participants whose 
prior and current medical 
history renders them 
unsuitable for this first clinical 
trial GSK3858279. 
Additional measurement of 
renal function at screening. 
 
Period remains within MHRA/ 
BfArM guidance. 
Section 2.3.1 
Risk Assessment. 
 
Non-clinical 26-week 
cynomolgus monkey data 
included: changes are 
described (considered non-
adverse) which were consistent 
with the development of ADAs 
in some animals (immune 
complex deposition giving rise 
to inflammatory vascular, and 
mesangioproliferative 
changes).  
 
FTIH data included: blinded 
partial data from Part A of this 
Study 207804: There was no 
report of an infection related 
SAE, a hypersensitivity or 
injection site reaction, nor a 
clinically significant change in 
urinalysis. 
 
Safety Mitigation and 
Monitoring: 
Duration of the in-house 
monitoring period: At least 4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Part B is the first instance 
where repeat subcutaneous 
injections are to be 
administered on a weekly 
basis for 8 weeks, therefore 
the duration of the in-house 
period allows close monitoring 
in case of hypersensitivity or 


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C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
1 1 1  
 
M AI N S e cti o n # a n d N a m e  
 
D e s cri pti o n of C h a n g e  
Bri ef R ati o n al e  
h o urs at i niti al d os e ( D ay 1) 
a n d at  l east 2 h ours on all 
r e m ai ni n g d osi n g d ays. 
 
C ar di ac M o nit oring: E C H O 
( Scr e e ni n g) a nd at a ny ot h er 
ti m e (if i n dic at ed); H olter: 24 
h o ur at i niti al Scre e n 
( o ut p ati e nt s ettin g); E C G i n 
tri plic at e at all visits. 
 
R e m ov al of “ Dis e as e 
Ex ac er bati o n” fr o m list o f 
P ot e nti al Risks.  
i nf usi o n r e acti ons, an d with 
o pti mi z e d car di ac m o nitoring. 
 
 
 
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Brief Rationale 
Section 8.1.4  
Clinical Safety Laboratory 
Assessments 
Additional Assessments: 
• NT-proBNP (N-terminal pro 
B-type natriuretic peptide 
[BNP]): Baseline (BL) and 
Day 57. 
• Complement proteins C3 
and C4 (BL). 
• Microscopic examination 
and laboratory 
quantification of proteinuria 
(if blood or protein is 
abnormal on dipstick) 
throughout. 
• Urine albumin-creatinine 
ratio (UACR) at Screening. 
Sensitive biochemical 
measures are now included to 
obtain a Baseline (BL) value 
and/or to monitor for early 
changes in cardiac (NT-
proBNP) and renal function 
(C3, C4, UACR) 
Section 4.1 and Section 
10.1.5 
Safety Management: Safety 
Review Team (SRT) and 
Safety Management Plan 
(SMP) 
 
AEs and clinical laboratory 
data, will be reviewed in-
stream (detailed in the Safety 
Review Team (SRT) Charter 
and Safety Management Plan 
(SMP) to ensure adherence to 
the Individual Participant and 
Study Stopping Criteria. 
Section 6.5  
Concomitant Therapy 
Permitted Therapies: if used 
at a stable dose for at least 30 
days prior to screening:- 
antidepressant medication 
(SSRI, SNRI); Nutraceuticals; 
Aspirin for cardiovascular 
indications. 
Rescue Medication: 
Paracetamol ≤ 3 g/d (originally 
≤ 2 g/d), except 24 h before an 
assessment visit.   
Maintaining stable doses of 
the listed therapies is not 
considered likely to impact on 
evaluation of either safety, 
pharmacokinetics or efficacy 
of GSK3858279 mAb. 
Daily dose permitted was 
increased (but remains within 
accepted limits). 
 
Section 6.6  
Prohibited Medications 
Prohibited Medications 
Added: 
Live vaccine; biologic agents 
(mAbs, therapeutic proteins); 
antiplatelet or anticoagulant 
agents; immunosuppressants; 
systemic corticosteroids; intra-
articular therapy of the index 
joint;. 
Prohibited Medications up to 
and including Day 71: pain 
 


T M F -1 4 4 4 7 9 5 3  
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2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
1 1 3  
 
M AI N S e cti o n # a n d N a m e  
 
D e s cri pti o n of C h a n g e  
Bri ef R ati o n al e  
m e dic ati o ns i ncl u di ng a nti -
n e ur op athic a ge nts ( e g 
G a b ap enti n a n d Pr e ga b ali n), 
o pi oi ds, N S AI Ds, t o pic al 
a n al gesics a nd  
A dj u nctive t her a pi es  
 
 
S ecti o n 5.3  
Lif estyl e C onsi d erati o ns   
Lif e st yl e C o n si d er ati o ns:  
S m oki n g is p er mitt e d.  
I ntr o duc e d: T o co nti nu e a 
r e gi me n of t h er a pe utic 
ex ercis e, pr ovid e d t hat it w as 
st a bl e f or at l e ast 4 w eeks prior 
t o e nr ol m e nt. 
 
 
 
I ntr o duc e d: H e at an d ic e 
t h er a py m ay b e use d. 
 
Cl arific ati o n.  
C o nti n uati on of re g ular 
t h er a pe utic ex ercis e is 
b e nefici al f or th e p ati ent 
p articip a nt an d p articip ants 
will b e e nc our a ge d t o d o s o 
t hr o u gh out ( but esp eci ally 
d urin g th e initi al p erio d of 
w as h o ut of ov er th e co unt er or 
pr escri pti o n m edic ati ons 
wit hi n 7 d ays prior to d osi n g).  
H e at an d ice t her a py m ay b e 
b e nefici al f or th e p ati ent 
p articip a nt, b ut p articip ants 
will b e ask e d t o refr ai n wit hin 
2 hrs of t he e Di ary 
ass ess m e nt a nd wit hi n 2 4 hrs 
of a cli nic visit).  
S ecti o n 8.3. 6   
F e e d back Qu esti on n air e  
F e e d back Qu esti on n aire ( Start 
of st u dy a n d l ast visit) w as 
i ntr o d uce d 
T o c oll ect p articip ants’ 
ex p erie nce of t his G S K tri al t o 
i mpr ov e f utur e stu dy 
c o nsi d er ati o ns a nd d esig ns. 
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C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
1 1 4  
 
M AI N S e cti o n # a n d N a m e  
 
D e s cri pti o n of C h a n g e  
Bri ef R ati o n al e  
S ecti o n 3  
O bj ectiv es  a n d E nd p oints,  
S ec o nd ary Effic acy En dp oint: 
D aily P ai n N R S ( aver a ge a n d 
w orst k n e e p ain i nte nsity)  
 
Cl arifi e d t h at t h e m e asur es 
ar e “c h a n g e fr o m b aseli n e” 
a n d ar e th e av er a g e d ov er th e 
7 d ays prior t o e ach 
ass ess m e nt visit.  
C orr ecti o n  
 
S ecti o n 2.3 B e n efit/ Risk 
Ass ess m e nt  
I nv esti gat or Broc h ur e v ersion 
n u m b er u p dat e d fr o m 00 to 0 1.   
 
 
 
 
 
 
R e m ov e d “c h all e n ge a g ent”  
I nv esti gat or Broc h ur e u pd ate d 
t o i ncl ud e th e bli n d ed s af ety 
r evi e w of Part A cli nic al d ata 
[ G S K D ocu m e nt N u m b er 
2 0 19 N 3 9 7 7 87] a n d t h e six 
m o nt h GL P cyn o m ol gus 
m o nk ey stu dy d ata [ G S K 
D oc u m e nt Nu m b er 
2 0 19 N 3 9 7 6 48 ( P 3 2 0 90 G)]. 
B ot h st u dies s u p p ort t his 
s u bst a nti al a me n d m ent # 3 of 
P art B.  
 
C orr ecti o n: N o c h all en g e 
a g ent i s use d i n t his stu dy. 
 
T hr o u gh o ut t h e pr ot oc ol  
C h a n ge d “ S u bj ect” t o 
“ P articip a nt.”  
 
R e m ov e d “s p o ns or o pe n”  
 
T o r efl ect curre nt G S K a n d 
I nt er nati o nal st a n dar ds 
 
T o cl arify t h at t h e s p o nsor is 
bli n d ed  
S ecti o n 5.4  
Scr e e n Fail ur es  
Scr e e ni ng ( F ail ur es): 
P articip a nts m ay b e r e -t ested 
o nc e withi n t h e scr ee ni n g 
wi n d o w.  Scre e n f ail ur es may 
r et ur n for s u bse q ue nt 
scr e e ni n g o nce. 
Cl arific ati o n: Intr o ducti o n of 
t h e sta nd ar d a p pr oac h. 
S ecti o n 1.3. 5 Sc h ed ul e of 
Activiti es  
N e w a d de d: C 3 an d C4 ( B L);  
B N P ( B L & D ay 5 7); U A C R 
( Scr e e ni n g) 
M ov e d: P h ar mac og en etic 
S a m pl e fr o m Day -1 to pr e -
d os e o n Day 1.  
S af ety M o nit oring 
i nc or p or ate d. 
 
P h ar mac og e netic s a m ples 
o nly r e quire d fr o m p articip ants 
w h o will b e r an d o miz ed t o 
tr e at m e nt. 
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MAIN Section # and Name  
 
Description of Change  
Brief Rationale 
Section 2.2 Background  
 
Removed “without potentiating 
disease progression.” 
Removed this inaccuracy, as 
no clinical data have been 
obtained to substantiate that 
GSK388279 will not potentiate 
disease progression. 
 
10.10.4. 
Amendment 4 14-NOV-2019 
Overall Rationale for the Amendment 4 (for Part B): To address the concerns from 
the Ethics Committees’ review of Amendment 3 (Part B). 
Section # and Name 
Description of Change 
Brief Rationale 
Section 3: Objectives and 
Endpoints 
Corrected the row structure 
of the table 
To properly reflect our 
intent to evaluate both 
safety and efficacy as the 
primary objectives for Part 
B. 
Section 5.1 Inclusion 
Criteria 
Reduce the upper limit of 
BMI from 39.9 kg/m2 to 
34.9 kg/m2 
To exclude participants of 
> Grade 1 Obesity (and so 
to reduce the risk. 
Section 5.2 Exclusion 
Criteria (No. 57, 60, 62 and 
69) 
No. 57: To also exclude 
participants with a history 
of primary cardiomyopathy 
No. 60: To clarify that 
participants who have a 
history of excessive 
bleeding or coagulation 
disorders, will also be 
excluded. 
No. 62: To also exclude 
participants with recurrent 
infections 
No. 69: To exclude 
participants who are 
unwilling to discontinue all 
pain medication 
To better define the 
participant population and 
achieve consistency with 
the Benefit/Risk 
Assessment. 


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Pr ot o c ol A m d 7  
 
1 1 6  
 
Secti o n # a n d N a me  
Descri pti o n of C h a n ge  
Brief R ati o n ale  
Secti o n 7. 1  
St u d y s t o p pi n g criteria 
I n cl u de d li n ks t o S A E 
re p orti n g a n d t o t he Safet y 
Ma na ge me nt Pla n.  
Re m o ve d “t he sa me,” s o 
t hat a n y 2 relate d S A Es 
w o ul d tri g ger t he st o p pi n g 
of t he st u d y.  
T o hi g hli g ht t he 
c o or di nati o n of S/ A E 
re p orti n g a n d t he 
c o n diti o ns of S A E 
re p orti n g. 
Secti o n 7. 2 
Disc o nti n uati o n of St u d y 
I nter ve nti o n 
I n cl u de d “cli nicall y 
si g nifica nt d eteri or ati o n of 
i n de x k nee pai n.” 
Cli nicall y si g nifica nt 
deteri orati o n of i n de x k nee 
pai n warra nts 
disc o nti n uati o n of st u d y 
treat me nt. 
T hr o u g h o ut t he d o c u me nt  
C ha n ge “ patie nts” t o 
“ partici pa nts.”  
C o nsiste nt use of 
ter mi n ol o g y  
1 0. 1 0. 5.  
A m e n d m e nt 5: 0 7 -S E P -2 0 2 0  
O ver all R ati o n ale f or A me n d me nt 5 (f or P art B):  
T w o m ai n re as o ns : 1)  T o i ntr o d uce C O VI D -1 9 s afet y ma na ge me nt a n d t o a dj ust t he 
visit sc he d ule t o acc o m m o date S A R S -C o v 2 testi n g. 2) T o re p ort o n t he re vise d safet y 
mar gi n a n d i ntr o d uce a d diti o nal P K sa m pli n g ti me p oi nts (res ulti n g fr o m a n i m pr o ve d P K 
bi oa nal ytical met h o d ol o g y).  
Mi n or c ha n ges are: 
Mi n or e d its/c orrecti o ns are ma de t hr o u g h o ut t o pr o vi de refi ne m e nt a n d clarificati o n. 
Secti o n # a n d N a me  
Descri pti o n of C h a n ge  
Brief R ati o n ale  
A p pe n di x 2 ( Cli nical 
La b orat or y T ests) a n d 
t hr o u g h o ut, as a p pr o priat e 
Secti o n 4. 1. O verall 
Desi g n.  
Secti o n 4. 3. Scie ntific 
Rati o nale ( St u d y 
P o p ulati o n).  
A d de d: “ C O VI D -1 9” T est 
( S A R S-C o V -2)  
 
 
I n cl u de d t he rati o nale f or 
w h y p artici pa nts bet w ee n 
4 0 t o 7 5  years (i ncl usi ve) 
a n d wit h a B MI wit hi n t he 
ra n ge 1 9-3 4. 9 k g/ m 2 
(i ncl usi ve) will c o nti n ue t o 
be per mitte d i nt o t he trial 
T o scree n (a n d e x cl u de) 
partici pa nts f or t he 
prese nce of S A R S -C o V -2 
vir us a n d t o m o nit or d uri n g 
t he Treat me nt Peri o d a n d at 
t he E n d of St u d y.  
Alt h o u g h i ncreasi n g a ge 
a n d B MI are b ot h 
ass ociate d wit h a 
hei g hte ne d rel ati ve ri s k f or 
C O VI D -1 9 s usce pti bilit y 
a n d p o orer o ut c o mes, 
[Willia ms o n,  2 0 2 0] t hese 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 5.2. Exclusion 
Criteria (Diagnostic 
Assessments). 
Section 5.3.1. Lifestyle 
Considerations (COVID-
19 related) 
(despite the COVID-19 
pandemic). 
 
 
 
Added: Note that refusal of 
any COVID test following 
the first dose of study 
treatment would not 
constitute a protocol 
deviation. 
same parameters are 
inherently associated to and 
largely encompass the OA 
population under study. 
 
To cover the event that a 
participant may decide to 
refuse COVID testing 
whilst participating in 
207804 (this will be 
tracked).  
Section 1.3.1. Part B 
Schedule of Activities 
(Screening) 
Added: COVID-19 Test 
Moved: Day -1 screening 
tests either to Day -4 or to 
immediately prior to first 
dose, as appropriate. 
At least 72 (up to 96) hours 
is required to obtain the 
result of the COVID-19 
test (up to Day -4).  
Day -4 is to be used for a 
repeat of haem/chem (to 
obviate the need to return 
to the clinic at Day -1). 
For clarity of importance, 
Baseline measurements are 
denoted as (x) on the 
Schedule of Activities, 
since these are divided 
between Day -4 and 
immediately prior to dosing 
on Day 1. 
Section 1.3.5. Part B 
Schedule of Activities 
(Treatment and Follow-Up 
Period) 
COVID-19: Monitoring is 
introduced after 2, 5 and 8 
weeks during the 
Treatment Period, at the 
End of Study Visit (Day 
141), and in case of early 
withdrawal. 
PK/TE: Additional Visits 
to site were included: Days 
5, 23, 26, 51 and 99 for at 
COVID-19: Sparse testing 
introduced to reduce the 
chance of dosing 
GSK3858279 in the case of 
pre- or asymptomatic 
COVID-19.  
 
PK/TE: Additional 
sampling is required to 
better understand the 
disposition of 


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Pr ot o c ol A m d 7  
 
1 1 8  
 
Secti o n # a n d N a me  
Descri pti o n of C h a n ge  
Brief R ati o n ale  
 
E n d of St u d y Visit was 
m o ve d fr o m Da y 1 1 3 t o 
Da y 1 4 1  
 
 
 
 
A tele p h o ne c o nt act was 
i ncl u de d at Da y 1 2 0.  
 
 
 
T o e x te n d t he peri o d of 
o bser vati o n si nce last d ose 
of st u d y tr eat me nt.  
Secti o n 1. 2 Sc he ma  
Re place d.  
U p date d t o better reflect 
t he d ose re gi me n a n d 
ma xi m u m n u m ber of 
partici pa nts per mitte d.  
Secti o n 2. 2. Bac k gr o u n d  
Re m o ve d “ C C L 1 7 le vels 
w o ul d be e x pecte d t o be  
hi g her i n i nfl a m mat or y 
c o n diti o ns; h o we ver, d ue 
t o t he lar ge varia bilit y i n 
healt h y h u m a n ser u m 
C C L 1 7 le vels, t he s yste mic 
e x p os ure of C C L 1 7 i n O A 
patie nts mi g ht be si milar t o 
O n reflecti o n, t his 
state me nt a p pears 
s pec ulati ve. N ote t hat t he 
bi ol o gical r ati o nale of 
C C L 1 7 as a tar get is 
f o u n de d o n c o ntr olle d pre-
cli nical st u dies.  
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Section # and Name 
Description of Change 
Brief Rationale 
that in a healthy 
population.” 
Section 2.3, Benefit Risk 
Assessment 
 
 
Included a reference to the 
updated blinded review of 
a partial data set from Part 
A of this first time in 
human (FTIH) study.  
Part A (remains blinded at 
this time) completed June 
2019. 
Section 2.3.1: Risks 
Infection: Added that 
“Anti-CCL17 has been 
shown to be protective in a 
mouse model of invasive 
aspergillosis [Carpenter, 
2005] 
Immunogenicity Data: 
Discrete pre-clinical data 
was summarised. 
 
Cardiac Data: 13week 
toxicology summary 
updated “The heavier heart 
weights were not dose 
related and generally did 
not show a consistent 
pattern of increased 
absolute weights, relative 
to body weight or brain 
weight.” 
 
Study Procedures: 
Evaluated the COVID-19 
risk and mitigation 
strategies as “Risk 
associated with attending 
an investigative site during 
the COVID-19 Pandemic.” 
 
To reflect the literature on 
the potential role of 
CCL17. 
 
 
Discrete pre-clinical data 
was summarised. 
 
 
Updated for consistency 
with IB Update. 
 
 
 
 
 
Mitigation Strategies 
documented for 
participants attending 
investigative sites where 
COVID-19 virus may be 
circulating (COVID testing 
to be performed prior to, 
during the Treatment 
Period and at End of Study.  


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C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
1 2 0  
 
Secti o n # a n d N a me  
Descri pti o n of C h a n ge  
Brief R ati o n ale  
2. 3. 3. Be n efit: Ris k 
C o ncl usi o n  
U p date d t he O v erall B: R 
C o ncl usi o n wit h res pect t o 
C O VI D -1 9.  
T here are meas ures 
pr o p ose d t o mi ni mize t he 
ris k of C O VI D-1 9 t o st u d y 
partici pa nts a n d we 
c o nsi der t hat it re mai ns 
j ustifie d t o pr o gress t o Part 
B.  
Secti o n 3. O bjecti ves a n d 
E n d p oi nts  
Pri m ar y Effic ac y 
E n d p oi nts : 
Re m o ve d e x cessi ve detail 
“ 2 4 hr” a n d “a v era ge of 7 
da ys pri or” fr o m t he 
c ha n ge fr o m b ot h  t he 
a vera ge k nee pai n i nte nsit y 
a n d w orst k nee p ai n 
i nte nsit y, at Wee k 8. 
Sec o n d ar y P K 
E n d p oi nts:  
Pri mar y E n d p oi nt 
defi niti o n f or pai n was 
si m plifie d a n d ali g ne d wit h 
t hat descri be d i n pi v otal 
clinical trials i n t his disease 
area ( details i n Secti o n 
9. 4. 1).  
 
 
Secti o n 4. 4. 2 J ustificati o n 
f or D ose ( Part B) 
Secti o n Re place d.  
Refere n ce ma de t o  
1)  Uses data fr o m t he re -
a nal ysis of Part A 
sa m ples  
2)   Uses data fr o m t he 6 
m o nt h c y n o m ol g us 
m o n ke y t o xic ol o g y 
data t o calc ulat e t he 
safet y mar gi n 
T he re -a nal ysis of Part A 
sa m ples uses a n i m pr o ve d 
bi oa nal ytical met h o d.  
 
T he defi niti ve 6 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 
s u perse des t he 3 m o nt h 
st u d y. 
 
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C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
Pr ot o c ol A m d 7  
 
1 2 1  
 
Secti o n # a n d N a me  
Descri pti o n of C h a n ge  
Brief R ati o n ale  
T he pre dict e d safet y 
mar gi ns ( A U C, C ma x) 
re mai n acce pta bl e a n d t h e 
pr o p ose d d ose re gi me n a n d 
d urati o n of d osi n g f or Part 
B re m ai n u nc ha n ge d.  
 
Secti o n 6. 3. 1. 
Ra n d o mizati o n  
Re m o ve d “ T he 
ra n d o misati o n ma y b e 
stratifie d b y site t o all o w 
f or o perati o nal effi cie nci es 
f or t he pre p arati o n of t he 
I P.” 
N o l o n ger re q uire d.  
Secti o n 7. 2. 2. Q Tc 
St o p pi n g Criteria  
Clarifie d/c orrecte d 
w or di n g t h at Q Tc st o p pi n g 
criteria are b ase d o n a n 
a vera ge of tri plicat e E C G 
rea di n gs. 
Clarificati o n of w or di n g is 
bei n g a p plie d 
retr os pecti vel y. 
Part A e val uate d a si n gle 
rea di n g, b ut i n cas e of a n y 
c o ncer n, t w o f urt her  
rea di n gs w o ul d nee d t o be 
o btai ne d t o a p pl y t h e Q Tc 
st o p pi n g r ule ( w hic h 
re q uires tri plicate rea di n gs) 
Secti o n 7. 2. 3. D ose 
A dj ust me nt 
P har mac o ki netic Criteria  
I n cl u de d: “ n o n-
c o m part me ntal”  
 
 
 
 
 
I n cl u de d: t hat a n o n -
c o m part me ntal a n al ysis 
ma y n o w als o be use d ( or a  
m o del -base d p ost -h oc 
a nal ysis ) of t he o bser ve d 
c o nce ntr ati o ns t o pr o vi de 
t he i n di vi d ual e x p os ure 
para meters ( C ma x, A U C( 0 -
ta u)). 
Re visi o ns are base d u p o n 
t he rece nt Part A ( bli n de d) 
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Brief Rationale 
Revised: Cmax and 
AUC(0-tau) values and the 
fold safety margin:  
“Cmax of 511 µg/mL or 
the AUC(0-tau) of 
2594μg*day/mL based on 
a 4-fold margin against the 
NOAEL from the 6-month 
toxicological study” 
 
PK data and the recent 6- 
month toxicology study. 
Section 8.6. Treatment and 
Overdose 
Replaced “140 days” with 
“at least 5 half-lives but 
not less than 90 days” as 
the monitoring period for 
AE/SAE and laboratory 
abnormalities. 
140 days was inadvertently 
carried over from original 
protocol when Part B was a 
single dose design.  
Section 8.7.3 
Proteome Research: 
Section deleted 
Proteome research already 
encompassed within 
Section 8.4.2 (Exploratory 
Biomarkers). 
Section 9.3. Populations 
for Analyses 
Included a PK Population: 
PK Population (now 
tailored for a repeat dose 
study design) 
Section 9.4.3. 
Pharmacokinetics 
Analyses 
Updated the 
pharmacokinetic 
parameters in the 
Statistical Analyses 
Improved quality 
(precision, clarity and 
transparency) 
Section 9.4.5. Interim 
Analysis 
Replaced a blinded sample 
size re-estimation with that 
of an unblinded sample 
size re-estimation. 
Removed the rationale of 
sample size re-estimation – 
“if the expected SD (daily 
pain NRS) is greater than 
1.8 or in the case of high 
dropout.” 
Removed the timing of the 
second interim – “a second 
interim analysis may occur 
The sample size re-
estimation was made 
unblinded and combined. 
with the second interim to 
avoid the scenario where 
the sample size could be 
increased despite the drug 
potentially meeting futility 
criteria. 
As the second interim and 
the sample size re-
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Section # and Name 
Description of Change 
Brief Rationale 
after approximately 28 
participants have 
completed the Week 8 
assessment, the exact 
timing will be determined 
during the sample size re-
estimation or at the first 
interim.”  
combined, the timing has 
been updated to reflect this. 
Appendix 6 Liver Safety: 
Required Actions 
Updated Liver Safety 
Required Actions for Phase 
I studies to include 
acquisition of a PK sample 
Drug concentrations at the 
time of a liver event 
provide important 
information. 
 
 
10.10.6. 
Amendment 6: 12-Nov-2021 
Rationale for Amendment 6 
To clarify that 1) Baseline CCL17 samples will be taken at day -4; 2) Non-re-screening 
of COVID positive participants; 3) Participants with Hep B Core Antibody at screening 
are excluded in Part B 4) Sample size re-estimation will allow for a decrease in sample 
size as well as the already planned potential increase 5) Additional Interim analyses may 
be conducted 6) Minor edits throughout to provide clarification. 
 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.3.5 Schedule of 
Activities -for Part B 
Under the analysis-PK and 
target engagement, added 
collection of baselines 
CCL17 to Day -4 from 
initial screening visit  
To reduce the impact of 
concomitant medications at 
initial screening  
Section 5.2 Exclusion 
Criteria 
Included exclusion for Hep 
B for participants enrolled 
in Part B 
To exclude participants 
with presence of Hep B 
surface antigen at 
screening 
Section 5.4.1 Re-screening 
Added no re-screening of 
COVID positive 
participants. 
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Section 6.3.2 Blinding 
Added the details on 
review process of 
unblinded data from Part B 
at interim analyses 
To provide details on 
review process at interim 
analysis. 
Section 9.2.2 Sample size 
sensitivity 
Added the sample size 
sensitivity table when the 
proportion of trials 
correctly deemed negative. 
More details on sample 
size sensitivity added 
Section 9.4.5. Interim 
Analyses and  
Section 1.1 Synopsis 
Sample size re-estimation 
may be reduced or 
increased at interim 
analysis 2 and potential 
additional interim analyses 
may occur during the study 
Additional interim analyses 
may occur to allow 
interactions with regulatory 
agencies and/or help 
inform internal decision 
making 
Throughout 
Minor edits throughout the 
document for consistency 
and abbreviations updated 
For consistency and clarity 


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11. 
REFERENCES 
Achuthan A, Cook A, Lee M, Saleh R, Khiew H, Chang M,et.al.. Granulocyte 
macrophage colony-stimulating factor induces CCL17 production via IRF4 to mediate 
inflammation. J Clin Invest. 2013. 126(9): 3453-3466. 
Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt L. Validation study of 
WOMAC: A health status instrument for measuring clinically important patient relevant 
outcomes following total hip or knee arthroplasty in osteoarthritis. J Orthopaedic 
Rheumatol 1988; 1: 95-108. 
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neutralization by a monoclonal antibody in healthy subjects selectively inhibits 
recruitment of CCR6+ cells in an experimental suction blister. Br J Clin Pharmacol. 
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antifungal responses during pulmonary invasive aspergillosis. Infect Immun. 2005 
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CP2015PK-002 TE Report, Janssen. ERIS Number: EDMS-ERI-116453323. Zheng S, 
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FDA Guidance for Industry, Immunogenicity Assessment for Therapeutic Protein 
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TMF-14447953 
CONFIDENTIAL 
 
 
 
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Protocol Amd 7 
 
126 
 
GSK Document Number 2017N327494_00 GSK3858279 The Effect of Anti-Murine 
CCL17 mAb in Complete Freund’s Adjuvant Inflammatory Pain Model, Effective Date -
12-SEP-2017 
GSK Document Number 2019N397787_00. An Interim Report of blinded data from Part 
A of Study 207804: A two-part phase I randomized double blind (sponsor open) placebo-
controlled study to evaluate safety, tolerability, pharmacokinetics, target engagement and 
potential for efficacy of single intravenous and subcutaneous doses of GSK3858279 in 
healthy and participants with osteoarthritis of the knee. Effective Date 11-JUN-2019 
GSK Document Number 2020N429762_00. Interim Report of blinded data from Part A 
of Study 207804: A two-part phase I randomized, double blind, placebo-controlled study 
to evaluate safety, tolerability, pharmacokinetics and target engagement of single 
intravenous and subcutaneous doses of GSK3858279 in healthy participants. Effective 
Date SEP-2020. 
GSK Document Number RPS-CLIN-004032: GSK3858279 Investigator’s Brochure V4. 
Feb 2021 
Guideline on Strategies to Identify and Mitigate Risks for First-In-Human Clinical Trials 
with Investigational Medicinal Products, 20 July 2017 EMEA/CHMP/SWP/28367/07 
Rev. 1. 
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SAP_001.pdf: 
 
 
 
 
Reporting and Analysis Plan 
 
 
Study ID: 207804 
 
Official Title of Study: Reporting and Analysis Plan for study 207804 A two-part phase I 
randomized, double-blind, placebo-controlled study toevaluate safety, tolerability, 
pharmacokinetics and target engagement of single intravenous and subcutaneous doses of 
GSK3858279 in healthy participants and to evaluate the efficacy of repeat subcutaneous doses in 
participants with osteoarthritis of the knee 
 
NCT Number: NCT03485365 
 
Date of Document: 28-JUL-2022 


 
C O N FI D E N TI A L  
 
T h e Gl a x o S mit h Kli n e gr o u p of c o m p a ni e s  
 
2 0 7 8 0 4  
 
1  
 
Di visi o n  
: W orl d wi de De vel o p me nt  
I nf or m ati o n T y pe 
: Re p orti n g a n d A nal ysis Pla n ( R A P)   
 
Title  
: Re p orti n g a n d A nal ysis Pla n f or St u d y 2 0 7 8 0 4: A t w o -part 
p hase I ra n d o mize d , d o u ble -bli n d , place b o -c o ntr olle d st u d y 
t o e val uate safet y, t olera bilit y, p h ar mac o ki n etics a n d tar get 
e n ga ge me nt of si n gle i ntr a ve n o us a n d s u bc ut a ne o us d oses 
of G S K 3 8 5 8 2 7 9 i n healt h y partici pa nts a n d t o e val uate t he 
effic ac y of re peat s u bc ut a ne o us d oses i n partici p a nts wit h 
oste oart hritis of t he k nee  
C o m p o u n d N u m ber  : G S K 3 8 5 8 2 7 9  
St u d y N u m ber  
:    2 0 7 8 0 4  
Effecti ve D ate   
: 2 8 -J U L-2 0 2 2  
 
Descri pti o n : 
T he p ur p ose of t his R A P  is t o descri be t he pla n ne d a nal ys es a n d o ut p ut t o b e i ncl u de d 
i n t he Cli nical St u d y Re p ort fr o m Part A a n d Part B of Pr ot oc ol  2 0 7 8 0 4 .  
T his R A P is i nte n de d t o e val uate t he: 
- safet y, t olera bilit y, p har mac o ki netics a n d tar get e n ga ge me nt of G S K 3 8 5 8 2 7 9  i n 
si n gle i ntra v e n o us a n d s u bc uta ne o us d oses i n healt h y partici pa nts ( Part A)  
- safet y, t olera bilit y, efficac y,  p h ar mac o ki netics , tar get e n ga ge m e nt a n d 
i m m u n o ge nicit y of re peat s u bc uta ne o us d oses i n p artici pa nts wit h  oste oart hritis 
of  t he k nee ( Part B). 
T his R A P will be pr o vi de d t o t he st u d y tea m me m bers t o c o n ve y t he c o nte nt of t h e 
Statistical A nal ysis C o m plete ( S A C) deli vera bles.  
 
 
A ut h or  
D ate  
St u d y Statisticia n  
2 8 -J U L-2 0 2 2  
C P M S St u d y Lea d  
 
 
C o p yri g ht 2 0 2 2  t he Gla x o S mit h Kli ne gr o u p of c o m pa nies. All ri g hts r eser ve d.  
U na ut h orise d c o p yi n g or use of  t his i nf or mati o n is pr o hi bite d
P P D
P P D


 
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
 
2  
 
R A P Te a m R e vie w C o nfir m ati o ns  
( Met h o d: E-mail)  
Re vie wer  
Date  
1 1 -J U L-2 0 2 2  
Cli nical Scie nce Lea d a n d Me dical  M o nit or  
1 2 -J U L-2 0 2 2  
C P M S  Pr oject Lea d  
1 2 -J U L-2 0 2 2  
Gl o bal Safet y Re pres e ntati ve  
 
Cli nic al St atistics Li ne A p pr o v als  
( Met h o d: e Si g nat ur e/e mail) 
A p pr o ver  
Date  
2 1 -J U L-2 0 2 2  
Pr oject Statisticia n   
2 8 -J U L-2 0 2 2  
Pr oject Pr o gra m mi n g Le a der   
 
P P D
P P D
P P D
P P D
P P D


 
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
3  
 
T A B L E O F C O N T E N T S  
1.  
I N T R O D U C TI O N ...................................................................................................... 6  
1. 1.  
V er si o n hi st or y  .............................................................................................. 6  
2.  
S U M M A R Y O F K E Y P R O T O C O L I N F O R M A TI O N  .................................................. 7  
2. 1.  
C h a n g e s t o t h e Pr ot o c ol D efi n e d St ati sti c al A n al y si s Pl a n  ............................ 7  
2. 2.  
St u d y O bj e cti v e s a n d E n d p oi nt s  ................................................................... 8  
2. 3.  
St u d y D e si g n  .............................................................................................. 1 0  
2. 4.  
St ati sti c al A n al y s e s  ..................................................................................... 1 3  
3.  
P L A N N E D A N A L Y S E S  .......................................................................................... 1 3  
3. 1.  
I nt eri m A n al y s e s ......................................................................................... 1 3  
3. 2.  
F i n al A n al y s e s ............................................................................................ 1 4  
4.  
A N A L Y SI S P O P U L A TI O N S  ................................................................................... 1 5  
4. 1.  
A n al y si s P o p ul ati o n s  ................................................................................... 1 5  
4. 1. 1.  
P art A a n d B  ................................................................................ 1 5  
4. 1. 2.  
P art A o nl y  ................................................................................... 1 5  
4. 1. 3.  
P art B o nl y  ................................................................................... 1 6  
4. 2.  
Pr ot o c ol D e vi ati o n s  ..................................................................................... 1 6  
5.  
C O N SI D E R A TI O N S F O R D A T A A N A L Y S E S A N D D A T A H A N D LI N G 
C O N V E N TI O N S  ..................................................................................................... 1 8  
5. 1.  
G e n er al  ....................................................................................................... 1 8  
5. 2.  
St u d y Tr e at m e nt Di s pl a y D e s cri pt or s  .......................................................... 1 8  
5. 3.  
B a s eli n e D efi niti o n s  .................................................................................... 1 8  
5. 4.  
Ot h er C o n si d er ati o n s f or D at a A n al y s e s a n d D at a H a n dli n g 
C o n v e nti o n s  ................................................................................................ 1 9  
6.  
S T U D Y P O P U L A TI O N A N A L Y S E S  ....................................................................... 2 0  
7.  
E F FI C A C Y A N A L Y S E S –  P A R T B O N L Y  .............................................................. 2 1  
7. 1.  
C o -pri m ar y Effi c a c y A n al y s e s  ..................................................................... 2 1  
7. 1. 1.  
E n d p oi nt / V ari a bl e s  ..................................................................... 2 1  
7. 1. 2.  
S u m m ar y M e a s ur e  ...................................................................... 2 1  
7. 1. 3.  
P o p ul ati o n of I nt er e st  ................................................................... 2 1  
7. 1. 4.  
Str at e g y f or I nt er c urr e nt ( P o st -R a n d o mi z ati o n) E v e nt s  ................ 2 1  
7. 1. 5.  
St ati sti c al A n al y s e s / M et h o d s  ..................................................... 2 2  
7. 2.  
E x pl or at or y Effi c a c y A n al y s e s  ..................................................................... 2 4  
7. 2. 2.  
S u m m ar y M e a s ur e  ...................................................................... 2 4  
7. 2. 3.  
P o p ul ati o n of I nt er e st  ................................................................... 2 4  
7. 2. 4.  
Str at e g y f or I nt er c urr e nt ( P o st -R a n d o mi z ati o n) E v e nt s  ................ 2 4  
7. 2. 5.  
St ati sti c al A n al y s e s / M et h o d s  ..................................................... 2 5  
8.  
S A F E T Y A N A L Y S E S  ............................................................................................. 2 6  
8. 1.  
A d v er s e E v e nt s A n al y s e s  ........................................................................... 2 6  
8. 2.  
Cli ni c al L a b or at or y A n al y s e s  ....................................................................... 2 6  
8. 3.  
Ot h er S af et y A n al y s e s  ................................................................................ 2 9  
8. 4.  
C O VI D -1 9 P a n d e mi c St ati sti c al Di s pl a y s  .................................................... 2 9  
9.  
P H A R M A C O KI N E TI C A N A L Y S E S  ......................................................................... 3 0  
C CI


 
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
4  
 
9. 1.  
S er u m P h ar m a c o ki n eti c s  ............................................................................ 3 0  
9. 1. 1.  
E n d p oi nt / V ari a bl e s  ..................................................................... 3 0  
9. 1. 2.  
S u m m ar y M e a s ur e  ...................................................................... 3 2  
9. 1. 3.  
P o p ul ati o n of I nt er e st  ................................................................... 3 2  
9. 1. 4.  
Str at e g y f or I nt er c urr e nt ( P o st -R a n d o mi z ati o n) E v e nt s  ................ 3 2  
9. 1. 5.  
St ati sti c al A n al y s e s / M et h o d s  ..................................................... 3 2  
9. 2. 1.  
E n d p oi nt / V ari a bl e s  ..................................................................... 3 4  
9. 2. 2.  
S u m m ar y M e a s ur e  ...................................................................... 3 4  
9. 2. 3.  
P o p ul ati o n of I nt er e st  ................................................................... 3 4  
9. 2. 4.  
Str at e g y f or I nt er c urr e nt ( P o st -R a n d o mi z ati o n) E v e nt s  ................ 3 4  
9. 2. 5.  
St ati sti c al A n al y s e s / M et h o d s  ..................................................... 3 4  
1 0.  P H A R M A C O D Y N A MI C A N A L Y S E S ....................................................................... 3 5  
1 0. 1.  S er u m T ar g et E n g a g e m e nt A n al y s e s  ......................................................... 3 5  
1 0. 1. 1.  
E n d p oi nt / V ari a bl e s  ..................................................................... 3 5  
1 0. 1. 2.  
S u m m ar y M e a s ur e  ...................................................................... 3 8  
1 0. 1. 3.  
P o p ul ati o n of I nt er e st  ................................................................... 3 8  
1 0. 1. 4.  
Str at e g y f or I nt er c urr e nt ( P o st -R a n d o mi z ati o n) E v e nt s  ................ 3 8  
1 0. 1. 5.  
St ati sti c al A n al y s e s / M et h o d s  ..................................................... 3 8  
1 0. 3.  I m m u n o g e ni cit y........................................................................................... 3 8  
1 0. 3. 1.  
S u m m ar y M e a s ur e  ...................................................................... 3 8  
1 0. 3. 2.  
P o p ul ati o n of I nt er e st  ................................................................... 3 9  
1 1.  P H A R M A C O KI N E TI C / T A R G E T E N G A G E M E N T / P H A R M A C O D Y N A MI C 
( P K/ T E/ P D) A N A L Y S E S ......................................................................................... 3 9  
1 1. 1.  P h ar m a c o ki n eti c / T ar g et E n g a g e m e nt / P h ar m a c o d y n a mi c D at a s et 
S p e cifi c ati o n  ............................................................................................... 3 9  
1 2.  BI O M A R K E R A N A L Y S E S –  P A R T A O N L Y  ........................................................... 4 0  
1 2. 1.  I m m u n e C ell P h e n ot y p e s ............................................................................ 4 0  
1 2. 1. 2.  
S u m m ar y M e a s ur e  ...................................................................... 4 0  
1 2. 1. 3.  
P o p ul ati o n of I nt er e st  ................................................................... 4 0  
1 2. 1. 4.  
St ati sti c al A n al y s e s / M et h o d s  ..................................................... 4 0  
1 3.  R E F E R E N C E S  ....................................................................................................... 4 3  
1 4.  A P P E N DI C E S  ........................................................................................................ 4 5  
1 4. 1.  A p p e n di x 1: Pr ot o c ol D e vi ati o n M a n a g e m e nt a n d D efi niti o n s f or 
F ull y Tr e at e d P o p ul ati o n  ............................................................................. 4 5  
1 4. 1. 1.  
E x cl u si o n s fr o m F ull y Tr e at e d P o p ul ati o n ( P art A) a n d P er 
Pr ot o c ol P o p ul ati o n ( P art B) ......................................................... 4 5  
1 4. 2.  A p p e n di x 2: S c h e d ul e of A cti viti e s  .............................................................. 4 7  
1 4. 2. 1.  
S cr e e ni n g  .................................................................................... 4 7  
1 4. 2. 2.  
P art A C o h ort s Wit h o ut Bli st er: 0. 1 a n d 0. 3 m g/ k g I V  ................... 4 8  
1 4. 2. 3.  
P art A C o h ort s Wit h Bli st er: 1 m g/ k g I V  ....................................... 4 9  
1 4. 2. 4.  
P art A C o h ort s Wit h Bli st er: 3 a n d 1 0 m g/ k g I V a n d S C  ............... 5 0  
1 4. 2. 5.  
P art B  .......................................................................................... 5 1  
1 4. 3.  A p p e n di x 3: A s s e s s m e nt Wi n d o w s  ............................................................. 5 2  
C CI
C CI
C CI
C CI


 
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
5  
 
1 4. 4.  A p p e n di x 4: St u d y P h a s e s a n d Tr e at m e nt E m er g e nt A d v er s e 
E v e nt s  ........................................................................................................ 5 3  
1 4. 4. 1.  
St u d y P h a s e s  .............................................................................. 5 3  
1 4. 4. 2.  
Tr e at m e nt E m er g e nt Fl a g f or A d v er s e E v e nt s  ............................. 5 3  
1 4. 5.  A p p e n di x 5: D at a Di s pl a y St a n d ar d s & H a n dli n g C o n v e nti o n s  .................... 5 4  
1 4. 5. 1.  
R e p orti n g Pr o c e s s  ....................................................................... 5 4  
1 4. 5. 2.  
R e p orti n g St a n d ar d s  .................................................................... 5 5  
1 4. 5. 3.  
R e p orti n g St a n d ar d s f or P h ar m a c o ki n eti c  .................................... 5 6  
1 4. 6.  A p p e n di x 6: D eri v e d a n d Tr a n sf or m e d D at a  ............................................... 5 8  
1 4. 6. 1.  
G e n er al  ........................................................................................ 5 8  
1 4. 6. 2.  
St u d y P o p ul ati o n  .......................................................................... 5 9  
1 4. 6 . 3. 
Effi c a c y  ........................................................................................ 6 0  
1 4. 6. 4.  
S af et y  .......................................................................................... 6 1  
1 4. 6. 5.  
I m m u n o g e ni cit y............................................................................ 6 2  
1 4. 7.  A p p e n di x 7: R e p orti n g St a n d ar d s f or Mi s si n g D at a  ..................................... 6 3  
1 4. 7. 1.  
Pr e m at ur e Wit h dr a w al s  ................................................................ 6 3  
1 4. 7. 2.  
H a n dli n g of Mi s si n g D at a  ............................................................. 6 3  
1 4. 8.  A p p e n di x 8: V al u e s of P ot e nti al Cli ni c al I m p ort a n c e  ................................... 6 6  
1 4. 8. 1.  
P CI V al u e s f or P art A  ................................................................... 6 6  
1 4. 8. 2.  
P CI V al u e s f or P art B  ................................................................... 6 7  
1 4. 9.  A p p e n di x 9: St ati sti c al Al g orit h m s a n d M o d el C h e c ki n g  .............................. 7 0  
1 4. 9. 1.  
C al c ul ati o n of S D fr o m B a y e si a n R e p e at e d M e a s ur e s 
m o d el  ........................................................................................... 7 0  
1 4. 9. 2.  
M o d el C h e c ki n g & Di a g n o sti c s  .................................................... 7 0  
1 4. 1 1.  A p p e n di x 1 0: A b br e vi ati o n s & Tr a d e M ar k s  ................................................ 7 3  
1 4. 1 1. 1.  A b br e vi ati o n s  ............................................................................... 7 3  
1 4. 1 1. 2.  Tr a d e m ar k s  ................................................................................. 7 4  
1 4. 1 2.  A p p e n di x 1 1: Li st of D at a Di s pl a y s .............................................................. 7 5  
1 4. 1 2. 1.  D at a Di s pl a y N u m b eri n g  .............................................................. 7 5  
1 4. 1 2. 2.  M o c k E x a m pl e S h ell R ef er e n ci n g  ................................................ 7 5  
1 4. 1 2. 3.  D eli v er a bl e s  ................................................................................. 7 5  
1 4. 1 2. 4.  S af et y R e vi e w T a bl e  .................................................................... 7 6  
1 4. 1 2. 5.  S a m pl e Si z e R e -e sti m ati o n t a bl e  ................................................. 7 6  
1 4. 1 2. 6.  St u d y P o p ul ati o n T a bl e s  .............................................................. 7 7  
1 4. 1 2. 7.  S af et y T a bl e s  ............................................................................... 8 0  
1 4. 1 2. 8.  P h ar m a c o ki n eti c T a bl e s  ............................................................... 8 5  
1 4. 1 2. 9.  P h ar m a c o ki n eti c Fi g ur e s  ............................................................. 8 8  
1 4. 1 2. 1 0.  P h ar m a c o d y n a mi c T a bl e s  ........................................................... 9 7  
1 4. 1 2. 1 1.  P h ar m a c o d y n a mi c Fi g ur e s  ........................................................ 1 0 5  
1 4. 1 2. 1 2.  Bi o m ar k er T a bl e s  ....................................................................... 1 1 0  
1 4. 1 2. 1 3.  Bi o m ar k er Fi g ur e s  ..................................................................... 1 1 1  
1 4. 1 2. 1 4.  Effi c a c y T a bl e s  .......................................................................... 1 1 1  
1 4. 1 2. 1 5.  Effi c a c y Fi g ur e s  ......................................................................... 1 1 4  
1 4. 1 2. 1 6.  I C H Li sti n g s ............................................................................... 1 1 6  
1 4. 1 2. 1 7.  I C H C o n diti o n al Li sti n g s ............................................................. 1 2 1  
1 4. 1 2. 1 8.  N o n -I C H Li sti n g s ........................................................................ 1 2 2  
 
 
 
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1. 
INTRODUCTION 
The purpose of this reporting and analysis plan (RAP) is to describe the analyses to be 
included in the Clinical Study Report for Protocol 207804: 
Revision Chronology: 
Amendment 7 
09-FEB-2022 
TMF-14447953 
Amendment 6 
12-NOV-2021 
TMF-11834237 
Amendment 5 
07-SEP-2020 
2017N342035_05 
Amendment 4 
14-NOV-2019 
2017N342035_04 
Amendment 3 
18-JUL-2019 
2017N342035_03 
Amendment 2 
21-NOV-2018 
2017N342035_02 
Amendment 1 
10-APR-2018 
2017N342035_01 
Original Protocol 
02-FEB-2018 
2017N342035_00 
 
1.1. 
Version history 
SAP 
Version 
Approval 
Date 
Protocol Version 
(Date) on which 
SAP is Based 
Change 
Rationale 
SAP  
01-MAR-
2021 
2017N342035_05 
(07-SEP-2020) 
Not Applicable 
Original version.  
SAP 
amendment 
1 
01-JUN-
2021 
2017N342035_05 
(07-SEP-2020) 
Part B sections 
Part A, unmodified from 
previous version, and 
amended Part B. 
SAP 
amendment 
2 
24-MAR-
2022 
TMF-14447953 
(09-FEB-2022) 
Part B Sections 
Programming 
notes for PK and 
TE outputs 
Adding additional 
Interim Analyses 
Information 
Protocol was amended to 
account for two additional 
Interim Analyses.  
SAP 
Amendment 
3 
28-JUL-
2022 
TMF-14447953 
(09-FEB-2022) 
Primary model 
update. 
Clarification on 
Intercurrent 
Events section. 
Additional outputs 
for IA4 and Part B 
SAC. 
Inclusion of safety 
tables (Part B 
2.37-2.39) 
Update to the model 
specification to avoid 
overparameterization by 
removal of the random 
subject intercept, and to 
include only data during 
the treatment period (i.e. 
up to week 8) in the 
primary analysis model. 
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2. 
SUMMARY OF KEY PROTOCOL INFORMATION 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan 
There were no changes or deviations to the originally planned statistical analysis 
specified in the protocol 2017N342035_05 [(Dated: 07-Sep-2020)]. 
 
 


 
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2 0 7 8 0 4  
8  
 
2. 2.  
St u d y O bj e cti v e s a n d E n d p oi nt s  
O bjecti ves  
E n d p oi nts  
Pri m ar y  
P arts A a n d B  
T o e val uate t he s afet y a n d t olera bilit y of 
escalati n g d oses of G S K 3 8 5 8 2 7 9  
f oll o wi n g si n gle I V, si n gle S C d osi n g i n 
healt h y p artici pa nts a n d re peat S C 
d osi n g i n O A partici pa nts . 
 
A d verse E v e nts ( A E) a n d Seri o us A d verse 
E ve nts ( S A E).  
Cli nical la b orat or y meas ure me nts,  1 2 -lea d 
electr ocar di o gra ms ( E C G) a n d vital si g ns.  
P art B  
T o as sess c ha n ges i n pai n i n partici pa nts 
wit h O A of t h e k nee f oll o wi n g re peat 
S C  d osi n g.  
 
C ha n ge fr o m bas eli ne i n a vera ge  k nee pai n 
i nte nsit y at wee k 8.  
C ha n ge fr o m bas eli ne i n w orst k nee pai n  
i nte nsit y at Wee k 8 .  
Sec o n d ar y  
T o descri be t he p h ar mac o ki netics  (P K ) 
of  G S K 3 8 5 8 2 7 9  f oll o wi n g si n gle I V, 
si n gle S C i n healt h y p arti ci pa nts a n d 
re peat S C d osi n g i n O A partici pa nts.  
T o e val uate  t he t ar get e n ga ge me nt ( T E) 
of  C C L 1 7 b y G S K 3 8 5 8 2 7 9 f oll o wi n g 
si n gle I V, si n gle S C d osi n g i n he alt h y 
partici pa nts a n d re peat S C d osi n g i n O A  
partici pa nts.  
 
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2. 3.  
St u d y D e si g n  
T his st u d y will be a ra n d o mize d, d o u ble -bli n d , place b o -c o ntr olle d, t w o -p art trial. A st u d y 
dia gra m is i ncl u de d i n Ta ble 1 . 
Part A will be a si n gl e as ce n di n g d ose es calati o n st u d y t o e val u ate t he safe t y, t olera bilit y, 
P K, a n d tar get e n ga ge me nt of G S K 3 8 5 8 2 7 9 i n healt h y  partici pa nts . Si n gle I V d oses a n d 
a si n gle S C d ose will be i n vesti gate d i n s e parate c o h orts of partici pa nts. Tar get 
e n ga ge me nt will be assesse d b ot h i n bl o o d a n d
U p t o fi ve si n gle asce n di n g I V 
d ose  le vels of G S K 3 8 5 8 2 7 9 will be i n vesti gate d. A si n gle S C d ose of G S K 3 8 5 8 2 7 9 will 
als o be assesse d t o d eter mi ne bi oa vaila bilit y, as f ut ure st u dies as well as t he tar get 
pr o d uct will li kel y i n v ol ve S C a d mi nistrati o n.  
A D ose Escalati o n C o m mittee ( D E C) will re vie w at least 1 5 da ys of safet y a n d P K data 
pri or t o pr o gressi o n t o t he ne xt d ose le vel.  T he d ecisi o n t o pr o gress  t he S C c o h ort will be 
base d u p o n u n derst a n di n g t he P K a n d T E data fr o m s o me I V c o h orts. O nce s ufficie nt 
safet y, P K a n d tar get e n ga ge me nt data is c ollecte d fr o m t he t o p I V d ose a n d S C c o h orts, 
a data re vie w will ta ke pl ace a n d a decisi o n t o pr ocee d wit h Part B of t he st u d y ma y b e 
ma de.  
I n Part A, se nti nel partici pa nts will be use d i n eac h d osi n g c o h ort: t w o partici pa nts will 
be d ose d first, o ne will b e ra n d o mize d t o G S K 3 8 5 8 2 7 9 a n d o ne t o place b o. 4 8-h o ur p ost 
d ose safet y dat a fr o m t he se nti nel partici pa nts will be re vie we d b y t he i n vesti gat or a n d 
t he re mai n der of t he c o h ort will t he n be d ose d if dee me d safe t o d o s o.  
Part B will i n vesti gat e t he safet y, t olera bilit y, cli nical effi cac y o n p ai n  (as pri mar y 
e n d p oi nts), P K , tar get e n ga ge me nt  a n d i m m u n o ge nicit y i n partici pa nts wit h O A of t he 
k nee aft er wee kl y S C d osi n g f or 8  wee ks of G S K 3 8 5 8 2 7 9 or place b o i n a 1: 1 rati o.  
T he ta ble bel o w pr o vi des a n o ver vie w of t he st u d y desi g n a n d t he ke y feat ures.  
 
 
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Table 1 
Study Design 
Study Design 
Figure 1: Parts A and B: Study Design  
  
 
 
 
Part A 
Design 
features 
• 
Within each cohort, and hence at each dose level, GSK3858279 and placebo will be 
administered in a 3:1 ratio according to the randomisation schedule, in a blinded 
manner.  
• 
Of the eight participants within each cohort, six will receive GSK3858279 and two 
will receive placebo, as per the randomisation schedule. 
• 
Up to a maximum of 5 IV dose levels and 1 SC dose level will be studied in total in 
Part A. To mitigate a risk of adverse reactions, sequential dosing will be 
implemented. Two sentinel participants will receive study intervention first (one on 
active, one on placebo) per dosing cohort and will be monitored in the clinical unit 
for approximately 48 hours. 
• 
Assuming adequate safety from these two participants over the first 48 hrs post-
dose, the remaining participants in the cohort can then be dosed. 
• 
Dose escalation data reviews will occur once sufficient safety and PK data is 
obtained from a cohort, and a dose escalation to the next planned dose may occur.  
• 
The decision to proceed to the next dose level of GSK3858279 will be made at a 
Dose Escalation Committee (DEC) meeting. Details are included in the Dose 
Escalation Plan (DEP). 
• 
Upon review of data from the 1 mg/kg IV cohort, the DEC may decide to trigger the 
SC cohort as well as the 3 mg/kg IV cohort, if data are satisfactory.  
• 
Once eight participants in the highest dose cohort in Part A have completed the Day 
15 visit, the DEC will review all available safety, PK, target engagement (i.e, free 
and total CCL17 levels) in serum and decide whether to proceed with Part B of the 
study.  


 
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
1 2  
 
St u d y D e si g n  
•  
I n c ase of e arly dro p o uts , a mini m u m of 6 partici p a nts c o m pleti n g t he D ay 1 5 visit 
will b e r eq uir e d f or d os e esc alati o n d at a r evi e w
•  
B as e d o n t h e e m er gi ng P K a nd T E d at a fr o m P art A , a si n gle I V d os e u p t o 10 
m g/k g  is not s uit a ble t o t est t he m ec ha nis m in O A p artici p a nts a n d  he nc e  a r e p eat  
S C  d os e  of 24 0 m g  is no w c o nsi d er e d m or e a p pr o pri at e  ( Pr ot oc ol A m e n d me nt # 3, 
J uly 2 0 1 9) an d Pr ot oc ol A me nd m e nt #5, S e pt 20 2 0  b as e d  on t h e o bs erv ed T E of 3 
m g/k g  S C a nd pr e dict e d T E aft er r e p e at S C d osi n g.  
P art A Ti m e 
& E v e nt s  
•  
R ef er t o A pp en dix 2  
P art A  
Tre at m e nt 
s e q u e n c e s  
Wit hi n eac h c o h ort, p artici p ants will be assi g ne d t o eit h er G S K 3 8 5 8 2 7 9 or pl ac e b o i n a 
3: 1 r ati o, w h er e t h e i nt erv e ntion c o d es ar e as f oll o ws:  
 
I nt erv e nti o n c o d e 
I nt erv e nti o n D escri pti o n 
A  
0. 1 m g/k g I V G S K38 5 8 2 79  
B  
0. 3 m g/k g I V G S K38 5 8 2 79  
C  
1 m g/kg I V G S K3 8 58 2 7 9  
D  
3 m g/kg I V G S K3 8 58 2 7 9  
E  
1 0 m g/k g I V G S K3 85 8 2 7 9  
F  
S C G S K 3 8 5 8 2 7 9  
P  
Pl ac e b o  
 
 
P art  B 
De si g n 
F e at ure s  
•  
I n P art B, t h e tot al dur ati on of th e st u dy (fr o m 1st scr ee ni n g visit  until fi n al f ollo w -u p) 
f or e ac h p artici p a nt will b e u p to 1 8 2  d ays  (i nclusiv e of a scree ni n g peri o d of a 
m axi m u m of 4 2 days ). 
•  
A p pr oxi mat ely 5 0 ( up t o a m axi m u m of 8 0) partici p a nts wit h O A  will be r a n d o mly  
assi gn e d t o G S K 3 8 58 2 7 9 or pl ac e b o i n a 1: 1 r ati o.  
•  
E ac h p artici pa nt will r ec eiv e we ekly S C d os es of eit h er 24 0 m g G S K 3 8 58 2 7 9 or 
pl ac e bo f or 8 w eeks.  
•  
Cl os e i n -str e a m s afety r evi e w ( A Es, cli nic al l a bor at ory, vital si g ns, c ar diac 
m o nit ori n g) is pla n n e d t hr o u g ho ut f or all p artici pa nts (s e e S afety M an a g e me nt Pl an). 
•  
A n e arly d et ail e d r evi e w of s afety, P K, T E a n d A D A d at a f ollo wi n g a d mi nistr atio n of 
r e p e at d os es is i nt e n de d f or t he first 8 p artici p ants ( 4 ra n d o miz e d t o activ e 
tr e at m e nt) w he n t h e 8 t h p articip a nt c o m pl et es t he W e ek 4  ass ess m e nt .  
•  
A  s ec o nd d et ail e d revi e w of s af ety, P K, T E a nd A D A d at a is int e n d e d for t h e first 20  
p articip a nts ( 1 0  r a nd o miz e d to active tr e at m e nt) w h en t h e 20 t h p artici p a nt c o mpl et es 
t h e W e ek 4 ass ess m ent.  
•  
A n i nt eri m a n alysis f or f utility will occ ur o nc e a ppr oxi m at ely 2 0 p artici p ants h av e 
c o m pl et e d th e W e ek 4 ass ess m e nt.  
•  
A s ec o nd i nt eri m an alysis f or a n u n bli n d e d s a mpl e siz e r e -esti m ati o n , i ncl u di ng a 
f utility ass ess m ent, m ay occ ur pri or t o enr olli n g t he 5 0t h p artici p a nt, w h er e t h e 
s a m pl e siz e c o ul d b e d ecr e ase d t o a mi ni m u m of 2 0 or i ncreas e d t o a m axi mu m of 
8 0 p artici p ants  e nroll ed  if th e o bs erve d S D of C h a n ge fr o m b as eli n e in t h e av er a ge  
k n e e p ai n int e nsity at w e ek 8 is s m all er or gr e at er t h a n 1. 8  res p ectiv ely. S a m pl e 
siz e i ncr eas e m ay als o occ ur to acc ou nt f or p artici p a nts w h o disc onti n ue t h e 
tr e at m e nt or st udy pri or t o Week 8. S e e S ecti on 7. 1.5. 1  f or m or e d etails 
•  
A d diti o nal i nt eri m a n alys es m ay occur f or int er n al d ecisio n maki n g a n d/ or i nt er acti o n 
wit h r e g ul at ory ag e nci es as a ppr o pri at e.   
 
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Study Design 
Part B Time 
& Events 
• 
Refer to Appendix 2 
Part B 
Treatment 
sequences 
• 
Participants will be assigned to either GSK3858279 or placebo in a 1:1 ratio, where 
the intervention codes are as follows: 
 
Intervention code 
Intervention Description 
G 
240 mg SC GSK3858279 
P 
Placebo 
2.4. 
Statistical Analyses 
As the primary objective for part A of the study is safety and tolerability, and for part B is 
safety, tolerability and efficacy there are no formal hypotheses to be evaluated.  
Part A: An assessment of dose proportionality will be conducted for selected 
pharmacokinetic endpoints (i.e. Cmax, and AUC(0-∞) and/or AUC(0-t)) following single 
IV dose. In addition, an exploratory comparison will be made between the IV and SC 
formulations at the dose level studied. This will be only done for the 3 mg/kg IV and SC 
doses. 
Part B: A comparison between GSK3858279 and Placebo will be made on the pain 
numerical rating scale. An assessment will be made comparing GSK3858279 to placebo 
with respect to the change from baseline in average pain intensity at week 8. The change 
from baseline in worst pain intensity at week 8 will also be assessed. 
3. 
PLANNED ANALYSES 
3.1. 
Interim Analyses 
Part A: No formal interim statistical analyses are planned. However, dose escalation 
meetings will occur at a relevant timepoint after each dose level; including between Parts 
A and B. 
The decision to proceed to the next cohort, and next dose strength to be studied, will be 
made by the Dose Escalation Committee (DEC) based on assessment of safety and serum 
GSK3858279 pharmacokinetic data obtained in all participants at the prior dose level. 
Individual safety data (adverse events, laboratory safety tests, ECGs and vital signs) will 
be reviewed. In addition, immunogenicity data may be reviewed by the DEC during the 
study. Once sufficient safety, PK and target engagement data is collected from the top IV 
dose and SC cohorts, a data review will take place and a decision to proceed with Part B 
of the study may be made. Further details are included in the Dose Escalation Plan (DEP) 
Version 003 dated 19-Nov-2018. 
Unblinded data from Part A may be reported out in full following the last subject last 
visit in this part of the study and prior to the conclusion of Part B. 
Part B:  The first interim analysis will occur once approximately 20 participants have 
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size re-estimation may occur prior to enrolling the 50th participant, where the sample size 
could be decreased to a minimum of 20 or increased to a maximum of 80 participants.  
Additional interim analyses may occur in order to inform internal decision making and/or 
for interaction with regulatory agencies as appropriate.  
In addition to the interim analyses, two planned blinded safety data reviews as specified 
in the protocol will be carried out to decide upon dose adjustment, participant 
continuation/ discontinuation and if need be, to stop the study due to safety concerns. The 
necessary unblinded data will be summarised in a blinded fashion either by using dummy 
participant IDs or by presenting only group level data. 
Further details of the part B interim analyses and safety reviews are outlined in the 
Interim Analysis Charter. 
3.2. 
Final Analyses 
The final planned analyses (Parts A and B) will be performed after the completion of the 
following sequential steps: 
1. All participants have completed the study as defined in the protocol (Section 4.5 
End of Study Definition of the protocol): The end of the study is defined as the 
date of the last visit (including follow-up) of the last participant in the study 
(Parts A and B). 
2. All required database cleaning activities have been completed and final database 
release (DBR) and database freeze (DBF) has been declared by Data 
Management. The final delivery for Part A may be generated in its own reporting 
area prior to the completion of Part B of the study once Data Management has 
declared DBF for Part A. Parts A and B final deliveries may be generated and 
kept in separated reporting areas. 
3. All criteria for unblinding the randomization codes have been met.  
4. Randomization codes have been distributed according to RandAll NG and 
RAMOS NG procedures. 
 
 


 
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4. 
ANALYSIS POPULATIONS 
4.1. 
Analysis Populations 
4.1.1. 
Part A and B 
Population 
Description 
Outputs 
Screened  
• All participants who were screened for eligibility 
• Study Population 
(specific only) 
Enrolled 
• All participants who passed screening and 
entered the study. 
 
• Note screening failures (who never passed 
screening even if rescreened) and participants 
screened but never enrolled into the study are 
excluded from the Enrolled population as they did 
not enter the study. 
• Study Population 
(Specific only) 
 
Randomized  
 
• All participants who were randomly assigned to 
treatment in the study. 
• This population will be based on the treatment 
the participant was randomized to. 
• Study Population  
Safety 
• All randomized participants who received at least 
one dose of study treatment. 
• This population will be based on the treatment 
the participant received. 
• Study Population 
(specific only) 
• Safety 
• PD 
Pharmacokinetic 
• All participants in the Safety population who had 
at least 1 reportable serum PK assessment. 
• This population will be based on the treatment 
the participant received. 
• Note: Non-quantifiable [NQ] values will be 
considered as reportable values 
• PK 
 
4.1.2. 
Part A only  
Population 
Description 
Outputs 
Blister 
• All participants in the Safety population who had 
at least one blister assessment. 
• This population will be based on the treatment 
the participant received. 
• PD 
Blister 
Pharmacokinetic  
• All participants in the Safety population who had 
at least 1 reportable blister PK assessment. 
• This population will be based on the treatment 
the participant received. 
• PK 


 
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
1 6  
 
•  N ot e: N on -q ua ntifi abl e [ N Q] v al u es will b e 
F ully tr e at e d  
•  All p artici p a nts i n th e S afety p o pul ati on w h o 
r ec eiv e d at l east 80 % of pl an n ed st udy 
tr e at m e nt*. 
•  T his p o pul ati on will b e i de ntifi e d by r evie w of 
pr ot oc ol d evi ati o ns  
•  P K, P D  
* P art A has a si n gle d ose. P erce nta ge of a ct u al a m o u nt a d mi nistere d  will be deri ve d  usi n g t h e pla n ne d d ose a n d t h e 
i njecte d i nf usi o n v ol u me.  
4. 1. 3.  
P art B o nl y  
P o p ul ati o n  
D e s cri pti o n  
O ut p ut s  
I nt e nt-t o-Tr e at  
•  All r a n d o miz ed p articip a nts w h o r ec eiv ed at l e ast 
o n e d ose of st u dy tr e at m e nt.  
•  T his p o pul ati on will b e b as ed o n t he tr e at m e nt 
t h e p artici p ant w as r an do miz e d to . 
A ny p artici p a nts w h o rec eive a tr eat m ent 
r a n d o miz ati on nu m b er will b e c o nsid er e d t o h ave 
b e en r a nd o miz e d.  
•  Effic acy  
P er Pr otoc ol  
•  All p artici p a nts i n th e I T T p op ul ati on w ho c o m ply 
wit h t h e pr otoc ol.  
•  Pr ot oc ol d evi atio ns th at w oul d excl ud e 
p artici p a nts fr o m th e P P p op ul ati on ar e d efi n ed i n 
S ecti o n 4.2  ( Pr otoc ol D evi ati o ns) a nd Ap p en dix 
1 : Excl usi ons fr o m Per Pr otocol P op ul ati o n *). 
•  Effic acy  
(s p ecific o nly) 
* T his p o p ul ati o n will b e b as e d o n t h e tr e at m e nt t h e p artici p a nt w as r a n d o miz e d t o. 
4. 2.  
Pr ot o c ol D e vi ati o n s  
I m p ort a nt pr ot oc ol de viati o ns (i ncl u di n g b ut n ot li mite d t o  de viati o ns relate d t o st u d y 
i ncl usi o n/e x cl usi o n criteria, a n d a d diti o nall y i n part B: pr o hi bite d me dicati o ns, resc ue 
me dicati o ns, st u d y me dicati o n a n d missi n g diar y d ata ) will be s u m marise d a n d liste d. 
I m p ort a nt de viati o ns w hic h res ult i n e xcl usi o n fr o m the a nal ysis p o p ulati o n will als o be 
s u m marise d a n d liste d.  
Please refer t o A p p e n di x 1 . 
Pr ot oc ol de viati o ns will be trac k e d b y t he st u d y tea m t hr o u g h o ut t he c o n d uct of t he st u d y 
i n acc or da nce wit h t he Pr ot oc ol De viati o n Ma na ge me nt Pla n. 
•  Data will be re vi e we d pri or t o u n bli n di n g a n d freezi n g t he data bas e t o e ns ure all 
i m p orta nt de viati o ns are ca pt ure d a n d cat e g orise d o n t he pr ot oc ol de viati o ns 
dataset.  
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• This dataset will be the basis for the listings of protocol deviations. 
A separate listing of all inclusion/exclusion criteria deviations will also be provided. This 
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5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS 
5.1. 
General 
Separate outputs will be generated for both Part A and Part B. 
5.2. 
Study Treatment Display Descriptors 
In the Tables, Listings and Figures (TLF), treatment should be presented with placebo 
first, then in order of increasing dose by route of administration within each part. 
Part A: Treatment group descriptions 
RandAll NG 
Data displays for reporting 
Code 
Description 
Description 
Order in TLF 
A 
0.1 mg/kg IV GSK3858279 
0.1 mg/kg IV GSK3858279 
2 
B 
0.3 mg/kg IV GSK3858279 
0.3 mg/kg IV GSK3858279 
3 
C 
1 mg/kg IV GSK3858279 
1 mg/kg IV GSK3858279 
4 
D 
3 mg/kg IV GSK3858279 
3 mg/kg IV GSK3858279 
5 
E 
10 mg/kg IV GSK3858279 
10 mg/kg IV GSK3858279 
6 
F 
SC GSK3858279 
3 mg/kg SC GSK3858279 
7 
P 
Placebo 
Placebo 
1 
 
 
5.3. 
Baseline Definitions 
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. Replicate assessments at a 
timepoint will be averaged, and the mean value will be used. Unless otherwise stated, if 
baseline data is missing, no derivation will be performed and baseline will be set to 
missing. 
For the average and worst knee pain intensity, the mean of the scores in index knee over 
7 days prior to dosing (Day -7 to Day -1) will be considered as baseline. Baseline should 
be calculated only if pain scores are recorded on at least 5 days out of 7. If pain scores are 
not recorded on at least 5 days, the baseline will be set to missing. 
For Part B of the study, the CCL17 levels (free, total) baseline value will be derived by 
averaging the two pre-dose measurements (i.e., average of Day-4 and Day 1). 
Part B: Treatment group descriptions 
RandAll NG 
Data displays for reporting 
Code 
Description 
Description 
Order in TLF 
G 
240 mg SC GSK3858279  
240 mg SC GSK3858279  
2 
P 
Placebo 
Placebo 
1 


 
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5.4. 
Other Considerations for Data Analyses and Data Handling 
Conventions 
Other considerations for data analyses and data handling conventions are outlined in the 
appendices 
Section 
Component 
Section 14.3 
Appendix 3: Assessment Windows 
Section 14.4 
Appendix 4: Study Phases and Treatment Emergent Adverse Events 
Section 14.5 
Appendix 5: Data Display Standards & Handling Conventions 
Section 14.6 
Appendix 6: Derived and Transformed Data 
Section 14.7 
Appendix 7: Reporting Standards for Missing Data 
Section 14.8 
Appendix 8: Values of Potential Clinical Importance 
 
 


 
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6. 
STUDY POPULATION ANALYSES 
The study population analyses will be based on the Randomized population, unless 
otherwise specified. 
Study population analyses including analyses of participants’ disposition, protocol 
deviations, demographic characteristics, prior and concomitant medications, baseline 
efficacy parameters, exposure, medical history and substance use will be based on GSK 
Core Data Standards.  
Details of the planned displays are presented in Appendix 11. 
 
 


 
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7. 
EFFICACY ANALYSES – PART B ONLY 
7.1. 
Co-primary Efficacy Analyses 
7.1.1. 
Endpoint / Variables 
The changes in pain in participants with OA of the knee following repeat SC 
administration are assessed using: 
• Change from baseline in the average knee pain intensity at week 8.  
• Change from baseline in the worst knee pain intensity at week 8.  
7.1.2. 
Summary Measure 
The primary summary measure will be the difference between treatments in mean change 
from baseline. The pain scores will be listed by participant and summarized descriptively 
by treatment.  
7.1.3. 
Population of Interest 
The analyses will be based on the Intent-to-Treat population, unless otherwise specified. 
7.1.4. 
Strategy for Intercurrent (Post-Randomization) Events 
There is one intercurrent event that is of interest: 
1. Treatment Withdrawal (Participant discontinues the study treatment but 
continues to stay in the study) 
No imputations would be carried out if there are missing data due to intercurrent events.  
A hypothetical strategy will be used to estimate what the treatment effect would have 
been had the subject not experienced the intercurrent event. Data collected after the 
occurrence of the Intercurrent Event will be listed but not used in summary stats and stats 
analysis TFLs. Since the dosing interval in this study is 7 days, the date of occurrence of 
the treatment withdrawal intercurrent event will be defined as the date of the first missed 
dose of study treatment i.e. date of last dose of study treatment + 7 days. Pain scores are 
measured daily in the evening, therefore pain scores on or after the date of last dose of 
study treatment + 7 days will be considered as occurring after treatment withdrawal. 


 
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7.1.5. 
Statistical Analyses / Methods 
7.1.5.1. 
Statistical Methodology Specification 
Endpoint / Variables 
• Change from baseline in Average Knee Pain Intensity at Week 8 
• Change from baseline in Worst Knee Pain Intensity at Week 8 
Model Specification 
• 
A Bayesian repeated measures model will be used to fit the change from baseline from 
Week 1 to Week 8. 
• 
The endpoints will be assumed to follow a multivariate (MVN) normal distribution to model all 
repeated measurements within the same participant. 
• 
Markov-Chain-Monte-Carlo (MCMC) method will be used to estimate the posterior 
distributions. 
• 
A linear model for Change from Baseline at each Week (visit) will be constructed to model 
the within-participant covariance structures. 
• 
Terms fitted in the model will include: 
o Categorical: Week (Week 1 to Week 8), Treatment (GSK3858279 and placebo), 
Treatment*Week Interaction, Baseline*Week Interaction 
o Continuous: Baseline 
o Repeated: Week 
 
• 
The prior for the Variance Covariance Matrix will follow an Inverse Wishart Distribution. 
• 
Vague priors (normal (0, var=1e6)) will be used for all other model parameters.  
• 
Set simulation size at a minimum of 10000 and 1000 burn-in iterations. The simulation size 
and number of burn-in iterations could be updated during the convergence check. 
• 
Refer to Appendix 6 - Bayesian Repeated Measures Model (PROC MCMC) for additional 
information 
• 
Refer to Appendix 3 for details on visit computation. 
• 
Refer to Appendix 9 for additional information 
 
Model Checking & Diagnostics 
o Bayesian Analyses: Refer to the relevant documentation (Bayesian Statistics Best 
Practice at GSK – Clinical Trials using Bayesian Inference). 
• 
Refer to Appendix 9 
Model Results Presentation 
• Medians and 95% credible intervals will be produced by treatment group and for the 
difference between treatment groups, for each of the endpoints,  
• The posterior distributions will be used to produce several probability statements: 
o P[True Difference (GSK3858279 – placebo) < X 
o where values of X to be generated are 0, -0.6, -0.8 and -1.0  
• For all tables/figures presenting results from a statistical model, a footnote including 
model, prior distributions, covariates and a very brief mention of intercurrent events will 
be added.  
• For all TFLs presenting efficacy endpoints, a footnote to state a range of the score for the 
endpoint specifying which direction of change is an improvement. 


 
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Interim Analysis 1 
• A first interim analysis will occur once 20 participants reach Week 4 
• The endpoint will be Change from baseline in average knee pain intensity at week 4 
 
Interim Analysis 2 
• A second interim analysis may occur once approximately 45 participants have been 
randomised (this estimated to happen when 28 participants reach Week 8) and will 
include a sample size re-estimation and a futility assessment. In addition to posterior 
probabilities, predictive probabilities of achieving criteria of interest at the end of the 
study will be estimated using a Bayesian Normal-Normal update. Vague priors for all 
modelling parameters will be used to compute the posterior distributions.  
• Criteria of interest are:  
o P[True Difference (GSK3858279 – placebo) < X] where values of X to be generated 
are 0, -0.6, -0.8 and -1.0  and  
o Predictive probability > X% 
• At the interim analysis an estimate of the standard deviation of the endpoint at week 8 
will be estimated from the Bayesian Repeated Measures model. Details are given in 
Section 14.9.1. All data available at the time of the interim will be used for this purpose 
• The ratio of the Estimated SD to Predicted SD (SD=1.8) for the change from baseline at 
Week 8 will be used to calculate the optimal sample size as follows: 
  
𝑆𝑆𝑜𝑝𝑡𝑖𝑚𝑎𝑙 = (𝑆𝐷𝑒𝑠𝑡𝑖𝑚𝑎𝑡𝑒𝑑
1.8
× √50)
2
 
 
 
• The optimal sample size must be within the range [# participants randomised, 80] 
subjects (i.e. if the optimal calculation is >80, the SS will be capped at 80/ if the optimal 
calculation is <50, the SS will be capped at # participants randomised). The number of 
participants resulting from the SS_optimal formula must be rounded up to the next even 
number. 
 
Subgroup Analyses 
• No subgroup analysis is planned for the study. 
Sensitivity Analyses 
• Refer to Section 14.9.2 for additional information. 
Supportive Analyses 
• The Bayesian Repeated Measures Model will be performed on the Per Protocol Population if 
the Per Protocol Population comprises 50 to 90% of the ITT population  
 


 
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2 4  
 
 
7. 2. 2.  
S u m m ar y M e a s ur e  
T he differe nce i n treat me nt mea n c ha n ge fr o m bas eli ne f or W O M A C  s u bscales sc ores 
a n d 
will be a nal yse d . I n a d diti o n, t he a bs ol ute a n d c h a n ge fr o m baseli ne val ues of 
W O M A C s u bscales sc ores,
a n d 
(I n di vi d ual a n d 
O verall ) will be s u m mari ze d descri pti vel y b y tr eat me nt. T hese  sc ores will be  als o be 
liste d b y eac h partici pa nt a n d treat me nt. 
Refer t o Secti o n 1 4. 6. 3  f or details o n calc ul ati o n of W O M A C s u bscales sc ores. 
T he n u m ber of partici pa nts w h o t o o k  resc ue me dicati o n will be s u m marise d b y treat me nt. 
I n a d diti o n, t he t otal wee kl y d ose, a vera ge wee kl y d ose a n d a vera ge res c ue me dicati o n 
use will be s u m mariz e d. A listi n g of res cue me dicati o n  will  be pr o d uce d.  
7. 2. 3.  
P o p ul ati o n of I nt er e st  
T he effi cac y a nal yses will be base d o n t he I nt e nt -t o-Treat p o p ulati o n, u nless ot her wise 
s pecifie d. 
7. 2. 4.  
Str at e g y f or I nt er c urr e nt ( P o st -R a n d o mi z ati o n) E v e nt s  
I nterc urre nt E ve nts: 
1.  Treat me nt Wit h dra wal  ( P artici pa nt disc o nti n ues t he st u d y tr eat me nt b ut 
c o nti n ues t o sta y i n t he st u d y)  
 
N o i m p utati o ns will be carrie d o ut if t here are missi n g data d ue t o i nterc urre nt e ve nts.  
A h y p ot hetic al strate g y will be use d t o esti mate w hat t he treat me nt effect w o ul d ha ve 
bee n ha d t he s u bject n ot e x perie nce d t he i nterc urre nt e ve nt. Dat a c ollecte d after t he 
occ urre nce of t he I nt erc urre nt E ve nt will t heref ore n ot be use d i n t he a nal ysis.  Si nce t he 
d osi n g i nter val i n t his st u d y is 7 da ys, t he d ate of o cc urre nce of t he tr eat me nt wit h dra wal 
i nterc urre nt e ve nt will be defi ne d as t he d ate of t h e first misse d d ose of st u d y treat me nt 
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2 0 7 8 0 4  
2 5  
 
i.e. date of last d ose of st u d y treat me nt + 7 da ys. W O M A C,
a n d Pai n Detect  
are me as ure d pre -d os e at eac h w ee kl y visit , t heref ore assess me nts  after t he date of last 
d ose of st u d y tr eat me nt + 7 da ys will be c o nsi dere d as occ urri n g after treat me nt 
wit h dra wal.  Re sc u e Me dicati o n is assesse d dail y i n t he e ve ni n g, t heref ore Resc ue 
Me dicati o n o n or aft er t h e date of last d ose of st u d y treat me nt + 7 da ys will be c o nsi dere d 
as occ urri n g after treat me nt wit h dra wal.  
7. 2. 5.  
St ati sti c al A n al y s e s / M et h o d s  
7. 2. 5. 1.  
St ati sti c al M et h o d ol o g y S p e cifi c ati o n  
E n d p oi nt / V aria bl e s  
•  W O M A C p ai n, stiffn ess a nd f u nctio n s u bsc al es sc or es  at  W e ek 1, 2, 4, 6, 8  
•  
M o d el S p e cific ati o n  
•  
A B ayesi a n r ep eat e d m e asur es m o del will b e use d to fit t h e c h an g e fr o m b as eli n e fr o m 
W e ek 1 to W e ek 8 . 
•  
T h e e n d poi nts will be ass u m e d t o f oll o w a m ultiv ari at e  ( M V N) n or mal distrib uti o n t o m o d el all 
r e p e ate d me as ur e m ents withi n t h e s a m e p articipa nt . 
•  
M ark ov -C h ai n -M o nt e -C arl o ( M C M C) m et h o d i n S A S will b e us e d t o esti m at e  t h e p ost erior 
distri b uti o ns of t h e e nd p oints.  
•  
A li n e ar m od el for C h a ng e fr o m B as eli n e at e ach W e ek (visit) will b e c o nstr uct e d to m o d el 
t h e wit hin-s u bj ect c ov ari ance str uct ures. 
•  
T er ms fitt e d i n  t h e m o del will i ncl u d e: 
o  C at e goric al: W e ek, Tr eat m ent ( G S K3 8 58 27 9 a n d pl aceb o),  Tr e at me nt* W eek 
I nt er actio n, B as eli ne* W e ek I nt er actio n 
o  C o nti n uo us: B aseli n e  
o  R e p e at e d: W e ek  
•  
T h e pri or for t h e V ari anc e Cov ari a nc e M atrix will f oll o w a n Inv ers e Wis h art Distri b uti o n. 
•  
S et si m ul ati on siz e at a mi ni m u m of 10 0 00 a n d 1 0 00 b ur n -i n it er ati o ns. T h e si m ul atio n siz e 
a n d n u m ber of b ur n -i n iter ati o ns c o ul d be u p d at e d d uring t he c o nv er g enc e ch eck. 
•  
T h e v a g u e pri ors ( n or mal ( 0, v ar = 1 e 6)) will b e us ed for th e hyp er par a m et ers/all mo del 
p ar a m eters   
•  
. 
•  
R ef er t o A pp e ndix 6  - Bay esi a n R e pe ate d M eas ur es Mo d el ( P R O C M C M C ) f or a dditi o n al 
i nf or mati o n 
•  
R ef er t o A pp e ndix 3  for details o n visit c o m put ati o n. 
•  
R ef er t o A pp e ndix 9  for ad diti o n al i nf or mati o n 
 
M o d el C h e c ki n g & Dia g n o sti c s  
•  
B ay esi an A n alys es: Ref er to t he r el ev a nt d oc u m ent ati on ( B ay esia n St atistics Best Pr actic e 
at G S K –  Cli nic al Tri als using B ayesi a n I nfer e nc e).  
•  
R ef er t o A pp e ndix 9  
M o d el R e s ult s Pr e se nt ati o n  
•  M e di a ns a n d 9 5 % cr e di bl e i nt erv als will b e pr o duc e d by tr e at m ent gr ou p a nd  f or th e 
diff er e nce b et w ee n tr eat m ent gr ou ps  e ac h of t h e e nd p oi nts  
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2 6  
 
•  T h e p ost eri or distri buti o ns will b e us e d t o pr o duc e sever al pr o ba bility st at e m e nts:  
•  F or W O M A C p ai n, stiff n ess a n d f u ncti o n su bsc ales sc ores  
▪ P[ Tr u e Diff ere nc e  ( G S K 38 58 2 79 –  pl ac e b o) < X] w her e v al u es of X t o b e 
g e ner at ed ar e 0, -0. 6, -0. 8 an d -1.0  
•  F or
•  F or all t a bl es/fi g ures pr ese nti n g r es ults fr o m a st atistic al m o d el, a f oot n ot e i ncl u di ng m o d el, 
pri or distri b uti ons, c ovari at es a n d a very brief m enti o n of i nt erc urre nt eve nts will b e a d de d.  
•  F or all T F Ls pr ese nti ng effic acy e nd poi nts, a f oot n ot e t o st at e a r an g e of  t h e sc or e for t h e 
e n dp oi nt s p ecifyi ng w h ic h dir ecti o n of c ha n ge is a n i m pr ov e m e nt. 
S u b gr o u p A n al y s es  
•  N o s u bgr o u p a nalys es is pla n ne d for t he st udy.  
 
8.  
S A F E T Y A N A L Y S E S  
T he safet y a nal yses will be base d o n t he Safet y p o p ulati o n, u nless ot her wise s pecifie d.  
8. 1.  
A d v er s e E v e nt s A n al y s e s  
T he defi niti o n of a n A E is detaile d i n  A p pe n di x 3  of t he pr ot oc ol  ( Secti o n 1 0. 3).  
A nal ys es of A Es will i ncl u de t h ose e ve nts t hat are o n -treat me nt ( Secti o n 1 4. 4. 1 ). 
A d verse e ve nts a n al ys es  i ncl u di n g t he a n al ysis of A d verse  E v e nts ( A Es), S eri o us ( 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 d ar ds.  
Details of t he pla n ne d dis pla ys ar e prese nte d i n  A p pe n di x 1 1 . 
8. 2.  
Cli ni c al L a b or at or y A n al y s e s  
La b orat or y e val uati o ns will be base d o n G S K C ore Data Sta n dar ds a n d will i ncl u de:  
•  He mat ol o g y l a b orat or y t ests  
•  C he mi str y la b orat or y tests 
•  Uri nal ysis  
•  Ot her scree ni n g tests  
Details of t he pla n ne d dis pla ys are prese nte d i n A p pe n di x 1 1 . 
T he la b orat or y assess me nts f or eac h cate g or y are dis pla ye d i n T a ble 2 . 
 
 
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Table 2 
Laboratory Assessments  
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count  
RBC Indices: 
MCV 
MCH 
%Reticulocytes 
WBC count with Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC Count 
Hemoglobin 
Hematocrit 
Clinical 
Chemistry1,2,3 
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 
Glucose 
(non-fasting) 
Calcium 
Alkaline phosphatase 
2Cardiac 
troponin T 
3NT-proBNP 
Routine 
Urinalysis1 
Specific gravity 
pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte 
esterase by dipstick 
Microscopic examination and laboratory quantification of proteinuria (if 
blood or protein is abnormal on dipstick) 
Part B: Alcohol 
Combined 
throat and 
nasopharyngeal 
swab 
 
COVID-19 (SARS-CoV2) (see SRM for further details) 
Other 
Screening 
Tests 
Blood (serum): 
Follicle-stimulating hormone and estradiol (as needed in women of non-
childbearing potential only) 
Serology (TB test, HIV antibody, HBsAg, HBcAb and hepatitis C virus 
antibody)  
QuantiFERON test 
Complement protein C3 and C4 
Urine: 
Urine drug screen to include at minimum: amphetamines, barbiturates, 
cocaine, opiates, cannabinoids and benzodiazepines. 
Urine albumin-creatinine ratio (UACR) 
Notes 
1. Details of liver chemistry stopping criteria and required actions and follow-up assessments after 
liver stopping or monitoring event are given in Protocol Section 7.2.1 and Appendix 6a and 6b of 
protocol. All events of ALT ≥3 × upper limit of normal (ULN) and bilirubin ≥2 × ULN (>35% direct 
bilirubin) or ALT ≥3 × ULN and international normalized ratio (INR) >1.5, if INR measured, which 


 
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may indicate severe liver injury (possible Hy’s Law), must be reported as an SAE (excluding 
studies of hepatic impairment or cirrhosis). 
2.Troponin T using high sensitivity test. 
3.NT-proBNP (N-terminal pro B-type natriuretic peptide) at baseline and Day 57 visit only. 
 
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. 
 
 


 
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8.3. 
Other Safety Analyses 
The analyses of non-laboratory safety test results will be based on GSK Core Data 
Standards, unless otherwise specified.  
The non-laboratory safety test results include: 
• Vital Signs 
• ECGs 
• Echocardiogram  
• Telemetry (for Part A only) 
• Holter monitoring (for Part B only at Screening) 
 
8.4. 
COVID-19 Pandemic Statistical Displays 
A summary of the following COVID-19 assessments may be produced:  Case Diagnosis, 
COVID-19, Test performed, and Results of the COVID-19 test. Additionally, a listing of 
all subjects with visits and assessments impacted by the pandemic may be produced. The 
listing will include: 
1. Site Identifier  
2. Treatment for parallel group studies 
3. Unique Subject Identifier 
4. Subject Identifier 
5. Impacted Visit 
6. Impact 
7. Reason for Impact 
Details of the planned displays are presented in Appendix 11. 
 
 


 
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9.  
P H A R M A C O KI N E TI C A N A L Y S E S  
9. 1.  
S er u m P h ar m a c o ki n eti c s  
T he P K a nal yses d escri b e d bel o w will be carrie d o ut f or  G S K 3 8 5 8 2 7 9  i n ser u m.  
9. 1. 1.  
E n d p oi nt / V ari a bl e s  
9. 1. 1. 1.  
Dr u g C o n c e ntr ati o n M e a s ur e s  
Refer t o A p pe n di x 5 ( Secti o n 1 4. 5. 3 ). 
9. 1. 1. 2.  
D eri v e d P h ar m a c o ki n eti c P ar a m et er s  
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N O T E S:  
 
9. 1. 1. 2. 2.  P art B  
N O T E S:  
A d diti on al par a m eters m ay b e i ncl ud e d as r eq uire d.  
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In the event that a robust and predictive population PK/TE model cannot be developed e.g. data 
limited by high levels of NR data, all parameters listed in the table will be derived directly from the 
observed data using standard non-compartmental analysis. In such case, PK parameters for 
subjects on sparse sampling schedule will be only calculated at weeks 1 and 8. 
9.1.2. 
Summary Measure 
Individual and mean/median concentration-time profiles of GSK3858279 in serum 
(stratified by treatment group in Part A) will be plotted and listed. Serum concentrations 
will be summarized descriptively. Derived serum PK parameters will be summarised 
using descriptive statistics, graphically presented (where appropriate) and listed. 
9.1.3. 
Population of Interest  
The serum pharmacokinetic analyses will be based on the Pharmacokinetic population, 
unless otherwise specified. 
9.1.4. 
Strategy for Intercurrent (Post-Randomization) Events 
Missing data would be considered as Missing at Random and no imputations for missing 
data would be carried out.  
9.1.5. 
Statistical Analyses / Methods 
Details of the planned displays are presented in Appendix 11 and will be based on GSK 
Data Standards and statistical principles. 
Unless otherwise specified, endpoints / variables defined in Section 9.1.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed. 
9.1.5.1. 
Dose proportionality  
Dose proportionality in Part A will be assessed by visual inspection of: 
• Dose normalised AUC(0-∞) [or if not available AUC(0-t)] and Cmax values 
versus dose. 
Dose proportionality may also be assessed using the power model described below. 
Dose proportionality 
Endpoints 
• AUC(0-t), AUC(0-∞) and Cmax 
Model specification 
• Power model (log-log linear model):  
𝑦=  𝛼 × 𝑑𝑜𝑠𝑒𝛽 ⟺ log𝑒(𝑦) = log𝑒(𝛼) +  𝛽 × log𝑒(𝑑𝑜𝑠𝑒) 
Where  
o y        = endpoint of interest 
o dose   = actual dose (mg) received under fasted condition 
o β        = parameter associated to dose (slope) 


 
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o  α       = su bj ect -s pecific r a nd o m effect (interc e pt) 
•  T er ms fitt e d i n t he p o w er m o d el:  
o  R es p o nse: l og tr ansf or matio n of t h e e n d poi nt of i nt er est l o g𝑒(𝑦)  
o  Fix e d c o nti n uo us c ovari at es: l o g𝑒(𝑑𝑜𝑠𝑒) 
o  R a n d o m: su bj ect  
M o d el c h e cki n g & di a g n osti c s  
•  N or m ality ass u m pti ons u nderlyi n g t he m o del us ed for an alysis will b e exa mi n e d by o bt aini n g a 
n or mal pr o b a bility pl ot of t he r esi d u als a nd a pl ot of th e r esi d u als vers us t h e fitte d val u es (i. e. 
c h ecki n g t h e n or mality ass u m pti o n a n d co nsta nt v aria nc e ass u m pti o n of th e m od el, 
r es p ectiv ely) t o g ain c o nfi d enc e th at t h e mo d el ass u m pti o ns ar e re as on a ble.  
•  If t her e ar e a ny d ep art ur es fr o m t h e distrib uti on al assu m pti o ns, alt er n ativ e m o dels will b e 
ex pl or e d usi ng a p pr o pri ate tr a nsf or me d d ata  
M o d el r e s ult s pr e se nt ati o n  
T a bl e of t h e esti m at e d sl o pes a nd 9 0 % CI (slo p e cl ose t o 1  i mpli es d ose pr op orti o nality) 
 
 
C CI


 
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
3 4  
 
9. 2. 1.  
E n d p oi nt /  V ari a bl e s  
Blister c o nce ntrati o ns  of G S K 3 8 5 8 2 7 9 . 
9. 2. 1. 1.  
Dr u g C o n c e ntr ati o n M e a s ur e s  
Refer t o A p pe n di x 5  ( Secti o n 1 4. 5. 3 ).  
9. 2. 1. 2.  
D eri v e d P h ar m a c o ki n eti c P ar a m et er s  
P har mac o ki netic para met ers will n ot be calc ul ate d d ue  t o t he s parsit y of blister fl ui d 
sa m ples.  
T he wit hi n s u bject a n d ti me p oi nt blister fl ui d:ser u m c o nce ntrati o n rati o f or G S K 3 8 5 8 2 7 9  
ma y  b e deter mi ne d fr o m t he c o nce ntr ati o n -ti me data if data per mit.  
9. 2. 2.  
S u m m ar y  M e a s ur e  
I n di vi d ual a n d m ea n/ media n  c o nce ntr ati o n -ti me pr ofiles  of G S K 3 8 5 8 2 7 9  i n blister  fl ui d 
(stratifie d b y treat me nt gr o u p ) will be  pl otte d a n d liste d. Blist er fl ui d c o nce ntrati o n s will 
be s u m mariz e d descri pti vel y.  
9. 2. 3.  
P o p ul ati o n of I nt er e st  
T he blister p har mac o ki netic a nal ys es will be base d o n t he  Blister P har mac o ki netic 
p o p ulati o n, u nless ot her wise s pecifie d.  
9. 2. 4.  
Str at e g y f or I nt er c urr e nt ( P o st -R a n d o mi z ati o n) E v e nt s  
Missi n g data w o ul d be c o nsi dere d as Missi n g at Ra n d o m a n d n o i m p utati o ns f or missi n g 
data w o ul d be carri e d o ut.   
9. 2. 5.  
St ati sti c al A n al y s e s / M et h o d s  
Details of t he pla n ne d dis pla ys are prese nte d i n A p pe n di x 1 1  a n d will be base d o n G S K 
Data Sta n dar ds a n d statistical pri nci ples.  
U nless ot her wise s pecifie d, e n d p oi nts / varia bles d efi ne d i n Secti o n 9. 1. 1  will be 
s u m marise d usi n g des cri pti ve statistics, gra p hicall y prese nte d ( w here a p pr o priate) a n d 
liste d. 
C CI


 
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
3 5  
 
1 0.  
P H A R M A C O D Y N A MI C  A N A L Y S E S  
1 0. 1.  
S er u m T ar g et E n g a g e m e nt  A n al y s e s  
T he Tar get E n ga ge me nt a nal ys es descri b e d bel o w will be carri e d o ut f or Free a n d T otal 
C C L 1 7  i n Ser u m.  
1 0. 1. 1.  
E n d p oi nt / V ari a bl e s  
Free a n d T otal C C L 1 7 le vels i n ser u m  a n d deri v e d Tar get E n ga ge me nt p ara meters . 
1 0. 1. 1. 1.  
T ar g et E n g a g e m e nt C o n c e ntr ati o n M e a s ur e s  
Refer t o A p pe n di x 5  ( Secti o n 1 4. 5. 4 ).  
1 0. 1. 1. 2.  
D eri v e d T ar g et E n g a g e m e nt  P ar a m et er s  
1 0. 1. 1. 2. 1.  P art A  
All Tar get E n ga ge me nt  p ara meters  i n Part A  will be deter mi ne d dir ectl y fr o m t he 
o bser ve d c o n ce ntr ati o n -ti me data, as dat a per mits. All calc ulati o ns will be base d o n 
act ual sa m pli n g ti mes.  
Tar get E n ga ge me nt para meters t hat will be calc ul ate d f or free C C L 1 7 i n Part A are liste d 
bel o w. A d diti o nal p ara m eters ma y be i n cl u de d as re q uire d.  
N O T E S:  
A d diti on al par a m eters m ay b e i ncl ud e d as r eq uire d . 
 
 
 
C CI


 
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
3 6  
 
Tar get e n ga ge me nt  para meters t hat will be calc ul ate d f or t otal C C L 1 7 i n P art A are liste d 
be l o w. A d diti o nal para m eters ma y be i n cl u de d as re q uire d. 
N O T E S:  
A d diti on al par a m eters m ay b e i ncl ud e d as r eq uire d . 
 
1 0. 1. 1. 2. 2.  P art B  
All Tar get E n ga ge me nt p ara meters i n Part B  will be calc ul ate d  usi n g a m o del base d p ost -
h oc a nal ysis a n d t he c urre ntl y s u p p orte d v ersi o n of  N O N M E M. T he m o d el base d p ost -
h oc a nal ysis is descri be d i n Secti o n 1 1 . All calc ulati o ns will be base d o n act ual sa m pli n g 
ti mes. 
Tar get E n ga ge me nt para meters t hat will be calc ul ate d f or free C C L 1 7 i n Part B are liste d 
C CI
C CI


 
C O N FI D E N TI A L  
 
3 7  
 
N O T E S:  
A d diti on al par a m eters m ay b e i ncl ud e d as r eq uire d . 
1I n t h e ev ent th at a r ob ust an d pr edictiv e p o pul ati on P K/ T E m o d el ca n not b e d ev el op e d e. g. dat a 
li mit e d by hi gh l ev els of N R d at a, T E  p ar a m eters will b e d eriv e d directly fr o m t h e o bs erv e d d at a.  
 
Tar get e n ga ge me nt  para meters t hat will be calc ul ate d f or t otal C C L 1 7 i n P art B  are liste d 
be l o w. A d diti o nal para m eters ma y be i n cl u de d as re q uire d. 
N O T E S:  
A d diti on al par a m eters m ay b e i ncl ud e d as r eq uire d.  
C CI
C CI


 
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
3 8  
 
1I n t he e v e nt t hat a r o b ust a n d pre dicti ve p o p ulati o n P K/ T E m o del ca n n ot be de vel o pe d 
e. g. d ata li mite d b y hi g h le vels of N R data, T E  p ara meters will be deri ve d directl y fr o m 
t he o bser ve d d ata. 
1 0. 1. 2.  
S u m m ar y  M e a s ur e  
I n di vi d ual a n d m e dia n/ mea n c o n ce ntrati o n -ti me pr ofiles of Free a n d T otal C C L 1 7  
(stratifie d b y treat me nt gr o u p i n Part A) will be  pl otte d a n d liste d. Free a n d T otal C C L 1 7 
c o nce ntr ati o n s i n ser u m will be s u m marize d descri pti vel y.  
Deri ve d ser u m T E para m eters will be s u m marise d usi n g descri pti ve statistics, gra p hicall y 
prese nte d ( w here a p pr o priate) a n d liste d.  
1 0. 1. 3.  
P o p ul ati o n of I nt er e st  
T he tar get e n ga ge me nt a nal yses will be base d o n t he Safet y p o p ulati o n, u nless ot her wise 
s pecifie d. 
1 0. 1. 4.  
Str at e g y f or I nt er c urr e nt ( P o st-R a n d o mi z ati o n) E v e nt s  
Missi n g data will n ot be i m p ute d , re gar dl ess t he reas o ns. 
1 0. 1. 5.  
St ati sti c al A n al y s e s / M et h o d s  
Details of t he pla n ne d dis p la ys are prese nte d i n A p pe n di x 1 1  a n d will be base d o n G S K 
Data Sta n dar ds a n d statistical pri nci ples.  
U nless ot her wise s pecifie d, e n d p oi nts / varia bles d efi ne d i n Secti o n 1 0. 1. 1  will be 
s u m marise d usi n g des cri pti ve statistics, gra p hicall y prese nte d ( w here a p pr o priate) a n d 
liste d. 
T he  wit hi n s u bject a n d ti me p oi nt blister fl ui d:ser u m c o nce ntrati o n rati o f or  free a n d t otal 
C C L 1 7 ma y be det er mi n e d fr o m t he c o n ce ntr ati o n -ti me data if data p er mit . T he free a n d 
t otal C C L 1 7 c o nce ntrati o ns will be s u m marise d usi n g descri pti ve statistics, gra p hicall y 
prese nte d ( w here a p pr o priate) a n d liste d.  
1 0. 3.  
I m m u n o g e ni cit y 
1 0. 3. 1.  
S u m m ar y M e a s ur e  
T he n u m ber a n d p erce nta ge of c o nfir m e d p ositi ve sa m ples i n eac h tr eat me nt gr o u p will 
be prese nt e d at e ac h ti me assesse d . O nl y bi n di n g a nti b o d y detecti o n is c ollecte d i n t his 
st u d y. Ne utr alisi n g a nti b o d y det ecti o n is n ot c ollecte d.  
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10.3.2. 
Population of Interest 
The immunogenicity analyses will be based on the safety population, unless otherwise 
specified. 
For the in-stream safety reviews 1 and 2, subject data will be anonymised as outlined in 
Appendix 6 
11. 
PHARMACOKINETIC / TARGET ENGAGEMENT / 
PHARMACODYNAMIC (PK/TE/PD) ANALYSES 
The primary goal of this analysis is to characterize the Pharmacokinetic / Target 
Engagement (PK/TE) relationship of GSK3858279 following IV and SC administration 
to healthy and OA participants. The influence of subject demographics and baseline 
characteristics, including disease activity, may be investigated. PK and TE data will be 
analysed using the currently supported version of NONMEM. Details of this analysis are 
described in a separate RAP [GSK Document number TMF-14343601.  
The relationship between Pharmacokinetic / Target Engagement / Pharmacodynamic 
(PK/TE/PD) of GSK3858279 following repeat SC administration to OA participants may 
also be explored. Details of this analysis are described in a separate RAP GSK Document 
number TMF-14343601. 
11.1. 
Pharmacokinetic / Target Engagement / Pharmacodynamic 
Dataset Specification 
The dataset specification to support any PK/TE/PD analysis will be provided as a 
separate document. 
The merging of PK, TE, treatment, demographic and efficacy data together with the 
creation of the NONMEM-specific dataset will be performed by, or under the direct 
auspices of, Clinical Statistics & Programming, GSK.  
This dataset programming will be conducted in a HARP environment using the currently 
supported version of SAS. 
 
 


 
C O N FI D E N TI A L  
 
 
 
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4 0  
 
1 2.  
BI O M A R K E R A N A L Y S E S  –  P A R T A O N L Y  
1 2. 1.  
I m m u n e C ell P h e n ot y pe s  
1 2. 1. 2.  
S u m m ar y M e a s ur e  
T w o s u m mar y meas ur es are of i nterest, t he treat me nt effect ( Place b o vs G S K 3 8 5 8 2 7 9) 
a n d t he differe nce bet w ee n sa m ple t y p es ( Bl o o d vs Blister). 
•  Mea n Treat me nt Differe nce i n C ha n ge fr o m baseli ne at all visits  
•  T he wit hi n s u bject a n d ti me p oi nt rati o of  Blister :Bl o o d  at all visits  –  o nl y f or 
blister i n d uce d c o h orts of Part A  
Meas ures of sa m ple relia bilit y ( Blister V ol u me a n d T otal W hite Bl o o d Cell C o u nt) will 
be liste d o nl y.  
1 2. 1. 4.  
St ati sti c al A n al y s e s / M et h o d s  
Details of t he pla n ne d dis pla ys are pr o vi d e d i n  A p pe n di x 1 1  a n d will be base d o n G S K 
Data Sta n dar ds  a n d statistical pri nci ples.  
U nless ot her wise s pecifie d, e n d p oi nts / varia bles d efi ne d i n Secti o n 1 0. 1. 1  will be 
s u m marise d usi n g des cri pti ve statistics, gra p hicall y prese nte d ( w here a p pr o priate) a n d 
liste d. 
 
 
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12.1.4.1. 
Statistical Methodology Specification 
Endpoint / Variables 
• Percentage of Immune Cell Phenotypes 
Model Specification 
• Endpoints will be analyzed for each flow cytometry cell type using generalized linear mixed 
models (GLMM) with appropriate link functions or transformations performed as required. 
• Terms in GLMM model will include: 
o categorical: baseline, treatment group, sample type, visit and two 3-way 
interactions 
▪ baseline with sample type with treatment group 
▪ visit with sample type with treatment group 
o Random effect: subject 
• The Kenward and Roger method for approximating the denominator degrees of freedom and 
correcting for bias in the estimated variance-covariance of the fixed effects will be used. 
• An unstructured covariance structure for the R matrix will be used by specifying ‘type=UN’ 
on the RANDOM line.  
o In the event that this model fails to converge, alternative correlation structures 
may be considered such as CSH or CS.  
o Akaike's Information Criteria (AIC) will be used to assist with the selection of 
covariance structure. 
• LS Means for the Sample Type by Treatment by Visit will be calculated using the observed 
baseline mean for each sample type separately. 
Model Checking & Diagnostics 
• Distributional assumptions underlying the model used for analysis will be examined by 
obtaining a normal probability plot of the residuals and a plot of the residuals versus the 
fitted values (i.e. checking the normality assumption and constant variance assumption of 
the model respectively) to gain confidence that the model assumptions are reasonable.  
• If there are any departures from the distributional assumptions, alternative models will be 
explored using appropriate transformed data. 
Model Results Presentation 
For summary measure 1 (mean treatment difference), for each sample type and each treatment 
group: 
• Number of subjects in analyses 
• Least Squares Mean of Change from Baseline with Standard Error 
For all GSK3858279 arms 
• Difference to Placebo, 95% Confidence Interval and p-value 
• In addition for 3 mg SC: 
• Difference to 3mg IV, 95% Confidence Interval. 
 
For summary measure 2 (Mean Sample Type Difference), for each treatment group and overall 
(see note) and each sample type: 
• Number of subjects in analyses 
• Least Squares Mean of Change from Baseline with Standard Error 
For Blister 
• Difference to Blood, 95% Confidence Interval  


 
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
4 2  
 
N ot e:  ov er all (tr e at m ent-i n d e p en d ent) m e an  will b e calc ul at e d f or  Blist er a nd Bl oo d , f or e ach 
visit. 
 
Pl ots of L S M e a ns ( +/ - S E) a n d Differ e nce ( 9 5 % CI) will b e pr es e nt e d.   
S e nsitivity an d S u pp ortiv e An alys es  
•  A c h ar act eris ati on of t he d os e a nd/ or ex p osur e r esp o nse m ay b e c arri e d o ut if d at a all o ws . 
 
 
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13. 
REFERENCES 
GlaxoSmithKline Document Number 2017N342035_00. Study ID 207804: A two-part 
phase I randomized double blind (sponsor open) placebo controlled study to evaluate 
safety, tolerability, pharmacokinetics, target engagement and potential for efficacy of 
single intravenous and subcutaneous doses of GSK3858279 in healthy volunteers and 
participants with osteoarthritis of the knee. 
GlaxoSmithKline Document Number 2017N342035_01. Study ID 207804: A two-part 
phase I randomized double blind (sponsor open) placebo controlled study to evaluate 
safety, tolerability, pharmacokinetics, target engagement and potential for efficacy of 
single intravenous and subcutaneous doses of GSK3858279 in healthy volunteers and 
participants with osteoarthritis of the knee. 
GlaxoSmithKline Document Number 2017N342035_02. Study ID 207804: A two-part 
phase I randomized double blind (sponsor open) placebo controlled study to evaluate 
safety, tolerability, pharmacokinetics, target engagement and potential for efficacy of 
single intravenous and subcutaneous doses of GSK3858279 in healthy volunteers and 
participants with osteoarthritis of the knee. 
GlaxoSmithKline Document Number 2017N342035_03. Study ID 207804: A two-part 
phase I randomized, double blind, placebo controlled study to evaluate safety, 
tolerability, pharmacokinetics and target engagement of single intravenous and 
subcutaneous doses of GSK3858279 in healthy participants and to evaluate the efficacy 
of repeat subcutaneous doses in participants with osteoarthritis of the knee. 
GlaxoSmithKline Document Number 2017N342035_04. Study ID 207804: A two-part 
phase I randomized, double blind, placebo controlled study to evaluate safety, 
tolerability, pharmacokinetics and target engagement of single intravenous and 
subcutaneous doses of GSK3858279 in healthy participants and to evaluate the efficacy 
of repeat subcutaneous doses in participants with osteoarthritis of the knee. 
GlaxoSmithKline Document Number 2017N342035_05. Study ID 207804: A two-part 
phase I randomized, double blind, placebo controlled study to evaluate safety, 
tolerability, pharmacokinetics and target engagement of single intravenous and 
subcutaneous doses of GSK3858279 in healthy participants and to evaluate the efficacy 
of repeat subcutaneous doses in participants with osteoarthritis of the knee. 
GlaxoSmithKline Document Number TMF-11834237. Study ID 207804: A two-part 
phase I randomized, double blind, placebo controlled study to evaluate safety, 
tolerability, pharmacokinetics and target engagement of single intravenous and 
subcutaneous doses of GSK3858279 in healthy participants and to evaluate the efficacy 
of repeat subcutaneous doses in participants with osteoarthritis of the knee. 
GlaxoSmithKline Document Number TMF- 14447953. Study ID 207804: A two-part 
phase I randomized, double blind, placebo controlled study to evaluate safety, 
tolerability, pharmacokinetics and target engagement of single intravenous and 
subcutaneous doses of GSK3858279 in healthy participants and to evaluate the efficacy 
of repeat subcutaneous doses in participants with osteoarthritis of the knee. 


 
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GlaxoSmithKline Document Number TMF-14343601 (v1.0). Project Data Analysis Plan 
for an Integrated Analysis of GSK3858279 Pharmacokinetic/Target 
Engagement/Pharmacodynamic relationship in Healthy Participants, Participants with 
Osteoarthritis of the Knee and other Indications. Effective Date 30-Dec-2021. 
 
 


 
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14. 
APPENDICES 
14.1. 
Appendix 1: Protocol Deviation Management and Definitions 
for Fully Treated Population 
14.1.1. 
Exclusions from Fully Treated Population (Part A) and Per 
Protocol Population (Part B) 
Part A: A participant meeting any of the following criteria will be excluded from the 
Fully Treated population: 
Exclusion Description 
Patient did not receive ≥ 80% of planned medication* 
*Part A has a single dose. Percentage of actual amount administered will be derived using the planned dose and the 
injected infusion volume. In case a subject didn't receive a full dose in PART A, the actual amount of drug 
administered (AMT) will be calculated as AMT [mg]= numerical part of treatment group [mg/kg] * WTBL [kg] * 
percentage of infusion volume / 100 when EXPOSURE.ACTTRT is "GSK3858279". In case a subject from the 3 
mg/kg SC treatment group didn’t receive a full dose and WTBL≥ 80 kg, then AMT [mg]= 240 [mg] * percentage of 
infusion volume / 100. The percentage of infusion volume (TVOLPCT) is assumed 100 for a full dose.  
Part B:  A participant who meets any of the below criteria will be excluded from the Per 
Protocol population: 
Violation 
Category 
Criterion 
Violated 
Deviation 
Inclusion/ 
Exclusion 
Criteria  
Inclusion Criteria 
No. 7 
Did not have OA of the index knee as defined by symptoms 
for ≥6 months with a clinical diagnosis of OA as per American 
College of Rheumatology (ACR) clinical diagnosis criteria 
Inclusion Criteria 
No. 8 
Did not have an average of daily pain score ≥4 and ≤9 by the 
11-point NRS (0-10) in index knee over 7 days prior to dosing 
(Day-7 to Day-1). Data should be recorded on at least 5 of 7 
occasions by the participant to obtain a valid baseline value. 
Inclusion Criteria 
No. 9 
Did not have a Kellgren and Lawrence (KL) score ≥2 on X-
ray obtained during screening (Kellgren, 1957).  
Exclusion 
Criteria No. 39 
Diagnosis of current inflammatory arthritis such as 
rheumatoid arthritis, autoimmune disorder affecting joints, 
seronegative spondyloarthritis, gout or pseudogout in any 
joint (defined as acute episodic attacks of swollen, painful 
joint in a patient with X-Ray chondrocalcinosis or calcium 
pyrophosphate dihydrate [CPPD] crystals). Note: 
asymptomatic CPPD crystals on X-ray are not an exclusion 
Exclusion 
Criteria No. 67 
Underwent intra-articular therapy within 3 months prior to 
signing the informed consent. 
Exclusion 
Criteria No. 68 
Intake of Immunosuppressants, including corticosteroids 
(parenteral within 3 months of screening; oral within 1 month 
of screening). 
Prohibited 
Medications* 
 
Any use of Systemic Corticosteriods from screening until the 
end of Week 8 


 
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
4 6  
 
Vi ol ati o n 
C at e g or y  
Crit eri o n 
Vi ol at e d  
D e vi ati o n  
 
A ny use  of I ntr a -artic ul ar t her a py of t h e i nd ex j oi nt fr o m 
scr e e ni n g u ntil t h e e nd of W e ek 8 
 
A ny  use of, opi o ids, N S AI Ds, t o pical a nal g esics or a nti -
n e ur op athic a ge nts 2 4 h ours b efor e a cli nical visit o n mor e 
t h a n 1 visit durin g t h e first 8 w e eks ( D ay 1 –  D ay 5 7)  
 
A ny  use of o pio ids, N S AI Ds, t o pical a nal g esics or a nti -
n e ur op athic a ge nts f or m ore t ha n 1 d ay  p er we ek o n mor e 
t h a n 1 visit durin g t h e first 8 w e eks ( D ay 1 –  D ay 5 7)  
St u dy 
M e dic ati o n  
 
Mi ssi n g m or e t h a n 1 d ose o ut of 8 d os es of stu dy tr e at m e nt  
Missi n g 
Di ary D at a  
 
Missi n g  av er a ge  k ne e p ai n or w orst k n ee p ai n  diary  d ata f or 
m or e t h an 2  d ays p er w eek i n m or e t h a n 1 w e ek o ut of  th e 
first 8 w e eks ( D ay 1 – D ay 5 7)  
 
Missi n g  r esc u e m edic ati on (p ar ac eta m ol) di ary dat a f or m or e 
t h a n 2 d ays p er w e ek i n m or e t h an 1 we ek o ut of  th e first 8 
w e eks ( D ay 1 –  D ay 5 7)  
* W here me dicati o ns liste d a b o ve nee d t o be i de ntifie d pr o gra m maticall y, a list of 
dicti o nar y c o des fr o m t he G S K Dr u g dicti o nar y will be defi ne d wit h i n p ut fr o m t he st u d y 
p h ysicia n a n d c o di n g dicti o nar y a nal yst. T he list will be creat e d pri or t o u n bli n di n g a n d 
st ore d i n a s prea ds heet i n ref dat a. 
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14.2. 
Appendix 2: Schedule of Activities 
14.2.1. 
Screening 
PROCEDURE
        SCREENING PERIOD
Screening may be performed 
across one or more visits.                   
Part A: up to 28 days before Day 
1. Part B: from Day -42 to Day -5       
(up to 42 days before Day 1)
NOTES                                                 
Informed consent
X
,
Inclusion and exclusion criteria
X
Demography
X
Full physical examination
X
Medical/medication/drug/alcoho
l history
X
Alcohol and tobacco screens
X
As per standard local practice.  Smoking permitted 
only in Part B.
Urine drug screen
X
HIV, Hepatitis B (HBsAg and 
HBcAb) and Hepatitis C (HepC 
antibody) screening
X
Holter monitoring
X
24 hour for Part B only
12-lead ECG
Triplicate
Vital signs
X
See SRM for details
Echocardiogram
X
Haematology, clinical chemistry, 
urinalysis
X
Refer to Appendix 2.   C3, C4 and BNP are included.
COVID-19 (SARS-CoV-2)
X
Documented negative COVID test within two days of 
initial screening OR test performed at the time of 
initial screening
TB Screening (QuantiFERON)
X
FSH and estradiol (in WNCBP)
X
Height and weight
X
X-ray (K&L of index knee joint)
Part B
Inclusion Criterium.  X ray performed only  if ALL 
other inclusion and exclusion criteria were already 
met at initial screening (except NRS).  Allow at least 
7 calendar days for the X-ray result to be returned 
from central reading.
Daily pain scores (Digital Tool)
Part B (Day -7 to Day -1)
Scores will be recorded over the 7 consecutive 
evenings preceding dosing. Average result (Baseline 
value) will be evaluated for inclusion.
SAE assessment
X
From signing consent


 
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4 8  
 
1 4. 2. 2.  
P art A C o h ort s Wit h o ut Bli st er: 0. 1 a n d 0. 3 m g/ k g I V  
 
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C O N FI D E N TI A L  
 
 
 
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4 9  
 
1 4. 2. 3.  
P art A C o h ort s Wit h Bli st er: 1  m g/ k g I V  
 
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C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
5 0  
 
1 4. 2. 4.  
P art A C o h ort s Wit h Bli st er: 3 a n d 1 0 m g/ k g I V a n d S C  
 
C CI


 
C O N FI D E N TI A L  
 
 
 
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5 1  
 
1 4. 2. 5.  
P art B  
 
 
C CI


 
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
5 2  
 
1 4. 3.  
A p p e n di x 3 : A s s e s s m e nt Wi n d o w s 
Acce pt a ble  ti me wi n d o ws ar o u n d t he n o mi nal ti me p oi nts f or s pecific assess me nts will be 
i ncl u de d i n t he St u d y Refere nce Ma n u al ( S R M) a n d assess me nts perf or me d wit hi n t hese 
ti me wi n d o ws will n ot c o nstit ute a pr ot oc ol de viati o n. 
T he ta ble bel o w d escri bes t he visit da y s f or eac h wee k ( Wee k 1-1 2). All a vaila ble diar y 
data i n eac h of t he w ee kl y i nter vals will be use d t o calc ulate t he A vera ge K nee Pai n 
I nte nsit y, W orst K nee Pai n I nte nsit y  a n d 
f or t hat st u d y wee k. 
St u dy W eek  
St u dy Day  
P h as e  
B L  
-7 t o -1 
B as eli n e  
1  
1 t o 7  
Tr e at m e nt  
2  
8  t o 1 4  
Tr e at m e nt  
3  
1 5  to 21  
Tr e at m e nt  
4  
2 2  to 28  
Tr e at m e nt  
5  
2 9  to 35  
Tr e at m e nt  
6  
3 6  to 42  
Tr e at m e nt  
7  
4 3  to 49  
Tr e at m e nt  
8  
5 0  to 56  
Tr e at m e nt  
9  
5 7  to 63  
F oll o w -u p * 
1 0  
6 4  to 70  
F oll o w -u p  
1 1  
7 1  to 77  
F oll o w -u p  
1 2  
7 8  to 84  
F oll o w -u p  
* F oll o w -u p here me a ns t h at t h e partici p a nt  is n o l o n ger recei vi n g t h e st u d y me dicati o n / place b o, s o o nl y f or i nf or mati ve 
p ur p oses. P artici pa nts will be c o nsi dere d o n treat me nt d uri n g t h e w h ole d urati o n of t h e st u d y  ( 2 0 we e ks). 
 
All ot her  assess me nts will use t he n o mi nal ti me p oi nts u nless ot her wise s pecifie d.  
 
 
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14.4. 
Appendix 4: Study Phases and Treatment Emergent 
Adverse Events 
14.4.1. 
Study Phases  
Assessments and events will be classified according to the time of occurrence relative to 
the first dose. 
 
Refer SOA in Appendix 2 for details of follow-up for each Cohort and Part. 
14.4.1.1. 
Study Phases for Concomitant Medication 
In addition, the following phase will also be calculated: 
14.4.2. 
Treatment Emergent Flag for Adverse Events 
 
 
Study Phase 
Definition 
Pre-Treatment  
Date/time < Study Treatment Start Date/time 
On-Treatment 
Study Treatment Start Date ≤ Date/time  
Study Phase 
Definition 
Prior 
If medication end date is not missing and is >7 days prior to first dose. 
Concomitant 
Any medication that is not a prior 
NOTE: Refer to Appendix 7: Reporting Standards for Missing Data for handling of missing and partial dates for 
concomitant medication. Use the rules in this table if concomitant medication date is completely missing 
Study Phase 
Definition 
Prohibited 
Medication 
Phase 
If medication has start date on or before Day 71 and is either ongoing or has 
end date on or after 7 days prior to first dose (Section 6.6 of the Protocol) 
Flag 
Definition 
Treatment Emergent 
If AE start date >= Study Treatment Start Date  
NOTES:  
• 
Time of study treatment dosing and start/stop time of AEs should be considered, if collected. 


 
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14.5. 
Appendix 5: Data Display Standards & Handling 
Conventions 
14.5.1. 
Reporting Process 
Software 
The currently supported versions of SAS software will be used. 
Reporting Area 
HARP Server 
UK1SALX00175 
HARP Compound 
\arprod\gsk3858279\mid207804 
Analysis Datasets  
Analysis datasets will be created according to Legacy GSK A&R dataset standards 
Generation of RTF and PDF Files 
RTF and PDF files will be generated. 
 
 
 


 
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14.5.2. 
Reporting Standards 
General 
• The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, 
unless otherwise stated:  
o 4.03 to 4.23: General Principles 
o 5.01 to 5.08: Principles Related to Data Listings 
o 6.01 to 6.11: Principles Related to Summary Tables 
o 7.01 to 7.13: Principles Related to Graphics  
• All data displays (Tables, Figures & Listings) will use the term “Subject” which reflects 
CDISC and GSK Data Display Standards terminology. 
Formats 
• GSK IDSL Statistical Principles (5.03 & 6.06.3) for decimal places (DPs) will be adopted for 
reporting of data based on the raw data collected, unless otherwise stated. 
• Numeric data will be reported at the precision collected on the eCRF. 
• The reported precision from non eCRF sources will follow the IDSL statistical principles but 
may be adjusted to a clinically interpretable number of DP’s.  
 
Actual values will be used in listings. The following criteria will be used in tables and figures: 
• For all Biomarkers , the following precision places will be applied: 
o Summary Statistics: 4 significant figures for Mean and Median, 5 significant figures for 
SD, 3 significant figures for Min and Max, in all cases but Blister Volume parameter. 
o For Blister Volume parameter: 2DP’s, 3 DP’s for Mean and Median, 4 DP’s for SD, 3 
DP’s for Min and Max 
• For PD endpoints, which are blinded until DBF, determination of an appropriate presentation 
of significant figures will be made after unblinding in line with the IDSL principles 
Planned and Actual Time 
• Reporting for tables, figures and formal statistical analyses: 
o Planned time relative to the first dosing will be used in figures, summaries and planned 
time relative to the last dosing will be used in statistical analyses and calculation of any 
derived parameters, unless otherwise stated. 
o The impact of any major deviation from the planned assessment times and/or scheduled 
visit days on the analyses and interpretation of the results will be assessed as 
appropriate. 
• Reporting for Data Listings:  
o Planned and actual time relative to study drug dosing will be shown in listings (Refer to 
IDSL Statistical Principle 5.05.1). 
o Unscheduled or unplanned readings will be presented within the subject’s listings.  
Unscheduled Visits 
• Unscheduled visits will not be included in by-visit summary tables and figures. 
• All unscheduled visits will be included in listings and determination of worst-case values. 
Descriptive Summary Statistics 
Continuous Data 
Refer to IDSL Statistical Principle 6.06.1 – do not report 95% CI unless 
otherwise specified. 
Categorical Data 
N, n, frequency, % 
Graphical Displays 
• Refer to IDSL Statistical Principals 7.01 to 7.13. 


 
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
5 6  
 
1 4. 5. 3.  
R e p orti n g St a n d ar d s f or P h ar m a c o ki n eti c  
P h ar m a c o ki n etic C o n c e ntr ati o n D at a  
P C Wi n d o ws N o n -
Li n e ar ( W N L) Fil e  
P C W N L fil e ( C S V for mat) for t h e n on c o m part m e ntal an alysis by Cli nic al 
P h ar mac ol ogy M o d elli n g a nd Si mul ati on f uncti on will b e cr e at e d accor di n g 
t o V Q D -G UI -0 00 72 2 ( 6. 0) .  
N ot e: C onc entr ati on v al ues will b e i m p ut e d as p er V Q D -G UI -0 0 0 72 2 (6. 0) . 
D escri ptiv e 
S u m m ary 
St atistics, 
Gr a p hic al Dis pl ays 
a n d Listi n gs  
R ef er t o I D S L P K Dis pl ay Sta n dar ds.  
R ef er t o I D S L St atistical Princi pl e  6. 0 6.1.  
N ot e: C onc entr ati on v al ues will b e i m p ut e d as p er V Q D -G UI -0 0 0 72 2 (6. 0)  
f or d escri ptiv e s u m m ary st atistics/ a n alysis a n d su m m ariz e d gr ap hic al 
dis pl ays o nly.  
N O N M E M/ P K/ T E / P
D  Fil e  
P K/ T E / P D fil e ( C S V for mat) f or t he P K/ T E/ P D a nalysis by Cli nic al 
P h ar mac ol ogy M o d elli n g a nd Si mul ati on f uncti on will b e cr e at e d accor di n g 
t o t he d at a s p ecific ati o n d etail e d i n S ecti on 11. 1  P har mac oki n etic /
 / P har mac o dyn a mic D at aset Sp ecific atio n .  
P h ar m a c o ki n etic P ar a met er D eriv ati o n  
P K P ar a m et er to b e 
D eriv e d by C P M S  
All  P K par a m et ers d escrib ed i n Secti o n  9.1. 1.2   ( Part A a n d P art B). 
 
P K P ar a m et er to b e 
D eriv e d by 
Pr o gr a m m er  
T h e f oll o wi ng P K par a m et ers will b e d eriv ed by pr o gr a m m er  f or P art A: 
•  Wit hi n s u bj ect a nd ti me poi nt blist er fl ui d: s er u m c onc entr ati o n r atio 
f or G S K3 8 58 27 9.  
P h ar m a c o ki n etic P ar a met er D at a  
Is N Q i m p act e d P K 
P ar a m et ers Rul e 
B ei n g Foll o w e d  
Y es, r efer t o S O P_ 3 14 00 0.  
D escri ptiv e 
S u m m ary 
St atistics, 
Gr a p hic al Dis pl ays 
a n d Listi n gs  
R ef er t o I D S L P K Dis pl ay Sta n dar ds.  
R ef er t o V Q D -G UI -0 00 7 22 (6. 0).  
 
 
 
C CI
C CI


 
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
5 7  
 
C CI


 
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14.6. 
Appendix 6: Derived and Transformed Data 
14.6.1. 
General 
Subject Number 
• Participants will be assigned a unique identification number: study number concatenated 
subject ID number. In the case of a subject being enrolled multiple times, the first subject ID 
number will be used. For more details, see the AR data set specifications. Listings will 
include both subject ID and unique subject ID. 
Multiple measurements at one analysis time point 
• Mean of the measurements will be calculated and used in any derivation of summary 
statistics but if listed, all data will be presented. 
• Participants having both high and low values for Normal Ranges at any post-baseline visit 
for safety parameters will be counted in both the High and Low categories of “Any visit post-
baseline” row of related summary tables. This will also be applicable to relevant Potential 
Clinical Importance summary tables. 
Study day 
• Calculated as the number of days from first dose date: 
o ref date = missing           → study day = missing  
o ref date < first dose date → study day = ref date – first dose date 
o ref date ≥ first dose date → study day = ref date – (first dose date) + 1     
Nominal Visit Day 
• Nominal Visit Days were updated in protocol, however some visits may be recorded under 
the incorrect visit number/label for Part A only: 
o Day 112 and Day 113 will be collapsed under the Nominal Visit:  Day 113. 
o Day 140 and Day 141 will be collapsed under the Nominal Visit:  Day 141.  


 
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14.6.2. 
Study Population 
Age 
• Birth date will be presented in listings as ‘YYYY’. 
• GSK standard IDSL algorithms will be used for calculating age where birth date will be 
imputed as follows: 
o Any participant with a missing day will have this imputed as day ‘15’. 
o Any participant with a missing date and month will have this imputed as ‘30th June’. 
• Calculated based on the screening date 
Body Mass Index (BMI) 
• Calculated as Weight (kg) / [Height (m)2] 
Race Category  
• The five high level FDA race categories and designated Asian subcategories will be 
summarised along with all combinations of high level categories which exist in the data.  
• The high level FDA race categories and designated Asian subcategories are: 
o AMERICAN INDIAN OR ALASKA NATIVE  
o ASIAN 
o CENTRAL/SOUTH ASIAN HERITAGE  
o JAPANESE HERTIAGE/EAST ASIAN HERITAGE/SOUTH EAST ASIAN 
HERITAGE 
o MIXED ASIAN RACE (only required if data exists) 
o BLACK OR AFRICAN AMERICAN 
o NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER  
o WHITE 
• A subject who selects a combination of races will be counted in a row within “MULTIPLE” or 
within the “MIXED ASIAN RACE”, not in each of the constituent terms. 
 
Extent of Exposure  
• Number of days of exposure to study drug in Part B will be calculated based on the formula:   
o Duration of Exposure in Days = Treatment Stop Date – (Treatment Start Date) + 1+18*5 
o Note: The half life of the drug is approximately 18 days. Hence 5*18 =~ 90 days is 
added in the equation of duration of exposure. 
• Participants who were randomized but did not report a treatment start date will be 
categorised as having zero days of exposure.  
• The summary statistics based on the frequency of injections would be provided in the 
exposure display for Part B. 
 


 
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
6 0  
 
1 4. 6. 3.  
Effi c a c y  
D eri v ati o n s  
W O M A C  O st e o art hriti s I n d e x  
•  W O M A C q u esti on n air e c overs p ai n, stiff n ess  an d fu nctio n r el ate d t o ost e o art hritis  in t he 
i n d ex kn e e. P artici pa nts will r es p o nd to e ac h q u esti o n usi n g a n 1 1 -p oi nt N R S ( 0 -1 0), wit h 
0 =
 a nd 10 = 
•  
F or e ac h of t h e su bscal es –  p ai n, stiff n ess a n d fu nctio n, t h e av er ag e of all th e scor es wit hi n 
t h at su bsc ale will b e calc ul at e d  for e ach s u bj ect at eac h ti me p oi nt s uc h t hat t h e aver a g e li es 
wit hi n t h e r a ng e of 0 t o 1 0 .  
•  
T h e q u esti ons 1 t o 5 c o nstitut e th e su bsc ale W O M A C pai n, q u esti ons 6 a nd 7 c o nstit ut e th e 
s u bsc al e W O M A C stiff n ess, q u esti o ns 8 t o 2 4  c o nstit ute t h e su bsc ale W O M A C f u ncti o n.   
•  If a ny of t h e scor es wit hi n a s u bsc al e is missi n g  f or a p articip a nt, th en t h e  s ubsc al e will n ot 
b e c o m put e d a n d will be s et t o missi n g for t hat particip ant. 
D ail y P ai n N R S  
•  A v er a g e k n e e p ai n i nt e nsity: m e a n  ov er th e 7 d ays prior t o e ac h ass ess m e nt visit  
•  W orst  k n e e p ai n i nt e nsity: m e a n  over t he 7 d ays prior to e ach assess m e nt visit  
 
 
 
 
C CI
C CI
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14.6.4. 
Safety 
ECG Parameters 
RR Interval 
• IF RR interval (msec) is not provided directly, then RR can be derived as: 
[1] If QTcB is machine read & QTcF is not provided, then : 
𝑅𝑅= [( 𝑄𝑇
𝑄𝑇𝑐𝐵)
2
] ∗1000 
[2] If QTcF is machine read and QTcB is not provided, then:  
𝑅𝑅= [( 𝑄𝑇
𝑄𝑇𝑐𝐹)
3
] ∗1000 
• if both the QTcB and QTcF values are machine read and provided, RR will not be calculated.  
• If ECGs are manually read, the RR value preceding the measurement QT interval should be a 
collected value, THEN do not derive. 
Corrected QT Intervals 
• When not entered directly in the eCRF, corrected QT intervals by Bazett’s (QTcB) and 
Fredericia’s (QTcF) formulas will be calculated, in msec, depending on the availability of other 
measurements. 
• IF RR interval (msec) is provided then missing QTcB and/or QTcF will be derived as:  
𝑄𝑇𝑐𝐵= 
𝑄𝑇
√𝑅𝑅
1000
 
𝑄𝑇𝑐𝐹= 
𝑄𝑇
3√𝑅𝑅
1000
 
Worst Case Rules 
Worst case finding based on the interpretation and the clinical significance: 
• Count the subject as ‘ABNORMAL’ and ‘CLINICALLY SIGNIFICANT’, if any of the findings are 
‘ABNORMAL’ and ‘CLINICALLY SIGNIFICANT’ during the time period/Post-Baseline.   
• Else count the subject as ‘ABNORMAL’ and ‘NOT CLINICALLY SIGNIFICANT’, if any of the 
findings are ‘ABNORMAL’ and ‘NOT CLINICALLY SIGNIFICANT’ and none of the findings are 
‘ABNORMAL’ and ‘CLINICALLY SIGNIFICANT’ during the time period/Post-Baseline.  
• Else count the subject as ‘NORMAL’ if there is a finding of ‘NORMAL’ and none of the findings 
are ‘ABNORMAL during the time period/Post-Baseline.  
• Otherwise, do not count the subject during the time period/Post-Baseline, i.e. little n will reflect 
that the subject is not counted in the time period/Post-Baseline.. 
 
Laboratory Parameters 
o All BLQ values will be imputed with ½ LLOQ.  
o All ALQ values will be imputed with the ALQ + [smallest positive number with the same 
number of decimal places as the ALQ is reported with] 
o Values reported as < x are assumed to have an LLOQ of x. 
o Values reported as > x are assumed to have an ALQ of x. 


 
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14.6.5. 
Immunogenicity 
A seed (5315) will be generated using code as outlined in Section 14.9.2. This will be 
saved in the refdata area. 
• 
Using the generated seed, random numbers will be generated for all subjects that exist 
in the imgen dataset. 
• 
These subjects will be ordered based on the random number and letters assigned 
sequentially (i.e. the patient with the smallest random number was ‘a’, the next patient ‘b’ 
and so on). 
 


 
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14.7. 
Appendix 7: Reporting Standards for Missing Data 
14.7.1. 
Premature Withdrawals 
Element 
Reporting Detail 
General 
• A participant is considered to have completed the study if he/she has completed 
all phases of the study including the final follow-up visit 
• All available data from participants who were withdrawn from the study will be 
listed and all available planned data will be included in summary tables and 
figures, unless otherwise specified.  
14.7.2. 
Handling of Missing Data 
Element 
Reporting Detail 
General 
• Missing data occurs when any requested data is not provided, leading to 
blank fields on the collection instrument: 
o These data will be indicated by the use of a “blank” in participant 
listing displays. Unless all data for a specific visit are missing in which 
case the data is excluded from the table.  
o Answers such as “Not applicable” and “Not evaluable” are not 
considered to be missing data and should be displayed as such. 
14.7.2.1. 
Handling of Missing and Partial Dates 
Element 
Reporting Detail 
General 
• Partial dates will be displayed as captured in participant listing displays. 
• 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 or for specific analysis purposes. 
Adverse 
Events 
• Imputations in the adverse events dataset are used for slotting events to the 
appropriate study time periods and for sorting in data listings. 
• Partial dates for AE recorded in the CRF will be imputed using the following 
conventions: 
 
Missing start day 
• 
If study treatment start date is missing (i.e. participant did 
not start study treatment), then set start date = 1st of 
month. 
• 
Else if study treatment start date is not missing: 
o 
If month and year of start date = month and year 
of study treatment start date then 
▪ 
If stop date contains a full date and 
stop date is earlier than study 
treatment start date then set start 
date= 1st of month. 
▪ 
Else set start date = study treatment 
start date. 
o 
Else set start date = 1st of month. 


 
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Element 
Reporting Detail 
Missing start day 
and month 
• 
If study treatment start date is missing (i.e. participant did 
not start study treatment), then set start date = January 1. 
• 
Else if study treatment start date is not missing: 
o 
If year of start date = year of study treatment 
start date then 
▪ 
If stop date contains a full date and 
stop date is earlier than study 
treatment start date then set start date 
= January 1. 
▪ 
Else set start date = study treatment 
start date.       
o 
Else set start date = January 1. 
Missing stop day  
Last day of the month will be used. 
Missing stop day 
and month 
No Imputation 
Completely missing 
start/end date 
No imputation 
 
 
Concomitant 
Medications 
• Partial dates for any concomitant medications recorded in the CRF will be 
imputed using the following convention: 
 
Missing start day 
• 
If study treatment start date is missing (i.e. participant did 
not start study treatment), then set start date = 1st of 
month. 
• 
Else if study treatment start date is not missing: 
o 
If month and year of start date = month and year 
of study treatment start date then 
▪ 
If stop date contains a full date and 
stop date is earlier than study 
treatment start date then set start 
date= 1st of month. 
▪ 
Else set start date = study treatment 
start date. 
o 
Else set start date = 1st of month. 
Missing start day 
and month 
• 
If study treatment start date is missing (i.e. participant did 
not start study treatment), then set start date = January 1. 
• 
Else if study treatment start date is not missing: 
o 
If year of start date = year of study treatment 
start date then 
▪ 
If stop date contains a full date and 
stop date is earlier than study 
treatment start date then set start date 
= January 1. 
▪ 
Else set start date = study treatment 
start date.       
o 
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)  


 
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Element 
Reporting Detail 
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 
 
• The recorded partial date will be displayed in listings. 
 
 
 


 
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14.8. 
Appendix 8: Values of Potential Clinical Importance 
14.8.1. 
PCI Values for Part A 
14.8.1.1. 
Vital Signs 
Vital Sign Parameter 
(Absolute) 
Units 
Clinical Concern Range 
Lower 
Upper 
Systolic Blood Pressure 
mmHg 
< 85 
> 160 
Diastolic Blood Pressure 
mmHg 
< 45 
> 100 
Heart Rate 
Bpm 
< 40 
> 110 
14.8.1.2. 
Laboratory Values 
Haematology 
Laboratory Parameter 
 
Units 
Category 
Clinical Concern Range 
Low Flag (< x) 
High Flag (>x) 
Hematocrit  
Ratio of 
1 
Male 
0.39 
0.54 
Female 
0.35 
0.49 
∆ from BL ↓0.075 
 
Hemoglobin  
g/L 
 
Male 
124 
180 
Female 
109 
180 
∆ from BL ↓25 
 
Lymphocytes  
x109/ L 
 
0.75 
 
Neutrophil Count  
x109/ L 
 
1.5 
 
Platelet Count  
x109/ L 
 
100 
550 
White Blood Cell Count (WBC) 
x109/ L 
 
2.5 
20 
 
Clinical Chemistry 
Laboratory Parameter 
Units 
Category 
Clinical Concern Range 
Low Flag (< x) 
High Flag (>x) 
Albumin  
g/L 
 
30 
 
Calcium 
mmol/L 
 
2 
2.75 
Creatinine 
umol/L 
 
 
1.3 X ULN 
Creatinine 
umol/L 
∆ from BL 
 
↑ 44.2 
Glucose 
mmol/L 
 
3 
9 
Potassium 
mmol/L 
 
3 
5.5 
Sodium 
mmol/L 
 
130 
150 
Total CO2 
mmol/L 
 
18 
32 
Creatinine Kinase 
mg/dL 
 
 
>1.6 X ULN 
C-reactive Protein 
mg/L 
 
 
≥3.0 
Troponin T 
ng/L 
 
 
14.1 
 
 
 


 
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Liver Function 
Test Analyte 
Units 
Category 
Clinical Concern Range 
ALT/SGPT  
IU/L 
High 
≥2xULN 
AST/SGOT  
IU/L 
High 
≥2xULN 
AlkPhos  
IU/L 
High 
≥2xULN 
T Bilirubin  
µmol/L 
High 
≥1.5xULN 
T. Bilirubin + ALT 
µmol/L 
High 
ALT≥3xULN AND bilirubin≥ 1.5xULN 
IU/L 
14.8.1.3. 
ECG 
ECG Parameter 
Units 
Clinical Concern Range 
Lower 
Upper 
Absolute 
Absolute QTc Interval 
msec 
 
>500 
Absolute PR Interval 
msec 
<110 
>220  
Absolute QRS Interval 
msec 
<75 
>120 
Change from Baseline 
Increase from Baseline QTc msec 
 
>60 
14.8.2. 
PCI Values for Part B 
14.8.2.1. 
Vital Signs 
Vital Sign Parameter 
(Absolute) 
Units 
Clinical Concern Range 
Lower 
Upper 
Systolic Blood Pressure 
mmHg 
< 85 
> 160 
Diastolic Blood Pressure 
mmHg 
< 45 
> 100 
Heart Rate 
bpm 
< 40 
> 110 
14.8.2.2. 
Laboratory Values 
Haematology 
Laboratory Parameter 
 
Units 
Category 
Clinical Concern Range 
Low Flag (< x) 
High Flag (>x) 
Hematocrit  
Ratio of 
1 
Male 
0.39 
0.54 
Female 
0.35 
0.49 
∆ from BL ↓0.075 
 
Hemoglobin  
g/L 
 
Male 
124 
180 
Female 
109 
180 
∆ from BL ↓25 
 
Lymphocytes  
x109/ L 
 
0.75 
4.5 
Neutrophil Count  
x109/ L 
 
1.5 
8.0 
Platelet Count  
x109/ L 
 
100 
550 
White Blood Cell Count (WBC) 
x109/ L 
 
2.5 
15 


 
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Haematology 
Laboratory Parameter 
 
Units 
Category 
Clinical Concern Range 
Low Flag (< x) 
High Flag (>x) 
Clinical Chemistry 
Laboratory Parameter 
Units 
Category 
Clinical Concern Range 
Low Flag (< x) 
High Flag (>x) 
Calcium 
mmol/L 
 
2 
2.60 
Creatinine 
umol/L 
Male 
 
120 
 
 
Female 
 
100 
Creatinine 
umol/L 
∆ from BL 
 
↑ 44.2 
Glucose 
mmol/L 
 
3 
8 
Potassium 
mmol/L 
 
3 
5.5 
Sodium 
mmol/L 
 
130 
150 
Troponin T 
ng/L 
 
 
14.1 
NT-pro BNP 
 ng/L 
 
 
125.2 
 
Liver Function 
Test Analyte 
Units 
Category 
Clinical Concern Range 
ALT/SGPT  
IU/L 
High 
≥1.5xULN 
AST/SGOT  
IU/L 
High 
≥1.5xULN 
AlkPhos  
IU/L 
High 
≥1.5xULN 
T Bilirubin  
µmol/L 
High 
≥1.5xULN 
T. Bilirubin + ALT 
µmol/L 
High 
ALT≥3xULN AND bilirubin≥ 1.5xULN 
IU/L 
 
 
Virology 
Test Analyte 
Units 
Category 
Clinical Concern Range 
Hepatitis C Antibody  
N/A 
High 
Reactive 
 
 
Immunology 
Test Analyte 
Units 
Category 
Clinical Concern Range 
Low Flag (<x) 
High Flag (>x) 
Complement C3  
g/L 
High 
0.85 
1.8 
Complement C4 
g/L 
High 
0.1 
0.4 


 
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14.8.2.3. 
ECG 
ECG Parameter 
Units 
Clinical Concern Range 
Lower 
Upper 
Absolute 
Absolute QTc Interval 
msec 
<350 
>450 
Absolute PR Interval 
msec 
<110 
>220  
Absolute QRS Interval 
msec 
<75 
>120 
Change from Baseline 
Increase from Baseline QTc msec 
 
>50 
 
 


 
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207804 
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14.9. 
Appendix 9: Statistical Algorithms and Model Checking 
14.9.1. 
Calculation of SD from Bayesian Repeated Measures model 
1. Calculate the R Correlation matrix (correlation matrix for the repeated measures 
[in this case visit]) 
𝑅𝑐𝑜𝑟𝑟= [
1
𝜌1,2
1
…
𝜌1,8
…
𝜌2,8
…
…
1
] 
2. Calculate the number of subject contributing data up to each week (e.g. 32 
subjects have up to week 8, a further 4 subjects contribute up to week 6 only, 3 
more contribute data up to week 4 only.  
𝒏𝑐𝑜𝑛𝑡= [
𝑛1,8
𝑛2,8
…
𝑛7,8
] = [
𝑛1
𝑛2
…
𝑛7
] −[
𝑛8
𝑛8
…
𝑛8
] 
𝐸𝑆𝑆8 = 𝑛8 + ∑𝜌𝑖,8𝑛𝑖,8
𝑖=1,…7
 
3. Calculate the SD 
𝑆𝐷𝑒𝑠𝑡𝑖𝑚𝑎𝑡𝑒,8 = 𝑆𝐸8 ∗√𝐸𝑆𝑆8  
 
14.9.2. 
Model Checking & Diagnostics 
Bayesian Repeated Measures Model 
Seeds for all planned analyses will be determined using the following SAS code  
 
data temp; 
 do i=1 to #seed; 
   number=round(10000*ranuni(207804),1); output; 
 end; 
run; 
 
The following points are for guidance and illustration and do not guarantee a successful model 
convergence.  They cannot cover all eventualities and do not remove the requirement to do what 
is best for the specific set of observed data being modelled. 
 
Priors 
Unless otherwise specified the following would be the default approach to selecting prior 
distributions: 
• Vague priors of the form Normal(0, Var=1E6) would be assigned to each fixed effect in the 
proposed statistical model. 


 
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• Vague Inverse-gamma priors of the form IGamma(0.001,0.001) would be assigned to stand-
alone variance parameters that are not expected to take values near zero (e.g. for the 
residual variance rather than a random effect variance component) 
• For stand-alone variance parameters that may take values close to zero a noninformative 
prior of the form Uniform(0, XXX) may be assigned for the SD 
• For repeated measures models Inverse-Wishart priors will be assigned for the Variance 
Covariance matrix (VCV). They would use degrees of freedom equal to the dimension of the 
VCV matrix and an Identity matrix (of the same dimension). 
o If there are issues with those variance parameters then the Identitity matrix may be 
replaced with a diagonal matrix that uses best guesses for the residual variance at 
each repeated measure time point (or the residual estimates from fitting simple 
models). 
o It is good practice to ensure that each prior distribution is visualised to ensure it 
appears sensible and allows clinically plausible response values, whilst not allowing 
impossible values to be drawn with high probability and that if it is intended to be 
non-informative it is doing so over the region of the likelihood function.   
 
Checking convergence and other diagnostics 
The key model diagnostic output is the MCSE/SD ratio for each parameter: 
• Adequate values for the number of MCMC samples / thinning / number of burn in samples 
should be chosen to ensure that the MCSE/SD for the key parameters is below 0.01 (e.g. 
key parameters those associated with treatment, or as pre-specified comparisons of 
interest) in each final model. 
• For other model parameters, try to get the MCSE/SD values as close to 0.01 as possible, 
but if there is significant autocorrelation then values below 0.05 would be considered 
acceptable. 
• In addition, the number of tuning units and maximum number of tuning iterations may be 
increased to find a better multivariate normal approximation to the parameters, which in turn 
may reduce the MCSE/SD values 
• Where possible the code should be written to allow the SAS compiler to identify and use 
conjugate sampling, since this can greatly reduce the corresponding MCSE/SD values 
• Models selected with MCSE/SD values above 0.01 (for key parameters) or 0.05(for other 
parameters) would need a brief remark/justification added to the CSR to clarify why it was 
not possible to reach the targets and why it is believed the subsequent model still has utility. 
 
Use of the default SAS PROC MCMC diagnostic plots should be made and where possible: 
• Autocorrelation should decline rapidly and show no oscillation patterns 
• Worm plots should show the chain appears to be stationary and mixing, i.e. 
o Constant mean, constant variance 
o Moving around the parameter space freely (not getting “stuck” at similar values for a 
large number of iterations before moving on again) 
o Moving rapidly between extremes 
o The posterior density should look reasonable for each parameter (e.g. for posterior 
parameters expected to follow a normal distribution the density plot should not 


 
CONFIDENTIAL 
 
 
 
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72 
 
appear bi-modal, but for parameters acting as binary flags then bi-modal is 
acceptable) 
o Correlation structures between relevant posterior parameters (and/or parameters in 
each PARMS block) should be explored using graphical methods.  This can provide 
information about what potential issues may be and also what corrective action(s) 
may be worthwhile attempting. 
 
 
 


 
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
7 3  
 
1 4. 1 0.  
A p p e n di x 1 0 : A b br e vi ati o n s & Tr a d e M ar k s 
1 4. 1 0. 1.  
A b br e vi ati o n s  
A b bre viati o n  
Descri pti o n  
A E  
A d verse E v e nt  
AI C  
A kai ke's I nf or mati o n Criteria  
A U C  
Area U n der t he C o n ce ntr ati o n -Ti me C ur ve  
A & R  
A nal ysis a n d R e p orti n g  
B N P  
N -ter mi nal pr o B-t y pe n atri uretic pe pti de 
B U N  
Bl o o d urea nitr o ge n  
CI  
C o nfi de nce I nter val  
C ma x  
Ma xi m u m o bser ve d c o nce ntrati o n  
C P M S  
Cli nical P har mac ol o g y M o delli n g & Si m ulati o n  
C S  
Cli nical Statistics  
C S R  
Cli nical St u d y Re p ort  
C T R  
Cli nical Trial Re gister  
C V b / C Vw  
C oefficie nt of Variati o n ( Bet wee n) / C oefficie nt of Variati o n ( Wit hi n)  
D B F  
Data base Freeze  
D B R  
Data base R elease  
D E C  
D ose Escalati o n C o m mittee  
D E P  
D ose  Escalati o n Pla n  
D O B  
Date of Birt h  
D P  
Deci mal Places  
e C R F 
Electr o nic Case Rec or d F or m  
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
F D A A A  
F o o d a n d Dr u g A d mi nistrati o n Cli nical Res ults Discl os ure 
Re q uire me nts  
G S K  
Gla x o S mit h Kli ne  
I A 
I nteri m A nal ysis 
I C H 
I nter nati o nal C o nfere nce o n Har m o nizati o n 
I D M C 
I n d e pe n de nt Data M o nit ori n g C o m mittee  
I D S L 
I nte grate d Data Sta n dar ds Li brar y 
I M M S 
I nter nati o nal M o d ules M a na ge me nt S yste m 
I P 
I n v esti gati o nal Pr o d uct 
I T T 
I nte nt-T o -Treat  
M C H  
Mea n C or p usc ular He m o gl o bi n  
M C V  
Mea n C or p usc ular V ol u me  
O A  
Oste oart hritis  
P CI  
P ote ntial Cli nical I m p orta nce  
P D  
P har mac o d y na mic  
P D M P  
Pr ot oc ol De viati o n Ma na ge m e nt Pla n  
P h G A  
P h ysicia n Gl o bal Ass ess me nt  
P K  
P har mac o ki netic s 
P P  
Per Pr ot oc ol  
C CI


 
CONFIDENTIAL 
 
 
 
207804 
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Abbreviation 
Description 
QC 
Quality Control 
QTcF 
Frederica’s QT Interval Corrected for Heart Rate 
QTcB 
Bazett’s QT Interval Corrected for Heart Rate 
RAP 
Reporting & Analysis Plan 
RAMOS 
Randomization & Medication Ordering System  
RBC 
Red Blood Cell Count 
SAC 
Statistical Analysis Complete 
SOA 
Schedule of Activities 
SOP 
Standard Operation Procedure 
TA 
Therapeutic Area 
TLF 
Tables, Listings and Figures  
WBC 
Whole Blood Count 
WOMAC 
Western Ontario & McMaster Universities Osteoarthritis 
Index 
14.10.2. 
Trademarks 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
None 
 
WinNonlin 
 
 
SAS 
 
 
NONMEM 
 
 


 
C O N FI D E N TI A L  
 
 
 
2 0 7 8 0 4  
7 5  
 
1 4. 1 1.  
A p p e n di x 1 1 : Li st of D at a Di s pl a y s 
1 4. 1 1. 1.  
D at a  Di s pl a y N u m b eri n g  
T he f oll o wi n g n u m b eri n g will be a p plie d f or R A P ge nerate d dis pla ys:  
S e cti o n  
T a bl e s  
Fi g ur e s  
 
P art A  
P art B  
P art A  
P art B  
S af ety R evi e w  
N/ A  
1  
N/ A  
N/ A  
S a m pl e Size R e -esti m atio n  
N/ A  
2  
N/ A  
N/ A  
St u dy P op ul ati on  
1. 0 1 t o 1. 09  1. 1 0 t o 1. 2 8 
N/ A  
N/ A  
S af ety  
2. 0 1 t o 2. 16  2. 1 7 t o 2. 3 9 
N/ A  
N/ A  
P h ar mac oki netic  
3. 0 1 t o 3. 06 3. 0 7 t o 3. 0 8  
3. 0 1 t o 3. 06 
3. 0 7 t o 3. 0 9  
P h ar mac ody n a mic  
4 .0 1 t o 4 .05 4. 0 6 t o 4. 0 8  
4 .0 1 t o 4 .03 
4. 0 4 t o 4. 0 6  
Effic acy  
N/ A  
6. 0 1 t o 6. 21 
N/ A  
6. 0 1 t o 6. 1 5 
 
 
 
 
 
S e cti o n  
Li sti n g s  
 
P art A  
P art B  
I C H Listi n gs 
1 t o 3 1, 6 4 t o 6 5  
3 2 to 6 3, 66  
Ot h er Listin gs  
6 7  to 76  
7 7 to 8 7  
1 4. 1 1. 2.  
M o c k E x a m pl e S h ell R ef er e n ci n g  
N o n I D S L s p ecificati o ns will be refere nce d as i n di cate d i n  a se p arate  T F L S hells 
d oc u me nt .  
S e cti o n  
Fi g ur e  
T a bl e  
Li sti n g  
S af ety R evi e w  
 
S R _ T n  
 
S a m pl e Size R e -esti m atio n  
 
S S R _ T n  
 
St u dy P op ul ati on  
 
 
 
S af ety  
 
S A F E _ Tn  
 
P h ar mac oki netic  
P K _ F n  
P K _ T n  
P K _ Ln  
P h ar mac ody n a mic  
 
P D _ T n  
 
Effic acy  
E F F _ F n  
E F F _ T n  
E F F _ L n  
 
1 4. 1 1. 3.  
D eli v er a bl e s  
D eli v ery  
D e s cri pti o n  
P art A S A C  
P art A Fi nal Statistic al An alysis C o m pl et e  
P art B S R 1  
S af ety R evi e w 1  
P art B S R 2  
S af ety R evi e w 2  
P art B I A 1  
I nt eri m A nalysis 1   
P art B I A 2  
I nt eri m A nalysis 2   
P art B I A 3  
I nt eri m A nalysis 3 
P art B I A 4  
I nt eri m A nalysis 4 
P art B S A C  
P art B Fi nal Statistic al An alysis C o m pl et e  
C CI
C CI


 
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14.11.4. 
Safety Review Table 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Immunogenicity – Part B 
1. Safety 
SR1 
Part B: Summary of Immunogenicity 
 
SR1, SR2 
 
14.11.5. 
Sample Size Re-estimation table 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Sample Size Re-estimation – Part B 
2. Safety 
SSR_1 
Part B: Summary of Sample Size Re-estimation 
 
IA2 
 
 


 
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14.11.6. 
Study Population Tables 
14.11.6.1. Part A 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Subject Disposition  
1.01. 
Randomized 
ES1 
Part A: Summary of Subject Disposition for the Subject 
Conclusion Record 
ICH E3, FDAAA, EudraCT 
Part A SAC 
1.02. 
Screened 
ES6 
Part A: Summary of Screening Status and Reasons for 
Screen Failure 
Journal Requirements 
Part A SAC  
Protocol Deviation  
1.03. 
Randomized 
DV1 
Part A: Summary of Important Protocol Deviations 
ICH E3 
Part A SAC 
Population Analysed  
1.04. 
Screened 
SP1 
Part A: Summary of Study Populations  
IDSL. Include footnote with 
population definitions. 
Part A SAC 
Demographic and Baseline Characteristics  
1.05. 
Randomized 
DM1 
Part A: Summary of Demographic Characteristics 
ICH E3, FDAAA, EudraCT 
Part A SAC 
1.06. 
Enrolled 
DM11 
Part A: Summary of Age Ranges 
EudraCT 
Part A SAC 
1.07. 
Randomized 
DM5 
Part A: Summary of Race and Racial Combinations 
ICH E3, FDA, FDAAA, EudraCT 
Part A SAC 
Prior and Concomitant Medications  
1.08. 
Safety 
CM1 
Part A: Summary of Prior Medications 
ICH E3 
Part A SAC 
1.09. 
Safety 
CM1 
Part A: Summary of Concomitant Medications 
ICH E3 
Part A SAC  
 
 
 


 
C O N FI D E N TI A L  
 
 
2 0 7 8 0 4  
7 8  
 
1 4. 1 1. 6. 2.  P art B  
N o.  
P o p ul ati o n  
I D S L / 
E x a m ple 
S h ell  
Titl e   
Pr o gr a m mi n g N ote s  
D eli v era bl e  
S u bj e ct Di s p ositi o n  
1. 1 0.  
 R a n d o miz ed  
E S 1  
P art B: S u m m ary of S ubj ect Dis p ositi o n for t he Su bj ect  
C o ncl usi o n Rec or d  
 
I A 1, I A 2, I A 3, 
I A 4, P art B 
S A C  
1. 1 1.  
 R a n d o miz ed  
S D 1  
P art B: S u m m ary of Tr e at me nt St atus a n d R eas ons f or 
Disc o nti n u ati o n of St u dy Tr e at m e nt  
 
I A 1, I A 2, I A 3, 
I A 4, 
P art B S A C  
1. 1 2.  
 Scr e e ne d  
E S 6  
P art B: S u m m ary of Scr e enin g Stat us a nd R eas o ns f or 
Scr e e n Fail ur e  
 
P art B S A C  
1. 1 3.  
 E nr oll e d  
N S 1  
P art B: S u m m ary of N u m b er of S ubj ects by C o untry and 
Sit e I D  
 
P art B S A C  
C O VI D -1 9   
1. 1 4.  
 R a n d o miz ed  
P A N 1 A  
P art B: C O VI D -1 9 Cas e Di ag n osis Eve nts  
 
P art B S A C  
Pr ot o c ol D e viati o n  
1. 1 5.  
 R a n d o miz ed  
D V 1  
P art B: S u m m ary of I m p ortant Pr otoc ol D evi ati o ns 
 
P art B S A C  
P o p ul ati o n A n al y s e d  
1. 1 6.  
 Scr e e ne d  
S P 1  
P art B: S u m m ary of Stu dy P o p ulati o ns  
I ncl u d e f oot n ot e with p o p ulati o n 
d efi niti ons.  
P art B S A C  
D e m o gr a p hi c a n d B a s eli ne C h ar a ct eri stic s  
1. 1 7.  
 R a n d o miz ed  
D M 1  
P art B: S u m m ary of D e m o gr a p hic C h aract eristics  
I C H E 3, F D A A A, Eu dr a C T 
I ncl u d e K L sc or es 
I A 1, IA 2 , I A 3, 
I A 4, P art B 
S A C  
1. 1 8.  
 R a n d o miz ed  
P O P _ T 1  
P art B: S u m m ary of B aseli ne Effic acy P ar a m et ers  
I ncl u d e A v er ag e & W orst K n e e 
P ai n Int e nsity, W O M A C,
a nd P ain D etect  
I A 1, I A 2, I A 3, 
I A 4, P art B 
S A C  
C CI
C CI


 
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207804 
79 
 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
1.19. 
Enrolled 
DM11 
Part B: Summary of Age Ranges 
EudraCT 
Part B SAC 
1.20. 
Randomized 
DM5 
Part B: Summary of Race and Racial Combinations 
ICH E3, FDA, FDAAA, EudraCT 
Part B SAC 
Medical Conditions 
1.21. 
Randomized 
MH4 
Part B: Summary of Past Medical Conditions 
ICH E3 
Part B SAC 
1.22. 
Randomized 
MH4 
Part B: Summary of Current Medical Conditions 
ICH E3 
Part B SAC 
Prior and Concomitant Medications  
1.23. 
Safety 
CM1 
Part B: Summary of Prior Medications 
ICH E3 
Part B SAC 
1.24. 
Safety 
CM1 
Part B: Summary of Concomitant Medications 
ICH E3 
Part B SAC 
1.25. 
Safety 
CM1 
Part B: Summary of Prior Osteoarthritis Medications 
OA meds are captured on a 
specific CRF page 
Part B SAC 
1.26. 
Safety 
CM1 
Part B: Summary of Osteoarthritis Concomitant 
Medications during Prohibited Medication Phase 
 
Part B SAC 
1.27. 
Safety 
CM1 
Part B: Summary of Osteoarthritis Concomitant 
Medications 
 
Part B SAC 
Exposure 
1.28. 
Safety 
EX1 
Part B: Summary of Exposure to Study Treatment  
Provide statistics for the 
categories by number of 
injections received (4 injections, 
≤ 3 injections) 
Part B SAC 
 
 
 


 
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207804 
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14.11.7. 
Safety Tables 
14.11.7.1. Part A 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Adverse Events (AEs) 
2.01. 
Safety 
AE1CP 
Part A: Summary of All Adverse Events by System Organ 
Class and Preferred Term 
 
Part A SAC  
2.02. 
Safety 
AE5A 
Part A: Summary of All Adverse Events by System Organ 
Class and Preferred Term and Maximum Intensity 
 
Part A SAC  
2.03. 
Safety 
AE5A 
Part A: Summary of All Drug-Related Adverse Events by 
System Organ Class and Preferred Term and Maximum 
Intensity 
 
Part A SAC  
2.04. 
Safety 
AE15 
Part A: Summary of All Non-serious Adverse Events by 
System Organ Class and Preferred Term (Number of 
Subjects and Occurrences) 
 
Part A SAC  
Vital Signs 
2.05. 
Safety 
VS1 
Part A: Summary of Change from Baseline in Vital Signs 
Includes Baseline values. 
Part A SAC  
2.06. 
Safety 
VS7 
Part A: Summary of Worst Case Vital Signs Results by 
PCI Criteria Post-Baseline Relative to Baseline 
Include all assessments post-
baseline 
Part A SAC  
Laboratory: Hematology 
2.07. 
Safety 
LB1 
Part A: Summary of Hematology Changes from Baseline 
Includes baseline values. 
Part A SAC  
2.08. 
Safety 
LB17 
Part A: Summary of Worst Case Hematology Results by 
PCI Criteria Post-Baseline Relative to Baseline 
Include all assessments post-
baseline 
Part A SAC  
Laboratory: Chemistry 
2.09. 
Safety 
LB1 
Part A: Summary of Chemistry Changes from Baseline  
ICH E3 
Part A SAC  
2.10. 
Safety 
LB17 
Part A: Summary of Worst Case Chemistry Results by 
PCI Criteria Post-Baseline Relative to Baseline 
ICH E3 
Include all assessments post-
baseline 
Part A SAC  


 
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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Laboratory: Urinalysis  
2.11. 
Safety 
UR1 
Part A: Summary of Worst Case Urinalysis Results 
(Discrete or Character Values) Post-Baseline Relative to 
Baseline 
 
Part A SAC  
ECG  
2.12. 
Safety 
EG1 
Part A: Summary of ECG Findings 
 
Part A SAC  
2.13. 
Safety 
EG10 
Part A: Summary of Maximum QTc Values Post-Baseline 
Relative to Baseline by Category 
Use QTcB and QTcF intervals 
Part A SAC  
2.14. 
Safety 
EG2 
Part A: Summary of Change from Baseline in ECG Values 
by Visit 
Use QTcB and QTcF intervals 
Part A SAC  
2.15. 
Safety 
EG11 
Part A: Summary of Maximum Increase in QTc Values 
Post-Baseline Relative to Baseline by Category 
Use QTcB and QTcF intervals 
Part A SAC  
Telemetry – Part A 
2.16. 
Safety 
EG1 
Part A: Summary of Telemetry Findings 
 
Part A SAC  
 
 


 
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14.11.7.2. Part B 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Adverse Events (AEs) – Part B 
2.17. 
Safety 
CP_AE1p 
Part B: Summary of All Adverse Events by System Organ 
Class and Preferred Term 
 
IA3, Part B 
SAC 
2.18. 
Safety 
AE5A 
Part B: Summary of All Adverse Events by System Organ 
Class and Preferred Term and Maximum Intensity 
 
IA3,  Part B 
SAC 
2.19. 
Safety 
AE3 
Part B: Summary of Common (≥5%) Adverse Events by 
Overall Frequency 
 
Part B SAC 
2.20. 
Safety 
AE5A 
Part B: Summary of All Drug-Related Adverse Events by 
System Organ Class and Preferred Term and Maximum 
Intensity 
Include Total column. 
IA3, Part B 
SAC 
2.21. 
Safety 
AE15 
Part B: Summary of All Non-serious Adverse Events by 
System Organ Class and Preferred Term (Number of 
Subjects and Occurrences) 
 
IA3, Part B 
SAC 
2.22. 
Safety 
AE15 
Part B: Summary of Common (≥5%) Non-serious Adverse 
Events by System Organ Class and Preferred Term 
(Number of Subjects and Occurrences) 
 
Part B SAC 
Serious and Other Significant Adverse Events 
2.23. 
Safety 
AE16 
Part B: Summary of Serious Adverse Events by System 
Organ Class and Preferred Term (Number of Subjects 
and Occurrences) 
 
IA3, Part B 
SAC 
2.24. 
Safety 
AE1 
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment or Withdrawal from 
Study by System Organ Class and Preferred Term 
 
IA3, Part B 
SAC 
2.25. 
Safety 
AE3 
Summary of Serious Drug-Related Adverse Events by 
Overall Frequency 
 
IA3, Part B 
SAC 


 
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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Vital Signs  
2.26. 
Safety 
VS1 
Part B: Summary of Change from Baseline in Vital Signs 
Include Baseline 
IA3, Part B 
SAC 
2.27. 
Safety 
VS7 
Part B: Summary of Worst Case Vital Signs Results by 
PCI Criteria Post-Baseline Relative to Baseline 
 
IA3,  Part B 
SAC 
Laboratory: Hematology 
2.28. 
Safety 
LB1 
Part B: Summary of Hematology Changes from Baseline 
Include Baseline 
IA3, Part B 
SAC 
2.29. 
Safety 
LB17 
Part B: Summary of Worst Case Hematology Results by 
PCI Criteria Post-Baseline Relative to Baseline 
 
IA3, Part B 
SAC 
Laboratory: Chemistry 
2.30. 
Safety 
LB1 
Part B: Summary of Chemistry Changes from Baseline  
 
IA3, Part B 
SAC 
2.31. 
Safety 
LB17 
Part B: Summary of Worst Case Chemistry Results by 
PCI Criteria Post-Baseline Relative to Baseline 
 
IA3, Part B 
SAC 
Laboratory: Urinalysis 
2.32. 
Safety 
UR1 
Part B: Summary of Worst Case Urinalysis Results 
(Discrete or Character Values) Post-Baseline Relative to 
Baseline 
 
IA3, Part B 
SAC 
ECG 
2.33. 
 Safety 
EG1 
Part B: Summary of ECG Findings 
 
IA3, Part B 
SAC 
2.34. 
Safety 
EG10 
Part B: Summary of Maximum QTc Values Post-Baseline 
Relative to Baseline by Category 
Use QTcB and QTcF intervals 
IA3, Part B 
SAC 
2.35. 
Safety 
EG2 
Part B: Summary of Change from Baseline in ECG Values 
by Visit 
Use QTcB and QTcF intervals 
IA3, Part B 
SAC 


 
CONFIDENTIAL 
 
 
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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
2.36. 
Safety 
EG11 
Part B: Summary of Maximum Increase in QTc Values 
Post-Baseline Relative to Baseline by Category 
 Use QTcB and QTcF intervals 
IA3, Part B 
SAC 
Immunogenicity 
2.37. 
 Safety 
AE1CP 
Part B: Summary of Treatment-Emergent Adverse Events 
by Highest Post-Baseline ADA Result 
Split table by Positive/ Negative 
ADA status 
Part B SAC 
Injection Site Reactions 
2.38. 
 Safety 
SAFE_T1 
Part B: Summary of Injection Site Reactions as per 
specified AE Term list 
Safety to provide list of HLT / 
Preferred Terms. Add a footnote 
explaining that this table was 
created using a pre-specified 
subset of MedDra AE Terms 
Part B SAC 
2.39. 
 Safety 
ESI1 
Part B: Summary of Characteristics of Injection Site 
Reactions as per specified AE Term list 
Safety to provide list of  HLT / 
Preferred Terms. Add a footnote 
explaining that this table was 
created using a pre-specified 
subset of MedDra AETerms 
Part B SAC 
 
 


 
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14.11.8. 
Pharmacokinetic Tables 
14.11.8.1. Part A 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable  
Serum GSK3858279 
3.01. 
PK 
PK01 
Part A: Summary of Serum GSK3858279 Concentration-
Time Data (ng/mL) 
Please only present the 
median, min, max, sd (log), 
geometric mean and 95% CI, 
back-transformed from the 
loge scale. 
Part A SAC  
3.02. 
PK 
PK06 
Part A: Summary of Derived Serum GSK3858279 
Pharmacokinetic Parameters (non-transformed and log-
transformed) 
Include Cmax, tmax, AUC(0-t), 
AUC(0-∞), t½, CL, Vss. 
Please note that tmax should 
not be loge-transformed and 
95% CI should not be 
presented. 
Please add the following 
footnote: CL= systemic 
clearance for IV, apparent 
systemic clearance for SC. 
Part A SAC 
3.03. 
PK 
PK_T1 
Part A: Summary of Serum GSK3858279 
Pharmacokinetic Dose Proportionality  
 
Part A SAC  
3.04. 
PK 
PK_T2 
Part A: Summary of SC:IV GSK3858279 Pharmacokinetic 
Comparison 
 
Part A SAC  
Blister GSK3858279  


 
C O N FI D E N TI A L  
 
 
2 0 7 8 0 4  
8 6  
 
N o.  
P o p ul ati o n  
I D S L / 
E x a m ple 
S h ell  
Titl e   
Pr o gr a m mi n g N ote s  
D eli v era bl e  
 
 
 
C CI


 
C O N FI D E N TI A L  
 
 
2 0 7 8 0 4  
8 7  
 
1 4. 1 1. 8. 2.  P art B  
N o.  
P o p ul ati o n  
I D S L / 
E x a m ple 
S h ell  
Titl e   
Pr o gr a m mi n g N ote s  
D eli v era bl e  
S er u m G S K3 8 58 27 9  
 
 
 
C CI


 
C O N FI D E N TI A L  
 
 
2 0 7 8 0 4  
8 8  
 
1 4. 1 1. 9.  
P h ar m a c o ki n eti c Fi g ur e s  
1 4. 1 1. 9. 1.  P art A  
N o.  
P o p ul ati o n  
I D S L / 
E x a m ple 
S h ell  
Titl e   
Pr o gr a m mi n g N ote s  
D eli v era bl e  
S er u m G S K3 8 58 27 9  
C CI


 
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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.02. 
PK 
PK17 
Part A: Mean Serum GSK3858279 Concentration-Time Plots 
(Linear and Semi-log) 
Add the following footnotes: 
Note: LLOQ=100 ng/mL. 
Note: Concentrations below 
LLOQ have been set to zero 
and included in the summary 
statistic calculations.  
Note: Any single mid-profile 
non-quantifiable (NQ) 
concentrations have been 
omitted. 
Note: Zero concentration 
values have been set to 
missing in the log-linear plot. 
Note: Samples have been 
excluded where results were 
missing or quantifiable pre-
dose concentrations. 
Part A SAC 


 
CONFIDENTIAL 
 
 
207804 
90 
 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.03. 
PK 
PK18 
Part A: Median Serum GSK3858279 Concentration-Time 
Plots (Linear and Semi-log) 
Add the following footnotes: 
Note: LLOQ=100 ng/mL. 
Note: Concentrations below 
LLOQ have been set to zero 
and included in the summary 
statistic calculations.  
Note: Any single mid-profile 
non-quantifiable (NQ) 
concentrations have been 
omitted. 
Note: Zero concentration 
values have been set to 
missing in the log-linear plot. 
Note: Samples have been 
excluded where results were 
missing or quantifiable pre-
dose concentrations. 
Part A SAC 


 
C O N FI D E N TI A L  
 
 
2 0 7 8 0 4  
9 1  
 
N o.  
P o p ul ati o n  
I D S L / 
E x a m ple 
S h ell  
Titl e   
Pr o gr a m mi n g N ote s  
D eli v era bl e  
C CI


 
C O N FI D E N TI A L  
 
 
2 0 7 8 0 4  
9 2  
 
N o.  
P o p ul ati o n  
I D S L / 
E x a m ple 
S h ell  
Titl e   
Pr o gr a m mi n g N ote s  
D eli v era bl e  
C CI


 
C O N FI D E N TI A L  
 
 
2 0 7 8 0 4  
9 3  
 
N o.  
P o p ul ati o n  
I D S L / 
E x a m ple 
S h ell  
Titl e   
Pr o gr a m mi n g N ote s  
D eli v era bl e  
 
 
 
C CI


 
C O N FI D E N TI A L  
 
 
2 0 7 8 0 4  
9 4  
 
1 4. 1 1. 9. 2.  P art B  
N o.  
P o p ul ati o n  
I D S L / 
E x a m ple S h ell  Titl e   
Pr o gr a m mi n g N ote s  
D eli v era bl e  
S er u m G S K3 8 58 27 9  
C CI


 
C O N FI D E N TI A L  
 
 
2 0 7 8 0 4  
9 5  
 
N o.  
P o p ul ati o n  
I D S L / 
E x a m ple S h ell  Titl e   
Pr o gr a m mi n g N ote s  
D eli v era bl e  
C CI


 
C O N FI D E N TI A L  
 
 
2 0 7 8 0 4  
9 6  
 
N o.  
P o p ul ati o n  
I D S L / 
E x a m ple S h ell  Titl e   
Pr o gr a m mi n g N ote s  
D eli v era bl e  
 
 
 
C CI


 
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14.11.10. Pharmacodynamic Tables 
14.11.10.1. Part A 
No. Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Serum Target Engagement 
4.01. Safety 
PD_T1 
Part A: 
Summary of 
Free & Total 
CCL17 in 
Serum 
Concentration-
Time Data 
(pg/mL) 
Please only present the median, min, max, sd (log), geometric mean and 95% CI 
back-transformed from the loge scale. 
Apply logit transformation for % reduction parameter and present median, min, max, 
sd (logit), geometric mean and 95% CI, back-transformed from the logit scale.  
If % reduction ≤0, set to 0.1. 
If % reduction ≥100, set to 99.9. 
These imputations are needed for logit transformation. 
Use Student’s t-distribution for CI. 
Add the following footnotes: 
Note: Free CCL17 values below the LLOQ have been imputed to ½* LLOQ. Total 
CCL17 values below the LLOQ have been imputed to 0. Values equal to zero at 
baseline have been imputed to LLOQ whilst missing baseline values have been 
imputed to the median of the non-missing baseline values. 
Note: Free CCL17 and Total CCL17 exceeding the upper limit of quantification 
(ULOQ) have been excluded from the summary statistics (ULOQ Free CCL17: 3600 
pg/mL, ULOQ Total CCL17: 50000 pg/mL). 
Note: If more than 30% of values have been imputed at any timepoint for a treatment 
group, then the standard deviation is not displayed. 
Note: Percentage reduction values <= 0 are imputed to be 0.1 and values >= 100 are 
imputed to be 99.9.  
Note: The percentage reduction parameter was logit transformed, summarised, and 
back-transformed using the logistic function to obtain the geometric summary 
statistics. The 95% CI of the geometric mean was calculated using Student's t 
distribution. 
Part A SAC 


 
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No. Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
4.02. Safety 
PD_T2 
Part A: 
Summary of 
Derived Free 
and Total 
CCL17 in 
Serum Target 
Engagement 
Parameters 
(non-
transformed 
and log-
transformed) 
Please only present the median, min, max, sd (log), geometric mean and 95% CI 
back-transformed from the loge scale. 
Please note that tmax and tmin should not be loge-transformed and 95% CI should 
not be presented. 
Apply logit transformation for maximum % reduction parameter and present median, 
min, max, sd (logit), geometric mean and 95% CI back-transformed from the logit 
scale.  
If maximum % reduction ≤0, set to 0.1. 
If maximum % reduction ≥100, set to 99.9. 
These imputations are needed for logit transformation. 
Use Student’s t-distribution for CI. 
Add the following footnote: 
Note: Percentage reduction values <= 0 are imputed to be 0.1 and values >= 100 are 
imputed to be 99.9. 
Note: The maximum percentage reduction parameter was logit transformed, 
summarised, and back-transformed using the logistic function to obtain the geometric 
summary statistics. The 95% CI of the geometric mean was calculated using 
Student's t distribution. 
Part A SAC 


 
CONFIDENTIAL 
 
 
207804 
99 
 
No. Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Blister Target Engagement 
4.03. Blister 
PD_T1 
Part A: 
Summary of 
Free & Total 
CCL17 in 
Blister Fluid 
Concentration-
Time Data 
(pg/mL) 
Please only present the median, min, max, sd (log), geometric mean and 95% CI 
back-transformed from the loge scale. 
Apply logit transformation for % reduction parameter and present median, min, max, 
sd (logit), geometric mean and 95% CI back-transformed from the logit scale.  
If % reduction ≤0, set to 0.1. 
If % reduction ≥100, set to 99.9. 
These imputations are needed for logit transformation. 
Use Student’s t-distribution for CI. 
Add the following footnotes: 
Note: Free CCL17 values below the LLOQ have been imputed to ½*LLOQ. Total 
CCL17 values below the LLOQ have been imputed to 0. Values equal to zero at 
baseline have been imputed to LLOQ whilst missing baseline values have been 
imputed to the median of the non-missing baseline values. 
Note: Free CCL17 and Total CCL17 exceeding the upper limit of quantification 
(ULOQ) have been excluded from the summary statistics (ULOQ Free CCL17: 3600 
pg/mL, ULOQ Total CCL17: 50000 pg/mL). 
Note: If more than 30% of values have been imputed at any timepoint for a treatment 
group, then the standard deviation is not displayed. 
Note: Percentage reduction values <= 0 are imputed to be 0.1 and values >= 100 are 
imputed to be 99.9. 
Note: The percentage reduction parameter was logit transformed, summarised, and 
back-transformed using the logistic function to obtain the geometric summary 
statistics. The 95% CI of the geometric mean was calculated using Student's t 
distribution. 
Part A SAC 
4.04. Blister 
PD_T1 
Part A: 
Summary of 
Derived Blister 
Please only present the median, min, max, sd (log), geometric mean and 95% CI 
back-transformed from the loge scale. 
Apply logit transformation for % reduction parameter and present median, min, max, 
Part A SAC 


 
CONFIDENTIAL 
 
 
207804 
100 
 
No. Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Fluid:Serum 
Free & Total 
CCL17 
concentration 
ratio 
sd (logit), geometric mean and 95% CI back-transformed from the logit scale.  
If % reduction ≤0, set to 0.1. 
If % reduction ≥100, set to 99.9. 
These imputations are needed for logit transformation. 
Use Student’s t-distribution for CI. 
Please only present the median, min, max, sd (log), geometric mean and 95% CI 
back-transformed from the loge scale. 
Apply logit transformation for % reduction parameter and present median, min, max, 
sd (logit), geometric mean and 95% CI back-transformed from the logit scale.  
If % reduction ≤0, set to 0.1. 
If % reduction ≥100, set to 99.9. 
These imputations are needed for logit transformation. 
Use Student’s t-distribution for CI. 
Add the following footnotes: 
Note: Free CCL17 values below the LLOQ have been imputed to ½*LLOQ. Total 
CCL17 values below the LLOQ have been imputed to 0. Values equal to zero at 
baseline have been imputed to LLOQ whilst missing baseline values have been 
imputed to the median of the non-missing baseline values. 
Note: Free CCL17 and Total CCL17 exceeding the upper limit of quantification 
(ULOQ) have been excluded from the summary statistics (ULOQ Free CCL17: 3600 
pg/mL, ULOQ Total CCL17: 50000 pg/mL). 
Note: If more than 30% of values have been imputed at any timepoint for a treatment 
group, then the standard deviation is not displayed. 
Note: Percentage reduction values <= 0 are imputed to be 0.1 and values >= 100 are 
imputed to be 99.9.  
Note: The percentage reduction parameter was logit transformed, summarised, and 
back-transformed using the logistic function to obtain the geometric summary 
statistics. The 95% CI of the geometric mean was calculated using Student's t 


 
CONFIDENTIAL 
 
 
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No. Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
distribution. 
Immunogenicity 
4.05. Safety 
IMM1 
Part A: 
Summary of 
Immunogenicity 
 
Part A SAC 
 
 
 


 
CONFIDENTIAL 
 
 
207804 
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14.11.10.2. Part B 
No. Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Serum Target Engagement 


 
CONFIDENTIAL 
 
 
207804 
103 
 
4.06. Safety 
PD_T1 
Part B: 
Summary of 
Free & Total 
CCL17 in 
Serum 
Concentration-
Time Data 
(pg/mL) 
Please only present the median, min, max, sd (log), geometric mean and 95% CI 
back-transformed from the loge scale. 
Apply logit transformation for % reduction parameter.  
If % reduction ≤0, set to 0.1. 
If % reduction ≥100, set to 99.9. 
These imputations are needed for logit transformation. 
Use Student’s t-distribution for CI. 
Please only present the median, min, max, sd (log), geometric mean and 95% CI 
back-transformed from the loge scale. 
Apply logit transformation for % reduction parameter and present median, min, max, 
sd (logit), geometric mean and 95% CI back-transformed from the logit scale.  
If % reduction ≤0, set to 0.1. 
If % reduction ≥100, set to 99.9. 
These imputations are needed for logit transformation. 
Use Student’s t-distribution for CI. 
Add the following footnotes: 
Note: Free CCL17 values below the LLOQ have been imputed to ½*LLOQ. Total 
CCL17 values below the LLOQ have been imputed to 0. Values equal to zero at 
baseline have been imputed to LLOQ whilst missing baseline values have been 
imputed to the median of the non-missing baseline values. 
Note: Free CCL17 and Total CCL17 exceeding the upper limit of quantification 
(ULOQ) have been excluded from the summary statistics (ULOQ Free CCL17: 3600 
pg/mL, ULOQ Total CCL17: 50000 pg/mL). 
Note: If more than 30% of values have been imputed at any timepoint for a treatment 
group, then the standard deviation is not displayed. 
Note: Baseline is the mean of the Day -4 and Day 1 Pre-Dose assessments. 
Note: Percentage reduction and fold increase parameters were calculated using a 
model based post-hoc analysis. 
Note: Percentage reduction values <= 0 are imputed to be 0.1 and values >= 100 are 
imputed to be 99.9. 
Part B SAC  


 
CONFIDENTIAL 
 
 
207804 
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No. Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Note: The percentage reduction parameter was logit transformed, summarised, and 
back-transformed using the logistic function to obtain the geometric summary 
statistics. The 95% CI of the geometric mean was calculated using Student's t 
distribution. 
4.07. Safety 
PD_T2 
Part B: 
Summary of 
Model-Derived 
Free and Total 
CCL17 in 
Serum Target 
Engagement 
Parameters 
(non-
transformed 
and log-
transformed) 
Please only present the median, min, max, sd (log), geometric mean and 95% CI 
back-transformed from the loge scale. 
Please note that tmin and tmax should not be loge-transformed and 95% CI should 
not be presented. 
Apply logit transformation for % reduction and maximum % reduction parameters.  
If % reduction ≤0, set to 0.1. 
If % reduction ≥100, set to 99.9. 
These imputations are needed for logit transformation. 
Use Student’s t-distribution for CI. 
Add the following footnotes: 
Note: All Target Engagement parameters were calculated using a model based post-
hoc analysis. 
Note: Percentage reduction values <= 0 are imputed to be 0.1 and values >= 100 are 
imputed to be 99.9. 
Note: The percentage reduction and maximum percentage reduction parameters 
were logit transformed, summarised, and back-transformed using the logistic function 
to obtain the geometric summary statistics. The 95% CI of the geometric mean was 
calculated using Student's t distribution. 
IA3, Part B 
SAC 
Immunogenicity 
4.08. Safety 
IMM1 
Part B: 
Summary of 
Immunogenicity 
Add extra row for Part B SAC - “Highest post-baseline” result. This would be 
#participants with at least one post-baseline positive result / # participants with at 
least one post baseline sample. 
IA3, Part B 
SAC 


 
CONFIDENTIAL 
 
 
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14.11.11. Pharmacodynamic Figures 
14.11.11.1. Part A 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Serum Target Engagement 
4.01. 
Safety 
PK16 
Part A: Individual 
Free & Total 
Serum CCL17 
Concentration-
Time Plots 
(Linear and 
Semi-log) 
One panel per dose group. 
Add the following footnotes: 
Note: Free CCL17 LLOQ = 2.93 pg/mL, ULOQ = 3600 pg/mL. 
Note: Total CCL17 LLOQ = 13.11 pg/mL, ULOQ = 50000 pg/mL. 
Note: The baseline value is presented at an actual relative time of 0 
days. 
Note: Any non-quantifiable (NQ) Free CCL17 concentration values have 
been set to ½*LLOQ.  
Note: Any NQ Total CCL17 concentration values before the first 
measurable concentration have been set to 0 and have been included in 
the linear plot.  
Note: Any single NQ values have been omitted. 
Note: Any multiple mid-profile NQ concentrations of Free CCL17 and 
Total CCL17 have been set to ½*LLOQ and 0, respectively, and the 
subsequent measurable concentrations have been retained.  
Note: Percentage reduction values <= 0 are imputed to be 0.1 and 
values >= 100 are imputed to be 99.9 
Part A SAC 


 
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207804 
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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
4.02. 
Safety 
PK17 
Part A: Mean 
Free & Total 
Serum CCL17 
Concentration-
Time Plots 
(Linear and 
Semi-log) 
Apply logit transformation for % reduction parameter.  
If % reduction ≤0, set to 0.1. 
If % reduction ≥100, set to 99.9. 
These imputations are needed for logit transformation. 
Use Student’s t-distribution for CI. 
Add the following footnotes: 
Note: Free CCL17 LLOQ = 2.93 pg/mL, ULOQ = 3600 pg/mL. 
Note: Total CCL17 LLOQ = 13.11 pg/mL, ULOQ = 50000 pg/mL. 
Note: Free CCL17 and Total CCL17 concentrations below LLOQ have 
been set to ½*LLOQ and 0, respectively, and have been included in the 
summary statistic calculations.  
Note: Any single mid-profile non-quantifiable (NQ) concentrations have 
been omitted. 
Note: Measurable Total CCL17 concentrations following more than one 
consecutive mid-profile NQ have been omitted. 
Note: Zero Total CCL17 concentration values have been set to missing 
in the log-linear plot. 
Note: The geometric mean is plotted as the data is not normally 
distributed. 
Note: Percentage reduction values <= 0 are imputed to be 0.1 and 
values >= 100 are imputed to be 99.9. 
Note: The percentage reduction parameter was logit transformed, 
summarised, and back-transformed using the logistic function to obtain 
the geometric summary statistics. 
Part A SAC  


 
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207804 
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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
4.03. 
Safety 
PK18 
Part A: Median 
Free & Total 
Serum CCL17 
Concentration-
Time Plots 
(Linear and 
Semi-log) 
.Add the following footnotes: 
Note: Free CCL17 LLOQ = 2.93 pg/mL, ULOQ = 3600 pg/mL. 
Note: Total CCL17 LLOQ = 13.11 pg/mL, ULOQ = 50000 pg/mL. 
Note: Free CCL17 and Total CCL17 concentrations below LLOQ have 
been set to ½*LLOQ and 0, respectively, and have been included in the 
summary statistic calculations.  
Note: Any single mid-profile non-quantifiable (NQ) concentrations have 
been omitted. 
Note: Measurable Total CCL17 concentrations following more than one 
consecutive mid-profile NQ have been omitted. 
Note: Zero Total CCL17 concentration values have been set to missing 
in the log-linear plot. 
Part A SAC  
 
 
 
 
 
 


 
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207804 
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14.11.11.2. Part B 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Serum Target Engagement 
4.04. 
Safety 
PK16 
Part B: Individual Free & 
Total Serum CCL17 
Concentration-Time Plots 
(Linear and Semi-log) 
One panel per dose group. 
Add the following footnotes: 
Note: Free CCL17 LLOQ = 2.93 pg/mL, ULOQ = 3600 
pg/mL. 
Note: Total CCL17 LLOQ = 13.11 pg/mL, ULOQ = 50000 
pg/mL. 
Note: The baseline value is presented at an actual relative 
time of 0 days. 
Note: Any non-quantifiable (NQ) Free CCL17 concentration 
values have been set to ½*LLOQ.  
Note: Any NQ Total CCL17 concentration values before the 
first measurable concentration have been set to 0 and have 
been included in the linear plot.  
Note: Any single NQ values have been omitted. 
Note: Any multiple mid-profile NQ concentrations of Free 
CCL17 and Total CCL17 have been set to ½*LLOQ and 0, 
respectively, and the subsequent measurable concentrations 
have been retained. 
Note: Percentage reduction values <= 0 are imputed to be 
0.1 and values >= 100 are imputed to be 99.9. 
Part B SAC  


 
CONFIDENTIAL 
 
 
207804 
109 
 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
4.05. 
Safety 
PK17 
Part B: Mean Free & Total 
Serum CCL17 
Concentration-Time Plots 
(Linear and Semi-log) 
Apply logit transformation for % reduction parameter.  
If % reduction ≤0, set to 0.1. 
If % reduction ≥100, set to 99.9. 
These imputations are needed for logit transformation. 
Use Student’s t-distribution for CI. 
Add the following footnotes: 
Note: Free CCL17 LLOQ = 2.93 pg/mL, ULOQ = 3600 
pg/mL. 
Note: Total CCL17 LLOQ = 13.11 pg/mL, ULOQ = 50000 
pg/mL. 
Note: Free CCL17 and Total CCL17 concentrations below 
LLOQ have been set to ½*LLOQ and 0, respectively, and 
have been included in the summary statistic calculations.  
Note: Any single mid-profile non-quantifiable (NQ) 
concentrations have been omitted. 
Note: Measurable Total CCL17 concentrations following 
more than one consecutive mid-profile NQ have been 
omitted. 
Note: Zero Total CCL17 concentration values have been set 
to missing in the log-linear plot. 
Note: The geometric mean is plotted as the data is not 
normally distributed. 
Note: Percentage reduction values <= 0 are imputed to be 
0.1 and values >= 100 are imputed to be 99.9. 
Note: The percentage reduction parameter was logit 
transformed, summarised, and back-transformed using the 
logistic function to obtain the geometric summary statistics. 
Part B SAC  


 
CONFIDENTIAL 
 
 
207804 
110 
 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
4.06. 
Safety 
PK18 
Part B: Median Free & Total 
Serum CCL17 
Concentration-Time Plots 
(Linear and Semi-log) 
Add the following footnotes: 
Note: Free CCL17 LLOQ = 2.93 pg/mL, ULOQ = 3600 
pg/mL. 
Note: Total CCL17 LLOQ = 13.11 pg/mL, ULOQ = 50000 
pg/mL. 
Note: Free CCL17 and Total CCL17 concentrations below 
LLOQ have been set to ½*LLOQ and 0, respectively, and 
have been included in the summary statistic calculations.  
Note: Any single mid-profile non-quantifiable (NQ) 
concentrations have been omitted. 
Note: Measurable Total CCL17 concentrations following 
more than one consecutive mid-profile NQ have been 
omitted. 
Note: Zero Total CCL17 concentration values have been set 
to missing in the log-linear plot. 
Part B SAC  
 
14.11.12. Biomarker Tables 
14.11.12.1. Part A 
No. 
Population 
IDSL/ 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Immune Cell Phenotype 
5.01. 
Biomarker 
BIO_T1 
Part A: Summary of Immune Cell Phenotypes 
 
Part A SAC  
5.02. 
Biomarker 
BIO_T2 
Part A: Analyses of Immune Cell Phenotypes: Treatment 
 
Part A SAC  
5.03. 
Biomarker 
BIO_T3 
Part A: Analyses of Immune Cell Phenotypes: Sample Type 
 
Part A SAC  


 
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14.11.13. Biomarker Figures 
14.11.13.1. Part A 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Immune Cell Phenotype 
5.01. 
Biomarker 
BIO_F1 
Part A: LS Mean Change from Baseline (+/- SE) of 
Immune Cell Phenotypes: Treatments by Visit 
 
Part A SAC  
5.02. 
Biomarker 
BIO_F2 
Part A: Differences and 95% CI of Immune Cell 
Phenotypes: Treatments by Visit 
 
Part A SAC  
5.03. 
Biomarker 
BIO_F1 
Part A: LS Mean Change from Baseline (+/- SE) of 
Immune Cell Phenotypes: Sample Type by Visit 
 
Part A SAC  
5.04. 
Biomarker 
BIO_F2 
Part A: Differences and 95% CI of Immune Cell 
Phenotypes: Sample Type by Visit 
 
Part A SAC  
 
14.11.14. Efficacy Tables 
14.11.14.1. Part B 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Primary Efficacy 
6.01. 
ITT 
EFF_T10 
Part B: Summary of Pain Intensity Data   
Frequency table showing at 
each visit, how many subjects 
had how many days of knee 
pain intensity data (presented 
by trt group).   
IA1, IA2, 
Part B SAC 


 
C O N FI D E N TI A L  
 
 
2 0 7 8 0 4  
1 1 2  
 
N o.  
P o p ul ati o n  
I D S L / 
E x a m ple 
S h ell  
Titl e   
Pr o gr a m mi n g N ote s  
D eli v era bl e 
[ Pri orit y] 
6. 0 2.  
I T T 
E F F _ T 1  
P art B: S u m m ary of A bsol ute V al ues a n d Ch a ng e fr o m 
B as eli n e i n A ver a ge K ne e P ai n Int e nsity  
 
I A1 , I A2 , I A 3, 
I A 4, 
P art B S A C   
6. 0 3.  
I T T 
E F F _ T 2  
P art B: B ayesi a n A n alysis of C h a ng e fr o m B aseli n e i n  
Av er a ge K ne e P ai n I nte nsity   
 
I A 1, I A 2, I A 3, 
I A 4, 
P art B S A C  
6. 0 4.  
P P  
E F F _ T 1  
P art B: S u m m ary of A bsol ute V al ues a n d Ch a ng e fr o m 
B as eli n e i n Aver a ge K ne e Pai n I nt e nsity  
 
P art B S A C   
6. 0 5.  
P P  
E F F _ T 2  
P art B: B ayesi a n A n alysis of C h a ng e fr o m B aseli n e i n 
Av er a ge K ne e P ai n I nte nsity   
 
P art B S A C  
6. 0 6 . 
I T T 
E F F _ T 1  
P art B: S u m m ary of A bsol ute V al ues a n d Ch a ng e fr o m 
B as eli n e i n W orst  K n ee P ain Inte nsity  
 
I A 3, I A4 , P art 
B S A C   
6. 0 7 . 
I T T 
E F F _ T 2  
P art B: B ayesi a n A n alysis of C h a ng e fr o m B aseli n e i n 
W orst K n ee P ain I nt e nsity  
 
I A 3, I A4 , P art 
B S A C   
C CI


 
C O N FI D E N TI A L  
 
 
2 0 7 8 0 4  
1 1 3  
 
C CI


 
C O N FI D E N TI A L  
 
 
2 0 7 8 0 4  
1 1 4  
 
 
1 4. 1 1. 1 5.  Effi c a c y Fi g ur e s  
1 4. 1 1. 1 5. 1.  P art B  
N o.  
P o p ul ati o n  
I D S L / 
E x a m ple 
S h ell  
Titl e   
Pr o gr a m mi n g N ote s  
D eli v era bl e 
[ Pri orit y] 
Pri m ary Effi c ac y  
6. 0 1 . I T T 
E F F _ F 1  
P art B: Pl ot of Post erior M edi a n a n d 9 5 % CI  of Av er age 
K n e e  P ain I nt e nsity  
 
P art B S A C  
6. 0 2.  I T T 
E F F _ F 1  
P art B: Pl ot of Post erior M edi a n a n d 9 5 % CI of C h an g e 
fr o m B as eli ne i n Aver a ge Kn e e P ai n I nte nsity   
 
I A 1, I A 2, I A 3, 
I A 4, 
P art B S A C  
6. 0 3 . I T T 
E F F _ F 1  
P art B: Pl ot of  Post erior M edi a n a n d 9 5 % CI  of W orst 
K n e e P ain I nt e nsity   
 
P art B S A C  
6. 0 4.  I T T 
E F F _ F 1  
P art B: Pl ot of Post erior M edi a n a n d 9 5 % CI of C h an g e 
fr o m B as eli ne i n W orst K n ee P ai n I nte nsity  
 
P art B S A C  
6. 0 5 . P P  
E F F _ F 1  
P art B: Pl ot of Post erior M edi a n a n d 9 5 % CI of Av er age 
K n e e P ain I nt e nsity  
 
P art B S A C  
6. 0 6.  P P  
E F F _ F 1  
P art B: Pl ot of Post erior M edi a n a n d 9 5 % CI of C h an g e 
fr o m B as eli ne i n Aver a ge Kn e e P ai n I nte nsity  
 
P art B S A C  
C CI


 
C O N FI D E N TI A L  
 
 
2 0 7 8 0 4  
1 1 5  
 
N o.  
P o p ul ati o n  
I D S L / 
E x a m ple 
S h ell  
Titl e   
Pr o gr a m mi n g N ote s  
D eli v era bl e 
[ Pri orit y] 
 
 
 
C CI


 
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14.11.16. ICH Listings 
14.11.16.1. Part A 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Subject Disposition 
1.  
Screened 
ES7 
Part A: Listing of Reasons for Screen Failure 
 
Part A SAC  
2.  
Screened 
ES9 
Part A: Listing of Subjects who were Rescreened 
 
Part A SAC  
3.  
Enrolled 
ES2 
Part A: Listing of Reasons for Study Withdrawal 
 
Part A SAC  
4.  
Randomized 
BL1 
Part A: Listing of Subjects for Whom the Treatment Blind was 
Broken 
 
Part A SAC  
5.  
Randomized 
TA1 
Part A: Listing of Planned and Actual Treatments 
 
Part A SAC  
Protocol Deviations  
6.  
Enrolled 
DV2 
Part A: Listing of Important Protocol Deviations  
 
Part A SAC  
7.  
Enrolled 
IE3 
Part A: Listing of Subjects with Inclusion/Exclusion Criteria 
Deviations 
 
Part A SAC  
Populations Analysed 
8.  
Enrolled 
SP3 
Part A: Listing of Subjects Excluded from Any Population 
 
Part A SAC  
Demographic and Baseline Characteristics 
9.  
Randomized 
DM2 
Part A: Listing of Demographic Characteristics 
 
Part A SAC  
10.  
Randomized 
DM9 
Part A: Listing of Race 
 
Part A SAC  
Medical History 
11.  
Safety 
MH2 
Part A: Listing of Current and Past Medical Conditions 
 
Part A SAC  


 
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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Concomitant Medications 
12.  
Safety 
CP_CM3 
Part A: Listing of Prior and Concomitant Medications 
 
Part A SAC  
Exposure 
13.  
Safety 
POP_L01 
Part A: Listing of Exposure Data 
 
Part A SAC  
Adverse Events 
14.  
Safety 
AE8CP 
Part A: Listing of All Adverse Events 
 
Part A SAC  
15.  
Safety 
AE7 
Part A: Listing of Subject Numbers for Individual Adverse Events  
Part A SAC  
16.  
Safety 
AE2 
Part A: Listing of Relationship Between Adverse Event System 
Organ Classes, Preferred Terms, and Verbatim Text 
 
Part A SAC  
Serious and Other Significant Adverse Events 
17.  
Safety 
AE8CPa 
Part A: Listing of Serious Adverse Events (Fatal and Non-Fatal) 
 
Part A SAC  
18.  
Safety 
AE14 
Part A: Listing of Reasons for Considering as a Serious Adverse 
Event 
 
Part A SAC  
19.  
Safety 
AE8CP 
Part A: Listing of Adverse Events Leading to Withdrawal from 
Study / Permanent Discontinuation of Study Treatment 
 
Part A SAC  
20.  
Safety 
AE8CP 
Part A: Listing of Other Significant Adverse Events 
 
Part A SAC  
Vital Signs  
21.  
Safety 
VS4 
Part A: Listing of Vital Signs of Potential Clinical Importance 
 
Part A SAC  
22.  
Safety 
VS4 
Part A: Listing of All Vital Signs Data for Subjects with Any Value 
of Potential Clinical Importance 
 
Part A SAC  
Laboratory: All 
23.  
Safety 
LB5 
Part A: Listing of Laboratory Values of Potential Clinical 
Importance 
 
Part A SAC  
24.  
Safety 
 
LB5 
Part A: Listing of All Laboratory Data for Subjects with Any Value 
of Potential Clinical Importance 
 
Part A SAC  
25.  
Safety 
LB14 
Part A: Listing of Laboratory Data with Character Results 
 
Part A SAC  


 
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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
26.  
Safety 
UR2A 
Part A: Listing of Urinalysis Data for Subjects with Any Value of 
Potential Clinical Importance 
 
Part A SAC  
ECG 
27.  
Safety 
EG3 
Part A: Listing of ECG Values of Potential Clinical Importance 
 
Part A SAC  
28.  
Safety 
EG3 
Part A: Listing of All ECG Values for Subjects with Any Value of 
Potential Clinical Importance 
 
Part A SAC  
29.  
Safety 
EG5 
Part A: Listing of Abnormal ECG Findings 
 
Part A SAC  
30.  
Safety 
EG5 
Part A: Listing of All ECG Findings for Subjects with an 
Abnormal ECG Finding 
 
Part A SAC  
Telemetry 
31.  
Safety 
EG5 
Part A: Listing of Abnormal Telemetry Findings 
. 
Part A SAC  
14.11.16.2. Part B 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Subject Disposition 
32. 
Screened 
ES7 
Part B: Listing of Reasons for Screen Failures 
 
Part B SAC  
33.  
Screened 
ES9 
Part B: Listing of Subjects who were Rescreened 
 
Part B SAC  
34.  
Enrolled 
ES2 
Part B: Listing of Reasons for Study Withdrawal 
 
Part B SAC  
35.  
Randomized 
BL1 
Part B: Listing of Subjects for Whom the Treatment Blind was 
Broken 
 
Part B SAC  
36.  
ITT 
SD2 
Part B: Listing of Reasons for Study Treatment Discontinuation 
 
Part B SAC  
37. 
Randomized 
TA1 
Part B: Listing of Planned and Actual Treatments 
 
Part B SAC  
Protocol Deviations 
38. 
Enrolled 
DV2 
Part B: Listing of Important Protocol Deviations  
 
Part B SAC  


 
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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
39. 
Enrolled 
IE3 
Part B: Listing of Subjects with Inclusion/Exclusion Criteria 
Deviations 
 
Part B SAC  
Populations Analysed 
40. 
Enrolled 
SP3 
Part B: Listing of Subjects Excluded from Any Population 
 
Part B SAC  
Demographic and Baseline Characteristics 
41. 
Randomized 
DM2 
Part B: Listing of Demographic Characteristics 
 
Part B SAC  
42. 
Randomized 
DM9 
Part B: Listing of Race 
 
Part B SAC  
Medical Conditions 
43. 
Safety 
MH2 
Part B: Listing of Current and Past Medical Conditions 
 
Part B SAC  
Concomitant Medications 
44. 
Safety 
CP_CM3 
Part B: Listing of Prior and Concomitant Medications 
 
Part B SAC  
45. 
Safety 
CP_CM3 
Part B: Listing of Prior and Concomitant Osteoarthritis 
Medications 
OA con-meds are 
captured on a specific 
CRF page 
Part B SAC  
Exposure 
46. 
Safety 
EX3 
Part B: Listing of Exposure Data 
Include number of 
injections received 
Part B SAC  
Adverse Events 
47. 
Safety 
AE8CP 
Part B: Listing of All Adverse Events 
 
Part B SAC  
48. 
Safety 
AE7 
Part B: Listing of Subject Numbers for Individual Adverse Events  
Part B SAC  
49. 
Safety 
AE2 
Part B: Listing of Relationship Between Adverse Event System 
Organ Classes, Preferred Terms, and Verbatim Text 
 
Part B SAC  
Serious and Other Significant Adverse Events 
50. 
Safety 
AE8CPa 
Part B: Listing of Serious Adverse Events (Fatal and Non-Fatal) 
 
Part B SAC  
51. 
Safety 
AE14 
Part B: Listing of Reasons for Considering as a Serious Adverse 
Event 
 
Part B SAC  


 
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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
52.  
Safety 
AE8CP 
Part B: Listing of Adverse Events Leading to Withdrawal from 
Study / Permanent Discontinuation of Study Treatment 
 
IA3, Part B 
SAC  
53.  
Safety 
AE8CP 
Part B: Listing of Other Significant Adverse Events 
 
Part B SAC  
Vital Signs 
54.  
Safety 
VS4 
Part B: Listing of Vital Signs of Potential Clinical Importance 
 
Part B SAC  
55.  
Safety 
VS4 
Part B: Listing of All Vital Signs Data for Subjects with Any Value 
of Potential Clinical Importance 
 
Part B SAC  
Laboratory: All 
56.  
Safety 
LB5 
Part B: Listing of Laboratory Values of Potential Clinical 
Importance 
 
IA3, Part B 
SAC  
57.  
Safety 
 
LB5 
Part B: Listing of All Laboratory Data for Subjects with Any Value 
of Potential Clinical Importance 
 
IA3, Part B 
SAC  
58.  
Safety 
LB14 
Part B: Listing of Laboratory Data with Character Results 
 
Part B SAC  
59.  
Safety 
UR2A 
Part B: Listing of Urinalysis Data for Subjects with Any Value of 
Potential Clinical Importance 
 
Part B SAC  
ECG  
60.  
Safety 
EG3 
Part B: Listing of ECG Values of Potential Clinical Importance 
 
Part B SAC  
61.  
Safety 
EG3 
Part B: Listing of All ECG Values for Subjects with Any Value of 
Potential Clinical Importance 
 
Part B SAC  
62.  
Safety 
EG5 
Part B: Listing of Abnormal ECG Findings 
 
Part B SAC  
63.  
Safety 
EG5 
Part B: Listing of All ECG Findings for Subjects with an 
Abnormal ECG Finding 
 
Part B SAC  
 
 
 


 
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14.11.17. ICH Conditional Listings 
The following listings will only be produced if a liver event is observed within the trial. 
 
14.11.17.1. Part A 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Hepatobiliary (Liver) 
64.  
Safety 
MH2 
Part A: Listing of Medical Conditions for Subjects with 
Liver Stopping Events 
Conditional on liver event being 
seen 
Part A SAC  
65.  
Safety 
SU2 
Part A: Listing of Substance Use for Subjects with Liver 
Stopping Events 
Conditional on liver event being 
seen 
Part A SAC  
14.11.17.2. Part B 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Hepatobiliary (Liver) 
66.  
Safety 
MH2 
Part B: Listing of Medical Conditions for Subjects with 
Liver Stopping Events 
Conditional on liver event being 
seen 
Part B SAC  
67.  
Safety 
MH2 
Part B: Listing of Substance Use for Subjects with Liver 
Stopping Events 
Conditional on liver event being 
seen 
Part B SAC  
 


 
C O N FI D E N TI A L  
 
 
2 0 7 8 0 4  
1 2 2  
 
1 4. 1 1. 1 8.  N o n -I C H Li sti n g s 
1 4. 1 1. 1 8. 1.  P art A  
N o.  
P o p ul ati o n  
I D S L / 
E x a m ple 
S h ell  
Titl e   
Pr o gr a m mi n g N ote s  
D eli v era bl e 
[ Pri orit y] 
S u b st a n c e Us e  
6 8.   
S af ety  
S U 2  
P art A: Listi n g of S u bst a nce Us e  
I ncl u d e c ol u m ns: S m oki ng hist ory, 
C urr e ntly S m ok e, L ast S m ok e d, 
Dri nk Alc o h ol, Units p er Week , 
C urr e ntly usi n g Illicit Dru gs  
P art A  S A C  
P h ar m a c o ki n etic s  
6 9.   
P K  
P K 0 7  
P art A: Listi n g of S er u m G S K 3 8 58 27 9 C onc entr ati on -
Ti me D at a ( n g/ m L) 
 
P art A  S A C  
7 0.   
P K  
P K 1 3  
P art A: Listi n g of Deriv e d Ser u m G S K3 8 58 27 9 
P h ar mac oki netic Par a m et ers  
A d d  a f oot n ot e s ayi ng t hat N Q 
m e a ns n o n -qu a ntifi a bl e a nd 
L L Q = 10 0 n g/ m L  
P art A  S A C  
C CI


 
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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Pharmacodynamic 
72.  
Safety 
PK07 
Part A: Listing of Free & Total CCL17 in Serum 
Concentration-Time Data (pg/mL) 
Including Percentage 
Inhibition/Fold Increase 
 
Add a footnote saying that NQ 
means non-quantifiable and Free 
CCL17  LLOQ=2.93 pg/mL and 
Total CCL17 LLOQ=13.11 pg/mL. 
Part A SAC  
73.  
Safety 
PK13 
Part A: Listing of Derived Free CCL17 in Serum 
Target Engagement Parameters 
 
Part A SAC  
74.  
Safety 
PK13 
Part A: Listing of Derived Total CCL17 in Serum 
Target Engagement Parameters 
 
Part A SAC  
75.  
Blister 
PK07 
Part A: Listing of Free & Total CCL17 in Blister Fluid 
Concentration-Time Data (pg/mL) 
Including Blister/Serum Ratio 
Part A SAC  
76.  
Safety 
IMM2 
Part A: Listing of Immunogenicity 
 
Part A SAC  
Biomarker 
77.  
Biomarker 
BIO_L1 
Part A: Listing of Immune Cell Phenotypes 
 
Part A SAC  
14.11.18.2. Part B 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Substance Use 
78.  
Safety 
SU2 
Part B: Listing of Substance Use 
Include columns: Smoking history, Currently 
Smoke, Last Smoked, Drink Alcohol, Units 
per Week, Currently using Illicit Drugs 
Part B SAC  


 
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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Pharmacokinetics  
79.  
PK 
PK07 
Part B: Listing of Serum GSK3858279 
Concentration-Time Data (ng/mL) 
Add a footnote saying that NQ means non-
quantifiable and LLOQ=100 ng/mL 
Part B SAC  
80.  
PK 
PK13 
Part B: Listing of Model-Derived Serum 
GSK3858279 Pharmacokinetic Parameters 
Add a footnote saying that “All 
Pharmacokinetic parameters were calculated 
using a model based post-hoc analysis”. 
Part B SAC  
Pharmacodynamic 
81.  
Safety 
PK07 
Part B: Listing of Free & Total CCL17 in Serum 
Concentration-Time Data (pg/mL) 
Add a footnote saying that LLOQ means 
lower limit of quantification and ULOQ means 
upper limit of quantification. LLOQ for free 
CCL17= 2.93 pg/mL. LLOQ for total CCL17= 
13.11 pg/mL.ULOQ for free CCL17= 3600 
pg/mL. ULOQ for total CCL17= 50000 pg/mL. 
Part B SAC  
82.  
Safety 
PK13 
Part B: Listing of Derived Free CCL17 in Serum 
Target Engagement Parameters 
Including Percentage Inhibition/Fold 
Increase. 
Add a footnote saying “All Target 
Engagement parameters were calculated 
using a model based post-hoc analysis.”. 
Part B SAC  
83.  
Safety 
PK13 
Part B: Listing of Derived Total CCL17 in 
Serum Target Engagement Parameters 
Add a footnote saying “All Target 
Engagement parameters were calculated 
using a model based post-hoc analysis.”. 
Part B SAC  
84.  
Safety 
IMM2 
Part B: Listing of Immunogenicity 
For IA3, include only participants with at least 
one positive confirmation assay result. 
IA3, Part B 
SAC  
Primary Efficacy 
85.  
ITT 
EFF_L01 
Part B: Listing of Average and Worst Knee Pain 
Intensity 
Include the number of records which make 
up the average 
IA1, IA2,  
Part B SAC  


 
C O N FI D E N TI A L  
 
 
2 0 7 8 0 4  
1 2 5  
 
N o.  
P o p ul ati o n  
I D S L / 
E x a m ple 
S h ell  
Titl e   
Pr o gr a m mi n g N ote s  
D eli v era bl e  
C O VI D -1 9  
8 8.   
R a n d o miz ed  P A N 7  
P art B:  Listi n g of All S ubj ects wit h Visits an d 
Ass ess m e nts I m p acte d by C O VI D -1 9 
P a n de mic  
 
 
P art B S A C  
 
C CI