Clinical trial NCT03201445
Conditions: Inflammatory Bowel Disease
Sponsor: Galapagos NV
Start date: 2017-07-11; Completion date: 2023-10-24
Enrollment: 139 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to evaluate the testicular safety of filgotinib in adult males with moderately to severely active inflammatory bowel disease (IBD).

Results of this study may be pooled with the results of a separate study being conducted in participants with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis (Protocol GLPG0634-CL-227; NCT03926195) with the same objective. The total planned number of participants in both studies combined will be up to approximately 250 participants.

Detailed description:
There are 5 parts to the study: 1) Part A: Double-Blind Phase (DB Phase; Day 1 through Week 13); 2) Part B: DB Phase (after Week 13 through Week 26); 3) Open-label (OL) Filgotinib Phase (after Week 13 study visit for up to 13 weeks); 4) Monitoring Phase (MP; up to 52 weeks); and 5) Long-term Extension (LTE) Phase (after Week 26 or end of OL Filgotinib Phase for up to 195 weeks).

Arms: arm 1: Participants received filgotinib up to Week 13 in the DB phase (Part A). At Week 13, participants who were IBD responders, without meeting pre-specified sperm decrease thresholds, continued DB treatment up to Week 26 (Part B). Participants who were IBD non-responders at Week 13 or had disease worsening after Week 13 and prior to Week 26, and whose sperm parameters did not meet a prespecified decrease threshold, entered the OL Phase and received OL filgotinib for up to Week 13. At Week 26/OL Week 13, participants who were IBD responders and who had not experienced disease worsening, and whose sperm parameters did not meet a prespecified decrease threshold, continued receiving the same study drug they were responding to as part of the LTE for up to 195 weeks. Participants who met pre-specified sperm decrease threshold(s) at any postbaseline visit discontinued study drug and switched to a standard of care (SOC) regimen selected by the investigator and entered the MP for up to 52 weeks. arm 2: Participants received placebo (matched to filgotinib) up to Week 13 in the DB phase (Part A). At Week 13, participants who were IBD responders, without meeting pre-specified sperm decrease thresholds, continued DB treatment up to Week 26 (Part B). Participants who were IBD non-responders at Week 13 or had disease worsening after Week 13 and prior to Week 26, and whose sperm parameters did not meet a prespecified decrease threshold, entered the OL Phase and received OL filgotinib for up to Week 13. At Week 26/OL Week 13, participants who were IBD responders and who had not experienced disease worsening, and whose sperm parameters did not meet a prespecified decrease threshold, continued receiving the same study drug they were responding to as part of the LTE for up to 195 weeks. Participants who met pre-specified sperm decrease threshold(s) at any postbaseline visit discontinued study drug and switched to SOC regimen selected by the investigator and entered the MP for up to 52 weeks.
Interventions: intervention 1: Filgotinib intervention 2: Placebo intervention 3: Standard of Care
Intervention descriptions: intervention 1: 200 mg tablet administered orally once daily intervention 2: Placebo to match filgotinib tablet administered orally once daily intervention 3: Locally approved treatment, accepted by medical experts as a proper treatment for IBD conditions, prescribed according to best clinical practice, with no known testicular toxicity.

Protocol documents:
Prot_000.pdf: 
 
 
 
C LI NI C A L S T U D Y P R O T O C O L  
 
 
St u d y Title:  
A Ra n d o mize d, D o u ble -bli n d, Place b o -c o ntr olle d P hase  2 St u d y t o 
E val uate t he Testic ul ar Safet y of Fil g oti ni b i n A d ult  Males wit h 
M o deratel y t o Se verel y Acti ve I nfla m mat or y B o wel Disease 
 
 
S p o ns or:  
Gala pa g os N V  
Ge neraal De Wittelaa n L 1 1 A 3  
2 8 0 0 Mec hele n, Bel gi u m  
 
 
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 2 9 6 4 7  
2 0 1 7 -0 0 0 4 0 2 -3 8  
 
N C T 0 3 2 0 1 4 4 5  
 
 
I n dic ati o n: 
I nfla m mat or y B o wel Dis ease  
 
 
Pr ot oc ol I D:  
G S -U S -4 1 8 -4 2 7 9   
 Me dic al Le a der : 
 
 
 
Pr ot oc ol 
Versi o n/ D ate:  
Ori gi nal:  
3 1 J a n uar y 2 0 1 7  
A me n d me nt 1:  
0 6 J ul y 2 0 1 7  
A me n d me nt 1. 1  ( V H P): 
2 1 Se pte m ber 2 0 1 7  
A me n d me nt 1. 2  ( 
): 
1 5 Oct o ber 2 0 1 8  
A me n d me nt 2:  
2 2  A u g ust 2 0 1 8  
A me n d me nt 3:  
1 8 J a n uar y 2 0 1 9 
A me n d me nt 3. 1 ( 
):  
2 5 J a n uar y 2 0 1 9  
A me n d me nt 4:  
1 7  Marc h  2 0 2 0  
A me n d me nt 4. 1  ( 
):  2 7 Marc h 2 0 2 0  
A me n d me nt 5:  
2 7  J u ne 2 0 2 2  
A me n d me nt 5. 1 ( 
):   2 7 J u ne  2 0 2 2  
A me n d me nt 6:   
0 9 Se pte m ber 2 0 2 2  
A me n d me nt 6. 1 ( 
):   0 9 Se pte m ber 2 0 2 2  
 
 
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  is pri vile ge d a n d c o nfi d e ntial. I t is t he pr o pert y of 
Gala pa g os N V a n d ma y n ot  be use d , discl ose d, re pr o d uce d  or ot h er wise disse mi nate d wit hi n 
y o ur or ga niz ati o n or c o m m u nicate d t o  a n y t hir d parties wit h o ut t he writte n a ut h orizati o n of 
Gala pa g os  N V . 
P P D
C CI
C CI
C CI
C CI
C CI


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2  
 
0 9 Se pte m ber 2 0 2 2  
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  ........................................................................................................................................ 4  
LI S T O F I N -T E X T FI G U R E S  ...................................................................................................................................... 5  
C LI NI C A L S T U D Y P R O T O C O L HI S T O R Y  .............................................................................................................. 6  
S U M M A R Y O F C H A N G E S  ......................................................................................................................................... 8  
P R O T O C O L S Y N O P SI S  ............................................................................................................................................ 1 0  
D E FI NI TI O N O F T E R M S  .......................................................................................................................................... 2 2  
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  .................................................................... 2 5  
1.  
I N T R O D U C TI O N .............................................................................................................................................. 2 9  
1. 1.  
B ac k gr o u n d  ............................................................................................................................................ 2 9  
1. 1. 1.  
Ulcerati ve C olitis  .................................................................................................................. 2 9  
1. 1. 2.  
Cr o h n’s Disease .................................................................................................................... 3 0  
1. 2.  
F il g oti ni b ( G S-6 0 3 4)  .............................................................................................................................. 3 2  
1. 2. 1.  
Ge neral I nf or mati o n  ............................................................................................................. 3 2  
1. 2. 2.  
Precli nical P har mac ol o g y a n d T o xic ol o g y  ........................................................................... 3 2  
1. 2. 3.  
Cli nical Trials of Fil g oti ni b  .................................................................................................. 3 4  
1. 3.  
Rati o nale f or t his St u d y a n d Pr o p ose d I B D P o p ulati o n  ......................................................................... 3 5  
1. 3. 1.  
Rati o nale f or t he O utc o me Me as ures  ................................................................................... 3 7  
1. 3. 2.  
Rati o nale f or t he C h oice of D ose a n d D osi n g I nter val  ......................................................... 3 8  
1. 4.  
Ris k/ Be nefit Assess me nt f or t he St u d y  .................................................................................................. 3 8  
1. 5.  
C o m plia nce  ............................................................................................................................................ 4 0  
2.  
O BJ E C TI V E S  ..................................................................................................................................................... 4 1  
3.  
S T U D Y D E SI G N  ................................................................................................................................................ 4 2  
3. 1.  
St u d y Treat me nts  ................................................................................................................................... 4 8  
3. 2.  
D urati o n of Treat me nt  ............................................................................................................................ 4 8  
3. 3.  
Criteria f or I nterr u pti o n or Dis c o nti n uati o n of St u d y Treat me nt  ........................................................... 4 8  
3. 3. 1.  
St u d y Dr u g I nterr u pti o n C o nsi derati o ns ............................................................................... 4 8  
3. 3. 2.  
St u d y Dr u g Disc o nti n uati o n C o nsi derati o ns  ........................................................................ 4 9  
3. 4.  
Disease W orse ni n g Criteria  .................................................................................................................... 5 1  
3. 5.  
E n d of St u d y  ........................................................................................................................................... 5 2  
3. 6.  
P ost -St u d y Care  ...................................................................................................................................... 5 2  
4.  
S U BJ E C T P O P U L A TI O N  .................................................................................................................................. 5 3  
4. 1.  
N u m ber of S u bj ects a n d S u bj ect Selecti o n  ............................................................................................ 5 3  
4. 2.  
I ncl usi o n Criteria .................................................................................................................................... 5 3  
4. 3.  
E xcl usi o n Criteria ................................................................................................................................... 5 8  
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  ........................................................................................... 6 2  
5. 1.  
Ra n d o mizati o n, Bli n di n g a n d Treat me nt C o des  .................................................................................... 6 2  
5. 1. 1.  
Ra n d o mizati o n  ..................................................................................................................... 6 2  
5. 1. 2.  
Bli n di n g  ................................................................................................................................ 6 2  
5. 1. 3.  
Pr oce d ures f or Brea ki n g Treat me nt C o des  ........................................................................... 6 3  
5. 2.  
Descri pti o n a n d Ha n dli n g of Fil g oti ni b a n d Place b o -t o-Matc h ( P T M)  .................................................. 6 3  
5. 2. 1.  
F or m ulati o n  .......................................................................................................................... 6 3  
5. 2. 2.  
P ac ka gi n g a n d La b eli n g  ....................................................................................................... 6 3  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3  
 
0 9 Se pte m ber 2 0 2 2  
5. 2. 3.  
St ora ge a n d Ha n dli n g  ........................................................................................................... 6 4  
5. 2. 4.  
D osa ge a n d A d mi nistrati o n of Fil g oti ni b  ............................................................................. 6 4  
5. 3.  
Pri or a n d C o nc o mita nt Me dic ati o ns  ....................................................................................................... 6 4  
5. 3. 1.  
All o we d C o nc o mita nt Me dicati o ns  ...................................................................................... 6 5  
5. 3. 2.  
Pr o hi bite d C o nc o mita nt Me dicati o ns  ................................................................................... 6 5  
5. 4.  
Vacci ne G ui deli nes  ................................................................................................................................ 6 7  
5. 5.  
Acc o u nta bilit y f or St u d y Dr u gs  ............................................................................................................. 6 7  
5. 5. 1.  
I n vesti gati o nal Me dici nal Pr o d uct Ret ur n or Dis p osal ......................................................... 6 8  
6.  
S T U D Y P R O C E D U R E S  .................................................................................................................................... 6 9  
6. 1.  
S u bj ect E nr oll me nt a n d Treat me nt Assi g n me nt  ..................................................................................... 6 9  
6. 2.  
Pretreat me nt Assess me nts  ...................................................................................................................... 6 9  
6. 2. 1.  
Scree ni n g Visit  ..................................................................................................................... 6 9  
6. 2. 2.  
Da y 1 Assess me nts  ............................................................................................................... 7 2  
6. 3.  
Ra n d o mizati o n  ....................................................................................................................................... 7 2  
6. 4.  
P art A ( Da y 1 t hr o u g h W ee k 1 3 St u d y Visit) ......................................................................................... 7 3  
6. 5.  
P art B ( After W ee k 1 3 t hr o u g h Wee k 2 6 St u d y Visit)  ........................................................................... 7 3  
6. 6.  
O pe n -La b el Fil g oti ni b P hase ( O pe n -La bel Da y  1  t hr o u g h O p e n-La bel Wee k  1 3 St u d y Visit)  ............. 7 3  
6. 7.  
M o nit ori n g P hase  ................................................................................................................................... 7 3  
6. 8.  
Earl y T er mi nati o n  .................................................................................................................................. 7 4  
6. 9.  
Safet y F oll o w -U p Visit 3 0 Da ys P ost Last D ose ( ± 5 da ys)  ................................................................... 7 4  
6. 1 0.  
L o n g T er m E xte nsi o n  ............................................................................................................................. 7 4  
6. 1 1.  
Safet y a n d T olera bilit y  ........................................................................................................................... 7 4  
6. 1 2.  
Cli nical La b orat or y E val uati o ns  ............................................................................................................. 7 4  
6. 1 3.  
Se me n C ollecti o n Pr oce d ure  .................................................................................................................. 7 5  
6. 1 4.  
Vital Si g ns  .............................................................................................................................................. 7 6  
6. 1 5.  
P h ysical E xa mi nati o n  ............................................................................................................................. 7 6  
6. 1 6.  
P har mac o ki netic Assess me nts  ................................................................................................................ 7 7  
6. 1 7.  
T hr o m b oe m b olic E ve nts  ........................................................................................................................ 7 7  
6. 1 8.  
Ma y o Cli nic Sc ore a n d P artial Ma y o Cli nic Sc ore ................................................................................. 7 7  
6. 1 9.  
Si m ple E n d osc o pic Sc ore f or Cr o h n’s Disease  ...................................................................................... 7 7  
6. 2 0.  
Cr o h n’s Disease Acti vit y I n de x  ............................................................................................................. 7 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  ............................................................................... 7 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  ................................. 7 8  
7. 1. 1.  
A d verse E ve nts  ..................................................................................................................... 7 8  
7. 1. 2.  
Seri o us A d verse E ve nts  ........................................................................................................ 7 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  ................................................................. 7 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  ................................................... 7 9  
7. 2. 2.  
Assess me nt of Se verit y  ........................................................................................................ 8 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 t he S p o ns or  ............................................................................................................... 8 0  
7. 4.  
S p o ns or Re p orti n g Re q uire me nts  ........................................................................................................... 8 2  
7. 5.  
Cli nical La b orat or y A b n or malities  ......................................................................................................... 8 2  
7. 6.  
T o xicit y Ma na ge me nt  ............................................................................................................................ 8 3  
7. 6. 1.  
Gra d es 1 a n d 2 La b orat or y A b n or malit y or Cli nical E ve nt  .................................................. 8 3  
7. 6. 2.  
Gra d es 3 La b orat or y A b n or malit y or Cli nical E ve nt  ........................................................... 8 3  
7. 6. 3.  
Gra d es 4 La b orat or y A b n or malit y or Cli nical E ve nt  ........................................................... 8 4  
7. 7.  
S pecial Sit uati o ns Re p orts  ...................................................................................................................... 8 4  
7. 7. 1.  
Defi niti o ns of S pecial Sit uati o ns  .......................................................................................... 8 4  
7. 7. 2.  
I nstr ucti o ns f or Re p orti n g S pe cial Sit uati o ns ....................................................................... 8 5  
8.  
S T A TI S TI C A L C O N SI D E R A TI O N S  ................................................................................................................ 8 7  
8. 1.  
A nal ysis O bj ecti ves a n d E n d p oi nts  ........................................................................................................ 8 7  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  4  
 
0 9 Se pte m ber 2 0 2 2  
8. 1. 1.  
A nal ysis O bj ecti ves  .............................................................................................................. 8 7  
8. 1. 2.  
Pri mar y E n d p oi nt  ................................................................................................................. 8 7  
8. 1. 3.  
Sec o n dar y E n d p oi nts  ............................................................................................................ 8 8  
8. 1. 4.  
E x pl orat or y E n d p oi nts  .......................................................................................................... 8 8  
8. 2.  
A nal ysis C o n ve nti o ns  ............................................................................................................................. 8 8  
8. 2. 1.  
A nal ysis Sets  ........................................................................................................................ 8 8  
8. 3.  
Data Ha n dli n g C o n ve nti o ns  ................................................................................................................... 8 9  
8. 4.  
De m o gra p hic Data a n d B aseli ne C haracteristics  ................................................................................... 8 9  
8. 5.  
Statistical A nal ysis  ................................................................................................................................. 8 9  
8. 5. 1.  
Pri mar y A nal ysis  .................................................................................................................. 8 9  
8. 5. 2.  
Sec o n dar y A nal yses  ............................................................................................................. 9 0  
8. 5. 3.  
E x pl orat or y A nal yses  ........................................................................................................... 9 0  
8. 5. 4.  
Ot her Safet y A nal ysis  ........................................................................................................... 9 0  
8. 5. 5.  
E xte nt of E x p os ure  ............................................................................................................... 9 0  
8. 5. 6.  
A d verse E ve nts  ..................................................................................................................... 9 1  
8. 5. 7.  
La b orat or y E val uati o ns  ........................................................................................................ 9 1  
8. 6.  
P har mac o ki netic A nal ysis  ...................................................................................................................... 9 1  
8. 7.  
Sa m ple Size  ............................................................................................................................................ 9 1  
8. 8.  
Data M o nit ori n g C o m mittee/ S p o ns or Safet y Ma na ge me nt T ea m  ......................................................... 9 2  
8. 9.  
Car di o vasc ular Safet y E n d p oi nt A dj u dicati o n C o m mittee ( C V E A C)  ................................................... 9 3  
8. 1 0.  
I nter nal I n de p e n de nt Safet y R e vie w ...................................................................................................... 9 3  
8. 1 1.  
U n bli n de d I nteri m A nal ysis  ................................................................................................................... 9 3  
8. 1 2.  
I nte grate d Se me n A nal ysis ..................................................................................................................... 9 4  
9.  
R E S P O N SI BI LI TI E S .......................................................................................................................................... 9 5  
9. 1.  
I n vesti gat or Res p o nsi bilities .................................................................................................................. 9 5  
9. 1. 1.  
G o o d Cli nical Practice .......................................................................................................... 9 5  
9. 1. 2.  
I nstit uti o nal Re vie w B oar d (I R B)/I n de pe n de nt Et hics C o m mittee (I E C) 
Re vie w a n d A p pr o val  ........................................................................................................... 9 5  
9. 1. 3.  
I nf or me d C o nse nt ................................................................................................................. 9 6  
9. 1. 4.  
C o nfi de ntialit y  ...................................................................................................................... 9 6  
9. 1. 5.  
St u d y Files a n d Rete nti o n of Rec or ds  .................................................................................. 9 6  
9. 1. 6.  
Case Re p ort F or ms  ............................................................................................................... 9 8  
9. 1. 7.  
I ns pecti o ns ............................................................................................................................ 9 8  
9. 1. 8.  
Pr ot oc ol C o m plia nce  ............................................................................................................ 9 8  
9. 2.  
S p o ns or Res p o nsi bilities  ........................................................................................................................ 9 8  
9. 2. 1.  
Pr ot oc ol M o dificati o ns  ......................................................................................................... 9 8  
9. 2. 2.  
St u d y Re p ort a n d P u blicati o ns  ............................................................................................. 9 9  
9. 3.  
J oi nt I n vesti gat or/ S p o ns or Res p o nsi bilities ........................................................................................... 9 9  
9. 3. 1.  
P a y me nt Re p orti n g  ............................................................................................................... 9 9  
9. 3. 2.  
Access t o I nf or mati o n f or M o nit ori n g  .................................................................................. 9 9  
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  ............................................................ 1 0 0  
9. 3. 4.  
St u d y Disc o nti n uati o n  ........................................................................................................ 1 0 0  
1 0.  R E F E R E N C E S  ................................................................................................................................................. 1 0 1  
1 1.  A P P E N DI C E S  .................................................................................................................................................. 1 0 4  
 
LI S T O F I N -T E X T T A B L E S  
 
T a ble  5 -1.  
Pr o hi bite d C o nc o mita nt Me dicati o ns  ..................................................................................... 6 6  
T a ble  7 -1.  
Gra di n g of A d verse E ve nt Se verit y  ........................................................................................ 8 0  
 
 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5  
 
0 9 Se pte m ber 2 0 2 2  
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 Sc he ma  ......................................................................................................................... 4 3  
Fi g ure  3 -2.  
P art A ( Da y  1 t hr o u g h Wee k 1 3 St u d y Visit)  ......................................................................... 4 4  
Fi g ure  3 -3.  
P art B ( After W ee k 1 3  t hr o u g h Wee k 2 6 St u d y Visit) ........................................................... 4 4  
Fi g ure  3 -4.  
O pe n -La b el Fil g oti ni b P hase ( O pe n -La bel Da y  1 t hr o u g h O p e n -La bel Wee k 1 3 
St u d y Visit) ............................................................................................................................. 4 5  
Fi g ure  3 -5.  
M o nit ori n g P hase ( u p t o 5 2 wee ks)  ........................................................................................ 4 6  
Fi g ure  3 -6.  
L o n g T er m E xte nsi o n ( u p t o 1 9 5 wee ks)  ............................................................................... 4 7  
Fi g ure  6 -1.  
Se me n C ollecti o n Sc he ma  ...................................................................................................... 7 6  
 
 
 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6  
 
0 9 Se pte m ber 2 0 2 2  
C LI NI C A L S T U D Y P R O T O C O L HI S T O R Y  
Cli nic al st u d y pr ot oc ol 
( C S P)/ A me n d me nt # 
D ate  
M ai n R ati o n ale  
Ge ner al/ C o u ntr y -S pecific  
C S P Versi o n 1. 0  
3 1 -J a n-2 0 1 7  
I nitial C S P Versi o n 
Ge neral  
A me n d me nt # 1  
0 6 -J ul-2 0 1 7  
U p date a n d/ or clarificati o n of st u d y 
desi g n, eli gi bilit y criteria, st u d y 
pr oce d ures, st u d y dr u g 
disc o nti n uati o n c o nsi derati o ns, a n d 
statistical a nal ys es 
Ge neral  
A me n d me nt # 1. 1  
2 1 -Se p -2 0 1 7  
U p date of st u d y desi g n a n d 
clarificati o n of patie nt safet y 
i nf or mati o n 
C o u ntr y -s pecific ( v ol u nt ar y 
har m o nisati o n pr oce d ure c o u ntries)  
A me n d me nt # 1. 2  
1 5 -Oct -2 0 1 8  
I n cl usi o n of s per m ba n ki n g 
rei m b urse me nt la n g ua ge a n d 
details of ne w me dical m o nit or a n d 
st u d y direct or 
C o u ntr y -s pecific ( 
) 
A me n d me nt # 2  
2 2 -A u g -2 0 1 8  
E x pa nsi o n of st u d y p o p ulati o n t o 
i ncl u de s u bjects wit h Cr o h n’s 
disease  a n d u p d ate of eli gi bilit y 
criteria ( n ot e: t his a me n d me nt was 
n ot i m ple me nte d)  
Ge neral  
A me n d me nt # 3  
1 8 -J a n-2 0 1 9  
E x pa nsi o n of st u d y p o p ulati o n t o 
i ncl u de s u bjects wit h Cr o h n’s 
disease a nd u p d ate of eli gi bilit y 
criteria  
Ge neral  
C CI




Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8  
 
0 9 Se pte m ber 2 0 2 2  
S U M M A R Y O F C H A N G E S  
A me n d me nt 6  (0 9 -Se p -2 0 2 2)  
T he o ver all re as o n f or t his a me n d me nt:  
T his st u d y has pr o gresse d be y o n d t h e a nal ysis ti me p oi nts of t he pri mar y, s ec o n dar y , a n d all 
e x pl orat or y e n d p oi nts , w hic h were t h e sc o pe of t he sec o n d u n bli n de d i nteri m a nal ysis (I A 2). 
T he S p o ns or pla ns t o discl ose t hese dat a of scie ntific i nterest i nt o a peer re vie we d j o ur nal 
w hile t he st u d y is still o n g oi n g, wit h o ut c o m pr o misi n g t he data i nte grit y a n d scie ntific 
val i dit y. T o t his p ur p ose, t he w or di n g a b o ut bli n di n g was re vise d t o all o w discl os ure of t he 
treat me nt assi g n me nts of s u bjects w h o c o m plete d t he st u d y bef ore I A 2.  
Ge neral mi n or a d mi nistrati ve u p dates were ma de t hr o u g h o ut t he pr ot o c ol, i ncl u di n g  
ter mi n ol o g y, p u nct uati o n, a b bre viati o ns, dates, n u m bers, a n d f or m at f or cl arit y a n d 
c o nsiste nc y.  
T he c ha n ges ma de t o t he cli nical st u d y pr ot o c ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8 ) 
Versi o n  5. 0,  2 7 -J u n-2 0 2 2  are liste d bel o w, reflecti n g a brief rati o nale f or eac h c ha n ge a n d t he 
a p plica ble secti o ns.  
R ati o n ale : Te xt was re vise d t o s pecif y t he dec o m missi o ni n g of t he D ata M o nit ori n g 
C o m mittee ( D M C ) a n d tra nsfer t he r ole of t he D M C t o t he S p o ns or S afet y M a na ge me nt T ea m 
(S S M T ). All pla n ne d D M C re vie ws ha ve b ee n c o m plete d a n d n o a d diti o nal re vie ws are 
e x pecte d. At t his a d va nce d sta ge of t he st u d y, tr eat me nt assi g n me nts ha ve bee n u n bli n de d f or 
t he maj orit y of s u bjects, n o l o n ger re q uiri n g a n e xter nal u n bli n de d re vi e w c o m mittee i n 
a d diti o n t o t he bli n de d S p o ns or st u d y  tea m. O versi g ht b y t he S S M T will i ncl u de re g ular 
re vie ws of s afet y s u m mar y u p d ates a n d will pr o vi de si milar o pti o ns f or escalate d iss ue re vi e w 
as descri be d i n t he D M C c harter b y f oll o wi n g t h e S S M T sta n dar d pr oce d ures . 
A p plic a ble secti o ns : S y n o psis  
1. 4  Ris k/ Be nefit Assess me nt f or t he St u d y  
8. 8  Data M o nit ori n g C o m mittee/ S p o ns or Safet y Ma na ge me nt T ea m  
R ati o n ale : Te xt a b o ut bli n di n g was r e vise d t o all o w p u blicati o n of t he treat me nt assi g n me nts 
of s u bjects w h o c o m plete d t he st u d y bef ore I A 2 . 
A p plic a ble secti o ns : S y n o psis  
5. 1. 2  Bli n di n g  
8. 1 1  U n bli n de d  I nteri m A nal ysis  
R ati o n ale:  A st u d y dr u g i nterr u pti o n criteri o n f or s u bjects e x perie nci n g m o derate re nal f ail ure 
(esti mate d creati ni ne cle ara nce  ≥3 5 m L/ mi n a n d < 6 0 m L/ mi n per C oc kcr oft -Ga ult f or m ula) 
was a d de d t o ali g n wit h I n vesti gat or’s Br oc h ure E diti o n 1 7, 1 5 -J ul-2 0 2 2.  
A p plic a ble Secti o n:  3. 3. 1  St u d y Dr u g I nterr u pti o n C o nsi derati o ns  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9  
 
0 9 Se pte m ber 2 0 2 2  
R ati o n ale:  Te xt was a d d e d t o s pecif y t he dec o m missi o ni n g of  t he I nter n al I n de p e n de nt 
Safet y R e vie w  Tea m as of t his a me n d me nt . T he i nter nal i n de pe n d e nt S S M T will c o ver t he 
o bjecti ves of t he D M C a n d t he I nt er nal I n d e pe n d e nt Safet y Re vie w T ea m .  
A p plic a ble Secti o n : 8. 1 0  I nter nal I n d e pe n de nt S afet y Re vie w 
A n o ver vie w of t he c h a n ges i ntr o d uce d i n pre vi o us a me n d me nts ca n b e f o u n d i n t he se parat e 
pr ot oc ol a me n d me nt s u m mar y of c h a n ges d oc u me nt f or eac h a me n d me nt.  
 
 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 0  
 
0 9 Se pte m ber 2 0 2 2  
P R O T O C O L S Y N O P SI S  
 
G al a p a g os N V  
Ge ner a al De Wittel a a n L 1 1 A 3  
2 8 0 0 Mec hele n, Bel gi u m  
 
 
St u d y Title:  
A Ra n d o mize d, D o u ble -bli n d, Place b o -c o ntr olle d P hase  2 St u d y t o 
E val uate t he Testic ul ar  Safet y of Fil g oti ni b i n A d ult  Males wit h 
M o deratel y t o Se verel y Acti ve I nfla m mat or y B o wel Disease 
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 2 9 6 4 7  
2 0 1 7 ‑0 0 0 4 0 2 ‑3 8  
 
N C T 0 3 2 0 1 4 4 5  
St u d y Ce nters 
Pl a n ne d:  
A p pr o xi matel y 1 7 5 ce nters w orl d wi de  
M ai n O bjecti ves:  
T he pri mar y o bjecti ve of t his st u d y is:  
•  T o e val uate t he effect of fil g oti ni b o n testic ular f u ncti o n as defi ne d 
b y t he pr o p orti o n of s u bjects wit h a ≥ 5 0 % decrease fr o m baseli ne i n 
s per m c o nce ntrati o n at Wee k 1 3  
T he sec o n d ar y o bjecti ves of t his st u d y i ncl u de:  
•  T o e val uate t he effect of fil g oti ni b o n testic ular f u ncti o n as defi ne d 
b y t he pr o p orti o n of s u bjects wit h a ≥ 5 0 % decrease fr o m baseli ne i n 
s per m c o nce ntrati o n at Wee k 2 6 
•  T o e val uate t he effect of fil g oti ni b o n s per m t otal m otilit y at 
Wee ks  1 3 a n d 2 6  
•  T o e val uate t he effect of fil g oti ni b o n t otal s per m c o u nt at Wee ks 1 3 
a n d 2 6 
•  T o e val uate t he effect of fil g oti ni b o n t he c ha n ge fr o m baseli ne i n 
s per m c o nce ntrati o n at Wee ks 1 3 a n d 2 6 
•  T o e val uate t he effect of fil g oti ni b o n ejac ulat e v ol u me at Wee ks  1 3 
a n d 2 6  
•  T o e val uate t he effect of fil g oti ni b o n s per m m or p h ol o g y at 
Wee ks  1 3 a n d 2 6  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 1  
 
0 9 Se pte m ber 2 0 2 2  
 
T he e x pl orat or y o bj ecti v es of t his st u d y i ncl u de:  
•  T o e val uate t he re versi bilit y of o bser ve d effects of fil g oti ni b o n 
testic ular f u ncti o n i n s u bjects w h o e x perie nce a ≥ 5 0 % decrease i n 
s per m c o nce ntrati o n a n d/ or m otilit y a n d/ or m or p h ol o g y 
•  T o e val uate t he effect of fil g oti ni b o n se x h or m o nes i ncl u di n g 
l utei nizi n g h or m o ne ( L H), f ollicle sti m ulati n g h or m o ne ( F S H), 
i n hi bi n B, a n d t otal test oster o ne at Wee ks 1 3 a n d 2 6  
•  T o e val uate t he s afet y a n d t olera bilit y of fil g oti ni b  
•  T o c haracterize t he plas ma p har mac o ki n etics ( P K) of fil g oti ni b a n d 
its meta b olite ( G S-8 2 9 8 4 5, f or merl y  
)  
St u d y Desi g n:  
T his is a ra n d o mize d, d o u ble -bli n d, place b o -c o ntr olle d P hase 2 st u d y i n 
a d ult males wit h m o derat el y t o se v erel y acti ve i nfl a m mat or y b o wel 
disease (I B D) w h o ma y b e o n pr ot oc ol -s pecifie d t hera p y.  
U p t o 2 5 0 males bet wee n t he a ge of 2 1 a n d 6 5 years (i ncl usi ve ) at t he 
ti me of c o nse nt will be ra n d o mize d t o recei ve 2 6 wee ks of fil g oti ni b 
2 0 0  m g or pla ce b o -t o-m atc h ( P T M) fil g oti ni b 2 0 0  m g o nce dail y.  
Ra n d o mizati o n will be stratifie d acc or di n g t o t he t y p e of I B D 
(ie, ulcerati ve c olitis [ U C ] vers us Cr o h n’s disease [C D ]), b y c o n c urre nt 
use of met h otre x ate ( M T X; yes or n o), a n d b y s p er m c o nce ntr ati o n 
meas ure d at Scree ni n g (“ Baseli ne”) acc or di n g t o t he f oll o wi n g str ata:  
•  1 5  t o 25  milli o n/ m L  
•  >  2 5  t o 5 0 milli o n/ m L 
•  >  5 0 milli o n/ m L  
St u d y Sc he m a  
 
 
 
C CI


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 2  
 
0 9 Se pte m ber 2 0 2 2  
 
T here  are 5 disti nct p arts t o t he st u d y w hic h s u bjects ma y e nter 
de pe n di n g u p o n t he i n di vi d ual s u bject’s res p o nse of t he u n derl yi n g I B D 
t o assi g ne d tr eat me nt a n d/ or o bser ve d c ha n ges i n s e me n para meters. T he 
5 parts w hic h are des cri b e d i n t he f oll o wi n g s ecti o ns c o m prise of t he 
f oll o wi n g: 
1)  Part A ( Da y 1 t hr o u g h W ee k  1 3 St u d y Visit)  
2)  Part B ( After Wee k  1 3 t hr o u g h Wee k 2 6 St u d y Visit)  
3)  O pe n -La b el Fil g oti ni b P hase  
4)  M o nit ori n g P hase  
5)  L o n g T er m E xte nsi o n  
T he st u d y p arts are descri be d i n t he f oll o wi n g secti o ns.  
P art A ( D a y  1 t hr o u g h Wee k 1 3 St u d y Visit)   
(A p pe n di x  1 1  a n d Fi g ure  3 -2 ) 
I n Part A, all s u bjects will recei ve bli n de d st u d y dr u g f or t he first 
1 3  wee ks , starti n g fr o m t he Da y 1/ Ra n d o mizati o n St u d y Visit. At t he 
Wee k 1 3 St u d y Visit, I B D res p o nse stat us (ie,  N o n -res p o n der vs 
Res p o n der, see Defi niti o n of Ter ms ) will be det er mi ne d base d o n t he 
partial Ma y o Cli nic Sc ore ( partial M C S) f or s u bjects wit h U C, or t he 
Cr o h n’s  Disease Acti vit y I n d e x ( C D AI) f or s u bjects wit h C D. I n 
a d diti o n, s per m para met ers (see Secti o n 6. 1 3  Se me n C ollecti o n 
Pr oce d ure ) will be e val u ate d t o deter mi ne w het her a n y of t he 
pre -s pecifie d decrease t hres h ol ds (see Defi niti o n of Ter ms ) ha v e bee n 
me t. 
•  S u bjects w h o are Res p o n ders a n d w h os e s per m para meters d o n ot 
meet a pre -s pecifie d decrease t hr es h ol d will c o nti n ue bli n de d st u d y 
dr u g i n Part B.  
•  S u bjects w h o are N o n -res p o n ders a n d w h ose s p er m para meters d o 
n ot meet a pre -s pecifie d decrease t hr es h ol d will disc o nti n ue bli n de d 
st u d y dr u g a n d c o m me nce o pe n-la bel ( O L) fil g oti ni b.  
•  S u bjects w h ose s per m para meters meet a pre -s pecifie d decrease 
t hres h ol d, re gar dless of I B D res p o nse stat us, will disc o nti n ue bli n de d 
st u d y dr u g a n d e nter t he M o nit ori n g P hase.  
 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 3  
 
0 9 Se pte m ber 2 0 2 2  
 
P art B ( After W ee k 1 3  t hr o u g h Wee k 2 6 St u d y Visit)  
(A p pe n di x  1 1  a n d Fi g ure  3 -3 ) 
I n Part B, all s u bjects will c o nti n ue bli n de d st u d y dr u g f or u p t o a n 
a d diti o nal 1 3  wee ks. S u bjects ma y e x perie nce Disease W orse ni n g 
(see D efi niti o n of Ter ms) of t heir u n derl yi n g I B D at a n y ti me d uri n g 
bli n de d st u d y dr u g  treat me nt (after Wee k 1 3 t hr o u g h Wee k 2 6). If 
Disease W orse ni n g is c o nfir me d, s per m para meters will be e val uate d t o 
deter mi ne  w het h er a pre -s pecifie d decrease t hr es h ol d has bee n met pri or 
t o a st u d y dr u g c ha n ge (c ha n gi n g fr o m bli n de d st u d y dr u g t o O L  
fil goti ni b). Base d u p o n t he s per m para meters at t his ti me p oi nt, s u bjects 
ma y f oll o w o n e of t he f oll o wi n g pat h w a ys:  
•  All s u bjects w h ose s per m para meters meet a pre -s pecifie d decrease 
t hres h ol d, re gar dless of I B D res p o nse stat us, will disc o nti n ue bli n de d 
st u d y dr u g a n d e nter t he M o nit ori n g P hase.  
•  S u bjects w h o e x perie nce Disease W orse ni n g after Wee k 1 3 a n d pri or 
t o W ee k 2 6, a n d w h ose s per m para meters d o n ot meet a pre-s pecifie d 
decrease t hr es h ol d will disc o nti n ue bli n de d st u d y dr u g a n d 
c o m me nce O L  fil g oti ni b.  
•  S u bjects w h o d o n ot e x perie nce Diseas e W orse ni n g, a n d are 
Res p o n ders at Wee k 2 6, a n d w h ose s per m para m eters d o n ot meet a 
pre -s pecifie d decrease t hres h ol d, will c o nti n ue bli n de d st u d y dr u g as 
part of t he L o n g T er m E xte nsi o n ( L T E).  
• S u bjects w h o d o n ot e x perie nce Diseas e W orse ni n g, b ut are 
N o n -res p o n d ers at Wee k 2 6, a n d w h ose s per m para meters d o n ot 
meet a pre -s pecifie d decrease t hr es h ol d, will disc o nti n ue bli n de d 
st u d y dr u g a n d c o m plete a safet y f oll o w-u p visit 3 0 da ys after l ast 
st u d y dr u g d ose.  
O pe n -L a bel Fil g oti ni b P h ase ( O pe n -L a bel D a y  1 t hr o u g h 
O pe n -L a bel  Wee k 1 3 St u d y Visit)   
(A p pe n di x  1 1  a n d Fi g ure  3 -4 ) 
After e x p os ure t o 1 3 wee ks of O L  fil g oti ni b, t he s u bject’s I B D res p o nse 
stat us will be deter mi ne d a n d s per m para meters will be e val uate d t o 
deter mi ne w het h er a pre -s pecifie d decrease t hres h ol d has bee n met. 
S u bjects will be e val uate d d uri n g t his p hase as f oll o ws:  
•  All s u bjects w h ose s per m para meters meet a pre -s pecifie d decrease 
t hres h ol d, re gar dless of Res p o n der stat us, will disc o nti n ue O L  
fil g oti ni b, c o m plete a safet y f oll o w-u p visit 3 0  da ys after last st u d y 
dr u g d os e, a n d e nt er t he M o nit ori n g P hase.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 4  
 
0 9 Se pte m ber 2 0 2 2  
•  S u bjects w h o e x perie nce Disease W orse ni n g a n d w h ose s per m 
para meters d o n ot meet a pre -s pecifie d decrease t hres h ol d will 
disc o nti n ue O L  fil g oti ni b, c o m plete Earl y T er mi nati o n  (E T ) a n d a 
safet y f oll o w-u p visit 3 0 da ys after l ast st u d y dr u g d ose.  
 
•  S u bjects w h o d o n ot e x perie nce Diseas e W orse ni n g, a n d are 
Res p o n ders at O L Wee k 1 3 after e x p os ure t o 1 3 wee ks of O L 
fil g oti ni b, a n d w h ose s per m para met ers d o n ot meet a pre-s pecifi e d 
decrease t hr es h ol d, ma y c o nti n ue recei vi n g O L fil g oti ni b as part of 
t he L T E. 
•  S u bjects w h o d o n ot e x perie nce Diseas e W orse ni n g, b ut are 
N o n -res p o n d ers aft er e x p os ure t o 1 3 wee ks of O L  fil g oti ni b, a n d 
w h ose s per m para meters d o n ot meet a pre -s pecifi e d decreas e 
t hres h ol d, will disc o nti n ue O L  fil g oti ni b a n d c o m plete a safet y 
f oll o w-u p visit 3 0 da ys after last st u d y dr u g d ose.  
M o nit ori n g P h ase ( u p t o 5 2 wee ks ) (A p pe n di x  1 1  a n d Fi g ure  3 -5 .) 
All s u bjects w h o e nter t h e M o nit ori n g P hase  will u n der g o se me n 
e val uati o ns e ver y 1 3 wee ks fr o m t he da y of st u d y dr u g disc o nti n uati o n, 
f or u p t o 5 2 wee ks or u ntil Re versi bilit y (see Defi niti o n  of  Ter ms ) is met, 
w hic he ver is ac hie ve d first. S u bjects will be offere d l ocall y a p pr o ve d 
sta n dar d of care (S O C) t hera p y d uri n g t he M o nit ori n g P hase.  
L o n g Ter m E xte nsi o n ( u p t o 1 9 5 wee ks )  
(A p pe n di x  1 1  a n d Fi g ure  3 -6 .) 
All s u bjects w h o e nter t h e L T E will u n der g o sc h e d ule d visits f or safet y 
assess me nts  e ver y 1 3 wee ks fr o m t he start of L T E, f or u p t o 1 9 5 wee ks , 
a n d se me n m o nit ori n g (e ver y 1 3 wee ks) u ntil t h e Wee k 1 3 pri mar y st u d y 
res ults are a nal yz e d. S u bjects will recei ve eit her O L  fil g oti ni b or bli n de d 
st u d y dr u g bas e d o n t he i n di vi d ual’s res p o nse criteria des cri be d a b o v e. If 
a s u bject e x perie nces Dis ease W orse ni n g d uri n g t he L T E, t he treat me nt 
(eit her O L  fil g oti ni b or bli n de d st u d y dr u g) will be disc o nti n ue d a n d t he 
s u bject will c o m plete a n E T visit, f oll o we d b y a s afet y f oll o w-u p visit 3 0 
da ys after l ast st u d y dr u g d ose.  
D at a M o nit ori n g C o m mittee ( D M C) /S p o ns or S afet y M a n a ge me nt 
Te a m ( S S M T)  
A n e xter nal, m u lti disci pli nar y D M C, i ncl u di n g a n e x pert i n male 
fertilit y, 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 
u n bli n de d re vie ws of s afet y d ata ( det ails i n Secti o n  8. 8 ).  
T he D M C  has m o nit ore d t he st u d y u ntil t he date of pr ot oc ol 
a me n d me nt  6 , i ncl u di n g t he data f or t he sec o n d u n bli n de d i nteri m 
a nal ysis (I A 2). As of a m e n d me nt 6 , t he D M C will be dec o m missi o ne d. 
T he safet y a n d pr o gress of t he re mai n d er of t he st u d y will c o nti n ue t o be 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 5  
 
0 9 Se pte m ber 2 0 2 2  
m o nit ore d b y t he S p o ns or me dical lea d er a n d m e dical m o nit or or 
desi g nee, pr o vi di n g u p dates d uri n g re g ular S p o ns or me dical m o nit ori n g 
o versi g ht meeti n gs acr oss t he fil g oti ni b pr o gra m. If nee d e d, safet y iss ues 
will be escalate d t o t he S S M T per i nter nal sta n dar d pr oce d ures. T he 
S S M T ca n c o ns ult e xter nal e x perts, if dee me d necessar y, a n d ca n re vie w 
data i n a n  u n bli n de d fas hi o n.   
Ke y C o nc o mit a nt Me dic ati o n  C o nsi der ati o ns  
S u bjects ma y be treat e d wit h 5 -a mi n osalic ylic aci d ( 5 -A S A), 
c o n ve nti o nal i m m u n o m o d ulat ors, a n d/ or c ortic ost er oi d t hera p y, as 
defi ne d b y t he i ncl usi o n criteria. S u bjects are pr o hi bite d fr o m recei vi n g 
s ulfasalazi ne, be gi n ni n g 2 6 wee ks pri or to Scree ni n g u ntil t he e n d of 
st u d y, as defi ne d b y E x cl usi o n Criteria. 
A list of per mitte d a n d pr o hi bite d me dicati o ns is pr o vi de d i n t he 
e x cl usi o n criteria a n d Secti o n 5. 3 . 
N u m ber of 
S u bjects 
Pla n ne d:  
U p t o 2 5 0 s u bjects f or 2 0 0 e val ua ble s u bjects  
Tar get 
P o p ulati o n:  
Males bet wee n t he a ges of 2 1 a n d 6 5 years (i ncl usi ve) wit h m o deratel y t o 
se verel y acti ve I B D 
D urati o n of 
Treat me nt:  
T he d urati o n of tr eat me nt is a p pr o xi matel y u p t o 2 6 wee ks  of bli n de d 
st u d y dr u g, a n d u p t o 1 3 wee ks of O L  fil g oti ni b (if eli gi ble). 
S u bse q ue ntl y, f or t h ose s u bjects q ualif yi n g, t his will be f oll o we d b y an  
L T E lasti n g u p t o 1 9 5  wee k s. S u bjects w h ose s per m para meters meet a 
pre -s pecifie d decrease t hres h ol d at a n y ti me d uri n g t he st u d y will 
disc o nti n ue st u d y dr u g , a n d s h o ul d be ma na ge d wit h all o we d sta n dar d of 
care t h era p y. T h ese s u bjects will be f oll o we d i n t he M o nit ori n g P hase of 
t he st u d y, f or u p t o 5 2 weeks or u ntil Re versi bilit y 
(see D efi niti o n  of  Ter ms ) of all para m eters meeti n g s per m decreas e 
t hres h ol d is met, w hic he ver is ac hie ve d first.  
Dia g n osis a n d 
Mai n 
Eli gi bilit y 
Criteria:  
F or a c o m plete list of st u d y i ncl usi o n a n d e x cl usi o n criteria, please refer 
t o Secti o ns 4. 2  a n d 4. 3 . 
Ke y I ncl usi o n Criteri a  
•  Males bet wee n t he a ge of 2 1 a n d 6 5 (i ncl usi ve) o n t he da y of si g ni n g 
i nf or me d c o nse nt 
•  D oc u me nte d dia g n osis of U C or C D of at least 4  m o nt hs d urati o n. 
D oc u me ntati o n m us t i ncl u de e n d osc o pic a n d hist o pat h ol o gic 
d oc u me ntati o n of eit her U C or C D, as f oll o ws:  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 6  
 
0 9 Se pte m ber 2 0 2 2  
⎯ U C  
■ Me dical rec or d d oc u m e ntati o n of, or a n e n d osc o p y re p ort 
date d ≥ 4 m o nt hs bef ore ra n d o mizati o n, w hic h s h o ws feat ur es 
c o nsiste nt wit h U C, deter mi ne d b y t he pr o ce d ure p e rf or mi n g 
p h ysicia n, A N D  
■ Me dical rec or d d oc u m e ntati o n of, or a hist o pat h ol o g y re p ort 
i n dicati n g feat ures c o nsiste nt wit h U C as deter mi ne d b y t h e 
pat h ol o gist  
N ote : S u bjects als o nee d t o ha ve mi ni m u m disease e xte nt of 
1 5  c m fr o m t he a n al ver ge  
 
⎯ C D  
■ Me dical rec or d d oc u m e ntati o n of, or a n ile oc ol o n osc o p y 
(f ull c ol o n osc o p y wit h i nt u bati o n of ter mi nal ile u m) re p orte d 
date d ≥ 4 m o nt hs bef ore ra n d o mizati o n, w hic h s h o ws feat ur es 
c o nsiste nt wit h C D, deter mi ne d b y t he pr o ce d ure p erf or mi n g 
p h ysicia n, A N D  
■ Me dic al rec or d d oc u m e ntati o n of, or a hist o pat h ol o g y re p ort 
i n dicati n g feat ures c o nsiste nt wit h, C D as deter mi ne d b y t h e 
pat h ol o gist  
•  M o deratel y t o se verel y acti ve U C, or m o derat el y t o se verel y acti ve 
C D, assesse d l ocall y a n d defi ne d b y:  
⎯  U C  
■ Ma y o Cli nic Sc ore ( M C S; A p pe n di x  3 ) ≥ 6, P h ysicia n’s 
Gl o bal Assess me nt ( P G A) of 2 or 3, a n d e n d osc o pic s u bsc ore 
≥ 2, at Scree ni n g or i n t h e pri or 9 0  da ys  
⎯ C D  
■ C D AI t otal s c ore ( A p pe n di x  9 ) ≥ 2 2 0, A N D  
■ E vi de nce of acti ve i nfla m mati o n, wit h a t otal sc ore of ≥ 6  b y 
t he Si m ple E n d osc o pic Acti vit y Sc ore i n Cr o h n’s Disease 
( S E S-C D; A p pe n di x  1 0 ), O R  if disease is li mite d t o t he ile u m 
a n d/ or ri g ht c ol o n, a c o m bi ne d S E S -C D sc ore ≥ 4 i n t hese 
2  se g me nts, at Scree ni n g or i n t he pri or 9 0  da ys  
 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 7  
 
0 9 Se pte m ber 2 0 2 2  
 
•  Pre vi o usl y de m o nstrat e d a n i na de q uat e cli nical r es p o nse, l oss of 
res p o nse t o, or i nt olera n ce of at least 1 of t h e f oll o wi n g 5  cl asses of 
a ge nts, as i n di vi d uall y d efi ne d i n Secti o n 4. 2  I ncl usi o n Criteria, # 6 
⎯ C ortic oster oi ds  
⎯ Azat hi o pri ne, 6 -merca pt o p uri ne, or met h otre x ate  
⎯ T N F α a nta g o nists (i nfli xi ma b, a dali m u ma b, g oli m u ma b [ U C 
o nl y], or cert oliz u ma b [ C D o nl y])  
⎯ Ve d oliz u ma b  
⎯ Uste ki n u ma b ( C D o nl y)  
•  T he mea n of 2 s e parate s e me n sa m ples c ollecte d at t he Scree ni n g 
visit m ust meet t he f oll o wi n g mi ni m u m criteria (i n acc or da nce wit h 
Secti o n  6. 1 4  a n d Fi g ure  6 -1 ): se me n v ol u me ≥ 1. 5 m L, t otal 
s per m/ejac ulate ≥ 3 9  milli o n, s per m c o nc e ntr ati o n ≥ 1 5  milli o n/ m L, 
s per m t otal m otilit y ≥ 4 0 %, a n d n or mal s per m m or p h ol o g y ≥ 3 0 %  
 
Ke y E xcl usi o n Criteri a  
•  Pre vi o usl y or c urre ntl y d oc u me nte d pr o ble ms wit h male 
re pr o d ucti ve h ealt h, i ncl u di n g b ut n ot li mite d t o pri mar y 
h y p o g o na dis m, sec o n dar y h y p o g o na dis m, or re d u ce d fertilit y  
•  C urre nt use of s ulfasalazi ne or its use wit hi n t he 2 6  wee ks lea di n g u p 
t o Scree ni n g; s ulfasalazi ne is n ot per mitte d at a n y p oi nt d uri n g t he 
st u d y 
•  C urre nt use of c ortic oster oi ds at a d osa ge of >  2 0  m g/ da y of 
pre d nis o ne or e q ui vale nt at ra n d o mizati o n  
•  Acti ve t u berc ul osis or u ntreate d late nt t u berc ul osis ( Secti o n  4. 2  
I n cl usi o n Criteria, # 1 2) 
I nfecti o n wit h acti ve He p atitis B, He patitis C, or HI V ( Secti o n 4. 3  
E x cl usi o n Criteria, # 3 1 -3 3)  
St u d y Pr oce d ures/  
Fre q u e nc y:  
After writte n i nf or me d c o nse nt is o btai ne d, scree ni n g pr oce d ures will 
c o m me nce, i ncl u di n g b ut n ot li mite d t o e val uati o n of eli gi bilit y criteria, 
me dical hist or y, r o uti ne bl o o d a n d uri ne c ollecti o n f or la b orat or y 
a nal ys es a n d s e me n sa m ple c ollecti o n. All s u bjects meeti n g eli gi bilit y 
criteria will be ra n d o mize d 1: 1 t o recei v e fil g oti ni b 2 0 0  m g o nce dail y or 
P T M fil g oti ni b 2 0 0 m g o nce dail y, f or u p t o 2 6 w ee ks.  
All s u bjects will ret ur n t o t he cli nical st u d y ce nter t o be e val uate d f or 
cli nical a n d la b orat or y a ssess me nts at Wee k 2, Wee k 4, Wee k 8, a n d 
Wee k 1 3, i ncl u di n g se me n sa m ple c ollecti o n d uri n g Wee k 1 3 visits. 
S u bjects c o nti n ui n g o n bli n de d st u d y dr u g will ret ur n f or Wee k 2 0 a n d 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 8  
 
0 9 Se pte m ber 2 0 2 2  
Wee k  2 6 assess me nts, i ncl u di n g se me n s a m ple c ollecti o n d uri n g 
Wee k  2 6 visits. S u bjects w h o are N o n -res p o n ders at Wee k 1 3 or w h o 
s h o w Disease W orse ni n g bet wee n t he Wee k 1 3 a n d Wee k 2 6 St u d y 
Visits will s witc h t o O L fil g oti ni b . After starti n g O L fil g oti ni b, s u bjects 
will ret ur n f or st u d y assess me nts at O L Da y 1, O L Wee k 2, O L Wee k  4, 
O L Wee k 8, a n d O L  Wee k 1 3, i ncl u di n g a se me n sa m ple c ollecti o n at 
O L Wee k 1 3.  S u bjects c o nti n ui n g o n t o t he L T E will u n der g o sc h e d ule d 
visits f or safet y assess me nts a n d se me n sa m ple c ollecti o n, e ver y 
1 3  wee ks u p t o 1 9 5  wee ks.  
S u bjects w h o are Res p o n ders at  Wee k 2 6 or at O L Wee k 1 3 a n d c h o ose 
n ot t o c o nti n ue t o t he L T E, as well as s u bjects w h o disc o nti n ue st u d y 
partici pati o n f or a n y reas o n pri or t o Wee k 2 6, O L Wee k 1 3, reac hi n g 
Re versi bilit y or M o nit ori n g P hase Wee k 5 2 ( w hic he ver occ urs first), or 
L T E Wee k 1 9 5, will c o m plete a n E T visit i n a d diti o n t o a r o uti ne safet y 
f oll o w-u p visit 3 0 da ys ( ±  5 da ys) after t he last d ose of st u d y dr u g.  
 
S p arse P l as m a P K S a m ple C ollecti o n: 
I n Parts A a n d B, s parse plas ma P K sa m ples will be c ollecte d at least 
3 0  mi n utes p ost d ose at t he Wee k 2 visit, a n yti me at t he Wee k  4 visit, 
a n d pre d ose d uri n g visits at Wee ks  1 3 a n d 2 6. I n t he O L Fil g oti ni b 
P hase, s parse plas m a P K sa m ples will be c ollecte d at least 3 0 mi n utes 
p ost d ose at t he O L  Wee k  2 visit, a n yti me at t he O L Wee k 4 visit , a n d 
pre d ose d uri n g visits at O L Wee k 1 3.  
Se me n C ollecti o n a n d A n al ysis : 
At eac h of t h e f oll o wi n g ti me p oi nts, s u bjects will pr o vi de 2  se me n 
sa m ples, c ollecte d wit hi n a 1 4-da y peri o d. Eac h s e me n sa m ple m ust be 
c ollecte d wit h a n ejac ulati o n free p eri o d of ≥ 4 8 h o urs a n d ≤ 7 da ys 
( Secti o n 6. 1 3 ):  
•  Scree ni n g ( Bas eli ne)  
•  After Part A ( Wee k 1 3 St u d y Visit)  
•  After Part B ( Wee k 2 6 St u d y Visit)  
O R  
F or S u bjects w h o e x perie nce c o nfir me d Diseas e W orse ni n g bet w ee n 
Wee ks 1 3 -2 6 i n Part B, pri or t o be gi n ni n g O L Fil g oti ni b P hase a n d 
at t he O L Wee k  1 3  St u d y Visit  
•  E ver y 1 3 wee ks d uri n g t he M o nit ori n g P hase (if a p plica ble)  
•  E ver y 1 3 wee ks d uri n g t he L T E  
I n s elect i nsta nces w here t he se me n sa m ple wit h q uesti o ne d val ue(s) is 
f o u n d t o be n o n-assess a ble or i n vali d (e g, c ollecti o n wit h o ut a d here nce 
t o ejac ulati o n-free p eri o ds; i nterc urre nt ill ness or d e h y drati o n at ti me of 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 9  
 
0 9 Se pte m ber 2 0 2 2  
c ollecti o n; i nc o m plete ca pt ure of se me n s a m ple; a n d/ or sa m ple 
pr ocessi n g or se m e n a nal ysis t hat de viates fr o m sta n dar dize d 
pr oce d ure), a t hir d se me n sa m ple, w he n i n dicate d, m ust be c ollecte d 
wit hi n 1 4 da ys of t he pri or sa m ple, wit h a n ejac ul ati o n free p eri o d of 
≥ 4 8 h o urs a n d ≤ 7 da ys. All decisi o n s of retesti n g a n y s e me n/s per m 
para meter (ie, o btai ni n g a t hir d  se me n sa m ple at a n y of t he a b o ve ti me 
p oi nts) m ust be a p pr o ve d b y t he S p o ns or Me di cal M o nit or or desi g n ee 
bef ore t h e retest.  
Test Pr o d uct, 
D ose, a n d M o de 
of 
A d mi nistr ati o n:  
2 0 0  m g fil g oti ni b ta blet orall y o n ce dail y 
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 -t o-matc h fil g oti ni b 2 0 0  m g ta blet orall y o nce dail y 
Re q uire d 
B ac k gr o u n d 
Me dic ati o n:  
Per mitte d me dicati o n as descri be d i n t he i ncl usi o n criteria , a n d 
a d mi nistere d acc or di n g t o t he l ocal pr o d uct la b el.  
Criteri a f or 
E v al u ati o n:  
 
Safet y  
Se me n sa m ples will be c ollecte d as o utli ne d i n Secti o n  6. 1 3 . Se x 
h or m o nes, i ncl u di n g L H, F S H, i n hi bi n B , a n d t otal test oster o ne will be 
meas ure d at vari o us ti me p oi nts d uri n g t his st u d y.  
Ot her as pects of safet y will be assesse d b y t he re p orti n g of A E s, cli nical 
la b orat or y e v al uati o ns ( h e mat ol o g y, c he mistr y a n d uri nal ysis), p h ysic al 
e x a mi nati o n, vital si g ns, a n d at vari o us ti me p oi nts d uri n g t he st u d y. 
C o nc o mita nt me dicati o n usa ge will als o be assess e d t hr o u g h o ut t he 
st u d y. 
P har mac o ki netics  Plas ma c o nce ntr ati o ns of fil g oti ni b a n d its meta b olite ( G S -8 2 9 8 4 5 ) will 
be a nal yz e d.  
St atistic al 
Met h o ds:  
T he pri mar y e n d p oi nt is t he pr o p orti o n of s u bjects wit h a 
≥ 5 0 %  decrease i n s per m c o nce ntr ati o n fr o m baseli ne at Wee k 1 3. A 
c u m ulati ve distri b uti o n pl ot f or t he perce nt c ha n ge fr o m baseli ne i n 
s per m c o nce ntrati o n at Wee k 1 3 f or eac h treat me nt gr o u p will be 
c o nstr ucte d. T he x -a xis will dis pla y p erce nt c ha n ges fr o m basel i ne 
s per m c o nce ntrati o n ra n gi n g fr o m 1 0 0 % decreas e (ie, -1 0 0 % or 
az o os per mia) t o t he ma xi mal o bser ve d i ncreas e. T he y -a xis will dis pla y 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2 0  
 
0 9 Se pte m ber 2 0 2 2  
t he pr o p orti o n of s u bjects w h o e x perie nce d a perce nta ge c h a n ge i n 
s per m c o nce ntrati o n e q u al t o or less t ha n t he c orres p on di n g x -a xis val ue 
at W ee k  1 3. T his met h o d is s u g geste d i n F D A’s G ui da nce f or I n d ustr y: 
Testic ular t o xicit y: E v al uati o n D uri n g Dr u g De v el o p me nt 
(Oct o ber  2 0 1 8 ).  
T he pr o p orti o n of s u bjects e x perie nci n g at least a 5 0 % decrease i n 
s per m c o nce ntrati o n fr o m baseli ne will be calc ul ate d t o get her wit h t he 
ass ociate d 9 5 % c o nfi de n ce i nter val f or t he differe nce bet w ee n t he 
fil g oti ni b a n d place b o gr o u ps. A d diti o nal assess me nt s of se me n 
para meters ma y be c o n d ucte d . 
All c o nti n u o us e n d p oi nts will be s u m marize d usi n g a n 8 -n u m ber 
s u m mar y ( n, mea n, sta n d ar d de viati o n [ S D], me dia n, 1 st q uartile [ Q 1], 
3 r d q uartile [ Q 3], mi ni m u m, ma xi m u m) b y treat me nt gr o u p. All 
cate g orical e n d p oi nts w ill be s u m marize d b y t he n u m ber a n d perce nt a ge 
of s u bjects w h o meet t he e n d p oi nt defi niti o n.  
Safet y e n d p oi nts will be a nal yze d b y t h e n u m ber a n d perce nt of s u bjects 
wit h e ve nts or a b n or malities f or cate g orical val u es or 8 -n u m ber 
s u m mar y ( n, mea n, S D, me dia n, Q 1, Q 3, mi ni m u m, ma xi m u m) f or 
c o nti n u o us data b y d osi n g gr o u p.  
A sa m ple siz e of 1 0 0 e val ua ble s u bjects per gr o u p, w here e val ua ble is 
defi ne d as s u bjects i n t he Se me n A nal ysis Set ( Secti o n 8. 2. 1. 2 ), is 
a de q uate f or t he p ur p os es of esti mati n g c u m ulati v e distri b uti o n c ur ves 
a n d pr o d uci n g a 9 5 % c o nfi de nce i nter val wi dt h t hat is reas o na bl y 
narr o w f or t he perce nt a ge of s u bjects i n eac h gr o u p w h o e x perie n ce a 
≥ 5 0 % decrease i n s per m c o nce ntr ati o n c o m pare d t o baseli ne . Ass u mi n g 
a 2 0 % rat e of n o n -e val ua ble s u bjects at Wee k 1 3, u p t o 1 2 5  s u bjects per 
ar m ma y be e nr olle d.  
Res ults of t his st u d y ma y be p o ole d wit h t he res ults of a se parate st u d y 
bei n g c o n d ucte d i n s u bjects wit h r he u matic diseas es 
( G L P G 0 6 3 4-C L -2 2 7) wit h t he sa me o bjecti ve. T h e t otal pla n ne d 
n u m ber of s u bjects i n b ot h st u dies c o m bi ne d will be a p pr o xi matel y 
2 5 0  s u bjects. 
U n bli n de d i nteri m a nal ys es of t he cli nical trial d ata will be perf or me d b y 
t he S p o ns or f or re g ul at or y s u b missi o ns w he n 2 0 0 s u bjects (e g, p o ole d 
data fr o m G S -U S -4 1 8 -4 2 7 9  a n d G L P G 0 6 3 4 -C L -2 2 7), a n d/ or w he n 
s o me defi ne d s u bset(s) of s u bjects, ha ve c o m plete d t he Wee k  1 3 a n d 
Wee k 2 6  ( or O L Wee k 1 3 ) assess me nts  (first u n bli n de d i nteri m a nal ysis 
[I A 1]), a n d w he n c o m plete re versi bilit y d ata f or all s u bjects w h o e ntere d 
t he M o nit ori n g P hase at t hese ti me p oi nts is a vaila ble (I A 2; see 
Defi niti o n  of  Ter ms ). A Data I nte grit y a n d C o m m u nicati o n Pla n f or t he 
i nteri m a nal ysis will be d e vel o pe d pri or t o un bli n di n g. T he a nal yses will 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2 1  
 
0 9 Se pte m ber 2 0 2 2  
be c o n d ucte d pri maril y t o e val uate t he testic ul ar safet y a n d f urt her 
details will be descri be d i n t he statistical a nal ysis pla n (S A P ).  
F or o n g oi n g s u bjects,  the st u d y tea m s a n d st u d y st aff at t he sites a n d all 
ot her staff directl y i n v ol ve d i n t he c o n d uct of t he st u d y  will re mai n 
bli n de d t o t he treat me nt assi g n me nts u ntil t he fi nal a nal ysis w he n t he 
data base h as bee n l o c ke d.  P u blicati o n of t he I A 2 d ata is pla n ne d b y t he 
S p o ns or. T his p u blicati o n will c o ntai n gr o u p le vel data f or t he e ntire  
st u d y p o p ulati o n, b ut will u n bli n d t he st u d y  tea ms a n d staff directl y 
i n v ol ve d i n t he c o n d uct of t he st u d y t o t he i n di vi d ual baseli ne treat me nt 
assi g n me nt of s u bjects w h o c o m plete d t he st u d y b ef ore I A 2 . 
 
T his st u d y will be c o n d u cte d i n acc or da n ce wit h t he g ui d eli nes 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. 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2 2  
 
0 9 Se pte m ber 2 0 2 2  
D E FI NI TI O N O F T E R M S  
Disease W orse ni n g  
F or s u bjects wit h U C, Disease W o rse ni n g is defi n e d b y a partial 
M C S after Wee k  1 3 c o nsisti n g of:  
a n i ncrease of ≥ 3 p oi nts t o at least 5 p oi nts fr o m t he Wee k  1 3 
val ue o n 2  c o nsec uti ve visits, O R  
a n i ncrease t o 9 p oi nts fr o m t he Wee k 1 3 val ue o n 2 c o nsec uti ve 
visits, if t he Wee k 1 3 val ue was > 6 p oi nts   
F or s u bjects wit h C D, Disease W orse ni n g is defi n e d b y a t otal 
C D AI s c ore after Wee k 1 3 c o nsisti n g of:  
a sc ore ≥ 2 2 0 o n 2 c o nsec uti ve visits, A N D  
a n i ncrease of ≥ 1 0 0 p oi nts fr o m t he Wee k 1 3 val u e o n 
2  c o nsec uti ve visits  
Disease W orse ni n g is c o nfir me d at t he ti me of t he sec o n d 
c o nsec uti ve visit.  
Ma y o Cli nic Sc ore 
( M C S) 
C o m p osite sc ore of U C acti vit y c o nsisti n g of s u b -sc ores fr o m 
e n d osc o p y, rectal bl ee di n g, st o ol fre q ue nc y, a n d P G A. S u bject 
recall f or t he last 2 4 h o urs will be use d f or t he pati e nt re p orte d 
c o m p o ne nts of t he c o m pl ete M C S.  
Partial Ma y o Cli nic 
Sc ore ( partial M C S)  
C o m p osite sc ore of U C acti vit y c o nsisti n g of s u b -sc ores fr o m 
rectal ble e din g, st o ol fre q ue nc y, a n d P G A. S u bject recall f or t he 
last 2 4 h o urs will be use d f or t he patie nt r e p orte d c o m p o ne nts of 
t he partial M C S. 
Cr o h n’s Disease A cti vit y 
I n d e x ( C D AI) 
C o m p osite sc ore of C D acti vit y c o nsisti n g of gastr oi ntesti nal  
s y m pt o ms (e g, a b d o mi nal pai n), si g ns (e g, a b d o mi nal mass), 
la b orat or y val u es (ie, he mat ocrit), a n d c o m plicati o ns 
(e g, art hritis/art hral gia), a m o n g ot her patie nt attri b utes.   
S u bject recall f or t he last 7 da ys will be use d f or t he patie nt 
re p orte d o utc o m e of t he C D AI. T he C D AI s c ore calc ulati o ns 
s h o ul d n ot be i ncl usi ve of da ys t hat i n v ol ve a n e n d osc o p y 
pr oce d ure or pre parati o n f or t hat pr oce d ure . 
Si m ple E n d osc o pic 
Acti vit y Sc ore i n 
Cr o h n’s Disease 
( S E S-C D)  
C o m p osite sc ore of m uc osal i nfla m mati o n i n C D c o nsisti n g of 
f o ur e n d osc o pi c varia bl es ( ulcer prese nce a n d size; l u mi nal s urface 
c o vere d b y ul cers; l u mi nal s urface wit h disease i n v ol ve me nt; a n d 
ste n osis prese nce a n d se v erit y). 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2 3  
 
0 9 Se pte m ber 2 0 2 2  
M o nit ori n g P hase  
A s u bject w h o e x perie nces a ≥ 5 0 % decrease i n s per m 
c o nce ntr ati o n, a n d/ or m otilit y, a n d/ or m or p h ol o g y at a n y ti me after 
1 3 wee ks o n st u d y dr u g will disc o nti n ue t he st u d y dr u g , c o m plete 
a r o uti ne safet y f oll o w u p visit 3 0 da ys ( ±  5  da ys) after t he l ast 
d ose of st u d y dr u g  a n d st art t he M o nit ori n g P has e. Se me n sa m ples 
will be c ollecte d e v er y 1 3 wee ks fr o m t he date of t he st u d y dr u g 
disc o nti n uati o n, f or u p t o 5 2  wee ks or u ntil Re versi bilit y is met, 
w hic he ver is ac hie ve d first.  
Res p o n der  
F or U C, a s u bject w h o has a re d ucti o n of ≥ 2 i n partial Ma y o 
Cli nic Sc ore c o m pare d t o baseli ne at t he s pecifie d assess me nt ti me 
(A p pe n di x  2 ). 
F or C D, a s u bject w h o has a re d ucti o n of ≥ 1 0 0 p oi nts i n t otal 
C D AI s c ore c o m pare d t o baseli ne at t he s pecifie d  assess me nt ti me 
(A p pe n di x  2 ). A s u bject wit h a baseli ne t otal C D AI sc ore 
of  ≥ 2 2 0  t o ≤ 2 5 0 will be c o nsi dere d t o be a Res p o n der if a C D AI 
sc ore of <  1 5 0 is attai ne d at t he s pecifie d assess me nt ti me.  
N o n -res p o n d er 
F or U C or C D, a s u bj ect w h o d oes n ot f ulfill t he defi niti o n of 
Res p o n der at t he s pecifie d assess me nt ti me ( A p pe n di x  2 ).  
Pre -s pecifi e d decreas e 
t hres h ol d 
A ≥ 5 0 % decreas e i n s per m c o nce ntr ati o n, a n d/ or m otilit y, a n d/ or 
m or p h ol o g y i n c o m paris o n t o Baseli ne. T h e mea n of val ues f or 
eac h of t h e s per m para m eters ( meas ure d fr o m 2 s e parat e se me n 
sa m ples) will be use d i n all a nal ys es. Sa m ples will be c ollecte d 
wit hi n a 1 4 -da y peri o d , wit h a n  ejac ulati o n -free peri o d of 
≥ 4 8  h o urs a n d  ≤ 7  da ys . 
Re versi bilit y  
Re versi bilit y is met w he n all s per m para m eter(s) q ualif yi n g t he 
s u bject t o e nter i nt o t he M o nit ori n g P hase ret ur n(s) t o greater t ha n 
5 0 % of Baseli ne (ie, t o greater t ha n [ 0. 5 0 x mea n of 2 s per m 
c ollecti o ns c ollecte d at t he Scree ni n g visit (e g, Bas eli ne )]).   
Wee k 1 3  
T he Wee k 1 3 St u d y Visit  occ urs o nce a s u bject c o m pletes t he first 
1 3 wee ks of bli n de d st u d y dr u g, a n d is i ncl usi ve of all st u d y 
assess me nts perf or me d at t he cli nic visit a n d t he se me n sa m ple 
c ollecti o n visits ass ociate d wit h t his ti me p oi nt.   
Wee k 2 6  
T he Wee k 2 6 St u d y Visit occ urs o nce a s u bject c o m pletes t he 
sec o n d 1 3 wee ks of bli n d e d st u d y, a n d is i ncl usi ve of all st u d y 
assess me nts perf or me d at t he cli nic visit a n d t he se me n sa m ple 
c ollecti o n visits ass ociate d wit h t his ti me p oi nt.   
O L We e k 1 3  
T he O L Wee k 1 3 St u d y Visit occ urs o nce a s u bject c o m pletes t he 
first 1 3 wee ks of O L  fil g oti ni b, a n d is i ncl usi ve of all st u d y 
assess me nts perf or me d at t he cli nic visit a n d t he se me n sa m ple 
c ollecti o n visits ass ociate d wit h t his ti me p oi nt.   


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2 4  
 
0 9 Se pte m ber 2 0 2 2  
First  u n bli n de d  i nteri m 
a nal ysis (I A 1)  
U n bli n de d Wee k 2 6 a nal ysis t o be perf or me d after at least 
2 0 0  e val ua ble s u bjects p o ole d acr oss st u dies G S -U S -4 1 8 -4 2 7 9 
( G L P G 0 6 3 4-C L -2 2 8) a n d G L P G 0 6 3 4 -C L -2 2 7 c o m plete Wee k 1 3 
a n d e val ua bl e s u bjects fr o m St u d y G S -U S -4 1 8 -4 2 7 9 c o m plete 
Wee k 2 6  ( or O L Wee k 1 3 ) or per ma n e ntl y dis c o nti n ue fr o m st u d y 
dr u g. Referre d t o as ‘ Wee k 2 6 A nal ysis’  i n t he S A P. 
Sec o n d u n bli n de d 
i nteri m a nal ysis (I A 2) 
U n bli n de d Wee k 2 6 a nal ysis t o be perf or me d after all s u bjects 
reac h Wee k 2 6 a n d all s u bjects wit h a ≥ 5 0 % decrease i n s per m 
c o nce ntr ati o n, a n d/ or m otilit y, a n d/ or m or p h ol o g y u p t o Wee k 2 6 
( or O L Wee k 1 3) e nter t h e M o nit ori n g P hase a n d eit her meet 
re versi bilit y criteria or are f oll o we d off-treat me nt f or 5 2 wee ks, 
w hic he ver occ urs first. Referre d t o as ‘ Wee k 2 6 a n d Re versi bilit y 
A nal ysis f or Pre -s p ecifie d S per m Decreases U p t o Wee k 2 6’ i n t he 
S A P.  
 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2 5  
 
0 9 Se pte m ber 2 0 2 2  
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  
5 -A S A  
5 -a mi n osalic ylate  
6 -M P  
6 -merca pt o p uri ne  
A b  
anti b o d y  
A E  
a d verse e ve nt  
A L T  
ala ni ne a mi n otra nsferase  
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 0 -Ʈ  
area u n der t he plas ma dr u g c o nce ntrati o n -ti me c ur ve of a d osi n g i nter val 
B U N  
bl o o d urea nitr o ge n  
C Ʈ  
tr o u g h plas ma c o nce ntrati o n (j ust bef ore t he ne xt d osi n g ie, pre d ose sa m ple)  
C C & G  
C oc kcr oft -Ga ult  
C D  
Cr o h n’s disease  
C D AI  
Cr o h n’s Disease Acti vit y I n de x  
C E S  
car b o x ylesterases  
CI  
c o nfi de nce i nter val  
CI A  
c olla ge n -i n d uce d art hritis 
C ma x  
ma xi m u m o bser ve d plas ma c o nce ntrati o n  
C M V  
c yt o me gal o vir us  
C N S  
ce ntral ner v o us s yste m  
Cr Cl  
creati ni ne cleara nce  
C R O  
C o ntract Researc h Or ga nizati o n  
C R P  
C -reacti ve pr otei n 
C S P  
cli nical st u d y pr ot oc ol  
C S R  
cli nical st u d y re p ort  
C T C A E  
C o m m o n T er mi n ol o g y Criteri a f or A d verse E ve nts  
C V E A C  
car di o vasc ular safet y e n d p oi nt a dj u dicati o n c o m mittee  
C X R  
c hest x-ra y 
C Y P  
c yt oc hr o me P 4 5 0  
D B P  
diast olic bl o o d press ure  
D M C  
Data M o nit ori n g C o m mittee  
D N A  
de o x yri b o n ucleic aci d  
D S S  
de xtra n s ulfate s o di u m  
E.c oli  
Esc h eric hi a c oli  
E C G  
electr ocar di o gra m 
e C R F  
electr o nic case re p ort f or m  
E T  
earl y ter mi nati o n  
E U  
E ur o pea n U ni o n  
E u dra C T  
E ur o pea n C li nical T rials D ata b ase  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2 6  
 
0 9 Se pte m ber 2 0 2 2  
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
F S H  
follicle -sti m ulati n g h or m o ne 
G C P  
G o o d Cli nical Practice  
GI  
g astr oi ntesti nal  
G L P  
Gala pa g os N V  
H B V  
he p atitis B vir us  
H C V  
he p atitis C vir us  
H D P E  
hi g h de nsit y p ol yet h yle ne  
H D L  
hi g h de nsit y li p o pr otei n  
h E R G  
h u ma n et her -a -g o -g o -relate d ge ne 
HI V  
h u ma n i m m u n o deficie nc y vir 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  
heart rate 
I A1/ 2  
first/sec o n d u n bli n de d i nteri m a nal ysis 
I B 
In vesti gat or’s B r oc h ure 
I B D 
i nfla m mat or y b o wel disease 
I C5 0 
half ma xi mal i n hi bit or y c o nce ntrati o n  
I C F 
i nf or me d c o nse nt f or m 
I C H 
I nter nati o nal C o u ncil f or Har m o nisati o n ( of T ec h nical Re q uire me nts f or 
P har mace uticals f or H u ma n Use)  
I E C 
i n de p e n de nt et hics c o m mittee 
I L 
interle u ki n  
I M P 
i n vesti gati o nal me dici nal pr o d uct 
I N D 
i n vesti gati o nal ne w dr u g 
I N R 
i nter nati o nal n or malize d rati o 
I R B 
i nstit uti o nal re vie w b oar d 
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 
j a n us ki nase 
L A M  
lactati o nal a me n orr hea met h o d 
L D L  
l o w de nsit y li p o pr otei n 
L H  
l utei nizi n g h or m o ne 
L L T  
l o w le vel ter m 
L T E  
l o n g ter m e xte nsi o n 
M A C E  
maj or a d verse car di o vasc ular e ve nts  
M C S  
Ma y o Cli nic Sc ore  
M C V  
mea n c or p usc ular v ol u me  
Me d D R A  
Me dical Dicti o nar y f or Re g ul at or y Acti vities  
M T X  
m et h otre xate  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2 7  
 
0 9 Se pte m ber 2 0 2 2  
N O E L  
n o -o bser ve d -effect -le vel 
N S AI Ds  
n o nster oi dal a nti -i nfla m mat or y dr u gs 
O & P  
o va & parasites  
O A Ts  
or ga nic a ni o n tra ns p orters  
O L  
o pe n la bel 
P -g p  
p -gl yc o pr otei n  
P D  
p har mac o d y na mic(s)  
P E G  
p ol yet h yle ne gl yc ol  
P G A  
P h ysicia n’s Gl o bal Assess me nt of disease acti vit y  
P K  
p har mac o ki netic(s)  
P T  
pr ot hr o m bi n ti me  
P T M  
place b o -t o-matc h  
P T T  
partial t hr o m b o plasti n ti me  
Q 1  
1st q uartile  
Q 3  
3r d q uartile  
R A  
r he u mat oi d art hritis 
R N A  
ri b o n ucleic aci d 
R R  
res pirat or y rate 
R T -P C R  
re verse tra nscri pti o n p ol y merase c hai n reacti o n 
S A D R  
seri o us a d verse dr u g reacti o ns 
S A E  
seri o us a d verse e ve nt 
S A P  
statistical a nal ysis pla n 
S B P  
s yst olic bl o o d press ure 
S D  
sta n dar d de viati o n 
S E S -C D  
Si m ple E n d osc o pic Sc ore f or Cr o h n’s Disease  
SI  
i nter nati o nal s yste m of u nits 
S O C  
sta n dar d of care 
S O P  
sta n dar d o perati n g pr oce d ure 
S S M T  
S p o ns or Safet y Ma na ge me nt T ea m  
S T A T  
si g nal tra ns d ucer a n d acti vat or of tra nscri pti o n 
S U S A R  
s us pecte d u ne x pecte d seri o us a d verse reacti o ns  
T B  
tu berc ul osis  
T E A Es  
treat me nt e mer ge nt a d verse e ve nts 
T N F α  
t u m or necr osis fact or al p ha 
T Y K  
t yr osi ne ki nase 
U C  
ulcerati ve c olitis  
U G T  
uri di ne 5’ -dis p h os p hate gl uc ur o n os yltra nsferase  
U L N  
u p per li mit of n or mal  
U S  
U nite d States  
vs.  
v ers us  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2 8  
 
0 9 Se pte m ber 2 0 2 2  
W B C  
w hite bl o o d cell  
W H O  
W orl d Healt h Or ga nizati o n  
 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2 9  
 
0 9 Se pte m ber 2 0 2 2  
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 disease (I B D) c o m prises 2 disti nct pat h ol o gic e ntities, ulcerati ve c olitis 
( U C) a n d Cr o h n’s diseas e ( C D). 
1. 1. 1.  
Ulcer ati ve C olitis  
U C is a c hr o nic, i nter mitte nt, rela psi n g diseas e c haracterize d b y i nfla m mati o n of t he c ol o nic 
m uc osa, w hic h is li mite d t o t he c ol o n a n d rect u m. T he disease c haracteristicall y c o m me nces i n 
t he rect u m a n d ma y e xte n d pr o xi mall y i n a n u ni nt err u pte d patter n i nt o t he c ol o n. It ca n i n v ol ve 
t he e ntire c ol o n ( p a n-c olitis), t he left c ol o n, or is olate d rect o -si g m oi d dise ase, wit h patie nts bei n g 
e q uall y distri b ute d i n t h ose 3 p he n ot y pes. I n t he U nite d States ( U S), t he pre vale nce of U C has 
bee n esti mate d t o be 2 3 8 per 1 0 0, 0 0 0 a d ults { Ka p pel ma n 2 0 0 7 } , w hereas E ur o pe has t he hi g hest 
re p orte d pre vale n ce at 5 0 5  per  1 0 0, 0 0 0 pers o ns f or U C . T he a n n u al i nci de nce of U C is 2 4. 3  per 
1 0 0, 0 0 0  pers o n -years i n E ur o p e a n d 6. 3 p er 1 0 0, 0 0 0  pers o n -years i n Asia { M ol o dec k y 2 0 1 2 } . 
T he i nci de nce a n d pre val e nce of U C a p pear t o be i nc reasi n g o v er ti me gl o ball y.  
T he hall mar k s y m pt o ms of U C are bl o o d y diarr hea, rect al ur ge n c y, a n d te nes m us. T he cli nical 
c o urse te n ds t o w a x a n d wa ne wit h peri o ds of re missi o n i nters perse d wit h peri o ds of acti ve 
disease. U C ma y als o be ass ociate d wit h e xtr a-i ntesti nal ma nifestati o ns i ncl u di n g oc ular lesi o ns, 
s ki n lesi o ns, art hritis, a n d pri mar y scler osi n g c h ol a n gitis. T he e x act pat h o p h ysi ol o g y is n ot 
k n o w n b ut i n ge n eral, ge netic pre dis p ositi o n i n c o nj u ncti o n wit h e n vir o n me ntal a n d s ocial 
fact ors (s u c h as hist or y of t o bacc o us e, me dicati o n hist or y, a n d ge o gra p h y) ma y i m pact 
de vel o p me nt of diseas e. Disc o or di nate d acti vit y of b ot h i n nate a n d a d a pti ve i m m u ne res p o nses 
i n c o m bi nati o n wit h e pit helial barrier defects a n d d ys bi osis lea d t o a n i nfla m mat or y casca de, 
res ulti n g i n cli nical si g ns a n d s y m pt o ms of U C { U n gar o 2 0 1 6 } .   
I n a d diti o n t o a b d o mi nal pai n a n d rectal blee di n g t hat b ot h i m pact acti vities of dail y li vi n g a n d 
q ualit y of life f or patie nts wit h U C, t he disease carries 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 rate of d e vel o pi n g c ol or ectal ca ncer 
i ncreas es wit h ti me. T he i nci de nce of c ol orectal ca ncer i n U C p atie nts is decreasi n g o ver ti me, 
partiall y d u e t o better c o ntr ol of i nfla m mati o n a n d c ol o n osc o pic s ur veilla nce { Bea u gerie 2 0 1 5 } . 
O v erall, U C patie nts still e x perie nce a n ele vat e d ris k of c ol orect al ca n cer; i n o ne meta -a n al ysis 
of p o p ulati o n base d c o h orts t he ris k was 2. 4 -f ol d { J ess 2 0 1 2} . T h us, U C re prese nts a seri o us, 
life-t hreat e ni n g dis ease f or w hic h ne w t h era pies are nee d e 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 ualit y of life, a n d re d uce t he ris k of c ol orectal ca ncer.  
Treat me nt of U C is de p e n de nt o n t he se verit y a n d t he l ocati o n of disease. G oals of treat me nt 
i ncl u de i m pr o ve d q ualit y of life, re d u cti 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 derate distal c olitis ma y be treate d wit h oral a mi n osalic yl ates, t o pical 
mesala mi ne, or t o pical st er oi ds { K or n bl ut h 2 0 1 0 } . F or m o derate diseas e, 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 d erat e t o se vere disease, p atie nts are c o m m o nl y treat e d wit h a t u m or 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3 0  
 
0 9 Se pte m ber 2 0 2 2  
necr osis fact or  al p ha ( T N F α) a nta g o nist i nf usi o n or i njecti o n, s uc h as i nfli xi ma b ( Re mica de ® ), 
a dali m u ma b ( H u mira ® ), or g oli m u mab ( Si m p o ni ® ). Ve d oliz u ma b ( E nt y vi o® ), a n i njecta ble 
i nte gri n α 4 β 7 m o n o cl o nal a nti b o d y, a n d t of aciti ni b ( Xelja nz® ), a J a n us ki nase (J A K) 
1/ 3  i n hi bit or, are i n dicate d f or a d ults wit h m o derat el y t o se v erel y acti ve U C. Uste ki n u ma b 
( Stelara® , C N T O 1 2 7 5; a n i nterleu ki n (I L) -1 2 a n d I L -2 3 m o n ocl o nal a nti b o d y), u pa daciti ni b 
(J A K i n hi bit or), etr oliz u ma b ( P R O 1 4 5 2 2 3; m o n ocl o nal a nti b o d y t ar geti n g t he β 7 s u b u nit of t he 
heter o di meric i nte gri ns α 4 β 7 a n d α E β 7), risa n kiz u ma b (I L -2 3 a nti b o d y) a n d oza ni m o d 
( R P C 1 0 6 3; selecti ve S 1 P 1 a n d S 1 P 5 rece pt or a g o nist) are c urre ntl y bei n g t este d i n P hase  3 
cli nical trials. Le u k oc yta p heresis t hera p y ma y be use d i n J a pa n { F u k u na ga 2 0 1 2 } . Des pite 
se veral classes of treat me nt 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, 
partic ularl y i n t he treat me nt of m o derat el y t o se v erel y acti ve dise ase. A ge nts wit h n o vel 
mec ha nis ms of acti o n t hat tar get t he i nfla m mat or y casca d e, wit h oral d osi n g a n d acce pta ble 
i m m u n o m o d ulat or y a n d he mat ol o gic effects, re m ai n t he m ost pr o misi n g o pti o n t o a d dress t hese 
u n met nee ds.  
1. 1. 2.  
Cr o h n’s Dise ase  
C D is a f or m of I B D ca use d b y i nfl a m mati o n of t he l u mi nal s urface of t he gast r oi ntesti nal tract 
t hat, i n c o ntrast t o U C, ca n e xte n d t hr o u g h t he f ull t hic k ness of t he gastr oi ntesti nal wall t o t he 
ser osal s urface. A n y se g me nt of t he gastr oi ntesti nal tract ma y be affecte d, a n d disc o nti n u o us 
re gi o ns of i n v ol ve me nt ma y o cc ur. C D is c h aract erize d b y p h e n ot y p e (i nfl a m mat or y, stri ct uri n g, 
or pe netr ati n g s u bt y pes) a n d b y l o cati o n a n d e xte nt of i n v ol ve me nt. T he i nci de nce a n d 
pre vale n ce of C D h a ve b ee n i ncreasi n g, wit h bi m o dal pea ks affecti n g y o u n g a d ults 
( 1 5 t o 3 5  years of a ge) a n d ol der a d ul ts a ge d 5 0 t o 7 0 years. T he o verall i nci de nce of C D i n t he 
N ort her n H e mis p here ra n ges fr o m 7 t o 2 0 per 1 0 0, 0 0 0 pers o n years, wit h E ur o pe ha vi n g t he 
hi g hest r e p orte d pre vale n ce at 3 2 2  per  1 0 0, 0 0 0 pers o ns.  I n t he U S a n d E ur o pe, u p t o 1. 5 milli o n 
i n di vi d uals ma y be affect e d, a n d C D i nci de nce is risi n g i n parts of Asia a n d t he Mi d dle  East 
{ M ol o dec k y 2 0 1 2 } . 
C D is a rela psi n g a n d re mitti n g dis or der c haracteri ze d b y diarr hea, a b d o mi nal pai n, wei g ht l oss, 
a n d t he passa ge of bl o o d or m uc us per rect u m. Strict ure f or m ati o n ca n res ult i n i ntesti nal 
o bstr ucti o n re q uiri n g s ur gic al ma na ge me nt. O ver ti me, patie nts wit h re peat e d s ur geries are at 
ris k f or de vel o pi n g s h ort b o wel s y n dr o me a n d/ or i ntesti nal fail ure. Pe netr ati n g diseas e is 
c haracteriz e d b y fist ula f or mati o n ( b o wel t o b o wel, b o wel t o s ki n, or b o wel t o a djace nt or ga n 
s uc h as bla d der or va gi na) t hat ma y als o re q uir e s ur gical ma na ge me nt. Pe netrati n g dise ase ca n 
ma nifest wit h i ntra -a b d o mi nal a bscess, a c o n diti o n w hic h ca n b e life t hreat e ni n g if n ot treate d 
earl y wit h s yste mic a nti bi otics. C D ma y affect ot her or ga n s yste ms lea di n g t o ras hes, j oi nt pai n 
a n d stiff ness, fe v er, a n d wei g ht l oss { Ba u m gart 2 0 1 2 } . T he ca us e of C D is p o orl y u n d erst o o d, 
h o we ver a c o m ple x i nter pla y of ge net ic pre dis p ositi o n, a berra nt i m m u ne acti vati o n, a n d earl y 
i nfecti o n d uri n g c hil d h o o d ma y b e i n v ol ve d. T he i m p orta nce of e n vir o n me ntal tri g gers is 
s u g geste d b y i n creasi n g i nci de nce s ee n d uri n g i n d ustrializati o n a n d wit h i m pr o ve d d o mestic 
h y gie n e a n d sa nitati o n. T his “ h y gie n e h y p ot hesis” has als o bee n i m plicate d i n vari o us ot her 
a ut oi m m u ne dis or ders { Ve nt ha m 2 0 1 3 } . 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3 1  
 
0 9 Se pte m ber 2 0 2 2  
T o assess disease s e verit y i n C D, a n u m ber of cli nical sc ori n g s yste ms are utilize d. T he C D AI is 
a o ne s uc h sc ori n g t o ol wit h sc ores ra n gi n g fr o m 0 t o o ver 6 0 0 base d u p o n a c o m p osite of 
s y m pt o ms (e g, a b d o mi nal pai n), si g ns (e g, a b d o mi nal mass), la b orat or y v al ues (ie, he mat o crit), 
a n d c o m plicati o ns (e g, art hritis/art hral gia), a m o n g ot her patie nt attri b utes. I n t his sc ori n g s yste m, 
patie nts wit h a sc ore > 2 2 0 are defi ne d as h a vi n g  m o deratel y t o se verel y acti ve disease; t hese 
patie nts c o m prise t he p o p ulati o n wit h t he greatest u n met me dical nee d. T h e C D AI ca n als o be 
use d t o deter mi ne h o w well a t hera p y is w or ki n g, wit h t hera pe utic re missi o n defi ne d as a C D AI 
of < 1 5 0 p oi nts { Di g n ass 2 0 1 0 } . 
T he Si m ple E n d osc o pic Sc ore f or Cr o h n’s Diseas e ( S E S -C D) was first v ali date d i n 2 0 0 4 a n d has 
bee n use d e xte nsi vel y i n cli nical trials. It m eas ures prese nce a n d size of ulcers, pr o p orti o n of 
s urface affect e d wit h ulcers, pr o p orti o n of s urface affecte d b y ot her l esi o ns, a n d t he pres e nce a n d 
se verit y of ste n otic lesi o ns { Da per n o 2 0 0 4 } . T h e b o wel is di vi de d i nt o se g me nts (ile u m, ri g ht 
c ol o n, tra ns vers e c ol o n, l eft c ol o n, a n d rect u m) a n d eac h se g m e nt is sc ore d i n di vi d uall y, t h e n t he 
se g me nt s c ores are s u m me d f or a t otal sc ore (ra n ge: 0 t o 6 0).  
O ver t he last deca d e, t hera pe utic g oals f or C D ha v e be g u n t o e xte n d be y o n d s y m pt o matic c o ntr ol 
a n d t o i ncl u de l o n g -ter m m uc osal a n d e n d osc o pi c re missi o n { C heifetz 2 0 1 3 }  i n or der t o sl o w 
d o w n or halt disease pr o gressi o n, a v oi di n g s ur geries a n d h os pitalizati o ns. Ris k assess me nt a n d 
pre dicti o n b y m ea ns of c o m ple x cli nical, bi oc he mical, a n d e n d osc o pi c mar kers ha ve b ec o me t h e 
ke y t o p atie nt ma na ge me nt, t hera p y o pti mizati o n, a n d pre dicti o n of t he t h era pe utic o utc o me a n d 
si de effects. C urre ntl y a vaila ble bi ol o gic t hera pies f or C D f oc us o n n e utrali zi n g c yt o ki n e acti vit y 
or alteri n g T -cell differe ntiati o n a n d h o mi n g. T hree m o n ocl o nal a nti b o dies w hic h i n hi bit t u m or 
necr osis fact or  al p ha ( T N F α), are c urre ntl y m ar ket e d f or t he treat me nt of C D: i nfli xi ma b 
( Re mica de® ), a d ali m u ma b ( H u mira®  [a p pr o ve d i n U S a n d E ur o pea n U ni o n { E U } ]), a n d 
cert oliz u ma b pe g ol ( Ci mzia ®  [a p pr o ve d i n U S]). Ve d oliz u ma b ( E nti v y o® ), a m o n ocl o nal 
a nti b o d y a gai nst α 4β 7 i nte gri n is als o a p pr o ve d f or m o deratel y t o se verel y acti ve C D. Rece ntl y, 
uste ki n u ma b ( Stelara ® ), a m o n ocl o nal a nti b o d y directe d a gai nst t he p 4 0 s u b u nit of I L-2 3 a n d a n 
a nta g o nist f or b ot h I L-1 2 a n d I L -2 3 si g nali n g, has bee n a p pr o ve d f or t he treat me nt of C D. 
Le u k o c yta p heresis t hera p y ma y b e use d i n J a pa n { F u k u na ga 2 0 1 2 } . Ot her i n vesti gati o nal 
treat me nt a p pr o ac hes i n cl u de t he a d mi nistrati o n of c yt o ki n es t o sti m ulate i n nate i m m u nit y, t he 
use of pre bi otics t o alter t he g ut fl ora, a n d bl o c ki n g t he I L -6 si g nali n g pat h wa y { It o 2 0 0 4, 
K orze ni k 2 0 1 6 } . Ne w treat me nts bei n g test e d i n cli nical trials i ncl u de J A K i n hi bit ors 
(e g, u pa daciti ni b), a n d ne w bi ol o gic a ge nts s uc h as I L -2 3 p 1 9 a nta g o nists (e g, risa n kiz u ma b) a n d 
a m o n ocl o nal a nti b o d y directe d a gai nst β 7 i nte gri n (e g, etr oliz u ma b). W hile t he i ntr o d ucti o n of 
bi ol o gic t hera pies has si g nifica ntl y i m pr o ve d res p o nse rates i n patie nts wit h m o deratel y t o 
se verel y acti ve C D, l o n g-ter m or d ura ble re missi o n rates are still l o w at a p pr o xi matel y 2 0 %. 
Ma n y p atie nts recei vi n g bi ol o gic t hera pies de v el o p ne utralizi n g a nti b o dies wit h res ulti n g l oss of 
effic ac y. T hes e a ge nts ma y b e ass oci ate d wit h s pecific safet y iss ues i n cl u di n g b ut n ot li mite d t o 
a na p h yla xis, i ncrease d ris k of i nfecti o n i ncl u di n g pr o gressi ve m ultif ocal le u k oe nce p h al o pat h y, 
a n d li ver i nj ur y. Safe a n d effecti ve treat me nt o pti o ns w hic h ma y be c o n v e nie ntl y a d mi nistere d i n 
a c hr o nic s etti n g w o ul d pr o vi de a si g nifica nt treat me nt a d va nce f or p atie nts wit h m o deratel y t o 
se verel y acti ve C D. 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3 2  
 
0 9 Se pte m ber 2 0 2 2  
1. 2.  
Fil g oti ni b  ( G S-6 0 3 4)  
1. 2. 1.  
Ge ner al I nf or m ati o n  
J a n us ki nases (J A Ks) are i ntracell ular c yt o plas mic t yr osi ne ki nas es ( T Y Ks) t hat tra ns d uce 
c yt o ki ne si g nali n g fr o m me m bra ne rece pt ors t hr o u g h si g nal tra ns d u cer a n d acti vat or of 
tra nscri pti o n ( S T A T) t o t he n ucle us of cells. J A K i n hi bit ors bl oc k t he si g nali n g of vari o us 
c yt o ki nes, gr o wt h fact ors, a n d h or m o nes, i ncl u di n g t he pr o -i nfla m mator y c yt o ki ne I L -6. 
F o ur  differe nt t y pes of J A Ks are k n o w n, J A K 1, J A K 2, J A K 3, a n d T Y K 2 w hic h i nteract wit h 
differe nt s ets of me m bra ne rece pt ors. I n hi biti o n of J A Ks is a pr o misi n g t hera pe utic o pti o n f or a 
ra n ge of i nfl a m mat or y c o n diti o ns i ncl u di n g r he u m at oi d art hritis ( R A) a n d C D. Fil g oti ni b 
( G S-6 0 3 4, f or merl y k n o w n as G L P G 0 6 3 4) is a p ote nt a n d selecti ve i n hi bit or of J A K 1. T he 
c o m p o u n d has s h o w n g o o d preli mi nar y efficac y i n s u bjects wit h R A a n d t h ose wit h C D i n 
P hase  2 st u dies.  
F or f urt her i nf or m ati o n o n fil g oti ni b, refer t o t he c urre nt I n vesti gat or’s Br oc h ure (I B).  
1. 2. 2.  
Precli nic al P h ar m ac ol o g y a n d T o xic ol o g y  
Fil g oti ni b a n d its meta b olite, G S -8 2 9 8 4 5, ha ve bee n e xte nsi vel y c h aracteri ze d i n n o ncli nical 
st u dies. T his pr o gra m i ncl u des cell ular ass a ys d e m o nstrati n g pote nc y a n d selecti vit y of t he 
c o m p o u n d a gai nst J A K 1; efficac y st u dies i n rats a n d mice; re peat d ose t o xicit y st u dies ( u p t o 
2 6  wee ks i n t he rat a n d 3 9 wee ks i n t he d o g), i n vitr o a n d i n vi v o safet y p har mac ol o g y a n d 
ge n etic t o xic ol o g y st u dies, carci n o ge nici t y st u dies i n rats a n d i n tra ns ge nic ( T gras H 2) mice, a n d 
re pr o d ucti ve t o xic ol o g y st u dies i n rats a n d ra b bits. A d diti o nal t o xic ol o g y st u dies c o n d ucte d 
i ncl u de p h ot ot o xicit y st u dies a n d d ose-ra n ge fi n di n g st u dies i n s u p p ort of a defi niti ve rat j u ve nile 
t o xicit y st u d y. A d efi niti ve j u ve nile t o xic ol o g y st u d y i n rats is o n g oi n g. 
1. 2. 2. 1.  
N o ncli nical P har mac ol o g y  
I n cell ular assa ys, fil g oti ni b i n hi bits J A K 1 si g nali n g wit h I C5 0 val ues of ≥ 1 7 9  n M, a n d 
de m o nstrates 3 0 -f ol d sel ecti vit y o ver J A K 2 i n a h u ma n w h ole bl o o d assa y. Fil g oti ni b has bee n 
pr ofile d a gai nst 4 5 1 ki nases a n d it is hi g hl y s electi ve f or J A K 1; o nl y 2. 5 % of ki nases were 
i n hi bite d ≥ 5 0 % at 5 0-f ol d hi g her c o nce ntrati o n t h a n I C5 0 f or J A K 1. Br oa d rece pt or pr ofili n g 
( ~ 7 0 rece pt ors, i o n c ha n n els, tra ns p orters a n d e nzy mes) di d n ot re veal a n y off -tar get lia bilities of 
t he c o m p o u n d. Fil g oti ni b de m o nstrate d hi g h p ote nc y i n t he rat c olla ge n-i n d uce d art hritis ( CI A) 
m o del as well as i n t he m o use de xtra n s ulfate s o di u m ( D S S) -i n d uce d c olitis m o del, t he latter of 
w hic h is detai le d bel o w. T he maj or h u ma n meta b olite of fil g oti ni b G S-8 2 9 8 4 5 e x hi bits a si milar 
J A K 1 selecti vit y pr ofile b ut is a p pr o xi matel y 1 0-f ol d less p ote nt as c o m pare d t o pare nt fil g oti ni b 
i n vitr o. 
T he effi cac y of fil g oti ni b was e val uat e d i n a pr o p h yl actic setti n g  of t he c hr o nic m o use D S S 
m o del i n t w o se parate st u dies. B ot h st u dies e val uat e d oral d ose le v els of 1 0 a n d 3 0  m g/ k g o nce 
dail y. I n a d diti o n t o assess me nts of cli nical sc ore ( disease acti vit y i n de x [ D AI] a n d c ol o n lesi o n 
sc ore), s er u m mar kers of i nfla m mati on, i m m u n o hist oc he mical a nal ysis, a n d e x pressi o n of 
vari o us c he m o ki nes a n d c yt o ki nes k n o w n t o be altere d i n C D a n d U C patie nts were als o 
e val uate d i n t he distal c ol o n of t hese mice.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3 3  
 
0 9 Se pte m ber 2 0 2 2  
I n b ot h st u dies, t he D AI sc ore, w hic h t a kes i nt o acc o u nt b o d y wei g ht l oss, rectal blee di n g, a n d 
st o ol c o nsiste nc y, w as re d uce d b y fil g oti ni b i n a d ose-de pe n d e nt ma n ner, de m o nstrati n g t hat 
fil g oti ni b pr otecte d mic e a gai nst c olitis i n d uce d b y D S S. Hist ol o g y of t he c ol o n re veale d a 
fil g oti ni b-me diate d d ose -relate d re d ucti o n i n c ol o n lesi o n sc ore, c orrelati n g wit h re d ucti o ns i n 
D AI sc ore.  
A d diti o nal e n d p oi nts e val uate d acr oss t he D S S c olitis m o del st u dies c o nfir me d t he s u p pressi o n 
of vari o us i nfla m mat or y mar kers i ncl u di n g ser u m le vels of C -reacti ve pr ot ei n ( C R P) a n d 
m yel o per o xi dase ( M P O) a n d e x pressi o n of I L -6 a n d T N F α ( b y R T -P C R) b y fil g oti ni b. 
I m m u n o hist oc he mical a n al ysis of t he c ol o n c o nfir me d i n hi biti o n of t he J A K-S T A T pat h wa y b y 
fil g oti ni b as e vi de n ce d b y a re d ucti o n of D S S-i n d uce d S T A T 3 p h os p h or yl ati o n. 
1. 2. 2. 2.  
Safet y P h ar mac ol o g y  
Fil g ot i ni b a n d G S-8 2 9 8 4 5 ha d n o rele va nt effects o n car di o vas c ular para m eters 
( h u ma n et her -a-g o -g o -relate d ge ne [ h E R G] a n d d o g tele m etr y st u dies), a p art fr o m a sli g ht 
n o n -a d vers e i ncrease i n h eart rate a n d arterial press ure wit h G S -8 2 9 8 4 5 at e x p os ures 8 -f ol d t hat 
of t he pea k s er u m c o nce ntrati o n ( C ma x ) i n s u bjects wit h C D treate d wit h 2 0 0 m g o nce dail y 
fil g oti ni b. T here were n o rele va nt effects o n electr ocar di o gra m ( E C G) a n d Q T. Fil g oti ni b a n d 
G S -8 2 9 8 4 5 ha d n o effects o n t he res pirat or y s yste m a n d ce ntral n er v o us s yste m ( C N S). 
1. 2. 2. 3.  
Ke y N o ncli nical Distri b uti o n, Meta b olis m, a n d E xcreti o n Data  
Fil g oti ni b de m o nstrates g o o d oral bi oa vaila bilit y i n mice, rats, d o gs, a n d mi ni -pi gs b ut less i n 
m o n ke ys. Plas ma pr otei n bi n di n g is l o w ( <  7 0 %) i n all s pecies, i ncl u di n g h u ma ns.  
T he  p har mac o ki netics ( P K) of fil g oti ni b is ge n erall y d ose pr o p orti o nal wit h o ut ge n d er 
differe n ces. N o acc u m ulati o n occ urs wit h re p eate d d osi n g. T he mea n ter mi nal half -life after oral 
a d mi nistrati o n is 4 h o urs a n d 5 h o urs i n rats a n d d o gs, res pecti vel y.  
I n t he rat, fil g oti ni b s h o we d a ra pi d a n d e ve n distri b uti o n t hr o u g h o ut t he b o d y. Hi g h 
c o nce ntr ati o ns were o bs er ve d o nl y i n t he gastr oi ntesti nal ( GI) tract a n d uri nar y bla d der. 
Fil g oti ni b d oes n ot pe netrate i nt o C N S tiss ues. T he distri b uti o n of fil g oti ni b i n dicat es s o me 
affi nit y f or mela ni n -c o nt ai ni n g tiss ues.  
E x creti o n is nearl y c o m plete wit hi n 2 4 h o urs (rat) a n d 4 8 h o urs ( d o g) p ost -d osi n g. I n t he rat, 
fecal a n d uri nar y e x creti o n acc o u nte d f or 4 0 % a n d 5 3 % of t he a d mi nistere d d ose, res pecti vel y, 
wit h a bile secret i o n of a b o ut 1 5 %. I n t h e d o g, fecal e xcreti o n was t he pri m ar y r o ute of e x creti o n, 
acc o u nti n g f or 5 9 % of t h e a d mi nistere d d ose, wit h uri nar y e x creti o n acc o u nti n g f or 2 5 %.  
I n vitr o met a b olis m st u dies i n all s pecies re veal e d o ne maj or meta b olite ( G S-8 2 9 8 4 5). T he 
f or mati o n of G S-8 2 9 8 4 5 is me diate d b y car b o x yl esterases ( C E S) a n d is n ot de pe n de nt o n 
c yt o c hr o me P 4 5 0 ( C Y P).  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3 4  
 
0 9 Se pte m ber 2 0 2 2  
I n vitr o e x peri me nts ha ve s h o w n t hat dr u g-dr u g i nteracti o ns wit h fil g oti ni b a n d G S -8 2 9 8 4 5 are 
u nli kel y. T here is n o i n hi biti o n or i n d ucti o n of C Y Ps or uri di ne 5’ -di p h os p h o -
gl uc ur o n os yltra nsferase ( U G Ts), a n d n o rele va nt i n hi biti o n of ke y dr u g tr a ns p orters, i ncl u di n g 
or ga nic a ni o n tra ns p orters ( O A Ts), b y fil g oti ni b or G S -8 2 9 8 4 5. O C T 2 was i n hi bite d b y b ot h 
fil g oti ni b (I C5 0: 8. 7 µ M) a n d G S-8 2 9 8 4 5 ( IC 5 0: 6 7 µ M). T he cli nical rel e va nce of t he I C5 0 val ues 
f or i n hi biti o n of O C T 2 will be f urt her e v al uate d. M A T E 1 was als o w ea kl y i n hi bite d b y fil g oti ni b 
(I C5 0: 9 4 µ M) a n d G S-8 2 9 8 4 5 ( I C5 0: > 1 0 0 µ M). Fil g oti ni b was f o u n d t o be a s u bstrate of P-g p.  
1. 2. 2. 4.  
N o ncli nical T o xic ol o g y  
I n re peat oral d ose t o xicit y st u dies i n b ot h rats a n d d o gs, t he pri mar y tar get tiss ues i de ntifie d f or 
fil g oti ni b were t he l y m p h oi d tiss ues w hic h are e x pecte d bas e d o n t he p har mac ol o g y of J A K 
i n hi biti o n. A d diti o nal fil g oti ni b-rel ate d fi n di n gs were o bs er ve d i n t he mal e re pr o d ucti ve or ga ns 
of b ot h s pecies, a n d i n t h e i ncis or teet h of rats o nl y. Effects o n t he l y m p h oi d s yste m were f ull y 
re versi ble. Testic ular t o xicit y de m o nstrat e d partial re versi bilit y; h o w e ver, s per m c o u nts 
re mai ne d l o w. W he n usi n g t he mea n e x p os ure ( A U C) at t he N O A E Ls f or t he m ost se nsiti ve 
s pecies (t he d o g), t he e x p os ure mar gi ns c o m pare d t o a 2 0 0 m g o nce dail y d ose of fil g oti ni b i n 
C D s u bjects are 2. 5, 1. 9, a n d 3. 6 -f ol d f or t h e 2 6-wee k a n d 3 9 -wee k c hr o nic t o xicit y st u dies a n d 
t he 39 -wee k t ar get e d e x p os ure t o xicit y st u d y, res pecti vel y.  
G S -8 2 9 8 4 5 -relat e d fi n di n gs i n ge n eral i n t he re peat-d ose t o xicit y st u dies w ere ge n erall y si milar 
t o t h ose of t he pare nt fil g oti ni b, h o we ver n o testic ular t o xicit y was n ote d f oll o wi n g 
a d mi nistrati o n of G S -8 2 9 8 4 5.  
Fil g oti ni b a n d G S -8 2 9 8 4 5 were n o n -ge n ot o xic w he n e val uat e d i n t he bacterial m uta ge nicit y 
assa y, t he i n vitr o m o use l y m p h o ma m uta ge nicit y assa y, a n d t he rat b o ne m arr o w micr o n ucle us 
assa y.  
I n e m br y ofet al de vel o p m e nt st u dies, fil g oti ni b a n d G S-8 2 9 8 4 5 ca use d e m br y olet halit y a n d 
terat o ge nicit y i n rats a n d ra b bits. Terat o ge nicit y was o bser ve d at e x p os ures sli g htl y hi g her or 
si milar t o t he h u ma n e x p os ure at 2 0 0 m g o nce  d ail y of fil g oti ni b i n s u bjects wit h C D. 
A d mi nistrati o n of fil g oti ni b di d n ot affect  fe male fertilit y b ut i m paire d fertilit y was o bser v e d i n 
male rats at e x p os ures a p pr o xi matel y 1 2 -f ol d t he h u ma n e x p os ure at 2 0 0 m g of fil g oti ni b i n 
s u bjects wit h C D. G S-8 2 9 8 4 5 di d n ot ha ve a n y effects o n fertilit y para met ers i n eit her male or 
fe male rats. 
I n a n i n vitr o p h ot ot o xicit y st u d y i n 3 T 3 cells, t he meta b olite G S-8 2 9 8 4 5 was p ositi ve f or 
p h ot ot o xic p ote ntial a n d res ults wit h fil g oti ni b were e q ui v ocal. A f oll o w -u p i n vi v o rat 
p h ot ot o xicit y assa y re veale d a lac k of p h ot ot o xic p ote ntial f or b ot h c o m p o u n ds.  
1. 2. 3.  
Cli nic al Tri als of Fil g oti ni b  
A n o ver vie w of e x p os ure a n d cli nical st u dies c o n d ucte d wit h fil g oti ni b is a vaila ble i n t he I B.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3 5  
 
0 9 Se pte m ber 2 0 2 2  
1. 2. 3. 1.  
P hase 2 S t u d y i n Cr o h n’s Disease ( G L P G 0 6 3 4-C L -2 1 1, FI T Z R O Y)  
A P hase 2, ra n d o mize d, d o u ble -bli n d, place b o -c o ntr olle d, m ultice nte r st u d y wit h fil g oti ni b was 
perf or me d i n s u bje cts wit h acti ve C D wit h e vi de nce of m uc osal ulcerati o n { Ver meir e 2 0 1 7 } . I n 
Part 1, a t otal of 1 7 4 s u bjects were ra n d o mize d ( 3: 1) t o recei ve eit her fil g oti ni b 2 0 0 m g o nce 
dail y or plac e b o f or 1 0 w ee ks. Base d o n t heir cli nical res p o nse i n Part 1, s u bjects i n Part  2 eit her 
c o nti n ue d t heir c urre nt treat me nt or were reassi g n e d t o a differe nt treat me nt f or a n a d diti o nal 
1 0  wee ks.  
T he effi cac y of fil g oti ni b was assesse d b y e val uati n g cli nical  re missi o n ( defi ne d as C D AI 
sc ore <  1 5 0), cli nical r es p o nse ( defi ne d as a d ecrease i n C D AI of at least 1 0 0 p oi nts fr o m 
baseli ne), a n d e n d osc o pi c res p o nse ( defi ne d as a decrease of at least 5 0 % fr o m baseli ne i n t he 
S E S -C D sc ore).  
T he pri mar y e n d p oi nt of t he  st u d y w as met: at Wee k 1 0, 6 0 of 1 2 8 s u bjects ( 4 6. 9 %) w h o 
recei v e d fil g oti ni b ac hie v e d cli nical re missi o n vers us 1 0 of 4 4 s u bjects ( 2 2. 7 %) w h o recei ve d 
place b o, a differe nce of 2 4. 1 % ( p -val ue = 0. 0 0 7 7). Fil g oti ni b treat me nt w as ass ociate d wit h 
i ncreas es in t he pr o p orti o n of s u bjects wit h cli nical re missi o n, cli nical res p o nse, a n d e n d osc o pi c 
res p o nse c o m p are d wit h place b o. 
O verall, t he safet y pr ofil e of fil g oti ni b i n C D s u bjects was c o nsiste nt wit h pri or st u dies.  
F or a d diti o nal details a b o ut t he effic ac y a n d s afet y of fil g oti ni b i n C D, refere nce is ma de t o t he 
I B. 
1. 2. 3. 2.  
P hase 2 b/ 3 S t u dies i n Ulcerati ve C olitis ( G S-U S -4 1 8 -3 8 9 8, S E L E C TI O N)  
T hese are P hase 2 b/ 3, d o u ble -bli n d, ra n d o mize d, place b o -c o ntr olle d st u dies e val uati n g t h e 
effic ac y a n d s afet y of fil g oti ni b i n t he i n d ucti o n a n d mai nte na nce of re missi o n i n s u bjects wit h 
m o deratel y t o se verel y acti ve U C. Pr ot oc ol G S -U S -4 1 8 -3 8 9 8  c o nsists of i n d ucti o n a n d 
mai nte na nce st u dies, e nr olli n g bi ol o gic-n aï ve a n d bi ol o gic -e x perie n ce d s u bjects. T he pri mar y 
e n d p oi nt of t he i n d ucti o n st u d y f or eac h c o h ort is t he effi cac y of fil g oti ni b c o m pare d t o place b o 
i n esta blis hi n g e n d osc o p y/ blee di n g/st o ol re missi o n at Wee k 1 0. T he pri mar y e n d p oi nt of t he 
mai nte na nce st u d y f or eac h c o h ort is t he efficac y of fil g oti ni b at esta blis hi n g 
e n d osco p y/ blee di n g/st o ol re missi o n at Wee k 5 8.  
I n M a y 2 0 1 8, a n i n de p e n de nt Data M o nit ori n g C o m mittee (D M C ) c o n d uct e d a n i nteri m f utilit y 
a nal ysis after 3 5 0  s u bjects ha d c o m plete d t he i n d u cti o n st u dies. T he D M C rec o m me n de d t hat t he 
trial pr ocee d as pla n ne d. 
1. 3.  
R ati o n ale f or t his St u d y a n d Pr o p ose d I B D P o p ul ati o n  
O ver t he last deca d e, c ha n ges i n I B D treat me nt strate gies, acc o m pa nie d b y a d va nces i n dr u g 
de vel o p me nt a n d t he a d diti o n of tar gete d bi ol o gical t hera pies, h a ve greatl y i m pr o ve d t he 
o utc o mes f or s u bjects wit h I B D. Des pite t hese de vel o p me nts, t hera pe utic c halle n ges re mai n. A 
s u bset of patie nts res p o n d t o c urre ntl y a v aila ble bi ol o gic t hera p y w hile ot h ers l ose res p o ns e o ver 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3 6  
 
0 9 Se pte m ber 2 0 2 2  
ti me or are i nt olera nt o ver ti me. T here is a n u n m et me dical nee d f or si m ple, orall y a d mi nistere d 
t hera pies wit h n o vel a n d tar gete d mec ha nis ms of acti o n t hat ca n effecti vel y i m pr o ve t he disease 
c o urse w hile b ei n g s afe a n d well t olerate d. Fil g oti ni b is a n orall y a d mi nistere d, s mall m olec ule 
i n hi bit or of J A K 1, a n i ntracell ular t yr osi ne ki n ase d ysreg ulate d i n s u bjects wit h i nfla m mat or y 
dis or ders i ncl u di n g I B D. Fil g oti ni b has de m o nstrat e d a fa v ora ble s afet y a n d t olera bilit y pr ofile i n 
a P hase 2 st u d y i n s u bje cts wit h m o deratel y t o se v erel y acti ve C D, w here it was efficaci o us at 
i n d uci n g cli nic al re missi o n at 1 0 wee ks ( Secti o n 1. 2. 3. 1 ). Fil g oti ni b is prese ntl y bei n g e v al uate d 
i n P hase 3 st u dies i n C D, U C, a n d R A. Fil g oti ni b is als o bei n g e val uated i n ps oriatic art hritis, 
a n k yl osi n g s p o n d ylitis, Sj ö gre ns s y n dr o me, c uta ne o us l u p us er yt he mat os us, u veitis a n d l u p us 
me m bra n o us ne p hritis.  
W hile pr o vi di n g a treat me nt o pti o n f or s u bjects wit h m o deratel y t o se verel y acti ve U C or C D, 
t he prese nt st u d y see ks t o e val uate t he i m pact, if a n y, of fil g oti ni b o n s per mat o ge n esis i n 
h u ma ns . T he o bser ve d effects of fil g oti ni b o n t he testes are c o nsiste nt acr oss t he n o n-cli nical 
s pecies teste d, wit h o bser vati o ns of hist o pat h ol o gical c ha n ges i n testes a n d e pi di d y mi des, 
t o get her wit h re d u cti o ns i n s per m c o u nts a n d re d u ce d fertilit y i n t he rat. A mec ha nistic st u d y i n 
t he rat s u g geste d a re v ersi ble direct i m pact o n t he ge n es i n v ol ve d i n cell c ycle. A d ose of 2 0 0  m g 
o nce dail y of fil g oti ni b res ults i n a n esti mate d mea n cli nical A U C of 2. 6 7 μ g•h/ m L i n s u bjects 
wit h C D, w hic h re prese nts a n e x p os ure mar gi n of 2. 5, 1. 9, a n d 3. 6 -f ol d w h e n c o nsi deri n g t he 
mea n A U C i n male d o gs at t he n o -o bser ve d -effect -le vels ( N O E Ls) i n t he 2 6-wee k a n d 3 9 -wee k 
c hr o nic t o xicit y st u dies, a n d 3 9 -wee k tar gete d e x p os ure t o xicit y st u d y, res pecti vel y. T he prese nt 
st u d y see ks t o assess t he i m pact o n me n of fil g oti ni b at 2 0 0 m g, t he hi g hest pr o p ose d d ose i n t he 
P hase  3 pr o gra m, assesse d b y t he pr o p orti o n of s u bjects w h o e x perie nce a ≥ 5 0 % decrease  i n 
s per m c o nce ntrati o n fr o m Baseli ne w h e n c o m pare d wit h place b o after 1 3 -wee ks of t hera p y . T h e 
pr o p ose d st u d y d esi g n a n d s u bject p o p ulati o n f or G S -U S -4 1 8 -4 2 7 9 ha ve b ee n selecte d t o 
ge n erat e cli nical safet y d ata w hic h w o ul d be br oa dl y a p plica ble t o patie nt p o p ul ati o ns wit h I B D 
a n d ot her c hr o nic i nfla m mat or y dise ases ot her t h a n I B D.   
T he prese nt st u d y ( Gilea d St u d y C o d e G S-U S -4 1 8 -4 2 7 9; Gala pa g os St u d y C o de: 
G L P G 0 6 3 4 -C L -2 2 8 ) has bee n desi g ne d i n acc or da nce wit h F D A’s G ui da n ce f or I n d ustr y: 
Testic ular t o xicit y: E v al uati o n D uri n g Dr u g De v el o p me nt ( Oct o ber 2 0 1 8)  a n d has als o bee n 
g ui de d b y C H M P Scie ntific A d vice E M E A/ H/ S A/ 2 3 8 0/ 1/ F U/ 2/ 2 0 1 6/III, 0 1 A pril 2 0 1 6) a n d 
i n p ut recei ve d b ase d o n disc ussi o ns wit h F D A a n d re g ulat ors i n t he E U. T h e st u d y p o p ulati o n 
will c o nsist of  s u bjects wit h eit her m o deratel y t o s e verel y acti ve U C ( defi n e d as a Ma y o Cli nic 
Sc ore of ≥ 6, wit h e n d osc o pic s u bsc ore ≥ 2 a n d P h ysicia n’s Gl o bal Assess me nt ≥ 2) or 
m o deratel y t o se verel y acti ve C D ( defi ne d as a C D AI sc ore of ≥ 2 2 0 a n d S E S -C D of 
≥ 6  [ or ≥ 4  i n cases of C D li mite d t o t he ile u m a n d/ or ri g ht c ol o n]). S u bjects m ust ha ve 
de m o nstrate d a pri or treat me nt fail ure/i nt olera nce t o U C or C D t hera p y, res pecti vel y b ut will be 
all o we d t o re mai n o n per mitte d t hera p y, wit h t he e x ce pti o n of s ulfasalazi ne w hi c h will be 
pr o hi bite d d ue t o k n o w n ris ks of oli g os per mia a n d i nfertilit y { P har macia & U pj o h n C o 2 0 1 4 } . 
S u bjects will be stratifie d b y bas eli ne s per m c o n ce ntrati o n a n d t y p e of u n derl yi n g I B D 
(ie, U C  vers us C D) . I n a d diti o n, s u bjects will als o be stratifie d b y use of m et h otre x ate 
( M T X; yes or n o) gi ve n its p ote ntial i m pact o n s per mat o ge nesis. T here ha v e bee n case re p orts of 
re versi ble oli g os per mia a n d az o os per mia wit h treat me nt wit h M T X { S uss ma n 1 9 8 0 } , t h o u g h a 
s mall case seri es i n 2 6 me n wit h ps oriasis a ge d 3 3 t o 5 2 treate d wit h M T X at a d ose of 2 5  m g 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3 7  
 
0 9 Se pte m ber 2 0 2 2  
wee kl y di d n ot re veal a n y i m pact of M T X o n mea n s per m c o u nt m otilit y a n d m or p h ol o g y  { El -
Be heir y 1 9 7 9 } .  
S u bjects wit h mil dl y decrease d t est oster o ne will als o be i ncl u de d i n t he st u d y. T he i n ci de nce of 
l o w test oster o ne i ncreases wit h i ncreasi n g a ge . T h e cr u de i n ci de nce of a n dr o ge n d eficie nc y i n 
1  lar ge c o h ort (t he Massa c h usetts Male A gi n g St u d y) was 1 2. 3 % o verall, b ut i ncrease d wit h 
i ncreasi n g a ge: 5. 9 % at 4 0 t o 4 9 years, 1 1. 2 % at 5 0 t o 5 9 years, a n d 2 3. 3 % at 6 0 t o 7 0  years 
{ Ara uj o 2 0 0 4 } . O ne c o h ort de m o nstrate d a pre val e nce of h y p o g o na dis m i n me n a ge d  4 5 a n d 
ol der ( base d o n t otal test oster o ne <  3 0 0 n g/ d L) of 3 8. 7 % { M ulli ga n 2 0 0 6 } . T he prese nt st u d y 
will i ncl u de me n wit h test oster o ne le vels at or a b o ve 8 0 %  of n or m al, gi ve n t he e x pecte d 
i nci de nce of h y p o g o n a dis m i n t he u p per a ge ra n ge of t he st u d y p o p ulati o n. 
1. 3. 1.  
R ati o n ale f or t he O utc o me Me as ures  
W hile n o si n gle s per m para meter ca n pre dict fertilit y p ote ntial, s per m c o nce ntrati o n ma y b e 
c o nsi dere d t he m ost relia bl y q ua ntifia ble para meter t hat has p ote ntial utilit y i n pr o vi di n g 
i nf or mati o n a b o ut male fertilit y{ U. S. De part me nt of Healt h a n d H u ma n Ser vices ( D H H S) 
2 0 1 8 } . S per m c o nce ntr ati o n ma y als o be c o nsi dere d t he m ost i m p orta nt para meter of testic ular 
d ysf u n cti o n { Si k ka 2 0 1 6 } . T he prese nt st u d y will e val uate t he re d ucti o n i n s per m c o nce ntrati o n 
of ≥ 5 0 % or m ore fr o m b aseli ne at 1 3  wee ks as t h e pri mar y e n d p oi nt i n acc or da nce wit h t he 
F D A draft g ui da nce. Si g nifica nt variati o ns i n s per m para meters are e x pecte d i n me n; a t hres h ol d 
of a ≥ 5 0 %  re d ucti o n, is c o nsi dere d t he a p pr o pri ate t hres h ol d t o acc o u nt f or n or mal varia bilit y 
a n d is c o nsiste nt wit h pri or st u dies e val uati n g i m pact of p ote ntial testic ular t o xi ns { Hellstr o m 
2 0 0 8 , Hellstr o m 2 0 0 3 , J ar vi 2 0 0 8, Si k ka 2 0 1 4 } . S u bsta ntial i ntra- a n d i nter - s u bject variati o n ca n 
occ ur partic ularl y i n s per m c o u nt i n patie nts wit h a n d wit h o ut fertilit y  iss u es; in o ne c o h ort, 
s per m c o u nts ra n ge d o ver a n or der of ma g nit u de i n a si n gle h ealt h y  patie nt o ver ti me { Keel 
2 0 0 6 } . T w o se me n sa m ples will be c ollecte d f or e val uati o n at eac h ti me p oi nt d uri n g t his st u d y, 
wit h c o ntr olle d a bsti ne nce peri o ds bef ore eac h s a m ple c ollecti o n; l o n ger or s h orter a bsti ne n ce 
peri o ds ma y ha ve a n  i m pact o n q ualit y of sa m ple. Ejac ulate v ol u me a n d s p er m n u m ber are 
mar ke dl y re d u ce d d uri n g peri o ds of hi g h ejac ul ati o n fre q ue n c y { Ol derei d 1 9 8 4 } . Si g nifica nt 
varia bilit y is n ote d e v e n i n healt h y s u bjects { W orl d Healt h O r ga nizati o n ( W H O) 1 9 9 9, W orl d 
Healt h Or ga niz ati o n ( W H O) 2 0 1 0 } . A d diti o nal s per m para meters at 1 3 w ee ks will be e val u ate d 
as sec o n dar y e n d p oi nts i n ali g n me nt wit h t he F D A g ui d a n ce.  
T he pri mar y e n d p oi nt at Wee k 1 3 will e na ble a direct assess me nt vers us pl ace b o i n s u bjects wit h 
m o deratel y t o se verel y acti ve U C or C D. E n d p oi nts at 2 6 wee ks of t hera p y ha ve bee n c h ose n f or 
sec o n dar y a nal yses t o ass ess i m pact after 2 f ull s per mat o genesis c ycles i n acc or da n ce wit h dr aft 
g ui da n ce, w hic h rec o m m e n ds treat me nt f or 2 6 wee ks f or dr u gs t hat are c hr o nicall y d ose d. T he 
2 6 -wee k e n d p oi nt will als o all o w assess me nt of t h e i m pact of l o n ger -ter m t hera p y o n se m e n 
para meters, gi ve n t he e x pectati o n f or c hr o nic d osi n g of t hera p y i n t he real w orl d setti n g. Fi nall y, 
i n t he prese nt st u d y, t otal m otilit y, w hic h is c o nsi d ere d t o be m ore c o nsiste ntl y meas ure d acr oss 
o bser vers, will r e mai n as a sec o n dar y e n d p oi nt.   
I n t his st u d y t he Ma y o Cli nic Sc ore ( M C S) will be utilize d t o defi ne m o deratel y t o se v erel y 
acti ve U C f or t he p ur p os e of eli gi bilit y. T he mi ni m u m M C S of 6 (i ncl u di n g e n d os c o pic a n d 
p h ysicia n gl o bal assess me nt sc ores of 2 or 3) e ns ures t hat s u bjects will ha ve e n d o sc o pic e vi de nce 
of disease (i e, acti ve dise ase), ha v e acti ve s y m pt o ms (e g, bl o o d i n t he st o ol or i ncrease d st o ol 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3 8  
 
0 9 Se pte m ber 2 0 2 2  
fre q ue n c y), a n d b e deter mi ne d b y t he pr o vi d er t o ha ve m o deratel y t o se verel y acti ve U C. Aft er 
ra n d o mizati o n, t he partial M C S will be utilize d to deter mi ne Res p o n der, N o n -res p o n der, a n d 
Disease W orse ni n g stat us f or s u bjects wit h U C.  
T he C D AI sc ore a n d S E S -C D will be j oi ntl y use d t o defi ne m o deratel y t o se verel y acti ve C D, 
e ns uri n g t h at s u bjects wit h C D will ha ve acti ve s y m pt o ms of t he c orres p o n di n g se verit y as well 
as e n d osc o pic e vi de nce of acti ve dise ase f or eli gi bilit y. After ra n d o mizati o n, t he C D AI sc ore 
will be use d t o deter mi ne Res p o n der, N o n -res p o n der, a n d Disease W orse ni n g stat us f or s u bj ects 
wit h C D.  
T his st u d y is base d u p o n real -w orl d o u t patie nt cli nical practice, w here ce ntr al e n d osc o p y d oes 
n ot pla y a r ole i n i nitiati o n of t hera p y, a n d w here cli nical si g ns/s y m pt o ms (a n d la bs as 
a p plica ble) a n d a pr o vi d er’s assess me nt are a d e q u ate t o assess t hera pe utic res p o nse or 
n o n -res p o nse. T his a p pro ac h has bee n e n d orse d b y t he T or o nt o C o nse ns us i n 2 0 1 5 { Bressler 
2 0 1 5 } . Safet y a n d t olera bilit y will be assesse d b y t he e val uati o n of a d v erse e ve nts ( A Es), 
selecte d cli nic al la b orat or y p ara m eters, vital si g ns, p h ysical e x a mi nati o ns, a n d E C Gs all of 
w hic h are st a n dar d s afet y e val uati o ns i n cli nical de vel o p me nt. All s u bjects w h o e x perie nce a 
≥ 5 0 % decrease i n s per m c o nce ntr ati o n a n d/ or t otal m otilit y a n d/ or m or p h ol o g y will be f oll o we d 
f or o ne or m ore s per m at o ge n esis c ycles, u p t o 1 year as nee de d, t o ass ess f or s per m para meter 
re versi bilit y. 
1. 3. 2.  
R ati o n ale f or t he C h oice of D ose a n d D osi n g I nter v al  
T he 2 0 0 m g o n ce dail y d ose le vel of fil g oti ni b is c urre ntl y t he hi g hes t cli nical d ose bei n g 
e val uate d i n P hase 3 st u dies of R A, U C, a n d C D . I n P hase 2 trials i n R A, p o ole d data wit h a n 
e x p os ure-res p o nse a nal ysis de m o nstrate d a d ose-de pe n de nt i ncreas e i n efficac y u p t o 2 0 0  m g 
t otal dail y d ose. I n t h e P hase 2 st u d y of C D, s u bjects treate d i n t he 2 0 0  m g ar m s h o we d fa v ora ble 
res p o nse a n d re missi o n rates ( 4 7 % re missi o n o ver 2 3 % place b o a n d 5 9 % res p o nse o ver 4 1 % 
place b o). T h ese res ults are c o nsiste nt wit h t he relati o ns hi p o bser ve d bet wee n fil g oti ni b 
e x p os ures a n d i n hi biti o n of p S T A T 1 acti vati o n (e x -vi v o) f oll o wi n g si n gle a n d m ulti ple fil g oti ni b 
d oses, w here ma xi mal i n hi biti o n of p S T A T 1 acti vati o n ( ~ 7 8 %) was ac hie ve d at or a b o v e 2 0 0  m g 
t otal dail y d ose a n d i nter me diate i n hi biti o n ( ~ 4 7 %) at 1 0 0 m g { Na m o ur 2 0 1 5 } . p S T A T 1 data, i n 
c o nj u ncti o n wit h c o nsi derati o ns ar o u n d t he mar gi n f or n o ncli nical testic ular fi n di n gs, s u g gests 
assessi n g d os es a b o ve 2 0 0  m g is n ot i n dicate d.  
1. 4.  
Ris k/ Be nefit Assess me nt f or t he St u d y  
I nfla m mat or y b o wel diseases are pr o gressi ve a n d p ote ntiall y life-t hr eate ni n g dis or ders wit h fe w 
treat me nt o pti o ns, ma n y of w hic h res ult i n pri mar y or sec o n dar y n o nres p o nse. I nfla m mat or y 
b o wel disease ma y l ea d t o i ncreas e d ris k of gastr oi ntesti nal mali g na ncies, i m pair me nt i n q ualit y 
of life, a n d ulti mate nee d f or life -alteri n g s ur ger y. C urre nt treat me nt o pti o ns are li mite d i n t heir 
a bilit y t o esta blis h m uc osal heali n g a n d cli nical re missi o n a n d ha ve si g nifica nt safet y a n d 
effic ac y li mitati o ns; f or e x a m ple, bi ol o gics ha ve si g nifica nt i m m u n o ge ni c ris ks, a n d ster oi ds are 
ass ociate d wit h i ncrease d m or bi dit y a n d m ortalit y. Re missi o n rates are ge nerall y l o w w he n 
c o m pare d t o place b o rates acr oss m ost t hera pies f or I B D. T here re m ai ns s u bsta ntial u n met nee d 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3 9  
 
0 9 Se pte m ber 2 0 2 2  
i n I B D, partic ularl y i n m o derate t o se v ere dis ease. T he lifel o n g nat ure of I B D i ncreases t h e 
pr o ba bilit y t hat s u bjects ha ve c ycl e d t hr o u g h vari o us t hera pies, lea vi n g fe w a p pr o ve d o pti o ns.  
N o ncli nical st u dies i n rats a n d d o gs i de ntifie d l y m p h oi d tiss ues a n d testes as tar get or ga ns f or 
fil g oti ni b i n l o n g-ter m re peat-d ose t o xicit y st u dies. Alt h o u g h decrease d l y m p h oc yte n u m b ers 
o bser ve d i n n o ncli nical st u dies ha ve n ot bee n s ee n i n cli nical st u dies, he mat ol o gical assess me nt 
will be perf or me d t hr o u g h o ut t he prese nt st u d y t o e ns ure t his p ote ntial ris k is a p pr o priatel y 
m o nit ore d. I n b ot h r ats a n d d o gs, micr osc o pic fi n di n gs i n t he testes i ncl u d e d ger m cell de pleti o n 
a n d de ge n erati o n, wit h re d uce d s per m c o nte nt a n d i ncreas e d cell de bris i n t he e pi di d y mis a n d 
re d ucti o n i n fertilit y i n m ale rats. T he d o g was deter mi ne d t o be t he m ost se nsiti ve s pecies. W he n 
usi n g t he A U C at t he N O A E Ls f or d o gs i n t he 2 6 -wee k a n d 3 9 -wee k c hr o nic t o xicit y st u dies, 
a n d t he 3 9-wee k tar gete d e x p os ure t o xicit y st u d y, t he e x p os ure mar gi ns c o m pare d wit h t he 
hi g hest pr o p os e d cli nical d ose  of 2 0 0 m g o n ce d ail y are 2. 5, 1. 9, a n d 3. 6 -f ol d res pecti vel y, i n 
s u bjects wit h C D. T o assess t his p ote ntial ris k t o male fertilit y, t he m ale safet y cli nical st u d y 
descri be d h erei n is pla n n e d t o e x a mi ne t he effect of fil g oti ni b (if a n y) o n s per m/ejac ulat e 
para meters. Male s u bjects w h o e nr oll will be a p pr o priatel y c o nse nte d vi a t he I C F w herei n ris k 
la n g u a ge is hi g hli g hte d. I m paire d s per mat o ge nesis is c o nsi dere d t o be a p ot e ntial ris k f or 
fil g oti ni b. Refer t o t he I B f or f urt her i nf or mati o n a b o ut n o ncli nical a n d cli nical testic ular 
fi n di n gs. 
Fil g oti ni b has s h o w n a n i ncreas e d ris k i n e m br y ofetal malf or mati o ns i n rats a n d ra b bits at 
e x p os ures si milar t o, or sli g htl y hi g her t ha n, e x p os ures ass ociat e d wit h a 2 0 0 m g o nce dail y d ose 
i n C D s u bjects. As a res ult, hi g hly effecti ve c o ntr ace pti o n a n d male c o n d o ms will be re q uire d f or 
male s u bjects wit h fe mal e part ners of c hil d beari n g p ote ntial, w hic h is e x pecte d t o miti gate t his 
ris k. 
J A K i n hi biti o n is e x pecte d t o i ncrease t h e ris k of i nfecti o n base d o n m ec ha nis m of acti o n. Acr oss 
t he gl o bal st u dies i n fil g oti ni b, i n ge neral, acti ve tr eat me nt ar ms ha v e i ncrease d i nci de nces of 
i nfecti o n versus place b o. I n t he prese nt pr ot oc ol, treat me nt i nterr u pti o n a n d disc o nti n uati o n 
c o nsi derati o ns s urr o u n di n g i nfecti o ns are i n c or p orate d,  a n d sites a n d i n v esti gat ors will be trai n e d 
re gar di n g s uc h circ u msta nces. All s u bjects will be scree n e d f or t u b erc ul osis ( T B), a n d s u bjects 
wit h acti ve or u ntreate d l ate nt i nfecti o ns will be e x cl u de d. Mali g na nc y h as bee n re p orte d i n 
s u bjects o n fil g oti ni b; i n t he prese nt trial, s u bjects will be re q uire d t o ha ve u p t o date c ol orectal 
ca ncer s ur veilla n ce i n a cc or da nce wit h l ocal g ui d eli nes, a n d s u bjects wit h rece nt mali g na n cies 
will be e x cl u de d as o utli ne d i n t he i ncl usi o n criteria. F or f urt her details a b o ut  i nfecti o ns a n d 
mali g na n cies, pleas e refere nce t h e I B.  
T he p ote ntial be nefits of J A K i n hi biti o n i ncl u de i m pr o ve me nt i n cli nical s y m pt o ms a n d m uc osal 
a n d e n d osc o pic h eali n g. J A K i n hi biti o n ma y be efficaci o us i n t he treat me nt of I B D base d o n 
res ults fr o m t he P hase 2 st u d y ( FI T Z R O Y) of s u bjects wit h C D. I n FI T Z R O Y, a n i ncrease i n 
mea n he m o gl o bi n c o nce ntrati o n was o bser v e d, wit h o ut differe nce bet wee n fil g oti ni b a n d 
place b o. N o cli nicall y si g nifica nt c ha n ges fr o m baseli ne i n mea n ne utr o p hil c o u nts or li ver 
f u ncti o n tests were o bs er ve d at 1 0 wee ks. Fil g oti ni b treate d s u bjects s h o we d a n i ncrease i n hi g h 
de nsit y li p o pr otei ns ( H D L) a n d n o si g nifica nt c ha n ge i n l o w de nsit y li p o pr otei ns ( L D L). Li pi d 
a n d he m o gl o bi n effects r e prese nt p ote ntial b e nefits i n t his p o p ulati o n . 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  4 0  
 
0 9 Se pte m ber 2 0 2 2  
O verall cli nical fi n di n gs a n d la b orat or y c ha n ges re p orte d wit h fil g oti ni b are c o nsiste nt wit h 
J A K 1 i n hi biti o n. Base d o n P hase 2 data t he e x pecte d be nefit of usi n g fil g oti ni b as pr o p ose d i n 
t his st u d y is c o nsi dere d t o o ut wei g h a n y ass ociat e d ris ks. I n a dditi o n, t he s u bject p o p ulati o n i n 
t he prese nt st u d y will c o nse nt t o a ris k of p ote ntiall y per ma n e nt i nfertilit y, t h us i n di vi d ual male 
s u bjects i n c o nj u ncti o n wit h t he treati n g p h ysicia n ma y e val uate t he be nefit-ris k pr ofile of 
fil g oti ni b. A lac k of res p o nse c o nti n ge nc y fr o m Wee k  1 3 o n war d i n t he c urre nt st u d y, tar geti n g 
N o n -res p o n d ers at W ee k 1 3 a n d a n y s u bject w h o e x perie nces Diseas e W orse ni n g t hereafter, will 
e na ble earl y access t o acti ve dr u g or sta n dar d of care tr eat me nt w he n cli nicall y i n dicate d. T his 
resc ue a p pr oac h, t he pr o visi o n of best s u p p orti ve care, a n d t he li mite d st u d y d urati o n, ma kes t he 
use of place b o et hicall y acce pta bl e f or t he s p ecifie d d urati o n.    
A n e xter nal m ulti disci pli nar y D M C, i ncl u di n g a n e x pert i n male fertilit y, will be a p p oi nte d t o 
m o nit or t he st u d y .  
T he D M C has  m o nit or e d  t he st u d y u ntil t he date of pr ot oc ol a me n d me nt 6, i ncl u di n g t he dat a f or 
t he sec o n d u n bli n de d i nteri m a nal ysis (I A 2). As of a me n d me nt 6, t he D M C will be 
dec o m missi o ne d. Details o n t he D M C’s r ole ha v e bee n descri be d i n a s pecific c harter. T h e 
D M C’s r ole will be tra nsferre d t o t he i nter nal S p o ns or Safet y Ma na ge me nt Tea m  ( S S M T). T he 
S S M T is n ot i n v ol ve d i n t he c o n d uct of t he st u d y a n d will e val uate safet y d ata t hr o u g h o ut t he  
re mai n der of t he st u d y as part of c o nti n u o us safet y o versi g ht acr oss t he fil g oti ni b pr o gra m. 
Ta ki n g all of t hese c o nsi derati o ns i nt o acc o u nt wit h res pect t o t he fil g oti ni b pr o gra m, t he earl y 
si g nals f or effi cac y d e m o nstrate d i n a P hase 2 cli nical trial i n C D, as well as t he be ne fici al 
fi n di n gs i n n o ncli nical m o dels of disease a n d t he o verall safet y, t olera bilit y, a n d P K 
c haracteristics of fil g oti ni b el uci date d t o date, t here is a fa v ora ble be n efit -ris k pr ofile f or t his 
a ge nt i n c o nti n ue d de v el o p me nt as a treat me nt f or U C a n d C D. T he o verall be nefit -ris k bal a nce 
of t his st u d y is c o nsi dere d fa v ora bl e.  
F or a d diti o nal i nf or mati o n a b o ut t he ris ks of fil g oti ni b, refere nce t h e latest versi o n of t he 
fil g oti ni b I B. 
1. 5.  
C o m pli a nce  
T his st u d y will be c o n d u cte 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 all a p plica ble re g ulat or y re q uire m e nts.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  4 1  
 
0 9 Se pte m ber 2 0 2 2  
2.  
O B J E C TI V E S  
T he pri mar y o bje cti ve of t his st u d y is:  
•  T o e val uate t he effect of fil g oti ni b o n testic ular f u ncti o n as defi ne d b y t he pr o p orti o n of 
s u bjects wit h a ≥ 5 0 % decreas e fr o m b as eli ne i n s per m c o nce ntrati o n at Wee k  1 3  
T he sec o n d ar y o bjecti ves of t his st u d y i ncl u de:  
•  T o e val uate t he effect of fil g oti ni b o n testic ular f u ncti o n as defi ne d b y t he pr o p orti o n of 
s u bjects wit h a ≥ 5 0 % decreas e fr o m b aseli ne i n s per m c o nce ntrati o n at Wee k  2 6  
•  T o e val uate t he effect of fil g oti ni b o n s per m t otal m otilit y at Wee ks  1 3 a n d 2 6  
•  T o e val uate t he effect of fil g oti ni b o n t otal s per m c o u nt at Wee ks  1 3 a n d 2 6  
•  T o e val uate t he effect of fil g oti ni b o n t he c ha n ge fr o m baseli ne i n s per m c o nce ntrati o n at 
Wee ks 1 3 a n d 2 6  
•  T o e val uate t he effect of fil g oti ni b o n ejac ulat e v ol u me at Wee ks  1 3 a n d 2 6  
•  T o e val uate t he effect of fil g oti ni b o n s per m m or p h ol o g y at Wee ks  1 3 a n d 2 6  
T he e x pl orat or y o bj ecti v es of t his st u d y i ncl u de:  
•  T o e val uate t he re versi bilit y of o bser ve d  effects of fil g oti ni b o n testic ular f u ncti o n i n s u bjects 
w h o e x perie nce a ≥ 5 0 % decrease i n s per m c o nce ntrati o n, a n d/ or m otilit y a n d/ or m or p h ol o g y  
•  T o e val uate t he effect of fil g oti ni b o n se x h or m o nes, i ncl u di n g l utei nizi n g h or m o ne ( L H), 
f ollicle sti m ulatin g h or m o ne ( F S H), i n hi bi n B, a n d t otal test oster o ne at Wee ks  1 3 a n d  2 6  
•  T o e val uate t he s afet y a n d t olera bilit y of fil g oti ni b  
•  T o c haracteriz e t he plas ma p har mac o ki n etics ( P K) of fil g oti ni b a n d its meta b olite 
( G S-8 2 9 8 4 5, f or merl y  
)  
C CI


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  4 2  
 
0 9 Se pte m ber 2 0 2 2  
3.  
S T U D Y D E SI G N  
T his i s a ra n d o mize d, d o u ble-bli n d, place b o -c o ntr olle d P hase 2 st u d y i n a d ult males wit h 
m o deratel y t o se verel y acti ve U C , or m o derat el y t o se verel y acti ve C D , w h o ma y b e o n 
pr ot oc ol -s pecifi e d c o nc o mita nt t hera p y.  
U p t o 2 5 0  males bet wee n t he a ge of 2 1 a n d 6 5 ye ars (i ncl usi ve) at t he ti me of c o nse nt will be 
ra n d o mize d t o recei ve u p t o 2 6 wee ks of fil g oti ni b 2 0 0 m g or place b o -t o-m atc h ( P T M ) fil g oti ni b 
2 0 0  m g o nce dail y, t o e ns ure a p pr o xi matel y 2 0 0 s u bjects are e val ua ble.  
Ra n d o mizati o n will be stratifie d acc or di n g  t o t he t y p e of I B D (ie, U C vers us C D), b y c o nc urre nt 
use of M T X ( yes or n o), a n d b y s p er m c o n ce ntrati o n meas ure d at Scree ni n g (“ Baseli ne”) 
acc or di n g t o t he f oll o wi n g strat a:  
•  1 5 t o 2 5 milli o n/ m L  
•  >  2 5 t o 5 0 milli o n/ m L 
•  >  5 0 milli o n/ m L  
Male s u bjects wit h m o de ratel y t o se verel y acti ve I B D w h o pr o vi d e writte n i nf or me d c o nse nt will 
be scree ne d t o det er mi ne eli gi bilit y as p er t he i ncl usi o n a n d e x cl usi o n criteria (see Secti o n  4. 2  
a n d 4. 3 , res pecti vel y). T h e Scree ni n g p eri o d will be u p t o 4 5 da ys , a n d ma y be e xte n de d i n 
c o ns ultati o n wit h t he  m e dical m o ni t or. 
T he assess me nts t o be perf or me d at eac h visit are detaile d i n t he st u d y pr oce d ures ta ble 
(A p pe n di x  2 ). A sc he matic of t he st u d y d esi g n is pr o vi de d bel o w.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  4 3  
 
0 9 Se pte m ber 2 0 2 2  
Fi g ure  3 -1 . 
St u d y Sc he m a  
 
T here are 5 disti nct parts t o t he st u d y w hic h s u bjects ma y e nter de p e n di n g u p o n t he i n di vi d ual 
res p o nse of t he u n d erl yi n g I B D t o assi g ne d treat m e nt a n d/ or o bser ve d c ha n ges i n se m e n 
para meters. T he 5 p arts w hic h are d escri b e d i n t he f oll o wi n g s ecti o ns c o m prise of t he f oll o wi n g:  
1)  Part A ( Da y 1 t hr o u g h W ee k 1 3 St u d y Visit ) 
2)  Part B ( After Wee k 1 3 t hr o u g h Wee k 2 6 St u d y Visit ) 
3)  O pe n -La b el Fil g oti ni b P hase  
4)  M o nit ori n g P hase  
5)  L o n g T er m E xte nsi o n  
T he st u d y p arts are descri be d i n t he f oll o wi n g secti o ns.  
S u bjects will visit t he cli nical st u d y ce nter t o b e e val uate d f or cli nical a n d l a b orat or y assess me nts 
at Scree ni n g, D a y 1, Wee k 2, Wee k 4, Wee k 8, a n d Wee k  1 3 , i ncl u di n g seme n sa m ple c ollecti o n 
d uri n g  Wee k 1 3  visits . S u bjects w h o c o nti n ue o n bli n de d treat me nt after t h e first 1 3 wee ks of 
treat me nt will ret ur n f or Wee k 2 0 a n d Wee k 2 6 assess me nts , i ncl u di n g se m e n sa m ple c ollecti o n 
d uri n g  Wee k 2 6  visits . 






Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  4 6  
 
0 9 Se pte m ber 2 0 2 2  
As a b o ve, after t he first 1 3 wee ks of e x p os ure t o bli n de d st u d y dr u g t h ose s u bjects w h o are 
dee me d N o n -res p o n d ers at W ee k 1 3 or t h ose w h o meet Disease W orse ni n g criteria after 
Wee k  1 3 a n d pri or t o Wee k  2 6 ma y q ualif y f or e ntr y i nt o t he O L Fil g oti ni b P hase a n d ret ur n f or 
st u d y assess me nts at O L Da y 1, O L Wee k 2, O L Wee k 4, O L Wee k 8, a n d O L  Wee k  1 3. After 
e x p os ure t o 1 3  wee ks of O L  fil g oti ni b i n t he O L  Fil g oti ni b  P hase , t he s u bject’s I B D res p o ns e 
stat us will a gai n be d eter mi ne d usi n g t he partial M C S (i n t he case of U C) or C D AI sc ore (i n t he 
case of C D), a n d s per m para meters will be e val u ate d t o deter mi ne w het her a pre -s p ecifie d 
de crease t hr es h ol d has bee n met:  
•  All s u bjects w h ose s per m para meters meet a pre -s pecifie d decrease t hr es h ol d, re gar dless of 
Res p o n der stat us, will disc o nti n ue O L  fil g oti ni b, c o m plete a safet y f oll o w-u p visit 3 0  da ys 
after last st u d y dr u g d ose,  a n d e nter t he M o nit ori n g P hase.  
•  S u bjects w h o e x perie nce Disease W orse ni n g d uri n g O L  fil g oti ni b treat me nt a n d w h ose 
s per m para m eters d o n ot meet a pre-s pecifie d decrease t hr es h ol d will disc o nti n ue O L  
fil g oti ni b, c o m plete E arl y T er mi nati o n (E T ) a n d a safet y f oll o w -u p vis it 3 0 da ys after l ast 
st u d y dr u g d ose.  
•  S u bjects w h o d o n ot e x perie nce Diseas e W orse ni n g, a n d are R es p o n ders at O L Wee k 1 3 
after e x p os ure t o 1 3  wee ks of O L  fil g oti ni b, a n d w h ose s per m para meters d o n ot meet a 
pre -s pecifie d decrease t hres h ol d, will c o nti n ue recei vi n g O L  fil g oti ni b as p art of t he L T E.  
•  S u bjects w h o d o n ot e x perie nce Diseas e W orse ni n g, b ut are N o n-res p o n ders after e x p os ure 
t o 1 3 wee ks of O L  fil g oti ni b, a n d w h ose s per m p ara meters d o n ot meet a pre-s pecifi e d 
decrease t hr es h ol d, will disc o nti n ue O L  fil g oti ni b a n d c o m plete a s afet y f oll o w -u p visit 
3 0  da ys after l ast st u d y dr u g d os e.  
Fi g ure  3 -5 . 
M o nit ori n g P h ase ( u p t o 5 2 wee ks)  
 
All s u bjects w h o e nter t h e M o nit ori n g P hase will u n der g o se me n e val uati o ns e ver y 1 3  wee ks 
fr o m t he da y of st u d y dr u g disc o nti n uati o n, f or u p t o 5 2 wee ks or u ntil Re versi bilit y is met, 
w hic he ver is ac hie v e d first. S u bjects will be offere d l ocall y a p pr o ve d S O C t hera p y d uri n g t he 
M o nit ori n g P hase . 




Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  4 8  
 
0 9 Se pte m ber 2 0 2 2  
•  E ver y 1 3 wee ks d uri n g t he M o nit ori n g P hase (if a p plica ble)  
•  E ver y 1 3 wee ks d uri n g t he L T E  
I n s elect i nsta nces w here t he se me n sa m ple wit h q uesti o ne d val ue(s) is f o u n d t o be 
n o n -assessa ble or i n vali d (e g, c ollecti o n wit h o ut a d here nce t o ejac ulati o n -free peri o ds; 
i nterc urre nt ill ness or de h y drati o n  at ti me of c ollecti o n; i nc o m plete ca pt ure of se me n sa m ple;  
a n d/ or sa m ple pr ocessi n g or se me n a n al ysis t hat d e viates fr o m sta n d ar dize d pr oce d ure) , a 
t hir d se me n sa m ple, w he n i n dicate d, m ust be c ollecte d wit hi n 1 4 da ys of t he pri or sa m ple, 
wit h a n ejac ulati o n free p eri o d of ≥ 4 8 h o urs a n d ≤ 7 da ys . All decisi o n s of  retesti n g a n y 
se me n/s per m para meter (ie, o btai ni n g a t hir d se me n sa m ple at a n y of t he a b o ve ti me p oi nts) 
m ust be c o nfir me d b y t he S p o ns or Me dical M o nit or or desi g nee  bef ore t he retest . 
3. 1.  
St u d y Tre at me nts  
U p t o 2 5 0 s u bjects will be ra n d o mize d i n a 1: 1 rati o  ( wit hi n strata) t o recei ve fil g oti ni b 2 0 0 m g 
o nce dail y or P T M fil g oti ni b 2 0 0  m g o nce d ail y.  
3. 2.  
D ur ati o n of Tre at me nt  
T he d urati o n of tr eat me nt is a p pr o xi matel y u p t o 2 6 wee ks of bli n de d st u d y dr u g a n d u p t o 
1 3  wee ks of O L  fil g oti ni b (if eli gi ble). S u bse q ue ntl y, f or s u bjects q ualif yi n g, t his will be 
f oll o we d b y an  L T E lasti n g u p t o  1 9 5  wee k s. S u bjects w h ose s per m para meters meet a 
pre -s pecifie d decrease t hres h ol d at a n y ti me d uri n g t he st u d y will disc o nti n ue st u d y dr u g a n d 
s h o ul d be ma na ge d wit h all o we d sta n dar d of care t hera p y. T hes e s u bjects will be f oll o we d i n t he 
M o nit ori n g P hase of t he st u d y, f or u p t o 5 2 w ee ks or u ntil Re versi bilit y 
(see D efi niti o n  of  Ter ms ) of all para m eters meeti n g s per m decreas e t hres h ol d is met, w hic he ver 
is ac hie ve d first .  
3. 3.  
Criteri a f or I nterr u pti o n or Disc o nti n u ati o n of St u d y Tre at me nt  
3. 3. 1.  
St u d y Dr u g I nterr u pti o n C o nsi der ati o ns  
T he m e dical m o nit or or d esi g nee s h o ul d be c o ns ulte d pri or t o st u d y dr u g i nterr u pti o n , w he n 
me dicall y feasi ble. St u d y dr u g i nterr u pti o n s h o ul d be c o nsi dere d i n t he f oll o wi n g cir c u msta nces:  
•  I nterc urre nt ill ness t hat w o ul d, i n t he j u d g me nt of t he i n vesti gat or, affect assess me nts of 
cli nical stat us t o a si g nifi ca nt de gree.  
•  S u bject is sc he d ule d f or electi ve or e mer ge n c y s ur ger y (e x cl u di n g mi n o r s ki n pr oce d ures 
u n der l ocal or n o a nest hesia); ti mi n g of st u d y dr u g i nterr u pti o n s h o ul d be deter mi ne d i n 
c o ns ultati o n wit h t he m e dical m o nit or or desi g n ee.    
•  A n y s u bject w h o de v el o ps a ne w i nfecti o n d uri n g t he st u d y s h o ul d u n der g o pr o m pt a n d 
c o m plete di a g n ostic testi n g a p pr o priate f or a n i m m u n oc o m pr o mise d i n di vi d ual, a n d t he 
s u bject s h o ul d be cl osel y m o nit ore d. 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  4 9  
 
0 9 Se pte m ber 2 0 2 2  
•  
After bec o mi n g a ware of a la b orat or y c ha n ge re prese nti n g m o derate re nal fail ure (esti mate d 
creati ni ne cleara nce [ Cr Cl] ≥3 5 m L/ mi n a n d < 6 0 m L/ mi n per C oc kcr oft -Ga ult [ C C & G] 
f or m ula) at a n y ti me d uri n g t he st u d y, t he f oll o wi n g acti o ns s h o ul d be ta ke n a n d 
d oc u me nte d:  
⎯ Esta blis h p ossi ble u n derl yi n g c o n diti o n a n d i nitiate a p pr o pri ate acti o n t o res ol ve . 
⎯ Retest Cr Cl wit hi n 8 wee ks . 
⎯ Caref ull y c o nsi der i n di vi d ual be nefit/ris k of c o nti n uati o n of fil g oti ni b 2 0 0 m g o nce dail y 
i n relati o n t o t he o bser vati o n. 
⎯ If c o nti n uati o n of fil g oti ni b 2 0 0 m g o nce d ail y is n ot c o nsi dere d a p pr o priate, i nterr u pt 
treat me nt u ntil retest c o nfir ms Cr Cl ≥6 0 m L/ mi n. 
⎯ T he  pri nci pal i n vesti gat or/ de p ut y s h o ul d ass ess i n di vi d ual patie nt be nefit/ris k wit h 
re gar ds t o re-i nitiati o n of treat me nt after re p eat or pr ol o n ge d i nterr u pti o ns, or if 
re-i nitiati o n is n ot c o nsi dere d a p pr o priate. C o ns ult ati o n wit h t he S p o ns or m e dical 
m o nit or or desi g n ee is pr eferre d i n t hese sit uati o ns. 
 
D uri n g t h e ti me of st u d y dr u g i nterr u pti o n, s u bject s are t o c o nti n ue wit h St u d y Visit  partici pati o n  
a n d c o m plete st u d y pr oce d ures a n d assess me nts, dee me d me dicall y a p pr o priate b y t he 
i n vesti gat or.  
After st u d y dr u g i nterr u pti o n, pri or t o res u m pti o n of st u d y dr u g, t h e i n vesti gat or s h o ul d disc uss 
t he case wit h t he m e di cal m o nit or or desi g nee . 
T he me dical m o nit or s h o ul d c o ns ult t he me dical lea der as nee de d.  
3. 3. 2.  
St u d y Dr u g Disc o nti n u ati o n C o nsi der ati o ns  
T he m e dical m o nit or or d esi g nee 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 , w he n 
me dicall y feasi ble.  
St u d y dr u g s h o ul d 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 o p p ort u nistic i nfecti o n  
•  A n y s eri o us i nfecti o n t hat re q uires a nti micr o bial t hera p y or h os pitalizati o n, or a n y i nfecti o n 
t hat meets seri o us a d vers e e ve nt (S A E ) re p orti n g criteria 
•  Fe brile n e utr o pe nia (te m perat ur e >  3 8. 3 ° C or a s ustai ne d te m perat ur e of >  3 8  ° C f or m ore 
t ha n 1 h o ur) wit h a bs ol ute ne utr o p hil c o u nt of < 1, 00 0/ m m 3 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5 0  
 
0 9 Se pte m ber 2 0 2 2  
•  S y m pt o matic a ne mia (e g, si g ns/s y m pt o ms i ncl u di n g pall or, s h ort ness of breat h, ne w h eart 
m ur m ur, pal pitati o ns, let har g y, fati g ue) wit h he m o gl o bi n <  7. 5  g/ d L, or if tra nsf usi o n is 
i n dicate d re gar dless of h e m o gl o bi n val ue 
•  C o m plicate d her pes z oster i nfe cti o n ( wit h m ulti -der mat o mal, disse mi nate d, o p ht hal mic, or 
C N S i n v ol ve me nt) 
•  E vi de nce of acti ve H C V d uri n g t he st u d y, as e vi de nce d b y H C V R N A p ositi vit y  
•  E vi de nce of acti ve H B V d uri n g t he st u d y, as e vi de nce d b y H B V D N A p ositi vit y  
•  A n y t hr o m b o e m b olic e ve nt t ha t meets S A E re p orti n g criteria 
•  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 
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 h e s u bject’s best 
i nterest 
•  A ≥ 5 0 % decreas e  fr o m Baseli ne ( base d o n t h e mea n of 2 se p arat e se me n s a m ples c ollecte d 
at t he Scree ni n g visit ) i n s per m c o nce ntrati o n, a n d/ or m otilit y a n d/ or m or p h ol o g y  
•  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 t o t he pr ot oc ol  
•  Disc o nti n uati o n of t he st u d y at t he re q uest of t h e S p o ns or, 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) 
•  S u bject’s use of pr o hi bite d c o nc urre nt t hera p y  m ay tri g ger st u d y disc o nti n uati o n; 
c o ns ultati o n s h o ul d  be ma de wit h t he m e dical m o nit or or desi g n ee  
•  W orse ni n g of U C or C D re q uiri n g i nte nsificati o n of t hera p y b e y o n d w hat is all o we d i n t he 
pr ot oc ol or re q uiri n g t he use of a pr o hi bite d me dicati o n  
•  S u bjects wit h ne wl y p ositi ve (c o n vert e d) Q ua nti F E R O N ®  [ or ce ntrall y re p orte d e q ui vale nt 
assa y] T B test a n d a n y s u bject wit h acti ve T B s h o ul d be disc o nti n ue d fr o m st u d y dr u g.  
•  A n y of t he bel o w d escri b e d a b n or mal la b orat or y c ha n ges  occ urri n g at a n y o ne ti me , a n d 
c o nfir me d b y re peat testi n g (refer t o g ui deli nes detaile d i n A p pe n di x  8 ):   
⎯ 2  se q ue ntial ne utr o p hil c o u nts < 0. 7 5 x 1 0 9 cells/ L ( 7 5 0 ne utr o p hils/ m m 3)  
⎯ 2  se q ue ntial platelet c o u nts < 7 5. 0 x 1 0 9 cells/ L ( 7 5, 0 0 0 plat elets/ m m 3)  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5 1  
 
0 9 Se pte m ber 2 0 2 2  
⎯ 2 se q ue ntial as part ate a mi n otra nsferase ( A S T) or ala ni ne a mi n otra nsferase ( A L T) 
ele vati o ns > 3 x t he u p per li mit of n or mal ( U L N) a n d at least 1 of t he f oll o wi n g c o nfir me d 
val ues: a) t otal bilir u bi n >  2 x U L N, b) i nter nati o nal n or malize d rati o (I N R) > 1. 5, or 
c) acc o m pa nie d b y 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 niti al A S T or A L T ele v ati o n > 3 x t he U L N, at t h e 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 ( P T) 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.  
⎯ 2  se q ue ntial A S T or A L T ele vati o ns > 5 x U L N  
⎯ 2 se q ue ntial val ues f or esti mate d Cr Cl <  3 5 m L/ mi n base d o n t he C C & G f or m ula 
S u bjects w h o per ma ne ntl y st o p bli n de d st u d y dr u g d ue t o N o n -res p o ns e at Wee k 1 3 or Diseas e 
W orse ni n g aft er Wee k 1 3  t hr o u g h Wee k 2 6,  will be offere d O L  2 0 0 m g o n ce dail y fil g oti ni b, 
a n d t h ose s u bjects s h o ul d be e nc o ura ge d t o c o nti n ue o n st u d y, if d ee me d m e dicall y a p pr o priate 
b y t he i n vesti gat or . S u bje cts w h o per ma n e ntl y st o p st u d y dr u g d ue t o  meeti n g a  pre -s p ecifie d 
dec rease t hr es h ol d i n s per m para met ers ( Secti o n 3. 4 ) will be offere d l ocall y a p pr o ve d sta n d ar d of 
care t h era p y as part of t h e M o nit ori n g P hase . 
S u bject s wit h dra wi n g fr o m t he st u d y s h o ul d c o m plete a n E T visit, f oll o we d b y a s afet y 
f oll o w-u p visit 3 0  da ys after last d ose of st u d y dr u g.  
S u bjects are free t o wit h dra w fr o m t he st u d y at a n y ti me wit h o ut pr o vi di n g reas o n(s) f or 
wit h dra wal a n d wit h o ut prej u dice  t o f urt h er me di cal treat me nt. T h e reas o n(s) f or wit h dr a wal will 
be d oc u me nte d i n t he ele ctr o nic cas e re p ort f or m (e C R F).  
Reas o na ble eff orts will b e 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.  
T he S p o ns or has t he ri g ht t o ter mi nate t he st u d y at a n y ti me i n case of safet y c o n cer ns , or if 
s pecial cir c u msta nces c o ncer ni n g t he st u d y dr u g or t he c o m pa n y occ ur, t hat ma k es f urt her 
treat me nt of s u bjects i m p ossi ble. I n t his e ve nt, the i n vesti gat or(s) a n d rele va nt a ut h orities will be 
i nf or me d of t he reas o n f or st u d y ter mi nati o n. 
T he me dical m o nit or s h o ul d c o ns ult t he me dical lea der as nee de d.  
3. 4.  
Dise ase W orse ni n g Crit eri a  
S u bjects meeti n g t he f oll o wi n g Disease W orse ni n g criteria , e val uate d after Wee k  1 3  t hr o u g h 
Wee k 2 6 , m ust be disc o nti n ue d fr o m bli n de d treat me nt. T hese s u bjects will be offere d t he o pti o n 
t o c o m me nce O L  fil g oti ni b 2 0 0 m g o nce d ail y , as l o n g as t he y h a ve n ot e x perie nce d a decrease 
of ≥ 5 0 %  fr o m bas eli ne i n s per m c o nce ntrati o n, a n d/ or m otilit y, a n d/ or m or p h ol o g y.   
U p o n c o nfir mati o n of Disease W orse ni n g a n d b ef ore s witc hi n g t o t he O L  Fil g oti ni b P hase, 
2  se me n sa m ples will be c ollecte d. Disease W orse ni n g is c o nfir me d at t he ti me of t he sec o n d 
c o nsec uti ve visit . If t he s ec o n d Diseas e W orse ni n g visit occ urs d uri n g t h e 1 4 -da y se me n 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5 2  
 
0 9 Se pte m ber 2 0 2 2  
c ollecti o n wi n d o w f or t h e Wee k 1 3 or Wee k 2 6 St u d y Visit , t he r o uti ne Wee k 1 3 or Wee k  2 6 
se me n c ollecti o n will s uffice.  
Disease W orse ni n g assess me nts will be dri ve n b y t he patie nt hist or y, p h ysi cal a n d la b orat or y 
e x a mi nati o ns a n d are bas e d o n t he f oll o wi n g criteria:  
F or s u bjects wit h U C, Disease W orse ni n g is defi n e d b y a partial M C S after Wee k  1 3 c o nsisti n g 
of:  
•  A n i ncreas e of ≥ 3 p oi nts t o at least 5 p oi nts fr o m t he Wee k 1 3 val ue o n 2 c o nsec uti ve visits, 
O R  
•  A n i ncreas e t o 9 p oi nts fr o m t he Wee k 1 3 val ue o n 2 c o nsec uti ve visits, if t he Wee k  1 3 val ue 
was > 6 p oi nts   
F or s u bjects wit h C D, Disease W orse ni n g is defi n e d b y a t otal C D AI sc ore after Wee k  1 3 
c o nsisti n g of:  
•  A sc ore ≥ 2 2 0 o n 2 c o nsec uti ve vis its, A N D 
•  A n i ncreas e of ≥ 1 0 0 p oi nts fr o m t he Wee k 1 3 val ue o n 2  c o nsec uti ve visits  
F or all s u bjects , Disease W orse ni n g is f urt her defi ne d b y:  
•  Disease W orse ni n g t o t he e xte nt t hat t he s u bject re q uires me dicati o ns pr o hi bite d b y t he st u d y 
(at i n vesti gat or’s discreti o n, wit h disc ussi o n wit h t he m e dical m o nit or or d esi g nee if 
feasi ble); t hes e s u bjects d o n ot q ualif y t o r ecei v e O L  fil g oti ni b 2 0 0 m g o n ce dail y. 
Disease W orse ni n g visits ma y i ncl u d e U nsc he d ul e d Visits (e g, a St u d y Visit  f oll o we d b y a n 
U nsc he d ule d Visit , or 2 s e q ue ntial U nsc he d ul e d Visits after Wee k  1 3).  
In t he L T E , s u bjects w h o meet Disease W orse ni n g criteria ( p er a b o ve criteri a) , or ha v e Diseas e 
W orse ni n g per i n vesti gat or j u d g me nt , s h o ul d be disc o nti n ue d fr o m st u d y dr u g. T h ese s u bjects 
s h o ul d c o m plete a n E T  visit ( w hic h i ncl u de s se me n c ollecti o n), f oll o we d b y a r o uti ne safet y 
f oll o w-u p visit 3 0  da ys after t he last d ose of st u d y dr u g.  
3. 5.  
E n d of St u d y  
E n d of St u d y is reac he d w he n t he last s u bject c o m plete s t he L T E Wee k 1 9 5 visit, or w he n t he 
last s u bject c o m pletes his  last visit, w hic he ver is s o o ner. 
3. 6.  
P ost -St u d y C are  
U p o n c o m pleti o n of st u d y partici pati o n, t he l o n g-ter m care of s u bjects will re mai n t he 
res p o nsi bilit y of t heir pri mar y treati n g p h ysicia n. 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5 3  
 
0 9 Se pte m ber 2 0 2 2  
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 b ject Selecti o n 
U p t o 2 5 0 s u bjects wit h m o deratel y t o se verel y acti ve U C or C D will be e nr olle d i n t he st u d y t o 
e ns ure a p pr o xi matel y 2 0 0 s u bjects are e val ua ble at Wee k  1 3 . E nr oll me nt will be e val uate d 
d uri n g t he c o urse of t he st u d y, a n d ma y b e e x pa n d e d if t he dr o p o ut rat e is hi g her t h a n e x pecte d.  
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 p artici pati o n i n t his 
st u d y.  
1)  A ble t o u n dersta n d a n d willi n g t o si g n t he i nf or m e d c o nse nt as a p pr o ve d b y t he I R B/I E C. 
Writte n c o nse nt m ust be pr o vi de d bef ore i nitiati n g a n y Scree ni n g e val uati o ns. S u bjects m ust 
ha ve rea d a n d u n d erst o o d t he i nf or me d c o nse nt f or m (I C F), m ust f ull y u n dersta n d t he 
re q uire me nts of t h e st u d y, a n d m ust be willi n g t o c o m pl y wit h all st u d y visits an d 
assess me nts; s u bjects w h o ca n n ot rea d or u n dersta n d t he I C F ma y n ot be e nr olle d i n t he 
st u d y b y a g u ar dia n or a n y ot her i n di vi d ual.  
2)  Male s bet wee n t he a ge of 2 1 a n d 6 5 (i ncl usi ve) o n t he da y of si g ni n g i nf or m e d c o nse nt  
3)  B o d y mass i n de x ( k g/ m 2) of ≥ 1 8. 5 t o ≤ 4 0 at Scree ni n g, wit h n o e vi d e nce of mal n utriti o n as 
deter mi ne d b y t he i n vesti gat or  
4)  D oc u me nte d dia g n osis of U C or C D of at least 4 m o nt hs d urati o n. D oc u me ntati o n m ust 
i ncl u de e n d osc o pic a n d hist o pat h ol o gic d oc u me nt ati o n, as f oll o ws:  
a)  U C  
i) Me dical rec or d  d oc u m e ntati o n of, or a n e n d osc o p y re p ort date d ≥ 4 m o nt hs bef ore 
ra n d o mizati o n, w hic h s h o ws feat ur es c o nsiste nt wit h U C, deter mi ne d b y t he 
pr oce d ure perf or mi n g p h ysicia n, A N D  
ii) Me dical rec or d d oc u m e ntati o n of, or a hist o pat h ol o g y re p ort i n dicati n g feat ures 
c o nsiste nt wit h U C as deter mi ne d b y t he pat h ol o gist, A N D  
N ote : S u bject als o nee ds t o ha ve m i ni m u m disease e xte nt of 1 5 c m fr o m t he a nal 
ver ge  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5 4  
 
0 9 Se pte m ber 2 0 2 2  
b)  C D  
i) Me dical rec or d d oc u m e ntati o n of, or a n ile oc ol o n osc o p y (f ull c ol o n osc o p y wit h 
i nt u bati o n of ter mi nal ile u m) re p orte d d ate d ≥ 4 m o nt hs bef ore ra n d o mizati o n, w hic h 
s h o ws feat ur es c o nsiste nt wit h C D, deter mi ne d b y t he pr oce d ure perf or mi n g 
p h ysicia n, A N D  
ii) Me dical rec or d d oc u m e ntati o n of, or a hist o pat h ol o g y re p ort i n dicati n g feat ures 
c o nsiste nt wit h, C D as deter mi ne d  b y t h e pat h ol o gist  
5)  M o deratel y t o se verel y acti ve U C , or m o derat el y t o se verel y acti ve C D, ass esse d l ocall y a n d 
defi ne d b y:  
a)  U C  
i) Ma y o Cli nic Sc ore ( M C S; A p pe n di x  3 ) ≥ 6, P h ysicia n Gl o bal Assess me nt ( P G A)  of 
2  or 3, a n d e n d osc o pi c  s u bsc ore ≥ 2, at Scree ni n g or i n t he pri or 9 0 da ys  
b)  C D  
i) C D AI t otal s c ore ( A p pe n di x  9 ) ≥ 2 2 0, A N D 
ii) E vi de nce of acti ve i nfla m mati o n, wit h a t otal sc ore of ≥ 6 b y t he Si m ple E n d osc o pic 
Acti vit y Sc ore i n Cr o h n’s Disease ( S E S -C D; A p pe n di x  1 0 ), O R  if disease is li mite d 
t o t he ile u m a n d/ or ri g ht c ol o n, a c o m bi ne d S E S -C D sc ore ≥ 4 i n t hese 2 s e g m e nts,  at 
Scree ni n g or i n t he pri or 9 0 da ys  
6)  Pre vi o usl y de m o nstrat e d a n i na de q uat e cli nica l r es p o nse, l oss of res p o nse t o, or i nt olera nce 
of at  least o ne of t h e f oll o wi n g a ge nts ( de p e n di n g o n c urre nt c o u ntr y treat me nt 
rec o m me n dati o ns/ g ui deli nes): 
a)  C ortic oster oi ds  
i) Acti ve disease d es pite a hist or y of at least a n i n d u cti o n re gi me n of a d os e e q ui val e nt 
t o pre d nis o ne ≥2 0 m g d ail y f or 2  wee ks or i ntra ve n o usl y (I V) f or 1  wee k, O R  
ii) T w o faile d atte m pts t o ta per ster oi ds bel o w a d ose e q ui vale nt of 1 0  m g dail y 
pre d nis o ne, O R  
iii) Hist or y of ster oi d i nt olera nce i ncl u di n g, b ut n ot li mite d t o, C us hi n g’s s y n dr o me, 
os te o pe nia/ oste o p or osis, h y per gl yce mia, i ns o m nia, seri o us i nfecti o ns, de pressi o n, 
aller gic reacti o ns, m o o d dist ur ba nces, or a n y ot her c o n diti o n t hat c o ntri b ute d t o 
disc o nti n uati o n of t he a ge nt  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5 5  
 
0 9 Se pte m ber 2 0 2 2  
b)  I m m u n o m o d ulat ors 
i) Acti ve disease d es pite a hist or y of at least a 1 2 -wee k re gi me n of oral azat hi o pri ne 
( ≥ 2 m g/ k g/ da y) or 6 M P ( ≥ 1 m g/ k g/ da y), or M T X ( 2 5 m g s u b c uta ne o usl y [ S C] or 
i ntra m usc ularl y [I M] per wee k f or i n d ucti o n a n d ≥ 1 5 m g I M per wee k f or 
mai nte na nce), O R  
ii) Hist or y of i nt olera nce t o at least o ne i m m u n o m o d ulat o r i ncl u di n g, b ut n ot li mite d t o, 
seri o us i nfecti o ns, he pat ot o xicit y, c yt o pe nia, p a ncreatitis, t hi o p uri ne 
met h yltra nsf erase ( T P M T) ge netic m utati o n, aller gic reacti o ns, or a n y ot her c o n diti o n 
t hat c o ntri b ute d t o disc o nti n uati o n of t he a ge nt 
c)  T N F α a nta g o nists  
i) Acti ve disease d es pite a n i n d ucti o n re gi me n wit h a T N F α a nta g o nists (i nfli xi ma b, 
a dali m u ma b, g oli m u ma b [ U C o nl y], or cert oliz u ma b [ C D o nl y]), or c orres p o n di n g 
bi osi milar prescri be d at a d ose a n d d urati o n c o nsiste nt wit h t he a p pr o ve d pr o d uct 
la beli n g, O R   
ii) Rec urre n ce of s y m pt o ms d uri n g mai nte na nce t h era p y wit h t he a b o ve a ge nts, O R  
iii) Hist or y of i nt olera nce t o a n y T N F α a nta g o nists i n cl u di n g, b ut n ot li mite d t o, seri o us 
i nfecti o ns, he pat ot o xicit y, heart fail ure, aller gi c reacti o ns, or a n y ot her c o n diti o n t hat 
c ontri b ute d t o disc o nti n uati o n of t he a ge nt  
d)  Ve d oliz u ma b  
i) Acti ve disease d es pite a n i n d ucti o n re gi me n prescri be d i n acc or da n ce wit h t he 
a p pr o ve d pr o d u ct la beli n g, O R  
ii) Rec urre n ce of s y m pt o ms d uri n g mai nte na nce t h era p y wit h ve d oliz u ma b, O R  
iii) Hist or y of i nt olera nce t o ve d oliz u ma b i ncl u di n g, b ut n ot li mite d t o, seri o us i nfecti o ns, 
he pat ot o xicit y, c yt o p e nia, aller gic reacti o ns, or a n y ot her c o n diti o n t hat c o ntri b ute d t o 
disc o nti n uati o n of t he a ge nt  
e)  Uste ki n u ma b [criteri o n a p plica ble o nl y t o s u bjects wit h C D]  
i) Acti ve dise ase d es pite a n i n d ucti o n re gi me n prescri be d i n acc or da n ce wit h t he 
a p pr o ve d pr o d u ct la beli n g, O R  
ii) Rec urre n ce of s y m pt o ms d uri n g mai nte na nce t h era p y wit h uste ki n u ma b, O R  
iii) Hist or y of i nt olera nce t o uste ki n u ma b i ncl u di n g, b ut n ot li mite d t o, seri o us i nfecti o ns,  
aller gic reacti o ns, or a n y ot her c o n diti o n t hat c o ntri b ute d t o disc o nti n uati o n of t he 
a ge nt  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5 6  
 
0 9 Se pte m ber 2 0 2 2  
7)  Ma y b e recei vi n g 1 or m ore of t he f oll o wi n g dr u gs (s u bjects o n t hese t hera pies m ust be 
willi n g t o re mai n o n sta ble d oses f or t he n ote d ti m es):  
a)  5 -a mi n osalic yl ate ( 5 -A S A) c o m p o u n ds pr o vi de d t he d ose prescri be d has b ee n sta ble f or 
at least 4 wee ks pri or t o r a n d o mizati o n; d ose m ust re mai n sta ble f or t he first  1 3  wee ks 
after ra n d o mizati o n  
b)  Azat hi o pri ne, 6 -M P, or M T X pr o vi de d t he d ose prescri be d h as bee n sta ble f or 4  wee ks  
pri or t o ra n d o mizati o n; d ose of M T X m ust re mai n sta ble f or 2 6 wee ks, a n d d ose of 
A Z A/ 6 -M P m ust re mai n sta ble f or t he first 1 3 wee ks , b ut ca n be a dj uste d if i n dicate d 
bet wee n 1 3 a n d 2 6 wee ks.  
c)  C ortic oster oi d t hera p y ( pre d nis o ne pres cri be d at a sta ble d ose ≤ 2 0  m g/ da y or b u des o ni de 
prescri be d at a sta ble d os e of ≤ 9  m g/ d a y); d ose s h o ul d n ot be c ha n ge d d uri n g t he 
first 1 3  wee ks. A ster oi d ta per s h o ul d o nl y c o m me nce aft er Wee k 1 3.  
8)  T he mea n of 2 s e parate se me n sa m ples c ollecte d at t he Scree ni n g  visit  m ust  meet t he 
f oll o wi n g mi ni m u m criteria (in acc or da n ce wit h S ecti o n  6. 1 3  a n d Fi g ure  6 -1 ): se me n v ol u me 
≥ 1. 5 m L, t otal s per m per ejac ulate ≥ 3 9 milli o n, s per m c o nce ntrati o n ≥ 1 5  milli o n per m L, 
s per m t otal m otilit y ≥ 4 0 %, a n d n or mal s per m m or p h ol o g y ≥ 3 0 %  
9)  L H, F S H, i n hi bi n B, a n d t otal test oster o ne val ues wit hi n 2 0 % of la b orat or y refere nce ra n ges 
at Scree ni n g  
1 0)  S u bjects w h o e n ga ge i n h eter ose x ual i nterc o urse m ust a gree t o use pr ot o c ol s pecifie d 
met h o d(s) of c o ntr ace pti o n as descri be d i n A p pe n di x  5 , i ncl u di n g use of c o n d o ms d uri n g t he 
st u d y a n d f or 9 0 da ys aft er t he last d ose of st u d y dr u g 
1 1)  Willi n g ness t o refrai n fr o m recei vi n g li ve atte n u ate d vacci nes wit hi n 3 0 da ys of Da y  1, 
t hr ou g h o ut t he st u d y, a n d f or 1 2 wee ks after t he last d ose of st u d y dr u g 
( Secti o n 5. 4 , Vacci ne  G ui deli nes).  
1 2)  Meet o ne of t he f oll o wi n g 3 t u berc ul osis ( T B) Scree ni n g criteria: 
a)  N o e vi de nce of acti ve or late nt T B:  
⎯ A ne gati ve Q u a nti F E R O N ®  T B -G ol d Pl us I n -T u b e test at Scree ni n g, A N D  
⎯ A c hest ra di o gra p h ( vie ws as per l ocal g ui deli nes) ta ke n at Scree ni n g or wit hi n t he 
3  m o nt hs pri or t o Scree ni n g ( wit h t he re p or t or fil ms a vaila ble f or i n vesti gat or 
re vie w) wit h o ut e vi de nce of acti ve or l ate nt T B i nf ecti o n, A N D 
⎯ N o hist or y of eit her u ntreate d or i na de q u atel y treate d late nt T B i nf ecti o n  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5 7  
 
0 9 Se pte m ber 2 0 2 2  
b)  Pre vi o usl y treate d f or T B:  
⎯ A  s u bject w h o has pr e vi o usl y recei ve d a n a d e q uat e c o urse of t hera p y as per l ocal 
sta n dar d of care f or eit her late nt T B (e g, 9 m o nt hs of is o niazi d i n a l ocati o n w here 
rates of pri mar y m ulti-dr u g resista nt T B i nf ecti o ns are <  5 %, or a n alter nati ve 
re gi me n acc or di n g t o l ocal c o u ntr y g ui deli nes) or acti ve T B (acce pt a ble m ulti-dr u g 
re gi me n). I n t hes e cases, n o Q ua nti F E R O N®  T B -G ol d Pl us I n -T u be t est 
( or a ce ntrall y re p orte d e q ui vale nt assa y) nee ds t o be o btai ne d   
⎯ A c hest ra di o gra p h m ust be o btai ne d if n ot d o ne wit hi n 3  m o nt hs pri or t o Scree ni n g 
( wit h t he re p ort or fil ms a vaila ble f or i n vesti gat or re vie w)  
⎯ It is t he res p o nsi bilit y of t he i n vesti gat or t o v erif y t he a de q uac y of pre vi o us 
a nti-T B  tr eat me nt a n d pr o vi de a p pr o priat e d oc u m e ntati o n 
c)  Ne wl y i de ntifie d late nt T B d uri n g Scree ni n g:  
⎯ A  s u bject w h o has a n e wl y i de ntifie d p ositi ve dia g n ostic T B test res ult ( defi ne d as a 
p ositi ve Q ua nti F E R O N ®  T B G ol d Pl us I n -T u be test or e q ui vale nt assa y) , i n w hic h 
acti ve T B has bee n r ule d o ut a n d f or w hic h a p pr o priate o n g oi n g treat me nt f or late nt 
T B has b ee n i nitiate d f or at least 4  wee ks pri or t o t he first  a d mi nistrati o n of st u d y 
dr u g.  
⎯ A de q uate treat me nt f or l ate nt T B is defi ne d acc or di n g t o l ocal c o u ntr y g ui deli nes f or 
i m m u n oc o m pr o mise d patie nts. 
Cases falli n g u n d er cate g or y “ b” a n d “c” m ust be a p pr o ve d b y t he Gilea d m e dical m o ni t or or 
desi g nee pri or t o e nr oll me nt i n t he st u d y. N o s u bject wit h c urre ntl y acti ve T B  or u ntr eate d 
late nt T B ma y b e e nr olle d i n t he st u d y. If a s u bject ha d a Q ua nti F E R O N ®  T B -G ol d Pl us 
I n-T u be test f or t he p ur p oses of cli nical care or f or t he p ur p ose of Scr ee ni n g f or a n ot her 
Gilea d -s p o ns ore d st u d y wit hi n 6 0 da ys, t he pri or res ult ma y b e use d t o ass ess eli gi bilit y.  
1 3)  La b orat or y p ara m eters n ee d t o be met as p er bel o w  
a)  He patic pa n el ( A S T, A L T, t otal bilir u bi n) ≤ 2 X t he U L N  
b)  Esti mate d Cr Cl ≥ 4 0 m L/ mi n as calc ulate d b y t he C C & G  e q uati o n  
c)  He m o gl o bi n ≥ 8 g/ d L  
d)  A bs ol ute ne utr o p hil c o u nt ( A N C) ≥ 1. 5 × 1 0 9/ L ( 1, 5 0 0/ m m3) 
e)  Platelets ≥ 1 0 0 × 1 0 9/ L 
f) W hite bl o o d cells ( W B C) ≥ 3. 0 x 1 0
9/ L 
g)  A bs ol ute L y m p h oc yt e c o u nt > 7 5 0/ m m 3 
1 4)  Be u p t o date o n c ol orect al ca ncer s ur v eilla nce (p er l ocal g ui deli nes ) pri or t o Scree ni n g.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5 8  
 
0 9 Se pte m ber 2 0 2 2  
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 x cl usi o n criteria are n ot t o be e nr olle d i n t his st u d y.  
[ N ote: “ Scree ni n g” refers t o t he first da y of Scree ni n g] 
1)  Pre vi o usl y d oc u me nt e d pr o ble ms wit h male re pr o d ucti ve healt h i ncl u di n g , b ut n ot li mite d t o , 
k n o w n h y p ot hal a mic -pit uitar y dis or d ers (e g, pit uitar y m acr oa de n o mas, pit uitar y i nf arcti o n, 
h y per pr ola cti ne mia, pa n h y p o pit uitaris m), pri mar y h y p o g o na dis m (e g,  cr y pt orc hi dis m, 
K li nefelter’s s y n dr o me) 
2)  Pri or dia g n osis of male i nfertilit y (i ncl u di n g re d u ce d fertilit y), or hist or y of a nti -s per m 
a nti b o dies  
3)  Cli nicall y si g nifica nt ( per j u d g me nt of i n v esti gat or) varic o cele or s per m at ocele  
4)  Hist or y of ra diati o n t o t he testicles  
5)  Hist or y of  cli nicall y si g nifica nt tra u ma t o, or s ur ger y o n, t he testicles, i ncl u di n g vasect o m y  
6)  C urre nt treat me nt wit h a ntia n dr o ge n t hera p y (i ncl u di n g b ut n ot li mite d t o s pir o n olact o ne or 
oral ket oc o naz ole), or treat me nt wit hi n 4 wee ks of Scree ni n g   
7)  C urre nt treat me n t wit h test oster o ne re place me nt t h era p y, or treat me nt wit hi n 1 2 wee ks of 
Scree ni n g  
8)  C urre nt treat me nt wit h 5 -α re d uct ase i n hi bit ors (i ncl u di n g b ut n ot li mite d t o fi nasteri de a n d 
d utasteri de)  
9)  C urre nt treat me nt wit h al p ha -1 bl oc kers (i ncl u di n g b ut n ot li mite d t o ta ms ul osi n, d o x az osi n, 
praz osi n)  
1 0)  C urre nt use of s ulfasalazi ne or use of s ulfasalazi ne wit hi n 2 6 wee ks of Scree ni n g; 
s ulfasalazi ne is n ot per mitte d at a n y p oi nt d uri n g t he st u d y 
1 1)  C urre nt use of al k ylati n g a ge nts or a n y rec o g nize d testic ular t o xi n wit hi n  2 6 wee ks of 
Scree ni n g ( ma y b e disc usse d wit h Gilea d  m e dical m o nit or or desi g nee)  
1 2)  Treat me nt wit h c ycl os p ori ne or ot her calci ne uri n i n hi bit ors wit hi n 3 0 da ys of Scree ni n g  
1 3)  Use of a n y T N F α a nta g o nist or ve d oliz u ma b wit hi n  8  wee ks pri or t o Scree ni n g, uste ki n u ma b 
wit hi n 1 2 wee ks pri or t o Scree ni n g, or a n y ot her bi ol o gic a ge nt wit hi n  8  wee ks pri or t o 
Scree ni n g or wit hi n 5 ti mes t he half -life of t he bi ol o gic a ge nt pri or t o Scree ni n g, w hic h e ver 
is l o n ger 
1 4)  Use of a n y pr o hi bite d c o nc o mita nt me dicati o n(s) as d escri be d i n Secti o n  5. 3  
1 5)  K n o w n h y p erse nsiti vit y t o fil g oti ni b, its meta b olites, or f or m ulati o n e xci pie nts  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5 9  
 
0 9 Se pte m ber 2 0 2 2  
1 6)  Prese nce of dis or ders of s per m tra ns p ort  incl u di n g , b ut n ot li mite d t o , retr o gra de ej ac ulati o n 
a n d i m m otile cilia s y n dr o me  
1 7)  Cli nicall y si g nifica nt uri nar y tract i nfecti o n, pr ost atitis, e pi di d y mitis, i ncl u di n g se x uall y 
tra ns mitte d i nfecti o n wit hi n 4 wee ks of Scree ni n g 
1 8)  P ositi ve uri ne test f or a m p heta mi nes or c o cai ne; p ositi ve test t o o pi oi ds wit h o ut a 
prescri pti o n, or hea v y t o bacc o use (c urre nt use of ≥ 2 pac ks per da y e q ui vale nt)  
1 9)  U nc o ntr olle d t h yr oi d d ysf u ncti o n (e g, u ntreate d h y p ot h yr oi dis m or h y pert h yr oi dis m)  
2 0)  A n y s e x ual d ysf u ncti o n of a nat ur e t ha t w o ul d pr e ve nt s per m c ollecti o n i n acc or da nce wit h 
pr ot oc ol g ui da n ce ( p h os p h o diesterase i n hi bit ors, h o we ver, are p er mitte d d uri n g t he st u d y)  
2 1)  Hist or y of m aj or s ur ger y or tra u ma wit hi n 3 0 da ys pri or t o Scree ni n g , or a ntici pate d nee d f or 
maj or s ur ger y  d uri n g  t he st u d y 
2 2)  Hist or y of t otal c ol ect o m y, s u bt otal c olect o m y, p artial or he mi -c olect o m y, ile ost o m y, 
c ol ost o m y, or a ntici p ate d nee d f or a n y of t hes e  i nter ve nti o ns d uri n g t he st u d y  
2 3)  C urre ntl y h a ve c o m plic ati o ns of C D as a n y of t he f oll o wi n g:  
a)  S y m pt o matic stri ct ur es, O R 
b)  Se vere (i m pass a ble) rect al/a nal ste n osis, O R  
c)  Fist ulae, O R  
d)  S h ort b o wel s y n dr o m e, O R  
e)  A n y ot her c o m plicati o ns w hic h c o ul d precl u de t he use of t he C D AI t o ass ess res p o nse t o 
t hera p y, or w o ul d p ossi bl y c o nf o u n d t he e v al uati o n of be nefit fr o m treat me nt wit h 
fil g oti ni b 
2 4)  Ha ve a n y c urre nt or pri or a bscesses, u nless t he y h a ve bee n drai ne d a n d treate d at least 
6  wee ks pri or t o D a y 1 , a n d are n ot a ntici pat e d t o re q uire s ur ger y  d uri n g t h e st u d y  
2 5)  I n d eter mi nate c olitis, isc he mic c olitis, f ul mi na nt c olitis, is olate d ulcerati ve pr octitis, or t o xic 
me ga -c ol o n  
2 6)  De pe n de n ce o n p are nteral n utriti o n  
2 7)  Hist or y or e vi de nce of i n c o m pletel y resecte d c ol o nic m uc osal d ys pl asia  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6 0  
 
0 9 Se pte m ber 2 0 2 2  
2 8)  Scree ni n g st o ol sa m ple p ositi ve f or Cl ostri di u m difficile (C. difficile ) t o xi n, pat h o ge nic 
Esc heric hi a  c oli (E.  c oli ), S al m o nell a  s pecies (s p p), S hi gell a  s p p, C a m pyl o b acter  s p p or 
Y ersi ni a  s p p, or o va a n d parasites ( O & P), u nless a p pr o ve d b y t he Gilea d m e dical m o nit or or 
desi g nee  
2 9)  C urre nt use of ster oi ds at a d ose >  2 0  m g/ da y of pre d nis o ne e q ui val e nts at ra n d o miz ati o n 
3 0)  A d mi nistrati o n of a li ve atte n uate d vacci ne wit hi n 3 0 da ys of Ra n d o mizati o n (see als o 
Secti o n  5. 4 , Vacci n e G ui deli nes)  
3 1)  A p ositi ve test res ul t f or HI V-1 or HI V -2 ( See A p pe n di x  6 ) 
3 2)  E vi de nce of acti ve H C V i nfecti o n. S u bjects wit h p ositi ve H C V a nti b o d y ( A b) at Scree ni n g, 
re q uire refle x testi n g f or H C V R N A. S u bjects wit h p ositi ve H C V R N A at Scree ni n g will be 
e x cl u de d. S u bjects wit h p ositi ve H C V A b, b ut ne gati ve H C V R N A are eli gi ble per 
i n vesti gat or j u d g me nt. S u bjects wit h acti ve H C V d uri n g t he st u d y, as e vi de nce d b y H C V 
R N A p ositi vit y will be dis c o nti n ue d fr o m st u d y dr u g as o utli ne d i n t he pr ot oc ol.  
3 3)  E vi de nce of acti ve H B V i nfecti o n. S u bjects wit h p ositi ve He patitis B s urface a nti ge n 
( H Bs A g) at Scree ni n g are e x cl u de d fr o m t he st u d y. S u bjects wit h p ositi ve H B V c ore A b a n d 
ne gati ve H Bs A g, re q uire ref le x testi n g f or H B V D N A. S u bjects wit h p ositi ve H B V D N A at 
Scree ni n g will be e x cl u de d. S u bjects wit h p ositi ve H B V c ore A b a n d n e gati ve H B V D N A 
are eli gi ble per i n vesti gat or j u d g me nt, b ut ma y re q uire pr o p h ylactic tr eat me nt i n acc or da n ce 
wit h H B V treat me nt g ui deli nes/l ocal sta n dar d of care a n d re q uir e o n g oi n g m o nit ori n g wit h 
bl o o d tests f or H B V D N A e ver y 3 m o nt hs. S u bjects wit h e vi de nce of acti v e He patitis  B 
d uri n g t he st u d y, as e vi de nce d b y H B V D N A p ositi vit y, will be disc o nti n u e d fr o m st u d y dr u g 
as o utli ne d  i n t he pr ot oc ol. 
3 4)  Prese nce of C hil d -P u g h Class C he patic i m pair me nt  
3 5)  Hist or y of m ali g na n c y wit hi n t he past 5 years pri or t o Scree ni n g, (e x ce pti o n will be ma de f or 
a de q uatel y tr eate d b asal cell carci n o ma or n o n -m etastatic s q ua m o us cell carci n o ma of t h e 
s ki n, wit h n o e vi de nce of rec urre nce)  
3 6)  Hist or y of l y m p h o pr oliferati ve dis or der, l y m p h o m a, le u ke mia, m yel o pr oliferati ve dis or der, 
or m ulti ple m yel o ma  
3 7)  Hist or y of treat me nt wit h l y m p h oc yte -d e pleti n g t hera pies, i ncl u di n g b ut n ot li mite d t o 
ale mt uz u ma b, c ycl o p h os p ha m i de, t otal l y m p h oi d irra diati o n, or rit u xi ma b 
3 8)  Hist or y of l e u k oc yta p heresis ≤ 6 m o nt hs pri or t o Scree ni n g  
3 9)  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 dis ease, 
or s u bsta nce a b use) or ps yc hi atric pr o ble m t hat, i n t he o pi ni o n of t he I n vesti gat 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 pr oce d ures  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6 1  
 
0 9 Se pte m ber 2 0 2 2  
4 0)  Acti ve cli nicall y si g nifi ca nt i nfecti o n, or a n y i nf ecti 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 nf ecti ves wit hi n 3 0 da ys of Scree ni n g ( or 8 wee ks of Da y 1); or a n y 
i nfecti o n re q uiri n g oral a nti-i nfecti ve t hera p y wit hi n 2 wee ks of Scree ni n g ( or 6 wee ks of 
da y  1)  
4 1)  Hist or y of o p p ort u nistic i nfecti o n or i m m u n o defici e nc y s y n dr o me  
4 2)  C urre ntl y o n a n y 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 p ne u m o c ystis p ne u m o nia ( P C P), c yt o me gal o vir us ( C M V), her pes z oster, at y pical 
m yc o b acteri a)  
4 3)  Hist or y of disse mi nate d St a p hyl oc occ us a ure us  i nfecti o n 
4 4)  Hist or y of s y m pt o matic her pes z o ster or her pes si m ple x wit hi n 1 2 wee ks of Scree ni n g, or 
a n y 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 yste m z oster  
4 5)  Partici pati o n i n a n y cli nical st u d y of a n i n vesti gati o nal de vice wit hi n 3 0 d a ys, i n vesti gati o nal 
n o n -bi ol o gic dr u g wit hi n 3 0 da ys, or i n vesti gati o nal bi ol o gic dr u g wit hi n 8 wee ks 
( or 5  half -li ves, w hic he v er is l o n ger), pri or t o Scree ni n g. 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6 2  
 
0 9 Se pte m ber 2 0 2 2  
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  
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  
A n I nteracti ve We b Res p o nse S yste m (I W R S) will be e m pl o ye d t o ma na ge s u bject 
ra n d o mizati o n a n d treat me nt assi g n me nts. It is t he res p o nsi bilit y of t he i n v esti gat or t o e ns ure t hat 
t he s u bject is eli gi ble f or t he st u d y pri or t o e nr oll me nt. S u bjects will be assi g ne d a Scree ni n g 
n u m ber at t he ti me of c o nse nt.  
5. 1. 1.  
R a n d o miz ati o n  
S u bjects w h o meet ra n d o mizati o n eli gi bilit y criteria will be ra n d o mize d i n a 1: 1 rati o t o 
Fil g oti ni b 2 0 0 m g or P T M fil g oti ni b 2 0 0  m g starti n g o n Da y 1, a n d assi g n e d a s u bject n u m ber. 
Ra n d o miza ti o n will be stratifie d b y t y pe of I B D ( U C vers us C D), c o nc urre nt use of M T X ( yes or 
n o), a n d s per m c o nce ntr ati o n ( 1 5 -2 5 milli o n/ m L; > 2 5 t o 5 0 milli o n/ m L; or > 5 0 milli o n/ m L) 
base d o n t he mea n of 2 eli gi ble se me n s a m ples c ollecte d at Scree ni n g . 
5. 1. 2.  
Bli n di n g  
D u ri n g t h e ra n d o mize d p hase, s u bjects a n d all pers o n nel directl y 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 treat me nt assi g n me nt. 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 h ar macist, or d esi 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 n ee, i n Bi oa nal yti cal 
O perati o ns a n d/ or Cli nical Data Ma n a ge me nt, w h o facilitates t he data tra nsfer of P K files 
bet wee n t he S p o ns or a n d ve n d ors, will re mai n u n bli n de d. I n di vi d uals i n Cli nical Pac ka gi n g & 
La b eli 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 v e nt or y M a na ger r ole i n t he 
IW R S s yste m f or p ur p os es of st u d y dr u g i n ve nt or y ma na ge me nt will re mai n u n bli n de d. 
I n di vi d uals r es p o nsi ble f or safet y si g nal det ecti o n, i n vesti gati o nal ne w dr u g (I N D) s afet y 
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 d ata a n d/ or gr o u p l e vel s u m maries. E xter nal 
(ie, C o ntract R esearc h O r ga niz ati o ns [ C R Os]) Bi ostatisticia ns a n d Pr o gra m mers will be 
u n bli n de d t o pr o d uce ta bles, fi g ures, a n d listi n gs f or u n bli n de d re vie w at D M C  meeti n gs, a n d t he 
e xter nal bi ostatistic ia n will ser ve as t he e xter nal st atisticia n t o t he D M C. Re g ul at or y Q u alit y a n d 
C o m plia nce pers o n nel i n Researc h a n d De vel o p me nt ma y als o be u n bli n de d f or p ur p oses of 
s u p p orti n g Q ualit y Ass ura nce acti vities a n d/ or Re g ulat or y A ge nc y i ns pe cti o ns.  
F or o n g oi n g s u bjects, t he st u d y tea ms a n d st u d y st aff at t he sites a n d all ot her staff directl y 
i n v ol ve d i n t he c o n d uct of t he st u d y will re m ai n bli n de d t o t he treat me nt assi g n me nts u ntil t he 
fi nal a nal ysis w he n t he d ata base h as bee n l o c ke d. P u blicati o n of t he I A 2 data is pla n ne d b y t h e 
S p o ns or. T his p u blicati o n will c o ntai n gr o u p le ve l data f or t he e ntire st u d y p o p ulati o n, b ut will 
u n bli n d t he st u d y t ea ms a n d staff directl y i n v ol ve d i n t he c o n d uct of t he st u d y t o t he i n di vi d ual 
baseli ne treat me nt assi g n me nt of s u bjects w h o c o m plete d t he st u d y bef ore I A 2.   


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6 3  
 
0 9 Se pte m ber 2 0 2 2  
5. 1. 3.  
Pr oce d ures f or Bre a ki n g Tre at m e nt C o des  
I n t he e ve nt of a me dical e mer ge n c y w here brea ki n g t he bli n d is re q uir e d t o pr o vi de me dical care 
t o t he s u bject, t he i n vesti gat or m a y o btai n t he i n di vi d ual s u bject treat me nt assi g n me nt directl y 
fr o m t he I W R S s yst e m. T he S p o ns or rec o m me n ds, b ut d oes n ot re q uire, t h at t he i n vesti gat or 
c o ntact t he m e dic al m o nit or or desi g nee b ef ore brea ki n g t he bli n d. Treat me nt assi g n me nts 
s h o ul d re mai n bli n de d u nless t hat k n o wle d ge is ne cessar y t o det er mi ne e m er ge nc y me dical care 
f or t he s u bject. T h e rati o nale f or un bli n di n g m ust be clearl y e x plai ne d i n s o urce d oc u m e ntati o n 
a n d o n t he ele ctr o nic cas e re p ort f or m (e C R F), al o n g wit h t he dat e o n w hi c h t he treat me nt 
assi g n me nt w as u n bli n de d.  T he i n vesti gat or is re q ueste d t o c o ntact t he m e dical m o nit or or 
desi g nee pr o m ptl y i n cas e of a n y tr eat me nt u n bli n di n g.  
Bli n di n g of st u d y tr eat m e nt is critical t o t he i nte grit y of t his cli nical trial a n d t heref ore, if a 
s u bject’s treat me nt assi g n me nt is discl ose d t o t he i n vesti gat or, t he s u bject will ha ve st u d y dr u g 
disc o nti n ue d. All s u bjects will be f oll o we d u ntil st u d y c o m pleti o n u nless c o nse nt t o d o s o is 
s pecificall y wit h dra w n b y t he s u bject. 
T he S p o ns or ma y i n de pe n de ntl y u n bli n d cas es f 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 vers e reacti o ns ( S U S A Rs) t o Re g ulat or y A ut h orities.  
5. 2.  
Descri pti o n a n d H a n dli n g of Fil g oti ni b a n d Pl ace b o -t o-M atc h ( P T M)  
5. 2. 1.  
F o r m ul ati o n   
Fil g oti ni b is a vaila ble as 2 0 0 m g stre n gt h ta blets. Fil g oti ni b 2 0 0 m g t a blets are bei ge, de b osse d 
wit h “ G SI” o n o ne si de a n d “ 2 0 0” o n t he ot her, ca ps ule -s ha pe d, bic o n v e x, fil m -c oate d ta blets f or 
cli nical use. Eac h t a blet c o ntai ns t he e q ui vale nt of 2 0 0 m g fil g oti ni b free b ase i n t he f or m of 
fil g oti ni b maleate. I n a d diti o n t o t he acti ve i n gre die nt, fil g oti ni b ta blets c o ntai n t he f oll o wi n g 
i nacti ve i n gre die nts: micr ocrystalli ne cell ul ose, lact ose m o n o h y drate, f u maric aci d, 
pre gelati nize d starc h, silic o n di o xi de, ma g nesi u m stearate, m acr o g ol/ P E G 3 3 5 0, p ol y vi n yl 
alc o h ol, talc, tita ni u m di o xi de, ir o n o xi de yell o w, a n d ir o n o xi de re d.  
Place b o -t o-matc h ( P T M) fil g oti ni b 2 0 0  m g ta blets are i de ntical i n a p peara n ce t o t he acti ve 
ta blets. Place b o -t o-matc h ( P T M) fil g oti ni b 2 0 0  m g ta blets c o ntai n t he f oll o wi n g i nacti ve 
i n gre di e nts: micr ocr ystalli ne cell ul ose, lact ose m o n o h y drate, cr oscar mell ose s o di u m, ma g nesi u m 
stearate, m acr o g ol/p ol yet h yle n e gl yc ol ( P E G ) 3 3 5 0, p ol y vi n yl alc o h ol, talc, tita ni u m di o xi de, 
ir o n o xi de yell o w, a n d ir o n o xi de re d. 
5. 2. 2.  
P a c k a gi n g a n d L a beli n g  
Fil g oti ni b a n d P T M fil g oti ni b ta blets are pac k a ge d i n w hite, hi g h de nsit y p ol yet h yle ne ( H D P E) 
b ottles. Eac h b ottle c o nt ai ns 3 0 ta blets, silica gel d esicca nt a n d p ol yester pac ki n g mat erial. 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 p ol y pr o p yl e n e scre w ca p fitte d 
wit h a n i n d ucti o n -seale d, al u mi n u m-face d li ner.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6 4  
 
0 9 Se pte m ber 2 0 2 2  
St u d y dr u gs t o be distri b ute d t o ce nters i n t he 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 plic a ble re q uir e 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 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 v esti gati o nal Me di ci nal 
Pr o d ucts) a n d/ or  ot her l o cal re g ulati o ns, as a p plica ble.  
5. 2. 3.  
St or a ge a n d H a n dli n g  
Fil g oti ni b a n d P T M fil g oti ni b ta blets, s h o ul d be st ore d at c o ntr olle d r o o m te m perat ur e of 
2 5  °C  ( 7 7 F) . Te m p erat ure vari a bilit y bet w ee n 1 5 C  a n d 3 0 C ( 5 9 F  t o 8 6 F) are per mitte d  
a n d are n ot c o nsi dere d e x c ursi o ns . St ora ge c o n diti o ns are s pecifie d o n t he l a bel. 
U ntil dis pe nse d t o t he s u bjects, all dr u g pr o d ucts s h o ul d be st ore d i n a sec urel y l o c ke d area, 
accessi ble o nl y t o a ut h ori ze d site pers o n nel. T o e ns ure t he sta bilit y of t h e s t u d y dr u g a n d t o 
e ns ure pr o per pr o d u ct i de ntificati o n, t he dr u g pr o d uct 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 hi c h t he y are s u p plie d. C o nsi derati o n s h o ul d be gi v e n t o ha n dli n g, 
pre parati o n, a n d dis p osal t hr o u g h me as 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. 2. 4.  
D os a ge a n d A d mi nistr ati o n of Fil g oti ni b  
Fil g oti ni b a n d P T M fil g oti ni b ta blets will be a d mi nistere d o nce d ail y , wit h or wit h o ut f o o d . Eac h 
s u bject m ust be gi ve n i nstr ucti o ns t o mai ntai n a p pr o xi matel y t he s a me dail y d osi n g i nter val 
bet wee n st u d y dr u g d os es.  
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 of 
st u d y me dicati o n as s o o n as p ossi ble d uri n g t he s a me da y. S u bjects s h o ul d n ot ta ke t he misse d 
d ose  wit h t he ne xt da y’s d ose (ie, d o u ble d ose). Misse d d ose (s) or u n use d st u d y dr u g s h o ul d n ot 
be discar de d.  
5. 3.  
Pri or a n d C o nc o mit a nt Me dic ati o ns  
All 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 s u bject’s 
partici pati o n i n t he st u d y nee d t o be rec or de d i n t he s o urce d o c u me nts a n d o n t he e C R F. T here 
s h o ul d be n o variati o n i n d ose or re gi me n d uri n g t he st u d y, if p ossi ble. At eac h st u d y visit, t he  
st u d y ce nt er will ca pt ur e a n y a n 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). C o nc o mita nt me dicati o ns i ncl u de pres cri pti o n, n o n -prescri pti o n 
me dicati o ns, dietar y s u p ple me nts, a n d mi nerals.  
Effecti ve c urre nt t hera pi es 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 I n vesti gat or or t he s u bject’s p h ysi cia n. S h o ul d s u bjects ha ve a n ee d  t o i nitiate treat me nt 
wit h a n y e x cl u de d c o nc o mita nt me dicati o n, t he m e dical m o nit or or desi g nee m ust be c o ns ulte d 
pri or t o i nitiati o n of t he ne w me dicati o n. I n i nsta n ces w here a n e x cl u de d me dicati o n is i nitiate d 
pri or t o disc ussi o n wit h t he S p o ns or, t he  In vesti gat or m ust n otif y t h e S p o ns or as s o o n as he/s he 
is a ware of t he use of t he e x cl u de d me dicati o n.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6 5  
 
0 9 Se pte m ber 2 0 2 2  
5. 3. 1.  
All o w e d C o nc o mit a nt Me dic ati o ns  
T he all o we d c o n c o mita nt me dicati o n(s) f or U C a n d f or C D m ust be mai ntai ne d at a sta ble d os e 
f or t he n ote d ti me wit h o ut d osi n g alterati o n or disc o nti n uati o n.  
T he all o we d me dicati o ns f or U C a n d f or C D are as f oll o ws:  
•  Oral 5 -A S A c o m p o u n ds , pr o vi de d t he d ose prescri be d has bee n st a ble f or at least 4  wee ks 
pri or t o ra n d o mizati o n; d ose m ust be sta ble f or t he first 1 3 wee ks after ra n d o mizati o n. 
•  Azat hi o pri ne, 6 -M P, or M T X , pr o vi de d t he d ose prescri be d h as bee n sta ble f or 4  wee ks pri or 
t o ra n d o mizati o n; d ose of M T X m ust re mai n sta bl e f or 2 6 wee ks, a n d d os e of A Z A/ 6-M P 
m ust re mai n sta ble f or t h e first 1 3 wee ks , b ut ca n be a dj uste d if i n dicate d bet wee n 1 3  a n d 
2 6  wee ks.  
•  C ortic oster oi d t hera p y ( pre d nis o ne pres cri be d at a sta ble d ose ≤ 2 0  m g/ da y or b u des o ni de 
prescri be d at a sta ble d os e of ≤ 9  m g/ d a y) ; d ose s h o ul d n ot be c ha n ge d d uri n g t he first 
1 3  wee ks. A ster oi d  ta per s h o ul d o nl y c o m me nce after Wee k 1 3. 
C o nc o mit a nt Ster oi d M a n a ge me nt:  
Starti n g at W ee k  1 3, s u bj ects w h o are o n c o n c o mita nt ster oi ds ma y b e gi n ta peri n g st er oi d 
t hera p y at t he discreti o n of t he i n vesti gat or. Ster oi ds ma y b e i ncrease d or restarte d if retur n of 
s y m pt o ms is a p pare nt ( b ut d ose ma y n ot e xcee d 2 0 m g pre d nis o ne e q ui val e nt).  
5. 3. 2.  
Pr o hi bite d C o nc o mit a nt Me dic ati o ns  
T he pr o hi bite d me dicati o ns w hile o n st u d y are as f oll o ws:  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6 6  
 
0 9 Se pte m ber 2 0 2 2  
T a ble  5 -1 . 
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 w e d  
Pr o hi bite d Peri o d  
Str o n g P -g p I n d ucers a 
A ntic o n v ulsa nts  
P he n o bar bital, p he n yt oi n, a n d 
car ba maze pi ne  
2 1 da ys pri or t o Scree ni n g t hr o u g h t he e n d 
of t he st u d y  
A nti m yc o bacterials  
Rif a b uti n, rif a pe nti ne, a n d rif a m pi n 
Her bal/ Nat ural 
S u p ple me nts  
St. J o h n’s w ort a n d da ns he n ( Sal via 
Milti orr hiza)  
Pr o hi bite d I B D Me dic ati o ns d  
C ortic oster oi ds  
D ose e q ui vale nt t o > 2 0 m g/ da y of 
pre d nis o ne  
Ra n d o mizati o n t hr o u g h t he e n d of t he st u d y 
( u nless i n M o nit ori n g P hase) 
T N F α a nta g o nist  
I nfli xi ma b, a dali m u ma b, g oli m u ma b, 
cert oliz u ma b, a n d bi osi milar a ge nts  
8 wee ks pri or t o Scree ni n g t hr o u g h t he e n d 
of t he st u d y ( u nless i n M o nit ori n g P hase)  
I nte gri n a nta g o nist 
Ve d oliz u ma b a n d nataliz u ma b  
8 wee ks pri or t o Scree ni n g t hr o u g h t he e n d 
of t he st u d y ( u nless i n M o nit ori n g P hase)  
I nterl e u ki n a nta g o nist 
Uste ki n u ma b  
1 2 wee ks pri or t o Scree ni n g t hr o u g h t he e n d 
of t he st u d y ( u nless i n M o nit ori n g P hase)  
J A K i n hi bit or 
A n y J A K i n hi bit or ot her t ha n fil g oti ni b  
9 0 da ys pri or t o Scree ni n g t hr o u g h t he e n d 
of t he st u d y ( u nless i n M o nit ori n g P hase)  
Fil g oti ni b  
A n y ti me pri or t o Ra n d o mizati o n i n t his 
st u d y 
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, a n d a n y i n vesti gati o nal a ge nt 
3 0 da ys pri or t o Scree ni n g t hr o u g h t he e n d 
of t he st u d y  
Ot her ( bi ol o gic) c 
A n y i n vesti gati o nal bi ol o gic a ge nt  
8 wee ks ( or 5 half -li ves, w hic he ver is 
l o n ger) pri or t o Scree ni n g t hr o u g h t he e n d of 
t he st u d y 
L y m p h oc yte -de pleti n g 
t hera pies 
Ale 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 d e pleti n g t hera p y  
A n y ti me b ef ore a n d t hr o u g h t he e n d of t he 
st u d y 
S ulf a dr u gs  
S ulf asalazi ne  
C urre nt use of s ulf asalazi ne or use of 
s ulf asalazi ne wit hi n 2 6 wee ks of Scree ni n g . 
S ulf asalazi ne is n ot per mitte d  at a n y p oi nt 
d uri n g t he st u d y  
Ot her P r o hi bite d Me dic ati o ns  
C hr o nic N o nster oi dal 
A nti -i nfla m mat or y 
Dr u gs ( N S AI Ds) b 
As piri n, i b u pr of e n, na pr o xe n, dicl of e nac, 
i n d o met haci n, C O X-2 i n hi bit ors  
Fr o m Scree ni n g t hr o u g h t he e n d of t he st u d y  
a 
Ma y decr ease st u d y dr u g e x p os ure a n d are e xcl u de d t o a v oi d p ote ntial re d ucti o n i n st u d y dr u g acti vit y.  
P K res ults i n dicate fil g oti ni b is a P -g p s u bstrate, as a si n gle d ose of 2 0 0 m g itrac o naz ole (a p ote nt P -g p i n hi bit or) i ncrease d 
fil g oti ni b Cma x  b y 6 4 % a n d A U C i nf b y 4 5 % a n d ha d n o effect o n t he maj or, acti ve meta b olite G S -8 2 9 8 4 5.  
b  
Occasi o nal use of N S AI Ds f or tra nsie nt s y m pt o ms a n d dail y use of as piri n u p t o 1 6 2. 5 m g f or t h e p ur p ose of car di o vasc ular 
pr o p h yla xis are per mitte d  
c 
Ot her a p pr o ve d bi ol o gics ( e g, a nti b o d y base d or ot her s yste mi c bi ol o gics) ma y be all o we d wit h t h e a p pr o val of t h e m e dical 
m o nit or or desi g nee w h o will als o s pecif y t h e c orres p o n di n g pr o hi bite d peri o d  
d  
S u bjects w h o disc o nti n ue st u d y dr u g a n d e nter t he M o nit ori n g P hase, will be offere d l o call y a p pr o ve d S O C  t h era p y; i n t his 
case, c o nc o mita nt me dicati o ns i n t h e a b o ve ta ble ma y be per mitte d u p o n disc ussi o n wit h t h e me dical m o nit or or desi g nee  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6 7  
 
0 9 Se pte m ber 2 0 2 2  
5. 4.  
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 h at 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 atte n uate d v acci n es (i ncl u di n g, b ut n ot li mite d t o, varicella a n d i ntra nasal i nfl ue nza 
vacci nes) are pr o hi bite d wit hi n 3 0 da ys of Da y  1, t hr o u g h o ut t he st u d y, a n d f or 1 2  w ee ks 
after t he l ast  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 d eli 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 b e a v oi de d f or t he bel o w state d ti me peri o ds:  
⎯ Varicella or li ve atte n uat e d ( oral) t y p h oi d vacci nes –  a v oi d c o ntact f or 4  wee ks f oll o wi n g 
h o use h ol d c o ntact va cci n ati o n  
⎯ Li ve atte n uate d ( oral) p oli o vacci ne –  a v oi d c o ntact f or 6 wee ks f oll o wi n g h o use h ol d 
c o ntact va cci nati o n  
⎯ Li ve atte n uate d r ot a vir us vacci ne –  a v oi d c o ntact f or 1 0 da ys f oll o wi n g h o use h ol d 
c o ntact va cci nati o n  
⎯ Li ve atte n uate d (i ntra nas al) i nfl ue nza vacci ne –  a v oi d c o ntact f or 1 wee k f oll o wi n g 
h o use h ol d c o ntact va cci n ati o n  
•  I n acti vate d v acci n es (s uc h as i nacti vate d i nfl ue nza 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 n e ver me dicall y a p pr o pri ate; h o we ver, t here are 
n o a vaila ble data o n t he c o nc urre nt use of fil g oti ni b 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. 5.  
Acc o u nt a bilit y f or St u d y Dr u gs  
T he i n vesti gat or is res p o nsi ble f or e ns uri n g a d e q u ate acc o u nta bilit y of all use d a n d u n use d st u d y 
dr u gs. 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 st u d y dr u gs ( q ua ntit y a n d 
c o n diti o n). All use d  a n d u n use d st u d y dr u gs 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 acc 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 dat e recei ve d a n d q ua ntit y of st u d y dr u g  
•  Rec or d t he dat e, s u bject n u m ber, t he i n vesti gati o nal m e dici nal pr o d uct (I M P) n u m ber 
dis pe nse d  
•  Rec or d t he dat e, q ua ntit y of use d a n d u n use d I M P 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  
•  Dis pe nsi n g rec or ds will i ncl u de t he i nitials of t he pers o n dis pe nsi n g t h e st u d y dr u g or 
s u p plies 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6 8  
 
0 9 Se pte m ber 2 0 2 2  
5. 5. 1.  
I n vesti g ati o n al Me dici n al Pr o d uct Ret ur n or Dis p os al 
T he S p o ns or rec o m me n ds t hat use d a n d u n use d st u d y dr u g s u p plies b e destr o ye d at t he site. If 
t he site has a n a p pr o priat e sta n dar d o perati n g pr oce d ure (S O P ) f or dr u g destr ucti o n as 
deter mi ne d b y t he S p o ns or , t he site ma y destr o y use d (e m pt y or partiall y e m pt y) a n d u n us e d 
st u d y dr u g s u p plies i n acc or da nce wit h t hat site’s a p pr o ve d S O P. A c o p y of t he site’s a p pr o ve d 
S O P will be o btai ne d f or t he S p o ns or’s site files. If st u d y dr u g is destr o ye d o n site, the 
i n vesti gat or m ust mai ntai n acc urate rec or ds f or all st u d y dr u gs destr o ye 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 st u d y dr u g. U p o n st u d y c o m pleti o n, c o pies of t he st u d y dr u g 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 t he S p o ns or.  
If t he site d oes n ot ha v e a n a p pr o priate S O P f or dr u g destr u cti o n, use d a n d u n use d st u d y dr u g 
s u p plies are t o be se nt t o t he desi g n ate d dis p osal f acilit y f or destr ucti o n. T h e st u d y m o nit or will 
pr o vi de i nstr ucti o ns f or ret ur n.  
T he st u d y m o nit or will re vie w st u d y dr u g s u p plies a n d ass ociate d rec or ds at peri o dic i nter vals.  
F or b ot h dis p osal o pti o ns liste d a b o ve, t he st u d y m o nit or m ust first perf o r m dr u g acc o u nt a bilit y 
d uri n g a n o n -site m o nit ori n g visit.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6 9  
 
0 9 Se pte m ber 2 0 2 2  
6.  
S T U D Y P R O C E D U R E S  
T he st u d y assess me nts as descri be d b el o w will be perf or me d at t he ti me p oi nts s pecifie d i n t he 
St u d y Pr oce d ures Ta ble ( A p pe n di x  2 ).  
T he i n vesti gat or m ust d oc u me nt a n y de viati o n fr o m pr ot oc ol pr oce d ures a n d n otif y t he s p o ns or 
or C R O . 
6. 1.  
S u bject E nr oll me nt a n d Tre at me nt Assi g n me nt  
S u bject eli gi bilit y will be esta blis he d at t he c o n cl usi o n of t he Scree ni n g e v al uati o ns. T he s u bject 
I D will be assi g ne d f or eac h s u bject b y I W R S.  
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 eac h s u bject is eli gi ble f or t he st u d y 
bef ore ra n d o mizati o n a n d t he start of treat me nt. A s u bject will be c o nsi dere d e nr olle d o n ce t he y 
ha ve bee n ra n d o mize d.  
S u bjects w h o meet pr ot o c ol criteria will be ra n d o mize d t o fil g oti ni b 2 0 0 m g or P T M fil g oti ni b 
2 0 0 m g  o nce dail y.  
6. 2.  
Pretre at me nt Assess me nts  
6. 2. 1.  
Scree ni n g Visit  
S u bjects will be scree ne d wit hi n 4 5  d ays bef ore r a n d o miz ati o n t o deter mi ne eli gi bility f or 
p artici p ati o n i n t he st u dy . T he 4 5 d ay Scree ni n g peri o d m ay be exte n de d i n c o ns ult ati o n wit h t he  
m e dic al m o nit or . Refer t o t he St u dy Pr oce d ure T a bles i n A p pe n di x  2  f or a c o m plete list of 
assess me nts t o be perf or me d a n d d oc u me nte d at Scree ni n g:  
•  O btai n writte n i nf or me d c o nse nt  
•  O btai n de m o gra p hics a n d me dical hist or y (i ncl u di n g o nset of I B D, pri or n u m ber of c hil dre n 
fat here d, disease c haract eristics, s m o ki n g ha bits, a vera ge wee kl y alc o h ol c o ns u m pti o n, a n d 
fa mil y hist or y of pre mat ure c or o nar y heart diseas e) 
•  Re vie w I ncl usi o n / E x cl usi o n Criteria  
•  C o m plete P h ysi cal E x a m ( P E)  as detaile d i n A p pe n di x  7  
•  V ital si g ns, wei g ht a n d h ei g ht  
•  Perf or m sta n dar d 1 2 -Lea d E C G  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  7 0  
 
0 9 Se pte m ber 2 0 2 2  
•  Q ua nti F E R O N ®  test a n d C hest X-ra y ( C X R) (if a p plica ble). Q ua nti F E R O N®  p ositi ve or 
ne gati ve r es ults m ust n ot be re peate d. A n i n det er mi nate res ult s h o ul d be re p eate d o nce a n d 
t he sec o n d res ult (if p ositi ve or ne gati ve) will be acce pte d. T w o se q ue ntial i n deter mi nate 
res ults c o nstit ute a scree n fail ure. S u bjects wit h pre vi o usl y tr eate d T B  or n e wl y i d e ntifie d 
late nt T B d uri n g Scree ni n g  re q uire s p o ns or a p pr o val ( See I n cl usi o n Criteri o n N o. 1 2 f or 
details). S u bjects w h o are dia g n ose d wit h late nt T B at Scree ni n g m ust i nitiate a n a d e q uate 
c o urse of pr o p h yl a xis acc or di n g t o l ocal c o u ntr y g ui deli nes f or i m m u n oc o m pr o mise d 
patie nts f or a mi ni m u m of 4 wee ks pri or t o ra n d o mizati o n. S u bject ma y i nitiate st u d y dr u g 
d osi n g o nl y after c o ns ult ati o n wit h t he m e dical m o nit or or desi g n ee. If a s u bject ha d a 
Q ua nti F E R O N ®  test f or t he p ur p oses of cli nical care or Scree ni n g f or a n ot h er 
Gilea d -s p o ns ore d st u d y wit hi n 6 0 da ys, t he pri or Gilea d res ult ma y be us e d t o assess 
eli gi bilit y wit h per missi o n of t he me dical m o nit or or desi g n ee.  
•  Uri nal ysis, i ncl u di n g a uri ne dr u g s cree n  
•  O btai n bl o o d sa m ples f or:  
⎯ He mat ol o g y a n d Ser u m C he mistr y  
⎯ Ser ol o g y  
⎯ Q ua ntitati ve I g s u bclasses  
⎯ E n d ocri ne tests: T h yr oi d sti m ulati n g h or m o ne ( T S H), H b A 1c  
⎯ Se x h or m o nes, i ncl u di n g L H, F S H, i n hi bi n B, a n d t otal test oster o ne t o be c ollecte d 
bet wee n 0 7: 0 0 –  1 1: 0 0 i n t he m or ni n g , if p ossi ble 
•  St o ol C ollecti o n f o r: 
⎯ C. difficile t o xi n, E. c oli, S al m o nell a s p p, S hi gell a s p p, C a m pyl o b acter s p p a n d 
Y ersi ni a  s p p testi n g 
⎯ O va & Parasites ( O & P)  
•  Re vie w a n d c ollecti o n of c o nc o mita nt me dicati o ns  
•  Rec or d all seri o us a d v ers e e ve nts ( S A Es) a n d a n y A Es relate d t o pr ot o c ol -ma n date d 
pr oce d ures occ urri n g after si g ni n g of t he c o nse nt f or m  
•  Se me n c ollecti o n ( 2 se p arate c ollecti o ns i n acc or da nce wit h Secti o n  6. 1 3 ) a n d rec or d date 
a n d ti me of last ejac ulati o n pri or t o sa m ple. Se me n c ollecti o n s h o ul d be c ollecte d t o c oi nci de 
wit h baseli ne visit as m uc h as p ossi ble.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  7 1  
 
0 9 Se pte m ber 2 0 2 2  
•  F or s u bjects wit h U C, c ollect t he varia bles t o calc ulate baseli ne M C S ( Defi niti o n  of  Ter ms 
a n d A p pe n di x  3 ), i ncl u di n g perf or mi n g fle xi ble si g m oi d osc o p y u nless perf or me d i n t he 
9 0  da ys pri or t o Scree ni n g. T he M C S is c o m p ose d of s u b -sc ores fr o m e n d osc o p y, rect al 
blee di n g, st o ol fre q ue n c y, a n d P G A. S u bject recall of t he last 2 4 h o urs will be use d f or t h e 
patie nt re p orte d c o m p o ne nts of t he M C S . F or t he c o m plete M C S, P G A will be e val uat e d 
after re vie wi n g t he e n d os c o p y.  
•  F or s u bjects wit h C D, c ollect t he varia bles t o calc ulate baseli ne t otal C D AI sc ore 
( Defi niti o n of  Ter ms a n d A p pe n di x  9 ) a n d t o calc ulate baseli ne S E S-C D ( Defi niti o n of 
Ter ms a n d A p p e n di x  1 0 ), i ncl u di n g perf or mi n g ile oc ol o n osc o p y u nless perf or me d i n t he 
9 0  da ys pri or t o Scree ni n g. S u bject r ecall of t h e last 7 da ys will be use d f or t he patie nt 
re p orte d c o m p o ne nts of t he C D AI. T he C D AI  sc ore cal c ulati o ns s h o ul d n ot be i ncl usi ve of 
da ys t hat i n v ol ve a n e n d osc o p y pr oce d ure or pre p arati o n f or t hat pr o ce d ure . 
A si n gle retest of a ny excl usi o n ary scree ni n g l a b ( n o n -se me n s a m pl es) is per mitte d: 
•  at t he discreti o n of t he i n vesti gat or, if t h e i ni tial e xcl usi o nar y val ue is i n vali d d ue t o a 
d oc u me nte d err or i n sa m ple c ollecti o n or la b orat or y pr ocessi n g, O R  
•  u p o n t he a p pr o val of t h e S p o ns or Me dical M o nit or or desi g nee, if t here  is a n e xte n uati n g 
circ u msta nc e ar o u n d t he e x cl usi o nar y val u e .  
Retesti n g of e x cl usi o nar y para meters i n S cree ni n g se me n sa m ples is disc usse d i n Secti o n 6. 1 3  
S u bjects meeti n g all of t he i ncl usi o n criteri a a n d n o ne  of t he excl usi o n criteri a will ret ur n t o t he 
cli nic after Scree ni n g, f or r a n d o miz ati o n i nt o t he st u dy.  
Fr o m t he ti me of o btai ni n g i nf or m e 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, r ec or d all S A Es, as well as a n y a d v er se e ve nts r elate d t o pr ot oc ol-ma n date d 
pr oce d ures o n t he a d v ers e e ve nts c ase re p ort f or m ( C R F/e C R F). All ot her u nt o war d me dical 
occ urre nces o bser ve d d uri n g t he Scree ni n g peri o d, i ncl u di n g e x acer bati o n or c ha n ges i n me di cal 
hist or y are t o be ca pt ure d o n t he  me dical hist or y C R F/e C R F. See Secti o n  7  A d verse E v e nts a n d 
T o xicit y Ma n a ge me nt f or a d diti o nal details.  
6. 2. 1. 1.  
Rescree ni n g  
S u bjects w h o d o n ot meet t he eli gi bilit y criteria will n ot be ra n d o mize d, b ut ma y b e c o nsi dere d 
f or a si n gle rescree ni n g after c o ns ultati o n wit h, a n d a p pr o val b y, t he S p o ns or Me dical M o nit or  or 
desi g nee. S u bjects w h o are res cree ne d d o n ot nee d t o ha ve a re peat Q u a nti F E R O N ®  a n d/ or C X R, 
if t hese were perf or me d wit hi n 9 0 da ys of writte n c o nse nt f or rescree ni n g, u nless a re peat is 
dee me d a p pr o priate b y t h e i n vesti gat or.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  7 2  
 
0 9 Se pte m ber 2 0 2 2  
6. 2. 2.  
D a y 1 Assess me nts  
O n Da y 1, after t he s u bject’s eli gi bilit y f or t he st u d y has b ee n c o nfir me d, t he s u bject wil l be 
ra n d o mize d i nt o t he st u d y t o recei ve fil g oti ni b 2 0 0 m g  or P T M fil g oti ni b 2 0 0 m g  o nce dail y. 
St u d y dr u g will be dis pe nse d as assi g ne d b y t he I W R S s yste m. T he s u bject will ta ke t he first 
d ose i n cli nic. I n vasi ve st u d y pr oce d ures s uc h as bl o o d dra ws s h o u l d be d o ne at t he e n d of t h e 
St u d y Visit . T he f oll o wi n g will be perf or me d a n d d oc u me nte d at D a y 1 pri or t o d osi n g: 
•  Re vie w I ncl usi o n / E x cl usi o n Criteria  
•  S y m pt o m -dri ve n p h ysical e x a mi nati o n, as nee de d  
•  Vital si g ns (resti n g bl o o d press ure, res pirat or y rate, p ulse a n d te m perat ure)  
•  Wei g ht ( wit h o ut s h oes)  
•  P h ysicia n’s Gl o b al Assess me nt [ a p plie d o nl y t o s u bjects wit h U C]  
•  O btai n bl o o d sa m ples f or:  
⎯ He mat ol o g y a n d Ser u m C he mistr y  
⎯ Li pi d pr ofile (fasti n g) [ T otal c h olester ol a n d s u bfracti o ns]  
⎯ Se x h or m o nes, i ncl u di n g L H , F S H, i n hi bi n B, a n d t otal Test oster o ne t o be c ollecte d 
bet wee n 0 7: 0 0 –  1 1: 0 0 i n t he m or ni n g , if p ossi ble 
•  Uri nal ysis  
•  Re vie w c o nc o mita nt me dicati o ns  
•  Rec or d a n y a d vers e e ve nts relate d t o pr ot oc ol ma n date d pr oce d ures a n d all seri o us a d verse 
e ve nts ( S A Es) occ urri n g after si g ni n g of t he c o nse nt f or m.  
6. 3.  
R a n d o miz ati o n  
S u bjects will be ra n d o ml y all ocate d t o d osi n g gr o u p acc or di n g t o a pre -s p ecifie d ra n d o mizati o n 
sc he me pre pare d b y a n i n de pe n de nt statisticia n. O nce c o nfir me d eli gi ble f or t he st u d y, s u bjects 
will b e ra n d o mize d usi n g a c o m p uterize d I W R S s yste m t o fil g oti ni b 2 0 0  m g or P T M fil g oti ni b 
2 0 0 m g  i n a 1: 1 rati o, wit hi n strata.  
Ra n d o mizati o n will be stratifie d acc or di n g t o t he t y p e of I B D ( U C v ers us C D), c o nc urre nt use of 
M T X ( yes or n o), a n d s p er m c o nce ntra ti o n meas ure d at Scree ni n g (“ Baseli ne”) acc or di n g t o t he 
f oll o wi n g strata: 
•  1 5 t o 2 5 milli o n/ m L  
•  >  2 5 t o 5 0 milli o n/ m L 
•  >  5 0 milli o n/ m L  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  7 3  
 
0 9 Se pte m ber 2 0 2 2  
6. 4.  
P a rt  A ( D a y 1 t hr o u g h Wee k 1 3 St u d y Visit)  
All s u bjects will recei ve bli n de d st u d y dr u g f or t he first 1 3 wee ks . 
St u d y assess me nts will be c o m plete d as s p ecifie 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 Fi g ure  3 -2 .  
I n v asi ve st u d y pr oce d ures s uc h as bl o o d dra ws s h o ul d be d o ne at t he e n d of a St u d y Visit , as 
m uc h as p ossi ble.  
6. 5.  
P a rt B ( After W ee k 1 3 t hr o u g h Wee k 2 6 St u d y Visit)  
S u bjects w h o are Res p o n ders at W ee k 1 3 a n d w h ose s per m para meters d o n ot meet a 
pre -s pecifie d decrease t hres h ol d will c o nti n ue bli n de d st u d y dr u g i n Part B.  
St u d y assess me nts will be c o m plete d as s p ecifie 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 Fi g ure  3 -3 .  
I n v asi ve st u d y pr oce d ures s uc h as bl o o d dra ws s h o ul d be d o ne at t he e n d of a St u d y Visit , as 
m uc h as p ossi ble.  
6. 6.  
O pe n -L a bel Fil g oti ni b P h ase ( O pe n -L a bel D a y  1 t hr o u g h O pe n -L a bel 
Wee k  1 3 St u d y Visit)  
S u bjects w h o are N o n -Res p o n ders  at Wee k 1 3  i n Part A, or ha ve Disease W orse ni n g aft er 
Wee k  1 3 a n d bef ore reac hi n g Wee k  2 6 i n Part B, will disc o nti n ue bli n de d st u d y dr u g a n d 
c o m me nce O L  fil g oti ni b i n t he O L  Fil g oti ni b P has e , if s u bjects’ s per m para meters d o n ot meet a 
pre -s pecifie d decrease t hres h ol d. T w o se parate s e me n sa m ples will be c ollecte d a n d a nal yz e d 
bef ore s witc hi n g a s u bject t o O L  fil g oti ni b. 
St u d y assess me nts will be c o m plete d as s p ecifie 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 Fi g ure  3 -4 .  
6. 7.  
M o nit ori n g P h ase   
S u bjects w h o se s per m para meters me et a pre -s pecifie d decrease t hres h ol d d uri n g t he st u d y  will 
disc o nti n ue st u d y dr u g , c o m plete a safet y f oll o w-u p visit 3 0 da ys after last d ose of st u d y dr u g,  
a n d e nter t he M o nit ori n g P hase . S u bjects will be offere d S O C t hera p y as part of t he M o nit ori n g 
P hase , a n d u n der g o s p er m e val uati o ns e ver y 1 3  wee ks ( 2  s e parate sa m ples at eac h time p oi nt) 
fr o m t he da y of st u d y dr u g disc o nti n uati o n, f or u p t o 5 2 wee ks or u ntil Re versi bilit y is met 
(see D efi niti o n of Ter ms), w hic he ver is ac hie ve d first.  
St u d y assess me nts will be c o m plete d as s p ecifie 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 Fi g ure  3 -5 . 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  7 4  
 
0 9 Se pte m ber 2 0 2 2  
6. 8.  
E arl y Ter mi n ati o n  
If a s u bject disc o nti n ues st u d y partici p ati o n f or a n y reas o n pri or t o Wee k 2 6, O L Wee k 1 3, 
reac hi n g Re v ersi bilit y or M o nit ori n g P hase Wee k 5 2  ( w hic he ver occ urs first), or L T E Wee k 1 9 5, 
E T visit assess me nts will be c o m plete d as s p ecifie d i n t he St u d y Pr oce d ures Ta ble ( A p pe n di x  2 ).  
S u bjects w h o are Res p o n ders at W ee k 2 6 a n d at O L  Wee k 1 3 a n d c h o ose n ot t o c o nti n ue t o t he 
L T E will als o c o m plete E T visit a ssess me nts. 
6. 9.  
S afet y F oll o w -U p Visit 3 0 D a ys P ost L ast D ose ( ± 5 d a ys)  
A n y ti me a s u bject disc o nti n ues st u d y dr u g, a s afet y f oll o w -u p visit , 3 0  da ys after t he last d ose of 
st u d y dr u g is re q uire d, e v e n if t he s u bject is e nteri n g t he M o nit ori n g P hase.  
St u d y assess me nts will be c o m plete d as s p ecifie d i n t he St u d y Pr oce d ures Ta ble ( A p pe n di x  2 ). 
6. 1 0.  
L o n g Ter m E xte nsi o n  
S u bjects w h o are Res p o n ders at eit her Wee k  2 6 ( P art B) or O L Wee k 1 3 ( O L  P hase ), a n d w h os e 
s per m para m eters d o n ot meet a pre-s pecifie d decrease t hr es h ol d, will e nter t he L T E a n d  
c o nti n ue o n t he sa me dr u g t he y w ere res p o n di n g t o  (ie, O L  fil g oti ni b or bli n de d st u d y dr u g). As 
s pecifie d i n t he St u d y Pr oce d ures T a ble ( A p pe n di x  2 ) a n d Fi g ure  3 -6 , s u bj ects c o nti n ui n g o n t o 
t he L T E will u n der g o sc h e d ule d visits f or safet y assess me nts e ver y 1 3 wee ks, u p t o 1 9 5 wee ks , 
a n d se me n m o nit ori n g will be c ollecte d e v er y 1 3 wee ks u ntil t he Wee k 1 3 pri mar y st u d y res ults 
are a n al yze d .  
S u bjects i n t he L T E w h o m eet Disease W orse ni n g criteria as descri b e d i n Secti o n  3. 4  or ha ve 
Disease W orse ni n g per i n vesti gat or j u d g me nt s h o ul d be disc o nti n ue d fr o m st u d y dr u g. T h ese 
s u bjects s h o ul d c o m plete E T a n d t he safet y f oll o w-u p visit 3 0  da ys after t he last d ose of st u d y 
dr u g.  
6. 1 1.  
S afet y a n d T oler a bilit y  
A Es, P E, vital si g ns, a n d la b orat or y ass ess me nts (sta n dar d he mat ol o g y, ser u m/ plas ma c he mistr y, 
a n d uri nal ysis) will be c ollecte d. Se me n sa m ples will be c ollecte d i n acc or da nce wit h 
Secti o n  6. 1 3 . 
6. 1 2.  
Cli nic al L a b or at or y E v al u ati o ns  
T he he mat ol o g y a n d ser u m c he mistr y la b orat or y a nal yses will be perf or me d at a ce ntr al 
la b orat or y. Refere n ce ra n ges will be s u p plie d b y t he centr al la b orat or y a n d will be use d b y t he 
i n vesti gat or t o ass ess t he la b orat or y dat a f or cli nical si g nifica nce a n d pat h ol o gical c ha n ges. 
Bl o o d sa m ples will be c ollecte d b y ve ni p u nct ure i n t he ar m at t he 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 ). I n a d diti o n, uri ne sa m ples f or t he cli nical la b orat or y 
assess me nts will be c ollecte d. S u bjects o nl y n ee d t o be faste d o n da ys w here li pi d p r ofili n g is 
sc he d ule d.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  7 5  
 
0 9 Se pte m ber 2 0 2 2  
Please refer t o A p p e n di x  6  f or ta ble of cli nical la b orat or y tests. 
T he la b orat or y v al 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 n ce 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 w ell as a d diti o nal tests ma y b e 
perf or me d , as i n dicate d a n d dee me d necessar y b y t he i n vesti gat or.  
N ote t hat i n t he case w here cli nicall y si g nifica nt la b orat or y test res ults are a p ote ntial reas o n f or 
disc o nti n uati o n fr o m t he st u d y dr u g a n d wit h dra wal fr o m t he st u d y, retesti n g of t he affecte d 
para meter(s) s h o ul d be pr o m pt ( wit hi n 3 t o 7  da ys) after t h e i n vesti gat or has c o ns ulte d wit h t he 
me dical m o nit or or desi g nee. A decisi o n re gar di n g s u bject disc o nti n uati o n s h o ul d be ma de aft er 
t he res ults fr o m t he retest are a v aila ble (s ee Secti o n 3. 3  f or a d diti o nal i nf or mati o n). 
T he details of sa m ple h a n dli n g a n d s hi p me nt i nstr ucti o ns will be pr o vi de d i n a se parate 
la b orat or y ma n u al.   
6. 1 3.  
Se me n C ollecti o n Pr o ce d ure  
Eac h s u bject will pr o vi de 2 se parat e se me n sa m ples c ollecte d wit hi n a 1 4 -d a y p eri o d a n d wit h a n  
ejac ulati o n -free p eri o d of ≥ 4 8 h o urs a n d ≤ 7 da ys , at t he f oll o wi n g ti me p oi nts:  
•  Scree ni n g ( Bas eli ne)  
•  After Part A ( Wee k 1 3 St u d y Visit ) 
•  After Part B ( Wee k 2 6 St u d y Visit )  
O R  
F or S u bjects w h o e x perie nce c o nfir me d Diseas e W orse ni n g bet w ee n Wee ks 1 3 -2 6 i n Part B, 
p ri or t o be gi n ni n g O L  Fil g oti ni b a n d at t he O L Wee k 1 3  St u d y Visit  
•  E ver y 1 3 wee ks d uri n g t he M o nit ori n g P hase (if a p plica ble)  
•  E ver y 1 3 wee ks d uri n g t he L T E  
All decisi o ns of rete sti n g a n y s e me n/s per m para m eter ( ie, o bt ai ni n g a t hir d se me n sa m ple at a n y 
of t he a b o ve ti me p oi nts), m ust be a p pr o ve d b y t h e S p o ns or Me dical M o nit or or desi g nee bef ore 
t he retest. S uc h i n q uiries will o nl y b e c o nsi dere d i n select i nsta nces w h ere t he se me n sa m ple 
wit h t he q uest i o ne d val ue(s) is f o u n d t o be n o n -assessa ble or i n vali d (e g , c ollecti o n wit h o ut 
a d here n ce t o ej ac ulati o n -free p eri o ds; i nterc urre nt ill ness or de h y drati o n  at ti me of c ollecti o n;  
i nc o m plete ca pt ur e of se me n sa m ple; a n d/ or sa m ple pr ocessi n g or s e me n a nal ysis  t hat d e viates 
fr o m sta n dar dize d pr oce d ure). T he t hir d se me n sa m ple , w he n i n dicate d, m ust be c ollecte d wit hi n 
1 4 da ys of t he pri or s a m ple a n d wit h a n  ejac ulati o n -free peri o d of ≥ 4 8 h o urs a n d ≤ 7 da ys  
(See  Fi g ure  6 -1 ). 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  7 6  
 
0 9 Se pte m ber 2 0 2 2  
At eac h ti me p oi nt, t he mea n of 2 se p arat e se me n s a m ples f or eac h para met er will be use d f or t he 
assess me nt  of st u d y eli gi bilit y, e ntr y i nt o t he M o nit ori n g P hase, a n d e xit fr o m t he M o nit ori n g 
P hase.  
Fi g ure  6 -1 . 
Se me n C ollecti o n Sc he m a  
 
 
A sta n dar dize d pr oce d ure f or se me n c ollecti o n a n d a nal ysis will be pr o vi d e d t o sites i n a se parate 
ma n ual . Se me n will be assesse d l oc all y f or all para meters ( m otilit y, c o n ce ntrati o n, c o u nt, a n d 
v ol u me) , e x ce pt m or p h ol o g y, w hic h will be assess e d ce ntr all y . 
6. 1 4.  
Vit al Si g ns  
Vital si g ns will be meas ure d at t he 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 ).  
Vital si g ns s h o ul d be ta k e n after t he s u bject has b ee n resti n g f or 5  mi n utes  ( please refer t o 
A p pe n di x  7  f or details) a n d will i ncl u de heart rate, res pirat or y rate, s yst olic bl o o d press ure 
( S B P), diast olic bl o o d press ure ( D B P), a n d b o d y t e m perat ur e. 
6. 1 5.  
P h ysic al E x a mi n ati o n  
A p h ysic al e x a mi nati o n wi ll be perf or me d at t he 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 p e n di x  2 ).  
A n y c ha n ges fr o m Baseli ne will be rec or de d. Hei g ht will be m eas ure d at Scree ni n g o nl y.  Wei g ht 
wit h o ut s h oes is meas ure d at all visits.  
A  c o m plete p h ysical e x a mi nati o n , as detaile d i n A p pe n di x  7 , will be perf or me d at Scree ni n g , 
o nl y . S y m pt o m-dir ecte d p h ysical e x a ms will be perf or me d at all ot her visits , as nee de d.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  7 7  
 
0 9 Se pte m ber 2 0 2 2  
6. 1 6.  
P h ar m a c o ki netic Assess me nts  
I n Parts A a n d B, bl o o d sa m ples f or P K a n al ysis will be c ollecte d at least 3 0 mi n utes p ost st u d y 
dr u g d osi n g at t he Wee k 2 visit, a n yti me at t he Wee k 4 visit, a n d pri or t o st u d y dr u g d osi n g at t he 
Wee k 1 3 a n d 2 6 visits. I n t he O L  Fil g oti ni b P hase, bl o o d sa m ples f or P K a n al ysis will be 
c ollecte d at least 3 0 mi n utes p ost st u d y dr u g d osi n g at t he O L Wee k  2 visit, a n yti me at t he 
O L  Wee k 4 visit, a n d pri or t o st u d y dr u g d osi n g at t he O L Wee k  1 3 visit. S u bjects s h o ul d be 
i nstr ucte d n ot t o ta ke t heir st u d y dr u g o n t h ese visit da ys (e x ce pt f or t he Wee k 4 visit) a n d bri n g 
it wit h t he m t o t he cli nic, i nstea d.   
S u bjects will be i nstr ucte d w he n t o ta ke t heir d os e d uri n g t heir s c he d ule d visit at t he st u d y site.  
Plas ma c o nce ntr ati o ns of fil g oti ni b a n d its meta b olite, G S -8 2 9 8 4 5, will be a nal yze d.  
6. 1 7.  
T hr o m b oe m b olic E ve nts  
S u bjects e x perie nci n g a t hr o m b oe m b olic e ve nt s h o ul d be e val uate d f or t he o verall ris k of 
rec urre nt t hr o m b oe m b olis m a n d referre d t o a s pecialist f or f urt her testi n g as a p pr o priate 
(i ncl u di n g b ut n ot li mite d t o e val uati o n f or a n u n derl yi n g i n herite d h y perc oa g ul a ble state). 
6. 1 8.  
M a y o Cli nic Sc ore a n d P a rti al M a y o Cli nic Sc ore  
M C S a n d partial M C S will be assesse d at t he ti me p oi nts i n dicate d i n t he St u d y Pr oce d ures T a ble 
(A p pe n di x  2 ). T he M C S (A p pe n di x  3 ) is all o we d t o ha ve bee n perf or me d wit hi n t he 9 0 da ys 
p ri or t o Scree ni n g a n d is c o m p ose d of s u b-sc ores fr o m e n d osc o p y, rectal bl ee di n g, st o ol 
fre q ue n c y, a n d P G A. T h e partial M C S i ncl u des t he rect al blee di n g, st o ol fre q ue nc y, a n d 
P G A  s u b-sc ores. S u bject recall of t h e last 2 4 h o urs will be use d f or t he patie nt re p orte d 
c o m p o ne nts of t he M C S a n d partial M C S. F or t he c o m plete M C S, P G A will be e val uate d after 
re vie wi n g t he e n d os c o p y, w hic h will be l ocall y rea d.  
6. 1 9.  
Si m ple E n d osc o pic Sc ore f or Cr o h n’s Dise ase  
S E S -C D will be assesse d at t he ti me p oi nts i n dicate d i n t he S t u d y Pr oce d ures Ta ble 
(A p pe n di x  2 ). T he S E S-C D ( A p pe n di x  1 0 ) is all o we d t o ha ve b ee n perf or me d wit hi n t he 9 0 da ys 
pri or  t o Scree ni n g a n d is a c o m p osite sc ore of m uc osal i nfla m mati o n c o nsisti n g of f o ur 
e n d osc o pic varia bles ( ulc er pres e nce a n d size; l u mi nal s urface c o vere d b y ulcers; l u mi nal s urface 
wit h disease i n v ol ve me nt; a n d ste n osis prese nce a n d se verit y). T he b o wel is di vi de d i nt o 
se g me nts (ile u m, ri g ht c ol o n, tra ns verse c ol o n, left c ol o n, a n d rect u m) a n d eac h se g me nt is 
sc ore d i n di vi d uall y, t h e n t he se g m e nt sc ores are s u m me d f or a t otal sc ore (ra n ge: 0 t o 6 0). T he 
S E S -C D will be l ocall y rea d.  
6. 2 0.  
Cr o h n’s Dise ase Acti vit y I n de x  
C D AI will be assesse d at t he ti me p oi nts i n dicate d i n t he St u d y Pr oce d ures Ta bles ( A p pe n di x  2 ). 
T he C D AI ( A p p e n di x  9 ) is a c o m p osite sc ore of C D acti vit y c o nsisti n g of gastr oi ntesti nal 
s y m pt o ms (e g, a b d o mi nal pai n), si g ns (e g, a b d o mi nal mass), la b orat or y v al ues (ie, he mat o crit), 
a n d c o m plicati o n s (e g, art hritis/art hral gia), a m o n g ot her attri b utes. S u bject recall f or t he last 
7  da ys will be use d f or t h e patie nt re p orte d c o m p o ne nts of t he C D AI . T h e C D AI s c ore 
calc ulati o ns s h o ul d n ot be i ncl usi ve of da ys t hat i n v ol ve a n e n d osc o p y pr oce d ure or pre p ar ati o n 
f or t hat pr oce d ure. 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  7 8  
 
0 9 Se pte m ber 2 0 2 2  
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  
7. 1.  
Defi niti o ns of A d verse E ve nts, A d verse Re a cti o ns, a n d Seri o us A d verse 
E ve nts  
7. 1. 1.  
A d verse E ve nts  
A n a d vers e e ve nt ( A E) is a n y u nt o w ar d me dical o cc 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 h a ve a ca us al relati o ns hi p wit h t he 
treat me nt. A n A E ca n t heref ore be a n y u nfa v ora bl e a n d/ or u ni nte n de d si g n, s y m pt o m, or disease 
te m p orall y ass ociate d wit h t he use of a me di ci nal pr o d uct, w het her or n ot c o nsidere d rel ate 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 ost -treat me nt c o m pli cati o ns t hat occ ur as a 
res ult of pr ot oc ol s pecifie d pr oce d ures, la c 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 v erit y or c h a n ge i n nat ure d uri n g or 
as a c o nse q u e nce of partici pati o n i n t he cli nical st u d y will als o be c o nsi d ere 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 gic al 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 ma y b e a n a d verse e ve nt a n d m ust b e re p ort e 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 det ecte d bef ore t h e 
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 w ar d me dical occ urre n ce 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 ose wit h o ut cli nical se q uelae (see Secti o n  7. 7. 1 ) 
•  A n y me di cal 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 h e 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 o ciate d pr oce d ure is n ot a n 
A E. It 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 m e dical hist or y 
C R F.  
7. 1. 2.  
Seri o us A d verse E ve nts  
A seri o us a d verse e v e nt ( 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  
•  Lif e -t hreate ni n g ( N ote: T he ter m “life-t hreat e ni n g” i n t he defi niti o n of “seri ous” 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 d eat h if it were m ore s e 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 pitaliza ti o n 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  7 9  
 
0 9 Se pte m ber 2 0 2 2  
•  Persiste nt or si g nifica nt disa bilit y/i nca pacit y  
•  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 v e nts ma y n ot be i m me diatel y 
life-t hreat e 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 pr e ve nt o ne of t he ot h er o utc o mes c o nstit uti n g S A Es. Me dical a n d 
scie ntific j u d g m e nt m ust be e x ercise d t o deter mi ne w het her s u c h a n e ve nt is a re p orta bl e 
u n der e x pe dite d re p orti n g r ules. E x a m ples of me dicall y i m p orta nt e ve nts i ncl u d e 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 n c 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 n c 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 verse E ve nts  
T he i n vesti gat or or q ualifie d s u bi n vesti gat or is r es 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 v erit y, a n d f or fi nal r e 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 r es p o nsi ble f or asses si n g t h e relati o ns hi p t o 
I M P t hera p y usi n g cli nic al j u d g me nt a n d t h e f oll o wi n g c o nsi d erati o ns: 
•  N o : E vi de nce e xists t hat t he a d verse e ve nt h as a n eti ol o g y ot her t ha n t h e st u d y dr u g. F or 
S A Es, a n alter nati ve ca us alit y m ust be pr o vi de d (e g, pre -e xisti n g c o n di ti 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 n a ble p ossi bilit y t hat t he e v e nt ma y h a ve bee n ca use d b y t he 
i n vesti gati o nal me dici nal pr o d 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 usall y relate d i n 
t he c o nte xt of a d verse e v e nt 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 v asi ve pr oce d ures s uc h as v e ni p u nct ure or bi o ps y) 
s h o ul d be assesse d usin g t he f oll o wi n g c o nsi d erati o ns:  
•  N o: E vi de nce e xists t hat t he a d verse e ve nt h as a n eti ol o g y ot her t ha n t h e st u d y pr oce d ure.  
•  Yes:  T he a d vers e e ve nt o cc urre d as a res ult of pr ot oc ol pr oce d ures (e g, ve ni p u n ct ure).  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8 0  
 
0 9 Se pte m ber 2 0 2 2  
7. 2. 2.  
Assess me nt of Se verit y  
T he se verit y of A Es w ill 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 v e nt ( C T C A E ), versi o n 4. 0 3. 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 d e or a djecti ves: 
Gra de  1  ( mil d), Gra d e 2 ( m o derate), Gra d e 3 (se v ere), Gra de 4 (life-t hr eate ni n g) or 
Gra de  5  (fatal) t o descri b e t he ma xi m u m i nte nsit y of t he a d verse e v e nt. 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 d efi ne d i n T a ble  7 -1  a n d A p pe n di x  4 . 
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 d e 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 d e 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 d e 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 d e 4  
Life -
t hreate ni n g 
Ur ge nt i nter ve nti o n i n dicate d  
Gra d e 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 h e tele p h o ne, ma na gi n g m o ne y, etc.  
* *  Self -car e 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 h e 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 t he S p o ns or  
Re q uire me nts f or c ollecti o n pri or t o st u d y dr u g i nitiati o n: 
After i nf or m e d c o nse nt, b ut pri or t o i nitiati o n of st u d y dr u g, t he f oll o wi n g t y pes of e ve nts s h o ul d 
be re p ort e d o n t he case re p ort f or m ( C R F/e C R F): all S A Es a n d a d verse e ve nts relate d t o 
pr ot oc ol -ma n date d pr oc e d ures.  
A d verse E v e nts  
F oll o wi n g i nitiati o n of st u d y dr u g, c ollect all A Es, re gar dl ess of ca us e or relati o ns hi p, 
u ntil  3 0 -da ys after last a d mi nistrati o n of st u d y dr u g(s)  m ust be  re p ort e 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 d verse e v e nt is sta ble, if p ossi ble. 
T he S p o ns or  ma y re q u est t hat certai n A Es b e f oll o we d be y o n d t he pr ot oc ol defi ne d f oll o w u p 
peri o d.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8 1  
 
0 9 Se pte m ber 2 0 2 2  
Seri o us A d verse E v e nts  
All S A Es, re gar dless of ca use or relati o ns hi p, t hat occ urs after  t he s u bject first c o nse nts t o 
partici pate i n t he st u d y (i e, si g ni n g t he i nf or m e d c o nse nt) a n d t hr o u g h o ut t he d urati o n of t he 
st u d y, i ncl u di n g t h e pr ot oc ol-re q uir e d p ost-treat me nt f oll o w-u p peri o d, m ust be re p orte d t o t he 
C R F/e C R F data base a n d  t he S p o ns or as i nstr ucte d. T his als o i ncl u des a n y S A Es res ulti n g fr o m 
pr ot oc ol -ass ociat e d pr oce d ures perf or me d after i nf or me d c o nse nt is si g ne d.  
A n y S A Es a n d d eat hs t hat occ ur d uri n g a n y p orti o n of t he st u d y or after st u d y disc o nti n uati o n 
b ut wit hi n 3 0 -da ys of t he las t d ose of st u d y I M P, re gar dless of ca usalit y, s h o ul d als o be re p orte d.  
I n v esti gat ors are n ot o bli gat e d t o acti vel y see k S A Es after t he pr ot oc ol defi ne d f oll o w u p peri o d 
h o we ver, if t h e i n vesti gat or lear ns of a n y S A Es t hat occ ur after st u d y p artici pati o n h as c o ncl u de d 
a n d t he e ve nt is dee me d rele va nt t o t he use of I M P, he/s he s h o ul d pr o m ptl y d oc u me nt a n d re p ort 
t he e ve nt t o t he S p o ns or. 
All A Es a n d S A Es will be rec or de d i n t he C R F/e C R F data bas e wit hi n t he ti meli nes o utli ne d i n 
t he C R F/e C R F c o m pleti o n g ui deli ne.  
Re q uire me nts f or c ollecti o n i n t he M o nit ori n g P hase :  
D uri n g t h e M o nit ori n g P hase, all A Es  rel ate d t o pr ot oc ol-ma n date d pr oce d ures, a n d all S A Es  
(re gar dless of relate d ness) s h o ul d be re p ort e d o n t he case re p ort f or m ( C R F/e C R F).  
Electr o nic Seri o us A d v erse E ve nt (e S A E) Re p orti n g Pr ocess   
•  Site pers o n nel rec or d all S A E data i n t he e C R F data base a n d fr o m t here tra ns mit t he S A E 
i nf or mati o n t o t he S p o ns or wit hi n 2 4 h o urs of t he i n vesti gat or’s k n o wle d ge of t he e ve nt. 
Detaile d i nstr ucti o ns ca n be f o u n d i n t he  e C R F c o m pleti o n g ui deli nes.  
•  If f or a n y reas o n it is n ot p ossi ble t o rec or d t he S A E i nf or mati o n electr o nicall y, ie, t he e C R F 
data base is n ot f u ncti o ni n g, rec or d t h e S A E o n t he pa per seri o us a d v erse e ve nt re p orti n g 
f or m a n d s u b mit wit hi n 2 4 h o urs as descri be d a b o ve.  
E mail:   
M A N T A _safet y @ gl p g. c o m  
•  As s o o n as it is p ossi ble t o d o s o, a n y S A E re p orte d via pa per m ust be tra ns cri be d i nt o t he 
e C R F Data b ase acc or di n g t o i nstr ucti o ns i n t he e C R F c o m pleti o n g ui deli n es.  
•  If a n S A E has b ee n re p orte d via a pa p er f or m b ecause t he e C R F data base h as bee n l oc ke d, 
n o  f urt her acti o n is necessar y. 
•  All A Es a n d S A Es will be rec or de d i n t he e C R F d ata base wit hi n t he ti meli nes o utli ne d i n t he 
e C R F c o m pleti o n g ui d eli ne.  
•  F or fatal or life -t hreate ni n g e v e nts, c o pies of h os pital case re ports, a ut o ps y re p orts, a n d ot her 
d oc u me nts are als o t o be s u b mitte d b y e -mail or fa x w he n re q ueste d a n d a p plica ble. 
Tra ns missi o n of s uc h d o c u me nts s h o ul d occ ur wit h o ut pers o nal s u bject i de ntificati o n, 
mai ntai ni n g t he tracea bilit y of a d o c u me nt t o t he s u bje ct i de ntifiers.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8 2  
 
0 9 Se pte m ber 2 0 2 2  
•  A d diti o nal i nf or mati o n ma y b e re q u este d t o e ns ure t he ti mel y c o m pleti o n of acc urate s afet y 
re p orts. 
•  A n y me di cati o ns necessar y f or treat me nt of t he S A E m ust be rec or de d o nt o t he c o nc o mita nt 
me dicati o n secti o n of t he s u bject’s C R F/e C R F a n d t he e ve nt descri pti o n secti o n of t he S A E 
f or m. 
7. 4.  
S p o ns or Re p orti n g Re q uire me nts  
De pe n di n g o n rele va nt l o cal le gislati o n or re g ulati o ns, i ncl u di n g t he a p plica ble U S F D A C o d e of 
Fe deral Re g ulati o ns, t he E U Cli nical Trials Directi ve ( 2 0 0 1/ 2 0/ E C) a n d rel e va nt u p dates, a n d 
ot her c o u ntr y -s p ecific le gislati o n or re g ul ati o ns, t he S p o ns or ma y b e re q uire d t o e x pe dite t o 
w orl d wi de re g ul at or y a ge ncies re p orts of S A Es, s eri o us a d verse dr u g reacti o ns ( S A D Rs), or 
s us pecte d u ne x pecte d seri o us a d verse reacti o ns ( S U S A Rs). I n acc or da n ce wit h t he E U Cli nical 
Trials Directi ve ( 2 0 0 1/ 2 0/ E C), t he S p o ns or or a s p ecifie d desi g n ee will n otif y w orl d wi de 
re g ulat or y a ge ncies a n d t he rele v a nt I E C i n c o ncer ne d Me m ber States of a p plica ble S U S A Rs as 
o utli ne d i n c urre nt re g ul ati o ns.  
Assess me nt of e x pecte d n ess f or fil g oti ni b S A Es will be deter mi ne d b y t he S p o ns or or desi g n ee 
usi n g refere nce safet y i nf or mati o n s pecifie d i n t he I B. Met h otre x ate ma y b e use d as sta n dar d of 
care t h era pi es i n t his st u d y; c o nse q ue ntl y, a n y S A Es t hat are attri b ute d t o me t h otre x ate b y t he 
i n vesti gat or will be f or war de d t o its mar keti n g a ut h orizati o n h ol der. 
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 ociat e d 
wit h a n y st u d y I M 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 h ere t his is re q uire d b y l ocal re g ulat or y a ge nci es, 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  
La b orat or y a b n or malities are us uall y n ot rec or de d as A Es or S A Es. H o we v er , la b orat or y 
a b n or malities (e g, cli nic al c he mistr y, h e mat ol o g y, a n d uri nal ysis) i n de pe n d e nt of t he 
u n derl yi n g  me di cal c o n diti o n t hat re q uire me dical or s ur gical i nter v e 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 ass ess me nts 
(e g, ele ctr ocar di o gra m, X -ra ys, vital si g ns) t hat are ass ociat e d wit h si g ns a n d/ or s y 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 orat or y a b n or m alit y is part of a s y n dr o m e, rec or d t he 
s y n dr o me or dia g n osis (i e, a ne mia) n ot t he l a 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 d e d acc or di n g t o t he C o m m o n Ter mi n ol o g y Criteria f or 
A d verse E v e nts ( C T C A E).  
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 d e 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 ma y or ma y  n ot be i n a gree m e nt 
wit h t he gra di n g of t he  la b orat or y a b n or malit y. 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8 3  
 
0 9 Se pte m ber 2 0 2 2  
7. 6.  
T o xicit y M a n a ge me nt  
All cli nical a n d cli nicall y si g nifica nt la b orat or y t o xicities will be ma na ge d acc or di n g t o u nif or m 
g ui deli nes det aile d i n A p pe n di x  8  a n d as o utli ne d bel o w.  
Refer t o Secti o n  3. 3 , Criteria f or St u d y Dr u g I nterr u pti o n or Disc o nti n uati o n, f or a d diti o nal 
s pecific disc o nti n uati o n criteria. S pecific t o xicit y disc o nti n uati o n criteria i n Secti o n  3. 3  
s u perse de b el o w ge n eral t o xicit y g ui deli nes, a n d i n ge n eral, w h ere discre p a nc y is pr ese nt, t he 
m ore c o nser vati ve criteri a a p pl y. T he m e dical m o nit or or desi g n ee 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 w he n me dicall y feasi bl e.    
7. 6. 1.  
Gr a des 1 a n d 2 L a b or at or y A b n or m alit y or Cli nic al E ve nt  
C o nti n ue st u d y dr u g at t h e discreti o n of t he i n vesti gat or.  
•  F or st u d y s pecifi c i nterr u pti o n a n d st o p pi n g criteri a, please refer t o Secti o n  3. 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) 
•  F or Gra des 1 a n d 2 La b orat or y A b n or m alit y or Cli nical E ve nt n ot s pecifie d i n Secti o n  3. 3 , 
c o nti n ue st u d y dr u g at t he discreti o n of t he i n vesti gat or.  
7. 6. 2.  
Gr a des 3 L a b or at or y A b n or m alit y or Cli nic al E ve nt  
•  F or st u d y s pecifi c i nterr u pti o n a n d st o p pi n g criteri a, please refer t o Secti o n  3. 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) 
•  F or Gra des 3 La b orat or y A b n or malit y or Cli nical E ve nt n ot s pecifie d i n Secti o n  3. 3 , t he 
f oll o wi n g t o xicit y m a na ge me nt g ui d eli nes a p pl y: 
⎯ F or Gra de  3 cli nicall y si g nifica nt la b orat or y a b n or malit y or cli nical e ve nt, i n vesti gati o nal 
me dici nal pr o d uct ma y  b e c o nti n ue d if t he e v e nt is c o nsi dere d t o be u nrelat e d t o 
i n vesti gati o nal me dici nal pr o d uct. 
⎯ F or a Gra d e  3 cli nical e v e nt, or cli nicall y si g nifi ca nt la b orat or y a b n or m alit y c o nfir me d b y 
re peat testi n g, t hat is c o nsi dere d t o be relate d t o i n vesti gati o nal me dici n al pr o d uct, 
i n vesti gati o nal me dici nal pr o d uct s h o ul d be wit h hel d u ntil t he t o xicit y ret ur ns 
t o ≤ Gra de  2.  
If a la b orat or y a b n or malit y rec urs t o ≥ Gra de  3 f oll o wi n g re -c h alle n ge wit h i n vesti gati o nal 
me dici nal pr o d uct a n d is c o nsi dere d relate d t o i n v es ti gati o nal me dici n al pr o d uct, t he n 
i n vesti gati o nal me dici nal pr o d uct s h o ul d be per ma ne ntl y disc o nti n ue d, a n d t he s u bject ma na ge d 
acc or di n g t o l ocal cli nical practice. Rec urre nce of la b orat or y a b n or malities c o nsi dere d u nrelate d 
t o i n vesti gati o nal me dici nal pr o d uct ma y n ot re q uire per ma n e nt disc o nti n uati o n.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8 4  
 
0 9 Se pte m ber 2 0 2 2  
7. 6. 3.  
Gr a des 4 L a b or at or y A b n or m alit y or Cli nic al E ve nt  
•  F or st u d y s pecifi c i nterr u pti o n a n d st o p pi n g criteri a, please refer t o Secti o n  3. 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). 
•  F or Gra de 4 La b orat or y A b n or malit y or Cli nical E ve nts n ot s pecifie d i n Secti o n  3. 3 , t he 
f oll o wi n g t o xicit y m a na ge me nt g ui d eli nes a p pl y: 
⎯ F or a Gra d e  4 cli nical e v e nt or cli nicall y si g nifi ca nt Gra de 4 la b orat or y a b n or malit y 
c o nfir me d b y re peat testi n g t hat is c o nsi dere d rel ate d t o i n vesti gati o nal me dici nal 
pr o d uct, i n vesti gati o nal me dici nal pr o d uct s h o ul d be per ma n e ntl y disc o nti n ue d a n d t he 
s u bject ma na ge d acc or di n g t o l ocal cli nical practice. T he s u bject s h o ul d be f oll o we d as 
cli nicall y i n dicat e d u ntil t he la b orat or y a b n or m alit y ret ur ns t o baseli ne or is ot her wise 
e x plai ne d, w hic he ver occ urs first. A cli nicall y si g nifica nt Gra d e  4 la b orat or y a b n or malit y 
t hat is n ot c o nfir me d b y re peat testi n g s h o ul d be m a na ge d acc or di n g t o t he al g orit h m f or 
t he ne w t o xicit y gra de. 
I n v esti gati o nal me dici nal pr o d uct ma y be c o nti n ue d wit h o ut d ose i nterr u pti o n f or a cli nicall y 
n o n -si g nifica nt Gra d e 4 l a b orat or y a b n or malit y (e g, Gra de  4 C K after stre n u o us e x ercise or 
tri gl yceri de ele v ati o n t hat is n o nfasti n g or t hat ca n be me dicall y ma na ge d) or a cli nical e ve nt 
c o nsi dere d u nrelate d t o i n vesti gati o nal me dici n al pr o d uct.  
Treat me nt -e mer ge nt t o xicities will be n ote d b y t h e i n vesti gat or a n d br o u g ht t o t he atte nti o n of 
t he m e dical m o nit or or d esi g nee, w h o will ha ve a disc ussi o n wit h t he i n vesti gat or a n d d eci de t h e 
a p pr o priate c o urse of acti o n. W het her or n ot c o nsi dere d tr eat me nt -relate d, all s u bjects 
e x perie nci n g A Es m ust be m o nit ore d peri o dicall y u ntil s y m pt o ms s u bsi de, a n y a b n or mal 
la b orat or y val u es ha ve res ol ve d or ret ur n e d t o bas eli ne le vels or t he y are c o nsi dere d irre versi ble, 
or u ntil t here is a satisfact or y e x pla nati o n f or t he c ha n ges o bser v e d.  
A n y q u esti o ns re gar di n g t o xicit y ma na ge me nt s h o ul d be directe d t o t he m e dical  m o nit or or 
desi g nee . T he m e dical m o nit or s h o ul d c o ns ult t he me dical lea der as n ee de d. 
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, pr o d uct 
c o m plai nts, occ u pati o nal e x p os ure,  dr u g i nteracti o ns, u ne x pecte d be nefit, tra ns missi o n o f 
i nfecti o us a ge nts via t he pr o d uct, c o u nterfeit or falsifie d me dici ne, e x p os ure via breastfee di n g, 
a n d part ner pre g n a nc y re p orts re gar dl ess of a n ass ociate d A E.   
Me dicati o n err or is a n y u ni nte nti o nal err or i n t he prescri bi n g, dis pe nsi n g, pre parati o n f or 
a d mi nistrati o n or a d mi nistrati o n of a me dici nal pr o d uct w hile t he me dicati o n is i n t he c o ntr ol of 
t he healt h care pr ofessi o nal, patie nt, or c o ns u mer. Me dicati o n err ors ma y b e classifie d as a 
me dicati o n err or wit h o ut a n A E, w hic h i ncl u des sit uati o ns of miss e d d ose; me dicati o n err or wit h 
a n A E; i nterce pte d me dic ati o n err or; or p ot e ntial me dicati o n err or.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8 5  
 
0 9 Se pte m ber 2 0 2 2  
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 m e dici nal pr o d uct 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 pri ate use of a m e 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 pres cri bi n g i nf or mati o n.  
A n o ver d ose is defi ne d as a n acci d e ntal or i nte nti o nal a d mi nistrati o n of a q ua ntit y of a m e dici nal 
pr o d uct gi v e 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 belli n g (as it a p plies t o t he dail y d os e of t he s u bject i n 
q uesti o n). I n cas es of a discre pa n c y i n dr u g acc o u nta bilit y, o v er 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 x cess d ose(s). O ver d ose ca n n ot be esta blis he d 
w he n t he s u bject c a n n ot acc o u nt f or t he discre pa n c y e x ce pt i n cases i n w hi c 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). 
Occ u pati o nal e x p os ure is defi ne d as e x p os ure t o a me dici nal pr o d uct as a res ult of o ne's 
pr ofessi o nal or n o n -pr ofessi o nal occ u pati o n.  
Dr u g i nteracti o n is defi ne d as a n y dr u g/ dr u g, dr u g/f o o d, or dr u g/ de vice i nt eracti o n.  
U ne x pecte d be nefit is defi ne d as a n  u ni nte n d e d t hera pe utic effect w h ere t h e res ults are j u d ge d t o 
be desira ble a n d be n efici al.  
Tra ns missi o n of i nfecti o us a ge nts is defi ne d as a n y s us pecte d tra ns missi o n of a n i nfecte d a ge nt 
t hr o u g h a me dici nal  pr o d uct.  
Pr o d uct c o m plai nt is defi ne d as c o m pla i nts arisi n g fr o m p ote ntial de viati o ns i n t he ma n ufact ur e, 
pac ka gi n g, or distri b uti o n of t he me dici nal pr o d u ct.   
C o u nterfeit or falsifie d m e dici ne: A n y me dici nal  pr o d uct wit h a false re pres e ntati o n of: a) its 
i de ntit y, b) its s o urce, or c) its hist or y. 
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 u cti o ns f or Re p orti n g Part ner Pre g n a ncies 
Pre g n a ncies of fe mal e part ners of male st u d y s u bj ects e x p ose d t o t he S p o ns or’s or ot her st u d y 
dr u gs m ust be re p orte d a n d rele va nt i nf or m ati o n s h o ul d be s u b mitte d t o 
M A N T A _safet y @ gl p g. c o m  usi n g t he pre g n a nc y a n d pre g na n c y o utc o me f or ms wit hi n 2 4 h o urs. 
If t he e n d of t h e pre g n a n c y o cc urs after t he st u d y has bee n c o m plet e d, t he o utc o me s h o ul d be 
re p orte d dir ectl y t o M A N T A _safet y @ gl p g. c o m .  
Ref er t o A p pe n di x  5  f or Pre g n a nc y Preca uti o ns, Defi niti o n of Fe m ales of C hil d beari n g P ote ntial 
a n d C o ntrace pti ve Re q uire me nts.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8 6  
 
0 9 Se pte m ber 2 0 2 2  
7. 7. 2. 2.  
Re p orti n g Ot her S pecial Si t 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 M A N T A _s afet y @ gl p g.c o m  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 orts m ust c o nsist of sit uati o ns t hat i n v ol ve st u d y dr u g, b ut d o n ot a p pl y t o 
c o nc o mita nt me dicati o ns.  
S pecial sit uati o ns i n v ol vi n g c o n c o mita nt me dicati o ns d o n ot nee d t o be re p orte d o n t he s peci al 
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 c o nc o mita nt 
me dicati o n, t he A E s h o ul d be re p ort e d o n t he A E f or m.  
A n y i na p pr o priate us e 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 b e m ore a p pr o priat el y d o c u me nte d as a pr ot oc ol de viati o n. 
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 peci al sit uati o ns re p orti n g.  
All cli nical se q uelae i n r elati 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 h e A E C R F/e C R F a n d/ or t he S A E re p ort f or m. Det ails of t he s y m pt o ms 
a n d si g ns, cli nic al ma na ge me nt, a n d o utc o me will be re p ort e d, w he n a vaila ble.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8 7  
 
0 9 Se pte m ber 2 0 2 2  
8.  
S T A TI S TI C A L C O N SI D E 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 pri mar y o bje cti ve of t his st u d y is:  
•  T o e val uate t he effect of fil g oti ni b o n testic ular f u ncti o n as defi ne d b y t he pr o p orti o n of 
s u bjects wit h a ≥ 5 0 % decreas e fr o m b aseli ne i n s per m c o nce ntrati o n at Wee k  1 3  
T he sec o n d ar y o bjecti ves of t his st u d y are:  
•  T o e va l uate t he effect of fil g oti ni b o n testic ular f u ncti o n as defi ne d b y t he pr o p orti o n of 
s u bjects wit h a ≥ 5 0 % decreas e fr o m b aseli ne i n s per m c o nce ntrati o n at Wee k 2 6  
•  T o e val uate t he effect of fil g oti ni b o n s per m t otal m otilit y at Wee ks  1 3 a n d 2 6  
•  T o e val uate  t he effect of fil g oti ni b o n t otal s per m c o u nt at Wee ks 1 3 a n d 2 6  
•  T o e val uate t he effect of fil g oti ni b o n t he c ha n ge fr o m baseli ne i n s per m c o nce ntrati o n at 
Wee ks 1 3 a n d 2 6  
•  T o e val uate t he effect of fil g oti ni b o n ejac ulat e v ol u me at Wee ks  1 3 a n d 2 6  
•  T o e val uate t he effect of fil g oti ni b o n s per m m or p h ol o g y at Wee ks  1 3 a n d 2 6  
T he e x pl orat or y o bj ecti v es of t his st u d y are:  
•  T o e val uate t he re versi bilit y of o bser ve d effects of fil g oti ni b o n testic ular f u ncti o n i n s u bjects 
w h o e x perie nce a ≥ 5 0 % decrease i n s per m c o nce ntrati o n, a n d/ or m otilit y, a n d/ or 
m or p h ol o g y  
•  T o e val uate t he effect of fil g oti ni b o n se x h or m o nes, i ncl u di n g l utei nizi n g h or m o ne ( L H), 
f ollicle sti m ulati n g h or m o ne ( F S H), i n hi bi n B, a n d t otal test oster o ne at Wee ks 1 3 a n d  2 6  
•  T o e val uate t he s afet y a n d t olera bilit y of fil g oti ni b 
•  T o c haracteriz e t he plas ma p har mac o ki n etics ( P K) of fil g oti ni b a n d its meta b olite 
( G S-8 2 9 8 4 5, f or merl y  
)  
8. 1. 2.  
Pri m ar y E n d p oi nt  
T he pri mar y e n d p oi nt is t he pr o p orti o n of s u bjects wit h a ≥ 5 0 % decreas e fr o m baseli ne i n s per m 
c o nce ntr ati o n at W ee k 1 3.  
C CI


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8 8  
 
0 9 Se pte m ber 2 0 2 2  
8. 1. 3.  
Sec o n d ar y E n d p oi nts  
T he sec o n d ar y e n d p oi nts are:  
•  T he pr o p orti o n of s u bjects wit h a ≥ 5 0 % decrease fr o m baseli ne i n s per m c o nce ntrati o n at 
Wee k  2 6  
•  C ha n ge fr o m bas eli ne i n perce nt m otile s per m at Wee ks 1 3 a n d 2 6  
•  C ha n ge fr o m bas eli ne i n t otal s per m c o u nt at Wee ks 1 3 a n d 2 6 
•  C ha n ge fr o m bas eli ne i n s per m c o nce ntrati o n at Wee ks 1 3 a n d 2 6  
•  C ha n ge fr o m bas eli ne i n ejac ulate v ol u me at Wee ks 1 3 a n d 2 6  
•  C ha n ge fr o m bas eli ne i n perce nt n or mal s per m m or p h ol o g y at Wee ks 1 3 a n d 2 6  
8. 1. 4.  
E x pl or at or y E n d p oi nts  
T he e x pl orat or y e n d p oi nts are:  
•  Perce nt of s u bjects w h o ac hie ve re versi bilit y a m o n g s u bjects w h o e x perie nce 
a ≥ 5 0 %  decreas e i n s per m c o nce ntrati o n, a n d/ or m otilit y, a n d/ or m or p h ol o g y  
•  C ha n ge fr o m bas eli ne i n se x h or m o nes, i ncl u di n g L H, F S H, i n hi bi n B, a n d t otal test oster o ne 
at W ee ks 1 3 a n d 2 6  
•  P K c haracteristics f or fil g oti ni b a n d its meta b olite G S -8 2 9 8 4 5  
8. 2.  
A n al ysis C o n ve nti o ns  
8. 2. 1.  
A n al ysis Sets  
8. 2. 1. 1.  
All Ra n d o mize d Set  
T he All Ra n d o mize d Set i ncl u des all s u bjects w h o were ra n d o mize d.  
8. 2. 1. 2.  
Se me n A nal ysis Set  
T he Se me n A nal ys is Set i ncl u des all ra n d o mize d s u bjects w h o ha ve b aseli n e a n d at least o ne 
p ost -baseli ne se me n sa m ple. T his is t he pri mar y a nal ysis set f or se me n -relate d para met ers. 
8. 2. 1. 3.  
Safet y A nal ysis Set  
T he Safet y A n al ysis Set i ncl u des all s u bjects w h o recei v e d at least o n e d ose of st u d y dr u g. T his 
is t he pri mar y a nal ysis set f or safet y e n d p oi nts. 
8. 2. 1. 4.  
P har mac o ki netic ( P K) A nal ysis Set  
T he P K a nal ysis set i ncl u des all s u bjects i n t he Safet y A nal ysis Set w h o ha v e at least 
1  n o n missi n g p ost d ose c o nce ntrati o n val ue f or fil g oti ni b a n d/ or its meta b olite G S -8 2 9 8 4 5. T his 
is t he pri mar y a nal ysis set f or all P K a nal yses. 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8 9  
 
0 9 Se pte m ber 2 0 2 2  
8. 3.  
D at a H a n dli n g C o n ve nti o ns  
P K c o nce ntrati o n val u es a n d P K para m eter val u es bel o w t he li mit of q ua ntitati o n ( B L Q) will be 
prese nte d as “ B L Q” i n t h e data listi n gs. B L Q val u e s t hat occ ur pri or t o t he first d ose will be 
treate d as 0, B L Q v al ues at all ot her ti me p oi nts will be treate d as 1/ 2 of t he l o wer li mit of 
q ua ntitati o n ( L L O Q).  
La b orat or y d ata t hat are c o nti n u o us i n nat ure b ut are less t ha n t he l o w er li mit of q ua ntitati o n  or 
a b o ve t he u p per li mit of q ua ntitati o n will be i m p ute d t o t he val ue of t he l o wer or u p p er li mit 
mi n us or pl us o ne si g nifi ca nt di git, res pecti vel y (e g, if t he res ult of a c o nti n u o us la b orat or y test 
is < 2 0, a val ue of 1 9 will be assi g n e d; if t he res ult o f a c o nti n u o us la b orat or y test is < 2 0. 0, a 
val ue of 1 9. 9 will be assi g ne d).  
I n ge neral, missi n g data will n ot be i m p ute d u nless met h o ds f or ha n dli n g missi n g data are 
s pecifie d. T o ass ess missi n g se me n d ata patter ns, missi n g ness b y treat me nt ar m, ra n d o miza ti o n 
strat u m a n d baseli ne de m o gra p hic c h aracteristics will be s u m marize d. D etails o n ha n dli n g 
missi n g data a n d se nsiti vit y a nal yses will be pr o vi de d i n t he statistical a nal ysis pla n ( S A P).  
8. 4.  
De m o gr a p hic D at a a n d B aseli ne C h ar acteristi cs  
De m o gra p hic a n d baseli n e c haracteristics will be s u m marize d b y treat me nt gr o u p usi n g sta n d ar d 
descri pti ve statistics i ncl u di n g sa m ple siz e, mea n, S D, me dia n, Q 1, Q 3, mi ni m u m, a n d ma xi m u m 
f or c o nti n u o us varia bl es a n d n u m bers a n d p erce nta ges f or cate g orical varia bles. 
De m o g ra p hic d ata will i ncl u de se x, race, et h nicit y, a n d a ge. 
Baseli ne c haracteristics ma y i ncl u d e s per m c o n ce ntrati o n, ejac ulate v ol u m e, t otal s per m per 
ejac ulate, a n d ot her v aria bles of i nterest.  
8. 5.  
St atistic al A n al ysis  
8. 5. 1.  
Pri m ar y A n al ysis  
T he pri mar y e n d p oi nt is t he pr o p orti o n of s u bjects wit h a ≥ 5 0 % decreas e fr o m baseli ne i n s per m 
c o nce ntr ati o n at W ee k 1 3. A c u m ulati ve distri b uti o n pl ot f or t he perce nt c ha n ge fr o m b aseli ne i n 
s per m c o nce ntrati o n at Wee k 1 3 f or eac h treat me nt gr o u p will be c o nstr ucte d. T he x -a xis will 
dis pla y perce nt c ha n ges fr o m baseli ne i n s per m c o nce ntrati o n ra n gi n g fr o m 1 0 0 % decrease 
(ie, -1 0 0 % or az o os per mia) t o t he ma xi mal o bser ve d i ncrease. T he y -a xis will dis pla y t he 
pr o p orti o n of s u bjects w h o e x perie nce d a p erce nt a ge c h a n ge i n s per m c o n ce ntrati o n e q u al t o or 
less t ha n t he c orres p o n di n g x-a xis val ue at Wee k 1 3. T his met h o d is s u g geste d i n F D A’s 
G ui da nce f or I n d ustr y ( O ct o ber 2 0 1 8): “ Testic ular t o xicit y: E val uati o n D uri n g Dr u g 
De vel o p me nt”. T h e pr o p orti o n of s u bjects e x perie nci n g at least a 5 0 % d ecrease i n s per m 
c o nce ntr ati o n fr o m baseli ne will be calc ulat e d f or eac h tr eat me nt gr o u p. T h e differe nce bet wee n 
t he fil g oti ni b a n d place b o gr o u ps will be calc ulat e d t o get her wit h t he ass o ciate d 9 5 % c o nfi de nce 
i nter val ( CI). 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9 0  
 
0 9 Se pte m ber 2 0 2 2  
S u bjects w h o ha ve 2 sa m ples a vaila ble at Wee k 1 3 will be i ncl u de d i n t he pri mar y a nal ysis. 
Se nsiti vit y a n al ys es will be perf or me d t o e val u ate t he i m pact of differe nt missi n g data patter ns 
o n t he pri mar y a n al ysis.  Details of t he se nsiti vit y a nal ys es will be pr o vi de d i n t he S A P.  
8. 5. 2.  
Sec o n d ar y A n al yses  
T he sec o n d ar y e n d p oi nts i ncl u de t he pr o p orti o n of s u bjects wit h a ≥ 5 0 % decrease fr o m baseli ne 
i n s per m c o nce ntr ati o n at Wee k 2 6, a n d c ha n ges fr o m baseli ne at Wee ks 1 3 a n d 2 6 i n s per m 
c o nce ntr ati o n, t otal s per m c o u nt, ejac ulate v ol u m e, perce nt m otile s per m, a n d perce nt n or mal 
s per m m or p h ol o g y.  
T he c o nti n u o us e n d p oi nts will be s u m marize d ( n, mea n, S D, me dia n, Q 1, Q 3, mi ni m u m, a n d 
ma xi m u m) b y treat me nt gr o u p at W ee ks 1 3 a n d 2 6 al o n g wit h c orres p o n di n g c h a n ge fr o m 
Baseli ne a n d 9 5 % CIs.  
A n a nal y sis of c o v aria nce ( A N C O V A) m o del a dj usti n g f or b aseli ne val ue a n d stratificati o n 
fact ors will be use d t o esti mate treat me nt differe n ces ( 9 5 % CI) f or t he c o nti n u o us e n d p oi nts. T he 
cate g orical e n d p oi nt at Wee k  2 6 will be s u m marize d descri pti vel y . 
8. 5. 3.  
E x pl or at or y  A n al yses  
T he e x pl orat or y a nal yses of se x h or m o nes will use t he sa me a n al ysis met h o ds use d f or t he 
c o nti n u o us sec o n dar y e n d p oi nts . F or re v ersi bilit y, t he n u m ber a n d perce nta ge a n d c u m ulati ve 
n u m ber a n d perce nt a ge of s u bjects w h o ac hie ve re versi bilit y will be dis pla ye d b y s p er m 
para meter a n d m o nit ori n g p has e visit f or t h ose s u bjects wit h a ≥ 5 0 % decrease i n t he s per m 
para meter(s) q u alif yi n g t he m f or e ntr y i nt o t he m o nit ori n g p hase.  
8. 5. 4.  
Ot her S afet y A n al ysis  
All ot her safet y a n al yses will be perf or me d usi n g t he s afet y a nal ysis set.  
Safet y will be e val uat e d b y ass ess me nt of cli nical la b orat or y tests, p h ysical e x a mi nati o ns, vital 
si g ns meas ur e me nts at vari o us ti me p oi nts d uri n g t he st u d y, a n d b y t he d oc u me ntati o n of A Es.  
All safet y data c ollecte d o n or after t h e first d ose of st u d y dr u g a d mi nistrati o n u p t o 3 0 da ys after 
t he last d ose of st u d y dr u g, u nless s pecifie d ot her wise, will be s u m marize d b y treat me nt gr o u p 
acc or di n g t o t he st u d y dr u g recei v e d.  
8. 5. 5.  
E xte nt of E x p os ure  
A s u bject’s e xte nt of e x p os ure t o st u d y dr u g  will be ge nerate d fr o m t he st u d y dr u g 
a d mi nistrati o n pa ge of t h e e C R F. E x p os ure data will be s u m marize d b y treat me nt gr o u p.  
D urati o n of e x p os ure t o st u d y dr u g will be e x press e d as t he n u m ber of wee ks bet wee n t he 
first a n d last d ose of t he st u d y dr u g, i nc l usi ve, re gar dless of te m p orar y i nterr u pti o ns i n st u d y 
dr u g a d mi nistrati o n a n d s u m mariz e d b y treat me nt gr o u p.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9 1  
 
0 9 Se pte m ber 2 0 2 2  
8. 5. 6.  
A d verse E ve nts  
Cli nical a n d la b orat or y a d verse e v e nts  will be c o d e d usi n g t he M e dical Dicti o nar y f or 
Re g ulat or y Acti vities ( Me d D R A). S yst e m Or ga n Class, Hi g h -Le vel Gr o u p Ter m ( H L G T), 
Hi g h -Le vel Ter m ( H L T), Preferre d Ter m ( P T), a n d L o wer -Le vel Ter m ( L L T) will be attac he d t o 
t he cli nical data bas e. 
Treat me nt -E m er ge nt A d verse E ve nts ( T E A Es) are:  
•  A n y A Es wit h a n o nset d ate o n or after t he st u d y dr u g start date a n d n o l ater t ha n 3 0  da ys 
after per ma ne nt disc o nti n uati o n of st u d y dr u g or  
•  A n y A Es lea di n g t o pre m at 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 nt a ge of s u bjects) of T E A Es b y 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. 5. 7.  
L a b or at or y E v al u ati o ns  
Selecte d la b orat or y data will be s u m marize d ( n, mea n, S D, me dia n, Q 1, Q 3, mi ni m u m, a n d 
ma xi m u m) b y treat me nt gr o u p a n d St u d y Visit  al o n g wit h c orres p o n di n g c ha n ge fr o m Bas eli ne. 
T he i nci de nce of treat me nt -e mer ge nt gra de d la b orat o r y a b n or malities will be s u m marize d 
si milarl y. 
Gra de d la b orat or y a b n or malities will be defi ne d usi n g C T C A E 4. 0 3 gra di n g scale i n A p pe n di x  4 . 
8. 6.  
P h ar m a c o ki netic A n al ysis  
Plas ma c o nce ntr ati o ns of fil g oti ni b a n d its meta b olite ( G S -8 2 9 8 4 5) will be liste d a n d 
s u m marize d f or all s u bjects usi n g des cri pti ve statistics (e g, s a m ple siz e, arit h metic mea n, 
ge o m etric mea n, %  c o efficie nt of variati o n, sta n dar d de viati o n ( S D), me dia n, mi ni m u m, a n d 
ma xi m u m). Plas ma c o nce ntrati o ns of t he fil g oti ni b a n d G S -8 2 9 8 4 5 o ver ti me ma y b e pl otte d i n 
se mi l o garit h mic a n d li near f or mats as mea n  sta n dar d de viati o n. 
E x p os ure -res p o nse a n al yses ma y b e perf or me d. 
8. 7.  
S a m ple Size  
A sa m ple siz e of a p pr o xi matel y 1 0 0 e val ua ble s u bjects per gr o u p, w here e v al ua ble is defi ne d as 
s u bjects i n t he Se me n A n al ysis Set, is a de q uat e f or t he p ur p oses of esti mati n g c u m ulati ve 
distri b uti o n c ur ves a n d pr o d uci n g a 9 5 % c o nfi de n ce i nter val wi dt h t hat is reas o na bl y narr o w f or 
t he perce nta ge of s u bjects i n eac h gr o u p w h o e x perie nce a ≥ 5 0 % decrease i n s per m 
c o nce ntr ati o n c o m pare d t o baseli ne. T his sa m ple size is s u g geste d i n F D A’s g ui da nce o n 
testic ular t o xicit y st u dies { U. S. De part me nt of Healt h a n d H u ma n Ser vices ( D H H S) 2 0 1 8 } . 
Ass u mi n g a 2 0 % rate of n o n -e val ua ble s u bj ects at Wee k  1 3, u p t o 1 2 5 s u bjec ts per ar m ma y be 
e nr olle d.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9 2  
 
0 9 Se pte m ber 2 0 2 2  
Res ults of t his st u d y ma y be p o ole d wit h t he res ults of a se parate st u d y bei n g c o n d u cte d i n 
s u bjects wit h r he u matic diseases ( G L P G 0 6 3 4-C L -2 2 7) wit h t he sa me o bjecti ve . T he t otal 
pla n ne d n u m ber of e nr oll e d s u bjects i n b ot h st u dies c o m bi ne d will be u p t o a p pr o xi matel y 
2 5 0  s u bjects. 
8. 8.  
D at a M o nit ori n g C o m mittee /S p o ns or S afet y M a n a ge me nt Te a m  
A n e xter nal D M C will re vie w t he pr o gress of t he st u d y a n d p erf or m i nteri m re vie ws of safet y 
data a n d pr o vi de rec o m me n dati o n t o t he S p o ns or w het he r t he n at ure, fre q u e nc y, a n d se v erit y of 
a d verse effects ass oci ate d wit h st u d y treat me nt w arra nt t he earl y ter mi nati o n of t he st u d y i n t he 
best i nterests of t he partici pa nts, w het her t h e st u d y s h o ul d c o nti n ue as pl a n ne d, or t he st u d y 
s h o ul d c o nti n ue wit h mo dificati o ns. T he i nitial meeti n g is pla n n e d t o occ ur after a p pr o xi matel y 
t he first 5 0 s u bjects reac h Wee k 1 3. F oll o wi n g t his, s u bse q ue nt meeti n gs will occ ur 
a p pr o xi matel y e ver y 4 m o nt hs (if e nr oll me nt s u p p orts t he nee d). A d diti o nal D M C meeti n gs ma y 
be sc h e d ule d as nee d e d.  
T he D M C’s s pecifi c acti vities will be defi ne d b y a m ut uall y a gree d u p o n c harter, w hi c h will 
defi ne t he D M C’s me m b ers hi p, c o n d uct a n d m eeti n g sc he d ule.  
W hile t he D M C will be as ke d t o a d vise t he S p o ns or 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 ossi ble earl y st u d y ter mi nati o n, t he S p o ns or 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.  
A n a d  h oc D M C meeti n g ma y b e tri g gere d b y t he f oll o wi n g c o n diti o ns or base d u p o n re vi e w of 
e mer gi n g se me n d ata:  
•  ≥ 2 s u bjects de ve l o p t he sa me ( b y preferre d ter m) relate d, Gra de 4, u n e x pecte d a d verse e v e nt 
( A E) i n t he i nfecti o ns a n d i nfestati o ns s yste m or ga n class; 
•  ≥ 2 s u bjects de vel o p a n y relate d, Gra de 4, t hr o m b oe m b olic e ve nt t hat has b ee n p ositi vel y 
a dj u dicate d b y t he a dj u dicati o n c o m mittee ( See Secti o n 8. 9 ); 
•  an y s u bject de vel o ps a Gra de 5, relate d, u n e x pecte d A E. T he d efi niti o n of a n u ne x pecte d A E 
will be base d o n t he Refere nce Safet y I nf or mati o n t hat is o n file at t he ti me t he e ve nt occ urs . 
T he D M C has m o nit ore d t he st u d y u ntil t he date of pr ot oc ol a me n d me nt 6 , i ncl u di n g t he dat a f or 
I A 2. As of a m e n d me nt 6 , t he D M C will be dec o m missi o ne d. T he safet y a n d pr o gress of t he 
re mai n der of t he st u d y will c o nti n ue t o be m o nit ore d b y t h e S p o ns or me dical lea der a n d me dical 
m o nit or , or desi g nee, pr o vi di n g u p dates d uri n g re g ular S p o ns or m e dical m o nit ori n g o versi g ht 
meeti n gs acr oss t he fil g oti ni b pr o gra m. If nee de d, safet y iss ues will be escalate d t o t he S S M T 
per i nter nal sta n d ar d pr o ce d ures , i n cl u di n g t he or ga nizati o n of a d h o c meeti n gs if re q uir e d. T he 
S S M T ca n c o ns ult e xt er nal e x perts, if dee me d necessar y, a n d ca n re vie w d ata i n a n  u n bli n de d 
fas hi o n. 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9 3  
 
0 9 Se pte m ber 2 0 2 2  
8. 9.  
C ar di o v asc ul ar S af et y E n d p oi nt A dj u dic ati o n C o m mittee ( C V E A C)  
A n i n de pe n de nt a dj u dic ati o n c o m mittee will be f or me d t o peri o dicall y re vie w a n d a dj u dicate all 
p ote ntial maj or a d vers e car di o vasc ular e ve nts ( M A C E) a n d t hr o m b oe m b olic e ve nts i n a bli n de d 
ma n ner.  
T he C V E A C’s s pecifi c acti vities will be g o ver ne d b y a m ut uall y a gree d c h arter, w hi c h will 
defi ne t he C V E A C’s me m bers hi p, c o n d uct a n d m eeti n g s c he d ule.  
T he f oll o wi n g e ve nts will be a dj u dicate d a n d classifie d b y t he C V E A C:  
•  Car di o vasc ular d eat h  
•  M y ocar dial infarcti o n  
•  Str o ke  
•  Arterial t hr o m b oe m b olis m  
•  Ve n o us t hr o m b oe m b olis m (e g, d ee p v e n o us t hr o m b osis, p ul m o nar y e m b olis m)  
F urt her details will be s pecifie d i n t he C V E A C C harter.  
8. 1 0.  
I nter n al I n de pe n de nt S afet y Re vie w 
A Gilea d i nter nal u n bli n de d tea m, i n de pe n d e nt of t he bli n de d st u d y tea m, will be asse m ble d. T he 
Gilea d i nter nal u n bli n de d tea m ma y be gra nte d t he access t o bli n de d a n d u n bli n de d cli nical data 
i ncl u di n g treat me nt assi g n me nt t o cl osel y m o nit or se me n para meters i n real-ti me. T his i nter nal 
tea m will be s u p p orte d b y a n e xter nal e x pert i n male fertilit y. T o miti gate t he ris k of 
i na d verte ntl y rele asi n g tr eat me nt assi g n me nt t o sites a n d s u bjects, t he i nter nal tea m will kee p t he 
u n bli n de d i nf or mati o n c o nfi de ntial a n d will n ot c o m m u nicate a n y i nf or mati o n t o t he bli n de d 
st u d y tea m, site staff or s u bjects. Data u n bli n di n g d ue t o me dical e mer ge nc y will f oll o w sta n dar d 
Gilea d pr oce d ures. Pri or t o a n y u n bli n di n g of t he c o m mittee, t he I nte r nal I n de pe n de nt Safet y 
Re vie w c o m mittee’s s pecific acti vities will be defi ne d b y a m ut uall y a gree d u p o n c harter, w hic h 
will defi ne t he c o m mittee me m bers hi p, c o n d u ct, a n d meeti n g sc he d ule.  
As of a me n d me nt 6, t he I nter nal I n de p e n de nt Safet y Re vie w T ea m will  be dec o m missi o ne d. 
Safet y re vie ws will be c o vere d b y t he S S M T.  
8. 1 1.  
U n bli n de d I nteri m A n al ysis  
U n bli n de d i nteri m a nal ys es of t he cli nical trial d ata will be perf or me d b y t h e S p o ns or f or 
re g ulat or y s u b missi o ns w he n 2 0 0 s u bjects  (e g, p o ole d data fr o m G S -U S -4 1 8 -4 2 7 9 a n d 
G L P G 0 6 3 4 -C L -2 2 7) , a n d/ or w he n s o me defi ne d s u bset(s) of s u bjects, ha v e c o m plete d t he 
Wee k  1 3 a n d Wee k 2 6  ( or O L Wee k 1 3 ) ass ess me nts  (first u n bli n de d i nteri m a nal ysis [I A 1]), 
a n d w he n c o m plet e re v ersi bilit y data f or all s u bjects w h o e ntere d t he M o nit ori n g P hase at t hese 
ti me p oi nts is a vaila ble (I A 2; see Defi niti o n  of  Ter ms ). A Data I nt e grit y a n d C o m m u nicati o n 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9 4  
 
0 9 Se pte m ber 2 0 2 2  
Pla n f or t he i nteri m a nal ysis will be de vel o pe d pri or t o u n bli n di n g . T he a n al yses will be 
c o n d ucte d pri maril y t o e val uate t he testic ular s afet y a n d f urt her details will be descri b e d i n t he 
S A P .  
F or o n g oi n g s u bjects, t he st u d y tea m s a n d st u d y st aff at t he sites a n d all ot her staff directl y 
i n v ol ve d i n t he c o n d uct of t he st u d y will re m ai n bli n de d t o t he treat me nt assi g n me nts u ntil t he 
fi nal anal ysis w he n t he d ata base h as bee n l o c ke d.  P u blicati o n of t he I A 2 data is pla n ne d b y t h e 
S p o ns or. T his p u blicati o n will c o ntai n gr o u p le vel data f or t he e ntire st u d y p o p ulati o n, b ut will 
u n bli n d t he st u d y t ea ms a n d staff directl y i n v ol ve d i n t he c o n d uct of  t he st u d y t o t he i n di vi d ual 
baseli ne treat me nt assi g n me nt of s u bjects w h o c o m plete d t he st u d y bef ore I A 2.  
8. 1 2.  
I nte gr ate d Se me n A n al ysis  
As part of t he male s afet y ass ess me nt of fil g oti ni b, i nte grate d a n al ys es ma y be p erf or me d i n 
w hic h data fr o m t he pres e nt st u d y, G S-U S -4 1 8 -4 2 7 9, will be c o m bi ne d wit h si milar data fr o m a 
se parat e st u d y b ei n g c o n d ucte d i n s u bjects wit h r he u matic disease. T h e a n al yses will be 
c o n d ucte d pri maril y t o e val uate t he testic ular s afet y. F urt her details of t he i nte grate d a n al ysis 
will be descri be d i n t he I nte grate d Se me n a n d H or m o ne S A P. 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9 5  
 
0 9 Se pte m ber 2 0 2 2  
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 a ctice  
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 n ce wit h t he pri nci ples of t he 
Declarati o n of Helsi n ki, I nter nati o nal C o u ncil f or Har m o nisati o n (I C H) g ui deli nes, or wit h t he 
la ws a n d re g ul ati o ns of t he c o u ntr y i n w hic h t he researc h is c o n d ucte d, w hic he ver aff or ds t he 
greater pr otecti o n t o t he st u d y s u bject. T h ese sta n d ar ds are c o nsiste nt wit h t he E ur o pea n U n i o n 
( E U) Cli nical Trials Dir ecti ve 2 0 0 1/ 2 0/ E C a n d G o o d Cli nical Practice Directi ve 2 0 0 5/ 2 8/ E C. 
T he i n vesti gat or will e ns ure a d here n ce t o t he basi c pri nci ples of G o o d Cli nical Practice, as 
o utli ne d i n 2 1  C F R  3 1 2, s u b part  D, “ Res p o nsi bilities of S p o ns ors a n d  I n vesti gat ors,” 2 1 C F R, 
part  5 0, a n d 2 1  C F R, part  5 6 . 
T he i n vesti gat or a n d all a p plica ble s u bi n vesti gat ors will c o m pl y wit h 2 1  C F R, Part  5 4, pr o vi di n g 
d oc u me ntati o n of t heir fi na ncial i nterest or arra n ge me nts wit h t he S p o ns or, or pr o prietar y 
i nterests i n t he i n vesti gati o nal dr u g u n d er 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) parti ci 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 t he S p o ns or of a n y c ha n ge i n r e p orta ble i nter ests d uri n g t h e 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 n e d acti vities.  
9. 1. 2.  
I nstit uti o n al Re vie w B o ar d (I R B)/I n de pe n de nt Et hics C o m mittee (I E C) 
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 r e g ulati o ns) will s u b mit t his 
pr ot oc ol, i nf or me d c o ns e nt f or m, a n d a n y acc o m p a n yi n g mat erial t o be pr o vi de d t o t he s u bject 
(s uc h as a d v ertise 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 n y 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 o c u m e nte d a n d pr o vi de d as a l etter 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 R B/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 R B/I E C a p pr o val, wit h t he e x ce pti o n of t h ose necessar y t o 
re d uce i mme diat e ris k t o st u d y s u bjects.  
I nitial s u b missi o n a n d s u bsta ntial a me n d me nt(s) s h o ul d be a p pr o ve d b y t he nati o nal c o m pete nt 
a ut h orities bef ore starti n g of e nr oll me nt a n d/ or i m ple me ntati o n of c ha n ges.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9 6  
 
0 9 Se pte m ber 2 0 2 2  
9. 1. 3.  
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 b tai ni n g writte n i nf or me d c o ns e 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 uat e 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 b ef ore u n derta ki n g a n y st u d y -relate d pr oce d ures. T h e 
i n vesti gat or m ust use t he m ost c urre nt I R B/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. E ac h i nf or me d c o ns e nt ( or ass e nt as a p plica ble) will be a p pr o priatel y si g ne d 
a n d date d b y 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 b y I R B/ I E C or l ocal re q uire me nts. T h e c o nse nt f or m will i nf or m 
s u bjects a b o ut ge n o mic t esti n g a n d s a 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.  
9. 1. 4.  
C o nfi de nti alit y  
T he i n vesti gat or m u st 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 s u bject i nitials, date of birt h, a n ot her 
u ni q ue i de ntifier (as all o we d b y l ocal la w) a n d a n i de ntificati o n c o de will be r ec or de d o n a n y 
f or m or bi ol o gic al sa m pl e s u b mitte d t o t he S p o ns or, I R B/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 dress es f or all s u bjects 
scree n e 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 ul ati o ns .  
T he i n vesti gat or a grees t hat all i nf or mati o n recei v e d fr o m t he S p o ns or, 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 M P, 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 x cl usi ve pr o pert y of t he S p o ns or 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 x ce 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 pri or writte n c o nse nt fr o m t he 
S p o ns or . 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 n y e m pl o yee or a ge nt of t he st u d y site t o a n y t hir d part y or ot her wise i nt o t he 
p u blic d o mai n.  
9. 1. 5.  
St u d y Files a n d Rete nti o n of Rec or ds  
T he i n vesti gat or m ust mai ntai n a de q uate a n d acc urate r ec or ds t o e na bl e t he c o n d uct of t he st u d y 
t o be f ull y d oc u m e nte d a n d t he st u d y data t o b e s u bse q ue ntl y v erifie d. T h es e 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 t w o 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 ur ce 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/ 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 ns e 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 pria te d oc u m e nts a n d c orres p o n de n ce. 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9 7  
 
0 9 Se pte m ber 2 0 2 2  
T he re q uir e 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 bj ect: 
•  S u bject i de ntificati o n ( na me, date of birt h, ge n d er);  
•  D oc u me ntati o n t hat s u bject meets eli gi bilit y cri teria, ie, hist or y, p h ysi cal e x a mi nati o n, 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 x cl usi o n criteria);  
•  D oc u me ntati o n of t he reas o n(s) a c o ns e nte d s u bject is n ot e nr olle d  
•  Partici pati o n i n st u d y (i n cl u di n g st u d y n u m ber);  
•  St u d y dis c usse d a n d d ate of i nf or me d c o ns e nt;  
•  Dates of all visits;  
•  D oc u me ntati o n t hat pr ot oc ol s pecific pr oce d ures were p erf or me d;  
•  Res ults of efficac y para meters, as r e q uire d b y t h e 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 d v erse e ve nts a n d ot her safet y p ara meters (start a n d e n d dat e, a n d i ncl u di n g 
ca usalit y a n d se v erit y);  
•  C o nc o mita nt me dicati o n (i ncl u di n g start a n d e n d d ate, d ose if rele va nt; d ose c ha n ges);  
•  Date of st u d y c o m pleti o n a n d reas o n f or earl y disc o nti n uati o n, if it occ urs.  
All cli nical st u d y d oc u m e nts m ust be retai ne d b y t he i n vesti gat or u ntil at least 2  years or 
acc or di n g t o l ocal la ws, w hic he ver is l o n ger, aft er t he last a p pr o val of a mar keti n g a p plicati o n i n 
a n I C H re gi o n (i e, U nite d S tates, 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 h e i n vesti gati o n is disc o nti n ue d a n d re g ul at or y 
a ut h orities ha ve bee n n otifie d. I n vesti gat ors ma y b e re q uir e 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 r e g ulati o ns, or b y a n a gree m e nt wit h t he S p o ns or. 
T he i n vesti gat or m ust n otif y t he S p o ns or bef ore d estr o yi 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, t he S p o ns or 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 uire me nt at t he st ud 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 d e bet wee n t he i n vesti gat or a n d t he S p o ns or t o 
st ore t hese rec or ds s ec urel y a wa y fr o m t he site s o t hat t he y ca n be ret ur n e d seale d t o t he 
i n vesti gat or i n case of a n i ns pecti o n. W he n s ource d oc u me nts are re q uir e d f or t he c o nti n ue d care 
of t he s u bject, a p pr o priat e c o pies s h o ul d be ma d e f or st ora ge a wa y fr o m t h e site.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9 8  
 
0 9 Se pte m ber 2 0 2 2  
9. 1. 6.  
C ase Re p ort F or ms  
F or eac h s u bject c o nse nt e 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 m ber 
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. T he  e C R F s h o ul d 
be c o m plete d o n t he d a 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 safet y dat a. T he Eli gi bilit y Criteri a e C R F s h o ul d be c o m plete d o nl y aft er all  data relat e d t o 
eli gi bilit y ha v e 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 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 b ee n re vie we d, a n d t hat t he e ntri es acc uratel y reflect 
t he i nf or mati on i n t he s o urce d oc u m e nts.  T he e C R F ca pt ur es t he data re q uire d per t he pr ot oc ol 
St u d y Pr oce d ures Ta ble ( A p pe n di x  2 ). S yste m -ge nerate d or ma n ual q uerie s will be iss ue d t o t he 
i n vesti gati ve site staff as data discre p a ncies are i d e ntifie d b y t h e m o nit or or data ma na g eme nt  
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 h e site 
c o or di nat or is res p o nsi bl e f or res p o n di n g t o t he q ueries i n a ti mel y ma n ner, wit hi n t he s yste m, 
eit her b y 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, dat a e ntr y err or). At t he c o n cl usi o n of t he trial, t he S p o ns or will pr o vi de t he 
site wit h a rea d -o nl y arc hi ve c o p y of t he dat a e ntere d b y t h at 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 uir e me nts o utli ne d i n Secti o n  9. 1. 5 .  
9. 1. 7.  
I ns pecti o ns 
T he i n vesti gat or will ma ke a vaila ble all s o urce d o c u me nts a n d ot her rec or ds f or t his trial t o t he 
S p o ns or’s a p p oi nte d st u d y m o nit ors, t o I R Bs/I E Cs, or t o re g ulat or y a ut h orit y or healt h a ut h orit y 
i ns pect ors. 
9. 1. 8.  
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 u cte d i n acc or da nce wit h t he 
pr oce d ures a n d e v al 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 x ce 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 b e 
ma de o nl y b y t h e S p o ns or. 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 R B/I E C i n acc or da n ce wit h l ocal re q uire m e nts a n d recei v e d oc u me nte d IR B/I E C a p pr o val 
bef ore m o dificati o ns ca n be i m ple me nte d.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9 9  
 
0 9 Se pte m ber 2 0 2 2  
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(i es). T he 
S p o ns or will e ns ure t hat t he re p ort meets t he sta n d ar 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 cas es.  
I n v esti gat ors i n t his st u d y ma y c o m m u nicate, orall y pres e 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 ntiret y ha v e bee n p u blicl y discl ose d b y or wit h t he c o nse nt 
of t he S p o ns or i n a n a bstract, ma n uscri pt, or pres e 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 sit es f or at least 2 years  
•  T he i n vesti gat or will s u b mit t o t he S p o ns or 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 s cie 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 pres e 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 de t he S p o ns or’s c o nfi de ntial 
i nf or mati o n (see Secti o n 9. 1. 4 ). 
•  T he i n vesti gat or will c o m pl y wit h t he S p o ns or’s re q uest t o delete refere n ces 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 p er 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 otecti o n if dee m e 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 v esti 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 n ce at I n v esti gat or's Meeti n gs . If re q uir e d u n der t h e a p plica ble stat ut or y a n d 
re g ulat or y re q uire me nts, t he S p o ns or will ca pt ure a n d discl ose t o Fe d eral 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 s er vices, i n cl u di n g a n y cli nical trial pa y m e nts, meal, tra v el 
e x pe nses or rei m b urse me nts, c o ns ulti n g fe es, a n d a n y ot h er tra nsfer of val u e.  
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 n ce wit h re g ul ati o ns a n d g ui deli nes, t h e 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 o c u me ntati o n i n or der t o verif y t h e acc urac y of t he d ata 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 h e c o m plete ness, c o nsiste nc y, a n d acc urac y of 
t he data bei n g e nt ere d o n t he m. T he m o nit or s h o ul d ha ve access t o a n y s u bj ect rec or ds nee de d t o 
verif y t he e ntri es 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 y p e of m o nit ori n g (ce ntr al, o n site) are res ol ve d.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 0 0  
 
0 9 Se pte m ber 2 0 2 2  
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 t he S p o ns or ma y c o n d u ct 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 m e di cal m o nit or or desi g n ee i m me diatel y. T he i n vesti gat or 
a grees t o pr o vi d e t o re prese ntati ves of a re g ulat or y a ge nc y or t h e S p o ns or access t o rec or ds, 
facilities, a n d pers o n n el 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 orit y(i es), I R Bs, a n d I E Cs. I n t er mi nati n g t he st u d y, t he S p o ns or a n d t he 
i n vesti gat or will ass ure t hat a de q uat e 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. 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 0 1  
 
0 9 Se pte m ber 2 0 2 2  
1 0.  
R E F E R E N C E S  
Ara uj o A B, O' D o n n ell A B, Bra m billa DJ, Si m ps o n W B, L o n gc o pe C, Mats u m ot o A M, et al. 
Pre vale nce a n d i nci de n ce of a n dr o ge n d eficie nc y i n mi d dle -a ge d a n d ol der me n: 
esti mates fr o m  t he Massa c h usetts Male A gi n g St u d y. J Cli n E n d ocri n ol Meta b 2 0 0 4; 8 9 
( 1 2): 5 9 2 0-6.  
Ba u m gart D C, Sa n d b or n WJ. Cr o h n's disease. La n cet 2 0 1 2; 3 8 0 ( 9 8 5 3): 1 5 9 0 -6 0 5.  
Bea u gerie L, Itz k o witz S H. Ca ncers C o m plicati n g I nfla m mat or y B o wel Disease. N E n gl J Me d 
2 0 1 5; 3 7 2 ( 1 5): 1 4 4 1-5 2.  
Bressler B, M ars hall J K, Ber nstei n C N, Bitt o n A, J o nes J, Le o ntia dis GI, et al. Cli nical practice 
g ui deli nes f or t he me dical ma na ge me nt of n o n h os pitalize d ulcerati ve c olitis: t he T or o nt o 
c o nse ns us. Gastr o e nter ol o g y 2 0 1 5; 1 4 8 ( 5): 1 0 3 5 -5 8 e 3.  
C h eifetz A S. Ma na ge me nt of acti ve Cr o h n diseas e. J A M A 2 0 1 3; 3 0 9 ( 2 0): 2 1 5 0 -8.  
C oc kcr oft D W, Ga ult M H. Pre dicti o n of creati ni ne cleara nce fr o m s er u m creati ni ne. Ne p hr o n 
1 9 7 6; 1 6: 3 1 -4 1.  
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.  
Da per n o M, D' Hae ns G, Va n Assc he G, Baert F, B ul ois P, Ma u n o ur y V, et al. De vel o p me nt a n d 
vali dati o n of a ne w, si m plifie d e n d osc o pic acti vit y sc ore f or Cr o h n's disease: t he S E S -
C D. Gastr oi ntesti nal e n d osc o p y 2 0 0 4; 6 0 ( 4): 5 0 5 -1 2.  
Di g nass A, Va n Ass c he G, Li n dsa y J O, Le ma n n M, S o der h ol m J, C ol o m bel J F, et al. T he sec o n d 
E ur o pea n e vi de nce -bas e d C o nse ns us o n t he dia g n osis a n d ma na ge me nt of Cr o h n's 
disease: C urre nt ma n a ge me nt. J o ur nal of Cr o h n's & c olitis 2 0 1 0; 4 ( 1): 2 8 -6 2.  
El -Be h eir y A, El -Ma ns y E, Ka mel N, Sala m a N. Met h otre x ate a n d fertilit y i n me n. Arc h A n dr ol 
1 9 7 9; 3 ( 2): 1 7 7 -9.  
F u k u na ga K, Mats u m ot o T. C urre nt stat us a n d f ut ure pers pecti ves of le u k o c yt a p heresis f or 
i nfla m mat or y b o wel disease. J Gastr oe nter ol H e pat ol 2 0 1 2; 2 7 ( 6): 9 9 7-1 0 0 3.  
Hellstr o m WJ, Gittel ma n  M, J ar o w J, Stei dle C, Mc M urra y J, Talle y D, et al. A n e val uati o n of 
se me n c haract eristics i n me n 4 5 years of a ge or ol der aft er dail y d osi n g wit h ta dalafil 
2 0 m g: res ults of a m ultice nter, ra n d o mize d, d o u ble -bli n d, place b o -c o ntr oll e d, 9 -m o nt h 
st u d y. E ur o pea n ur ol o g y 2 0 0 8; 5 3 ( 5): 1 0 5 8 -6 5.  
Hellstr o m WJ, O verstreet J W, Y u A, Sai kali K, S he n W, Beasle y C M, Jr., et al. Ta dalafil has n o 
detri me ntal effect o n h u ma n s per mat o ge n esis or re pr o d ucti ve h or m o nes. J Ur ol 2 0 0 3; 1 7 0 
( 3): 8 8 7-9 1.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 0 2  
 
0 9 Se pte m ber 2 0 2 2  
It o H, T a kaz oe M, F u k u d a Y, Hibi T, K us u ga mi K, A n d o h A, et al. A pil ot ra n d o mize d trial of a 
h u ma n a nti -i nterle u ki n-6 rece pt or m o n ocl o nal a nti b o d y i n acti ve Cr o h n's disease. 
Gastr oe nter ol o g y 2 0 0 4; 1 2 6 ( 4): 9 8 9 -9 6; disc ussi o n 4 7.  
J ar vi K, D ula E, Dre h o bl M, Pr y or J, S ha pir o J, Se ger M. Dail y v ar de n afil f or 6 m o nt hs has n o 
detri me ntal effects o n se me n c haracteristics or re pr o d ucti ve h or m o nes i n me n wit h 
n or mal baseli ne le v els. J Ur ol 2 0 0 8; 1 7 9 ( 3): 1 0 6 0 -5.  
J ess T, R u n g oe C, Pe yri n-Bir o ulet L. Ris k of C ol orectal Ca n cer i n Patie nts Wit h Ulcera ti 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.  
Ka p pel ma n M D, Rifas -S hi ma n S L, Klei n ma n K, Olle n d orf D, B o us var os A, Gra n d RJ, et al. T he 
pre vale n ce a n d ge o gra p hic distri b uti o n of Cr o h n's dis ease a n d ulcerati ve c olitis i n t he 
U nite d States. Cli n Gastr oe nter ol He p at ol 2 0 0 7; 5 ( 1 2): 1 4 2 4 -9.  
Keel B A. Wit hi n - a n d bet wee n -s u bject variati o n i n se me n para meters i n i nfertile me n a n d 
n or mal se me n d o n ors. Fertilit y a n d sterilit y 2 0 0 6; 8 5 ( 1): 1 2 8 -3 4.  
K or n bl ut h A, Sac har D B. Errat u m: Ulcerati ve C olitis Practice G ui deli nes i n A d ults: A merica n 
C olle ge of Gastr oe nt er ol o g y, Practice Para meters C o m mittee. T he A merica n J o ur nal of 
Gastr oe nter ol o g y 2 0 1 0.  
K orze ni k J R. I n vesti gati o nal t hera pies i n t he me dical ma na ge me n t of Cr o h n disease. A vaila bl e 
at: w w w. u pt o date.c o m/c o nte nts/ 4 0 7 6. U p T o Date 2 0 1 6.  
M ol o dec k y N A, S o o n I S, Ra bi D M, G hali W A, Ferris M, C her n off G, et al. I n creasi n g i n ci de nce 
a n d pre val e nce of t he i nfl a m mat or y b o wel diseas es wit h ti me, base d o n s yste matic 
re vie w. G astr oe nter ol o g y 2 0 1 2; 1 4 2 ( 1): 4 6-5 4 e 4 2; q uiz e 3 0.  
M ulli ga n T, Fric k M F, Z ura w Q C, Ste m ha ge n A, Mc W hirter C. Pre vale nce of h y p o g o na dis m i n 
males a ge d at least 4 5 years: t he HI M st u d y. I nt J Cli n Pract 2 0 0 6; 6 0 ( 7): 7 6 2-9.  
Na m o ur F, Di deric hs e n P M, C o x E, Va yssiere B, Va n der Aa A, Tasset C, et al. 
P har mac o ki netics a n d P h ar mac o ki netic/ P har mac o d y na mic M o d eli n g of Fil g oti ni b 
( G L P G 0 6 3 4), a Sele cti ve J A K 1 I n hi bit or, i n S u p p ort of P hase II B D os e Selecti o n. Cli n 
P har mac o ki net 2 0 1 5; 5 4 ( 8): 8 5 9 -7 4.  
Ol derei d N B,  G or d ela dze J O, Kir k h us B, P ur vis K. H u ma n s per m c h aract eristics d uri n g fre q u e nt 
ejac ulati o n. J Re pr o d Fertil 1 9 8 4; 7 1 ( 1): 1 3 5 -4 0.  
P har macia & U pj o h n C o. Az ulfi di ne ® Ta blets c o ntai n s ulfasalazi ne, 5 0 0 m g, f or oral 
a d mi nistrati o n. U S Prescri bi n g I nf o mati o n. 2 0 1 4:  
Sa n d b or n WJ, Fea ga n B G, Ha na u er S B, L o c hs H, L of ber g R, M o di glia ni R, et al. A re vie w of 
acti vit y i n dices a n d efficac y e n d p oi nts f or cli nical trials of me dical t hera p y i n a d ults wit h 
Cr o h n's diseas e. Gastr o e nter ol o g y 2 0 0 2; 1 2 2 ( 2): 5 1 2 -3 0.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 0 3  
 
0 9 Se pte m ber 2 0 2 2  
Si k ka S C, C h e n C, Al mas M, D ula E, K na p p L E, Hellstr o m WJ. Pre ga bali n d oes n ot affect 
s per m pr o d ucti o n i n healt h y v ol u nteers: a ra n d o mize d, d o u ble-bli n d, place b o -c o ntr olle d, 
n o ni nferi orit y st u d y. Pai n Pract 2 0 1 4.  
Si k ka S C, Hellstr o m WJ. C urre nt u p dates o n la b orat or y t ec h ni q ues f or t he dia g n osis of male 
re pr o d ucti ve fail ure. Asia n J A n dr ol 2 0 1 6. 
S uss ma n A, Le o n ar d J M. Ps oriasis, met h otre x ate, a n d oli g os per mia. Arc h Der mat ol 1 9 8 0; 1 1 6 
( 2): 2 1 5-7.  
U. S. De part me nt of Healt h a n d H u ma n Ser vices ( D H H S), F o o d a n d Dr u g A d mi nistr ati o n 
( F D A), Ce nter f or Dr u g E val uati o n a n d Researc h ( C D E R). Testic ular T o xicit y: 
E val uati o n D uri n g Dr u g De vel o p me nt G ui da nce f or I n d ustr y.  2 0 1 8.  
U n gar o R, Me ha n dr u S, Alle n P B, Pe yri n -Bir o ulet L, C ol o m bel J F. Ulcerati ve c olitis. La n cet 
2 0 1 6: 1 -1 5.  
Ve nt ha m  N T, K e n ne d y N A, Ni m m o E R, Satsa n gi J. Be y o n d ge n e disc o ver y i n i nfla m mat or y 
b o wel disease: t he e mer gi n g r ole of e pi ge n etics. Gastr oe nter ol o g y 2 0 1 3; 1 4 5 ( 2): 2 9 3 -3 0 8.  
Ver meir e S, Sc hrei ber S, Petr y ka R, K ue h bac her T, He b uter ne X, R o bli n X, et al. Cli nical 
remissi o n i n patie nts wit h m o derate -t o-s e vere Cr o h n's diseas e treate d wit h fil g oti ni b (t he 
FI T Z R O Y st u d y): res ults fr o m a p hase 2, d o u ble -bli n d, ra n d o mise d, place b o -c o ntr olle d 
trial. La ncet 2 0 1 7; 3 8 9: 2 6 6-7 5.  
W orl d Healt h Or ga niz ati o n ( W H O). W H O La b orat or y M a n ual f or t he e x a mi nati o n of h u ma n 
se me n a n d s per m-cer vical m uc us i nterati o n. F o urt h E diti o n.  1 9 9 9.  
W orl d Healt h Or ga niz ati o n ( W H O). W H O La b orat or y m a n ual f or t h e E x a mi nati o n a n d 
pr ocessi n g of h u ma n s e me n. Fift h E diti o n.  2 0 1 0.  
 
 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 0 4  
 
0 9 Se pte m ber 2 0 2 2  
1 1.  
A P P E N DI C E S  
A p pe n di x  1.  
S p o ns or a n d I n vesti gat or Si g nat ure P a ge  
A p pe n di x  2.  
St u d y Pr oce d ures T a bles  
A p pe n di x  3.  
Ma y o Sc ori n g S yste m * f or Asse ss me nt of Ulcerati ve C olitis Acti vit y 
A p pe n di x  4.  
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  5.  
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  
A p pe n di x  6.  
Cli nical La b orat or y Assess me nt T a ble  
A p pe n di x  7.  
Pr oce d ures a n d S pecificati o ns  
A p pe n di x  8.  
Ma na ge me nt of Cli nical a n d L a b orat or y A d verse E ve nts  
A p pe n di x  9.  
Cr o h n’s Disease Acti vit y I n de x ( C D AI)  
A p pe n di x  1 0.  
Si m ple E n d osc o pic Sc ore f or Cr o h n’s Disease ( S E S -C D)  
A p pe n di x  1 1.  
St u d y Fl o w  
 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 0 5  
 
0 9 Se pte m ber 2 0 2 2  
A p pe n di x  1 . 
S p o ns or a n d I n vesti g at or Si g n at ure P a g e 
 
G A L A P A G O S N V  
G E N E R A A L D E WI T T E L A A N L 1 1 A 3  
2 8 0 0 M E C H E L E N, B E L GI U M  
 
S T U D Y A C K N O W L E D G E M E N T  
 
A Ra n d o mize d, D o u ble -bli n d, Place b o -c o ntr olle d P hase  2 St u d y t o E val uate t he Testic ular 
Safet y of Fil g oti ni b i n A d ult  Males  wit h M o derat el y t o Se verel y Acti ve I nfla m mat or y B o wel 
Disease   
G S -U S -4 1 8 -4 2 7 9 , A me n d me nt # 6 , 0 9 Se pte m ber  2 0 2 2
 
T his pr ot oc ol has bee n a p pr o ve d b y Gal a pa g os N V . T he f oll o wi n g si g n at ure d ocu me nts t his 
a p pr o val.  
 
 
A n electr o nic si g n at ure of t he s p o ns or’s 
res p o nsi ble pers o n is pr o vi de d at t he e n d of 
t he d oc u me nt. 
 (Cli nical De vel o p me nt 
Lea der ) i n a bse n ce of 
 
(Me dical Lea der ) 
 
Si g nat ure  
 
 
 
 
Date  
 
 
 
I N V E S TI G A T O R S T A T E M E N T  
I h a ve rea d t he pr ot oc ol, i ncl u di n g all a p p e n dices, a n d I a gree t hat it c o ntai ns all necessar y 
details f or me a n d m y staff t o c o n d uct t his st u d y as descri be d. I will c o n d uct t his st u d y as 
o utli ne d herei n a n d will ma ke a reas o na bl e eff ort t o c o m pl ete t he st u d y wit hi n t he ti me 
desi g nat e d.  
I will pr o vi de all st u d y p ers o n nel u n der m y s u p er visi o n c o pies of t he pr ot o c ol a n d access t o all 
i nf or mati o n pr o vi de d b y Gala pa g os N V . I will disc uss t his material wit h t he m t o e ns ure t hat t he y 
are f ull y i nf or m e d a b o ut t he dr u gs a n d t he st u d y.  
 
 
 
Pri nci pal I n v esti gat or Na me ( Pri nte d)  
 
Si g nat ure  
 
 
 
 
Date  
 
Site N u m ber  
P P D
P P D


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
 
Fi nal  
Gala pa g os N V  
 
A me n d me nt 6  
C O N FI D E N TI A L  
 
P a ge  1 0 6  
 
0 9 Se pte m ber 2 0 2 2  
A p pe n di x  2 . 
St u d y Pr oce d ures T a bles  
St u d y Pr o ce d ure  
Scree ni n g  
P art A  
( Secti o n 6. 4 ) 
P art B  
( Secti o n 6. 5 ) 
O pe n -L a bel Fil g oti ni b P h ase  
( Secti o n 6. 6 ) 
L o n g  Ter m 
E xte nsi o n  
( Secti o n 6. 1 0 ) 
3 0 D a y S afet y  
F oll o w -u p e 
E T f 
D a y 
1  
W k 
2  
W k 
4  
W k 
8  
W k 
1 3 a  
W k 
2 0  
W k 
2 6 a  
S per m 
P ar a meter 
Eli gi bilit y 
C o nfir m ati o n b 
O L 
D a y 
1  
O L 
W k 
2  
O L 
W k 
4  
O L 
W k 
8  
O L 
W k 
1 3 c 
L T E Wee k  1 3 
t hr o u g h L T E 
Wee k  1 9 5 d  
4 5  
d a ys  
 
± 5  
d a ys  
± 5  
d a ys  
± 5  
d a ys  
+  5  
d a ys  
± 5  
d a ys  
+  5  
d a ys  
 
 
± 5  
d a ys  
± 5  
d a ys  
± 5  
d a ys  
+  5  
d a ys  
± 1 0  d a ys  
± 5  
d a ys  
 
I nf or me d C o nse nt 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Me dical Hist or y, N u m ber 
of ti mes s u bj ect 
i m pre g nate d w o me n, I B D 
Hist or y, a n d 
De m o gra p hics  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I ncl usi o n/e xcl usi o n 
criteria re vie w  
X  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C o m plete P h ysical E xa m g  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
S y m pt o m -directe d 
P h ysical E xa m, as nee de d  
 
X  
X  
X  
X  
X  
X  
X  
 
X  
X  
X  
X  
X  
X  
X  
X  
Vital Si g ns g a n d W ei g ht  
X  
X  
X  
X  
X  
X  
X  
X  
 
X  
X  
X  
X  
X  
X  
X  
X  
Hei g ht  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 2 -lea d E C Gg  
X  
 
 
 
 
 
 
X  
 
 
 
 
 
X  
X h 
 
X  
Fle xi ble Si g m oi d osc o p y i 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ile oc ol o n osc o p yi 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C o m plete Ma y o Cli nic 
Sc ore  (c o m plete M C S)j 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
P artial Ma y o Cli nic Sc ore   
( partial M C S)j 
 
X  
X  
X  
X  
X  
X  
X  
 
X  
X  
X  
X  
X  
X  
 
X  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
 
Fi nal  
Gala pa g os N V  
 
A me n d me nt 6  
C O N FI D E N TI A L  
 
P a ge  1 0 7  
 
0 9 Se pte m ber 2 0 2 2  
St u d y Pr o ce d ure  
Scree ni n g  
P art A  
( Secti o n 6. 4 ) 
P art B  
( Secti o n 6. 5 ) 
O pe n -L a bel Fil g oti ni b P h ase  
( Secti o n 6. 6 ) 
L o n g  Ter m 
E xte nsi o n  
( Secti o n 6. 1 0 ) 
3 0 D a y S afet y  
F oll o w -u p e 
E T f 
D a y 
1  
W k 
2  
W k 
4  
W k 
8  
W k 
1 3 a  
W k 
2 0  
W k 
2 6 a  
S per m 
P ar a meter 
Eli gi bilit y 
C o nfir m ati o n b 
O L 
D a y 
1  
O L 
W k 
2  
O L 
W k 
4  
O L 
W k 
8  
O L 
W k 
1 3 c 
L T E Wee k  1 3 
t hr o u g h L T E 
Wee k  1 9 5 d  
4 5  
d a ys  
 
± 5  
d a ys  
± 5  
d a ys  
± 5  
d a ys  
+  5  
d a ys  
± 5  
d a ys  
+  5  
d a ys  
 
 
± 5  
d a ys  
± 5  
d a ys  
± 5  
d a ys  
+  5  
d a ys  
± 1 0  d a ys  
± 5  
d a ys  
 
Si m ple E n d osc o pic Sc ore 
f or Cr o h n’s Disease 
( S E S-C D)  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cr o h n’s Disease Acti vit y 
I n de x ( C D AI)k  
X  
X  
X  
X  
X  
X  
X  
X  
 
X  
X  
X  
X  
X  
X  
 
X  
T B ( Q ua nti F E R O N ® ) T est 
X l 
 
 
 
 
 
 
 
 
 
 
 
 
 
X m  
 
 
C hest X -ra yn  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Uri nal ysis o  
X  
X  
 
 
 
X  
 
X  
 
X  
 
 
 
X  
X  
 
X  
Uri ne dr u g scree n o 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
He mat ol o g y a n d 
C he mistr y o  
X  
X  
X  
X  
X  
X  
X  
X  
 
X  
X  
X  
X  
X  
X  
X  
X  
Li pi d pr ofile (fasti n g) o  
 
X  
 
 
 
X  
 
X  
 
X  
 
 
 
X  
X p 
 
 
Ser u m I m m u n o gl o b uli n o  
X  
 
 
 
 
X  
 
X  
 
 
 
 
 
X  
X  
 
 
E n d ocri ne: T S H, H b A 1c o  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
L H, F S H, i n hi bi n B, t otal 
T est oster o ne o c ollecti o n 
ti me bet wee n 0 7: 0 0-1 1: 0 0 
i n t he m or ni n g 
X  
X  
 
X  
 
X  
 
X  
 
X  
 
X  
 
X  
X  
X  
X  
St o ol o  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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  
Assess me nt of A d verse 
E ve nts  
X  
X  
X  
X  
X  
X  
X  
X  
 
X  
X  
X  
X  
X  
X  
X  
X  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
 
Fi nal  
Gala pa g os N V  
 
A me n d me nt 6  
C O N FI D E N TI A L  
 
P a ge  1 0 8  
 
0 9 Se pte m ber 2 0 2 2  
St u d y Pr o ce d ure  
Scree ni n g  
P art A  
( Secti o n 6. 4 ) 
P art B  
( Secti o n 6. 5 ) 
O pe n -L a bel Fil g oti ni b P h ase  
( Secti o n 6. 6 ) 
L o n g  Ter m 
E xte nsi o n  
( Secti o n 6. 1 0 ) 
3 0 D a y S afet y  
F oll o w -u p e 
E T f 
D a y 
1  
W k 
2  
W k 
4  
W k 
8  
W k 
1 3 a  
W k 
2 0  
W k 
2 6 a  
S per m 
P ar a meter 
Eli gi bilit y 
C o nfir m ati o n b 
O L 
D a y 
1  
O L 
W k 
2  
O L 
W k 
4  
O L 
W k 
8  
O L 
W k 
1 3 c 
L T E Wee k  1 3 
t hr o u g h L T E 
Wee k  1 9 5 d  
4 5  
d a ys  
 
± 5  
d a ys  
± 5  
d a ys  
± 5  
d a ys  
+  5  
d a ys  
± 5  
d a ys  
+  5  
d a ys  
 
 
± 5  
d a ys  
± 5  
d a ys  
± 5  
d a ys  
+  5  
d a ys  
± 1 0  d a ys  
± 5  
d a ys  
 
Se me n C ollecti o n  
( 2 sa m ples as p er 
c ollecti o n i nstr ucti o ns i n 
Secti o n  6. 1 3 )q  
X r 
 
 
 
 
X  
 
X  
X s 
 
 
 
 
X t 
X  
 
X  
Date a n d ti me of m ost 
rece nt ej ac ulati o nu  
X  
 
 
 
 
X  
 
X  
X  
 
 
 
 
X  
X  
 
X  
HI V, He p atitis B, a n d 
He p atitis C v  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
H B V D N A w  
 
 
 
 
 
X  
 
X  
 
 
 
 
 
X  
X  
 
 
Ra n d o mizati o n  
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
St u d y Dr u g 
Acc o u nta bilit y  
 
 
 
X  
X  
X  
X  
X  
 
X  
 
X  
X  
X  
X  
 
X  
St u d y Dr u g Dis pe nsati o n  
 
X  
 
X  
X  
X  
X  
X  
 
X  
 
X  
X  
X  
X  
 
 
P K c ollecti o n (s parse)  
 
 
X x  
X y  
 
X z 
 
X z 
 
 
X x  
X y  
 
X z 
 
 
 
I n-Cli nic D osi n g aa  
 
X  
X  
 
 
X  
 
X  
 
 
X  
 
 
X  
 
 
 
a 
Wee ks 1 3 a n d 2 6 m ust o cc ur after 1 3 wee ks a n d 2 6 wee ks of dr u g e x p os ure, res pecti vel y . T heref ore, visit wi n d o w f or t h ese visits are + 5 da ys  
b  
S u bjects o n bli n de d st u d y dr u g meeti n g criteria as a n o n -res p o n der ( Wee k 1 3) or f or Disease W orse ni n g (after Wee k 1 3 t hr o u g h 2 6), a n d n ot meeti n g  t h e pre-s pecifie d 
decrease t hres h ol d i n s per m para meters,  are eli gi ble f or o pe n -la bel fil g oti ni b (refer A p pe n di x  1 1  a n d Secti o n 3 ). F or defi niti o ns of I B D res p o nse stat us, Disease W orse ni n g, 
a n d/ or pre -s pecifie d decrease t hres h ol d i n s per m para meters pleas e refer t o Defi niti o n  of  Ter ms a n d Secti o n 3. 4 . 
c 
O L Wee k 1 3 m ust o cc ur after 1 3 we e ks of starti n g o pe n -la bel fil g oti ni b. T heref ore, visit wi n d o w is + 5 da ys. 
d  
S u bjects i n t he L T E will u n der g o sc he d ule d visits f or safet y assess me nts a n d se me n sa m ple c ollecti o n e ver y 1 3 we e ks, starti n g  wit h L T E We e k  1 3 . S e me n m o nit ori n g will be 
c ollecte d u ntil t he Wee k 1 3 pri mar y st u d y res ults are a nal yze d . 
e 
A n y ti me a s u bject disc o nti n ues st u d y dr u g, a safet y f oll o w -u p visit, 3 0 da ys ( ±  5 da ys) after t he last d ose of st u d y dr u g is re q uire d, e ve n if t h e s u bject is e nteri n g  t he 
M o nit ori n g P hase  
f 
A n y ti me a s u bject disc o nti n ues partici p ati o n i n t h e st u d y pri or t o Wee k 2 6, O L Wee k 1 3, reac hi n g re versi bilit y or M o nit ori n g P hase Wee k 5 2  ( w hic he ver occ urs first), or 
L T E We e k 1 9 5, a n E T Visit is re q uire d . S u bjects w h o are Res p o n der s at Wee k 2 6 or at O L Wee k 1 3 a n d c h o ose n ot t o c o nti n ue i n t h e L T E ar e als o re q uire d t o c o m plete E T 
visit assess me nts.  
g  
As detaile d i n A p pe n di x  7  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
 
Fi nal  
Gala pa g os N V  
 
A me n d me nt 6  
C O N FI D E N TI A L  
 
P a ge  1 0 9  
 
0 9 Se pte m ber 2 0 2 2  
h  
1 2 -Lea d E C G will be perf or me d at L T E Wee k 1 9 5 or E T, w hic he ver occ urs s o o ner  
i 
Fle xi ble Si g m oi d osc o p y ( U C p atie nts) or ile oc ol o n osc o p y ( C D p atie nts) is o nl y re q uire d if it has n ot bee n d o ne i n t he last 9 0  da ys.  
j 
P artial M C S i ncl u des all parts of t h e c o m plete M C S e xce pt e n d osc o p y. F or defi niti o ns of I B D res p o nse stat us, please refer t o Defi niti o n of Ter ms ; f or defi niti o ns of Disease 
W orse ni n g, please refer t o Secti o n 3. 4  a n d Defi niti o n of Ter ms. S u bject recall f or t h e last 2 4 h o urs will be use d f or t h e patie nt re p orte d c o m p o ne nts of t h e c o m plet e M C S a n d 
partial M C S. S u bjects o n bli n de d st u d y dr u g meeti n g criteria f or N o n -Res p o n der at Wee k 1 3 or Disease W or se ni n g after Wee k 1 3 t hr o u g h Wee k 2 6 (a n d n ot meeti n g t h e 
pre -s pecifie d decrease t hres h ol d i n s per m para meters) will be eli gi ble f or o pe n -la bel fil g oti ni b (see Secti o n 3 ). M C S a n d partial M C S will be c ollecte d f or U C patie nts. 
P h ysicia n Gl o bal Assess me nt is a c o m p o ne nt of M C S a n d partial M C S.  
k  
C D AI will be c ollecte d f or C D p atie nts. S u bject recall f or t h e last 7 da ys will be use d f or t h e patie nt re p or te d o utc o mes of t h e C D AI.  T h e C D AI sc ore calc ulati o ns s h o ul d n ot 
be i n cl usi ve of da ys t h at i n v ol ve a n e n d osc o p y pr oce d ure or pre parati o n f or t hat pr oce d ure.  
l 
Pr o of of n o acti ve or u ntreate d late nt T B at Scree ni n g. S u bjects w h o are dia g n ose d wit h late nt T B a t scree ni n g m ust i nitiate a n a de q uate c o urse of pr o p h yla xis, as per l o cal 
sta n dar d of care, f or a mi ni m u m of 4 we e ks pri or t o ra n d o mizati o n. S u bject ma y i nitiate st u d y dr u g d osi n g o nl y after c o ns ulta ti o n wit h t h e m e dical m o nit or or desi g nee.  
m  
I n t h e L T E s u bjects m ust h a ve ye arl y Q ua nti F E R O N®  testi n g. Yearl y T B testi n g be gi ns 1  year fr o m t h e scree ni n g T B test date. If yearl y T B testi n g falls bet we e n st u d y visits, 
t h e yearl y T B testi n g s h o ul d be perf or me d at t h e visit pri or t o 1  ye ar fr o m t h e scree ni n g T B test date. S u bjects wit h ne wl y p ositi ve (c o n verte d) Q ua nti F E R O N ®  [ or ce ntrall y 
re p orte d e q ui vale nt assa y] T B test s h o ul d be disc o nti n ue d fr o m st u d y dr u g. S u bjects w h o were pre vi o usl y treate d f or T B wit h a c o m plete a n d a de q ua te co urse of t h era p y as 
per l o cal sta n dar d of care a n d as v erifie d b y t h e i n vesti gat or d o n ot nee d t o ha ve yearl y Q ua nti F E R O N ®  tests. S u bjects pre vi o usl y treate d f or T B s h o ul d be scree ne d at least 
yearl y f or si g ns a n d s y m pt o ms c o nsiste nt wit h reacti vati o n of T B. A n y s u bject wit h acti ve T B s h o ul d be disc o nti n ue d fr o m st u d y.  
n  
C hest x -ra y ( vie ws as p er l o cal g ui d eli nes) ta ke n at Scree ni n g or wit hi n t h e 3 m o nt hs pri or t o Scree ni n g ( wit h t h e re p ort or fil ms a v aila ble f or i n vesti gat or re vie w) wit h o ut 
e vi d e nce of acti v e or late nt T B i nfe cti o n  
o  
As detaile d i n A p pe n di x  6 . F or visits t hat re q uire fasti n g, s u bjects s h o ul d n ot ha ve a n y f o o d or dri n k (e xce pt water) f or at least 8 h o urs bef ore t h e visit. 
p  
Li pi d pr ofile s h o ul d be perf or me d e ver y 2 6 we e ks  
q  
Se me n sa m ples will be c ollecte d o n t he visit da y a n d/ or after t he visit. T h ose meeti n g t h e pre -s pecifi e d decrease t hres h ol d i n s per m para meters (as defi n e d i n t he Defi niti o n of 
Ter ms) m ust e nter t he M o nit ori n g P hase (see sc he d ule b el o w).  
r 
T he scree ni n g se me n sa m ple c ollecti o n s h o ul d c oi n ci d e wit h t he Da y 1 ( baseli ne) visit as m uc h as p ossi ble.  
s 
At ti me of c o nfir mati o n of N o n -res p o n der stat us/ Disease W orse ni n g a n d pri or t o i nitiati o n of o pe n-la bel fil g oti ni b, Se me n A nal ysis m ust c o nfir m s u bject di d n ot meet t h e pre-
s pecifie d decreas e t hres h ol d i n s per m para meters.  
t 
At ti me of c o nfir mati o n of N o n -res p o n der stat us/ Disease W orse ni n g a n d pri or t o e ntr y i nt o t he L T E, Se me n A nal ysis m ust c o nfir m s u bject di d n ot meet t h e pre -s pecifie d 
decrease t hres h ol d i n s per m para meters.  
u  
T his q uesti o n will be as ke d pri or t o eac h se me n c ollecti o n.  
v  
A n HI V -1/ HI V -2 a nti ge n/a nti b o d y test, a He patitis C vir us a nti b o d y test, a He patitis B s urface a nti ge n, a He p atitis B s urface a nti b o d y a n d a He patitis c ore a nti b o d y test will 
be c o n d ucte d o n all s u bjects; S u bjects wit h p ositi ve He patitis B s urface a nti ge n ( H Bs A g) at Scree ni n g are e xcl u de d fr o m t h e st u d y. S u bjects wit h p ositi ve H B V c ore A b a n d 
ne gati ve H Bs A g, re q u ire refle x testi n g f or H B V D N A. S u bjects wit h p ositi ve H B V D N A at Scree ni n g will be e xcl u de d. S u bjects wit h p ositi ve H B V c ore A b a n d ne gati ve 
H B V D N A are eli gi ble p er i n vesti gat or j u d g me nt, b ut ma y re q uire pr o p h ylactic treat me nt i n acc or da nce wit h H B V trea t me nt g ui d eli nes/l ocal sta n dar d of care a n d re q uire 
o n g oi n g m o nit ori n g wit h bl o o d tests f or H B V D N A e ver y 3 m o nt hs. S u bjects wit h e vi d e nce of acti ve He patitis  B d uri n g t he st u d y, as e vi d e nce d b y H B V D N A p ositi vit y, will 
be disc o nti n ue d fr o m st u d y dr u g as o utli ne d i n t he pr ot o c ol. S u bjects wit h p ositi ve H C V a nti b o d y ( A b) at Scree ni n g, re q uire refle x testi n g f or H C V R N A. S u bjects wit h 
p ositi ve H C V R N A at Scree ni n g will be e xcl u de d. S u bjects wit h p ositi ve H C V A b, b ut ne gati ve H C V R N A are eli gi ble per i n vesti g at or j u d g me nt. 
w  
S u bjects wit h p ositi ve H B V c ore A b a n d ne gati ve H B V D N A at Scree ni n g re q uire o n g oi n g m o nit ori n g wit h bl o o d tests f or H B V D N A e ver y 3 m o nt hs 
x  
S parse plas ma P K sa m ples ar e c ollecte d at least 3 0 mi n utes p ost -d ose.   
y  
S parse plas ma P K sa m ples c a n b e c ollecte d at a n y ti me wit h o ut re gar d t o d osi n g.   
z 
S parse plas ma P K sa m ples ar e c ollecte d pre -d ose.  
aa  
T he s u bject will ta ke t h e first d ose ( Da y 1) i n t he cli nical st u d y ce nter . F or P K c ollecti o n p ur p oses, at Wee ks 2, 1 3, a n d 2 6, a n d O L Wee ks 2 a n d 1 3, su bje cts s h o ul d be 
i nstr ucte d n ot  t o ta ke t h eir st u d y dr u g, b ut rat her t o bri n g it wit h t he m t o t h e cli nic. S u bjects will be i nstr ucte d t o ta ke t h eir d ose d uri n g t h eir sc he d ule d visit, as detaile d i n 
Secti o n 6. 1 6 . 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
 
Fi nal  
Gala pa g os N V  
 
A me n d me nt 6  
C O N FI D E N TI A L  
 
P a ge  1 1 0  
 
0 9 Se pte m ber 2 0 2 2  
St u d y Pr o ce d ure  
M o nit ori n g P h ase  
( Secti o n 6. 7 ) 
E T a  
Visits occ ur e ver y 1 3 w ee ks ( ± 5 d a ys)  
f or u p t o 5 2 w ee ks or u ntil R e versi bilit y is met, 
w hic he ver is s o o ner  
S y m pt o m -directe d P h ysical E xa m, as nee de d  
X  
X  
Vital Si g ns b a n d W ei g ht  
X  
X  
1 2 -lea d E C G 
 
X  
P artial Ma y o Cli nic Sc ore  
( partial M C S)c 
 
X  
Cr o h n’s Disease Acti vit y I n de x ( C D AI) d  
 
X  
Uri nal ysis e  
X  
X  
He mat ol o g y a n d C he mistr y e  
X  
X  
L H, F S H, i n hi bi n B, t otal T est oster o ne e  
c ollecti o n ti me bet wee n 0 7: 0 0 -1 1: 0 0 i n t he 
m or ni n g   
X  
X  
C o nc o mita nt Me dicati o ns  
X  
X  
Assess me nt of A d verse E ve nts f 
X  
X  
Se me n C ollecti o n  
( 2 sa m ples as p er c ollecti o n i nstr ucti o ns i n 
Secti o n 6. 1 3 )g  
X  
 
Date  a n d ti me of m ost rece nt ej ac ulati o n h  
X  
 
a 
N ot re q uire d if Re versi bilit y is met or if s u bject c o m pletes Wee k 5 2  
b  
As detaile d i n A p pe n di x  7  
c 
P artial M C S i ncl u des all parts of t h e c o m plete M C S e xce pt e n d osc o p y. F or defi niti o ns of I B D res p o nse stat us, please refer t o Defi niti o n of Ter ms; f or defi niti o ns of Disease 
W orse ni n g, please refer t o Secti o n 3. 4  a n d Defi niti o n of Ter ms. S u bject recall f or t h e last 2 4 h o urs will be use d f or t h e patie nt re p orte d c o m p o ne nts of t h e c o m plet e M C S a n d 
partial M C S. M C S a n d partial M C S will be c ollecte d f or U C p atie nts. P h ysicia n Gl o bal Assess me nt is a c o m p o ne nt of M C S a n d par tial M C S. 
d  
C D AI will be c ollecte d f or C D p atie nts. S u bject recall f or t h e last 7 da ys will be use d f or t h e patie nt re p orte d o utc o me s of t h e C D AI . T h e C D AI sc ore calc ulati o ns s h o ul d n ot 
be i n cl usi ve of da ys t h at i n v ol ve a n e n d osc o p y pr oce d ure or pre parati o n f or t hat pr oce d ure.  
e 
As detaile d i n A p pe n di x  6  
f 
As detaile d i n Secti o n 7. 3  
g  
Se me n sa m ples will be c ollecte d o n t he visit da y a n d/ or after t he visit  
h  
T his q uesti o n will be as ke d pri or t o eac h se me n c ollecti o n  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 1 1  
 
0 9 Se pte m ber 2 0 2 2  
A p pe n di x  3 . 
M a y o Sc ori n g S yste m * f or Assess me nt of Ulcer ati ve C olitis Acti vit y 
St o ol Fre q ue nc y * * –  E ac h s u bject serves as his 
or her o w n c o ntr ol t o est a blis h t he de gree of 
a b n or m ality of t he st o ol fre q ue n cy  
 
0  
N or mal n u m ber of st o ols f or s u bj ect  
 
1  
1 t o 2 st o ols per da y m ore t ha n n or mal  
 
2  
3  t o 4 st o ols m ore t ha n n or mal 
 
3  
≥ 5 st o ols m ore t ha n n or mal  
Rect al Blee di n g * * –  T he d aily blee di n g sc ore 
re prese nts t he m ost severe blee di n g of t he d ay. 
 
0  
N o bl o o d see n  
 
1  
Strea ks of bl o o d wit h st o ol less t ha n half t he ti me  
 
2  
O b vi o us bl o o d wit h st o ol half or m ore t ha n half of 
 
t he ti me 
 
3  
Bl o o d al o ne passes  
E n d osc o pic fi n di n gs –  Assesse d b y L ocal 
Rea der (i ncl u de o nl y f or M C S assess me nt *)  
 
0  
N or mal or i nacti ve disease  
 
1  
Mil d Disease (eryt he m a, decr e ase d v asc ul ar 
p atter n)  
 
2  
M o derate Disease ( m arke d er yt he m a, l ack of 
 
v asc ul ar p atter n, fri a bility, er osi o ns)  
 
3  
Se vere Disease (s p o nt a ne o us blee di n g, ulcer ati o n) 
P h ysici a n's Gl o b al Assess me nt –  T he 
p hysici a n’s gl o b al assess me nt ack n o wle d ges t he 
t hree ot her criteri a, t he s u bject’s d aily 
rec ollecti o n of a b d o mi n al disc o mf ort a n d ge ner al 
se nse of well-bei n g, a n d ot her o bserv ati o n, s uc h 
as p hysic al fi n di n gs a n d t he s u bject’s 
perf or m a nce st at us.  
 
0  
N or mal  
 
1  
Mil d disease  
 
2  
M o derate disease  
 
3  
Se vere disease  
*  
T he partial Ma y o Cli nic Sc ore ( partial M C S; ra n ge: 0 - 9) uses t he 3 n o n -i n vasi ve s u b-sc ores fr o m, a n d o mits t h e 
e n d osc o pic s u b -sc ore of, t h e f ull Ma y o Cli nic Sc ore (ra n ge: 0 - 1 2)  
* *  S u bject recall f or t h e last 2 4 h o urs will be use d f or t h e patie nt re p orte d c o m p o ne nts of t h e c o m plete M C S a n d partial M C S  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 1 2  
 
0 9 Se pte m ber 2 0 2 2  
A p pe n di x  4 . 
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 Criteri a f or A d verse E ve nts ( C T C A E) Versi o n  4. 0 3, 
w hic h ca n b e f o u n d at:  
htt ps://e vs. nci. ni h. g o v/ft p 1/ C T C A E / C T C A E _ 4. 0 3/ C T C A E _ 4. 0 3 _ 2 0 1 0-0 6 -
1 4 _ Q uic k Refere nce _ 8. 5 x 1 1. p df . 
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 d e 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 ma y or ma y n ot be i n a gree m e nt  
wit h t he gra di n g of t he la b orat or y a b n or malit y.  
T he o nl y m o dificati o n t o t he C T C A E criteria is t he a d diti o n of a Gra d e 1 u p per res pir at or y 
i nfecti o n as f oll o ws: 
C T C A E 
v 4. 0 Ter m  
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
Gr a de  5  
C T C A E v 4. 0 3 
A E Ter m 
Defi niti o n  
U p per 
res pirat or y 
i nfecti o n 
Mil d 
s y m pt o ms; 
s y m pt o matic 
relief 
(e g, c o u g h 
s u p pressa nt, 
dec o n gesta nt)  
M o derate 
s y m pt o ms; 
oral 
i nter ve nti o n 
i n dicate d 
(e g, a nti bi otic, 
a ntif u n gal, 
a nti viral)  
I V a nti bi otic, 
a ntif u n gal, or 
a nti viral 
i nter ve nti o n 
i n dicate d; 
ra di ol o gic, 
e n d osc o pic, or 
o perati ve 
i nter ve nti o n 
i n dicate d 
Life -
t hreate ni n g 
c o nse q ue nces; 
ur ge nt 
i nter ve nti o n 
i n dicate d 
Deat h  
A dis or der 
c haracterize d b y 
a n i nfecti o us 
pr ocess 
i n v ol vi n g t he 
u p per res pirat or y 
tract 
( n ose, para nasal 
si n uses, 
p har y n x, lar y n x, 
or trac hea). 
 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 1 3  
 
0 9 Se pte m ber 2 0 2 2  
A p pe n di x  5 . 
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  
T he a d mi nistrati o n of fil g oti ni b i n e m br y o -fetal a ni mal de vel o p me nt st u dies res ulte d i n 
decrease d n u m bers of via ble rat fet uses, i n crease d res or pti o ns, a n d visceral a n d s keletal 
malf or mati o ns. Si milar effects w ere n ot e d i n t he ra b bit. A safet y mar gi n relati ve t o h u ma n 
e x p os ure has n ot bee n i d e ntifie d. Pre g na n c y is c o ntrai n dicate d d uri n g use of fil g oti ni b.  
F or partici pati o n i n t his st u d y, me n m ust a gree t o use c o n d o ms d uri n g t he st u d y a n d f or 9 0  da ys 
after t he l ast d ose of st u d y dr u g. Fe m ale se x ual part ners of c hil d beari n g p ot e ntial, defi ne d bel o w, 
s h o ul d als o c o nsi der use of hi g hl y effecti ve c o ntr ace pti o n as o utli ne d bel o w.  
1)  Defi niti o ns  
a.  Defi niti o n of C hil d be ari n g P ote nti al (f or fe m ale se x u al p art ners of m ale s u bjects)  
F or t he p ur p os es of t his st u d y, a fe male -b or n part ner is c o nsi dere d of c hil d b eari n g p ote ntial 
f oll o wi n g t he i nitiati o n of p u bert y ( 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 o c u me nte d o varia n fail ure.   
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  years of a ge wit h 
cessati o n of pre vi o usl y o cc urri n g me ns es f or ≥ 1 2 m o nt hs wit h o ut a n alter nati ve ca use.  
Per ma ne nt steriliz ati o n i ncl u des h yst erect o m y, bilateral o o p h or ect o m y, or bilateral 
sal pi n gect o m y i n a fe mal e s u bject of a n y a ge. 
b.  Defi niti o n of M ale Fertilit y  
F or t he p ur p os es of t his st u d y, a mal e -b or n s u bject is c o nsi dere d fertile aft er t he i nitiati o n of 
p u bert y u nless per ma n e ntl y steriliz e d b y bilateral orc hi dect o m y or has me dical d oc u me ntati o n of 
per ma ne nt male i nfertilit y.  
2)  C o ntr ace pti o n f or Fe m ale Se x u al P art ners of 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  
Fil g oti ni b is c o ntrai n dicate d i n pre g na nc y as t here is a p ossi bilit y of h u ma n 
terat o ge nicit y/fet ot o xicit y i n e arl y pre g n a nc y b ase d o n n o n-cli nical data. Data fr o m a dr u g -dr u g 
i nteracti o n st u d y of fil g oti ni b a n d h or m o nal c o ntrace pti ves ( G S-U S -4 1 7 -3 9 1 6) ha ve 
de m o nstrate d c o -a d mi nistrati o n wit h fil g oti ni b di d n ot alter t he p har m ac o ki netics of 
re pres e ntati ve h or m o nal c o ntrace pti ves (le v o n or gestrel/et hi n yl estra di ol). F or male s u bjects, 
male c o n d o m s h o ul d be use d; f or t heir fe male part ners  of c hil d beari n g p ote ntial a n acce pte d 
c o ntrace pti ve met h o d s h o ul d als o be c o nsi dere d . Details are o utli ne d bel o w.  
Please refer t o t he latest versi o n of t he fil g oti ni b I B f or a d diti o nal i nf or mati o n.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 1 4  
 
0 9 Se pte m ber 2 0 2 2  
b.  C o ntr ace pti o n f or Fe m ale Se x u al P art ners of C hil d be ari n g P ote nti al  
Male s u bjects i n t his st u d y wit h fe m ale se x ual part ners of c hil d beari n g p ote ntial m ust a gree t o 
use a c o n d o m. Male s u bj ects m ust s hare t he f oll o wi n g i nf or m ati o n wit h fe male se x ual part ners 
re gar di n g w hi c h c o ntrace pti ve met h o ds are rec o m me n de d, starti n g at t he ti me of Scree ni n g u ntil 
9 0 da ys f oll o wi n g t he l ast d ose of st u d y dr u g i n t h e male s u bject.  
C o ntrace pti ve Met h o ds i ncl u de:  
C o m plete a bsti ne nce fr o m se x ual i nterc o urse of re pr o d ucti ve p ote ntial wit h t he male s u bject. 
A bsti ne nce is a n acce pta ble  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 fe male 
se x ual part ner a n d male s u bject’s preferre d a n d us ual lifest yle.  
O R  
C o nsiste nt a n d c orrect us e of 1 of t he f oll o wi n g m et h o ds of birt h c o ntr ol liste d bel o w.  
•  I ntr a uteri ne d e vice (I U D) wit h a fail ure rate of < 1 % per year  
•  T u bal steriliz ati o n  
•  Ess ure micr o -i nsert s yste m ( pr o vi de d c o nfir m ati o n of s uccess 3 m o nt hs aft er pr oce d ure) 
•  H or m o nal met h o ds (eac h met h o d m ust be use d wit h a c o n d o m i n t he male part ner)  
⎯ Oral c o ntrace pti ves (eit h er c o m bi ne d or pr o gester o ne o nl y)  
⎯ I nje cta ble pr o gester o n e 
⎯ I m pla nts of le v o n or gestr el 
⎯ Tra ns der m al c o ntrace pti ve patc h  
⎯ C o ntrace pti ve va gi n al ri n g  
All fe male se x ual part ners of male s u bjects s h o ul d refrai n fr o m i n vitr o fertilizati o n wit h e x p ose d 
male’s s per m d uri n g mal e s u bject st u d y p artici pati o n a n d u ntil at least 9 0 da ys after t h e last  d ose 
of st u d y dr u g i n t he mal e part ner.  
3)  C o ntr ace pti o n f or M ale S u bjects  
It is t he oreticall y p ossi ble t hat a rel e va nt c o nce ntr ati o n of st u d y dr u g ma y be ac hie ve d i n a 
fe male part ner fr o m e xp 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 p artici pati o n a n d f or 
9 0  da ys after t h e last st u d y dr u g d os e . Fe male part ners of male st u d y s u bjects s h o ul d c onsi der 
usi n g o ne  of t h e a b o ve m et 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 9 0 da ys after t h e last st u d y dr u g d osi n g . 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 1 5  
 
0 9 Se pte m ber 2 0 2 2  
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 h at  are u n acce pta ble i ncl u de peri o dic a bsti ne n ce (e g,  cale n dar, o v ulati o n, 
s y m 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 m et h o d ( L A M). 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)  Pr o ce d ures t o be F oll o w e d i n t he E ve nt of Pre g n a nc y i n a Fe m ale Se x u al P art ner  
S u bjects will be i nstr ucte d t o n otif y t he i n vesti gat or if t heir fe m ale part n er bec o mes pre g na nt at 
a n y ti me d uri n g t he st u d y, or if s he bec o mes pre g n a nt wit hi n 9 0 da ys of  his last st u d y dr u g d ose . 
S u bjects w h o ha ve se x ual part ners w h o b ec o me pre g n a nt or w h o s us pect t hat t he y are pre g n a 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.  
I nstr u cti o ns f or re p orti n g part ner pre g na n c y a n d p art ner pre g na n c y o utc o m e are o utli ne d i n 
Secti o n  7. 7. 2. 1 . 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 1 6  
 
0 9 Se pte m ber 2 0 2 2  
A p pe n di x  6 . 
Cli nic al L a b or at or y Assess me nt T a ble  
He m at ol o g y  
C he mistr y  
Uri n al ysi s 
Ot her  
He mat ocrit  
He 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  
B as 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  
Creati ni ne cleara nce 
( Cr Cl) 
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) 
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  
Ket o nes  
Bilir u bi n  
Nitrite  
S pecific Gra vit y  
Micr osc o pic  
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  
 
Q ua nti F E R O N ® T B –  
G ol d Pl us I n -T u be 
A nal ysis ( w he n re q uire d, 
per i ncl usi o n criteria)  
 
Fecal (st o ol)  
Bacterial St o ol C ult ure  
C -Diff T o xi n  
O va a n d P arasites ( O & P)  
 
P har mac 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 ( P T)  
P artial 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 p atitis B S urface A g 
He p atitis B S urface A b  
He p atitis B C ore A b 
He p atitis C A b  
HI V A g/ A b  
Refle x he patitis B D N A 
( w he n i n dicate d) 
Refle x he patitis C R N A 
( w he n i n dicate d) 
E n d ocri ne  
( at Scree ni n g O nl y) 
H b A 1c  
T S H  
Se x H or m o nes  
L utei nizi n g h or m o ne ( L H)  
F ollicle sti m ulati n g 
h or m o ne ( F S H)  
T est oster o ne (t otal)  
I n hi bi n B 
F asti n g Li pi ds  
Tri gl yceri des  
C h olester ol a n d its  
s u bfracti o ns ( hi g h-de nsit y  
li p o pr otei n [ H D L] a n d l o w 
de nsit y li p o pr otei n [ L D L])  
 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 1 7  
 
0 9 Se pte m ber 2 0 2 2  
A p pe n di x  7 . 
Pr o ce d ures a n d S pecific ati o ns  
C o m plete P h ysic al E x a mi n ati o n  
A c o m plete p h ysical e x a mi nati o n s h o ul d i ncl u de s o urce d oc u m e ntati o n of ge n eral a p peara n ce, 
a n 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 ut h a n d 
t o n g ue; c h est (e x cl 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.  
Vit al Si g ns  
Assess me nt of vital si g ns s h o ul d i ncl u de meas ure me nt of resti n g bl o o d press ure, p ulse, 
res pirat or y rate, a n d t e m perat ur e. 
Bl o o d press ur e s h o ul d be meas ure d usi n g t he f oll o wi n g sta n d ar dize d pr ocess: 
•  S u bject s h o ul d be resti n g f or  5 mi n utes wit h feet flat o n t he fl o or a n d meas ure me nt ar m 
s u p p orte d s o t hat t he mi d p oi nt of t he ma n o meter c uff is at heart le vel;  
•  Use a merc ur y s p h y g m o ma n o meter or a ut o matic bl o o d press ure de vi ce wit h a n a p pr o priat el y 
siz e d c uff wit h t he bla d d er ce nt ere d o v er t he brac hial arter y;  
•  Meas ure a n d rec or d t he bl o o d press ure t o t he nearest 2 m m H g mar k o n t h e ma n o meter or t o 
t he nearest w h ole n u m ber o n a n a ut o matic de vi ce. 
Cre ati ni ne Cle ar a nce  
Creati ni ne cleara n ce is c alc ulate d b y t he C oc k cr oft -Ga ult e q uati o n { C oc kcr oft 1 9 7 6 }  usi n g 
act ual b o d y wei g ht ( B W).  
Male:   
C r Cl ( m L/ mi n) =  [1 4 0  - a ge ( years)]  B W( k g)  
 
 
 
 
 
 
7 2   S cr 
 
S cr = ser u m creati ni ne ( m g/ d L)  
1 2 -Le a d E C G  
S u bjects s h o ul d rest i n a s u pi ne p ositi o n f or  5  mi n utes pri or t o ma ki n g a rec or di n g.   
T he i n vesti gat or ( or q ualifie d desi g nee) s h o ul d re vie w t he E C G traces rec or de d i n real ti me f or 
cli nicall y si g nifica nt a b n or malities.   


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 1 8  
 
0 9 Se pte m ber 2 0 2 2  
A p pe n di x  8 . 
M a n a ge me nt of Cli nic al a n d L a b or at or y A d verse E ve nts  
 
 
N O T E : Re peat la bs s h o ul d occ ur wit hi n 3 t o 7 da ys of t he i nitial a b n or m al la b val ue (e x ce pt f or 
creati ni ne cleara nce, w hi c h s h o ul d be re p eate d wit hi n 7 t o 1 4 da ys of t he i nitial a b n or mal val ue). 
A n u nsc he d ule d visit (ie, se q ue ntial visit) s h o ul d be utilize d t o o btai n t he re peat l a b v al ues.  
 
Gr a de 1  
Gr a de 4  
Gr a de 3  
Gr a de 2  
M a y c o nti n ue 
d osi n g at t he 
discreti o n of t he 
i n vesti g at or 
Re pe at l a b t o 
c o nfir m t o xicit y 
gr a de  
Re pe at l a b t o 
c o nfir m t o xicit y 
gr a de  
If c o nfir me d a n d p ossi bl y a n d/ or pr o b a bl y rel ate d t o 
i n vesti g ati o n al me dici n al pr o d ucts: 
 
1.
Wit h h ol d i n vesti g ati o n al me dici n al pr o d ucts u ntil  
 Gr a de 2 
2.
Rest art all i n vesti g ati o n al me dici n al pr o d ucts at f ull d ose  
If c o nfir me d a n d u nrel ate d t o 
i n vesti g ati o n al me dici n al 
pr o d ucts, d osi n g m a y c o nti n ue at 
t he discreti o n of t he i n vesti g at or 
If c o nfir me d a n d 
p ossi bl y or pr o b a bl y 
rel ate d t o 
i n vesti g ati o n al 
me dici n al pr o d ucts , 
disc o nti n ue 
i n vesti g ati o n al 
me dici n al pr o d ucts 
d osi n g per m a ne ntl y 
a n d f oll o w at 
peri o dic i nter v als at 
le ast w ee kl y u ntil a 
ret ur n t o b aseli ne or 
is ot her wise 
e x pl ai ne d  
If Gr a de 3 or 4 rec urre nce t h at is c o nfir me d a n d p ossi bl y or 
pr o b a bl y rel ate d t o i n vesti g ati o n al me dici n al pr o d ucts, 
disc o nti n ue all i n vesti g ati o n al me dici n al pr o d ucts d osi n g 
per m a ne ntl y  
If Gr a de 3 or 4 rec urre nce t h at is c o nsi dere d u nrel ate d t o 
i n vesti g ati o n al me dici n al pr o d ucts, c o nti n ue all 
i n vesti g ati o n al me dici n al pr o d ucts at t he s a me d ose at t h e 
discreti o n of t he i n vesti g at or 


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 1 9  
 
0 9 Se pte m ber 2 0 2 2  
A p pe n di x  9 . 
Cr o h n’s Dise ase Acti vit y I n de x ( C D AI)  
T he C D AI will be calc ul ate d as f oll o ws:  
V ari a ble  n o.  
V ari a ble  
V ari a ble descri pti o n  
M ulti plier  
1  
Li q ui d or ver y s oft st o ol *  
Dail y st o ol c o u nt is s u m me d f or 7  da ys  
2  
2  
A b d o mi nal pai n *  
S u m of 7 da ys of dail y rati n gs as  
0 = n o ne, 1 = mil d, 2 = m o derate, 
3  =  se vere 
5  
3  
Ge neral well bei n g *  
S u m of 7 da ys of dail y rati n gs as  
0 = ge nerall y well, 1 = sli g htl y bel o w 
par, 2  =  p o or, 3  =  ver y p o or, 
4  =  terri ble 
7  
4  
C o m plicati o ns  
N u m ber of liste d c o m plicati o ns:  
Art hritis or art hral gia  
Er yt he ma n o d os u m, p y o der ma 
ga n gre n os u m or a p h t h o us st o matitis 
Iritis or u veitis 
A nal fiss ures or fist ulae or a bscess  
Ot her fist ula  
Fe ver o ver 3 7. 8  ℃ [ 1 0 0 ℉] d uri n g past 
wee k  
2 0 eac h  
5  
Use of a nti -dia rr heal me dicati o ns 
Use of di p he n o x ylate or l o pera mi de or 
ot her o piate f or diarr hea  
0 = N o, 1 = Yes  
3 0  
6  
A b d o mi nal mass  
0 = n o ne, 2 = q uesti o na ble, 5  = defi nite  
1 0  
7  
He mat ocrit †  
Males: 4 7 –  Hct [ %]  
Fe males: 4 2 –  Hct [ %]  
† Res ult m ust be greater t ha n or e q ual 
t o 0. If ne gati ve res ult e nter 0  
6 × differe nce  
8  
W ei g ht ‡  
P erce nta ge de viati o n fr o m sta n dar d 
wei g ht  
[1 –  (c urre nt wei g ht / sta n dar d wei g ht) ] 
× 1 0 0  
‡ Li mit of -1 0  
1  
C D AI sc ore  
 
 
T O T A L  
C D AI = Cr o h n’s Disease Acti vit y I n de x; Hct = he mat o crit  
{ Sa n d b or n 2 0 0 2 }  
*  
S u bject recall f or t h e last 7 da ys will be use d f or t h e patie nt re p orte d c o m p o ne nts of t h e C D AI . T he C D AI s c ore calc ulati o ns 
s h o ul d n ot be i ncl usi ve of da ys t h at i n v ol ve a n e n d osc o p y pr oce d ure or pre parati o n f or t hat pr oce d ure.  


Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 2 0  
 
0 9 Se pte m ber 2 0 2 2  
A p pe n di x  1 0 . 
Si m ple E n d osc o pic Sc ore f or Cr o h n’s Dise ase ( S E S -C D)  
V ari a bles  
Sc ore  
0  
1  
2  
3  
Size of ulcers (c m)  
N o ne  
A p ht h o us ulcers  
( dia meter 0. 1-0 .5)  
Lar ge ulcers  
( dia meter 0. 5-2)  
Ver y lar ge ulcers  
( dia meter > 2) 
Ulcerate d surface ( %)  
N o ne  
< 1 0  
1 0 -3 0  
> 3 0  
Affecte d s urface ( %)  
U naffecte d 
se g me nt 
< 5 0  
5 0 -7 5  
> 7 5  
Prese nce of narr o wi n gs  
N o ne  
Si n gle,  
ca n be passe d  
M ulti ple,  
ca n be passe d  
Ca n n ot be passe d  
T otal S E S -C D (ra n ge: 0 -6 0): s u m of t h e val u es of t h e 4 varia bles f or t h e 5 b o wel se g me nts. V al u es are gi ve n t o eac h varia ble a n d 
f or e ver y e xa mi n e d b o wel se g me nt (e g, rect u m, left c ol o n, tra ns verse c ol o n, ri g ht c ol o n, a n d ile u m) { Da per n o 2 0 0 4 }  






Si g nat ure Pa ge f or gl p g 0 6 3 4-cl- 2 2 8- pr ot oc ol-a me n d # 6 2 4 2 3 6
Si g nat ure Pa ge f or gl p g 0 6 3 4-cl- 2 2 8- pr ot oc ol-a me n d # 6 4 3 9 5 2 _ 7 7 4 9 8 _ 1 0 4 3 1 7
A p pr o val
o p me nt Lea der
Cli nical De vel o p me nt
0 9- Se p- 2 0 2 2 1 2: 2 6: 2 6 G M T + 0 0 0 0
P P D

SAP_001.pdf: 
S T A TI S TI C A L A N A L Y SI S P L A N
St u d y Title:
A Ra n d o mize d, D o u ble -bli n d, Place b o -c o ntr olle d P hase 2 
St u d y  t o E val uate t he Testic ular Safety of Fil g oti ni b i n A d ult 
Males wit h M o deratel y t o Se verel y Acti ve I nfla m mat or y 
B o wel Disease
N a me of Test Dr u g:
Fil g oti ni b
St u d y N u m ber:
G S -U S - 4 1 8- 4 2 7 9
Pr ot oc ol Versi o n ( D ate):
Ori gi nal:
3 1 Ja n uar y  2 0 1 7
A me n d me nt 1:
0 6 J ul y  2 0 1 7
A me n d me nt 2:
2 2 A u g ust 2 0 1 8
A me n d me nt 3:
1 8 Ja n uar y  2 0 1 9
A me n d me nt 4:
1 8 Marc h 2 0 2 0
A n al ysis T y pe:
I nteri ms ( Wee k 2 6 a n d Wee k 2 6 pl us Re versi bilit y)
a n d Fi nal A nal y sis
A n al ysis Pl a n Versi o n:
Versi o n 1. 0
A n al ysis Pl a n D ate:
1 3 Ja n uar y 2 0 2 1
A n al ysis Pl a n A ut h or(s):
C O N FI D E N TI A L A N D P R O P RI E T A R Y I N F O R M A TI O N
P P D


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 2
1 3 Ja n uar y 2 0 2 1
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 ........................................................................................................................................4
LI S T O F I N -T E X T FI G U R E S ......................................................................................................................................4
LI S T O F A B B R E VI A TI O N S ........................................................................................................................................5
1.
I N T R O D U C TI O N ................................................................................................................................................7
1. 1.
St u d y O bjecti ves ......................................................................................................................................7
1. 2.
St u d y Desi g n ............................................................................................................................................8
1. 3.
Sa m ple Size a n d P o w er ..........................................................................................................................1 0
2.
T Y P E O F P L A N N E D A N A L Y SI S ....................................................................................................................1 1
2. 1.
Data M o nit ori n g C o m mittee A nal yses ...................................................................................................1 1
2. 2.
I nter nal I n de pe n de nt Safet y Re vie w ......................................................................................................1 1
2. 3.
Wee k 2 6 A nal ysis
..................................................................................................................................1 2
2. 4.
Wee k 2 6 a n d Re versi bilit y A nal ysis f or Pre -s pecifie d S per m Decreases U p t o Wee k 2 6 .....................1 2
2. 5.
Fi nal A nal ysis ........................................................................................................................................1 2
3.
G E N E R A L C O N SI D E R A TI O N S F O R D A T A A N A L Y S E S ............................................................................1 3
3. 1.
A nal ysis Sets ..........................................................................................................................................1 3
3. 1. 1.
All Ra n d o mize d A nal ysis Set ...............................................................................................1 3
3. 1. 2.
Se m e n A nal ysis Sets ............................................................................................................1 3
3. 1. 3.
Safet y A nal ysis Sets .............................................................................................................1 4
3. 1. 4.
P har m ac o ki netic A nal ysis Set ..............................................................................................1 4
3. 2.
S u bject Gr o u pi n g ...................................................................................................................................1 5
3. 3.
Strata a n d C o variates ..............................................................................................................................1 6
3. 4.
E xa mi nati o n of S u bject S u b gr o u ps ........................................................................................................1 7
3. 5.
Missi n g Data a n d O utliers ......................................................................................................................1 7
3. 5. 1.
Missi n g Data
........................................................................................................................1 7
3. 5. 2.
O utliers .................................................................................................................................1 7
3. 6.
Data Ha n dli n g C o n ve nti o ns a n d Tra nsf or mati o ns .................................................................................1 7
3. 7.
A nal ysis Visit Wi n d o ws .........................................................................................................................1 8
3. 7. 1.
Defi niti o n of St u d y Da y .......................................................................................................1 8
3. 7. 2.
A nal ysis Visit Wi n d o ws .......................................................................................................1 8
3. 7. 3.
Selecti o n of Data i n t he E ve nt of M ulti ple Rec or ds i n a n A nal ys is Visit 
Wi n d o w ................................................................................................................................2 4
4.
S U BJ E C T DI S P O SI TI O N ..................................................................................................................................2 6
4. 1.
S u bject Ra n d o mizati o n a n d Dis p ositi o n ................................................................................................2 6
4. 2.
E xte nt of St u d y Dr u g E x p os ure a n d A d here nce .....................................................................................2 9
4. 2. 1.
D urati o n of E x p os ure t o St u d y Dr u g ....................................................................................3 0
4. 2. 2.
A d here nce t o St u d y Dr u g .....................................................................................................3 1
4. 3.
Pr ot oc ol De viati o ns ................................................................................................................................3 2
5.
B A S E LI N E C H A R A C T E RI S TI C S ....................................................................................................................3 3
5. 1.
D e mo gra p hics ........................................................................................................................................3 3
5. 2.
Baseli ne C haracteristics .........................................................................................................................3 3
5. 3.
Me dical Hist or y ......................................................................................................................................3 4
6.
S E M E N A N D H O R M O N E A N A L Y S E S ...........................................................................................................3 5
6. 1.
Ge neral C o nsi derati o ns ..........................................................................................................................3 5


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 3
1 3 Ja n uar y 2 0 2 1
6. 2.
P ri mar y A nal ysis of Pri mar y a n d Sec o n dar y E n d p oi nts ........................................................................3 6
6. 3.
S u b gr o u p A nal ysis  f or S per m C o nce ntrati o n Para meter at Wee k 1 3 ....................................................3 8
6. 4.
S u p p orti ve A nal ysis f or Pri mar y a n d Sec o n dar y E n d p oi nts at Wee k 1 3 ...............................................3 8
6. 5.
Ot her Dis pla ys of S per m/ Se me n Data ....................................................................................................3 9
6. 5. 1.
Treat me nt- Se q ue nce Se me n Dis pla ys ( Wee k 2 6/ O L Wee k 1 3 a n d 
E xte nsi o n P hase) ..................................................................................................................3 9
6. 5. 2.
Pr e -S pecifie d S per m Decrease T hres h ol d Criteria a n d C o nfir me d Se me n 
A b n or m alities .......................................................................................................................4 0
6. 6.
E x pl orat or y E n d p oi nts ...........................................................................................................................4 1
6. 6. 1.
Defi niti o n of t he E x pl orat or y E n d p oi nts ..............................................................................4 1
6. 6. 2.
Re versi bilit y A nal ysis ..........................................................................................................4 2
6. 6. 3.
H or m o nes .............................................................................................................................4 2
6. 7.
C ha n ges t o Pr ot oc ol -S pecifie d A nal yses of Se me n a n d H or m o ne Data ................................................4 3
7.
A S S E S S M E N T O F R E S P O N D E R/ N O N- R E S P O N D E R A N D DI S E A S E W O R S E NI N G ...............................4 5
7. 1. 1.
Calc ulati o ns of M C S a n d p M C S wit h t he S u bsc ores ...........................................................4 5
7. 1. 2.
Calc ulati o n of C D AI S c ores .................................................................................................4 6
8.
S A F E T Y A N A L Y S E S ........................................................................................................................................4 8
8. 1.
A d verse E ve nts a n d Deat hs ....................................................................................................................4 8
8. 1. 1.
A d verse E ve nt Dicti o nar y ....................................................................................................4 8
8. 1. 2.
A d verse E ve nt Se verit y ........................................................................................................4 9
8. 1. 3.
Relati o ns hi p of A d verse E ve nts t o St u d y Dr u g ....................................................................4 9
8. 1. 4.
Seri o us A d verse E ve nts ........................................................................................................4 9
8. 1. 5.
Treat me nt- E mer ge nt A d verse E ve nts ...................................................................................4 9
8. 1. 6.
S u m maries of A d verse E ve nts a n d Deat hs ...........................................................................5 2
8. 1. 7.
A d verse E ve nts of I nterest ...................................................................................................5 5
8. 1. 8.
A nal ysis of A d verse E ve nts b y Treat me nt Se q ue nce ( Fi nal A nal ysis o nl y) ........................5 7
8. 2.
La b orat or y E val uati o ns ..........................................................................................................................5 7
8. 2. 1.
S u m maries of N u meric La b orat or y Res ults .........................................................................5 8
8. 2. 2.
Gra de d La b orat or y Val ues ...................................................................................................5 8
8. 2. 3.
Li ver -relate d La b orat or y E val uati o ns...................................................................................6 0
8. 3.
B o d y  Wei g ht a n d Vital Si g ns.................................................................................................................6 1
8. 4.
Pri or a n d C o nc o mita nt Me dicati o ns .......................................................................................................6 1
8. 4. 1.
Pri or Me dicati o ns .................................................................................................................6 2
8. 4. 2.
C o nc o mita nt Me dicati o ns .....................................................................................................6 2
8. 5.
Electr ocar di o gra m ( E C G) Res ults ..........................................................................................................6 3
9.
P H A R M A C O KI N E TI C A N A L Y S E S ................................................................................................................6 4
1 0.
R E F E R E N C E S ...................................................................................................................................................6 5
1 1.
S O F T W A R E .......................................................................................................................................................6 6
1 2.
S A P R E VI SI O N ..................................................................................................................................................6 7
1 3.
A P P E N DI C E S ....................................................................................................................................................6 8
A p pe n di x 1.
St u d y Pr oce d ures Ta ble ..........................................................................................................6 9
A p pe n di x 2.
Calc ulati o n of Differe nce i n Pr o p orti o ns a n d 9 5 % CI ( Strat u m -A dj uste d Ma ntel -
Hae nszel Pr o p orti o ns) ............................................................................................................7 4


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4
1 3 Ja n uar y 2 0 2 1
LI S T O F I N -T E X T T A B L E S
Ta ble 3- 1.
A nal ysis Visit Wi n d o ws f or Li pi d Pr ofile, Ser u m I m m u n o gl o b uli n,  a n d Uri nal ysis.............2 0
Ta ble 3- 2.
A nal ysis Visit Wi n d o ws f or Partial M C S, C D AI, Vital Si g ns, Wei g ht, He mat ol o g y, 
a n d C he mistr y La b orat ories ....................................................................................................2 1
Ta ble 3- 3.
A nal ysis Visit Wi n d o ws f or L H, F S H, I n hi bi n B, a n d T otal Test oster o ne ............................2 2
Ta ble 3- 4.
A nal ysis Visit Wi n d o ws f or O n -Treat m e nt Se me n Para meters ..............................................2 3
Ta ble 3- 5.
A nal ysis Visit Wi n d o ws f or Se me n Para meters i n M o nit ori n g P hase  ( Calc ulate d 
fr o m Last D ose Date of A n y St u d y Dr u g) ..............................................................................2 3
Ta ble 6- 1.
Defi niti o ns f or t he Pri mar y a n d Sec o n dar y E n d p oi nts ...........................................................3 5
Ta ble 6- 2. 
Se m e n Para meter Eli gi bilit y Criteria ......................................................................................3 5
Ta ble 6- 3.
H y p ot hetical Pr o p orti o n of S u bjects W h o Met Re versi bilit y Criteria  b y M o nit ori n g 
Visit N u m ber a n d Treat me nt Gr o u p ( S u bjects w it h a ≥5 0 % Decrease i n S per m 
C o nce ntrati o n at Wee k 1 3) .....................................................................................................4 2
Ta ble 7- 1.
M a y o Cli nic Sc ore ..................................................................................................................4 5
Ta ble 7- 2.
Calc ulati o n o f T otal C D AI Sc ore ...........................................................................................4 6
LI S T O F I N -T E X T FI G U R E S
Fi g ure 1- 1.
G S -U S -4 1 8 -4 2 7 9 ( M A N T A): St u d y Sc he ma ( Pr ot oc ol A me n d me nt 4) ..................................9


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 5
1 3 Ja n uar y 2 0 2 1
L I S T O F A B B R E VI A TI O N S
A E
a d verse e ve nt
A E Is
a d verse e ve nt s of i nterest
A L T
ala ni ne a mi n otra nsferase
A S T
as partate a mi n otra nsferase
A T C
A nat o mical T hera pe utic C he mical
B L Q
bel o w  t he li mit of q ua ntitati o n
B MI
b o d y mass i n de x
C D
Cr o h n’s d isease
C D AI
Cr o h n’s Disease Acti vit y I n de x
CI
co nfi de nce i nter val
C O VI D -1 9
C or o na vir us Disease 2 0 1 9
C S R
cli nical st u d y re p ort
C T C A E
C o m m o n T er m i n ol o g y Criteria f or A d verse E ve nts
C V E A C
Car di o vasc ular E ve nt A dj u dicati o n C o m mittee
D B
d o u ble -bli n d
D M C
Data M o nit ori n g C o m mittee 
D V T
dee p vei n t hr o m b osis
E AI R
ex p os ure -a dj uste d i nci de nce rates
E C G
electr ocar di o gra m
e C R F
electr o nic case re p ort f or m
E T
earl y ter mi nati o n
F D A
F o o d a n d Dr u g A d mi nistrati o n
F S H
follicle -sti m ulati n g h or m o ne
F U
f oll o w-u p
G L P G
Gala pa g os , N V
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
I B D
i nfla m mat or y b o w el disease
I C
i ncl usi o n criteria
I D
Ide ntificati o n
I P D
i mp orta nt pr ot oc ol de viati o n
I T T
I nte nt-t o-Treat
I U T
I nter nal U n bli n de d Tea m
I W R S
i nteracti ve we b res p o nse s yste m
L H
l utei nizi n g h or m o ne
L L T
lo w -le vel ter m
L O Q
li mit of q ua ntitati o n
L T E
lo n g ter m e xte nsi o n


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 6
1 3 Ja n uar y 2 0 2 1
M
M illi o n
M A C E
maj or a d verse car diac e ve nts
M A R
missi n g at ra n d o m
M C S
M a y o Cli nic Sc ore
Me d D R A
Me dical Dicti o nar y f or Re g ulat or y Affairs
M H
Ma ntel- Hae nszel
MI
m ulti ple i m p utati o n
M S T
Me d D R A searc h t er m
M T X
M et h otre xate
OI
o p p ort u nistic i nfecti o n
O L
o pe n -la bel
P E
p ul m o nar y e m b oli s m
P G A
P h y sicia n’s Gl o bal Assess me nt
P K
P har mac o ki netics
p M C S
p artial Ma y o Cli nic Sc ore
P T
preferre d ter m
P T M
p lace b o-t o-matc h
P Y E
p atie nt -years of e x p os ure
Q 1
first q uartile
Q 3
t hir d q uartile
R B
rectal blee di n g
S A E
seri o us a d verse e ve nt
S A P
Statistical A nal ysis Pla n
S D
sta n dar d de viati o n
S E
sta n dar d err or
S F
st o ol fre q ue nc y
S M Q
sta n dar dize d Me d D R A q uer y
S O C
s yste m or ga n class
T E A Es
treat me nt e mer ge nt a d verse e ve nts
T F L s
ta bles, fi g ures a n d listi n gs
U C
ulcerati ve c olitis
U L N
u p per li mit of n or mal
U S
U nite d States
V T E
ve n o us t hr o m b oe m b olis m e ve nt
W H O
W orl d Healt h Or ga nizati o n


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 7
1 3 Ja n uar y 2 0 2 1
1.
I N T R O D U C TI O N
T his statistical a nal y sis pla n ( S A P) descri bes t he statistical a nal ysis met h o ds a n d data 
prese ntati o ns t o be use d i n ta bles, fi g ures, a n d listi n gs ( T F Ls) f or St u d y G S-U S -4 1 8 - 4 2 7 9
[ M A N T A]. T his S A P is base d o n st u d y pr ot oc ol A me n d me nt 4 date d 1 8 Marc h
2 0 2 0 a n d t he 
electr o nic case re p ort f or m (e C R F). T he S A P will be fi nalize d pri or t o u n bli n di n g f or t he 
Wee k
2 6 i nteri m a nal ysis after at least 2 0 0 e val ua ble s u bjects p o ole d acr oss st u dies 
G S -U S - 4 1 8-4 2 7 9 [ M A N T A] a n d G L P G 0 6 3 4 -C L -2 2 7 [ M A N T A -R A y ] c o m plete Wee k 1 3; a n d
e val ua ble s u bjects fr o m St u d y  G S-U S - 4 1 8- 4 2 7 9 c o m plete Wee k 2 6 or per ma ne ntl y  disc o nti n ue 
fr o m st u d y dr u g. A n y c ha n ges ma de after t he fi nalizati o n of t he S A P will be d oc u me nte d i n t he 
cli nical st u d y re p ort (C S R ).
1. 1. 
St u d y O bjecti ves
T he pri m ar y o bjecti ve of t he st u d y is as f oll o ws:

T o e val uate t he effect of fil g oti ni b o n testic ular f u ncti o n as defi ne d b y t he pr o p o rti o n of 
s u bjects wit h a ≥5 0 % decrease fr o m baseli ne i n s per m c o nce ntrati o n at Wee k 1 3
T he sec o n d ar y o bjecti ves of t he st u d y are as f oll o ws:

T o e val uate t he effect of fil g oti ni b o n testic ular f u ncti o n as defi ne d b y t he pr o p orti o n of 
s u bjects wit h a ≥5 0 % decrease fr o m baseli ne i n s per m c o nce ntrati o n at Wee k 2 6

T o e val uate t he effect of fil g oti ni b o n s per m t otal m otilit y  at Wee ks 1 3 a n d 2 6

T o e val uate t he effect of fil g oti ni b o n t otal s per m c o u nt at Wee ks 1 3 a n d 2 6

T o e val uate t he effect of fil g oti ni b o n t he c ha n ge fr o m baseli ne i n s per m c o nce ntrati o n at 
Wee ks 1 3 a n d 2 6

T o e val uate t he effect of fil g oti ni b o n ejac ulate v ol u me at Wee ks 1 3 a n d 2 6

T o e val uate t he effect of fil g oti ni b o n perce nt n or mal s per m m or p h ol o g y  at Wee ks 1 3 a n d 2 6
T he e x p lor at or y o bjecti ves of t he st u d y are as f oll o ws:

T o e val uate t he re versi bilit y  of o bser ve d effects of fil g oti ni b o n testic ular f u ncti o n i n s u bjects 
w h o e x perie nce a ≥5 0 % decrease i n s per m c o nce n trati o n a n d/ or m otilit y a n d/ or m or p h ol o g y

T o e val uate t he effect of fil g oti ni b o n h or m o nes, i ncl u di n g l utei nizi n g h or m o ne ( L H), 
f ollicle-sti m ulati n g h or m o ne ( F S H), i n hi bi n B, a n d t otal test oster o ne at Wee ks 1 3 a n d 2 6

T o e val uate t he safet y a n d t olera bilit y of fil g oti ni b

T o c haracterize t he plas ma p har mac o ki netics ( P K) of fil g oti ni b a n d its meta b olite 
( G S-8 2 9 8 4 5, f or merl y   
)
C CI


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1. 2.
St u d y Desi g n
T his is a ra n d o mize d, d o u ble -bli n d, place b o -c o ntr olle d, P hase 2 st u d y  i n a d ult males wit h 
m o deratel y t o se verel y acti ve i nfla m mat or y b o wel disease (I B D).
U p t o 2 5 0 males were pla n ne d t o be ra n d o mize d i n a 1: 1 rati o t o recei ve u p t o 2 6 wee ks of 
fil g oti ni b 2 0 0 m g or place b o -t o-matc h ( P T M) o nce dail y , t o e ns ure a p pr o xi matel y 2 0 0 e val ua ble 
s u bjects. Pr ot oc ol A me n d me nt 3 ra n d o mizati o n wa s stratifie d by t y pe of disease ( U C or C D), 
c o nc urre nt use of met h otre xate ( M T X; yes or n o), a n d s per m c o nce ntrati o n ( 1 5 t o 
2 5 milli o n [ M]/ m L, > 2 5 t o 5 0 M/ m L , or > 5 0 M/ m L ). S u bje cts ma y ha ve be e n o n 
pr ot oc ol -s pecifie d c o nc o mita nt t hera p y. Ori gi nal a n d Pr ot oc ol A me n d me nt 1 ra n d o mizati o n was 
stratifie d b y c o nc urre nt use of M T X ( yes or n o) o nl y. N o s u bjects were ra n d o mize d u n der 
Pr ot oc ol A me n d me nts 2 or 4.
T he mai n i ncl usi o n criter ia rele va nt t o t his st u d y are:

Male s u bjects bet wee n t he a ge of 2 1 a n d 6 5 (i ncl usi ve) o n t he da y  of si g ni n g i nf or me d 
c o nse nt

T he mea n of 2 se parate e val ua ble se me n sa m ples c ollecte d at t he scree ni n g visit m ust meet 
t he f oll o wi n g mi ni m u m criteria ( Pr ot oc ol A me n d me nt 4, Secti o n 6. 1 4): se me n v ol u me 
≥1. 5 m L , t otal s per m/ejac ulate ≥3 9 M/ejac ulate , s per m c o nce ntrati o n ≥1 5
M / m L, s per m 
t otal m otilit y ≥ 4 0 %, a n d perce nt n or mal s per m m or p h ol o g y  ≥ 3 0 % usi n g W orl d Healt h 
Or ga nizati o n ( W H O ) 2 0 1 0 criteria { W orl d Healt h Or ga nizati o n ( W H O) 2 0 1 0 }).
T he m ai n excl usi o n criteri o n rele va nt t o this st u d y is:

Pre vi o usl y  or c urre ntl y d oc u me nte d pr o ble ms wit h male re pr o d ucti ve healt h, i ncl u di n g b ut 
n ot li mite d t o pri mar y  h y p o g o na dis m, sec o n dar y h yp o g o na dis m, or re d uce d fertilit y
A c o m plete list of eli gi bilit y  criteria is pr o vi de d i n Secti o ns 4. 2 a n d 4. 3 of St u d y Pr ot oc ol 
A me n d me nt 4. T he Scree ni n g peri o d w as u p t o 4 5 da y s pri or t o ra n d o mizatio n. T he assess me nts 
pla n ne d t o be perf or me d at eac h visit are detaile d i n t he st u d y  pr oce d ures ta ble (A p pe n di x 1 ). 
T he st u d y i ncl u des 5 parts: Part A (D o u ble- bli n d P hase: Da y  1 t hr o u g h Wee k 1 3 st u d y visit); 
Part B ( D o u ble -Bli n d P hase: after Wee k 1 3 t hr o u g h Wee k 2 6 st u d y visit); O pe n -La bel ( O L) 
Fil g oti ni b P hase ( O L Da y  1 t o O L Wee k 1 3 visit); Lo n g Ter m E xte nsi o n ( L T E, d o u ble- bl i n d or 
O L  f or u p t o 1 9 5 wee ks); a n d M o nit ori n g P hase ( u p t o 5 2 wee ks). A sc he matic of t he st u d y  
desi g n is pr o vi de d i n Fi g ure 1- 1 .


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Fi g ure 1- 1.
G S -U S - 4 1 8-4 2 7 9 ( M A N T A): St u d y Sc he m a ( Pr ot oc ol A me n d me nt 4)
S u bjects will visit t he cli nical st u d y  ce nter at Scree ni n g, Da y 1, Wee k 2, Wee k 4, Wee k 8, a n d 
Wee k
1 3 ( Part A of st u d y). S u bjects w h o are I B D res p o n ders at Wee k 1 3 wit h o ut meeti n g
pre -s pecifie d s per m decrease t hres h ol ds will c o nti n ue o n bli n de d treat me nt a n d ret ur n f or 
Wee k 2 0 a n d Wee k
2 6 assess me nts. A pre -s pecifie d s per m decrease t hres h ol d was defi ne d as a 
≥5 0 % decrease fr o m baseli ne i n s per m c o nce ntrati o n pri or t o Pr ot oc ol A me n d me nt 2 ; a n d a 
≥5 0 % decrease fr o m baseli ne i n s per m c o nce ntrati o n a n d/ or m otilit y  a n d/ or m or p h ol o g y at/after
P r ot oc ol A me n d me nt 2 . Si nce n o s u bject de m o nstrate d a ≥ 5 0 % decrease i n s per m m otilit y  or 
m or p h ol o g y pri or t o Pr ot oc ol A me n d me nt 2 , t his S A P will hereafter refer t o a “pre -s pecifie d 
s per m decrease t hres h ol d” as a s u bject de m o nstrati n g a ≥5 0 % decrease fr o m baseli ne i n s per m 
c o nce ntrati o n a n d/ or m otilit y a n d/ or m or p h ol o g y. S u bjects w h o are n o n -res p o n ders at Wee k 1 3 
a n d s u bjects w h o ha ve disease w orse ni n g after Wee k 1 3 u p t o Wee k 2 6 w h o d o n ot meet 
pre -s pecifie d s per m decrease t hres h ol ds will e nter t he O pe n-La bel P has e a n d ret ur n f or visits at 
Wee k 2, Wee k 4, Wee k 8, a n d Wee k
1 3 d uri n g t he o pe n -la bel p hase. S u bjects w h o are 
res p o n ders at Wee k 2 6/ O pe n-la bel Wee k 1 3 wit h o ut disease w orse ni n g a n d wit h o ut meeti n g 
pre -s pecifie d s per m decrease t hres h ol ds ma y c o nti n ue ta ki n g st u d y dr u g i n t he LT E p hase f or u p 
t o 1 9 5 wee ks ( or u ntil t he y ha ve disease w orse ni n g or meet pre -s pecifie d s per m decrease 
t hres h ol d[s]).
S u bjects w h o meet pre -s pecifie d s per m decrease t hres h ol d(s) at a n y p ost baseli ne visit will st o p 
st u d y dr u g, s witc h t o a sta n dar d of care re gi me n selecte d b y t he i n vesti gat or (i n acc or da nce wit h 
t he pr ot oc ol) a n d e nter t he M o nit ori n g P hase. S u bjects will u n der g o se me n e val uati o ns e ver y  
1 3 wee ks starti n g fr o m t heir e ntr y  i nt o t he M o nit ori n g P hase f or u p t o 5 2 wee ks or u ntil 
re versi bilit y is met, w hic he ver is ac hie ve d first. Re versi bilit y  is defi ne d as a ret ur n t o
> 0. 5 x ( mea n of 2 e val ua ble sa m ples c ollecte d at scree ni n g visit) of all s per m para meter(s)
q ualif y i n g t he s u bject f or t he m o nit ori n g p hase —base d o n 2 e val ua ble sa m ples c ollecte d at t he 
m o nit ori n g p hase visit.


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Pri or t o Pr ot oc ol A me n d me nt 2 , s u bjects w h o s witc he d t o O L fil g oti ni b a n d s u bjects w h o 
disc o nti n ue d st u d y  dr u g after meeti n g pre-s pecifie d sper m decrease t hres h ol d(s) c o nti n ue d t o 
atte n d visits sc he d ule d relati ve t o t he date of t heir first d ose of d o u ble -bli n d st u d y  dr u g 
(e g, t he Wee k
2 6 visit was sc he d ule d a p pr o xi matel y  2 6 wee ks after t he first d ose of d o u ble-bli n d 
st u d y dr u g). H o we ver, beca use of t he ti me re q uire d t o c ollect a n d e val uate se me n sa m ples, 
s u bjects ma y n ot ha ve s witc he d or disc o nti n ue d, res pecti vel y, u ntil after t he Wee k 1 3 visit. 
T heref ore, a f ull 1 3 wee ks (ie, a f ull s per mat o ge nic c ycle) m a y  n ot ha ve passe d bef ore t heir ne xt 
sc he d ule d se me n assess me nt u n der t he ne w c o n diti o n (ie, si nce s witc hi n g t o O L fil g oti ni b or 
disc o nti n ui n g st u d y  dr u g, res pecti vely) . At/after Pr ot oc ol A me n d me nt 2 , st u d y visits i n t he O L 
Fil g oti ni b P hase a n d M o nit ori n g P hase are sc he d ule d relati ve t o t he first da y  of starti n g O L 
fil g oti ni b a n d t he last da y of st u d y dr u g, res pecti vel y, all o wi n g a f ull 1 3 wee ks bef ore t he first 
se me n assess me nt u n der t he ne w c o n diti o n.
Please refer t o t he st u d y pr ot oc ol f or detaile d descri pti o ns of t he visit sc he d ule a n d res pecti ve 
e val uati o ns.
1. 3.
S a m ple Size a n d P o wer
Res ults of t his st u d y  will be p o ole d wit h t he res ults of a se parate st u d y bei n g c o n d ucte d i n 
s u bjects wit h r he u matic diseases ( G L P G 0 6 3 4 -C L -2 2 7 [ M A N T A -R A y ]) wit h t he sa me 
o bjecti ves . T he t otal pla n ne d n u m ber of s u bjects i n b ot h st u dies c o m bi ne d will be u p t o 
a p pr o xi matel y 2 5 0 s u bjects.
A sa m ple size of a p pr o xi matel y  1 0 0 e val ua ble s u bjects per gr o u p (ie, 1 0 0 s u bjects i n t he 
fil g oti ni b 2 0 0 m g gr o u p a n d 1 0 0 s u bjects i n t he place b o gr o u p) is a de q uate f or t he p ur p oses of 
esti mati n g c u m ulati ve distri b uti o n c ur ves a n d pr o d uci n g a 9 5 % c o nfi de nce i nter val ( CI) wi dt h 
t hat is reas o na bly narr o w f or t he p r o p orti o n of s u bjects i n eac h gr o u p w h o e x perie nce a 
≥5 0 % decrease i n s per m c o nce ntrati o n c o m pare d t o baseli ne. A n e val ua ble s u bject is defi ne d as 
a s u bject wit h 2 se me n sa m ples at b ot h baseli ne a n d at Wee k 1 3 t hat are eli gi ble f or mea n 
calc ulati o n f or s per m c o nce ntratio n, wit h visit wi n d o w assi g n me nt f or t he mea n calc ulati o n 
base d o n t he date of t he first of 2 e val ua ble sa m ple c ollecti o ns. T his 2 0 0 s u bject sa m ple size is 
s u g geste d i n F D A’s g ui da nce o n testic ular t o xicit y st u dies { U. S. De part me nt of Healt h a n d 
H u ma n Ser vices ( D H H S) 2 0 1 8 } . Ass u mi n g a 2 0 % rate of n o n-e val ua ble s u bjects at Wee k 1 3, u p 
t o 2 5 0 s u bjects ma y be e nr olle d t o o btai n 2 0 0 e val ua ble s u bjects.


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2.
T Y P E O F  P L A N N E D A N A L Y SI S
2. 1.  
D at a M o nit ori n g C o m mittee A n al yses
A n e xter nal D M C re vi e w s t he pr o gress of t he st u d y, perf or ms u n bli n de d i nteri m re vie ws of 
safety data, a n d pr o vi de s a 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 earl y ter mi nati o n of t he 
st u d y i n t he best i nterests of t he partici pa nts, w het her t he st u dy s h o ul d c o nti n ue as pla n ne d, or 
the st u d y  s h o ul d c o nti n ue wit h m o dificati o ns. T he i nitial u n bli n de d data re vie w meeti n g
occ urre d after a p pr o xi matel y t he first 5 0 s u bjects c o m plete d t he Wee k 1 3 visit. F oll o wi n g t his, 
s u bse q ue nt u n bli n de d data re vie w meeti n gs were t o occ ur a p pr o xi matel y e ver y 4 m o nt hs 
(if e nr oll me nt s u p p orts t he nee d). P o ole d s per m/se me n data fr o m S t u dies G S- U S- 4 1 8- 4 2 7 9
[ M A N T A] a n d G L P G 0 6 3 4- C L - 2 2 7 [ M A N T A-R A y ] were re vie we d after a p pr o xi matel y 
1 0 0 s u bjects c o m plete Wee k 1 3. 
T he D M C ma y  a d diti o nall y re q uest t o re vie w bli n de d s per m/se me n data pri or t o t he first 
u n bli n de d D M C meeti n g a n d/ or i n bet wee n u n bli n de d re vie w meeti n gs. A d -h oc D M C meet i n gs 
ma y  be sc he d ule d as nee de d. A d-h oc D M C meeti n gs ma y  be tri g gere d f or reas o ns o utline d i n t he 
D M C C harter a n d/ or pr ot oc ol.
T he D M C’s r ole a n d res p o nsi bilities a n d t he sc o pe of a nal ys is t o be pr o vi de d t o t he D M C are 
pr o vi de d i n a m ut uall y  a gree d u p o n c harter, w hic h defi nes t he D M C me m bers hi p, meeti n g 
l o gistics, a n d meeti n g fre q ue nc y.
W hil e t he D M C will be as ke d t o a d vise Gilea d re gar di n g t he f ut ure c o n d uct of t he st u d y, 
i ncl u di n g p ossi ble earl y 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. 
2. 2. 
I nter n al I n de pe n de nt S afet y Re vie w
A S p o ns or I nter nal U n bli n de d T ea m (IU T) , 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 he S p o ns or I U T will m o nit or bli n de d c u m ulati ve i nter val s per m/se me n data a n d 
ma y be gra nte d access t o u n bli n de d cli nical data at pre-s pecifie d ti me p oi nts t o re vie w 
s per m/se me n data. T his i nter nal re vie w tea m will be s u p p orte d b y a n e xter nal Ur ol o g y e x pert. T o 
miti gate t he ris k of i na d verte ntl y  releasi n g treat me nt assi g n me nt t o sites a n d s u bjects, t he i nter nal 
tea m will kee p u n bli n de d i nf or mati o n c o nfi de ntial an d will n ot c o m m u nicate a n y i nf or mati o n t o 
t he bli n de d st u d y tea m, site staff or s u bjects. T o date, t he S p o ns or I U T has n ot bee n u tilize d t o 
re vie w u n bli n de d se me n data at pre -s pecifie d ti me p oi nts t o m o nit or safet y ( D M C has perf or me d 
t his d ut y). If the S p o ns or I U T is utilize d t o re vie w u n bli n de d data f or t he p ur p oses of m o nit ori n g 
safety pri or t o u n bli n di n g of t he st u d y, t he c o m mittee’s s pecific acti vities will be defi ne d b y a 
m ut uall y  a gree d u p o n c harter, w hic h will defi ne t he c o m mittee me m bers hi p, c o n duct, a n d 
meeti n g sc he d ule. Data u n bli n di n g d ue t o me dical e mer ge nc y  will f oll o w sta n dar d Gilea d 
pr oce d ures.


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2. 3.
Wee k 2 6
A n al ysis
T he u n bli n de d Wee k 2 6 a nal ys is of St u d y  G S-U S - 4 1 8- 4 2 7 9 will be perf or me d after at least 
2 0 0 e val ua ble s u bjects p o ole d acr oss st u die s G S-U S - 4 1 8-4 2 7 9 [ M A N T A] a n d 
G L P G 0 6 3 4 -C L -2 2 7 [ M A N T A -R A y ] c o m plete Wee k 1 3 a n d e val ua ble s u bjects fr o m St u d y  
G S -U S -4 1 8- 4 2 7 9 c o m plete Wee k 2 6 or per ma ne ntl y  disc o nti n ue fr o m st u d y dr u g. T his a nal ys is 
will be c o n d ucte d i n or der t o f ulfill e x -U S re g ulat or y  c o mmit me nts.
A Data I nte grit y  a n d C o m m u nicati o n Pla n will be de vel o pe d pri or t o u n bli n di n g f or a n y i nteri m 
a nal ys is. T he G S -U S -4 1 8 - 4 2 7 9 st u d y tea m will re mai n bli n de d t o d o u ble -bli n d treat me nt 
assi g n me nts ( w here p ossi ble b y st u d y desi g n) u ntil t he fi nal a nal ys is w he n t he data base has bee n 
l oc ke d, a n d t he st u dy has bee n c o m pletel y u n bli n de d.
2. 4.
Wee k 2 6 a n d Re versi bilit y A n al ysis
f or Pre-s pecifie d S per m Decre ases U p t o 
Wee k 2 6
A se parate u n bli n de d Wee k 2 6 a nal ys is of St u d y GS- U S - 4 1 8- 4 2 7 9 will be perf or me d after all 
s u bjects reac h Wee k 2 6 a n d all s u bjects wit h a ≥ 5 0 % decli ne i n s per m c o nce ntrati o n a n d/ or 
m otilit y  a n d/ or m or p h ol o g y u p t o Wee k 2 6 ( or O pe n-La bel Wee k 1 3) e nter t he m o nit ori n g p hase 
a n d eit her meet re versi bilit y  criteria or are f oll o we d off-treat me nt f or 5 2 wee ks, w hic he ver 
occ urs s o o ner. T his a nal ysis will be c o n d ucte d at t he re q uest of t he U S F o o d a n d Dr u g 
A d mi nistrati o n.
T he Data I nte grity a n d C o m m u nicati o n Pla n will c o nti n ue t o be i n place, a n d t he 
G S- U S - 4 1 8- 4 2 7 9 st u d y tea m will re mai n bli n de d t o d o u ble-bli n d treat me nt assi g n me nts ( w here 
p ossi ble b y  st u d y desi g n) u ntil t he fi nal a nal y sis w he n t he data base has bee n l oc ke d a n d t he 
st u d y has bee n c o m pletel y u n bli n de d.
2. 5.
Fi n al A n al ysis
After all s u bjects ha ve c o m plete d t he st u d y (e g, co m plete d Wee k 1 9 5 a n d di d n ot meet 
pre -s pecifie d s per m decrease t hres h ol ds [a ≥5 0 % decrease i n s per m c o nce ntrati o n a n d/ or 
m otilit y  a n d/ or m or p h ol o g y]; met pre -s pecifie d s per m decrease t hres h ol d criteria a n d eit her met 
re versi bilit y criteria or c o m plete d 5 2 wee ks of off -st u d y dr u g f oll o w-u p f or re versi bilit y ; or 
pre mat urel y disc o nti n ue d fr o m st u d y) o utsta n di n g data q ueries ha ve bee n res ol ve d or a dj u dicate d 
as u nres ol va ble , a n d t he data ha ve bee n clea ne d a n d fi nalize d , the st u d y bli n d will be br o ke n a n d 
t he fi nal a nalys is of t he data will be perf or me d.


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3.
G E N E R A L  C O N SI D E R ATI O N S F O R D A T A  AN A L Y S E S
A nal y sis res ults will be prese nte d usi n g descri pti ve statistics. F or cate g orical varia bles, t he 
n u m ber a n d perce nta ge of s u bjects i n eac h cate g or y will be prese nte d; f or c o nti n u o us varia bles, 
t he n u m ber of s u bjects ( n), mea n, sta n dar d de viati o n (S D ) or sta n dar d err or (S E ), me dia n, first 
q uartile (Q 1 ), t hir d q uartile (Q 3 ), mi ni m u m, a n d ma xi m u m will be prese nte d.
All statistical tests will be 2 -si de d a n d perf or me d at t he 5 % si g nifica nce le vel u nless ot her wise 
s pecifie d.
B y -s u bject listi n gs will be prese nte d f or all s u bjects i n t he All Ra n d o mize d A nal y sis Set a n d b e
s orte d b y s u bject I D n u m ber, visit date, a n d ti me (if a p plica ble). Data c ollecte d o n l o g f orms, 
s uc h as A Es, will be prese nte d i n c hr o n ol o gical or der wit hi n t he s u bject. T he treat me nt gr o u p t o 
w hic h s u bje cts were ra n d o mize d or t he treat me nt se q ue nce recei ve d will be prese nte d i n t he 
listi n gs. A ge, se x, race, et h nicit y, start a n d e n d date of t he do u ble -bli n d st u d y  dr u g a n d 
o pe n -la bel st u dy dr u g (if a p plica ble) w ill be i ncl u de d i n t he listi n gs, as s pace per mits. A 
b y -s u bject listi n g will be pr o vi de d f or s u bjects wit h a n y visits or assess me nts i m pacte d b y 
C or o na vir us Disease 2 0 1 9 ( C O VI D -1 9).
3. 1.
A n al ysis Sets
A nal y sis sets defi ne t he s u bjects t o be i ncl u de d i n a n anal ys is. A nal ys is sets a n d t heir defi niti o ns 
are pr o vi de d i n t his secti o n. T he a nal ys is set will be i de ntifie d a n d i ncl u de d as a s u btitle of eac h 
ta ble, fi g ure, a n d listi n g.
F or eac h a nal ys is set, the n u m ber a n d perce nta ge of s u bjects eli gi ble f or i ncl usi o n will be 
s u m marize d b y  treat me nt gr o u p.
A listi n g of reas o ns f or e xcl usi o n fr o m a nal y sis sets will be pr o vi de d b y s u bject.
3. 1. 1.
All R a n d o mize d A n al ysis Set
T he All Ra n d o mize d A nal y sis Set i ncl u des all su bjects w h o w ere ra n d o mize d i n t he st u d y. T his 
is t he pri mar y a nalys is set f or ra n d o mizati o n s u m maries a n d b y -s u bject listi n gs.
3. 1. 2.
Se me n A n al ysis Set s
T he Se me n A nal ys is Set i ncl u des all ra n d o mize d a n d treate d (recei ve d ≥1 d ose of d o u ble -bli n d 
st u d y dr u g) s u bjects w h o ha ve 2 se me n sa m ples t hat are eli gi ble f or mea n calc ulati o n at baseli ne 
a n d at t he Wee k 1 3 a nalysis visit wit h t he date of t he first c hr o n ol o gic se me n sa m ple use d f or 
p ur p oses of assi g ni n g a nal y sis visit wi n do ws . 
A n i n di vi d ual se me n sa m ple is e li gi ble f or mea n calc ulati o n if it met criteria o utli ne d i n t he 
pr ot oc ol wit h res pect t o ejac ulati o n -free ti me a n d da ys bet wee n e val ua ble se me n c ollecti o ns. 
S u bject I D 1 0 6 0 3 -3 5 0 4 3 ha d a t hir d sa m ple c ollecte d 1 7 da y s after t he sec o n d sa m ple at 
Wee k
1 3 w he n it was n ote d t hat his first sa m ple ha d bee n c ollecte d pri or t o t he l o wer b o u n d of 


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 1 4
1 3 Ja n uar y 2 0 2 1
t he Wee k 1 3 a nal ys is visit wi n d o w (first 2 se me n sa m ples were c ollecte d wit hi n 1 4 da y s of eac h 
ot her; t hir d sa m ple wit hi n Wee k 1 3 a nal ys is visit wi n d o w). T his sa m ple will be c o nsi dere d a n 
e xce pti o n a n d will be “eli gi ble f or mea n calc ulati o n”. F o ur a d diti o nal s u bjects ( S u bject 
I Ds 1 4 6 2 0- 3 5 1 0 6, 1 4 9 3 0- 3 5 1 1 5, 1 4 6 2 0- 3 5 1 1 6, 1 4 6 2 0 -3 5 1 1 9) ha d Wee k 1 3 se me n sa m ple 
c ollecti o ns late f or t he Wee k 1 3 a nal ysis visit wi n d o w d ue t o C O VI D -1 9 s helter i n place or ders 
a n d tra vel restricti o ns. T hese sa m ples will be use d f or t he Wee k 1 3 ti me p oi nt as s u bjects ha d 
m ore t ha n 1 3 wee ks of e x p os ure t o d o u ble -bli n d st u d y  dr u g w he n se me n sa m ples were c ollecte d.
T he Wee k 2 6/ L T E Se me n A nal y sis Set i ncl u des all s u bjects w h o t o o k ≥ 1 d ose of st u d y  dr u g a n d 
ha ve 2 e val ua ble sa m ples at baseli ne a n d at ≥ 1 p ost baseli ne meas ure me nt at/after Wee k 2 6 or 
O pe n -La bel Wee k 1 3. T his a nal y sis set will be use d f or a nal ys es of s per m a n d h or m o ne data b y  
treat me nt se q ue nce.
T he pri mar y  a nalys is of se me n data f or t he pri mar y  a n d sec o n dar y e n d p oi nt s at d o u ble-bli n d 
Wee k 1 3 will be base d o n t he Se me n A nal ys is Set a n d s u bjects wit h 2 e val ua ble se me n sa m ples 
w hic h are re q u ire d at eac h se me n sa m ple c ollecti o n ti me p oi nt. A s u p p orti ve a nal ys is 
( Secti o n 6. 4 ) will als o i ncl u de s u bjects i n t he f oll o wi n g a nalys is set:
T he I nte nt-t o-Treat (IT T) Se me n A nal ys is Set i ncl u des all ra n d o mize d s u bjects w h o ha ve 
2 se me n sa m ples t hat are eli gi ble f or mea n calc ulati o n at Baseli ne.
Si nce all s u bjects w h o were ra n d o mize d t o o k at least 1 d ose of st u d y  dr u g a n d als o ha d 
2 e val ua ble se me n sa m ples at baseli ne, t he I nte nt-t o-Treat Se me n A nal ys is Set will i ncl u de t he 
sa me s u bjects as t he Safet y A nal ys is Set.
3. 1. 3. 
S afet y A n al ysis Sets
T he S afet y A nal y sis S et i ncl u des all ra n d o mize d s u bjects w h o t o o k ≥1 d ose of d o u ble -bli n d 
st u d y dr u g. T his is t he a nal y sis set utilize d f or safet y a nal yses d uri n g t he d o u ble -bli n d p hase of 
t he st u d y.
T he O pe n -La bel Safet y A nal y sis Set i ncl u des all ra n d o mize d s u bjects w h o t o o k ≥ 1 d ose of 
o pe n -la bel fil g oti ni b st u d y dr u g i n t he O pe n- La bel P hase of t he st u dy. T his a nal ys is set will be 
use d f or selecte d safety dis pla y s d uri n g o pe n -la bel fil g oti ni b treat me nt (e g, brief s u m mar y  of 
A Es, i nterr u pti o n of o pe n -la bel fil g oti ni b, disc o nti n uati o n of o pe n -la bel fil g oti ni b).
T he As - Treate d Safety A nal ysis Set i ncl u des all s u bjects i n t he Safety A nal ysis Set ; s u bjects 
i nitiall y ra n d o mize d t o place b o w h o s witc he d t o o pe n-la bel fil g oti ni b wi ll als o be i ncl u de d f or 
t he fil g oti ni b gr o u p. T his a nal ys is set will be utilize d t o s u m marize all a vaila ble o n- treat me nt 
safety data d uri n g t he st u d y .
3. 1. 4. 
P h ar m ac o ki netic A n al ysis Set
T he P har mac o ki netic ( P K ) A nal ys is S et i ncl u des all s u bjects w h o t o o k ≥ 1 d os e of fil g oti ni b 
( d o u ble-bli n d or o pe n -la bel st u d y dr u g) w h o ha ve at least 1 n o n missi n g p ost d ose c o nce ntrati o n 
val ue f or fil g oti ni b a n d/or its meta b olite G S - 8 2 9 8 4 5. T his is t he pri mar y a nal ysis set f or all P K 
a nal ys es.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 1 5
1 3 Ja n uar y 2 0 2 1
3. 2.
S u bject Gr o u p i n g
F or a nal y ses base d o n t he All Ra n d o mize d a n d IT T Se me n A nal ys is Sets, s u bjects will be 
gr o u pe d acc or di n g t o t heir ra n d o mize d treat me nt. F or all ot her a nal ys is sets, s u bjects will be 
gr o u pe d acc or di n g t o t he act ual treat me nt recei ve d. T he act ual treat me nt r ecei ve d will differ 
fr o m t he ra n d o mize d treat me nt o nl y w he n t he act ual treat me nt differs fr o m ra n d o mize d 
treat me nt f or t he e ntire treat me nt d urati o n of t he st u d y  dr u g a d mi nistrati o n peri o d.
T he f oll o wi n g s u bject gr o u pi n gs will be a p plie d t o t he se me n a n d h or m o ne data acc or di n g t o t he 
act ual treat me nt recei ve d :

F or t he d o u ble-bli n d treat me nt peri o d , data fr o m s u bjects w h o t o o k d o u ble-bli n d treat me nt 
will be s u m marize d b y  treat me nt gr o u p (ie, fil g oti ni b 2 0 0 m g a n d place b o).

Se me n a n d h or m o ne data c ollect e d after Wee k 1 3 will be s u m marize d b y  treat me nt se q ue nce 
(ie, d o u ble -bli n d fil g oti ni b, d o u ble - bli n d fil g oti ni b t o o pe n-la bel fil g oti ni b, d o u ble-bli n d 
place b o , a n d d o u ble -bli n d place b o t o o pe n -la bel fil g oti ni b) f or s u bjects wit h baseli ne a n d 
≥1 visit at/a fter Wee k 2 6. A nal y sis visit wi n d o ws f or t he d o u ble-bli n d place b o t o o pe n -la bel 
fil g oti ni b gr o u p will be wi n d o we d fr o m t he first d ose date of o pe n-la bel fil g oti ni b a n d will be 
1 3- wee ks pri or t o t h ose w h o re mai ne d o n ori gi nal treat me nt . All ot her treat me nt se q ue nces 
will ha ve a nal ys is visit wi n d o ws assi g ne d base d o n da ys fr o m first d ose of d o u ble-bli n d 
st u d y dr u g.

S u bjects wit h a decrease of ≥ 5 0 % i n s per m c o nce ntrati o n a n d/ or m otilit y  a n d/ or m or p h ol o g y 
fr o m baseli ne will ha ve st u d y  dr u g st o p pe d a n d a n i n ves ti gat or selecte d sta n dar d of care 
treat me nt t hat is i n acc or da nce wit h t he pr ot oc ol starte d . Se me n sa m ples will be c ollecte d off
st u d y dr u g treat me nt e ver y 1 3 wee ks d uri n g t he M o nit ori n g P hase u ntil re versi bilit y  is met or 
f or u p t o 5 2 wee ks , w hic he ver occ urs first . Re versi bilit y is met w he n all s per m para meter(s) 
q ualif y i n g t he s u bject t o e nter t he M o nit ori n g P hase ret ur n t o greater t ha n 5 0 % of t he 
baseli ne val ue (ie , greater t ha n 0. 5 x [ mea n of 2 e val ua ble sa m ples c ollecte d at t he scree ni n g 
visit]). Data will be s u m marize d f or eac h s per m para meter meeti n g a pre -s pecifie d s per m 
decrease t hres h ol d at t he visit w he n st u d y  dr u g was st o p pe d. The n u m ber ( perce nt) w h o met 
re versi bilit y criteria a n d t he c u m u lati ve n u m ber ( perce nt) w h o met re versi bilit y criteria at
eac h M o nit ori n g P hase visit will be prese nte d se parately f or s u bjects w h o met pre -s pecifie d 
s per m decreases at Wee k 1 3
(s u m marize d b y d o u ble- bli n d treat me nt gr o u p) a n d f or s u bjects
meeti n g pre -s pecifie d s per m para meter decrease t hres h ol ds at t he Wee k 2 6/ O L  Wee k 1 3 
a nal ys is visit or at/after Wee k 3 9/ O L Wee k 2 6 a n d u p t o last d ose date of a n y st u d y 
dr u g + 7 d a y s (s u m marize d b y treat me nt se q ue nce).


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 1 6
1 3 Ja n uar y 2 0 2 1
T he f oll o wi n g s u bject gr o u pi n gs will be a p plie d t o safet y data acc or di n g t o t he act ual treat me nt 
recei ve d (fil g oti ni b or place b o) u nless ot her wise state d :

A n “as -treate d” a nalys is will be perf or me d f or safet y data. Su bjects w h o t o o k d o u ble -bli n d
place b o a n d s witc h e d t o o pe n -la bel fil g oti ni b will ha ve data re p orte d d uri n g t he place b o 
peri o d s u m marize d wit h t he place b o gr o u p, a n d data re p orte d d uri n g t he o pe n -la bel fil g oti ni b 
peri o d s u m marize d wit h t he fil g oti ni b gr o u p ( baseli ne will be o pe n-la bel baseli ne). S u bjects 
w h o s witc h fr o m d o u ble - bli n d fil g oti ni b t o o pe n-la bel fil g oti ni b a n d s u bjects w h o sta y o n 
d o u ble -bli n d st u d y  dr u g f or t he d urati o n of st u dy will be s u m marize d b y  t heir d o u ble-bli n d 
treat me nt gr o u p ( baseli ne will be d o u ble-bli n d baseli ne) .
A d verse e ve nts will a d diti o nall y  be dis pla ye d f or t he d o u ble-bli n d treat me nt p hase (t o ali g n 
wit h t he peri o d s u m ma rize d f or t he pri mar y a nalysis of se me n data) . Data will be 
s u m marize d b y d o u ble-bli n d treat me nt gr o u p (ie, fil g oti ni b 2 0 0 m g or place b o) fr o m first 
d ose date of d o u ble -bli n d st u d y  dr u g u p t o t he first d ose date of o pe n-la bel fil g oti ni b 
( mi n us 1 da y  f or A Es) f or s u bjects w h o s witc h t o o pe n-la bel fil g oti ni b; t o last d ose date of 
d o u ble -bli n d st u d y  dr u g + 3 0 da ys f or s u bjects w h o st o p d o u ble-bli n d st u d y  dr u g a n d d o n ot 
s witc h t o o pe n-la bel fil g oti ni b; or all a vaila ble data at ti me of i nteri m a nal ysis (f or s u bjects 
o n g oi n g o n d o u ble -bli n d treat me nt at t he ti me of a n i nteri m a nal y sis).  
Select A E s u m maries (e g, b rief s u m mar y of A Es w hile o n o pe n-la bel fil g oti ni b, A Es lea di n g 
t o i nterr u pti o n of o pe n-la bel fil g oti ni b, a n d A Es lea di n g t o disc o nti n uati o n of o pe n -la bel 
fil g oti ni b) will be dis pla ye d f or s u bjects i n t he O pe n -La bel Fil g oti ni b Safet y A nal ysis Set . 
A Es occ urri n g fr o m first t o last d ose date of o pe n -la bel fil g oti ni b pl us 3 0 da ys (f or t h ose 
per ma ne ntl y disc o nti n ue d fr o m dr u g) or all e ve nts o n/af ter o pe n-la bel first d ose date f or 
t h ose o n g oi n g o n o pe n-la bel fil g oti ni b will be i ncl u de d.
3. 3.
Str at a a n d C o v ari ates
S u bjects ra n d o mize d u n der P r ot oc ol A me n d me nt 3 w ere ra n d o mly assi g ne d t o treat me nt gr o u ps
via t he i nteracti ve we b res p o nse s yste m (I WR S ) i n a 1: 1 rati o usi n g a stratifie d ra n d o mizati o n 
sc he d ule. S tratificati o n was base d o n t he f oll o wi n g varia ble s:

T y pe of I B D dis or der ( U C , C D)

C o nc urre nt use of M T X ( Yes , N o)

S per m c o nce ntrati o n ( mea n of 2 e val ua ble se me n sa m ples) meas ure d at t he Scree ni n g visit :
1) 1 5 t o 2 5
M / m L; 2) > 2 5 t o 5 0 M / m L; 3) > 5 0 M / m L
S u bjects ra n d o miz e d u n der t he ori gi nal pr ot oc ol or u n der P r ot oc ol A me n d me nt 1 were 
ra n d o mize d base d o n a stratificati o n fact or of c o nc urre nt use of M T X ( yes, n o). T hese s u bjects
will be assi g ne d t o diseas e t ype of U C a n d t he res pecti ve s per m c o nce ntrati o n strat u m base d o n 
t he mea n of 2 e val ua ble s per m c o nce ntrati o n meas ure me nt s c ollecte d at t he scree ni n g visit , 
res pecti vely.
If t here are discre pa ncies i n stratificati o n fact or val ues bet wee n t he I WR S a n d t he cli nical 
data base, t he val ues rec or de d i n t he cli nical data base will be use d f or a nal ysis.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 1 7
1 3 Ja n uar y 2 0 2 1
3. 4.
E x a mi n ati o n of S u bject S u b gr o u ps
S u b gr o u p a nal ys es f or t he pri mar y  e n d p oi nt are s pecifie d i n Secti o n 6. 3.
3. 5.
Missi n g D at a a n d O utliers
3. 5. 1.  
Missi n g D at a
I n ge neral, mis si n g data will n ot be i m p ute d u nless met h o ds f or ha n dli n g missi n g data are 
s pecifie d. E xce pti o ns are prese nte d i n t his d oc u me nt.
F or missi n g last d osi n g date of st u d y  dr u g, i m p utati o n r ules are descri be d i n Secti o n 4. 2. 1 . T he 
ha n dli n g of missi n g or i nc o m plete dates f or A E o nset is descri be d i n Secti o n 8. 1. 5. 2 , a n d f or
pri or a n d c o nc o mita nt me dicati o n s i n Secti o n 8. 4 .
3. 5. 2.  
O utliers
O utliers will be i de ntifie d d uri n g t he data ma na ge me nt a n d data a n al y sis pr ocess . All data, 
i ncl u di n g o utliers, will be i ncl u de d i n data a nal ys es.
3. 6.  
D at a H a n dli n g C o n ve nti o ns a n d Tr a nsf or m ati o ns
I n ge neral, a ge (i n years) o n t he date of t he first d ose of a n y st u d y dr u g will be use d f or a nalys es 
a n d prese ntati o n i n listi n gs. If a ra n d o mize d s u bject was n ot d ose d wit h a n y st u d y dr u g, t he 
ra n d o mizati o n date will be use d i nstea d of t he first d osi n g date of st u d y dr u g f or a ge calc ulati o n. 
F or scree n fail ures, t he date t he i nf or me d c o nse nt was si g ne d will be use d f or a ge calc ulati o n. If 
o nl y  t he birt h y ear is c ollecte d o n t he C R F, “ 0 1 J ul y” will be use d f or t he u n k n o w n birt h da y  a n d 
m o nt h f or t he p ur p ose of a ge calc ulati o n . If o nly birt h y ear a n d m o nt h are c ollecte d, “ 1 5 ” will be 
use d f or t he u n k n o w n birt h da y .
N o n -P K d ata t hat are c o nti n u o us i n nat ure b ut are less t ha n t he l o wer li mit of q ua ntitati o n ( L O Q)
or a b o ve t he u p per L O Q will be i m p ute d as f oll o ws:

A val ue t hat is 1 u nit less t ha n t he L O Q will be use d t o calc ulate descri pti ve statistics if t he 
dat u m is re p orte d i n t he f or m of “x” ( w here x is c o nsi dere d t he L O Q ). F or e xa m ple, if t he 
val ues are re p orte d as < 5 0 a n d < 5. 0, val ues of 4 9 a n d 4. 9 , res pecti vely, will be use d t o 
calc ulate s u m mar y statistics. A n e xce pti o n t o t his r ule is a ny val ue re p orte d as < 1 or < 0. 1, 
etc. F or val ues re p orte d as < 1 or < 0. 1, a val ue of 0. 9 or 0. 0 9 , res pecti vel y, will be use d t o 
calc ulate s u m mar y statistics.

A val ue t hat is 1 u nit a b o ve t he L O Q will be use d t o calc ulate descri pti ve statistics if t he 
dat u m is re p orte d i n t he f or m of “ > x” ( w here x is c o nsi dere d t he L O Q ). Val ues wit h deci mal 
p oi nts will f oll o w t he sa me l o gic as a b o ve.

T he L O Q will be use d t o calc ulate descri pti ve statistics if t he dat u m is re p orte d i n t he f or m of 
“≤ x” or “ ≥ x” ( w here x is c o nsi dere d t he L O Q ).
Plas ma c o nce ntrati o n val ues t hat are bel o w t he li mit of q ua ntitati o n ( B L Q) will be prese nte d as 
“ B L Q” i n t he c o nce ntrati o n data listi n g.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 1 8
1 3 Ja n uar y 2 0 2 1
3. 7.
A n al ysis Visit Wi n d o ws
3. 7. 1.
Defi niti o n of St u d y D a y
T he First D osi n g Date of Fil g oti ni b/ P lace b o is defi ne d as t he date w he n s u bjects ta ke t heir
first d ose of fi l goti ni b/ place b o, eit her d o u ble -bli n d or o pe n -la bel dr u g, w hic he ver is t he earliest
as rec or de d i n t he St u d y Dr u g A d mi nistrati o n e C R F.
T he Last D osi n g Date of Fil g oti ni b/ P lace b o is defi ne d as t he date w he n s u bjects ta ke t he last 
d ose of fil g oti ni b/ place b o, eit her d o u ble-bli n d or o pe n -la bel dr u g, w hic he ver is later as rec or de d 
i n t he St u d y Dr u g A d mi nistrati o n e C R F.
St u d y  D a y will be calc ulate d fr o m t he first d osi n g date of d o u ble -bli n d fil g oti ni b/ place b o a n d 
deri ve d as f oll o ws:

F or p ost d ose st u d y da ys : Assess me nt Date – O n -Fil g oti ni b/ Place b o St u d y  D a y 1 + 1

F or da y s pri or t o t he first d ose: Assess me nt Date – O pe n- Fil g oti ni b/ Place b o St u d y  D a y 1
F or s u bjects w h o are o n place b o a n d s witc h t o o pe n-la bel fil g oti ni b, t he O n-Fil g oti ni b St u d y  
D a y 1 is defi ne d as t he first d ose date of o pe n -la bel fil g oti ni b. 
F oll o w -u p ( F U) Da y f or s u bjects w h o disc o nti n ue st u d y  dr u g a n d/ or e nter t he M o nit ori n g P hase 
will be calc ulate d fr o m t he last d osi n g date of a n y st u d y dr u g, w hic h is defi ne d as t he date w he n 
a s u bject ta kes t heir last d ose of a n y st u d y dr u g c o nsi deri n g b ot h d o u ble -bli n d a n d o pe n-la bel
dr u gs. T he F U da y  is deri ve d as Assess me nt Date – Last D osi n g Date. T heref ore, F oll o w - u p 
D a y 1 is t he first da y  after per ma ne nt disc o nti n uati o n of all st u d y dr u gs.
Baseli ne is defi ne d as t he last a vaila ble o bser vati o n ta ke n o n or pri or t o t he first d ose date of 
d o u ble -bli n d fil g oti ni b/ place b o st u d y dr u g.
O pe n -la bel Baseli ne is defi ne d as t he last a vaila ble o bser vati o n ta ke n o n or pri or t o t he first 
d osi n g date of o pe n -la bel fil g oti ni b (use d f or safet y  assess me nts f or place b o s u bjects w h o s witc h 
t o o pe n-la bel fil g oti ni b wit h t he e xce pti o n of se me n a n d h or m o ne para meters) . F or se me n 
para meters, incl u di n g s per m c o nce ntrati o n, t otal s per m c o u nt, ejac ulate v ol u me, s per m t otal
m otilit y , a n d s per m m or p h ol o g y, t he baseli ne val ue is t he mea n of 2 e val ua ble sa m ples fr o m t he 
scree ni n g visit . T he baseli ne val ue f or s per m/se me n para meters is use d t o e val uate w het her 
s u bjects ha ve met pre -s pecifie d sper m para meter decrease t hres h ol ds (ie, ≥ 5 0 % decrease i n 
s per m c o nce ntrati o n a n d/ or m otilit y a n d/ or m or p h ol o g y). F or h or m o ne para meters, t he baseli ne 
val ue will be t he last val ue o n / pri or t o starti n g d o u ble-bli n d st u d y  dr u g, t o be c o nsiste nt wit h t he 
r ules t hat are use d f or s per m/se me n data.
3. 7. 2.
A n al ysis Visit Wi n d o ws
S u bject visits mi g ht n ot occ ur o n pr ot oc ol -s pecifie d da ys. T heref ore, f or t he p ur p oses of a nal y sis, 
o bser vati o ns will be assi g ne d t o a nal ys is visit wi n d o ws.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 1 9
1 3 Ja n uar y 2 0 2 1
T he a nal ys is visit wi n d o ws f or li pi d pr ofile, ser um i m m u n o gl o b uli n a n d uri nal y sis are pr o vi de d 
i n Ta ble 3- 1 . T he a nal ys is visit wi n d o ws f or p M C S, C D AI , vital si g ns, wei g ht, he mat ol o g y  a n d 
c he mistr y la b orat ories are pr o vi de d i n
Ta ble 3- 2 . T he a nalys is visit wi n d o ws f or LH, F S H, i n hi bi n B, a n d total test oster o ne are 
pr o vi de d i n Ta ble 3- 3 . T he a nalys is wi n d o ws f or “ o n-treat me nt” a n d “re versi bilit y” se me n 
para meters are pr o vi de d i n Ta ble 3- 4 a n d Ta ble 3- 5 , res pecti vely.
Visit Wi n d o w R ules f or “ As Ra n d o mize d” (e g, w hile o n d o u ble-bli n d treat me n t) Dis pla y s
S per m /se me n a n d h or m o ne data will ha ve visit wi n d o ws assi g ne d base d o n st u d y  da y calc ulate d 
fr o m first d ose date of d o u ble-bli n d st u d y  dr u g.
Visit Wi n d o w R ules f or “ As -Treate d” Safet y Dis pla y s
F or s u bjects w h o t o o k d o u ble -bli n d place b o a n d s witc he d t o o pe n -la bel fil g oti ni b, t he date of 
first d o u ble-bli n d st u d y  dr u g will be use d t o calc ulate st u d y d a ys f or visit wi n d o ws f or t he 
place b o peri o d (s u m marize d wit h place b o treat me nt gr o u p) w hile t he first o pe n -la bel fil g oti ni b 
d ose date will be use d t o calc ulate st u d y  da ys f or visit wi n d o w assi g n me nts f or t he fil g oti ni b 
peri o d (s u m marize d wit h fil g oti ni b treat me nt gr o u p). S u bjects w h o t o o k d o u ble -bli n d fil g oti ni b 
a n d s witc he d t o o pe n -la bel fil g oti ni b a n d s u bjects w h o re mai ne d o n d o u ble -bli n d st u d y  dr u g 
t hr o u g h o ut t he st u dy will ha ve st u d y da ys  calc ulate d relati ve t o t he first d ose date of 
d o u ble -bli n d st u d y  dr u g f or “as-treate d” visit wi n d o w assi g n me nt s.
Visit Wi n d o w R ules f or “ O pe n -La bel Fil g oti ni b” Safet y  Dis pla y s
O pe n -la bel fil g oti ni b a nal ysis visit wi n d o ws assi g ne d base d o n t he st u d y da y calc ulate d fr o m 
first d ose date of o pe n-la bel fil g oti ni b st u d y dr u g.
Visit Wi n d o w R ules f or “ Wee k 2 6/ L T E” Dis pla ys
F or s u bjects w h o t o o k d o u ble- bli n d place b o a n d s witc he d t o o pe n-la bel fil g oti ni b, t he date of t he 
first o pe n-la bel fil g oti ni b d ose date will be use d t o calc ulate st u dy da ys  f or o pe n-la bel a nalys is 
visit wi n d o ws. S u bjects w h o s witc h fr o m d o u ble -bli n d t o o pe n -la bel fil g oti ni b a n d t h ose w h o 
re mai n o n d o uble -bli n d st u d y  dr u g will ha ve a nalysis visit wi n d o ws assi g ne d base d o n t he st u d y 
da y  calc ulate d fr o m first d ose date of d o u ble-bli n d st u d y  dr u g.
Visit Wi n d o w R ules f or S per m/ Se me n Para meters D uri n g t he M o nit ori n g P hase
S per m/se me n data c ollecte d d uri n g t h e M o nit ori n g P hase t o assess re versi bilit y of s per m 
para meters wit h a ≥5 0 % decrease fr o m baseli ne will ha ve t he last d ose date of a n y st u d y dr u g 
use d t o calc ulate st u d y da ys f or M o nit ori n g P hase visit wi n d o ws.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 2 0
1 3 Ja n uar y 2 0 2 1
T a ble 3- 1.  
A n al ysis Visit Wi n d o ws f or Li pi d Pr ofile , Ser u m I m m u n o gl o b uli n ,
a n d Uri n al ysis
A n al ysis Visit
N o m i n al D a y
( St u d y D a y)
L o wer Li mit
( St u d y D a y)
U p per Li mit
( St u d y D a y)
Baseli ne
1
N o ne
1
Wee k 1 3
9 2
2
1 3 7
Wee k 2 6
1 8 3
1 3 8
2 2 8
Wee k 3 9
2 7 4
2 2 9
3 1 9
Wee k 5 2
3 6 5
3 2 0
4 1 0
Wee k 6 5
4 5 6
4 1 1
5 0 1
Wee k 7 8
5 4 7
5 0 2
5 9 2
Wee k 9 1
6 3 8
5 9 3
6 8 3
Wee k 1 0 4
7 2 9
6 8 4
7 7 4
Wee k 1 1 7
8 2 0
7 7 5
8 6 5
Wee k 1 3 0
9 1 1
8 6 6
9 5 6
Wee k 1 4 3
1 0 0 2
9 5 7
1 0 4 7
Wee k 1 5 6
1 0 9 3
1 0 4 8
1 1 3 8
Wee k 1 6 9
1 1 8 4
1 1 3 9
1 2 2 9
Wee k 1 8 2
1 2 7 5
1 2 3 0
1 3 2 0
Wee k 1 9 5
1 3 6 6
1 3 2 1
1 4 1 1
Wee k 2 0 8
1 4 5 7
1 4 1 2
1 5 0 2
Wee k 2 2 1
1 5 4 8
1 5 0 3
≥1 5 4 8


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 2 1
1 3 Ja n uar y 2 0 2 1
T a ble 3- 2.  
A n al ysis Visit Wi n d o ws f or P arti al M C S, C D AI, Vit al Si g ns, Wei g ht, 
He m at ol o g y , a n d C he mistr y L a b or at ories 
A n al ysis 
Visit
N o m i n al D a y
( St u d y D a y)
L o wer Li mit
( St u d y D a y)
U p per Li mit
( St u d y D a y)
Baseli ne
1
N o ne
1
Wee k 2
1 5
2
2 2
Wee k 4
2 9
2 3
4 3
Wee k 8
5 7
4 4
7 4
Wee k 1 3
9 2
7 5
1 1 6
Wee k 2 0
1 4 1
1 1 7
1 6 2
Wee k 2 6
1 8 3
1 6 3
2 2 8
Wee k 3 9
2 7 4
2 2 9
3 1 9
Wee k 5 2
3 6 5
3 2 0
4 1 0
Wee k 6 5
4 5 6
4 1 1
5 0 1
Wee k 7 8
5 4 7
5 0 2
5 9 2
Wee k 9 1
6 3 8
5 9 3
6 8 3
Wee k 1 0 4
7 2 9
6 8 4
7 7 4
Wee k 1 1 7
8 2 0
7 7 5
8 6 5
Wee k 1 3 0
9 1 1
8 6 6
9 5 6
Wee k 1 4 3
1 0 0 2
9 5 7
1 0 4 7
Wee k 1 5 6
1 0 9 3
1 0 4 8
1 1 3 8
Wee k 1 6 9
1 1 8 4
1 1 3 9
1 2 2 9
Wee k 1 8 2
1 2 7 5
1 2 3 0
1 3 2 0
Wee k 1 9 5
1 3 6 6
1 3 2 1
1 4 1 1
Wee k 2 0 8
1 4 5 7
1 4 1 2
1 5 0 2
Wee k 2 2 1
1 5 4 8
1 5 0 3
≥1 5 4 8
F U -4 *
Last D ose Date a n y st u d y dr u g 
+ 3 0 da ys
Last D ose Date a n y st u d y 
dr u g + 8 da ys
Last D ose Date a n y st u d y dr u g 
+ 3 5 da ys
N ote: Data will be i ncl u de d f or “ o n -treat me nt” visits u p t o t he last d ose date of a n y st u d y dr u g + 7 da ys.
* F U -4 visit f or s u bjects w h o ha ve st o p pe d all st u d y dr u gs a n d ha d a 3 0 -da y safet y F U visit ± 5 da ys . F U -4 visit wi n d o w is 
a p plica ble f or he mat ol o g y, c he mistr y, vitals , a n d wei g ht. F U - 4 visit will be dis pla ye d i n listi n gs o nl y.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 2 2
1 3 Ja n uar y 2 0 2 1
T a ble 3- 3.  
A n al ysis Visit Wi n d o ws f or L H, F S H, I n hi bi n B, a n d T ot al 
Test oster o ne
A n al ysis 
Visit
N o m i n al D a y
( St u d y D a y)
L o wer Li mit
( St u d y D a y)
U p per Li mit
( St u dy D a y)
Baseli ne
1
N o ne
1
Wee k 4
2 9
2
8 4
Wee k 1 3
9 2
8 5
1 1 2
Wee k 2 6
1 8 3
1 7 0
2 6 0
Wee k 3 9
2 7 4
2 6 1
3 5 1
Wee k 5 2
3 6 5
3 5 2
4 4 2
Wee k 6 5
4 5 6
4 4 3
5 3 3
Wee k 7 8
5 4 7
5 3 4
6 2 4
Wee k 9 1
6 3 8
6 2 5
7 1 5
Wee k 1 0 4
7 2 9
7 1 6
8 0 6
Wee k 1 1 7
8 2 0
8 0 7
8 9 7
Wee k 1 3 0
9 1 1
8 9 8
9 8 8
Wee k 1 4 3
1 0 0 2
9 8 9
1 0 7 9
Wee k 1 5 6
1 0 9 3
1 0 8 0
1 1 7 0
Wee k 1 6 9
1 1 8 4
1 1 7 1
1 2 6 1
Wee k 1 8 2
1 2 7 5
1 2 6 2
1 3 5 2
Wee k 1 9 5
1 3 6 6
1 3 5 3
1 4 4 3
Wee k 2 0 8
1 4 5 7
1 4 4 4
1 5 3 4
Wee k 2 2 1
1 5 4 8
1 5 3 5
≥  1 5 4 8
F U -4 *
Last D ose Date a n y st u d y dr u g 
+ 3 0 da ys
Last D ose Date a n y st u d y dr u g 
+ 8 da ys
Last D ose Date a n y st u d y dr u g
+ 3 5 da ys
N ote: Pri mar y a nal ysis i ncl u des data u p t o first d ose date of o pe n -la bel fil g oti ni b (if n o n-missi n g) or t o last d ose date of d o u ble-
bli n d dr u g + 7 da ys (f or t h ose w h o d o n ot s witc h t o o pe n -la bel fil g oti ni b).
Sec o n dar y a nal ysis i ncl u des all “ o n- treat me nt” data u p t o t he last d ose date of a n y st u d y dr u g + 7 da ys.
* F U -4 visit f or s u bjects w h o ha ve st o p pe d all st u d y dr u gs a n d ha d a 3 0 -da y safet y F U visit ± 5 da ys will be dis pla ye d i n listi n gs 
o nl y.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 2 3
1 3 Ja n uar y 2 0 2 1
T a ble 3- 4.  
A n al ysis Visit Wi n d o ws f or O n- Tre at me nt Se me n P ar a meters
A n al ysis Visit
N o m i n al D a y
( St u d y D a y)
L o wer Li mit
( St u d y D a y)
U p per Li mit
( St u d y D a y)
Baseli ne
1
N o ne
1
Wee k 1 3
9 2
8 5
1 1 2
Wee k 2 6
1 8 3
1 7 0
2 6 0
Wee k 3 9
2 7 4
2 6 1
3 5 1
Wee k 5 2
3 6 5
3 5 2
4 4 2
Wee k 6 5
4 5 6
4 4 3
5 3 3
Wee k 7 8
5 4 7
5 3 4
6 2 4
Wee k 9 1
6 3 8
6 2 5
7 1 5
Wee k 1 0 4
7 2 9
7 1 6
8 0 6
Wee k 1 1 7
8 2 0
8 0 7
8 9 7
Wee k 1 3 0
9 1 1
8 9 8
9 8 8
Wee k 1 4 3
1 0 0 2
9 8 9
1 0 7 9
Wee k 1 5 6
1 0 9 3
1 0 8 0
1 1 7 0
Wee k 1 6 9 
1 1 8 4
1 1 7 1
1 2 6 1
Wee k 1 8 2
1 2 7 5
1 2 6 2
1 3 5 2
Wee k 1 9 5
1 3 6 6
1 3 5 3
1 4 4 3
Wee k 2 0 8
1 4 5 7
1 4 4 4
1 5 3 4
Wee k 2 2 1
1 5 4 8
1 5 3 5
≥1 5 4 8
N ote: Pri mar y a nal ysis i ncl u des data u p t o first d ose date of o pe n -la bel fil g oti ni b (if n o n-missi n g) or t o last d ose date of d o u ble-
bli n d dr u g + 7 da ys (f or t h ose w h o d o n ot s witc h t o o pe n-la bel fil g oti ni b).
Sec o n dar y a nal ysis i ncl u des all “ o n- treat me nt” data u p t o t he last d ose date of a n y st u d y dr u g + 7 da ys .
T a ble 3- 5.  
A n al ysis Visit Wi n d o ws f or Se me n P ar a m eters i n M o nit ori n g P h ase 
( C alc ul ate d fr o m L ast D ose D ate of A n y St u d y Dr u g)
A n al ysis Visit
N o m i n al D a y
( F U D a y)
L o wer Li mit
( F U D a y)
U p per Li mit
( F U D a y)
M P Wee k 1 3
9 1
8
1 0 4
M P Wee k 2 6
1 8 2
1 0 5
1 9 5
M P Wee k 3 9
2 7 3
1 9 6
2 8 6
M P Wee k 5 2
3 6 4
2 8 7
3 7 7
M P = M o nit ori n g P hase; F U = F oll o w- U p.
N O T E: All visit wi n d o ws f or m o nit ori n g p hase will be calc ulate d fr o m l ast d ose date of a n y st u d y dr u g.
F U Da y = visit date – last d ose date of a n y st u d y dr u g.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 2 4
1 3 Ja n uar y 2 0 2 1
I n vesti gat or Assess me nt of EC G Visit Assi g n me nt
N o mi nal visits fr o m t he cli nical data base will be use d t o assi g n ti me p oi nts f or t he i n vesti gat or’s
assess me nt of electr ocar di o gra m. Baseli ne will use t he n o mi nal visit “ Scree ni n g”; Wee k 2 6 will 
use n o mi nal visits “ Wee k 2 6” , “ O pe n -La bel Wee k 1 3” , or “ Earl y Ter mi nati o n” if t he ot her visits 
are n ot a vaila ble a n d t he s u bject is n ot e nr olle d i n L T E ; a n d L T E Wee k 1 9 5 or “ Earl y 
Ter mi nati o n ” visit will use n o mi nal visits of “ L T E Wee k 1 9 5” or “ Earl y Ter mi nati o n” if L T E 
Wee k 1 9 5 is n ot a vaila ble a n d s u bject is e nr olle d i n LT E P has e.
3. 7. 3.
Selecti o n of D at a i n t he E ve nt of M ulti ple Rec or ds i n a n A n al ysis Visit 
Wi n d o w
De pe n di n g o n t he statistical a nal ys is met h o d utilize d , si n gle val ues ma y be re q uire d fr o m eac h 
a nal ys is wi n d o w. F or e xa m ple, c ha n ge fr o m baseli ne b y visit us ually re q uires a si n gle val ue, 
w hereas a ti me -t o-e ve nt a nal ys is w o ul d n ot re q uire 1 val ue per a nalys is wi n d o w. 
If m ulti ple vali d, n o n missi n g, c o nti n u o us meas ure me nts e xist i n a n a nal ysis wi n d o w, rec or ds 
will be c h ose n base d o n t he f oll o wi n g r ules if a si n gle val ue is nee de d. 

I n ge neral, t he baseli ne val ue will be t he last n o n missi n g val ue o n or pri or t o t he first d osi n g 
date of st u d y dr u g, u nless s pecifie d differ e ntl y.

If m ulti ple meas ure me nts occ ur o n t he sa me da y, t he last n o n missi n g val ue pri or t o t he ti me 
of first d osi n g of st u d y dr u g will be c o nsi dere d as t he baseli ne val ue. If t hese m ulti ple 
meas ure me nts occ ur at t he sa me ti me or t he ti me is n ot a vaila ble, t he a ver a ge of t hese 
meas ure me nts (f or c o nti n u o us data) will be c o nsi dere d t he baseli ne val ue.

F or p ost baseli ne val ues:

T he rec or d cl osest t o t he n o mi nal da y  f or t hat visit will be selecte d.

If t here are 2 rec or ds t hat are e q ui dista nt fr o m t he n o mi nal da y, t he later rec or d will be 
selecte d.

If t here is m ore t ha n 1 rec or d o n t he selecte d da y, t he a vera ge will be ta ke n, u nless 
ot her wise s pecifie d.
If m ulti ple vali d, n o n missi n g, cate g orical meas ure me nts e xist i n a n a nal ysis wi n d o w, rec or ds 
will be c h ose n base d o n t he f oll o wi n g r ules if a si n gle val ue is nee de d:

F or baseli ne, t he last a vaila ble rec or d o n or pri or t o t he date of t he first d ose of st u d y dr u g 
will be selecte d. If t here are m ulti ple rec or ds wit h t he sa me ti me or n o ti me rec or de d o n t he 
sa me da y, t he val ue wit h t he l o west se verity will be selecte d (e g, n or mal will be selecte d o ver 
a b n or mal f or safet y fi n di n gs).

F or p ost baseli ne visits, if t here are m ulti ple rec or ds wit h t he sa me ti me or n o ti me rec or de d 
o n t he sa me da y , t he val ue wit h t he w orst se verit y wit hin t he wi n d o w will be selecte d 
(e g, a b n or mal will be selecte d o ver n or mal f or safet y  fi n di n gs).


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 2 5
1 3 Ja n uar y 2 0 2 1
F or se me n data, si nce 2 e val ua ble se me n sa m ples are re q uire d at eac h se me n sa m ple c ollecti o n 
ti me p oi nt , t he a vera ge of t he meas ure me nts will be ta ke n a n d t he stu d y  da y ass ociate d wit h t he 
earliest vali d meas ure me nt will be use d f or assi g n me nt of t he visit t o a n a nal ysis visit wi n d o w. 
F or t he se nsiti vit y  a nalys is of s per m c o nce ntrati o n at Wee k 1 3 t hat i ncl u des s u bjects wit h o nl y 
1 e val ua ble meas ure me nt at a c ollecti o n ti me p oi nt, t he date of t he si n gle s a m ple will be use d t o 
calc ulate t he st u d y d a y f or assi g n me nt t o a n a nal ys is visit wi n d o w. If m ulti ple c ollecti o n ti me
p oi nts fall wit hi n a visit wi n d o w , t he a b o ve r ule will be a p plie d.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 2 6
1 3 Ja n uar y 2 0 2 1
4.
S U B J E C T DI S P O SI TI O N
4. 1.
S u bject R a n d o miz ati o n a n d Dis p ositi o n
S u m maries descri be d u n der t his secti o n will be base d o n t he All Ra n d o mize d A nal ysis Set a n d
ra n d o mize d treat me nt gr o u ps.
A s u m mar y  of s u bject ra n d o mizati o n will be pr o vi de d b y ra n d o mize d treat me nt gr o u p a n d 
o verall f or eac h c o u ntr y, a n d i n vesti gat or wit hi n a c o u ntr y. T he s u m mar y will prese nt t he 
n u m ber a n d perce nta ge of s u bjects ra n d o mize d. F or eac h c ol u m n, the de n o mi nat or f or t he 
perce nta ge calc ulati o n will be t he t otal n u m ber of s u bjects ra n d o mize d f or t hat c ol u m n.
A si mila r ra n d o mizati o n ta ble will be pr o vi de d by ra n d o mizati o n strat u m. T he de n o mi nat or f or 
t he perce nta ge of s u bjects i n t he strat u m will be t he t otal n u m ber of ra n d o mize d s u bjects. If t here 
are discre pa ncies i n t he val ue use d f or stratificati o n assi g n me nt bet we e n t he I WR S a n d t he 
cli nical data base, t he val ue c ollecte d i n t he cli nical data base will be use d f or t he s u m mar y . A 
listi n g of s u bjects wit h discre pa ncies i n t he val ue use d f or stratificati o n assi g n me nt bet wee n t he 
I WR S a n d t he cli nical data base at t he ti me of data fi nalizati o n will be pr o vi de d.
T he ra n d o mizati o n sc he d ule use d f or t he st u d y will be pr o vi de d as a n a p pe n di x t o t he C S R.
T he fl o w t hr o u g h t he st u d y  f or a n i n di vi d ual s u bject will be deter mi ne d by t he res p o nse of t he 
u n derl y i n g I B D t o assi g ne d treat me nt a n d b y t he s u bject meeti n g a pre -s pecifie d s per m decrease 
t hres h ol d (e g, a ≥5 0 % decrease i n s per m c o nce ntrati o n a n d/ or m otilit y  a nd/ or m or p h ol o g y  fr o m
baseli ne ). Su bject s meeti n g a pre -s pecifie d s per m decrease t hres h ol d will st o p st u d y  dr u g a n d 
s witc h t o a sta n dar d of care selecte d by t he i n vesti gat or (i n acc or da nce wit h t he pr ot oc ol) a n d 
e nter t he M o nit ori n g P hase of t he st u d y . T he mea n val ue at a st u d y visit f or eac h of t he s per m 
para meters ( meas ure d fr o m 2 se parate e val ua ble se me n c ollecti o n sa m ples) will be use d t o 
deter mi ne w het her a pre -s pecifie d s per m decrease t hres h ol d has bee n met. I n t he s pecial case 
w he re t he 2 se me n c ollecti o ns at a visit are e val ua ble, b ut data f or a n i n di vi d ual s per m para meter
(ie, m otilit y is n ot e val ua ble d ue t o tec h nical pr o ble ms whe n perf or mi n g se me n a nal ys is) is n ot 
e val ua ble a n d c ollecti o n of a t hir d se me n sa m ple at t he visit is n ot p ossi ble , t he 1 e val ua ble val ue 
will be use d t o deter mi ne w het her a pre -s pecifie d s per m decrease t hres h ol d was met f or t hat 
s per m para meter, w hile t he mea n of t he 2 sa m ples will be use d f or s per m para meters wit h 
2 e val ua ble c ollecti o ns.
A s u m mar y  of s u bject dis p ositi o n will be pr o vi de d b y ra n d o mize d treat me nt gr o u p a n d o verall. 
T his s u m mar y  will prese nt t he n u m ber of s u bjects scree ne d (rescree ns c o u nte d o nce), t he n u m ber 
of s u bjects ra n d o mize d, a n d t he n u m ber of s u bjects i n t he safet y a nal ys is set. In a d diti o n, t he 
n u m ber a n d perce nta ge of s u bjects i n eac h cate g or y  bel o w will be s u m marize d:


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 2 7
1 3 Ja n uar y 2 0 2 1
D o u ble -Bli n d St u d y Dr u g C o m pleti o n St at us T hr o u g h Wee k 1 3

C o m plete d bli n de d st u d y dr u g t hr o u g h Wee k 1 3

S witc he d t o M o nit ori n g P hase after Wee k 1 3 (s u bject met pre -s pecifie d s per m decrease 
t hres h ol d[s])

C o nti n ue d d o u ble -bli n d treat me nt after Wee k 1 3 (res p o n der, s u bject di d n ot meet 
pre -s pecifie d s per m decrease t hres h ol d [s])

S witc he d t o O pe n - La bel F il g oti ni b Phase after Wee k 1 3 ( n o n-res p o n der, s u bject di d n ot
meet pre -s pecifie d s per m decrease t hres h ol d [s])

Di d n ot c o m plete bli n de d st u d y  dr u g t hr o u g h Wee k 1 3 wit h reas o ns f or pre mat ure 
disc o nti n uati o n of st u d y  dr u g
D o u ble -Bli n d St u d y Dr u g C o m pleti o n St at us ( > Wee k 1 3 T hr o u g h Wee k 2 6)

C o m plete d bli n de d st u d y dr u g t hr o u g h Wee k 2 6

S witc he d t o M o nit ori n g P hase after Wee k 2 6 (s u bject met pre -s pecifie d s per m decrease 
t hres h ol d[s])

C o nti n ue d bl i n de d st u d y dr u g (res p o n der a n d n o disease w orse ni n g , s u bject di d n ot meet 
pre -s pecifie d s per m decrease t hres h ol d [s])

Disc o nti n ue d st u d y dr u g at Wee k 2 6 ( n o n -res p o n der, s u bject di d n ot meet pre -s pecifie d 
s per m decrease t hres h ol d [s])

Di d n ot c o m plete bli n de d st u d y  dr u g t hr o u g h Wee k 2 6 wit h reas o ns f or pre mat ure 
disc o nti n uati o n of st u d y  dr u g
O pe n -L a bel Fil g oti ni b P h ase St u d y Dr u g C o m pleti o n St at us

C o m plete d o pe n -la bel st u d y dr u g t hr o u g h O pe n - La bel Wee k 1 3

S witc he d t o M o nit ori n g P hase after O pe n - La bel Wee k 1 3 (s u bject met pre -s pecifie d 
s per m decrease t hres h ol d [s])

C o nti n ue d o pe n -la bel fil g oti ni b after O pe n - La bel Wee k 1 3 ( res p o n der a n d n o disease 
w orse ni n g , s u bject di d n ot meet pre -s pecifie d s per m decrease t hres h ol d [s])

Disc o nti n ue d O pe n -La bel Fil g oti ni b P hase at O pe n - La bel Wee k 1 3 ( n o n-res p on d er,
s u bject di d n ot meet pre -s pecifie d s per m decrease t hres h ol d [s])

Di d n ot c o m plete o pe n -la bel st u d y dr u g t hr o u g h O pe n - La bel Wee k 1 3 wit h reas o ns f or 
pre mat ure disc o nti n uati o n of st u d y  dr u g


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 2 8
1 3 Ja n uar y 2 0 2 1
L T E D o u ble -Bli n d St u d y Dr u g C o m pleti o n St at us

C o m plete d L T E D o u ble -Bli n d P hase of s t u d y

O n g oi n g i n L o n g Ter m E xte nsi o n ( L T E) D o u ble -Bli n d P hase of st u d y (f or i nteri m a nal ysis 
o nl y , i ncl u des s u bjects w h o c o m plete d 2 6 wee ks of d o u ble-bli n d st u d y  dr u g a n d are o n g oi n g 
o n d o u ble -bli n d dr u g i n t he e xte nsi o n p hase at t he ti me of i nteri m a nal y sis)

Di d n ot c o m plete L T E D o u ble -Bli n d P hase of s t u d y a n d reas o n f or pre mat ure 
disc o nti n uati o n
L T E O pe n -L a bel Fil g oti ni b St u d y Dr u g C o m pleti o n St at us

C o m plete d L T E o n o pe n -la bel fil g oti ni b 

O n g oi n g i n L T E o pe n -la bel fil g oti ni b phase of st u d y (f or i nteri m a nal ysis o nl y, i ncl u des 
s u bjects w h o c o m plete d O pe n La bel Wee k 1 3 a n d are o n g oi n g o n o pe n-la bel fil g oti ni b i n t he 
e xte nsi o n p hase at t he ti me of i nteri m a nal ys is)

Di d n ot c o m plete L T E o pe n -la bel p has e of st u d y a n d reas o n f or pre mat ure disc o nti n uati o n
M o nit ori n g P h ase C o m pleti o n St at us

C o m plete d M o nit ori n g P hase of st u d y

Met re versi bilit y criteria f or all s per m para meters meeti n g pre-s pecifie d s per m decrease 
t hres h ol d[s]

C o m plete d 5 2 -wee ks of off -treat me nt f oll o w- u p

C o nti n ui n g M o nit ori n g P hase of st u d y (f or i nteri m a nalys is o nly), re prese nts t h ose w h o 
re mai n u n der o bser vati o n i n t he M o nit ori n g P hase
at t he ti me of data c ut off date)

Di d n ot c o m plete M o nit ori n g P hase a n d reas o n f or pre mat ure disc o nti n uati o n
N ote f or pr o gra m mi n g : Reas o ns f or Early Ter mi nati o n fr o m M o nit ori n g P hase a n d C o m pleti o n 
of M o nit ori n g P hase will be p ulle d fr o m t he St u d y C o m pleti o n e C R F.
St u d y C o m pleti o n St at us

C o m plete d st u d y

O n g oi n g i n st u d y (f or i nteri m a nalys is o nl y, i ncl u des s u bjects c urre ntl y  partici pati n g i n t he 
st u d y at t he ti me of a n i nteri m a nalys is)

Di d n ot c o m plete st u d y wit h reas o ns f or pre mat ure disc o nti n uati o n of st u d y


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 2 9
1 3 Ja n uar y 2 0 2 1
F or t he stat us of st u d y dr u g, st u d y c o m pleti o n a n d reas o ns f or pre mat ure disc o nti n uati o n of st u d y 
dr u g or st u d y , t he n u m ber a n d perce nta ge of s u bjects i n eac h cate g or y will be pr o vi de d. T he 
de n o mi nat or f or t he perce nta ge calc ulati o n will be t he t otal n u m ber of s u bjects i n t he Safet y
A nal y sis Set w h o e ntere d i nt o t he st u d y p hase f or t he c ol u m n bein g s u m marize d . 
T he n u m ber of s u bjects scree ne d f or t he st u d y t hat di d n ot meet eli gi bilit y  criteria will be 
s u m marize d o verall a n d b y  i ncl usi o n/e xcl usi o n criteria n ot met ( m ulti ple reas o ns ma y be mar ke d 
f or a n i n di vi d ual scree n). Scree n fail ure reas o ns f or t u berc ul osis a n d f or fail ure t o meet I B D 
criteria (acr oss differe nt versi o ns of t he pr ot oc ol) will be c o u nte d o nce f or t he cate g or y . S u bjects 
w h o were rescree ne d will be s u m marize d b ase d o n t heir last c hr o n ol o gic scree ni n g atte m pt. 
Scree ns t hat di d n ot e x plicitl y  fail ≥1 eli gi bilit y criteria b ut were n ot ra n d o mize d will be 
s u m marize d b y t he reas o n t he s u bject was n ot ra n d o mize d.
T he f oll o wi n g b y- s u bject listi n gs will be pr o vi de d b y s u bject i de ntificati o n (I D) n u m ber i n 
asce n di n g or der t o s u p p ort t he a b o ve s u m mar y  ta bles:

Reas o ns f or pre mat ure st u d y  dr u g or st u d y disc o nti n uati o n

Reas o ns f or scree n fail ure ( will be pr o vi de d b y scree ni n g I D n u m ber i n asce n di n g or der)
Scree n F ail ure f or S per m/ Se me n P ar a meters
T he n u m ber of s u bjects w h o ha d ≥1 s per m/se me n a b n or malit y f or i ncl usi o n criteria (I C)
# 8 base d o n t he mea n of 2 e val ua ble se me n sa m ples at t he scree ni n g visit will be dis pla ye d. 
S u bjects w h o were rescree ne d will be i ncl u de d i n a nal ys is base d o n t heir last c hr o n ol o gic 
scree ni n g atte m pt. I ncl usi o n criteria # 8 was defi ne d as: se me n v ol u me ≥1. 5 m L ; t otal 
s per m/ejac ulate ≥3 9 M/ejac ulate ; s per m c o nce ntrati o n ≥1 5
M / m L; s per m t otal m otilit y ≥4 0 %; 
a n d n or mal s per m m or p h ol o g y  ≥3 0 % [ W H O 1 9 9 2 criteria] f or s u bjects ra n d o mize d u n der
pr ot oc ol A me n d me nt 3 or n or mal s per m m or p h ol o g y  ≥4 % [ W H O 2 0 1 0 criteria] f or s u bjects 
ra n d o mize d u n der t he ori gi nal pr ot oc ol or Pr ot oc ol A me n d me nt 1. S per m m or p h ol o g y  was
assesse d f or i ncl usi o n/e xcl usi o n criteria base d o n t he pr ot oc ol versi o n t he s u bject e nr olle d u n der.
T he n u m ber a n d perce nta ge of s u bjects n ot meeti n g eac h i n di vi d ual s per m/se me n para meter
( de n o mi nat or f or perce nta ge calc ulati o n is n u m ber of s u bjects w h o ha d ≥1 s per m/se me n 
a b n or malit y) will be dis pla y e d. M ulti ple s per m/se me n para mete rs ma y n ot q ualif y f or a gi ve n 
scree ni n g atte m pt.
A listi n g of scree ne d s u bjects wit h 2 e val ua ble se me n sa m ples at t he scree ni n g visit w h o scree n 
faile d f or I C # 8 will be pr o vi de d wit h s per m/se me n para meters n ot meeti n g criteria fla g ge d i n 
t he listi n g.
4. 2.
E xte nt of St u d y D r u g E x p os ure a n d A d here nce
E xte nt of e x p os ure t o st u d y  dr u g will be e xa mi ne d b y assessi n g t he t otal d urati o n of e x p os ure t o 
st u d y dr u g a n d t he le vel of a d here nce t o t he st u d y dr u g s pecifie d i n t he pr ot oc ol.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 3 0
1 3 Ja n uar y 2 0 2 1
4. 2. 1.
D ur ati o n of E x p os ure t o St u d y Dr u g
T otal d urati o n of e x p os ure t o d o u ble -bli n d st u d y dr u g (i n wee ks) will be defi ne d as: ([last d osi n g 
date of d o u ble -bli n d st u d y dr u g mi n us first d osi n g date of d o u ble -bli n d st u d y dr u g pl us 1] 
di vi de d b y  7), re gar dless of a n y te m p orar y i nterr u pti o ns i n st u d y dr u g a d mi nistrati o n. Res ults f or 
all calc ulati o ns of d urati o n will be dis pla y e d t o 1 deci mal place (e g, 4. 5 wee ks) .
T otal d urati o n of e x p os ure t o o pe n -la bel fil g oti nib st u d y  dr u g (i n wee ks) will be defi ne d as: 
([last d osi n g date of o pe n -la bel fil g oti ni b st u d y dr u g mi n us first d osi n g date of o pe n-la bel 
fil g oti ni b st u d y dr u g pl us 1] di vi de d b y 7), re gar dless of a n y te m p orar y i nterr u pti o ns i n st u d y 
dr u g a d mi nistr ati o n. 
T otal d urati o n of e x p os ure t o a n y fil g oti ni b st u d y dr u g (i n wee ks) will be defi ne d as :
([last d osi n g date of a n y fil g oti ni b st u d y dr u g mi n us first d osi n g date of a n y fil g oti ni b st u d y dr u g 
pl us 1] di vi de d b y  7), re gar dless of a ny t e m p orar y i nterr u ptio ns i n st u d y  dr u g a d mi nistrati o n.
F or s u bjects w h o t o o k d o u ble- bli n d place b o a n d t he n s witc he d t o o pe n-la bel fil g oti ni b, t he 
d urati o n of e x p os ure will be calc ulate d fr o m t he first d ose of d o u ble -bli n d place b o t o t he last 
d ose of d o u ble -bli n d place b o f or do u ble -bli n d st u d y  dr u g; a n d fr o m t he first d ose of o pe n -la bel 
fil g oti ni b t o last d ose of o pe n -la bel fil g oti ni b f or o pe n-la bel fil g oti ni b a n d f or a n y fil g oti ni b . 
T he a n y fil g oti ni b e x p os ure (i n wee ks) f or a s u bject w h o s witc he d fr o m d o u ble-bli n d fil g oti ni b
t o o pe n-la bel fil g oti ni b w ill be calc ulate d as: ([last d ose date of o pe n-la bel fil g oti ni b mi n us 
first d ose date of d o u ble -bli n d fil g oti ni b + 1 ] di vi de d b y 7).
F or s u bjects wit h a partial last d osi n g date (ie, m o n t h a n d year of last d ose are k n o w n), t he latest 
of t he dis pe nsi n g dates of st u d y  dr u g b ottles, st u d y dr u g start dates a n d e n d dates, a n d t he 
i m p ute d last d osi n g date ( da y i m p ute d as 1 5) will be use d as t he fi nal i m p ute d last d osi n g date. If 
t he s u bject die d a n d t he deat h date is c o m plete (ie, n ot partial date) a n d bef ore t he i m p ute d last 
d osi n g date, t he c o m plete deat h date will be use d as t he i m p ute d last d osi n g date.
If o nl y year is rec or de d (ie, m o nt h a n d da y of last d ose are missi n g), t he latest of t he dis pe nsi n g 
m o nt h of st u d y  dr u g b ottles, st ud y  dr u g start m o nt h, a n d st u d y dr u g e n d m o nt h will be use d t o 
i m p ute t he u n k n o w n last d ose m o nt h. If t he s u bject die d a n d t he deat h date has m o nt h a n d year 
a vaila ble a n d bef ore t he i m p ute d last d ose m o nt h, t he n t he m o nt h of deat h will be use d i nstea d. 
Wit h
t he m o nt h i m p ute d, t he af ore me nti o ne d met h o d will be use d t o i m p ute t he last d ose date.
If s u bjects are c o nti n ui n g o n st u d y dr u g at t he ti me of a n i nteri m a nalys is, t he earliest of t he date 
of deat h or data c ut off date f or t he i nteri m a nal y sis will be used t o i m p ute t he last d osi n g date f or 
t he calc ulati o n of d urati o n of e x p os ure t o st u d y dr u g.
T he t otal d urati o n of e x p os ure t o d o u ble -bli n d st u d y  dr u g, o pe n-la bel fil g oti ni b, a n d a n y 
fil g oti ni b st u d y dr u g will be s u m marize d usi n g descri pti ve statistics a n d usi n g t he n u m ber 
(ie, c u m ulati ve c o u nts) a n d perce nta ge of s u bjects e x p ose d t hr o u g h t he f oll o wi n g ti me peri o ds: 
Baseli ne ( Da y 1), Wee k 2 ( Da y  1 4), Wee k 4 ( Da y 2 8), Wee k 8 ( Da y 5 6), Wee k 13 ( Da y 9 1 ), 
Wee k
2 0 ( Da y  1 4 0), Wee k 2 6 ( 1 8 2), Wee k 3 9 ( 2 7 3), a n d u p t o Wee k 2 2 1 ( Da y 1 5 4 8) at 
1 3- w ee k i nter vals (as a p pr o priate).


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 3 1
1 3 Ja n uar y 2 0 2 1
S u m maries will be pr o vi de d b y  d o u ble -bli n d treat me nt gr o u p f or d o u ble-bli n d dr u g; a n d b y  
treat me nt gr o u p a n d o verall f or “ o pe n- la bel fil g oti ni b” a n d “a ny fil g oti ni b” f or t he Safety 
A nal y sis Set. N o f or mal statistical testi n g is pla n ne d.
4. 2. 2.
A d here nce t o St u d y Dr u g
F or t he fi nal a nal ys is, the o n -treat me nt ad here nce will be calc ulate d f or d o u ble-bli n d fil g oti ni b 
2 0 0 m g/ P T M (ta blets), t hr o u g h o ut t he d o u ble -bli n d p hase f or t he Se me n A nal ysis Set.
T he t ot al n u m ber of d o u ble -bli n d ta blets a d mi nistere d will be s u m marize d usi n g descri pti ve 
statistics. 
T he pres u me d t otal n u m ber of ta blets a d mi nistere d t o a s u bject will be deter mi ne d b y  t he data 
c ollecte d o n t he dr u g acc o u nta bilit y C R F usi n g t he f oll o wi n g f or mula:
T otal N u m ber of Ta blets A d mi nistere d 
=  N o. of Ta blets Dis pe nse d  − N o. of Ta blets Ret ur ne d B ottles f or d o u ble-bli n d dr u g dis pe nse d t hr o u g h o ut t he st u d y will be i ncl u de d i n t he calc ulati o ns.
If a b ottle is dis pe nse d a n d t he b ottle is ret ur ne d e m pt y, t he n t he n u m ber of ta blets ret ur ne d will 
be e ntere d as zer o. If a b ottle is dis pe nse d b ut n ot ret ur ne d ( missi n g), t he n u m ber of ta blets 
a d mi nistere d will be c o u nte d as zer o b y ass u mi n g t hat a s u bject di d n ot ta ke st u d y dr u g as 
prescri be d d uri n g t he peri o d f or w hic h t he b ottle was dis pe nse d.
4. 2. 2. 1.
O n -Treat me nt A d here nce
T he le vel of o n -treat me nt a d here nce t o t he st u d y dr u g (d uri n g d o u ble -bli n d treat me nt) will be 
deter mi ne d b y t he t otal a m o u nt of st u d y  dr u g a d mi nistere d relati ve t o t he t otal a m o u nt of st u d y 
dr u g e x pecte d t o be a d mi nistere d d uri n g a s u bject’s act ual o n -treat me nt peri o d base d o n t he 
st u d y dr u g re gi me n.
T he le vel of o n -treat me nt a d here nce (w hile o n d o u ble -bli n d treat me nt ) will be e x presse d as a 
perce nta ge usi n g t he f oll o wi n g f or m ula:
T otal A m o u nt of St u d y  Dr u g A d mi nistere d
O n- Treat m e nt A d here nce ( %) = 
 x 1 0 0
St u d y Dr u g E x pecte d t o  be A d mi nistere d on Treat me nt






N ote: If calc ulate d a d here nce is greater t ha n 1 0 0 %, t he res ult will be set t o 1 0 0 %.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 3 2
1 3 Ja n uar y 2 0 2 1
St u d y  dr u g e x pecte d t o be a d mi nistere d f or fil g oti ni b 2 0 0 m g/ P T M (ta blets) = 1 × t otal d urati o n 
of e x p os ure t o d o u ble -bli n d st u d y dr u g ( da ys) u p t o last visit (e g, last d o u ble-bli n d d ose 
date – d o u ble -bli n d first d ose date + 1) .
Descri pti ve statistics f or t he le vel of o n -treat me nt a d here nce wit h t he n u m ber a n d perce nta ge of 
s u bjects bel o n gi n g t o a d here nce cate g ories (e g, < 8 0 %, ≥ 8 0 % t o < 9 0 %, ≥ 9 0 %) will be 
pr o vi de d b y treat me nt gr o u p d uri n g t he d o u ble -bli n d p hase of t he st u d y f or t he Se me n A nal ys is 
Set f or t he fi nal a nal ysis. F or t he i nteri m a nal ys es, a listi n g of s u bjects w h o i nterr u pte d st u d y 
dr u g as rec or de d o n t he st u d y dr u g a d mi nistrati o n e C R F will be liste d, si nce all d o u ble- bli n d 
b ottles f or t he st u d y  will n ot ha ve bee n ret ur ne d.
N o f or mal statistical testi n g is pla n ne d.
A b y -s u bject listi n g of st u d y dr u g a d mi nistrati o n a n d dr u g acc o u nta bilit y will be pr o vi de d 
separatel y  b y s u bject I D n u m ber (i n asce n di n g or der) a n d visit (i n c hr o n ol o gical or der).
A listi n g of s u bjects w h o ha d i nterr u pti o ns i n st u d y dr u g d osi n g will be pr o d uce d f or b ot h t he 
i nteri m a n d fi nal a nalys es.
4. 3. 
Pr ot oc ol De vi ati o ns 
A b y -s u bject listi n g will be pr o vi de d f or t h ose s u bjects w h o di d n ot meet at least 1 eli gi bilit y  
(i ncl usi o n or e xcl usi o n) criteri o n b ut were e nr olle d i nt o t he st u d y f or t he All Ra n d o mize d 
A nal y sis Set. T he listi n g will prese nt t he eli gi bilit y criteri o n ( or criteria if m ore t ha n 1 de viati o n) 
t hat t he s u bject di d n ot meet a n d relate d c o m me nts, if c ollecte d.
Pr ot oc ol de viati o ns occ urri n g after s u bjects e ntere d t he st u d y  are d oc u me nte d d uri n g r o uti ne 
m o nit ori n g. T he n u m ber a n d perce nta ge of s u bjects wit h ≥ 1 i m p orta nt pr ot oc ol de viati o n (I P D) 
will be s u m marize d b y  treat me nt gr o u p. I n a d diti o n, i m p orta nt pr ot oc ol de viati o ns will be 
s u m marize d b y treat me nt gr o u p a n d I P D cate g or y f or t he All Ra n d o mize d A nal ysis Set. 
A b y -s u bject listi n g will be pr o vi de d f or t h ose s u bjects wit h a n I PD. I n a d diti o n, 2 se parate 
b y -s u bject listi n gs will be pr o vi de d f or s u bjects wit h : 1) a n y i m p orta nt pr ot oc ol de viati o n relate d 
t o C O VID- 1 9 , a n d 2) a n y n o n-i m p orta nt pr ot oc ol de viati o n relate d t o C O VI D- 1 9.   


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G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 3 3
1 3 Ja n uar y 2 0 2 1
5.
B A S E LI N E C H A R A C T E RI S TI C S
5. 1.
De m o gr a p hics
S u bject de m o gra p hic varia bles (ie, a ge, se x, race, a n d et h nicit y) will be s u m marize d f or t he 
d o u ble -bli n d p hase of t he st u d y  b y  treat me nt gr o u p a n d o verall f or t he I T T/Safet y  A nalys is Sets
a n d t he Se me n A nal ys is Set usi n g descri pti ve statistics f or a ge , a n d usi n g n u m ber a n d perce nta ge 
of s u bjects f or se x, race a n d et h nicit y. Se parate dis pla ys will prese nt data f or t he “as-treate d 
a nal ys is” b y treat me nt f or t he Safet y A nal y sis Set a n d b y treat me nt se q ue nce f or t he 
Wee k
2 6/ L T E Se me n A nal y sis Set. S u bjects w h o were ra n d o mize d t o place b o a n d s witc he d t o 
o pe n -la bel fil g oti ni b will be c o u nte d i n b ot h t he place b o a n d t he fil g oti ni b gr o u p f or “as-treate d” 
dis pla y s.
A ge is calc ulate d i n y ears o n t he date of first st u d y  dr u g a d mi nistrati o n. If a s u bject d oes n ot 
recei ve st u d y dr u g after ra n d o mizati o n, t he s u bject’s a ge will be calc ulate d fr o m t he 
D a y 1/ b aseli ne assess me nt . A b y -s u bject de m o gra p hic listi n g, i ncl u di n g t he i nf or me d c o nse nt 
date , will be pr o vi de d b y s u bject I D n u m ber i n asce n di n g or der.
5. 2.
B aseli ne C h ar acteristics
Ot her baseli ne c haracteristics will i ncl u de:

B o d y  wei g ht (i n k g)

H ei g ht (i n c m)

B o d y  mass i n de x ( B MI; i n k g/ m2)

T y pe of I B D dis or der ( U C vers us C D)

D urati o n of U C / C D (i n years)

M C S sc ore
(cate g orical f or eac h sc ore) f or U C s u bjects o nl y

E n d osc o pic s u bsc ore of M C S
( 2 or 3) f or U C s u bjects o nl y

C D AI  sc ore f or C D s u bjects o nl y

S m o ki n g stat us (f or mer, c urre nt, ne ver)

Alc o h ol Use ─ fre q ue nc y of dri n ki n g i n past 1 2 m o nt hs ( n o alc o h ol i n m y life, n o alc o h ol i n 
past 1 2 m o nt hs, 1 or 2 ti mes i n past y ear, 3-1 1 ti mes i n t he past y ear, 1 -3 ti mes a m o nt h, 
˂ 4 ti mes a wee k, ≥ 4 ti mes a wee k)

Alc o h olic dri n ks per da y  c o ns u me d o n a dri n ki n g da y ─ past 1 2 m o nt hs ( 1 dri n k, 2 dri n ks, 
3 - 4 dri n ks, ≥ 5 dri n ks)

N u m ber of c hil dre n fat here d


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
C o nc urre nt M T X
use stat us ( yes, n o)

S per m c o nce ntrati o n ( 1 5 t o 2 5 M / m L, > 2 5 t o 5 0 M / m L, > 5 0 M / m L)

S per m c o nce ntrati o n ( M/ m L)

S per m t otal m otilit y ( %)

T otal s per m c o u nt ( M/ejac ulate)

E jac ulate v ol u me ( m L)

S per m m or p h ol o g y ( % n or mal) usi n g W H O 1 9 9 2 criteria

L ute inizi n g h or m o ne ( mI U/ m L )

F ollicle -sti m ulati n g h or m o ne ( mI U/ m L) 

In hi bi n B ( p g/ m L) 

T otal test oster o ne ( n g/ d L)
D urati o n of U C/ C D (i n years) calc ulate d as:
([first d ose date] – [date of i nitial dia g n osis of U C/ C D ] + 1 da y ) / 3 6 5. 2 5 
If t he date of i nitial dia g n osis is i nc o m plete, t he n t he f oll o wi n g r ules will be a p plie d:

missi n g da y : use t he first of t he m o nt h

missi n g m o nt h: use Ja n uar y
B aseli ne c haracteristics will be s u m marize d b y  d o u ble -bli n d treat me nt gr o u p a n d o verall usi n g 
descri pti ve statistics f or c o nti n u o us varia bles a n d usi n g n u m ber a n d perce nta ge of s u bjects f or 
cate g orical varia bles f or t he Safet y /IT T Se me n A nal y sis Sets a n d t he Se me n A nal ysis Set.
Se parate dis pla y s will be prese nte d b y  treat me nt f or t he As-Treate d Safet y A nal y sis Set a n d b y  
treat me nt se q ue nce f or t he Wee k 2 6/ L T E Se me n A nal y sis Set.
A b y -s u bject listi n g of baseli ne c haracteristics will be pr o vi de d b y  s u bject I D n u m ber i n 
asce n di n g or der.
5. 3.
Me dic al Hist or y
Disease -s pecific a n d ge neral me dical hist or y data will be c ollecte d at scree ni n g. Me dical hist or y  
data will n ot be c o de d.
A b y -s u bject listi n g of me dical hist or y  will be pr o vi de d b y s u bject I D n u m ber i n asce n di n g or der 
a n d a b n or malities i n c hr o n ol o gical or der.


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Statistical A nal ysis Pla n
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C O N FI D E N TI A L
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1 3 Ja n uar y 2 0 2 1
6.
S E M E N A N D H O R M O N E A N A L Y S E S
6. 1.  
Ge ner al C o nsi der ati o ns
T he defi niti o ns f or t he pri mar y  a n d sec o n dar y e n d p oi nts are liste d i n Ta ble 6- 1 .
T a ble 6- 1.
Defi niti o ns f or t he Pri m ar y a n d Sec o n d ar y E n d p oi nts
T y pe
E ve nt E n d p oi nt
Pri mar y
Pr o p orti o n of s u bjects wit h a ≥ 5 0 % decrease fr o m baseli ne i n s per m c o nce ntrati o n at Wee k 1 3
Sec o n dar y
Pr o p orti o n of s u bjects w it h a ≥ 5 0 % decrease fr o m baseli ne i n s per m c o nce ntrati o n at Wee k 2 6
Sec o n dar y
C ha n ge fr o m baseli ne i n s per m t otal m otilit y at Wee ks 1 3 a n d 2 6
Sec o n dar y
C ha n ge fr o m baseli ne i n t otal s per m c o u nt at Wee ks 1 3 a n d 2 6
Sec o n dar y
C ha n ge fr o m baseli ne i n s per m c o nc e ntrati o n at Wee ks 1 3 a n d 2 6
Sec o n dar y
C ha n ge fr o m baseli ne i n ejac ulate v ol u me at Wee ks 1 3 a n d 2 6
Sec o n dar y
C ha n ge fr o m baseli ne i n perce nt n or mal s per m m or p h ol o g y at Wee ks 1 3 a n d 2 6
N ote: Val ue at a visit is t he mea n of 2 e val ua ble se me n sa m ple c ollecti o ns at a gi ve n c ollecti o n ti me p oi nt f or pri mar y a nal ysis.
W he n calc ulati n g t he perce nt a ge c ha n ge fr o m baseli ne i n s per m c o nce ntrati o n, n o r o u n di n g will 
be perf or me d i n t he a nal ysis. F or t he p ur p oses of ta bles a n d listi n gs, t he perce nta ge will be 
ro u n de d t o 1 deci mal place.
Eli gi ble s u bjects were re q uire d at scree ni n g t o ha ve t he mea n of 2 e val ua ble se me n c ollecti o ns 
f or eac h of t he 5 s per m/se me n para meters greater t ha n or e q ual t o t he val ue ass ociate d wit h t he 
5 t h perce ntile of t he W H O refere nce set per Incl usi o n C riteria # 8. S u bjects ra n d o mize d u n der t he 
ori gi nal pr ot oc ol/ Pr ot oc ol A me n d me nt 1 were e nr olle d base d o n W H O 2 0 1 0 criteria f or s per m 
m or p h ol o g y . Up o n c o ns ultati o n wit h t he U S F D A, m or p h ol o g y  gra di n g was c ha n ge d t o t hat 
s pecifie d by W H O 1 9 9 2 i n Pr ot oc ol A me n d me nt 2. M or p h ol o g y  sli des c ollecte d usi n g W H O 
2 0 1 0 criteria were re -rea d usi n g W H O 1 9 9 2 criteria f or p ur p oses of s u m marizi n g m or p h ol o g y 
data o ver ti me. S e me n para meters ot her t ha n s per m m or p h ol o g y used W H O 2 0 1 0 criteria { W orl d 
Healt h Or ga nizati o n ( W H O) 2 0 1 0 }. Se me n para meter eli gi bilit y  criteria are pr o vi de d i n 
Ta ble 6- 2 .
T a ble 6- 2.
Se me n P ar a meter Eli gi bilit y Criteri a
P a r a m eter
Refere nce R a n ge
S per m  c o nce ntrati o n
≥ 1 5 milli o n per milliliter ( m L)
S p er m  t otal m o tilit y
≥ 4 0 %
T otal s per m per ejac ulate
≥ 3 9 milli o n
Ejac ulate v ol u me
≥ 1. 5 m L
S p er m  mor p h ol o g y
≥ 3 0 % n or mal * 
Liste d se me n para meters use 2 0 1 0 W H O Refere nce val ues { C o o per 2 0 1 0 , W orl d Healt h Or ga niz ati o n ( W H O) 2 0 1 0 } f or h u ma n 
se me n c haracteristics e xce pt *( m or p h ol o g y) w hic h utilizes t he 1 9 9 2 W H O s per m m or p h ol o g y criteri o n { W orl d Healt h 
Or ga nizati o n ( W H O) 1 9 9 2 }.
N O T E: Pri or t o a me n d me nt 2, s u bjects were re q uire d t o ha ve s per m m or p h ol o g y ≥4 % n or mal at scree ni n g usi n g t he strict 
“ T y ger ber g” met h o d per i ncl usi o n criteria # 8. M or p h ol o g y f or se me n sa m ples c ollecte d pri or t o c o nse nt/re-c o nse nt f or Pr ot oc ol 
A me n d me nt 3 were re-rea d usi n g W H O 1 9 9 2 met h o d ol o g y . W H O 1 9 9 2
will be use d f or all p ost baseli ne m or p h ol o g y a nal ysis.


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G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 3 6
1 3 Ja n uar y 2 0 2 1
6. 2.
Pri m ar y A n al ysis of Pri m ar y a n d Sec o n d ar y E n d p oi nt s
T he pri mar y  a nalys is will be a n o bser ve d cases a nal ysis at Wee k 1 3 w hile s u bjects are on 
d o u ble -bli n d st u d y  dr u g as descri be d i n F D A’s g ui da nce f or i n d ustr y o n testic ular t o xicit y 
st u dies { U. S. De part me nt of Healt h a n d H u ma n Ser vices ( D H H S) 2 0 1 8 }. 
T he mai n esti mat ors of a W hile o n Treat me nt Strate g y  esti ma n d will be utilize d f or t he pri mar y 
a nal ys is of pri mar y a n d sec o n dar y e n d p oi nts at Wee k 1 3:
BI N A R Y E N D P OI N T
W HI L E O N -T R E A T M E N T S T R A T E G Y
P o p ulati o n
Se m e n A nal ysis Set (s u bjects wit h 2 e val ua ble se me n sa m ples c ollecte d at 
baseli ne a n d at t he Wee k 1 3 a nal ysis visit) as defi ne d i n Secti o n 3. 1. 2 of t his 
S A P .
Patie nt Le vel O utc o me t o be 
Meas ure d
Bi nar y o utc o me f or a s u bje ct meeti n g a ≥5 0 % decrease fr o m baseli ne i n s per m 
c o nce ntrati o n at Wee k 1 3 . O utc o me is deter mi ne d base d o n t he mea n of 
2 e val ua ble se me n sa m ples at a visit.
Meas ure of i nter ve nti o n 
effect a n d ha n dli n g of 
i nterc urre nt e ve nts
Meas ure of treat me nt effect a ss u mi n g t hat t he treat me nt effect pri or t o t he 
i nterc urre nt e ve nt of treat me nt earl y ter mi nati o n is of i nterest . Data i ncl u de d t o 
last d ose date d o u ble-bli n d dr u g + 7 da ys will be c o nsi dere d “ w hile o n -
treat me nt” f or t h ose w h o per ma ne ntl y disc o nti n ue d o u ble-bli n d st u d y dr u g.
P o p ulati o n le vel s u m mar y 
meas ure
Differe nce i n a bi nar y o utc o me, c o m pari n g t h ose assi g ne d t o fil g oti ni b vers us 
t h ose assi g ne d t o place b o.
Esti mat ors
Mai n esti mat or: A stratifie d Ma ntel-Hae nszel test (stratificati o n fact or: s per m 
c o nce ntrati o n [ 1 5 - 5 0 a n d > 5 0 M/ m L]) will be use d t o esti mate t he differe nce i n 
pr o p orti o ns ( fil g oti ni b – p lace b o) a n d c orres p o n di n g 9 5 % CI { K oc h 1 9 8 9 } . 
Calc ulati o ns are pr o vi de d i n A p pe n di x 2 .
N ote: W he n perf or mi n g t he stratifie d Ma ntel -Hae nszel test, t he 1 5 - 2 5  a n d 
> 2 5 - 5 0 M/ m L strata f or s per m c o nce ntrati o n will be c o m bi ne d (e g, 1 5 - 5 0 
M/ m L) d ue t o t he s mall n u m ber of s u bjec ts i n t he l o west strat u m; disease t y pe 
will n ot be i ncl u de d as a stratificati o n fact or d ue t o t he s mall n u m ber of s u bjects 
wit h C D; a n d n o s u bjects i n t his st u d y recei ve d M T X.
T he n u m ber a n d pr o p orti o n of s u bjects wit h a ≥
5 0 % decrease i n s per m c o nce ntr ati o n at 
Wee k
2 6 ( o bser ve d cases) will be prese nte d b y d o u ble -bli n d treat me nt gr o u p. T he n u m ber of 
s u bjects w h o ha ve a ≥5 0 % decrease i n s per m c o nce ntrati o n at a n y ti me u p t o Wee k 2 6 (t o u p per 
b o u n d of a nal ys is visit wi n d o w) will be dis pla ye d t o e ns ure t hat ≥5 0 % decreases fr o m baseli ne 
i n s per m c o nce ntrati o n t hat fell o utsi de of t he a nal ysis visit wi n d o ws are acc o u nte d f or.


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C O N TI N U O U S 
E N D P OI N T S
W HI L E O N T R E A T M E N T
S T R A T E G Y
P o p ulati o n
Se m e n A nal ysis Set (s u bjects wit h 2 e val ua ble se me n sa m ples c ollecte d at
baseli ne a n d at t he Wee k 1 3 a nal ysis visit ) as defi ne d i n Secti o n 3. 1. 2 of t his 
S A P .
Patie nt Le vel O utc o me t o be 
Meas ure d
C ha n ge a n d Perce nta ge C ha n ge fr o m Baseli ne (c o nti n u o us o utc o me) at 
Wee k
1 3. O utc o me is deter mi ne d base d o n t he mea n of 2 e val ua ble se me n 
sa m ples at a visit, a n d a nal ysis visit wi n d o ws are assi g ne d base d o n first of 
2 e val ua ble se me n sa m ples.
Meas ure of i nter ve nti o n effect 
a n d ha n dli n g of i nterc urre nt 
e ve nts
Meas ure of treat me nt effect ass u mi n g t hat t he treat me nt effect pri or t o t he 
interc urre nt e ve nt of treat me nt earl y ter mi nati o n is of i nterest . Data i ncl u de d t o 
last d ose date d o u ble-bli n d dr u g + 7 da ys will be c o nsi dere d “ w hile 
o n -treat me nt” f or t h ose w h o per ma ne ntl y disc o nti n ue d o u ble-bli n d st u d y dr u g.
P o p ulati o n le vel s u m mar y 
meas ure
Me dia n Differe nce bet w ee n treat me nt gr o u ps, c o m pari n g t h ose assi g ne d t o 
fil g oti ni b vers us t h ose assi g ne d t o place b o i n t he c ha n ge a n d perce nta ge c ha n ge 
fr o m baseli ne at Wee k 1 3 f or a c o nti n u o us o utc o me.
Esti mat ors
Mai n esti mat or: Q ua ntile re gressi o n m o dels will be use d t o esti mate t he me dia n 
differe nce ( fil g oti ni b – p lace b o) i n c ha n ge a n d perce nta ge c ha n ge fr o m baseli ne
at Wee k 1 3 , 9 5 % CI f or t he s per m/se me n para meter of i nterest. T he CI = R A N K 
o pti o n w ill be s pecifie d i n P R O C Q U A N T R E G i n S A S.
F or s per m c o nce ntrati o n ( M/ m L) , t he mo del will i ncl u de : baseli ne s per m 
c o nce ntrati o n (c o nti n u o us) .
F or s per m t otal m otilit y ( %), perce nt n or mal m or p h ol o g y, t otal s per m c o u nt 
( M/ejac ulate) a n d ejac ulati o n v ol u me ( m L), t he m o del will i ncl u de:
baseli ne val ue f or para meter (c o nti n u o us), a n d s per m c o nce ntrati o n 
( 1 5 – 5 0 M/ m L, >
5 0 M/ m L) .
Ei g ht -p oi nt s u m mar y  statistics ( n, mea n, S D, me dia n, Q 1, Q 3, mi ni m u m, a n d ma xi m u m) b y 
d o u ble -bli n d treat me nt gr o u p will be prese nte d f or baseli ne val ue, a bs ol ute val ue at t he visit, a n d 
c ha n ge a n d perce nta ge c ha n ge fr o m baseli ne f or eac h s per m  para meter at Wee k 1 3. A 9 5 % 
distri b uti o n -free CI o n t he me dia n c ha n ge a n d perce nta ge c ha n ge fr o m baseli ne f or eac h se me n
para meter will be c o nstr ucte d b y  treat me nt gr o u p at Wee k 1 3 usi n g t he CIP C T L D F o pti o n i n 
P R O C U NI V A RI A T E i n S A S. 
Base d o n F D A’s g ui da nce f or i n d ustr y  o n testic ular t o xicit y st u dies { U. S. De part me nt of Healt h 
a n d H u ma n Ser vices ( D H H S) 2 0 1 8 } a n d c o m m u nicati o n wit h t he F D A, a c u m ulati ve 
distri b uti o n pl ot f or perce nt a ge c ha n ge fr o m baseli ne i n s per m c o nce ntrati o n at Wee k 1 3 will be 
c o nstr ucte d b y d o u ble -bli n d treat me nt gr o u p. C u m ulati ve distri b uti o n pl ots f or perce nta ge 
c ha n ge fr o m baseli ne at d o u ble -bli n d Wee k 1 3 f or t otal s per m m otilit y  ( %) a n d s per m 
m or p h ol o g y  ( % n or mal) will als o be prese nte d b y d o u ble -bli n d treat me nt gr o u p.
A waterfall pl ot will be c o ns tr ucte d t o prese nt t he distri b uti o n of perce nta ge c ha n ge fr o m 
baseli ne i n s per m c o nce ntrati o n at Wee k 1 3. Eac h li ne o n t he x-a xis of t he waterfall pl ot will 
re prese nt t he perce nta ge c ha n ge fr o m baseli ne i n s per m c o nce ntrati o n f or a n i n di vi d ual s u bject 
wit h t heir treat me nt assi g n me nt dis pla ye d base d o n t he c ol or /s ym b ol dis pla y e d f or t he li ne.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 3 8
1 3 Ja n uar y 2 0 2 1
6. 3.
S u b gr o u p A n al ysis f or S per m C o nce ntr ati o n P ar a meter at Wee k 1 3
T he f oll o wi n g s u b gr o u p a nal ys es will be perf or me d b y  treat me nt gr o u p f or t he e n d p oi nts
pr o p orti o n of s u bjects wit h a ≥ 5 0 % decrease fr o m baseli ne i n s per m c o nce ntrati o n at Wee k 1 3, 
a n d c ha n ge a n d perce nta ge c ha n ge fr o m baseli ne i n s per m c o nce ntrati o n at Wee k 1 3:

T y pe of I B D dis or der ( U C , C D)

S per m c o nce ntrati o n ( mea n of 2 e val ua ble sa m ples) meas ure d at Sc ree ni n g visit: 
( 1 5 - 5 0
M/ m L,  > 5 0 M/ m L)
A s u b gr o u p a nal ys is of c o nc urre nt M T X use ( yes, n o) w as n ot perf or me d si nce n o s u bjects t o o k 
c o nc urre nt M T X.
6. 4. 
S u p p orti ve A n al ysis f or Pri m ar y a n d Sec o n d ar y E n d p oi nts at Wee k 1 3
I n a d diti o n t o t he pri mar y a n al ysis, t he mai n esti mat ors of a h yp ot hetical strate g y esti ma n d will 
pr o vi de s u p p ort t o t he pri mar y  a nalys is of pri mar y a n d sec o n dar y e n d p oi nts at t he Wee k 1 3 
ti me p oi nt. T he esti ma n ds f or bi nar y a n d c o nti n u o us e n d p oi nts are descri be d bel o w.
Esti m a n d f or Bi n ar y E n d p oi nt
BI N A R Y E N D P OI N T
H Y P O T H E TI C A L S T R A T E G Y
P o p ulati o n
I T T Se me n A nal ysis Set (s u bjects wit h 2 e val ua ble se me n sa m ples c ollecte d at 
baseli ne) as defi ne d i n Secti o n 3. 1. 2 of t his S A P .
Patie nt Le vel O utc o me t o be 
Meas ur e d
Bi nar y o utc o me f or a s u bject meeti n g a ≥ 5 0 % decrease fr o m baseli ne i n s per m 
c o nce ntrati o n at Wee k 1 3 . O utc o me is deter mi ne d base d o n t he mea n of 
2 e val ua ble se me n sa m ples at a visit . A su bject w it h o nl y 1 of t he 2 e val ua ble 
se me n sa m ples at Wee k 1 3 wil l be i ncl u de d wit h t heir 1 sa m ple [S u bject I D 
1 0 5 5 6 -3 5 0 3 5 ]. If a meas ure me nt f or a s pecific se me n para meter is dee me d 
i neli gi ble at Wee k 1 3, t he 1 e val ua ble res ult will be use d.
Meas ure of i nter ve nti o n 
effect a n d ha n dli n g of 
i nterc urre nt e ve nts
Meas ure of treat me nt effect ass u mi n g t hat t he i nterc urre nt e ve nt of earl y 
ter mi nati o n pri or t o Wee k 1 3 d oes n ot occ ur. S u bjects w h o ha d missi n g data at 
Wee k 1 3 w ill be ass u me d t o be missi n g at ra n d o m ( M A R) a n d data will be 
i mp ute d usi n g P R O C MI i n S A S a n d a l o gistic re gressi o n m o del wit h treat me nt 
gr o u p , a n d baseli ne s per m c o nce ntrati o n cate g or y ( 1 5 - 5 0 M/ m l, > 5 0 M/ m l) as 
i n de pe n de nt varia bles i n t he m o del.
P o p ulati o n le vel s u m mar y 
meas ure
Differe nce i n a bi nar y o utc o me, c o m pari n g t h ose assi g ne d t o fil g o ti ni b vers us 
t h ose assi g ne d t o place b o.
Esti mat ors
Mai n esti mat or: I m p ute d datasets will be a nal yze d usi n g t he stratifie d 
Ma ntel- Hae nszel met h o d (stratificati o n fact ors: s per m c o nce ntrati o n 
[1 5 – 5 0 M/ m L , > 5 0 M/ m L]) . Res ults will be c o m bi ne d usi n g R u bi n’s r ule 
{ R u bi n 1 9 8 7 }t o esti mate t he differe nc e i n pr o p orti o ns ( fil g oti ni b – p lace b o) a n d 
c orres p o n di n g 9 5 % CI.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 3 9
1 3 Ja n uar y 2 0 2 1
Esti m a n d f or C o nti n u o us E n d p oi nts
C O N TI N U O U S 
E N D P OI N T S
H Y P O T H E TI C A L S T R A T E G Y
P o p ulati o n
I T T Se me n A nal ysis Set (s u bjects wit h 2 e val ua ble se me n sa m ples c ollecte d at 
baseli ne) as defi ne d i n Secti o n 3. 1. 2 of t his S A P .
Patie nt Le vel O utc o me t o be 
Meas ure d
C ha n ge a n d Perce nta ge C ha n ge fr o m Baseli ne (c o nti n u o us o utc o me) at 
Wee k
1 3. O utc o me is deter mi ne d base d o n t he mea n of 2 e val ua ble se me n 
sa m ples at a visit. A s u bject wit h o nl y 1 of t he 2 e val ua ble se me n sa m ples at 
Wee k 1 3 w ill be i ncl u de d wit h t heir 1 sa m ple [ S u bject I D 1 0 5 5 6-3 5 0 3 5 ]. If a 
meas ure me nt f or a s pecific se me n para meter is dee me d i neli gi ble at Wee k 1 3, 
t he 1 e val ua ble res ult will be use d.
Meas ure of i nter ve nti o n effect 
a n d ha n d li n g of i nterc urre nt 
e ve nts
Meas ure of treat me nt effect ass u mi n g t hat i nterc urre nt e ve nt of earl y 
ter mi nati o n pri or t o Wee k 1 3 d oes n ot occ ur. S u bjects w h o ha d missi n g data at 
Wee k 1 3 d ue t o earl y ter mi nati o n will be ass u me d t o be M A R
a n d data will be 
i mp u te d b y c o n diti o nal q ua ntile esti mati o n usi n g t he q ua ntile re gressi o n m o del 
s pecifie d f or t he pri mar y a nal ysis usi n g t he met h o ds of B ottai a n d Z he n.
P o p ulati o n le vel s u m mar y 
meas ure
Me dia n Differe nce bet w ee n treat me nt gr o u ps, c o m pari n g t h ose assi g ne d t o 
fil g oti ni b vers us t h ose assi g ne d t o place b o i n t he c ha n ge a n d perce nta ge c ha n ge 
fr o m baseli ne at Wee k 1 3 f or a c o nti n u o us o utc o me.
Esti mat ors
Mai n esti mat or: I mp ute d datasets will be a nal yze d usi n g q ua ntile re gressi o n
m o dels use d f or pri mar y a nal ysis t o o btai n esti mates a n d sta n dar d err ors 
(sta n dar d err ors o btai ne d t hr o u g h b o otstra p met h o ds). Res ults of t he esti mates 
a n d sta n dar d err ors will be c o m bi ne d usi n g R u bi n’s r ule t o esti mate t he me dia n 
differe nce ( fil g oti ni b – p lace b o) i n c ha n ge or perce nta ge c han ge fr o m baseli ne, 
9 5 % CI f or t he s per m/se me n para meter of i nterest.
6. 5.
Ot her Dis pl a ys of S per m/ Se me n D at a
6. 5. 1.
Tre at me nt -Se q ue nce Se me n Dis pl a ys ( Wee k 2 6/ O L Wee k 1 3 a n d E xte nsi o n 
P h ase)
T he pr o p orti o n of s u bjects wit h a ≥ 5 0 % decrease fr o m baseli ne i n s per m c o nce ntrati o n will be 
prese nte d b y treat me nt se q ue nce a n d a nal ys is visit. A n e xact 9 5 % CI f or t he pr o p orti o n of 
s u bjects wit h a ≥ 5 0 % decrease fr o m baseli ne i n s per m c o nce ntrati o n at Wee k 2 6 / O L Wee k 1 3
wit hi n treat me nt se q ue nce will be prese nte d base d o n t he Cl o p per -Pears o n met h o d. 
Descri pti ve statistics will be prese nte d at Baseli ne, Wee k 2 6/ O L  Wee k 1 3 a n d s u bse q ue nt visits 
b y  act ual treat me nt se q ue nce t o e x pl ore t he c o nf o u n di n g effects of I B D res p o nse t o treat me nt. A 
9 5 % distri b uti o n -free CI o n t he me dian c ha n ge a n d perce nta ge c ha n ge fr o m baseli ne i n 
s per m/se me n para meters at Wee k 2 6/ O L Wee k 1 3 will be c o nstr ucte d b y  treat me nt se q ue nce 
usi n g t he CI P C T L D F o pti o n i n P R O C U NI V A RI A T E i n S A S. St u d y  da ys will be use d f or 
assi g n me nt of a nal ys is visit wi n d o ws f or s u bjects w h o sta ye d o n ra n d o mize d dr u g t hr o u g h o ut 
st u d y a n d f or s u bjects w h o starte d o n d o u ble-bli n d fil g oti ni b a n d s witc he d t o o pe n -la bel 
fil g oti ni b. F or s u bjects w h o s witc he d fr o m place b o t o o pe n-la bel fil g oti ni b, da ys o n o pe n-la bel 
fil g oti ni b will be use d t o assi g n a nalys is visit wi n d o ws. Wee k 2 6 f or t he first 3 treat me nt 


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 0
1 3 Ja n uar y 2 0 2 1
se q ue nces will be dis pla ye d al o n g-si de O L Wee k 1 3 f or place b o t o O L fil g oti ni b gr o u p; 
Wee k
3 9 al o n gsi de O L Wee k 2 6 f or place b o t o O L  fil g oti ni b gr o u p, etc. t o ali g n wit h t he 
ori gi nall y pla n ne d st u d y wee ks, b ut usi n g t he at/after Pr ot oc ol A me n d me nt 3 visit sc he d ule t o 
e ns ure t hat s u bjects w h o s witc he d fr o m place b o t o o pe n- la bel fil g oti ni b ha d at least 8 5 d a y s o n 
fil g oti ni b pri or t o t heir first se me n c ollecti o n w hile o n fil g oti ni b treat me nt (e g, a f ull s per m 
c ycle). 
A c u m ulati ve distri b uti o n pl ot f or perce nta ge c ha n ge fr o m baseli ne i n s per m c o nce ntrati o n at t he 
Wee k 2 6 / O L Wee k 1 3 visit will be c o nstr ucte d b y treat me nt se q ue nce f or s u bjects w h o are still 
o n st u d y  dr u g at Wee k 2 6/ O L Wee k 1 3.
T he n u m ber of da y s o n fil g oti ni b at t he ti me of t he first of 2 se me n assess me nts at t he 
Wee k
2 6/ O pe n -La bel Wee k 1 3 a nal y sis visit will be s u m marize d b y treat me nt se q ue nce f or 
s u bjects wit h e val ua ble sa m ples i n t he a nalys is visit wi n d o w.
A listi n g of s u bj ects i n t he place b o t o o pe n -la bel fil g oti ni b treat me nt se q ue nce w h o ha d n o mi nal 
visits f or Wee k 2 6 or O pe n -La bel Wee k 1 3 t hat were o utsi de of t he a nal ys is visit wi n d o w f or O L 
Wee k 1 3 will be pr o vi de d — pri maril y  t o assess t he n u m ber of s u bjects w h o were o n ori gi nal/ 
Pr ot oc ol A me n d me nt 1 visit sc he d ule a n d di d n ot ha ve s ufficie nt e x p os ure ( mi ni m u m of 
8 5 da y s) o n o pe n-la bel fil g oti ni b at t he ti me of t heir first c ollecti o n t o fall wit hi n t he O pe n-La bel 
Wee k
1 3 a nal ys is visit wi n d o w
6. 5. 2.
Pre -S pecifie d S per m Decre ase T hres h ol d Criteri a a n d C o nfir me d Se me n 
A b n or m alities
S u bjects w h o met a pre -s pecifie d s per m decrease t hres h ol d criteria (a ≥ 5 0 % decrease i n s per m 
c o nce ntrati o n a n d/ or m otilit y a n d/ or m or p h ol o g y) were t o st o p st u d y dr u g a n d be gi n a sta n dar d 
of care re gi me n selecte d b y t he i n vesti gat or i n acc or da nce wit h t he pr ot oc ol a n d be f oll o we d off 
st u d y dr u g t o e val uate f or re versi bilit y criteria.
A “c o nfir me d se me n a b n or malit y ” as defi ne d b y J ar vi a n d c ollea g ues { Jar vi 2 0 0 8} reflects t he 
prese nce of a b n or mal s per m para meters p ote ntiall y ass ociate d wit h decrease d male fertilit y ; t he 
criteri o n is met w he n o ne or m ore of t he f oll o wi n g are o bser ve d: a s per m c o nce ntrati o n 
˂ 5 M / m L, or s per m m otilit y ˂ 2 0 %, or a perce nt n or mal s per m m or p h ol o g y of ˂ 1 0 %.
T he n u m ber a n d pr o p orti o n of s u bjects meeti n g a n y  of t he pre -s pecifie d s per m decrease 
t hres h ol ds (fr o m t he baseli ne val ue [ mea n of 2 e val ua ble se me n c ollecti o ns at scree ni n g]) or a n y 
of t he c o m p o ne nts of a c o nfir me d se me n a b n or malit y  ( mea n of 2 e val ua ble sa m ples at a st u d y 
visit) at t he d o u ble -bli n d Wee k 1 3 ( pri mar y e n d p oi nt) visit will be dis pla y e d b y d o u ble -bli n d 
treat me nt gr o u p:


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 1
1 3 Ja n uar y 2 0 2 1
S per m Decrease Criteria

≥5 0 % decrease i n s per m c o nce ntrati o n

≥5 0 % decrease i n s per m t otal m otilit y

≥5 0 % decrease i n s per m m or p h ol o g y [ % n or mal] ( W H O 1 9 9 2 criteria)

≥5 0 % decrease i n s per m c o nce ntrati o n a n d ( ≥5 0 % decrease i n t otal m otilit y  a n d/or
m or p h ol o g y [ % n or mal] at t he sa me visit)
C o nfir me d Se me n A b n or malit y  Criteria (as defi ne d b y Jar vi et al)

S per m c o nce ntrati o n < 5 M / m L

S per m t otal m otilit y  < 2 0 %

S per m m or p h ol o g y ( % n or mal) < 1 0 %

C o nfir me d Se me n A b n or malit y  (S per m c o nce ntrati o n < 5 M / m L or s per m t otal m otilit y  
< 2 0 % or s per m m or p h ol o g y [% n or mal ] < 1 0 % at t he sa me visit)
T he n u m ber a n d pr o p orti o n of s u bjects meeti n g a n y  of t he pre-s pecifie d s per m decrease 
t hres h ol ds or c o m p o ne nts of a c o nfir me d se me n a b n or malit y (as descri be d a b o ve) at t he 
Wee k
2 6/ O L  Wee k 1 3 a nal ysis visit a n d at/after t he Wee k 3 9/ O L Wee k 2 6 visit will be 
dis pla y e d b y treat me nt se q ue nce. Treat me nt se q ue nces t o be prese nte d are:

d o u ble -bli n d ( D B) fil g oti ni b 

D B fil g oti ni b t o o pe n -la bel ( O L) fil goti ni b

D B p lace b o

D B place b o t o O L fil g oti ni b  
A listi n g of s u bjects w h o met a n y  of t he c o m p o ne nts of a c o nfir me d se me n a b n or malit y will be 
pr o vi de d .
6. 6.
E x pl or at or y E n d p oi nts
6. 6. 1.
Defi niti o n of t he E x pl or at or y E n d p oi nts
T he e x pl orat or y  e n d p oi nts are:

Perce nt of r e versi bilit y a m o n g s u bjects w h o e x perie nce a ≥ 5 0 % decrease i n s per m 
c o nce ntrati o n, a n d/ or m otilit y, a nd/ or m or p h ol o g y 

C ha n ge fr o m baseli ne i n h or m o nes, i ncl u di n g L H, F S H, i n hi bi n B, a n d t otal test oster o ne at 
Wee ks 1 3 a n d 2 6


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 2
1 3 Ja n uar y 2 0 2 1
6. 6. 2.
Re versi bilit y A n al ysis
Re versi bilit y will be s u m marize d se paratel y f or eac h s per m para meter t hat met a pre-s pecifie d 
s per m para meter decrease. T he n u m ber ( perce nt) w h o met re versi bilit y criteria a n d t he 
c u m ulati ve n u m ber ( perce nt) w h o met re versi bilit y criteria at eac h M o nit ori n g P hase visit will be 
prese nte d . Re versi bilit y f or s u bjects meeti n g pre -s pecifie d s per m para meter decrease t hres h ol d[s]
at Wee k 1 3 will be dis pla ye d b y d o u ble -bli n d treat me nt gr o u p; a t Wee k 2 6/ O L Wee k 1 3 a n d 
at/after Wee k 3 9 / O L Wee k 2 6 will be dis pla ye d b y act ual treat me nt se q ue nce. F or t he Wee k 2 6 
interi m a nal y sis, a n a d diti o nal re versi bilit y  ta ble f or “c o m pleters” (ie, s u bjects w h o ha ve 
c o m plete d t he f ull 5 2 wee ks of off -st u d y dr u g f oll o w- u p, met re versi bilit y criteria, or 
pre mat urel y disc o nti n ue d fr o m st u d y  w hile bei n g f oll o we d i n t he m o nit ori n g p hase) will be 
pr o d uce d if at least 1 s u bject has a n e val ua ble m o nit ori n g p hase visit a n d is o n g oi n g i n t he 
m o nit ori n g p hase at t he ti me of data c ut off.
N o f or m al testi n g or CI is pla n ne d. A b y -s u bject data listi n g of se me n data ( wit h meas ure me nt 
w here re versi bilit y  criteria was met fla g ge d) will be pr o vi de d f or s u bjects w h o e ntere d t he 
M o nit ori n g P hase.
Ta ble 6- 3 s h o ws a n e xa m ple f or h y p ot hetical pr o p orti o n s of s u bjects (at fi nal a nalys is) wit h 
re verse d s per m c o nce ntrati o n f or a ≥5 0 % decrease fr o m baseli ne at/ pri or t o Wee k 1 3 b y  
m o nit ori n g visit n u m ber a n d last treat me nt recei ve d .
T a ble 6- 3.
H y p ot hetic al Pr o p orti o n of S u bjects W h o Met Re versi bilit y Criteri a 
b y M o nit ori n g Visit N u m ber a n d Tre at me nt Gr o u p ( S u bjects wit h a 
≥5 0 % Decre ase i n S per m C o nce ntr ati o n at Wee k 1 3)
Tre at m e nt bef ore 
M o nit ori n g
M o nit ori n g 
Vi sit 1
M o nit ori n g 
Visit 2
M o nit ori n g 
Visit 3
M o nit ori n g 
Visit 4
Re versi bilit y i n 
M o nit ori n g 
P h ase
F il g oti ni b
3 / 5
1 / 2
1 / 1
0 / 0
5 / 5
C u m ulati ve Rate
3 / 5 = 6 0. 0 % 
4 / 5 = 8 0. 0 %
5 / 5 = 1 0 0. 0 % 
5 / 5 = 1 0 0. 0 % 
5 / 5 = 1 0 0. 0 %
P lace b o
3 / 6
1 / 3
1 / 2
0 / 1
5 / 6 
C u m ulati ve Rate
3 / 6 = 5 0 % 
4 / 6 = 6 8 %
5 / 6 = 8 3. 3 % 
5 / 6 = 8 3. 3 % 
5 / 6 = 8 3. 3 %
6. 6. 3.
H or m o nes
Si milar a nal y sis met h o ds use d t o s u m marize c o nti n u o us sec o n dar y se me n para meters will be 
use d t o a nal yz e h or m o nes L H, F S H, i n hi bi n B, a n d t ota l test oster o ne. Baseli ne will be t he last 
val ue pri or t o a d mi nistrati o n of a n y st u d y dr u g.  
F or all c o nti n u o us h or m o ne para meters, 8- p oi nt s u m mar y  statistics ( n, mea n, S D, me dia n, Q 1, 
Q 3, mi ni m u m, a n d ma xi m u m) b y  d o u ble -bli n d treat me nt gr o u p will be pr o vi de d f or t he val ue at 
t he visit, c ha n ge fr o m baseli ne, a n d perce nta ge c ha n ge fr o m baseli ne i n h or m o ne para meter at 
Wee ks 4 a n d 1 3 (c ha n ge a n d perce nta ge c ha n ge val ues will be calc ulate d fr o m d o u ble -bli n d 
baseli ne) . A 9 5 % distri b uti o n-free CI o n t he me dia n c ha n ge a n d perce nta ge c ha n ge fr o m baseli ne 
i n all h or m o ne para meters will be c o nstr ucte d by t reat me nt at Wee k 4 a n d Wee k 1 3
usi n g t he 


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 3
1 3 Ja n uar y 2 0 2 1
CI P C T L D F o pti o n i n P R O C U NI V A RI A T E i n S A S. Q ua ntile re gressi o n will be use d t o esti mate 
t he differe nce (fil g oti ni b mi n us place b o) i n me dia n c ha n ge a n d perce nta ge c ha n ge fr o m baseli ne 
i n h or m o nes at d o u ble -bli n d Wee ks 4 a n d 1 3 a n d t o c o nstr uct a 9 5 % CI . T he m o del will a dj ust 
f or t he baseli ne val ue of t he h or m o ne para meter as a c o nti n uo us varia ble , a n d s per m 
c o nce ntrati o n ( 1 5 - 5 0 M/ m L , a n d > 5 0 M/ m L). Si nce n o s u bjects t o o k c o nc urre nt M T X, a n d 
ver y  fe w C D s u bjects were e nr olle d, t hese stratificati o n fact ors will n ot be i ncl u de d i n t he m o del. 
T he CI = R A N K o pti o n will be s pecifie d i n P R O C Q U A N T R E G i n S A S.
S hift ta bles fr o m baseli ne t o Wee k 4 a n d Wee k 1 3
will be s u m marize d b y  d o u ble-bli n d treat me nt 
gr o u p f or t he Se me n A nal y sis Set f or L H, F S H, i n hi bi n B, a n d t otal test oster o ne. T he s hift ta bles 
i ncl u de s hift a nalys is f or h or m o ne para meters bel o w, wit hi n, a n d a b o ve t he ce ntral la b orat or y 
defi ne d n or mal ra n ge f or eac h s pecific h or m o ne at baseli ne t o bel o w, wit hi n a n d a b o ve t he 
n or mal ra n ge at Wee k 4 a n d Wee k 1 3 .
Tre at me nt - Se q ue nce H or m o ne Dis pl a ys f or Wee k 2 6/ O L Wee k 1 3 a n d E xte nsi o n P h ase
Descri pti ve statistics will be prese nte d at Baseli ne, Wee k 2 6 / O L Wee k 1 3, a n d s u bse q ue nt visits 
b y  act ual treat me nt se q ue nce t o e x pl ore t he c o nf o u n di n g effects of res p o nse t o treat me nt. St u d y 
da y s will be use d f or assi g n me nt of a nalys is visit wi n d o ws f or su bjects w h o sta y e d o n 
ra n d o mize d dr u g t hr o u g h o ut st u d y a n d f or s u bjects w h o starte d o n d o u ble-bli n d fil g oti ni b a n d 
s witc he d t o o pe n-la bel fil g oti ni b. F or s u bjects w h o s witc he d fr o m place b o t o o pe n-la bel 
fil g oti ni b, da ys o n o pe n-la bel fil g oti ni b will be used t o assi g n a nal y sis visit wi n d o ws at/after 
O pe n -La bel Wee k 1 3 . Wee k 2 6 f or t he first 3 treat me nt se q ue nces will be dis pla ye d al o n g-si de 
O L  Wee k 1 3 f or place b o t o O L fil g oti ni b gr o u p; Wee k 3 9 al o n gsi de O L Wee k 2 6 f or place b o t o 
O L  fil g oti ni b gr o u p, etc. t o ali g n wit h t he ori gi nall y pla n ne d st u d y wee ks; b ut usi n g t he at/after 
Pr ot oc ol A me n d me nt 3 visit sc he d ule t o e ns ure t hat s u bjects were o n o pe n -la bel fil g oti ni b f or a n 
e ntire s per m c ycle f or t he place b o t o o pe n -la bel fil g oti ni b gr o u p.
A s u m mar y of t he 4 h or m o ne para meters a n d c ha n ge a n d perce nta ge c ha n ge fr o m baseli ne b y  
visit will be prese nte d f or s u bjects wit h e val ua ble se me n data at b ot h baseli ne a n d ≥1 of t he 
a nal ys is visits at/after Wee k 2 6/ O L Wee k 1 3. S hift ta bles fr o m baseli ne t o Wee k 2 6/ O L Wee k 1 3
f or L H, F S H, i n hi bi n B, a n d t otal test oster o ne will be s u m marize d b y  treat me nt se q ue nce f or t he 
Wee k 2 6/ E xte nsi o n P hase Se me n A nal ys is Set.
A b y -s u bject listi n g will be pr o vi de d f or h or m o nes . A se parate listi n g of t he h or m o ne data f or 
s u bjects w h o e ntere d t he M o nit orin g P hase of t he st u d y  will be pr o vi de d.
6. 7.
C h a n ges t o Pr ot oc ol -S pecifie d A n al yses of Se me n a n d H or m o ne D at a
T he pr ot oc ol s pecifie d a n a nal ys is of c o varia nce ( A N C O V A) m o del a dj usti n g f or baseli ne val ue 
a n d stratificati o n fact ors t o esti mate treat me nt differe nces ( 9 5 % CI) f or t he c o nti n u o us e n d p oi nts
at ti me p oi nts w here a nal ysis was t o be c o n d ucte d f or se me n para meters a n d h or m o ne data.
Q ua ntile re gressi o n was use d i n place of a n A N C O V A m o del as me dia ns were t h o u g ht t o be a
m ore a p pr o priate esti mat e t ha n mea ns f or t his data w hic h is p ote ntiall y  s ke we d wit h o utliers.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 4
1 3 Ja n uar y 2 0 2 1
Si nce n o s u bjects t o o k c o nc urre nt M T X i n t his st u d y, t he s u b gr o u p a nalys is b y M T X ( yes, n o) 
was n ot perf or me d . M T X use ( yes, n o) a n d disease t ype were n ot i ncl u de d as stratificati o n 
factors f or t he stratifie d Ma ntel -Hae nszel test f or t he pri mar y  e n d p oi nt or as a de pe n de nt varia ble 
i n q ua ntile re gressi o n m o dels f or s per m/se me n para meters (sec o n dar y e n d p oi nts) or h or m o nes 
(e x pl orat or y e n d p oi nts) si nce n o s u bjects t o o k M T X i n t his st u d y, a n d o nl y  a fe w C D s u bjects 
were e nr olle d. T he l o west 2 le vels ( 1 5 - 2 5 M/ m L  a n d > 2 5 - 5 0 M/ m L) f or s per m c o nce ntrati o n 
strata were c o m bi ne d i n t hese a nalys es d ue t o t he s mall n u m ber of s u bjects i n t he l o west s per m 
c o nce ntrati o n strat u m.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 5
1 3 Ja n uar y 2 0 2 1
7.
A S S E S S M E N T O F  R E S P O N D E R/ N O N -R E S P O N D E R A N D 
DI S E A S E W O R S E NI N G
C o m p osite sc ores i ncl u di n g p M C S f or U C a n d C D AI f or C D will be liste d usi n g all t he o bser ve d 
data base d o n t he All Ra n d o mize d A nal y sis Set.
7. 1. 1.
C alc ul ati o ns of M C S a n d p M C S wit h t he S u bsc ores
T he M C S is a n i nstr u me nt desi g ne d t o meas ure disease acti vit y  i n ulcerati ve c olitis (Ta b le 7- 1 ). 
T he M C S s y ste m is a c o m p osite i n de x of 4 disease acti vit y varia bles. Eac h varia ble is sc ore d 
i n di vi d uall y o n a n i nte ger scale of 0 t o 3, i ncl usi ve, wit h hi g her sc ores i n dicati n g greater disease 
acti vit y. T he i n di vi d ual c o m p o ne nts of t he M C S i ncl u de st o ol fre q ue nc y ( S F), rectal blee di n g 
( R B), e n d osc o pic s u bsc ore, a n d t he p hys icia n’s gl o bal assess me nt ( P G A). I n di vi d ual 
c o m p o ne nts of t he M C S are descri be d i n Ta b le 7- 1 a n d M C S
is calc ulate d as t he s u m of t he 
4 s u bsc ores, ra n gi n g fr o m 0 t o 1 2. A p M C S is calc ulate d as t he s u m of t he 3 s u bsc ores e xcl u di n g 
t he e n d osc o pic s u bsc ore; p M C S ra n ges fr o m 0 t o 9.  
T a b le 7- 1.
M a y o Cli nic Sc ore
V ari a bles
Sc ore
0
1
2
3
E n d osc o pic Fi n di n gs
N or mal or i nacti ve
Mil d disease
M o derate disease
Se vere disease
Rect al Blee di n g
N o ne
Strea ks of bl o o d i n 
st o ol less t ha n half 
t he ti me
O b vi o us bl o o d i n 
st o ol half or m ore 
t ha n half of t he ti me
Bl o o d al o ne 
passes
St o ol Fre q ue nc y
( per s u bject rec all)
N or mal n u m ber of 
dail y st o ols f or 
patie nt
1- 2 st o ols per da y  
m o re t ha n n or mal
3- 4 st o ols per da y 
m o re t ha n n or mal
≥5 st o ols per da y 
m o re t ha n n or mal
P h ysici a n Gl o b al 
Assess me nt
N o ne
Mil d disease
M o derate disease
Se vere disease
A Res p o n der f or U C is defi ne d as a s u bject w h o has a re d ucti o n of ≥2 i n p M C S c o m pare d t o 
baseli ne at t he s pe cifie d assess me nt ti me p oi nt. A N o n-res p o n der will be defi ne d as a s u bject w h o 
d oes n ot f ulfill t he defi niti o n of res p o n der at t he s pecifie d assess me nt ti me p oi nt. 
Disease W orse ni n g f or U C is defi ne d b y a p M C S after Wee k 1 3 c o nsisti n g of: 

a n i ncrease of ≥3 p oi nt s t o at least 5 p oi nts fr o m t he Wee k 1 3 val ue o n 2 c o nsec uti ve visits, 
or

a n i ncrease t o 9 p oi nts fr o m t he Wee k 1 3 val ue o n 2 c o nsec uti ve visits, if t he Wee k 1 3 val ue 
was > 6 p oi nts


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 6
1 3 Ja n uar y 2 0 2 1
7. 1. 2.
C alc ul ati o n of C D AI S c ores
T he C D AI s ys te m is a c o m p osite i n de x of 8 disease acti vit y varia bles wit h sc ores ra n gi n g fr o m 
0 t o o ver 6 0 0 base d u p o n a c o m p osite of sy m pt o ms (e g, a b d o mi nal pai n), si g ns (t he prese nce of 
a b d o mi nal mass a n d wei g ht), la b orat or y  val ues (e g, he mat ocrit), a n d p h y sicia n assess me nt 
a m o n gst ot hers. T he C D AI has 3 patie nt re p orte d o utc o me c o m p o ne nts: li q ui d or ver y  s oft st o ol 
fre q ue nc y, a b d o mi nal pai n a n d ge neral well bei n g. 
T he t otal C D AI sc ore f or a s pecific visit is base d o n a wei g hte d s u m (r o u n de d t o t he nearest 
i nte ger) of all 8 varia bles as s pecifie d i n Ta ble 7- 2 . T he C D AI t otal sc ore will be set t o 0 i n t he 
case t he calc ulati o n lea ds t o a C D AI t otal sc ore of < 0. Eac h c o m p o ne nt will be selecte d wit hi n 
t he a nalys is wi n d o w as defi ne d i n Secti o n 3. 7. 3 .
T a ble 7- 2.
C alc ul ati o n of T ot al C D AI Sc ore
V ari a ble n o.
V ari a ble
V ari a ble descri pti o n
M ulti plier
1
Li q ui d or ver y s oft st o ol
( per s u bject recall)
Dail y st o ol c o u nt is s u m me d f or 7 da ys
2
2
A b d o mi nal pai n
( per s u bject recall)
S u m of 7 da ys of dail y rati n gs as
0 = n o ne, 1 = mil d, 2 = m o derate, 3 = se vere
5
3
Ge neral well bei n g
( per s u bject recall)
S u m of 7 da ys of dail y rati n gs as
0 = ge nerall y well, 1 = sli g htl y bel o w  par, 2 = p o or, 
3 = ver y p o or, 4 = terri ble
7
4
C o m plicati o ns
N u m ber of liste d c o m plicati o ns:
- Art hritis or art hral gia
- Er y t he ma n o d os u m, p y o der ma ga n gre n os u m or 
a pt h o us st o matitis
- Iritis or u veitis
- A nal fiss ures or fist ulae or a bscess
- Ot her fist ula
- Fe ver o ver 3 7. 8 C [ 1 0 0 F] d uri n g past wee k
2 0 eac h
5
Use of a nti -diarr heal
Use of di p he n o x ylate or l o pera mi de or ot her o piate 
f or diarr hea
0 = N o, 1 = Yes
3 0
6
A b d o mi nal mass
0 = n o ne, 2 = q uesti o na ble, 5 = defi nite
1 0
7
H e m at ocrit *
Males: 4 7 – Hct [ %]
Fe m ales: 4 2 – Hct [ %]
* Res ult m ust be greater t ha n or e q ual t o 0. 
If ne gati ve res ult e nter 0
6 x differe nce
8
Wei g ht
#
Perce nta ge de viati o n fr o m sta n dar d we i g ht is
( 1-[ wei g ht/sta n dar d wei g ht]) * 1 0 0 .
# Li mit of -1 0 (res ult m ust be ≥- 1 0)
1
C D AI sc ore
T O T A L
C D AI = Cr o h n’s Disease Acti vit y I n de x; Hct = he mat ocrit
{ Sa n d b or n 2 0 0 2 }


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 7
1 3 Ja n uar y 2 0 2 1
T here are 2 l o o k u p ta bles ( 1 f or males; 1 f or fe males) t hat are use d t o deter mi ne t he sta n dar d 
wei g ht f or eac h s u bject. T w o ce nti meters s h o ul d be a d de d t o t h e e C R F c ollecte d hei g ht t o 
acc o u nt f or hei g ht bei n g c ollecte d s h oeless. T he l o o k u p ta bles were ge nerate d b y  a c hart t hat is 
c o m m o nl y use d f or C D st u dies f or t he Fil g oti ni b pr o gra m. T he l o o k u p ta bles e xist as S A S 
datasets i n t he f oll o wi n g cel b o o k area: \\gsas data \bi o metrics \gl o bal \cel \cel b o o ks \I B D _ S T _ W T\ 0. 
A Res p o n der f or C D is defi ne d as a s u bject w h o has a re d ucti o n of ≥ 1 0 0 p oi nts i n t otal C D AI  
sc ore c o m pare d t o baseli ne at t he s pecifie d assess me nt ti me p oi nt. A s u bject wit h a baseli ne t otal 
C D AI  sc ore of ≥2 2 0 t o ≤ 2 5 0 will be c o nsi dere d t o be a Res p o n der if a C D AI sc ore of < 1 5 0 is 
attai ne d at t he s pecifie d ti me p oi nt. A N o n -res p o n der will be defi ne d as a s u bject w h o d oes n ot 
f ulfill t he defi niti o n of res p o n der at t he s pecifie d assess me nt ti me p oi nt.
Disease W orse ni n g f or s u bjects wit h C D is defi ne d b y  a t otal C D AI sc ore after Wee k 1 3 
c o nsisti n g of: 

a sc ore ≥2 2 0 o n 2 c o ns ec uti ve visits, a n d

a n i ncrease of ≥1 0 0 p oi nts fr o m t he Wee k 1 3 val ue o n 2 c o nsec uti ve visits


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 8
1 3 Ja n uar y 2 0 2 1
8.
S A F E T Y  AN A L Y S E S
T he safet y a nal ys is will be c o n d ucte d o n t he Safet y A nal ysis Set, defi ne d i n Secti o n 3. 1. 3 u nless 
ot her wise n ote d.
8. 1.
A d verse E ve nts a n d De at hs
U p t o 3 differe nt dis pla y s of a d verse e ve nt data ma y be prese nte d as descri be d i n Secti o n 3. 2 of 
t his S A P:
“ As-treate d” a nalys is: S u bjects w h o s witc he d fr o m place b o t o o pe n- la bel fil g oti ni b will ha ve 
a d verse e ve nts occ urri n g w hile o n d o u ble- bli n d st u d y  dr u g s u m marize d wit h place b o, a n d 
a d verse e ve nts occ urri n g o n/after first d ose date of o pe n -la bel fil g oti nib t o last d ose date of 
fil goti ni b pl us 3 0 da y s (if per ma ne ntly disc o nti n ue d), or all a vaila ble data if o n g oi n g at ti me of 
a n i nteri m a nal ys is s u m marize d wit h fil g oti ni b. All ot her s u bjects will ha ve a d verse e ve nts 
occ urri n g o n/after first d ose date of a n y st u d y dr u g t o last d ose date of a n y dr u g pl us 3 0 da y s 
(if per ma ne ntl y  disc o nti n ue d), or all a vaila ble data if o n g oi n g at ti me of i nteri m a nal y sis 
s u m marize d b y treat me nt recei ve d. T his a nal ys is will s u m marize all o n-treat me nt a d verse e ve nts
a n d will be use d t o sca n f or all safet y e ve nts d uri n g t he st u d y.
D uri n g D o u ble - Bli n d P hase of t he S t u d y: Data will be i ncl u de d u p t o first d ose date of 
o pe n -la bel fil g oti ni b mi n us 1 da y  f or s u bjects w h o s witc he d t o o pe n-la bel fil g oti ni b; last d ose 
date of d o u ble -bli n d st u d y  dr u g pl us 3 0 da ys f or t h ose w h o ha ve per ma ne ntl y disc o nti n ue d fr o m 
st u d y dr u g; or all availa ble data w hile o n d o u ble- bli n d dr u g if o n g oi n g at t he ti me of a n i nteri m 
a nal ys is. T his a nal ys is will s u m marize a d verse e ve nts d uri n g t he sa me ti mefra me as t he pri mar y 
a nal ys is f or s per m/se me n data.
D uri n g O pe n -La bel Fil g oti ni b P hase of t he St u d y : Dat a will be i ncl u de d fr o m O L D a y 1 t o last 
d ose date of o pe n -la bel fil g oti ni b pl us 3 0 da ys f or t h ose w h o ha ve per ma ne ntl y disc o nti n ue d 
fr o m o pe n-la bel fil g oti ni b; or all a vaila ble data if o n g oi n g at t he ti me of a n i nteri m a nal ysis. 
T hese dis pla y s will s u m mar ize data f or s u bjects i n t he O pe n-La bel Fil g oti ni b Safet y  A nalys is 
Set. T his a nal y sis a p pr o priatel y a dj usts t he de n o mi nat or f or i nterr u pti o ns a n d disc o nti n uati o ns 
f or o pe n-la bel fil g oti ni b t o o nl y t h ose s u bjects w h o t o o k o pe n-la bel fil g oti ni b.
8. 1. 1.
A d verse E ve nt Dicti o n ar y
Cli nical a n d la b orat or y  a d verse e ve nts ( A Es) will be c o de d usi n g t he c urre nt versi o n of 
Me d D R A. S y ste m or ga n class ( S O C), hi g h-le vel gr o u p ter m ( H L G T), hi g h-le vel ter m ( H L T), 
preferre d ter m ( P T), a n d l o wer -le vel ter m ( L L T) will be pr o vi de d i n t he A E dataset.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 9
1 3 Ja n uar y 2 0 2 1
8. 1. 2.
A d verse E ve nt Se verit y
A d verse e ve nts are gra de d b y  t he i n vesti gat or as Gra de 1, 2, 3, 4, or 5 acc or di n g t o 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) Gra di n g Scale . If C T C A E criteria d o n ot 
e xist f or a s pecific e ve nt, Ta b le 7- 1 of t he st u d y pr ot oc ol pr o vi des g ui da nce f or t he i n vesti gat or 
t o gra de t he e ve nt. T he se verity gra de of e ve nts f or w hic h t he i n vesti gat or di d n ot rec or d se verit y 
will be cate g orize d as “ missi n g” f or ta b ular s u m maries a n d data listi n gs . T he missi n g cate g or y
will be liste d last i n s u m mar y prese ntati o n.
8. 1. 3.  
Rel ati o ns hi p of A d verse E ve nts t o St u d y Dr u g
Relate d A Es are t h ose f or w hic h t he i n vesti gat or selecte d “ Relate d” o n t he A E eC R F t o t he 
q uesti o n of “ Relate d t o St u d y  Treat me nt.” Relate d ness will al wa ys defa ult t o t he i n vesti gat or’s
c h oice, n ot t hat of t he me dical m o nit or. E ve nts f or w hic h t he i n vesti gat or di d n ot rec or d 
relati o ns hi p t o st u d y dr u g will be c o nsi dere d relate d to st u d y  dr u g f or s u m mar y p ur p oses. 
H o we ver, b y- s u bject data listi n gs will s h o w t he relati o ns hi p as missi n g.
8. 1. 4.
Seri o us A d verse E ve nts
Seri o us a d verse e ve nts ( S A Es) will be i de ntifie d a n d ca pt ure d as S A Es if t he A Es met t he 
defi niti o ns of S A E s t hat were s pecifie d i n t he st u d y pr ot oc ol. S A Es ca pt ure d a n d st ore d i n t he 
cli nical data base will be rec o ncile d wit h t he S A E data base fr o m t he Gilea d Gl o bal Patie nt Safet y  
(f or merl y Gilea d P har mac o vi gil ance a n d E pi de mi ol o g y ) De part me nt bef ore data base
fi nalizati o n.
8. 1. 5.
Tre at me nt -E m er ge nt A d verse E ve nts
8. 1. 5. 1.
Defi niti o n of Treat me nt -E mer ge nt A d verse E ve nts
Treat me nt -e mer ge nt a d verse e ve nts ( T E A Es) are defi ne d as 1 or b ot h of t he f oll o wi n g:

A n y  A Es 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 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
I n “as-treate d” dis pla ys, su bjects w h o t o o k d o u ble-bli n d place b o a n d s witc he d t o o pe n -la bel
fil g oti ni b wit h T E A Es wit h a n o nset date o n/after first d ose date of d o u ble -bli n d place b o a n d 
pri or t o t he first d ose date of o pe n -la bel fil g oti ni b will be attri b ute d t o t he place b o peri o d (a n d 
s u m marize d wit h t he place b o treat me nt gr o u p). T E A Es wit h a n o nset date o n or after t he 
first d ose date of o pe n -la bel fil g oti ni b u p t o last d ose date of o pe n- la bel fil g oti ni b + 3 0 d a y s or 
A Es t hat le d t o pre mat ure disc o nti n uati o n of O L fil g oti ni b will be attri b ute d t o t he fil g oti ni b 
peri o d (a n d s u m marize d wit h t he fil g oti ni b treat me nt gr o u p). 


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 5 0
1 3 Ja n uar y 2 0 2 1
8. 1. 5. 2.
I nc o m plet e Dates
If t he o nset date of t he A E is i nc o m plete a n d t he A E st o p date is n ot pri or t o t he first d osi n g date 
of st u d y  dr u g, t he n t he m o nt h a n d year ( or year al o ne if m o nt h is n ot rec or de d) of o nset 
deter mi ne w het her a n A E is treat me nt e mer ge nt . T he e ve nt i s c o nsi dere d treat me nt e mer ge nt if 
b ot h of t he f oll o wi n g 2 criteria are met:

T he A E o nset is t he sa me as or after t he m o nt h a n d year ( or year) of t he first d osi n g date of 
st u d y dr u g, a n d

T he A E o nset date is t he sa me as or bef ore t he m o nt h a n d year ( or year) of t he date 
c orres p o n di n g t o 3 0 da ys after t he date of t he last d ose of st u d y dr u g 
A n A E wit h c o m pletel y missi n g o nset a n d st o p dates, or wit h t he o nset date missi n g a n d a st o p 
date l ater t ha n t he first d osi n g date of st u d y dr u g, will be c o nsi dere d t o be treat me nt e mer ge nt. I n 
a d diti o n, a n A E wit h t he o nset date missi n g a n d i nc o m plete st o p date wit h t he sa me or later 
m o nt h a n d y ear ( or year al o ne if m o nt h is n ot rec or de d) as t he first d osi n g date of st u d y dr u g will 
be c o nsi dere d treat me nt e mer ge nt.
F or “as-treate d” dis pla ys, s u bjects w h o t o o k d o u ble-bli n d place b o a n d s witc he d t o o pe n -la bel
fil g oti ni b, re p orti n g a n A E wit h i nc o m plete o nset date t hat is pri or t o t he m o nt h a n d year 
( or yea r) of t he first d ose date of o pe n -la bel fil g oti ni b will ha ve t hat A E attri b ute d t o t he place b o 
peri o d (a n d s u m marize d wit h t he place b o treat me nt gr o u p). A n A E wit h i nc o m plete o nset date 
t hat is i n t he sa me or after t he m o nt h a n d year ( or year) of t he first d ose date of o pe n -la bel 
fil g oti ni b u p t o last d ose date of o pe n -la bel fil g oti ni b + 3 0 da ys will be attri b ute d t o t he fil g oti ni b 
peri o d (a n d s u m marize d wit h t he fil g oti ni b treat me nt gr o u p).
I n a d diti o n, a n A E wit h c o m pletel y missi n g o nset date or i nc o m plete o nset date t hat is sa me as 
t he m o nt h a n d year ( or year) of t he first d ose date of o pe n -la bel fil g oti ni b, a n d st o p date t hat is 
pri or t o t he date ( or m o nt h a n d year if da y is n ot rec or de d; or year al o ne if m o nt h is n ot rec or de d) 
of t he first d ose of o pe n -la bel fil g oti ni b will be attri b ute d t o t he place b o peri o d (a n d s u m marize d 
wit h t he place b o treat me nt gr o u p) . A n A E wit h c o m pletel y missi n g o nset date or i nc o m plete 
o nset date t hat is sa me as t he m o nt h a n d year ( or year) of t he first d ose date of o pe n -la bel 
fil g oti ni b, a n d st o p date t hat is missi n g, or t he sa me as, or after t he date ( or m o nt h a n d year if da y 
is n ot rec or de d; or ye ar al o ne if m o nt h is n ot rec or de d) of t he first d ose of o pe n -la bel fil g oti ni b 
u p t o last d ose date of o pe n -la bel fil g otini b + 3 0 d a y s will be attri b ute d t o t he fil g oti ni b peri o d
(a n d s u m marize d wit h t he fil g oti ni b treat me nt gr o u p).
8. 1. 5. 3.
A nal y sis of E x p os ure -A dj uste d I nci de nce Rates
T he E x p os ure -A dj uste d I nci de nce Rate ( E AI R) is defi ne d as:


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T he t otal patie nt -years of e x p os ure ( P Y E) t o a treat me nt is t he s u m of t he i n di vi d ual s u bject’s 
P Y E, w hic h is defi ne d as:

F or s u bjects wit h a n e ve nt:
W he n calc ulati n g P Y E, a partial A E o nset date will be i m p ute d as f oll o ws:
─
If t he n o n-missi n g p orti o n of t he A E o nset date ( m o nt h a n d/ or ye ar) is t he sa me as t he 
p orti o n of t he first d osi n g date ( m o nt h a n d/ or ye ar) of start of st u d y dr u g, t he A E o nset 
date will be i m p ute d as t he first d osi n g date of st u d y  dr u g; ot her wise it will be i m p ute d as 
t he 1st da y  of m o nt h (if o nl y da y is missi n g) or Ja n uar y 1st of t he year (if da y a n d m o nt h 
are missi n g).
─
If t he A E o nset date is c o m pletel y missi n g, t he A E o nset date will be i m p ute d as t he first 
d osi n g date of st u d y  dr u g.

F or s u bjects wit h n o e ve nt:
F or d o u ble -bli n d p h ase:
First d osi n g date = d o u bl e- bli n d first d ose date
Calc ulati o n e n d date = earliest n o n- missi n g date of (last d osi n g date of d o u ble-bli n d dr u g 
+ 3 0, first d osi n g date of O L  fil g oti ni b (if a p plica ble) – 1, data c ut off date, deat h date)
F or as -tre ate d a n alysis: 
Fil g oti ni b e x p os ure f or Pl ace b o t o O L fil g oti ni b : first d osi n g date = first d ose date O L 
fil g oti ni b; calc ulati o n e n d date is earliest n o n -missi n g date a m o n g (last d ose date of O L 
fil g oti ni b + 3 0 da ys, data c ut off date, deat h date)
Pl ace b o e x p os ure f or Pl ace b o t o O L fil g oti ni b: first d osi n g date = first d ose date 
place b o; calc ulati o n e n d da y  is earliest n o n - missi n g date a m o n g (first d ose date O L 
fil g oti ni b – 1 , data c ut off date, deat h date).
E x p os ure f or s u bjects re m ai ni n g o n d o u ble -bli n d dr u g : first d osi n g date = first d ose 
date d o u ble -bli n d dr u g; calc ulati o n e n d date is earliest date a m o n g (last d ose date d o u ble -
bli n d dr u g + 3 0, data c ut off date, deat h date)
Fil g oti ni b e x p os ure f or Fil g oti ni b t o O L fil g oti ni b : first d osi n g date = first d ose date 
d o u ble -bli n d dr u g; calc ulati o n e n d da y  is earliest n o n-missi n g date a m o n g (last d ose date 
of o pe n -la bel fil g oti ni b + 3 0, data c ut off date, deat h date).


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T he e xact 9 5 % CI base d o n P oiss o n distri b uti o n { Ul m 1 9 9 0 } f or E AI R is defi ne d as:
P artial last d osi n g date s of d o u ble-bli n d p hase will be i m p ute d as descri be d i n secti o n 4. 2. 1. 
I n a d diti o n t o b y treat me nt gr o u p s u m mar y, t he E AIR differe nce wit h 9 5 % CI  f or fil g oti ni b 
mi n us place b o will be prese nte d. T he Met h o d of Varia nc e Esti mates Rec o ver y ( M O V E R)-t ype 
c o nfi de nce i nter val descri be d i n { Li  2 0 1 1} will be use d t o calc ulate E AI R differe nce a n d 9 5 % 
CI :
w here n a is t he t otal n u m ber of s u bjects wit h t he e ve nt, T a is t he t otal P Y E, la is t he l o wer b o u n d 
a n d u a is t he u p per b o u n d of t he e xact 9 5 % CI base d o n P oiss o n distri b uti o n f or gr o u p a . 
Si milarl y  f or gr o u p b .
8. 1. 6.
S u m m aries of A d verse E ve nts a n d De at hs
A brief , hi g h -le vel s u m mar y of t he n u m ber a n d perce nta ge of s u bjects w h o e x perie nce d at least 
1 T E A E i n t he cate g ories descri be d bel o w will be pr o vi de d b y  treat me nt f or t he d o u ble-bli n d 
p hase, o pe n -la bel fil g oti ni b p hase, a n d f or a n “as -treate d” dis pla y:

T E A E

T E A Es wit h Gra de 3 or hi g her (f urt her br o ke n d o w n t o Gra de 3, Gra de 4, a n d Gra de 5 )

T E A Es wit h Gra de 2 or hi g her

T E treat me nt -relate d A E

T E treat me nt -relate d A Es wit h Gra de 3 or hi g her (f urt her br o ke n d o w n t o Gra de 3, Gra de 4, 
a n d Gra de 5)

T E treat me nt -relate d A Es wit h Gra de 2 or hi g her

T E S A E

T E treat me nt-relate d S A E 


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
T E A E t hat le d t o pre mat ure disc o nti n uati o n of d o u ble -bli n d st u d y dr u g ( dis pla ye d f or 
d o u ble -bli n d p hase a nal ysis o nl y )

T E A E t hat le d t o pre mat ure disc o nti n uati o n of o pe n- la bel fil g oti ni b st u d y dr u g ( dis pla ye d f or 
o pe n -la bel p hase a nal ysis o nl y )

T E A E t hat le d t o te m p orar y i nterr u pti o n of d o u ble -bli n d st u d y  dr u g ( dis pla ye d f or 
d o u ble -bli n d p hase a nal ysis o nl y )

T E A E t hat le d t o te m p orar y  i nterr u pti o n of o pe n -la bel st u d y dr u g ( dis pla ye d f or o pe n -la bel 
p hase a nal ys is o nly)

T E A E t hat le d t o pre mat ure disc o nti n uati o n of st u d y

A ll deat hs o bser ve d i n t he st u d y (if s u bject recei ve d ≥1 d ose of o pe n la bel fil g oti ni b will be 
s u m marized wit h o pe n -la bel fil g oti ni b; if last st u d y dr u g recei ve d was d o u ble-bli n d, will be 
s u m marize d wit h d o u ble bli n d st u d y  dr u g)
T he n u m ber a n d perce nta ge o f s u bjects w h o e x perie nce d at least 1 T E A E will be pr o vi de d a n d 
s u m marize d b y SO C, H L T, P T, a n d treat me n t f or t he d o u ble-bli n d p hase a n d f or a n “as-treate d”
a nal ys is.
T he f oll o wi n g 2 ta bles will be dis pla y e d f or t he d o u ble-bli n d p hase of t he st u d y  f or s u bjects i n 
t he Safety A nal ys is Set: 

T he n u m ber a n d perce nta ge of s u bjects w h o e x perie nce d T E A Es lea di n g t o te m p orar y  
i nterr u pti o n of d o u ble-bli n d st u d y  dr u g

A Es lea di n g t o pre mat ure disc o nti n uati o n of d o u ble -bli n d st u d y dr u g
Si milar ta bles will be dis pla y e d f or t he o pe n-la bel fil g oti ni b p hase of t he st u d y f or s u bjects i n t he 
O pe n -La bel Fil g oti ni b Safet y  A nalys is Set:

T he n u m ber a n d perce nta ge of s u bjects w h o e x perie nce d T E A Es lea di n g t o te m p orar y  
i nterr u pti o n of o pe n-la bel fil g oti ni b

A Es lea di n g t o pre mat ure disc o nti n uati o n of o pe n -la bel fil g oti ni b
F or ot her A Es descri be d bel o w, s u m maries (f or t he d o u ble- bli n d p hase a n d f or “as-treate d” 
a nal ys is) will be pr o vi de d b y  S O C, P T, a n d treat me nt:

All T E A E s

All T E A Es b y  C o nc o mita nt Me dicati o n Use (I m m u n o m o d ulat or a n d C ortic oster oi d Use)

T E A Es of Gra de 3 or hi g her ( by ma xi m u m se verit y)


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
T E A Es of Gra de 2 or hi g her

T E treat me nt-relate d A Es

T E Treat me nt -relate d A Es of Gra de 3 or hi g her ( b y ma xi m u m se verit y)

T E S A Es

T E S A Es b y  C o nc o mita nt Me dicati o n Use (I m m u n o m o d ulat or a n d C ortic oster oi d Use)

T E treat me nt-relate d S A Es

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

T E A Es lea di n g t o deat h
M ulti ple e ve nts will be c o u nte d o nl y  o nce per s u bject i n eac h s u m mar y . A d verse e ve nts will be 
s u m marize d a n d liste d first i n al p ha betic or der of S O C a n d H L T wit hi n eac h S O C (if a p plica ble), 
a n d t he n b y P T i n desce n di n g or der of t otal fre q ue nc y wit hi n eac h S O C. F or s u m maries by 
se verity gra de, t he m ost se vere gra de will be use d f or t h ose A Es t hat occ urre d m ore t ha n o nce i n 
an i n di vi d ual s u bject d uri n g t he st u d y. 
I n a d diti o n t o t he a b o ve s u m mar y ta bles, all T E A Es , S A Es, a n d T E treat me nt-relate d A Es will be 
su m marize d (f or t he d o u ble- bli n d p hase a n d f or “as-treate d” a nalys is) b y  P T o nl y, i n desce n di n g 
or der of t otal fre q ue nc y .
I n a d diti o n, data listi n gs will be pr o vi de d f or t he f oll o wi n g:

All A Es , i n dicati n g w het her t he e ve nt is treat me nt e mer ge nt

All A Es of Gra de 3 or hi g her

S A Es

Deat hs

C O VI D -1 9 A d verse E ve nts

All A Es lea di n g t o te m p orar y  i nterr u pti o n of d o u ble-bli n d st u d y dr u g

All A Es lea di n g t o te m p orar y  i nterr u pti o n of o pe n-la bel fil g oti ni b st u d y dr u g

A Es lea di n g t o pre mat ure disc o nti n uati o n of d o u ble -bli n d st u d y dr u g

A Es lea di n g t o pre mat ure disc o nti n uati o n of o pe n -la bel fil g oti ni b st u d y dr u g


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8. 1. 7.  
A d verse E ve nts of I nterest
A d verse e ve nts of i nterest ( A EIs) i ncl u de i nfecti o ns, gastr oi ntesti nal perf orati o ns, her pes z oster, 
mali g na ncies (e xcl u di n g n o n -mela n o ma s ki n ca ncers), n o n - mela n o ma s ki n ca ncers, a n d 
t hr o m b oe m b olic e ve nts. S u m maries of t he f oll o wi n g treat me nt-e mer ge nt A EIs will be pr o d uce d 
t o e n ha nce t he a nalys is of safety data. 

E ve nts of i nfecti o n prese nte d i n t he f oll o wi n g s u bcate g ories:

A Es of i nfecti o ns, utilizi n g all A Es i n t he Me d D R A I nfecti o ns a n d I nfestati o ns S O C

A Es of seri o us i nfecti o ns, usi n g all A Es i n t he Me d D R A I nfecti o ns a n d I nfestati o ns S O C 
t hat are classifie d as S A Es

A Es of her pes z oster, utilizi n g a Me d D R A searc h ter m ( M S T) list d e vel o pe d b y Gilea d 

A Es of o p p ort u nistic i nfecti o ns ( OIs), usi n g a Sta n dar dize d Me d D R A Q uer y  
( S M Q)--narr o w sc o pe

Acti ve t u berc ul osis , usi n g a n M S T list de vel o pe d b y Gilea d

He patitis B or C i nfecti o ns , usi n g a n M S T list de vel o pe d by Gilea d

A Es of mali g na nci es, e xcl u di n g n o n -mela n o ma s ki n ca ncers, utilizi n g a M S T list de vel o pe d 
b y  Gilea d 

A Es of n o n -mela n o ma s ki n ca ncers, utilizi n g a M S T list de vel o pe d b y  Gilea d

A Es of gastr oi ntesti nal perf orati o n, utilizi n g a M S T list  de vel o pe d b y  Gilea d 

A Es of arterial or ve n o us t hr o m b osis a n d/ or t hr o m b oe m b olis m, prese nte d i n t he f oll o wi n g 
s u bcate g ories:

A Es of ve n o us t hr o m b osis, utilizi n g a M S T list de vel o pe d b y Gilea d 

A Es of p ul m o nar y  e m b olis m, utilizi n g a M S T list de vel o pe d b y Gilea d

A Es of arterial t hr o m b osis, utilizi n g t he e m b olic a n d t hr o m b otic e ve nts, arterial 
Sta n dar dise d Me d D R A Q ueries ( S M Q)

A Es of cere br o vasc ular e ve nts, utilizi n g t he isc hae mic ce ntral ner v o us sys te m vasc ular 
c o n diti o ns S M Q


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F or t he d o u ble -bli n d p hase, t he n u m ber of s u bjects wit h a T E A EI (a n d S A E ), t he c orres p o n di n g 
P Y E, t he calc ulate d E AI R, a n d t he e xact 9 5 % CI s ( defi ne d i n Secti o n 8. 1.5. 3 ) will be 
s u m marize d f or eac h treat me nt gr o u p b y P T. T he E AIR differe nce ( fil g oti ni b – p lace b o) a n d 
c orres p o n di n g 9 5 % CIs f or t he differe nce bet wee n treat me nt g r o u ps will als o be prese nte d f or 
t he d o u ble-bli n d p hase of t he st u d y . 
F or t he o verall st u d y , t he n u m ber of s u bjects wit h a T E A EI i n eac h cate g or y (a n d se parately f or 
S A E s), t he c orres p o n di n g P Y E, t he calc ulate d E AIR, a n d t he e xact 9 5 % CI s ( defi ne d i n Secti o n 
8. 1. 5. 3) will be s u m marize d f or eac h treat me nt gr o u p (fil g oti ni b a n d place b o) b y P T usi n g a n 
as-treate d a nalys is. Fil g oti ni b gr o u p i ncl u des t he fil g oti ni b e x p os ure f or t he place b o t o fil g oti ni b
se q ue nce, a n d e x p os ure f or D B fil g oti ni b a n d fil g oti ni b t o O L  fil g oti ni b treat me nt se q ue nces. 
Place b o will i ncl u de D B Place b o a n d t he place b o e x p os ure f or t he Place b o t o O L  fil g oti ni b 
treat me nt se q ue nce.
Data listi n gs f or eac h A EI  will als o be pr o vi de d.
8. 1. 7. 1.
Car di o vasc ular E ve nt A dj u dicati o n C o m mittee
A n i n de pe n de nt car di o vasc ular e ve nt a dj u dicati o n c o m mittee ( C V E A C) re vie ws a n d a dj u dicates
all p ote ntial M A C E a n d t hr o m b oe m b olic e ve nts i n a bli n de d ma n ner.  T o i de ntif y  p ote ntial 
M A C E a n d t hr o m b oe m b olic e ve nts, t he f oll o wi n g A Es will be se nt f or a dj u dicat i o n. Please refer 
t o t he Car di o vasc ular E ve nt A dj u dicati o n C o m mittee C harter f or m ore details.

All A Es lea di n g t o deat h

C V e ve nts ( meeti n g seri o us criteria), utilizi n g a M S T list de vel o pe d b y  Gilea d

MI , utilizi n g a narr o w sc o pe Sta n dar dize d Me d D R A Q uer y ( SM Q) 

U nsta ble a n gi na ( meeti n g h os pitalizati o n criteria), utilizi n g a M S T list de vel o pe d b y  Gilea d

Tra nsie nt isc he mic attac k, utilizi n g a M S T list de vel o pe d b y Gilea d

Str o ke, utilizi n g a M S T list de vel o pe d b y  Gilea d

Car diac fail ure ( meeti n g h os pitalizati o n criteria), utilizi n g a M S T list de vel o pe d b y Gilea d

Perc uta ne o us c or o nar y  i nter ve nti o n, utilizi n g a M S T list de vel o pe d b y Gilea d

E m b olic a n d t hr o m b otic e ve nts, utilizi n g a narr o w sc o pe S M Q  
T he C V E A C will re vie w t he a b o ve A Es, a n d relate d cli nical data t o a dj u dicate w het her t he 
criteria f or M A C E ( C V deat h, MI, a n d/ or str o ke), A S T E, a n d V T E ha ve bee n met f or eac h A E. 


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T he n u m ber a n d perce nta ge of s u bjects wit h p ositi vel y  a dj u dicate d T E M A C E, T E A S T E, a n d 
T E V T E will be s u m marize d b y  treat me nt gr o u p usi n g t he a dj u dicate d cate g or y if a p plica ble f or 
t he fi nal a nalys is of t he st u d y o nl y.
A b y -s u bject listi n g f or s u bjects wit h p ote ntial e ve nts f or a dj u dicati o n ( M A C E, A S T E, a n d V T E) 
a n d t heir res pecti ve a dj u dicati o n res ults will be pr o vi de d f or i nteri m a n d fi nal anal ys es of t he 
st u d y.
A b y -s u bject listi n g of t hr o m b oe m b olic hist or y a n d ris k fact ors will be pr o vi de d f or s u bjects wit h 
p ote ntial e ve nts f or a dj u dicati o n ( M A C E, A S T E, a n d V T E) , if a p plica ble.
8. 1. 8.
A n al ysis of A d verse E ve nts b y Tre at me nt Se q ue nce (Fi n al A n al ysis o nl y )
F or t he fi nal a nal ys is ( w he n all l o n g-ter m data is a vaila ble), a n a d diti o nal “as-treate d” a nalys is of 
All T E A Es, S A Es, a n d A EI s will be pr o vi de d.  T he n u m ber a n d perce nta ge of s u bjects wit h 
e ve nts will be dis pla ye d b y o verall treat me nt gr o u p a n d f or eac h of t he treat me nt se q ue nces 
wit hi n a treat me nt gr o u p as s h o w n bel o w:
F or p lace b o gr o u p,
All Place b o
D B Place b o
E/ T Pri or t o 
Wee k 2 6
*
Place b o e x p os ure:
D B Place b o t o 
O L  Fil g oti ni b
D B Place b o
at/after 
Wee k 2 6
*
F or fil g oti ni b gr o u p,
All Fil g oti ni b
D B Fil g oti ni b 
E/ T Pri or t o 
Wee k 2 6
*
Fil g oti ni b e x p os ure:
D B Place b o t o 
O L  Fil g oti ni b
D B Fil g oti ni b 
t o
O L  Fil g oti ni b
D B Fil g oti ni b 
at/after 
Wee k 2 6
*
D B = d o u ble -bli n d; E/ T = earl y ter mi nati o n of st u d y dr u g; O L = o pe n -la bel;  * = s u bject ne ver recei ve d O L fil g oti ni b (eit her met 
s per m st o p pi n g criteria a n d e ntere d m o nit ori n g p hase or E/ T f or ot her reas o ns).
8. 2.
L a b or at or y E v al u ati o ns
La b orat or y  data c ollected d uri n g t he st u d y  will be s u m marize d usi n g b ot h q ua ntitati ve a n d 
q ualitati ve met h o ds. S u m maries of la b orat or y data will be pr o vi de d f or t he Safet y  A nalys is Set 
a n d will be b y act ual treat me nt usi n g a n “as-treate d” a nal ys is. F or “as -treate d” dis pla ys, su bjects 
o n d o u ble - bli n d place b o w h o s witc h t o o pe n-la bel fil g oti ni b will ha ve data c ollecte d u p t o first 
d ose date of fil g oti ni b attri b ute d t o place b o (s u m marize d wit h place b o) a n d data c ollecte d after
first d ose of o pe n-la bel fil g oti ni b t o last d ose date of fil g oti ni b + 3 0 da ys attri b ute d t o fil g oti ni b 
(s u m marize d wit h fil g oti ni b). Ot her s u bjects will ha ve p ost -baseli ne data i ncl u de d u p t o last d ose 
date + 3 0 da y s if ter mi nate d fr o m st u d y dr u g; or all a vaila ble data at ti me of a n i nteri m a nalys is. 
A nal y sis will be base d o n val ues re p orte d i n c o n ve nti o nal u nits. W he n val ues are bel o w t he 
L O Q, t he y  will be liste d as s uc h, a n d t he cl osest i m p ute d val ue will be use d f or t he p ur p ose of 
calc ulati n g s u m mar y statistics as s pecifie d i n Secti o n 3. 7 . He m oly ze d test res ults will n ot be 
i ncl u de d i n t he a nalys is, b ut t he y will be liste d i n b y-s u bject la b orat or y listi n gs.  


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A b y -s u bject listi n g f or la b orat or y test res ults will be pr o vi de d b y s u bject I D n u m ber a n d ti me 
p oi nt i n c hr o n ol o gical or der f or he mat ol o g y , ser u m c he mistr y, a n d uri nalysis se paratel y. Val ues 
falli n g o utsi de of t he rele va nt refere nce ra n ge a n d/ or ha vi n g a se verit y  gra de of 1 or hi g her base d 
o n C T C A E criteria will be fla g ge d i n t he data listi n gs, as a p pr o priate.
N o f or mal statistical testi n g is pla n ne d.
8. 2. 1. 
S u m m aries of N u meric L a b or at or y Res ults
Descri pti ve statistics will be pr o vi de d b y treat me nt gr o u p f or selecte d la b orat or y tests as f oll o ws:

Baseli n e val ues 

Val ues at eac h p ost baseli ne ti me p oi nt

C ha n ge fr o m baseli ne at eac h p ost baseli ne ti me p oi nt
A baseli ne la b orat or y  val ue will be defi ne d as t he last meas ure me nt o btai ne d o n or pri or t o t he 
first d ose date of d o u ble -bli n d st u d y dr u g. F or “as -treate d” dis pla ys, s u bjects w h o t o o k 
d o u ble -bli n d place b o a n d s witc he d t o o pe n -la bel fil g oti ni b will ha ve t he baseli ne val ue use d f or 
place b o peri o d a n d t he O pe n -la bel B aseli ne will be use d f or t he a nal ys is f or data c ollecte d after 
t he first d ose of o pe n -la bel fil g oti ni b. Data c ollecte d w hile o n d o u ble -bli n d place b o will be 
s u m marize d wit h place b o treat me nt, a n d data c ollecte d w hile o n o pe n-la bel fil g oti ni b will be 
s u m marize d wit h fil g oti ni b. C ha n ge fr o m baseli ne t o a p ost baseli ne visit will be defi ne d as t he 
visit val ue mi n us t he baseli ne val ue ( or mi n us O L baseli ne f or t he fil g oti ni b peri o d f or 
“as-treate d” a nalys is f or s u bjects w h o s witc he d fr o m d o u ble-bli n d place b o t o O L  fil g oti ni b). T he 
mea n, me dia n, Q 1, Q 3, mi ni m u m, a n d ma xi m u m val ues will be dis pl a ye d t o t he re p orte d n u m ber 
of di gits; S D val ues will be dis pla y e d t o t he re p orte d n u m ber of di gits pl us 1.
Me dia n ( Q 1, Q 3 ) c ha n ge fr o m baseli ne f or selecte d la b orat or y tests w ill be pl otte d usi n g a li ne 
pl ot b y  treat me nt gr o u p a n d ti me p oi nt.
I n t he case of m ulti ple val ues i n a n a nalys is wi n d o w, data will be selecte d f or a nalys is as 
descri be d i n Secti o n 3. 7. 3 .
8. 2. 2.
Gr a de d L a b or at or y V al ues
T he C T C A E versi o n 4. 0 3 will be use d t o assi g n t o xicit y gra des ( 0 t o 4) t o la b orat or y res ults f or 
a nal ys is. Gra de 0 i ncl u des all val ues t hat d o n ot meet t he criteria f or a n a b n or malit y of at least 
Gra de 1. F or la b orat or y tests wit h criteria f or b ot h i ncrease d a n d decrease d le vels, a nal ys es f or 
eac h directi o n (ie, i ncrease d, decrease d) will be prese nte d se paratel y. 


Fil g oti ni b
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1 3 Ja n uar y 2 0 2 1
8. 2. 2. 1.
Treat me nt -E mer ge nt La b orat or y  A b n or malities
Treat me nt -e mer ge nt la b orat or y a b n or malities are 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 ny p ost baseli ne ti me p oi nt, u p t o a n d i ncl u di n g t he date of last 
d ose of a n y st u d y dr u g pl us 3 0 da ys f or s u bjects w h o per ma ne ntl y di sc o nti n ue d st u d y dr u g, or 
t he last a vaila ble date i n t he data base s na ps h ot f or s u bjects w h o were still o n treat me nt at t he 
ti me of a n i nteri m a nalys is. 
F or “as-treate d” dis pla ys a n d s u bjects w h o t o o k d o u ble-bli n d place b o a n d s witc he d t o o pe n -la bel 
fil g otini b , treat me nt-e mer ge nt la b orat or y a b n or malities f or t he place b o peri o d (s u m marize d wit h 
place b o gr o u p) are 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 
p ost baseli ne ti me p oi nt, u p t o a n d i ncl u di n g t he first d ose date of o pe n -la bel fil g oti ni b. 
Treat me nt -e mer ge nt la b orat or y a b n or malities of t he fil g oti nib peri o d (s u m marize d wit h 
fil g oti ni b gr o u p) are defi ne d as val ues t hat i ncrease at least 1 t o xicit y  gra de fr o m t he O pe n -la bel 
B aseli ne u p t o a n d i ncl u di n g t he date of last d o se of a n y st u d y dr u g pl us 3 0 da ys, or t he last 
a vaila ble date i n t he data base s na ps h ot f or s u bjects w h o were still o n treat me nt at t he ti me of a n 
i nteri m a nal ysis.
F or all ot her s u bjects, treat me nt-e mer ge nt la b orat or y a b n or malities are defi ne d as val ues t h at 
i ncrease 1 t o xicit y gra de fr o m t he d o u ble -bli n d baseli ne at a n y p ost baseli ne ti me p oi nt, u p t o a n d 
i ncl u di n g t he date of last d ose of a ny st u d y dr u g pl us 3 0 da y s ( or all a vaila ble data if o n g oi n g at 
a n i nteri m a nal ys is).
If t he rele va nt baseli ne la b orator y  val ue is missi n g, a n y a b n or mality of at least Gra de 1 o bser ve d 
wit hi n t he ti me fra me s pecifie d a b o ve will be c o nsi dere d treat me nt e mer ge nt.
8. 2. 2. 2.
Treat me nt -E mer ge nt Mar ke d La b orat or y  A b n or malities
Treat me nt -e mer ge nt mar ke d la b orat or y a b n or malities are defi ne d as val ues t hat i ncrease fr o m 
baseli ne b y at least 3 t o xicit y gra des at a n y p ost baseli ne ti me p oi nt, u p t o a n d i ncl u di n g t he date 
of t he last d ose of a n y st u d y  dr u g pl us 3 0 da ys f or s u bjects w h o per ma ne ntl y disc o nti n ue d st u d y 
dr u g or t he last a vaila ble da te i n t he data base s na ps h ot f or s u bjects w h o were still o n treat me nt at 
t he ti me of a n i nteri m a nal ysis.
F or “as-treate d” dis pla y s a n d place b o -treate d s u bjects w h o s witc h t o o pe n -la bel fil g oti ni b, 
treat me nt-e mer ge nt mar ke d la b orat or y  a b n or malities of t he place b o peri o d (s u m marize d wit h 
place b o gr o u p) are defi ne d as val ues t hat i ncrease at least 3 t o xicit y gra des fr o m baseli ne at a ny 
p ost baseli ne ti me p oi nt, u p t o a n d i ncl u di n g t he first d ose date of o pe n -la bel fil g oti ni b. 
Treat me nt -e mer ge nt la b orat or y a b n or malities d uri n g t he o pe n-la bel fil g oti nib peri o d 
(s u m marize d wit h fil g oti ni b gr o u p) are defi ne d as val ues t hat i ncrease at least 3 t o xicit y  gra des
fr o m O pe n-la bel Baseli ne at a n y p ost baseli ne ti m e p oi nt, u p t o a n d i ncl u di n g t he date of last d ose 
of a n y st u d y dr u g pl us 3 0 da y s, or t he last a vaila ble date i n t he data base s na ps h ot f or s u bjects 
w h o were still o n treat me nt at t he ti me of a n i nteri m a nal y sis.


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Versi o n 1. 0
C O N FI D E N TI A L
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1 3 Ja n uar y 2 0 2 1
F or all ot her s u bjects, treat me nt -e mer ge nt la b orat or y a b n or malities are defi ne d as val ues t hat 
i ncrease 3 t o xicit y gra des fr o m t he d o u ble-bli n d baseli ne at a n y  p ost baseli ne ti me p oi nt, u p t o 
a n d i ncl u di n g t he date of last d ose of a n y st u d y dr u g pl us 3 0 d a y s ( or all a vaila ble data if 
o n g oi n g at a n i n teri m a nal ysis).
If t he rele va nt baseli ne la b orat or y val ue is missi n g, a n y Gra de 3 or 4 val ues o bser ve d wit hi n t he 
ti mefra me s pecifie d a b o ve will be c o nsi dere d treat me nt-e mer ge nt mar ke d a b n or malities.
8. 2. 2. 3.
S u m maries of La b orat or y  A b n or malities
T he f oll o wi n g s u m maries ( n u m ber a n d perce nta ge of s u bjects) f or treat me nt -e mer ge nt la b orat or y 
a b n or malities will be pr o vi de d b y  la b test a n d treat me nt gr o u p; s u bjects will be cate g orize d 
acc or di n g t o t he m ost se vere p ost baseli ne a b n or malit y  gra de f or a gi ve n la b test:

Gra d e d la b orat or y a b n or malities (f or t he fi nal a nal ysis of t he st u d y o nl y )

Gra de 3 or 4 la b orat or y a b n or malities

Mar ke d la b orat or y  a b n or malities
F or all s u m maries of la b orat or y  a b n or malities, t he de n o mi nat or is t he n u m ber of s u bjects wit h 
n o n missi n g p ost baseli ne val ues u p t o t he first d ose date of o pe n la bel fil g oti ni b f or place b o 
s u bjects w h o s witc h t o o pe n-la bel fil g oti ni b; u p t o 3 0 da y s after per ma ne nt disc o nti n uati o n of 
dr u g ; or t o t he last a vaila ble date i n t he data base s na ps h ot f or s u bjects w h o were still o n 
treat me nt at t he ti me of a n i nteri m a nal ysis.
A b y -s u bject listi n g of treat me nt-e mer ge nt Gra de 3 or 4 la b orat or y a b n or malities will be 
pr o vi de d b y s u bject I D n u m ber a n d ti me p oi nt i n c hr o n ol o gical or der. T his listi n g will i ncl u de all 
test res ults t hat were c ollecte d t hr o u g h o ut t he st u d y f or t he la b test of i nterest, wit h all a p plica ble 
se verity gra de s dis pla y e d .
8. 2. 3.
Li ver -rel ate d L a b or at or y E v al u ati o ns
L i ver-relate d a b n or malities will be e xa mi ne d a n d s u m marize d usi n g a n “as -treate d” a nal ysis of 
t he n u m ber a n d perce nta ge of s u bjects wit h at least 1 val ue i n t he re p orti n g peri o d f or t he 
f oll o wi n g:

A S T: (a) > 3 ti mes t he u p per li mit of n or mal ra n ge ( U L N); ( b) > 5 x U LN; (c) > 1 0 x U L N; 
( d) > 2 0 x U L N

A L T: (a) > 3 x U L N; ( b) > 5 x U L N; (c) > 1 0 x U L N; ( d) > 2 0 x U L N

(A S T or A L T > 3 x U L N ) a n d (t otal bilir u bi n > 2 x U L N)


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F or i n di vi d ual la b orat or y tests, s u bjects will be c o u nte d o nce base d o n t he ir m ost se vere
p ost baseli ne val ue u p t o last d ose date pl us 3 0 da ys . F or t he c o m p osite e n d p oi nt of A S T or A L T 
a n d t otal bilir u bi n, s u bjects will be c o u nte d o nce w he n t he criteria are met at t he sa me 
p ost baseli ne visit date. T he de n o mi nat or is t he n u m ber of s u bjects i n t he Safet y A nal ys is Set w h o 
ha ve at least 1 n o n missi n g p ost baseli ne val ue of all rele va nt tests at t he sa me p ost baseli ne visit 
date. A listi n g of s u bjects w h o met at least 1 of t he a b o ve criteria will be pr o vi de d.
F or “as-treate d” dis pla ys a n d s u bjects ra n d o mize d t o place b o w h o s witc he d t o o pe n-la bel 
fil g oti ni b, t he m ost se vere p ost baseli ne val ue c ollecte d u p t o t he first d ose date of o pe n-la bel 
fil g oti ni b will be s u m marize d wit h t he place b o gr o u p. T he m ost se vere p ost baseli ne val ue 
c ollecte d after first d ose date a n d u p t o t he last d ose date of o pe n -la bel fil g oti ni b pl us 3 0 da ys 
will be s u m marize d w it h t he fil g oti ni b gr o u p. 
8. 3.
B o d y Wei g ht a n d Vit al Si g ns
D escri pti ve statistics will be pr o vi de d b y treat me nt usi n g a n “as -treate d” a nal ysis f or b o dy 
wei g ht, B MI a n d vital si g ns ( p ulse, sys t olic a n d diast olic bl o o d press ure, res pirati o n rate, a n d 
te m perat ure) as f oll o ws:

Baseli ne val ue

Val ues at eac h p ost baseli ne ti me p oi nt

C ha n ge fr o m baseli ne at eac h p ost baseli ne ti me p oi nt
A baseli ne val ue will be defi ne d as t he last a vaila ble val ue c ollec te d o n or pri or t o t he date of 
first d ose of st u d y dr u g. F or “as-treate d” dis pla ys a n d s u bjects w h o t o o k d o u ble -bli n d place b o 
a n d s witc he d t o o pe n -la bel fil g oti ni b, t he baseli ne val ue will be use d t o calc ulate c ha n ge fr o m 
baseli ne d uri n g t he d o u ble- bli n d place b o peri o d (s u m marize d wit h place b o gr o u p). T he 
O pe n -La bel B aseline will be use d t o calc ulate c ha n ge fr o m baseli ne f or val ues c ollecte d after t he 
first d ose date a n d u p t o last d ose date of o pe n-la bel fil g oti ni b pl us 3 0 da ys (s u m marize d wit h 
fil g oti ni b gr o u p). C ha n ge fr o m baseli ne t o a p ost baseli ne visit will be defi ne d as t he p ost baseli ne
val ue mi n us t he baseli ne val ue.
I n t he case of m ulti ple val ues i n a n a nalys is wi n d o w, data will be selecte d f or a nalys is as 
descri be d i n Secti o n 3. 7. 3 . N o f or mal statistical testi n g is pla n ne d.
A b y -s u bject listi n g of vital si g ns will be pr o vi de d b y s u bject I D n u m ber a n d ti me p oi nt i n 
c hr o n ol o gical or der. B o d y  wei g ht , hei g ht, a n d B MI will b e i ncl u de d i n t he vital si g ns listi n g, if 
s pace per mits. If n ot, t he y will be pr o vi de d se paratel y .
8. 4.
Pri or a n d C o nc o mit a nt Me dic ati o ns
Me dicati o ns c ollecte d at s cree ni n g a n d d uri n g t he st u d y  will be c o de d usi n g t he c urre nt versi o n 
of t he W H O Dr u g dicti o nar y .


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8. 4. 1. 
Pri or Me dic ati o ns
Pri or me dicati o ns are defi ne d as a n y me dicati o n s ta ke n bef ore a s u bject t o o k t heir first d ose of 
st u d y dr u g.
If a partial start date is e ntere d, t he me dicati o n will be c o nsi dere d pri or u nless t he m o nt h a n d 
ye ar (if da y is missi n g) or year (if da y a n d m o nt h are missi n g) of t he start date are after t he first 
d osi n g date. Me dicati o ns wit h a c o m pletel y missi n g start date will be ass u me d t o be a pri or 
me dicati o n , u nless ot her wise s pecifie d.
Pri or me dicati o ns will be liste d as part of t he Pri or a n d C o nc o mita nt Me dicati o ns listi n g.
8. 4. 2.
C o nc o mit a nt Me dic ati o ns
C o nc o mita nt me dicati o ns are defi ne d as me dicati o ns ta ke n w hile a s u bject is als o ta ki n g st u d y 
dr u g. F or “as-treate d” dis pla ys a n d s u bjects ra n d o mized t o place b o a n d s witc hi n g t o o pe n -la bel 
fil g oti ni b, t he me dicati o ns ta ke n bet wee n first a n d last d ose dates of d o u ble-bli n d place b o will be 
s u m marize d wit h t he place b o gr o u p. F or t he o pe n-la bel p hase, me dicati o ns ta ke n bet wee n first 
a n d last d ose dates of o pe n -la bel fil g oti ni b will be s u m marize d wit h t he fil g oti ni b gr o u p. Use of 
c o nc o mita nt medicati o ns will be s u m marize d b y  A T C preferre d na me usi n g t he n u m ber a n d 
perce nta ge of s u bjects f or eac h treat me nt gr o u p. A s u bject re p orti n g t he sa me me dicati o n m ore 
t ha n o nce will be c o u nte d o nl y o nce w he n calc ulati n g t he n u m ber a n d perce nta ge of s u bjects 
w h o recei ve d t hat me dicati o n. T he s u m mar y  will be pr o vi de d by preferre d ter m i n desce n di n g 
o verall fre q ue nc y . F or dr u gs wit h t he sa me fre q ue nc y, s orti n g will be d o ne al p ha beticall y.
F or t he p ur p oses of a nal ysis, a n y me dicati o n s wit h a start date pri or t o or o n t he first d osi n g date 
of st u d y  dr u g a n d c o nti n ue d t o be ta ken after t he first d osi n g date or starte d after t he first d osi n g 
date b ut pri or t o or o n t he last d osi n g date of st u dy dr u g will be c o nsi dere d c o nc o mita nt 
me dicati o ns. Me dicati o ns starte d a n d st o p pe d o n t he sa me da y  as t he first d osi n g date or t he last 
d osi n g date of st u d y  dr u g will als o be c o nsi dere d c o nc o mita nt. Me dicati o ns wit h a st o p date pri or 
t o t he date of first d osi n g date of st u dy dr u g or a start date after t he last d osi n g date of st u d y dr u g 
will be e xcl u de d fr o m t he c o nc o mita nt me dicati o n s u m mar y . If a partial st o p date is e ntere d, a ny 
me dicati o n wit h t he m o nt h a n d y ear (if da y is missi ng) or ye ar (if da y a n d m o nt h are missi n g) 
pri or t o t he date of first st u d y  dr u g a d mi nistrati o n will be e xcl u de d fr o m t he c o nc o mita nt 
me dicati o n s u m mar y . If a partial start date is e ntere d, a ny me dicati o n wit h t he m o nt h a n d year 
(if d a y  is missi n g) or ye ar (if da y a n d m o nt h are missi n g) after t he st u d y dr u g st o p date will be 
e xcl u de d fr o m t he c o nc o mita nt me dicati o n s u m mar y . Me dicati o ns wit h c o m pletel y missi n g start 
a n d st o p dates will be i ncl u de d i n t he c o nc o mita nt me dicati o n s u m mar y , u nless ot her wise 
s pecifie d (ie, t he me dicati o n is s pecificall y mar ke d as a pri or me dicati o n o n t he e C R F).
S u m maries will be base d o n t he Safety A nal ys is Set. N o f or mal statistical testi n g is pla n ne d.
All pri or a n d c o nc o mita nt me dicati o ns ( ot her t ha n per-pr ot oc ol st u d y  dr u gs) wil l be pr o vi de d i n a 
b y -s u bject listi n g s orte d b y  s u bject I D n u m ber a n d a d mi nistrati o n date i n c hr o n ol o gical or der.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 6 3
1 3 Ja n uar y 2 0 2 1
8. 5.
Electr oc ar di o gr a m ( E C G) Res ults
A s hift ta ble of t he i n vesti gat or’s assess me nt of E C G res ults at St u d y  Wee k 2 6/O L  Wee k 1 3/E T
a n d at L T E Wee k 1 9 5/ E T c o m pare d wit h baseli ne val ues will be prese nte d b y  treat me nt 
se q ue nce ( D B Fil g oti ni b; D B Fil g oti ni b t o O L Fil g oti ni b, D B Place b o; D B Place b o t o O L 
Fil g oti ni b) usi n g t he f oll o wi n g cate g ories: n or mal; a b n or mal ( n ot cli nicall y si g nific a nt); 
a b n or mal (cli nicall y si g nifica nt); or missi n g . Baseli ne val ues will be E C Gs c ollecte d wit h a 
n o mi nal visit of “ Scree ni n g”; Wee k 2 6 will ha ve n o mi nal visits of “ Wee k 2 6” , “ O L Wee k 1 3”; 
or “ E arl y Ter mi nati o n ”--if early ter mi nati o n ( E T) pri or t o Wee k 2 6 (s u bject di d n ot e nr oll i n 
L T E) , a n d L T E Wee k 1 9 5 /E T will ha ve n o mi nal visits of “ L T E Wee k 1 9 5” or “ E arl y 
Ter mi nati o n ” if earl y ter mi nati o n after Wee k 2 6 (e nr olle d i n L T E).
T he n u m ber a n d perce nta ge of s u bjects i n eac h cr oss -classificati o n gr o u p of t he s h ift ta ble will 
be prese nte d b y  treat me nt se q ue nce. S u bjects wit h a missi n g val ue at baseli ne or p ost baseli ne 
will n ot be i ncl u de d i n t he de n o mi nat or f or perce nta ge calc ulati o n.
N o f or mal statistical testi n g is pla n ne d. A b y- s u bject listi n g f or E C G assess me nt res ults will be 
pr o vi de d b y s u bject I D n u m ber a n d visit i n c hr o n ol o gical or der.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 6 4
1 3 Ja n uar y 2 0 2 1
9.
P H A R M A C O KI N E TI C A N A L Y S E S
C o nce ntrati o ns of fil g oti ni b a n d G S -8 2 9 8 4 5 i n plas ma will be deter mi ne d usi n g vali date d 
bi oa nal y tical met h o ds. T he P K a nalys is will be c o n d ucte d o n t he P K A nalysis Set, defi ne d i n 
Secti o n 3. 1. 4 .
I n di vi d ual s u bject c o nce ntrati o n data f or fil g oti ni b a n d G S-8 2 9 8 4 5 will be liste d (i ncl u di n g date 
a n d ti me of last fil g oti ni b st u d y  dr u g a d mi nistrati o n; P K c ollecti o n date a n d ti me; a n d ti me 
p ost - d ose t hat t he P K sa m ple was c ollecte d).


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 6 5
1 3 Ja n uar y 2 0 2 1
1 0.
R E F E R E N C E S
C o o per T G, N o o na n E, v o n Ec kar dstei n S, A u ger J, Ba ker H W, Be hre H M, et al. W orl d Healt h 
Or ga nizati o n refere nce val ues f or h u ma n se me n c haracteristics. H u ma n 
re pr o d ucti o n u p date 2 0 1 0; 1 6 ( 3): 2 3 1- 4 5.
Jar vi K, D ula E, Dre h o bl M, Pr yor J, S ha pir o J, Se ger M. Dail y  var de nafil f or 6 m o nt hs has n o 
detri me ntal effects o n se me n c haract eristics or re pr o d ucti ve h or m o nes i n me n 
wit h n or mal baseli ne le vels. J Ur ol 2 0 0 8; 1 7 9 ( 3): 1 0 6 0 - 5.
K oc h G G, Carr GJ, A mara I A, St o kes M E, Ur y nia k TJ. Cate g orical Data A nal y sis. C ha pter 1 3 i n 
Berr y , D. A. (e d.).  Statistical Met h o d ol o g y i n t he P har mace utical Scie nces. Ne w 
Y or k: Marcel De k ker, I nc., 1 9 8 9: p p. 4 1 4- 2 1. 
R u bi n D B. M ulti ple I m p utati o n f or N o nres p o nse i n S ur ve y s. Ne w Y or k, N Y: J o h n Wile y & 
S o ns, I nc; 1 9 8 7. 
Sa n d b or n WJ, Fea ga n B G, Ha na uer S B, L oc hs H, L of ber g R, M o di glia ni R, et al. A re vie w of 
acti vit y i n dices a n d efficac y e n d p oi nts f or cli nical trials of me dical t hera p y i n 
a d ults wit h Cr o h n's disease. Gastr oe nter ol o g y  2 0 0 2; 1 2 2 ( 2): 5 1 2- 3 0.
U. S. De part me nt of Healt h a n d H u ma n Ser vices ( D H H S), F o o d a n d Dr u g A d mi nistrati o n 
( F D A), Ce nter f or Dr u g E val uati o n a n d Researc h ( C D E R). Testic ular T o xicit y: 
E val uati o n D uri n g Dr u g De vel o p me nt G ui da nce f or I n d ustr y .  2 0 1 8.
W orl d Healt h Or ga nizati o n ( W H O). W H O La b orat or y  ma n ual f or t he e xa mi nati o n of h u ma n 
se me n a n d s per m-cer vical m uc us i nteracti o n. T hir d E diti o n.  1 9 9 2.
W orl d Healt h Or ga nizati o n ( W H O). W H O La b orat or y  ma n ual f or t he E xa mi nati o n a n d 
pr ocessi n g of h u ma n se me n. Fift h E diti o n.  2 0 1 0.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 6 6
1 3 Ja n uar y 2 0 2 1
1 1.
S O F T WA R E
S A S ® S oft ware Versi o n 9. 4 . S A S Instit ute I nc., Car y , N C, U S A.
n Q uer y  A d vis or( R) Versi o n 4 . 0. Statistical S ol uti o ns, C or k, Irela n d.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 6 7
1 3 Ja n uar y 2 0 2 1
1 2.
S A P  R E VI SI O N
Re visi o n D ate
(D D M M M Y Y Y Y )
Secti o n
S u m m ar y of Re visi o n
Re as o n f or Re visi o n


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 6 8
1 3 Ja n uar y 2 0 2 1
1 3.
A P P E N DI C E S
A p pe n di x 1.
St u d y Pr oce d ures Ta ble
A p pe n di x 2.
Calc ulati o n of Differe nce i n Pr o p orti o ns a n d 9 5 % CI ( Strat u m -A dj uste d Ma ntel -
Hae nszel Pr o p orti o ns)


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n 
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 6 9
1 3 Ja n uar y 2 0 2 1
A p pe n di x 1.
St u d y Pr oce d ures T a ble
St u d y Pr oce d ure
Scree ni n g
P art A
( Secti o n 6. 4 Pr ot oc ol)
P art B
( Secti o n 6. 5 
Pr ot oc ol)
O pe n -L a bel Fil g oti ni b P h ase
( Secti o n 6. 6 Pr ot oc ol)
L o n g Ter m 
E xte nsi o n
( Secti o n 6. 1 0 
Pr ot oc ol)
3 0 D a y S afet y
F oll o w- u p e
E T f
D a y 
1
W k 
2
W k 
4
W k 
8
W k 
1 3 a
W k 
2 0
W k 
2 6 a
S per m 
P ar a meter 
Eli gi bilit y 
C o nfir m ati o n b
O L 
D a y 
1
O L 
W k 
2
O L 
W k 
4
O L 
W k 
8
O L 
W k 
1 3 c
L T E Wee k 1 3 
t hr o u g h L T E 
Wee k
1 9 5 d
4 5
d a ys
± 5
d a ys
± 5
d a ys
± 5
d a ys
+ 5
d a ys
± 5
d a ys
+ 5
d a ys
± 5
d a ys
± 5
d a ys
± 5
d a ys
+ 5
d a ys
± 1 0 d a ys
± 5
d a ys
I nf or me d C o nse nt
X
Me dical Hist or y, N u m ber 
of ti mes s u bject 
i mpre g nate d w o m e n, I B D 
Hist or y, a n d 
D e m o gra p hics
X
I ncl usi o n/e xcl usi o n 
criteria re vie w
X  
X
C o m plete P h ysical E xa m g
X
S y m pt o m -directe d 
P h y sical E xa m, as nee de d
X  
X  
X  
X  
X  
X  
X
X  
X  
X  
X  
X  
X  
X  
X
Vital Si g ns g a n d Wei g ht
X  
X  
X  
X  
X  
X  
X  
X
X  
X  
X  
X  
X  
X  
X  
X
Hei g ht
X
1 2 -lea d E C Gg
X
X
X  
X h
X
Fle xi ble Si g m oi d osc o p y i
X
Ile oc ol o n osc o p yi
X
C o m plete Ma y o Cli nic 
Sc ore
(c o m plete M C S)j
X
Partial Ma y o Cli nic Sc ore
( partial M C S)j
X  
X  
X  
X  
X  
X  
X
X  
X  
X  
X  
X  
X
X


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n 
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 7 0
1 3 Ja n uar y 2 0 2 1
St u d y Pr oce d ure
Scree ni n g
P art A
( Secti o n 6. 4 Pr ot oc ol)
P art B
( Secti o n 6. 5 
Pr ot oc ol)
O pe n -L a bel Fil g oti ni b P h ase
( Secti o n 6. 6 Pr ot oc ol)
L o n g Ter m 
E xte nsi o n
( Secti o n 6. 1 0 
Pr ot oc ol)
3 0 D a y S afet y
F oll o w- u p e
E T f
D a y 
1
W k 
2
W k 
4
W k 
8
W k 
1 3 a
W k 
2 0
W k 
2 6 a
S per m 
P ar a meter 
Eli gi bilit y 
C o nfir m ati o n b
O L 
D a y 
1
O L 
W k 
2
O L 
W k 
4
O L 
W k 
8
O L 
W k 
1 3 c
L T E Wee k 1 3 
t hr o u g h L T E 
Wee k
1 9 5 d
4 5
d a ys
± 5
d a ys
± 5
d a ys
± 5
d a ys
+ 5
d a ys
± 5
d a ys
+ 5
d a ys
± 5
d a ys
± 5
d a ys
± 5
d a ys
+ 5
d a ys
± 1 0 d a ys
± 5
d a ys
Si m ple E n d osc o pic Sc ore 
f or Cr o h n’s Disease 
( S E S-C D)
X
Cr o h n’s Disease Acti vit y 
I n de x ( C D AI)k
X  
X  
X  
X  
X  
X  
X  
X
X  
X  
X  
X  
X  
X
X
T B ( Q ua nti F E R O N ® ) Test
X l
X m
C hest X -r a yn
X
Uri nal ysis o
X  
X
X  
X
X
X  
X
X
Uri ne dr u g scree n o
X
H e m at ol o g y a n d 
C he mistr y o
X  
X  
X  
X  
X  
X  
X  
X
X  
X  
X  
X  
X  
X  
X  
X
Li pi d pr ofile (fasti n g) o
X
X  
X
X
X  
X p
Ser u m I m m u n o gl o b uli n o
X
X  
X
X  
X
E n d ocri ne: T S H, H b A 1c o
X
L H, F S H, i n hi bi n B, t otal 
Test oster o ne o c ollecti o n 
ti me bet wee n 0 7: 0 0-1 1: 0 0 
i n t he m or ni n g
X  
X  
X  
X  
X
X  
X  
X  
X  
X  
X
St o ol o
X
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
Assess me nt of A d verse 
E ve nts
X  
X  
X  
X  
X  
X  
X  
X
X  
X  
X  
X  
X  
X  
X  
X


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n 
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 7 1
1 3 Ja n uar y 2 0 2 1
St u d y Pr oce d ure
Scree ni n g
P art A
( Secti o n 6. 4 Pr ot oc ol)
P art B
( Secti o n 6. 5 
Pr ot oc ol)
O pe n -L a bel Fil g oti ni b P h ase
( Secti o n 6. 6 Pr ot oc ol)
L o n g Ter m 
E xte nsi o n
( Secti o n 6. 1 0 
Pr ot oc ol)
3 0 D a y S afet y
F oll o w- u p e
E T f
D a y 
1
W k 
2
W k 
4
W k 
8
W k 
1 3 a
W k 
2 0
W k 
2 6 a
S per m 
P ar a meter 
Eli gi bilit y 
C o nfir m ati o n b
O L 
D a y 
1
O L 
W k 
2
O L 
W k 
4
O L 
W k 
8
O L 
W k 
1 3 c
L T E Wee k 1 3 
t hr o u g h L T E 
Wee k
1 9 5 d
4 5
d a ys
± 5
d a ys
± 5
d a ys
± 5
d a ys
+ 5
d a ys
± 5
d a ys
+ 5
d a ys
± 5
d a ys
± 5
d a ys
± 5
d a ys
+ 5
d a ys
± 1 0 d a ys
± 5
d a ys
Se m e n C ollecti o n 
( 2 sa m ples as per 
c ollecti o n i nstr ucti o ns i n 
Pr ot oc ol Secti o n 6. 1 3) q
X r
X  
X  
X s
X t
X
X
Date a n d ti me of m ost 
rece nt ejac ulati o nu
X
X  
X  
X
X  
X
X
HI V, He patitis B, a n d 
He patitis C v
X
H B V D N A w
X  
X
X  
X
Ra n d o mizati o n
X
St u d y Dr u g 
Acc o u nta bilit y
X  
X  
X  
X  
X
X  
X  
X  
X  
X
X
St u d y Dr u g Dis pe nsati o n
X  
X  
X  
X  
X  
X
X  
X  
X  
X  
X
P K c ollecti o n (s parse)
X x
X y
X z
X z
X x
X y
X z
I n-Cli nic D osi n g aa
X  
X
X  
X
X
X
a
Wee ks 1 3 a n d 2 6 m ust occ ur after 1 3 wee ks a n d 2 6 wee ks of dr u g e x p os ure, res pecti vel y.  T heref ore, visit wi n d o w f or t hese visits are + 5 da ys
b
S u bjects o n bli n de d st u d y dr u g meeti n g criteria as a n o n -res p o n der ( Wee k 1 3) or f or Disease W orse ni n g (after Wee k 1 3 t hr o u g h 2 6), a n d n ot meeti n g t he pre-s pecifie d 
decrease t hres h ol d i n s per m para meters, are eli gi ble f or o pe n -la bel fil g oti ni b (refer t o A p pe n di x 1 1 a n d Secti o n 3 of t he pr ot oc ol). F or defi niti o ns of I B D res p o nse stat us, 
Disease W orse ni n g, a n d/ or pre -s pecifie d decrease t hres h ol d i n s per m para meters please refer t o Defi niti o n of Ter ms a n d Secti o n 3. 4 of t he pr ot oc ol .
c
O L Wee k 1 3 m ust occ ur after 1 3 wee ks of starti n g o pe n -la bel fil g oti ni b. T heref ore, visit wi n d o w is + 5 da ys.
d
S u bjects i n t he L T E will u n der g o sc he d ule d visits f or safet y assess me nts a n d se me n sa m ple c ollecti o n e ver y 1 3 wee ks, starti n g wit h L T E Wee k 1 3. Se me n m o nit ori n g will be 
c ollecte d u ntil t he Wee k 1 3 pri mar y st u d y res ults are a nal yze d.
e
A n y ti me a s u bject disc o nti n ues st u d y dr u g, a safet y f oll o w-u p visit, 3 0 da ys ( ± 5 da ys) after t he last d ose of st u d y dr u g is re q uire d, e ve n if t he s u bject is e nteri n g t he 
M o nit ori n g P hase
f
A n y ti me a s u bject disc o nti n ues partici pati o n i n t he st u d y pri or t o Wee k 2 6, O L Wee k 1 3, reac hi n g re versi bilit y or M o nit ori n g P hase Wee k 5 2 ( w hic he ver occ urs first), or 
L T E Wee k 1 9 5, a n E T Visit is re q uire d.  S u bjects w h o are Res p o n ders at Wee k 2 6 or at O L Wee k 1 3 a n d c h o ose n ot t o c o nti n ue i n t he L T E are als o re q uire d t o c o m plete E T 
visit assess me nts. 
g
As detaile d i n pr ot o c ol A p pe n di x 7.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n 
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 7 2
1 3 Ja n uar y 2 0 2 1
h
1 2 -Lea d E C G will be perf or me d at L T E Wee k 1 9 5 or E T, w hic he ver occ urs s o o ner
i 
Fle xi ble Si g m oi d osc o p y ( U C patie nts) or ile oc ol o n osc o p y ( C D patie nts) is o nl y re q uire d if it has n ot bee n d o ne i n t he last 9 0 da ys.
j
Partial M C S i ncl u des all parts of t he c o m plete M C S e xce pt e n d osc o p y. F or defi niti o ns of I B D res p o nse stat us, please refer t o Defi niti o n of Ter ms ; f or defi niti o ns of Disease 
W orse ni n g, please refer t o pr ot oc ol Secti o n 3. 4 a n d Defi niti o n of Ter ms. S u bject recall f or t he last 2 4 h o urs will
be use d f or t he patie nt re p orte d c o m p o ne nts of t he c o m plete 
M C S a n d partial M C S. S u bjects o n bli n de d st u d y dr u g meeti n g criteria f or N o n -Res p o n der at Wee k 1 3 or Disease W orse ni n g after Wee k 1 3 t hr o u g h Wee k 2 6 (a n d n ot 
meeti n g t he pre-s pecifie d decrease t hres h ol d i n s per m para meters) will be eli gi ble f or o pe n-la bel fil g oti ni b (see pr ot oc ol Secti o n 3). M C S a n d partial M C S will be c ollecte d 
f or U C patie nts. P h ysicia n Gl o bal Assess me nt is a c o m p o ne nt of M C S a n d partial M C S.
k
C D AI will be c ollecte d f or C D patie n ts. S u bject recall f or t he last 7 da ys will be use d f or t he patie nt re p orte d o utc o mes of t he C D AI. T he C D AI sc ore calc ulati o ns s h o ul d n ot 
be i ncl usi ve of da ys t hat i n v ol ve a n e n d osc o p y pr oce d ure or pre parati o n f or t hat pr oce d ure.
l
Pr o of of n o acti ve or u ntr eate d late nt T B at Scree ni n g. S u bjects w h o are dia g n ose d wit h late nt T B at scree ni n g m ust i nitiate a n a de q uate c o urse of pr o p h yla xis, as per l ocal 
sta n dar d of care, f or a mi ni m u m of 4 wee ks pri or t o ra n d o mizati o n. S u bject ma y i nitiate st u d y dr u g d osi n g o nl y after c o ns ultati o n wit h t he Gilea d Me dical M o nit or or 
desi g nee.
m
I n t he L T E s u bjects m ust ha ve yearl y Q ua nti F E R O N® testi n g. Yearl y T B testi n g be gi ns 1 year fr o m t he scree ni n g T B test date. If yearl y T B testi n g falls bet wee n st u d y visits, 
t he yearl y T B testi n g s h o ul d be perf or me d at t he visit pri or t o 1 year fr o m t he scree ni n g T B test date. S u bjects wit h ne wl y p ositi ve (c o n verted) Q ua nti F E R O N ® [ or ce ntrall y 
re p orte d e q ui vale nt assa y] T B test s h o ul d be disc o nti n ue d fr o m st u d y dr u g. S u bjects w h o were pre vi o usl y treate d f or T B wit h a c o m plete a n d a de q uate c o urse of t hera p y as 
per l ocal sta n dar d of care a n d as verifie d b y t he i n vesti gat or d o n ot nee d t o ha ve yearl y Q ua nti F E R O N ® tests. S u bjects pre vi o usl y treate d f or T B s h o ul d be scree ne d at least 
yearl y f or si g n s a n d s y m pt o ms c o nsiste nt wit h reacti vati o n of T B. A n y s u bject wit h acti ve T B s h o ul d be disc o nti n ue d fr o m st u d y.
n
C hest x -ra y ( vie ws as per l ocal g ui deli nes) ta ke n at Scree ni n g or wit hi n t he 3 m o nt hs pri or t o Scree ni n g ( wit h t he re p ort or fil ms a vaila ble f o r i n vesti gat or re vie w) wit h o ut 
e vi de nce of acti ve or late nt T B i nfecti o n
o
As detaile d i n pr ot oc ol A p pe n di x 6. F or visits t hat re q uire fasti n g, s u bjects s h o ul d n ot ha ve a n y f o o d or dri n k (e xce pt water ) f or at least 8 h o urs bef ore t he visit.
p
Li pi d pr ofile s h o ul d be perf or me d e ver y 2 6 wee ks
q 
Se me n sa m ples will be c ollecte d o n t he visit da y a n d/ or after t he visit. T h ose meeti n g t he pre- s pecifie d decrease t hres h ol d i n s per m para meters (as defi ne d i n t he Defi niti o n of 
Ter ms) m ust e nter t he M o nit ori n g P hase (see sc h e d ule bel o w).
r
T he scree ni n g se me n sa m ple c ollecti o n s h o ul d c oi nci de wit h t he Da y 1 ( baseli ne) visit as m uc h as p ossi ble.
s
At ti me of c o nfir mati o n of N o n -res p o n der stat us/ Disease W orse ni n g a n d pri or t o i nitiati o n of o pe n-la bel fil g oti ni b, Se me n A nal ysis m ust c o nfir m s u bject di d n ot meet t he pre -
s pecifie d decrease t hres h ol d i n s per m para meters.
t
At ti me of c o nfir mati o n of N o n -res p o n der stat us/ Disease W orse ni n g a n d pri or t o e ntr y i nt o t he L T E, Se me n A nal ysis m ust c o nfir m s u bject di d n ot meet t he pre-s pecifie d 
de crease t hres h ol d i n s per m para meters.
u
T his q uesti o n will be as ke d pri or t o eac h se me n c ollecti o n.
v
A n HI V -1/ HI V -2 a nti ge n/a nti b o d y test, a He patitis C vir us a nti b o d y test, a He patitis B s urface a nti ge n, a He patitis B s urface a nti b o d y a n d a He patitis c ore a n ti b o d y test will 
be c o n d ucte d o n all s u bjects; S u bjects wit h p ositi ve He patitis B s urface a nti ge n ( H Bs A g) at Scree ni n g are e xcl u de d fr o m t he st u d y. S u bjects wit h p ositi ve H B V c ore A b a n d 
ne gati ve H Bs A g, re q uire refle x testi n g f or H B V D N A. S u bjects wit h p os iti ve H B V D N A at Scree ni n g will be e xcl u de d. S u bjects wit h p ositi ve H B V c ore A b a n d ne gati ve 
H B V D N A are eli gi ble per i n vesti gat or j u d g me nt b ut ma y re q uire pr o p h ylactic treat me nt i n acc or da nce wit h H B V treat me nt g ui del i nes/l ocal sta n dar d of care a n d re q uire 
o n g oi n g m o nit ori n g wit h bl o o d tests f or H B V D N A e ver y 3 m o nt hs. S u bjects wit h e vi de nce of acti ve He patitis B d uri n g t he st u d y, as e vi de nce d b y H B V D N A p ositi vit y, will 
be disc o nti n ue d fr o m st u d y dr u g as o utli ne d i n t he pr ot oc ol. S u bjects wit h p ositi ve H C V a nti b o d y ( A b) at Scree ni n g, re q uire refle x testi n g f or H C V R N A. S u bjects wit h 
p ositi ve H C V R N A at Scree ni n g will be e xcl u de d. S u bjects wit h p ositi ve H C V A b, b ut ne gati ve H C V R N A are eli gi ble per i n vesti g at or j u d g me nt.
w
S u bjects wit h p ositi ve H B V c ore A b a n d ne gati ve H B V D N A at Scree ni n g re q uire o n g oi n g m o nit ori n g wit h bl o o d tests f or H B V D N A e ver y 3 m o nt hs
x
S parse plas ma P K sa m ples are c ollecte d at least 3 0 mi n utes p ost -d ose.  
y
S parse plas ma P K sa m ples ca n be c ollecte d at a n y ti me wit h o ut re gar d t o d osi n g. 
z
S parse plas ma P K sa m ples are c ollecte d pre -d ose.
aa
T he s u bject will ta ke t he first d ose ( Da y 1) i n t he cli nical st u d y ce nter . F or P K c ollecti o n p ur p oses, at Wee ks 2, 1 3, a n d 2 6, a n d O L Wee ks 2 a n d 1 3, su bjects s h o ul d be 
i nstr ucte d n ot t o ta ke t heir st u d y dr u g, b ut rat her t o bri n g it wit h t he m t o t he cli nic. S u bjects will be i nstr ucte d t o ta ke t heir d ose d uri n g t heir sc he d ule d visit, as detaile d i n 
pr ot oc ol Secti o n 6. 1. 6.


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n 
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 7 3
1 3 Ja n uar y 2 0 2 1
St u d y Pr oce d ure
M o nit ori n g P h ase
( Secti o n 6. 7 )
E T a
Visits occ ur e ver y 1 3 wee ks ( ± 5 d a ys) 
f or u p t o 5 2 wee ks or u ntil Re versi bilit y is met, 
w hic he ver is s o o ner
S y m pt o m -directe d P h ysical E xa m, as nee de d
X
X
Vital Si g ns b a n d Wei g ht
X
X
1 2 -lea d E C G
X
Partial Ma y o Cli nic Sc ore 
( partial M C S)c
X
Cr o h n’s Disease Acti vit y I n de x ( C D AI) d
X
Uri nal ysis e
X
X
H e m at ol o g y a n d C he mistr y e
X
X
L H, F S H, i n hi bi n B, t otal Test oster o ne e
c ollecti o n ti me bet wee n 0 7: 0 0 -1 1: 0 0 i n t he 
m o r ni n g 
X
X
C o nc o mita nt Me dicati o ns
X
X
Assess me nt of A d verse E ve nts f
X
X
Se m e n C ollecti o n 
( 2 sa m ples as per c ollecti o n i nstr ucti o ns i n 
pr ot oc ol Secti o n 6. 1 2) g
X
Date a n d ti me of m ost rece nt ejac ulati o n h
X
a  
N ot re q uire d if Re versi bilit y is met or if s u bject c o m pletes Wee k 5 2
b  
As detaile d i n pr ot oc ol A p pe n di x 7.
c 
Partial M C S i ncl u des all parts of t he c o m plete M C S e xce pt e n d osc o p y. F or defi niti o ns of I B D res p o nse stat us, please refer t o Defi niti o n of Ter ms; f or defi niti o ns of Disease 
W orse ni n g, please refer t o pr ot oc ol Secti o n 3. 4 a n d Defi niti o n of Ter ms. S u bject recall f or t he last 2 4 h o urs will be use d f or t he patie nt re p orte d c o m p o ne nts of t he c o m plete 
M C S a n d partial M C S. M C S a n d partial M C S will be c ollecte d f or U C patie nts. P h ysicia n Gl o bal Assess me nt is a c o m p o ne nt of M C S
a n d partial M C S.
d 
C D AI will be c ollecte d f or C D patie nts. S u bject recall f or t he last 7 da ys will be use d f or t he patie nt re p orte d o utc o mes of t he C D AI. T he C D AI sc ore calc ulati o ns s h o ul d n ot 
be i ncl usi ve of da ys t hat i n v ol ve a n e n d osc o p y pr oce d ure or pre parati o n f or t hat pr oce d ure.
e
As detaile d i n pr ot oc ol A p pe n di x 6
f
As detaile d i n pr ot oc ol Secti o n 7. 3
g 
Se me n sa m ples will be c ollecte d o n t he visit da y a n d/ or after t he visit
h
T his q uesti o n will be as ke d pri or t o eac h se me n c ollecti o n .


Fil g oti ni b
G S -U S -4 1 8 -4 2 7 9
Statistical A nal ysis Pla n 
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 7 4
1 3 Ja n uar y 2 0 2 1
A p pe n di x 2.
C alc ul ati o n of Differe nce i n Pr o p orti o ns a n d 9 5 % CI 
( Str at u m-A dj uste d M a ntel -H ae nszel Pr o p orti o ns)
T he 9 5 % c o nfi de nce i nter val o n t he differe nce i n pr o p orti o ns ( pr o p orti o n of s u bjects wit h a 
≥5 0 % decrease fr o m baseli ne i n s per m c o nce ntrati o n) bet wee n Treat me nt A (fil g oti ni b) a n d 
Treat me nt B ( place b o) will be c o nstr ucte d base d o n strat u m -a dj uste d M H pr o p orti o ns 
{ K oc h 1 9 8 9 }:
w here 

( PA – P B ) = 

h
h
h
w
d
w
, is t he strat u m-a dj uste d M H pr o p orti o n differe nce, w here 
hd
=
B h
A h
p
p

is t he differe nce i n t he pr o p orti o n of s u bjects wit h a ≥ 5 0 % decrease fr o m 
baseli ne i n s per m c o nce ntrati o n bet wee n fil g oti ni b a n d place b o i n strat u m h ( h = 1 t o 2).  
Stra ta are ( 1) s per m c o nce ntrati o n 1 5-5 0 M/ m L ; ( 2) s per m c o nce ntrati o n > 5 0 M/ m L.

h
w
=
B h
A h
B h
A h
n
n
n
n

, is t he wei g ht base d o n t he har m o nic mea n of sa m ple size per treat me nt gr o u p 
f or eac h strat u m w here 
A h
n
a n d 
B h
n
are t he sa m ple sizes of t he Treat me nt Gr o u ps A 
(fil g oti ni b) a n d B ( place b o) i n strat u m h. 

S E( P A – P B ) = 
2
*
*
*
*
2
)
(
1
)
1(
1
)
1(













h
B h
B h
B h
A h
A h
A h
h
w
n
p
p
n
p
p
w
, w here 
1
5.0
*



A h
A h
A h
n
m
p
a n d 
1
5.0
*



B h
B h
B h
n
m
p
a n d 
A h
m
a n d 
B h
m
are t he n u m ber of s u bjects wit h a ≥ 5 0 % decrease i n s per m 
c o nce ntrati o n i n t he Treat me nt Gr o u ps A (fil g oti ni b) a n d B ( place b o) i n strat u m h.  

α = 0. 0 5 f or t his st u dy 

Z ( 1-α/ 2 ) = Z 0. 9 7 5 = 1. 9 6 is t he 9 7. 5t h perce ntile of t he n or mal distri b uti o n
If t he c o m p ute d l o wer c o nfi de nce b o u n d is less t ha n – 1, t he l o wer b o u n d is defi ne d as – 1. If t he 
c o m p ute d u p per c o nfi de nce b o u n d is greater t ha n 1, t he n t he u p per b o u n d is defi ne d as 1. If t he
r o w or c ol u m n mar gi nal totals are zer o i n a n y strata, t he n s o me re gr o u pi n g of strata ma y be 
perf or me d.


G S- U S- 4 1 8- 4 2 7 9 _ S A P _ v 1. 0
E L E C T R O NI C SI G N A T U R E S
Si g n e d b y
M e a ni n g of Si g n at ur e
S er v er D at e
( d d- M M M-
y y y y h h: m m: s s)
R e g ul at or y Aff air s e Si g n e d
1 8- J a n- 2 0 2 1
0 4: 4 8: 4 8
Cli ni c al R e s e ar c h e Si g n e d
1 9- J a n- 2 0 2 1
1 6: 0 5: 0 7
Bi o st ati sti c s e Si g n e d
1 9- J a n- 2 0 2 1
1 7: 3 7: 4 0
P P D
P P D
P P D