Clinical trial NCT04130919
Conditions: Ulcerative Colitis
Sponsor: Gilead Sciences
Start date: 2019-12-20; Completion date: 2021-12-14
Enrollment: 19 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to demonstrate the efficacy of tilpisertib (formerly GS-4875) compared with placebo control in achieving clinical remission per modified Mayo Clinic Score (MCS) in adults with moderately to severely active ulcerative colitis (UC).

Detailed description:

Arms: arm 1: Participants will receive blinded tilpisertib 300 mg for up to 10 weeks. An efficacy assessment will be performed at Week 10. Participants who achieve MCS response will continue on the blinded treatment for up to 50 weeks. arm 2: Participants will receive blinded tilpisertib 100 mg for up to 10 weeks. An efficacy assessment will be performed at Week 10. Participants who achieve MCS response will continue on the blinded treatment for up to 50 weeks. arm 3: Participants will receive blinded tilpisertib matching placebo for up to 10 weeks. An efficacy assessment will be performed at Week 10. Participants who achieve MCS response will continue on the blinded treatment for up to 50 weeks. arm 4: Based on the efficacy assessment results at Week 10, participants who do not achieve MCS response will have the option to receive open-label tilpisertib 300 mg for up to 50 weeks.
Interventions: intervention 1: Tilpisertib intervention 2: Placebo
Intervention descriptions: intervention 1: Tablets administered orally once daily intervention 2: Tablets administered orally once daily

Protocol documents:
Prot_000.pdf: 
C LI NI C A L S T U D Y P R O T O C O L
St u d y Title:
A P hase 2, Bli n de d , Ra n d o mize d, Place b o -C o ntr olle d St u d y  
E val uati n g t he Efficac y  a n d Safet y of G S - 4 8 7 5 i n S u bjects wit h
M o deratel y t o Se verel y Acti ve Ulcerati ve C olitis
S p o ns or:
Gilea d Scie nces, I nc.
3 3 3 L a kesi de Dri ve
F oster Cit y , C A 9 4 4 0 4
I N D N u m ber:
E u dr a C T N u m ber:
Cli nic al Tri als. g o v 
I de ntifier:
1 4 3 1 7 4
2 0 1 9- 0 0 1 4 3 0- 3 3
N C T 0 4 1 3 0 9 1 9
I n dic ati o n:
Ulcerati ve C olitis
Pr ot oc ol I D:
G S -U S -3 6 5- 4 2 3 7
C o nt act I nf or m ati o n:
T he me dical m o nit or na me a n d c o ntact i nf or mati o n will be 
pr o vi de d o n t he Ke y  St u d y Tea m C o ntact List.
Pr ot oc ol Versi o n/ D ate:
Ori gi nal :
2 5 Marc h 2 0 1 9
A me n d me nt 1:
1 8 J ul y  2 0 1 9
A me n d me nt 1. 1 *: 1 1  Dece m ber 2 0 1 9
* S witzerla n d, R ussia, a n d V H P  c o u ntries o nly
A me n d me nt 2: 
1 9 J u ne 2 0 2 0
T his st u d y will be c o n d ucte d u n der U S F o o d & Dr u g A d mi nistrati o n I N D re g ulati o ns ( 2 1 C F R Part 3 1 2); 
h o we ver, sites l ocate d i n t he E ur o pea n Ec o n o mic Area , U nite d Ki n g d o m, a n d S witzerla n d are n ot 
i ncl u de d u n der t he I N D a n d are c o nsi dere d n o n-I N D sites.
C O N FI D E N TI A LI T Y S T A T E M E N T
T he i nf or mati o n c o ntai ne d i n t his d oc u me nt, partic ularl y u n p u blis he d data, is t he pr o pert y or u n der 
c o ntr ol of Gilea d Scie nces, I nc., a n d is pr o vi de d t o y o u i n c o nfi de nce as a n i n vesti gat or, p ote ntial 
i n vesti gat or, or c o ns ulta nt, f or re vie w b y y o u, y o ur staff, a n d a n a p plica ble I nstit uti o nal Re vie w B oar d 
or I n de pe n de nt Et hics C o m mittee. T he i nf or mati o n is o nl y t o be use d b y y o u i n c o n necti o n wit h 
a ut h orize d cli nical st u dies of t he i n vesti gati o nal dr u g descri be d i n t he pr ot oc ol. Y o u will n ot discl ose 
a n y of t he i nf or mati o n t o ot hers wit h o ut writte n a ut h orizati o n fr o m Gilea d Scie nces, I nc., e xce pt t o t he 
e xte nt necessar y t o o btai n i nf or me d c o nse nt fr o m t h ose pers o ns t o w h o m t he dr u g ma y be 
a d mi nistere d.
(rJ GI L E Ai J 


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 2
1 9 J u ne 2 0 2 0
T A B L E O F C O N T E N T S
T A B L E O F C O N T E N T S ..............................................................................................................................................2
LI S T O F I N -T E X T T A B L E S ........................................................................................................................................5
LI S T O F I N - TE X T FI G U R E S ......................................................................................................................................5
P R O T O C O L S Y N O P SI S ..............................................................................................................................................6
G L O S S A R Y O F A B B R E VI A TI O N S A N D D E FI NI TI O N O F T E R M S ....................................................................1 3
1.
I N T R O D U C TI O N ..............................................................................................................................................1 6
1. 1.
Bac k gr o u n d ............................................................................................................................................1 6
1. 2.
Rati o nale f or T his St u d y ........................................................................................................................1 7
1. 3.
G S -4 8 7 5 .................................................................................................................................................1 7
1. 3. 1.
Ge neral I nf or mati o n .............................................................................................................1 7
1. 3. 2.
S u m mar y of A d diti o nal N o ncli nical E x perie nce of G S -4 8 7 5 ..............................................1 7
1. 3. 3.
S u m mar y of A d diti o nal Cli nical E x perie nce of G S -4 8 7 5 ....................................................1 8
1. 4.
Ris k/ Be nefit Assess me nt f or t he St u d y ..................................................................................................2 0
1. 5.
C o m plia nce ............................................................................................................................................2 1
2.
O BJ E C TI V E S A N D E N D P O I N T S ....................................................................................................................2 2
3.
S T U D Y D E SI G N ................................................................................................................................................2 4
3. 1.
St u d y Desi g n ..........................................................................................................................................2 4
3. 2.
D urati o n of Treat me nt ............................................................................................................................2 6
3. 2. 1.
Rati o nale f or St u d y Desi g n ..................................................................................................2 6
4.
S U BJ E C T P O P U L A TI O N ..................................................................................................................................2 8
4. 1.
N u m ber of S u bjects a n d S u bject Selecti o n ............................................................................................2 8
4. 2.
I ncl usi o n Criteria....................................................................................................................................2 8
4. 3.
E xcl u si o n Criteria...................................................................................................................................3 0
5.
I N V E S TI G A TI O N A L M E DICI N A L P R O D U C T S ........................................................................................... 3 2
5. 1.
Ra n d o mizati o n, Bli n di n g, a n d Treat me nt C o des ...................................................................................3 2
5. 1. 1.
Ra n d o mizati o n .....................................................................................................................3 2
5. 1. 2.
Bli n di n g ................................................................................................................................3 2
5. 1. 3.
Pla n ne d I nteri m U n bli n di n g .................................................................................................3 2
5. 1. 4.
Pr oce d ures f or Brea ki n g Treat me nt C o des ...........................................................................3 3
5. 2.
Descri pti o n a n d Ha n dli n g of G S -4 8 7 5 ...................................................................................................3 3
5. 2. 1.
F or m ulati o n ..........................................................................................................................3 3
5. 2. 2.
Pac ka gi n g a n d La beli n g .......................................................................................................3 3
5. 2. 3.
St ora ge a n d Ha n dli n g ...........................................................................................................3 3
5. 3.
D osa ge a n d A d mi nistra ti o n of G S-4 8 7 5 ................................................................................................3 4
5. 3. 1.
Rati o nale f or D ose Selecti o n ................................................................................................3 4
5. 4.
Pri or a n d C o nc o mita nt Me dicati o ns .......................................................................................................3 5
5. 4. 1.
All o we d C o nc o mita nt Me dicati o ns f or U C ..........................................................................3 5
5. 4. 2.
Pr o hi bite d C o nc o mita nt Me dicati o ns ...................................................................................3 6
5. 5.
Vacci ne G ui deli nes ................................................................................................................................3 9
5. 6.
Acc o u nta bilit y f or St u d y Dr u g ...............................................................................................................4 0
5. 6. 1.
I n vesti gati o nal Me dici nal Pr o d uct Ret ur n or Dis p osal.........................................................4 0
6.
S T U D Y P R O C E D U R E S ....................................................................................................................................4 1
6. 1.
S u bject I nf or me d C o nse nt ......................................................................................................................4 1
C CI-


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 3
1 9 J u ne 2 0 2 0
6. 2.
Se q ue nce of Assess me nts at Visits .........................................................................................................4 1
6. 3.
Pretreat me nt Assess me nts ......................................................................................................................4 1
6. 3. 1.
Scree ni n g ..............................................................................................................................4 1
6. 3. 2.
Baseli ne/ Da y 1 Assess me nts – Bli n de d Treat me nt P hase ....................................................4 3
6. 3. 3.
D a y  1 Assess me nts – O pe n -La bel Treat me nt P hase ............................................................4 3
6. 4.
Ra n d o mizati o n a n d St u d y Dr u g A d mi nistrati o n – Bli n de d Treat me nt P hase ........................................4 3
6. 4. 1.
Ra n d o mizati o n a n d Treat me nt Assi g n me nt .........................................................................4 3
6. 4. 2.
St u d y Dr u g A d mi nistrati o n ..................................................................................................4 3
6. 5.
Treat me nt Assess me nts ..........................................................................................................................4 4
6. 5. 1.
Wee ks 2, 4 a n d 6 – Bli n de d Treat me nt & O pe n -La bel Treat me nt P hases ...........................4 4
6. 5. 2.
Wee k 1 0 – Bli n de d Treat me nt & O pe n -La bel Treat me nt P hases ........................................4 4
6. 5. 3.
Wee ks 1 4, 1 8, 2 2, 2 6, 3 0, 3 4, 3 8, 4 2, a n d 4 6 - Bli n de d Treat me nt & 
O pe n -La bel Treat me nt P hases .............................................................................................4 4
6. 5. 4.
Wee k 5 0 - Bli n de d Treat me nt & O pe n -La bel Treat me nt P hases .........................................4 5
6. 6.
Earl y Ter mi nati o n ( E T) Assess me nts .....................................................................................................4 5
6. 7.
P osttreat me nt ( P T x) Assess me nts ..........................................................................................................4 5
6. 8.
Efficac y Assess me nts .............................................................................................................................4 5
6. 8. 1.
M a y o Cli nic Sc ore ( M C S) ....................................................................................................4 5
6. 8. 2.
Healt h -Relate d Q ualit y of Life ( H R Q o L) S ur ve ys ...............................................................4 7
6. 8. 3.
Healt h Care Res o urce Utilizati o n S ur ve y .............................................................................4 8
6. 9.
Safet y Assess me nts ................................................................................................................................4 8
6. 9. 1.
Re vie w of  Ad verse E ve nts ...................................................................................................4 8
6. 9. 2.
Re vie w of  C o nc o mita nt Me dicati o ns...................................................................................4 8
6. 9. 3.
P h y sical E xa mi nati o n ...........................................................................................................4 9
6. 9. 4.
1 2 -lea d Electr ocar di o gra m ...................................................................................................4 9
6. 9. 5.
Cli nical La b orat or y Assess me nts .........................................................................................4 9
6. 1 1.
Bi o mar ker Assess me nts .........................................................................................................................5 2
6. 1 1. 1.
Bl o o d Bi o mar ker Sa m ples ....................................................................................................5 2
6. 1 1. 2.
Ma n dat or y Ge n o mic Sa m ples
..............................................................................................5 3
6. 1 1. 4.
St o ol Bi o mar ker Sa m ples .....................................................................................................5 3
6. 1 2.
St u d y Dr u g Dis pe nsi n g ..........................................................................................................................5 4
6. 1 3.
Criteria f or I nterr u pti o n or Disc o nti n uati o n of St u d y Treat me nt ...........................................................5 4
6. 1 3. 1.
Ge neral C o nsi derati o ns ........................................................................................................5 4
6. 1 3. 2.
St u d y Dr u g I nterr u pti o n C o nsi derati o ns ...............................................................................5 4
6. 1 3. 3.
St u d y Dr u g Disc o nti n uati o n C o nsi derati o ns ........................................................................5 5
6. 1 4 .
I nstr ucti o ns f or Dr u g Assi g n me nts after St u d y U n bli n di n g ...................................................................5 7
6. 1 5.
E n d of St u d y ...........................................................................................................................................5 7
6. 1 6.
P ost St u d y Care ......................................................................................................................................5 7
7.
A D V E R S E E V E N T S A N D T O XI CI T Y M A N A G E M E N T ...............................................................................5 8
7. 1.
Defi niti o ns of A d verse E ve nts, A d verse Reacti o ns, a n d Seri o us A d verse E ve nts .................................5 8
7. 1. 1.
A d verse E ve nts .....................................................................................................................5 8
7. 1. 2.
Seri o us A d verse E ve nts ........................................................................................................5 8
7. 2.
Assess me nt of A d verse E ve nts a n d Seri o us A d verse E ve nts .................................................................5 9
7. 2. 1.
Assess me nt of Ca usalit y f or St u d y  Dr u gs a n d Pr oce d ures...................................................5 9
7. 2. 2.
Assess me nt of Se verit y ........................................................................................................6 0
7. 3.
I n vesti gat or Re q uire me nts a n d I nstr ucti o ns f or Re p orti n g A d verse E ve nts a n d Seri o us 
A d verse E ve nts t o Gilea d .......................................................................................................................6 0
7. 3. 1.
A d verse E ve nts .....................................................................................................................6 0
7. 3. 2.
Seri o us A d verse E ve nts ........................................................................................................6 1
7. 4.
Gilea d Re p orti n g Re q uire me nts .............................................................................................................6 2
C CI
C CI
C CI-
1 1 1 1 
1 1 1 1 


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 4
1 9 J u ne 2 0 2 0
7. 5.
Cli nical La b orat or y A b n or malities a n d Ot her A b n or mal Assess me nt s as A d verse E ve nts or 
Seri o us A d verse E ve nts ..........................................................................................................................6 2
7. 6.
T o xicit y Ma na ge m e nt ............................................................................................................................6 2
7. 7.
S pecial Sit uati o ns Re p orts ......................................................................................................................6 3
7. 7. 1.
Defi niti o ns of S pecial Sit uati o ns ..........................................................................................6 3
7. 7. 2.
I nstr ucti o ns f or Re p orti n g S pecial Sit uati o ns.......................................................................6 3
7. 8.
Safet y S ur veilla nce .................................................................................................................................6 5
8.
S T A TI S TI C A L C O N SI D E R A T I O N S................................................................................................................6 6
8. 1.
A nal ysis O bjecti ves a n d E n d p oi nts ........................................................................................................6 6
8. 1. 1.
A nal ysis O bjecti ves ..............................................................................................................6 6
8. 1. 2.
St u d y E n d p oi nts ...................................................................................................................6 6
8. 2.
Pla n n e d A nal yses ...................................................................................................................................6 6
8. 2. 1.
I nteri m A nal ysis ...................................................................................................................6 6
8. 2. 2.
Wee k 1 0 A nal ysis .................................................................................................................6 6
8. 3.
A nal ysis C o n ve nti o ns .............................................................................................................................6 7
8. 3. 1.
A nal ysis Sets ........................................................................................................................6 7
8. 4.
Data Ha n dli n g C o n ve nti o ns ...................................................................................................................6 7
8. 5.
Efficac y A nal ysis ...................................................................................................................................6 8
8. 5. 1.
Pri mar y A nal ysis ..................................................................................................................6 8
8. 5. 2.
Sec o n dar y A nal yses .............................................................................................................6 8
8. 6.
Safet y A nal ysis .......................................................................................................................................6 8
8. 6. 1.
E xte n t of E x p os ure...............................................................................................................6 8
8. 6. 2.
A d verse E ve nts .....................................................................................................................6 8
8. 6. 3.
La b orat or y E val uati o ns ........................................................................................................6 9
8. 6. 4.
Ot her Safet y E val uati o ns ......................................................................................................6 9
8. 7.
A dj ust me nts f or M ulti plicit y ..................................................................................................................6 9
8. 9.
Bi o mar ker A nal ysis ................................................................................................................................7 0
8. 1 0.
Sa m p le Size............................................................................................................................................7 1
8. 1 1.
Data M o nit ori n g C o m mittee ..................................................................................................................7 1
9.
R E S P O N SI BI LI TI E S ..........................................................................................................................................7 3
9. 1.
I n vesti gat or Res p o nsi bilities ..................................................................................................................7 3
9. 1. 1.
G o o d Cli nical Practice ..........................................................................................................7 3
9. 1. 2.
Fi na ncial Discl os ure .............................................................................................................7 3
9. 1. 3.
I nstit uti o nal Re vie w B oar d/I n de pe n de nt Et hics C o m mittee Re view a n d 
A p pr o val ...............................................................................................................................7 3
9. 1. 4.
I nf or me d C o nse nt .................................................................................................................7 3
9. 1. 5.
C o nfi de ntialit y ......................................................................................................................7 4
9. 1. 6.
St u d y Files a n d Rete nti o n of Rec or ds ..................................................................................7 4
9. 1. 7.
Case Re p ort F or ms ...............................................................................................................7 5
9. 1. 8.
I n vesti gati o nal Me dici nal Pr o d uct Acc o u nta bilit y a n d Ret ur n.............................................7 6
9. 1. 9.
I ns pecti o ns............................................................................................................................7 6
9. 1. 1 0.
Pr ot oc ol C o m plia nce ............................................................................................................7 6
9. 2.
S p o ns or Res p o nsi bilities ........................................................................................................................7 6
9. 2. 1.
Pr ot oc ol M o dificati o ns .........................................................................................................7 6
9. 2. 2.
St u d y Re p ort a n d P u blicati o ns .............................................................................................7 7
9. 3.
J oi nt I n vesti gat or/ S p o ns or Res p o nsi bilities ...........................................................................................7 7
9. 3. 1.
Pa y me nt Re p orti n g ...............................................................................................................7 7
9. 3. 2.
A ccess t o I nf or mati o n f or M o nit ori n g ..................................................................................7 7
9. 3. 3.
Access t o I nf or mati o n f or A u diti n g or I ns pecti o ns ..............................................................7 8
9. 3. 4.
St u d y Disc o nti n uati o n ..........................................................................................................7 8
C CI
C CI
-


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 5
1 9 J u ne 2 0 2 0
1 0.
R E F E R E N C E S ...................................................................................................................................................7 9
1 1.
A P P E N DI C E S ....................................................................................................................................................8 1
A p pe n di x 1.
I n vesti gat or Si g nat ure Pa ge ....................................................................................................8 2
A p pe n di x 2.
St u d y Pr oce d ures Ta ble – Bli n de d Treat me nt ........................................................................8 3
A p pe n di x 3.
St u d y Pr oce d ures Ta ble – O pe n -La bel Treat me nt ..................................................................8 5
A p pe n di x 4.
M o difie d Ma y o Sc ori n g S yste m f or Assess me nt of Ulcerati ve C olitis Acti vit y
....................8 7
A p pe n di x 5.
Ge b oes Hist ol o gical Sc ore Gra des .........................................................................................8 8
A p pe n di x 6.
C T C A E Gra di n g Scale f or Se verit y of A d ve rse E ve nts .........................................................8 9
A p pe n di x 7.
Cli nical La b orat or y Assess me nt Ta ble ...................................................................................9 0
A p pe n di x 8.
Pre g na nc y Preca uti o ns, Defi niti o n f or Fe male of C hil d beari n g P o te ntial, a n d 
C o ntrace pti ve Re q uire me nts ...................................................................................................9 1
LI S T O F I N -T E X T T A B L E S
Ta ble 2- 1.
O bjecti ves a n d E n d p oi nts of St u d y G S -U S -3 6 5 -4 2 3 7 ...........................................................2 2
Ta ble 5 -1.
E xa m ples of Pr o hi bite d C o nc o mita nt Me dicati o ns f or P ote ntial Dr u g -Dr u g 
I nteracti o nsa, b ..........................................................................................................................3 7
Ta ble 5- 2.
Pr o hi bite d C o nc o mita nt Me dicati o ns t hat Ma y I m pact Efficac y Ass ess me nts or 
I mpact S u bject Safet y .............................................................................................................3 8
Ta ble 5- 3.
Ot her Pr o hi bite d C o nc o mita nt Me dicati o ns ...........................................................................3 9
T a bl e 7-1.
Gra di n g of A d verse E ve nt Se verit y ........................................................................................6 0
LI S T O F I N -T E X T FI G U R E S
Fi g ure 3- 1.
St u d y Desi g n ..........................................................................................................................2 4


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 6
1 9 J u ne 2 0 2 0
P R O T O C O L S Y N O P SI S
Gile a d Scie nces, I nc.
3 3 3 L a kesi de Dri ve
F oster Cit y, C A 9 4 4 0 4
St u d y Title : 
A P hase 2, Bli n de d , Ra n d o mize d, Place b o-C o ntr olle d St u d y  
E val uati n g t he Efficac y  a n d Safet y of G S - 4 8 7 5 i n S u bjects wit h 
M o deratel y t o Se verel y Acti ve Ulcerati ve C olitis 
I N D N u m ber:
E u dr a C T N u m ber:
Cli nic al Tri als. g o v 
I de ntifier:
1 4 3 1 7 4
2 0 1 9- 0 0 1 4 3 0- 3 3
N C T 0 4 1 3 0 9 1 9
St u d y Ce nters 
Pl a n ne d:
A p pr o xi matel y  1 0 0 ce nters gl o ball y
O bjecti ves a n d 
E n d p oi nts:
Pri m ar y O bjecti ve
Pri m ar y E n d p oi nt
T o de m o nstrate t he efficac y of 
G S -4 8 7 5 , c o m pare d wit h place b o 
c o ntr ol, i n ac hie vi n g Cli nical 
Re missi o n per M o difie d Ma y o Cli nic 
Sc ore ( M C S) at Wee k 1 0 
Cli nical Re missi o n per M o difie d M C S, 
defi ne d as St o ol Fre q ue nc y s u bsc ore 
≤1 a n d n ot greater t ha n baseli ne, 
Rectal Blee di n g s u bsc ore of 0, a n d
E n d osc o pic s u bsc ore ≤ 1 at Wee k 1 0
Ke y Sec o n d ar y O bjecti ves
Ke y Sec o n d ar y E n d p oi nts
T o de m o nstrate t he efficac y of
G S -4 8 7 5 , c o m pare d wit h place b o 
c o ntr ol, i n ac hie vi n g e n d osc o pic 
res p o nse at Wee k 1 0
E n d osc o pic Res p o nse, defi ne d as a n 
E n d osc o pic s u bsc ore ≤1 at Wee k 1 0
T o de m o nstrate t he efficac y of
G S -4 8 7 5 , c o m pare d wit h place b o 
c o ntr ol, i n ac hie vi n g M C S Re s p o nse
at Wee k 1 0
M C S Res p o nse, defi ne d as a decrease 
fr o m baseli ne of ≥ 3 p oi nts a n d at least 
3 0 % i n M C S, i n a d diti o n t o a ≥ 1 p oi nt 
decrease fr o m baseli ne i n t he Rectal 
Blee di n g s u bsc ore or a Rectal Blee di n g 
s u bsc ore ≤1 at Wee k 1 0
T o de m o nstrate t he efficac y of
G S -4 8 7 5 , c o m pare d wit h place b o 
c o ntr ol, i n ac hie vi n g M C S Re missi o n
at Wee k 1 0
M C S Re missi o n, defi ne d as a M C S 
sc ore of ≤2 a n d n o i n di vi d ual s u bsc ore 
> 1 at Wee k 1 0
T o e val uate G S -4 8 7 5 , as c o m pare d 
wit h place b o c o ntr ol, i n ac hie vi n g 
hist ol o gic re missi o n at Wee k 1 0
Hist ol o gic re missi o n base d u p o n t he
Ge b oes Scale w here all of t he f oll o wi n g 
m ust be met at Wee k 1 0: Gra de 0 of 
≤0. 3, Gra de 1 of ≤1. 1, Gra de 2a of 
≤2 A. 3, Gra de 2 b of 2 B. 0 , Gra de 3 of 
3. 0, Gra de 4 of 4. 0, a n d Gra de 5 of 5. 0
(A p pe n di x 5 )


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 7
1 9 J u ne 2 0 2 0
Ot her Sec o n d ar y O bjecti ves
Ot her Sec o n d ar y E n d p oi nts
T o e val uate t he s afet y a n d t olera bilit y 
of G S -4 8 7 5
I nci de nce a n d c haracterizati o n of 
ad verse eve nts ( A Es ) a n d la b orat or y 
a b n or malities
P h y sical e xa mi nati o n ( P E) fi n di n gs, 
electr ocar di o gra m ( E C G ), a n d vital 
si g ns
C CI


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 8
1 9 J u ne 2 0 2 0
St u d y Desi g n:
T his is a P hase 2 , bli n de d, ra n d o mize d, p lace b o-co ntr olle d st u d y 
eval uati n g t he efficac y a n d safet y of G S - 4 8 7 5 f or t he treat me nt of 
s u bjects wit h mo deratel y t o se verel y acti ve u lcerati ve colitis ( U C).
T his st u d y  i ncl u des:

Scree ni n g peri o d ( Da ys 3 0 t o 1)

Baseli ne/ Ra n d o mizati o n ( Da y 1)
A p pr o xi matel y  1 8 0 su bjects w h o meet pr ot oc ol eli gi bilit y  criteria 
will be ra n d o mize d i n a 1: 1: 1 rati o t o 1 of 3 treat me nt gr o u ps as 
f oll o ws:
Tre at me nt gr o u p 1 ( n  6 0) : G S - 4 8 7 5 3 0 0 m g o nce dail y 
Tre at me nt gr o u p 2 ( n 
 6 0): G S - 4 8 7 5 1 0 0 m g o nce dail y
Tre at me nt gr o u p 3 ( n  6 0) : P lace b o o nce dail y
Treat me nt assi g n me nts will be stratifie d acc or di n g t o t he s u m 
( ≤6 or > 6) of 3 M C S s u bsc ores f or St o ol Fre q ue nc y , Rectal 
Blee di n g, a n d E n d osc o pic Fi n di n gs at scree ni n g.

Bli n de d Tre at me nt p hase ( Da y  1 u p t o Wee k 5 0)
At Wee k 1 0 visit , all s u bjects will ha ve a n efficac y 
assess me nt .

O pe n -L a bel ( O L) Treat me nt p hase (O L Da y  1 u p t o O L Wee k 5 0)
At O L  Wee k 1 0 visit, all s u bjects will ha ve a n efficac y 
assess me nt.

Gilea d Data Re vie w C o m mittee ( G D R C) 
After a p pr o xi matel y  9 0 s u bjects c o m plete t he Wee k 1 0 visit 
or disc o nti n ue fr o m t he st u d y  pri or t o Wee k 1 0, t he G DR C
will re vie w e n d p oi nt data f or p ote ntial st u d y  ter mi nati o n d ue 
t o lac k of efficac y. 

U n bli n di n g
T he st u d y will be u n bli n de d w he n all ra n d o mize d s u bjects
(a p pr o xi matel y 1 8 0) ha ve c o m plete d 1 0 wee ks of bli n de d 
st u d y dr u g, or disc o nti n ue d fr o m t he st u dy, a n d ass ociate d 
safety a n d efficac y assess me nts ha ve bee n c o m plete d.

P ost treat me nt ( P T x) Assess me nts 
S u bject s w h o disc o nti n ue st u d y  dr u g will ret ur n 3 0 da y s after 
t he last d ose f or P T x assess me nts .


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 9
1 9 J u ne 2 0 2 0
N u m ber of 
S u bjects Pla n ne d:
1 8 0
Tar get P o p ulati o n:
A d ult s u bjects wit h m o deratel y t o se verel y acti ve U C .
D urati o n of 
Treat me nt:
I n t he Bli n de d Treat me nt p hase, ra n d o mize d s u bjects ma y  recei ve a 
ma xi m u m of 5 0 wee ks of treat me nt.
S u bjects w h o m o ve t o t he O L Treat me nt p hase will ha ve recei ve d 
1 0 wee ks of bli n de d treat me nt a n d m a y  recei ve u p t o 5 0 wee ks of O L 
treat me nt. T h us, t otal d urati o n of treat me nt ma y be a ma xi mu m of 
6 0 wee ks .
Dia g n osis a n d 
Mai n Eli gi bilit y  
Criteria:
Select Eli gi bilit y  Criteria:
1)
U C of at least 3 m o nt hs d urati o n bef ore ra n d o mizati o n c o nfir me d 
b y  e n d osc o p y a n d hist ol o g y at a n y ti me i n t he past A N D wit h a 
mi ni m u m disease e xte nt of 1 5 c m fr o m t he a nal ver ge. 
D oc u me ntati o n of e n d osc o p y  a n d hist ol o g y c o nsiste nt wit h t he 
dia g n osis of U C m ust be a vaila ble i n t he s o urce d oc u me nts pri or 
t o t he i nitiati o n of scree ni n g.
2)
M o deratel y t o se verel y acti ve U C as deter mi ne d d uri n g s cree ni n g 
b y  a ce ntrall y rea d e n d osc o p y sc ore ≥2, a Rectal Blee di n g
s u bsc ore ≥ 1, a St o ol Fre q ue nc y s u bsc ore ≥ 1 a n d P h y sicia ns 
Gl o bal Assess me nt ( P G A ) of ≥ 2 as de fi ne d b y  t he Ma yo Cli nic 
Sc ore (A p pe n di x 4 ); t otal M C S
m ust be bet wee n 6 a n d 1 2, 
i ncl usi ve.
3)
Pre vi o usl y  de m o nstrate d a n i na de q uate res p o nse ( pri mar y 
n o n- res p o nse) or l oss of res p o nse (sec o ndar y  n o n-res p o nse) t o a 
T N F α i n hi bit or (ie, i nfli xi ma b, a dali m u ma b, g oli m u ma b, or 
bi osi milars ). T he i n d ucti o n treat me nt re gi me n res ulti n g i n 
i na de q uate res p o nse or l oss of res p o nse s h o ul d ha ve bee n i n 
acc or da nce wit h l ocal prescri bi n g i nf or mati o n/ g ui deli ne s.
St u d y  Pr oce d ures/
Fre q ue nc y :
Refer t o A p pe n di x 2 a n d A p pe n di x 3 f or t he St u d y Pr oce d ures 
Ta ble s.
Test Pr o d uct, D ose, 
a n d M o de of 
A d mi nistr ati o n:
G S - 4 8 7 5 3 0 0 m g: 2 G S -4 8 7 5 1 5 0 m g ta blets, orall y  o nce dail y 
G S - 4 8 7 5 1 0 0 m g: 2 G S -4 8 7 5 5 0 m g ta blets, orall y  o nce dail y
G S - 4 8 7 5 s h o ul d n ot be a d mi nistere d wit h f o o d .
Refere nce T her a p y, 
D ose, a n d M o de of 
A d mi nistr ati o n:
Place b o : 2 place b o -t o-matc h ( P T M ) ta blets, orall y o nce dail y


G S -4 8 7 5 
Pr ot o c ol G S -U S -3 6 5- 4 2 3 7 
Gil e a d S ci e n c es, Inc. 
C rit e ri a f o r 
E v al u ati o n: 
S af et y: 
Effi c a c y: 
Bi o m ar k ers: 
C O N FI D E N T IA L 
Fi nal 
A m e n d m e nt 2 
Ass ess m e nt of A Es a n d c o n c o mit a nt m e d ic at io ns w ill c o nt in u e 
t hr o u g h o ut t h e d ur ati o n of t he st u d y. S af et y e v a lu ati o ns i n cl u de 
d o c m n e nt at io n of A Es, P E (c om pl et e or s ym pt o m dr iv e n), vi t al si g ns, 
cli ni c al la b or at or y e v alu atio ns ( h em at ol o g y, c h e m istr y, ur in a lys is, 
st o o l a n a lys is), a n d E C G . 
D at a M o nit o ri n g C o m mitt e e ( D M C) 
T h e i niti al m e et i ng w ill o c c ur aft er a p pr o x i mat el y 2 0 s u bje cts 
c o m p let e t h e W e e k 4 visit or dis c onti n u e fr o m t h e st u d y pr ior t o 
W e e k 4. 
S u bs e q u e nt D M C m e et in gs f or s af et y r e vi e w w ill b e h e l d aft er 
a p pr o xi m at e l y 6 0 s u bj e cts c o m p let e t he W e e k 4 visit or dis c o ntin u e 
fr o m t he st u d y a n d aft er a p pr o x i mat e l y 9 0 s u bje cts c o m pl et e t h e 
W e e k 1 0 visit or di s c o ntin u e fr o m t h e st u d y. T h e fr e q u e n c y of 
m e et i ngs m a y b e a dj ust e d as r e q u est e d b y t h e D M C . 
Effi c a c y w ill b e ass ess e d b y C lini c a l R emi ssio n p er M o d ifie d M C S, 
d efi n e d as St o o l Fr e q u e n c y s u bs c or e : S 1 a n d n ot gr e at er t h a n 
b as e lin e, R e ct al Bl e e d in g s u bs c or e of 0 a n d a n E n d os c o p ic s u bs c or e 
( b y c e ntr al r e a d) : S 1 at W e e k 1 0 . 
Bl o o d Bi o m a r k e r S a m pl es 
Bl o o d s am pl es w ill b e c o lle ct e d at D a y  1 a n d W e e ks 2, 4, 1 0, 2 6, a n d 
5 0 . 
P a g e 1 0 
1 9 Ju n e 2 0 2 0 


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 1 1
1 9 J u ne 2 0 2 0
M a n d at or y Ge n o mic
S a m ples 
Ma n dat or y  ge n o mic sa m ples will be c ollecte d at t he Da y  1 visit.
A bl o o d sa m ple will be o btai ne d f or ge ne tic a nalysis of t he uri di ne 5’ -
di p h os p h o -gl uc ur o n os y ltra nsferase fa mil y 1 me m ber A 1 
(U G T 1 A 1 ) * 2 8 ge netic varia nt s. 
A bl o o d sa m ple will be o btai ne d t o deter mi ne t he t u m or pr o gressi o n 
l oc us 2 (T P L 2) ge n ot y pe a n d si n gle n ucle oti de p ol y m or p his ms 
( S N Ps) ass ociate d wit h infla m mat or y  bo wel d isease (I B D). 
St o ol Bi o m ar ker S a m ples
St o o l sa m ples will be c ollecte d at scree ni n g a n d Wee ks 1 0, 2 6 , a n d 
5 0. 
St atistic al Met h o ds:
Pri m ar y A n al ysis
T he pri mar y  a nalys is will c o m pare eac h G S - 4 8 7 5 d ose gr o u p t o 
place b o o n t he pr o p orti o n of s u bjects ac hie vi n g Cli nical Re missi o n 
per M o difie d M C S at Wee k
1 0. T he C oc hra n -Ma ntel -Hae nszel 
( C M H) a p pr oac h a dj usti n g f or stratificati o n fact or will be use d f or 
h y p ot hesis testi n g of t he pri mar y  e n d p oi nt. F or e val uati o n of Cli nical
Re missi o n per M o difie d M C S at Wee k 1 0, M C S sc ore at scree ni n g 
will be use d as baseli ne val ue.
S u bjects w h o d o n ot ha ve s ufficie nt meas ure me nts t o deter mi ne 
efficac y e n d p oi nts will be c o nsi dere d fail ures (ie, n o n-res p o n der 
i m p utati o n [ N RI]).
Wee k 1 0 A n al ysis
A Wee k 1 0 a nal ys is will be c o n d ucte d w he n all ra n d o mize d s u bjects
(a p pr o xi matel y 1 8 0) ha ve c o m plete d 1 0 wee ks of bli n de d st u d y  dr u g, 
or disc o nti n ue d fr o m t he st u d y, a n d ass ociate d safet y a n d efficac y 
assess me nts ha ve bee n c o m plete d . T he st u d y will be u n bli n de d a n d 
safet y a nal ysis a n d W ee k 1 0 efficac y a nalys is (i ncl u di n g pri mar y 
a nal ys is) will be perf or me d. The p ur p ose of t hese a nal ys es is t o 
i nf or m st u d y disc o nti n uati o n or f urt her de vel o p me nt of G S - 4 8 7 5 f or 
t he treat me nt of U C . If t he sp o ns or c o ncl u des t hat treat me nt wit h 
G S - 4 8 7 5 has a n u nfa v ora ble be nefit -ris k pr ofile, t he sp o ns or will 
re q uest a n a d h oc D M C meeti n g. T he D M C will be re q ueste d t o 
e val uate t he a vaila ble st u d y data a n d t o ma ke rec o m me n dati o n o n 
w het her t he st u d y s h o ul d be st o p pe d, c o nti n ue d, or c o nti n ue d wit h 
m o dificati o ns.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 1 2
1 9 J u ne 2 0 2 0
A dj ust me nts of M ulti plicit y
T he f oll o wi n g pri mar y  a n d ke y sec o n dar y e n dp oi nts will be teste d 
se q ue ntiall y at a o ne- si de d T ype 1 err or rate of 2. 5 % i n t he f oll o wi n g 
or der:
G S - 4 8 7 5 3 0 0 m g vs place b o
1.
T he pr o p orti o n of s u bjects wit h cli nical re missi o n per m o difie d 
M C S at Wee k 1 0
2.
T he pr o p orti o n of s u bjects wit h e n d osc o pic res p o nse at Wee k 1 0
3.
T he pr o p orti o n of s u bjects wit h M C S Re s p o nse at Wee k 1 0
4.
T he pr o p orti o n of s u bjects wit h M C S Re missi o n at Wee k 1 0
5.
T he pr o p orti o n of s u bjects wit h hist ol o gic re missi o n at Wee k 1 0 
G S - 4 8 7 5 1 0 0 m g vs place b o
6.
T he pr o p orti o n of s u bjects wit h cli nical re missi o n per m o difie d 
M C S at Wee k 1 0 
7.
T he pr o p orti o n of s u bjects wit h e n d osc o pic res p o nse at Wee k 1 0
8.
T he pr o p orti o n of s u bjects wit h M C S r es p o nse at Wee k 1 0
9.
T he pr o p orti o n of s u bjects wit h M C S re missi o n at Wee k 1 0
1 0. T he pr o p orti o n of s u bjects wit h hist ol o gic re missi o n at Wee k 1 0
Testi n g will st o p wit h t he first of t hese e n d p oi nts faili n g t o reac h 
statistical si g nifica nce a n d all s u bse q ue nt e n d p oi nts w o ul d n ot be 
c o nsi dere d f or statistical si g nifica nce a n d o nl y n o mi nal p- val ues will 
be re p orte d.
S a m ple Size
A sa m ple size of 6 0 s u bjects i n t he place b o gr o u p a n d 6 0 s u bjects i n 
eac h G S - 4 8 7 5 d ose gr o u p ( n 1 2 0 t otal f or G S -4 8 7 5 ) will pr o vi de 
a p pr o xi matel y 7 5 % p o wer f or eac h G S -4 8 7 5 d ose gr o u p c o m paris o n 
t o place b o at a 1- si de d 0. 0 2 5 si g nifica nce le vel t o detect a treat me nt 
differe nce i n C li nical R e missi o n per m o difie d M C S res p o nse rate of 
1 7. 5 % ( 2 2. 5 % o n G S -4 8 7 5 a n d 5 % o n place b o) base d o n Fis her’s 
e xact test.
T his st u d y  will be c o n d ucte d i n acc or da nce wit h t he g ui delines of G o o d Cli nical Practice ( G C P) 
i ncl u di n g arc hi vi n g of esse ntial d oc u me nts.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 1 3
1 9 J u ne 2 0 2 0
G L O S S A R Y O F A B B R E VI A TI O N S A N D D E FI NI TI O N O F T E R M S
6- M P
6- merca pt o p uri ne
A D L 
Acti vities of Dail y Li vi n g
A E
a d verse e ve nt
A L T
ala ni ne a mi n otra nsferase
A N C
a bs ol ute ne utr o p hil c o u nt
A N C O V A
a nal ysis of c o varia nce
A S T
as partate a mi n otra nsferase
A U C i nf
area u n der t he c o nce ntrati o n vers us ti me c ur ve e xtra p olate d t o i nfi nite ti me, 
calc ulate d as A U C last + ( Clast/z)
A U C 0- 2 4
partial area u n der t he c o nce ntrati o n vers us ti me c ur ve fr o m ti me “0 ” t o ti me 
“2 4 h o urs ”
B A P
Bi o mar ker A nal ysis Pla n
B C R P
breast ca ncer resista nce pr otei n
C diff icile
Cl ostri di u m difficile
C D
Cr o h n’s disease
CI
c o nfi de nce i nter val
C K
creati ne ki nase
C K D -E PI
C hr o nic Ki d ne y Disease E pi de mi ol o g y C olla b orati o n
C ma x
t he ma xi m u m o bser ve d ser u m/ plas ma/ peri p heral bl o o d m o n o n uclear ( P B M C) 
c o nce ntrati o n of dr u g
C M H
C oc hra n -Ma ntel -Hae nszel
C P K 
creati ne p h os p h o ki nase
C R F
case re p ort f or m(s)
C R O
c o ntract researc h or ga nizati o n 
C R P
c-reacti ve pr otei n
C S R
cli nical st u d y re p ort
C T C A E
C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts
C Y P
c yt oc hr o me P 4 5 0 e nz y me
D M C
data m o nit ori n g c o m mittee
E C G
electr ocar di o gra m
e C R F
electr o nic case re p ort f or m(s)
eG F R
esti mate d gl o mer ular filtrati o n rate
e G F R cr
esti mate d gl o mer ular filtrati o n rate base d o n ser u m creati ni ne 
e G F R c ys
esti mate d gl o mer ular filtrati o n rate base d o n ser u m c ystati n C
E D C
Electr o nic Data Ca pt ure 
E M A
E ur o pea n Me dici nes A ge nc y
E R K
e xtracell ular si g nal -re g ulate d ki nases
E Q -5 D
E ur o Q ol 5 di me nsi o ns
E T
earl y ter mi nati o n
E U
E ur o pea n U ni o n


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 1 4
1 9 J u ne 2 0 2 0
E u dra C T
E ur o pea n cli nical trials data base
F A S
F ull A nal ysis Set
F D A
F o o d a n d Dr u g A d mi nistrati o n
F F P E
F or m ali n Fi xe d Paraffi n E m be d de d
G C P
G o o d Cli nical Practice ( G ui deli nes)
G D R C
Gilea d Data Re vie w C o m mittee
G F R
gl o mer ular filtrati o n rate
G L S M
ge o metric least -s q uares mea n
Gilea d
Gilea d Scie nces
H Bc A b
he patitis B vir us c ore a nti b o d y
H Bs A g
he patitis B vir us s urface a nti ge n
H B V
h e patitis B v ir us
H C V
h e patitis C v ir us
H C R U
healt hcare res o urce utilizati o n
H D L
hi g h -de nsit y li p o pr otei n
H D P E
hi g h de nsit y p ol yet h yle ne
HI V
h u ma n im m u n o deficie nc y v ir us
H L G T
Hi g h -Le vel Gr o u p Ter m
H L T
Hi g h -Le vel Ter m
H R Q o L
healt h -relate d q ualit y of life
I B
In vesti gat or br oc h ure
I B D
i nfla m mat or y b o wel disease
I B D Q
I nfla m mat or y B o wel Disease Q uesti o n naire
I C H
I nter nati o nal C o u ncil f or Har m o nisati o n (of Tec h nical Re q uire me nts f or 
P har m ace uticals f or H u ma n Use )
I E C
i n de pe n de nt et hics c o m mittee
I L-1 β
interle u ki n -1 beta
I M P
i n vesti gati o nal me dici nal pr o d uct
I N D
in vesti gati o nal n e w dr u g
I N R
inter nati o nal n or m alize d rati o
I R B
i nstit uti o nal re vie w b oar d
I U D
i ntra uteri ne de vice
I V
intra ve n o us
I W R S
i nteracti ve we b res p o nse s yste m
J A K
Ja n us Ki nase
L D L
l o w-de nsit y li p o pr otei n
L L T
l o wer -le vel ter m
L L O Q
lo w er li mit of q ua ntificati o n
L O C F
last o bser vati o n carrie d f or war d
L P S
li p o p ol ysacc hari des
M A T E 1
m ulti dr u g a n d t o xi n e xtr usi o n tra ns p orter 1
M C S
M a y o Cli nic Sc ore


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 1 5
1 9 J u ne 2 0 2 0
Me d D R A
Me dical Dicti o nar y f or Re g ulat or y Acti vities
N O A E L
n o o bser ve d a d verse effect le vel
N RI
n o n- res p o n der i m p utati o n
N S F
n or m al st o ol fre q ue nc y
O A T P
or ga nic a ni o n -tra ns p orti n g p ol y pe pti de
O L
o pe n -la bel 
P- g p
P- gl yc o pr otei n
P B M C
peri p heral bl o o d m o n o n uclear cell
P E
p h ysical e xa mi nati o n
P G A
P h y sicia ns gl o bal assess me nt
PI
pri nci pal i n vesti gat or
P K
P har m ac o ki netic (s)
P T
preferre d ter m
P T x
p ostt reat me nt
P T M
place b o t o matc h
P V E
P har m ac o vi gila nce a n d E pi de mi ol o g y
Q D
o nce dail y
R N A
ri b o n ucleic aci d
S A C
Safet y Assess me nt C o m mittee
S A D R
seri o us a d verse dr u g reacti o n
S A E
seri o us a d verse e ve nt
S A P
statistical anal ysis p la n
S D
sta n dar d de viati o n
S F -3 6
3 6 -Ite m S h ort F or m S ur ve y
S N P
si n gle n ucle oti de p ol y m or p his m
S O C
s yste m or ga n class
S O P
sta n dar d o perati n g pr oce d ure
sp p
species
S U S A R
s us pecte d u ne x pecte d seri o us a d verse r eacti o n
T B
tu berc ul osis
T E A E
treat me nt-e mer ge nt a d verse e ve nt
T N F α
t u m or necr osis fact or-al p ha
T P L 2
t u m or pr o gressi o n l oc us 2
U C
ulcerati ve c olitis
U G T 1 A 1
uri di ne 5’ -di p h os p h o -gl uc ur o n os yltra nsferase fa mil y 1 me m ber A 1
U L N
u p per li mit of n or mal 
U S
U nite d States
W B C
w hite bl o o d cell
W P AI -U C
W or k Pr o d ucti vit y a n d Acti vit y I m pair me nt -Ulcerati ve C olitis


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 1 6
1 9 J u ne 2 0 2 0
1.
I N T R O D U C TI O N
1. 1.
B ac k gr o u n d
I nfla m mat or y b o wel diseases (I B D), w hic h i ncl u de Cr o h n’s disease ( C D) a n d ulcerati ve c olitis 
( U C), are c hr o nic i nfla m mat or y diseases of t he gastr oi ntesti nal tract c haracterize d b y peri o ds of 
rela pses a n d re missi o n. I n U C, t he i nfla m mati o n is li mite d t o t he m uc osa of t he c ol o n a n d 
rect u m, w hile i n C D a ny part of t he gastr oi ntesti nal tract, fr o m m o u t h t o a n us, ca n be affecte d. 
Cr o h n’s disease a n d U C are t h o u g ht t o res ult fr o m a n i na p pr o priate i m m u ne res p o nse t o 
i ntesti nal micr o bi ota i n ge netically s usce pti ble h osts, wit h e n vir o n me ntal fact ors tri g geri n g 
disease i nitiat i o n a n d reacti vat i o n. T his h yp ot hesis i m plicates reci pr ocal i nteracti o ns bet wee n 
h ost ge netics, e n vir o n me ntal fact ors, resi de nt micr o bi ota, a n d i m m u ne res p o nses t hat n or mall y  
me diate m uc osal h o me ostasis, b ut w he n d y sre g ulate d, i n d uce a n d per pet uate c hr o nic i m m u ne-
me diate d i nfla m mati o n { U n gar o 2 0 1 6 }.
T he i nci de nce a n d pre vale nce of U C ha ve bee n i ncreasi n g w orl d wi de. I n E ur o pe , the i nci de nce 
a n d pre vale nce ra n ge fr o m 0. 9 7
5 7. 9 per 1 0 0, 0 0 0 pers o n year s a n d 2. 42
5 0 5 per 1 0 0, 0 0 0 
pers o n years, res pecti vel y. H o we ver, wit hi n E ur o pe t here a p pears t o be differe nces i n U C
i nci de nce, wit h c o u ntries l ocate d i n t he wester n a n d n ort her n re gi o ns ha vi n g hi g her i nci de nces 
t ha n easter n c o u ntries. I n N ort h A merica, the i nci de nce a n d pre vale nce ra n ge fr o m 8. 8 
2 3. 1 4
per 1 0 0, 0 0 0 pers o n ye ars a n d 1 3 9. 8
2 8 6. 3 per 1 0 0, 0 0 0 pers o n years, res pecti vel y. D uri n g t he 
2 0t h ce nt ur y , U C was mai nl y a disease of wester nize d c o u ntries of N ort h A merica, E ur o pe, a n d 
Ocea nia. T he pre vale nce of U C i n ne wl y i n d ustrialize d c o u ntries is l o w, b ut gi ve n t he risi n g 
i nci de nce i de ntified i n ma n y  of t hese c o u ntries, is e x pecte d t o cli m b. T his i ncreasi n g gl o bal 
b ur de n of U C will bri n g i m p orta nt c halle n ges t o healt h -care s ys te ms ar o u n d t he w orl d as t he y 
w or k t o care f or t his c o m ple x a n d c ostl y  disease { N g 2 0 1 7 } .
T he m ost c o m m o n prese ntati o ns of U C are bl o o d i n t he st o ol a n d diarr hea. U p t o 1 5 % of patie nt s 
ca n i nitiall y prese nt wit h se vere disease. Sy m pt o ms ca n i ncl u de ur ge nc y , i nc o nti ne nce, fati g ue, 
i ncrease d fre q ue nc y of b o wel m o ve me nts, m uc us dis c har ge, n oct ur nal defecati o ns, a n d 
a b d o mi nal disc o mf ort (cra m ps), alt h o u g h a b d o mi nal pai n te n ds t o be less of a hall mar k feat ure 
t ha n i n C D . Fe vers a n d wei g ht l oss ca n als o be prese nt i n se vere disease . U C is ass ociate d wit h
a n i ncrease d ris k of c ol orectal ca ncer { U n gar o 2 0 1 6 }. Wit h p o orl y  c o ntr olle d disease, t he ris k of 
de vel o pi n g c ol orectal ca ncer i ncreases wit h ti me { Jess 2 0 1 2}. 
Treat me nt of U C is de pe n de nt o n t he se verit y a n d t he l ocati o n of disease. G oals o f treat me nt 
i ncl u de i m pr o ve d q ualit y of life, re d ucti o n i n l o n g-ter m c ortic oster oi d use, a n d mi ni mizati o n of 
ca ncer ris k. Mil d t o m o deratel y acti ve distal c olitis ma y  be treate d wit h oral a mi n osalic ylates, 
t o pical mesala mi ne, or t o pical ster oi ds. F or m o der atel y acti ve disease, oral c ortic oster oi ds, a n d 
i m m u n o m o d ulat ors s uc h as azat hi o pri ne a n d 6-merca pt o p uri ne ( 6 -M P) ma y be utilize d { Da nese 
2 0 1 1 } . F or m ore m o deratel y t o se verel y acti ve disease, patie nts are c o m m o nl y  treate d wit h a 
t u m or necr osis fact or-al p ha ( T N F α) a nta g o nist s uc h as i nfli xi ma b ( Re mica de ® ), a dali m u ma b 
( H u mira® ), a n d g oli m u ma b ( Si m p o ni® ), or a n α 4 β 7 i nte gri n a nta g o nist s uc h as v e d oliz u ma b 
( E nt yvi o ® ). Tofaciti ni b, a n oral Ja n us ki nase (J A K) i n hi bit or, a n d uste ki n u ma b , a m o n ocl o nal 
a nti b o d y a gai nst I L 1 2/ 2 3, are a p pr o ve d f or m o deratel y t o se verel y acti ve disease { Har b or d 2 0 1 7 , 
S T E L A R A 2 0 2 0 }.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 1 7
1 9 J u ne 2 0 2 0
1. 2.
R ati o n ale f or T his St u d y
Des pite t he n u m ber of a vaila ble t hera pe utic o pti o ns f or patie nts wit h U C, t here re mai ns a n u n met 
me dical nee d beca use e xisti n g a ge nts are li mite d b y l o w efficac y a n d safety c o ncer ns .
M o deratel y t o se verel y acti ve U C re prese nts a seri o us, life -t hreate ni n g disease f or w hic h ne w 
t hera pies are nee de d t o i nterr u pt t he i nfla m mat or y pr ocess t o: pre ve nt disease pr o gressi o n, 
rest ore q uality of life, a n d re d uce t he ris k of c ol orectal ca ncer .
G S - 48 7 5 is a first-i n-class i n hi bit or of t u m or pr o gressi o n l oc us 2 (T P L 2), a c yt o plas mic 
seri ne/t hre o ni ne ki nase a n d t he pri mar y  re g ulat or of e xtracell ular si g nal-re g ulate d ki nase
(E R K )-me diate d ge ne e x pressi o n d o w nstrea m of m ulti ple pr o -i nfla m mat or y sti m uli i ncl u di n g:
bacterial pr o d ucts (e g, li p o p ol ysacc hari des [L P S] a n d bacterial pe pti d o gl yc a ns), T N F α , a n d
i nterle u ki n-1 beta ( I L- 1 β) {Ga nt ke 2 0 1 1 }. U p o n sti m ulati o n , t he T P L2 -E R K pat h wa y  is 
acti vate d i n a br oa d ra n ge of i m m u ne cells an d dri ves t he pr o d ucti o n of pr o -i nfla m mat or y 
c yt o ki nes i ncl u di n g T N F α, I L- 1 β, a n d I L- 6; all of w hic h are c yt o ki nes i n v ol ve d i n t he 
pat h o ge nesis of U C . T P L 2 ri b o n ucleic aci d (R N A ) is u pre g ulate d i n U C patie nt c ol o n bi o psies
a n d its e x pressi o n c orrelates wit h I B D-ass ociate d ge nes. A T P L 2 gai n of f u ncti o n p ol y m or p his m 
has bee n i de ntifie d as a ris k allele i n U C { He dl 2 0 1 5 , J osti ns 2 0 1 2}. T heref ore, T P L 2 i n hi biti o n
b y  G S -4 8 7 5 has t he p ote ntial t o reesta blis h a pr o per h o me ostasis bet wee n i ntesti nal micr o bi ota
i n t he g ut a n d t he i m m u ne s yste m, p ote ntially e na bli n g t he res ol uti o n of c hr o nic i ntesti nal 
i nfla m mati o n i n U C patie nts.
1. 3.
G S - 4 8 7 5
1. 3. 1.
Ge ner al I nf or m ati o n
Please refer t o t he in vesti gat or’s b r oc h ure (I B) f or i nf or mati o n o n G S - 4 8 7 5.
1. 3. 2.
S u m m ar y of A d diti o n al N o n cli nic al E x perie nce of G S -4 8 7 5
1. 3. 2. 1.
T X - 4 5 7- 2 0 1 8
T he p h ot ot o xic p ote ntial of G S -4 8 7 5 o n t he e y es a n d s ki n of Lo n g -E va ns ( Crl: LE) pi g me nte d 
rats was deter mi ne d i n St u d y T X - 4 5 7- 2 0 1 8. Crl: L E rats were e x p ose d t o ultra vi olet B, 
ultra vi olet A, a n d visi ble li g ht f oll o wi n g sys te mic e x p os ure t o G S -4 8 7 5 via a d mi nistrati o n of a n 
i ntesti nall y clea ve d pr o-dr u g of G S - 4 8 7 5 f or 3 da ys. G S - 4 8 7 5 ha d n o p h ot ot o xic lia bilit y  at t he 
hi g hest d oses e val uate d ( A U C 0 2 4 6 3 µ g• h/ m L a n d C ma x 7. 2 µ g/ m L) . T he hi g hest e x p os ures 
( A U C0 2 4) teste d were 2. 8-f ol d a b o ve t he h u ma n e x p os ure e x pecte d t o occ ur wit h t he hi g hest 
d ose of G S - 4 8 7 5 (3 0 0 m g o nce dail y) i n S t u d y G S -U S - 3 6 5- 4 2 3 7. T hese res ult s s u g gest t hat 
G S -4 8 7 5 is n ot p h ot oreacti ve ; t heref ore, p h ot ot o xicit y  preca uti o ns are n ot warra nte d f or s u bjects
e x p ose d t o G S - 4 8 7 5.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 1 8
1 9 J u ne 2 0 2 0
1. 3. 2. 2.
T X - 3 6 5- 2 0 1 6
T X -3 6 5- 2 0 1 6 was a 3 9 -wee k c hr o nic t o xic ol o g y st u dy of G S - 4 8 7 5 i n m o n ke ys wit h a 2 6- wee k
i nteri m necr o psy a n d a 4- wee k rec o ver y peri o d. T he 2 6 -wee k i nteri m necr o ps y  o bser vati o ns 
ha ve bee n s u m marize d i n t he I B. The f oll o wi n g data s u m marize t he G S - 4 8 7 5-relate d 
o bser vati o ns t hr o u g h t he e n d of 3 9 -wee ks of d osi n g a n d 4 -wee k rec o ver y  peri o d. N o G S - 4 8 7 5-
relate d m ortality, cli nical o bser vati o ns , or alterati o ns i n b o d y  wei g ht, f o o d c o ns u m pti o n or 
cli nical pat h ol o g y  para meters were o bser ve d. N o G S -4 8 7 5- relate d macr osc o pic or micr osc o pic 
fi n di n gs were o bser ve d at t he e n d of t he d osi n g or rec o ver y p hase. N o a d verse fi n di n gs were
ide ntifie d . T he n o o bser ve d a d verse effect le vel ( N O A E L) was 6 0 m g/ k g/ da y , t he hig hest d ose 
e val uate d. G S - 4 8 7 5 e x p os ures ( A U C 0 2 4) at N O A E L i n t he m o n ke y  calc ulate d as t wice t he 
re p orte d A U C0 1 2 val ues was 8 8 µ g• h/ m L. T his res ults i n a n e x p os ure mar gi n of 3. 8 -f ol d a b o ve
t he a ntici pate d stea dy- state h u ma n e x p os ure at t he hi g hest d ose of G S - 4 8 7 5 ( 3 0 0 m g ) i n 
S t u d y G S -U S - 3 6 5- 4 2 3 7.
1. 3. 3.
S u m m ar y of A d diti o n al Cli nic al E x perie nce of G S - 4 8 7 5
1. 3. 3. 1.
G S -U S - 3 6 5- 4 2 3 5
1. 3. 3. 1. 1.
St u d y  Desi g n
St u d y  G S-U S - 3 6 5- 4 2 3 5 was a n o pe n -la bel, m ulti ple c o h ort st u d y desi g ne d t o e val uate 
c yt oc hr o me P 4 5 0 e nz ym e (C Y P )-me diate d dr u g -dr u g i nteracti o ns b et wee n G S -4 8 7 5 ( 5 0, 3 0 0, or 
4 5 0 m g) a n d vari o us pr o be dr u gs i n healt h y s u bjects.
1. 3. 3. 1. 2.
P har mac o ki netic Res ults
G S - 4 8 7 5 ( 4 5 0 m g o nce dail y) ha d mi ni mal effect o n t he p har mac o ki netic ( P K ) of a pr o be 
C Y P 3 A s u bstrate ( mi daz ola m 2 m g, si n gle d ose). C o-a d mi nistrati o n wit h G S - 4 8 7 5 di d n ot 
c ha n ge mi daz ola m C ma x (ge o metric mea n rati o [9 0 % CI ]: 1. 0 4 [ 0. 8 8, 1. 2 3]). Mi daz ola m A U Ci nf
was mi ni mall y  i ncrease d b y 1 9 % (ge o metric mea n rati o [9 0 % CI ]: 1. 1 9 [1. 0 5, 1. 3 6] ). T heref ore , 
G S -4 8 7 5 is c o nsi dere d a wea k C Y P 3 A i n hi bit or. Acc or di n gl y , se nsiti ve C Y P 3 A s u bstrates ma y 
be a d mi nistere d wit h G S - 4 8 7 5.
A str o n g C Y P 3 A i n hi bit or ( v oric o naz ole 2 0 0 m g t wice daily), w he n c o -a d mi nistere d wit h 
G S -4 8 7 5 ( 5 0 m g, si n gle d ose), i ncrease d G S -4 8 7 5 e x p os ure ( A U Ci nf) b y 2. 10- f ol d ( 9 0 % CI: 
1. 7 4, 2. 5 4 ) wit h n o c ha n ge i n t he Cma x (ge o metric mea n rati o [9 0 % CI ]: 1. 0 6 [0. 8 7, 1. 2 9 ]). 
T heref ore, a d mi nistrati o n of G S - 4 8 7 5 wit h m o derate a n d str o n g C Y P 3 A i n hi bit ors is n ot all o we d 
i n St u d y  G S-U S - 3 6 5-4 2 3 7 (see Secti o n 5. 4 ).
A m o derate C Y P 3 A i n d ucer (rifa m pi n 1 0 m g o nce dail y ), w he n c o-a d mi nistere d wit h G S - 4 8 7 5
( 3 0 0 m g, si n gle d ose), re d uce d G S -4 8 7 5 plas ma e x p os ure ( A U C i nf) b y 2 7 % (ge o metric mea n 
rati o [9 0 % CI ]: 0. 7 3 [ 0. 5 9 , 0. 9 0 ]) wit h n o c ha n ge i n t he Cma x (ge o metric mea n rati o [9 0 % CI ]: 
0. 9 6 [ 0. 7 5, 1. 2 3]). T heref ore , m o derate a n d str o n g C Y P 3 A i n d ucers are n ot all o we d i n St u d y  
G S -U S -3 6 5 - 4 2 3 7 (Secti o n 5. 4 ).


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 1 9
1 9 J u ne 2 0 2 0
1. 3. 3. 1. 3.
Safet y Res ults
All 4 2 e nr olle d s u bjects recei ve d at least 1 d ose of G S - 4 8 7 5. N o deat hs, seri o us a d verse e ve nts 
(S A Es ), or a d verse e ve nts (A Es ) t hat le d t o pre mat ure disc o nti n uati o n of st u d y dr u g or st u d y  
were re p orte d d uri n g t he st u d y . All A Es were mil d ( Gra de 1) or m o derate ( Gra de 2) i n se verity. 
T he m ost c o m m o n A Es i ncl u de d hea dac he, dizzi ness, decrease d a p petite, i nfre q ue nt b o wel 
m o ve me nts , a n d na usea. T he maj orit y  of la b orat or y a b n or malities were Gra de 1 or Gra de 2.
1. 3. 3. 2.
G S -U S - 3 6 5- 5 5 8 8
1. 3. 3. 2. 1.
St u d y  Desi g n
St u d y  G S-U S - 3 6 5- 5 5 8 8 was a ra n d o mize d, place b o -c o ntr olle d st u d y t o e val uate t he effect of 
G S -4 8 7 5 o n re nal f u ncti o n usi n g t he plas ma cleara nce of i o he x ol as a s urr o gate mar ker f or 
meas ure d gl o mer ular filtrati o n rate ( G F R). Esti mate d G F R s, base d o n ser u m creati ni ne (e G F R cr) 
a n d c ystati n C (e G F R c ys) as calc ulate d b y t he C hr o nic Ki d ne y  Disease E pi de mi ol o g y 
C olla b orati o n ( C K D -E PI ) e q uati o ns ( Secti o n 6. 9. 5. 2 ), were e val uate d d uri n g t he o n-treat me nt 
peri o d ( Da y s 1 t hr o u g h 1 0) a n d d uri n g t he f oll o w-u p peri o d ( Da y s 2 4 t hr o u g h 6 6).
1. 3. 3. 2. 2.
P har mac o ki netic Res ults
Plas ma e x p os ures of G S - 4 8 7 5 ( 3 0 0 m g o nce daily) o n Da y  10 were c o nsiste nt wit h pre vi o us 
st u dies. N o differe nces i n c ha n ge fr o m baseli ne i n meas ure d G F R were o bser ve d bet wee n t he 
G S - 4 8 7 5 a n d place b o gr o u ps o n Da y 1 0 (l o wer b o u n d of CI s f or GF Rs was a b o ve t he 
pre -defi ne d, n o -alterati o n b o u n dar y of 8 5 %). Si milarl y, n o differe nces i n c ha n ge fr o m baseli ne 
i n e G F Rc ys were o bser ve d bet wee n t he G S - 4 8 7 5 a n d place b o gr o u ps d uri n g t he o n-treat me nt a n d 
f oll o w-u p peri o ds. T here was a decrease i n t he ge o metric least -s q uares mea n (G L S M ) rati o of 
e G F R cr i n t he G S -4 8 7 5 gr o u p relati ve t o t he place b o gr o u p d uri n g t he o n -treat me nt peri o d 
( Da ys 1 t hr o u g h 1 0) t hat was re versi ble, as e vi de nce d b y  n or malizati o n of t he G L S M rati o of 
e G F R cr e q ui vale nt t o place b o d uri n g t he f oll o w -u p peri o d ( Da y s 2 4 t hr o u g h 6 6). T hese res ults 
s u ggest t hat c ha n ges i n ser u m creati ni ne o bser ve d wit h G S - 4 8 7 5 treat me nt at d oses u p t o 3 0 0 m g 
o nce dail y are d ue t o i n hi biti o n of t he re nal tra ns p orter m ulti dr u g a n d t o xi n e xtr usi o n 
tra ns p orter 1 ( M A T E 1 ) a n d d o n ot re prese nt c ha n ges i n act ual G F R or re nal f uncti o n.
1. 3. 3. 2. 3.
Safet y Res ults
All 3 2 e nr olle d s u bjects recei ve d at least 1 d ose of st u d y  dr u g a n d i o he x ol . N o deat hs or S A Es 
were re p orte d d uri n g t he st u d y . M ost A Es were mil d ( Gra de 1) or m o derate ( Gra de 2) i n 
se verity. O ne s u bject a d mi nistere d G S - 4 8 7 5 a n d i o he x ol e x perie nce d a Gra de 3 A E (i ncrease d 
creati ne p h os p h o ki nase) t hat le d t o disc o nti n uati o n of st u d y  dr u g per pr ot oc ol g ui da nce. T he 
m ost c o m m o n A Es i ncl u de d hea dac he, c o nsti pati o n, a n d dizzi ness. T he maj orit y of la b orat or y 
a b n or malities were Gra de 1 or Gra de 2. T w o s u bjects a d mi nistere d G S -4 8 7 5 a n d i o he x ol ha d 
Gra de 3 la b orat or y  a b n or malities. O ne s u bject ha d Gra de 3 creati ne p h os p h o ki nase i ncreases a n d 
disc o nti n ue d st u d y dr u g ; creati ne p h os p h o ki nase le vels ret ur ne d t o n or mal 5 da y s later. T he ot her
s u bject ha d Gra de 3 l o w-de nsit y  li p o pr otei n (L D L ) i ncreases a n d a Gra de 3 t otal bilir u bi n 
i ncrease wit h o ut ele vati o ns i n direct bilir u bi n . T his s u bject has a k n o w n i n herite d s usce pti bilit y


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 2 0
1 9 J u ne 2 0 2 0
t o u nc o nj u gate d h y per bilir u bi ne mia ( h o m oz yg o us f or uri di ne 5’ -di p h os p h o -
gl uc ur o n os y ltra nsferase fa mil y 1 me m ber A 1 [ U G T 1 A 1] * 2 8 varia nt allele ) a n d ha d a G ra de 3 
L D L at scree ni n g. T w o s u bjects a d mi nistere d place b o a n d i o he x ol ha d Gra de 3 or hi g her 
la b orat or y a b n or malities. O ne s u bject ha d a Gra de 3 a m y lase i ncrease. T he ot her su bject ha d a 
Gra de 4 creati ne p h os p h o ki nase i ncrease.
1. 4.
Ris k/ Be nefit Assess me nt f or t he S t u d y
N o s pecific ris ks of G S -4 8 7 5 ha ve bee n i de ntifie d i n st u dies of chr o nic t o xicit y i n rats a n d 
c yn o m o l gus m o n ke y s. A s u m mar y of t he data fr o m n o n-cli nical c hr o nic t o x icit y st u dies are 
pr o vi de d i n t he c urre nt e diti o n of t he G S -4 8 7 5 I B a n d Secti o n 1. 3. 2 .
G S -4 8 7 5 has bee n a d mi nistere d t o 1 0 2 healt h y s u bjects i n t he P hase 1a first-i n-h u ma n st u d y, 
G S -U S - 3 6 5- 4 2 3 3. A s u m mar y  of t he safety a n d P K data fr o m t his st u d y  is pr o vi de d i n t he 
c urre nt e diti o n of t he G S -4 8 7 5 I B. G S - 4 8 7 5 has bee n a d mi nistere d t o 5 8 healt h y  s u bjects i n 
2 P hase 1 S t u dies, G S-U S - 3 6 5-4 2 3 5 a n d G S -U S -3 6 5 -5 5 8 8. A s u m mar y of t he data fr o m t hese 
st u dies is pr o vi de d i n Secti o n 1. 3. 3 .
I n S t u d y G S-U S -3 6 5- 4 2 3 3, G S -4 8 7 5 was well -t olerate d i n healt h y s u bjects w he n a d mi nistere d 
f or u p t o 1 0 da ys at d oses ra n gi n g fr o m 1 5 m g  o nce dail y  t o 4 5 0 m g o nce dail y . T here were n o 
deat hs re p orte d, n o S A Es re p orte d , a n d n o s u bjects disc o nti n ue d st u d y  dr u g f or A Es. 
N o n -cli nical st u dies i n dicate t hat G S - 4 8 7 5 is a n i n hi bit or of t he or ga nic a ni o n-tra ns p orti n g 
p ol y pe pti de ( O A T P) is of or ms O A T P 1 B 1, O A T P 1 B 3, a n d O A T P 2 B 1 a n d is a n i n hi bit or of 
U G T 1 A 1. T heref ore , a c o h ort of 1 2 s u bjects h o m oz y g o us f or t he U G T 1 A 1 * 2 8 allele ( T A 7/ T A 7) 
was a d mi nistere d place b o or G S -4 8 7 5 4 5 0 m g o nce dail y f or 1 0 da ys t o assess w het her G S - 4 8 7 5
w o ul d e xacer bate h y p er bilir u bi ne mia i n patie nts w h o were ge neticall y  s usce pti ble. G S - 4 8 7 5 was 
well -t olerate d i n t he 8 s u bjects t hat recei ve d G S -4 8 7 5 wit h mil d ele vati o ns i n t otal bilir u bi n 
o bser ve d b ut wit h o ut ele vati o ns i n direct bilir u bi n or s ym pt o matic h y per bilir u bi ne mia.
N o n -cli nical st u dies i n dicate t hat G S - 4 8 7 5 is a n i n hi bit or of M A T E 1 a n d ma y t heref ore affect 
t he P K of M A T E 1 s u bstrates, i ncl u di n g creati ni ne. In St u d y  G S -U S -3 6 5- 5 5 8 8 , i ncreases i n 
ser u m creati ni ne a n d c o nse q ue ntl y, decreases i n e G F Rcr were o bser ve d i n s u bjects a d mi nistere d 
G S -4 8 7 5 . H o we ver, t he res ults of St u d y G S -U S -3 6 5 -5 5 8 8 de m o nstrate d t hat G S - 4 8 7 5 ha d n o 
effect o n re nal f u ncti o n as deter mi ne d b y meas ure d G F R a n d e G F R c ys ( See Secti o n 1. 3. 3. 2 ). 
T heref ore, i n or der t o mai ntai n t he st u d y  bli n d, res ults of ser u m creati ni ne a n d e G F Rcr
assess me nts will n ot be pr o vi de d t o i n vesti gat ors. Assess me nt of re nal f u ncti o n usi n g c y stati n C 
a n d e G F R c ys will be r o uti nel y  meas ure d, a n d t hese data will be pr o vi de d t o i n vesti gat ors.
T he u n k n o w n ris ks of G S - 4 8 7 5 are ass ociate d wit h its p ote ntial t o i n hi bit i nfla m mat or y  si g nali n g 
casca des a n d t here b y i m pair t he i m m u ne res p o nse i n patie nts wit h U C. Base d o n t he mec ha nis m 
of acti o n, t here is a p ote ntial f or i m m u n os u p pressi o n b ut als o a t he oretical ris k t hat i n hi biti o n of 
T P L 2 c o ul d e xacer bat e U C .
T hese ris ks are miti gate d b y  t he selecti o n of t he a p pr o priate patie nt p o p ulati o n as defi ne d b y t he 
eli gi bilit y criteria, t he fre q ue nc y of sc he d ule d visits d uri n g w hic h la b orat or y a n d cli nical 
assess me nts will be perf or me d a n d t he i m ple me ntati o n of disc o nti n uati o n criteria f or patie nts 
w h o are n ot be nefitti n g fr o m treat me nt wit h G S - 4 8 7 5 or w h o ha ve w orse ni n g disease. I n 


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 2 1
1 9 J u ne 2 0 2 0
a d diti o n , a n i n de pe n de nt a n d e x perie nce d data m o nit ori n g c o m mittee ( D M C) will be c o n ve ne d
t o m o nit or t he safet y of s u bjects i n t he st u d y. T he fre q ue nc y of D M C meeti n gs is descri be d i n 
S ecti o n 8. 1 1 .
G S -4 8 7 5 is a first-i n-class i n hi bit or of T P L2 . T he mec ha nis m of acti o n of G S -4 8 7 5 is n o vel a n d 
treat me nt effect has n ot yet bee n esta blis he d i n patie nts wit h U C. St u d y  G S -U S -3 6 5- 4 2 3 7 is a 
pr o of -of- c o nce pt st u d y i n w hic h G S -4 8 7 5 m a y  s h o w n o treat me nt e ffect or lea d t o disease 
w orse ni n g. I n c o nsi derati o n of t his early sta ge of de vel o p me nt , efficac y e n d p oi nts a n d disease 
ass ociate d bi o mar kers will be re vie we d b y  t he Gilea d Data Re vie w C o m mittee ( G D R C) ( See 
Secti o n 5. 1. 3 ) all o wi n g f or early ter mi nati o n ( E T) of t he st u d y  a n d a v oi di n g u n necessar y  
e x p os ure t o st u d y dr u g f or t he s u bjects. T he ti mi n g of t he G D R C meeti n g is descri be d i n Secti o n 
8. 2. 1. 1 .
I n s u m mar y, t he be nefit-ris k pr ofile f or G S - 4 8 7 5 is fa v ora ble f or e val uati o n i n s u bjects wit h 
m o deratel y t o se verel y acti ve U C base d o n t he lac k of safet y  fi n di n gs i n healt h y s u bjects, t he 
lac k of c o ncer ni n g n o n-cli nical t o xic ol o g y fi n di n gs, t he a d diti o nal o versi g ht fr o m safety a n d 
efficac y c o m mittees, t he be neficial fi n di n gs i n n o n-cli nical m o dels of disease, as well as, t he 
o verall safet y , t olera bilit y, a n d P K c haracteristics of G S - 4 8 7 5.
1. 5.
C o m pli a nce
T his st u d y  will be c o n d ucte d i n c o m plia nce wit h t his pr ot oc ol, G o o d Cli nical Practice ( G C P), 
a n d a p plica ble re g ulat or y re q uire me nts. In case of s u bsta ntial a me n d me nt t o t he pr ot oc ol, a n 
a p pr o val fr o m t h e C o m pete nt Re g ulat or y A ut h orities will be s o u g ht bef ore i m ple me ntati o n.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 2 2
1 9 J u ne 2 0 2 0
2.
O B J E C TI V E S A N D E N D P OI N T S
T he o bjecti ves a n d ass ociate d e n d p oi nts of t his st u d y  are prese nte d i n Ta ble 2- 1 .
T a ble 2- 1.
O bjecti ves a n d E n d p oi nts of St u d y G S -U S -3 6 5- 4 2 3 7
Pri m ar y O bjecti ve
Pri m ar y E n d p oi nt
T o de m o nstrate t he efficac y of G S -4 8 7 5 , 
c o m pare d wit h place b o c o ntr ol, i n ac hie vi n g
Cli nical Re missi o n per M o difie d Ma y o Cli nic 
Sc ore ( M C S) at Wee k 1 0 
Cli nical Re missi o n per M o difie d M C S , defi ne d as St o ol 
Fre q ue nc y s u bsc ore ≤1 a n d n ot greater t ha n baseli ne, 
Rectal Blee di n g s u bsc ore of 0 , a n d E n d osc o pic s u bsc ore 
≤1 at Wee k 1 0
Ke y Sec o n d ar y O bjecti ves
Ke y Sec o n d ar y E n d p oi nts
T o de m o nstrate t he efficac y of G S -4 8 7 5 , 
c o m pare d wit h place b o c o ntr ol, i n ac hie vi n g 
e n d osc o pic res p o nse at Wee k 1 0
E n d osc o pic Res p o nse , defi ne d as a n E n d osc o pic s u bsc ore 
≤1 at Wee k 1 0
T o de m o nstrate t he efficac y of G S -4 8 7 5 , 
c o m pare d wit h place b o c o ntr ol, i n ac hie vi n g M C S 
Res p o nse at Wee k 1 0
M C S Res p o nse, defi ne d as
a decrease fr o m baseli ne of 
≥3 p oi nts a n d at least 3 0 % i n M C S, i n a d diti o n t o a
≥1 p oi nt decrease fr o m bas eli ne i n t he Rectal Blee di n g 
s u bsc ore or a Rectal Blee di n g s u bsc ore ≤1 at Wee k 1 0
T o de m o nstrate t he efficac y of G S -4 8 7 5 , 
c o m pare d wit h place b o c o ntr ol, i n ac hie vi n g M C S 
Re missi o n at Wee k 1 0
M C S Re missi o n , defi ne d as a M C S sc ore of ≤2 a n d n o 
i n di vi d ual s u bsc ore > 1 at Wee k 1 0
T o e val uate G S -4 8 7 5 , as c o m pare d wit h place b o 
c o ntr ol, i n ac hie vi n g hist ol o gic re missi o n at 
Wee k
1 0
Hist ol o gic re missi o n base d u p o n t he Ge b oes Scale w here 
all of t he f oll o wi n g m ust be met at Wee k 1 0: Gra de 0 of 
≤0. 3, Gra de 1 of ≤1. 1, Gra de 2a of ≤2 A. 3, Gra de 2 b of 
2 B. 0 , Gra de 3 of 3. 0, Gra de 4 of 4. 0, a n d Gra de 5 of 5. 0
(A p pe n di x 5 )
Ot her Sec o n d ar y O bjecti ves
Ot her Sec o n d ar y E n d p oi nts
T o e val uate t he safet y a n d t olera bilit y of G S -4 8 7 5
I nci de nce a n d c haracterizati o n of A Es a n d la b orat or y 
a b n or malities
P h y sical e xa mi nati o n ( P E) fi n di n gs, electr ocar di o gra m 
(E C G ), a n d vital si g ns


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 2 3
1 9 J u ne 2 0 2 0
C CI


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 2 4
1 9 J u ne 2 0 2 0
3.
S T U D Y  D E SI G N
T his is a P hase 2 , bli n de d, ra n d o mize d, p lace b o-co ntr olle d st u d y eval uati n g t he efficac y a n d 
safet y of G S -4 8 7 5 f or t he treat me nt of su bjects wit h m o deratel y t o se verel y acti ve U C . T he 
o bjecti ves a n d ass ociate d e n d p oi nts of t his st u d y  are descri be d i n Secti o n 2 . 
3. 1.
St u d y Desi g n
A sc he matic of t his st u d y desi g n is pr o vi de d i n Fi g ure 3- 1 .
Fi g ure 3 - 1.
St u d y Desi g n
A b bre viati o ns: Q D 
o nce dail y
T his st u d y  i ncl u des:

Scree ni n g peri o d ( Da ys 3 0 t o 1)

Baseli ne/ Ra n d o mizati o n ( Da y 1)
A p pr o xi matel y  1 8 0 su bjects w h o meet pr ot oc ol eli gi bilit y  criteria will be ra n d o mize d i n a 
1: 1: 1 rati o t o 1 of 3 treat me nt gr o u ps as f oll o ws:
Tre at me nt gr o u p 1 ( n  6 0): G S - 4 8 7 5 3 0 0 m g o nce dail y 
Tre at me nt gr o u p 2 ( n  6 0) : G S - 4 8 7 5 1 0 0 m g o nce dail y
Tre at me nt gr o u p 3 ( n  6 0): P lace b o o nce dail y
Treat me nt assi g n me nts will be stratifie d acc or di n g t o t he s u m (≤ 6 or > 6) of 3 M C S 
s u bsc ores f or St o ol Fre q ue nc y , Rectal Blee di n g, a n d E n d osc o pic Fi n di n gs at Scree ni n g.
S cr e e ni n g & 
R a n d o mi z ati o n 
B a s eli n e 
2 
4 
6 
W e e k 1 O 
W e e k 5 0 
'----'-----'-- ~ = = = ~-~-~-=- ~-~---------------------J 
~-- ~ ~ --- ~I 
~I-- ~- ~ ----
I 
I 
V N o n-r e s p o n d er s at W e e k 1 0 
D a y 1 O L 
W e e k 1 0 
W e e k 5 0 O L 
L _ _ _ _ _ _ _ _ L _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ J 
O p e n L a b el G S- 4 8 7 5 3 0 0 m g Q D 
'f' 
W e e k 1 0 M C S 
R e s p o n s e A s s e s s m e nt 
'f' 
Effi c a c y 
A s s e s s m e nt s 


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 2 5
1 9 J u ne 2 0 2 0

Bli n de d Treat me nt p hase ( Da y  1 u p t o Wee k 5 0)
At Wee k 1 0 visit , all s u bjects will ha ve a n efficac y assess me nt.
■
U ntil res p o nse ca n be assesse d base d o n Wee k 1 0 res ults, s u bjects will c o nti n ue o n 
t heir c urre nt assi g ne d st u d y dr u g re gi me n. S u bject s w h o ac hie ve M C S Res p o nse 
( Secti o n 2 ) base d o n res ults fr o m Wee k 1 0 will c o nti n ue i n t he Bli n de d T reat me nt 
p hase. All s u bjects w h o d o n ot ac hie ve M C S Res p o nse will disc o nti n ue t he Bli n de d 
T reat me nt p hase a n d have t he o pti o n t o e nter t he o pe n -la bel ( O L) p hase.
■
S u bjects wit h i ns ufficie nt data t o assess M C S Res p o nse will disc o nti n ue st u d y dr u g
a n d are n ot eli gi ble f or t he O L Treat me nt p hase.

O pe n -la bel Treat me nt p hase (O L Da y  1 u p t o O L Wee k 5 0)
O L  D a y 1 visit s h o ul d occ ur wit hi n 1 4 da y s of Bli n de d Treat me nt p hase Wee k 1 0 visit
u n less ot her wise a p pr o ve d b y t he me dical mo nit or.
At O L  Wee k 1 0 visit, all s u bjects will ha ve a n efficac y assess me nt.
■
U ntil res p o nse ca n be assesse d base d o n Wee k 1 0 res ults, s u bjects will c o nti n ue O L  
st u d y dr u g. S u bjects w h o ac hie ve M C S Res p o nse ( Secti o n 2 ) base d o n res ults fr o m
O L  Wee k 1 0 will c o nti n ue i n t he O L Treat me nt p hase. All s u bjects w h o d o n ot 
ac hie ve M C S Res p o nse will disc o nti n ue st u d y dr u g.
■
S u bjects wit h i ns ufficie nt data t o assess M C S Res p o nse will disc o nti n ue st u d y dr u g.

Gilea d Data Re vie w C o m mittee
After a p pr o xi matel y  9 0 s u bjects c o m plete t he Wee k 1 0 visit or disc o nti n ue fr o m t he 
st u d y pri or t o Wee k 1 0, t he G DR C will re vie w e n d p oi nt data f or p ote ntial st u d y  
ter mi nati o n d ue t o lac k of efficac y.

U n bli n di n g
T he st u d y  will be u n bli n de d whe n all ra n d o mize d s u bjects (a p pr o xi matel y 1 8 0) ha ve 
eit her c o m plete d t he Bli n de d Treat me nt p hase Wee k 1 0 visit a n d all ass ociate d efficac y 
a n d safet y assess me n ts, or disc o nti n ue d t he st u d y bef ore Wee k 1 0.
After st u d y- wi de u n bli n di n g, s u bjects w h o were recei vi n g place b o will disc o nti n ue st u d y  
dr u g . S u bjects s h o ul d atte n d t he cli nic at t heir ne xt sc he d ule d st u d y  visit or earlier, a n d 
u n der g o t he E T assess me nts f oll o we d b y t he P osttreat me nt ( P T x) assess me nts 3 0 da ys 
after t he last d ose of st u d y dr u g.
After st u d y- wi de u n bli n di n g, s u bjects w h o were recei vi n g bli n de d G S - 4 8 7 5 3 0 0 m g a n d
G S -4 8 7 5 1 0 0 m g will re mai n o n t he sa me d ose. T hese s u bjects will c o n ti n ue t he B li n de d 
Treat me nt p hase visit sc he d ule u p t o Wee k 5 0. 


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 2 6
1 9 J u ne 2 0 2 0

P ost treat me nt ( P T x) A ssess me nts 
S u bjects w h o disc o nti n ue st u d y  dr u g will ret ur n 3 0 da y s after t he last d ose f or P T x 
assess me nts .
3. 2.
D ur ati o n of Tre at me nt
I n t he Bli n de d Treat me nt p hase, ra n d o mize d s u bjects ma y  recei ve a ma xi m u m of 5 0 wee ks of 
treat me nt.
S u bjects, w h o m o ve t o t he O L Treat me nt p hase, will ha ve recei ve d 1 0 wee ks of bli n de d 
treat me nt a n d m a y  recei ve u p t o 5 0 wee ks of O L treat me nt. T h us, t otal d urati o n of treat me nt ma y  
be a ma x i m u m of 6 0 wee ks.
3. 2. 1.
R ati o n ale f or St u d y Desi g n
T his st u d y  is desi g ne d as a bli n de d, ra n d o mize d, p lace b o-c o ntr olle d st u d y.
T his st u d y  has bee n desi g ne d t o mi ni mize bias t hat c o ul d be i ntr o d uce d by s u bject or p h ys icia n 
k n o wle d ge of t he ra n d o mize d treat me nt ass i g n me nt beca use t he efficac y e n d p oi nts utilize 
s u bject-re p orte d a n d p hysicia n -re p orte d c o m p o ne nts i n t he M C S. I nvesti gat ors, s u bjects , a n d all 
S p o ns or pers o n nel i n v ol ve d i n t he c o n d uct of t he st u d y will be bli n de d t o ra n d o mize d treat me nt 
assi g n me nt . As U C has a rela psi n g a n d re mitti n g c o urse, t he use of a place b o c o m paris o n f or 
safety a n d efficac y e n d p oi nts will e ns ure t hat a treat me nt effect is bei n g assesse d. 
A ssess me nt of t he efficac y of treat me nt will be ma de after 1 0 wee ks of treat me nt i n t he Bli n de d
T reat me nt p hase. T his d urati o n is c o nsi dere d a p pr o priate base d o n e vi de nce fr o m o za ni m o d a n d 
tofaciti ni b cli nical st u dies de m o nstrati n g t hat 8 wee ks of treat me nt was s ufficie nt f or 
i m pr o ve ment of si g ns a n d s y m pt o ms of U C { Fea ga n 2 0 1 3 , Sa n d b or n 2 0 1 6 , Sa n d b or n 2 0 1 7 }.
T he mai nte na nce of res p o nse t hr o u g h Wee k 5 0 will be e x pl ore d i n s u bjects w h o de m o nstrate a 
M C S res p o nse at Wee k 1 0 i n t he Bli n de d T reat me nt p hase. 
S u bjects w h o d o n ot de m o nstrate a M C S res p o nse at Wee k 1 0 will be gi n treat me nt wit h 
G S -4 8 7 5 3 0 0 m g f or 1 0 wee ks i n t he O L Treat me nt p hase. T he O L Treat me nt p hase will t here b y 
e x pl ore t he effect of d ose escalati o n i n s u bjects treate d wit h G S - 4 8 7 5 1 0 0 m g i n t he Bli n de d 
Treat me nt p hase , w h o di d n ot ac hie ve M C S res p o nse , a n d will als o e x pl ore t he effect of 
G S -4 8 7 5 3 0 0 m g f or a n a d diti o nal 1 0 wee ks i n patie nts tr eate d wit h G S -4 8 7 5 3 0 0 m g i n t he 
Bli n de d Treat me nt p hase , w h o di d n ot ac hie ve M C S res p o nse. I n a d diti o n, place b o -treate d 
s u bjects w h o d o n ot ac hie ve M C S res p o nse at Wee k 1 0 i n t he Bli n de d Treat me nt p hase ca n 
be gi n treat me nt wit h G S - 4 8 7 5 3 0 0 m g i n t he O L Tr eat me nt p hase t here b y e ns uri n g t hat e ver y 
e nr olle d s u bject ma y ha ve access t o G S -4 8 7 5. A n assess me nt of t he efficac y of G S -4 8 7 5 3 0 0 m g 
i n t he OL Treat me nt p hase will occ ur after 1 0 wee ks of treat me nt. S u bjects w h o ac hie ve M C S 
res p o nse i n t he O L Treat me nt p hase ma y  c o nti n ue treat me nt wit h o pe n -la bel G S -4 8 7 5 3 0 0 m g 
u ntil Wee k 5 0 .


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 2 7
1 9 J u ne 2 0 2 0
G S -U S - 3 6 5-4 2 3 7 is a pr o of -of- c o nce pt st u d y of G S - 4 8 7 5, a first-i n-class T P L2 i n hi bit or, i n 
s u bjects wit h U C. In c o nsi derati o n of t his early sta ge of de vel o p me nt f or G S - 4 8 7 5 wit h a n o vel 
a n d u n pr o ve n mec ha nis m of acti o n, peri o dic assess me nts of G S - 4 8 7 5 safet y a n d efficac y will be 
perf or me d i n t his st u d y  b y t he i n de pe n de nt D M C a n d G D R C, res pecti vel y. Neit her of t hese 
c o m mittees will i ncl u de pers o n nel i n v ol ve d i n t he c o n d uct of t he st u d y. Earl y peri o dic efficac y 
a n d safet y assess me nts i n t his P hase 2 pr o of -of- c o nce pt st u d y wit h G S - 4 8 7 5 will a p pr o priatel y 
bala nce t he safet y  of s u bjects t hat partici pate i n t his cli nical trial wit h t he a bilit y t o i nf or m 
pi v otal P hase 3 cli nical trials base d o n t he res ults fr o m a n a de q uatel y p o were d a n d bli n de d st u d y.
W he n all ra n d o mize d s u bjects
(a p pr o xi matel y 1 8 0) ha ve eit her c o m plete d t he Bli n de d Treat me nt 
p hase Wee k 1 0 visit a n d all ass ociate d efficac y  a n d safety assess me nts, or disc o nti n ue d t he st u d y 
bef ore Wee k 1 0, a Wee k 1 0
safety a n d efficac y a nal ysis will be perf or me d t o i nf or m st u d y 
disc o nti n uati o n or f urt her de vel o p me nt of G S -4 8 7 5 f or t he treat me nt of U C. F or f urt her details, 
see S ecti o n 8. 2. 2 Wee k 1 0 A nal y sis.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 2 8
1 9 J u ne 2 0 2 0
4.
S U B J E C T P O P U L A TI O N
4. 1.  
N u m ber of S u bjects a n d S u bject Selecti o n
A p pr o xi matel y  1 8 0 s u bjects w h o meet all eli gi bilit y criteria at scree ni n g will be ra n d o mize d t o 
recei ve G S - 4 8 7 5 1 00 m g , G S - 4 8 7 5 3 0 0 m g , or place b o i n a 1: 1: 1 rati o. 
It is t he res p o nsi bilit y of t he in vesti gat or t o e ns ure t hat s u bjects are eli gi ble t o partici pate i n t he 
st u d y pri or t o ra n d o mizati o n or e nr oll me nt a n d t hr o u g h o ut t he st u d y. E ntr y i nt o scree ni n g d oes 
n ot g uara ntee e nr oll me nt i nt o t he st u d y . In or der t o ma na ge t he t otal trial e nr oll me nt , Gilea d ma y 
s us pe n d scree ni n g a n d/ or e nr oll me nt at a ny site or trial -wi de at a n y ti me.
4. 2. 
I ncl usi o n Criteri a
S u bjects m ust meet all of t he f oll o wi n g i ncl usi o n criteria t o be eli gi ble f or partici pati o n i n t his 
st u d y:
1)
M ust ha ve t he a bilit y  t o u n dersta n d a n d si g n a writte n i nf or me d c o nse nt f or m, w hic h m ust be 
o btai ne d pri or t o i nitiati o n of a n y st u d y pr oce d ures.
2)
Males , or n o n-pre g na nt, n o n -lactati n g fe males, at least 1 8 years of a ge base d o n t he date of 
t he scree ni n g visit.
3)
U C of at least 3 m o nt hs d urati o n bef ore ra n d o mizati o n c o nfir me d b y e n d osc o p y a n d 
hist ol o g y at a n y ti me i n t he past A N D a mi ni m u m disease e xte nt of 1 5 c m fr o m t he a nal 
ver ge. D oc u me ntati o n o f e n d osc o p y a n d hist ol o g y c o nsiste nt wit h t he dia g n osis of U C m ust 
be a vaila ble i n t he s o urce d oc u me nts pri or t o t he i nitiati o n of scree ni n g.
4)
M o deratel y t o se verel y acti ve U C as deter mi ne d d uri n g scree ni n g b y  a ce ntrall y rea d 
e n d osc o p y sc ore ≥2, a Rectal Blee di n g s u bsc ore ≥ 1, a St o ol Fre q ue nc y s u bsc ore ≥ 1 , a n d 
P h y sicia ns G l o bal A ssess me nt ( P G A) of ≥ 2 as d e fi ne d b y  t he Ma yo Cli nic Sc ore
(A p pe n di x 4 ); t otal M C S
m ust be bet wee n 6 a n d 1 2, i ncl usi ve.
5)
Pre vi o usl y  de m o nstrate d a n i na de q uate res p o nse ( pri mar y n o n-res p o nse) or l oss of res p o nse 
(sec o n dar y n o n-res p o nse) t o a T N F α i n hi bit or (ie, i nfli xi ma b, a dali m u ma b, g oli m u ma b, or 
bi osi milars ). T he i n d ucti o n treat me nt re gi me n res ulti n g i n i na de q uate res p o nse or l oss of 
res p o nse s h o ul d ha ve bee n i n acc or da nce wit h l ocal prescri bi n g i nf or mati o n/ g ui deli nes or as 
o utli ne d bel o w.
a)
I nfli xi ma b: 5 m g/ k g at Wee ks
0, 2, a n d 6
b)
A dali m u ma b: 1 6 0 m g o n Da y  1 ( gi ve n i n 1 d a y  or s plit o ver c o nsec uti ve da ys), f oll o we d 
b y  8 0 m g 2 wee ks later ( D a y 1 5), 4 0 m g 2 wee ks later ( Da y  2 9) a n d e very 2 wee ks 
t hereafter u ntil Da y 5 7
c)
G oli m u ma b: 2 0 0 m g o n Da y  1 f oll o we d by 1 0 0 m g at Wee k 2


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 2 9
1 9 J u ne 2 0 2 0
6)
M a y be recei vi n g c o nc o mita nt t hera p y f or U C at t he ti me of e nr oll me nt as s pecifie d i n 
Secti o n 5. 4 , pr o vi de d t he d ose prescri be d has bee n sta ble as i n dicate d pri or t o 
ra n d o mizati o n.
7)
A s ur veilla nce c ol o n osc o p y  is re q uire d pri or t o scree ni n g i n s u bjects wit h a hist or y of U C 
f or 8 or m ore ye ars, if o ne was n ot perf or me d i n t he pri or 2 4 m o nt hs .
8)
Meet t he f oll o wi n g tu berc ul osis ( T B) scree ni n g criteria:
a)
N o e vi de nce of acti ve T B , late nt T B , or i na de q uatel y  treate d T B as e vi de nce d b y 1 of t he 
f oll o wi n g: 
i)
A ne gati ve Q ua nti F E R O N test or e q ui vale nt assa y  re p orte d by t he ce ntral la b at 
scree ni n g or wit hi n 9 0 da ys pri or t o ra n d o mizati o n date . 
O R
ii) A hist or y  of f ull y treate d acti ve or late nt T B acc or di n g t o l ocal sta n dar d of care . 
In vesti gat or m ust verif y  a de q uate pre vi o us a nti -T B treat me nt a n d pr o vi de 
d oc u me ntati o n; t hese s u bjects d o n ot re q uire Q ua nti F E R O N testi n g a n d eli gi bilit y 
m ust be a p pr o ve d b y  t he sp o ns or pri or t o e nr oll me nt i n t he st u d y.
A N D
b)
A c hest ra di o gra p h ( vie ws as per l ocal g ui deli nes wit h t he re p or t or fil ms a vaila ble f or 
i n vesti gat or re vie w) ta ke n at scree ni n g or wit hi n t he 4 m o nt hs pri or t o ra n d o mizati o n
wit h o ut e vi de nce of acti ve or late nt T B i nfecti o n .
9)
La b orat or y  assess me nts at scree ni n g wit hi n t he f oll o wi n g para meters :
a)
As partate a mi n otra nsferase ( A S T ) a n d ala ni ne a mi n otra nsferase ( A L T ) a n d t otal bilir u bi n 
≤2 u p per li mit of n or mal ( U L N)
b)
Esti mate d gl o mer ular filtrati o n rate ( eG F R) ≥6 0 m L / mi n (1. 0 m L /sec) as calc ulate d b y  
t he C K D -E PI { I n ker 2 0 1 2}c ys tati n C f or m ula as descri be d i n S ecti o n 6. 9. 5. 2 . 
c)
He m o gl o bi n ≥ 8 g/ d L ( ≥8 0 g/ L)
d)
A bs ol ute ne utr o p hil c o u nt ( A N C) ≥ 1. 5 × 1 0 3/ µ L (≥ 1. 5 GI / L)
e)
Platelets ≥ 1 0 0 × 1 0 3/ µ L (≥ 1 0 0 GI/ L)
f)
W hite bl o o d cells ( W B C) ≥3 × 1 0 3/ µ L ( ≥3 GI/ L)
g)
A bs ol ute ly m p h oc y te c o u nt ≥0. 7 5 × 1 0 3/ µ L (≥0. 7 5 GI / L)
1 0) S t o ol sa m ple test res ult ne gati ve f or e nteric pat h o ge ns


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 3 0
1 9 J u ne 2 0 2 0
1 1) St o ol sa m ple test res ult ne gati ve f or o va a n d parasites u nless a p pr o ve d b y t he me dical 
m o nit or .
1 2) Ne gati ve HI V a nti b o d y test .
1 3) Ne gati ve he patitis B vir us (H B V ) s urface a nti ge n test. Su bjects wit h ne gati ve he patitis B 
vir us s urface a nti ge n (H Bs A g ) test a n d p ositi ve he patitis B vir us c ore a nti b o d y ( H Bc A b) 
test m ust ha ve a H B V D N A < l o wer li mit of q ua ntificati o n (L L O Q ).
1 4) Ne gati ve he patitis C vir us (H C V ) a nti b o d y test or H C V R N A < L L O Q as descri be d i n 
S ecti o n 6. 9. 5. 6 .
1 5) Ne gati ve uri ne dr u g scree n res ult . A p ositi ve dr u g scree n will e xcl u de s u bjects u nless it ca n 
be e x plai ne d b y  t he use of a me dicati o n ( prescri pti o n or n o n prescri pti o n) t hat is bei n g use d 
u n der t he directi o n of a p h y sicia n. C ocai ne use is e xcl usi o nar y. 
1 6) Fe males of c hil d beari n g p ote ntial (as defi ne d i n A p pe n di x 8 ) m ust ha ve a ne gati ve 
pre g na nc y  test res ult at scree ni n g a n d Da y  1 pri or t o ra n d o mizati o n.
1 7) Male s u bjects a n d fe male s u bjects of c hil d beari n g p ote ntia l w h o e n ga ge i n heter ose x ual 
i nterc o urse m ust be willi n g t o use pr ot oc ol -s pecifie d met h o d(s) of c o ntrace pti o n as 
descri be d i n A p pe n di x 8 .
4. 3.
E xcl usi o n Criteri a
S u bjects w h o meet a ny of t he f oll o wi n g e xcl usi o n criteria are n ot t o be e nr olle d i n t his st u d y .
1)
C urre ntl y  dis pla yi n g cli nical si g ns of ac ute se vere c olitis, f ul mi na nt c olitis, or t o xic 
me gac ol o n .
2)
Pr i or s ur ger y f or U C.
3)
S u bjects w h o are li kely t o re q uire a n y t y p e of maj or s ur ger y d uri n g t he st u d y. Cataract 
s ur ger y, breast s ur ger y wit h o ut rec o nstr ucti o n, la par osc o pic c h olec ystect o m y, la par osc o pic 
t u bal li gati o n a n d m ost c uta ne o us, s u perficial, e n d osc o pic a n d art hr osc o pic pr oce d ures ca n 
be c o nsi dere d mi n or s ur geries.
4)
Ha ve ha d a n y maj or s ur ger y  or tra u ma wit hi n 8 wee ks pri or t o ra n d o mizati o n.
5)
Hist or y  or e vi de nce of i nc o m pletel y resecte d c ol o nic m uc osal d ys plasia.
6)
Hist or y  of mali g na nc y i n t he last 5 years e xce pt f or s u bjects w h o ha ve bee n treate d or 
resecte d f or eit her n o n- mela n o ma s ki n ca ncer or cer vical carci n o ma i n sit u .
7)
Hist or y  of ly m p h o pr oliferati ve dis or der, l y m p h o ma, le u ke mia, m yel o pr oliferati ve dis or der, 
or m ulti ple m y el o ma.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 3 1
1 9 J u ne 2 0 2 0
8)
A n y  c hr o nic me dical c o n diti o n (i ncl u di n g, b ut n ot li mite d t o car diac or p ul m o nar y disease) 
or ps y c hiatric pr o ble m (i ncl u di n g, b ut n ot li mite d t o alc o h ol or dr u g a b use) t hat, i n t he 
o pi ni o n of t he i n vesti gat or or s p o ns or, w o ul d ma ke t he s u bject u ns uita ble f or t he st u d y  or 
w o ul d pre ve nt c o m plia nce wit h t he st u d y  pr ot oc ol.
9)
Hist or y  of i m m u n o deficie nc y sy n dr o me .
1 0) Ha ve a st o ma or ile oa nal p o uc h .
1 1)
De pe n de nce o n t otal pare nteral n utriti o n.
1 2) Ha ve a tra ns pla nte d or ga n wit h e xce pti o n of a c or neal tra ns pla nt .
1 3) Acti ve cli nicall y si g nifica nt i nfecti o n, or a n y i nfecti o n re q uiri n g h os pitalizati o n or treat me nt 
wit h i ntra ve n o us a nti -i nfecti ves wit hi n 8 wee ks of ra n d o mizati o n; or a n y i nfecti o n re q uiri n g 
ora l a nti-i nfecti ve t hera p y wit hi n 6 wee ks of ra n d o mizati o n.
1 4) Hist or y  of o p p ort u nistic i nfecti o n.
1 5) Hist or y  of sy m pt o matic her pes z oster wit hi n 1 6 wee ks o f ra n d o mizati o n, or a ny hist or y  of 
disse mi nate d her pes si m ple x, disse mi nate d her pes z oster, o p ht hal mic z oster, or ce ntral 
ner v o us s ys te m z oster.
1 6) C urre ntl y  o n a n y c hr o nic s yste mic ( oral or i ntra ve n o us) a nti-i nfecti ve t hera p y f or c hr o nic 
i nfecti o n (s uc h as pne u m oc y stis, c yt o me gal o vir us, her pes z oster, or at y pical m yc o bacteria).
1 7) Use of pr o hi bite d c o nc o mita nt me dicati o ns as descri be d i n Secti o n 5. 4. 2 .
1 8) A d mi nistrati o n of a li ve or atte n uate d vacci ne wit hi n 4 wee ks of ra n d o mizati o n ( Secti o n 5. 5 )
1 9) Fe males w h o ma y  wis h t o bec o me pre g na nt a n d/ or pla n t o u n der g o e g g d o nati o n or e g g 
har vesti n g f or t he p ur p ose of c urre nt or f ut ure fertilizati o n d uri n g t he c o urse of t he st u d y  a n d 
u p t o 7 da y s after last d ose of t he st u d y dr u g .
2 0) Male s u bjects u n willi n g t o refrai n fr o m s per m d o nati o n f or at least 7 d a y s after last d ose of 
t he st u d y dr u g.
2 1) K n o w n h y perse nsiti vit y  t o G S -4 8 7 5 , its meta b olites, or f or m ulati o n e xci pie nts.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 3 2
1 9 J u ne 2 0 2 0
5.
I N V E S TI G ATI O N A L  M E DICI N A L  P R O D U C T S
5. 1.
R a n d o miz ati o n, Bli n di n g , a n d Tre at me nt C o des
5. 1. 1.
R a n d o miz ati o n
A n interacti ve w e b res p o nse sys te m (IW R S) will be e m pl o y e d t o ma na ge s u bject ra n d o mizati o n , 
treat me nt assi g n me nts, a n d st u d y dr u g s u p plies. It is t he res p o nsi bilit y of t he i n vesti gat or t o 
e ns ure t hat s u bject s are eli gi ble f or t he st u d y pri or t o e nr oll me nt. T he I W R S will assi g n s u bjects 
wit h a s u bject I D at t he ti me of e nr oll me nt.
5. 1. 2.
Bli n di n g
T his is a bli n de d st u d y  w here t he s p o ns or Gilea d is u n bli n de d as descri be d i n S ecti o n 5. 1. 3 a n d 
t he i n vesti gat ors a n d s u bjects are bli n de d. 
Bli n di n g of st u d y treat me nt is critical t o t he i nte grit y  of t his cli nical trial. H o we ver, s pecifie d 
pers o n nel ma y  be u n bli n de d base d o n t heir st u d y r ole. St u d y dr u g will be dis pe nse d b y t he st u d y 
p har macist, or desi g nee, i n a bli n de d fas hi o n t o t he s u bjects. T he P har mac o ki netics File 
A d mi nistrat or, or desi g nee, i n Bi oa nal yt ical O perati o ns a n d/ or Cli nical Data Ma na ge me nt, w h o 
facilitates t he data tra nsfer of P K files bet wee n Gilea d a n d ve n d ors, will be u n bli n de d. 
I n di vi d uals i n Cli nical Pac ka gi n g & La beli n g or Cli nical S u p pl y Ma na ge me nt w h o ha ve a n 
U n bli n de d I n ve nt or y  Ma na ger r ole i n t he IW R S s y ste m f or p ur p oses of st u d y dr u g i n ve nt or y 
ma na ge me nt will re ma i n u n bli n de d. In di vi d uals i n P har mac o vi gila nce a n d E pi de mi ol o g y  ( P V E) 
res p o nsi ble f or safety si g nal detecti o n ( Secti o n 7. 8 ), i n vesti gati o nal ne w dr u g (I N D) safety 
re p orti n g a n d/ or e x pe dite d re p orti n g of s us pecte d u ne x pecte d seri o us a d verse reacti o ns 
( S U S A Rs) ma y be u n bli n de d t o i n di vi d ual case data a n d/ or gr o u p level s u m maries. T he c o ntract 
researc h or ga nizati o n (C R O ) bi ostatisticia ns a n d pr o gra m mers will be u n bli n de d f or t he D M C 
data re vie ws a n d safet y s ur veilla nce.
5. 1. 3.
Pl a n ne d I nteri m U n bli n di n g
T o assess t he efficac y  of G S - 4 8 7 5 f or p ote ntial st u d y ter mi nati o n d ue to lac k of efficac y , a 
Gilea d i nter nal u n bli n de d tea m, t he G S -U S - 3 6 5-4 2 3 7 G D R C, i n de pe n de nt of t he bli n de d st u d y 
tea m, will be asse m ble d t o re vie w t he u n bli n de d st u d y res ults. T he G D R C will c o nsist of at least 
1 re prese ntati ve fr o m Gilea d Cli nical Researc h, Bi ostatistics, P V E , a n d Re g ulat or y Affairs, a n d 
ma y  i ncl u de ot her pers o n nel as necessar y i ncl u di n g e xter nal c o ns ulta nts wit h e x pertise i n I B D. 
T he G D R C will kee p t he u n bli n de d i nf or mati o n c o nfi de ntial. Site pers o n nel, s u bjects, Gilea d 
Me dical M o nit or, Gilea d/ C R O staff direct l y i nteracti n g wit h t he st u dy ce nter or me m bers of t he 
G S -U S -3 6 5- 4 2 3 7 St u d y  Ma na ge me nt Tea m will n ot be u n bli n de d t o t he s u bject treat me nt 
assi g n me nt a n d will n ot ha ve access t o u n bli n de d st u d y  data. T he G D R C will be gra nte d access 
t o u n bli n de d cli nical data at t he i n di vi d ual s u bject a n d/ or gr o u p s u m mar y le vel, i ncl u di n g 
treat me nt assi g n me nts, t o re vie w t he i nteri m a nalysis descri be d i n Secti o n 8. 2 .
T he me m bers hi p, c o n d uct, a n d meeti n g sc he d ule of t he G D R C will be s pecifie d i n t he Gilea d 
Data Re vie w C o m mittee C harter.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 3 3
1 9 J u ne 2 0 2 0
5. 1. 4.
Pr oce d ures f or Bre a ki n g Tre at me nt C o des
Treat me nt assi g n me nt s h o ul d re mai n bli n de d u nless k n o wi n g a s u bject’s treat me nt assi g n me nt is 
necessar y f or me dical care. I n t he e ve nt of a me dical e mer ge nc y w here brea ki n g t he bli n d is 
re q uire d t o pr o vi de me dical care t o t he s u bject, t he i n vesti gat or ma y o btai n treat me nt assi g n me nt 
directl y  fr o m t he IW R S s y ste m f or t hat s u bject. Gilea d rec o m me n ds, b ut d oes n ot re q uir e, t hat 
t he i n vesti gat or c o ntact t he me dical m o nit or bef ore brea ki n g t he bli n d. T he rati o nale f or 
u n bli n di n g m ust be clearl y e x plai ne d i n s o urce d oc u me ntati o n, al o n g wit h t he date o n w hic h t he 
treat me nt assi g n me nt was o btai ne d. If a s u bject’s treat me nt assi gn me nt is u n bli n de d, t he 
i n vesti gat or is re q uire d t o pr o m ptl y  c o ntact t he me dical mo nit or a n d t he s u bject will be 
disc o nti n ue d fr o m st u d y  dr u g.
5. 2.  
Descri pti o n a n d H a n dli n g of G S - 4 8 7 5
5. 2. 1.
F o r m ul ati o n
G S - 4 8 7 5 ta blets are a vaila ble i n 5 0 m g a n d 1 5 0 m g stre n gt hs. B ot h stre n gt hs of t he G S - 4 8 7 5
ta blets are w hite, plai n-face d, ca ps ule-s ha pe d, fil m-c oate d ta blets. I n a d diti o n t o t he acti ve 
i n gre die nt, G S - 4 8 7 5 ta blets als o c o ntai n c o p o vi d o ne, lact ose m o n o h ydrate, micr ocr y stalli ne 
cell ul ose, cr oscar mell ose s o di u m, ma g nes i u m stearate, p oly vi n yl alc o h ol, tita ni u m di o xi de, 
macr o g ol , a n d talc.
Place b o ta blets t o matc h t he G S - 4 8 7 5 ta blets will be use d f or bli n di n g p ur p oses. Place b o-t o-
matc h ( P T M) G S - 4 8 7 5 ta blets are i de ntical i n size, s ha pe, c ol or, a n d a p peara nce t o b ot h 
stre ngt hs ( 5 0 m g  a n d 1 5 0 m g) of acti ve G S - 4 8 7 5 ta blets. P T M ta blets c o ntai n lact ose 
m o n o h y drate, micr ocr y stalli ne cell ul ose, cr oscar mell ose s o di u m, ma g nesi u m stearate, p oly vi n yl  
alc o h ol, tita ni u m di o xi de, macr o g ol , a n d talc.
5. 2. 2.
P a c k a gi n g a n d L a beli n g
G S - 4 8 7 5 ta blets a n d matc hi n g place b o ta blets are pac ka ge d i n white, hi g h de nsit y  p olyet h yl e ne 
b ottles. Eac h b ottle c o ntai ns 3 0 ta blets, silica gel desicca nt a n d p olye ster pac ki n g material. Eac h 
b ottle is e ncl ose d wit h a w hite, c o nti n u o us t hrea d, c hil d -resista nt pol y pr o p y le ne scre w ca p wit h 
a n i n d ucti o n-seale d a n d al u mi n u m-face d li ner. 
St u d y  dr u g(s) t o be distri b ute d t o ce nters i n t he U nite d States (U S ) a n d ot her partici pati n g 
c o u ntries s hall be la bele d t o meet a p plica ble re q uire me nts of t he U nite d States F o o d a n d Dr u g 
A d mi nistrati o n ( F D A ), E ur o pea n U ni o n (E U ) G ui deli ne t o G o o d Ma n ufact uri n g Practice -A n ne x 
1 3 (I n vesti gati o nal Me dici nal Pr o d ucts), a n d/ or ot her l ocal re g ulati o ns.
5. 2. 3.
St or a ge a n d H a n dli n g
G S -4 8 7 5 a n d P T M ta blets s h o ul d be st ore d bel o w 3 0 ° C ( 8 6 ° F). St ora ge c o n diti o ns are s pecifie d 
o n t he la bel. U ntil dis pe nse d t o t he s u bjects, all b ottles of st u d y  dr u gs s h o ul d be st ore d i n a 
sec urely l oc ke d area, accessi ble o nl y t o a ut h orize d site pers o n nel.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 3 4
1 9 J u ne 2 0 2 0
T o e ns ure t he sta bilit y a n d pr o per i de ntificati o n, st u d y dr u gs s h o ul d n ot be st ore d i n a c o ntai ner 
ot her t ha n t he c o ntai ner i n w hic h t he y  were s u p plie d. Kee p t he c o ntai ner ti g htl y cl ose d t o pr otect 
fr o m m oist ure. C o nsi derati o n s h o ul d be gi ve n t o ha n dli n g, pre parati o n, a n d dis p osal t hr o u g h 
meas ures t hat mi ni mize dr u g c o ntact wit h t he b o d y . A p pr o priate preca uti o ns s h o ul d be f oll o we d 
t o a v oi d direct e ye c o ntact or e x p os ure w he n ha n dli n g.
5. 3.
D os a ge a n d A d mi nistr ati o n of G S - 4 8 7 5
T he st u d y  me dicati o n will c o nsist of G S - 4 8 7 5 5 0 m g ta blets, G S - 4 8 7 5 1 5 0 m g ta blets , a n d P T M 
ta blets f or oral a d mi nistrati o n .
T he treat me nts a d mi nistere d t o eac h treat me nt gr o u p i n t he Bli n de d Treat me nt p hase are as 
f oll o ws:

Tre at me nt gr o u p 1 : (G S -4 8 7 5 3 0 0 m g ) 2 G S -4 8 7 5 1 5 0 m g ta blets, orall y  o nce dail y 

Tre at me nt gr o u p 2: (G S - 4 8 7 5 1 0 0 m g) 2 G S - 4 8 7 5 5 0 m g ta blets, orall y  o nce daily 

Tre at me nt gr o u p 3: ( Place b o) 2 P T M ta blets, orall y  o nce dail y
T he treat me nt a d mi nistere d i n t he O L Treat me nt p hase is as f oll o ws:

O pe n -l a bel Tre at me nt: (G S -4 8 7 5 3 0 0 m g) 2 G S - 4 8 7 5 1 5 0 m g ta blets, orall y  o nce dail y
T he treat me nts a d mi nistere d t o eac h treat me nt gr o u p, after t he st u d y is u n bli n de d, as descri be d i n 
Secti o n 3 , are as f oll o ws:

Tre at me nt gr o u p 1: (G S - 4 8 7 5 3 0 0 m g) 2 G S -4 8 7 5 1 5 0 m g ta blets, orall y  o nce dail y 

Tre at me nt gr o u p 2: (G S - 4 8 7 5 1 0 0 m g) 2 G S -4 8 7 5 5 0 m g ta blets, orall y o nce dail y 

Tre at me nt gr o u p 3: Place b o s u bjects d isc o nti n ue st u d y dr u g
G S - 4 8 7 5 s h o ul d n ot be a d mi nistere d wit h f o o d . 
F or misse d d ose(s) of st u d y  me dicati o n, s u bjects s h o ul d be i nstr ucte d t o ta ke t he misse d d ose(s) 
of st u d y  me dicati o n as s o o n as p ossi ble d uri n g t he sa me da y. If t he misse d d ose is n ot ta ke n o n 
t he ori gi nal da y, t he n s u bjects s h o ul d n ot ta ke t he misse d d ose a n d t he misse d d ose s h o ul d be 
ret ur ne d t o t he st u dy dr u g b ottle. S u bjects s h o ul d be ca uti o ne d n ot t o d o u ble t he ne xt d ose 
(ie, ta ki n g t he misse d d ose of st u d y dr u g wit h t hat da y’s d ose).
5. 3. 1.  
R ati o n ale f or D ose Selecti o n
Gi ve n t he n o velt y of tar geti n g t he T P L 2 pat h wa y, G S - 4 8 7 5 d ose selecti o n was g ui de d b y t he 
g oal t o de m o nstrate a d ose/e x p os ure efficac y  relati o ns hi p. T he 3 0 0 m g d ose was selecte d s uc h 
t hat tr o u g h dr u g le vels, base d o n P hase 1 data, w o ul d be E C 6 0 f or t he i n vitr o LP S -sti m ulate d 
p h os p h or y late d E R K ( p E R K) assa y i n h u ma n w h ole bl o o d. T he 1 0 0 m g d ose was selecte d s uc h 


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 3 5
1 9 J u ne 2 0 2 0
t hat si m ulati o ns of tr o u g h dr u g le vels, w hic h were base d o n t he P hase 1 data , w o ul d be E C 5 0 at 
tr o u g h. T he selecti o n of t hese d oses of G S - 4 8 7 5 ( 1 0 0 a n d 3 0 0 m g) is s u p p orte d b y  t he safet y a n d 
P K data i n t he first -i n-h u ma n S t u d y G S-U S - 3 6 5-4 2 3 3.
5. 4.
Pri or a n d C o nc o mit a nt Me dic ati o ns
All me dicati o n s ta ke n u p t o 3 0 da ys pri or t o t he scree ni n g visit t hr o u g h t he e n d of st u d y 
( 3 0 d a y s after t he last d ose of st u d y  dr u g) nee d t o be rec or de d i n t he s o urce d oc u me nts a n d o n 
t he electr o nic case re p ort f or m ( e C R F). At eac h st u d y visit, t he st u d y ce nter will rec or d all
me dicati o ns ta ke n b y t he s u bject si nce t he last visit or d uri n g t he visit (as a p plica ble). All 
co nc o mita nt me dicati o ns (prescri pti o n, peri - pr oce d ural me dicati ons, o ver -t he-c o u nter 
me dicati o ns, i ncl u di n g vacci nes, vita mi ns, her bal , dietar y s u p ple me nts, a n d mi nerals) m ust be 
rec or de d i n t he c o nc o mita nt t hera p y secti o n of t he e C R F.
S u bjects usi n g oral c o ntrace pti ves or patc h c o ntrace pti ves m ust use ot her met h o ds of 
c o ntrace pti o n w hile o n st u d y . Please refer t o A p pe n di x 8 f or Pre g na nc y Preca uti o ns, Defi niti o n 
f or Fe male of C hil d beari n g P ote ntial, a n d C o ntrace pti ve Re q uire me nts.
Effecti ve t hera pies s h o ul d n ot be disc o nti n ue d f or t he s ole p ur p ose of partici pati n g i n t his st u d y . 
S u bjects ma y  recei ve me dicati o ns as s u p p orti ve care or t o treat A Es as dee me d necessar y b y t he 
in vesti gat or or t he s u bject’s p h y sicia n. Base d o n t heir cli nical j u d g me nt, in vesti gat or s a n d 
treati n g p h y sicia ns s h o ul d d o w hate ver is me dicall y a p pr o priate t o ma na ge s u bjects. As 
descri be d bel o w, c ha n ges i n c o nc o mita nt me dicati o ns ma y i m pact a s u bject’s partici pati o n i n t he 
st u d y. T he m e dical m o nit or ca n be c o ns ulte d pri or t o i nitiati o n of ne w me dicati o n s f or t he 
treat me nt of U C. 
5. 4. 1.  
All o we d C o nc o mit a nt Me dic ati o ns f or U C
T he all o we d c o nc o mita nt me dicati o n(s) f or U C s h o ul d be mai ntai ne d at a sta ble d ose f or t he 
d urati o n of t he st u d y . Su bjects o n c ortic oster oi ds f or t he treat me nt of U C at t he ti me of 
ra n d o mizati o n s h o ul d i nitiate a ster oi d ta per after t he Wee k 1 0 Visit (Secti o n 5. 4. 1. 1 ).
T he all o we d me dicati o ns f or U C are as f oll o ws:

Oral mesala mi ne c o m p o u n ds ( 5-A S A) pr o vi de d t he d ose prescri be d has bee n sta ble f or at 
least 4 wee ks pri or t o ra n d o mizati o n .

T hi o p uri nes (e g, a zat hi o pri ne, 6- M P ) a n d met h otre xate pr o vi de d t he d osi n g d urati o n m ust 
be f or at least 8 wee ks pri or t o ra n d o mizati o n a n d t he d ose m ust ha ve bee n sta ble f or at least 
4 wee ks pri or t o ra n d o mizati o n 

S y ste mically a bs or be d c ortic oster oi ds prescri be d at a sta ble d ose e q ui vale nt t o ≤ 3 0 m g/ da y  
pre d nis o ne or b u des o ni de prescri be d at a st a ble d ose of ≤ 9 m g/ da y . The d ose s prescri be d 
m ust ha ve bee n sta ble f or 2 wee ks pri or t o t he scree ni n g e n d osc o p y. 
D ue t o t he p ote ntial f or dr u g-dr u g i nteracti o ns, s ulfasalazi ne is pr o hi bite d fr o m 2 wee ks pri or t o 
t he scree ni n g e n d osc o py a n d t hr o u g h o ut treat me nt wit h st u d y  dr u g.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 3 6
1 9 J u ne 2 0 2 0
C ha n ges t o all o we d c o nc o mita nt me dicati o ns f or U C ma y  c o nf o u n d t he efficac y a n d safety 
assess me nt s of G S - 4 8 7 5. T heref ore, s u bjects w h o start or i ncrease t he d ose (c o m pare d wit h t he 
d ose at Da y 1) of t he a b o ve all o we d c o nc o mita nt me dicati o n s, d uri n g eit her t he Bli n de d 
Treat me nt p hase or t he O L Treat me nt p hase , m ust disc o nti n ue st u d y dr u g a n d st u d y 
partici pati o n.
5. 4. 1. 1. 
C ortic oster oi d Ta peri n g
A ster oi d ta per s h o ul d be i nitiate d a fter M C S Res p o nse ha d bee n e val uate d at Wee k 1 0 ( Bli n de d 
Tre at me nt p hase or O L Treat me nt p hase ) a n d it is deter mi ne d t hat t he s u bject has ac hie ve d M C S 
res p o nse a n d will c o nti n ue o n st u d y . T he ti mi n g of t he ster oi d ta per is at t he discreti o n of t he 
i n vesti gat or b ut s h o ul d be gi n n o later t ha n Wee k 1 4. T he d ose s h o ul d be re d uce d at a rate 
starti n g at 2. 5 m g  per wee k u p t o a n d i ncl u di n g 5 m g per wee k ( or e q ui vale nt ta per if n ot 
pre d nis o ne) u ntil t he s u bject is n o l o n ger o n ster oi ds. S u bjects w h o are o n b u des o ni de s h o ul d 
ha ve t heir dail y d ose re d uce d b y 3 m g e ver y  3 wee ks u ntil t he y are c o m pletel y off ster oi ds. F or 
s u bjects u n der g oi n g ta per, ster oi ds ma y be i ncrease d or re-starte d at d oses u p t o a n d i ncl u di n g 
t heir Bli n de d Treat me nt p hase Da y  1 d ose if ret ur n of s y m pt o ms is a p pare nt. S u bjects w h o are 
u na ble t o ster oi d ta p er are all o we d t o c o nti n ue i n t he st u d y . S u bjects w h o nee d t o i ncrease ster oi d 
d ose or i nte nsif y  ster oi d treat me nt d ose o ver t heir baseli ne d ose m ust be disc o nti n ue d fr o m st u d y
dr u g . 
5. 4. 2.
Pr o hi bite d C o nc o mit a nt Me dic ati o ns
C o -a d mi nistrati o n of C Y P 3 A i n hi bit ors ma y  i ncrease G S - 4 8 7 5 e x p os ure. I n a dr u g -dr u g 
i nteracti o n st u d y of G S -4 8 7 5 c o-a d mi nistere d wit h v oric o naz ole (str o n g C Y P 3 A i n hi bit or), 
G S - 4 8 7 5 e x p os ures were si g nifica ntl y i ncrease d. T heref ore, c o -a d mi nistrati o n of str o n g or 
m o derate C Y P 3 A i n hi bit ors wit h st u d y dr u g are pr o hi bite d.
C o -a d mi nistrati o n of C Y P 3 A i n d ucers ma y  decrease G S - 4 8 7 5 e x p os ure. I n a dr u g -dr u g 
i nteracti o n st u d y of G S -4 8 7 5 c o-a d mi nistere d wit h m ulti ple d ose rifa m pi n ( C Y P 3 A i n d ucer), 
G S - 4 8 7 5 e x p os ures were re d uce d. T heref ore, c o -a d mi nistrati o n of str o n g or m o derate C Y P 3 A
i n d ucers wit h st u d y dr u g is pr o hi bite d.
I n vitr o data i n dicate t hat G S - 4 8 7 5 is a s u bstrate of P-gl yc o pr otei n ( P-g p ) a n d breast ca ncer 
resista nce pr otei n (B C R P ). C o-a d mi nistrati o n of P-g p a n d B C R P i n hi bit ors ma y i ncrease 
G S - 4 8 7 5 e x p os ure. T heref ore, c o -a d mi nistrati o n of P- g p a n d B C R P i n hi bit ors are n ot all o we d 
wit h st u d y  dr u g. C o -a d mi nistrati o n of P- g p i n d ucers ma y decrease G S -4 8 7 5 e x p os ure. T heref ore, 
c o-a d mi nistrati o n of P-g p i n d ucers are n ot all o we d wit h st u d y  dr u g.
I n vitr o data s u g gest t hat G S - 4 8 7 5 has t he p ote ntial t o i n hi bit M A T E 1, O A T P 1 B 1 , O A T P 1 B 3 , 
a n d O A T P 2 B 1 . G S -4 8 7 5 has t he p ote ntial t o i ncrease t he e x p os ure of M A T E 1 a n d
O A T P 
se nsiti ve s u bstrates. T heref ore, c o-a d mi nistrati o n of M A T E 1 a n d
O A T P se nsiti ve s u bstrates wit h 
st u d y dr u g is pr o hi bite d.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 3 7
1 9 J u ne 2 0 2 0
I n vitr o data s u g gest t hat G S - 4 8 7 5 has t he p ote ntial t o i n hi bit P -g p a n d B C R P. C o -a d mi nistrati o n 
of P -g p a n d B C R P se nsiti ve s u bstrates wit h a narr o w t hera pe utic i n de x is pr o hi bite d. 
C o -a d mi nistrati o n of G S - 4 8 7 5 wit h s ulfasalazi ne ma y  i ncrease e x p os ure of s ulfasalazi ne. 
T heref ore, s ulfasalazi ne is pr o hi bite d 2 wee ks pri or t o scree ni n g e n d osc o py t hr o u g h t he e n d of 
treat me nt. Besi des s ulfasalazi ne, ot her mesala mi ne - base d me dicati o ns ma y be c o-a d mi nistere d 
wit h G S -4 8 7 5.
F or m ore i nf or mati o n ar o u n d G S -4 8 7 5 dr u g -dr u g i nteracti o ns refer t o t he G S - 4 8 7 5 I B a n d 
Secti o n 1. 3. 3. 1 . E xa m ples of re prese ntati ve me dicati o ns w hic h are p r o hi bite d are prese nte d i n
Ta ble 5- 1 . If a pr o hi bite d c o nc o mita nt me dicati o n wit h p ote ntial dr u g -dr u g i nter acti o ns is ta ke n 
b y  a s u bject, i n vesti gat ors m ust c o ntact t he me dical m o nit or.
T a ble 5- 1. 
E x a m ples of Pr o hi bite d C o nc o mit a nt Me dic ati o ns f or P ote nti al 
Dr u g -Dr u g I nter acti o ns a , b
P ossi ble Mec h a nis m of 
Acti o n or Dr u g Cl ass
A ge nts Dis all o we d
Pr o hi bite d Peri o d
Str o n g C Y P 3 A I n hi bit ors
clarit hr o m yci n, c o ni va pta n, itrac o naz ole, 
ket oc o naz ole, nefaz o d o ne, p osac o naz ole, 
telit hr o m yci n, v oric o naz ole, rit o na vir, c o bicistat, 
tela pre vir, b oce pre vir, i delalisi b
2 wee ks pri or t o ra n d o mizati o n 
t hr o u g h t he e n d of treat me nt
Str o n g C Y P 3 A I n d ucers
car ba maze pi ne, p he n yt oi n, rifa m pi n, f os p he n yt oi n, 
pe nt o bar bital, pri mi d o ne, rifa b uti n, rifa pe nti ne, 
p he n o bar bital, o xcar baze pi ne, mit ota ne, a vasi mi be
2 wee ks pri or t o ra n d o mizati o n
t hr o u g h t he e n d of treat me nt
M o derate C Y P 3 A 
I n hi bit ors
fl uc o naz ole, er yt hr o m yci n, diltiaze m, dr o ne dar o ne, 
a pre pita nt, i mati ni b, vera pa mil, t ofis o pa m, 
ci pr ofl o xaci n, ci meti di ne, c ycl os p ori ne c, Sc hisa n dra
s p he na nt hera
2 wee ks pri or t o ra n d o mizati o n
t hr o u g h t he e n d of treat me nt
M o derate C Y P 3 A 
I n d ucers
efa vire nz, ti pra na vir/rit o na vir, b ose nta n, t hi ori dazi ne, 
nafcilli n, tal virali ne, l o pi na vir, m o dafi nil, etra viri ne, 
lersi viri ne, se ma gacestat, ge nistei n
2 wee ks pri or t o ra n d o mizati o n
t hr o u g h t he e n d of treat me nt
P g p I n hi bit ors
a mi o dar o ne, car ve dil ol, clarit hr o m yci n, dr o ne dar o ne, 
itrac o naz ole, la pati ni b, pr o pafe n o ne, q ui ni di ne, 
ra n olazi ne, rit o na vir, tela pre vir, vera pa mil
2 wee ks pri or t o ra n d o mizati o n 
t hr o u g h t he e n d of treat me nt
P g p I n d ucers
rifa m pi n, p he n yt oi n, car ba maze pi ne, rifa b uti n, 
rifa pe nti ne
2 wee ks pri or t o ra n d o mizati o n 
t hr o u g h t he e n d of treat me nt
B C R P I n hi bit ors
c ycl os p ori ne c, gefiti ni b, s ulfasalazi nee, c urc u mi n, 
eltr o m b o pa g
2 wee ks pri or t o ra n d o mizati o n 
t hr o u g h t he e n d of treat me nt
O A T P 1 B 1 , O A T P 1 B 3 , 
a n d O A T P 2 B 1 S u bstrates
as u na pre vir, at or vastati n, b ose nta n, ceri vastati n, 
da n o pre vir, d oceta xel, fe x ofe na di ne, paclita xel,
fl u vastati n, l o vastati n, pita vastati n, pra vastati n, 
r os u vastati n
2 wee ks pri or t o ra n d o mizati o n 
t hr o u g h t he e n d of treat me nt
M A T E 1 Se nsiti ve 
S u bstrates
d ofetili de, metf or mi n
2 wee ks pri or t o ra n d o mizati o n 
t hr o u g h t he e n d of treat me nt
P g p Se nsiti ve S u bstrates
d a bi gatra n, di g o xi n, fe x ofe na di ne
2 wee ks pri or t o ra n d o mizati o n 
t hr o u g h t he e n d of treat me nt


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 3 8
1 9 J u ne 2 0 2 0
P ossi ble Mec h a nis m of 
Acti o n or Dr u g Cl ass
A ge nts Dis all o we d
Pr o hi bite d Peri o d
B C R P Se nsiti ve 
S u bstrates
r os u vastati n, s ulfasalazi ned
2 wee ks pri or t o ra n d o mizati o n 
t hr o u g h t he e n d of treat me nt
Her bal/ Nat ural 
S u p ple me nts e
Gra pefr uit j uice, St J o h n’s W ort 
2 wee ks pri or t o ra n d o miz ati o n 
t hr o u g h t he e n d of treat me nt
a  
N ot all of t hese e xa m ple me dicati o ns ma y be a p pr o ve d i n eac h of t he c o u ntries w here t he st u d y is bei n g c o n d ucte d; please 
refer t o l ocal pr o d uct i nf or mati o n.
b
Ta ble is n ot all i ncl usi ve.
c
C y cl os p ori ne is pr o hi bite d 2 wee ks pri or t o scree ni n g e n d osc o p y t hr o u g h t he e n d of treat me nt ( please refer t o Ta ble 5 2 ).
d
S ulfasalazi ne is pr o hi bite d 2 wee ks pri or t o scree ni n g e n d osc o p y ( please re fer t o Ta ble 5 2 ).
e
C o ns ult t he me dical m o nit or f or a n y h er bal/ n at ural s u p ple me nts n ot liste d t hat ma y ha ve p ote ntial dr u g dr u g i nteracti o ns 
wit h st u d y dr u g or if it is u n k n o w n w het her t here is a p ote ntial dr u g dr u g i nteracti o n wit h st u d y dr u g.
S o me me dicati o n s a n d treat me nts ma y ha ve a n i m pact o n t he safet y of t he s u bject s a n d/ or efficac y 
assess me nts of t his st u d y. Pr o hi bite d co nc o mita nt m e dicati o ns t hat m a y im pact efficac y 
assess me nts or i m pact s u bject safety are prese nte d i n Ta ble 5- 2 . S u bjects t hat i nitiate a n y of 
t hese c o nc o mita nt me dicati o ns at a n y  ti me d uri n g t he Bli n de d Treat me nt p hase st u d y m ust be 
disc o nti n ue d fr o m st u d y  dr u g a n d will n ot be eli gi ble f or t he O L p hase of t he st u d y. S u bjects t hat 
i nitiate a n y of t hese c o nc o mita nt me dicati o ns at a n y ti me d uri n g t he O L p hase of t he st u d y m ust 
be disc o nti n ue d fr o m st u d y  dr u g.
T a ble 5- 2.
Pr o hi bite d C o nc o mit a nt Me dic ati o ns t h at M a y I m p act Effic ac y 
Assess me nts or I m p act S u bject S afet y
Dr u g Cl ass
A ge nts Dis all o we d 
Pr o hi bite d Peri o d
T N F α a nta g o nist
infli xi ma b, a dali m u ma b, g oli m u ma b, 
cert oliz u ma b, or bi osi milar a ge nt
1 2 we e ks pri or t o ra n d o mizati o n or a n 
u n detecta ble ser u m le vel o n a 
c o m merciall y a vaila ble assa y t hr o u g h t he 
e n d of treat me nt
I nte gri n a nta g o nist
v e d oliz u ma b , nataliz u ma b
1 2 we e ks pri or t o ra n d o mizati o n or a n 
u n detecta ble ser u m le vel o n a 
c o m merciall y a vaila ble assa y t hr o u g h t he 
e n d of treat me nt
I nterle u ki n a nta g o nist
u ste ki n u ma b
1 6 we e ks pri or t o ra n d o mizati o n or a n 
u n detecta ble ser u m le vel o n a 
c o m merciall y a vaila ble assa y t hr o u g h t he 
e n d of treat me nt
Rectal c o m p o u n ds
rectal mesala mi ne , rectal c ortic oster oi ds
2 we e ks pri or t o scree ni n g e n d osc o p y 
t hr o u g h t he e n d of treat me nt
A nti diarr heal a ge nts
lo pera mi de , di p he n o x ylate/atr o pi ne
2 we e ks pri or t o scree ni n g e n d osc o p y 
t hr o u g h t he e n d of treat me nt
U C me dicati o n wit h 
p ote n tial dr u g-dr u g 
i nteracti o ns
sulfasalazi ne 
2 we e ks pri or t o scree ni n g e n d osc o p y
t hr o u g h t he e n d of treat me nt


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 3 9
1 9 J u ne 2 0 2 0
Dr u g Cl ass
A ge nts Dis all o we d 
Pr o hi bite d Peri o d
Ot her ( n o n -bi ol o gic)
c ycl os p ori ne, t hali d o mi de, tacr oli m us, 
lefl u n o mi de, J A K i n hi bit ors, a n d a n y 
i n vesti gati o nal a ge nt
2 we e ks pri or t o scree ni n g e n d osc o p y 
t hr o u g h t he e n d of treat me nt
I n vesti gati o nal 
bi ol o gics
A n y i n vesti gati o nal bi ol o gic a ge nt
1 2 we e ks pri or t o ra n d o mizati o n t hr o u g h 
t he e n d of treat me nt ( or at least 5 half-
li ves)
L y m p h oc yte -de pleti n g 
t hera pies
al e mt uz u ma b, c ycl o p h os p ha mi de, t otal 
l y m p h oi d irra diati o n, rit u xi ma b, a n d a n y 
ot her l y m p h oc yte -de pleti n g t hera p y
A n y ti me bef ore a n d t hr o u g h t he e n d of 
treat me nt
If ot her pr o hi bite d c o nc o mita nt me dicati o ns, as prese nte d i n Ta ble 5- 3 are ta ke n b y a s u bject 
pri or t o st u d y  partici pati o n or i nitiate d d uri n g t he st u d y, i n vesti gat ors m ust c o ntact t he me dical 
m o nit or.
T a ble 5 - 3.
Ot her Pr o hi bite d C o nc o mit a nt Me dic ati o ns
Dr u g Cl ass
A ge nts Dis all o we d 
Pr o hi bite d Peri o d
Ot her bi ol o gics
Fecal Micr o bi ota Tra ns pla nt ( F M T), 
A nti b o d y base d or ot her s yste mic 
bi ol o gics, e g, de n os u ma b, trast uz u ma b
Re q uires me dical m o nit or c o ns ultati o n
5. 5.
V acci ne G ui deli nes

Pri or t o st u d y  partici pati o n, it is rec o m me n de d t hat t he s u bject’s vacci nati o ns be br o u g ht u p 
t o date acc or di n g t o l ocal vacci nati o n sta n dar ds.

Li ve or atte n uate d vacci nes (i ncl u di n g, b ut n ot li mite d t o varicella a n d i n hale d fl u vacci ne)
are pr o hi bite d wit hi n 4 wee ks of ra n d o mizati o n, t hr o u g h o ut t he st u dy, a n d f or 1 2 wee ks after 
t he last d ose of st u d y dr u g

S u bjects s h o ul d be a d vise d t o a v oi d r o uti ne h o use h ol d c o ntact wit h pers o ns vacci nate d wit h 
li ve/atte n uate d vacci ne c o m p o ne nts. Ge neral g ui deli nes s u g gest t hat a st u d y s u bject’s 
e x p os ure t o h o use h ol d c o ntacts s h o ul d be a v oi de d f or t he bel o w state d ti me peri o ds:
Varicella or atte n uate d t y p h oi d fe ver vacci nati o n 
a v oi d c o ntact f or 4 wee ks f oll o wi n g 
vacci nati o n
Oral p oli o vacci nati o n 
a v oi d c o ntact f or 6 wee ks f oll o wi n g vacci nati o n
Atte n uate d r ota vir us vacci ne 
a v oi d c o ntact f or 1 0 da ys f oll o wi n g vacci nati o n
I n haled fl u vacci ne 
a v oi d c o ntact f or 1 wee k f oll o wi n g vacci nati o n


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 4 0
1 9 J u ne 2 0 2 0

I nacti vate d vacci nes (s uc h as i nacti vate d fl u vacci nes) s h o ul d be a d mi nistere d acc or di n g t o 
l ocal vacci nati o n sta n dar ds w he ne ver me dically a p pr o priate; h o we ver, t here are n o a vaila ble 
data o n t he c o nc urre nt use of G S - 4 8 7 5 a n d its i m pact o n i m m u ne res p o nses f oll o wi n g 
vacci nati o n .
5. 6.
Acc o u nt a bilit y for St u d y Dr u g
T he i n vesti gat or is res p o nsi ble f or e ns uri n g a de q uate acc o u nta bilit y  of all use d a n d u n use d 
i n vesti gati o nal me dici nal pr o d uct (I M P) b ottles . T his i ncl u des ac k n o wle d ge me nt of recei pt of 
eac h s hi p me nt of I M P ( q ua ntit y a n d c o n diti o n). All use d a n d u n use d I M P b ottles dis pe nse d t o 
s u bjects m ust be ret ur ne d t o t he site.
St u d y  dr u g a cc o u nta bilit y rec or ds will be pr o vi de d t o eac h st u d y site t o:

Rec or d t he date recei ve d a n d q ua ntit y  of I M P b ottles

Rec or d t he date , s u bject n u m ber a n d t he I M P kit n u m ber dis pe nse d

Rec or d t he date, q ua ntit y of use d a n d u n use d I M P b ottles ret ur ne d, al o n g wit h t he i nitials of 
t he pers o n rec or di n g t he i nf or mati o n.
If p ote ntial de viati o ns i n t he ma n ufact ure, pac ka gi n g, or distri b uti o n of t he me dici nal pr o d uct are 
i de ntifie d, t he n a pr o d uct c o m plai nt s h o ul d be file d wit h t he s p o ns or u p o n i de ntificati o n.
5. 6. 1. 
I n vesti g ati o n al M e dici n al Pr o d uct Ret ur n or Dis p os al
Please refer t o Secti o n 9. 1. 8 .


G S -4 8 7 5 
Pr ot o c ol G S -U S -3 6 5- 4 2 3 7 
Gil e a d S ci e n c es, I nc. 
Fi nal 
A m e n d m e nt 2 
6. 
S T U D Y P R O C E D U R E S 
T h e fr e q u e n c y a n d ti min g of st u d y pr o c e d ur es t o b e c o n d u ct e d f or e a c h s u bj e ct i n t h e Bli n de d 
T r e at m e nt p h as e are pr es e nt e d i n t a b ular f o n n i n A p p e n di x 2 a n d i n A p p e n di x 3 f or t h e O L 
T r e at m e nt p h as e . T h e a p pr o x im at e t ot al a m o u nt of bl o o d t a k e n at e a c h visit is i n cl u d e d i n t he 
St u d y Pr o c e d ur es T a b les i n A p p e n di x 2 a n d A p p e n di x 3. A d d iti o n al i nf o n n atio n is pr o v ide d i n 
t he st u d y la b or at or y m a n u a l a n d v e n d or m a n u a ls. 
T h e in v estig at or m ust d o c u m e nt a n y d e v iat io n fr o m pr ot o c o l pr o c e d ur es a n d n ot if y t h e s p o ns or 
or C R O . 
6. 1. 
S u bj e ct I nf o r m e d C o ns e nt 
At t he s cr e e nin g visi t, inf o n n e d c o ns e nt m ust b e o bt a in e d b y t h e i n v estig at or or a p pr o priat e 
d es ig n e e b ef or e a n y pr ot o c o l-s p e cifie d pr o c e d ur es o c c ur or a n y pr ot o c o l-s p e cifie d s a m p les ar e 
c o lle ct e d . Pr ior t o c o ns e ntin g t o t he st u d y, e a c h s u bj e ct s h o u l d u n d erst a n d t h e n at ur e of t he st u d y 
a n d t h e ris ks ass o c iat e d wi t h t h e st u d y as w e ll as t he s u bj e ct p arti cip at io n r e q uir e m e nts. 
-
6. 2.  
S e q u e n c e of A ss ess m e nts at Visits 
H e a lt h-relat e d q u a lit y of life ( H R Q o L) a n d h e alt h c ar e r es o ur c e ut iliz at io n ( H C R U) 
q u estio 1 maires ( S e ctio ns 6. 8. 2 a n d 6. 8. 3) s h o u l d b e c o m p let e d pri or t o a n y ot h er st u d y 
pr o c e d ur es . 
6. 3. 
6. 3. 1. 
P r et r e at m e nt A ss ess m e nts 
S c r e e ni n g 
S u b je cts w ill b e s cr e e n e d u p t o 3 0 d a ys b ef or e r a n d o miz at io n t o d et e n n in e e ligi b ilit y f or 
p art icip atio n i n t he st u d y. Th e f ollo w in g w ill b e c o m p let e d a n d d o c u m e nt e d i n s o ur c e d at a at 
s cr e e m n g: 
• 
O bt a i n wr itt e n inf o n n e d c o ns e nt 
C O N FI D E N T IA L 
P a g e 4 1 
1 9 Ju n e 2 0 2 0 


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 4 2
1 9 J u ne 2 0 2 0

Re vie w i ncl usi o n/e xcl usi o n criteria a n d ot her pr ot oc ol restricti o ns ( Secti o n 4 )

T he asse ss me nts t o be c o m plete d at t he scree ni n g visit are o utli ne d i n t he St u d y Pr oce d ures 
Ta ble i n A p pe n di x 2 .
I m p orta nt i nf or mati o n a b o ut safety assess me nts, cli nical la b orat or y e val uati o ns i ncl u di n g 
ser u m c he mistr y, he mat ol o g y, pre g na nc y  testi n g, T B , HI V a n d he patitis scree ni n g , a n d 
uri nal y sis is pr o vi de d i n Secti o n 6. 9 . St o ol sa m ples will be c ollecte d at scree ni n g t o
ide ntif y  a ny e nteric pat h o ge ns , f or micr o bi o me a nal ysis, a n d f or meas uri n g bi o mar kers: 
fecal cal protecti n a n d lact oferri n. T he uri nal ys is at scree ni n g will i ncl u de a dr u g scree n. 

e-Diar y  i nstr ucti o ns
S u bjects m ust be p r o vi ded wit h t he electr o nic diar y ( e-Diar y ) de vice a n d i nstr ucti o ns f or 
dail y  d oc u me ntati o n of St o ol Fre q ue nc y a n d Rectal Blee di n g s u b sc ores. T hese data are 
use d t o calc ulate 2 of t he 4 s u bsc ores t hat c o m p ose t he M C S. S u bjects s h o ul d be gi n 
filli n g o ut t he electr o nic diar y (e- Diar y ) t he da y of t heir i nitial scree ni n g visit a n d 
c o nti n ue t o fill it o ut o n a dail y  basis t hr o u g h o ut t he re mai nder of t he st u d y .
S u bjects s h o ul d be c o u nsele d t hat t heir n or mal st o ol fre q ue nc y (N S F ) is t he a vera ge dail y 
st o ol c o u nt t he s u bject e x perie nces w he n disease-free (i e, i n re missi o n). If t he s u bject has 
ne ver bee n i n re missi o n, t he s u bject s h o ul d be c o u nsel e d t hat t heir N S F is w he n t he y 
were healt h y  (ie, pri or t o i nitial o nset of si g ns a n d s ym pt o ms of U C ).

C ol o n o sc o p y/ Fle xi ble Si g m oi d osc o p y wit h bi o psies
S u bject d iar y data a n d ot her eli gi bilit y criteria s h o ul d be re vie we d pri or t o sc he d uli n g t he 
scree ni n g visit e n d osc o p y t o e ns ure a s u bject is eli gi ble (ie, meets St o ol Fre q ue nc y a n d 
Rectal Blee di n g re q uire me nts) pri or t o perf or mi n g t he e n d osc o p y , see A p pe n di x 4 .
C ollect i ntesti nal bi o psies. See Secti o n 6. 8. 1. 2 f or m ore i nf or mati o n. Res ults of scree ni n g 
bi o psies will n ot be pr o vi de d t o t he sites; a d diti o nal sa m ples s h o ul d be o btai ne d if t he 
in vesti gat or re q uires hist ol o gical assess me nt f or patie nt ma na ge me nt.

T he E n d osc o pic F i n di n gs s u bsc ore will be pr o vi de d t o t he sites b y  t he ce ntral rea d er. T he 
val ue pr o vi de d b y t he ce ntral rea der a n d t h e P G A is t o be rec or de d by t he i n vesti gat or ( or 
desi g nee) f or ce ntral calc ulati o n of M C S a n d deter mi nati o n of st u d y  eli gi bilit y.
S u bjects meeti n g all of t he i ncl usi o n criteria a n d n o ne of t he e xcl usi o n criteria will ret ur n t o t he 
cli nic wit hi n 3 0 da y s of t he i nitiati o n of scree ni n g f or ra n d o mizati o n i nt o t he st u d y. S u bjects ma y  
be ra n d o mize d m ore t ha n 3 0 da y s after i nitial scree ni n g if per missi o n is o btai ne d fr o m t he 
me dical m o nit or. If t he s u bject is n ot ra n d o mize d wit hi n t his 3 0 -da y wi n d o w, s pecific scree ni n g 
e val uati o n pr oce d ures ma y nee d t o be repeate d at t he directi o n of t he me dical m o nit or. N o m ore 
t ha n 1 re peat scree ni n g visit is all o we d f or eac h s u bject t hat was pre vi o usl y scree n faile d, u nless 
pri or writte n a p pr o val has bee n pr o vi de d b y t he sp o ns or. Re fer t o Secti o n 6. 9. 5. 1 f or m ore 
i nf or mati o n a b o ut la b orat or y retesti n g.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 4 3
1 9 J u ne 2 0 2 0
6. 3. 2.
B aseli ne / D a y 1 Assess me nts – Bli n de d Tre at me nt P h ase
T he Bli n de d Treat me nt p hase D a y 1 assess me nts t o be c o m plete d at t his visit are o utli ne d i n t he 
St u d y  Pr oce d ures Ta ble i n A p pe n di x 2 wit h a d diti o nal i nf or mati o n o n assess me nts pr o vi de d i n 
Secti o ns 6. 8 t o 6. 1 2 .
Pri or t o a d mi nistrati o n of st u d y  dr u g, e ns ure all Da y 1 assess me nts are c o m plete d. 
6. 3. 3.
D a y 1 Assess me nts – O pe n -L a bel Tre at me nt P h ase
T he O L Treat me nt p hase Da y  1 s h o ul d occ ur wit hi n 1 4 da y s of Bli n de d Treat me nt p hase 
Wee k
1 0 visit u n less ot her wise a p pr o ve d by t he me dical m o nit or. T he O L Treat me nt p hase 
D a y 1 assess me nts t o be c o m plete d at t his visit are o utli ne d i n t he St u d y Pr oce d ures Ta ble i n
A p pe n di x 3 wit h a d diti o nal i nf or mati o n o n assess me nts pr o vi de d i n Secti o ns 6. 8 t o 6. 1 2 .
Pri or t o a d mi nistrati o n of st u d y  dr u g, e ns ure all Da y 1 assess me nts are c o m plete d. 
6. 4.
R a n d o miz ati o n a n d St u d y Dr u g A d mi nistr ati o n – Bli n de d Tre at me nt P h ase
6. 4. 1.
R a n d o miz ati o n a n d Tre at me nt Assi g n me nt
S u bjects w h o meet pr ot oc ol eli gi bilit y  criteria will be ra n d o mize d i n a 1: 1: 1 rati o t o 1 of 
3 treat me nt gr o u ps as descri be d i n Secti o n 3 . 
Ra n d o mizati o n, stratif icati o n, a n d st u d y dr u g dis pe nsi n g will be ma na ge d usi n g a n I W R s yste m. 
6. 4. 2.
St u d y Dr u g A d mi nistr ati o n
T he pr oce d ure f or a d mi nistrati o n of t he first d ose of st u d y  dr u g is as f oll o ws:

E nter s u bject i nf or mati o n i n t he I W R S t o recei ve treat me nt assi g n me nt

Dis pe nse st u d y dr u g as directe d b y t he I WR S

I nstr uct t he s u bject o n t he pac ka gi n g, st ora ge, a n d a d mi nistrati o n of t he st u d y dr u g
I nstr uct t he s u bject t o ta ke 2 pills at eac h d osi n g
I nstr uct t he s u bject n ot t o ta ke t he st u d y dr u g wit h f o o d

O bser ve t he s u bject ta ki n g t he first d ose of st u d y dr u g a n d rec or d t he ti me of first d ose
At eac h s u bse q ue nt st u d y dr u g dis pe nsi n g visit, a ut h orize d pers o n nel will l o g i nt o t he I W R S 
s yste m f or t he a p pr o priate b ottle n u m ber(s) t o be dis pe nse d. T he b ottles dis pe nse d will c o ntai n 
t he rele va nt st u d y me dicati o n f or t he peri o d u ntil t he ne xt visit.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 4 4
1 9 J u ne 2 0 2 0
6. 5.
Tre at me nt Assess me nts
6. 5. 1.
Wee ks 2, 4 a n d 6 – Bli n de d Tre at me nt & O pe n -L a bel Tre at me nt P h ases
T he Bli n de d Treat me nt p hase assess me nts t o be c o m plete d at t hese visits are o utli ne d i n t he 
St u d y  Pr oce d ures Ta ble i n A p pe n di x 2 a n d t he O L Treat me nt p hase assess me nts t o be c o m plete d 
at t hese visits are o utli ne d i n t he St u d y Pr oce d ures Ta ble i n A p pe n di x 3 wit h a d diti o nal 
i nf or mati o n o n assess me nts pr o vi de d i n Secti o ns 6. 8 t o 6. 1 2 .
6. 5. 2.
Wee k 1 0 – Bli n de d Tre at me nt & O pe n -L a bel Tre at me nt P h ases
T he Bli n de d Treat me nt p hase assess me nts t o be c o m plete d at t his visit are o utli ne d i n t he St u d y 
Pr oce d ures Ta ble i n A p pe n di x 2 a n d t he O L Treat me nt p hase assess me nts t o be c o m plete d at 
t hese visits are o utli ne d i n t he St u d y Pr oce d ures Ta ble i n A p pe n di x 3 wit h a d diti o nal i nf or mati o n 
o n assess me nts pr o vi de d i n Secti o ns 6. 8 t o 6. 1 2 .
At t his visit, all s u bjects will ha ve a n efficac y  assess me nt t hat i ncl u des a C ol o n osc o p y / Fle xi ble 
Si g m oi d osc o p y  wit h c ollecti o n of bi o ps ies. S u bject d iar y data e ntr y s h o ul d be re vie we d pri or t o 
perf or mi n g t he Wee k 1 0 e n d osc o p y t o e ns ure s u bject s ha ve s ufficie nt data e ntr y  t o calc ulate 
Wee k 1 0 M C S s u bsc ores. F oll o wi n g t he visit, t he E n d osc o pic F i n di n gs will be pr o vi de d t o t he 
sites after ce ntral rea d. T he val ue pr o vi de d by t he ce ntral rea der a n d t he P G A is t o be rec or de d
b y t he i n vesti gat or ( or desi g nee) f or ce ntral calc ulati o n of M C S a n d s u bject M C S Res p o nse 
deter mi nati o n .
U ntil res p o nse ca n be assesse d base d o n Wee k 1 0 res ults, s u bjects will c o nti n ue o n t heir c urre nt 
assi g ne d st u d y dr u g re gi me n. I n t he Bli n de d Treat me nt P hase, s u bjects w h o ac hie ve M C S 
Res p o nse ( Secti o n 2 ) base d o n res ults fr o m Wee k 1 0 will c o nti n ue i n t he Bli n de d Treat me nt 
p hase. S u bjects w h o d o n ot ac hie ve M C S Res p o nse ( Secti o n 2 ) at Wee k 1 0 will ha ve t he o pti o n 
t o e nter t he O L Treat me nt p hase . S u bjects wit h i nc o m plete data t o assess M C S Res p o nse will 
disc o nti n ue st u d y dr u g a n d are n ot eligi ble f or t he O L  Treat me nt p hase.
I n t he O L Treat me nt p hase, s u bjects w h o ac hie ve M C S Res p o nse ( Secti o n 2 ) at Wee k 1 0 will 
c o nti n ue i n t he O L Treat me nt p hase. All ot her s u bjects will disc o nti n ue t he O L Treat me nt p hase.
S u bjects wit h i nc o m plete data t o assess M C S Re s p o nse will disc o nti n ue st u d y  dr u g.
6. 5. 3.
Wee ks 1 4, 1 8, 2 2, 2 6, 3 0, 3 4, 3 8, 4 2, a n d 4 6 - Bli n de d Tre at me nt & 
O pe n -L a bel Tre at me nt P h ases
T he Bli n de d Treat me nt p hase assess me nts t o be c o m plete d at t hese visits are o utli ne d i n t he 
St u d y  Pr oce d ures Ta ble i n A p pe n di x 2 a n d t he O L Treat me nt p hase assess me nts t o be c o m plete d 
at t hese visits are o utli ne d i n t he St u d y Pr oce d ures Ta ble i n A p pe n di x 3 wit h a d diti o nal 
i nf or mati o n o n assess me nts pr o vi de d i n Secti o ns 6. 8 t o 6. 1 2 . 


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 4 5
1 9 J u ne 2 0 2 0
6. 5. 4.
Wee k 5 0 - Bli n de d Tre at me nt & O pe n -L a bel Tre at me nt P h ases
T he Bli n de d Treat me nt p hase assess me n ts t o be c o m plete d at t his visit are o utli ne d i n t he St u d y 
Pr oce d ures Ta ble i n A p pe n di x 2 a n d t he O L  Treat me nt p hase assess me nts t o be c o m plete d at t his 
visit are o utli ne d i n t he St u d y Pr oce d ures Ta ble i n A p pe n di x 3 wit h a d diti o nal i nf or mati o n o n 
assess me nts pr o vi de d i n Secti o ns 6. 8 t o 6. 1 2 .
At t his visit, all s u bjects will ha ve a n efficac y  assess me nt t hat i ncl u des a C ol o n osc o p y/ Fle xi ble 
Si g m oi d osc o p y  wit h c ollecti o n of i ntesti nal bi o psies. F oll o wi n g t he visit, t he e n d osc o pic 
fi n di n gs will be pr o vi de d t o t he sites after ce ntral rea d. T he val ue pr o vi de d b y t he ce ntral rea der 
a n d t he P G A is t o be rec or de d b y t he i n vesti gat or ( or desi g nee) f or ce ntral calc ulati o n of M C S.
6. 6. 
E arl y Ter mi n ati o n ( E T) Assess me nts
If a s u bject disc o nti n ues st u d y dr u g (e g, as a res ult of a n A E), e ver y atte m pt s h o ul d be ma de t o 
perf or m t he E T assess me nt a n d t he P osttreat me nt ( P T x) assess me nt . If t his is n ot p ossi ble or 
acce pta ble t o t he s u bject or in vesti gat or, t he s u bject ma y  be wit h dra w n fr o m t he st u d y.
T he Bli n de d Treat me nt p hase E T assess me nts are o utli ne d i n t he St u d y  Pr oce d ures Ta ble i n 
A p pe n di x 2 a n d t he O L Treat me nt p hase E T assess me nts are o utli ne d i n t he St u d y  Pr oce d ures 
Ta ble i n A p pe n di x 3 wit h a d di ti o nal i nf or mati o n o n assess me nts pr o vi de d i n Secti o ns 6. 8 t o 
6. 1 2 .
6. 7.
P ost tre at me nt ( P T x) Assess me nts
All s u bjects s h o ul d c o m plete t he P T x assess me nts 3 0 da y s after t he last d ose of st u d y dr u g. 
T he Bli n de d Treat me nt p hase P T x assess me nts are o utli ne d i n t he St u d y  Pr oce d ures Ta ble i n 
A p pe n di x 2 a n d t he O L Treat me nt p hase P T x assess me nts are o utli ne d i n t he St u d y  Pr oce d ures 
Ta ble i n A p pe n di x 3 wit h a d diti o nal i nf or mati o n o n assess me nts pr o vi de d i n Secti o ns  6. 8 t o 
6. 1 2 .
6. 8.
Effic ac y Assess me nts
6. 8. 1.
M a y o Cli nic Sc ore ( M C S)
T he M C S is a s c ori n g s yste m f or assess me nt of U C acti vit y a n d utilizes 4 s u bsc ores: St o ol 
Fre q ue nc y , Rectal Blee di n g, E n d osc o pic Fi n di n gs, a n d t he P G A . Eac h s u bsc ore is gra de d fr o m 
0 t o 3 a n d t he s u m of t he s u bsc ores (ra n gi n g fr o m 0 t o 1 2) deter mi nes t he o verall M C S. Refer t o 
A p pe n di x 4 f or details.
T he St o ol Fr e q ue nc y a n d Rectal Blee di n g s u bsc ores are rec or de d i n t he electr o nic diar y 
(e-Diar y ) a n d s h o ul d be c ollecte d dail y. T he P G A is rec or de d at all st u d y visits a n d s h o ul d be 
ca pt ure d i n s o urce d oc u me nts. T he E n d osc o pic Fi n di n g s u bsc ore is re p orte d b y t he ce ntral rea der 
d uri n g Scree ni n g, Wee k 1 0, a n d Wee k 5 0 . T he sc ore pr o vi de d b y t he ce ntral rea der will be use d 
f or all efficac y assess me nts.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 4 6
1 9 J u ne 2 0 2 0
6. 8. 1. 1. 
e- Diar y I nstr ucti o n & Re vie w
T he S t o ol F re q ue nc y a n d R ectal B lee di n g s u bsc ores are rec or de d dail y i n a n e-Diar y . S u bjects 
s h o ul d be pr o vi ded wit h t he e-Diar y a n d i nstr ucti o ns f or dail y d oc u me ntati o n of St o ol Fre q ue nc y
a n d Rectal Blee di n g . S u bjects s h o ul d be gi n filli n g it o ut t he da y  of t heir i nitial scree ni n g visit 
a n d c o nti n ue t o fill it o ut dail y t hr o u g h o ut t he re mai n der of t he st u d y.
S u bjects s h o ul d be c o u nsele d a b o ut w hat is mea nt b y NS F : t he a vera ge dail y st o ol fre q ue nc y t he 
s u bject e x perie nce d t he last ti me t he s u bject was i n re missi o n. If t he s u bject has ne ver bee n i n 
re missi o n, t he N S F is defi ne d as: t he a vera ge dail y st o ol fre q ue nc y bef ore t he i nitial o nset of 
si g ns a n d sy m pt o ms of U C .
F or t he dail y St o ol Fre q ue nc y  q uesti o n, su bjects s h o ul d be c o u nsele d t hat a st o ol is defi ne d as a 
visit t o t he t oilet w he n t he y ha ve eit her a b o wel m o ve me nt, pass bl o o d o nl y, pass m uc us o nl y , or 
pass bl o o d a n d m uc us .
F or t he Rectal Blee di n g q uesti o n, s u bjects s h o ul d be c o u nsele d t o select t he cate g or y t hat 
descri bes t heir m ost se vere rectal blee di n g o ver t he last 2 4 h o urs . S u bjects s h o ul d be c o u nsele d
t o select “ N o Bl o o d See n” if th e y  d o n ot ha ve a st o ol d uri n g a gi ve n da y.
F or t he p u r p oses of deter mi ni n g eli gi bilit y a n d efficac y assess me nts, t he M C S s u bsc ores f or 
R ectal Blee di n g a n d St o ol Fre q ue nc y will be calc ulate d base d o n t he data rec or de d i n t he diar y  
f or t he wee k pri or t o t he e n d osc o py. T h us, sites nee d t o e ns ure s u bjects are e nteri n g e Diar y  data 
dail y , es peciall y pri or t o a n e n d osc o p y. S u bjects m ust be i nstr ucte d t o d oc u me nt St o ol Fre q ue nc y 
a n d Rectal Blee di n g dail y a n d site pers o n nel s h o ul d be m o nit ori n g s u bject’s c o m plia nce.
6. 8. 1. 2.
C ol o n osc o p y / Fle xi ble Si g m oi d osc o p y wit h Bi o psies
A c ol o n osc o p y or fle xi ble si g m oi d osc o py will be perf or me d a n d rec or de d f or ce ntral rea der 
re vie w. T he E n d osc o pic F i n di n gs s u bsc ore will be pr o vi de d t o t he i n vesti gat or b y a ve n d or 
res p o nsi ble f or ce ntral rea di n g. T he val ue pr o vi de d b y t he ce ntral rea der will be use d f or 
calc ulati o n of M C S at S cree ni n g, Wee k 1 0 , a n d Wee k 5 0 .
As st o ol fre q ue nc y  a n d rectal blee di n g m a y  be affecte d b y b o wel pre parati o n f or t he e n d osc o py, 
t he st o ol fre q ue nc y a n d rectal blee di n g s u bsc ores o n t he da y pri or t o e n d osc o p y, da y of 
e n d osc o p y a n d da y  after e n d osc o p y are n ot i ncl u de d i n t he calc ulati o n of t he M C S. F or t his 
reas o n, e xte n de d b o wel pre parati o n ( > 2 4 h o urs pri or t o t he pr oce d ure) is disc o ura ge d as st o ol 
fre q ue nc y a n d rectal blee di n g s u bsc ores d uri n g t his peri o d ma y  be use d f or t he deter mi nati o n of 
eli gi bilit y a n d res p o nse t o treat me nt.
I ntesti nal bi o psies will be c ollecte d d uri n g e n d osc o p y  f or efficac y assess me nts a n d as bi o mar ker 
sa m ples. At scree ni n g, a t otal of 9 bi o psies s h o ul d be c ollecte d fr o m t he c ol o n. At Wee ks 1 0 a n d 
5 0, 7 bi o psies s h o ul d be c ollecte d fr o m t he si g m oi d c ol o n. Please refer t o t he la b ma n ual s f or 
s pecific c ollecti o n i nstr ucti o ns . T he n u m ber of bi o psies, site of c ollecti o n, a n d pla n ne d a nal ys es 
are liste d bel o w:


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 4 7
1 9 J u ne 2 0 2 0
T iss ue bi o ps y c ollecti o n 1 0 c m pr o xi m al t o e n d of acti ve dise ase (l oc ati o n will v ar y b y 
s u bject) d uri n g Scree ni n g e n d osc o p y o nl y

1 x F F P E : Bi o psies will be f or mali n fi xe d a n d paraffi n e m be d de d ( F F P E) f or hist ol o gical a n d 
i m m u n o hist oc he mical/i m m u n ofl u oresce nce assess me nt.

1 x R N Al ater: Bi o psies will be c ollecte d i n R N Alater t o meas ure c ha n ges i n ge ne e x pressi o n.
Tiss ue bi o ps y c ollecti o n fr o m si g m oi d c ol o n d u ri n g e n d osc o p y at Scree ni n g, Wee ks 1 0 
a n d 5 0 

1 x F F P E : B i o psies will be F F P E f or hist ol o gical a n d 
i m m u n o hist oc he mical/i m m u n ofl u oresce nce assess me nt. 

1 x R N Al ater : B i o psies will be c ollecte d i n R N Alater t o meas ure c ha n ges i n ge ne e x pressi o n.

4 x Freezi n g Me di a : B i o psies will be c ollecte d i n freezi n g me dia t o all o w si n gle cell 
is olati o n. Cells will be a nal yze d f or R N A e x pressi o n or c haracterize d f or a b u n da nce of 
i m m u ne cell s u bsets a n d/ or mar kers of i ntracell ular si g nali n g.

1 x Fl as h Fr oze n: Bi o psies will be f las h fr oze n f or tiss ue micr o bi o me a n d/ or pr ote o mic
a nal ys is.
6. 8. 1. 3.
P G A f or M C S
Calc ulati o n
T he P G A s u bsc ore is assesse d b y t he i n vesti gat or a n d t he sc ore rec or de d f or calc ulati o n of M C S. 
(A p pe n di x 4 ).
6. 8. 1. 4.
E val uati o n of Disease W orse ni n g usi n g Partial M C S
Disease w orse ni n g starti n g after Wee k 1 0 i n t he Bli n de d Treat me nt p hase or O L Treat me nt 
P hase s h o ul d be assesse d b y  t he i n vesti gat or usi n g t he f oll o wi n g criteria: partial M C S (s u m of all 
M C S s u bsc ores e xce pt E n d osc o pic Fi n di n gs) i ncrease of ≥ 3 p oi nts t o at least 5 p oi nts fr o m t he 
res pecti ve Wee k 1 0 val ue o n 2 c o nsec uti ve visits O R a n i ncrease i n partial M C S t o 9 p oi nts o n 
2 c o nsec uti ve visits if t he res pecti ve Wee k 1 0 partial M C S is > 6. T he disease w orse ni n g visits 
ma y  i ncl u de u nsc he d ule d visits.
6. 8. 2.
He alt h - Rel ate d Q u alit y of Life ( H R Q o L) S ur ve ys
T he st u d y i ncl u des 4 H R Q o L S ur ve ys; S F - 3 6, W P AI -U C , E Q-5 D- 5 L , a n d I B D Q. 
H R Q o L  s ur ve ys are t o be c o mplete d at t he site o n t he site ta blet w he n i n dicate d i n t he St u d y  
Pr oce d ures Ta ble (A p pe n di x 2 a n d A p pe n di x 3 ). It is rec o m me n de d f or s u bjects t o c o m plete 
H R Q o L  s ur ve ys bef ore a n y ot her st u dy pr oce d ures at t hese visits.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 4 8
1 9 J u ne 2 0 2 0
T he S F -3 6 is a H R Q o L i nstr u me nt c o nsisti n g of 3 6 q uesti o ns bel o n gi n g t o 8 d o mai ns i n 
2 c o m p o ne nts; p h ysical well- bei n g a n d me ntal well-bei n g; a n d c o vers a 4 -wee k recall peri o d . 
T he re mai ni n g ite m ( healt h tra nsiti o n) is n ot part of t he a b o v e d o mai ns b ut is ke pt se paratel y . 
T he S F -3 6 is n ot disease s pecific a n d has bee n vali date d i n n u mer o us healt h states.
T he W P AI -U C is desi g ne d t o meas ure t he effect of ge neral healt h a n d s y m pt o m se verit y o n 
w or k pr o d ucti vit y  a n d re g ular acti vities d uri n g t he past 7 d a y s.
T he E Q -5 D is a sta n dar dize d i nstr u me nt de vel o pe d b y  t he E ur o Q ol Gr o u p as a meas ure of 
H R Q o L  t hat ca n be use d i n a wi de ra n ge of healt h c o n diti o ns a n d treat me nts.
T he I B D Q is a disease -s pecific q uesti o n naire c o m prise d of 3 2 q uesti o ns di vi de d i nt o 4 healt h 
s u bscales: b o wel sy m pt o ms ( 1 0 q uesti o ns); s y ste mic s ym pt o ms, i ncl u di n g slee p dis or ders a n d 
fati g ue ( 5 q uesti o ns); e m oti o nal f u ncti o n s uc h as de pressi o n, a g gressi o n a n d irritati o n 
( 1 2 q uesti o ns); a n d s ocial f u ncti o n, mea ni n g t he a bilit y  t o partici pate i n s ocial acti vities a n d t o 
w or k ( 5 q uesti o ns).
6. 8. 3.  
He alt h C are Res o urce Utiliz ati o n S ur ve y
H C R U s ur ve y  is t o be c o m plete d w he n i n dicate d i n t he St u d y  Pr oce d ures Ta ble (A p pe n di x 2 a n d 
A p pe n di x 3 ). D uri n g visi ts, it is rec o m me n de d f or t he H C R U s ur ve y s t o be c o m plete d after t he 
H R Q o L s a n d bef ore a n y ot her st u d y  pr oce d ures at t hese visits.
6. 9.
S afet y Assess me nts
Safet y  will be assesse d usi n g A Es, c o nc o mita nt me dicati o ns, P Es (c o m plete a n d 
s ym pt o m -dri ve n), vital si g ns, E C Gs, a n d cli nical la b orat or y res ults. T he ti mi n g of safet y 
assess me nts is s u m marize d i n A p pe n di x 2 a n d A p pe n di x 3 .
6. 9. 1.
Re vie w of A d verse E ve nts
Fr o m t he ti me of o btai ni n g i nf or me d c o nse nt t hr o u g h t he first a d mi nistrati o n of i n vesti gati o nal 
me dici nal pr o d uct, rec or d all S A Es, as well as a n y A Es relate d t o pr ot oc ol-ma n date d pr oce d ures . 
F oll o wi n g i nitiati o n of st u d y  me dicati o n, rec or d all A Es, re gar dless of ca use or relati o ns hi p, u ntil 
3 0- d a y s after last a d mi nistrati o n of st u d y dr u g .
F or m ore i nf or mati o n o n A Es a n d S A Es, see S ecti o n 7 .
6. 9. 2.  
Re vie w of C o nc o mit a nt Me dic ati o ns
Re vie w a ll me dicati o ns ta ke n u p t o 3 0 da ys pri or t o t he scree ni n g visit t hr o u g h t he e n d of st u d y 
( 3 0 d a y s after t he last d ose of st u d y  dr u g). At eac h st u d y visit, rec or d all me dicati o ns ta ke n by 
t he s u bject si nce t he last visit or d uri n g t he visit (as a p plica ble). All c o nc o mita nt me dicati o ns 
(prescri pti o n, peri - pr oce d ural me dicati o ns, o ver-t he-c o u nter me dicati o ns, i ncl u di n g vacci nes, 
vita mi ns, her bal , dietar y s u p ple me nts, a n d mi nerals) m ust be rec or de d.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 4 9
1 9 J u ne 2 0 2 0
6. 9. 3. 
P h ysic al E x a mi n ati o n
A P E s h o ul d be perf or me d at t h e ti me p oi nts i n dicate d i n t he St u d y  Pr oce d ures 
Ta ble (A p pe n di x 2 a n d A p pe n di x 3 ). A n y  c ha n ges fr o m scree ni n g will be rec or de d. At 
scree ni n g, a c o m plete P E i ncl u di n g, vital si g ns, b o d y wei g ht, a n d hei g ht will be perf or me d.
S u bjects s h o ul d be i nstr ucte d t o re m o ve s h oes pri or t o meas ure me nt of hei g ht. Vital si g ns a n d 
wei g ht will be c ollecte d at e ver y  visit.
A c o m plete P E will i ncl u de s o urce d oc ume ntati o n of ge neral a p peara nce an d t he f oll o wi n g b o d y  
s yste ms: hea d, nec k , a n d t h yr oi d; e yes, ears, n ose, t hr oat, m o u t h a n d t o n g ue; c hest 
(e xcl u di n g breasts); res pirat or y ; car di o vasc ular; l y m p h n o des; a b d o me n; s ki n, hair, nails; 
m usc ul os keletal; a n d ne ur ol o gical. S y m pt o m -dri ve n P Es will be perf or me d at all ot her visits 
base d o n re p orte d si g ns a n d s y m pt o ms.
Vital si g ns s h o ul d be ta ke n after t he s u bject has bee n resti n g i n t he seate d or s u pi ne p ositi o n f or 
at least 5 mi n utes a n d will i ncl u de p ulse rate, res pirat or y  rate, sys t olic a n d diast olic bl o o d 
press ure, a n d te m perat ure.
6. 9. 4. 
1 2- le a d Electr oc ar di o gr a m
A resti n g 1 2 -lea d E C G will be perf or me d at t h e ti me p oi nts i n dicate d i n t he St u d y  Pr oce d ures 
Ta ble (A p pe n di x 2 a n d A p pe n di x 3 ).
T he E C G s h o ul d be o btai ne d after t he s u bject has bee n resti n g i n t he s u pi ne p ositi o n f or at least 
5 mi n utes a n d will i ncl u de heart r ate, i nter-beat , Q R S, u nc orrecte d Q T, m or p h ol o g y, a n d r h yt h m 
a nal ys is. Electr ocar di o gra ms will be i nter prete d b y t he i n vesti gat or ( or q ualifie d desi g nee) f or 
cli nical si g nifica nce a n d res ults will be e ntere d i nt o t he e C R F.
6. 9. 5.
Cli nic al L a b or at or y Asses sme nts
T he cli nical la borat or y  assess me nts will be perf or me d at t he ce ntral la b orat or y. Refere nce ra n ges 
will be s u p plie d b y  t he ce ntral la b orat or y a n d will be use d b y t he i n vesti gat or t o assess t he 
la b orat or y data f or cli nical si g nifica nce a n d pat h ol o gical c ha n ges. T he details of sa m ple ha n dli n g 
a n d s hi p me nt i nstr ucti o ns will be pr o vi de d b y  t he ce ntral la b orat or y i n a se parate la b orat or y 
m a n ual. R efer t o t he St u d y  Pr oce d ures Ta ble (A p pe n di x 2 a n d A p pe n di x 3 ) f or c ollecti o n ti me 
p oi nts a n d t o t he Cli nical La b orat or y Assess me nt Ta ble (A p pe n di x 7 ) f or m ore i nf or mati o n .
6. 9. 5. 1.
La b orat or y  Retesti n g G ui da nce
A si n gle retest of scree ni n g la bs is per mitte d o nl y  if t here is reas o n t o belie ve t he retest val ue will 
be wit hi n acce pte d para meters, or if t he i nitial val ue was eit her d ue t o a sa m ple pr ocessi n g err or 
or d ue t o a n e xte n uati n g circ u msta nce.
La b orat or y  val ues o utsi de t he n or mal ra n ge will be fla g ge d a n d cli nical rele va nce will be 
assesse d b y t he i n vesti gat or. M ore fre q ue nt sa m pli n g as well as a d diti o nal tests ma y  be 
perf or me d as dee me d necessar y  b y t he i n vesti gat or.


G S -4 8 7 5 
Pr ot o c ol G S -U S -3 6 5- 4 2 3 7 
Gil e a d S ci e n c es, Inc. 
Fi nal 
A m e n d m e nt 2 
N ot e t h at i n t h e c as e w h er e cli nic a lly si g n ifi c a nt la b or at or y t est r es ults are a p ot e nti al r e as o n f or 
dis c o ntin u at io n fr o m st u d y dr u g a n d/or wi t h dr a w al fr o m t h e st u d y, r et estin g of t h e aff e ct e d 
p ar a m et er( s) s h o u l d b e pr o m pt ( e g, wi t hi n 7 da ys, e x c e pt s er u m c yst at i n C, w h ic h s h o ul d b e 
r et est e d wi t hi n 1 4 da ys) . 
6. 9. 5. 2. 
H e m at ol o g y a n d C h e m istr y 
les w ill b e c o lle ct e d b y v e n ip u n ct ur e 
i n t h e a n n at t h e tim e p o ints in di c at e 
(A p p e n d i x 2 a n d A p p e n di x 3). 
R es u lts of s er u m cr e ati n in e a n d e G F Rcr w ill n ot b e pr o vi d e d t o i n v estig at ors . R ef er t o S e cti o n 1. 4 
f or m or e d et a ils. 
I n or d er t o a llo w f or ass ess m e nt of r e n al f u n ctio n, c yst at in C a n d e G F Rc ys w ill b e r o uti n el y 
m e as ur e d a n d t h es e d at a w ill b e pr o vi d e d t o i n v estig at ors . 
V a lu es f or e G F Rc ys b y t h e C K D- E PI e q u at io n {I n ker 2 0 1 2 } ar e s h o w n b e lo w . 
Male: 
1 3 3 X Mi n( S Cys 
1)- 0 ·4 9 9 X M ax( S Cys 
1)- 1 ·3 2 8 X 0. 9 9 6 A g e 
0.8 
' 
0. 8 ' 
' 
F e m a le: 
1 3 3 X Mi n( S Cys 
1)- 0 ·4 9 9 X M ax( S Cys 
1)- 1 ·3 2 8 X 0. 9 9 6 A g e X 0. 9 3 2 
0.8 
' 
0. 8 ' 
' 
w h er e S C ys is s er u m c yst ati n C  in m g/ L a n d a g e is i n y e ars . 
6. 9. 5. 3. 
Ur in a lys is 
Ur in e s a m p les f or cl ini c a l la b or at or y ass ess m e nts w ill b e c o lle ct e d d ur in g st u d y visi ts f or 
c o m p let e ur in a lys is. 
A ur in e dr u g t est w ill b e p erf o n n e d at s cr e e nin g . A p os itiv e dr u g t est r es ult e x cl u d es s u bj e cts 
u nl ess it c a n b e e x p lain e d b y a m e d ic at io n t h at is b e in g us e d u n d er t he di r e cti o n of a p h ys icia n 
( pr es cripti o n or n o n pr es cr iptio n) . C o c a in e is e x cl us io n ar y . 
6. 9. 5. 4 . 
St o o l Sa m p les f or E nt eri c I nf e ctio ns 
Sa m p les w ill b e c o lle ct e d t o t est f or e nt eri c p at h o g e ns ( e g . Cl ostri di u m diffi cil e t o xin, p at h o g e n ic 
Es c h eri c hi a c oli, S a lm o n e lla s p e ci es (s p p ), S h ig e lla s p p, C a m p y lo b a ct er s p p, Y ers i nia s p p ), as 
w e ll as o v a a n d p ar as it es. 
A st o o l s a m p le s h o u l d als o b e c o lle ct e d at a n y tim e d ur in g t h e st u d y f or c ult ur e f or p at h o g e ni c 
b a ct er ia, o v a a n d p ar as it es, a n d C diffi cil e t o xi n ass a y w h e n a s u bj e ct b e c o m es s y m pt o m atic, 
i n cl u di n g w ors e ni n g or r et ur n of dis e as e a ct ivit y. 
C O N FI D E N T IA L 
P a g e 5 0 
1 9 Ju n e 2 0 2 0 


G S -4 8 7 5 
Pr ot o c ol G S -U S -3 6 5- 4 2 3 7 
Gil e a d S ci e n c es, I nc. 
6. 9. 5. 5. 
T u b er c ul os is S cr e e n in g 
Fi nal 
A m e n d m e nt 2 
A T B ass ess m e nt ( Q u a nti F E R O N t est or e q u iv al e nt ass a y) p erf o n n e d b y t h e c e ntr al la b m ust b e 
c o n d u ct e d at s cr e e ni n g m 1 less t h e s u bj e ct h as a hist or y of a ct iv e or lat e nt T B t h at h as b e e n f ully 
tr e at e d a n d t h e s u bj e ct's e ligi b ilit y h as b e e n c o nfi n n e d b y t h e s p o ns or. P os itiv e or n e g ativ e T B 
ass ess m e nt r es ults m ust n ot b e r e p e at e d. A n i n d et e n nin at e r es ult c a n b e r e p e at e d o n c e a n d t h e 
s e c o n d r es ult (if p os itiv e or n e g ativ e) w ill b e c o ns id er e d fi n al. T w o s e q u e ntial in d et e n n in at e 
r es ults c o nst it ut e a s cr e e n failur e . R ef er t o S e cti o n 4. 2 f or c h est ra dio gr a p h r e q uir e m e nts. 
6. 9. 5. 6. 
H B V, H C V, a n d HI V S cr e e ni n g 
S u bj e cts wi t h p os itiv e H C V a nt ib o d y at s cr e e ni n g m ust h a v e f urt h er t estin g f or H C V R N A. 
S u bj e cts wi t h H C V R N A ~ L L O Q w ill n ot b e e ligi ble f or t h e st u d y. S u bj e cts w i t h p os itiv e H C V 
a nt ib o d y b ut H C V R N A < L L O Q ar e e ligi ble. 
S u bj e cts wi t h p os itiv e H Bs A g w ill b e e x cl u d e d fr o m t h e st u d y. S u bj e cts w i t h n e g at iv e H Bs A g 
a n d p os itiv e H B c A b m ust h a v e f urt h er t estin g f or H B V D N A. S u bj e cts wi t h H B V D N A ~ L L O Q 
w ill n ot b e e ligi ble f or t h e st u d y. S u bj e cts wi t h H B V D N A < L L O Q w ill b e e ligi ble. 
S u bj e cts w h o h a v e HI V inf e cti o n ( p ositiv e a nt ib o d y t est) r e g ar dless of vi r olo g ic st at us ar e 
e x cl u d e d fr o m t h e st u d y. 
6. 9. 5. 7. 
H B V M o n it orin g 
S u bj e cts wi t h n e g ativ e H Bs A g a n d p os itiv e H B c A b at S cr e e n in g r e q uir e H B V D N A m o n it ori n g 
p er t h e St u d y Pr o c e d ur es T a bl e (A p p e n di x 2 a n d A p p e n di x 3). 
6. 9. 5. 8. 
Pr e g n a n c y T est in g 
A ll f e m ales of c h ild b e ar in g p ot e nt ial (A p p e n di x 8) m ust h a v e a s er u m pr e g n a n c y t est at 
s cr e e nin g t h at w ill b e p erf o n n e d b y t h e c e ntr al la b a n d a n i n- cli nic uri n e pr e g n a n c y t est o n 
D a y 1. T h er e aft er, in- cl i nic uri n e pr e g n a n c y t ests m ust b e c o m p let e d e v er y 4 w e e ks at a 
mi ni m m n . If a n y pr e g n a n c y t est is p os itive, st u d y dr u g s h o u l d b e im m e d iat e l y int err u pt e d, a n d 
t h e s u bj e ct s h o u l d h a v e a s er u m pr e g n a n c y t est i n cli ni c p erf o n n e d b y t h e c e ntr a l la b . C o nfir m e d 
pr e g n a n ci es s h o ul d b e r e p ort e d as o utl in e d i n S e cti o n 7. 7 . 2. 1. 
• 
C O N FI D E N T IA L 
P a g e 5 1 
1 9 Ju n e 2 0 2 0 


G S -4 8 7 5 
Pr ot o c ol G S -U S -3 6 5- 4 2 3 7 
Gil e a d S ci e n c es, Inc. 
6. 1 1. 
Bi o m a r k e r Ass ess m e nts 
Fi nal 
A m e n d m e nt 2 
Bi ol o gi c al s p e ci me ns w ill b e c o lle ct e d i n t his st u d y t o e v alu at e t h e ass o c iati o n b et w e e n s yst emi c 
a n d lo c a liz e d bi o m ar k ers wi t h dis e as e a ct ivit y, a n d tr e at m e nt r es p o ns e (in cl u d i ng effi c a c y a nc V or 
A Es) . Bi o m ar k ers ass o c iat e d wi t h U C , i nfla 1 m natio n, a n d t h e T P L 2 p at h w a y w ill b e ass ess e d i n 
bl o o d, st o o l, ur ine, a n d c ol o n ic bi o psi es . 
B e c a us e bi o m ar k er s cie n c e is a ra pi dl y e v o l vi ng ar e a of in v est ig at io n, it is n ot p oss i ble t o s p e c if y 
pr os p e ct iv e l y all a n alys es t h at w ill b e d o n e o n t h e s p e c i me ns c o lle ct e d . T h e a n alys es o utli n e d 
b e lo w ar e b as e d u p o n t h e c urr e nt st at e of s cientifi c k n o wl e d g e . T h e y m a y b e m o difi e d d ur i ng or 
aft er t h e e n d of t h e st ud y b as e d u p o n n e w s cientifi c k n o wl e d g e . 
Bi o m ar k er s am pl e c o lle ctio n fr e q u e n c y is list e d i n St u d y Pr o c e d ur es T a bl e (A p p e n d ix 2 a n d 
A p p e n d ix 3). S a m p les c o lle ct e d f or bi o m ar k er ass ess m e nts w ill b e d estr o y e d n o lat er t h a n 
1 5 y e ars aft er t h e e n d of st u d y. 
6. 1 1. 1. 
Bl o o d Bi o m a r k e r S a m pl es 
Bl o o d s am pl es w ill b e c o lle ct e d at D a y 1 a n d W e e ks 2, 4, 1 0, 2 6, a n d 5 0 as o utli n e d i n t h e 
St u d y Pr o c e d ur es T a bl e (A p p e n d i x 2 a n d A p p e n d i x 3). Pl e as e r ef er t o t h e la b m a n u al f or s p e c ific 
c o lle ct i o n i nstr u ctio ns f or t h e f ollo w i ng s am pl es: 
• 
Bl o o d S a m pl e : w h o le blo o d c o lle ct e d f or m e as ur em e nt of t h e p er c e nt a g es a n d a bs o lut e 
n u m b ers of i m mu n e c e ll p o p u lati o ns, a n d f or p ot e nti al B- c e ll/T- c e ll r e c e pt or r e p ert oir e 
s e q u e n c m g. 
• 
Pl as m a a n d S e r u m : w h ol e bl o o d c o lle ct e d t o ass ess le v e ls of cir c u lat in g pr ot e ins, 
m et a b o lit es a n d mi R N A s. 
• 
Bl o o d T r a ns c ri pt o m e : w h o le blo o d c o lle ct e d f or R N A is o lati o n t o ass ess c h a n g es i n g e n e 
e x press 1 0 n . 
• 
P e ri p h e r al Bl o o d M o n o n u cl e a r C ells ( P B M C): w h o le bl o o d c o lle ct e d f or P B M C is o lat io n 
t o c h ar a ct eriz e i1 m n u ne c e ll s u bs ets (in cl u di n g tr a ns cri pt o mic a n alys is of k e y i1 m n u ne c e ll 
s u bs ets), intr a c e ll ular si gn ali n g a n d/or c e ll f u n cti o n. 
C O N FI D E N T IA L 
P a g e 5 2 
1 9 Ju n e 2 0 2 0 


G S -4 8 7 5 
Pr ot o c ol G S -U S -3 6 5- 4 2 3 7 
Gil e a d S ci e n c es, I nc. 
6. 1 1. 2. 
M a n d at o r y G e n o mi c S a m pl es 
Fi nal 
A m e n dm e nt 2 
A bl o o d s am pl e w ill b e o bt a ine d f or g e n et ic a n alys is of t he U G Tl Al * 2 8 g e n et ic v ar ia nts . 
R es u lts of t h e t est w ill b e m a d e a v aila b le t o t h e in v est ig at or a n d t h e m e d ic a l m o nit or t o i de nti f y 
s u bje cts f or m o nit ori n g p ur p os es w h o m a y b e m or e s us c e ptible t o G S - 4 8 75 -relat e d 
h y p er b iliru b i ne mia. R es u lts of t his t est w ill n ot b e us e d f or d et e n n i nat io n of e ligib ilit y. 
A bl o o d s am pl e w ill b e o bt a ine d t o d et e n ni n e t he T P L 2 g e n ot y p e a n d s i ngle n u cl e oti de 
p o l ym or p hi s ms ( S NP s) ass o c iat e d wi t h I B D. T h e T P L 2 g e n ot y p e a n d I B D- ass o ciat e d S N Ps of 
e a c h p at ie nt w ill b e us e d t o st u d y ass o c iati o ns wi t h dis e as e a ct i vit y a n d r es p o ns e t o G S - 4 8 7 5. 
R es u lts of t h e t est w ill n ot b e m a d e a v a ila b le t o sit es a n d w ill n ot b e us e d f or d et e n ni n at io n of 
e ligib ilit y. 
M a n d at o r y g e n o mi c s am pl es w ill b e c o lle ct e d at t h e D a y  1 visi t. 
-
6. 1 1. 4. 
St o ol Bi o m a r k e r S a m pl es 
St o o l s am pl es w ill b e c o lle ct e d at S cr e e n in g a n d W e e ks 1 0, 2 6, a n d 5 0 . S a m p les c a n b e c o lle ct e d 
at h o m e b y t h e s u bject. Pl e as e r ef er t o t he la b m a n u al f or s p e c ific c o lle ct i o n instr u ctio n f or t h e 
f ollo w i ng s am pl es: 
• 
St o ol Mi c r o bi o m e a n d M et a b ol o m e : s am pl es t o ass ess t he st o o l mi cr o bi o m e a n d st o o l 
m et a b o lo m e . 
C O N FI D E N T IA L 
P a g e 5 3 
1 9 Ju n e 2 0 2 0 


G S -4 8 7 5 
Pr ot o c ol G S -U S -3 6 5- 4 2 3 7 
Gil e a d S ci e n c es, Inc. 
• 
St o ol C al p r ot e cti n, L a ct of e r ri n : s am pl es t o ass ess c h a n g es i n t h es e m ar k ers of 
i nfl a m m ati o n. 
Fi nal 
A m e n d m e nt 2 
• 
A d diti o n al St o ol Ali q u ot: s am pl es t o ass ess le v e ls of pr ot e ins, m et a b o lit es, R N A, a n d 
mi R N A. 
-
6. 1 2. 
St u d y D r u g Dis p e nsi n g 
R ef er t o S e ct io n 5. 3 f or d et a ils o n st ud y d r u g di s p en s atio n . 
6. 1 3. 
6. 1 3. 1. 
C rit e ri a f o r I nt e r r u pti o n o r Dis c o nti n u ati o n of St u d y T r e at m e nt 
G e n e r al C o nsi d e r ati o ns 
S u b je cts a d m i nist er ed G S- 4 8 7 5 m a y e x p erie n c e ele v at io ns i n i ndir e ct ( u n c onj u g at e d) b ilir u bi n 
d u e t o t h e i n hibiti o n of h e p ati c tr a ns p ort ers a nd U G T l Al b y G S- 4 8 7 5. S u b je cts wi t h G ilb ert's 
s y nd r o m e m a y b e m or e s us c e pti ble t o G S- 4 8 7 5- m e diat ed el e v at io ns i n i n dir e ct b ilir u bi n. H e p ati c 
tr a ns a mi n as e ele v atio ns t h at o c c ur wi t h h y p er b ilir u bin e m ia s h o u l d b e e v a lu at e d f or alt er n ativ e 
et iol o g ies . 
I ncre as es i n s er um cr e at ini n e h a v e b e e n o bs er v e d i n s u bje cts a d mi nist er ed G S- 4 8 7 5 d u e t o 
i n hi bitio n of t h e r e n al tr a ns p ort er M A T El b y G S- 4 8 7 5 . C o ns e q u e n tly, d e cr e as es i n e G F Rc r w er e 
o bs er v e d i n s u bje cts a d mi ni st er ed G S- 4 8 7 5 i n St u d y G S- U S- 3 6 5- 5 5 8 8 ( S e e S e ct io n 1. 3. 3. 2). T o 
m ai nt ai n t h e st ud y b lin d, r es ults of s er um cr e at i nin e a nd e G F Rcr ass ess m e nts w ill n ot b e pr o v i d e d 
t o i nv est ig at ors . T o allo w f or ass ess m e nt of r e n al f u nctio n, c yst ati n C a nd e G F Rcys w ill b e 
r o uti nel y m e as ur e d a nd t h es e d at a w ill b e pr o v i d e d t o i nv estig at ors . 
A n y s u bje ct w h o d e v e lo ps a n e w i nfectio n d uri n g t h e st ud y s h o u l d u n d er g o pr o m pt dia g n ost ic 
t estin g a p pr o priat e f or a n n m n u n o c o m pr o mi s ed i n di v i du a l, a nd t he s u bje ct s h o u l d b e cl o s e l y 
m o nit or e d. 
6. 1 3. 2. 
St u d y D r u g I nt e r r u pti o n C o nsi d e r ati o ns 
W h e n feasible, t h e me di c a l m o nit or s h o u l d b e c o ns u lt ed pri or t o st ud y dr u g i nterr u ptio n . T h e 
me di c a l m o nit or m u st b e inf o n n e d of a ll c as es of st ud y d r u g int err u pt io n f or me di c a l r e as o ns. 
St u d y d r u g int err u pt io n m u st o c c ur i n t he f ollo wi n g cir c u mst a n c es: 
• 
I nter c urr e nt ill ness t h at w o u l d, i n t he j u d g me nt of t he i nv estig at or, aff e ct ass ess m e nts of 
cli ni c al st at us t o a sig n ific a nt d e gr e e . 
• 
P o sitiv e ur in e pr e g n a n c y test. 
C O N FI D E N T IA L 
P a g e 5 4 
1 9 Ju n e 2 0 2 0 


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 5 5
1 9 J u ne 2 0 2 0

S u bject is sc he d ule d f or electi ve or e mer ge nc y  s ur ger y (e xcl u di n g mi n or s ki n pr oce d ures 
u n der l ocal or n o a nest h esia).

A n y  Gra de 3 A E assesse d as relate d t o st u d y dr u g.
D uri n g t he ti me of st u d y dr u g i nterr u pti o n f or a ny of t he a b o ve, t he s u bject ma y  c o nti n ue t o ha ve 
st u d y visits a n d t o ta ke part i n pr oce d ures a n d assess me nts if dee me d me dicall y a p pr o priate b y 
t he i nvesti gat or.
6. 1 3. 3.
St u d y Dr u g Disc o nti n u ati o n C o nsi der ati o ns
W he n feasi ble , t he me dical m o nit or s h o ul d be c o ns ulte d pri or t o st u d y dr u g disc o nti n uati o n. T he 
me dical m o nit or m ust be i nf or me d of all cases of st u d y  dr u g disc o nti n uati o n.
St u d y  dr u g m ust be per ma ne ntl y disc o nti n ue d i n t he f oll o wi n g i nsta nces:

A n y  Gra de 3 or greater ras h ass ociate d wit h c o nstit uti o nal s ym pt o ms

A n y  Gra de 4 A E assesse d as relate d t o st u d y dr u g

A n y c o nfir me d Gra de 4 la b orat or y  a b n or malit y assesse d as relate d t o st u d y dr u g wit h t he 
e xce pti o n of c h olester ol, tri gl yceri de, gl uc ose, creati ne ki nase ( C K), or bilir u bi n 
a b n or malities t hat are assesse d as n ot cli nicall y si g nifica nt

S u bjects i n t he Bli n de d Treat me nt p hase a n d O L Treat me nt p hase t hat i nitiate or i ncrease t he 
d ose a b o ve t heir Bli n de d Treat me nt p hase Da y  1 d ose of t he f oll o wi n g me dicati o ns f or t he 
treat me nt of U C: oral mesala mi ne c o m p o u n ds, t hi o p uri nes, met h otre xate, or s y ste micall y 
a bs or be d c ortic oster oi ds , see Secti o n 5. 4. 1

S u bject e x perie nces si g nifica nt disease w orse ni n g or l oss of res p o nse base d o n 1 or m ore of 
t he f oll o wi n g:
In vesti gat or j u d g me nt
I nitiati o n of a pr o hi bite d me dicati o n t hat ma y i m pact efficac y assess me nts or s u bject 
safety ( Ta ble 5- 2 ), or s ur gical i nter ve nti o n f or U C 
Disease w orse ni n g as descri be d i n Secti o n 6. 8. 1. 4

A n y  o p p ort u nistic i nfecti o n

A n y  i nfecti o n t hat meets S A E re p orti n g criteria.

Fe brile ne utr o pe nia (te m perat ure ≥3 8. 3 o C or a s ustai ne d te m perat ure of ≥3 8° C f or m ore 
t ha n o ne h o ur) wit h a bs ol ute ne utr o p hil c o u nt of < 1 × 1 0 3/ µ L ( < 1 GI / L)

2 se q ue ntial he m o gl o bi n le vels < 7. 0 g/ d L ( 7 0 g/ L), or a ne mia re q uiri n g tra nsf usi o n 
re gar dless of he m o gl o bi n val ue 


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 5 6
1 9 J u ne 2 0 2 0

C o m plicate d her pes z oster i nfecti o n ( wit h m ulti- der mat o mal, disse mi nate d, o p ht hal mic, 
or ce ntral ner v o us s ys te m i n v ol ve me nt)

E vi de nce of acti ve He patitis C Vir us ( H C V) d uri n g t he st u d y, as e vi de nce d b y  a H C V R N A 
≥L L O Q

E vi de nce of acti ve He patitis B Vir us ( H B V) d uri n g t he st u d y, as e vi de nce d b y  a H B V D N A 
≥L L O Q

U nacce pta ble t o xicit y , or t o xicit y t hat, i n t he j u d g me nt of t he i n vesti gat or, c o m pr o mises t he 
s u bject’s a bilit y t o c o nti n ue st u d y-s pecific pr oce d ures or is c o nsi dere d t o n ot be i n t he 
s u bject’s best i nterest

S u bject re q uest t o disc o nti n ue f or a n y reas o n

S u bject n o nc o m plia nce

Pre g na nc y  d uri n g t he st u d y; refer t o Secti o n 7. 7. 2. 1 a n d A p pe n di x 8

Disc o nti n uati o n of t he st u d y  at t he re q uest of Gilea d, a re g ulat or y a ge nc y or a n i nstit uti o nal 
re vie w b oar d or i n de pe n de nt et hics c o m mittee (I R B/I E C).

A n y of t he f oll o wi n g a b n or mal la b orat or y fi n di n gs c o nfir me d b y i m me diate re peat testi n g:
2 se q ue ntial A S T or A L T ele vati o ns > 3 U L N A N D at least o ne of t he f oll o wi n g 
c o nfir me d val ues or s y m pt o ms : 
■
T otal bilir u bi n > 2 U L N 
■
I nter nati o nal n or malize d rati o (I N R) > 1. 5
■
S y m pt o ms c o nsiste nt wit h he patic i nj ur y
F or a n y s u bject wit h a n i nitial A S T or A L T ele vati o n > 3 U L N, at t he ti me of t he 
sec o n d c o nfir mat or y dra w, a n I N R, pr ot hr o m bi n ti me) a n d partial t hr o m b o plasti n ti me 
( P T T) m ust als o be dra w n
T w o se q ue ntial A S T or A L T > 5 U L N
T w o se q ue ntial val ues f or e G F R < 3 0 m L / mi n ( < 0. 5 m L/sec) base d o n t he C K D-E PI  
c ys tati n C f or m ula { I n ker 2 0 1 2}
S u bjects wit h dra wi n g fr o m t he st u d y  s h o ul d c o m plete t he E T visit , f oll o we d b y p osttreat me nt
assess me nts 3 0 da y s after t he last d ose of st u d y dr u g.
Reas o na ble eff orts s h o ul d be ma de t o c o ntact s u bjects w h o are l ost t o f oll o w u p. All c o ntacts a n d 
c o ntact atte m pts m ust be d oc u me nte d i n t he s u bject’s file.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 5 7
1 9 J u ne 2 0 2 0
6. 1 4.
I nstr ucti o ns f or Dr u g Assi g n me nts after St u d y U n bli n di n g 
After st u d y- wi de u n bli n di n g, s u bjects recei vi n g place b o will disc o nti n ue st u d y  dr u g. S u bjects 
s h o ul d atte n d t he cli nic at t heir ne xt sc he d ule d st u d y visit or earlier a n d u n der g o t he E T
assess me nts as descri be d i n Secti o n 6. 6 f oll o we d b y t he P osttreat me nt assess me nts 3 0 da ys after 
t he last d ose of st u d y dr u g i n Secti o n 6. 7 .
After st u d y -wi de u n bli n di n g, s u bjects w h o were recei vi n g G S - 4 8 7 5 will c o nti n ue t o recei ve t he 
sa me d ose (as recei ve d bli n de d) of G S - 4 8 7 5. S u bjects s h o ul d atte n d t he cli nic at t heir ne xt 
sc he d ule d st u dy visit t o recei ve O L G S -4 8 7 5 a n d c o m plete st u d y pr oce d ures as per t heir ne xt 
sc he d ule d st u dy visit. 
6. 1 5.
E n d of St u d y
E n d of St u d y  is defi ne d as w he n all s u bjects ha ve c o m plete d treat me nt pl us 3 0 da y s f oll o w- u p or 
disc o nti n ue d fr o m t he st u d y. 
6. 1 6.
P ost St u d y C are
A fter t he s u bject has c o m plete d t heir st u d y partici pati o n, t he l o n g-ter m care of t he partici pa nt 
will re mai n t he res p o nsi bilit y  of t he pri mar y treati n g p h ysicia n.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 5 8
1 9 J u ne 2 0 2 0
7.
A D V E R S E E V E N T S A N D T O XI CI T Y  M A N A G E ME N T
7. 1.  
Defi niti o ns of A d verse E ve nts, A d verse Re acti o ns, a n d Seri o us A d verse 
E ve nt s
7. 1. 1.
A d verse E ve nts
A n A E is a n y u nt o war d me dical occ urre nce i n a cli nical st u d y s u bject a d mi nistere d a me dici nal 
pr o d uct , w hic h d oes n ot necessaril y  ha ve a ca usal relati o ns hi p wit h t he treat me nt. A n A E ca n 
t heref ore be a ny u nfa v ora ble a n d / or u ni nte n de d si g n, s ym pt o m, or disease te m p orall y  ass ociate d 
wit h t he use of a me dici nal pr o d uct, w het her or n ot c o nsi dere d relate d t o t he me dici nal pr o d uct.
A Es ma y  als o i ncl u de pre- or p osttreat me nt c o m plicati o ns t hat occ ur as a res ult of pr ot oc ol 
s pecifie d pr oce d ures, lac k of efficac y, o ver d ose, dr u g a b use/ mis use re p orts, or occ u pati o nal 
e x p os ure . Pree xisti n g e ve nts t hat i ncrease i n se verit y or c ha n ge i n nat ure d uri n g or as a 
c o nse q ue nce of partici pati o n i n t he cli nical st u d y  will als o be c o nsi dere d A Es.
A n A E d oes n ot i ncl u de t he f oll o wi n g:

Me dical or s ur gical pr oce d ures s uc h as s ur ger y, e n d osc o p y, t o ot h e xtracti o n, a n d tra nsf usi o n.
T he c o n diti o n t hat le d t o t he pr oce d ure m a y  be a n A E a n d m ust be re p orte d.

Pre -e xisti n g diseases , c o n diti o ns , or la b orat or y  a b n or malities prese nt or detecte d bef ore t he 
scree ni n g visit t hat d o n ot w orse n

Sit uati o ns w here a n u nt o war d me dical occ urre nce has n ot occ urre d ( e g, h os pitalizati o n f or 
electi ve s ur ger y, s ocial a n d/ or c o n ve nie nce a d missi o ns)

O ver d os e wit h o ut cli nical se q uelae (Secti o n 7. 7. 1 )

A n y  me dical c o n diti o n or cli nicall y si g nifica nt la b orat or y a b n or malit y wit h a n o nset date 
bef ore t he c o nse nt f or m is si g ne d a n d n ot relate d t o a pr ot oc ol -ass ociate d pr oce d ure is n ot a n 
A E. I t is c o nsi dere d t o be pre-e xisti n g a n d s h o ul d be d oc u me nte d o n t he me dical hist or y  case 
re p ort f or m (C R F ).
7. 1. 2.
Seri o us A d verse E ve nts
A n S A E is defi ne d as a n e ve nt t hat, at a n y d ose, res ults i n t he f oll o wi n g:

Deat h

Life -t hreate ni n g ( N ote: T he ter m “life-t hreate ni n g” i n t he defi niti o n of “seri o us” refers t o a n 
e ve nt i n w hic h t he s u bject was at ris k of deat h at t he ti me of t he e ve nt . It d oes n ot refer t o a n 
e ve nt t hat h y p ot heticall y mi g ht ha ve ca use d deat h if it were m ore se vere.)

I n-patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 5 9
1 9 J u ne 2 0 2 0

Persiste nt or si g nifica nt disa bilit y /i nca pacity

A c o n ge nital a n o mal y/ birt h defect

A me dicall y i m p orta nt e ve nt or reacti o n: s uc h e ve nts ma y n ot be i m me diatel y 
life-t hreate ni n g or res ult i n deat h or h os pitalizati o n b ut ma y  je o par dize t he s u bject or ma y 
re q uire i nter ve nti o n t o pre ve nt o ne of t he ot her o utc o mes c o nstit uti n g S A Es. Me dical a n d 
scie ntific j u d g me nt m ust be e xercise d t o deter mi ne w het her s uc h a n e ve nt is a re p orta ble 
u n der e x pe dite d re p orti n g r ules. E xa m ples of me dicall y i m p orta nt e ve nts i ncl u de i nte nsi ve 
treat me nt i n a n e mer ge nc y r o o m or at h o me f or aller gic br o nc h os pas m; bl o o d d yscrasias or 
c o n v ulsi o ns t hat d o n ot res ult i n h os pitalizati o n; a n d de vel o p me nt of dr u g de pe n de nc y  or 
dr u g a b use. F or t he a v oi da nce of d o u bt, i nfecti o ns res ulti n g fr o m c o nta mi nate d me dici nal 
pr o d uct will be c o nsi dere d a me dicall y i m p orta nt e ve nt a n d s u bject t o e x pe dite d re p orti n g 
re q uire me nts.
7. 2.  
Assess me nt of A d verse E ve nts a n d Seri o us A d v erse E ve nts
T he i n vesti gat or or q ualifie d s u bi n vesti gat or is res p o nsi ble f or assessi n g A Es a n d S A Es f or 
ca usalit y a n d se verit y, a n d f or fi nal re vie w a n d c o nfir mati o n of acc urac y of e ve nt i nf or mati o n 
a n d assess me nts.
7. 2. 1.
Assess me nt of C a us alit y f or St u d y Dr u gs a n d Pr oce d ures
T he i n vesti gat or or q ualifie d s u bi n vesti gat or is res p o nsi ble f or assessi n g t he relati o ns hi p t o I M P 
t hera py usi n g cli nical j u d g me nt a n d t he f oll o wi n g c o nsi derati o ns:

N o : E vi de nce e xists t hat t he A E has a n eti ol o g y  ot her t ha n t he I M P. F or S A Es, a n alter nati ve 
ca usalit y m ust be pr o vi de d (e g, pre-e xisti n g c o n diti o n, u n derl yi n g disease, i nterc urre nt 
ill ness, or c o nc o mita nt me dicati o n).

Yes : T here is reas o na ble p ossi bilit y  t hat t he e ve nt ma y ha ve bee n ca use d b y t he 
i n vesti gati o nal me dici nal pr od uct.
It s h o ul d be e m p hasize d t hat i neffecti ve treat me nt s h o ul d n ot be c o nsi dere d as ca usally relate d i n 
t he c o nte xt of A E re p orti n g. 
T he relati o ns hi p t o st u d y  pr oce d ures (e g, i n vasi ve pr oce d ures s uc h as ve ni p u nct ure or bi o psy) 
s h o ul d be assesse d usi n g t he f oll o wi n g c o nsi derati o ns:

N o: E vi de nce e xists t hat t he A E has a n eti ol o g y  ot her t ha n t he st u d y pr oce d ure.

Yes: T he A E occ urre d as a res ult of pr ot oc ol pr oce d ures (e g, ve ni p u n ct ure).


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 6 0
1 9 J u ne 2 0 2 0
7. 2. 2.
Assess me nt of Se verit y
T he se verit y of A Es will be gra de d usi n g t he m o difie d C o m m o n Ter mi n ol o g y Criteria f or 
A d verse E ve nts ( C T C A E), V ersi o n 5. 0 ( A p pe n di x 6 ). F or eac h e pis o de, t he hi g hest gra de
attai ne d s h o ul d be re p orte d.
If a C T C A E criteri o n d oes n ot e xist, t he i n vesti gat or s h o ul d use t he gra de or a djecti ves: 
Gra de 1 ( mil d), Gra de 2 ( m o derate), Gra de 3 (se vere), Gra de 4 (life-t hreate ni n g) or 
Gra de 5 (fatal) t o descri be t he ma xi m u m i nte nsit y of t he A E. F or p ur p oses of c o nsiste nc y wit h 
t he C T C A E, t hese i nte nsit y gra des are defi ne d i n Ta ble 7- 1 .
T a ble 7- 1.
Gr a di n g of A d verse E ve nt Se verit y
Gr a de
A djecti ve
Descri pti o n
Gra de 1
Mil d
As y m pt o matic or mil d s y m pt o ms; cli nical or dia g n ostic o bser vati o ns o nl y; 
i nter ve nti o n n ot i n dicate d
Gra de 2
M o derate
L ocal or n o ni n vasi ve i nter ve nti o n i n dicate d; li miti n g a ge-a p pr o priate 
i nstr u me ntal A D L
Gra de 3
Se vere
Se vere or me dicall y si g nifica nt b ut n ot i m me diatel y life -t hreate ni n g; 
h os pitalizati o n or pr ol o n gati o n of h os pitalizati o n i n dicate d; disa bli n g; 
li miti n g self-care A D L
Gra de 4
Life -t hreate ni n g
Ur ge nt i nter ve nti o n i n dicate d
Gra de 5
Deat h
Deat h relate d A E
*  
Acti vities of Dail y Li vi n g ( A D L) I nstr u me ntal A D L refer t o o pe ni n g pre pari n g meals, s h o p pi n g f or gr oceries or cl ot hes, 
usi n g t he tele p h o ne, ma na gi n g m o ne y, etc. 
* *
Self care A D L refer t o bat hi n g, dressi n g a n d u n dressi n g, fee di n g self, usi n g t he t oilet, ta ki n g me dicati o ns, a n d n ot be dri d de n
7. 3. 
I n vesti g at or Re q uire me nts a n d I nstr ucti o ns f or Re p orti n g A d verse E ve nts 
a n d Seri o us A d verse E ve nts t o Gile a d 
After i nf or me d c o ns e nt, b ut pri or t o i nitiati o n of st u d y  me dicati o n, t he f oll o wi n g ty pes of e ve nts 
s h o ul d be re p orte d o n t he C R F/e C R F: all S A Es a n d A Es relate d t o pr ot oc ol-ma n date d 
pr oce d ures.
7. 3. 1.
A d verse E ve nts
F oll o wi n g i nitiati o n of st u d y  me dicati o n, re p ort all A Es, re gar dless of ca use or relati o ns hi p, u ntil 
3 0 da y s after last a d mi nistrati o n of st u d y IM P m ust be re p orte d t o t he C R F/e C R F data base as 
i nstr ucte d.
All A Es s h o ul d be f oll o we d u p u ntil res ol uti o n or u ntil t he A E is sta ble, if p ossi ble. Gilea d 
Scie nces ma y  re q uest t hat certai n A Es be f oll o we d be yo n d t he pr ot oc ol -defi ne d f oll o w- u p 
peri o d.


G S -4 8 7 5 
Pr ot o c ol G S -U S -3 6 5- 4 2 3 7 
Gil e a d S ci e n c es, Inc. 
7. 3. 2. 
S e ri o us A d v e rs e E v e nts 
Fi nal 
A m e n dm e nt 2 
All S A Es, r e g ar dless of c a us e or r elati o ns h ip, t h at o c c urs aft er t h e s u bje ct first c o ns e nts t o 
p art icip at e i n t he st u d y (ie, si gni n g t h e i nf o n n e d c o ns e nt) a n d t hr o u g h o ut t h e d ur atio n of t he 
st u d y, i n cl u di n g t h e pr ot o c o l-r e q uir e d p ost tr e at m e nt f ollo w- u p p eri o d, m u st b e r e p ort e d t o t h e 
C R F /e C R F d at a b as e a n d G ile a d P Y E as i nstr u ct e d. T hi s als o in cl u d es a n y S A Es r es ultin g fr o m 
pr ot o c o l- ass o ciat e d pr o c e d ur es p erf o n n e d aft er inf o n n e d c o ns e nt is sig n e d . 
A n y S A Es a n d d e at hs t h at o c c ur aft er t he p ost tr e at m e nt f ollo w- u p visit b ut wi t hi n 3 0- d a ys of t he 
last d os e of st u d y I M P, r e g ar dl ess of c a us a lit y, s h o u l d als o b e r e p ort e d. 
I nv estig at ors are n ot o b lig at e d t o a ctiv e l y s e e k S A Es aft er t h e pr ot o c o l- d efi n e d f ollo w- u p p er io d; 
h o w e v er, if t h e i nv est ig at or le ar ns of a n y S A Es t h at o c c ur aft er st u d y p arti c ip at io n h as c o n cl u d e d 
a n d t h e e v e nt is d e e m e d r el e v a nt t o t h e us e of I M P, h e /s h e s h o u l d pr o m ptl y d o c u m e nt a n d r e p ort 
t he e v e nt t o G ile a d P Y E. 
All A E s a n d S A Es w ill b e r e c or d e d i n t he C R F /e C R F d at a b as e wi t hi n t h e ti mel i nes o utli n e d i n 
t he C R F /e C R F c o m p letio n g ui d e li ne. 
El e ctr o ni c S er io us A d v ers e E v e nt ( e S A E) R e p ortin g Pr o c ess 
•  
Site pers o 1 me l r e c or d a ll S A E d at a i n t he e C R F d at a b as e a n d fr o m t h er e tr a ns mit t he S A E 
i nf o n n ati o n t o G ile a d P Y E wi t hi n 2 4 h o urs of t h e i nv est ig at or's k n o wl e d g e of t he e v e nt. 
D et a ile d instr u ct io ns c a n b e f o m 1 d i n t h e e C R F c o m p let io n g ui d e li nes . 
• 
If f or a n y r e as o n it is n ot p oss i ble t o r e c or d t h e S A E i nf o n n atio n ele ctr o ni c all y, ie, t h e e C R F 
d at a b as e is n ot f u n ctio n i ng, r e c or d t he S A E o n t h e p a p er S A E r e p orti ng f o n n a n d s u bmit 
wi t hi n 2 4 h o ur s t o: 
•  
Gile a d P Y E 
•  
As s o o n as it is p oss ible t o d o s o, a n y S A E r e p ort e d via p a p er m u st b e tr a ns crib e d i nt o t h e 
e C R F D at a b a s e a c c or di n g t o instr u ct io ns i n t he e C R F c o m p letio n g u id e lin es . 
• 
If a n S A E h as b e e n r e p ort e d via a p a p er f o n n b e c a us e t he e C R F d at a b as e h as b e e n lo c k e d, n o 
f urt her a ct io n is n e c ess ar y . 
• 
F or fatal or lif e-t hr e at e ni n g e v e nts , c o p ies of h os p it al c as e r e p orts, a ut o ps y r e p orts, a n d ot h er 
d o c u m e nts are als o t o b e s u bmitt e d b y e- m ail or fa x w h e n r e q u est e d a n d a p p lic a bl e . 
Tr a n smi ssio n of s u ch d o c u m e nts s h o u l d o c c ur wi t h o ut p ers o n a l s u bje ct id e nt ifi c atio n, 
m ai nt ai ni n g t h e tr a c e a bilit y of a d o c u m e nt t o t h e s u bje ct i d e ntifiers . 
• 
A d diti o n al i nf o n n atio n m a y b e r e q u est e d t o e n s ur e t h e ti mel y c o m p let i o n of a c c ur at e s af et y 
r e p orts. 
• 
A n y m e d ic at io ns n e c ess ar y f or tr e at m e nt of t he S A E m u st b e r e c or d e d o nt o t h e c o n c o m it a nt 
m e d ic ati o n s e cti o n of t h e s u bje ct's C R F /e C R F a n d t he e v e nt d es cri pt io n s e cti o n of t h e S A E 
f o n n. 
C O N FI D E N T IA L 
P a g e 6 1 
1 9 Ju n e 2 0 2 0 


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 6 2
1 9 J u ne 2 0 2 0
7. 4.
Gile a d Re p orti n g Re q uire me nts
De pe n di n g o n rele va nt l ocal le gislati o n o r re g ulati o ns, i ncl u di n g t he a p plica ble U S F D A C o de of 
Fe deral Re g u lati o ns, t he E U Cli nical Trials Directi ve ( 2 0 0 1/ 2 0/ E C) a n d rele va nt u p dates, a n d 
ot her c o u ntr y -s pecific le gislati o n or re g ulati o ns, Gilea d ma y be re q uire d t o e x pe dite t o 
w orl d wi de re g ulat or y a ge ncies re p orts of S A Es, seri o us a d verse dr u g reacti o ns ( S A D Rs), or 
S U S A Rs. I n acc or da nce wit h t he E U Cli nical Trials Directi ve ( 2 0 0 1/ 2 0/ E C), Gilea d or a 
s pecifie d desi g nee will n otif y w orl d wi de re g ulat or y a ge ncies a n d t he rele va nt I E C i n c o ncer ne d 
Me m b er States of a p plica ble S U S A Rs as o utli ne d i n c urre nt re g ulati o ns.
Assess me nt of e x pecte d ness f or S A Es will be deter mi ne d b y  Gilea d usi n g refere nce safet y 
i nf or mati o n s pecifie d i n t he G S - 4 8 7 5 I B or rele va nt l ocal la bel as a p plica ble. 
All i n vesti gat ors will recei ve a safet y letter n otif yi n g t he m of rele va nt S U S A R re p orts ass ociate d 
wit h a n y  st u d y IM P . T he i n vesti gat or s h o ul d n otif y t he I R B or I E C of S U S A R re p orts as s o o n as 
is practical, w here t his is re q uire d by l ocal re g ulat or y a ge ncies, a n d i n acc or da nce wit h t he l ocal 
i nstit uti o nal p olic y. 
7. 5.
Cli nic al L a b or at or y A b n or m alities a n d Ot her A b n or m al Assess me nts as 
A d verse E ve nts or Seri o us A d verse E ve nts
La b orat or y  a b n or malities are us ually n ot rec or de d as A Es or S A Es. H o we ver, la b orat or y  
a b n or malities (e g, cli nical c he mistr y, he mat ol o g y, a n d uri nalys is) i n de pe n de nt of t he 
u n derl y i n g me dical c o n diti o n t hat re q uire me dical or s ur gical i nter ve nti o n or lea d t o 
i n vesti gati o nal me dici nal pr o d uct i nterr u pti o n or disc o nti n uati o n m ust be rec or de d as a n A E, 
as well as a n S A E, if a p plica ble. I n a d diti o n, la b orat or y  or ot her a b n or mal assess me nts (e g, E C G, 
X- ra ys, a n d vital si g ns) t hat are ass ociate d wit h si g ns a n d/ or sy m pt o ms m ust be rec or de d as a n 
A E or S A E if t he y  meet t he defi niti o n of a n A E ( or S A E) as descri be d i n Secti o ns 7. 1. 1
a n d 7. 1. 2 . If t he la b orator y  a b n or malit y is part of a s yn dr o me, rec or d t he sy n dr o me or dia g n osis 
(ie, a ne mia) n ot t he la b orat or y res ult (ie, decrease d he m o gl o bi n).
Se verit y  s h o ul d be rec or de d a n d gra de d acc or di n g t o t he C T C A E Gra di n g Scale f or Se verit y of 
A E s a n d La b orat or y A b n or malities (A p pe n di x 6 ). F or A Es ass ociate d wit h la b orat or y 
a b n or malities, t he e ve nt s h o ul d be gra de d o n t he basis of t he cli nical se verit y i n t he c o nte xt of 
t he u n derlyi n g c o n diti o ns; t his ma y  or ma y n ot be i n a gree me nt wit h t he gra di n g of t he 
la b orat or y a b n or malit y.
7. 6. 
T o xicit y M a n a ge me nt
T he i n vesti gat or is res p o nsi ble f or m o nit ori n g of A Es a n d la b or at or y para meters f or gra de d 
t o xicities. Refer t o Secti o n 6. 1 3 , f or g ui da nce o n f urt her acti o ns i n case of treat me nt-e mer ge nt 
t o xicities.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 6 3
1 9 J u ne 2 0 2 0
Ma na ge me nt of A Es a n d la b orat or y  t o xicities n ot c o vere d by Secti o n 6. 1 3 is at t he discreti o n of 
t he i n vesti gat or. F or Gra de 3 a n d 4 t o xicities, relati o ns hi p t o st u d y dr u g, cli nical stat us of 
s u bject, a n d t he i n vesti gat or assess me nt of s u bject safety s h o ul d i nf or m st u d y dr u g i nterr u pti o n 
a n d s u bse q ue nt re- i ntr o d ucti o n or per ma ne nt disc o nti n uati o n. A b n or mal la b orat or y val ues s h o uld 
be re peate d w he n necessar y  a n d f oll o we d u ntil res ol uti o n w he n cli nicall y a p pr o priate.
A n y  q uesti o ns re gar di n g t o xicit y ma na ge me nt or ma na ge me nt of s pecific la b orat or y val ues 
s h o ul d be directe d t o t he st u d y me dical m o nit or.
7. 7.
S peci al Sit u ati o ns Re p orts
7. 7. 1.
Defi niti o ns of S peci al Sit u ati o ns
S pecial sit uati o n re p orts i ncl u de all re p orts of me dicati o n err or, a b use, mis use, o ver d ose, re p orts 
of A E s ass ociate d wit h pr o d uct c o m plai nts, a n d pre g na nc y re p orts re gar dless of a n ass ociate d 
A E.
Me dicati o n err or is a ny u ni nte nti o nal err or i n t he prescri bi n g, dis pe nsi n g, or a d mi nistrati o n of a 
me dici nal pr o d uct w hile i n t he c o ntr ol of t he healt h care pr o vi der, s u bject, or c o ns u mer.
A b use is defi ne d as persiste nt or s p ora dic i nte nti o nal e xcessi ve use of a me dici nal pr o d uc t b y a 
s u bject.
Mis use is defi ne d as a n y i nte nti o nal a n d i na p pr o priate use of a me dici nal pr o d uct t hat is n ot i n 
acc or da nce wit h t he pr ot oc ol i nstr ucti o ns or t he l ocal prescri bi n g i nf or mati o n.
A n o ver d ose is defi ne d as a n acci de ntal or i nte nti o nal a d mi nist rati o n of a q ua ntit y of a me dici nal 
pr o d uct gi ve n per a d mi nistrati o n or c u m ulati vel y  w hic h is a b o ve t he ma xi m u m rec o m me n de d 
d ose as per pr ot oc ol or i n t he pr o d uct la beli n g (as it a p plies t o t he dail y  d ose of t he s u bject i n 
q uesti o n). I n cases of a discre pan c y  i n dr u g acc o u nta bilit y, o ver d ose will be esta blis he d o nl y 
w he n it is clear t hat t he s u bject has ta ke n t he e xcess d ose(s). O ver d ose ca n n ot be esta blis he d 
w he n t he s u bject ca n n ot acc o u nt f or t he discre pa nc y  e xce pt i n cases i n w hic h t he i n vesti gat or has 
reas o n t o s us pect t hat t he s u bject has ta ke n t he a d diti o nal d ose(s).
Pr o d uct c o m plai nt is defi ne d as c o m plai nts arisi n g fr o m p ote ntial de viati o ns i n t he ma n ufact ure, 
pac ka gi n g, or distri b uti o n of t he me dici nal pr o d uct.
7. 7. 2.
I nstr ucti o ns f or Re p orti n g S peci al Sit u ati o ns
7. 7. 2. 1.
I nstr ucti o ns f or Re p orti n g Pre g na ncies
T he i n vesti gat or s h o ul d re p ort pre g na ncies i n fe male st u d y s u bjects t hat are i de ntifie d after 
i nitiati o n of st u d y  me dicati o n a n d t hr o u g h o ut t he st u d y, i ncl u di n g t he p ost st u d y dr u g f oll o w -u p 
peri o d, t o t he Gilea d P V E usi n g t he pre g na nc y  re p ort f or m wit hi n 2 4 h o urs of bec o mi n g a ware 
of t he pre g na nc y .


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 6 4
1 9 J u ne 2 0 2 0
Refer t o Secti o n 7. 3 a n d t he C R F/e C R F c o m pleti o n g ui deli nes f or f ull i nstr ucti o ns o n t he 
mec ha nis m of pre g na nc y re p orti n g.
T he pre g na nc y  itself is n ot c o nsi dere d a n A E n or is a n i n d uce d electi ve a b orti o n t o ter mi nate a 
pre g na nc y  wit h o ut me dical reas o ns.
A n y  pre mat ure ter mi nati o n of pre g na nc y (e g, a s p o nta neo us a b orti o n, a n i n d uce d t hera pe utic 
a b orti o n d ue t o c o m plicati o ns or ot her me dical reas o ns) m ust be re p orte d wit hi n 2 4 h o urs as a n 
S A E. T he u n derl yi n g me dical reas o n f or t his pr oce d ure s h o ul d be rec or de d as t he A E ter m.
A s p o nta ne o us a b orti o n is al wa y s c onsi dere d t o be a n S A E a n d w ill be re p orte d as descri be d i n 
S ecti o ns 7. 1. 2 a n d 7. 3. 2 . F urt her m ore, a ny S A E occ urri n g as a n a d verse pre g na nc y  o utc o me p ost 
st u d y m ust be re p orte d t o Gilea d P V E
T he s u bject s h o ul d recei ve a p pr o priate m o nit ori n g a n d care u ntil t he c o ncl usi o n of t he 
pre g na nc y . T he o utc o me s h o ul d be re p orte d t o Gilea d P V E usi n g t he pre g na nc y  o utc o me re p ort 
f or m. If t he e n d of t he pre g na nc y occ urs after t he st u d y has bee n c o m plete d, t he o utc o me s h o ul d 
be re p orte d directl y t o Gilea d P V E . Gilea d P V E c o ntact i nf or mati o n is as f oll o ws: E mail: 
 a n d Fa x: 
.
Pre g na ncies of fe male part ners of male st u d y s u bjects e x p ose d t o Gilea d or ot her st u d y  dr u gs 
m ust als o be re p orte d a n d rele va nt i nf or mati o n s h o ul d be s u b mitte d t o Gilea d P V E usi n g t he 
pre g na nc y  a n d pre g na nc y o utc o me f or ms wit hi n 2 4 h o urs of t he i n vesti gat or bec o mi n g a ware of 
t he sit uati o n. 
M o nit ori n g of t he s u bject s h o ul d c o nti n ue u ntil t he c o ncl usi o n of t he pre g na nc y . If t he e n d of t he 
pre g na nc y  occ urs after t he st u d y has bee n c o m plete d, t he o utc o me s h o ul d be re p orte d directly t o 
Gilea d P V E , fa x n u m ber 
 or e mail
 
Refer t o A p pe n di x 8 f or Pre g na nc y Preca uti o ns, Defi niti o n f or Fe male of C hil d beari n g P ote ntial, 
a n d C o ntrace pti ve Re q uire me nts .
7. 7. 2. 2.
Re p orti n g Ot her S pecial Sit uati o ns
All ot her s pecial sit uati o n re p orts m ust be re p orte d o n t he s pecial sit uati o ns re p ort f or m a n d 
f or war de d t o Gilea d P V E wit hi n 2 4 h o urs of t he i n vesti gat or bec o mi n g a ware of t he sit uati o n. 
T hese re p ort s m ust c o nsist of sit uati o ns t hat i n v ol ve st u d y IM P
a n d/ or Gilea d c o nc o mita nt 
me dicati o ns , b ut d o n ot a p pl y t o n o n- Gilea d c o nc o mita nt me dicati o ns. 
S pecial sit uati o ns i n v ol vi n g n o n- Gilea d c o nc o mita nt me dicati o ns d oes n ot nee d t o be re p orte d o n 
t he s pecial sit uati o ns re p ort f or m; h o we ver, f or s pecial sit uati o ns t hat res ult i n A Es d ue t o a 
n o n- Gilea d c o nc o mita nt me dicati o n, t he A E s h o ul d be re p orte d o n t he A E f or m. 
A n y  i na p pr o priate use of c o nc o mita nt me dicati o ns pr o hi bite d b y  t his pr ot oc ol s h o ul d n ot be 
re p orte d as “ mis use,” b ut ma y be m ore a p pr o priatel y d oc u me nte d as a pr ot oc ol de viati o n.
P P D
P P D
P P D
P P D


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 6 5
1 9 J u ne 2 0 2 0
Refer t o Secti o n 7. 3 a n d t he C R F/e C R F c o m pleti o n g ui deli nes f or f ull i nstr ucti o ns o n t he 
mec ha nis m of s pecial sit uati o ns re p orti n g.
All cli nical se q uelae i n relati o n t o t hese s pecial sit uati o n re p orts will be re p orte d as A Es or S A Es 
at t he sa me ti me usi n g t he A E C R F/e C R F a n d/ or t he S A E re p ort f or m. Details of t he s y m pt o ms 
a n d si g ns, cli nical ma na ge me nt, a n d o utc o me will be re p orte d, w he n a vaila ble.
7. 8.
S afet y S ur veill a nce
Gilea d P V E peri o dicall y  re vie ws acc u m ulati n g safet y data acr oss c o m plete d a n d o n g oi n g st u dies 
wit hi n t he G S - 4 8 7 5 de vel o p me nt pr o gra m t o detect seri o us a n d u ne x pecte d s us pecte d a d verse 
reacti o ns a n d cli nicall y i m p orta nt i ncrease d rates of pre vi o usly rec o g nize d seri o us a d verse 
reacti o ns. If, d uri n g t he peri o dic re vie w of safety data fr o m cli nical st u dies, a si g nifica n t 
n u merical i m bala nce is o bser ve d f or a n A E acr oss treat me nt gr o u ps base d o n pre defi ne d 
re p orti n g t hres h ol ds, a Safet y  Assess me nt C o m mittee ( S A C) will re vie w u n bli n de d safety data 
a n d deter mi ne if a n y acti o ns are necessar y t o pr otect s u bjects i n v ol ve d i n t he G S - 4 8 7 5
de vel o p me nt pr o gra m. I n or der t o preser ve t he scie ntific i nte grit y  of t he trial data, t he S A C 
me m bers will be Gilea d e m pl o yees w h o are n ot i n v ol ve d i n t he c o n d uct a n d a nal ys is of st u dies 
wit hi n t he G S - 4 8 7 5 de vel o p me nt pr o gra m.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 6 6
1 9 J u ne 2 0 2 0
8.
S T A T I S TI C A L C O N SI DE R A TI O N S
8. 1.
A n al ysis O bjecti ves a n d E n d p oi nts
8. 1. 1.
A n al ysis O bjecti ves
T he o bjecti ves of t he st u d y  are descri be d i n Secti o n 2 .
8. 1. 2.
St u d y E n d p oi nts
T he st u d y  e n d p oi nts are liste d i n Secti o n 2 .
8. 2.
Pl a n ne d A n al yses
8. 2. 1. 
I nteri m A n al ysis
8. 2. 1. 1.
Pla n ne d I nter nal U n bli n de d A nal ys is
T he G D R C defi ne d i n Secti o n 5. 1. 3 will perf or m t he data re vie w of st u d y data after 9 0 s u bjects 
c o m plete t he Wee k 1 0 visit or earl y disc o nti n ue fr o m t he st u d y. Base d o n t he i nteri m a nal ys is, 
t he G D R C ma y pr o p ose c ha n ges i n t he st u d y desi g n, i ncl u di n g p ote ntial ter mi nati o n of st u d y d ue 
t o f utilit y. A d h oc data re vie ws at a d diti o nal ti me p oi nts ma y als o be c o n d ucte d b y t he G D R C if 
nee de d.
T he st u d y  data t hat will be pr o vi de d t o t he G D R C ma y be u n bli n de d at i n di vi d ual s u bject le vel
a n d/ or gr o u p le vel, i ncl u di n g t he f oll o wi n g cli nical, e n d osc o pic, hist ol o gic a n d bi o mar ker 
e n d p oi nts: Cli nical re missi o n per m o difie d M C S, M C S res p o nse, e n d osc o pic res p o nse, U C - 1 0 0, 
Ge b oes re missi o n, fecal cal pr otecti n, fecal lact oferri n, a n d C R P.
A d diti o nal data ma y  be pr o vi de d t o t he G D R C u p o n re q uest.
If, base d o n t he re vie w of st u d y data, t he G D R C c o ncl u des t hat treat me nt wit h G S - 4 8 7 5 d oes n ot 
p ositi vel y  i m pact t he disease u n der st u d y, t he G D R C ma y re q uest a n a d- h oc D M C meeti n g t o 
f urt her e val uate w het her c o nti n uati o n of t he trial warra nte d.
8. 2. 2.
Wee k 1 0 A n al ysis
A Wee k 1 0 a nal ys is will be c o n d ucte d w he n all ra n d o mize d s u bjects (a p pr o xi matel y 1 8 0) ha ve 
c o m plete d 1 0 wee ks of bli n de d st u d y  dr u g or disc o nti n ue d fr o m t he st u d y, a n d ass ociate d safety 
a n d efficac y assess me nts ha ve bee n c o m plete d. T he st u d y  will be u n bli n de d a n d Wee k 1 0 safet y 
a n d efficac y a nal ys es (i ncl u di n g pri mar y a nalys is [ See Secti o n 8. 5. 1 ]) will be perf or me d. T he 
p ur p ose of t hese a nal ys es is t o i nf or m st u d y disc o nti n uati o n or f urt her de vel o p me nt of G S -4 8 7 5
f or t he treat me nt of U C. If t he s p o ns or c o ncl u des t hat treat me nt wit h G S -4 8 7 5 has a n 
u nfa v ora ble be nefit -ris k pr ofile, t he s p o ns or will re q uest a n a d-h oc D M C meeti n g. T he D M C 
will be re q ueste d t o e val uate t he a vaila ble st u d y  data a n d t o ma ke rec o m me n dati o n o n w het her 
t he st u d y s h o ul d be st o p pe d, c o nti n ue d, or c o nti n ue d wit h m o dificati o ns.


G S -4 8 7 5 
Pr ot o c ol G S -U S -3 6 5- 4 2 3 7 
Gil e a d S ci e n c es, Inc. 
8. 3. 
8. 3. 1. 
8. 3. 1. 1. 
A n al ysis C o n v e nti o ns 
A n al ysis S ets 
Effi c a c y 
Fi nal 
A m e n dm e nt 2 
T h e pr i mar y a n a lys is s et f or effi c a c y a n alys is is t h e F u ll A n a lys is S et ( F A S), d efi n e d as a ll 
r a n d o miz e d s ubj e cts w h o r e c eiv e d at le ast 1 d os e of st u d y dr u g . 
S u bj e cts w ill b e a n aly z e d a c c or d i ng t o t h e tr e at m e nt gr o u p t h e y w er e r a n d o miz e d t o f or t h e 
a n a lys is p er io d . 
8. 3. 1. 2 . 
S af et y 
T h e pr i mar y a n a lys is s et f or s af et y a n alys es is t h e S af et y A n a lys is S et , d efi n e d as a ll s u bje cts 
w h o r e c eiv e at le ast o n e d os e of st u d y dr u g . 
S u bj e cts w ill b e a n aly z e d a c c or d i ng t o t h e st ud y dr u g t h e y a ct u a lly r e c eiv e d f or t h e a n al ys is 
p er io d . 
A ll d at a c o lle ct e d d uri n g tr e at m e nt u p t o t he d at e of last d os e of I M P pl us 3 0 d a ys w ill b e 
i n cl u d e d i n t he s af et y s mm n ari es . 
-
8. 3. 1. 4 . 
Bi o m ar k ers 
T h e Bi o m ar k er A n a lys is S et in cl u d es a ll s u bje cts w h o r e c eiv e at le ast o n e d os e of st u d y dr u g a n d 
h a v e t h e n e c ess ar y b as e lin e a n d o n-st u d y m e as ur e m e nts t o pr o vi d e i nt er pr et a ble r es ults f or t h e 
s p e cific p ar a m et ers of i nt er est. 
8. 4. 
D at a H a n dli n g C o n v e nti o ns 
Pr o c e d ur es f or h a n d lin g mi ssi ng d at a f or M C S ( a n d c o m p o n e nts) w ill b e d es cr ib e d i n t he 
st atisti c al a n al ys is pla n ( S AP). 
C O N FI D E N T IA L 
P a g e 6 7 
1 9 Ju n e 2 0 2 0 


G S -4 8 7 5 
Pr ot o c ol G S -U S -3 6 5- 4 2 3 7 
Gil e a d S ci e n c es, I nc. 
8. 5. 
E ffic acy A n al y sis 
8. 5. 1. 
Pri m ar y A n al y sis 
Fi nal 
A m e n d m e nt 2 
T h e pr im ar y a n a lys is will c o m p ar e e a c h G S- 4 8 7 5 d os e gr o u p t o pl a c e b o o n t h e pr o p ort io n of 
s u bje cts a c h ie vi n g Cli ni c a l R e mi ssio n p er M o d ifie d M C S at W e e k 1 0 . Th e 
C o c hr a n- M a nt e l- H a e ns z el ( C M H) a p pr o a c h a djust in g f or str atifi c ati o n f a ct ors w ill b e us e d f or 
h y p ot h es is t esti n g of t he pr im ar y e n d p o int. F or e v alu atio n of cli ni c a l r emi ssio n p er m o d ifie d 
M C S at W e e k 1 0, M C S s c or e at s cr e e ni n g w ill b e us e d as b as e lin e v a lu e . 
S u b je cts w h o d o n ot h a v e s uffi ci e nt m e as ur e m e nts t o d et e nn i ne effi c a c y e n d p o ints w ill b e 
c o nsi d er e d failur es (ie, n o n-r es p o n d er i mp ut at io n [ N RI]). 
8. 5. 2. 
S e c o n d a r y A n al y s es 
T h e s am e st atistic al met h o ds us e d f or a n al y z in g t he pr i mar y effi c a c y e nd p o int w ill b e ut iliz e d f or 
a n a lyz in g t he bi n ar y s e c o n d ar y e n d p o ints . S u b je cts w h o d o n ot h a v e s uffi cie nt m e as ur em e nts t o 
d et e nni n e t he effi c a c y e n d p o i nts w ill b e c o ns id er e d failur es (ie, N RI) . 
-
8. 6. 
S af et y A n al y sis 
A ll s af et y d at a c o lle ct e d o n or aft er t h e d at e t h at IM P w as first di s p e ns e d u p t o t he d at e of last 
d os e of IM P pl us 3 0 d a ys w ill b e s u m m ariz e d b y tr e at m e nt gr o u p ( a c c or din g t o t he IM P 
r e c eiv e d) . Dat a f or t h e pr etr e at m e nt w ill b e i ncl u d e d i n d at a listin gs . 
8. 6. 1. 
E xt e nt of E x p os ure 
A s u bje ct's e xt e nt of e x p os ur e t o IM P d at a w ill b e g e n er at e d fr om t he IM P a d 1ni ni str atio n d at a . 
E x p os ur e d at a w ill b e s m mn ariz e d b y tr e atm e nt gr o u p . 
8. 6. 2. 
A d v e rs e E ve nts 
C lini c a l a n d la b or at or y A Es w ill b e c o d e d us in g t he M e d ic a l Di ct io n ar y f or R e g u lat or y 
A ct i vities ( M ed D R A) . S yst e m or g a n class ( S O C), Hi g h- L e v e l Gr o u p T e nn ( H L GT ), Hi g h- L e v e l 
T e nn ( H L T ), Pr ef err e d T e nn ( PT ), a n d L o w er- L e v e l Te nn ( L LT) w ill b e att a c h e d t o t h e clin i c al 
d at a b as e . 
C O N FI D E N T IA L 
P a g e 6 8 
1 9 Ju n e 2 0 2 0 


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 6 9
1 9 J u ne 2 0 2 0
T reat me nt- e mer ge nt a d verse e ve nt ( T E A E) will be defi ne d as 1 or b ot h of t he f ol l o wi n g:

A n y  A E wit h a n o nset date o n or after t he st u d y dr u g start date a n d n o later t ha n 3 0 d a y s after 
per ma ne nt disc o nti n uati o n of st u d y  dr u g.

A n y  A E lea di n g t o pre mat ure disc o nti n uati o n of st u d y dr u g
S u m maries ( n u m ber a n d perce nta ge of s u bjects) of T E A Es ( by S O C, a n d P T) will be pr o vi de d 
b y  treat me nt gr o u p. T E A Es will als o be s u m marize d b y  relati o ns hi p t o st u d y dr u g a n d se verit y. 
I n a d diti o n, T E A Es lea di n g t o pre mat ure disc o nti n uati o n of st u d y dr u g will be s u m marize d a n d 
liste d. 
8. 6. 3.
L a b or at or y E v al u ati o ns
Selecte d la b orat or y  data ( usi n g c o n ve nti o nal u nits) will be s u m marize d usi n g o nl y o bser ve d data. 
A bs ol ute val ue a n d c ha n ge fr o m baseli ne at all sc he d ule d ti me p oi nts will be s u m marize d.
Gra de d la b orat or y  a b n or malities will be defi ne d usi n g t he C T C A E i n A p pe n di x 6 .
I nci de nce of treat me nt -e mer ge nt la b orat or y a b n or malities, defi ne d as val ues t hat i ncrease at least 
1 t o xicit y  gra de fr o m baseli ne at a n y ti me p ost baseli ne, will be s u m marize d b y  treat me nt gr o u p.
If baseli ne data are missi n g, t he n a ny gra de a b n or malit y  (ie, at least a Gra de 1) will be 
c o nsi dere d treat me nt e mer ge nt. 
8. 6. 4.
Ot her S afet y E v al u ati o ns
I n di vi d ual data f or P E fi n di n gs, pri or a n d c o nc o mita nt me dicati o ns a n d me dical hist or y  will be 
pr o vi de d. T wel ve -lea d E C Gs a n d vital si g ns meas ure me nts will be liste d b y s u bject a n d 
s u m marize d b y i nci de nce of e ve nts/a b n or malities or descri pti ve statistics as a p pr o priate.
8. 7.
A dj ust me nts f or M ulti plicit y
T here are n o i nteri m a nal yses f or efficac y a n d n o pla ns t o st o p t his st u d y earl y f or fa v ora ble 
efficac y. T he f oll o wi n g pri mar y  a n d ke y sec o n dar y e n d p oi nts will be teste d se q ue ntiall y  at a
o ne- si de d T ype 1 err or rate of 2. 5 % i n t he f oll o wi n g or der:
G S - 4 8 7 5 3 0 0 m g vs pl ace b o
1.
T he pr o p orti o n of s u bjects wit h cli nical re missi o n per m o difie d M C S at Wee k 1 0
2.
T he pr o p orti o n of s u bjects wit h e n d osc o pic res p o nse at Wee k 1 0
3.
T he pr o p orti o n of s u bjects wit h M C S r es p o nse at Wee k 1 0
4.
T he pr o p orti o n of s u bjects wit h M C S re missi o n at Wee k 1 0
5.
T he pr o p orti o n of s u bjects wit h hist ol o gic re missi o n at Wee k 1 0


G S -4 8 7 5 
Pr ot o c ol G S -U S -3 6 5- 4 2 3 7 
Gil e a d S ci e n c es, Inc. 
G S- 4 8 7 5 1 0 0 m g vs pl a c e b o 
6. T h e pr o p orti o n of s u bje cts wi t h cli ni c al r e missi o n p er m o difi e d M C S at W e e k 1 0 
7. T h e pr o p orti o n of s u bje cts wi t h e n d os c o p ic r es p o ns e at W e e k 1 0 
8. T h e pr o p orti o n of s u bje cts wi t h M C S r es p o ns e at W e e k 1 0 
9. T h e pr o p orti o n of s u bje cts wi t h M C S r e missi o n at W e e k 1 0 
1 0 . T h e pr o p orti o n of s u bje cts wi t h hi st o lo gi c r e missi o n at W e e k 1 0 
Fi nal 
A m e n dm e nt 2 
T est in g w ill st o p wi t h t he first of t h es e e n d p o ints faili ng t o r e a c h st atistic al sig n ific a n c e a n d a ll 
s u bs eq u e nt e n d p o ints w o u l d n ot b e c o ns id er e d f or st atistic a l sig n ific a n c e a n d o n ly n o m in a l 
p- v a lu es w ill b e r e p ort e d. I n t his wa y, t h e o v er a ll o n e-s id e d T y p e I err or rate i n t esti n g t h es e 
e n d p o i nts is c o ntr o lle d at a 2. 5 % le ve l. 
8. 9. 
Bi o m a r k e r A n al ysis 
D es cript iv e st atistics of b as e li ne a n d c h a n g e i n bi o m ar k ers w ill b e pr o vi d e d at e a ch s am pli n g 
ti me b y tr e at m e nt. T o e v a luate tr e at m e nt eff e ct, a mi x e d- eff e ct a n alys is of v ar ia n c e m o d el w ill 
b e use d t o c alc u lat e a p o int est i mat e a n d 2-s ide d 9 5 % CI f or t h e m e an p er c e nt c h a n g e fr o m 
b as e lin e i n bi o m ar k er le v e l f or e a c h tr e at m e nt gr o u p at in d ivi d u a l ti me p o i nts. T h e est i mate a n d 
9 5 % CI of di ffere nce i n m e an p er c e nt c h a n g e fr o m b as e li ne b et w e e n e a ch G S- 4 8 7 5 d os e gr o u p 
a n d pl a c e b o w ill b e pr o vi d e d as we ll. 
C O N FI D E N T IA L 
P a g e 7 0 
1 9 Ju n e 2 0 2 0 


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 7 1
1 9 J u ne 2 0 2 0
8. 1 0.
S a m ple Size
A sa m ple size of 6 0 s u bjects i n t he place b o gr o u p a n d 6 0 s u bjects i n eac h G S - 4 8 7 5 d ose gr o u p
( n
1 2 0 t otal f or G S -4 8 7 5 ) will pr o vi de a p pr o xi matel y 7 5% p o wer f or eac h G S 4 8 7 5 d ose gr o u p 
c o m paris o n t o p lace b o at a 1- si de d 0. 0 2 5 si g nifica nce le vel t o detect a treat me nt differe nce i n 
cli nical re missi o n per m o difie d M C S res p o nse rate of 1 7. 5 % ( 2 2. 5 % o n G S -4 8 7 5 a n d 5 % o n 
place b o) base d o n Fis her’s e xact test.
St u d y  G S-U S - 3 6 5-4 2 3 7 c o m pares G S -4 8 7 5 t o place b o i n s u bjects w h o pre vi o usl y de m o nstrate d 
a n i na de q uate res p o nse or l oss of res p o nse t o a T N F α i n hi bit or ( T N F α fail ures). Res ults fr o m 
pre vi o usl y  c o n d ucte d st u dies i n dicate t hat place b o res p o nse rates f or T N F α fail ures are l o w, 
2. 5 % t o 6. 9 %, c o m pare d t o t he rates f or s u bjects n a ive t o T N F α i n hi bit ors, 8. 7 % t o 1 1 %
{ Sa n d b or n 2 0 2 0a , Sa n d b or n 2 0 1 2 }. F urt her , acr oss a vaila ble cli nical st u d y res ults, t he defi niti o n 
f or cli nical re missi o n ca n var y  bet wee n st u dies. F or St u d y G S-U S - 3 6 5-4 2 3 7, t he defi niti o n f or 
cli nical re missi o n is nearl y  i de ntical t o t hat use d b y  2 rece ntl y p u blis he d st u dies i n w hic h t he 
place b o res p o nse rates i n T N F α fail ures s u b gr o u ps were 2. 5 % a n d 0 % { Sa n d b or n 2 0 2 0a , 
Sa n d b or n 2 0 2 0 b }. Acc o r di n gly, a c o nser vati ve place b o res p o nse rate of 5 % has bee n utilize d i n 
t he sa m ple size calc ulati o n. 
T o j ustif y  f urt her de vel o p me nt, G S -4 8 7 5 s h o ul d be as g o o d or better t ha n ot her dr u g ca n di dates 
i n de vel o p me nt or o n t he mar ket. A mi ni m u m treat me nt differe nce of 1 7. 5 % was selecte d f or 
St u d y  G S-U S - 3 6 5- 4 2 3 7 base d o n data fr o m a si milar P hase 2 st u d y  i n U C w hic h de m o nstrate d a 
1 9. 6 % treat me nt differe nce bet wee n st u d y dr u g a n d place b o as assesse d b y Cli nical Re missi o n 
per t he M o difie d Ma y o Cli nical Sc ore { Sa n d b or n 2 0 2 0 b }. T he pati e nt p o p ulati o n i n t his st u d y 
c o nsiste d mai nl y of bi ol o gicall y e x perie nce d s u bjects ( 7 8 %) a n d t h us s h o ul d be si milar t o t he 
patie nt p o p ulati o n e nr olle d i n St u d y  G S-U S -3 6 5- 4 2 3 7. I n s u m mar y, a treat me nt differe nce of 
1 7. 5 % a n d a place b o res p o nse rate of 5 % is ass u me d i n t he sa m ple size calc ulati o n f or 
G S -U S - 3 6 5- 4 2 3 7.
8. 1 1.
D at a M o nit ori n g C o m mittee
A n e xter nal m ulti disci pli nar y  D M C will re vie w t he pr o gress of t he st u d y a n d perf or m i nteri m 
re vie ws of st u d y data a n d pr o vi de rec o m me n dati o n t o Gilea d w het her t he nat ure , fre q ue nc y, a n d 
se verity of a d verse effects ass ociate d wit h st u d y treat me nt warra nt t he E T of t he st u d y , w het her 
t he st u d y s h o ul d c o nti n ue as pla n ne d, or t he st u d y s h o ul d c o nti n ue wit h m o dificati o ns. T he D M C 
ma y  als o pr o vi de rec o m me n dati o ns as nee de d re gar di n g m o dificati o ns t o st u d y desi g n.
T he i nitial D M C safet y re vie w meeti n g will occ ur after a p pr o xi matel y  2 0 s u bjects eit her 
c o m plete t he Wee k
4 visit or disc o nti n ue fr o m t he st u d y  pri or t o Wee k 4.
S u bse q ue nt D M C meeti n gs f or safet y  re vie w will be hel d after a p pr o xi matel y 6 0 s u bjects eit her 
c o m plete t he Wee k 4 visit or disc o nti n ue fr o m t he st u d y a n d after a p pr o xi matel y 9 0 s u bjects eit her 
c o m plete Wee k 1 0
visit or disc o nti n ue fr o m t he st u d y . T he fre q ue nc y of meeti n gs m a y be a dj uste d 
as re q ueste d b y  t he D M C.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 7 2
1 9 J u ne 2 0 2 0
T he D M C’s s pecific acti vities will be defi ne d b y a m ut uall y a gree d c harter, w hic h will defi ne t he 
D M C’s me m bers hi p, c o n d uct a n d meeti n g sc he d ule.
W hile t he D M C will be as ke d t o a d vise Gilea d re gar di n g f ut ure c o n d uct of t he st u d y , i ncl u di n g 
p os si ble early st u d y ter mi nati o n, Gilea d retai ns fi nal decisi o n -ma ki n g a ut h orit y  o n all as pects of 
t he st u d y.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 7 3
1 9 J u ne 2 0 2 0
9.
R E S P O N SI BI LI TI E S
9. 1.
I n vesti g at or Res p o nsi bilities
9. 1. 1.  
G o o d Cli nic al Pr actice
T he i n vesti gat or will e ns ure t hat t his st u d y is c o n d ucte d i n acc or da nce wit h I CH E 6 ( R 2) G o o d 
Cli nical Practice s a n d a p plica ble la ws a n d re g ulati o ns.
9. 1. 2. 
Fi n a nci al Discl os ure
T he i n vesti gat or a n d s u bi n vesti gat ors will pr o vi d e d oc u me ntati o n of t heir fi na ncial i nterest or 
arra n ge me nts wit h Gilea d, or pr o prietar y  i nterests i n t he i n vesti gati o nal dr u g u n der st u d y. T his 
d oc u me ntati o n m ust be pr o vi de d pri or t o t he i n vesti gat or’s (a n d a n y s u bi n vesti gat or’s) 
partici pati o n i n t he st u d y. T he i n vesti gat or a n d s u bi n vesti gat or a gree t o n otif y  Gilea d of a n y 
c ha n ge i n re p orta ble i nterests d uri n g t he st u d y  a n d f or 1 year f oll o wi n g c o m pleti o n of t he st u d y . 
St u d y  c o m pleti o n is defi ne d as t he date w he n t he last s u bject c o m pletes t he pr ot oc ol-defi ne d 
acti vities.
9. 1. 3. 
I nstit uti o n al Re vie w B o ar d/I n de pe n de nt Et hics C o m mittee Re vie w a n d 
A p pr o v al
T he i n vesti gat or ( or s p o ns or as a p pr o priate acc or di n g t o l ocal re g ulati o ns) will s u b mit t his 
pr ot oc ol, i nf or me d c o nse nt f or m, a n d a n y acc o m pa n yi n g material t o be pr o vi de d t o t he s u bject 
(s uc h as a d vertise me nts, s u bject i nf or mati o n s heets, or descri pti o ns of t he st u d y use d t o o btai n 
i nf or me d c o nse nt) t o a n I R B/I E C. T he i n vesti gat or will n ot be gi n a ny st u d y s u bject acti vities 
u ntil a p pr o val fr o m t he I R B/I E C has bee n d oc u me nte d a n d pr o vi de d as a letter t o t he 
i n vesti gat or.
Bef ore i m ple me ntati o n, t he i n vesti gat or will s u b mit t o a n d recei ve d oc u me nte d a p pr o val fr o m 
t he I RB/I E C a n y m o dificati o ns ma de t o t he pr ot oc ol or a n y acc o m pa n yi n g material t o be 
pr o vi de d t o t he s u bject after i nitial I RB/I E C a p pr o val, wit h t he e xce pti o n of t h ose necessar y  t o 
re d uce i m me diate ris k t o st u d y s u bjects.
9. 1. 4.
I nf or me d C o nse nt
T he i n vesti gat or is res p o nsi ble f or o btai ni n g writte n i nf or me d c o nse nt fr o m eac h i n di vi d ual 
partici pati n g i n t his st u d y after a de q uate e x pla nati o n of t he ai ms, met h o ds, o bjecti ves, a n d 
p ote ntial hazar ds of t he st u d y  a n d bef ore u n derta ki n g a n y st u d y-relate d pr oce d ures. T he 
i n vesti gat or m ust use t he m ost c urre nt I R B or I E C a p pr o ve d c o nse nt f or m f or d oc u me nti n g 
writte n i nf or me d c o nse nt. Eac h i nf or me d c o nse nt ( or asse nt as a p plica ble) will be a p pr o priatel y 
si g ne d a n d date d by t he s u bject a n d t he pers o n c o n d ucti n g t he c o nse nt disc ussi o n, a n d als o b y  a n 
i m partial wit ness if re q uire d by I R B or I E C or l ocal re q uire me nts. F or p har mac o ge n o mics
testi n g, t he c o nse nt f or m will i nf or m s u bjects a b o ut ge n o mic testi n g a n d sa m ple rete nti o n, a n d 
t heir ri g ht t o recei ve cli nicall y rele va nt ge n o mic a nal ysis res ults. F or m ore i nf or mati o n see 
Secti o n 6. 1 .


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 7 4
1 9 J u ne 2 0 2 0
9. 1. 5.
C o nfi de nti alit y
T he i n vesti gat or m ust ass ure t hat s u bjects’ a n o n y mit y  will be strictl y mai ntai ne d a n d t hat t heir 
i de ntities are pr otecte d fr o m u na ut h orize d parties. O nl y a n i de ntificati o n c o de a n d a n y ot her 
u ni q ue i de ntifier (s) as all o we d b y l ocal la w (s uc h as year of birt h) will be rec or de d o n a n y f or m 
or bi ol o gical sa m ple s u b mitte d t o t he s p o ns or, I RB or I E C , or la b orat or y . La b orat or y  s peci me ns 
m ust be la bele d i n s uc h a wa y  as t o pr otect s u bject i de ntit y w hile all o wi n g t he res ults t o be 
rec or de d t o t he pr o per s u bject. Refer t o s pecific la b orat or y  i nstr ucti o ns. N O T E : T he i n vesti gat or 
m ust kee p a scree ni n g l o g s h o wi n g c o des, na mes, a n d a d dresses f or all s u bjects scree ne d a n d f or 
all s u bjects e nr olle d i n t he trial. S u bject data will be pr ocesse d i n acc or da nce wit h all a p plica ble 
re g ulati o ns.
T he i n vesti gat or a grees t hat all i nf or mati o n recei ve d fr o m Gilea d, i ncl u di n g b ut n ot li mite d t o t he 
I B, t his pr ot oc ol, C R F/e C R F, t he I MP , a n d a n y ot her st u d y i nf or mati o n, re mai n t he s ole a n d 
e xcl usi ve pr o pert y of Gilea d d uri n g t he c o n d uct of t he st u d y a n d t hereafter. T his i nf or mati o n is 
n ot t o be discl ose d t o a n y t hir d part y  (e xce pt e m pl o yees or a ge nts directl y i n v ol ve d i n t he 
c o n d uct of t he st u d y or as re q uire d b y la w) wit h o ut p ri or writte n c o nse nt fr o m Gilea d. T he 
i n vesti gat or f urt her a grees t o ta ke all reas o na ble preca uti o ns t o pre ve nt t he discl os ure b y a ny 
e m pl o yee or a ge nt of t he st u d y site t o a ny t hir d part y or ot her wise i nt o t he p u blic d o mai n.
9. 1. 6.
St u d y Files a n d Rete nti o n of R ec or ds
T he i n vesti gat or m ust mai ntai n a de q uate a n d acc urate rec or ds t o e na ble t he c o n d uct of t he st u d y 
t o be f ull y d oc u me nte d a n d t he st u d y data t o be s u bse q ue ntl y verifie d. T hese d oc u me nts s h o ul d 
be classifie d i nt o at least t he f oll o wi n g 2 cate g ories: ( 1) i n vesti gat or’s st u d y file, a n d ( 2) s u bject 
cli nical s o urce d oc u me nts.
T he i n vesti gat or’s st u d y file will c o ntai n t he pr ot oc ol/a me n d me nts, C R F a n d q uer y f or ms, I R B 
or I E C a n d g o ver n me ntal a p pr o val wit h c orres p o n de nce, i nf or me d c o nse nt, dr u g rec or ds, staff 
c urric ul u m vitae a n d a ut h orizati o n f or ms, a n d ot her a p pr o priate d oc u me nts a n d c orres p o n de nce.
T he re q uire d s o urce data s h o ul d i ncl u de se q ue ntial n otes c o ntai ni n g at least t he f oll o wi n g 
i nf or mati o n f or eac h s u bject:

S u bject i de ntificati o n ( na me, date of birt h, ge n der);

D oc u me ntati o n t hat s u bject meets eli gi bilit y criteria, ie, hist or y, P E , a n d c o nfir mati o n of 
dia g n osis (t o s u p p ort i ncl usi o n a n d e xcl usi o n criteria);

D oc u me ntati o n of t he reas o n(s) a c o nse nte d s u bject is n ot e nr olle d ;

Partici pati o n i n st u d y (i ncl u di n g st u d y n u m ber);

St u d y  disc usse d a n d date of i nf or me d c o nse nt;

Dates of all visits;


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 7 5
1 9 J u ne 2 0 2 0

D oc u me ntati o n t hat pr ot oc ol s pecific pr oce d ures were perf or me d;

Res ults of efficac y  para meters, as re q uire d by t he pr ot oc ol;

Start a n d e n d date (i ncl u di n g d ose re gi me n) of I M P, i ncl u di n g dates of dis pe nsi n g a n d ret ur n;

Rec or d of all A Es a n d ot her safet y para meters (start a n d e n d date, a n d i ncl u di n g ca usalit y 
a n d se verit y );

C o nc o mita nt me dicati o n (i ncl u di n g start a n d e n d date, d ose if rele va nt; d ose c ha n ges);

Date of stu d y  c o m pleti o n a n d reas o n f or early disc o nti n uati o n, if it occ urs.
All cli nical st u d y  d oc u me nts m ust be retai ne d by t he i n vesti gat or u ntil at least 2 ye ars or 
acc or di n g t o l ocal la ws, w hic he ver is l o n ger, after t he last a p pr o val of a mar keti n g a p plicati o n i n 
a n IC H re gi o n (ie, U nite d States, E ur o pe, or Ja pa n) a n d u ntil t here are n o pe n di n g or pla n ne d 
mar keti n g a p plicati o ns i n a n I C H re gi o n; or, if n o a p plicati o n is file d or if t he a p plicati o n is n ot 
a p pr o ve d f or s uc h i n dicati o n, u ntil 2 years after t he i n ve sti gati o n is disc o nti n ue d a n d re g ulat or y 
a ut h orities ha ve bee n n otifie d. I n vesti gat ors ma y  be re q uire d t o retai n d oc u me nts l o n ger if 
s pecifie d b y  re g ulat or y re q uire me nts, b y l ocal re g ulati o ns, or b y a n a gree me nt wit h Gilea d. T he 
i n vesti gat or m ust n otif y Gilea d bef ore destr oyi n g a n y  cli nical st u d y rec or ds.
S h o ul d t he i n vesti gat or wis h t o assi g n t he st u d y rec or ds t o a n ot her part y or m o ve t he m t o a n ot her 
l ocati o n, Gilea d m ust be n otifie d i n a d va nce.
If t he i n vesti gat or ca n n ot pr o vi de f or t his arc hi vi n g re q uireme nt at t he st u d y  site f or a n y or all of 
t he d oc u me nts, s pecial arra n ge me nts m ust be ma de bet wee n t he i n vesti gat or a n d Gilea d t o st ore 
t hese rec or ds sec urely a wa y fr o m t he site s o t hat t he y ca n be ret ur ne d seale d t o t he i n vesti gat or 
i n case of an i ns pecti o n. W he n s o urce d oc u me nts are re q uire d f or t he c o nti n ue d care of t he 
s u bject, a p pr o priate c o pies s h o ul d be ma de f or st ora ge a wa y fr o m t he site.
9. 1. 7.
C ase Re p ort F or ms
F or eac h s u bject c o nse nte d, a n e C R F will be c o m plete d b y  a n a ut h orize d st u d y staff me mber 
w h ose trai ni n g f or t his f u ncti o n is d oc u me nte d acc or di n g t o st u d y  pr oce d ures. e C R F s h o ul d be 
c o m plete d o n t he da y of t he s u bject visit t o e na ble t he s p o ns or t o perf or m ce ntral m o nit ori n g of 
safety data. T he Eli gi bilit y  Criteria e C R F s h o ul d be c o m plete d o nl y after all data relate d t o 
eli gi bilit y ha ve bee n recei ve d. S u bse q ue nt t o data e ntr y , a st u d y m o nit or will perf or m s o urce data 
verificati o n wit hi n t he electr o nic data ca pt ure (E D C ) s yste m. Ori gi nal e ntries as well as a n y  
c ha n ges t o data fiel ds will be st ore d i n t he a u dit trail of t he s yste m. Pri or t o data base l oc k ( or a n y 
i nteri m ti me p oi nts as descri be d i n t he cli nical data ma na ge me nt pla n), t he i n vesti gat or will use 
his/ her l o g i n cre de ntials t o c o nfir m t hat t he f or ms ha ve bee n re vie we d, a n d t hat t he e ntries 
acc uratel y reflect t he i nf or mati o n i n t he s o urce d oc u me nts. T he e C R F ca pt ure t he data re q uire d 
per t he pr ot oc ol sc he d ule of e ve nts a n d pr oce d ures. S y ste m-ge nerate d or ma n ual q ueries will be 
iss ue d t o t he i n vesti gati ve site staff as data discre pa ncies are i de ntifie d b y t he m o nit or or i nter nal 
Gilea d staff, w h o r o uti nel y  re vie w t he data f or c o m plete ness, c orrect ness, a n d c o nsiste nc y. T he 


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 7 6
1 9 J u ne 2 0 2 0
site c o or di nat or is res p o nsi ble f or res p o n di n g t o t he q ueries i n a ti mely ma n ner, wit hi n t he 
s yste m, eit her by c o nfir mi n g t he data as c orrect or u p dati n g t he ori gi nal e ntr y, a n d pr o vi di n g t he 
reas o n f or t he u p date (e g, data e ntr y  err or). At t he c o ncl usi o n of t he trial, Gilea d will pr o vi de t he 
site wit h a rea d- o nly arc hi ve c o p y of t he data e ntere d b y t hat site. T his arc hi ve m ust be st ore d i n 
acc or da nce wit h t he rec or ds rete nti o n re q uire me nts o utli ne d i n Secti o n 9. 1. 6 .
9. 1. 8.
I n vesti g ati o n al Me dici n al Pr o d uct Acc o u nt a bilit y a n d Ret ur n
W here p ossi ble, I M P s h o ul d be destr o ye d at t he site. At t he start of t he st u d y, t he st u d y m o nit or 
will e val uate eac h st u d y ce nter’s I M P dis p osal pr oce d ures a n d pr o vi de a p pr o priate i nstr ucti o n f or 
dis p osal or ret ur n of u n use d I M P s u p plies. If t he site has a n a p pr o priate S O P f or dr u g destr ucti o n 
as deter mi ne d b y Gilea d Scie nces, t he site ma y  destr o y use d (e m pty or partiall y e m pt y) a n d 
u n use d I M P s u p plies as l o n g as perf or me d i n acc or da nce wit h t he site’s S O P. T his ca n occ ur 
o nl y  after t he st u d y m o nit or has perf or me d dr u g acc o u nta bilit y d uri n g a n o n-site m o nit ori n g 
visit.
A c o p y of t he site’s I MP Dis p osal S O P or writte n pr oce d ure (si g ne d a n d date d b y  t he pri nci pal 
i n vesti gat or [PI ] or desi g nee) will be o btai ne d f or Gilea d site files. If t he site d oes n ot ha ve 
acce pta ble pr oce d ures i n place, arra n ge me nts will be ma de bet wee n t he site a n d Gilea d Scie nces 
( or Gilea d Scie nces’ re prese ntati ve) f or ret ur n of u n use d st u d y dr u g s u p plies.
If I M P is destr oye d o n site, t he i n vesti gat or m ust mai ntai n acc urate rec or ds f or a ll I M P 
destr o y e d. Rec or ds m ust s h o w t he i de ntificati o n a n d q ua ntit y  of eac h u nit destr o ye d, t he met h o d 
of destr ucti o n, a n d t he pers o n w h o dis p ose d of t he I M P. U p o n st u d y  c o m pleti o n, c o pies of t he 
I M P acc o u nta bilit y rec or ds m ust be file d at t he site. A n ot her c o p y will be ret ur ne d t o Gilea d.
T he st u d y  m o nit or will re vie w I M P s u p plies a n d ass ociate d rec or ds at peri o dic i nter vals.
9. 1. 9.
I ns pecti o ns
T he i n vesti gat or will ma ke a vaila ble all s o urce d oc u me nts a n d ot her rec or ds f or t his trial t o 
Gilea d ’s a p p oi nte d st u dy m o nit ors , t o I RBs or I ECs , or t o re g ulat or y a ut h orit y or healt h a ut h ority 
i ns pect ors.
9. 1. 1 0.
Pr ot oc ol C o m pli a nce
T he i n vesti gat or is res p o nsi ble f or e ns uri n g t he st u d y  is c o n d ucte d i n acc or da nce wit h t he 
pr oce d ures a n d e val uati o ns descri be d i n t his pr ot oc ol.
9. 2.
S p o ns or Res p o nsi bilities
9. 2. 1. 
Pr ot oc ol M o dific ati o ns
Pr ot oc ol m o dificati o ns, e xce pt t h ose i nte n de d t o re d uce i m me diate ris k t o st u d y  s u bjects, ma y be 
ma de o nl y  b y Gilea d. T he i n vesti gat or m ust s u b mit all pr ot oc ol m o dificati o ns t o t he I RB or I E C
i n acc or da nce wit h l ocal re q uire me nts a n d recei ve d oc u me nte d I R B or I E C a p pr o val bef ore 
m o dificati o ns ca n be i m ple me nte d.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 7 7
1 9 J u ne 2 0 2 0
9. 2. 2.
St u d y Re p ort a n d P u blic ati o ns
A cli nical st u d y  re p ort ( C S R) will be pre pare d a n d pr o vi de d t o t he re g ulat or y a ge nc y (ies). Gilea d 
will e ns ure t hat t he re p ort meets t he sta n dar ds set o ut i n t he I C H G ui deli ne f or Str uct ure a n d 
C o nte nt of Cli nical St u d y Re p orts (I C H E 3). N ote t hat a n a b bre viate d re p ort ma y  be pre pare d i n 
certai n cases.
In vesti gat ors i n t his st u d y  m a y c o m m u nicate, orall y prese nt, or p u blis h i n scie ntific j o ur nals or 
ot her sc h olarl y me dia o nl y after t he f oll o wi n g c o n diti o ns ha ve bee n met:
t he res ults of t he st u d y i n t heir e ntirety ha ve bee n p u blicl y discl ose d b y or wit h t he c o nse nt of 
Gilea d i n a n a bstract, ma n uscri pt, or prese ntati o n f or m or t he st u d y has bee n c o m plete d at all 
st u d y sites f or at least 2 years
T he i n vesti gat or will s u b mit t o Gilea d a n y  pr o p ose d p u blicati o n or prese ntati o n al o n g wit h t he 
res pecti ve scie ntific j o ur nal or prese ntati o n f or u m at least 3 0 da ys bef ore s u b missi o n of t he 
p u blicati o n or prese ntati o n. 
N o s uc h c o m m u nicati o n, prese ntati o n, or p u blicati o n will i ncl u d e Gilea d’s c o nfi de ntial 
i nf or mati o n (Secti o n 9. 1. 5 ).
T he i n vesti gat or wi ll c o m pl y wit h Gilea d’s re q uest t o delete refere nces t o its c o nfi de ntial 
i nf or mati o n ( ot her t ha n t he st u d y res ults) i n a n y pa per or prese ntati o n a n d a grees t o wit h h ol d 
p u blicati o n or prese ntati o n f or a n a d diti o nal 6 0 da ys i n or der t o o btai n pate nt pr otectio n if 
dee me d necessar y .
9. 3.
J oi nt I n vesti g at or/ S p o ns or Res p o nsi bilities
9. 3. 1.
P a y me nt Re p orti n g
I n vesti gat ors a n d t heir st u d y staff ma y be as ke d t o pr o vi de ser vices perf or me d u n der t his 
pr ot oc ol, e g, atte n da nce at In vesti gat or's Meeti n gs. If re q uire d u n der t he a p plica ble stat ut or y a n d 
re g ulat or y re q uire me nts, Gilea d will ca pt ure a n d discl ose t o Fe deral a n d State a ge ncies a n y 
e x pe nses pai d or rei m b urse d f or s uc h ser vices, i ncl u di n g a n y cli nical trial pa y me nts, meal, tra vel 
e x pe nses or rei m b urse me nts, c o ns ulti n g fees, a n d a n y ot her tra nsfer of val ue.
9. 3. 2.
Access t o I nf or m ati o n f or M o nit ori n g
I n acc or da nce wit h re g ulati o ns a n d g ui deli nes, t he st u d y  m o nit or m ust ha ve direct access t o t he 
i n vesti gat or’s s o urce d oc u me ntati o n i n or der t o verif y t he acc urac y of t he data rec or de d i n t he 
C R F /e C R F.
T he m o nit or is res p o nsi ble f or r o uti ne re vie w of t he C R F /e C R F at re g ular i nter vals t hr o u g h o ut 
t he st u d y t o verif y a d here nce t o t he pr ot oc ol a n d t he c o m plete ness, c o nsiste nc y, a n d acc urac y of 
t he data bei n g e ntere d o n t he m. T he m o nit or s h o uld ha ve access t o a n y s u bject rec or ds nee de d t o 
verif y  t he e ntries o n t he C R F/e C R F. T he i n vesti gat or a grees t o c o o perate wit h t he m o nit or t o 
e ns ure t hat a n y pr o ble ms detecte d t hr o u g h a n y t ype of m o nit ori n g (ce ntral, o n site) are res ol ve d.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 7 8
1 9 J u ne 2 0 2 0
9. 3. 3.
Access t o I nf or m ati o n f or A u diti n g or I ns pecti o ns
Re prese ntati ves of re g ulat or y  a ut h orities or of Gilea d ma y c o n d uct i ns pecti o ns or a u dits of t he 
cli nical st u d y. If t he i n vesti gat or is n otifie d of a n i ns pecti o n b y a re g ulat or y a ut h orit y t he 
i n vesti gat or a grees t o n otif y t he Gilea d me dical m o nit or i m me diatel y. T he i n vesti gat or a grees t o 
pr o vi de t o re prese ntati ves of a re g ulat or y  a ge nc y or Gilea d access t o rec or ds, facilities, a n d 
pers o n nel f or t he effecti ve c o n d uct of a n y i ns pecti o n or a u dit.
9. 3. 4.
St u d y Disc o nti n u ati o n
B ot h t he s p o ns or a n d t he i n vesti gat or reser ve t he ri g ht t o ter mi nate t he st u d y at a n y ti me. S h o ul d 
t his be necessar y, b ot h parties will arra n ge disc o nti n uati o n pr oce d ures a n d n otif y t he a p pr o priate 
re g ulat or y a ut h ority(i es), IR Bs, a n d I E Cs. I n ter mi nati n g t he st u d y, Gilea d a n d t he i n vesti gat or 
will ass ure t hat a de q uate c o nsi derati o n is gi ve n t o t he pr otecti o n of t he s u bjects’ i nterests.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 7 9
1 9 J u ne 2 0 2 0
1 0.
R E F E R E N C E S
Da nese S, Fi occ hi C. Ulcerati ve c olitis. N E n gl J Me d 2 0 1 1; 3 6 5 ( 1 8): 1 7 1 3 - 2 5.
Fea ga n B G, R ut ge erts P, Sa n ds B E, Ha na uer S, C ol o m bel J F, Sa n d b or n WJ, et al. Ve d oliz u ma b 
as i n d ucti o n a n d mai nte na nce t hera p y f or ulcerati ve c olitis. N E n gl J Me d 
2 0 1 3; 3 6 9 ( 8): 6 9 9 - 7 1 0.
Ga nt ke T, Sris ka nt haraja h S, L e y S C. Re g ulati o n a n d F u ncti o n of T P L- 2, A n I ka p pa B Ki nas e-
Re g ulate d M A P Ki nase Ki nase Ki nase. Cell researc h 2 0 1 1; 2 1 ( 1): 1 3 1 - 4 5.
Har b or d M, Elia ki m R, Bette n w ort h D, Kar miris K, Katsa n os K, K o p yl o v U, et al. T hir d 
E ur o pea n E vi de nce - base d C o nse ns us o n Dia g n osis a n d Ma na ge me nt of 
Ulcerati ve C olitis. Part 2: C urre nt Ma na ge me nt. J o ur nal of Cr o h n's & c olitis 
2 0 1 7; 1 1 ( 7): 7 6 9 - 8 4.
He dl M, A bra ha m C. A T P L 2 ( M A P 3 K 8) Disease -Ris k P ol y m or p his m I ncreases T P L 2 
E x pressi o n T here b y Lea di n g t o I ncrease d Patter n Rec o g niti o n Rece pt or -I nitiate d 
Cas pase -1 a n d Cas pase -8 Acti vati o n, S i g nalli n g a n d C yt o ki ne Secreti o n. G ut 
2 0 1 5: 1 - 1 4.
I n ker L A, Sc h mi d C H, Ti g hi o uart H, Ec kfel dt J H, Fel d ma n HI, Gree ne T, et al. Esti mati n g 
gl o mer ular filtrati o n rate fr o m ser u m creati ni ne a n d c y stati n C. N E n gl J Me d 
2 0 1 2; 3 6 7 ( 1): 2 0 - 9.
Jess T, R u n g oe C, Pe yri n- Bir o ulet L. Ris k of C ol orectal Ca ncer i n Patie nts Wit h Ulcerati ve 
C olitis: A Meta -a nal ysis of P o p ulati o n- Base d C o h ort St u dies. Cli n Gastr oe nter ol 
He pat ol 2 0 1 2; 1 0 ( 6): 6 3 9 - 4 5.
J osti ns L, Ri p ke S, Weers ma R K, D uerr R H, Mc G o ver n D P, H ui K Y, et al. H ost-micr o be 
i nteracti o ns ha ve s ha pe d t he ge netic arc hitect ure of i nfla m mat or y b o wel disease. 
Nat ure 2 0 1 2; 4 9 1 ( 7 4 2 2): 1 1 9 - 2 4.
N g S C, S hi H Y, Ha mi di N, U n der w o o d F E, Ta n g W, Be nc hi m ol EI, et al. W orl d wi de I nci de nce 
a n d Pre vale nce of I nfla m mat or y B o wel Disease i n t he 2 1st Ce nt ur y : A Sys te matic 
Re vie w of P o p ulati o n- Base d St u dies. L a ncet 2 0 1 7; 3 9 0: 2 7 6 9 - 7 8.
Sa n d b or n WJ, Fea ga n B G, W olf D C, D' Hae ns G, Ver meire S, Ha na uer S B, et al. Oza ni m o d 
I n d ucti o n a n d Mai nte na nce Treat me nt f or Ulcerati ve C olitis. N E n gl J Me d 
2 0 1 6; 3 7 4 ( 1 8): 1 7 5 4 - 6 2.
Sa n d b or n WJ, Ferra nte M, B ha n dari B R, Berli ba E, Fea ga n B G, Hi bi T, et al. Efficac y  a n d 
Safet y  of Miri kiz u ma b i n a Ra n d o mize d P hase 2 St u d y of Patie nts Wit h 
Ulcerati ve C olitis. Gastr oe nter ol o g y  2 0 2 0a; 1 5 8 ( 3): 5 3 7-4 9 e 1 0.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 8 0
1 9 J u ne 2 0 2 0
Sa n d b or n WJ, G h os h S, Pa nes J, Sc hrei ber S, D' Hae ns G, Ta ni da S, et al. Efficac y  of 
U pa daciti ni b i n a Ra n d o mize d Trial of Patie nts Wit h Acti ve Ulcerati ve C olitis. 
Gastr oe nter ol o g y 2 0 2 0 b; 1 5 8 ( 8): 2 1 3 9 -4 9 e 1 4.
Sa n d b or n WJ, S u C, Sa n ds B E, D' Hae ns G R, Ver meire S, Sc hrei ber S, et al. T ofaciti ni b as 
I n d ucti o n a n d Mai nte na nce T hera py f or Ulcerati ve C olitis. N E n gl J Me d 
2 0 1 7; 3 7 6 ( 1 8): 1 7 2 3 - 3 6.
Sa n d b or n WJ, va n Assc he G, Rei nisc h W, C ol o m bel J F, D' Hae ns G, W olf D C, et al. 
A dali m u ma b i n d uces a n d mai ntai ns cli nical re missi o n i n patie nts wit h m o derate -
t o-se vere ulcerati ve c olitis. Gastr oe nter ol o g y 2 0 1 2; 1 4 2 ( 2): 2 5 7-6 5 e 1 - 3.
S T E L A R A, Ja nsse n Bi otec h I nc. S T E L A R A ® ( uste ki n u ma b) I njecti o n, f or S u bc uta ne o us or 
I ntra ve n o us Use. U. S. Prescri bi n g I nf or mati o n. H ors ha m, P A. Marc h. 2 0 2 0:
U n gar o R, Me ha n dr u S, Alle n P B, Pe y ri n-Bir o ulet L , C ol o m bel J F. Ulcerati ve c olitis. La ncet 
2 0 1 6: 1 - 1 5.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 8 1
1 9 J u ne 2 0 2 0
1 1.
A P P E N DI C E S
A p pe n di x 1.
I n vesti gat or Si g nat ure Pa ge
A p pe n di x 2.
St u d y Pr oce d ures Ta ble – Bli n de d Treat me nt
A p pe n di x 3.
St u d y Pr oce d ures Ta ble – O pe n -La bel Treat me nt
A p pe n di x 4.
M o difie d Ma y o Sc ori n g S yste m f or Assess me nt of Ulcerati ve C olit is Acti vit y
A p pe n di x 5.
Ge b oes Hist ol o gical Sc ore Gra des
A p pe n di x 6.
C T C A E Gra di n g Scale f or Se verit y of A d verse E ve nts
A p pe n di x 7.
Cli nical La b orat or y Assess me nt Ta ble
A p pe n di x 8.
Pre g na nc y Preca uti o ns, Defi niti o n f or Fe male of C hil d beari n g P o te ntial, a n d 
C o ntrace pti ve Re q ui re me nts


G S- 4 8 7 5 
Pr ot oc ol G S- U S- 3 6 5- 4 2 3 7 
F i nal 
Gil e a d S ci e n c es, I nc. 
A m e n d m e nt 2 
A p p e n di x 1. 
I n v esti g at o r Si g n at u r e P a g e 
GI L E A D S CI E N C E S, I N C. 
3 3 3 L A K E SI D E D RI V E 
F O S T E R CI T Y, C A 9 4 4 0 4, U S A 
S T U D Y A C K N O W L E D G E M E N T 
A P h as e 2, Bli n d e d, R a n d o mi z e d, P l a c eb o- C o ntr oll e d St u d y E v al u ati n g t h e Effi c a c y a n d S af et y 
of G S- 4 8 7 5 i n S u bj e cts wit h M o d er at el y t o S e v er el y A cti v e Ul c er ati v e C olitis 
A m e n d m e nt 2, 1 9 J u n e 2 0 2 0 
T his pr ot o c ol h as b e e n a p pr o v e d b y Gil e a d S ci e n c es, I n c. T h e f oll o wi n g si gn at ur e d o c u m e nts 
t his a p pr o v al. 
P P D 
~ P D 
-----------.-.-----...._ _ _ _ _ 
N a m e ( Pri nt e d) 
St u d y Dir e ct or 
/9 
D at e 
Si g n at ur e 
I N V E S TI G A T O R S T A T E M E N T 
I h a v e r e a d t h e pr ot o c ol, i n cl u di n g all a p p e n di c es, a n d I a gr e e t h at it c o nt ai ns all n e c ess ar y 
d et ails f or m e a n d m y st aff t o c o n d u ct t his st u d y as d es cri b e d. I will c o n d u ct t his st u d y as 
o utli n e d h er ei n a n d will m a k e a r e as o n a bl e eff ort t o c o m pl et e t h e st u d y wit hi n t h e ti m e 
d esi g n at e d. 
I will pr o vi d e all st u d y p ers o n n el u n d er m y s u p er visi o n c o pi es of t h e pr ot o c ol a n d a c c ess t o all 
i nf or m ati o n pr o vi d e d b y Gil e a d S ci e n c es, I n c. I will dis c uss t his m at eri al wit h t h e m t o e ns ur e 
t h at t h e y ar e f ull y i nf or m e d a b o ut t h e dr u gs a n d t h e st u d y. 
Pri n ci p al I n v esti g at or N a m e ( Pri nt e d) 
Si g n at ur e 
D at e 
Sit e N u m b er 
C O N FI D E N TI A L 
Pa ge 8 2 
1 9 J u n e 2 0 2 0 


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
1 1 C O N FI D E N TI A L
Pa ge 8 3
1 9 J u ne 2 0 2 0
A p pe n di x 2.
St u d y Pr oce d ures T a ble – Bli n de d Tre at me nt
Peri o d
Scree n
Bli n de d Tre at me nt
F oll o w -u p
Wee k
0 
2 
4 
6
1 0 
1 4 
1 8 
2 2 
2 6 
3 0 
3 4 
3 8 
4 2 
4 6 
5 0
P T x
E T
St u d y D a y
-3 0 t o - 1 
1
1 5 
2 9 
4 3 
7 1 
9 9 
1 2 7 
1 5 5 
1 8 3 
2 1 1 
2 3 9 
2 6 7 
2 9 5 
3 2 3 
3 5 1
Visit Wi n d o w
3
3
3
5
5
5
5
5
7
7
7
7
7
7
3
I nf or me d C o nse nt 
X
1 2 lea d E C G
X
X
X
X
X
P h ysical E xa m
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Re vie w of A d verse E ve nts
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Re vie w of C o nc o mita nt 
Me dicati o ns
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
S t u d y Dr u g Dis pe nsi n g
X
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
C ol o n osc o p y/ Fle xi ble 
Si g m oi d osc o p y wit h 
Bi o psies
X
X
X
P G A f or M C S Calc ulati o n
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
X
E val uati o n of Disease 
W orse ni n g
usi n g Partial 
M C S
X  
X  
X  
X  
X  
X  
X  
X  
X
eDiar y i nstr ucti o n & re vie w
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
St o ol Sa m ple f or E nteric 
I nfecti o ns
X
St o ol Bi o mar ker Sa m ples
X
X
X
X
U ri nal ysis 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
P re g na nc y Test
X  
X
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
T B Assess me nt 
X
C CI


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
1 1 C O N FI D E N TI A L
Pa ge 8 4
1 9 J u ne 2 0 2 0
Peri o d
Scree n
Bli n de d Tre at me nt
F oll o w -u p
Wee k
0 
2 
4 
6
1 0 
1 4 
1 8 
2 2 
2 6 
3 0 
3 4 
3 8 
4 2 
4 6 
5 0
P T x
E T
St u d y D a y
-3 0 t o - 1 
1
1 5 
2 9 
4 3 
7 1 
9 9 
1 2 7 
1 5 5 
1 8 3 
2 1 1 
2 3 9 
2 6 7 
2 9 5 
3 2 3 
3 5 1
Visit Wi n d o w
3
3
3
5
5
5
5
5
7
7
7
7
7
7
3
H B V, H C V, HI V scree ni n g
X
H B V M o nit ori n g , As 
N ee de d
X
X
X
X
H e mat ol o g y & C he mistr y
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
F asti n g Li pi d s
X  
X
X
X
X
B l o o d Bi o mar ker Sa m ples
X  
X  
X
X
X
X
Ma n dat or y Ge n o mic 
Sa m ples
X
H R Q o L S ur ve ys
X
X
X
H C R U Q uesti o n naire
X  
X  
X  
X  
X  
X
X
X  
X
X
A p pr o xi mate T otal A m o u nt 
of B l o o d T a ke n at T his V isit
2 3. 5 m L
4 4. 5
m L
3 4. 0
m L
3 4. 0
m L
1 2 . 0 
m L
3 4. 0 
or 
4 0. 0
m L
8 . 0 
m L
8 . 0 
m L
8 . 0 
or 
1 4 . 0 
m L
3 0. 0
m L
8. 0
m L
8 . 0 
or 
1 4 . 0 
m L
8 . 0 
m L
8 . 0 
m L
8 . 0
or 
1 4. 0
m L
3 0. 0 m L
8. 0
m L
8. 0 
m L
C CI
C CI
C CI


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
1 1 C O N FI D E N TI A L
Pa ge 8 5
1 9 J u ne 2 0 2 0
A p pe n di x 3.
St u d y Pr oce d ures T a ble – O pe n -L a bel Tre at me nt
Peri o d
O pe n -L a bel Tre at me nt
F oll o w -u p
Wee k
0 
2 
4 
6
1 0 
1 4 
1 8 
2 2 
2 6 
3 0 
3 4 
3 8 
4 2 
4 6 
5 0
P T x
E T
St u d y D a y
1
1 5 
2 9 
4 3 
7 1 
9 9 
1 2 7 
1 5 5 
1 8 3 
2 1 1 
2 3 9 
2 6 7 
2 9 5 
3 2 3 
3 5 1
Visit Wi n d o w
3
3
3
5
5
5
5
5
7
7
7
7
7
7
3
1 2 lea d E C G
X
X
X
X
P h ysical E xa m
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Re vie w of A d verse E ve nts
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Re vie w of C o nc o mita nt 
Me dicati o ns
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
St u d y Dr u g Dis pe nsi n g
X
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
C ol o n osc o p y/ Fle xi ble 
Si g m oi d osc o p y wit h Bi o psies
X
X
P G A f or M C S Calc ulati o n
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
X
E val uati o n f or Disease 
W orse ni n g
usi n g Partial M C S
X  
X  
X  
X  
X  
X  
X  
X  
X
e Diar y i nstr ucti o n & re vie w
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
St o ol Bi o mar ker Sa m ples 
X
X
X
Uri nal ysis 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Pre g na nc y Test
X
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
H B V M o nit ori n g
X
X
X
X
He mat ol o g y & C he mistr y 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Fasti n g Li pi ds
X
X
X
Bl o o d Bi o mar ker Sa m ples
X  
X  
X
X
X
X
H R Q o L S ur ve ys
X
X
X
C CI


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
1 1 C O N FI D E N TI A L
Pa ge 8 6
1 9 J u ne 2 0 2 0
Peri o d
O pe n -L a bel Tre at me nt
F oll o w -u p
Wee k
0 
2 
4 
6
1 0 
1 4 
1 8 
2 2 
2 6 
3 0 
3 4 
3 8 
4 2 
4 6 
5 0
P T x
E T
St u d y D a y
1
1 5 
2 9 
4 3 
7 1 
9 9 
1 2 7 
1 5 5 
1 8 3 
2 1 1 
2 3 9 
2 6 7 
2 9 5 
3 2 3 
3 5 1
Visit Wi n d o w
3
3
3
5
5
5
5
5
7
7
7
7
7
7
3
H C R U Q uesti o n naire
X  
X  
X  
X  
X
X
X
X
X
X
A p pr o xi mate T otal A m o u nt 
of B l o o d T a ke n at T his V isit
3 0. 0 m L
3 4. 0
m L
3 4. 0
m L
1 2. 0
m L
3 4. 0
or 
4 0. 0
m L
8. 0
m L
8. 0
m L
8. 0
or 
1 4. 0
m L
3 0. 0
m L
8. 0
m L
8. 0
or 
1 4. 0
m L
8. 0
m L
8. 0
m L
8. 0
or 
1 4. 0
m L
3 0. 0 m L
8. 0
m L
8. 0 
m L




G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 8 8
1 9 J u ne 2 0 2 0
A p pe n di x 5.
Ge b oes Hist ol o gic al Sc ore Gr a des
S u b gr a des
Str uct ur al ( Arc hitect ur al C h a n ge)
Gr a de 0
0. 0
N o a b n or malit y
0. 1
Mil d a b n or malit y
0. 2
Mil d or m o derate diff use or m ultif ocal a b n or malities
0. 3
Se vere diff use or m ultif ocal a b n or malities
Gr a de 1
C hr o nic i nfl a m m at or y i nfiltr ate
1. 0
N o i ncrease
1. 1
Mil d b ut u ne q ui v ocal i ncrease
1. 2
M o derate i ncrease
1. 3
Mar ke d i ncrease
Gr a de 2
L a mi n a pr o pri a ne utr o p hils a n d e osi n o p hils
2 A E osi n o p hils
2 A. 0
N o i ncrease
2 A. 1
Mil d b ut u ne q ui v ocal i ncrease
2 A. 2
M o derate i ncrease
2 A. 3
Mar ke d i ncrease
2 B Ne utr o p hils
2 B. 0
N o ne
2 B. 1
Mil d b ut u ne q ui v ocal i ncrease
2 B. 2
M o derate i ncrease
2 B. 3
Mar ke d i ncrease
Gr a de 3
Ne utr o p hils i n e pit heli u m
3. 0
N o ne
3. 1
< 5 % cr y pts i n v ol ve d
3. 2
< 5 0 % cr y pts i n v ol ve d
3. 3
> 5 0 % cr y pts i n v ol ve d
Gr a de 4
Cr y pt destr ucti o n
4. 0
N o ne
4. 1
Pr o ba ble 
l ocal e xcess of ne utr o p hils i n part of cr y pt
4. 2
Pr o ba ble 
mar ke d atte n uati o n
4. 3
U ne q ui v ocal cr y pt destr ucti o n
Gr a de 5
Er osi o n or ulcer ati o n
5. 0
N o er osi o n, ulcerati o n, or gra n ulati o n tiss ue
5. 1
Rec o veri n g e pit heli u m + a djace nt i nfla m mati o n
5. 2
Pr o ba ble er osi o n 
f ocall y stri p pe d
5. 3
U ne q ui v ocal er osi o n
5. 4
Ulcer or gra n ulati o n tiss ue


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 8 9
1 9 J u ne 2 0 2 0
A p pe n di x 6.  
C T C A E Gr a di n g Sc ale f or Se verit y of A d verse E ve nts
Please refer t o t he C o m m o n Ter mi n ol o g y  Criteria f or A d verse E ve nts ( C T C A E) Versi o n 5. 0 , 
w hic h ca n be f o u n d at:
htt ps://cte p.ca ncer. g o v/ pr ot oc ol De vel o p me nt/electr o nic _a p plicati o ns/ d ocs/ctcae _ v 5. 0. xls x 
F or A Es ass ociate d wit h la b orat or y  a b n or malities, t he e ve nt s h o ul d be gra de d o n t he basis of t he 
cli nical se verit y i n t he c o nte xt of t he u n derl yi n g c o n diti o ns; t his m a y or ma y n ot be i n a gree me nt 
wit h t he gra di n g of t he la b orat or y  a b n or malit y.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 9 0
1 9 J u ne 2 0 2 0
A p pe n di x 7.  
Cli nic al L a b or at or y Assess me nt T a ble
H e m at ol o g y
C he mistr y
Uri n al ysis
Ot her
H e m at ocrit
H e m o gl o bi n
Platelet c o u nt
Re d bl o o d cell ( R B C) 
c o u nt
W hite bl o o d cell ( W B C) 
c o u nt
Differe ntials (a bs ol ute a n d 
perce nta ge), i ncl u di n g:
L y m p h oc ytes
M o n oc ytes
Ne utr o p hils
E osi n o p hils
Bas o p hils
Retic ul oc yte c o u nt
Mea n c or p usc ular v ol u me 
( M C V)
Al kali ne p h os p hatase
As partate a mi n otra nsferase 
( A S T)
Ala ni ne a mi n otra nsferase 
( A L T)
T otal bilir u bi n
Direct a n d i n direct 
bilir u bi n
T otal pr otei n
Al b u mi n
Bicar b o nate
Bl o o d urea nitr o ge n ( B U N)
Calci u m
C hl ori de
Ser u m creati ni ne
Ser u m c ystati n C
Gl uc ose
P h os p h or us
Ma g nesi u m
P otassi u m
S o di u m
Creati ne p h os p h o ki nase 
( C P K)
eG F R cr
e G F R c ys
A p peara nce:
Bl o o d
C ol or
Gl uc ose
Le u k oc yte esterase
p H
Pr otei n
Ur o bili n o ge n
Uri ne dr u g scree n f or:
A m p heta mi nes
C ocai ne
Bar bit urates
O piates
Be nz o diaze pi nes
C- reacti ve pr otei n (hs -
C R P )
T B A nal ysis 
(Q ua nti F E R O N or 
e q ui vale nt assa y)
St o ol Sa m ples
Micr o bi o me
a n d 
Meta b ol o me
Cal pr otecti n , Lact oferri n 
Bacterial St o ol C ult ure
C d ifficile T o xi n
O va a n d Parasites 
( O & P) 
P har m ac o ki netics ( P K)
Ser u m I m m u n o gl o b uli n
Pr ot hr o m bi n Ti me
Partial t hr o m b o plasti n 
ti me ( P T T)
I nter nati o nal N or malize d 
Rati o (I N R)
Ser ol o g y
He patitis B S urface A g 
He patitis B S urface A b
He patitis B C ore A b 
H B V D N A 
He patitis C A b
H C V R N A
HI V
Pre g n a nc y
I n fe m ales of c hil d be ari n g 
p ote nti al:
Ser u m pre g na nc y
Uri ne pre g na nc y
Li pi ds
Tri gl yceri des
T otal c h olester ol 
Hi g h -de nsit y li p o pr otei n
[ H D L] – c h olester ol
L o w -de nsit y li p o pr otei n 
[ L D L] – c h olester ol


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 9 1
1 9 J u ne 2 0 2 0
A p pe n di x 8. 
Pre g n a nc y Prec a uti o ns, Defi niti o n f or Fe m ale of C hil d be ari n g 
P ote nti al, a n d C o ntr ace pti ve Re q uire me nts
1)
Defi niti o ns
a)
Defi niti o n of C hil d be ari n g P ote nti al
F or t he p ur p oses of t his st u d y , a fe male-b or n s u bject is c o nsi dere d of c hil d beari n g p ote ntial 
f oll o wi n g t he i nitiati o n of p u berty ( Ta n ner sta ge 2) u ntil bec o mi n g p ost -me n o pa usal, u nless 
per ma ne ntl y sterile or wit h me dicall y d oc u me nte d o varia n fail ure. W o me n w h o d o n ot meet 
bel o w criteria f or bei n g p ost- me n o pa usal, are n ot per ma ne ntl y sterile, or d o n ot ha ve me dicall y 
d oc u me nte d o varia n fail ure m ust ha ve pre g na nc y  testi ng as o utli ne d b y t he pr ot oc ol. 
W o me n are c o nsi dere d t o be i n a p ost me n o pa usal state w he n t he y  are > 5 4 ye ars of a ge wit h 
cessati o n of pre vi o usl y occ urri n g me nses f or > 1 2 m o nt hs wit h o ut a n alter nati ve ca use.
Per ma ne nt sterilizati o n i ncl u des h y sterect o m y, bilateral o o p h orect o m y, or bilateral 
sal pi n gect o m y i n a fe male s u bject of a ny a ge. Bilateral t u bal li gati o n is n ot c o nsi dere d 
per ma ne nt sterilizati o n.
b)
Defi niti o n of M ale Fertilit y
F or t he p ur p oses of t his st u d y , a male-b or n s u bject is c o nsi dere d fertile after t he i nitiati o n of 
p u bert y  u nless per ma ne ntl y sterilize d b y  bilateral orc hi dect o my or has me dical d oc u me ntati o n of 
per ma ne nt male i nfertilit y . Vasect o m y is n ot c o nsi dere d per ma ne nt sterilizati o n.
2)
C o ntr ace pti o n f or Fe m ale S u bjects
a)
St u d y Dr u g Effects o n Pre g n a nc y a n d H or m o n al C o ntr ace pti o n
G S - 4 8 7 5 is c o ntrai n dicate d i n pre g na nc y beca use its terat o ge nicit y /fet ot o xicit y pr ofile is 
u n k n o w n. G S - 4 8 7 5 is n ot ge n ot o xic. Cli nicall y rele va nt dr u g- dr u g i nteracti o ns bet wee n 
h or m o nall y -base d c o ntrace pti ves a n d G S - 4 8 7 5 are n ot e x pecte d. I n vitr o st u dies i n He pa R G cells 
usi n g refere nce s u bstrates i n dicate t hat G S - 4 8 7 5 d oes n ot i n d uce C Y P 1 A 2, C Y P 2 B 6, or 
C Y P 3 A 4 e nz y mes i n v ol ve d i n meta b olis m of c o m m o n h or m o nal c o ntrace pti ves. T he lac k of 
i n d ucti o n p ote ntial of G S - 4 8 7 5 o n C Y P 3 A 4 was f urt her c o nfir me d i n a cli nical dr u g -dr u g 
i nteracti o n st u d y, w here m ulti ple d ose a d mi nistrati o n of 4 5 0 m g G S - 4 8 7 5 di d n ot affect t he 
p har mac o ki netics of mi daz ola m (a pr ot ot y pical i n vi v o pr o be C Y P 3 A 4 s u bstrate)
(see Secti o n 1. 3. 3. 1 ). A d diti o nall y, cli nicall y rele va nt i n hi biti o n of C Y Ps d uri n g G S - 4 8 7 5
treat me nt is u nli kel y, base d o n i n vitr o a n d cli nical data. Base d o n t he t otalit y  of t he i n vitr o a n d 
cli nical data, cli nicall y rele va nt dr u g i nteracti o ns bet wee n G S - 4 8 7 5 wit h h or m o nal 
c o ntrace pti ves are n ot e x pecte d . T heref ore, h or m o nal c o ntrace pti ves ma y  be all o we d as a 
c o m p o ne nt of a hi g hl y effecti ve c o ntrace pt i ve re gi me n b ut o nl y  w he n use d i n c o nj u ncti o n wit h a 
barrier met h o d, prefera bl y a male c o n d o m (see bel o w). Please refer t o t he latest versi o n of t he 
G S - 4 8 7 5 I B f or a d diti o nal i nf or mati o n.


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 9 2
1 9 J u ne 2 0 2 0
b)
C o ntr ace pti o n f or Fe m ale S u bjects of C hil d be ari n g P ote nti al
T he i ncl usi o n of fe male s u bjects of c hil d beari n g p ote ntial re q uires t he use of hi g hly effective
c o ntrace pti ve meas ures. W o me n m ust ha ve a ne gati ve ser u m pre g na nc y  test at scree ni n g a n d a 
ne gati v e uri ne pre g na nc y test o n t he Da y 1 visit pri or t o ra n d o mizati o n. P re g na nc y tests will be 
perf or me d as defi ne d b y t he sc he d ule of assess me nts i n t he St u d y Pr oce d ures Ta bles 
(A p pe n di x 2 a n d A p pe n di x 3 ). I n t he e ve nt of a dela y e d me nstr ual peri o d ( > 1 m o nt h bet wee n 
me nstr uati o ns), a pre g na nc y  test m ust be perf or me d t o r ule o ut pre g na nc y. T his als o a p plies f or 
w o me n of c hil d beari n g p ote ntial w it h i nfre q ue nt or irre g ular peri o ds.
Fe male s u bjects m ust a gree t o use 1 of t he f oll o wi n g met h o ds fr o m scree ni n g u ntil 7 d a y s 
f oll o wi n g t he last d ose of st u d y dr u g:

C o m plete a bsti ne nce fr o m i nterc o urse of re pr o d ucti ve p ote ntial. A bsti ne nce is a n acce pta bl e 
met h o d of c o ntrace pti o n o nl y  w he n it is i n li ne wit h t he s u bject’s preferre d a n d us ual 
lifest yle.
O R

C o nsiste nt a n d c orrect use of 1 of t he f oll o wi n g met h o ds of birt h c o ntr ol liste d bel o w :
I ntra uteri ne de vice (I U D) wit h a fail ure rate of < 1 % per ye ar
Intra uteri ne h or m o ne -releasi n g sys te m (I U S) wit h a fail ure rate of < 1 % per y ear
T u bal sterilizati o n
Vasect o m y i n t he male part ner ( pr o vi de d t hat t he part ner is t he s ole se x ual part ner a n d 
ha d c o nfir mati o n of s ur gical s uccess 3 m o nt hs after pr oce d ure)
Ess ur e ® micr o -i nsert sys te m ( pr o vi de d c o nfir mati o n of s uccess 3 m o nt hs after pr oce d ure)
O R

C o m bi nati o n of h or m o nal c o ntrace pti ves a n d barrier met h o ds. Fe male s u bjects w h o wis h t o 
use a h or m o nall y- base d met h o d m ust use it i n c o nj u ncti o n wit h a barrier met h o d, prefera bl y 
a male c o n d o m. Fe male s u bjects w h o utilize a h or m o nal c o ntrace pti ve as o ne of t heir birt h 
c o ntr ol met h o ds m ust ha ve c o nsiste ntl y  use d t he sa me met h o d f or at least 3 m o nt hs pri or t o 
st u d y d osi n g. H or m o nall y-base d c o ntrace pti ves a n d barrier met h o ds per mitte d f or use i n t his 
pr ot oc ol are as f oll o ws: 
Barrier met h o ds (eac h met h o d m ust be use d wit h a h or m o nal met h o d)
■
Male c o n d o m ( wit h or wit h o ut s per mici de)
■
Fe male c o n d o m ( wit h or wit h o ut s per mici de)
■
Dia p hra g m wit h s per mici de


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 9 3
1 9 J u ne 2 0 2 0
■
Cer vical ca p wit h s per mici de
■
S p o n ge wit h s per mici de 
H or m o nal met h o ds (eac h m ust be use d wit h a barrier met h o d, prefera bl y  male c o n d o m)
■
Oral c o ntrace pti ves (eit her c o m bi ne d or pr o gester o ne o nl y )
■
I njecta ble pr o gester o ne
■
S u b der mal c o ntrace pti ve i m pla nt
■
Tra ns der mal c o ntrace pti ve patc h
■
C o ntrace pti ve va gi nal ri n g
All fe male s u bjects m ust als o refrai n fr o m e g g d o nati o n a n d i n vitr o fertilizati o n d uri n g treat me nt 
a n d u ntil at least 7 d a y s after t he last st u d y dr u g d ose.
3)
C o nt r ace pti o n Re q uire me nts f or M ale S u bjects
It is t he oretically p ossi ble t hat a rel e va nt c o nce ntrati o n of st u d y  dr u g m a y  be ac hie ve d i n a 
fe male part ner fr o m e x p os ure t o t he male s u bject’s se mi nal fl ui d. T heref ore, male s u bjects wit h 
fe male part ners of c hil d beari n g p ote ntial m ust use c o n d o ms d uri n g st u d y partici pati o n a n d f or 
7 da y s after t he last st u d y of dr u g d ose . Fe male part ners of male st u d y s u bjects s h o ul d c o nsi der 
usi n g o ne of t he a b o ve met h o ds of c o ntrace pti o n as well .
Male s u bjects m ust als o refrai n fr o m s per m d o nati o n d uri n g treat me nt a n d u ntil at least 7 da y s 
after t he e n d of st u d y dr u g d osi n g .
4)
U n acce pt a ble Birt h C o ntr ol Met h o ds
Birt h c o ntr ol met h o ds t hat are u nacce pta ble i ncl u de peri o dic a bsti ne nce (e g, cale n dar, o v ulati o n, 
s ym pt ot her mal, p ost- o v ulati o n met h o ds), wit h dra wal (c oit us i nterr u pt us), s per mici des o nl y, a n d 
lactati o nal a me n orr hea met h o d. Fe male c o n d o m a n d male c o n d o m s h o ul d n ot be use d t o get her.
5)
P r oce d ures t o be F oll o we d i n t he E ve nt of Pre g n a nc y
S u bjects will be i nstr ucte d t o n otif y t he i n vesti gat or if t he y ( or t heir part ner if s u bject is male) 
bec o me pre g na nt at a n y t i me d uri n g t he st u dy, or wit hi n 7 da y s of last st u d y  dr u g d ose. S u bjects 
w h o bec o me pre g na nt or w h o s us pect t hat t he y  are pre g na nt d uri n g t he st u d y m ust re p ort t he 
i nf or mati o n t o t he i n vesti gat or a n d disc o nti n ue st u d y dr u g i m me diately. Male s u bjects w h ose 
part ner has bec o me pre g na nt or s us pect s he is pre g na nt d uri n g t he st u d y are t o re p ort t he 
i nf or mati o n t o t he i n vesti gat or.
I nstr ucti o ns f or re p orti n g pre g na nc y, part ner pre g na nc y , a n d pre g na nc y o utc o me are o utli ne d i n 
Secti o n 7. 7. 2. 1 .


G S -4 8 7 5
Pr ot oc ol G S -U S -3 6 5 -4 2 3 7
Fi nal
Gilea d Scie nces, I nc. 
A me n d me nt 2
C O N FI D E N TI A L
Pa ge 9 4
1 9 J u ne 2 0 2 0
6)
Pre g n a nc y Testi n g
All fe males of c hil d beari n g p ote ntial will ha ve uri ne pre g na nc y  testi n g e ver y 4 wee ks , at a 
mi ni m u m, (i n cli nic) d uri n g t heir st u d y partici pati o n. If a uri ne pre g na nc y test is p ositi ve, t he 
s u bject s h o ul d st o p st u d y dr u g i m me diately, c o ntact t he i n vesti gat or, a n d ha ve c o nfir mat or y  
ser u m pre g na nc y test i n cli nic.

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 2, Blinded, Randomized, Placebo-Controlled Study 
Evaluating the Efficacy and Safety of GS-4875 in Subjects 
with Moderately to Severely Active Ulcerative Colitis
Name of Test Drug:
GS-4875
Study Number:
GS-US-365-4237
Protocol Version (Date):
Amendment 2 (19 June 2020)
Analysis Type:
Final Analysis
Analysis Plan Version:
1.0
Analysis Plan Date:
05 April 2021
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
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TABLE OF CONTENTS 
TABLE OF CONTENTS ................................................................................................................................................ 2 
LIST OF ABBREVIATIONS ......................................................................................................................................... 5 
1. 
INTRODUCTION .................................................................................................................................................. 6 
1.1. 
1.2. 
1.3. 
Study Objectives ........................................................................................................................................ 6 
1. 1. 1. 
Pri1nruy Objectives .................................................................................................................. 6 
1. 1.2. 
Secondru ob·ectives .............................................................................................................. 6 
• 
Design ............................................................................................................................................. 7 
Sainple Size and Power ............................................................................................................................. 9 
2. 
TYPE OF PLANNED ANALYSIS ...................................................................................................................... 10 
2. 1. 
Interi1n Analyses ...................................................................................................................................... 10 
2.1. 1. 
Planned Internal Unblinded Analysis .................................................................................... 10 
2.1.2. 
DMC Analysis ....................................................................................................................... 10 
2.2. 
Pri1nruy Analysis ..................................................................................................................................... 11 
2.3. 
Final Analysis .......................................................................................................................................... 11 
3. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES ............................................................................. 12 
3.1. 
3.2. 
3.3. 
3.4. 
3.5. 
3.6. 
3.7. 
3.8. 
Analysis Sets ........................................................................................................................................... 12 
3 .1. 1. 
All Randomized Analysis Set ................................................................................................ 12 
3.1.2. 
Full Analysis Set. ................................................................................................................... 12 
3.1.3. 
Safe Anal sis Set ................................................................................................................ 12 
3.1.6. 
B1omar er Ana ys1s Set ......................................................................................................... 13 
Subject Grouping ..................................................................................................................................... 13 
Strata and Covru'iates ............................................................................................................................... 13 
Examination of Subject Subgroups ......................................................................................................... 13 
Multiple Co1npa11sons ............................................................................................................................. 13 
Missing Data and Outliers ....................................................................................................................... 14 
3.6.1. 
Missing Data .......................................................................................................................... 14 
3. 6. 2. 
Outliers .................................................................................................................................. 14 
Data Handling Conventions and Transfo1mations .................................................................................. 14 
Analysis Visit Windows .......................................................................................................................... 15 
3.8.1. 
Definition of Study Day ........................................................................................................ 15 
3.8.2. 
Analysis Visit Windows ........................................................................................................ 15 
3.8.3. 
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window ................................................................................................................................. 21 
4. 
SUBJECT DISPOSITION ................................................................................................................................... 22 
4.1. 
Subject Enrollment and Disposition ........................................................................................................ 22 
4.2. 
Extent of Study Thug Exposme and Adherence ...................................................................................... 23 
4.2.1. 
Duration of Exposw·e to Study Thug ..................................................................................... 23 
4.3. 
Protocol Deviations ................................................................................................................................. 23 
5. 
BASELINE CHARACTERISTICS ..................................................................................................................... 25 
5.1. 
Demographics and Baseline Characteristics ........................................................................................... 25 
5.2. 
Other Baseline Characteristics ................................................................................................................ 25 
5.3. 
Medical Histo1y ....................................................................................................................................... 26 
6. 
EFFICACY ANALYSES ..................................................................................................................................... 27 
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6.1.
General Considerations ...........................................................................................................................27
6.1.1.
Calculations of MCS and pMCS with the Subscores............................................................27
6.2.
Primary Efficacy Endpoints ....................................................................................................................28
6.2.1.
Definition of the Primary Efficacy Endpoints.......................................................................28
6.2.2.
Analysis of the Primary Efficacy Endpoint...........................................................................29
6.3.
Secondary Efficacy Endpoints ................................................................................................................29
6.3.1.
Definition of the Secondary Efficacy Endpoints...................................................................29
6.3.2.
Analysis of the Secondary Efficacy Endpoint.......................................................................29
7.
SAFETY ANALYSES.........................................................................................................................................30
7.1.
Adverse Events and Deaths.....................................................................................................................30
7.1.1.
Adverse Event Dictionary .....................................................................................................30
7.1.2.
Adverse Event Severity .........................................................................................................30
7.1.3.
Relationship of Adverse Events to Study Drug.....................................................................30
7.1.4.
Serious Adverse Events.........................................................................................................30
7.1.5.
Treatment-Emergent Adverse Events....................................................................................31
7.1.5.1.
Definition of Treatment-Emergent Adverse Events........................................31
7.1.5.2.
Incomplete Dates .............................................................................................31
7.1.6.
Summaries of Adverse Events and Deaths............................................................................32
7.1.6.1.
Summaries of AE Incidence in Combined Severity Grade 
Subsets .............................................................................................................32
7.2.
Laboratory Evaluations ...........................................................................................................................33
7.2.1.
Summaries of Numeric Laboratory Results ..........................................................................33
7.2.2.
Graded Laboratory Values ....................................................................................................33
7.2.2.1.
Treatment-Emergent Laboratory Abnormalities .............................................33
7.2.2.2.
Summaries of Laboratory Abnormalities ........................................................34
7.3.
Body Weight and Vital Signs..................................................................................................................34
7.4.
Prior and Concomitant Medications........................................................................................................34
7.4.1.
Prior Medications ..................................................................................................................34
7.4.2.
Concomitant Medications......................................................................................................35
7.5.
Electrocardiogram Results.......................................................................................................................35
7.6.
Other Safety Measures ............................................................................................................................35
7.7.
Changes From Protocol-Specified Safety Analyses................................................................................35
9.
BIOMARKER ANALYSES ................................................................................................................................37
10.
REFERENCES.....................................................................................................................................................38
11.
SOFTWARE.........................................................................................................................................................39
12.
SAP REVISION...................................................................................................................................................40
LIST OF IN-TEXT TABLES
Table 3-1.
Analysis Visit Windows for Endoscopic Subscore – Blinded Treatment Phase.....................16
Table 3-2.
Analysis Visit Windows for Endoscopic Subscore – OL Treatment Phase............................16
Table 3-3.
Analysis Visit Windows for Stool Frequency, Rectal Bleeding and PGA Subscores 
– Blinded Treatment Phase......................................................................................................17
Table 3-4.
Analysis Visit Windows for Stool Frequency, Rectal Bleeding and PGA Subscores 
– OL Treatment Phase .............................................................................................................18
Table 3-5.
Analysis Visit Windows for Hematology, Chemistry and Urinalysis Laboratory 
Assessments – Blinded Treatment Phase ................................................................................19
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Table 3-6.
Analysis Visit Windows for Hematology, Chemistry and Urinalysis Laboratory 
Assessments – OL Treatment Phase........................................................................................20
Table 3-7.
Analysis Visit Windows for hs-CRP, Fecal Calprotectin and Fecal Lactoferrin – 
Blinded Treatment Phase.........................................................................................................20
Table 3-8.
Analysis Visit Windows for hs-CRP, Fecal Calprotectin and Fecal Lactoferrin – OL 
Treatment Phase ......................................................................................................................21
Table 6-1.
Definitions for Primary and Key Secondary Efficacy Endpoints............................................27
Table 6-2.
Modified Mayo Clinic Score (MCS).......................................................................................28
LIST OF IN-TEXT FIGURES
Figure 1.
Study Schema ............................................................................................................................8


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LIST OF ABBREVIATIONS
AE
adverse event
BMI
body mass index
COVID-19
coronavirus disease 2019
CRF
case report form
CSR
clinical study report
CTCAE
Common Toxicity Criteria for Adverse Events
DMC
data monitoring committee
ECG
electrocardiogram
ET
early termination
FAS
Full Analysis Set
GDRC
Gilead Data Review Committee
HLGT
high-level group term
HLT
high-level term
hs-CRP
high-sensitivity C-reactive protein
ID
identification
LTT
lower-level term
LOQ
limit of quantitation
MCS
Mayo Clinic Score
MedDRA
Medical Dictionary for Regulatory Activities
NRI
non-responder imputation
OL
open-label
PE
physical examination
PGA
Physician’s Global Assessment
PK
pharmacokinetic(s)
pMCS
partial Mayo Clinic Score
PT
preferred term
PTx
posttreatment
Q1, Q3
first quartile, third quartile
SAE
serious adverse events
SAP
statistical analysis plan
SD
standard deviation
SE
standard error
SOC
system organ class
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
UC
ulcerative colitis
WHO
World Health Organization


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1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) in a synoptic clinical study report 
(CSR) for Study GS-US-365-4237. This SAP is based on the study protocol Amendment 2 dated 
19 June 2020 and the electronic case report form (eCRF). The SAP will be finalized prior to data 
finalization for the primary analysis. Subject enrollment in Study GS-US-365-4237 was 
terminated early by Gilead. Data Monitoring Committee (DMC) meetings and  Gilead Data 
Review Committee (GDRC) meetings will not be held for this study due to small number of 
subjects enrolled in this study. As well, some of the statistical analyses and all statistical testings 
planned in the study protocol will not be performed. Any changes made after the finalization of 
the SAP will be documented in the synoptic CSR.
1.1.
Study Objectives
1.1.1.
Primary Objectives
The primary objective of this study is as follows:

To demonstrate the efficacy of GS-4875, compared with placebo control, in achieving 
Clinical Remission per Modified Mayo Clinic Score (MCS) at Week 10
1.1.2.
Secondary Objectives
The secondary objectives of this study are as follows:

To demonstrate the efficacy of GS-4875, compared with placebo control, in achieving 
endoscopic response at Week 10

To demonstrate the efficacy of GS-4875, compared with placebo control, in achieving MCS 
Response at Week 10

To demonstrate the efficacy of GS-4875, compared with placebo control, in achieving MCS 
Remission at Week 10

To evaluate GS-4875, as compared with placebo control, in achieving histologic remission at 
Week 10

To evaluate the safety and tolerability of GS-4875


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1.2.
Study Design
This is a Phase 2, blinded, randomized, placebo-controlled study evaluating the efficacy and 
safety of GS-4875 for the treatment of subjects with moderately to severely active ulcerative 
colitis (UC). Adult male or female subjects 18 years of age or older who have documented 
evidence of UC and previously demonstrated an inadequate response or loss of response to a 
TNFα inhibitor may be eligible for entry (refer to the protocol for complete inclusion and 
exclusion criteria).
Approximately 180 subjects who meet protocol eligibility criteria will be randomized in a 1:1:1 
ratio to 1 of 3 treatment groups as follows:
Treatment group 1 (n = 60): GS-4875 300 mg once daily 
Treatment group 2 (n = 60): GS-4875 100 mg once daily 
Treatment group 3 (n = 60): Placebo once daily 
Central randomization is used. Treatment assignments will be stratified according to the sum 
(≤ 6 or > 6) of 3 MCS subscores for Stool Frequency, Rectal Bleeding, and Endoscopic Findings 
at Screening.
The study was terminated after 19 subjects were enrolled in the study.
A schematic of this study design is provided in Figure 1.
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Figure 1.
Study Schema
This study includes:

Screening period (Days −30 to −1)

Baseline/Randomization (Day 1)

Blinded Treatment phase (Day 1 up to Week 50)
At Week 10 visit, all subjects will have an efficacy assessment.
Subjects who achieve MCS Response based on results from Week 10 will continue in the 
Blinded Treatment phase.

Open-label Treatment phase (OL Day 1 up to OL Week 50)
All subjects who do not achieve MCS Response based on results from Week 10 will 
discontinue the Blinded Treatment phase and have the option to enter the OL Treatment 
phase.
At OL Week 10 visit, all subjects will have an efficacy assessment.
Subjects who achieve MCS Response based on results from OL Week 10 will continue in 
the OL Treatment phase. All subjects who do not achieve MCS Response will 
discontinue study drug.

Posttreatment (PTx) Assessments
In the Blinded Treatment phase, randomized subjects may receive a maximum of 50 weeks of 
treatment. Subjects, who move to the OL Treatment phase, will have received 10 weeks of 
blinded treatment and may receive up to 50 weeks of OL treatment. Thus, total duration of 
treatment may be a maximum of 60 weeks. 
Screening& 
Randomization 
Baseline 
2 
4 
6 
Week 10 
Week 50 
.___._ _ _.__~~==~~-~-~-~-~-~-~--------------------J 
~--~~ ---~I 
~I--~~ ~ --~ 
Non-responders at Week 1 o 
Day 1 OL 
Week 10 
Week 50 OL 
L ________ l ____________________ J 
Open Label GS-4875 300 mg QD 
T 
Week 10 MCS 
Response Assessment 
T 
Efficacy 
Assessments 


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Efficacy will be assessed primarily through modified MCS. MCS will be assessed at Screening, 
Blinded Treatment phase Week 10 and Week 50, and OL Treatment phase Week 10 and 
Week 50, if applicable.
Additional details on efficacy assessments are presented in Section 6, Appendix 1, and Appendix 
2.
Safety will be assessed primarily through adverse events (AEs), laboratory analyses, 
electrocardiogram (ECG), physical examination (PE) and vital signs. Laboratory testing, PE and 
vital signs will be assessed at every visit.
Additional details on safety assessments are presented in Section 7, Appendix 1 and Appendix 2.
1.3.
Sample Size and Power
A total of 180 subjects, i.e. 60 subjects in the placebo group and 60 subjects in each GS-4875 
dose group (n = 120 total for GS-4875), will provide approximately 75% power when comparing 
each GS-4875 dose group to placebo at a 1-sided 0.025 significance level to detect a treatment 
difference in clinical remission rate per modified MCS of 17.5% (22.5% on GS-4875 and 5% on 
placebo) based on Fisher’s exact test.


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Interim Analyses
2.1.1.
Planned Internal Unblinded Analysis
A Gilead internal unblinded team, the GS-US-365-4237 Gilead Data Review Committee 
(GDRC), independent of the blinded study team, was to perform the data review of study data 
after 90 subjects either complete the Week 10 visit or early discontinue from the study. Based on 
the interim analysis, the GDRC may propose changes in the study design, including potential 
termination of study due to lack of efficacy.
Ad hoc interim analyses at additional timepoints may also be requested, and data reviews be 
conducted by the GDRC, if needed.
The membership, conduct, and meeting schedule of the GDRC was to be specified in the GDRC 
Charter.
Due to small number of subjects enrolled in the study, the planned internal unblinded analysis to 
be reviewed by GDRC will not be performed.
2.1.2.
DMC Analysis
An external multidisciplinary Data Monitoring Committee (DMC) was to review the progress of 
the study and perform interim reviews of the safety data in order to protect subject welfare and 
preserve study integrity. To ensure the best interests of the participants, the DMC was to make 
recommendations to the sponsor if the nature, frequency, and severity of adverse effects 
associated with the study treatment warrant the early termination of the study, the continuation of 
the study, or the continuation of the study with modifications.
The initial safety review was to be conducted after approximately 20 subjects either complete the 
Week 4 visit or discontinue from the study prior to Week 4. Subsequent DMC meetings for 
safety review was to be held after approximately 60 subjects either complete the Week 4 visit or 
discontinue from the study and after approximately 90 subjects either complete Week 10 visit or 
discontinue from the study. The frequency of meetings may be adjusted as requested by the 
DMC.
The DMC’s role and responsibilities and the scope of analysis to be provided to the DMC were 
to be provided in a mutually agreed upon charter, which defines the DMC membership, meeting 
logistics, and meeting frequency.
Due to the fact that less than 20 subjects were enrolled in the study, no DMC meeting will be 
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2.2.
Primary Analysis
The unblinded primary analysis of the primary endpoint, i.e. Clinical Remission per Modified 
MCS, and secondary endpoints including safety was to be conducted when all randomized 
subjects (approximately 180) have completed Week 10 or discontinued from the study, and was 
to be tested at the 0.025 significance level.
Due to limited subject enrollment in the study, the unblinded primary analysis will be conducted 
for all randomized subjects. Some of the statistical analyses and all statistical testings planned in 
the study protocol will not be performed.
The analysis will be conducted after all subjects have completed 10 weeks of blinded study drug 
or discontinued from the study, associated safety and efficacy assessments have been completed, 
outstanding data queries have been resolved or adjudicated as unresolvable, and the data have 
been cleaned and finalized for the analysis.
2.3.
Final Analysis
The unblinded final analysis will be performed after all subjects have completed the study, 
outstanding data queries have been resolved or adjudicated as unresolvable, and the data have 
been cleaned and finalized. The analysis of the other secondary endpoints 
 
 will be conducted at the time of the final analysis.
Due to limited subject enrollment in the study, some of the statistical analyses and all statistical 
testings planned in the study protocol will not be performed.
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GENERAL CONSIDERATIONS FOR DATA ANALYSES 
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of subjects in each catego1y will be presented; for continuous variables, 
the number of subjects (n), mean, standard deviation (SD) or standard eITor (SE), median, first 
quaiiile (QI), third quaiiile (Q3), minimum, and maximum will be presented. 
By-subject listings will be presented for all subjects in the All Randomized Analysis Set and 
so1ied by subject identification (ID) number, visit date, and time (if applicable). Data collected 
on log fonns, such as AEs, will be presented in chronological order within the subject. The 
treatment group to which subjects were randomized or initially assigned will be used in the 
listings. Age, sex at biiih, race, and ethnicity may be included in the listings, as space pennits. 
3.1. 
Analysis Sets 
Analysis sets define the subjects to be included in an analysis. Analysis sets and theii· definitions 
ai·e provided in this section. Subjects included in each analysis set will be detennined before the 
study blind is broken for analysis. The analysis set will be identified and included as a subtitle of 
each table, figure, and listing. 
For each analysis set, the number and percentage of subjects eligible for inclusion, as well as the 
number and percentage of subjects who were excluded and the reasons for their exclusion, will 
be sUllllllai·ized by treatment group. 
3.1.1. 
All Randomized Analysis Set 
The All Randomized Analysis Set includes all subjects who were randomized in the study. 
This is the primaiy analysis set for by-subject listings. 
3.1.2. 
Full Analysis Set 
The Full Analysis Set (FAS) includes all randomized subjects who took at least 1 dose of study 
diug. This is the primaiy analysis set for efficacy analyses. 
3.1.3. 
Safety Analysis Set 
The Safety Analysis Set includes all subjects who took at least 1 dose of study diug. This is the 
primaiy analysis set for safety analyses. 
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3.1.6. 
Biomarker Analysis Set 
Version 1.0 
The Biomarker Analysis Set includes all subjects in the FAS who have nonmissing baseline and 
at least 1 postbaseline measurement for at least 1 of the 3 biomarkers (high-sensitivity C-reactive 
protein [hs-CRP], fecal calprotectin, and fecal lactofenin). 
3.2. 
Subject Grouping 
For analyses based on the All Randomized Analysis Sets and FAS, subjects will be grouped 
according to the treatment to which they were randomized. For analyses based on the Safety 
Analysis Set, and Biomarker Analysis Set, subjects will be grouped according to the actual 
treatment received. The actual treatment received will differ from the randomized ti·eatment only 
when their actual ti·eatment differs from randomized ti·eatment for the entire ti·eatment duration. 
For subjects who entered the OL Treatment phase and took at least 1 dose of study chug (OL 
GS-4875), all data collected during the OL Treatment phase will be grouped according to the 
actual ti·eatment received across the Blinded Treatment phase and OL Treatment phase, if 
applicable. 
3.3. 
Strata and Covariates 
Subjects will be randomly assigned to treatment groups via the interactive voice or web response 
system (IXRS) in a 1: 1: 1 ratio using a sti·atified randomization schedule. Sti·atification will be 
based on the sum (:S 6 or > 6) of 3 MCS subscores for Stool Frequency, Rectal Bleeding, and 
Endoscopic Findings at Screening. 
No stratification factors or covariates will be used in the analyses suppo1i ing the synoptic CSR. 
3.4. 
Examination of Subject Subgroups 
There are no prespecified subject subgroupings for efficacy and safety analyses. 
3.5. 
Multiple Comparisons 
No statistical testings will be perfo1med. Adjustments for multiplicity will not be applied. 
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3.6.
Missing Data and Outliers
3.6.1.
Missing Data
In general, missing data will not be imputed unless methods for handling missing data are 
specified. Exceptions are presented in this document.
For missing last dosing date of study drug, imputation rules are described in Section 4.2.1. The 
handling of missing or incomplete dates for AE onset is described in Section 7.1.5.2.
3.6.2.
Outliers
Outliers will be identified during the data management and data analysis process. All data, 
including outliers, will be included in analyses, unless otherwise specified.
3.7.
Data Handling Conventions and Transformations
The following conventions will be used for the imputation of date of birth when it is partially 
missing or not collected:

If only month and year of birth is collected, then “15” will be imputed as the day of birth

If only year of birth is collected, then “01 July” will be imputed as the day and month of birth

If year of birth is missing, then date of birth will not be imputed.
In general, age collected at Day 1 (in years) will be used for analyses and presented in listings. If 
age at Day 1 is not available for a subject, then age derived based on date of birth and the Day 1 
visit date will be used instead. If an enrolled subject was not dosed with any study drug, the 
randomization date will be used instead of the Day 1 visit date. For screen failures, the date the 
first informed consent was signed will be used for the age derivation. Age required for 
longitudinal and temporal calculations and analyses (e.g., estimates of creatinine clearance, age 
at date of AE) will be based on age derived from date of birth and the date of the measurement or 
event, unless otherwise specified.
Non-PK data that are continuous in nature but are less than the lower limit of quantitation (LOQ) 
or above the upper LOQ will be imputed as follows:

A value that is 1 unit less than the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “ x” (where x is considered the LOQ). For example, if the 
values are reported as < 50 and < 5.0, values of 49 and 4.9, respectively, will be used to 
calculate summary statistics. An exception to this rule is any value reported as < 1 or < 0.1, 
etc. For values reported as < 1 or < 0.1, a value of 0.9 or 0.09, respectively, will be used to 
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
A value that is 1 unit above the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “> x” (where x is considered the LOQ). Values with decimal 
points will follow the same logic as above.

The LOQ will be used to calculate descriptive statistics if the datum is reported in the form of 
“≤ x” or “≥ x” (where x is considered the LOQ).
3.8.
Analysis Visit Windows
3.8.1.
Definition of Study Day
For all subjects who received at least 1 dose of study drug, Study Day will be calculated from the 
first dosing date of study drug and derived as follows:

For postdose study days: Assessment Date – First Dosing Date + 1

For days prior to the first dose: Assessment Date – First Dosing Date
Therefore, Study Day 1 is the day of first dose of study drug administration.
Baseline is defined as the last available observation on or prior to Study Day 1, unless otherwise 
specified.
For subjects who entered OL Treatment phase and received at least 1 dose of study drug (OL 
GS-4875), OL Study Day will be calculated from the first dosing date of study drug in OL 
Treatment phase and derived as follows:

For postdose OL study days: Assessment Date – First Dosing Date of study drug in OL 
Treatment phase + 1
Therefore, OL (Study) Day 1 is the day of first dose of study drug administration in OL 
Treatment phase.
OL baseline is defined as the last available observation on or prior to OL Study Day 1, unless 
otherwise specified.
3.8.2.
Analysis Visit Windows
Subject visits might not occur on protocol-specified days. Therefore, for the purpose of analysis, 
observations will be assigned to analysis windows.
Endoscopic Subscore
The analysis windows for Endoscopic Subscore are provided in Table 3-1 for Blinded Treatment 
phase and Table 3-2 for OL Treatment phase.


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Table 3-1.
Analysis Visit Windows for Endoscopic Subscore – Blinded 
Treatment Phase
Visit Window Study Day
Nominal Visit
Analysis Visit
Nominal Study Day
Lower Limit
Upper Limit
Screening
Baseline
(none)
(none)
1
Week 10
Week 10
71
58
minimum of 85 and 
OL Day 1 (if applicable)
Week 50
Week 50
351
324
379
Note: Anchor day defined in Appendix 4 will be used for analysis visit window calculation of MCS and all efficacy endpoints 
based on MCS; endoscopic day will be used for analysis visit window calculation of endoscopic subscore
Table 3-2.
Analysis Visit Windows for Endoscopic Subscore – OL Treatment 
Phase
Visit Window Study Day (OL Day)
Nominal Visit
Analysis Visit
Nominal Study Day
(OL Day)
Lower Limit
Upper Limit
OL Week 10
OL Week 10
71
58
85
OL Week 50
OL Week 50
351
324
379
Note: Anchor day defined in Appendix 4 will be used for analysis visit window calculation of MCS and all efficacy endpoints 
based on MCS; endoscopic day will be used for analysis visit window calculation of endoscopic subscore
Stool Frequency, Rectal Bleeding and Physician’s Global Assessment (PGA) Subscores
The analysis windows for Stool Frequency, Rectal Bleeding and PGA subscores are provided in 
Table 3-3 for Blinded Treatment phase and Table 3-4 for OL Treatment phase.
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Table 3-3.
Analysis Visit Windows for Stool Frequency, Rectal Bleeding and 
PGA Subscores – Blinded Treatment Phase
Visit Window Study Day
Nominal Visit
Analysis Visit
Nominal Study Day
Lower Limit
Upper Limit
Screening/Day 1
Baseline
1
(none)
1
Week 2
Week 2
15
2
22
Week 4
Week 4
29
23
36
Week 6
Week 6
43
37
57
Week 10
Week 10
71
58
minimum of 85 and 
OL Day 1 (if applicable)
Week 14
Week 14
99
86
113
Week 18
Week 18
127
114
141
Week 22
Week 22
155
142
169
Week 26
Week 26
183
170
197
Week 30
Week 30
211
198
225
Week 34
Week 34
239
226
253
Week 38
Week 38
267
254
281
Week 42
Week 42
295
282
309
Week 46
Week 46
323
310
337
Week 50
Week 50
351
338
365
Note: Anchor day defined in Appendix 4 will be used for analysis visit window calculation of MCS and all efficacy endpoints 
based on MCS; endoscopic day will be used for analysis visit window calculation of endoscopic subscore
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Table 3-4.
Analysis Visit Windows for Stool Frequency, Rectal Bleeding and 
PGA Subscores – OL Treatment Phase
Visit Window Study Day (OL Day)
Nominal Visit
Analysis Visit
Nominal Study Day
(OL Day)
Lower Limit
Upper Limit
OL Day 1
OL Day 1
1
1
1
OL Week 2
OL Week 2
15
2
22
OL Week 4
OL Week 4
29
23
36
OL Week 6
OL Week 6
43
37
57
OL Week 10
OL Week 10
71
58
85
OL Week 14
OL Week 14
99
86
113
OL Week 18
OL Week 18
127
114
141
OL Week 22
OL Week 22
155
142
169
OL Week 26
OL Week 26
183
170
197
OL Week 30
OL Week 30
211
198
225
OL Week 34
OL Week 34
239
226
253
OL Week 38
OL Week 38
267
254
281
OL Week 42
OL Week 42
295
282
309
OL Week 46
OL Week 46
323
310
337
OL Week 50
OL Week 50
351
338
365
Note: Anchor day defined in Appendix 4 will be used for analysis visit window calculation of MCS and all efficacy endpoints 
based on MCS; endoscopic day will be used for analysis visit window calculation of endoscopic subscore
Clinical Laboratory Assessments
The analysis windows for hematology, chemistry and urinalysis laboratory assessments are 
provided in Table 3-5 for Blinded Treatment phase and Table 3-6 for OL Treatment phase.
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Table 3-5.
Analysis Visit Windows for Hematology, Chemistry and Urinalysis 
Laboratory Assessments – Blinded Treatment Phase
Visit Window Study Day
Nominal Visit
Analysis Visit
Nominal Study Day
Lower Limit
Upper Limit
Screening/Day 1
Baseline
1
(none)
1
Week 2
Week 2
15
2
22
Week 4
Week 4
29
23
36
Week 6
Week 6
43
37
57
Week 10
Week 10
71
58
minimum of 85 and OL 
Day 1 (if applicable)
Week 14
Week 14
99
86
113
Week 18
Week 18
127
114
141
Week 22
Week 22
155
142
169
Week 26
Week 26
183
170
197
Week 30
Week 30
211
198
225
Week 34
Week 34
239
226
253
Week 38
Week 38
267
254
281
Week 42
Week 42
295
282
309
Week 46
Week 46
323
310
337
Week 50
Week 50
351
338
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Table 3-6.
Analysis Visit Windows for Hematology, Chemistry and Urinalysis 
Laboratory Assessments – OL Treatment Phase
Visit Window Study Day (OL Day)
Nominal Visit
Analysis Visit
Nominal Study Day
(OL Day)
Lower Limit
Upper Limit
OL Day 1
OL Baseline
1
(none)
1
OL Week 2
OL Week 2
15
2
22
OL Week 4
OL Week 4
29
23
36
OL Week 6
OL Week 6
43
37
57
OL Week 10
OL Week 10
71
58
85
OL Week 14
OL Week 14
99
86
113
OL Week 18
OL Week 18
127
114
141
OL Week 22
OL Week 22
155
142
169
OL Week 26
OL Week 26
183
170
197
OL Week 30
OL Week 30
211
198
225
OL Week 34
OL Week 34
239
226
253
OL Week 38
OL Week 38
267
254
281
OL Week 42
OL Week 42
295
282
309
OL Week 46
OL Week 46
323
310
337
OL Week 50
OL Week 50
351
338
>351
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3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window
Depending on the statistical analysis method, single values may be required for each analysis 
window. For example, change from baseline by visit usually requires a single value, whereas a 
time-to-event analysis would not require 1 value per analysis window.
If multiple valid, nonmissing measurements exist in an analysis window, records will be chosen 
based on the following rules if a single value is needed:

For baseline, the last nonmissing value on or prior to the first dosing date of study drug will 
be selected, unless specified differently. If there are multiple records with the same time or 
no time recorded on the same day, the baseline value will be the average of the 
measurements for continuous data, or the measurement with the lowest severity (e.g., normal 
will be selected over abnormal for safety ECG findings) for categorical data.

For postbaseline values:
The record closest to the nominal day for that visit will be selected.
If there are 2 records that are equidistant from the nominal day, the later record will be 
selected.
If there is more than 1 record on the selected day, the average will be taken for 
continuous data and the worse severity will be taken for categorical data, unless 
otherwise specified.
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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
Key study dates (i.e., first subject screened, first subject randomized, last subject randomized, 
last subject last visit for the primary endpoint, and last subject last visit for the clinical study 
report) will be provided.
A summary of subject disposition will be provided by treatment group. This summary will 
present the number of subjects screened, the number of subjects randomized in Blinded 
Treatment phase, the number of subjects entered OL Treatment phase, and the number of 
subjects in each of the categories listed below:

Safety Analysis Set

Full Analysis Set

Completed study drug dosing through Week 10 (indicated in Study Drug Completion CRF)

Did not complete study drug up to Week 10 with reasons for premature discontinuation of 
study drug

Continuing study drug (for analyses other than the final analysis)

Completed study drug dosing through Week 50 (indicated in Study Drug Completion CRF)

Continued Blinded Treatment phase after Week 10 but did not complete study drug up to 
Week 50 with reasons for premature discontinuation of study drug

Entered OL Treatment phase after Week 10 and completed study drug dosing through OL 
Week 50 (indicated in Study Drug Completion CRF)

Entered OL Treatment phase after Week 10 but did not complete study drug up to OL 
Week 50 with reasons for premature discontinuation of study drug

Completed study

Did not complete the study with reasons for premature discontinuation of study
For the status of study drug and study completion and reasons for premature discontinuation, the 
number and percentage of subjects in each category will be provided. The denominator for the 
percentage calculation will be the total number of subjects in the Safety Analysis Set 
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4.2.
Extent of Study Drug Exposure and Adherence
Extent of exposure to study drug will be examined by assessing the total duration of exposure to 
study drug.
Summaries of extent of study drug exposure and adherence will be provided by:

Blinded Treatment phase

OL Treatment phase
4.2.1.
Duration of Exposure to Study Drug
Total duration of exposure to study drug will be defined as last dosing date minus first dosing 
date plus 1, regardless of any temporary interruptions in study drug administration, and will be 
expressed in weeks using up to 1 decimal place (e.g., 4.5 weeks). If the last study drug dosing 
date is missing, the latest date among the study drug end date, clinical visit date, laboratory 
sample collection date, and vital signs assessment date that occurred during the on-treatment 
period will be used for subjects included in the final analyses or the last available date in the 
database snapshot for subjects who were still on treatment at the time of an interim analysis.
The total duration of exposure to study drug will be summarized using descriptive statistics and 
using the number (i.e., cumulative counts) and percentage of subjects exposed through the 
following time periods:

Blinded Treatment phase: 1 day, 4 weeks, 6 weeks, 10 weeks, 14 weeks, 18 weeks, 
22 weeks, 26 weeks, 30 weeks, 34 weeks, 38 weeks, 42 weeks, 46 weeks and 50 weeks

OL Treatment phase: 1 day, 4 weeks, 6 weeks, 10 weeks, 14 weeks, 18 weeks, 22 weeks, 
26 weeks, 30 weeks, 34 weeks, 38 weeks, 42 weeks, 46 weeks and 50 weeks
Summaries will be provided by treatment group for the Safety Analysis Set. No formal statistical 
testing is planned.
A by-subject listing of study drug administration will be provided separately by subject ID 
number (in ascending order) and visit (in chronological order).
4.3.
Protocol Deviations 
Subjects who did not meet the eligibility criteria for study entry but enrolled in the study, will be 
summarized regardless of whether they were exempted by the sponsor or not. A by-subject listing 
will be provided for those subjects who did not meet at least 1 eligibility (inclusion or exclusion) 
criterion. The listing will present the eligibility criterion (or criteria if more than 1 deviation) that 
subjects did not meet and related comments, if collected.


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Protocol deviations occurring after subjects entered the study are documented during routine 
monitoring. A by-subject listing will be provided for those subjects with important protocol 
deviation.
This study was ongoing during the coronavirus disease 2019 (COVID-19) pandemic. A by-
subject listing will be provided for subjects with important protocol deviations related to 
COVID-19, if applicable. A separate listing will be provided for subjects with non-important 
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5.
BASELINE CHARACTERISTICS
5.1.
Demographics and Baseline Characteristics
Subject demographic variables (i.e., age, sex, race, and ethnicity) and baseline characteristics 
(body weight [in kg], height [in cm], and body mass index [BMI; in kg/m2]) will be summarized 
by treatment group and overall using descriptive statistics for continuous variables and using 
number and percentage of subjects for categorical variables. The summary of demographic data 
will be provided for the Safety Analysis Set.
A by-subject demographic listing, including the informed consent date, will be provided by 
subject ID number in ascending order.
5.2.
Other Baseline Characteristics
The following baseline disease characteristics will be summarized by treatment group and overall 
using descriptive statistics for continuous variables and using number and percentage of subjects 
for categorical variables:

Duration of UC (in years) from date of diagnosis to first dosing date

MCS

Partial MCS (pMCS)

Endoscopic subscore of 3 (yes, no)
The summary of these baseline characteristics will be provided for the Safety Analysis Set. No 
formal statistical testing is planned.
A by-subject listing of baseline disease characteristics will be provided by subject ID number in 
ascending order. The following baseline disease characteristics will also be included in the 
listing:

Extent of UC from medical history

UC treatment history
Prior use of biologic agents (yes, no)
Number of TNFα antagonist used (1, 2, ≥ 3)
Prior use of vedolizumab (yes, no)
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
UC concomitant medication
Systemically absorbed corticosteroids (yes, no)
5.3.
Medical History
The extent of UC will be included in the by-subject listing of baseline disease characteristics. 
Other medical history data will not be summarized or listed.


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6.
EFFICACY ANALYSES
6.1.
General Considerations
The efficacy analysis will be conducted on the FAS, defined in Section 3.1.2, unless otherwise 
specified.
The definitions for the key efficacy endpoints (i.e. primary and key secondary efficacy 
endpoints) are listed in Table 6-1. All of the key efficacy endpoints are dichotomous.
Table 6-1.
Definitions for Primary and Key Secondary Efficacy Endpoints
Type
Event Endpoint
Definition
Primary
Clinical Remission per Modified MCS at 
Week 10
Stool Frequency subscore ≤ 1 and not greater 
than baseline, Rectal Bleeding subscore of 0, 
and Endoscopic subscore ≤ 1 at Week 10
Secondary
Endoscopic Response at Week 10
Endoscopic subscore ≤ 1 at Week 10
Secondary
MCS Response at Week 10
A decrease from baseline of ≥ 3 points and at 
least 30% in MCS, in addition to a ≥ 1 point 
decrease from baseline in the Rectal 
Bleeding subscore or a Rectal Bleeding 
subscore ≤ 1 at Week 10
Secondary
MCS Remission at Week 10
MCS score of ≤ 2 and no individual subscore 
> 1 at Week 10
Secondary
Histologic Remission at Week 10
Geboes Scale with all of the following must 
be met at Week 10: Grade 0 of ≤ 0.3, 
Grade 1 of ≤ 1.1, Grade 2a of ≤ 2A.3, 
Grade 2b of 2B.0, Grade 3 of 3.0, Grade 4 of 
4.0, and Grade 5 of 5.0 {Geboes 2000}
For each of the key efficacy endpoints defined above, responders are subjects who achieved the 
endpoint based on assessment. Subjects who do not have sufficient measurements to determine 
the endpoint will be considered non-responders (i.e., non-responder imputation [NRI]).
MCS Response at Week 10 will be used to determine whether a subject is eligible to continue 
Blinded Treatment phase or enter OL Treatment phase. Subjects with insufficient data to assess 
MCS Response will discontinue study drug and are not eligible for the OL Treatment phase, 
even if they are considered as non-responder by NRI.
6.1.1.
Calculations of MCS and pMCS with the Subscores
The MCS is an instrument designed to measure disease activity in UC (Table 6-2). The MCS 
system is a composite index of 4 disease activity variables. Each variable is scored individually 
on an integer scale of 0 to 3, inclusive, with higher scores indicating greater disease activity. The 


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individual components of the MCS include Stool Frequency, Rectal Bleeding, Endoscopic 
Findings subscore, and the Physician’s Global Assessment (PGA). Stool Frequency and Rectal 
Bleeding are determined using an electronic daily diary, which collects subject reported 
components directly.
The efficacy endpoints described in Table 6-1, except for Histologic Remission, are all based on 
the 4 individual components. MCS is calculated as the sum of the 4 subscores, ranging from 0 to 
12. A pMCS is calculated as the sum of the 3 subscores excluding the Endoscopic subscore, 
ranging from 0 to 9. Further information on the MCS and calculation rules are listed in 
Appendix 4.
Table 6-2.
Modified Mayo Clinic Score (MCS)
Score
Variables
0
1
2
3
Stool Frequency
Normal number of 
stools for subject
1 to 2 stools per day 
more than normal
3 to 4 stools per day 
more than normal
≥ 5 stools per day 
more than normal
Rectal Bleeding
No blood seen
Streaks of blood 
with stool less than 
half the time
Obvious blood or 
streaks of blood 
with stool most of 
the time
Blood alone passes
Endoscopic Findings
Normal or inactive 
disease
Mild disease
Moderate disease
Severe disease
Physician Global 
Assessment
Normal
Mild disease
Moderate disease
Severe disease
A by-subject listing will be provided by subject ID number and visit for the following scores:

MCS

MCS subscores in Stool Frequency, Rectal Bleeding, Endoscopic Findings (locally and 
centrally read), and PGA

pMCS
6.2.
Primary Efficacy Endpoints
6.2.1.
Definition of the Primary Efficacy Endpoints
The primary efficacy endpoint is the proportion of subjects achieving Clinical Remission per 
Modified MCS at Week 10, as defined in Table 6-1. MCS subscores collected at Screening will 
be used as baseline values.
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Due to limited subject enrollment in the study, the sunnnaiy of primaiy efficacy endpoint will 
not be provided. No statistical testing will be perfonned. A by-subject listing of Clinical 
Remission status per Modified MCS at Week 10 will be provided by subject ID nlllllber. 
6.3. 
6.3.1. 
Secondary Efficacy Endpoints 
Definition of the Secondary Efficacy Endpoints 
The key secondaiy efficacy endpoints ai·e: 
• 
The propo1tion of subjects with Endoscopic Response at Week 10 
• 
The propo1tion of subjects with MCS Response at Week 10 
• 
The proportion of subjects with MCS Remission at Week 10 
• 
The propo1tion of subjects with Histologic Remission at Week 10 
6.3.2. 
Analysis of the Secondary Efficacy Endpoint 
Due to limited subject enrollment in the study, the summaiy of secondaiy efficacy endpoints will 
not be provided. No statistical testing will be perfonned. A by-subject listing of response status 
will be provided for the following secondaiy efficacy endpoints: 
• 
Endoscopic Response (yes, no) at Week 10 
• 
MCS Response (yes, no) at Week 10 
• 
MCS Remission (yes, no) at Week 10 
Histologic data will not be read or processed. Consequently, Histologic Remission (yes, no) at 
Week 10 will not be listed. 
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7.
SAFETY ANALYSES
7.1.
Adverse Events and Deaths
If an AE occurred in Blinded Treatment phase, this AE will be summarized under blinded 
treatment group. For subjects who entered OL Treatment phase, an AE will be summarized 
under OL treatment if this AE start date is on or after the first dose of OL treatment.
7.1.1.
Adverse Event Dictionary
Clinical and laboratory AEs will be coded using the current version of Medical Dictionary for 
Regulatory Activities (MedDRA). System organ class (SOC), high-level group term (HLGT), 
high-level term (HLT), preferred term (PT), and lower-level term (LLT) will be provided in the 
AE dataset.
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Grade 1, 2, 3, 4, or 5 according to toxicity 
criteria specified in the protocol. The severity grade of events for which the investigator did not 
record severity will be categorized as “missing” for tabular summaries and data listings. The 
missing category will be listed last in summary presentation.
7.1.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” on the AE CRF to the 
question of “Related to Study Treatment.” Relatedness will always default to the investigator’s 
choice, not that of the medical monitor. Events for which the investigator did not record 
relationship to study drug will be considered related to study drug for summary purposes. 
However, by-subject data listings will show the relationship as missing.
7.1.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if the AEs met the 
definitions of SAEs that were specified in the study protocol. SAEs captured and stored in the 
clinical database will be reconciled with the SAE database from the Gilead Drug Safety and 
Public Health Department before data finalization.


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7.1.5.
Treatment-Emergent Adverse Events 
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) for the Blinded Treatment phase are defined as 1 or 
both of the following:

Any AEs with an onset date on or after the Blinded Treatment phase study drug start date and 
no later than 30 days after permanent discontinuation of the Blinded Treatment phase study 
drug if no OL Treatment phase study drug was taken, OR any AEs with an onset date on or 
after the Blinded Treatment phase study drug start date and before the OL Treatment phase 
study drug start date if OL Treatment phase study drug was taken.

Any AEs leading to premature discontinuation of Blinded Treatment phase study drug.
TEAEs for the OL Treatment phase are defined as 1 or both of the following:

Any AEs with an onset date on or after the OL Treatment phase study drug start date and no 
later than 30 days after permanent discontinuation of the OL Treatment phase study drug.

Any AEs leading to premature discontinuation of OL Treatment phase study drug.
7.1.5.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date 
of study drug, then the month and year (or year alone if month is not recorded) of onset 
determine whether an AE is treatment emergent. The event is considered treatment emergent if 
both of the following 2 criteria are met:

The AE onset is the same as or after the month and year (or year) of the first dosing date of 
study drug, and

The AE onset date is the same as or before the month and year (or year) of the date 
corresponding to 30 days after the date of the last dose of study drug
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date later than the first dosing date of study drug, will be considered to be treatment emergent. In 
addition, an AE with the onset date missing and incomplete stop date with the same or later 
month and year (or year alone if month is not recorded) as the first dosing date of study drug will 
be considered treatment emergent.


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7.1.6.
Summaries of Adverse Events and Deaths
Treatment-emergent AEs will be summarized based on the Safety Analysis Set.
7.1.6.1.
Summaries of AE Incidence in Combined Severity Grade Subsets 
A brief, high-level summary of the number and percentage of subjects who experienced at least 1 
TEAE in the categories described below will be provided by treatment group. All deaths 
observed in the study will also be included in this summary.

TEAE

TEAEs with Grade 3 or higher

TEAEs with Grade 2 or higher

TE treatment-related AEs

TE treatment-related AEs with Grade 3 or higher

TE SAEs

TE treatment-related SAEs 

TEAEs leading to premature discontinuation of study drug
The number and percentage of subjects who experienced at least 1 TEAE will be provided and 
summarized by PT and treatment group. For the other AE categories described below, 
summaries will be provided by SOC, PT, and treatment group:

TE treatment-related AEs

TE SAEs

TEAEs leading to premature discontinuation of study drug
Multiple events will be counted only once per subject in each summary. Adverse events will be 
summarized and listed first in alphabetic order of SOC within each SOC (if applicable), and then 
by PT in descending order of total frequency within each SOC. For summaries by severity grade, 
the most severe grade will be used for those AEs that occurred more than once in an individual 
subject during the study.
Data listings will be provided for the following:

All AEs, indicating whether the event is treatment emergent

All SAEs

All Deaths

All AEs leading to premature discontinuation of study drug


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7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the 
Safety Analysis Set and will include data collected up to the last dose of study drug plus 30 days 
for subjects who have permanently discontinued study drug. The analysis will be based on values 
reported in conventional units. When values are below the LOQ, they will be listed as such, and 
the closest imputed value will be used for the purpose of calculating summary statistics as 
specified in Section 3.7. Hemolized test results will not be included in the analysis, but they will 
be listed in by-subject laboratory listings.
A by-subject listing for laboratory test results will be provided by subject ID number and time 
point in chronological order for hematology, serum chemistry, and urinalysis separately. Values 
falling outside of the relevant reference range and/or having a severity grade of 1 or higher on 
the CTCAE severity grade will be flagged in the data listings, as appropriate.
No formal statistical testing is planned.
7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics for laboratory tests will not be provided.
7.2.2.
Graded Laboratory Values
The CTCAE Version 5.0 will be used to assign toxicity grades (0 to 4) to laboratory results for 
analysis. Grade 0 includes all values that do not meet the criteria for an abnormality of at least 
Grade 1. For laboratory tests with criteria for both increased and decreased levels, analyses for 
each direction (i.e., increased, decreased) will be presented separately.
7.2.2.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities for Blinded Treatment phase are defined as values 
that increase at least 1 toxicity grade from baseline at any postbaseline time point,

up to and including the date of last dose of Blinded Treatment phase study drug plus 30 days 
for subjects who permanently discontinued Blinded Treatment phase study drug

or before the first dose of OL Treatment phase study drug for subjects who entered OL 
Treatment phase
For subjects who entered the OL Treatment phase, treatment-emergent laboratory abnormalities 
for OL Treatment phase are defined as values that increase at least 1 toxicity grade from OL 
baseline at any postbaseline time point, up to and including the date of last dose of OL Treatment 
phase study drug plus 30 days for subjects who permanently discontinued OL phase study drug.
If the relevant baseline laboratory value is missing, any abnormality of at least Grade 1 observed 
within the time frame specified above will be considered treatment emergent.


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7.2.2.2.
Summaries of Laboratory Abnormalities
Laboratory data that are categorical will be summarized using the number and percentage of 
subjects in the study with the given response at baseline and each scheduled postbaseline time 
point for both Blinded Treatment phase and OL Treatment phase.
The following summary (number and percentage of subjects) for treatment-emergent laboratory 
abnormalities will be provided by laboratory test and treatment group; subjects will be 
categorized according to the most severe postbaseline abnormality grade for a given laboratory 
test:

Graded laboratory abnormalities
For all summaries of laboratory abnormalities, the denominator is the number of subjects with 
nonmissing postbaseline values.
7.3.
Body Weight and Vital Signs
Body weight and vital signs will not be summarized or listed.
7.4.
Prior and Concomitant Medications
Medications collected at screening and during the study will be coded using the current version 
of the World Health Organization (WHO) Drug dictionary.
UC-specific prior and concomitant medications at baseline will be included in the listing of other 
baseline characteristics as described in Section 5.2. No other prior and concomitant medications 
will be summarized or listed.
7.4.1.
Prior Medications
Prior medications are defined as any medications taken before a subject took the first study drug.
For the purposes of analysis, any UC-specific medication with a start date prior to the first 
dosing date of study drug will be included in the UC treatment history summary in the listing of 
other baseline characteristics as described in Section 5.2, regardless of when the stop date is. If a 
partial start date is entered the medication will be considered prior unless the month and year (if 
day is missing) or year (if day and month are missing) of the start date are after the first dosing 
date. Medications with a completely missing start date will be included in the UC treatment 
history summary, unless otherwise specified.


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7.4.2.
Concomitant Medications
Concomitant medications are defined as medications taken while a subject took study drug.
For the purposes of analysis, any UC-specific medications with a start date prior to or on the first 
dosing date of study drug and continued to be taken after the first dosing date, or started after the 
first dosing date but prior to or on the last dosing date of study drug will be considered 
concomitant medications. Medications started and stopped on the same day as the first dosing 
date or the last dosing date of study drug will also be considered concomitant. Medications with 
a stop date prior to the date of first dosing date of study drug or a start date after the last dosing 
date of study drug will be excluded from the UC concomitant medication summary in the listing 
of other baseline characteristics as described in Section 5.2. If a partial stop date is entered, any 
medication with the month and year (if day is missing) or year (if day and month are missing) 
prior to the date of first study drug administration will be excluded from the UC concomitant 
medication summary. If a partial start date is entered, any medication with the month and year (if 
day is missing) or year (if day and month are missing) after the study drug stop date will be 
excluded from the UC concomitant medication summary. Medications with completely missing 
start and stop dates will be included in the UC concomitant medication summary, unless 
otherwise specified.
7.5.
Electrocardiogram Results
Electrocardiogram (ECG) data will not be summarized or listed.
7.6.
Other Safety Measures
A data listing will be provided for subjects who become pregnant during the study.
7.7.
Changes From Protocol-Specified Safety Analyses
Due to limited subject enrollment in the study, only part of safety summaries and listings planned 
in the protocol will be provided.


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9.
BIOMARKER ANALYSES
The biological marker analysis will be conducted on the Biomarker Analysis Set, defined in 
Section 3.1.6.
A by-subject listing will be provided for serum hs-CRP, fecal calprotectin, and fecal lactoferrin 
by subject ID number and visit.


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10.
REFERENCES
Geboes K, Riddell R, Ost A, Jensfelt B, Persson T, Lofberg R. A reproducible grading scale for 
histological assessment of inflammation in ulcerative colitis. Gut 2000;47 
(3):404-9.


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11.
SOFTWARE
SAS® Software Version 9.4. SAS Institute Inc., Cary, NC, USA.
nQuery Advisor(R) Version 8.6. Statistical Solutions, Cork, Ireland.


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12.
SAP REVISION
Revision Date
(DD MMM YYYY)
Section
Summary of Revision
Reason for Revision
(n/a)
(n/a)
(n/a)
(n/a)


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13.
APPENDICES
Appendix 1. 
Study Procedures Table – Blinded Treatment
Appendix 2. 
Study Procedures Table – Open-Label Treatment
Appendix 3. 
Modified Mayo Scoring System for Assessment of Ulcerative Colitis Activity
Appendix 4.
Mayo Clinic Score Calculation


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Appendix 1. 
Study Procedures Table – Blinded Treatment
Period
Screen
Blinded Treatment
Follow-up
Week
0
2
4
6
10
14
18
22
26
30
34
38
42
46
50
PTx
ET
Study Day
-30 to -1
1
15
29
43
71
99
127
155
183
211
239
267
295
323
351
Visit Window
3
3
3
5
5
5
5
5
7
7
7
7
7
7
3
Informed Consent 
X
12-lead ECG
X
X
X
X
X
Physical Exam
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Review of Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Review of Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study Drug Dispensing
X
X
X
X
X
X
X
X
X
X
X
X
X
Colonoscopy/Flexible 
Sigmoidoscopy with 
Biopsies
X
X
X
PGA for MCS Calculation
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Evaluation of Disease 
Worsening using Partial 
MCS
X
X
X
X
X
X
X
X
X
eDiary instruction & review
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Stool Sample for Enteric 
Infections
X
Stool Biomarker Samples
X
X
X
X
Urinalysis 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine Biomarker Samples 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy Test
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
TB Assessment 
X


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Period
Screen
Blinded Treatment
Follow-up
Week
0
2
4
6
10
14
18
22
26
30
34
38
42
46
50
PTx
ET
Study Day
-30 to -1
1
15
29
43
71
99
127
155
183
211
239
267
295
323
351
Visit Window
3
3
3
5
5
5
5
5
7
7
7
7
7
7
3
HBV, HCV, HIV screening
X
HBV Monitoring, As 
Needed
X
X
X
X
Hematology & Chemistry 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Fasting Lipids
X
X
X
X
X
Blood Biomarker Samples
X
X
X
X
X
X
Mandatory Genomic 
Samples
X
HRQoL Surveys
X
X
X
HCRU Questionnaire
X
X
X
X
X
X
X
X
X
X
Approximate Total Amount 
of Blood Taken at This Visit
23.5 mL
44.5 
mL
34.0 
mL
34.0 
mL
12.0 
mL
34.0 
or 
40.0 
mL
8.0 
mL
8.0 
mL
8.0 
or 
14.0 
mL
30.0 
mL
8.0 
mL
8.0 
or 
14.0 
mL
8.0 
mL
8.0 
mL
8.0 
or 
14.0 
mL
30.0 mL
8.0 
mL
8.0 
mL
CCI
CCI
CCI
----------------------------------------------------------------------


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Appendix 2. 
Study Procedures Table – Open-Label Treatment
Period
Open-Label Treatment
Follow-up
Week
0
2
4
6
10
14
18
22
26
30
34
38
42
46
50
PTx
ET
Study Day
1
15
29
43
71
99
127
155
183
211
239
267
295
323
351
Visit Window
 
3
3
3
5
5
5
5
5
7
7
7
7
7
7
3
12-lead ECG
X
X
X
X
Physical Exam
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Review of Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Review of Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study Drug Dispensing
X
X
X
X
X
X
X
X
X
X
X
X
X
Colonoscopy/Flexible 
Sigmoidoscopy with Biopsies
X
X
PGA for MCS Calculation
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Evaluation for Disease 
Worsening using Partial MCS
X
X
X
X
X
X
X
X
X
eDiary instruction & review
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Stool Biomarker Samples 
X
X
X
Urinalysis 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine Biomarker Samples 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy Test
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HBV Monitoring
X
X
X
X
Hematology & Chemistry 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Fasting Lipids
X
X
X
Blood Biomarker Samples
X
X
X
X
X
X
HRQoL Surveys
X
X
X


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Period
Open-Label Treatment
Follow-up
Week
0
2
4
6
10
14
18
22
26
30
34
38
42
46
50
PTx
ET
Study Day
1
15
29
43
71
99
127
155
183
211
239
267
295
323
351
Visit Window
 
3
3
3
5
5
5
5
5
7
7
7
7
7
7
3
HCRU Questionnaire
X
X
X
X
X
X
X
X
X
X
Approximate Total Amount 
of Blood Taken at This Visit
30.0 mL
34.0 
mL
34.0 
mL
12.0 
mL
34.0 
or 
40.0 
mL
8.0 
mL
8.0 
mL
8.0 
or 
14.0 
mL
30.0 
mL
8.0 
mL
8.0 
or 
14.0 
mL
8.0 
mL
8.0 
mL
8.0 
or 
14.0 
mL
30.0 mL
8.0 
mL
8.0 
mL


G S- 4 8 7 5
G S- U S- 3 6 5- 4 2 3 7
Statistical A nal ysis Pla n – Fi nal A nal ysis
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 6
0 5 A pril 2 0 2 1
A p pe n di x 3.  
M o difie d M a y o Sc ori n g S yste m f or Assess me nt of Ulcer ati ve C olitis 
Acti vit y
St o ol Fre q ue nc y – E ac h s u bject serves as his 
or her o w n c o ntr ol t o est a blis h t he de gree of 
a b n or m ality of t he st o ol fre q ue ncy

0  
N or mal n u m ber of st o ols f or s u bject

1 
1 t o 2 st o ols per da y m ore t ha n n or mal

2 
3 t o 4 st o ols per da y m ore t ha n n or mal

3
≥ 5 st o ols per da y m ore t ha n n or mal
Rect al Blee di n g – T he d aily blee di n g sc ore 
re prese nts t he m ost severe blee di n g of t he d ay.

0  
N o bl o o d see n

1 
Strea ks of bl o o d wit h st o ol less t ha n half t he ti me

2  
O b vi o us bl o o d ( m ore t ha n j ust strea ks) or strea ks of 
bl o o d wit h st o ol m ost of t he ti me 

3 
Bl o o d al o ne passes
E n d osc o pic fi n di n gs – Assesse d by 
Ce ntr al Re a der (i ncl u de o nly f or M C S 
assess me nt)

0  
N or mal or i nacti ve disease

1  
Mil d Disease (eryt he m a, decre ase d v asc ul ar p atter n)

2  
M o derate Disease ( m arke d eryt he m a, l ack of 
v asc ul ar p atter n, fri a bility, er osi o ns)

3 
Se vere Disease (s p o nt a ne o us blee di n g, ulcer ati o n)
P h ysici a n's Gl o b al Assess me nt –  T he 
p hysici a n’s gl o b al assess me nt ack n o wle d ges 
t he t hree ot her criteri a, t he s u bject’s d aily 
rec ollecti o n of a b d o mi n al disc o mf ort a n d 
ge ner al se nse of well- bei n g, a n d ot her 
o bserv ati o n, s uc h as p hysic al fi n di n gs a n d t he 
s u bject’s perf or m a nce st at us.

0  
N or mal

1  
Mil d disease

2  
M o derate disease

3 
Se vere disease


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Appendix 4.
Mayo Clinic Score Calculation
Definition of the Mayo Clinic Score and Component Subscores
The (Modified) Mayo Clinic Score (MCS) is a composite index of 4 disease activity variables in 
stool frequency, rectal bleeding, endoscopic findings, and the physician global assessment 
(PGA). Each of the 4 variables is assigned an integer subscore from 0 – 3 as described in 
Table 6-2 and Appendix 3.
The MCS is calculated as the sum of the 4 subscores for stool frequency, rectal bleeding, 
endoscopic findings, and the PGA.
Partial MCS (pMCS) is the sum of the 3 subscores for stool frequency, rectal bleeding, and the 
PGA.
Calculation of Mayo Clinic Score and Component Subscores
Subjects report daily stool frequency and rectal bleeding symptoms on the study electronic diary. 
Results of endoscopic evaluation are reported by a central reader and site personnel enters the 
score on the web diary. PGA is recorded by the investigator for specified visits.
For the purposes of calculation of the specific MCS and component subscores an anchor date is 
assigned and stool frequency and rectal bleeding records prior to the anchor date are used in the 
calculation of the subscores.
For MCS calculation at Screening, the anchor date is considered the date of the endoscopy as 
endoscopic subscore will be only evaluated over screening period and not at Day 1 baseline. 
Screening MCS will be used as baseline evaluation.
For all calculations at other visits, including baseline pMCS, postbaseline MCS and postbaseline 
pMCS, the anchor date is the study visit date.
Because the preparation for endoscopy procedure may impact the validity of the diary data, the 
patients reported daily stool frequency and rectal bleeding records collected 1 day prior to, the 
day of, and the day after the procedure will not be used in the calculation of stool frequency and 
rectal bleeding subscores. These above mentioned days are considered as non-evaluable days for 
those 2 subscores.


GS-4875 
GS-US-365-4237 
Statistical Analysis Plan - Final Analysis 
Calculation of MCS at Screening (Baseline) 
Version 1.0 
The calculation of the screening stool frequency subscore and screening rectal bleeding subscore 
for the pmposes of calculation of MCS at Screening is as follows: 
1) The endoscopic procedure date is defined as the E-Day 1. 
2) A 7-day window is defined in which the staii of the window begins 7 days prior to the 
endoscopic procedure date and the window ends on the day prior to the endoscopic procedure 
date. 
3) The subscore is calculated as the average of the 3 evaluable diaiy data entries within the 7-
day window closest to the endoscopic procedure date (discarding the day prior to endoscopy) 
and rounded to the nearest integer. 
4) If a subject does not have 3 or more evaluable diaiy day enti·ies within the 7-day window, 
this subject will have a missing subscore and missing baseline MCS at Screening. 
5) The PGA subscore used in the MCS at Screening is that recorded during the screening period 
(prior to Day 1) . 
A schema of this approach (Appendix Figure 1) and examples (Appendix Table 1) are provided 
below: 
Appendix Figure 1. Stool Frequency and Rectal Bleeding Subscores Calculation at 
Screening 
11 
Thr 
1' 
7 
daylool:b-.+........._.tpcaJcnate 
l)a, 
1' 
Endo,ropyDay 
fF: _D;i v I) 
1 
(AnmmI>ay) 
1 
Dayl 
1'~ 
CONFIDENTIAL 
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GS-4875
GS-US-365-4237
Statistical Analysis Plan – Final Analysis
Version 1.0
CONFIDENTIAL
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05 April 2021
Appendix Table 1. 
Examples of Stool Frequency and Rectal Bleeding Subscores 
Calculation for MCS at Screening
Diary Day Looking Back from Endoscopy Date
(E-Day)
Anchor Day
-7
-6
-5
-4
-3
-2
-1
E-Day 1
Example
3
Jun
4
Jun
5
Jun
6
Jun
7
Jun
8
Jun
9
Jun
10
Jun
Days for 
Calculation
Average 
Subscore
Final 
Subscore
Diary 1
M
M
2
M
1
2
X
X
-2, -3, -5
1.67
2
Diary 2
M
M
M
M
0
1
X
X
-2, -3
Missing
Missing
Diary 3
M
M
M
M
0
M
X
X
-3
Missing
Missing
Diary 4
M
2
M
2
1
1
X
X
-2, -3, -4
1.33
1
Days are named relative to Anchor Day Endoscopy Date (E-Day 1), M = Missing, X = non-evaluable. The diary data collected on 
E-Day 1 and E-Day -1 will be discarded as endoscopy and its preparation may impact the validity of the diary data.
Calculation of Postbaseline MCS, Baseline and Postbaseline pMCS
The calculation of postbaseline MCS, baseline and postbaseline pMCS use the study visit date as 
the anchor date. The calculations are as follows:
1) Subject diary data collected within 7 days prior to the visit day will be used for calculation, 
and some of the days within this 7-day window may be considered non-evaluable due to the 
endoscopy procedure and its preparation (i.e., the day of the endoscopy and the day prior to 
or after the endoscopy).
2) The average of the 3 evaluable diary day entries within the 7-day window closest to the visit 
day (V-Day 1), rounded to the nearest integer, will be considered the stool frequency and 
rectal bleeding subscore for that visit.
3) The PGA subscore used in the calculation of baseline pMCS is the PGA subscore recorded 
on Day 1. At subsequent postbaseline visits, the PGA subscore used in calculation of MCS 
and pMCS is that recorded within the visit window.
4) If there are 2 or less evaluable diary day entries for stool frequency or rectal bleeding within 
the 7-day window, no missing data imputation will be done. MCS and pMCS will be 
considered as missing.
5) For MCS, if endoscopic subscore or PGA subscore is missing, MCS will be left as missing. 
For pMCS, if PGA is missing, pMCS will be left as missing.


GS-4875 
GS-US-365-4237 
Statistical Analysis Plan - Final Analysis 
Version 1.0 
A schema of this approach (Appendix Figure 2) and examples (Appendix Table 2) are provided 
below: 
Appendix Figure 2. Stool Frequency and Rectal Bleeding Subscores Calculation at 
Baseline and Postbaseline 
' Day : 
' Da: 
(Anchor Da) 
1' 
1' 
.. 
.. 
l 
r 
day look back window to calculat1 
VisitDa~ I 
subsc01 
Appendix Table 2. 
Examples of Stool Frequency and Rectal Bleeding Subscores 
Calculation for MCS at Postbaseline, and pMCS at Baseline and 
Postbaseline 
Diary Day Looking Back from Visit Date 
(V-Day) 
Anchor Day 
-7 
-6 
-5 
-4 
-3 
-2 
-1 
V-Day 1 
3 
4 
5 
6 
7 
8 
9 
10 
Days for 
Average 
Final 
Example 
Jun 
Jun 
Jun 
Jun 
Jun 
Jun 
Jun 
Jun 
Calculation 
Subscore 
Subscore 
Diary 1 
E 
X 
3 
M 
M 
M 
0 
X 
-1, -5 
Missing 
Missing 
Diary2 
4 
4 
X 
E 
X 
3 
3 
X 
-1, -2, -6 
3.33 
3 
Diary 3 
3 
X 
E 
X 
1 
M 
2 
X 
-1, -3, -7 
2 
2 
Diary4 
2 
3 
4 
4 
X 
E 
X 
X 
-4, -5, -6 
3.67 
4 
Diary 5 
2 
M 
M 
X 
E 
X 
2 
X 
-1, -7 
Missing 
Missing 
Diary 6 
X 
E 
X 
2 
3 
0 
1 
X 
-1, -2, -3 
1.33 
1 
Diary 7 
M 
3 
X 
E 
X 
M 
M 
X 
-6 
NIA 
Missing 
Days are named relative to Anchor Day Visit Date (V-Day 1 ), M = Missing, X = non-evaluable, E = Endoscopy Day 
CONFIDENTIAL 
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05 April 2021 


GS-US-365-4237 Final SAP
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Biostatistics eSigned
06-Apr-2021
15:01:37
Clinical Research eSigned
06-Apr-2021
20:30:50
PPD
PPD-