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
Phase: PHASE2
Conditions: Ulcerative Colitis
Sponsor: Gilead Sciences

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.