A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Dose-Ranging, Efficacy, and Safety Study of Povorcitinib in Participants With Chronic Spontaneous Urticaria
Phase: PHASE2
Conditions: Urticaria, Chronic Spontaneous Urticaria, Chronic Idiopathic Urticaria, Hives, Angioedema, Pruritis
Sponsor: Incyte Corporation

Offici al Title:  
A P hase 2, D o u ble -Bli n d, Ra n d o mize d, Place b o -C o ntr olle d,  
D ose - Ra n gi n g, Efficac y, a n d Safet y St u d y of P o v orciti ni b i n 
Partici pa nts Wit h C hr o nic S p o nta ne o us Urticaria 
N C T N u m ber:  
N C T 0 5 9 3 6 5 6 7  
D oc u me nt D ate:  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7 Versi o n 1 0 7 M A R 2 0 2 3  
 
 
 

I nc yte C or p orati o n 
P a ge 1  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
 
Cli nic al St u d y Pr ot oc ol  
 
TI T L E P A G E  
I N C B 5 4 7 0 7-2 0 7  
A P hase 2, D o u ble -Bli n d, Ra n d o mi ze d, Place b o -C o ntr olle d, 
D ose -Ra n gi n g, Efficac y, a n d Safet y St u d y of P o v orciti ni b i n 
Partici pa nts Wit h C hr o nic S p o nta ne o us Urticaria  
 
P r o d uct:  
P o v orciti ni b  (I N C B 0 5 4 7 0 7) 
I N D N u m ber: 
 
E U C T N u m ber:  
2 0 2 2 -5 0 3 0 6 2 -7 2 -0 0  
P h ase of St u d y:  
2  
Brief Title:  
St u d y E v al u ati n g t he Effic ac y a n d S afet y of P o v orciti ni b  i n 
A d ults W it h C hr o nic S p o nt a ne o us Urtic ari a  
S p o ns or:  
I nc yte C or p or ati o n 
1 8 0 1 A u g usti ne C ut -Off  
Wil mi n gt o n, D E 1 9 8 0 3 U S A  
Ori gi n al P r ot oc ol:  
0 7 M A R  2 0 2 3  
 
T his st u d y will be perf or me d i n acc or da nce wit h et hical pri nci ples t hat ha ve t heir ori gi n i n t he Declarati o n of 
Helsi n ki ( Brazil 2 0 1 3) a n d c o n d ucte d i n a d here nce t o t he st u d y Pr ot oc ol, a p plica ble G o o d Cli nical Practices, a n d 
a p plica ble la ws a n d c o u ntr y -s pecific re g ulati o ns, i ncl u di n g W M O ( Me dical Researc h I n v ol vi n g H u ma n P artici pa nts 
Act) a n d Cli nical Trials Re g ul ati o n ( E U) N o. 5 3 6/ 2 0 1 4, i n w hic h t he st u d y is bei n g c o n d ucte d. 
T he i nf or mati o n i n t his d oc u me nt is c o nfi de ntial. N o part of t his i nf or mati o n ma y be d u plicate d, refere nce d, or 
tra ns mitte d i n a n y f or m or b y a n y mea ns (electr o nic, mec ha nical, p h ot oc o p y, rec or di n g, or ot her wise) wit ho ut pri or 
writte n c o nse nt.  

I nc yte C or p orati o n 
P a ge 2  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
I N V E S TI G A T O R'S A G R E E M E N T  
I h a ve rea d t he I N C B 5 4 7 0 7-2 0 7 Pr o t oc ol ( date d 0 7 M A R  2 0 2 3 ) a n d a gree t o c o n d uct t he st u d y 
as o utli ne d. I a gree t o mai ntai n t he c o nfi de ntialit y of all i nf or mati o n recei ve d or de vel o pe d i n 
c o n necti o n wit h t his Pr ot oc ol.  
 
 
 
 
 
( Pri nte d Na me of I n vesti gat or) 
 
 
 
 
 
 
 
 
( Si g nat ur e of I n v esti gat or) 
 
( Date) 

I nc yte C or p orati o n 
P a ge 3  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
T A B L E O F C O N T E N T S  
TI T L E P A G E  ...................................................................................................................................1  
I N V E S TI G A T O R' S A G R E EM E N T  ................................................................................................2  
T A B L E O F C O N T E N T S  .................................................................................................................3  
LI S T O F A B B R E VI A TI O N S  ..........................................................................................................9  
1.  
P R O T O C O L S U M M A R Y  ..........................................................................................1 3  
2.  
I N T R O D U C TI O N ......................................................................................................2 0  
2. 1.  
Bac k gr o u n d  .................................................................................................................2 0  
2. 2.  
St u d y R ati o nale  ...........................................................................................................2 1  
2. 2. 1.  
S cie ntific Rati o nale f or St u d y Desi g n  ........................................................................2 1  
2. 2. 2.  
J ustificati o n f or D ose ..................................................................................................2 3  
2. 3.  
Be nefit/ Ris k Assess me nt  ............................................................................................2 4  
3.  
O BJ E C TI V E S A N D E N D P O I N T S ............................................................................2 7  
4.  
S T U D Y D E SI G N  .......................................................................................................3 0  
4. 1.  
O verall Desi g n  ............................................................................................................3 0  
4. 2.  
O verall St u d y D urati o n  ...............................................................................................3 0  
4. 3.  
St u d y Ter mi nati o n  ......................................................................................................3 1  
5.  
S T U D Y P O P U L A TI O N  .............................................................................................3 2  
5. 1.  
I n cl usi o n Criteria ........................................................................................................3 2  
5. 2.  
E x cl usi o n Criteria  .......................................................................................................3 3  
5. 3.  
Lif est yle C o nsi derati o ns  .............................................................................................3 6  
5. 3. 1.  
C o ntrace pti o n  ..............................................................................................................3 6  
5. 3. 1. 1.  
Fe male Partici pa nts  .....................................................................................................3 6  
5. 3. 1. 2.  
Male Partici pa nts  ........................................................................................................3 6  
5. 3. 1. 3.  
All Partici pa nts  ...........................................................................................................3 6  
5. 3. 2.  
Meals a n d Dietar y Restri cti o ns  ...................................................................................3 7  
5. 4.  
Scree n Fail ures  ............................................................................................................3 7  
5. 5.  
Re place me nt of Partici pa nts  .......................................................................................3 8  
5. 6.  
Data Safet y M o nit ori n g B oar d  ....................................................................................3 8  
5. 7.  
Car di o vasc ular A dj u dicati o n C o m mittee  ...................................................................3 8  
6.  
S T U D Y T R E A T M E N T  ..............................................................................................3 9  
6. 1.  
St u d y Treat me nts A d mi nistere d  .................................................................................3 9  

I nc yte C or p orati o n 
P a ge 4  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
6. 2.  
Bac k gr o u n d T hera p y  ..................................................................................................3 9  
6. 3.  
Pre parati o n, H a n dli n g, a n d Acc o u nta bilit y  ................................................................4 0  
6. 4.  
Meas ures t o Mi ni mize Bias: Ra n d o mizati o n a n d Bli n di n g  ........................................4 1  
6. 5.  
St u d y Treat me nt C o m plia nce  .....................................................................................4 1  
6. 5. 1.  
C o m plia nce Wit h P o v orciti ni b/ Place b o  .....................................................................4 1  
6. 5. 2.  
C o m plia nce Wit h Bac k gr o u n d T hera p y  .....................................................................4 2  
6. 6.  
D ose M o dificati o ns  .....................................................................................................4 2  
6. 6. 1.  
Criteria a n d Pr oce d ures f or D ose I nterr u pti o ns a n d A dj ust me nts of St u d y 
Dr u g  ............................................................................................................................4 2  
6. 6. 1. 1.  
Ma na ge me nt of Seri o us I nfecti o ns  .............................................................................4 6  
6. 6. 1. 2.  
Ma na ge me nt of Her pes Z oster  ....................................................................................4 6  
6. 6. 1. 3.  
Ma na ge me nt of C O VI D -1 9  ........................................................................................4 6  
6. 6. 1. 4.  
Ma na ge me nt of T hr o m b osis E ve nts  ...........................................................................4 6  
6. 6. 1. 5.  
Ma na ge me nt of M ali g n a nc y  .......................................................................................4 6  
6. 6. 1. 6.  
E mer ge nc y a n d Electi ve S ur geries  .............................................................................4 7  
6. 6. 2.  
Criteria f or Per m a ne nt Disc o nti n uati o n of St u d y Dr u g  ..............................................4 7  
6. 7.  
Pri or a n d C o nc o mita nt Me dicati o ns a n d Pr oce d ures  ..................................................4 7  
6. 7. 1.  
Pri or T hera p y f or C hr o ni c S p o nta ne o us Urticaria  ......................................................4 7  
6. 7. 2.  
Bac k gr o u n d ( Sta n dar d of Care) T h era p y  ....................................................................4 7  
6. 7. 3.  
Resc ue Me dic ati o n  ......................................................................................................4 8  
6. 7. 4.  
Pr o hi bite d Me dicati o ns a n d Pr oce d ures  .....................................................................4 8  
6. 8.  
Treat me nt Aft er t he E n d of t he St u d y  .........................................................................4 9  
7.  
DI S C O N TI N U A TI O N O F S T U D Y T R E A T M E N T A N D P A R TI CI P A N T 
WI T H D R A W A L  ........................................................................................................5 0  
7. 1.  
Disc o nti n uati o n of St u d y Treat me nt  ...........................................................................5 0  
7. 1. 1.  
Reas o ns f or Disc o nti n uati o n  .......................................................................................5 0  
7. 1. 2.  
Disc o nti n uati o n Pr oce d ures  ........................................................................................5 0  
7. 2.  
Partici pa nt Wit h dra wal Fr o m t he St u d y  .....................................................................5 1  
7. 3.  
L ost t o F oll o w -U p .......................................................................................................5 1  
8.  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  ......................................................5 2  
8. 1.  
A d mi nistrati ve a n d Ge neral Pr oce d ures  .....................................................................5 2  
8. 1. 1.  
I nf or me d C o nse nt Pr ocess ..........................................................................................5 2  
8. 1. 2.  
Scree ni n g Pr oce d ures  ..................................................................................................5 3  

I nc yte C or p orati o n 
P a ge 5  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
8. 1. 3.  
I nteracti ve Res p o nse Tec h n ol o g y Pr oce d ure ..............................................................5 3  
8. 1. 4.  
Distri b uti o n of Re mi n der Car ds  ..................................................................................5 3  
8. 1. 5.  
Distri b uti o n of Partici pa nt Car ds  ................................................................................5 3  
8. 1. 6.  
Distri b uti o n of Electr o nic Diaries  ...............................................................................5 3  
8. 1. 7.  
De m o gra p h y a n d Me dical Hist or y  ..............................................................................5 4  
8. 1. 7. 1.  
De m o gra p hics a n d Ge n eral Me dical Hist or y  .............................................................5 4  
8. 1. 7. 2.  
Disease C haracteristics a n d Treat me nt Hist or y  ..........................................................5 4  
8. 2.  
Efficac y Assess me nts  .................................................................................................5 4  
8. 2. 1.  
Patie nt -Re p orte d O utc o mes  ........................................................................................5 4  
8. 2. 1. 1.  
Dail y Di ar y Patie nt -Re p orte d O utc o mes  ....................................................................5 5  
8. 2. 1. 2.  
A d mi nistrati ve Pr oce d ures  ..........................................................................................5 5  
8. 2. 1. 3.  
Dail y e Diar y  ................................................................................................................5 5  
8. 2. 2.  
Me dical Res o urce Utiliz ati o n a n d Healt h Ec o n o mi cs  ................................................5 7  
8. 3.  
Safet y Assess me nts  .....................................................................................................5 8  
8. 3. 1.  
A d verse E v e nts  ...........................................................................................................5 8  
8. 3. 2.  
P h ysical E x a mi nati o ns  ................................................................................................5 8  
8. 3. 3.  
Vital Si g ns  ..................................................................................................................5 9  
8. 3. 4.  
Electr ocar di o gra ms  .....................................................................................................5 9  
8. 3. 5.  
La b orat or y Ass ess me nts  .............................................................................................5 9  
8. 3. 5. 1.  
Pre g n a nc y T esti n g  ......................................................................................................6 2  
8. 3. 5. 2.  
T u berc ul osis Assess me nt  ............................................................................................6 2  
8. 3. 5. 3.  
HI V Testi n g  ................................................................................................................6 4  
8. 3. 5. 4.  
He patitis Testi n g  .........................................................................................................6 4  

I nc yte C or p orati o n 
P a ge 6  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
8. 6.  
U nsc he d ule d Visits  .....................................................................................................6 6  
8. 7.  
E n d of Treat me nt a n d Earl y T er mi nati o n  ...................................................................6 6  
8. 8.  
F oll o w -U p  ...................................................................................................................6 6  
8. 8. 1.  
P ost -Treat me nt F oll o w -U p  .........................................................................................6 6  
9.  
A D V E R S E E V E N T S: D E FI NI TI O N S A N D P R O C E D U R E S F O R 
R E C O R DI N G, E V A L U A TI N G, F O L L O W -U P, A N D R E P O R TI N G  ......................6 7  
9. 1.  
Defi niti o n of A d vers e E v e nt  .......................................................................................6 7  
9. 2.  
Defi niti o n of Seri o us A d verse E ve nt  ..........................................................................6 8  
9. 3.  
Rec or di n g a n d F oll o w -U p of A d verse E ve nts a n d/ or Seri o us A d verse E ve nts  .........6 9  
9. 4.  
Re p orti n g of Seri o us A d verse E ve nts  .........................................................................7 1  
9. 5.  
P ote ntial Dr u g -I n d uce d Li ver I nj ur y ..........................................................................7 2  
9. 6.  
E ve nts of Cli nical I nt erest  ..........................................................................................7 3  
9. 6. 1.  
A d verse E v e nts of S peci al I nt erest  .............................................................................7 3  
9. 7.  
E mer ge nc y U n bli n di n g of Treat me nt Assi g n me nt  .....................................................7 4  
9. 8.  
Pre g n a nc y  ...................................................................................................................7 4  
9. 9.  
War ni n gs a n d Preca uti o ns  ..........................................................................................7 5  
9. 1 0.  
Pr o d uct C o m plai nts  ....................................................................................................7 5  
9. 1 1.  
Treat me nt of O v er d ose  ...............................................................................................7 5  
1 0.  
S T A TI S TI C S  ..............................................................................................................7 6  
1 0. 1.  
Sa m ple Siz e Deter mi nati o n  ........................................................................................7 6  
1 0. 2.  
P o p ulati o ns f or A nal ysis  .............................................................................................7 7  
1 0. 3.  
Le v el of Si g nifi ca nce  ..................................................................................................7 8  
1 0. 4.  
Statistical A nal yses  .....................................................................................................7 8  
1 0. 4. 1.  
Pri mar y A n al ysis  ........................................................................................................7 8  
1 0. 4 . 2. 
Sec o n dar y A n al ysis  ....................................................................................................8 0  
1 0. 4. 3.  
Safet y A nal yses  ..........................................................................................................8 0  
1 0. 4. 4.  
E x pl orat or y A nal ysis  ..................................................................................................8 1  
1 0. 5.  
I nteri m A nal ysis ..........................................................................................................8 1  
1 1.  
S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L  
C O N SI D E R A TI O N S  ..................................................................................................8 2  
1 1. 1.  
I n v esti gat or Res p o nsi bilities .......................................................................................8 2  

I nc yte C or p orati o n 
P a ge 7  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
1 1. 1. 1.  
I d e ntificati o n of t he C o or di nati n g Pri nci pal I n v esti gat or ...........................................8 3  
1 1. 2.  
Data Ma na ge me nt  .......................................................................................................8 3  
1 1. 3.  
Data Q ualit y Ass ura nce  ..............................................................................................8 5  
1 1. 4.  
Data Pri vac y a n d C o nfi de ntialit y of St u d y R ec or ds  ...................................................8 5  
1 1. 5.  
Fi na ncial Discl os ur e  ...................................................................................................8 6  
1 1 . 6. 
P u blicati o n P olic y  .......................................................................................................8 6  
1 1. 7.  
St u d y a n d Site Cl os ure ................................................................................................8 7  
1 2.  
R E F E R E N C E S  ...........................................................................................................8 8  
A P P E N DI X  A.  I N F O R M A TI O N R E G A R DI NG E F F E C TI V E N E S S O F 
C O N T R A C E P TI V E M E T H O D S A N D D E FI NI TI O N S  ............................................9 1  
A P P E N DI X  B.  LI S T O F S T R O N G S Y S T E MI C C Y P 3 A 4 I N HI BI T O R S A N D 
S T R O N G/ M O D E R A T E S Y S T E MI C C Y P 3 A 4 I N D U C E R S ....................................9 3  
A P P E N DI X  C.  I N S T R U C TI O N T O P A R TICI P A N T S F O R H A N D LI N G  S T U D Y 
D R U G  .........................................................................................................................9 4  
A P P E N DI X  D.  M A N A G E M E N T O F P O T E N TI A L H Y' S L A W C A S E S / P O T E N TI A L 
DI LI  9 5  
A P P E N DI X  E.  C O VI D -1 9 P A N D E MI C MI TI G A TI O N S T R A T E GI E S A N D 
I N S T R U C TI O N S .......................................................................................................9 9  
A P P E N DI X  F.  P R O T O C O L A M E N D M E N T S U M M A R Y O F C H A N G E S  ..........................1 0 2  
 

I nc yte C or p orati o n 
P a ge 8  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
LI S T O F T A B L E S  
Ta ble  1:  
Pri mar y a n d Sec o n dar y O bjecti ves a n d E n d p oi nts  .....................................................1 3  
Ta ble  2:  
Ke y St u d y D esi g n El e me nts  .......................................................................................1 4  
Ta ble  3:  
Sc he d ule of A cti vities  .................................................................................................1 6  
Ta ble  4:  
Ris k -Miti gati o n Assess me nt f or P o v orciti ni b  ............................................................2 5  
Ta ble  5:  
O bjecti ves a n d E n d p oi nts  ...........................................................................................2 7  
Ta ble  6:  
E x cl usi o nar y La b orat or y Val ues  ................................................................................3 5  
Ta ble  7:  
St u d y Treat me nt I nf or mati o n  .....................................................................................3 9  
Ta ble  8:  
G ui deli nes f or I nterr u pti o n, Restarti n g, a n d Disc o nti n uati o n of St u d y  Dr u g .............4 3  
Ta ble  9:  
Re q uire d La b orat or y A n al ytes  ....................................................................................6 1  
Ta ble  1 0:  I nter pret ati o n a n d Ma na ge me nt of He p atitis B Vir us Ser ol o gic Test Res ults ............6 4  
 
 
Ta ble  1 2:  Pres pecifie d Ca n di d ate M o dels  ..................................................................................7 6  
Ta ble  1 3:  Sa m ples Siz es a n d Mi ni m u m P o wer Acr oss t he 6 Pres pecifie d Ca n di d ate 
M o dels U n der Differe nt Ass u m pti o ns of Sta n dar d De viati o n  ...................................7 7  
Ta ble  1 4:  P o p ulati o ns f or A nal ysis  .............................................................................................7 8  
Ta ble  1 5:  Esti ma n d f or Pri mar y E n d p oi nt  ..................................................................................7 9  
Ta ble  1 6:  I nterc urre nt E ve nts a n d Strate gies f or t h e Pri mar y Esti ma n d  ....................................7 9  
 
LI S T O F FI G U R E S  
Fi g ure  1:  
St u d y Desi g n Sc he ma  .................................................................................................1 5  
Fi g ure  2:  
Pres pecifie d D ose -Res p o nse C ur ves  ..........................................................................7 7  
 

I nc yte C or p orati o n 
P a ge 9  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
LI S T O F A B B R E VI A TI O N S  
A b bre vi ati o ns a n d 
S peci al Ter ms  
Defi niti o n  
A A S  
a n gi oe de ma acti vit y sc ore  
A D  
at o pic der matitis  
A E  
a d verse e ve nt  
 
 
A E SI  
a d verse e ve nt of s pecial i nterest  
A L P  
al kali ne p h os p hatase  
A L T  
ala ni ne a mi n otra nsferase  
A N C  
a bs ol ute ne utr o p hil c o u nt  
a P T T 
acti vate d partial t hr o m b o plasti n ti me  
A S T  
as partate a mi n otra nsferase  
B C G  
Bacill us Cal mette – G uéri n  
C A B G  
c or o nar y arterial re vasc ularizati o n wit h b y pass graft 
C A C  
car di o vasc ular a dj u dicati o n c o m mittee  
CI  
c o nfi de nce i nter val  
C O VI D -1 9  
c or o na vir us disease 2 0 1 9  
C P K  
creati ne p h os p h o ki nase  
C S R  
Cli nical St u d y Re p ort  
C S U  
c hr o nic s p o nta ne o us urticaria  
C T  
c o m p ute d t o m o gra p h y  
C T C A E  
C o m m o n T er mi n ol o g y Criteria f or A d verse E ve nts  
 
 
C X R  
c hest x -ra y 
DI LI  
dr u g -i n d uce d li ver i nj ur y 
 
 
D N A  
de o x yri b o n ucleic aci d  
D S M B  
data safet y m o nit ori n g b oar d  
E C G  
electr ocar di o gra m  
E CI  
e ve nt of cli nical i nterest  
e C O A 
electr o nic cli nical o utc o me assess me nt  
E D C  
electr o nic data ca pt ure  
E O S  
e n d of st u d y 
E O T  
e n d of treat me nt  
E O T 1  
e n d of treat me nt d uri n g t he place b o -c o ntr olle d peri o d 
E O T 2  
e n d of treat me nt d uri n g t he e xte nsi o n peri o d 

I nc yte C or p orati o n 
P a ge 1 0  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
A b bre vi ati o ns a n d 
S peci al Ter ms  
Defi niti o n  
E Q  
E ur o Q ol  
 
  
E T  
earl y ter mi nati o n  
E X T  
e xte nsi o n 
F A S  
f ull a nal ysis set 
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
F S H  
f ollicle-sti m ulati n g h or m o ne 
G C P  
G o o d Cli nical Practice  
G D P R  
Ge neral Data Pr otecti o n Re g ulati o n  
G G T  
ga m ma -gl uta m yl tra nsferase  
H Bc A b  
he patitis B c ore a nti b o d y  
H Bs A b  
he patitis B s urface a nti b o d y  
H Bs A g  
he patitis B s urface a nti ge n  
H B V  
he patitis B vir us  
H C V  
he patitis C vir us  
H D L  
hi g h -de nsit y li p o pr otei n  
HI P A A  
Healt h I ns ura nce P orta bilit y a n d Acc o u nta bilit y Act  
HI V  
h u ma n i m m u n o deficie nc y vir us  
H R T  
h or m o ne re place me nt t hera p y  
H S  
hi dra de nitis s u p p urati va  
hs C R P  
hi g h -se nsiti vit y C-reacti ve pr otei n 
H S S  
hi ve se verit y sc ore  
 
 
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 pe n de nt et hics c o m mittee 
I F N 
i nterfer o n 
I g E 
i m m u n o gl o b uli n E 
I G R A 
i nterfer o n-ga m ma release assa y  
I L 
i nterle u ki n 
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 R T 
i nteracti ve res p o nse tec h n ol o g y  
I S S  
itc h se verit y sc ore  
 
 

I nc yte C or p orati o n 
P a ge 1 1  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
A b bre vi ati o ns a n d 
S peci al Ter ms  
Defi niti o n  
I T T 
i nte nt-t o-treat 
J A K 
Ja n us ki nase 
L D L  
l o w-de nsit y li p o pr otei n  
M A C E  
maj or a d verse car di o vasc ular e ve nt  
M C P -m o d  
m ulti ple -c o m paris o n pr oce d ure  a n d m o deli n g 
Me d D R A  
Me dical Dicti o nar y f or Re g ulat or y Acti vities  
MI  
m y ocar dial i nfarcti o n  
MI D  
mi ni mall y i m p orta nt differe nce 
M M R M  
mi xe d m o del f or re peate d meas ures  
M RI  
ma g netic res o na nce i ma gi n g 
N Y H A  
Ne w Y or k Heart Ass ociati o n  
P C  
place b o -c o ntr olle d 
P C R  
p ol y merase c hai n reacti o n  
P D  
p har mac o d y na mic (s) 
 
 
 
 
P K  
p har mac o ki netic(s)  
P P D  
p urifie d pr otei n deri vati ve  
P R O  
patie nt -re p orte d o utc o me 
P T  
pr ot hr o m bi n ti me  
Q D  
o nce dail y  
Q T F  
Q ua nti F E R O N ® -T B  
R N A  
ri b o n ucleic aci d 
R SI  
Refere nce Safet y I nf or mati o n  
S A E  
seri o us a d verse e ve nt 
S A P  
statistical a nal ysis pla n 
S o A  
sc he d ule of acti vities 
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 T A T  
si g nal tra ns d ucer a n d acti vat or of tra nscri pti o n 
S T D  
sta n dar d de viati o n 
T B  
t u berc ul osis 
T E A E  
treat me nt-e mer ge nt a d verse e ve nt  
U A S  
urticaria acti vit y sc ore  
U A S 7  
urticaria acti vit y sc ore o ver 7 da ys  

I nc yte C or p orati o n 
P a ge 1 2  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
A b bre vi ati o ns a n d 
S peci al Ter ms  
Defi niti o n  
U C T  
urticaria c o ntr ol test  
U L N  
u p per li mit of n or mal  
V A S  
vis ual a nal o g ue scale  
W B C  
w hite bl o o d cell  
W O C B P  
w o me n of c hil d beari n g p ote ntial  
W O N C B P  
w o me n of n o nc hil d beari n g p ote ntial  
 
 

I nc yte C or p orati o n 
Pa ge 1 3 of 1 0 2 
Pr ot oc ol I N C B 5 4 7 0 7- 2 0 7 
Versi o n 1 
0 7 M A R 2 0 2 3 
V V- C LI N- 0 2 2 4 5 3 
C O N FI D E N TI A L 
1.  
P R O T O C O L S U M M A R Y 
Pr ot oc ol Title: A P hase 2, D o u ble- Bli n d, Ra n d o mize d, Place b o- C o ntr olle d, D ose- Ra n gi n g, 
Efficac y, a n d Safet y St u d y of P o v orciti ni b i n Part ici pa nts Wit h C hr o nic S p o nta ne o us Urticaria 
Brief Title: A St u d y E val uati n g t he Efficac y a n d Safet y of  P o v orciti ni b i n A d ults Wit h C hr o nic 
S p o nta ne o us Urticaria 
Pr ot oc ol N u m ber: I N C B 5 4 7 0 7- 2 0 7 
O bjecti ves a n d E n d p oi nts: 
Ta ble 1  prese nts t he pri mar y a n d seco n dar y o bjecti ves a n d e n d p oi nts. 
T a ble 1:  
Pri m ar y a n d Sec o n d ar y  O bjecti ves a n d E n d p oi nts 
O bjecti ves 
E n d p oi nts 
Pri m ar y 
T o e val uate t he efficac y of p o v orciti ni b i n 
partici pa nts wit h C S U. 
C ha n ge fr o m baseli ne i n t he U A S 7, defi ne d as t he 
7- da y s u m of t he i n di vi d ual, dail y rec or de d sc ores 
f or H S S a n d I S S, at Wee k 1 2. 
Sec o n d ar y  
T o f urt her e val uate t he efficac y of p o v orciti ni b i n 
partici pa nts wit h C S U. 
 Pr o p orti o n of partici pa nts w h o ac hie ve 
U A S 7 ≤ 6 (c o ntr olle d disease) at Wee k 1 2. 
 Ti me t o first ac hie ve me nt of U A S 7 ≤ 6 
(c o ntr olle d disease) d uri n g t he P C peri o d. 
 Pr o p orti o n of partici pa nts wit h U A S 7 = 0 at 
Wee k 1 2. 
O ver all Desi g n: 
Ta ble 2  prese nts t he ke y st u d y desi g n ele me nts. F urt her st u d y details are prese nte d after t he 
ta ble. 

I nc yte C or p orati o n 
P a ge 1 4  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
T a ble  2 : 
Ke y St u d y Desi g n Ele me nts  
St u d y P h ase  
P ha se 2 
Cli nic al I n dic ati o n  
Treat me nt of patie nts wit h C S U t hat is i na de q uatel y c o ntr olle d b y 
sec o n d-ge nerati o n H 1  a nti hista mi nes. 
P o p ul ati o n  
Partici pa nts a ge d  1 8 t o 6 5 years w h o ha ve ha d a dia g n osis of C S U f or 
≥ 3  m o nt hs t hat is i na de q uatel y c o ntr olle d b y sec o n d-ge nerati o n 
H 1  a nti hista mi nes. I na de q uatel y c o ntr olle d C S U is defi ne d as U A S 7 ≥ 1 6 
d uri n g t he 7 da ys pri or t o ra n d o mizati o n.  
N u m ber of 
P artici p a nts  
A p pr o xi matel y 1 3 6 partici pa nts will be ra n d o mize d 1: 1: 1: 1 t o 1 of 4 treat me nt 
gr o u ps ( ≈ 3 4 partici pa nts per gr o u p).  Partici pa nts will be stratifie d b y pre vi o us 
treat me nt of C S U wit h a n a nti -I g E bi ol o gic a ge nt ( yes or n o). 
St u d y Desi g n  
M ultice nter, parallel -gr o u p, d o u ble -bli n d, ra n d o m ize d, place b o-c o ntr olle d, 
d ose -ra n gi n g st u d y.  
Esti m ate d D ur ati o n 
of St u d y 
P artici p ati o n  
It is esti mate d t hat a n i n di vi d ual will partici pate f or a p pr o xi matel y 4 8 wee ks 
( 1 1 m o nt hs) as f oll o ws:  
•  Scree ni n g : u p t o 2 8 da ys  
•  P C peri o d ( d o u ble -bli n de d) : 1 2 wee ks  
•  E X T peri o d ( d o u ble -bli n de d) : 2 4 wee ks  
•  P ost -treat me nt f oll o w-u p : 6 0 da ys ( ±  7  da ys ) after last d ose of st u d y dr u g 
D S M B  
Yes (i nter nal)  
C A C  
Yes  
C o or di n ati n g 
P ri nci p al 
I n vesti g at or 
Pr of. Dr. Marc us Ma urer  
Tre at me nt Gr o u ps a n d D ur ati o n:  
T he st u d y will e nr oll a p pr o xi matel y 1 3 6 p artici pa nts i n a 1: 1: 1: 1 ra n d o mizati o n rati o, stratifie d 
b y pre vi o us a nti -I g E bi ol o gic use, i nt o 1 of 4 tr eat me nt gr o u ps d uri n g t he d o u ble-bli n d , P C 
peri o d ( 1 2 wee ks) . 
After c o m pleti n g t he 1 2 -wee k P C peri o d, partici pa nt s will e nter t he 2 4 -wee k E X T peri o d. 
D uri n g t h e E X T peri o d, t h e partici pa nts i nitiall y ra n d o mize d t o p o v orciti ni b  will c o nti n ue ta ki n g 
p o v orciti ni b  at t he sa me d ose  re gi me n (ie, p o v orciti ni b  1 5, 4 5, or 7 5 m g Q D). T he partici pa nts 
i nitiall y ra n d o mize d t o place b o at baseli ne will recei ve p o v orciti ni b  1 5, 4 5, or 7 5 m g Q D.  
Partici pa nts will recei ve st u d y dr u g u ntil c o m pleti o n of t he 3 6 -wee k treat me nt peri o d or u ntil 
1  of t he criteri a f or st u d y treat me nt disc o nti n uati o n are met. Partici pa nts will ret ur n f or a 
f oll o w-u p visit a p pr o xi matel y 6 0  d a ys aft er t heir l ast d ose of st u d y dr u g. 

I nc yte C or p orati o n 
P a ge 1 5  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
All partici pa nts are re q uire d t o mai ntai n a bac k gr o u n d t hera p y of a sta ble d ose of 
sec o n d-ge n erati o n H 1  a nti hista mi ne ( S O C) d uri n g t he st u d y (ie,  fr o m scree ni n g t hr o u g h 
f oll o w-u p). T he S O C will be deter mi ne d b y t he i n vesti gat or. F urt her d oses o f sec o n d-ge nerati o n 
H 1  a nti hista mi ne ma y b e use d as res c ue me dicati o n t o treat w orse ni n g C S U s y m pt o ms at a n y 
ti me d uri n g t he st u d y. A 1 -ti me, s h ort c o urse ( m a xi m u m d urati o n of 7 da ys) of 
gl uc o c ortic oster oi ds ma y be use d as r esc ue m e dicati o n after Wee k 4 i n  t he case of se vere 
e x acer bati o n.  
Fi g ure  1  prese nts t he st u d y desi g n sc h e ma, a n d T a ble  3  pres e nt s t he S o A. A d here n ce t o t he st u d y 
desi g n re q uire me nts, i ncl u di n g t h ose s pecifie d i n t he S o A, is esse ntial a n d re q uire d f or st u d y 
c o n d uct.  
Fi g ure  1 : 
St u d y Desi g n Sc he m a  
 
 

I nc yte C or p orati o n 
P a ge 1 6  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
T a ble  3 : 
Sc he d ule of Acti vities  
Visit D a y ( R a n ge)  
Scree ni n g  
P C Peri o d  
( 1 2 Wee ks) 
E X T Peri o d  
( 2 4 Wee ks ) 
P ost -
Tre at me nt 
F oll o w -U p  
N otes  a n d 
Pr ot oc ol Secti o n  
D a ys  
−2 8 t o −1  
B aseli ne  
D a y 1  
W e e k 4  
( ± 3 d) 
W e e k  8  
( ± 3 d) 
W e e k  1 2/  
E O T 1  
( or E T 1) 
( ± 3 d) 
W e e k  1 6  
( ± 3 d) 
W e e k  2 0  
( ± 3 d) 
W e e k  2 4  
( ± 3 d) 
W e e k  2 8  
( ± 3 d) 
W e e k  3 2  
( ± 3 d) 
W e e k  3 6/  
E O T 2  
( or E T 2) 
( ± 3 d)  
W e e k  4 4 / 
E O S  
( ± 7 d) 
A d mi nistr at i ve pr oce d ures  
I nf or me d c o nse nt 
X  
 
 
 
 
 
 
 
 
 
 
 
Secti o n  8. 1. 1  
I ncl usi o n/e xcl usi o n criteria 
X  
X  
 
 
 
 
 
 
 
 
 
 
Secti o n  5  
De m o gra p hic d ata, ge neral 
me dical hist or y, a n d C S U 
me dical a n d treat me nt 
hist or y  
X  
 
 
 
 
 
 
 
 
 
 
 
Secti o n  8. 1. 7  
Pre vi o us use of a nti -I g E 
bi ol o gic  
X  
 
 
 
 
 
 
 
 
 
 
 
Pri or/c o nc o mita nt 
me dicati o ns  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Secti o n  6. 7  
Resc ue me dicati o n use  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Secti o n  6. 7. 3  
C o ntact I R T  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
Secti o n  8. 1. 3  
Dis pe nse e Diar y ( ha n d hel d 
de vice) a n d i nstr uct 
partici p a nt o n use  
X  
 
 
 
 
 
 
 
 
 
 
 
Secti o n  8. 2. 1. 3  
Ra n d o mizati o n  
 
X  
 
 
 
 
 
 
 
 
 
 
Secti o n  6. 4   
Dis pe nse st u d y dr u g  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
 
Secti o n  6. 1  
A d mi nister st u d y dr u g at 
site 
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
A d mi nister bac k gr o u n d 
t h era p y at site 
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
Distri b ute re mi n der car d  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
Secti o n  8. 1. 4  
Distri b ute partici p a ti o n 
car d  
X  
 
 
 
 
 
 
 
 
 
 
 
Secti o n  8. 1. 5  

I nc yte C or p orati o n 
P a ge 1 7  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
T a ble  3 : 
Sc he d ule of Acti vities  ( C o nti n ue d) 
Visit D a y ( R a n ge)  
Scree ni n g  
P C Peri o d  
( 1 2 Wee ks) 
E X T Peri o d  
( 2 4 Wee ks) 
P ost -
Tre at me nt 
F oll o w -U p  
N otes a n d 
Pr ot oc ol Secti o n  
D a ys  
−2 8 t o −1  
B aseli ne  
D a y 1  
W e e k 4  
( ± 3 d) 
W e e k 8  
( ± 3 d) 
W e e k  1 2/  
E O T 1  
( or E T 1) 
( ± 3 d) 
W e e k  1 6  
( ± 3 d) 
W e e k 2 0  
( ± 3 d) 
W e e k 2 4  
( ± 3 d) 
W e e k  2 8  
( ± 3 d) 
W e e k  3 2  
( ± 3 d) 
W e e k  3 6/  
E O T 2  
( or E T 2) 
( ± 3 d) 
W e e k  4 4/  
E O S  
( ± 7 d) 
A d mi nistr ati ve pr oce d ures (c o nti n ue d)  
C ollect st u d y dr u g a n d 
re vie w dr u g c o m plia nce 
 
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
Secti o n  6. 5  
F oll o w -u p p h o ne call f or 
e Diar y c o m plia nce  
X *  
 
X †  
 
X *  
 
 
 
 
 
 
 
Secti o n  8. 2. 1. 2. 1  
* 1 wee k bef ore 
visit.  
† 2 wee ks bef ore 
visit.  
Re vie w e Diar y c o m plia nce  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
Secti o n  8. 2. 1. 2. 2   
S afet y assess me nts  
A E ass ess me nts  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Secti o n  8. 3. 1   
C o ntrace pti o n c hec k  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Secti o n  5. 3. 1  
C o m pre he nsi ve p h ysic al 
e xa mi n ati o n  
X  
  
 
 
X  
 
 
 
 
 
X  
 
Secti o n  8. 3. 2  
Tar gete d p h ysical 
e xa mi n ati o n  
 
X  
X  
X  
 
X  
X  
X  
X  
X  
 
X  
Wei g ht/ hei g ht  
X  
X  
 
 
X  
 
 
X  
 
 
X  
X  
Secti o n  8. 3. 2  
Hei g ht at 
scree ni n g o nl y. 
Vital si g ns  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Secti o n  8. 3. 3   
1 2 -lea d E C G 
X  
 
 
 
X  
 
 
 
 
 
X  
 
Secti o n  8. 3. 4   

I nc yte C or p orati o n 
P a ge 1 8  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
T a ble  3 : 
Sc he d ule of Acti vities  ( C o nti n ue d) 
Visit D a y ( R a n ge)  
Scree ni n g  
P C Peri o d  
( 1 2 Wee ks) 
E X T Peri o d  
( 2 4 Wee ks) 
P ost -
Tre at me nt 
F oll o w -U p  
N otes a n d 
Pr ot oc ol Secti o n  
D a ys  
−2 8 t o −1  
B aseli ne  
D a y 1  
W e e k 4  
( ± 3 d) 
W e e k 8  
( ± 3 d) 
W e e k  1 2/  
E O T 1  
( or E T 1) 
( ± 3 d) 
W e e k  1 6  
( ± 3 d) 
W e e k 2 0  
( ± 3 d) 
W e e k 2 4  
( ± 3 d) 
W e e k  2 8  
( ± 3 d) 
W e e k  3 2  
( ± 3 d) 
W e e k  3 6/  
E O T 2  
( or E T 2) 
( ± 3 d) 
W e e k  4 4/  
E O S  
( ± 7 d) 
Effic ac y assess me nts  
P R Os  
e Diar y ( U A S/ A A S)  
Dail y fr o m scr ee ni n g t hr o u g h Wee k 4 4 ( or E T, if a p plica ble)  
Secti o n s 8. 2. 1. 3 , 
8. 2. 1. 4 , a n d 
8. 2. 1. 5  
Ha n d hel d de vice.  
Q u alit y of life assess me nts  
L a b or at or y ass ess me nts  
Ser u m F S H ( W O N C B P 
o nl y)  
X  
 
 
 
 
 
 
 
 
 
 
 
Secti o n  8. 3. 5  
Pre g na nc y testi n g 
( W O C B P o nl y) 
X *  
X †  
X †  
X †  
X †  
X †  
X †  
X †  
X †  
X †  
X †  
X *  
Secti o n  8. 3. 5. 1  
* Ser u m test  
† Uri ne test 
( p ositi ve res ult t o 
be c o nfir me d b y 
ser u m test) 
T B scre e ni n g  
X  
 
 
 
 
 
 
 
 
 
 
 
Secti o n  8. 3. 5. 2   
HI V testi n g  
X  
 
 
 
 
 
 
 
 
 
 
 
Secti o n  8. 3. 5. 3   

I nc yte C or p orati o n 
P a ge 1 9  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
T a ble  3 : 
Sc he d ule of Acti vities  ( C o nti n ue d) 
Visit D a y ( R a n ge)  
Scree ni n g  
P C Peri o d  
( 1 2 Wee ks) 
E X T Peri o d  
( 2 4 Wee ks) 
P ost -
Tre at me nt 
F oll o w -U p  
N otes a n d 
Pr ot oc ol Secti o n  
D a ys  
−2 8 t o −1  
B aseli ne  
D a y 1  
W e e k 4  
( ± 3 d) 
W e e k 8  
( ± 3 d) 
W e e k  1 2/  
E O T 1  
( or E T 1) 
( ± 3 d) 
W e e k  1 6  
( ± 3 d) 
W e e k 2 0  
( ± 3 d) 
W e e k 2 4  
( ± 3 d) 
W e e k  2 8  
( ± 3 d) 
W e e k  3 2  
( ± 3 d) 
W e e k  3 6/  
E O T 2  
( or E T 2) 
( ± 3 d) 
W e e k  4 4/  
E O S  
( ± 7 d) 
L a b or at or y ass ess me nts  (c o nti n ue d) 
He patitis testi n g  
X  
 
 
 
 
 
 
 
 
 
 
 
Secti o n  8. 3. 5. 4   
H B V D N A (f or re q uire d 
partici p a nts)  
X  
 
 
 
X  
 
 
X  
 
 
X  
 
C he mistr y a n d he mat ol o g y  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Secti o n  8. 3. 5  
C oa g ulati o n pa nel  
X  
X  
 
 
X  
 
 
X  
 
 
X  
X  
Uri nal ysis  
X  
 
 
 
X  
 
 
 
 
 
X  
 
Nic oti ne meta b olite scree n 
( uri n e) 
 
X  
 
 
X  
 
 
 
 
 
X  
 
Li pi d pa nel  
 
X  
 
 
X  
 
 
X  
 
 
X  
X  
hs C R P  
 
X  
X  
X  
X  
 
 
X  
 
 
X  
X  
N ote: U nsc he d ule d visits ma y oc c ur at a n y ti me as me dicall y warr a nte d. A n y assess me nts p erf or me d at t h ose visits s h o ul d be rec or de d i n t h e e C R F. 
 

I nc yte C or p orati o n 
P a ge 2 0  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
2.  
I N T R O D U C TI O N 
2. 1.  
B ac k gr o u n d  
Urticaria is a h eter o ge ne o us gr o u p of diseases c haracterize d b y itc h y hi ves a n d/ or a n gi oe de m a . 
C hr o nic s p o nta ne o us urticaria, f or merl y k n o w n as c h r o nic i di o pat hic urticaria, is defi ne d b y t he 
prese nce of w h eals ( hi ves), a n gi oe de ma, or b ot h f or m ore t ha n 6 wee ks wit h o ut a n i de ntifia ble 
ca use ( Z u b er bier  et al 2 0 2 2 ). T he o verall w orl d wi de pre val e nce of C S U is a p pr o xi matel y 1 % 
wit h t he p ote ntial f or a hi g h diseas e b ur de n ( G o n çal o et al 2 0 2 1). Affect e d patie nts ca n 
e x perie nce a n u n pre dicta ble disease c o urse a n d d urati o n wit h s y m pt o ms occ urri n g i n a 
s p o nta ne o us a n d rec urre nt ma n ner a n d lasti n g o ver se veral years ( F o k  et al 2 0 2 1 ). F urt her m ore, 
se vere pr urit us a n d t he s u d de n a n d u n pre dicta ble a p peara n ce of w heals a n d a n gi o e de ma ca n 
i m pact slee p a n d patie nts' w ell -bei n g ( G o n çal o et al 2 0 2 1 ). 
Treat me nt of C S U re m ai ns c halle n gi n g wit h n o nse dati n g, s ec o n d -ge nerati o n , H 1  a nti hista mi nes 
bei n g first -li ne t hera p y at u p t o 4 ti mes t he rec o m me n de d dail y d ose if nee de d (Z u ber bi er  
et al 2 0 2 2 ). W hile sec o n d -ge nerati o n , H 1 a nti hista mi nes are effecti ve i n r elie vi n g s y m pt o ms f or 
s o me patie nts, a p pr o xi matel y 5 0 % of i n di vi d uals s h o w i ns ufficie nt res p o ns e t o hi g h -d os e , 
sec o n d-ge n erati o n a nti hista mi nes ( G o n çal o et al 2 0 2 1 ). O mali z u ma b, a n a nti -I g E m o n ocl o n al 
a nti b o d y (a d mi nistere d s u bc uta ne o usl y) , is rec o m me n de d i n c o m bi nati o n wit h 
sec o n d-ge n erati o n , H 1 – a nti hista mi ne treat me nt as  a sec o n d li ne i n t he tr eat me nt al g orit h m, wit h 
o nl y a p pr o xi matel y 3 5 % of patie nts ac hie vi n g a c o m plete  res p o nse after 1 2 wee ks (Ka pla n  
et al 2 0 1 3 ). F or t h ose patie nts w h o c o nti n ue t o re mai n s y m pt o matic wit h i na de q uate disease 
c o ntr ol, c ycl os p ori n is rec o m me n de d as a t hir d -li ne treat me nt o pti o n i n c o m bi nati o n wit h 
sec o n d-ge n erati o n , H 1  a nti hista mi nes, alt h o u g h it is n ot lice nse d f or urticaria a n d has a hi g h 
i nci de nce of a d verse effects, li miti n g its use i n ma n y patie nts wit h C S U ( Z u ber bier  et al 2 0 2 2 ). 
T h us, t here is a nee d f or ot her sec o n d- a n d t hir d-li ne treat me nt o pti o ns t hat ca n be a d mi nistere d 
orall y a n d p ote ntiall y offer a n i m pr o ve d effi cac y a n d si de -effect pr ofile f or t he ma na ge me nt of 
C S U.  
T he pat h o ge nesis of C S U is n ot f ull y u n derst o o d . Preli mi nar y e vi de nce s u g gests it is a n 
aut oi m m u ne, mast  cell– dri ve n disease wit h at least 2 e n d ot y pes. I n T y pe I a ut oi m m u ne C S U, 
a ut oreacti ve I g E a nti b o di es directe d a gai nst a ut oa nti ge ns are t h o u g ht t o de gra n ulate s ki n 
mast  cells via t he acti vati o n of t he hi g h -affi nit y I g E rece pt or Fcɛ RI α. I n T y pe II b a ut oi m m u ne 
C S U, de gra n ulati o n of mast cells is t h o u g ht t o be ca use d b y i m m u n o gl o b uli n G a n d/ or 
i m m u n o gl o b uli n M a ut oa nti b o dies directe d a gai nst Fcɛ RI α or Fcɛ RI α -b o u n d I g E ( Altric hter  
et al 2 0 2 1 ). 
Hista mi ne a n d  ot her me diat ors, s uc h as platelet -acti vati n g fact or a n d c yt o ki nes release d fr o m 
acti vate d s ki n mast cells , res ult i n se ns or y ner ve acti vati o n, vas o dilati o n, a n d plas ma 
e xtra vasati o n as well as cell recr uit me nt t o urticarial lesi o ns ( Z u b er bier  et al 2 0 2 2 ). I ncrease d 
ser u m le vels of T h 1/ T h 2 a n d T h 1 7 res p o nses a n d relate d c yt o ki nes i n C S U are c orrel ate d wit h 
t he se verit y of t he dise as e, w hic h s u p p ort t he e xiste nce of a n a ut oi m m u ne basis a n d 
pr oi nfla m mat or y pr ocess i n C S U  (C he n  et al 2 0 18 ). 
I n crease d e x pressi o n of J A K-me diate d i nfl a m mat or y c yt o ki n es s uc h as I L -9, I L -1 0, a n d S T A T 3 
i n t he s ki n of patie nts wit h C S U (Fe n g et al  2 0 2 0 ) as well as hi g h ser u m le vels of I F N-ɣ, I L -2 , 

I nc yte C or p orati o n 
P a ge 2 1  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
a n d I L-2 1 ( C h e n et al 2 0 1 8 ) s u g gest p ositi ve re g ulati o n of t he J A K-S T A T si g nali n g pat h wa y i n 
C S U . I L-6 a n d I L -2 3, b ot h acti vati n g t h e J A K/ S T A T 3 si g nali n g pat h w a ys, are i ncreas e d i n C S U, 
a n d t heir ser u m co n ce ntr ati o n s are relate d t o t he acti vit y of t he dise ase ( At wa et al 2 0 1 4 , Z ha n g  
et al 2 0 2 1). O nc ostati n M rece pt or, a me m ber of t he I L-6 rece pt or fa mil y, als o partici pates i n t he 
pat h o ge nesis of C S U t hr o u g h t he J A K/ S T A T pat h wa y ( Z ha n g  et al 2 0 2 1). 
J a n us ki nase si g nali n g re g ulates s e veral pr oi nfla m mat or y p at h wa ys a n d h as bee n 
well -rec o g niz e d as a ke y dri ver f or n u m er o us s ki n diseases. S mall -m olec ul e J A K i n hi bit ors 
pr o vi de a nti -i nfla m mat or y effects t hr o u g h disr u pti o n of t he J A K-S T A T si g nali n g pat h w a y use d 
b y m ulti ple c yt o ki ne rece pt ors, i ncl u di n g t h ose f or I L -4, I L -6, I L -1 3, I L -3 1 , a n d 
T h 1/ T h 2/ T h 2 2 -relate d c yt o ki nes. J A K 1/ 2 i n hi biti o n ca n als o m o d ulate mast cell – acti vati o n, 
i ncl u di n g de gra n ulati o n a n d c yt o ki ne pr o d ucti o n (Her ma ns et al 2 0 1 8 ) a n d re d uces c he m o ki ne 
secreti o n, le a di n g t o less cell ular i nfiltrate (i e, C X C L 1 0; Fe n wic k et al 2 0 1 5 ). 
J a n us ki nase i n hi bit ors als o li kel y ha ve itc h-s pecific ne ur o m o d ulat or y effects. J a n us ki nase 1 is 
selecti vel y e x presse d i n itc h-se ns or y ne ur o ns c o m pare d wit h J A K 2 a n d J A K 3, a n d i n m o use 
m o dels of A D -li ke diseas e, ne ur o n-s p ecific ge neti c deleti o n of J A K 1 res ults i n mar ke dl y re d uce d 
pr urit us i n de pe n de nt of t he le vel of s ki n i nfla m mati o n ( Oetje n et al 2 0 1 7 ). J a n us ki nase 
i n hi bit ors ha ve de m o nstrate d s u bsta ntial i m pr o ve me nt i n itc h acr oss diseas es s uc h as A D  
(Eri ks o n  et al 2 0 2 1). 
C hr o nic s p o nta ne o us urticaria case re p orts i ncl u de a case st u d y of a patie nt w h o was treate d f or 
m yel ofi br osis wit h oral r u x oliti ni b (a J A K 1/ 2 i n hi bit or) a n d e x perie nce d c o m plete c o ntr ol of 
t heir refract or y C S U wit hi n 5 wee ks (F u k u na ga  et al 2 0 1 8 ). A n ot her p u bli cati o n re p orts 4  cases 
of l o n g -t er m refract or y c hr o nic urticari a a n d 1  cas e of urticarial vasc ulitis t hat were s u ccessf ull y 
ma na ge d wit h t ofaciti ni b (a J A K 1/ 3 i n hi bit or) a n d ulti matel y le d t o ta peri n g a n d dis c o nti n uati o n 
of c ycl os p ori ne or a nti hista mi nes ( Ma ns o uri  et al 2 0 2 2 ). 
P o v orciti ni b  (I N C B 0 5 4 7 0 7) is a n o vel, p ote nt, oral, s mall-m olec ule, selecti ve , J A K 1 i n hi bit or 
u n der e val u ati o n i n H S, vitili g o, pr uri g o n o d ul aris, a n d ast h ma cli nical trials . P o v orciti ni b  
p ote ntl y i n hi bits J A K 1 (I C 5 0 ≈ 9 n M), wit h a p pr o xi matel y 4 5 - t o greater t ha n  1 0 0 0 -f ol d 
selecti vit y o ver t he ot her J A K fa mil y m e m bers (ie, J A K 2, J A K 3, a n d T Y K 2). 
 
2. 2.  
St u d y R ati o n ale  
Des pite t he a vaila bilit y of se veral a p pr o v e d treat m e nts a n d defi ne d m a na ge me nt g ui deli nes f or 
C S U, ma n y patie nts wit h C S U ha ve disease t hat re mai ns u nc o ntr olle d b y S O C  t hera pies, 
i n dicati n g a si g nifica nt u n met me dical nee d f or ne w treat me nt o pti o ns. 
O verall, J A K -me diate d si g nali n g has bee n i m plicate d i n t he pat h o ge n esis of C S U , a n d J A K 
i n hi bit ors ha ve t he p ote ntial t o tar get u n derl yi n g p at h o p h ysi ol o gical mec ha nis ms of disease. T his 
st u d y will e val uate t h e efficac y a n d safet y of t he J A K 1 i n hi bit or p o v orciti ni b  i n a d ults wit h C S U 
t hat is i na de q uatel y c o ntr olle d usi n g S O C  treat me nt wit h sec o n d-ge nerati o n H 1  a nti hista mi nes.  
2. 2. 1.  
Scie ntific R ati o n ale f or St u d y Desi g n  
I n t his pr o of -of -c o nce pt st u d y, t he cli nical efficac y a n d safet y of 3 d ose  re gi me ns ( 1 5, 4 5, a n d 
7 5  m g Q D)  of t he oral J A K 1 i n hi bit or p o v orciti ni b  will be e val uate d i n a d ult partici pa nts wit h 
C S U c o m pare d wit h place b o f or 1 2 wee ks f oll o we d b y a 2 4 -wee k E X T  p eri o d . D uri n g t h e 

I nc yte C or p orati o n 
P a ge 2 2  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
E X T  peri o d, partici pa nts ra n d o mize d t o p o v orciti ni b  at baseli ne will re mai n o n t heir ra n d o mize d 
treat me nt d ose re gi me n (p o v orciti ni b  1 5, 4 5, or 7 5 m g Q D) w hile partici p a nts recei vi n g place b o 
will be assi g ne d acti ve tr eat me nt ( p o v orciti ni b  1 5, 4 5 , or 7 5 m g) i n a 1: 1: 1 rati o. All partici pa nts 
will re mai n o n a bac k gr o u n d t hera p y of sta ble -d os e , sec o n d-ge nerati o n H 1  a nti hista mi ne ( S O C ) 
t hr o u g h o ut t he st u d y. T h e ra n d o mize d, d o u ble-bli n d, place b o -c o ntr olle d desi g n s u p p orts t he d ose  
ra n ge-fi n di n g a n d assess me nt of effic ac y as well as safet y. 
T he use of place b o is c o nsi dere d a p pr o priate si nce partici pa nts will c o nti n ue wit h a sta ble d ose 
of bac k gr o u n d t h era p y of  sec o n d-ge n erati o n  H 1  a nti hista mi ne ( S O C ). Partici pa nts will als o be 
all o we d res c ue t hera p y wit h f urt her d oses of a sec o n d-ge nerati o n H 1  a nti hista mi ne t hr o u g h o ut 
t he st u d y if nee de d. I n a d diti o n, fr o m Wee k 5, a 1 -ti me, s h ort c o urse ( ma xi m u m of 7 da ys) of 
gl uc o c ortic oster oi ds ma y be use d as r esc ue m e dicati o n i n t he case of se vere s y m pt o m 
e x acer bati o n. D uri n g t he E X T  peri o d, partici pa nts i n t he place b o gr o u p will recei v e acti ve 
treat me nt (p o v orciti ni b  1 5, 4 5, or 7 5 m g Q D).  
D uri n g t h e p ost -treat me nt f oll o w-u p peri o d all partici pa nts e x perie nci n g a w ors e ni n g of 
s y m pt o ms ma y  recei ve a resc ue t h era p y d ee me d a p pr o priate b y t he i n vesti gat or ( see 
Secti o n  6. 7. 3 ). 
T he baseli ne str atificati o n criteri o n  selecte d f or t his st u d y is pr e vi o us treat me nt of C S U wit h a n 
a nti-I g E bi ol o gic. Partici pa nts wit h pri or e x p os ure t o bi ol o gic t hera pi es ma y ha v e m ore s e vere 
disease a n d p ote ntiall y disti nct res p o nse t o t hera p y, s u g gesti n g t he i m p orta n ce of a n a de q u ate 
dist ri b uti o n of t hese partici pa nts acr oss t he differe nt st u d y treat me nt gr o u ps. T he pr o p ose d 
stratificati o n criterio n  ma y hel p b ala nce t he n u m ber of partici pa nts w h o h a v e pre vi o usl y recei ve d 
a nti-I g E bi ol o gics acr oss t he st u d y treat me nt gr o u ps, p ote ntiall y allo wi n g a better u n dersta n di n g 
of t he treat me nt effect of p o v orciti ni b . 
T he ti me i nter val of 1 2 wee ks f or t he P C peri o d a n d t he pri mar y e n d p oi nt is s ufficie nt t o all o w 
f or assess me nt of b ot h itc h a n d a n gi oede m a res ol uti o n a n d is ali g ne d wit h s e veral ot her cl i nical 
trials i n C S U, t here b y i m p osi n g n o i ncrease d ti me b ur de n f or p artici pa nts e nteri n g t his st u d y 
vers us  ot hers . D ata of p o v orciti ni b  i n H S de m o nstrate a tr eat me nt effect o n itc h at 2 wee ks, wit h 
c o nti n ue d re d ucti o n of it c h s y m pt o ms o ver 1 2 wee ks ( Kir b y et al 2 0 2 2c ). Cli nical st u dies of 
ot her J A K i n hi bit ors f or t he treat me nt of A D  re p orte d re d ucti o n of itc h earl y i n treat me nt a n d 
c o nti n ue d i m pr o ve me nts i n disease se verit y at 1 6 wee ks ( Eri ks o n  et al 2 0 2 1). 
Fi n di n gs fr o m cas e st u dies re p orte d o n t he use of t ofaciti ni b i n C S U ( Ma ns o uri et al 2 0 2 2 ) 
s u g gest patie nts wit h t he m ost se vere s y m pt o ms ma y re q uir e a l o n ger peri o d of treat me nt a n d 
j ustifies a 2 4-wee k E X T  peri o d i n t he prese nt st u d y , w hic h will i ncl u de partici pa nts wit h C S U 
t hat is i na de q uatel y c o ntr olle d o n H 1 a nti hista mi nes, w h o ma y ha v e  e x perie nce d tr eat me nt 
fail ure o n or after m o n o cl o nal a nti b o d y t hera p y, or  wit h C S U t hat  is m ore diffic ult t o treat.  
After c o m pleti o n of t he P C peri o d, partici pa nts will c o nti n ue t he st u d y i n t h e 2 4 -wee k 
E X T  peri o d , w hic h  all o ws partici pa nts i nitiall y ra n d o mize d t o place b o t o recei ve acti ve dr u g a n d 
f urt her e v al uati o n of t he effic ac y a n d s afet y of p o v orciti ni b . T he 6 0-da y , p ost -treat me nt, 
f oll o w-u p peri o d all o ws f or assess me nt of persiste nce of t he effect of p o v orciti ni b  i n C S U 
wit h o ut c o m pr o misi n g partici pa nts w h o wis h t o e nr oll i n ot her o n g oi n g st u dies or nee d t o r ecei v e 
alter nati ve treat me nt f or t heir C S U.  
Details of t he o bjecti ves a n d e n d p oi nts are i n cl u de d i n Secti o n  3 . T he pri m ar y efficac y e n d p oi nt 
of c ha n ge fr o m bas eli ne i n t he U A S 7 at Wee k 1 2 has bee n c h os e n beca use it is a vali date d 

I nc yte C or p orati o n 
P a ge 2 3  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
q uesti o n naire a n d h as bee n use d i n pi v otal trials i n C S U t o meas ure re d u cti o n i n C S U disease 
se verit y. 
T he sec o n d ar y  efficac y e n d p oi nts are c o m m o nl y use d i n C S U cli nical trials . T he safet y 
e n d p oi nts are t y pical f or me dici nes i n P hase 2 cli nical de vel o p me nt , a n d A E SIs rele va nt t o t he 
J A K i n hi bit or class of c o m p o u n ds will als o be m o nit ore d t o e n ha nce safet y f or partici pa nts. 
Safet y will be assesse d b y e v al uati o n of A E a n d la b orat or y d ata . Ot her e n d p oi nts i n t he st u d y 
will assess healt h -rel ate d q ualit y of life  usi n g vali date d P R Os, w hic h will pr o vi de i nsi g ht i nt o t he 
partici pa nt 's e x perie nce of t heir C S U a n d t he i m pact of treat me nt o n t heir disease. As t his is t he 
first use of p o v orciti ni b  i n a C S U p o p ulati o n, s yste mic dr u g c o nce ntrati o n data a n d bi o mar kers 
will be assesse d t o c haracteriz e e x p os ure a n d t he P K/ P D relati o ns hi p of  p o v orciti ni b  i n 
partici pa nts wit h C S U.  
2. 2. 2.  
J ustific ati o n f or D ose  
T his is t he first cli nical trial of p o v orciti ni b  i n C S U, a n d t h us, t here are n o p o v orciti ni b  data i n 
patie nts wit h C S U t o directl y i nf or m d ose re gi me ns . T heref ore, d ose s electi o n f or t his st u d y  was 
base d o n t he res ults of pre vi o us st u dies wit h p o v orciti ni b  i n partici pa nts wit h H S, a 
der mat ol o gi cal i n dicati o n ass ociate d wit h a s yste mic i nfla m mat or y b ur de n, w hic h dis pla ys s o me 
si milarities wit h C S U re gar di n g its i m m u n ol o gical si g nat ur e. T he d oses of p o v orciti ni b  ( 1 5, 4 5, 
a n d 7 5 m g) t o be e val u ate d i n t he c urre nt st u d y fall wit hi n t he ra n ge of d oses pre vi o usl y s h o w n 
t o ha ve a fa v ora bl e safet y pr ofile i n c o m plete d a n d o n g oi n g P hase 2 trials i n H S . 
Pr o of of c o nce pt was i nitiall y de m o nstrat e d f or p o v or citi ni b i n 2 c o m plete d P hase 2 , H S st u dies 
o ver 8 wee ks of treat me nt wit h eit her a d ose of 1 5 m g Q D ( St u d y I N C B 5 4 7 0 7 -2 0 2 
[ N C T 0 3 5 6 9 3 7 1]; n =  1 0 e x p ose d t o p o v orciti ni b ) or d oses of 3 0, 6 0, a n d 9 0 m g Q D ( St u d y 
I N C B 5 4 7 0 7-2 0 3 [ N C T 0 3 6 0 7 4 8 7]; n  =  2 6 e x p ose d t o p o v orciti ni b ). I n b ot h of t hese c o m plete d 
st u dies, all d oses were ge nerall y well-t olerate d wit h n o S A Es (Ala vi  et al 2 0 2 2 ). A t hir d P hase 2 , 
H S  st u d y is o n g oi n g 
 a n d is e val uati n g p o v orciti ni b  
1 5, 4 5, a n d 7 5 m g Q D a d mi nistere d u p t o 2 3 m o nt hs. T he d oses selecte d f or t he c urre nt st u d y are 
base d o n t he pri mar y a nal ysis res ults fr o m t he 1 6 -wee k , P C  peri o d of 
. I n 
t hat st u d y, partici p a nts treate d wit h p o v orc iti ni b 1 5 m g Q D d e m o nstrate d cli nical i m pr o ve me nt 
acr oss m ost of t he cli nici a n - a n d patie nt -re p orte d o utc o mes, alt h o u g h ge nerall y n ot statisticall y 
differe nt fr o m place b o ( Kir b y  et al 2 0 2 2a, Kir b y  et al 2 0 2 2 b , Kir b y  et al 2 0 2 2c); t hese res ults 
c ollecti vel y s u g gest t hat p o v orciti ni b 1 5 m g w o ul d be a n a d e q uate  mi ni m u m effecti ve d ose . 
Partici pa nts treate d wit h  p o v orciti ni b  4 5 a n d 7 5 m g Q D e x perie nce d a si g nifica nt i m pr o ve me nt 
c o m pare d wit h pla ce b o acr oss all assess me nts. F urt her, partici p a nts wit h m ore se vere dise ase 
de m o nstrate d directi o nall y better i m pr o ve me nt w he n treate d wit h  p o v orciti ni b  7 5  m g ( data o n 
file), s u g gesti n g t h at t his w o ul d be a n a d e q uate u p per d ose le vel. Safet y res ults de m o nstrate d t hat 
p o v orciti ni b  was well -t olerate d, wit h n o i ncreas e i n t he i nci de nce of T E A Es or ot her safet y si g ns 
wit h i ncreasi n g d oses of p o v orciti ni b . O verall, t he fi n di n gs fr o m t he Wee k 1 6 p ri mar y a nal ysis 
of 
 s u g gest a tre n d t o war d d ose-d e pe n de nt efficac y bet w ee n 1 5 m g a n d t he 
2  hi g her d oses wit h n o e vi de nce f or i ncrease d ris k of seri o us t o xicit y at hi g her d oses.  
All partici pa nts will c o nti n ue wit h a sta ble d ose of bac k gr o u n d t hera p y of  s ec o n d-ge n erati o n  
H 1  a nti hista mi ne ( S O C ), a n d partici pa nts recei vi n g place b o will be assi g ne d acti ve treat me nt 
(p o v orciti ni b  1 5, 4 5, or 7 5 m g ) i n a 1: 1: 1 r ati o i n t he E X T  peri o d.  

I nc yte C or p orati o n 
P a ge 2 4  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
I n c o ncl usi o n, it is e x pecte d t hat t he d oses select e d i n t he c urre nt st u d y are a de q uate a n d safe t o 
e x pl ore t he d ose res p o ns e of p o v orciti ni b  i n partici pa nts wit h C S U. 
2. 3.  
Be nefit/ Ris k Assess me nt  
T he p ote ntial ris ks t o partici pa nts base d o n t he a v aila ble n o ncl i nical a n d cli nical data f or 
p o v orciti ni b  a n d ris ks ass ociate d wit h ot her J A K i n hi bit ors are s u m marize d i n  Ta ble  4 . 
Base d o n t h e e x pecte d m o de of acti o n  of p o v orciti ni b , partici pa nts ra n d o ml y assi g ne d t o a n 
acti ve treat me nt gr o u p ma y e x perie nce cli nicall y mea ni n gf ul i m pr o ve me nts i n t heir C S U d uri n g 
t he d o u ble -bli n d, P C  peri o d  ( 1 2 wee ks) . F urt h er m ore, all partici pa nts will be offere d tr eat me nt 
wit h  p o v orciti ni b  d uri n g t he E X T  peri o d ( 2 4 wee ks), w hic h will pr o vi de t he o p p ort u nit y f or 
s y m pt o m i m pr o ve me nt i n a disease wit h a n u n m et nee d t hat has a si g nifica nt i m pact o n 
partici pa nts ' well -bei n g a n d dail y f u ncti o ni n g.  
T he safet y of partici pa nts will be m o nit ore d t hr o u g h o ut t he st u d y, a n d bas e d o n i n di vi d ual 
res p o nse, t he d ose m a y b e te m p oraril y i nterr u pte d if t here are A Es or la b orat or y a b n or malities 
t hat ma y h a ve a n u n clear relati o ns hi p t o st u d y dr u g. A d dit i o nall y, a n i nter nal D S M B will re vie w 
safet y data p eri o dicall y t hr o u g h o ut t he st u d y , a n d a C A C will assess p ote ntial car di o vas c ular a n d 
t hr o m b oe m b olic A Es. 
C o nsi deri n g t he c u m ulati ve safet y i nf or mati o n o n p o v orciti ni b , t he p ote ntial ris ks i de ntifie d are 
j ustifia ble a n d a p pr o pri atel y b ala nce d b y t he a ntici pate d efficac y be nefits e x pecte d t o be aff or de d 
t o partici pa nts. M ore det aile d i nf or mati o n a b o ut t he k n o w n a n d e x pecte d be nefits a n d ris ks a n d 
reas o na bl y e x pecte d A E s of p o v orciti ni b  ma y b e f o u n d i n 
 

I nc yte C or p orati o n 
P a ge 2 5  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
T a ble  4 : 
Ris k -Miti g ati o n Assess me nt f or P o v o rciti ni b  
P ote nti al Ris k of Cli nic al 
Si g nific a nce  
S u m m ar y of D at a 
A v ail a ble/ R ati o n ale f or Ris k  
Miti g ati o n Str ate g y  
Gra d e 3 or hi g her ( <  5 0  ×  1 0 9/ L) 
decreases i n platelet c o u nt s 
Gra d e 3 or hi g her decreases i n 
platelet c o u nt s ha ve n ot yet bee n 
o bser ve d wit h p o v orciti ni b . 
Tra nsie nt a n d n o ncli nicall y 
si g nifica nt e ve nts of Gra de 1 
( < 1 0 0  t o 7 5 × 1 09/ L) or Gra de 2 
( < 7 5 t o 5 0 × 1 0 9/ L) decreases i n 
platelet c o u nt s ha ve bee n o bser ve d 
i n rare cases. 
P ote ntial partici pa nts wit h a hist or y 
of t hr o m b oc yt o pe nia, 
c oa g ul o pat h y, or platelet 
d ysf u ncti o n will be e xcl u de d.  
Ra n d o mize d partici pa nts will be 
m o nit ore d f or p ossi ble decrease d 
platelet c o u nts, a n d acti o ns will be 
ta ke n acc or di n g t o t he st u dy 
pr oce d ures (see  Secti o n  6. 6. 1 ) 
T hr o m b oe m b olic e ve nts  
I ncrease d i nci de nce of M A C E, 
p ul m o nar y e m b olis m, a n d ve n o us 
a n d arterial t hr o m b osis has be e n 
o bser ve d wit h ot her J A K i n hi bit ors 
(F D A 2 0 2 1 ). 
T he ass ociati o n of t hr o m b oe m b olic 
e ve nts wit h p o v orciti ni b  has n ot 
bee n esta blis he d. P ul m o nar y 
e m b olis m has occ urre d i n 
2  partici pa nts wit h m ulti ple 
i n de p e n de nt ris k fact ors. 
P ote ntial partici pa nts wit h a hist or y 
of t he f oll o wi n g e ve nts will be 
e xcl u de d: ve n o us a n d arterial 
t hr o m b osis, dee p vei n t hr o m b osis, 
p ul m o nar y e m b olis m, str o ke, 
m o derate t o se vere heart fail ur e 
( N Y H A Class III or I V), 
cere br o vasc ular acci de nt, MI , 
c or o nar y ste nti n g,  or  C A B G 
s ur ger y. 
Ra n d o mize d partici pa nts will be 
m o nit ore d f or car di o vasc ular e ve nts 
a n d e m b olic a n d t hr o m b otic e ve nts 
(see Secti o ns  6. 6. 1  a n d 9. 6. 1 ). 
A d diti o nall y, a C A C will be 
i m ple me nte d f or t his st u d y (se e 
Secti o n  5. 7 ). 
Seri o us bacterial, f u n gal, viral, a n d 
o p p ort u nistic i nfecti o ns  
I ncrease d ris k of seri o us bacterial, 
f u n gal, viral, a n d o p p ort u nisti c 
i nfecti o ns has bee n o bser ve d wit h 
ot her J A K i n hi bit ors ( F D A 2 0 2 1 ). 
T he ass ociati o n of s yste mic 
i nfecti ons wit h p o v orciti ni b  has n ot 
bee n esta blis he d.  
Gra d e 1 a n d Gra de 2 i nfecti o ns 
ha ve bee n o bser ve d b ut di d n ot 
re q uire st u d y dr u g i nterr u pti o n. 
P artici pa nts will be scree ne d f or T B 
i nfecti o n, c hr o nic he patitis, HI V, 
a n d c hr o nic/rec urre nt i nfecti o ns.  
Ra n d o miz e d partici pa nts will be 
m o nit ore d f or a n y si g ns a n d 
s y m pt o ms of i nfecti o n t hr o u g h o ut 
t he st u d y (e g, cli nical la b orat or y 
tests, vital si g ns, a n d A E 
m o nit ori n g; see  Secti o ns  6. 6. 1 , 
6. 6. 1. 3 , a n d  9. 6. 1 ). 
Mali g na ncies  
I ncrease d ris k of mali g na ncies has 
bee n o bser ve d wit h ot her J A K 
i n hi bit ors (F D A 2 0 2 1 ). 
T he ass ociati o n of mali g na nci es 
wit h p o v orciti ni b  has n ot bee n 
esta blis he d.  
P artici pa nts will be scree ne d f or 
mali g na ncies or hist or y of 
mali g na ncies, wit h t he e xce pti o n of 
a de q uatel y treate d or e xcise d 
n o n metastatic basal cell or 
s q ua m o us cell ca ncer of t he s ki n or 
cer vical carci n o ma i n sit u.  
Ra n d o mize d partici pa nts will be 
m o nit ore d f or all t y pes of 
mali g na ncies (see  Secti o n s 6. 6. 1 , 
6. 6. 1. 5 , a n d  9. 6. 1 ). 

I nc yte C or p orati o n 
P a ge 2 6  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
T a ble  4 : 
Ris k -Miti g ati o n Assess me nt f or P o v o rciti ni b  ( C o nti n ue d) 
P ote nti al Ris k of Cli nic al 
Si g nific a nce  
S u m m ar y of D at a 
A v ail a ble/ R ati o n ale f or Ris k  
Miti g ati o n Str ate g y  
Reti nal de ge nerati o n i n i n di vi d uals 
wit h al bi nis m  
Bilateral reti nal de ge nerati o n has 
bee n o bser ve d i n al bi n o rats.  
I n di vi d uals wit h al bi nis m will n ot 
be e nr olle d i n t he st u d y.  
Re pr o d ucti ve a n d de vel o p me ntal 
t o xicit y 
Prei m pla ntati o n a n d 
p osti m pla ntati o n l oss a n d d ecrease d 
fetal wei g ht ha ve bee n o bser ve d i n 
rat a n d ra b bit st u dies. 
P artici pa nts of re pr o d ucti ve 
p ote ntial will be re q uire d t o us e 
strict c o ntrace pti ve meas ures (see 
Secti o n  5. 1  a n d A p pe n di x  A ). 
A g gra vati o n of C S U  
W orse ni n g of C S U ma y occ ur 
eit her as a s p o nta ne o us e ve nt or d ue 
t o i ns ufficie nt efficac y of t he st u d y 
dr u g . 
All partici pa nts will be ta ki n g 
bac k gr o u n d t hera p y ( S O C) f or t he 
d urati o n of t he st u d y. P artici pa nts 
will als o be per mitte d t o use r esc ue 
me dicati o n  i n t he e ve nt of 
w orse ni n g C S U s y m pt o ms (se e  
Secti o n  6. 7. 3 ). 
P artici pa nts ma y wit h dra w fr o m t he 
st u d y at a n y ti me f or a n y reas o n, i n 
w hic h case t he y  w o ul d be a ble t o 
use alter nati ve c o n ve nti o nal 
treat me nts f or t heir C S U. 

I nc yte C or p orati o n 
P a ge 2 7  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
3.  
O B J E C TI V E S A N D E N D P OI N T S  
Ta ble  5  pres e nts t he o bje cti ves a n d e n d p oi nts.  
T a ble  5 : 
O bjecti ves a n d E n d p oi nts  
O bjecti ves  
E n d p oi nts  
P ri m ar y  
T o e val uate t he efficac y of p o v orciti ni b  i n 
partici pa nts wit h C S U.  
C ha n ge fr o m baseli ne i n t he U A S 7, defi ne d as t he 
7 -da y s u m of t he i n di vi d ual, dail y rec or de d sc ores 
f or H S S a n d I S S, at Wee k 1 2. 
Sec o n d ar y  
T o f urt her e val uate t he efficac y of p o v orciti ni b  i n 
partici pa nts wit h C S U.  
•  Pr o p orti o n of partici pa nts w h o ac hie ve 
U A S 7  ≤ 6 (c o ntr olle d disease) at Wee k 1 2.  
•  Ti me t o first ac hi e ve me nt of  U A S 7 ≤ 6 
(c o ntr olle d disease) d uri n g t he P C peri o d.  
•  P r o p orti o n of partici pa nts wit h U A S 7 = 0 at 
Wee k 1 2.  
S af et y  
T o e val uate t he safet y a n d t olera bilit y of 
p o v orciti ni b . 
A Es, assesse d b y c ha n ges i n vital si g ns  a n d E C Gs 
a n d t hr o u g h cli nical la b orat or y sa m ple e val uati o ns 
a n d t he res ults of p h ysical e xa mi nati o ns. 
E x pl or at or y  

I nc yte C or p orati o n 
P a ge 2 8  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
T a ble  5 : 
O bjecti ves a n d E n d p oi nts  ( C o nti n ue d) 
O bjecti ves  
E n d p oi nts  
E x pl or at or y  (c o nti n ue d) 

I nc yte C or p orati o n 
P a ge 2 9  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
T a ble  5 : 
O bjecti ves a n d E n d p oi nts  ( C o nti n ue d) 
O bjecti ves  
E n d p oi nts  
E x pl or at or y  (c o nti n ue d) 

I nc yte C or p orati o n 
P a ge 3 0  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
4.  
S T U D Y D E SI G N  
4. 1.  
O ver all Desi g n  
T his is a P hase 2, d o u ble -bli n d, place b o -c o ntr olle d, m ultice nter st u d y of p o v orciti ni b  i n 
partici pa nts wit h C S U o n sta ble S O C wit h sec o n d-ge n erati o n H 1  a nti hista mi nes. T he st u d y will 
e nr oll a p pr o xi matel y 1 3 6  partici pa nts i n a 1: 1: 1: 1 ra n d o mizati o n rati o, stratifie d at baseli ne b y 
pre vi o us a nti -I g E bi ol o gic use ( yes or n o), i nt o 1 of 4 treat me nt gr o u ps d uri n g t he P C peri o d 
( 1 2 wee ks) as s h o w n  i n Fi g ure  1 . 
T reat me nt wit h st u d y dr u g will start o n Da y 1  ( bas eli ne). After c o m pleti n g t he 1 2-wee k P C 
peri o d, partici pa nts will e nter t he 2 4 -w ee k E X T p eri o d. D uri n g t h e E X T peri o d, t he partici pa nts 
i nitiall y ra n d o mize d t o p o v orciti ni b  1 5, 4 5, or 7 5 m g Q D will c o nti n ue ta ki n g p o v orciti ni b  at t he 
sa me d ose re gi me n. T he partici pa nts i nitiall y ra n d o mize d t o place b o will be assi g n e d t o ta ke 1 of 
t hese 3 d ose re gi me ns (ie, p o v orciti ni b  1 5, 4 5, or 7 5 m g Q D). Partici pa nts, i n vesti gat ors, a n d t he 
s p o ns or will re mai n bli n de d t o eac h p artici pa nt 's treat me nt assi g n me nt d uri n g t he P C  peri o d. 
Partici pa nts a n d i n vesti gat ors will c o nti n ue t o re mai n bli n de d d uri n g t he E X T peri o d a n d 
p ost -treat me nt f oll o w-u p  peri o d . 
Partici pa nts will recei ve st u d y dr u g u ntil c o m pleti o n of t he 3 6 -wee k treat me nt peri o d or u ntil 
1  of t he criteri a f or st u d y treat me nt disc o nti n uati o n are met. Partici pa nts will ret ur n f or a 
f oll o w-u p visit a p pr o xi matel y 6 0  d a ys aft er t heir l ast d ose of st u d y dr u g.  
All partici pa nts are re q uire d t o mai ntai n a sta ble d ose of sec o n d -ge nerati o n H 1  a nti hista mi ne 
( S O C) d uri n g t he st u d y fr o m t he ti me of i nf or me d c o nse nt u ntil t he c o m pleti o n of t he 
p ost -treat me nt f oll o w-u p visit . T he S O C will be deter mi ne d b y t h e i n vesti gat or. F urt her d oses of  
sec o n d-ge n erati o n  H 1 a nti hista mi nes ma y be use d as resc u e me dicati o n t o treat w ors e ni n g C S U 
s y m pt o ms at a n y ti me d uri n g t he st u d y. A 1 -ti me, s h ort c o urse ( m a xi m u m d urati o n of 7 da ys) of 
gl uc o c ortic oster oi ds ma y be use d as r esc ue  m e dicati o n after Wee k 4 i n t he case of se vere 
e x acer bati o n ( see Secti o n  6. 7. 3 ). 
Efficac y will be e val u ate d usi n g P R O s, i ncl u di n g t he U A S 7. A d diti o nal P R O o utc o mes are 
o utli ne d i n t he S o A ( see Ta ble  3 ). 
Safet y a n d t olera bilit y will be m o nit ore d t hr o u g h o ut t he st u d y. T he st u d y will utilize a n i nter nal 
D S M B t o m o nit or safet y i n a d diti o n t o a C A C t o a dj u dicate p ote ntial car di o vasc ular a n d 
t hr o m b oe m b olic A Es. 
Ser u m sa m ples will be c ollecte d f or bi o mar k er/tra nslati o nal a nal ysis, a n d bl o o d sa m ples will be 
c ollecte d t hr o u g h o u t t he st u d y f or m eas ure me nt of s yste mic c o nce ntrati o ns of p o v orciti ni b . 
Fi nal st u d y a nal ysis will be c o n d ucte d after t he last partici pa nt c o m pletes t h e last visit i n t he 
st u d y. 
4. 2.  
O ver all St u d y D ur ati o n  
T he st u d y b e gi ns w he n t he first partici pa nt si g ns t he st u d y I C F. T he e n d of t he st u d y is defi ne d 
as t he date of t h e last visit s h o w n i n Ta ble  3  f or t h e last partici pa nt i n t he st u d y gl o ball y. A 
partici pa nt is c o nsi dere d t o ha ve c o m plete d t he st u d y if t he y h a ve c o m plet e d all peri o ds/ parts of 
t he st u d y, i ncl u di n g t he l ast visit. The st u d y is c o nsi dere d c o m plete w he n t he last partici pa nt 's 
last visit has occ urre d. 

I nc yte C or p orati o n 
P a ge 3 1  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
I n E ur o pea n U ni o n/ E ur o pea n Ec o n o mic Area, t he res ults of t he st u d y will be base d o n t he d ate 
of t he last visit of t he last partici pa nt i n t he st u d y gl o ball y t o e ns ure t he res ults are r o b ust, 
mea ni n gf ul, a n d re pres e ntati ve of all m ultire gi o ns b y ha vi n g c o m plete f oll o w -u p data det er mi ne d 
b y t he statistic al h y p ot heses f or t he o bjecti ves esta blis he d. N ot usi n g t he gl o bal date c o ul d 
p ote ntiall y je o par dize t he trial i nte grit y a n d i n vali d ate t he trial c o ncl usi o ns d ue t o p ote ntial bias 
a n d u n bli n di n g of st u d y treat me nts, t h us p ote ntiall y vi olati n g t he statistic al a nal ysis ass u m pti o ns.  
T he st u d y will i ncl u de u p t o 2 8 da ys f or scree ni n g, c o nti n u o us treat me nt f or 3 6 wee ks (i ncl u di n g 
t he P C a n d E X T peri o ds), a n d 6 0 (±  7) da ys f or f oll o w -u p after t he l ast d ose of st u d y dr u g. It is 
esti mate d t hat a n i n di vi d ual will pa rtici pate f or a p pr o xi matel y 1 1 m o nt hs.  
4. 3.  
St u d y Ter mi n ati o n  
T he i n vesti gat or ret ai ns t he ri g ht t o ter mi nate st u d y partici pati o n at a n y ti me, acc or di n g t o t he 
ter ms s pecifie d i n t he st u d y c o ntr act. T h e i n vesti gat or is t o n otif y t he I R B/I E C of t he st u d y's 
c o m pl eti o n or earl y ter mi nati o n i n writi n g, se n d a c o p y of t he n otificati o n t o t he s p o ns or or 
s p o ns or's desi g n ee, a n d retai n 1 c o p y f or t h e site st u d y re g ul at or y file.  
T he s p o ns or ma y ter mi nate t he st u d y el ecti vel y if, f or e x a m ple, re q uir e d b y re g ulat or y decisi o n 
or u p o n a d vice of t he D S M B (see Secti o n  5. 6 ). If t he st u d y is ter mi nate d pre mat urel y, t he 
s p o ns or will n otif y t he i n vesti gat ors, t he I R Bs a n d I E Cs, a n d t h e re g ulat or y b o dies of t he 
decisi o n a n d reas o n f or t er mi nati o n of t he st u d y.  

I nc yte C or p orati o n 
P a ge 3 2  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
5.  
S T U D Y  P O P U L A TI O N  
De viati o ns fr o m eli gi bilit y criteria are n ot all o w e d beca use t h e y ca n p ot e ntiall y je o par dize t he 
scie ntific i nte grit y of t he st u d y, re g ul at or y acce pta bilit y, a n d/ or partici pa nt safet y. T heref ore, 
a d here n ce t o t he criteria as s pecifie d i n t his Pr ot oc ol is esse ntial. Pr os pecti ve a p pr o val of 
Pr ot oc ol de viati o ns t o recr uit me nt a n d e nr oll me nt criteria, als o k n o w n as Pr ot oc ol wai vers or 
e x e m pti o ns, are n ot per mitte d.  
5. 1.  
I ncl usi o n Criteri a 
Partici pa nts are eli gi ble t o be i ncl u de d i n t he st u d y o nl y if all of t he f oll o wi n g criteria a p pl y:  
1.  A bilit y t o c o m pre he n d a n d willi n g ness t o si g n a writte n I C F f or t he st u d y.  
2.  A ge 1 8 t o 6 5 years i ncl usi ve at t he ti me of si gni n g t he I C F.  
3.  C S U dia g n osis f or ≥ 3 m o nt hs pri or t o scree ni n g. 
4.  C S U refract or y t o  sec o n d-ge nerati o n  H 1 a nti hista mi nes as defi ne d b y all of t he 
f oll o wi n g: 
a. T he prese n ce of persiste nt (al m ost dail y) itc h a n d hi ves f or > 6 wee ks at a n y ti me 
pri or t o  scree ni n g d es pite c urre nt use of sec o n d -ge nerati o n H 1  a nti hista mi nes, 
c o nsiste nt wit h S O C  d uri n g t his ti me peri o d.  
b.  U A S 7 ≥ 1 6 d uri n g t he 7 da ys pri or t o ra n d o mizati o n ( Da y 1).  
− N ote:  Partici pa nts m ust ha ve at least 5 n o n missi n g U A S  dail y sc ores o ut of t he 
7  da ys b ef ore  Da y 1 t o  calc ulate U A S 7 . 
c. Partici pa nts m ust ha ve bee n o n a sta ble d os e of sec o n d-ge nerati o n H 1  a nti hista mi ne, 
c o nsiste nt wit h S O C  t hera p y f or C S U, starti n g at least 3 c o nsec uti ve da ys 
i m me diatel y pri or t o t he scree ni n g visit t hr o u g h Da y 1, a n d partici p a nts m ust a gree t o 
mai ntai n t he sta ble d ose of  sec o n d-ge nerati o n  H 1  a nti hista mi ne t hr o u g h o ut st u d y a n d 
d oc u me nt its use i n t he e Diar y.  
5.  Willi n g ness  a n d a bilit y t o c o m pl y wit h t he st u d y Pr ot oc ol a n d pr oce d ures.  
6.  Willi n g ness  a n d a bilit y t o c o m plete dai l y e Diar y f or t he d urati o n of t he st u d y. 
7.  A gree me nt t o use c o ntrace pti o n (see A p pe n di x  A ), as f oll o ws: 
a. Fe male p artici pa nts of c hil d beari n g p ot e ntial ( W O C B P) m ust a gree t o ta k e 
a p pr o priate preca uti o ns t o a v oi d pre g na n c y wit h a hi g hl y effecti ve m et h o d (ie, at least 
9 9 % cert ai nt y) fr o m scree ni n g t hr o u g h 9 0 d a ys aft er t he last d ose of st u d y dr u g. 
Per mitte d met h o ds t hat are at least 9 9 % effecti ve i n pre ve nti n g pre g n a nc y s h o ul d be 
c o m m u nicate d t o t he partici pa nts a n d t heir u n derst a n di n g c o nfir me d . 
− N ote: T his criteri o n d oes n ot a p pl y t o W O N C B P, as defi ne d i n A p pe n di x  A . 
b.  All w o me n m ust a gree t o n ot d o nate e g gs ( o va, o o c yt es) f or t h e p ur p oses of assiste d 
re pr o d ucti o n d uri n g t he st u d y a n d f or at least 9 0 da ys after recei vi n g t he last d ose of 
st u d y dr u g. 

I nc yte C or p orati o n 
P a ge 3 3  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
c. A male partici pa nt w h o is se x uall y acti ve wit h a w o ma n of c hil d beari n g p ote ntial 
( W O C B P) m ust a gree t o use a hi g hl y effecti ve barrier met h o d of birt h c o ntr ol (as 
descri be d i n A p p e n di x  A ) d uri n g t h e st u d y a n d f or at least 9 0 da ys aft er recei vi n g t he 
last d ose of st u d y dr u g. 
d.  All me n m ust a gree t o n ot d o nate s per m d uri n g t he st u d y a n d f or at least 9 0 da ys after 
recei vi n g t he last d ose of st u d y dr u g. 
5. 2.  
E xcl usi o n Crit eri a 
Partici pa nts are e x cl u de d fr o m t he st u d y if a n y of t he f oll o wi n g criteria a p pl y:  
1.  Treat me nt wit h a n a nti -I g E bi ol o gic (e g, o maliz u ma b) wit hi n 8 wee ks pri or t o scree ni n g.  
2.  Clearl y d efi ne d pre d o mi na nt or s ole tri g ger of c hr o nic urticaria (c hr o nic i n d uci bl e 
urticaria) i n cl u di n g urticaria factitial (s y m pt o matic de m o gra p his m), c ol d -, h eat-, s olar-, 
press ure -, dela ye d press ure– , a q ua ge nic, c h oli ner gic-, or c o ntact-urticaria.  
3.  Ot her c uta n e o us or s yste mic diseases wit h s y m pt o ms of urticaria or a n gi o e de ma.  
4.  Ot her s ki n or s yste mic diseases ass o ciate d wit h c hr o nic itc hi n g  (e g, A D, b ull o us 
pe m p hi g oi d, der m atitis her petif or mis, se nile pr urit us, or ps oriasis)  t hat, i n t he 
i n vesti gat or's o pi ni o n, mi g ht i nfl ue nce t he st u d y e val uati o ns a n d res ults. 
5.  W o me n w h o are pre g na nt ( or w h o are c o nsi deri n g pre g na nc y) or breastf ee di n g. 
6.  C o nc urre nt c o n diti o ns or hist or y of ot her diseases, as f oll o ws:  
a. T hr o m b oc yt o p e nia, c o a g ul o pat h y, or plat elet d ysf u ncti o n.  
b.  Ve n o us a n d arterial t hr o m b osis, dee p vei n t hr o m b osis, p ul m o nar y e m b olis m, str o ke, 
m o derate t o se v ere h eart fail ure ( N Y H A Class III or I V), cere br o vas c ular acci de nt, 
MI , c or o nar y ste nti n g, or C A B G  s ur ger y. 
c. Dia g n osis of ot h er si g nifica nt car di o vasc ular diseases, i ncl u di n g b ut n ot li mite d t o 
a n gi n a, peri p heral arterial disease, or u nc o ntr o lle d arr h yt h mias s uc h as atrial 
fi brillati o n, s u pra ve ntric ular tac h ycar dia, v e ntric ul ar tac h ycar di a, a n d f or ms of 
car ditis. 
d.  U nc o ntr olle d h y pert e nsi o n, as defi ne d b y a c o nfir me d s yst olic bl o o d press ure 
>  1 6 0  m m H g or diast olic bl o o d press ure > 1 0 0 m m H g.  
e. Pa rtici pa nts w h o are p er ma ne ntl y b e dri d de n or w heelc hair assiste d. 
f. Reci pie nt of a n or ga n tra ns pla nt t hat re q uires c o nti n ue d i m m u n os u p pressi o n.  
g.  A n y mali g na n cies or hist or y of mali g n a ncies wit h t he e x ce pti o n of a de q uat el y tr eate d 
or e x cise d n o n metastatic basal  cell or s q ua m o us cell ca ncer of t he s ki n, or cer vical 
carci n o ma i n sit u.  
h.  C o n diti o ns t hat c o ul d i nterfere wit h dr u g a bs or pti o n, i ncl u di n g b ut n ot li mite d t o 
s h ort-b o wel s y n dr o me.  
i. C hr o nic or rec urre nt i nfecti o us disease, i ncl u di n g b ut n ot li mite d t o c hr o nic  re nal 
i nfecti o n, c hr o nic c hest i nfecti o n (e g, br o nc hiectasis), rec urre nt uri nar y tract i nfecti o n 
(rec urre nt p yel o n e p hritis or c hr o nic n o nre mitti n g c ystitis), f u n gal i nfecti o n, pri or 
pr ost hetic j oi nt i nfecti o n at a n y ti me, or o pe n, drai ni n g, or i nfecte d s k i n w o u n ds or 
ulcers.  
j. C urre nt or hist or y of diss e mi nate d her pes z oster, or rec urre nt ( m ore t ha n 1 e pis o de of) 
der mat o mal her p es z oster.  

I nc yte C or p orati o n 
P a ge 3 4  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
k.  C urre nt or hist or y of diss e mi nate d her pes si m ple x.  
l. Acti ve s yst e mic i nfecti o n or a n y acti ve i nfecti o n t hat, base d o n t he i n vesti gat or 's 
cli nical assess me nt, ma k es t he partici pa nt a n u ns uita ble ca n di date f or t he st u d y.  
m.  A n y ot her acti ve s ki n dis ease or c o n diti o n (e g, bacterial, f u n gal, or viral i nfecti o n) 
t hat ma y i nterfere wit h t he c o urse, s e verit y, or assess me nts of C S U. 
n.  A n y cli nicall y si g nifica nt me dical c o n diti o n ( ot her t ha n C S U) or a n y ot her reas o n t hat 
t he i n vesti gat or d eter mi n es w o ul d i nterfere wit h t he partici pa nt's partici pati o n i n t his 
st u d y or w o ul d ma k e t he partici pa nt a n u ns uita ble ca n di date t o r ecei v e st u d y dr u g or  
w o ul d p ut t he partici pa nt at ris k b y p artici pati n g i n t he st u d y.  
o.  A n y cli nicall y si g nifica nt me dical c o n diti o n ot her t h a n C S U, as deter mi ne d b y t he 
i n vesti gat or, t hat is n ot a de q uatel y c o ntr olle d wit h a p pr o priate treat me nt or ma y 
i nterfere wit h t he c o urs e, se verit y, or ass ess me nts of C S U. 
p.  Al bi nis m.  
7.  A scree ni n g 1 2 -lea d E C G t hat de m o nstrates cli ni call y si g nifica nt a b n or malities re q uiri n g 
treat me nt (e g, ac ute MI , seri o us tac h yarr h yt h mias or bra d yarr h yt h mias) or t hat is 
i n dicati ve of seri o us u n d erl yi n g h eart disease (e g, car di o m y o pat h y, maj or c o n ge nital 
heart diseas e, l o w v olta ge i n all lea ds, W olff -Par ki ns o n -W hite s y n dr o me) or criteria 
ass ociate d wit h Q wa ve i nter val ( Q T)/ Fri dericia -c orrect e d Q wa v e i nter val ( Q Tc F) 
a b n or malities.  
8.  Ha ve u n der g o ne si g nifica nt tra u ma or maj or s ur ger y ( per i n vesti gat or 's ass ess me nt) 
wit hi n 3 0 da ys pr ece di n g t he scree ni n g visit.  
9.  Hist or y of cli nicall y si g nifica nt ( per i n v esti gat or 's j u d g me nt) dr u g or alc o h ol a b use wit hi n 
6 m o nt hs prece di n g t he s cree ni n g visit.  
1 0.  Hist or y of treat me nt f ail ure wit h a n y s yste mic or t o pical J A K i n hi bit or  (e g, a br ociti ni b, 
bariciti ni b, bre p ociti ni b, cer d ulati ni b, del g ociti ni b, de ucra v aciti ni b, fil g oti ni b, 
i var maciti ni b, pacriti ni b, ritleciti ni b, r o psaciti ni b, r u x oliti ni b, t ofaciti ni b, u pa daciti ni b) 
f or C S U or an y ot her i nfl a m mat or y c o n diti o n.  
1 1.  Recei pt of me dical treat me nt or i n vesti gati o nal dr u gs wit hi n t he f oll o wi n g i nter val bef ore 
t he baseli ne visit ( Da y 1): 
a. < 1 2 wee ks or 5 half -li ves (if k n o w n), w hic h e ver is l o n ger, f or a n y i n v esti gati o nal or 
e x peri me ntal trea t me nts. 
b.  < 1 2 wee ks or 5 half -li ves (if k n o w n), w hic h e ver is l o n ger, f or i m m u n o m o d ulati n g 
bi ol o gic dr u gs ( e g, a dali m u ma b, a na ki nra, b er me ki ma b, bi me kiz u ma b, br o dal u ma b, 
cert oliz u ma b, d u pil u ma b, eta nerce pt, g oli m u ma b, g usel k u ma b, i nfli xi ma b, iscali ma b, 
i x e kiz u ma b, risa n kiz u ma b, rit u xi ma b, sec u ki n u ma b, vil o beli ma b, uste ki n u ma b) 
e x cl u di n g a nti -I g E bi ol o gics. 
c. < 8 wee ks f or li ve vacci n e, or pla n ni n g t o recei ve li ve vacci n e d uri n g t he c o urse of 
t he st u d y or wit hi n 8 wee ks after t he last d ose of st u d y dr u g. 
d.  < 4 wee ks f or a n y t o pical or s yste mic J A K i n hi bit or (e g, a br ociti ni b, bariciti ni b, 
bre p ociti ni b, cer d ul ati ni b, del g o citi ni b, de ucra v aciti ni b, fil g oti ni b, i var maciti ni b, 
pacriti ni b, ritleciti ni b, r o psaciti ni b, r u x oliti ni b, t ofaciti ni b, u pa daciti ni b).  

I nc yte C or p orati o n 
P a ge 3 5  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
e. < 4 wee ks f or  s yste mic i m m u n os u p pressi ve or i m m u n o m o d ulati n g s mall-m olec ule 
dr u gs (e g, c ortic oster oi ds [ oral or i ntra ve n o us], a vac o pa n, I R A K 4 i n hi bit ors, 
met h otre x ate, c ycl os p ori ne, da ps o ne, azat hi o pri ne).  
− N ote: Use of c ortic oster oi d i n halers a n d i ntra nas al s pra ys is a ll o we d. 
− N ote: Use of oral c ortic oster oi ds f or n o n der m at ol o gic c o n diti o ns (e g, ast h ma 
e x acer bati o n, br o n c hitis) is all o we d f or n o l o n ger t ha n 7 da ys if dee me d 
acce pta ble b y t he i n vesti gat or a n d t he s p o ns or ( or desi g nee).  
f. < 1 wee k f or a n y oral or t o pical P D E 4 i n hi bit or (e g, a pre milast, crisa b or ole).  
g.  < 1 wee k f or str o n g s yste mic C Y P 3 A 4 i n hi bit ors a n d str o n g a n d m o d erate s yste mic 
C Y P 3 A 4 i n d ucers (see A p pe n di x  B ). E x a m ples i ncl u de b ut are n ot li mite d t o t he 
f oll o wi n g: rifa m pici n/rifa m pi n, ket oc o naz ole, itrac o naz ole, car ba maze pi ne, rit o na vir, 
St  J o h n's w ort, gra p efr uit/ gra p efr uit j uice, a n d Se ville ora n ges.  
1 2.  C o nc urre nt e nr oll me nt i n a n ot her cli nical st u d y.  
1 3.  At t he scree ni n g visit, a n y of t he l a b orat or y a b n or malities defi ne d i n  Ta ble  6 . 
T a ble  6 : 
E xcl usi o n ar y L a b or at or y V al ues  
L a b or at or y P ar a meter  
E xcl usi o n Criteri o n  
He m at ol o g y  
a 
Platelets  
< 1 0 0 × 1 0 9/ L 
b  
He m o gl o bi n  
< 1 0 g/ d L  
c 
A N C  
< 1. 5 × 1 0 9/ L 
d  
T otal W B C c o u nt (le u k oc yte c o u nt)  
< 3. 0 × 1 0 9/ L 
e 
A bs ol ute l y m p h oc yte c o u nt  
< 0. 8 × 1 0 9/ L 
He p atic  
f 
A L T  
> 2 × U L N  
g  
A S T  
> 2 × U L N  
h  
T otal bilir u bi n  
> 1. 5 × U L N  
( N ote: Partici pa nts wit h cli nical dia g n osis of Gil bert 
s y n dr o me ma y ha ve a direct bilir u bi n meas ure d a n d 
w o ul d be eli gi ble pr o vi de d t he direct bilir u bi n is < U L N)  
Re n al  
i 
Esti mate d gl o mer ular filtrati o n rate  
< 4 5 m L/ mi n per 1. 7 3 m 2 
N ote: Base d o n t he si m plifie d , 4 -varia ble M o dificati o n of 
Diet i n Re nal Disease F or m ula  

I nc yte C or p orati o n 
P a ge 3 6  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
1 4.  E vi de nce of i nfecti o n wit h Myc o b act eri u m t u berc ul osis  (ie, T B) as d efi ne d i n 
Secti o n  8. 3. 5. 2 . 
1 5.  Acti ve HI V or ac q uire d i m m u n o deficie nc y s y n dr o me . Acti ve HI V is defi ne d as 
c o nfir me d p ositi ve a nti -HI V a nti b o d y test (see Secti o n 8. 3. 5. 3 ). 
1 6.  E vi de nce of H B V or H C V i nfecti o n or ris k of reacti vati o n (see  Secti o n 8. 3. 5. 4 ). 
1 7.  K n o w n h y p erse nsiti vit y or se vere reacti o n t o p o v orciti ni b  or e x ci pie nts of p o v orciti ni b  
(refer t o t he I B) a n d/ or ot her pr o d ucts i n t he sa m e class.  
1 8.  A n y c o n diti o n, la b orat or y res ult, or res ult of scree ni n g assess me nts t hat w o ul d, i n t he 
i n vesti gat or's a n d s p o ns or's ( or desi g nee's) j u d g me nt, i nterfere wit h f ull partici pati o n i n 
t he st u d y, i ncl u di n g a d mi nistrati o n of st u d y dr u g a n d atte n di n g re q uire d st u d y visits, p ose 
a si g nifica nt ris k t o t he p artici pa nt, or i nterfere wit h i nter pretati o n of st u d y data.  
5. 3.  
Lifest yle C o nsi der ati o ns  
5. 3. 1.  
C o ntr ace pti o n  
5. 3. 1. 1.  
Fe m ale P artici p a nts  
All fe male partici pa nts w h o are W O C B P  m ust a gree t o u se a hi g hl y effecti ve met h o d of 
c o ntrace pti o n (ie, at least 9 9 % cert ai nt y) c o nsiste ntl y a n d c orrectl y f or t he d urati o n of t he st u d y 
a n d f or at least 9 0 da ys after t he last d ose of i n v esti gati o nal pr o d uct.  
5. 3. 1. 2.  
M ale P arti ci p a nts  
All male partici pa nts m ust be wil li n g t o ta ke a p pr o priate preca uti o ns t o a v oi d fat heri n g c hil dre n 
( wit h at least 9 9 % certai nt y) c o nsiste ntl y a n d c orrectl y (as o utli ne d i n A p pe n di x  A ) for t he 
d urati o n of t he st u d y a n d f or at least 9 0 da ys after t he last d ose of i n vesti gati o nal pr o d uct. If t he 
male partici pa nt has a part ner w h o is of c hil d beari n g p ote ntial, t he part ner s h o ul d als o use 
c o ntrace pti o n as o utli ne d i n A p pe n di x  A . 
5. 3. 1. 3.  
All P artic ip a nts  
T he i n vesti gat or or desi g nee, i n c o ns ultati o n wit h t he partici pa nt, will c o nfir m t hat t he 
partici pa nt has selecte d a n a p pr o priate m et h o d of c o ntrace pti o n f or t he i n di vi d ual partici pa nt 
fr o m t he per mitte d list of c o ntrace pti o n met h o ds (see A p pe n di x  A ) a n d will c o nfir m t hat t he 
partici pa nt has bee n i nstr ucte d i n its c o nsiste nt a n d c orrect use.  
At ti me p oi nts i n dicate d i n t he S o A (see T a ble  3 ), t he i n vesti gat or or desi g n ee will i nf or m t he 
partici pa nt of t he n ee d t o use hi g hl y effecti ve c o ntrace pti o n c o nsiste ntl y a n d c orrectl y. 
Partici pa nts nee d t o affir m t heir c o nsiste nt a n d c orrect use of at least 1 of t he selecte d m et h o ds of 
c o ntrace pti o n (see A p p e n di x  A ). I n a d diti o n, t he i n vesti gat or or desi g nee will i nstr uct t he 
partici pa nt t o call i m me diatel y if t he s electe d c o ntrace pti o n met h o d is disc o nti n ue d or if 
pre g na nc y is k n o w n or s us pecte d.  

I nc yte C or p orati o n 
P a ge 3 7  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
5. 3. 2.  
Me als a n d Diet ar y Restricti o ns  
•  St u d y dr u g will be ta ke n orall y, prefera bl y i n t he m or ni n g a n d at a b o ut t he sa me ti me  
eac h d a y, wit h a f ull glass of water. T h e st u d y dr u g ca n be ta ke n wit h or wit h o ut f o o d. 
O n t he da y of st u d y visits at Wee k  4, Wee k 1 2, a n d Wee k 1 6, partici pa nts will 
wit h h ol d st u d y dr u g self -a d mi nistrati o n, as t he d ose will be a d mi nistere d at t he cli nic 
after c ollecti o n of P D a n d/ or P K sa m ples as o utli ne d i n t he S o A (see T a ble  3 ). F urt her 
i nstr ucti o ns o n st u d y dr u g ha n dli n g are o utli ne d i n A p pe n di x  C . 
•  O n a n y of t he st u d y visit da ys, p artici pa nts s h o ul d n ot s m o ke or i n gest c affei ne d uri n g 
t he 3 0 mi n utes pri or t o bl o o d press ure a n d heart rate meas ure m e nts. 
•  Partici pa nts m ust a bstai n fr o m c o ns u m pti o n of gra pefr uit or gra pefr uit j uice 
( p o mel os, e x otic citr us fr uits, gra p efr uit h y bri ds) a n d Se ville ora n ges fr o m 7 da ys 
bef ore t h e start of st u d y dr u g u ntil aft er t he fi n al d ose of st u d y dr u g.  
•  Partici pa nts m ust a bstai n fr o m c o ns u m pti o n of dietar y s u p pl e me nts c o ntai ni n g 
St  J o h n's w ort (H y peric u m perf or at u m ) fr o m 7 da ys bef ore t he st art of st u d y dr u g 
u ntil after t he fi nal d ose of st u d y dr u g.  
5. 4.  
Scree n F ail ures  
Scree n fail ures are defi ne d as partici pa nts w h o c o nse nt t o partici pate i n t he cli nical st u d y b ut are 
n ot s u bse q ue ntl y ra n d o ml y assi g ne d t o st u d y dr u g. 
Tests wit h res ults t h at fail eli gi bilit y re q uir e me nts ma y b e re p eate d o nce d uri n g scree ni n g if t h e 
i n vesti gat or b elie ves t he res ult t o be i n err or. A d diti o nall y, a partici pa nt w h o fails scree ni n g m a y 
re peat t he s cree ni n g pr ocess 1 ti me if t he i n vesti gat or belie ves t hat t here has bee n a c ha n ge i n 
eli gi bilit y stat us . Partici p a nts w h o rescree n m ust r ec o nse nt a n d be assi g ne d a ne w partici pa nt 
n u m ber.  
All scree ni n g pr oce d ures wit h t he p ossi ble e x ce pti o ns n ote d bel o w will be re peate d d uri n g 
rescree ni n g. T he p artici p a nt m ust meet all t he eli gi bilit y criteria at t he ti me of rescree ni n g i n 
or der t o q ualif y f or t he st u d y . T here is n o mi ni m u m peri o d of ti me a partici pa nt m ust wait t o 
rescree n f or t he st u d y. If t he partici pa nt ha d a c o m plete i nitial scree ni n g e v al uati o n i ncl u di n g t he 
f oll o wi n g ass ess me nts, t hese tests will n ot be re q uire d t o be re p eate d f or rescree ni n g, pr o vi de d 
t he c o n diti o ns n ote d i n Secti o ns 5. 1  a n d 5. 2  are m et, t here are n o c ha n ges i n t he partici pa nt 's 
me dical hist or y t h at w o ul d warra nt retesti n g, a n d n o m ore t ha n 9 0 da ys ha v e passe d:  
•  H B V, H C V, a n d HI V s er ol o g y  
•  I G R A (Q T F  G ol d test [ or I G R A e q ui vale nt s uc h as T -S P O T ®  test] a n d/ or l ocal P P D 
s ki n test, if re q uire d) 
•  E C G  

I nc yte C or p orati o n 
P a ge 3 8  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
5. 5.  
Re pl ace me nt of P artici p a nts  
N o partici pa nts will be re place d at a n y ti me d uri n g t his st u d y. H o we ver, as n ote d i n A p pe n di x  E , 
d ue t o t he e v ol vi n g sit uati o n of t he C O VI D -1 9 p a n de mic, t he s p o ns or ma y deci de t o recr uit 
a d diti o nal partici pa nts i n t he st u d y be y o n d t he e x pecte d n u m ber (e g, if a s u bsta ntial n u m ber of 
partici pa nts wit h dra w earl y fr o m t he st u d y).  
5. 6.  
D at a S afet y M o nit ori n g B o ar d  
T his st u d y will use a n i nter nal D S M B t o m o nit or safet y as d etaile d i n t he D S M B c hart er.  
T he v oti n g me m bers of t he c o m mittee will be bli n de d t o partici pa nts ' treat me nt assi g n me nt f or 
t he i nitial safet y re vie w; h o we ver, t he D S M B me m bers ma y re q u est u n bli n di n g at a n y ti me. 
T he me m bers of t h e D S M B will n ot be i n v ol ve d wit h t he st u d y i n a n y ot h er wa y a n d will ha ve 
n o c o m peti n g i nterests t hat c o ul d affect t heir r ol es w it h res pect t o t he st u d y. 
T he D S M B will ma ke rec o m me n dati o ns t o t he st u d y tea m re gar di n g ste ps t o e ns ure b ot h 
partici pa nt safet y a n d t he c o nti n ue d et hical i nte grit y of t he st u d y. S pecifi c details re gar di n g 
c o m p ositi o n, res p o nsi bilities, a n d g o v er na n ce, i nc l u di n g t he r oles a n d res p o nsi bilities of t he 
vari o us me m bers a n d t h e s p o ns or, a n d re q uir e me nts f or t he pr o per d oc u me ntati o n of D S M B 
re p orts, meeti n g mi n utes, a n d rec o m me n d ati o ns will be descri be d i n t he D S M B c harter, w hi c h 
will be re vie we d a n d a p pr o ve d b y all D S M B me m bers.  
5. 7.  
C ar di o v asc ul ar A dj u dic ati o n C o m mittee  
A n i n de pe n de nt c o m mittee of p h ysicia n e x perts i n car di o vas c ular a dj u dicati o n will be utilize d t o 
assess p ote ntial car di o v asc ular a n d t hr o m b oe m b olic A Es . Details will be descri be d i n a se p arat e 
C A C c ha rter. 

I nc yte C or p orati o n 
P a ge 3 9  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
6.  
S T U D Y T R E A T M E N T  
6. 1.  
St u d y Tre at me nts A d mi nistere d  
Ta ble  7  pres e nts t he st u d y treat me nt i nf or mati o n. Partici pa nts will rec or d st u d y dr u g 
a d mi nistrati o n i n a n e Diar y. St u d y dr u g a d mi nistrati o n a n d a n y i nterr u pti o ns a n d disc o nti n uati o n 
of treat me nt wil l als o be rec or de d i n t he e C R F. F urt her i nf or mati o n re gar di n g st u d y dr u g 
a d mi nistrati o n is pr o vi de d i n A p pe n di x  C . 
T he C O VI D -1 9 gl o b al pa n de mic ma y prese nt c halle n ges t o t he n or mal c o n d uct of t his st u d y, 
re q uiri n g t he o utli ne of p ote ntial miti gati o n strate gies des cri be d i n A p pe n di x  E . 
T a ble  7 : 
St u d y Tre at me nt I nf or m ati o n  
St u d y tre at me nt n a me:  
P o v orciti ni b  
P o v orciti ni b  matc hi n g place b o  
Mec h a nis m of acti o n:  
J A K i n hi bit or 
N o t a p plica ble 
D ose f or m ul ati o n:  
T a blet oral  
Matc hi n g ta blet  
U nit d ose stre n gt h(s) /  
d os e le vel(s): 
1 5 m g = 1 p o v orciti ni b  1 5 -m g ta blet 
a n d 4 place b o ta blets  
4 5 m g = 3 p o v orciti ni b  1 5 -m g ta blets 
a n d 2 place b o ta blets  
7 5 m g =  5 p o v orciti ni b  1 5 -m g  ta blets 
Matc hi n g place b o = 5 ta blets  
A d mi nistr ati o n 
i nstr ucti o ns: 
P o v orciti ni b  or matc hi n g place b o will be ta ke n orall y Q D wit h water at 
a p pr o xi matel y t he sa me ti me eac h da y u nless ot her wise i nstr ucte d b y site 
pers o n nel. T he st u d y dr u g ca n be ta ke n wit h or wit h o ut f o o d.  
N ote: D ose will be a d mi n istere d at t he st u d y site d uri n g visits. 
Partici pa nts will wit h h ol d self -a d mi nistrati o n o n t he da ys of t h ose visits.  
P ac k a gi n g a n d l a beli n g:  
P o v orciti ni b  will be pr o vi de d as 1 5 m g ta blets; place b o ta blets will matc h 
t he p o v orciti ni b  ta blets i n s mell, taste, a n d a p peara nce. T a blets will be 
pac ka ge d i n blister car ds.  
Eac h blister car d will be la bele d as re q uire d per c o u ntr y re q uire me nt.  
St or a ge:  
A m bie nt ( 1 5 °C -3 0 °C/ 5 9 °F -8 6 °F).  
St at us of tre at me nt i n 
p artici p ati n g c o u ntries:  
I n vesti gati o nal 
6. 2.  
B ac k gr o u n d T her a p y  
All partici pa nts will be re q uire d t o re mai n o n a c o nc urre nt, sta ble d os e of sec o n d -ge n erati o n 
H 1  a nti hista mi ne as bac k gr o u n d t h era p y ( S O C ), w hic h will n ot be c ha n ge d t hr o u g h o ut t he st u d y. 

I nc yte C or p orati o n 
P a ge 4 0  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
6. 3.  
Pre p ar ati o n, H a n dli n g, a n d Acc o u nt a bilit y  
T he i n vesti gat or or desi g nee m ust c o nfir m a p pr o priate te m perat ure c o n diti o ns ha ve bee n 
mai ntai ne d d uri n g tra nsit f or all st u d y tr eat me nts r ecei ve d a n d a n y discre pa ncies are re p orte d a n d 
res ol ve d bef ore us e of t h e st u d y tr eat me nt. 
O nl y partici pa nts e nr olle d i n t he st u d y ma y recei v e st u d y tr eat me nt, a n d o nl y a ut h orize d site 
staff ma y s u p pl y or a d mi nister st u d y treat me nt. All st u d y treat me nt m ust be st ore d i n a sec ure, 
e n vir o n me ntall y c o ntr olle d, a n d m o nit ore d ( ma n u al or a ut o mate d) area i n  acc or da n ce wit h t he 
la bele d st ora ge c o n diti o ns wit h access li mite d t o t he i n vesti gat or a n d a ut h orize d site staff. 
T he i n vesti gat or or desi g nee is res p o nsi ble f or st u d y treat me nt acc o u nta bilit y, rec o nciliati o n, a n d 
rec or d m ai nte na nce (ie, recei pt, rec o nciliati o n, a n d fi nal dis p ositi o n rec or ds). I n ve nt or y a n d 
acc o u nta bilit y rec or ds m ust be mai ntai ne d a n d rea dil y a vaila ble f or i ns pe cti o n b y t he st u d y 
m o nit or a n d are o p e n t o i ns pecti o n at a n y ti me b y a n y a p plica ble re g ulat or y a ut h orities. T he 
i n vesti gat or or desi g nee m ust mai ntai n rec or ds t h at d oc u me nt t he f oll o wi n g:  
•  Deli ver y of st u d y dr u g t o t he st u d y site.  
•  I n v e nt or y of st u d y dr u g at t he site. 
•  Partici pa nt use of t he st u d y dr u g, i n cl u di n g ta blet c o u nts fr o m eac h s u p pl y dis pe nse d.  
•  Ret ur n of st u d y dr u g t o t he i n v esti gat or or desi g n ee b y partici p a nts.  
T he i n vesti gati o nal pr o d uct m ust be use d o nl y i n acc or da nce wit h t he Pr ot oc ol (see A p pe n di x  C ). 
T he i n vesti gat or or desi g nee will als o mai ntai n rec or ds a de q u atel y d oc u me nti n g t hat t he 
partici pa nts were pr o vi de d t he s pecifie d st u d y dr u g. T hes e rec or ds s h o ul d i ncl u de dates, 
q ua ntities, a n d a n y a vaila ble batc h or serial n u m bers or u ni q ue c o d e n u m bers assi g n e d t o t he 
i n vesti gati o nal pr o d u ct a n d st u d y partici p a nts. 
C o m plete d acc o u nta bilit y rec or ds will be arc hi v e d b y t he site. T h e i n vesti gat or or desi g nee will 
be e x pecte d t o c ollect a n d retai n all use d, u n use d, a n d partiall y use d c o nt ai ners of st u d y dr u g 
u ntil  verifie d b y t h e st u d y m o nit or ( u nless ot her wise a gree d t o b y t h e s p o ns or). At t he c o n cl usi o n 
of t he st u d y, t he i n v esti gat or or desi g nee will o versee t he destr u cti o n of a n y re mai ni n g st u d y 
dr u g acc or di n g t o i nstit uti o nal S O Ps. If, h o we ver, l ocal pr oce d ures  d o n ot all o w o n -site 
destr ucti o n, s hi p me nt of t he st u d y dr u g b ac k t o t he s p o ns or is all o we d. I n t his case, t he site 
s h o ul d ( w here l o cal pr oce d ures all o w) m ai ntai n t he i n vesti gati o nal s u p pl y u ntil t he st u d y m o nit or 
i ns pects t he acc o u nta bilit y rec or ds i n ord er t o e v al uate c o m plia nce a n d acc urac y of 
acc o u nta bilit y b y t he i n vesti gati ve site. At sites w here t he st u d y dr u g is destr o ye d b ef ore m o nit or 
i ns pecti o n, t he m o nit ors rel y o n d o c u me ntati o n of destr ucti o n per t he site S O P. 
F urt her g ui d a nce a n d i nf or mati o n f or t he fi nal dis p ositi o n of u n use d st u d y treat me nts are 
pr o vi de d i n t he st u d y mat erials pr o vi de d t o t he sites.  

I nc yte C or p orati o n 
P a ge 4 1  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
6. 4.  
Me as ures t o Mi ni mize Bi as: R a n d o miz ati o n a n d Bli n di n g  
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 st u d y.  
All partici pa nts will be ce n trall y assi g n e d t o st u d y treat me nt usi n g a n I R T s yste m. St u d y dr u g 
will be dis pe nse d at t he st u d y visits s u m marize d i n t he S o A (see T a ble  3 ). Ret ur ne d st u d y dr u g 
s h o ul d n ot be re dis pe nse d t o t he partici pa nts. F ull details will be pr o vi de d i n t he I R T St u d y 
Refere n ce M a n ual.  
T he s p o ns or will be bli n de d t o t he treat me nt t hr o u g h o ut t he P C peri o d a n d will be u n bli n de d at 
t he ti me of pri mar y a n al ysis . Partici p a nts a n d i n vesti gat ors will re mai n bli n de d t o eac h 
partici pa nt's treat me nt assi g n me nt t hr o u g h o ut t he st u d y.  T his is i m ple me nte d t o mi ni mize bias 
t hr o u g h o ut t he P C a n d E X T peri o ds of t he st u d y.  
E mer ge nc y u n bli n di n g will occ ur if a n A E re q uires t he i n vesti g at or t o be m a de a ware of t he 
partici pa nt 's treat me nt assi g n me nt (see e mer ge nc y u n bli n di n g pr oce d ures i n Secti o n  9. 7  a n d refer 
t o t he St u d y Refere nce Ma n ual). 
6. 5.  
St u d y Tre at me nt C o m pli a nce  
C o m plia nce wit h all st u d y -relate d tr eat me nts s h o ul d be e m p hasize d t o t he partici pa nt b y t he site 
pers o n nel, a n d a p pr o priat e ste ps s h o ul d be ta ke n t o o pti mize c o m plia nce d uri n g t he st u d y.  
6. 5. 1.  
C o m pli a nce Wit h P o v o rciti ni b / Pl ace b o 
C o m plia nce wit h st u d y dr u g will be calc ulat e d b y t he s p o ns or base d o n t he dr u g acc o u nt a bilit y 
(e g, ta blet c o u nts) d o c u me nte d b y t he site staff a n d m o nit ore d b y t he s p o ns or/ desi g n ee. 
Partici pa nts will be i nstr ucte d t o bri n g all u n use d st u d y dr u gs w it h t he m t o t he st u d y visits i n 
or der f or site pers o n n el t o c o n d uct ta blet c o u nts t o assess st u d y dr u g acc o u nta bilit y.  
C o m plia nce wit h st u d y dr u g will be calc ulat e d f or t he P C a n d E X T peri o ds base d o n t he 
f oll o wi n g: 
Wit hi n t he P C peri o d:  
•  T he first d ose wil l occ ur o n Da y 1  ( bas eli ne). 
•  T he last d ose will occ ur o n t he da y of t he Wee k 1 2 visit or  t he da y of t h e last st u d y dr u g 
a d mi nistrati o n k n o w n t o t he i n vesti gat or ( or desi g nee) as re p ort e d i n t he E D C f or 
partici pa nts w h o pre m at urel y dis c o nti n ue st u d y  tr eat ment  or are l ost t o f oll o w -u p.  
Wit hi n t he E X T peri o d:  
•  T he first d ose will occ ur t he da y after t he Wee k 1 2 visit.  
•  T he last d ose will occ ur o n t he da y of t he Wee k 3 6 visit or  t he da y of t h e last st u d y dr u g 
a d mi nistrati o n k n o w n t o t he i n vesti gat or ( or desi g nee) as re p ort e d i n t he E D C f or 
partici pa nts w h o pre m at urel y dis c o nti n ue st u d y  tr eat me nt or are l ost t o f oll o w -u p.  
Partici pa nts ' c o m plia nce m ust be wit hi n 8 0 % t o 1 2 0 % assesse d at eac h st u d y  visit b y t he 
i n vesti gat or ( or desi g nee). If o utsi de of t his ra n ge, it will be c o nsi dere d a Pr ot oc ol de viati o n. 
Partici pa nts c o nsiste ntl y n o nc o m plia nt wit h t he st u d y dr u g m a y be wit h dra w n fr o m t he st u d y. 
T he decisi o n o n wit h dra wal will be ma de b y t he i n ves ti gat or after c o ns ultati o n wit h t he s p o ns or, 
a n d rele v a nt c orres p o n de nce will be arc hi ve d i n t h e site st u d y file.  

I nc yte C or p orati o n 
P a ge 4 2  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
6. 5. 2.  
C o m pli a nce Wit h B ac k gr o u n d T her a p y  
Partici pa nts will be i nstr ucte d t o rec or d bac k gr o u n d t hera p y a d mi nistrati o n i n t he e Diar y fr o m 
t he scree ni ng visit u ntil c o m pleti o n of t he p ost -treat me nt f oll o w-u p visit ( E O S). C o m plia nce 
wit h bac k gr o u n d t hera p y will als o be d oc u me nte d i n t he partici pa nt 's st u d y s o urce 
d oc u me ntati o n a n d m o nit ore d b y t he i n vesti gat or ( or desi g n ee).  
6. 6.  
D ose M o dific ati o ns  
N o d ose m o dificati o ns will be all o we d d uri n g t h e st u d y. I n s o me circ u msta nces, it ma y b e 
necessar y t o te m p oraril y i nterr u pt treat me nt wit h st u d y dr u g as a res ult of A Es or la b orat or y 
a b n or malities t hat ha ve a n u nclear relati o ns hi p t o t he st u d y dr u g.  
Decisi o ns b y t h e i n vesti gat or ( or desi g n ee) re gar di n g d ose i nterr u pti o n/ disc o nti n uati o n of st u d y 
dr u g s h o ul d be m a de usi n g cli nic al j u d g me nt, ta ki n g i nt o acc o u nt relat e d ness of t he A E t o t he 
st u d y dr u g a n d t h e partici pa nt 's u n d erl yi n g c o n diti o n. T he s p o ns or ( or desi g nee) ma y b e 
c o ns ulte d as nee d e d. I nstr ucti o ns f or d ose i nterr u pti o n or disc o nti n uati o n of st u d y dr u g are 
o utli ne d i n  Secti o n s 6. 6. 1  a n d 6. 6. 2 . 
6. 6. 1.  
Criteri a a n d Pr oce d ures f or D ose I nterr u pti o ns a n d A dj ust me nts of St u d y Dr u g  
Safet y c o ncer ns s h o ul d b e disc usse d wit h t he s p o ns or i m me diatel y u p o n o cc urre n c e or a ware n ess 
t o deter mi ne if t he partici pa nt s h o ul d c o nti n ue or disc o nti n ue st u d y dr u g . 
Treat me nt wit h st u d y dr u g ma y b e i nterr u pte d f or u p t o 2 8 da ys,  u nless ot h er wise s pecifie d i n t he 
Pr ot oc ol or a l o n ger peri o d is a p pr o ve d b y t he s p o ns or ( or desi g nee) , t o all o w f or res ol uti o n of 
t o xicit y. T he pri n ci pal i n vesti gat or ( or desi g nee) s h o ul d c o ntact t he s p o ns or t o disc uss t he case of 
a n y p artici pa nt w h os e treat me nt has bee n i nterr u pt e d f or m ore t h a n 2 1 da ys ( b ut less t ha n 
2 8  da ys) bef ore restarti n g treat me nt. Partici pa nts ma y res u me treat me nt if n o me dical c o n diti o n 
or ot her cir c u msta nce e xists 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 partici pa nt 
u ns uita ble f or f urt her partici pati o n i n t he st u d y.  
G ui deli nes f or i nterr u pti o n, restarti n g, a n d disc o nti n uati o n of st u d y dr u g are o utli ne d i n Ta ble  8  
as well as i n  A p pe n di x  E  (f or C O VI D-1 9) a n d Secti o n  6. 6. 1. 6  (f or e mer ge n c y a n d electi ve 
s ur geries). 

I nc yte C or p orati o n 
P a ge 4 3  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
T a ble  8 : 
G ui deli nes f or I nterr u pti o n , Rest arti n g, a n d Disc o nti n u ati o n of St u d y Dr u g  
L a b or at or y V al ue  
Acti o n T a ke n  
C he mistr y  
A L T a n d/ or A S T is > 3. 0 × <  2 0 U L N  
Ste p 1:  I nterr u pt st u d y dr u g. 
Ste p 2:  C o nfir m w het her p ote ntial H y 's la w criteria ha ve be e n 
met (see A p pe n di x  D ), f oll o wi n g a p plica ble pr oce d ures. If 
p ote ntial H y 's la w criteria are n ot met, pr ocee d t o Ste p 3. 
Ste p 3:  Re peat A L T/ A S T assess me nts wee kl y f or u p t o 3 we e ks 
or u ntil A L T a n d/ or A S T res ults are < 3. 0 × U L N a n d  t he n 
restart st u d y dr u g at t he sa me d ose. 
If A L T a n d/ or A S T res ult(s) d o n ot decrease t o < 3. 0 × U L N 
after 3 wee ks of dr u g i nterr u pti o n, st u d y dr u g w ill be 
per ma ne ntl y disc o nti n ue d , a n d t he partici pa nt will f oll o w E O T 
visit pr oce d ures; a  p ost -treat me nt f oll o w-u p visit ( E O S) is als o 
rec o m me n de d. 
If t he d ose has bee n i nterr u pte d/restarte d i n 2 ot her i nsta nces d ue 
t o A L T a n d/ or A S T res ults, a n d A L T a n d/ or A S T res ults are 
>  3. 0 × U L N f or a t hir d ti me, st u d y dr u g will be per ma ne ntl y 
disc o nti n ue d , a n d t he partici pa nt will f oll o w E O T visit 
pr oce d ures; a p ost -treat me nt f oll o w-u p visit ( E O S) is als o 
rec o m me n de d. 
I n parallel t o t he partici pa nt st arti n g t he p ost -treat me nt f oll o w-u p 
peri o d, t he i n vesti gat or, i n c oll a b orati o n wit h t he me dical 
m o nit or, will deter mi ne f urt her ste ps.  
A L T a n d/ or A S T is > 2 0. 0 × U L N  
Ste p 1:  Disc o nti n ue st u d y dr u g a d mi nistrati o n a n d ha ve t he 
partici pa nt f oll o w E O T visit pr oce d ures; a p ost -treat me nt 
f oll o w-u p visit ( E O S) is als o rec o m me n de d.  
Ste p 2: I n parallel t o t he partici pa nt starti n g t he p ost -treat me nt 
f oll o w-u p peri o d, t he i n vesti gat or, i n c olla b orati o n wit h t he 
me dical m o nit or, will deter mi ne f urt her ste ps.  
C P K  is > 5. 0 × U L N 
Ste p 1:  E val uate if t here are s y m pt o ms s u g gesti ve of m y ositis or 
r ha b d o m y ol ysis. A d diti o nall y, t he i n vesti gat or ma y re peat t he 
test f or c o nfir mat or y p ur p oses. 
Ste p 2:  If t here are n o s y m pt o ms s u g gesti ve of m y ositis or 
r ha b d o m y ol ysis, t he partici pa nt ma y c o nti n ue st u d y dr u g at t he 
i n vesti gat or's discreti o n. A p pr o priate m o nit ori n g s h o ul d be 
c o n d ucte d.  
Ste p 3:  If s y m pt o ms s u g gesti ve of m y ositis or r ha b d o m y ol ysis 
are i de ntifie d, i nterr u pt st u d y dr u g a n d c o ntact t he me dical 
m o nit or ( or desi g nee).  

I nc yte C or p orati o n 
P a ge 4 4  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
T a ble  8 : 
G ui deli nes f or I nterr u pti o n, Rest arti n g, a n d Disc o nti n u ati o n of St u d y Dr u g  
( C o nti n ue d) 
L a b or at or y V al ue  
Acti o n T a ke n  
He m at ol o g y  
Platelet c o u nt is < 5 0 × 1 0 9/ L 
Ste p 1:  I nterr u pt st u d y dr u g a d mi nistrati o n. 
Ste p 2:  Re peat platelet c o u nt assess me nt pr o m ptl y, wit hi n 
7  d a ys , t o c o nfir m val ue. 
Ste p 3:  Re peat platelet c o u nt assess me nt wee kl y u ntil platel et 
c o u nt reac hes ≥ 1 0 0  ×  1 0 9/ L a n d t he n restart st u d y dr u g at t he 
sa me d ose. 
If pl atelet c o u nt d oes n ot i ncre ase t o ≥ 1 0 0 × 1 0 9/ L after 
3  w ee ks of dr u g i nterr u pti o n, st u d y dr u g will be per m a ne ntl y 
disc o nti n ue d , a n d t he p artici p a nt will f oll o w E O T visit 
pr oce d ures;  a p ost -tre at me nt f oll o w-u p visit ( E O S) is als o 
rec o m me n de d.  
A N C is < 1. 0 × 1 0 9/ L 
Ste p 1:  I nterr u pt st u d y dr u g a d mi nistrati o n u ntil t he t o xicit y has 
res ol ve d t o ≥ 1 × 1 09/ L or t he baseli ne val ue. 
Ste p 2:  Restart st u d y dr u g at t he sa me d ose a n d  m o nit or as 
cli nicall y i n dicate d . 
He m o gl o bi n is 8 t o <  9 g/ d L or > 2 -g/ d L 
decrease fr o m baseli ne.  
N ot e: If t he decrease res ults i n a val ue 
<  8  g/ d L, t he n f oll o w t he g ui d a nce bel o w.  
Ste p 1:  I nterr u pt st u d y dr u g a d mi nistrati o n u ntil t he t o xicit y has 
res ol ve d, wit h he m o gl o bi n me eti n g t he criteria of ≤ 2-g/ d L 
decrease fr o m baseli ne.  
Ste p 2 : E val uate me dical hist or y t o deter mi ne if t he decrease i n 
he m o gl o bi n was li kel y relate d t o u n derl yi n g disease or 
i n vesti gati o nal dr u g. 
Ste p 3:  Restart st u d y dr u g a n d m o nit or as cli nicall y i n dicate d.  
He m o gl o bi n is < 8 g/ d L  
Disc o nti n ue st u d y dr u g a d mi nistrati o n a n d ha ve t he partici pa nt 
f oll o w E O T visit pr oce d ures; a p ost -treat me nt f oll o w-u p visit 
( E O S) is als o rec o m me n de d. 
Creati ni ne ≥ 2 m g/ d L  
Ste p 1:  Re peat t he test f or ser u m creati ni ne ( wit h t he partici pa nt 
i n a e u v ole mic state) wit hi n 7 da ys t o c o nfir m t he res ult. 
Ste p 2:  If t he res ults of t he re peat testi n g c o nfir ms creati ni ne 
≥ 2  m g/ d L, i nterr u pt st u d y dr u g.  
Ste p 3:  P erf or m creati ni ne ass ess me nt w ee kl y f or u p t o 3 we e ks, 
or u ntil creati ni ne ret ur ns t o less t ha n or e q ual t o t he partici pa nt 's 
baseli ne. St u d y dr u g ma y be restarte d.  
If cre ati ni ne d oes n ot decre ase t o less t h a n or e q u al t o t he 
p artici p a nt 's b aseli ne after 3 w ee ks of dr u g i nterr u pti o n, 
st u d y dr u g will be per m a ne ntl y disc o nti n ue d a n d t he 
p artici p a nt will f oll o w E O T visit pr oce d ures; a 
p ost -tre at me nt f oll o w-u p visit ( E O S) is als o rec o m me n de d.  

I nc yte C or p orati o n 
P a ge 4 5  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
T a ble  8 : 
G ui deli nes f or I nterr u pti o n, Rest arti n g, a n d Disc o nti n u ati o n of St u d y Dr u g  
( C o nti n ue d) 
L a b or at or y V al ue  
Acti o n T a ke n  
Ot her t o xicities  
Seri o us i nfecti o n/ o p p ort u nisti c i nfecti o n 
( defi ne d as a n y i nfecti o n or o p p ort u nistic 
i nfecti o n meeti n g S A E criteria [see 
Secti o n  9. 2 ]) 
Ste p 1 : I nterr u pt st u d y dr u g a d mi nistrati o n. 
Ste p 2:  I nitiate pr o m pt dia 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 partici pa nt. As a p pr o priate, a nti micr o bial 
t hera p y s h o ul d be i nitiate d, a n d t he partici pa nt s h o ul d be cl osel y 
m o nit ore d.  
Ste p 3:  Restart st u d y dr u g o nc e t he i nfecti o n has bee n 
s uccessf ull y treate d a n d cl osel y m o nit or as cli nicall y i n dicat e d.  
Ne w e vi de nce of T B  
Disc o nti n ue st u d y dr u g a d mi nistrati o n a n d ha ve t he partici pa nt 
f oll o w E O T visit pr oce d ures; a p ost -treat me nt f oll o w-u p visit 
( E O S) is als o rec o m me n de d. 
Her pes z oster  
C o nsi der i nterr u pti n g st u d y dr u g a d mi nistrati o n u ntil t he e pis o de 
res ol ves. 
T hr o m b osis e ve nts  
Ste p 1:  Pr o m ptl y e val uate a n d treat a p pr o priatel y if s y m pt o ms 
of t hr o m b osis  de vel o p . 
Ste p 2:  Disc o nti n ue st u d y dr u g a d mi nistrati o n if a n y of t he 
f oll o wi n g dia g n oses is c o nfir me d: 
•  Ve n o us t hr o m b osis (s uc h as b ut n ot li mite d t o dee p vei n 
t hr o m b osis a n d p ul m o nar y e m b olis m)  
•  Arterial t hr o m b osis (s uc h as b ut n ot li mite d t o MI  a n d 
str o ke) 
•  A n y ot her t hr o m b oe m b olic e ve nt  
Ha ve t he partici pa nt f oll o w E O T visit pr oce d ures; a 
p ost -treat me nt f oll o w-u p visit ( E O S) is als o rec o m me n de d.  
A n y mali g na nc y e xce pt n o n mela n o ma s ki n 
ca ncer or carci n o ma i n sit u of t he  cer vi x (see 
Secti o n  6. 6. 1. 5  f or a d diti o nal ma na ge me nt 
g ui da nce)  
Disc o nti n ue st u d y dr u g a d mi nistra ti o n a n d ha ve t he partici pa nt 
f oll o w E O T visit pr oce d ures; a p ost -treat me nt f oll o w-u p visit 
( E O S) is als o rec o m me n de d. 
A n y Gra de 1 or Gra d e 2 t o xicit y  
C o nti n ue st u d y dr u g a d mi nistr ati o n a n d treat t he t o xicit y; 
m o nit or as cli nicall y i n dicate d.  
A n y Gra de 3  t o xicit y (e xce pt if s pecificall y 
descri be d i n t his ta ble) if cli ni call y 
si g nifica nt a n d n ot ma na gea bl e b y s u p p orti ve 
care  
Ste p 1:  I nterr u pt st u d y dr u g u p t o 2 wee ks ( 1 4 da ys), u ntil 
t o xicit y res ol ves t o ≤ Gra de 1. 
Ste p 2:  Restart st u d y dr u g a n d m o nit or as cli nicall y i n dicate d.  
A n y ot her Gra de 4 t o xicit y  
Disc o nti n ue st u d y dr u g a d mi nistrati o n a n d ha ve t he partici pa nt 
f oll o w E O T visit pr oce d ures; a p ost -treat me nt f oll o w-u p visit 
( E O S) is als o rec o m me n de d. 

I nc yte C or p orati o n 
P a ge 4 6  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
6. 6. 1. 1.  
M a n a ge me nt of Seri o us I nfecti o ns  
Partici pa nts s h o ul d be cl osel y m o nit ore d f or t he d e vel o p me nt of si g ns a n d s y m pt o ms of i nfecti o n 
d uri n g a n d after treat me nt wit h st u d y dr u g. St u d y dr u g s h o ul d be i nterr u pte d if a partici pa nt 
de vel o ps a seri o us i nf ecti o n or a seri o us o p p or t u nistic i nfecti o n. A partici pa nt w h o de vel o ps a 
ne w i nfecti o n d uri n g tr eat me nt wit h st u d y dr u g s h o ul d u n der g o pr o m pt dia 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 partici pa nt. As a p pr o priate, a nti micr o bial t hera p y 
s h o ul d be i nitiate d, a n d t he partici pa nt s h o ul d be cl osel y m o nit ore d. St u d y dr u g ma y be restarte d 
o nce t he i nfecti o n has bee n s uccessf ull y tr eate d. P artici pa nts wit h ne w e vi d e nce of T B m ust be 
per ma ne ntl y disc o nti n ue d fr o m st u d y dr u g.  
6. 6. 1. 2.  
M a n a ge me nt of Her pes Z oster  
If a partici pa nt de vel o ps her pes z oster, c o nsi der te m p oraril y i nterr u pti n g st u d y dr u g u ntil t he 
e pis o de res ol ves.  
6. 6. 1. 3.  
M a n a ge me nt of C O VI D -1 9  
Partici pa nts w h o de vel o p s y m pt o ms of C O VI D -1 9 ma y c o nti n ue treat me nt wit h st u d y dr u g.  
I n cases w here treat me nt of C O VI D-1 9 wit h nir matrel vir/ri t o na vir ( or a n ot her str o n g C Y P 3 A 4 
i n hi bit or or str o n g/ m o derate i n d ucer f or C O VI D-1 9 treat me nt) is re q uir e d, st u d y dr u g m ust be 
i nterr u pte d f or u p t o 7 d a ys t o all o w t he a nti vir al treat me nt c o urse t o c o m pl ete. St u d y dr u g ma y 
be restart e d aft er a mi ni m u m of 7 da ys after t h e last d ose of t he a nti viral t hera p y.  
6. 6. 1. 4.  
M a n a ge me nt of T hr o m b osis E ve nts  
Partici pa nts w h o de vel o p s y m pt o ms of t hr o m b osis s h o ul d be pr o m ptl y e v al uate d a n d treate d 
a p pr o priatel y.  
T he partici pa nt m ust be disc o nti n ue d fr o m st u d y dr u g if t h e dia g n osis of t he f oll o wi n g is 
c o nfir me d: ve n o us t hr o m b osis (s uc h as b ut n ot li mite d t o dee p vei n t hr o m b osis a n d p ul m o nar y 
e m b olis m), arterial t hr o m b osis (s uc h as b ut n ot li mite d t o MI  a n d str o ke),  or a n y ot her 
t hr o m b oe m b olic e ve nt. 
6. 6. 1. 5.  
M a n a ge me nt of M ali g n a nc y  
Partici pa nts w h o de vel o p mali g na n c y ot her t ha n n o n mela n o ma s ki n ca ncer or carci n o ma i n sit u 
of t he cer vi x m ust be disc o nti n ue d fr o m st u d y dr u g. I nf or mati o n i ncl u di n g hist o pat h ol o gical 
res ults s h oul d be q uerie d f or t he c o nfir mati o n of t he dia g n osis.  
Peri o dic s ki n e x a mi nati o n is rec o m me n de d f or partici pa nts w h o are at i ncrease d ris k f or s ki n 
ca ncer.  

I nc yte C or p orati o n 
P a ge 4 7  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
6. 6. 1. 6.  
E mer ge nc y a n d Electi v e S ur geries  
If a partici pa nt m ust u n der g o e mer ge nc y s ur ger y, t he st u d y dr u g s h o u l d be i nterr u pte d at t he ti me 
of t he s ur ger y. After e mer ge nc y s ur ger y, all o w rei ntr o d ucti o n of st u d y dr u g o nce t he p h ysicia n 
has e x a mi ne d t he s ur gi cal site a n d deter mi ne d t hat it has heale d a n d t here is n o si g n of i nfecti o n.  
Electi ve s ur ger y, a n d i nterr u pt i o n of st u d y dr u g f or s uc h a s ur ger y, ma y be all o we d d uri n g t he 
E X T peri o d. If t he partici pa nt u n der g oes electi ve s ur ger y, t he st u d y dr u g s h o ul d be i nterr u pte d at 
least 1 wee k pri or t o t he pla n ne d s ur ger y. All o w rei ntr o d ucti o n of st u d y dr u g o nce t he p h ysicia n 
has e x a mi ne d t he s ur gi cal site a n d deter mi ne d t hat it has heale d a n d t here is n o si g n of i nfecti o n.  
6. 6. 2.  
Criteri a f or Per m a ne nt Disc o nti n u ati o n of St u d y Dr u g  
T he occ urre n ce of u nacce pta ble t o xicit y n ot ca use d b y t he u n derl yi n g dis ease will re q uire t hat 
t he st u d y dr u g  b e per ma n e ntl y disc o nti n ue d. U nacce pta ble t o xicit y is defi n e d as f oll o ws:  
•  T he occ urre n ce of a n A E t hat is relate d t o st u d y dr u g t hat, i n t he j u d g me nt of t he 
i n vesti gat or or t h e s p o ns or's me di cal m o nit or, c o m pr o mises t he partici pa nt's a bilit y t o 
c o nti n ue st u d y-s p ecific pr oce d ures or is c o nsi dere d t o n ot be i n t he partici pa nt's b est 
i nterest. 
•  A persiste nt A E re q uiri n g a n i nterr u pti o n of st u d y dr u g f or m ore t h a n 2 8 da ys u nless 
a great er del a y has bee n a p pr o ve d b y t he s p o ns or ( or desi g nee).  
•  Rec urre n c e of a n i nitial A E(s) t hat pre vi o usl y le d t o st u d y dr u g i nterr u pti o n after 
restarti n g t he st u d y dr u g ( u nless ot her wise s pecifi e d i n Ta ble  8 ). 
•  S pecific A Es r e q uiri n g p er ma ne nt disc o nti n uati o n of st u d y dr u g as descri be d i n 
Secti o n 6. 6. 1 . 
See Secti o n  7  f or disc o nti n uati o n pr oce d ures. 
6. 7.  
Pri or a n d C o nc o mit a nt Me dic ati o ns a n d Pr oce d ures  
6. 7. 1.  
Pri o r T her a p y f or C hr o nic S p o nt a ne o us Urtic ari a  
A n y t o pical or s yste mic treat me nts f or C S U si nce i nitial dia g n osis will be rec or de d i n t he e C R F. 
I nf or mati o n ass ociat e d wit h res p o nse t o pri or C S U t hera p y a n d reas o n f or disc o nti n uati o n will 
als o be rec or de d i n t he e C R F. E x a m ples of c o m m o nl y use d  t hera pies f or C S U i ncl u de b ut are n ot 
li mited t o t he f oll o wi n g: sec o n d-ge n erati o n H 1  a nti hista mi nes, o maliz u ma b , c ortic oster oi ds, a n d 
c ycl os p ori n . 
6. 7. 2.  
B ac k gr o u n d  (St a n d ar d of C are ) T her a p y  
All partici pa nts will be re q uire d t o re mai n o n a c o nc urre nt, sta ble d os e of sec o n d -ge n erati o n 
H 1  a nti hista mi ne as bac k gr o u n d t h era p y ( S O C ), w hic h will n ot be c ha n ge d t hr o u g h o ut t he st u d y. 
C h oice of S O C  re gi me n will be left t o i n vesti gat or discreti o n. 

I nc yte C or p orati o n 
P a ge 4 8  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
6. 7. 3.  
Resc ue Me dic ati o n  
Initiati o n of n o n – st u d y dr u g t hera p y t o treat t he w orse ni n g of pr urit us, C S U, or flare of 
pre vi o usl y i na cti ve s ki n disease is str o n gl y disc o ura ge d t hr o u g h o ut t he P C  peri o d. If dee me d t o 
be me dicall y necessar y b y t he i n vesti gat or, resc u e treat me nts f or C S U n ote d bel o w ma y be 
a d de d t o st u d y dr u g a n d bac k gr o u n d t hera p y . 
All resc ue me di cati o n m ust be e ntere d i nt o t he E D C a n d class ifie d as resc ue me dicati o n wit h t he 
f oll o wi n g i nf or mati o n: 
•  Na me a n d d os e re gi me n of t he resc u e me dicati o n . 
•  Date a n d ti me of a d mi nistrati o n.  
Fr o m Wee k 1 t o W ee k 4:  
•  A d d a n ot her sec o n d -ge nerati o n  H 1  a nti hista mi ne t o treat me nt re gi me n . 
Fr o m Wee k 5 t o W ee k 3 6:  
•  A d d a n ot her  sec o n d-ge nerati o n  H 1  a nti hista mi ne t o treat me nt re gi me n.  
•  I n t he cas e of se v ere e x acer bati o n of pr urit us, a 1 -ti me, s h ort c o urse ( ma xi m u m 
7  da ys)  of gl uc o c ortic oster oi ds m a y be use d as res c ue me dicati o n  fr o m Da y 1 of 
Wee k 5 . 
•  If res c ue me dicati o n is t o be a d de d, t he effi cac y a n d safet y assess me nts f or t he visit 
s h o ul d be c o m plete d bef ore t he start of resc u e t hera p y. 
•  T he partici pa nt ma y re m ai n o n st u d y dr u g u nless t he resc u e t hera p y is a pr o hi bite d 
me dicati o n or pr oce d ure.  
Fr o m Wee k 3 6 t o W ee k 4 4 ( P ost -Treat me nt F oll o w -U p Peri o d ): 
•  A n y  p artici pa nt e x perie n ci n g a w orse ni n g of s y m pt o ms ca n be treate d wit h a n y 
resc ue t h era p y d ee me d a p pr o priate b y t he i n vesti gat or. 
6. 7. 4.  
Pr o hi bite d Me dic ati o ns a n d Pr oce d ures  
T he f oll o wi n g m e dicati o ns a n d pr oce d ures are pr o hi bite d f or all partici pa nts i n t he st u d y:  
•  C o n ve nti o nal t hera pies wit h p ote ntial t hera pe utic i m pact o n C S U, per discreti o n of 
t he i n vesti gat or or desi g n ee, wit h t he e x ce pti o n of S O C a n d resc ue m e dicati o n. 
•  J A K i n hi bit ors (s yste mic or to pical) ot her t ha n p o v orciti ni b . 
•  Use of bi ol o gi cs wit h i m m u n o m o d ulat or y effect . 
•  S yste mic i m m u n os u p pressi ve or i m m u n o m o d ulati n g dr u gs (e g, oral or i njecta ble 
c ortic oster oi ds, met h otre x ate, c ycl os p ori n e, da ps o ne, azat hi o pri ne) . 
•  A pre milast, crisa b or ol e, or a n y ot her s yste mic or t o pical P D E -4 i n hi bit or.  

I nc yte C or p orati o n 
P a ge 4 9  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
•  Str o n g s yste mic C Y P 3 A 4 i n hi bit ors a n d str o n g a n d m o derate s yste mic C Y P 3 A 4 
i n d ucers (see A p pe n di x  B ). E x a m ples i ncl u de b ut are n ot li mite d t o t he f oll o wi n g 
me dicati o ns: rifa m pici n/rifa m pi n, ket oc o naz ole, itrac o naz ole, car ba maze pi ne, 
rit o na vir, St J o h n's w ort, a n d gra pefr uit/ gra p efr uit j uice. 
− I n e x ce pti o nal cases (e g, C O VI D -1 9 treat me nt wit h nir matrel vir/rit o na vir), a n d 
after st u d y dr u g i nterr u pti o n, str o n g C Y P 3 A 4 i n hi bit ors or str o n g/ m o derate 
i n d ucers ma y be us e d f or u p t o 7 da ys. T h e s p o ns or ( or desi g nee) m ust be 
i nf or me d of t he i n vesti gat or's ( or desi g nee's) decisi o n a n d rati o nale wit hi n a 
reas o na bl e ti mefra me. St u d y dr u g m a y be restarte d after a mi ni m u m of 7 da ys of 
disc o nti n uati o n of t he str o n g C Y P 3 A 4 i n hi bit or or str o n g/ m o derate i n d ucer.  
− If treat me nt wit h str o n g C Y P 3 A 4 i n hi bit ors or str o n g/ m o derate C Y P 3A 4 i n d ucers 
is re q uire d f or l o n ger t ha n 7 da ys after st u d y dr u g i nterr u pti o n, t he partici pa nt 
ma y b e disc o nti n ue d fr o m t he st u d y a n d t he E T visit perf or me d.  
•  Li ve , atte n uate d v acci n es ( d uri n g t h e st u d y a n d wit hi n 8 wee ks after t he last d ose of 
st u d y dr u g). E x a m ples of li ve vacci nes i ncl u d e b ut are n ot li mite d t o t he f oll o wi n g:  
− B C G  
− her pes z oster  
− measles -m u m ps -r u bella or measles-m u m ps -r u bella-vari cella  
− m o n o vale nt , li ve, atte n uate d i nfl ue nza A (i ntra nas al)  
− oral p oli o vacci ne  
− r ota vir us 
− seas o nal, tri vale nt, li ve, atte n uate d i nfl ue nza (i ntra nasal)  
− s mall p o x 
− t y p h oi d 
− varicella (c hic ke n p o x)  
− yell o w fe ver  
•  Electi ve s ur ger y  
− P C peri o d: Will n ot be all o we d  
− E X T peri o d: Ma y be all o we d per deter mi nati o n of t he i n vesti gat or ( or desi g nee) 
after c o ns ultati o n wit h t he s p o ns or ( or d esi g n ee). See Secti o n  6. 6. 1. 6  f or d etails 
o n st u d y dr u g i nterr u pti o n.  
N ote: If a p artici pa nt m ust u n der g o e mer ge nc y s ur ger y, t he st u d y dr u g s h o ul d be  
i nterr u pte d at t he ti me of t he s ur ger y. See Secti o n 6. 6. 1. 6  f or details o n st u d y dr u g 
i nterr u pti o n. 
6. 8.  
Tre at me nt After t he E n d of t he St u d y  
U p o n c o m pl eti o n of t h e 3 6 wee ks of treat me nt, p artici pa nts will n ot be pr o vi de d a d diti o nal 
treat me nt wit hi n t his st u d y. 

I nc yte C or p orati o n 
P a ge 5 0  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
7.  
DI S C O N TI N U A TI O N O F S T U D Y T R E A T M E N T A N D 
P A R TI CI P A N T WI T H D R A W A L  
7. 1.  
Disc o nti n u ati o n of St u d y Tre at me nt  
7. 1. 1.  
Re as o ns f or Disc o nti n u ati o n  
Partici pa nts m ust  b e disc o nti n ue d fr o m st u d y tr eat me nt f or t he f oll o wi n g reas o ns:  
•  T he partici pa nt bec o mes pre g na nt.  
•  C o nse nt is wit h dra w n.  
N ote: C o nse nt wit h dra w n mea ns t hat t he partici p a nt has e x plicitl y i n dicate d t hat t he y 
d o n ot wa nt t o be f oll o we d a n y l o n ger; i n t his ca s e n o f urt her data, e x ce pt data i n t he 
p u blic d o mai n, ma y b e s olicite d fr o m or c ollect e d o n t he partici pa nt. C o nse nt ma y 
als o be partial. Partici pa nts ma y c h o os e t o disc o nti n ue st u d y dr u g a n d re mai n i n t he 
st u d y t o c o m plete t he p ost -treat me nt f oll o w-u p vis it. 
•  F urt her partici pati o n w o ul d be i nj uri o us t o t he partici pa nt 's healt h or well-b ei n g, i n 
t he i n vesti gat or's me di cal j u d g me nt. 
•  Occ urre nce of u nacce pta ble t o xicit y as n ote d i n S ecti o n  6. 6 . 
•  Has recei ve d a pr o hi bite d me dicati o n or pr oce d ure as descri be d i n Secti o n  6. 7. 4 . 
•  T he st u d y is ter mi nat e d b y t he s p o ns or. 
•  T he st u d y is ter mi nat e d b y t he l ocal healt h a ut h orit y, I R B, or I E C.  
A partici pa nt  m a y b e disc o nti n ue d fr o m st u d y treat me nt as f oll o ws:  
•  If a partici pa nt is c o nsiste ntl y n o nc o m plia nt wit h st u d y pr oce d ures or wit h st u d y dr u g 
or bac k gr o u n d t h era p y  a d mi nistrati o n i n t he i n vesti gat or 's o pi ni o n, t he s p o ns or s h o ul d 
be c o ns ulte d f or i nstr ucti o n o n ha n dli n g t he partici pa nt.  
7. 1. 2.  
Disc o nti n u ati o n Pr oce d ures  
I n t he e ve nt t hat t he d ecisi o n is ma de t o per ma ne ntl y disc o nti n ue t he st u d y treat me nt, t he 
E O T/ E T visit s h o ul d be c o n d ucte d (see Secti o n  8. 7 ). Reas o na ble eff orts s h o ul d be ma de t o ha ve 
t he partici pa nt ret ur n f or a p ost -treat me nt f oll o w-u p visit. T hese vi sits are descri be d i n Ta bl e  3 . 
T he last date of t he l ast d ose of st u d y dr u g a n d t he reas o n f or disc o nti n uati o n of st u d y dr u g will 
be rec or de d i n t he e C R F.  
If a p artici p a nt is disc o nti n ue d fr o m st u d y tre at me nt:  
•  T he st u d y m o nit or or s p o ns or m ust be n otifie d.  
•  T he reas o n(s) f or disc o nti n uati o n m ust be d oc u me nte d i n t he partici pa nt 's me dical 
rec or d a n d t he pri mar y reas o n f or disc o nti n uati o n m ust be i ncl u de d i n t he e C R F. 
•  T he E O T/ E T visit s h o ul d be perf or me d a n d d ate rec or de d.  

I nc yte C or p orati o n 
P a ge 5 1  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
•  T he stat us of t he partici p a nt s h o ul d be u p date d t o E O T i n t he I R T.  
•  Partici pa nts m ust be f oll o we d f or s afet y u ntil t he ti me of t he p ost -treat me nt f oll o w-u p 
visit or u ntil st u d y dr u g – relate d t o xicities res ol ve, ret ur n t o baseli ne, or are dee me d 
irre versi ble, w hic he v er is l o n gest. 
If t he partici p a nt disc o nti n ues st u d y tr eat me nt a n d acti vel y wit h dra ws c o nse nt f or c ollecti o n of 
f oll o w-u p data ( p ost -tr eat me nt f oll o w-u p or diseas e assess me nt), t he n n o a d diti o nal data 
c ollecti o n s h o ul d occ ur; h o we ver, partici pa nts will ha ve t he o pti o n of wit h dra wi n g c o nse nt f or 
st u d y treat me nt b ut c o nti n ui n g i n t he f oll o w-u p p eri o d of t he st u d y f or safet y/ efficac y 
assess me nts.  
7. 2.  
P artici p a nt Wit h dr a w al Fr o m t he St u d y  
A partici pa nt ma y wit h dr a w fr o m t he st u d y at a n y ti me at t heir o w n re q u est or ma y b e wit h dra w n 
at a n y ti me at t he discreti o n of t he i n vesti gat or f or safet y, be h a vi oral, c o m plia nce, or 
a d mi nistrati ve reas o ns.  
If a partici pa nt wit h dra ws fr o m t he st u d y, t he y m a y re q uest destr u cti o n of a n y sa m ples ta k e n a n d 
n ot teste d, a n d t he i n vesti gat or m ust d oc u m e nt t his i n t he site st u d y rec or ds. If t he partici p a nt 
wit h dra ws c o nse nt f or discl os ure of f ut ur e i nf or m ati o n, t he s p o ns or ma y retai n a n d c o nti n ue t o 
use a n y data c ollecte d b ef ore s uc h a wit h dra wal of c o nse nt.  
See Ta ble  3  f or data t o b e c ollecte d at t he ti me of st u d y wit h dra wal a n d f oll o w-u p a n d f or a n y 
f urt her e v al uati o ns t hat n ee d t o be c o m plet e d.  
7. 3.  
L ost t o F oll o w -U p  
A partici pa nt  will be c o nsi dere d l ost t o f oll o w -u p if t he y re peate dl y fail t o r et ur n f or sc h e d ule d 
visits a n d are u na ble t o b e c o ntact e d b y t he st u d y site.  
T he f oll o wi n g acti o ns m ust be ta ke n if a p artici pa nt fails t o ret ur n t o t he cli nic f or a re q uire d 
st u d y visit: 
•  T he site m ust atte m pt t o c o ntact t he partici pa nt a n d resc he d ul e t he misse d visit as 
s o o n as p ossi ble a n d c o u nsel t he partici pa nt o n t h e i m p orta nce of mai ntai ni n g t he 
assi g ne d visit sc he d ul e a n d ascert ai n w het her or n ot t he partici pa nt wis hes t o a n d/ or 
s h o ul d c o nti n ue i n t he st u d y. 
•  Bef ore a p artici pa nt is dee me d l ost t o f oll o w -u p, t he i n vesti gat or or desi g n ee m ust 
ma ke e ver y eff ort t o re gai n c o ntact wit h t he partici pa nt ( w here p ossi ble, 3 tele p h o ne 
calls a n d, if necessar y, a certifie d letter t o t he parti ci pa nt 's last k n o w n m aili n g a d dress 
or l ocal e q ui vale nt met h o ds). T hese c o nt act atte m pts s h o ul d be d oc u me nte d i n t he 
partici pa nt 's me dical r ec or d. 
•  S h o ul d t he partici pa nt c o nti n ue t o be u nrea c ha ble, t he y will be c o nsi dere d t o ha ve 
wit h dra w n fr o m t he st u d y.  

I nc yte C or p orati o n 
P a ge 5 2  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
8.  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  
See A p pe n di x  E  f or C O VI D-1 9 – relate d g ui da nce. 
8. 1.  
A d mi nistr ati ve a n d Ge ner al Pr oce d ures  
8. 1. 1.  
I nf or me d C o nse nt Pr ocess 
•  T he i n vesti gat or or t heir re pres e ntati ve will e x plai n t he nat ure of t h e st u d y t o t he 
partici pa nt a n d a ns wer all q uesti o ns re gar di n g t he st u d y.  
− I nf or me d c o ns e nt m ust be o btai ne d bef ore a n y st u d y-relate d pr oce d ures are 
c o n d ucte d, u nless ot her wise s pecifie d b y t he Pr ot o c ol.  
− I nf or me d c o ns e nt m ust be o btai ne d usi n g t h e I R B/I E C-a p pr o ve d versi o n i n a 
la n g u a ge t hat is nati ve a n d u n dersta n da ble t o t he partici pa nt. A n I C F t e m plate 
will be pr o vi de d b y  t h e s p o ns or or its desi g n ee. T he s p o ns or or its desi g n ee m ust 
re vie w a n d ac k n o wle d ge t he site-s pecific c ha n ges t o t he I C F te m plate. T he I C F 
m ust i ncl u de a state me nt t hat t he s p o ns or or its desi g nee a n d re g ulat or y 
a ut h orities ha ve direct access t o partici p a nt r ec or ds.  
− T he I C F m ust c o ntai n all re q uire d ele me nts i ncl u di n g o pti o nal 
sa m ples/ pr oce d ures (e g, o pti o nal bi o ps y) a n d d escri be t he nat ure, sc o p e, a n d 
p ossi ble c o nse q ue nces of t he st u d y i n a f or m u n dersta n da ble t o t he st u d y 
partici pa nt.  
•  Partici pa nts m ust be i nf or me d t hat t heir partici p ati o n is v ol u ntar y. Partici pa nts will be 
re q uire d t o si g n a state m e nt of i nf or me d c o ns e nt t hat meets t he a p plica bl e 
re q uire me nts a n d re g ulati o ns f or t he c o u ntries i n w hic h t he st u d y is bei n g c o n d ucte d 
as well as t he I R B/I E C o r st u d y ce nter. 
•  T he partici pa nt m ust be i nf or me d t hat t heir pers o nal data c ollect e d f or t he st u d y will 
be use d b y t he s p o ns or a n d/ or t heir desi g n ee(s) i n acc or da nce wit h l ocal data 
pr otecti o n la ws. T he le v el of discl os ure m ust als o be e x plai ne d t o t he part ici pa nt. 
•  T he partici pa nt m ust be i nf or me d t hat t heir me dical rec or ds ma y be e x a mi ne d b y 
Cli nical Q ualit y Ass ura n ce a u dit ors or ot her a ut h orize d pers o n nel a p p oi nte d b y t he 
s p o ns or, b y a p pr o priat e I R B/I E C me m bers, a n d b y i ns pect ors fr o m re g ulat or y 
a ut h orities. 
•  T he me dical r ec or d m ust i ncl u de a state me nt t hat writte n i nf or me d c o ns e nt was 
o btai ne d bef ore t he partici pa nt was e nr olle d i n t he st u d y a n d t he date t he writte n 
c o nse nt was o btai ne d. T h e a ut h orize d pers o n o btai ni n g t he i nf or m e d c o nse nt m ust 
als o si g n t h e I C F.  
•  Partici pa nts m ust pr o vi de c o nse nt t o t he m ost c urre nt versi o n of t he I C F d uri n g t heir 
partici pati o n i n t he st u d y.  
•  A c o p y of t he I C F(s) m ust be pr o vi de d t o t he partici pa nt or t he partici pa nt 's le gall y 
a ut h orize d re pres e ntati ve.  
Partici pa nts w h o are r escree ne d are re q uir e d t o si g n a ne w I C F a n d be assi g ne d a ne w partici pa nt 
n u m ber (see S ecti o n  8. 1. 3 ). 

I nc yte C or p orati o n 
P a ge 5 3  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
8. 1. 2.  
Scree ni n g Pr oce d ures  
Scree ni n g is t he i nter val bet wee n si g ni n g t he I C F a n d t he da y t he partici pa nt is ra n d o mize d i n t he 
st u d y ( Da y 1/ b aseli ne). S cree ni n g ma y n ot e x cee d 2 8  da ys. Assess me nts  t hat are re q uire d t o 
de m o nstrate eli gi bilit y ma y b e perf or me d o ver t he c o urse of 1  or m ore d a ys d uri n g t he s cree ni n g 
pr ocess. A si g ne d I C F m ust be o btai ne d as t he first ste p a n d bef ore I R T scree ni n g re gistrati o n or 
a n y ot h er st u d y-s pecific assess me nts. T he scree ni n g of a partici p a nt s h o ul d be re gistere d i n t he 
I R T, w hi c h will assi g n t h e st u d y-s p ecific I D. Eac h partici pa nt w h o has si g n e d t he I C F s h o ul d be 
re gistere d i n t he I R T c o nte m p ora ne o usl y a n d wit h o ut u n d ue dela ys. 
Res ults fr o m t he scree ni n g visit e val uati o ns will be re vie we d t o c o nfir m eli gi bilit y bef ore t h e 
ra n d o mizati o n tra nsacti o n is re gistere d i n t he I R T a n d bef ore t he a d mi nistrati o n of st u d y dr u g. 
Tests wit h res ults t hat fail eli gi bilit y re q uir e me nts ma y b e re p eate d o nce d uri n g scree ni n g if t h e 
i nvesti gat or b elie ves t he res ults t o be i n err or. F or scree ni n g assess me nts t hat are re peate d, t he 
m ost rece nt a v aila ble res ult bef ore ra n d o mizati o n will be use d t o deter mi ne eli gi bilit y.  
See Secti o ns  5. 4  a n d 5. 5  f or i nf or mati o n re gar di n g scree n fail ures a n d re pl ace me nt of 
partici pa nts, res p ecti ve l y. 
8. 1. 3.  
I nter acti ve Res p o nse Tec h n ol o g y Pr o ce d ure 
Eac h partici pa nt will be i de ntifie d i n t he st u d y b y a partici pa nt I D n u m ber, w hic h is a 
c o m bi nati o n of t he c o u ntr y's a b bre vi ati o n, t he site I D, a n d t he partici pa nt n u m ber . Site staff 
s h o ul d c o ntact t he I R T t o obtai n t he partici pa nt I D n u m ber d uri n g scree ni n g.  
U p o n deter mi ni n g t h at t he partici pa nt is eli gi ble f or ra n d o mizati o n, t he I R T will be c o ntacte d t o 
o btai n t he treat me nt assi g n me nt. A d diti o nall y, t he I R T will be c o ntact e d at t he st u d y visits 
i n dicate d i n Ta ble  3  t o u p date t he st u d y dr u g s u p pl y. A d diti o nal details will be pr o vi de d i n t he 
I R T ma n u al . 
8. 1. 4.  
Distri b uti o n of Re mi n der C ar d s 
Partici pa nts will be pr o vi de d wit h a re mi n der car d at eac h visit  i n dicate d i n Ta ble  3 . 
T he re mi n der car d will pr o vi de ge neral i nf or mati o n re gar di n g st u d y dr u g a d mi nistrati o n, 
i ncl u di n g o n w hic h st u d y visit da y s t he partici pa nt s h o ul d n ot self -a d mi nister t heir d ose of st u d y 
dr u g.  
8. 1. 5.  
Distri b uti o n of P artici p a nt C ar d s 
Partici pa nts will be pr o vi de d wit h a partici pa nt car d at scree ni n g.  
Partici pa nts s h o ul d be i nstr ucte d t o carr y t his car d at all ti mes a n d t o prese nt it t o all healt h care 
pr ofessi o nals w he n eit her visiti n g a n y ot h er me dical facilit y or de part me nt ot her t ha n t he st u d y 
site or h os pitalize d. T he partici pa nt car d will c o ntai n t he na me a n d c o ntact details f or t he 
i n vesti gat or. 
8. 1. 6.  
Distri b uti o n of Electr o nic Di aries  
Partici pa nts  will be pr o vi de d wit h a n e Diar y at scree ni n g.  
Sites will be pr o vi de d wit h trai ni n g materials a n d i nstr ucti o ns o n t he use of e C O A a n d will be 
res p o nsi ble f or trai ni n g p artici pa nts o n e Diar y use a n d e C O A c o m pleti o n. F urt her details o n use 

I nc yte C or p orati o n 
P a ge 5 4  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
of t he e Diaries a n d e C O A will be pr o vi de d i n res pecti ve st u d y d o c u me ntati o n. F or P R Os 
sc he d ule d t o be c o m plet e d at st u d y visits, q uesti o n naires will be c o m plete d b y t he partici pa nt 
bef ore site p ers o n nel perf or m a n y cli nic assess me nts t o a v oi d biasi n g t he partici pa nt's res p o nse . 
8. 1. 7.  
De m o gr a p h y a n d Me dic al Hist or y  
8. 1. 7. 1.  
De m o gr a p hics a n d Ge n er al Me dic al Hist or y  
De m o gra p hic d ata a n d ge neral me di cal hist or y will be c ollecte d at scree ni n g b y t he i n vesti gat or 
or q ualifie d desi g nee a n d will i ncl u de year of birt h/a ge, race, et h nicit y, me dical a n d s ur gical 
hist or y, fa mil y hist or y of car di o vas c ular dise ase, fa mil y hist or y of cl otti n g dis or ders, ris k fact ors 
ass ociate d wit h car di o vas c ular diseas e, hist or y of nic oti ne a n d alc o h ol use, a n d c urre nt ill nesses. 
Me dical hist or y will i ncl u de rele v a nt me d ical a n d s ur gical treat me nts t hat are c o nsi d ere d t o be 
cli nicall y si g nifica nt b y t he i n vesti gat or.  
Hist or y of cli nical her p es z oster, her pes z oster vacci nati o n, c hic ke n p o x vacci nati o n, i nfl ue nza 
vacci nati o n, a n d h e patitis B vacci nati o n stat us will be rec or de d as part of t h e me dical hist or y.  
Hist or y of C O VI D -1 9 v acci nati o n a n d C O VI D -1 9 i nfecti o n (a n d/ or h os pitalizati o n) will be 
rec or de d as part of t he m e dical hist or y. 
A detaile d me dical hist or y wit h res p ect t o T B ris k fact ors will be d oc u m e nte d i n t he st u d y s o urce 
d oc u me ntati o n. T his i nf or mati o n will i ncl u de B C G vacci n ati o n; c o ha bitati o n wit h i n di vi d uals 
w h o ha ve ha d T B; a n d tra vel t o, resi de n ce i n, or w or k i n T B e n de mic l ocati o ns.  
8. 1. 7. 1. 1.  J ustific ati o n f or C ollecti o n of R ace a n d Et h nicit y  
E pi de mi ol o gic esti mates f or  C S U are s p arse , a n d t he i m pact of race a n d et h nicit y o n C S U is n ot 
yet u n d erst o o d. De m o gra p hic data, i ncl u di n g race a n d et h nicit y , will be c ollecte d d uri n g t he 
scree ni n g p eri o d f or t his st u d y a n d c o nsi dere d as part of assess me nts f or treat me nt res p o nse 
he ter o ge n eit y. 
8. 1. 7. 2.  
Dise ase C h ar acteristi cs a n d Tre at me nt Hist or y  
C o m plete C S U me dical  a n d treat me nt hist or y, i n cl u di n g date of dia g n osis, rele va nt diseas e 
c haracteristics, a n d pri or treat me nts, i ncl u di n g s yste mic treat me nts , will be c ollecte d at 
scree ni n g. A m e dical hist or y of ot her c o n diti o ns relate d t o C S U or rele va nt t o t he c o n d uct of t his 
st u d y will als o be c ollecte d at scree ni n g . 
A d diti o nal i nf or mati o n o n t he pr oce d ure f or c ollecti o n of pri or C S U t hera p y  a n d o n g oi n g 
bac k gr o u n d t hera p y  i nf or mati o n is prese nted i n Secti o n s 6. 7. 1  a n d 6. 7. 2 , res pecti vel y. 
8. 2.  
Effic ac y Assess me nts  
Efficac y will be e val u ate d usi n g P R O  meas ures i n t his st u d y.  
8. 2. 1.  
P ati e nt -Re p orte d O utc o mes  
All P R Os will be c ollecte d via e C O A.  

I nc yte C or p orati o n 
P a ge 5 5  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
8. 2. 1. 1.  
D ail y Di ar y P atie nt -R e p orte d O utc o mes  
8. 2. 1. 2.  
A d mi nistr ati ve Pr oce d ures  
8. 2. 1. 2. 1.  F oll o w -U p P h o ne C all  
St u d y sites s h o ul d c o nt act partici pa nts 1 wee k pri or t o t he baseli ne visit, 2 wee ks pri or t o t he 
Wee k 4 visit, a n d 1 wee k pri or t o t he Wee k 1 2 visit t o c o nfir m c o m plia nce wit h t he dail y diar y 
assess me nts.  
8. 2. 1. 2. 2.  C o m pli a nce Wit h D ail y Di ar y P atie nt -Re p orte d O utc o mes  
Partici pa nts ' c o m plia nce wit h dail y diar y P R O ass ess me nts ( ie, I S S, H S S,
) s h o ul d be 
m o nit ore d b y t he i n vesti gat or ( or desi g n ee) t hr o u g h o ut t he st u d y. C o m plia nce will be e v al uate d 
as o utli ne d bel o w:  
•  Scree ni n g peri o d:  
− A mi ni m u m of 5 dail y di ar y assess me nts s h o ul d b e c o m plete d wit hi n t he 7 da ys 
bef ore t h e baseli ne visit.  
•  P C a n d E X T peri o ds:  
− Partici pa nts ' c o m plia nce wit h t he dail y diar y assess me nts s h o ul d be assesse d at 
eac h st u d y visit d uri n g t h e P C a n d E X T peri o ds.  
− Partici pa nts w h o are c o nsiste ntl y n o n c o m pli a nt wit h t he dail y diar y assess me nts 
ma y b e wit h dra w n fr o m t he st u d y.  
8. 2. 1. 3.  
D ail y e Di ar y  
T he dail y e Diar y  i ncl u des t he U A S, w hic h will be use d t o calc ulate t h e U A S 7 , a n d t he 
.  
T he dail y e Diar y  is t o be c o m plete d o nce p er da y b y t he partici pa nt f or t h e d urati o n of t he st u d y . 
T he diar y ta blet will be gi ve n t o t he partici pa nt at t he scree ni n g visit.  
8. 2. 1. 4.  
Urtic ari a A cti vit y Sc ore  
T he U A S is a c o m p osite, e Diar y-rec or de d sc ore wit h n u meric se verit y i nte nsit y rati n gs ( 0 = n o n e 
t o 3 = i nte nse/se vere) f or a) t he n u m b er of hi ves ( i e, H S S)  a n d b) t he inte nsit y of t he pr urit us 
(ie, IS S) o v er t h e p ast 2 4 h o urs . 
8. 2. 1. 4. 1.  Urtic ari a A cti vit y Sc ore O ver 7 D a ys  
T he U A S 7 is t he 7 -da y s u m of t he dail y U A S. T he U A S 7 ( ra n ge 0 t o 4 2) is e q ual t o t he I S S 7 
(ra n ge 0 t o 2 1) pl us t he H S S 7 ( ra n ge 0 t o 2 1) . 
If a partici pa nt has e nt ere d at least 5 dail y U A S sc ores wit hi n t he 7 da ys pri or t o t he st u d y visit, 
t he U A S 7 sc ore is c alc ul ate d as t he s u m of t he a v aila ble U A S sc ores, di vi de d b y t h e n u m ber of 
da ys t hat h a ve a U A S sc ore, m ulti plie d b y 7.  
If t here are m ore t ha n 2 d ail y U A S sc ores missi n g wit hi n t he pri or 7 da ys, t he n t he U A S 7 sc ore 
is missi n g f or t he wee k. 

I nc yte C or p orati o n 
P a ge 5 6  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  

I nc yte C or p orati o n 
P a ge 5 7  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
8. 2. 2.  
Me dic al Res o urce Utiliz ati o n a n d He alt h Ec o n o mics  
Healt h ec o n o mic p ara m eters a re i n cl u de d i n t he P R Os, E Q-5 D -5 L q uesti o n naire (see 
Secti o n  8. 2. 1. 1 0 ), a n d W P AI -C U q u esti o n naire (see Secti o n  8. 2. 1. 9 ). 

I nc yte C or p orati o n 
P a ge 5 8  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
8. 3.  
S afet y Assess me nts  
Pla n ne d ti me p oi nts f or all safet y assess me nts are pr o vi de d i n Ta ble  3 . 
See Secti o n  6. 6  f or g ui deli nes re gar di n g t he ma n a ge m e nt of rel e va nt la b orat or y or ot her s afet y 
assess me nt a b n or malities.  
8. 3. 1.  
A d verse E ve nts  
A d verse e ve nts will be m o nit ore d fr o m t he ti me t he partici pa nt si g ns t he I C F u ntil at least 
6 0  da ys after t h e last d ose of st u d y dr u g. A d verse e ve nts f or ra n d o mize d partici pa nts t hat be gi n 
or w orse n afte r i nf or me d c o nse nt s h o ul d be rec or de d o n t he A d verse E ve nts F or m i n t he e C R F 
re gar dl ess of t he ass u m pti o n of a ca us al relati o ns hi p wit h t he st u d y dr u g. C o n diti o ns t hat were 
alrea d y prese nt at t he ti m e of i nf or me d c o nse nt s h o ul d be rec or de d o n t he Me dical H ist or y F or m 
i n t he e C R F. A d vers e e v e nts (i ncl u di n g la b orat or y a b n or malities t hat c o nstit ute A Es) s h o ul d be 
descri be d usi n g a dia g n osis w he ne ver p ossi ble rat her t ha n b y i n di vi d ual u n derl yi n g si g ns a n d 
s y m pt o ms. 
A d verse e ve nts will be re p orte d b y t h e partici p a nt ( or, w he n a p pr o priat e, b y a care gi ver, 
s urr o gate, or t h e partici p a nt's le gall y a ut h orize d re prese nt ati ve). T he i n v esti gat or a n d a n y 
q ualifie d desi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g, a n d rec or di n g e v e nts t hat meet 
t he defi niti o n of a n A E or S A E a n d re m ai n res p o nsi ble f or f oll o wi n g u p o n A Es t hat are s eri o us, 
t hat are c o nsi d ere d relate d t o t he st u d y dr u g pr oce d ures, or t hat ca use d t he partici pa nt t o 
disc o nti n ue t he st u d y dr u g. Care will be ta ke n n ot t o i ntr o d uce bias w he n d etecti n g A Es a n d/ or 
S A Es. O pe n -e n d e d a n d n o nlea di n g v er bal q u esti o ni n g of t he p artici pa nt, s uc h as "H o w are y o u 
feeli n g?", is t he preferre d met h o d t o i n q uire a b o ut A E occ urre nces. A d verse e ve nts ma y als o be 
detecte d w h e n t he y are v ol u nteere d b y t he partici pa nt d uri n g t he s cree ni n g pr ocess or b et wee n 
visits or t hr o u g h p h ysical e x a mi nati o ns, la b orat or y tests, or ot her assess me nts. T he defi niti o n, 
re p orti n g, a n d rec or di n g re q uire me nts f or A Es are descri be d i n Secti o n  9 . 
All S A Es will be re p orte d t o t he s p o ns or or desi g nee wit hi n 2 4 h o urs. T he i n vesti gat or will 
s u b mit a n y u p date d S A E data t o t he s p o ns or wit hi n 2 4 h o urs of it bei n g a vaila ble.  
After t he i nitial A E/ S A E re p ort, t he i n vesti gat or is re q uire d t o pr o acti vel y f oll o w eac h partici pa nt 
at s u bse q ue nt visits/c o ntacts. All A Es a n d S A Es (as defi ne d i n Secti o n  9. 2 ) will be f oll o we d u ntil 
res ol uti o n, sta bilizati o n, t he e ve nt is ot her wise e x plai ne d, or t he partici pa nt is l ost t o f oll o w-u p 
(as defi ne d i n Secti o n  7. 3 ). 
8. 3. 2.  
P h ysic al E x a mi n ati o ns  
P h ysical e x a mi nati o ns m ust be perf or m e d b y a me dicall y q u alifie d i n di vi d ual, s uc h as a lice nse d 
p h ysicia n, a p h ysicia n assista nt, or a n a d va nce d re gistere d n urse practiti o ner, as l ocal la w 
per mits . A b n or malities i de ntifie d after t he first d ose of st u d y tr eat me nt c o nstit ute a n A E if t he y 
are c o nsi d ere d cli nicall y mea ni n gf ul, i n d uce cli nical si g ns or s y m pt o ms, re q uire c o nc o mita nt 
t hera p y, or re q uire c ha n ges i n st u d y dr u g . I n v esti gat ors s h o ul d pa y s pecial atte nti o n t o cli nical 
si g ns relat e d t o pre vi o us seri o us ill nesses. 
A c o m pre he nsi v e p h ysic al e x a mi nati o n, at visits s pecifie d i n Ta ble  3 , will assess t he f oll o wi n g 
or ga n or b o d y s yste ms: s ki n; hea d, e yes, ears, n os e, a n d t hr oat; t h yr oi d; l u n gs; car di o vasc ular 
s yste m; a b d o me n (li ver, s plee n); e xtre mities; a n d l y m p h n o des. A bri ef ne ur ol o gic e x a mi nati o n 
will als o be perf or m e d.  

I nc yte C or p orati o n 
P a ge 5 9  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
D uri n g t h e st u d y, p artici pa nts  will ha ve tar get e d p h ysical e x a mi nati o ns. Partici pa nts will be 
assesse d b y t he i n vesti gat or or me dicall y q ualifie d desi g nee per i nstit uti o nal S O C. T hese 
assess me nts s h o ul d be a n e val uati o n as i n dicate d b y partici pa nt s y m pt o ms, A Es, or ot her 
fi n di n gs a n d do c u me nte d o n t he A d verse E ve nts F or m i n t he e C R F.  
Hei g ht a n d b o d y wei g ht will be assesse d as i n dicate d i n t he S o A (see Ta bl e  3 ). 
8. 3. 3.  
Vit al Si g ns  
Vital si g ns meas ur e me nts i ncl u de bl o o d press ure, p ulse, res pirat or y rate, a n d b o d y te m perat ur e 
a n d will be o btai ne d at e ac h st u d y visit . Partici pa nts s h o ul d n ot s m o ke or i n gest c affei ne d uri n g 
t he 3 0 mi n utes pri or t o bl o o d press ure a n d heart rate meas ure m ents (see Secti o n  5. 3. 2  f or details) 
Vital si g ns s h o ul d be c oll ecte d bef ore bl o o d c ollecti o n pr oce d ures. Alter nati vel y, a mi ni m u m 
i nter val of 3 0 mi n utes bet wee n t he c o m pleti o n of t he bl o o d c ollecti o n pr oce d ures a n d t he 
be gi n ni n g of t he vital si g ns c ollecti o n is rec o m me n de d. Bl o o d pr ess ure a n d p ulse will be ta ke n 
wit h t he partici pa nt i n t he rec u m b e nt, se mirec u m be nt, or sitti n g p ositi o n after 5 mi n ut es of rest . 
A b n or mal vital si g n res ults i de ntifie d after t he first d ose of st u d y dr u g c o nstit ute a n A E if t he y 
are c o nsi d ere d cli nicall y mea ni n gf ul, i n d uce cli nical si g ns or s y m pt o ms, re q uire c o nc o mita nt 
t hera p y, or re q uire c ha n ges i n st u d y dr u g. 
8. 3. 4.  
Electr oc a r di o gr a ms  
Si n gle , 1 2 -lea d E C Gs will be o btai ne d as o utli ne d i n t he S o A (see Ta ble  3 ) usi n g a n E C G 
mac hi ne t hat a ut o maticall y calc ulates t he h eart rat e a n d meas ures P R, Q R S, Q T, a n d Q Tc 
i nter vals. All 1 2-lea d E C Gs will be perf or m e d wit h t he partici pa nt i n a rec u m be nt or 
se mirec u m be nt p ositi o n after 5 mi n utes of rest.  
T he 1 2 -lea d E C Gs will be i nter pret e d b y t he i n vesti gat or or q u alifie d desi g nee f or a de q u ate 
partici pa nt ma na ge me nt. A d diti o nal 1 2 -lea d E C Gs ma y b e perf or me d as cli nicall y i n dicat e d t o 
ma na ge partici pa nt safet y. Cli nicall y n ot a ble a b n or malities t hat are c o nsi d ere d cli nicall y 
si g nifica nt i n t he j u d g me nt of t he i n vesti gat or are t o be re p orte d as A Es.  
8. 3. 5.  
L a b or at or y Assess me nts  
See Ta ble  9  f or t he list of cli nical la b orat or y tests t o be perf or me d a n d T a bl e  3  f or t he ti mi n g a n d 
fre q ue n c y. A ce ntral la b orat or y will perf or m all cli nical la b orat or y assess me nts f or safet y 
(ie, bl o o d c he mistries, he mat ol o g y assess me nts, c oa g ul ati o n tests, ser ol o g y, li pi d pa nel , a n d 
uri nal ysis); uri ne pre g n a nc y t ests will be perf or m e d l ocall y. A d diti o nal testi n g ma y be re q uire d 
b y t he i n vesti gat or or s p o ns or base d o n e m er gi n g s afet y data. All Pr ot oc ol -re q uire d la b orat or y 
assess me nts m ust be c o n d ucte d i n acc or da n ce wit h t he  La b orat or y M a n ual a n d  Ta ble  3 . 
I nf or mati o n re gar di n g c ollecti o n, pr ocessi n g, a n d s hi p pi n g of sa m ples f or la b orat or y assess me nt 
is pr o vi de d i n t he La b orat or y Ma n u al.  
Cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n gs are t h ose t hat are n ot ass ociate d wit h t he 
u n derl yi n g dise ase, u nless j u d ge d b y t he i n vesti gat or t o be m ore se v ere t h a n e x pecte d f or t he 
partici pa nt 's c o n diti o n. All la b orat or y tests wit h va l ues c o nsi dere d cli nicall y si g nifica ntl y 
a b n or mal d uri n g partici p ati o n i n t he st u d y or wit hi n  6 0 da ys a fter t he l ast d ose of st u d y dr u g 
s h o ul d be re peate d u ntil t he val ues ret ur n t o n or mal or baseli ne or are n o l o n ger c o nsi dere d 
cli nicall y si g nifica nt b y t he i n vesti gat or or me dical m o nit or.  

I nc yte C or p orati o n 
P a ge 6 0  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
Scree ni n g la b orat or y ass ess me nts m ust be perf or me d wit hi n 2 8 da ys bef ore D a y 1  ( baseli ne). If 
perf or me d m ore t ha n 2 8 da ys b ef ore D a y 1, t h e n t he tests m ust be re peate d a n d eli gi bilit y 
c o nfir me d bef ore st u d y dr u g a d mi nist rati o n o n Da y 1 . See Secti o n  5. 4  f or p ossi ble e x ce pti o ns if 
a partici pa nt re peats t he s cree ni n g pr ocess.  
La b orat or y s a m ple c ollecti o n o n Da y 1  m ust be perf or me d bef ore st u d y dr u g a d mi nistrati o n.  
See Secti o n  9. 1  f or i nf or mati o n re gar di n g la b orat or y a b n or malities t hat s h o ul d be rec or de d as a n 
A E i n t he e C R F. A d diti o nall y, if la b orat or y val u es fr o m la b orat or y assess me nts p erf or me d at t he 
i nstit uti o n's l ocal la b orat or y re q uire a c h a n ge i n p artici pa nt ma na ge me nt (e g, re q uire tr eat me nt) 
or are c o nsi dere d cli nicall y si g nifica nt b y t he i n vesti gat or (e g, S A E, A E), t he n t he res ult(s) of t he 
s pecific l a b or at or y assess me nt(s) m ust b e rec or de d i n t he e C R F.  

I nc yte C or p orati o n 
P a ge 6 1  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
T a ble  9 : 
Re q uire d L a b or at or y A n al ytes  
C he mistr y  
He m at ol o g y  
Uri n al ysis a 
Ser ol o g y  
Pre g n a nc y Testi n g  
Al b u mi n  
A L P  
A L T  
A S T  
A m ylase  
Bicar b o nate or C O 2 
Bilir u bi n: t otal, direct, a n d 
i n direct 
Bl o o d urea nitr o ge n or urea  
Calci u m  
C hl ori de  
C P K  
Creati ni ne  
G G T  
Gl uc ose  
Lactate de h y dr o ge nase  
P h os p hate  
P otassi u m  
S o di u m  
T otal pr otei n  
C o m plete bl o o d c o u nt, 
i ncl u di n g: 
•  He m o gl o bi n  
•  He m o gl o bi n A 1c 
•  Mea n  c or p usc ular v ol u me  
•  He mat ocrit  
•  Platelet c o u nt  
•  Mea n platelet v ol u me
b  
•  Re d bl o o d cell c o u nt  
•  Re d bl o o d cell 
distri b uti o n wi dt h  
•  W B C c o u nt  
•  He p ci di n  
•  Ferriti n  
•  B a n ds  
Differe ntial c o u nt ( % a n d 
a bs ol ute val ues), i ncl u di n g: 
•  B as o p hils  
•  E osi n o p hils  
•  L y m p h oc ytes  
•  M o n oc ytes  
•  Ne utr o p hils  
C ol or a n d a p peara nce  
p H a n d s pecific gra vit y  
Bilir u bi n  
Gl uc ose  
Ket o nes  
Le u k oc yte esterase  
Nitrite  
Occ ult bl o o d  
Pr otei n  
HI V  
H Bs A g c 
H Bs A b  
H B c A b c 
H C V  a nti b o d y d  
H B V D N A (refle x)  
H C V R N A (refle x)  
Q T F G ol d test.  
Pre g na nc y testi n g will be 
perf or me d o nl y f or fe male 
partici pa nts.  
•  Ser u m F S H : at 
scree ni n g f or fe male 
partici pa nts t o 
c o nfir m W O N C B P 
stat us (see g ui da nce 
i n A p pe n di x  A ). 
•  Ser u m pre g n a nc y 
test ( W O C B P): t o 
be perf or me d at visits 
i n dicate d i n t he S o A 
(see T a ble  3 ). 
•  Uri ne pre g n a nc y test 
( W O C B P): t o be 
perf or me d l ocall y at 
visits i n dicate d i n t he 
S o A (see T a ble  3 ) 
P ositi ve uri ne 
pre g na nc y test m ust 
be c o nfir me d wit h 
ser u m pre g na nc y test. 
Pre g na nc y tests (ser u m or 
uri ne) s h o ul d be re p eate d 
if re q uire d b y l ocal 
re g ulati o ns. 
Li pi d P a nel  
C o a g ul ati o n P a nel  
T otal c h olester ol  
Tri gl yceri des  
H D L  
L D L  
N o n -H D L c h olester ol  
a P T T  
P T  
I N R 
Ot her  
Bi o m ar ker S a m ples  
hs C R P  
Nic oti ne meta b olite scree n 
( uri ne) 
I g E 
C hr o nic urticaria pa nel 2 
(c o m pre he nsi ve) 
Bas o p hil acti vati o n test  
N ote: A d diti o nal tests ma y be re q uire d, as a gree d u p o n b y t h e i n vesti gat or a n d s p o ns or, base d o n e mer gi n g safet y data or t o r ule o ut a dia g n osis.  
a Micr osc o pic e val u ati o n ma y be  re q uire d i n t h e case of a b n or mal uri nal ysis res ults. 
b I n sa m ples wit h a b n or malities i n platelet c o u nt or size distri b uti o n (as i n dicate d b y a n a ut o mate d a nal yzer), a bl o o d fil m s h o ul d be e xa mi n e d.  
c If eit her H Bs A g or H Bc A b is p ositi ve, a refle xi ve H B V D N A m ust b e o btai ne d (see Secti o n 8. 3. 5. 4 ). 
d If H C V a nti b o d y is p ositi ve, a refle xi ve H C V R N A m ust b e o btai ne d (see Secti o n 8 . 3. 5. 4). 

I nc yte C or p orati o n 
P a ge 6 2  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
8. 3. 5. 1.  
Pre g n a nc y Testi n g  
A ser u m pre g n a nc y test will be re q uire d f or all W O C B P d uri n g s cree ni n g  a n d at t he 
p ost -treat me nt f oll o w-u p visit . Uri ne pre g na nc y t ests will be perf or me d l ocall y as o utli ne d i n 
Ta ble  3 , as me dicall y i n dicate d (e g, i n case of l oss of me nstr ual c ycl e, w he n pre g na nc y is 
s us pecte d), or per c o u ntr y-s p ecific re q uire m e nt ( n ote t hat co u ntr y -re q uire d uri ne pre g n a nc y 
testi n g will be o utli ne d a n d c o m m u nicate d t o i n vesti gati o nal sites u n der se parate c o ver). If a 
uri ne pre g n a nc y test is p ositi ve, t he res ult s h o ul d be c o nfir me d wit h a ser u m pre g n a nc y test.  
If t he ser u m pre g na n c y test res ult is ne gati ve after a uri ne test res ult was p ositi ve, the 
i n vesti gat or will assess t he p ote ntial be nefit/ris k t o t he partici pa nt a n d d eter mi ne w het her it is i n 
t he partici pa nt's best i nterest t o res u me st u d y dr u g a n d c o nti n ue partici p ati o n i n t he st u d y. 
If a pre g na nc y is c o nfir m e d b y a ser u m pre g na n c y test res ult, see Secti o n  9. 8  f or re p orti n g 
re q uire me nts. 
8. 3. 5. 2.  
T u berc ul osis Assess me nt  
D uri n g t h e scree ni n g pe ri o d, all partici pa nts will be scree ne d f or T B i nfecti o n via ce ntral 
la b orat or y ass ess me nt (see Secti o n 8. 3. 5. 2. 1 ). C o nfir me d ne gati ve stat us m ust be o btai ne d bef ore 
t he partici pa nt is ra n d o miz e d i n t he st u d y a n d recei ves st u d y dr u g. T h e f oll o wi n g o utc o mes ma y 
be c o nsi dere d : 
•  If Q T F G ol d ( or I G R A e q ui vale nt) test (a n d P P D s ki n test, if a p plica ble) is ne gati ve, 
t he partici pa nt ma y be ra n d o mize d. 
•  If Q T F G ol d ( or I G R A e q ui vale nt) test ( or P P D s ki n test, if a p plica ble) is p ositi ve, t he 
partici pa nt m ust be f urt h er e val u ate d via C X R ( or alter nati ve i ma gi n g met h o d, s uc h 
as M RI or C T) f or c o nfir mati o n of T B stat us (acti ve or late nt).  
− Partici pa nts wit h e vi de nce o f acti ve T B m ust n ot b e ra n d o mize d. 
− Partici pa nts wit h e vi de nce of late nt T B m ust n ot be ra n d o mize d, u nless a c o urse 
of at least 2 m o nt hs of a p pr o priate t hera p y has b ee n c o m plete d pri or t o 
ra n d o mizati o n. 
D uri n g t h e st u d y, if a partici pa nt is e x perie nci n g sig ns or s y m pt o ms s us pici o us f or T B, a n a d h o c 
T B test (i ncl u di n g C X R or alter nati ve i ma gi n g m et h o d, s uc h as M RI or C T ) ma y be perf or me d 
a hea d of t h e ne xt sc he d ule d assess me nt. T he s p o ns or 's me di cal m o nit or s h o ul d be i nf or me d of 
s uc h cases. C o nfir m e d T B i nfecti o n, after t h e partici pa nt has starte d t he st u d y, s h o ul d be 
re p orte d as a n A E. 

I nc yte C or p orati o n 
P a ge 6 3  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
8. 3. 5. 2. 1.  T u berc ul osis Test  
•  Q T F  G ol d test ( or I G R A e q ui vale nt, s uc h as T-S P O T T B test) is a d efa ult ce ntral 
la b orat or y ass ess me nt f or T B. W he n re q uir e d as p er l ocal sta n d ar ds, a P P D s kin test 
(als o k n o w n as t u berc uli n s ki n test or Ma nt o u x) ca n be perf or me d. T h e sa me T B 
testi n g met h o d s h o ul d be use d t hr o u g h o ut t he st u d y. 
N ote: T he P P D s ki n test s h o ul d be rea d b y a lice nse d healt h care pr ofessi o nal 
bet wee n 4 8  a n d 7 2 h o urs after a d mi nistrat i o n. A partici pa nt w h o d oes n ot ret ur n 
wit hi n 7 2  h o urs will nee d t o be resc h e d ule d f or a n ot her s ki n test. T he reacti o n will be 
meas ure d i n milli meters of i n d urati o n, a n d i n d urati o n ≥ 5 m m is c o nsi dere d a p ositi ve 
reacti o n. T h e a bse n ce of i n d urati o n will be rec or de d as "0 m m, " n ot "ne gati ve. " 
Partici pa nts w h o ha ve h a d a n ulcerati n g reacti o n t o t he P P D i n t he past s h o ul d n ot be 
re-e x p ose d , a n d t he P P D  test s h o ul d be c o nsi dere d p ositi ve. 
•  F or re gi o ns t hat re q uire b ot h P P D a n d Q T F  G ol d testi n g ( or I G R A e q ui v ale n t, s uc h as 
T -S P O T T B test), b ot h will be perf or me d. If eit her P P D or Q T F  G ol d ( or I G R A 
e q ui vale nt, s uc h as T -S P O T T B test) is p ositi ve, t he T B test is c o nsi dere d p ositi ve.  
•  If t he first Q T F  G ol d ( or I G R A e q ui vale nt) test is i n deter mi nate, t he n t he i n vesti ga t or 
s h o ul d perf or m a s ec o n d Q T F  G ol d ( or I G R A e q ui vale nt) test t o r ule o ut a p ositi ve 
test res ult. T he sec o n d Q T F  G ol d ( or I G R A e q ui v ale nt) test s h o ul d be perf or me d 
ce ntrall y; if n ot p ossi ble t o be perf or me d ce ntrall y, a l ocal la b orat or y res ult ma y b e 
accepta ble. If testi n g re m ai ns i n deter mi nate after t he sec o n d Q T F  G ol d ( or I G R A 
e q ui vale nt) test, t he n a P P D s ki n test will be perf or me d.  
8. 3. 5. 2. 2.  C hest X -R a y  
Partici pa nts ca n ha v e a C X R ( or alter nati ve i ma gi n g met h o d, s uc h as M RI or C T ) at a n y ti me 
d uri n g t he st u d y as  warra nte d base d o n t he o pi ni o n of t he i n vesti gat or ( or desi g nee). T h e C X R 
re q uires p osteri or-a nteri or a n d lateral vie ws. A ra di ol o gist or p ul m o n ol o gist m ust perf or m a n d 
d oc u me nt a n assess me nt of t he C X R. T he i n vesti gat or ( or desi g n ee) will i n dicate t he cl i nical 
si g nifica n ce of a n y fi n di n gs a n d will si g n a n d dat e t he re p ort. I n t he assess me nt of t he C X R, t he 
i n vesti gat or ( or desi g nee) m ust i n dicate t he prese n ce or a bs e nce of ( 1) calcifie d gra n ul o mas, 
( 2) ple ural s carri n g/t hic k e ni n g, a n d ( 3) si g ns of acti ve T B. If t h e C X R de m o nstrates c ha n ges 
s u g gesti ve of pre vi o us T B (e g, calcifi e d n o d ule, fi br otic scar, a pical or b asilar ple ural t hic ke ni n g) 
or ot her fi n di n gs t hat are cli nicall y si g nifica nt, t he i n vesti gat or ( or desi g nee) s h o ul d c o ntact t he 
s p o ns or's me dical m o nit or ( or desi g nee) bef ore ra n d o mizi n g t he partici pa nt. Partici pa nts w h o 
ha ve alr ea d y bee n ra n d o mize d i n t he st u d y b ut ha ve a C X R after ra n d o mizati o n t hat is cli nicall y 
si g nifica nt f or T B m ust be disc o nti n ue d fr o m st u d y dr u g. 

I nc yte C or p orati o n 
P a ge 6 4  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
8. 3. 5. 2. 3.  T u berc ul osis Pr o p h yl a xis  
At  scree ni n g, if a partici p a nt has e vi de nce of lat e nt T B i nfecti o n, pr o p h yl actic treat me nt m ust be 
i nitiate d at least 2 m o nt hs pri or t o a d mi nistrati o n of t he first d ose of st u d y dr u g ( or per l ocal 
g ui deli nes, w hic h e ver is l o n ger). Pr o p h yla xis nee ds t o be c o m plete d per l o cal g ui deli nes; 
h o we ver, t he f ull c o urse of pr o p h yl a xis d oes n ot nee d t o be c o m plet e d pri or t o t he first d ose of 
st u d y dr u g. 
N ote: Rifa m pici n a n d rif a pe nti ne are n ot all o we d f or c o nc urre nt T B pr o p h yl a xis. See 
Secti o n  6. 7. 4  f or a list of ot her pr o hi bite d me dicati o ns. 
Partici pa nts wit h a pri or hist or y of late nt T B w h o ha ve d oc u me nt e d c o m pleti o n of a f ull c o urse 
of a nti -T B t h era p y ma y b e all o we d t o be ra n d o mize d i n t he st u d y, pr o vi d e d n ot hi n g has c h a n ge d 
i n t he partici pa nt's me dical hist or y t o warra nt r e peat treat me nt. F or partici p a nts wit h c o m pleti o n 
of a f ull c o urs e of a nti -T B t hera p y b ut i ns ufficie nt d oc u me ntati o n, t he i n vesti gat or s h o ul d c o ns ult 
wit h t he s p o ns or 's me dical m o nit or ( or desi g nee) bef ore ra n d o mizi n g t he partici pa nt.  
D uri n g t h e st u d y, p artici pa nts wit h ne w e vi de nce of T B m ust be disc o nti n u e d  fr o m st u d y dr u g. 
8. 3. 5. 3.  
HI V Testi n g  
All partici pa nts will be teste d f or t he prese nce of HI V at scree ni n g. Partici pa nts will be scree n 
faile d if t he y test p ositi ve f or HI V i nfecti o n. 
8. 3. 5. 4.  
He p atitis Testi n g  
All partici pa nts will be teste d f or t he prese nce of H B V a n d H C V at scree ni n g. Ge nerall y, 
he patitis tests s h o ul d be perf or me d earl y i n t he s cree ni n g pr o cess d ue t o t h e le n gt h of ti me 
nee de d t o o btai n t he res ults.  
8. 3. 5. 4. 1.  He p atitis B Vir us  
Partici pa nts m ust u n der g o scree ni n g f or H B V at t he st u d y visits i n dicate d i n Ta ble  3 . At a 
mi ni m u m, t his i ncl u des testi n g f or H Bs A g, H Bc A b, a n d H Bs A b.  
I nter pret ati o n a n d ma na ge me nt of H B V test res ults are s h o w n i n Ta bl e  1 0  wit h f urt her 
e x pla nati o n bel o w.  
T a ble  1 0 : 
I nter pret ati o n a n d M a n a ge me nt of He p atitis B Vir us  Ser ol o gic Test Res ults  
Sce n ari o  
H Bs A g  
H Bc A b  
H Bs A b  
St at us  
A  
P ositi ve  
Ne gati ve or p ositi ve  
Ne gati ve or p ositi ve  
N ot eli gi ble  
B  
Ne gati ve  
Ne gati ve  
Ne gati ve  
Eli gi ble  
C  
Ne gati ve  
Ne gati ve  
P ositi ve  
H B V D N A P C R re q uire d  
P ositi ve res ults: n ot eli gi ble  
Ne gati ve res ults: eli gi ble  
D  
Ne gati ve  
P ositi ve  
P ositi ve  
E  
Ne gati ve  
P ositi ve  
Ne gati ve  

I nc yte C or p orati o n 
P a ge 6 5  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
T he f oll o wi n g a p plies t o  partici pa nts i n Sce nari os C, D, a n d E:  
•  If t he H B V D N A test is ne gati ve, t he partici pa nt is eli gi ble a n d m a y be ra n d o mize d. 
− F or partici pa nts w h o test H B V D N A ne gati ve a n d are ra n d o mize d i n t he st u d y,  a n 
H B V D N A P C R test s h o ul d be re peate d a p pr o xi matel y e ver y 1 2  wee ks (as 
o utli ne d i n Ta ble  3 ). N ot e: H B V D N A P C R testi n g is n ot necessar y f or 
partici pa nts i n Sce nari o C wit h a d oc u me nte d hist or y of H B V vacci nati o n.  
•  If t he H B V D N A test is p ositi ve, t he partici pa nt is n ot eli gi ble a n d will be s cree n 
faile d. 
•  I n t he e ve nt t he H B V D N A test ca n n ot be perf or me d, t he partici pant is n ot e li gi ble 
a n d will be scree n faile d.  
8. 3. 5. 4. 2.  He p atitis C Vir us  
Bl o o d sa m ples f or H C V ser ol o g y will be o btai ne d at t he scree ni n g visit a n d teste d. A p ositi ve 
H C V  a nti b o d y will tri g ger a n H C V R N A t est (refle x test). A partici pa nt will n ot be eli gi ble a n d 
will be scree n faile d if test res ults i n dicate acti ve he pati tis C ( H C V R N A detecta ble i n a n y 
partici pa nt wit h a nti -H C V  a nti b o d y). Partici pa nts w h o test p ositi ve f or H C V b ut are s uccessf ull y 
treate d f or H C V i nfecti o n a n d ha ve t heir s cree ni n g visit at least 1 2 wee ks after t he last d ose of 
H C V t hera p y ma y b e eli gi ble if H C V R N A is u n detecta ble. 

I nc yte C or p orati o n 
P a ge 6 6  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
8. 6.  
U nsc he d ule d Visits  
U nsc he d ule d visits ma y occ ur as cli nicall y i n dicate d. A n y assess me nts perf or me d at t h ose visits 
s h o ul d be rec or de d i n t he e C R F a n d n ote d as a n u nsc he d ule d visit.  
8. 7.  
E n d of Tre at me nt a n d E arl y Ter mi n ati o n  
T he E O T 1 ( P C peri o d ) c oi nci des wit h t he Wee k 1 2  vi sit, a n d t he E O T 2 ( E X T peri o d) c oi n ci des 
wit h t he Wee k 3 6 visit . A partici pa nt w h o c o m pl etes t he Wee k 1 2/ E O T 1 visit will h a ve 
c o m plete d t he P C peri o d a n d ma y c o nti n ue i nt o t he E X T peri o d. A partici p a nt w h o c o m pletes 
t he Wee k 3 6/ E O T 2 visit will ha ve c o m plete d t he E X T peri o d. 
If a decisi o n is ma de t hat t he partici pa nt will per m a ne ntl y disc o nti n ue st u d y dr u g pri or t o t he 
Wee k 3 6 / E O T2  visit, t he n t he E T visit s h o ul d be c o n d ucte d  a n d will be det er mi ne d as E T 1 (if 
d uri n g t he P C peri o d) or E T 2 (if d uri n g t he E X T p eri o d) . If t h e E T visit c oi nci des wit h a re g ul ar 
st u d y visit, t he n t he E T e val uati o ns will s u perse de t h ose of t hat sc he d ule d visit, a n d t he data 
s h o ul d be e ntere d i n t he E T visit i n t he e C R F. If t his decisi o n d oes n ot c oi nci de wit h a re g ul ar 
visit, reas o na ble eff orts s h o ul d be ma de t o ha ve t h e partici pa nt ret ur n t o t he site t o c o m plete t he 
E T pr oce d ures . T he p arti ci pa n t s h o ul d be e nc o ura ge d t o r et ur n f or t he f oll o w-u p visit.  
8. 8.  
F oll o w -U p  
8. 8. 1.  
P ost -Tre at me nt  F oll o w -U p  
T he p ost -treat me nt f oll o w-u p peri o d is t he i nter val bet wee n t h e Wee k 3 6  visit a n d t he sc he d ule d 
f oll o w-u p visit, w hic h s h o ul d occ ur 6 0 ( ±  7) da ys after t he Wee k 3 6  visit ( or after t h e last d ose of 
st u d y dr u g if t he Wee k 3 6 visit was n ot perf or me d ). A d verse e ve nts a n d S A Es m ust be re p orte d 
u p u ntil 1)  at least 6 0  da ys after t he last d ose of st u d y dr u g or 2) u ntil t o xicities res ol ve, ret ur n t o 
baseli ne, or are dee me d irre versi ble, w hic he v er is l o n ger. R eas o na ble eff orts s h o ul d be ma de t o 
ha ve t he partici pa nt ret ur n f or t he p ost -treat me nt f oll o w-u p visit a n d re p ort a n y A Es t hat ma y 
occ ur d uri n g t his peri o d. If t he partici p a nt ca n n ot r et ur n t o t he site f or t he p ost -treatme nt  f oll o w-
u p visit, t he n t he partici pa nt s h o ul d be c o ntacte d b y tele p h o n e f or assess me nt of A Es a n d S A Es 
a n d sites s h o ul d pr o perl y d oc u me nt t his c o ntact i n t he s o urce.  

I nc yte C or p orati o n 
P a ge 6 7  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
9.  
A D V E R S E E V E N T S: D E FI NI TI O N S A N D P R O C E D U R E S F O R 
R E C O R DI N G, E V A L U A TI N G, F O L L O W -U P, A N D R E P O R TI N G  
9. 1.  
Defi niti o n of A d verse E ve nt  
A d verse E ve nt Defi niti o n  
•  A n A E is a n y u nt o war d me dical occ urre nce ass ociate d wit h t he use of a dr u g i n h u ma ns, w het her or 
n ot it is c o nsi dere d dr u g -relate d. 
•  A n A E ca n t heref ore be a n y u nfa v ora ble or u ni nte n de d si g n (i ncl u di n g a n a b n or mal la b orat or y 
fi n di n g), s y m pt o m, or disease ( ne w or e xacer bate d) te m p orall y ass ociate d wit h t he use of st u d y dr u g. 
A d diti o n al G ui d a nce f or E ve nts Meeti n g t he A d verse E ve nt Defi niti o n  
•  A n y safet y assess me nts (e g, E C G, vital si g ns meas ur e me nts), i ncl u di n g t h ose t hat w orse n fr o m 
baseli ne, c o nsi dere d cli nicall y si g nifica nt i n t he me dical a n d scie ntific j u d g me nt of t he i n vesti gat or 
(ie, n ot relate d t o disease pr o gressi o n ) are t o be re p orte d as a n A E. 
•  A b n or mal la b orat or y test res ults are t o b e re p orte d as a n A E if t he y are c o nsi dere d cli nicall y 
mea ni n gf ul, i n d uce cli nical si g ns or s y m pt o ms, re q uire c o nc o mita nt t hera p y, or re q uire c ha n ges i n 
st u d y dr u g. W he ne ver p ossi ble, a dia g n osis (e g, a ne mia, t hr o m b oc yt o pe nia) s h o ul d be rec or de d i n 
t he e C R F rat her t ha n t he a b n or mal la b orat or y test res ult (e g, l o w he m o gl o bi n, platelet c o u nt 
decrease d).  
•  E xacer bati o n of a c hr o nic or i nter mitte nt pre -e xisti n g c o n diti o n/ disease, i ncl u di n g eit her a n i ncrease 
i n t he fre q ue nc y a n d/ or i nte nsit y of t he c o n diti o n, is to be re p orte d as a n A E.  
•  Ne w c o n diti o ns detecte d or dia g n ose d after t he start of st u d y dr u g a d mi nistrati o n are t o be re p orte d 
as a n A E. 
•  Ne w si g ns a n d/ or s y m pt o ms d ue t o t he st u d y disease t hat de vel o p after t he first d ose of st u d y dr u g 
are t o be re p orte d as a n A E. 
•  Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d dr u g -dr u g i nteracti o n are t o be re p orte d as 
a n A E. 
•  Si g ns a n d/ or s y m pt o ms fr o m d ose a d mi nistrati o n err ors of a st u d y dr u g (e g, o ver d ose) or a 
c o nc o mita nt me dicati o n are t o be re p orte d as a n A E.  
•  "Lac k of efficac y, " "disease pr o gressi o n ," or "fail ure of e x pecte d p har mac ol o gical acti o n" will n ot be 
re p orte d as a n A E or S A E. S uc h i nsta nces will be ca pt ure d i n t he efficac y assess me nts. H o we ver, t he 
si g ns, s y m pt o ms, a n d/ or cli nical se q uelae res ulti n g fr o m lac k of efficac y will be re p orte d as A E or 
S A E if t he y f ulfil t he defi niti o n of a n A E or S A E . If j u d ge d b y t he i n vesti gat or m ore se vere t ha n 
e x pecte d f or t he partici pa nt 's c o n diti o n, a n y cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n gs or 
ot her a b n or mal safet y assess me nts t hat are ass ociate d wit h t he u n derl yi n g disease ca n be re p orte d as 
a n A E or S A E. A n d if j u d ge d b y t he i n vesti gat or m ore se vere t ha n e x pecte d f or t he partici pa nt 's 
c o n diti o n, t he disease/ dis or der bei n g st u die d or its e x pecte d pr o gre ssi o n, si g ns, or s y m pt o ms ca n be 
re p orte d as a n A E or S A E . 
•  A c o n diti o n t hat lea ds t o a me dical or s ur gical pr oce d ure (e g, e n d osc o p y, a p pe n dect o m y) will be 
re p orte d as a n A E if it occ urs after o btai ni n g i nf or me d c o nse nt. If t he c o n diti o n is prese nt bef ore 
enteri n g t he st u d y, t he n it s h o ul d be ca pt ure d as me dical hist or y.  
•  Pre -e xisti n g diseases , pre-e xisti n g c o n diti o ns, or ne w  c o n diti o ns wit h e x pecte d fl uct uati o ns i n si g ns 
or s y m pt o ms s h o ul d be re p orte d as a n A E o nl y if t he i n vesti gat or j u d ges t he fl uct uati o n t o ha ve 
w orse ne d m ore t ha n e x pecte d d uri n g st u d y partici pati o n.  

I nc yte C or p orati o n 
P a ge 6 8  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
9. 2.  
Defi niti o n of Seri o us A d verse E ve nt  
If a n e v e nt is n ot a n A E per t he defi niti o n a b o ve, t he n it ca n n ot be a n S A E e ve n if seri o us 
c o n diti o ns are met (e g, h os pitaliz ati o n  or  deat h d ue t o disease  pr o gressi o n ). 
A seri o us a d verse e ve nt is defi ne d as a n y u nt o w ar d me dic al occ urre nce t h at, at a n y d ose:  
a.  Res ults i n de at h  
b.  Is life-t hre ate ni n g 
T he ter m "life-t hreate ni n g" i n t he defi niti o n of "seri o us" refers t o a n a d verse dr u g e x perie nce t hat 
places t he partici pa nt, i n t he o pi ni o n of t he i nitial re p orter, at i m me diate ris k of deat h fr o m t he a d verse 
e x perie nce as it occ urs. T his d oes n ot i ncl u de a n a d verse dr u g e x perie nce t hat, ha d it occ urre d i n a 
m ore se vere f or m, mi g ht ha ve ca use d deat h . 
c. Re q uires i n p at ie nt h os pit aliz ati o n or pr ol o n g ati o n of e xisti n g h os pit aliz ati o n 
I n ge neral, h os pitalizati o n si g nifies t hat t he partici pa nt has bee n detai ne d (i n v ol vi n g at least a n 
o ver ni g ht sta y) at t he h os pital or e mer ge nc y de part me nt f or o bser vati o n a n d/ or treat me nt t h at w o ul d 
n ot ha ve bee n a p pr o priate i n t he p h ysicia n 's office or o ut patie nt setti n g. C o m plicati o ns t hat occ ur 
d uri n g h os pitalizati o n are A Es. If a c o m plicati o n pr ol o n gs h os pitalizati o n or f ulfills a n y ot her seri o us 
criteria, t he e ve nt is seri o us. W he n i n d o u bt as t o w het her h os pitalizati o n occ urre d or was necessar y, 
t he A E s h o ul d be c o nsi dere d seri o us. 
H os pitalizati o n f or electi ve treat me nt or pla n ne d s ur ger y (e g, ste nt re place me nt, hi p s ur ger y) is n ot 
c o nsi dere d a n S A E.  
H os pitalizati o n f or me dical i nter ve nti o ns i n w hic h n o u nfa v ora ble me dical occ urre nce occ urre d 
(ie, electi ve pr oce d ures or r o uti ne me dical visits) is n ot c o nsi dere d a n S A E.  
d.  Res ults i n persiste nt or si g nific a nt dis a bilit y/i nc a p acit y  
T he ter m "disa bilit y " mea ns a s u bsta ntial disr u pti o n  of a pers o n 's a bilit y t o c o n d uct n or mal life 
f u ncti o ns. T his defi niti o n is n ot i nte n de d t o i ncl u de e x perie nces of relati vel y mi n or me dical 
si g nifica nce, s uc h as u nc o m plicate d hea dac he, na usea, v o miti n g, diarr hea, i nfl ue nza, a n d acci de ntal 
tra u ma (e g, s prai ne d a n kle), t hat ma y i nterfere wit h or pre ve nt e ver y da y life f u ncti o ns b ut d o n ot 
c o nstit ute a s u bsta ntial disr u pti o n.  
e. Is a c o n ge nit al a n o m al y/ birt h defect 
f. Is a n i m p ort a nt me dic al e ve nt 
A n i m p orta nt me dical e ve nt is a n e ve nt t hat ma y n ot res ult i n deat h , be i m me diatel y life-t hreate ni n g, or 
re q uire h os pitalizati o n b ut ma y be c o nsi dere d seri o us w he n, base d o n a p pr o priate me dical j u d g me nt, 
t he e ve nt ma y j e o par dize t he partici pa nt a n d ma y re q uire me dical or s ur gical i nter ve nti o n t o pre ve nt 
o ne of t he o utc o me s liste d i n t he a b o ve defi niti o n. E xa m ples of s uc h e ve nts i ncl u de ne w i n vasi ve or 
mali g na nt ca ncers; i nte nsi ve treat me nt i n a n e mer ge nc y de part me nt or at h o me f or aller gic 
br o nc h os pas m, bl o o d d yscrasias, or c o n v ulsi o ns t hat d o n ot res ult i n h os pitalizati o n ; de vel o p me nt of 
dr u g de pe n de nc y or dr u g a b use; or s us pecte d tra ns missi o n of a n i nfecti o us a ge nt via a me dici nal 
pr o d uct. Sec o n dar y mali g na ncies s h o ul d al wa ys be c o nsi dere d S A Es . 

I nc yte C or p orati o n 
P a ge 6 9  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
9. 3.  
Rec or di n g a n d F oll o w -U p of A d verse E ve nts a n d/ or Seri o us A d verse 
E ve nts  
A d ve rse E ve nt a n d Seri o us A d verse E ve nt Rec or di n g  
•  A n A E/ S A E t hat be gi ns or w orse ns after i nf or me d c o nse nt is si g ne d s h o ul d be rec or de d o n t he 
A d verse E ve nts F or m i n t he e C R F. All A Es/ S A Es s h o ul d be re p orte d f or ra n d o mize d partici pa nts, 
b ut o nl y S A Es nee d t o be re p orte d f or scree n fail ure partici pa nts. F or ra n d o mize d partici pa nts, 
c o n diti o ns t hat were prese nt at t he ti me i nf or me d c o nse nt was gi ve n s h o ul d be rec or de d o n t he 
Me dical Hist or y F or m i n t he e C R F. F or detaile d i nf or mati o n, refer t o t he e C R F g ui deli nes . 
•  W he n a n A E/ S A E occ urs, it is t he res p o nsi bilit y of t he i n vesti gat or t o re vie w all d oc u me ntati o n 
(e g, h os pital pr o gress n otes, la b orat or y re p orts, a n d dia g n ostic re p orts) relate d t o t he e ve nt.  
•  T he i n vesti gat or ( or desi g nee) will t he n rec or d all rele va nt A E/ S A E i nf or mati o n i n t he e C R F.  
•  It is n ot  acce pta ble f or t he i n vesti gat or t o se n d p h ot oc o pies of t he partici pa nt 's me dical rec or ds 
i n lie u of c o m pleti n g t he A d verse E ve nts F or m i n t he e C R F. 
•  T here ma y be rare i nsta nces w he n c o pies of me dical rec or ds f or cert ai n cases are re q ueste d. I n t his 
case, all partici pa nt i de ntifiers, wit h t he e xce pti o n of t he partici pa nt n u m ber, will be re dacte d b y t he 
site staff o n t he c o pies of t he me dical rec or ds bef ore s u b missi o n . T hese rec or ds ca n be s u b mitte d t o 
I nc yte P har mac o vi gila nce b y e mail/fa x per t he c o ntact i nf or mati o n liste d i n t he St u d y Bi n der as per 
S A E c o m pleti n g g ui deli nes.  
•  T he i n vesti gat or will atte m pt t o esta blis h a dia g n osis of t he e ve nt base d o n si g ns, s y m pt o ms, a n d/ or 
ot her cli nical i nf or mati o n. W he ne ve r p ossi ble, t he dia g n osis ( n ot t he i n di vi d ual si g ns/s y m pt o ms) will 
be d oc u me nte d as t he A E/ S A E. W he n a clear dia g n osis ca n n ot be i de ntifie d, eac h si g n or s y m pt o m 
s h o ul d be re p orte d as a se parate A E/ S A E. 
T o t he e xte nt p ossi ble, eac h A E/ S A E s h o ul d be e val uat e d t o deter mi ne t he f oll o wi n g:  
•  T he se verit y gra de ( C T C A E v 5. 0 Gra de 1 t o 5). See bel o w f or f urt her i nstr ucti o ns o n t he assess me nt 
of i nte nsit y.  
•  W het her t here is at least a reas o na ble p ossi bilit y t hat t he A E is relate d t o t he st u d y dr u g: s us pecte d 
( yes) or n ot s us pecte d ( n o). See bel o w f or f urt her i nstr ucti o ns o n t he assess me nt of ca usalit y.  
•  T he start a n d e n d dates, u nless u nres ol ve d at t he fi nal p ost -treat me nt f oll o w-u p visit.  
•  T he acti o n t a ke n wit h re gar d t o st u d y dr u g as a res ult of t he A E/ S A E(s).  
•  T he e ve n t o utc o me (e g, n ot rec o vere d/ n ot res ol ve d, rec o vere d/res ol ve d, rec o veri n g/res ol vi n g, 
rec o vere d/res ol ve d wit h se q uelae, fatal, u n k n o w n). 
•  T he seri o us ness, as per t he S A E defi niti o n pr o vi de d i n Secti o n  9. 2 . 
•  T he acti o n ta ke n wit h re gar d t o t he e ve nt. N ote: If a n A E is treate d wit h a c o nc o mita nt me dicati o n or 
n o n dr u g t hera p y, t his acti o n s h o ul d be rec or de d o n t he A d verse E ve nts F or m a n d t he treat me nt 
s h o ul d be s pecifie d o n t he a p pr o priate e C R F (e g, Pri or/ C o nc o mita nt Me dicati o ns, Pr oce d ures a n d 
N o n -Dr u g T hera p y).  

I nc yte C or p orati o n 
P a ge 7 0  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
Assess me nt of I nte nsit y  
T he se verit y of A Es will be assesse d usi n g C T C A E v 5. 0 Gra des 1 t hr o u g h 5. If a n e ve nt is n ot 
classifie d b y C T C A E, t he se verit y of t he A E will be gra de d acc or di n g t o t he scale bel o w t o esti mate 
t he gra de of se verit y. 
T he i n vesti gat or will ma ke a n assess me nt of i nte nsit y f or eac h A E a n d S A E re p orte d d uri n g t he st u d y 
a n d assi g n it t o 1 of t he f oll o wi n g cate g ories:  
•  Gr a de 1: M il 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; treat me nt 
n ot i n dicate d.  
•  Gr a de 2: M o derate; mi ni mal, l ocal, or n o ni n vasi ve treat me nt i n dicate d; li miti n g a ge -a p pr o priate 
acti vities of dail y li vi n g.  
•  Gr a de 3: 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 acti vities of dail y li vi n g.  
•  Gr a de 4: Life -t hreate ni n g c o nse q ue nces; ur ge nt treat me nt i n dicate d. 
•  Gr a de 5: Fatal.  
A ssess me nt of C a us alit y 
•  T he i n vesti gat or is o bli gate d t o assess t he relati o ns hi p bet wee n st u d y dr u g a n d eac h occ urre nce of 
eac h A E/ S A E.  
•  A "reas o na ble p ossi bilit y" of a relati o ns hi p c o n ve ys t hat t here are me dical facts, e vi de nce, a n d/ or 
ar g u me nts t o s u g gest a ca usal relati o ns hi p, rat her t ha n t hat a relati o ns hi p ca n n ot be r ule d o ut.  
•  T he i n vesti gat or will use cli nical j u d g me nt t o deter mi ne t he p ossi bilit y of a relati o ns hi p.  
•  T he i n vesti gat or will als o c o ns ult t he R SI i n t he I B i n ma ki n g t heir assess me nt.  
•  Alter nati ve ca uses, s uc h as u n derl yi n g or c o nc urre nt disease(s), c o nc o mita nt t hera p y, a n d ot her ris k 
fact ors, as well as t he te m p oral relati o ns hi p of t he e ve nt t o st u d y dr u g a d mi nistrati o n, will be 
c o nsi dere d a n d i n vesti gate d.  
•  F or eac h A E/ S A E, t he i n vesti gat or m ust  d oc u me nt i n t he me dical n otes t hat t he y ha ve re vie we d t he 
A E/ S A E a n d ha ve pr o vi de d a n assess me nt of ca usalit y.  
•  Wit h re gar d t o assessi n g ca usalit y of S A Es:  
− T he re ma y be sit uati o ns i n w hic h a n S A E has occ urre d a n d t he i n vesti gat or has mi ni mal 
i nf or mati o n t o i ncl u de i n t he i nitial re p ort. H o we ver, t he ca usalit y assess me nt is o ne of t he criteria 
use d w he n deter mi ni n g re g ulat or y re p orti n g re q uire me nts. T heref ore, it  is ver y i m p ort a nt t h at 
t he i n vesti g at or al w a ys m a ke a n assess me nt of c a us alit y b ase d o n t he a v ail a ble i nf or m ati o n 
f or e ver y e ve nt bef ore t he i niti al tr a ns missi o n of t he S A E. 
− T he i n vesti gat or ma y c ha n ge t heir o pi ni o n of ca usalit y i n li g ht of f oll o w -u p i nf o r mati o n a n d 
s u b mit t he u p date d ca usalit y assess me nt. 

I nc yte C or p orati o n 
P a ge 7 1  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
F oll o w -U p 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 is o bli gate d t o perf or m or arra n ge f or t he c o n d uct of s u p ple me ntal meas ure me nts 
a n d/ or e val uati o ns as me dicall y i n dicate d or as re q ueste d b y t he s p o ns or t o el uci date t he nat ure 
a n d/ or ca usalit y of t he A E or S A E as f ull y as p ossi ble. T his ma y i ncl u de a d diti o nal la b orat or y tests 
or i n vesti gati o ns, hist o pat h ol o gical e xa mi nati o ns, or c o ns ultati o n wit h ot her healt h care 
pr ofessi o nals.  
•  O nce a n A E is detecte d, it s h o ul d be f oll o we d i n t he A d verse E ve nts F or m i n t he e C R F u ntil it has 
res ol ve d or u ntil it is j u d ge d t o be per ma ne nt; assess me nt s h o ul d be ma de at eac h visit ( or m ore 
fre q ue ntl y if necessar y) of a n y c ha n ges i n se verit y, t he s us pecte d relati o ns hi p t o t he st u d y dr u g, t he 
i nter ve nti o ns re q uire d t o treat t he e ve nt, a n d t he o utc o me. 
•  W he n t he se verit y of a n A E c ha n ges o ver ti me f or a re p orti n g peri o d (e g, bet wee n visits), eac h 
c ha n ge i n se verit y will be re p orte d as a se parate A E.  
•  If a partici pa nt dies d uri n g partici pati o n i n t he st u d y or d uri n g a rec o g nize d f oll o w -u p peri o d, t he 
i n vesti gat or will pr o vi de t he s p o ns or wit h a c o p y of a n y p ost m orte m fi n di n gs, i ncl u di n g 
hist o pat h ol o g y.  
•  U p date d S A E i nf or mati o n will be rec or de d i n t he ori gi nall y c o m plete d e C R F a n d re p orte d t o I nc yte 
P har mac o vi gila nce (i n t he S A E E D C C R F) u ntil res ol uti o n, sta bilizati o n, t he e ve nt is ot her wise 
e x plai ne d, or t he partici pa nt is l ost t o f oll o w -u p.  
•  A n y u p date d S A E data (i ncl u di n g S A Es bei n g d o w n gra de d t o n o nseri o us) will be s u b mitte d t o t he 
s p o ns or ( or desi g nee) wit hi n 2 4 h o urs of recei pt of t he i nf or mati o n.  
9. 4.  
Re p orti n g of Seri o us A d verse E ve nts  
Re gar dless of s us pecte d ca usalit y (e g, relati o ns hi p t o st u d y dr u g or st u d y pr oce d ure[s]), all S A Es 
occ urri n g after t h e partic i pa nt has si g n e d t he I C F t hr o u g h at least 6 0 da ys after t he last d ose of 
st u d y dr u g m ust be re p orte d t o t he s p o ns or ( or desi g nee) i m me diatel y, wit h o ut u n d ue dela y b ut 
n ot later t ha n wit hi n 2 4 h o urs  of o btai ni n g k n o wle d ge of its occ urre nce u nl ess ot her wise 
s pecifie d b y t he Pr ot oc ol. T he i n vesti gat or will s u b mit a n y u p date d S A E d ata t o t he s p o ns or ( or 
desi g nee) i m me diatel y, wit h o ut u n d ue dela y b ut n ot later t ha n wit hi n 2 4 h o urs of it bei n g 
a vaila ble.  
I n v esti gat ors are n ot o bli gat e d t o acti vel y see k S A E i nf or mati o n after t h e p ost -treat me nt 
f oll o w-u p visit or m ore t ha n 6 0 da ys aft er t he last d ose of st u d y dr u g. If t he i n vesti gat or lear ns of 
a n y S A E, i n cl u di n g deat h, at a n y ti me d uri n g t his peri o d , a n d t he y c o nsi d er t he e ve nt t o be 
reas o na bl y relate d t o t he st u d y dr u g or st u d y partici pati o n, t he n t he i n vesti gat or m ust n otif y t he 
s p o ns or ( or desi g nee) wit hi n 2 4 h o urs of bec o mi n g a ware of t he e ve nt.  
After t he i nitial A E/ S A E re p ort, t he i n vesti gat or is  re q uire d t o pr o acti vel y f oll o w eac h partici pa nt 
at s u bse q ue nt visits/c o ntacts. All S A Es  a n d A E SIs (as defi ne d i n Secti o n  9. 6. 1 ) will be f oll o we d 
u nti l res ol uti o n, sta bilizati o n, t he e ve nt is ot her wis e e x plai ne d, or t he partici pa nt is l ost t o 
f oll o w-u p (as defi ne d i n Secti o n  7. 3 ). 
Pr o m pt n otificati o n b y t he i n vesti gat or t o t he s p o ns or re gar di n g a n S A E is esse ntial s o t hat le gal 
o bli gati o ns a n d et hical res p o nsi bilities f or t he safet y of partici pa nts a n d t he safet y of a st u d y dr u g 
u n der cli nical i n vesti gati o n are met.  
If t he S A E is n ot d oc u me nte d i n t he R SI of t he I B f or t he st u d y dr u g ( ne w occ urre nce) a n d is 
t h o u g ht t o be rel ate d t o t he st u d y dr u g, t h e s p o ns or or its desi g n ee ma y ur ge ntl y re q uire f urt her 

I nc yte C or p orati o n 
P a ge 7 2  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
i nf or mati o n fr o m t he i n v esti gat or f or e x pe dite d re p orti n g t o healt h a ut h orities. T he s p o ns or or its 
desi g nee ma y nee d t o iss ue a n I n vesti gat or N otificati o n t o i nf or m all i n vesti gat ors i n v ol ve d i n 
a n y st u d y wit h t he sa m e dr u g t hat t his S A E has bee n re p ort e d. S us pecte d u ne x pecte d seri o us 
a d verse reacti o ns will be c ollecte d a n d re p ort e d t o t he c o m pete nt a ut h orities a n d rele va nt et hics 
c o m mittees i n acc or da nce wit h Directi ve 2 0 0 1/ 2 0/ E C or as per nati o nal r e g ulat or y re q uire m e nts 
i n partici pati n g c o u ntries. 
T he s p o ns or has a l e gal r es p o nsi bilit y t o n otif y b ot h t he l ocal re g ulat or y a ut h ori t y a n d ot her 
re g ulat or y a ge ncies a b o ut t he safet y of a st u d y dr u g u n der cli nical i n vesti gati o n. T he s p o ns or 
will c o m pl y wit h c o u ntr y -s pecific re g ulat or y re q uire me nts relati n g t o safet y re p orti n g t o t he 
re g ulat or y a ut h orit y, I R B/I E C, a n d i n vesti gat ors. 
I n v esti gat or safet y re p orts m ust be pre pare d f or s us pecte d u ne x pecte d s eri o us a d verse reacti o ns 
acc or di n g t o l ocal re g ulat or y re q uire m e nts a n d s p o ns or p olic y a n d f or war de d t o i n vesti gat ors as 
necessar y.  
A n i n vesti gat or w h o recei ves a n i n vesti gat or safet y re p or t descri bi n g a n S A E or ot her s pecific 
safet y i nf or mati o n ( e g, s u m mar y or listi n g of S A Es) fr o m t he s p o ns or will re vie w a n d t h e n file it 
al o n g wit h t he I B a n d will n otif y t he I R B/I E C, if a p pr o priate, acc or di n g t o l ocal re q uir e me nts.  
Seri o us A d verse E ve nt Re p orti n g  
•  I nf or mati o n a b o ut all S A Es is c ollecte d a n d rec or de d o n t he A d verse E ve nts F or m i n t he e C R F. 
•  T he i n vesti gat or m ust re p ort wit hi n 2 4 h o urs of lear ni n g of its occ urre nce a n y S A E via t he E D C 
s yste m ( pri mar y met h o d) or b y c o m pleti n g t he Seri o us A d verse E ve nt Re p ort F or m i n E n glis h ( o nl y 
if t he E D C s yste m is n ot a vaila ble). T he c o ntact i nf or mati o n f or I nc yte P har mac o vi gila nce b y 
e mail/fa x is liste d i n t he I nc yte Refere nce G ui de f or C o m pleti n g t he Seri o us A d verse E ve nt Re p ort 
F or m.  
•  I n circ u msta nces w here t he E D C s yste m is n ot accessi ble f or re p orti n g S A E i nf or mati o n (i nitial 
a n d/ or f oll o w-u p 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, refer t o t he I nc yte Refere nce 
G ui de f or C o m pleti n g t he Seri o us A d verse E ve nt Re p ort F or m. O nce t he E D C s yste m i s f u ncti o nal, 
t he S A E re p ort s h o ul d be retr os pecti vel y a d de d t o t he E D C s yste m a n d f oll o w-u p s h o ul d be 
c o m plete d t hr o u g h t he E D C. T he ori gi nal c o p y of t he Seri o us A d verse E ve nt Re p ort F or m a n d t he 
e mail or facsi mile c o nfir mati o n s heet m ust be ke pt at t he s t u d y site (refer t o t he I nc yte Refere nce 
G ui de f or C o m pleti n g t he Seri o us A d verse E ve nt Re p ort F or m f or details a n d f or t he e mail a d dress 
or fa x n u m ber).  
•  F oll o w -u p i nf or mati o n is als o rec or de d i n t he e C R F a n d tra ns mitte d t o I nc yte P har mac o vi gila nce via 
t he E D C s yste m. T he f oll o w -u p re p ort s h o ul d i ncl u de i nf or mati o n t hat was n ot pr o vi de d pre vi o usl y, 
s uc h as t he o utc o me of t he e ve nt, treat me nt pr o vi de d, acti o n ta ke n wit h st u d y dr u g beca use of t he 
S A E (e g, d ose re d uce d, i nterr u pte d, or disc o nti n ue d), or partic i pa nt dis p ositi o n (e g, c o nti n ue d or 
wit h dre w fr o m st u d y partici pati o n). Eac h rec urre nce, c o m plicati o n, or pr o gressi o n of t he ori gi nal 
e ve nt s h o ul d be re p orte d as f oll o w -u p t o t hat e ve nt, re gar dless of w he n it occ urs.  
9. 5.  
P ote nti al Dr u g -I n d uce d Li ver I nj ur y 
Se e A p pe n di x  D  f or details o n ma na ge me nt of p ot e ntial H y's la w cas es/ DI LI. 
F oll o w t he S A E a n d f oll o w -u p re p orti n g re q uire me nts per Secti o n  9. 2  as p ote ntial DI LI A E s 
ma y b e p ote ntial S A E s cl assifie d i n t he cate g or y of i m p orta nt me dical e ve nt.  

I nc yte C or p orati o n 
P a ge 7 3  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
9. 6.  
E ve nts of Cli nic al I nterest  
A n E CI is a n A E (se ri o us or n o nseri o us) t hat I n c yt e wis hes t o d oc u me nt i n a n or ga nize d ma n ner 
f or m o nit ori n g or u n d erst a n di n g. T h e E CIs will be ca pt ure d i n s pecific e C R Fs.  
A n E CI d o es n ot re q uir e ra pi d c o m m u nicati o n b y a n i n vesti gat or t o I nc yte u nless it meets criteria 
f or ra pi d c o m m u nicati o n as a n S A E (see Secti o n  9. 2 ). 
T hese E CIs i ncl u de la b orat or y a b n or malities a n d cli nical A Es as f oll o ws:  
•  I n crease d ser u m creati ni ne ( > 3 × U L N or > 3 × b aseli ne) a n d re nal d ysf u ncti o n  
•  He patic e v e nts a n d i ncrease d he patic tra nsa mi nas es ( > 5 × U L N)  
•  I n crease d C P K ( > 5 × U L N) 
•  Ac ne  
9. 6. 1.  
A d verse E ve nts of S peci al I nterest  
I n c yt e defi nes A E SIs as a s u bset of E CIs t hat a n i n vesti gat or m ust ra pi dl y c om m u nicate t o I nc yte 
f or f urt her e val u ati o n. 
If a n A E SI me ets t he S A E defi niti o n (see Secti o n  9. 2 ), it m ust be re p orte d f oll o wi n g t he 
re q uire me nts f or an S A E i n dicate d i n Secti o n  9. 4 . 
T he A E SIs are as f oll o ws:  
•  Seri o us i nfecti o ns  
− Defi ne d as a n y i nfecti o n meeti n g S A E criteria (see Secti o n  9. 2 ) 
•  O p p ort u nistic i nfecti o ns  
•  Her pes z oster  
•  T B  
•  Mali g na n c y (all t y pes)  
•  M A C E, defi ne d as  a n y of t he f oll o wi n g: 
− N o nfatal MI  
− N o nfatal str o ke of a n y cl ass ificati o n, i ncl u di n g re versi ble f ocal ne ur ol o gic defects 
wit h i m a gi n g e vi de n ce of  a ne w cere bral lesi o n c o nsiste nt wit h isc he m ia or 
he m orr ha ge  
− Car di o vasc ular d eat h defi ne d as a n y of t he f oll o wi n g:  
•  Deat h d ue t o ac ute MI  
•  S u d de n car diac deat h  
•  Deat h d ue t o heart fail ure  
•  Deat h d ue t o str o ke  
•  Deat h d ue t o car di o vas c ular pr oce d ures  
•  Deat h d ue t o car di o vas c ular he m orr h a ge  
•  Deat h d ue t o ot her car di o vasc ular  ca us es: peri p h eral arter y disease  
•  Ot her e m b olic a n d t hr o m b otic e ve nts (e g, p ul m o n ar y e m b olis m, dee p vei n 
t hr o m b osis, ot her t hr o m b osis) 

I nc yte C or p orati o n 
P a ge 7 4  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
9. 7.  
E mer ge nc y U n bli n di n g o f Tre at me nt Assi g n me nt 
I n case of a me dical e mer ge nc y, f or a partici pa nt's safet y ma na ge me nt, t he pr oce d ure f or 
e mer ge n c y u n bli n di n g is pr o vi de d t o t he i n vesti gat or i n t he I R T M a n ual. T h e i n vesti gat or has t he 
pri mar y ri g ht t o brea k t h e bli n d t o treat a par tici pa nt i n e mer ge n c y circ u msta nces. 
If a partici pa nt's treat me nt assi g n me nt is u n bli n de d, t he s p o ns or or its desi g n ee s h o ul d be n otifie d 
i m me diatel y b y I R T f or a ware n ess. 
If a n i n vesti gat or, t he site pers o n nel perf or mi n g assess me nts, or a partici p a nt is un bli n de d, t he n 
t he partici pa nt m ust disc o nti n ue st u d y dr u g u nless t here are et hical reas o ns t o ha ve t he 
partici pa nt re mai n o n t he st u d y treat me nt. I n t hese cases, t he i n vesti gat or m ust o btai n s pecific 
a p pr o val fr o m t he s p o ns or 's ( or its desi g n ee's) m e dical m o nit or f or t he partici pa nt t o c o nti n ue i n 
t he st u d y. 
9. 8.  
Pre g n a nc y  
Pre g n a nc y, i n a n d of itself, is n ot re gar de d as a n A E u nless t here is s us pici o n t hat t he st u d y dr u g 
ma y h a ve i nterfere d wit h t he effecti ve ness of a c o ntrace pti ve me di cati o n or met h o d. W he n a 
pre g na nc y h as bee n c o nfir me d i n a partici p a nt d uri n g mater nal or p ater nal e x p os ure t o st u d y 
dr u g, t he f oll o wi n g pr oce d ures s h o ul d be f oll o we d i n or der t o e ns ure safet y:  
•  T he st u d y tr eat me nt m ust be disc o nti n ue d i m me diatel y (fe m ale partici p a nts o nl y). 
•  T he i n vesti gat or m ust c o m plete a n d s u b mit t he I n c yt e Cli nical Trial Pre g n a nc y F or m 
t o t he s p o ns or or its desi g nee wit hi n 2 4 h o urs  of lear ni n g of t he pre g na n c y.  
Data o n fet al o utc o me are c ollecte d f or re g ulat or y re p orti n g a n d dr u g s afet y e v al uati o ns. 
F oll o w -u p s h o ul d be c o n d ucte d f or eac h pre g na n c y t o deter mi ne o utc o me, i ncl u di n g s p o nta ne o us 
or v ol u ntar y ter mi nati o n, details of t he birt h, a n d t he prese n ce or a bse n ce of a n y birt h defects, 
c o n ge nital a b n or malities, or mater nal a n d/ or ne w b or n c o m plicati o ns, b y f oll o w i n g u ntil t he first 
well -ba b y visit. Pre g n a nc y s h o ul d be rec or de d o n a Cli nical Trial Pre g na nc y F or m a n d re p orte d 
b y t he i n vesti gat or t o t he s p o ns or or its desi g nee. Pre g na nc y f oll o w -u p i nf or mati o n s h o ul d be 
rec or de d o n t he sa me f or m a n d s h o ul d i ncl u de a n assess me nt of t he p ossi ble ca usal relati o ns hi p 
t o t he s p o ns or's st u d y dr u g t o a n y pre g na n c y o utc o me, as well as f oll o w-u p t o t he first well -ba b y 
visit or t he d urati o n s pecifie d i n l ocal re g ul ati o ns, w hic he ver is lat er. Refer t o t he I n c yt e 
Refere n ce G ui d e f or C o m pleti n g t he Cli nical Tri al Pre g n a nc y F or m.  
A n y S A E occ urri n g d uri n g t he pre g n a nc y of a st u d y p artici p a nt m ust be rec or de d a n d 
re p orte d as descri be d i n Secti o n  9. 4 . 
A b n or mal pre g n a nc y o ut c o mes (e g, s p o nta n e o us a b orti o n, fetal deat h, still birt h, c o n ge nital 
a n o malies, or ect o pic pre g na n c y) are c o nsi dere d S A Es (if occ urri n g i n t he st u d y partici p a nt) a n d 
m us t be re p orte d as d escri be d i n Secti o n 9. 4 . If a n a b n or mal pre g n a nc y o utc o me is re p orte d i n a 
st u d y partici p a nt's p art ner, t he e ve nt s h o ul d be re p orte d t o t he s p o ns or o n t he Cli nical Trial 
Pre g n a nc y F or m.  

I nc yte C or p orati o n 
P a ge 7 5  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
9. 9.  
W ar ni n gs a n d Prec a uti o ns  
S pecial war ni n gs or preca uti o ns f or t he st u d y dr u g, deri ve d fr o m s afet y i nf or mati o n c ollecte d b y 
t he s p o ns or or its desi g n ee, are prese nt e d i n t he I B. A d diti o nal safet y i nf or mati o n c ollecte d 
bet wee n I B u p d ates will be c o m m u nicate d i n t he f or m of I n vesti gat or N otificati o ns. A n y 
i m p orta nt ne w safet y i nf or mati o n s h o ul d be disc usse d wit h t he partici pa nt d uri n g t he st u d y as 
necessar y. If ne w si g nifica nt ris ks are  i de ntifie d, t h e y will be a d de d t o t he I C F. 
9. 1 0.  
Pr o d uct C o m pl ai nts  
T he s p o ns or c ollects pr o d uct c o m plai nts o n st u d y dr u gs a n d dr u g deli ver y s yste ms use d i n 
cli nical st u dies i n or der t o e ns ure t he s afet y of st u d y partici pa nts, m o nit or q ualit y, a n d facilitate 
pr ocess a n d pr o d uct i m pr o ve me nts.  
All pr o d uct c o m plai nts ass ociate d wit h material p ac ka ge d, la bele d, a n d rel ease d b y t he s p o ns or 
or its desi g nee will be re p orte d t o t he s p o ns or. All pr o d uct c o m plai nts ass o ciate d wit h ot her 
st u d y materi al will be re p orte d directl y t o t he res pecti ve ma n ufact urer.  
T he i n vesti gat or or t heir desi g nee is res p o nsi ble f or re p orti n g a c o m plete descri pti o n of t he 
pr o d uct c o m plai nt via e mail or ot her writte n c o m m u nicati o n t o t he s p o ns or c o ntact or res pecti ve 
ma n ufact ur er as n ot e d i n t he  pac ka gi n g i nf or mati o n. A n y A E ass ociat e d wit h a pr o d uct 
c o m plai nt s h o ul d be rec or de d as des cri be d i n Secti o n  9. 3 . 
If t he i n vesti gat or is as ke d t o ret ur n t he pr o d uct f or i n vesti gati o n, t he y will ret ur n a c o p y of t he 
pr o d uct c o m plai nt c o m m u nicati o n wit h t he pr o d uct.  
9. 1 1.  
Tre at me nt of O ver d ose  
T here h as bee n n o cli nical e x perie nce wit h o ver d ose of p o v orciti ni b . Treat me nt of o ver d ose 
s h o ul d c o nsist of ge n eral s u p p orti ve meas ures. 

I nc yte C or p orati o n 
P a ge 7 6  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
1 0.  
S T A TI S TI C S  
1 0. 1.  
S a m ple Size Deter mi n ati o n  
A p pr o xi matel y 1 3 6 p arti ci pa nts will be ra n d o ml y assi g ne d t o 4 tr eat me nt gr o u ps (place b o  or 
p o v orciti ni b  1 5, 4 5, or 7 5 m g) i n a 1: 1: 1: 1 rati o.  
T he sa m ple siz e is base d o n t he pri mar y efficac y e n d p o i nt, t he c ha n ge i n w ee kl y U A S 7 sc ore 
fr o m baseli ne at W ee k 1 2. Base d o n a P hase 2 b st u d y ( M a urer et al 2 0 2 2 ), t he mea n c h a n ge i n 
U A S 7 sc ore at W ee k 1 2 is ass u me d t o be −8 i n t he place b o gr o u p a n d −1 7 i n t he p o v orciti ni b 
7 5 -m g gr o u p , wit h a c o m m o n S T D  of 1 3. A sa m ple siz e of 3 4 partici pa nts per gr o u p is s uffici e nt 
t o test f or t he prese n ce of a d ose-res p o nse relati o ns hi p, base d o n t he M C P -m o d  a p pr oac h (Bretz 
et al 2 0 0 5 , Pi n heir o et al 2 0 1 3 ). 
T his sa m ple siz e pr o vi des a mi ni m u m p o wer of 0. 8 5 t o detect a d ose effect at a 1 -si de d 2. 5 % 
si g nifica n ce le v el wit h t he li near, l o g-li near, E ma x , a n d q ua dratic m o d els pres pecifie d as 
ca n di dates t o c h aracteriz e t he u n derl yi n g d ose -res p o nse c ur ve f or p o v orciti ni b  o n t he mea n 
c ha n ge i n w ee kl y U A S 7 sc ore at W ee k 1 2. T h e set of ca n di date d os e -res p o nse m o dels a n d t heir 
c orres p o n di n g d ose -res p o nse c ur ves are s h o w n i n Ta ble  1 2  a n d Fi g ure  2 , res pecti vel y. 
T a ble  1 2 : 
Pre specifie d C a n di d ate M o dels  
M o del  
f( d, θ)a 
f 0( d, θ)b 
I niti al V al ue (s) f or 
P ar a meter (s) 
Li near  
E 0 + δ d  
d  
N ot a p plica ble  
Li near l o g -d ose  
E 0 + δl o g ( d  + 1)  
l o g (d  + 1)  
N ot a p plica ble  
E m ax 1  
𝐸0 +
𝐸𝑚𝑎𝑥𝑑
𝐸𝐷5 0 + 𝑑 
𝑑
𝐸𝐷5 0 + 𝑑 
E D 5 0 = 2 0  
E m ax 2  
E D 5 0 = 3 0  
Si g m oi d -E m ax  
𝐸0 +
𝐸𝑚𝑎𝑥𝑑ℎ
𝐸𝐷5 0
ℎ+ 𝑑ℎ 
𝑑ℎ
𝐸𝐷5 0
ℎ+ 𝑑ℎ 
E D 5 0 = 3 0, h  = 2  
Q ua dratic  
𝐸0 + 𝛽1 𝑑+ 𝛽2 𝑑2  
𝑑+
𝛽2
|𝛽1 | 𝑑2  
𝛿=
𝛽2
|𝛽1 | = −0 .0 0 8 3  
a d  is d ose (d  = 0 f or place b o gr o u p), θ  refers t o t he vect or of m o del para meters, E 0 is t he pl ace b o effect f or all 
ca n di date m o dels ( 0. 1), E m ax  is t he ma xi m u m treat me nt effect o ver place b o, E D 5 0 is t he d ose t hat gi ves 5 0 % of t he 
ma xi m u m effect f or E m ax  m o del.  
b  Sta n dar dize d m o del.  

I nc yte C or p orati o n 
Pa ge 7 7 of 1 0 2 
Pr ot oc ol I N C B 5 4 7 0 7- 2 0 7 
Versi o n 1 
0 7 M A R 2 0 2 3 
V V- C LI N- 0 2 2 4 5 3 
C O N FI D E N TI A L 
Fi g ure 2:  
Pres pecifie d D ose- Res p o nse C ur ves 
 
F or a refere nce of differe nt ass u m pti o ns of S T D of t he c ha n ge i n U A S 7 sc ore fr o m baseli ne at 
Wee k 1 2, t he sa m ple sizes a n d t he c orres p o n di n g mi ni m u m p o wer t o de tect a si g nifica nt 
d ose-res p o nse si g nal at a 1-si de d 2. 5 % si g nifica n ce le vel are pr o vi de d i n Ta ble 1 3 . 
T a ble 1 3:  
S a m ples Sizes a n d Mi ni m u m P o wer Acr oss t he 6 Pres pecifie d C a n di d ate 
M o dels U n der Differe nt Ass u m p ti o ns of St a n d ar d De vi ati o n 
St a n d ar d De vi ati o n  
S a m ple Size ( Pl ace b o: 1 5 m g: 4 5 m g: 7 5 m g)  
Mi ni m u m P o wer 
1 1 
1 0 0 ( 2 5: 2 5: 2 5: 2 5) 
0. 8 5 
1 2 
1 1 6 ( 2 9: 2 9: 2 9: 2 9) 
0. 8 4 
1 3 
1 3 6 ( 3 4: 3 4: 3 4: 3 4) 
0. 8 5 
1 0. 2.  
P o p ul ati o ns f or A n al ysis 
T he p o p ulati o ns f or a nal ysis are pr o vi de d i n  Ta ble 1 4. 

I nc yte C or p orati o n 
P a ge 7 8  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
T a ble  1 4 : 
P o p ul ati o ns f or A n al ysis  
P o p ul ati o n  
Descri pti o n  
F A S  
T he F A S i ncl u des all ra n d o mize d partici pa nts w h o recei ve d at least 1  d ose of 
st u d y dr u g. Treat me nt gr o u ps f or t his p o p ulati o n will be deter mi ne d acc or di n g t o 
t he treat me nt t he y were assi g ne d at t he ti me of ra n d o mizati o n. 
T he F A S will be use d f or t he s u m mar y of de m o gra p hics, baseli ne c haracteristics, 
partici pa nt dis p ositi o n a n d f or t he a nal yses of all efficac y data.  
Safet y  
T he safet y p o p ulati o n i ncl u des all partici pa nts w h o recei ve d at least 1  d ose of 
st u d y dr u g. Treat me nt gr o u ps f or t his p o p ulati o n will be deter mi ne d acc or di n g t o 
t he act ual treat me nt t he partici pa nt recei ve d re gar dless of assi g ne d st u d y dr u g 
treat me nt. 
All safet y a nal yses will be c o n d ucte d usi n g t he safet y p o p ulati o n.  
P K/ P D -e val ua ble 
T he P K -e val ua ble p o p ulati o n will i ncl u de all partici pa nts w h o recei ve d at least 
1  d ose of st u d y dr u g a n d pr o vi de d at least 1  P K sa m ple.  
T he p har mac o d y na mic -e val ua ble p o p ulati o n will i ncl u de all partici pa nts w h o 
recei ve d at least 1 d ose of st u d y dr u g a n d pr o vi de d at least 1  p har mac o d y na mic 
sa m ple. 
1 0. 3.  
Le vel of Si g nific a nce  
T he d ose res p o ns e will be teste d at a 1 -si de d 0. 0 2 5 le vel. N o m ulti plicit y a dj ust me nt will be 
a p plie d f or ot her st atistical tests. T w o -si de d 9 5 % CIs will be re p orte d f or all a nal yses w he n 
a p pr o priate.  
1 0. 4.  
St atist ic al A n al yses 
T he  pri mar y 1 2 -wee k a n al ysis will be perf or me d after all partici pa nts ha ve eit her c o m plete d t he 
Wee k 1 2  visit or disc o nti n ue d fr o m t he st u d y.  
T he fi nal a n al ysis t o s u m marize a d diti o nal efficac y a n d s afet y ( wit h o ut statistical c o m paris o n t o 
place b o) will be c o n d uct e d o nce t he l ast partici pa nt c o m pletes t he last visit i n t he st u d y.  
C o m plete a n d s pecific d etails of t he statistical a nal ysis will be descri be d a n d f ull y d oc u me nt e d i n 
t he S A P. T he S A P will be fi nalize d pri or t o t he data base l oc k f or t he 1 2-wee k a nal ysis. T his 
secti o n is a s u m mar y of t he pla n ne d statistical a nal yses of t h e pri mar y a n d sec o n dar y e n d p oi nts.  
1 0. 4. 1.  
Pri m ar y A n al ysis  
T he pri mar y esti ma n d a n d t he strate gies f or a d dressi n g t he defi ne d i nterc urre nt e ve nts are 
pr o vi de d i n Ta ble  1 5  a n d Ta ble  1 6 , res p ecti vel y. 

I nc yte C or p orati o n 
P a ge 7 9  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
T a ble  1 5 : 
Esti m a n d f or Pri m ar y E n d p oi nt  
P ri m ar y E n d p oi nt  
P o p ul ati o n  
Tre at me nt  
P o p ul ati o n -Le vel 
S u m m ar y  
C ha n ge fr o m baseli ne 
i n t he wee kl y U A S 7 at 
Wee k 1 2.  
Partici pa nts a ge d  1 8 t o 
6 5 years w h o ha ve ha d 
a dia g n osis of C S U f or 
≥ 3 m o nt hs t hat is 
i na de q uatel y c o ntr olle d 
b y sec o n d -ge nerati o n 
H 1  a nti hista mi nes. 
Eac h of t he 
p o v orciti ni b  d ose 
gr o u ps c o m pare d wit h 
place b o  
T he esti mate d mea n 
c ha n ge fr o m baseli ne i n 
U A S 7 f or eac h 
treat me nt gr o u p, as 
well as t he differe nce i n 
t he esti mated mea n 
c ha n ge fr o m baseli ne i n 
U A S 7 sc ore i n eac h 
acti ve treat me nt gr o u p 
as c o m pare d wit h t he 
place b o gr o u p , at 
Wee k  1 2.  
T a ble  1 6 : 
I nterc urre nt E ve nts a n d Str ate gies f or t he Pri m a r y Esti m a n d  
I nterc urre nt E ve nt 
Str ate gies f or A d dressi n g t he I nterc urre nt 
E ve nt  
Treat me nt disc o nti n uati o n d ue t o a n y reas o n  
T he data c ollecte d f or t he varia ble are use d 
re gar dless of w het her or n ot t he partici pa nt 
disc o nti n ues treat me nt d ue t o a n y reas o n 
(treat me nt p olic y strate g y) 
I nitiati o n of Pr ot oc ol -all o we d resc ue me dicati o n  
T he data c ollecte d f or t he varia ble are use d 
re gar dless of w het her or n ot t he partici pa nt starts 
t he use of a n y Pr ot oc ol -all o we d resc ue me dicati o n 
(treat me nt p olic y strate g y) 
T he pri mar y a n al ysis will be perf or m e d i n t he F A S. T he mea n c ha n ge fr o m baseli ne at Wee k 1 2 
i n wee kl y U A S 7 sc ore will be assesse d usi n g a n M M R M t o i ncl u de all a vaila ble data at 
p ost baseli ne visits i n t he P C peri o d u p t o Wee k 1 2. Partici pa nts w h o ha ve a baseli ne val ue a n d at 
least 1 p ost baseli ne val ue i n t he P C peri o d will be i ncl u de d i n t he a nal ysis. T he M M R M will 
i ncl u de c ha n ge fr o m bas eli ne t o W ee k 1 2 as a res p o nse varia ble, a n d t he fi x e d effect of treat me nt 
gr o u p, ra n d o mizati o n stratificati o n fact or ( pre vi o us use of a n a nti -I g E bi olo gic [ yes or n o ]), visit, 
treat me nt-b y -visit i nteracti o n, a n d c o variates of baseli ne val ue a n d b aseli ne val ue b y visit 
i nteracti o n. U nstr uct ur e d c o varia n ce matri x will be ass u me d f or t h e wit hi n -partici pa nt err ors. 
C o m p o u n d s y m metr y c o varia nce matri x will b e use d if t he m o del wit h u nstr uct ure d varia nce 
c o varia n ce d oes n ot c o n v er ge. T h e Ke n war d -R o ger met h o d will be use d t o esti mate t he de grees 
of free d o m. Missi n g data will n ot be i m p ute d. T he least s q uares me a n esti mates f or eac h 
treat me nt gr o u p a n d t h e ass ociate d c o varia nce matri x o btai ne d fr o m t he M M R M will be 
pr o vi de d a n d f urt her use d i n ge n eralize d M C P -m o d fra me w or k . 
At t he M C P sta ge, a c o ntrast test statistics a n d m ulti plicit y a dj uste d p -v al ue f or t he c o ntr ast test 
will be pr o vi de d f or eac h pres pecifi e d c a n di d ate m o del. A d ose -res p o nse relati o ns hi p will be 
declare d if at least 1  m o d el a m o n g t h e set of 6 pres pecifie d ca n di date m o dels is i de ntifie d t o be 

I nc yte C or p orati o n 
P a ge 8 0  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
statisticall y si g nifica nt at t he le vel α = 0. 0 2 5 1 -si de d tre n d test. O nce a si g nifica nt d ose-res p o nse 
is esta blis he d, t he best m o del will be selecte d usi n g A kai ke I nf or mati o n Criteri o n.  
At t he M o d sta ge , t he sel ecte d m o del will be  use d t o o btai n t he d ose -res p o nse c ur ve a n d t he 
9 5 %  CI . T h e esti mate d d ose-res p o ns e c ur ve will be prese nt e d gra p hicall y. 
1 0. 4. 2.  
Sec o n d ar y A n al ysis  
T he sec o n d ar y efficac y e n d p oi nt s are liste d i n  Ta ble  5 . T he sec o n d ar y efficac y a n al ysis will be 
base d o n t he F A S.  
T he o d ds rati os f or t he pr o p orti o n of partici pa nts wit h U A S 7  6 at Wee k 1 2 i n eac h of t he 
p o v orciti ni b  gr o u ps a n d t he place b o gr o u p  a n d t he c orres p o n di n g 9 5 % CI s will be assesse d usi n g 
l o gistic re gressi o n wit h treat me nt a n d stratificati o n fact or ( pre vi o us use of a n a nti-I g E bi ol o gic 
[yes or n o ]). All partici pa nts w h o ha ve n ot ac hie ve d U A S 7 6 i n t he P C  peri o d, as well as all 
partici pa nts w h o are missi n g p ost baseli ne v al ues, will be defi ne d as n o nres p o n ders f or t he 
n o nres p o n der i m p utati o n a nal ysis.  
T he o d ds rati os f or t he pr o p orti o n of partici pa nts wit h U A S 7 =  0 at Wee k 1 2 i n eac h of t he 
p o v orciti ni b  gr o u ps a n d t he place b o gr o u p a n d t he  c orres p o n di n g 9 5 % CI s will be assesse d usi n g 
l o gistic re gressi o n wit h treat me nt a n d stratificati o n fact or ( pre vi o us use of a n a nti-I g E bi ol o gic 
[yes or n o ]). All partici pa nts w h o ha ve n ot ac hie ve d U A S 7 =  0 i n t he P C  peri o d, as well as all 
partici pa nts w h o  are missi n g p ost baseli ne v al ues, will be defi ne d as n o nres p o n ders f or t he 
n o nres p o n der i m p utati o n a nal ysis.  
Ti me t o first ac hie veme nt of U A S 7  ≤ 6 d uri n g t he P C peri o d is defi ne d as t he ti me fr o m t he date 
of ra n d o mizati o n u ntil t he earliest d ate of ac hie vi n g U A S 7  ≤ 6 d uri n g t he P C peri o d. Partici pa nts 
w h o ha ve n ot a c hie ve d U A S 7  ≤ 6 d uri n g t he P C peri o d will be ce ns ore d at t he last a vaila ble 
U A S 7 meas ure me nt ti me.  S u m maries of ti me t o  first ac hie vem e nt of  U A S 7  ≤ 6 d uri n g t he 
P C  peri o d will be assesse d  usi n g t he Ka pla n -Meier met h o d , a n d t he esti mat e d Ka pla n -M eier 
c ur ve will be dis pla ye d gra p hicall y.  
All ot her sec o n dar y efficac y vari a bles will be s u m marize d usi n g descri pti ve statistics. F or 
cate g orical meas ur e me nts, s u m mar y statistics will i ncl u de t he n u m ber a n d perce nt a ge of 
partici pa nts i n eac h cate g or y. F or c o nti n u o us meas ure me nts, s u m mar y statistics will i ncl u de t he 
n u m ber of o bser vati o n s, mea n, me dia n, S T D , mi ni m u m, a n d ma xi m u m. S u m mar y statistics f or 
c o nti n u o us meas ures will be pr o vi de d f or baseli ne , t he act ual meas ure me nts at eac h visit, a n d t he 
c ha n ge a n d perce nta ge c ha n ge fr o m b aseli ne at eac h visit, if a p plica ble.  
1 0. 4. 3.  
S afet y A n al yses  
Safet y a nal yses will be c o n d ucte d f or t he s afet y p o p ulati o n. A d verse e v e nts will be c o de d b y t he 
Me d D R A dicti o nar y, a n d T E A E s (ie, A Es re p orte d f or t he first ti me or w orse ni n g of a 
pre -e xisti n g e ve nt after first d ose of st u d y dr u g a n d u ntil 6 0 da ys aft er t he l ast d ose of st u d y 
dr u g) will be ta b ulate d b y preferre d t er m a n d s yst e m or ga n class f or all e v e nts, relate d e ve nts,  
a n d e ve nts of Gra d e 3 or hi g her. T he Pr ot oc ol -d efi ne d E CI s a n d A E SIs will be ta b ulate d b y 
preferre d t er m a n d Pr ot o c ol -defi ne d cate g ories f or all e ve nts. Q ua ntitati ve safet y vari a bles  
(e g, la b orat or y val ues, vital si g ns) a n d t heir c ha n ges fr o m baseli ne wil l be s u m marize d wit h 
descri pti ve statistics. Cli nicall y n ota bl e a b n or mal val ues will be fla g ge d a n d ta b ulate d base d o n 
pre defi n e d criteria.  

I nc yte C or p orati o n 
P a ge 8 1  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
T he s u bset of A Es c o nsi d ere d b y t he i n vesti gat or t o ha ve a relati o ns hi p t o st u d y dr u g will be  
c o nsi dere d t o be treat me nt -relate d A Es. If t he i n v esti gat or d o es n ot s pecif y t he relati o ns hi p of t he 
A E t o st u d y dr u g, t he n t h e A E will be c o nsi dere d treat me nt -relate d. T h e i nci de nce of A Es a n d 
treat me nt-relate d A Es will be ta b ulate d. 
T he cli nical la b orat or y d ata will be a nal yz e d usi n g s u m mar y statistics; n o f or mal treat me nt gr o u p 
c o m paris o ns are pla n ne d. I n a d diti o n, distri b uti o ns of ke y la b orat or y para m eters ma y be pl otte d 
o ver ti me; t hese val ues will als o be classifie d i nt o C T C A E v 5. 0 t o xicit y gra des a n d ta b ulate d. 
Desc ri pti ve statistics a n d mea n c ha n ge fr o m b aseli ne will be deter mi ne d f or vital si g ns at eac h 
assess me nt ti me. Vital si g n res ults will be re vie we d f or cli nicall y n ota ble a b n or malities. 
Descri pti ve statistics a n d mea n c ha n ge fr o m b aseli ne will be deter mi ne d f or eac h E C G para meter 
at eac h assess me nt ti me . 
1 0. 4. 4.  
E x pl or at or y A n al ysis  
All e x pl orat or y efficac y varia bles will be s u m marize d usi n g descri pti ve statistics , if a p plica ble. 
F or cate g orical meas ur e me nts, s u m mar y statistics will i ncl u de t he n u m ber a n d perce nta ge of 
partici pa nts i n eac h cate g or y. F or c o nti n u o us meas ure me nts, s u m mar y statistics will i ncl u de t he 
n u m ber of o bser vati o n s, mea n, me dia n, S T D , mi ni m u m, a n d ma xi m u m. S u m mar y statistics f or 
c o nti n u o us meas ures will be pr o vi de d f or baseli ne, t he act ual meas ure m e nts at eac h visit, a n d t he 
c ha n ge a n d perce nta ge c ha n ge fr o m b aseli ne at eac h visit, if a p plica ble.  
1 0. 4. 4. 1.  P h ar m a c o ki netic a n d P h ar m a c o ki netic/ P h ar m ac o d y n a mic A n al yses  
P har mac o ki netic a n al yses will be perf or me d f or t he P K-e val ua ble p o p ulati o n. T he p o v orciti ni b  
p las ma c o nce ntrati o n dat a will be a nal yz e d b y a p o p ulati o n P K m o deli n g a p pr oac h. S uc h d ata 
ma y b e c o m bi ne d wit h d ata fr o m ot her st u dies i n t he cli nical de vel o p me nt pr o gra m t o de vel o p or 
refi ne p o p ulati o n P K m o dels, i n w hic h p o p ulati o ns of healt h y partici pa nts, partici pa nts wit h 
m o derate t o se v ere ast h ma, a n d/ or partici pa nts wit h ot her diseases will be e val uate d a n d i ncl u d e d 
i nt o t he m o del if si g nifica nt as a c o v ariate. T his m o del ma y b e use d t o e val uate t he effects of 
i ntri nsic a n d e xtri nsic c o variates o n t he P K of p o v orciti ni b  a n d t o deter mi ne meas ures of 
i n di vi d ual plas ma e x p os ures (s uc h as stea d y-stat e pea k, tr o u g h, a n d/ or ti me-a vera ge d 
c o nce ntr ati o ns). T he p o p ulati o n P K a nal ysis will be re p ort e d se paratel y.  
Relati o ns hi ps bet wee n p o v orciti ni b  P K e x p os ures a n d cli nical res p o ns es (efficac y a n d safet y) 
will be e x pl ore d usi n g a n e x p os ure -res p o nse a nal ysis fra me w or k as dee m e d a p pr o priate. F or 
dic h ot o m o us e n d p oi nts, a ge neralize d li near or n o nli near m o del wit h bi n o mial li n k f u ncti o n will 
be use d. F or c o nti n u o us e n d p oi nts, li near or n o nli near re gressi o ns will be use d. Ra n d o m effects 
o n i nteri n di vi d ual varia bilit y will be c o nsi dere d w he n s u p p orte d b y data. Cli nical res p o nses s uc h 
as t he pri mar y a n d s ec o n dar y efficac y res p o ns es a n d T E A Es wit h > 1 0 % i n ci de nce rate wil l be 
a nal yze d. T h e e x p os ure -res p o nse a nal ysis will be re p orte d se p aratel y. 
1 0. 5.  
I nteri m A n al ysis 
N o f or mal i nteri m a nal ysis is pla n ne d i n t his st u d y . H o we ver, pre pla n ne d a nal yses of safet y will 
be pr o vi de d t o a n i nter n al D S M B (see Secti o n 5. 6 ) as s pecifi e d i n t he D S M B c harter. T h e 
pr ocess b y w hic h t h e D S M B will re vie w d ata a n d ma ke rec o m me n dati o ns a n d decisi o ns will be 
d oc u me nte d i n t he D S M B c harter.  

I nc yte C or p orati o n 
P a ge 8 2  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
1 1.  
S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L 
C O N SI D E R A TI O N S  
1 1. 1.  
I n vesti g at or Res p o nsi bilities 
•  T he Pr ot oc ol, Pr ot oc ol A me n d me nts, I C F, I B, a n d ot her rele va nt d oc u me nts 
(e g, a d vertise me nts) m ust be s u b mitte d t o a n I R B/I E C b y t he i n vesti gat or a n d 
re vie we d a n d a p pr o ve d b y t he I R B/I E C a n d healt h a ut h orities bef ore t he st u d y is 
i nitiate d. 
•  T he i n vesti gat or is res p o nsi ble f or e ns uri n g t hat t he safet y re p orts pr o vi de d b y t he 
s p o ns or are re vie we d a n d pr ocesse d i n acc or da nce wit h re g ul at or y re q uire m e nts, t he 
p olicies a n d pr oce d ures esta blis he d b y t he I R B/I E C, a n d i nstit uti o nal re q uire me nts.  
•  A n y a me n d me nts t o t he Pr ot oc ol will re q uire a p pr o val fr o m b ot h healt h a ut h orities 
a n d t he I R B/I E C b ef ore i m ple me ntati o n of c ha n ges ma de t o t he st u d y d esi g n, e x ce pt 
f or c ha n ges necessar y t o eli mi nate a n i m me diate hazard t o st u d y partici pa nts.  
•  T he i n vesti gat or will be res p o nsi ble f or t he f oll o wi n g:  
− Pr o vi di n g writte n s u m maries of t he stat us of t he st u d y t o t he I R B/I E C a n n uall y or 
m ore fre q u e ntl y i n acc or da nce wit h t he re q uire m e nts, p olicies, a n d pr oce d ures 
esta blis he d b y t h e I R B/I E C. 
− N otif yi n g t he I R B/I E C of S A Es or ot her si g nifica nt safet y fi n di n gs as re q uire d b y 
I R B/I E C pr oce d ures. 
− Pr o vi di n g o versi g ht of t h e c o n d uct of t he st u d y at t he site a n d a d here nce t o G C P, 
I R B/I E C re q uir e me nts, i nstit uti o nal re q uire me nts, a n d a p plica ble la ws a n d 
c o u ntr y-s pecific re g ul ati o ns. 
•  A d heri n g t o t he Pr ot oc ol as descri be d i n t his d oc u me nt a n d a greei n g t hat c ha n ges t o 
t he Pr ot oc ol pr oce d ures, wit h t he e x ce pti o n of me dical e mer ge ncies, m ust be 
disc usse d a n d a p pr o ve d, first, b y t he s p o ns or or it s desi g nee a n d, s ec o n d, b y t he 
I R B/I E C. Eac h i n v esti gat or is res p o nsi ble f or e nr olli n g partici pa nts w h o h a ve met t he 
s pecifie d eli gi bilit y criteria. 
•  Retai ni n g rec or ds i n acc or da nce wit h all l ocal, nati o nal, a n d re g ulat or y la ws b ut f or a 
mi ni m u m peri o d of a t least 2 years aft er t he last m ar keti n g a p plicati o n a p pr o val i n a n 
I C H re gi o n a n d u ntil t here are n o p e n di n g or c o nt e m plate d mar keti n g a p plicati o ns i n 
a n I C H re gi o n, or if n ot a p pr o ve d, 2  years aft er t he ter mi nati o n of t he test article f or 
i n vesti gati o n to e ns ure t h e a vaila bilit y of st u d y d o c u me ntati o n s h o ul d it bec o me 
necessar y f or t he s p o ns or or a re g ul at or y a ut h orit y t o re vie w.  
− T he i n vesti gat or m ust n ot destr o y a n y rec or ds ass ociate d wit h t he st u d y d uri n g t he 
rete nti o n peri o d wit h o ut recei vi n g a p pr o val fr o m t he s p o ns or. T he i n vesti gat or 
m ust n otif y t h e s p o ns or or its desi g nee i n t he e ve nt of acci d e ntal l oss or 
destr ucti o n of a n y st u d y rec or ds. If t he i n vesti gat or lea ves t he i nstit uti o n w here 
t he st u d y w as c o n d ucte d, t he s p o ns or or its desi g n ee m ust be c ontacte d t o arra n ge 
alter nati ve rec or d st ora ge o pti o ns.  

I nc yte C or p orati o n 
P a ge 8 3  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
− All e C R F data e ntere d b y t he site (i ncl u di n g a u dit trail), as well as c o m p uter 
har d ware a n d s oft ware (f or accessi n g t h e data), will be mai ntai ne d or ma de 
a vaila ble at t he site i n c o m plia nce wit h a p plic a ble rec or d rete nti o n r e g ulati o ns. 
T he s p o ns or will retai n t he ori gi n al e C R F data a n d a u dit trail.  
1 1. 1. 1.  
I de ntific ati o n of t he C o or di n ati n g Pri nci p al I n vesti g at or  
A c o or di nati n g pri nci pal i n vesti gat or will be a p p oi nte d b y t he s p o ns or bef ore t he e n d of t he 
st u d y. As part of t heir res p o nsi bilities, t he c o or di nati n g pri nci p al i n vesti gat or will re vie w t he 
fi nal C S R. A gree me nt wit h t he fi nal C S R will be d oc u me nte d b y t he dat e d si g nat ur e of t he 
c o or di nati n g pri nci pal i n vesti gat or.  
1 1. 2.  
D at a M a n a ge me nt  
Data ma na ge me nt will b e perf or me d i n a vali dat e d E D C s yste m. T he i n vesti gat or will be 
pr o vi de d wit h access t o a n E D C s yste m s o t hat a n e C R F ca n b e c o m plete d f or eac h p artici pa nt.  
T he site will be pr o vi de d wit h e C R F c o m pleti o n g ui deli nes f or i nstr ucti o ns o n data e ntr y i n t he 
e C R F. T he st u d y m o nit or will refere nce t h e M o nit ori n g Pla n i n or der t o e ns ure t hat eac h iss ue 
i de ntifie d is a p pr o priatel y d oc u m e nte d, re p orte d, a n d res ol ve d i n a ti mel y ma n ner i n acc or da nce 
wit h t he pla n 's r e q uire me nts. Ot her data o utsi de t h e E D C s yste m re q uire d i n t he st u d y c o n d u ct of 
t he Pr ot oc ol, s uc h as d oc u me nts or res ults tra ns mitte d t o t he s p o ns or via a ce ntral la b orat or y or 
s pecializ e d tec h nical v e n d ors a n d as desi g nat e d b y t he s p o ns or, will ha ve t heir o w n data fl o w 
ma na ge me nt pla ns, st u d y c harters, or  bi o mar ker pl a ns, as a p plica bl e.  
T he s p o ns or ( or desi g n ee) will be res p o nsi ble f or t he f oll o wi n g:  
•  Ma na gi n g t he i nte grit y of t he data a n d t h e q ualit y of t he c o n d uct of t h e st u d y, s uc h as 
e ns uri n g t h at st u d y m o nit ors perf or m o n g oi n g s o urce data verificati o n t o c o nfir m t hat 
data e ntere d i nt o t he e C R F b y a ut h orize d site pers o n nel are acc urate, c o m plete, a n d 
verifia ble fr o m s o urce d o c u me nts; t hat t he safet y a n d ri g hts of p artici pa nts are bei n g 
pr otecte d; a n d t hat t he st u d y is bei n g c o n d u cte d i n acc or da nce wit h t he c urre ntl y 
a p pr o ve d Pr ot oc ol a n d a n y ot her st u d y a gree me nts, I C H G C P, a n d all a p plica ble 
re g ulat or y re q uire me nts. 
•  Ma na gi n g a n d rec o ncili n g t he data ge n erate d a n d/ or c ollecte d, i ncl u di n g d o c u me nts 
a n d res ults s uc h as la b orat or y or i ma gi n g d ata a n al yz e d ce ntrall y b y a desi g nate d 
ve n d or of t he s p o ns or.  
T he i n vesti gat or will be res p o nsi ble f or t he f oll o wi n g:  
•  Rec or di n g, or e ns uri n g t h e rec or di n g of, all rele va nt data relati n g t o t he st u d y i n t he 
e C R F. 
•  Deli veri n g, or e ns uri n g t he deli ver y of, all ot her res ults,  d oc u me nts, data, k n o w -h o w, 
or f or m ulas rel ati n g t o t h e st u d y t o t he s p o ns or or desi g nee electr o nicall y a n d/ or 
ce ntrall y (e g, la b orat or y data, i ma gi n g d ata, bi o mar ker data, p h ot o gra p hs, diar y d ata) 
or as ot her wise s p ecifie d i n t he Pr ot oc ol.  

I nc yte C or p orati o n 
P a ge 8 4  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
•  Mai ntai ni n g a d e q uate a n d acc urate s o urce d oc u m e nts a n d trial rec or ds t hat i ncl u de all 
perti ne nt o bser vati o ns o n eac h of t h e site 's trial partici pa nts. S o urce data s h o ul d be 
attri b uta ble, le gi ble, c o nt e m p ora ne o us, ori gi nal, acc urat e, a n d c o m plet e. C ha n ges t o 
s o urce data s h o ul d be tracea ble, s h o ul d n ot o bsc ure t he ori gi nal e ntr y, a n d s h o ul d be 
e x plai ne d if necessar y (e g, via a n a u dit trail). S o urce dat a are, i n ge neral, all 
i nf or mati o n i n ori gi nal rec or ds a n d certifie d c o pies of ori gi n al rec or ds of cli nical 
fi n di n gs, o bser vati o ns, or ot her acti vities i n a cli nical trial necessar y f or t he 
rec o nstr ucti o n a n d e val u ati o n of t he trial. S o urce data are c o ntai ne d i n s o urce 
d oc u me nts ( ori gi nal rec or ds or certifie d c o pies).  
•  Verif yi n g t hat data e ntries are acc urate a n d c orrect b y p h ysic all y or electr o nicall y 
si g ni n g t he e C R F. 
•  Mai ntai ni n g acc urate d oc u me ntati o n (s o urce d ata) t hat s u p p orts t he i nf or mati o n 
e ntere d i n t he e C R F, se nt t o a ce ntral v e n d or desi g nate d b y t he s p o ns or, or as 
descri be d i n ot her st u d y a n d data fl o w ma n uals.  
− S o u rce d oc u me nts pr o vi d e e vi de nce f or t h e e xiste nce of t he p artici pa nt a n d 
s u bsta ntiate t he i nte grit y of t he data c ollecte d. S o urce d oc u m e nts are file d a n d 
a vaila ble at t he i n vesti gat or 's site. E xa m ples of s o urce d oc u m e nts are ori gi nal 
d oc u me nts, data, a n d re c or ds (e g, h os pital rec or ds; electr o nic h os pital rec or ds; 
cli nical a n d office c h arts; la b orat or y n otes; me m or a n da; partici pa nts ' diaries or 
e val uati o n c hec klists; p har mac y dis pe nsi n g rec or ds; rec or de d d ata fr o m 
a ut o mate d i nstr u me nts; c o pies or tra nscri pti o ns certifie d after verificati o n as 
bei n g acc urate c o pies; micr ofic h es; p h ot o gra p hic ne gati ves; micr ofil m or 
ma g n etic me dia; x -ra ys; partici pa nts' files; a n d e-rec or ds/rec or ds ke pt at t he 
p har mac y, at t he la b orat ories, a n d at me dic o -tec h nical de part me nts i nv ol ve d i n 
t he cli nical trial). 
− Data e ntere d i n t he e C R F t hat are tr a nscri be d fr o m s o urce d oc u m e nts m ust be 
c o nsiste nt wit h t he s o urce d oc u me nts or t he discre pa ncies m ust be e x plai ne d. T he 
i n vesti gat or ma y n ee d t o re q uest pre vi o us me di cal rec or ds or tra nsfer rec or ds, 
de pe n di n g o n t he st u d y. C urre nt a p plica ble m e dical rec or ds m ust be a vaila ble.  
•  Se n di n g partici pa nts ' d at a, eit her as u ni q u e sa m ples, c o pies, or p h ot o gra p hs, t o be 
e val uate d ce ntrall y or a n al yze d ce ntrall y, or b ot h, b y a q u alifie d ve n d or desi g nate d b y 
t he s p o ns or. 
− As re q uire d b y pri vac y a n d data pr otecti o n re g ulati o ns a n d I n c yt e 's pri vac y 
p olicies, if a n y p h ot o gra p hs of partici pa nts are t o b e ta ke n, t he p h ot o gra p hs m ust 
be li mite d t o t he area of t he face or t he b o d y t h at is strictl y necessar y a n d t he 
p h ot o gra p hs s h o ul d be mas ke d (ie, i de ntif yi n g feat ures s uc h as e yes, m o ut h, scars, 
tatt o os, or u ni q ue mar ki n gs or feat ur es s h o ul d be eit her o bsc ure d wit h a blac k bar 
or di gitall y pi x elate d s o as t o n ot per mit t he rei de ntificati o n of t he partici pa nts a n d  
preser ve t heir c o nfi de ntialit y) b y a s peciall y desi g nate d p h ot o gra p h y ve n d or pri or 
t o se n di n g t he p h ot o gra p hs t o I nc yt e or a n y ot her t hir d-part y ve n d ors f or a nal ysis 
or f urt her pr ocessi n g.  

I nc yte C or p orati o n 
P a ge 8 5  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
•  Per mitti n g st u d y -relate d m o nit ori n g, s p o ns or a u dits, I R B/I E C re view, a n d re g ul at or y 
i ns pecti o ns b y pr o vi di n g direct access t o s o urce data a n d ot her rele va nt cli ni cal st u d y 
d oc u me nts.  
− M o nit ori n g: Q ualifie d re prese ntati ves of t h e s p o ns or or its desi g n ee, st u d y 
m o nit ors, will m o nit or t he st u d y acc or di n g t o a pre deter mi ne d p la n. T he 
i n vesti gat or m ust all o w t he st u d y m o nit ors t o re vi e w a n y st u d y materi als a n d 
partici pa nt rec or ds at e ac h m o nit ori n g visit.  
− A u diti n g: Q ualifie d re prese ntati ves of t he s p o ns or or its desi g nee ma y a u dit t he 
cli nical st u d y site a n d st u d y dat a t o e val u at e c o m plia nce wit h t he Pr ot oc ol, 
a p plica ble l ocal cli nical st u d y re g ul ati o ns, a n d o verall st u d y c o n d u ct. T he 
i n vesti gat or m ust all o w t he a u dit ors t o re vie w ori gi nal s o urce rec or ds a n d st u d y 
d oc u me ntati o n f or all partici pa nts.  
− Re g ulat or y i ns pe cti o n: Re g ul a t or y a ut h orities ma y c o n d uct a n i ns pecti o n of t he 
st u d y a n d t he site at a n y ti me d uri n g t he de vel o p m e nt of a n i n vesti gati o nal 
pr o d uct. T he i n vesti gat or a n d staff are e x pecte d t o c o o perat e wit h t he i ns pe ct ors 
a n d all o w access t o all s o urce d oc u m e nts s u p p ort i n g t he e C R Fs a n d ot her 
st u d y-relate d d oc u m e nts. T he i n vesti gat or m ust i m me diatel y n otif y t he s p o ns or 
w he n c o nta cte d b y a n y re g ulat or y a ut h orit y f or t he p ur p oses of c o n d u cti n g a n 
i ns pecti o n. 
1 1. 3.  
D at a Q u alit y Ass ur a nce  
T he s p o ns or ass u mes acc o u nta bilit y f or act i o ns dele gate d t o ot her i n di vi d uals (e g, c o ntr act 
researc h or ga niz ati o ns). T he s p o ns or or desi g nee is res p o nsi ble f or t he dat a ma na ge m e nt of t his 
st u d y, i ncl u di n g q u alit y c hec ki n g of t he dat a. F urt her, m o nit ori n g d etails descri bi n g strate g y, 
i ncl u di n g definiti o n of st u d y -critical data ite ms a n d pr ocesses (e g, ris k -b ase d i nitiati ves i n 
o perati o ns a n d q ualit y s u c h as ris k ma na ge me nt a n d miti gati o n strate gies a n d a nal yti cal ris k -
base d m o nit ori n g), m et h o ds, res p o nsi bilities, a n d re q uire me nts, i ncl u di n g ha n dli n g  of 
n o nc o m plia nce iss ues, Pr ot oc ol de viati o ns, a n d m o nit ori n g tec h ni q ues (e g, ce ntral, r e m ote, or 
o n -site m o nit ori n g) are pr o vi de d i n t he rele va nt st u d y pla ns. 
Q ualit y t olera nce li mits will be pre defi n e d i n t he o perati o nal ma n ual or e q ui vale nt t o i de ntif y 
s yste matic iss ues t hat ca n i m pact partici pa nts' safet y, efficac y res ults a n d a nal ysis, a n d/ or 
relia bilit y of st u d y res ults. T hese pre d efi ne d p ara meters will be m o nit ore d d uri n g t he st u d y a n d 
ca n be a dj uste d d uri n g t he st u d y u p o n d ata re vi e w. I m p ort a nt de vi ati o ns fr o m t he q ualit y 
t olera nce li mits a n d re m e dial acti o ns ta ke n, i ncl u di n g re p orti n g t o I R Bs/I E Cs a n d healt h 
a ut h orities if a p plica ble, will be s u m marize d i n t he C S R.  
1 1. 4.  
D at a Pri v ac y a n d C o nfi de nti alit y of St u d y Rec or ds  
T he i n vesti gat or a n d t he s p o ns or or  its desi g nee m ust a d here t o a p plica ble data pr otecti o n la ws 
a n d re g ulati o ns. T he i n vesti gat or a n d t h e s p o ns or or its desi g nee are res p o nsi ble f or e ns uri n g t hat 
pers o nal i nf or mati o n is h a n dle d i n acc or da n ce wit h l ocal data pr otecti o n la ws (i ncl u di n g b ut n o t 
li mite d t o HI P A A a n d G D P R) as a p plica ble, a n d t he s p o ns or o perates c o m pre he nsi ve d ata 
pri vac y a n d d ata sec urit y pr o gra ms t hat are a p plica ble t o t his st u d y. A p pr o priate n otice, or n otice 
a n d c o nse nt ( as ma y be re q uire d b y eac h a p plica ble j uris dicti o n), f o r c ollecti o n, use, discl os ure, 

I nc yte C or p orati o n 
P a ge 8 6  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
a n d/ or tra nsf er (if a p plica ble) of pers o nal i nf or mati o n m ust be o btai ne d i n acc or da n ce wit h l ocal 
data pr otecti o n la ws. A p pr o priate dat a pr otecti o n ter ms t hat c o m pl y wit h a p plica ble la ws will be 
i ncl u de d i n rele va nt st u d y a gree m e nts.  
T o e ns ure c o nfi de ntialit y of rec or ds a n d pr ot ect pers o nal data, partici pa nt n a mes will n ot be 
s u p plie d t o t he s p o ns or or its desi g nee. O nl y t he partici pa nt n u m ber will be rec or de d i n t he 
e C R F; if t he partici pa nt 's na me a p pears o n a n y ot h er d oc u me nt ( e g, la b orat or y re p ort), it m ust be 
o bliterate d o n t he c o p y of t he d oc u me nt t o be s u p plie d t o t he s p o ns or or its desi g nee. St u d y 
fi n di n gs st ore d o n a c o m p uter will be st ore d i n acc or da nce wit h a p pr o priat e tec h nical a n d 
or ga niz ati o nal meas ures as re q uire d  b y l o cal data pr otecti o n la ws.  
I n t he e ve nt of a data breac h i n v ol vi n g p artici pa nt data, t he s p o ns or or its d esi g nee will f oll o w 
t he s p o ns or's i nci d e nt res p o nse pr oce d ures. T h e precise defi niti o n of a data breac h v aries i n 
acc or da nce wit h a p plica ble la w b ut ma y ge nerall y be u n derst o o d as a breac h of sec urit y lea di n g 
t o t he acci de ntal or u nla wf ul destr ucti o n, l oss, alterati o n, u na ut h orize d discl os ure of, or access t o, 
pers o nal data. I n acc or da nce wit h its i nci de nt res p o nse pr oce d ures, t he s p o ns or will asses s t he 
breac h t o c o nsi der its n otificati o n a n d re me diati o n o bli gati o ns u n der a p plica ble la w.  
1 1. 5.  
Fi n a nci al Discl os ure  
Bef ore st u d y i nitiati o n, all cli nical i n vesti gat ors p artici pati n g i n cli nical st u dies s u bject t o F D A 
Re g ulati o n Title 2 1 C F R Part 5 4 –  Fi na ncia l Dis cl os ure b y Cli nical I n vesti gat ors (ie, "c o vere d 
st u dies") are re q uire d t o s u b mit a c o m plete d Cli nical I n vesti gat or Fi na nci al Discl os ure F or m t hat 
s ufficie ntl y d etails a n y fi na ncial i nterests a n d arra n ge m e nts t hat a p pl y. F or t he p ur p ose of t his 
re g ulati o n, "cli nical i n vesti gat or " is defi ne d as a n y i n vesti gat or or s u bi n v esti gat or w h o is directl y 
i n v ol ve d i n t he treat me nt or e val uati o n of researc h partici pa nts, i ncl u di n g t h e s p o use a n d eac h 
de pe n de nt c hil d of t he cli nical i n vesti gat or or s u bi n vesti gat or. T h ese re q uir e me nts a p pl y t o b ot h 
U S a n d f orei g n cli nic al i n vesti gat ors c o n d ucti n g c o vere d cli nical st u dies.  
A n y n e w cli nical i n vesti gat ors a d de d t o t he c o vere d cli nical st u d y d uri n g its c o n d uct m ust als o 
s u b mit a c o m plete d Cli nical I n vesti gat or Fi na nci al Discl os ure F or m. D uri n g a c o vere d cli nical 
st u d y, a n y c ha n ges t o t he fi na ncial i nf or mati o n pr e vi o usl y re p orte d b y a cli nical i n vesti gat or 
m ust be re p orte d t o t he s p o ns or or its desi g n ee. At t he c o ncl usi o n of t he c o vere d cli nical st u d y, 
t he cli nical i n vesti gat ors will be re mi n de d of t heir o bli gati o ns. I n t he e v e nt t hat t he cli nical 
i n vesti gat or is n ot re mi n de d, t he y ne vert heless will re mai n o bli gate d t o re p ort t o t he s p o ns or or 
its desi g nee a n y c h a n ges t o t he fi na ncial i nf or mati o n pre vi o usl y re p orte d, as well as a n y c h a n ges 
i n t heir fi na ncial i nf or mati o n f or a peri o d of 1 year after c o m pleti o n of t he c o vere d cli nical st u d y. 
1 1. 6.  
P u blic ati o n P olic y  
B y si g ni n g t he st u d y Pr ot oc ol, t he i n vesti gat or a n d t heir i nstit uti o n a gree t h at t he res ults of t he 
st u d y ma y be us e d by t he s p o ns or, I n c yte C or p orati o n (I n c yte), f or t he p ur p oses of nati o nal a n d 
i nter nati o nal re gistrati o n, p u blicati o n, a n d i nf or mati o n f or me dical a n d p har mace utical 
pr ofessi o nals. St u d y res ults will be p u blis he d i n acc or da n ce wit h a p plica bl e l ocal a n d nati o nal 
re g ulati o ns. If necessar y, t he a ut h orities will be n otifie d of t he i n vesti gat or's na me, a d dress, 
q ualificati o ns, a n d e xte nt of i n v ol ve me nt. T he ter ms re gar di n g t he p u blicati o n of st u d y res ults 
are c o nt ai ne d i n t he a gree me nt si g ne d wit h t he s p o ns or or its desi g n ee. A si g ne d a gree me nt will 
be retai ne d b y t h e s p o ns or or its desi g n ee.  

I nc yte C or p orati o n 
P a ge 8 7  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
T he res ults of t his st u d y ma y b e p u blis he d or pres e nte d at scie ntific meeti n gs. If t his is f oresee n, 
t he i n vesti gat or a grees t o s u b mit all ma n uscri pts or a bstracts t o t he s p ons or bef ore s u b missi o n. 
T his all o ws t he s p o ns or t o pr otect pr o priet ar y i nf or mati o n a n d t o pr o vi de c o m me nts.  
T he s p o ns or will c o m pl y wit h t he re q uire me nts f or p u blicati o n of st u d y res ults. I n acc or da nce 
wit h sta n dar d e dit orial a n d et hical practice, t he s p o n s or will ge n erall y s u p p ort p u blicati o n of 
m ultice nter st u dies o nl y i n t heir e ntiret y a n d n ot as i n di vi d ual site data. I n t his case, a 
c o or di nati n g i n v esti gat or will be desi g nat e d b y m ut ual a gree m e nt.  
A ut h ors hi p will be deter mi ne d i n li ne wit h I nter n ati o nal  C o m mittee of Me dical J o ur nal E dit ors 
a ut h ors hi p re q uire m e nts.  
1 1. 7.  
St u d y a n d Site Cl os ure  
T he s p o ns or or desi g nee reser ves t he ri g ht t o cl ose t he st u d y site or ter mi nate t he st u d y at a n y 
ti me f or a n y reas o n at t he s ole discreti o n of t he s p o ns or. St u d y sites will be cl ose d u p o n st u d y 
c o m pleti o n. A st u d y site is c o nsi dere d cl ose d w he n all re q uire d d o c u me nts a n d st u d y s u p plies 
ha ve bee n c ollecte d a n d a st u d y -site cl os ure visit has bee n perf or m e d. 
T he i n vesti gat or ma y i nitiate st u d y -site cl os ure at a n y ti me, pr o vi d e d t here is reas o na ble ca use 
a n d s ufficie nt n otice is gi ve n i n a d va nce of t he i nt e n de d ter mi nati o n.  
Reas o ns f or t he earl y cl os ure of a st u d y site b y t he s p o ns or or i n vesti gat or ma y i ncl u d e b ut are 
n ot li mite d t o:  
•  Fail ure of t he i n vesti gat or t o c o m pl y wit h t he Pr ot oc ol, t he re q uir e me nts of t he 
I R B/I E C or l ocal h ealt h a ut h orities, t he s p o ns or's pr oce d ures, or G C P g ui deli nes. 
•  I n a de q uat e recr uit me nt of partici pa nts b y t he i n vesti gat or. 
•  Disc o nti n uati o n of f urt her st u d y tr eat me nt de vel o p me nt.  

I nc yte C or p orati o n 
P a ge 8 8  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
1 2.  
R E F E R E N C E S  
Ala vi A , Ha mz a vi I, Br o w n K, et al. J a n us ki nase 1 i n hi bit or I N C B 0 5 4 7 0 7 f or patie nts wit h 
m o derate -t o-s e vere hi dra de nitis s u p p urati va: res ults fr o m t w o p hase II st u dies. Br J Der mat ol 
2 0 2 2; 1 8 6: 8 0 3 -8 1 3.  
Altric hter S, F o k J S, Jia o Q, et al. T otal I g E as a mar ker f o r c hr o ni c s p o nta ne o us urticaria. 
Aller g y Ast h ma I m m u n ol Res 2 0 2 1; 1 3: 2 0 6 -2 1 8.  
At wa M A, E mara A S, Y o ussef N, Ba y o u m y N M. Ser u m c o nce ntr ati o n of I L -1 7, I L -2 3 a n d 
T N F -α a m o n g patie nts wit h c hr o nic s p o nta ne o us urticaria: ass o ciati o n wit h disease acti vit y a n d 
a ut ol o g o us ser u m s ki n test. J E ur Aca d Der mat ol Ve nere ol 2 0 1 4; 2 8: 4 6 9-4 7 4.  
Baiar di ni I, Pas q u ali M, Brai d o F, et al. A ne w t o ol t o e val uate t he i m pact of c hr o nic urticaria o n 
q ualit y of life: c hr o nic urticaria q ualit y of life q u esti o n naire ( C U -Q o L). Aller g y 2 0 0 5; 6 0: 1 0 7 3 -
1 0 7 8.  
Biss o n nette R, L u c hi M, Fi del us -G ort R, et al. A ra n d o mize d, d o u ble -bli n d, place b o -c o ntr olle d, 
d ose -escalati o n st u d y of t he safet y a n d efficac y of I N C B 0 3 9 1 1 0, a n oral ja n us ki nase 1 i n hi bit or, 
i n patie nts wit h sta ble, c hr o nic pla q ue ps oriasis. J Der mat ol o g Treat 2 0 1 6; 2 7: 3 3 2 -3 3 8.  
Bretz F, Pi n heir o J C, Bra ns o n M. C o m bi ni n g m ulti ple c o m paris o ns a n d m o deli n g tec h ni q ues i n 
d ose -res p o ns e st u dies. Bi o metrics 2 0 0 5; 6 1: 7 3 8-7 4 8.  
C he n Q, Z h o n g H, C he n W C, et al. Differe nt e x pressi o n patter ns of plas m a T h 1-, T h 2-, T h 1 7- 
a n d T h 2 2-rel ate d c yt o ki n es c orrelate wit h ser u m a ut oreacti vit y a n d aller ge n se nsiti vit y i n c hr o nic 
s p o nta ne o us urticari a. J E ur Aca d Der mat ol Ve nere ol 2 0 1 8; 3 2: 4 4 1-4 4 8.  
Cli nical Trial s Facilitati o n  a n d C o or di nati o n  Gr o u p. Rec o m me n dati o ns  relate d t o c o ntrace pti o n 
a n d pre g na n c y testi n g i n cli nical trials.  2 0 2 0 . 
Eric ks o n S, He ul A V, Ki m B S. Ne w a n d e mer gi n g treat me nts f or i nfla m m at or y itc h. A n n 
Aller g y Ast h ma I m m u n ol 2 0 2 1; 1 2 6: 1 3 -2 0.  
Fe n g H, Fe n g J, Z h a n g Z, et al. R ole of I L -9 a n d I L -1 0 i n t he p at h o ge nesis of c hr o nic 
s p o nta ne o us urticari a t hr o u g h t he J A K/ S T A T si g nalli n g pat h w a y. Cell Bi oc he m F u n ct 
2 0 2 0; 3 8: 4 8 0 -4 8 9.  
Fe n wic k P S, Mace d o P, Kilt y I C, Bar nes PJ, D o n nell y L E. Effect of J A K I n hi bit ors o n Release 
of C X C L 9, C X C L 1 0 a n d C X C L 1 1 fr o m H u m a n  Air wa y E pit helial Cells. P L o S O ne 
2 0 1 5; 1 0:e 0 1 2 8 7 5 7.  
Fi nla y A Y, K h a n G K. D er mat ol o g y Life Q ualit y I n d e x ( D L QI) —  a si m ple practical meas ure f or 
r o uti ne cli nical use. Cli n E x p Der mat ol 1 9 9 4; 1 9: 2 1 0-2 1 6.  
F o k J S, K ol k hir P, C h urc h M K, Ma urer M. Pr e dict ors of t reat me nt r es p o nse i n c hr o nic 
s p o nta ne o us urticari a. Aller g y 2 0 2 1; 7 6: 2 9 6 5-2 9 8 1.  
F o o d a n d Dr u g A d mi nistrati o n. F D A Dr u g Safet y C o m m u nicati o n: F D A re q uires war ni n gs 
a b o ut i ncreas e d ris k of seri o us heart‑relate d e ve nts, ca ncer, bl o o d cl ots, a n d deat h f or J A K 
i n hi bit ors t hat treat certai n c hr o nic i nfla m mat or y c o n diti o ns. 2 0 2 1. 
F u k u na ga A, It o M, Nis hi g ori C. Effic ac y of Oral R u x oliti ni b i n a Patie nt wit h Refract or y 
C hr o nic S p o nta ne o us Urticaria. A cta Der m Ve n ere ol 2 0 1 8; 9 8: 9 0 4 -9 0 5.  

I nc yte C or p orati o n 
P a ge 8 9  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
Gi mé nez -Ar na u A M, De M o nt oj o ye L, As er o R, et al. T he pat h o ge nesis of c hr o nic s p o nta ne o us 
urticaria: t he r ol e of i nfiltrati n g cells [ p u blis he d c orrecti o n a p p ears i n J Aller g y Cli n I m m u n ol 
Pract 2 0 2 1; 9: 3 5 3 3] [ p u blis he d c orrecti o n a p pears i n J Aller g y Cli n I m m u n ol Pract 2 0 2 1; 9: 4 5 0 9 -
4 5 1 1].  J Aller g y Cli n I m m u n ol Pract 2 0 2 1; 9: 2 1 9 5-2 2 0 8.  
G o nçal o M, Gi me néz -Ar na u A, Al -A h ma d M, et al. T he gl o bal b ur de n of c hr o nic urticaria f or 
t he patie nt a n d s ociet y. Br J Der mat ol 2 0 2 1; 1 8 4: 2 2 6-2 3 6.  
G o o der ha m MJ, F or ma n S B, Biss o n nette R, et al. Efficac y a n d safet y of oral J a n us ki nase 1 
i n hi bit or a br ociti ni b f or patie nts wit h at o pic der matitis: a p hase 2 ra n d o mize d cli nical trial. 
J A M A Der mat ol 2 0 1 9; 1 5 5: 1 3 7 1-1 3 7 9.  
Her d ma n M, G u d e x C, Ll o y d A, et al. De vel o p me nt a n d preli mi nar y testi n g of t he n e w fi v e -le vel 
ve rsi o n of E Q-5 D ( E Q -5 D -5 L). Q u al Life Res 2 0 1 1; 2 0: 1 7 2 7 -1 7 3 6.  
Her ma ns M A W, Sc hrij ver B, v a n H olte n -Neele n C C P A, et al. T he J A K 1/J A K 2 - i n hi bit or 
r u x oliti ni b i n hi bits mast cell de gra n ul ati o n a n d c yt o ki ne releas e. Cli n E x p Aller g y  
2 0 1 8; 4 8: 1 4 1 2 -1 4 2 0.  
Ka pla n A, L e df or d D, As h b y M, et al. O maliz u ma b i n patie nts wit h s y m pt o matic c hr o nic 
i di o pat hic/s p o nta ne o us urticaria d es pite sta n dar d c o m bi nati o n t hera p y. J Aller g y Cli n I m m u n ol 
2 0 1 3; 1 3 2: 1 0 1 -1 0 9.  
Kir b y J S, O k u n M M, Ala vi A, et al. Efficac y a n d s afet y of t he J a n us ki nase 1 i n hi bit or 
p o v orciti ni b (I N C B 0 5 4 7 0 7) i n patie nts wit h hi dra de nitis s u p p urati va: res ults fr o m a ra n d o mize d, 
place b o -c o ntr olle d, p has e 2 d ose -ra n gi n g st u d y. P oster P 0 0 4 prese nte d at: 3 1st E ur o pea n 
Aca de m y of Der m at ol o g y a n d Ve nere ol o g y C o n gress; Se pte m ber 7‑ 1 0, 2 0 2 2a; Mila n, It al y.  
Kir b y J S, O k u n M M, Ala vi A, et al. Effects of t he J a n us ki nase 1 i n hi bit or p o v orciti ni b 
(I N C B 0 5 4 7 0 7) o n patie nt-re p orte d q u alit y of life i n hi dra de nitis s u p p urati va: res ults fr o m a 
ra n d o mize d, place b o-c o ntr olle d, p hase 2 d os e-ra n gi n g st u d y. P oster P 0 0 5 prese nte d at: 3 1st 
E ur o pea n A ca d e m y of Der mat ol o g y a n d Ve n ere ol o g y C o n gress; Se pte m ber 7 -1 0, 2 0 2 2 b; Mila n, 
Ital y.  
Kir b y J S, O k u n M M, Ala vi A, et al. Effects of t he J a n us ki nase 1 i n hi bit or p o v orciti ni b 
(I N C B 0 5 4 7 0 7) o n patie nt-re p orte d s ki n pai n, a nal gesic us e, a n d itc h i n hi dra de nitis s u p p urati va: 
res ults fr o m a ra n d o mize d, place b o-c o ntr olle d, p h ase 2 d ose -ra n gi n g st u d y. P oster P 0 0 6 
prese nte d at: 3 1st E ur o pea n Aca d e m y of Der mat ol o g y a n d Ve nere ol o g y C o n gress; Se pte m ber 
7‑ 1 0, 2 0 2 2c; Mila n, It al y.  
L a n g D M. C hr o nic urticaria. N E n gl J Me d 2 0 2 2; 3 8 7: 8 2 4 -8 3 1.  
Ma ns o uri P, M ozafari N, C hala n gari R, Martits -C hala n gari K. Efficac y of oral t ofaciti ni b i n 
refract or y c hr o nic s p o nta ne o us urticaria a n d urticarial vasc ulitis. Der mat ol T her 2 0 2 2 ; 3 5:e 1 5 9 3 2. 
Ma urer M, Ber ger W, Gi mé nez -Ar na u A, et al. Re mi br uti ni b, a n o vel B T K i n hi bit or, 
de m o nstrates pr o misi n g effic ac y a n d s afet y i n c hr o nic s p o nta ne o us urticaria [ p u blis he d 
c orrecti o n a p pears i n J Aller g y Cli n I m m u n ol 2 0 2 3; 1 5 1: 5 7 9]. J Aller g y Cli n I m m u n ol 
2 0 2 2; 1 5 0: 1 4 9 8 -1 5 0 6.e 2.  
Me hta C R, Patel N R. E xact l o gistic re gressi o n: t h e or y a n d e x a m ples. Stat Me d 1 9 9 5; 1 4: 2 1 4 3 -
2 1 6 0.  

I nc yte C or p orati o n 
P a ge 9 0  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
Metz M, Altric hter S, B utt gereit T, et al. T he dia g n ostic w or k u p i n c hr o nic s p o nta ne o us 
urticaria -w hat t o test a n d w h y. J Aller g y Cli n I m m u n ol Pract 2 0 2 1; 9: 2 2 7 4 -2 2 8 3.  
M orris R, Kers ha w NJ, Ba b o n JJ. T he m olec ular d etails of c yt o ki ne si g n ali n g via t he J A K/ S T A T 
pat h wa y. Pr otei n Sci 2 0 1 8; 2 7: 1 9 8 4 -2 0 0 9.   
Oetje n  L K, Mac k M R, Fe n g J, et al. Se ns or y ne ur o ns c o -o pt classical i m m u ne si g nali n g 
pat h wa ys t o me diate c hr o nic itc h. Cell 2 0 1 7; 1 7 1: 2 1 7 -2 2 8.  
Pi n heir o J, B or n ka m p B, Gli m m E, Bretz F. M o del -base d d ose fi n di n g u n d er m o del u ncertai nt y 
usi n g ge n eral para metri c m o de ls. Stat Me d 2 0 1 4; 3 3: 1 6 4 6-1 6 6 1.  
P o v orciti ni b I n vesti gat or's Br oc h ure. Wil mi n gt o n, D E: I n c yte C or p orati o n.  
Reill y M C, Z br oze k A S, D u kes E M. T he vali dit y a n d re pr o d uci bilit y of a w or k pr o d ucti vit y a n d 
acti vit y i m pair me nt i nstr u me nt. P har mac oec o n o mics 1 9 9 3; 4: 3 5 3 -3 6 5.  
Sc h oe p ke N, As er o R, Ellric h A, et al. Bi o mar kers a n d cli nical c haracteristics of a ut oi m m u ne 
c hr o nic s p o nta ne o us urticaria: Res ults of t he P U RI S T St u d y. Aller g y 2 0 1 9; 7 4: 2 4 2 7 -2 4 3 6.  
Weller K, Gr offi k A, M a gerl M, et al. De v el o p me nt a n d c o nstr uct val i dati o n of t he a n gi oe de m a 
q ualit y of life q u esti o n naire. Aller g y 2 0 1 2; 6 7: 1 2 8 9 -1 2 9 8.  
Z ha n g Y, Z ha n g H, D u S, Ya n S, Ze n g J. A d va nce d bi o mar kers: t hera pe utic a n d dia g n ostic 
tar gets i n urticaria. I nt Arc h Aller g y I m m u n ol 2 0 2 1; 1 8 2: 9 1 7-9 3 1.  
Z u ber bier T, A b d ul L atiff A H, A b uza k o u k M, et al. T he i nter nati o nal 
E A A CI/ G A² L E N/ E ur o G ui Der m/ A P A A A CI g ui d eli ne f or t he defi niti o n, classificati o n, 
dia g n osis, a n d ma n a ge m e nt of urticari a. Aller g y 2 0 2 2; 7 7: 7 3 4 -7 6 6.  

I nc yte C or p orati o n 
P a ge 9 1  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
A P P E N DI X  A.  I N F O R M A TI O N R E G A R DI NG E F F E C TI V E N E S S O F 
C O N T R A C E P TI V E M E T H O D S A N D  D E FI NI TI O N S  
Defi niti o ns  
W O C B P: A w o ma n w h o is c o nsi dere d fertile f oll o wi n g me narc he a n d u ntil bec o mi n g p ost me n o pa usal u nless 
per ma ne ntl y sterile (see bel o w).  
W o me n i n t he f oll o wi n g cate g ories are c o nsi dere d W O N C B P:  
•  Pre me narc hal  
•  Pre me n o pa usal wit h 1 of t he f oll o wi n g:a 
− D oc u me nte d h ysterect o m y  
− D oc u me nte d bilateral sal pi n ge ct o m y  
− D oc u me nte d bilateral o o p h orect o m y  
•  P ost me n o pa usal  
− A p ost me n o pa usal state is defi ne d as n o me nses f or 1 2 m o nt hs wit h o ut a n alter nati ve me di cal ca use.  
o  A hi g h F S H le vel i n t he p ost me n o pa usal ra n ge ma y be use d t o c o nfir m a p ost me n o pa usal st ate i n 
w o me n n ot usi n g h or m o nal c o ntrace pti o n or H R T. H o we ver, i n t he a bse nce of 1 2 m o nt hs of 
a me n orr hea, c o nfir mati o n wit h 2 F S H meas ure me nts  i n t he p ost me n o pa usal ra n ge is re q uire d. 
− 
La b alert will be defi ne d i n t he st u d y refere nce ma n ual.  
− Fe male partici pa nts o n H R T a n d w h ose me n o pa usal stat us is i n d o u bt will be re q uire d t o use 1 of t he 
n o n h or m o nal, hi g hl y effecti ve c o ntrace pti o n met h o ds if t h e y wis h t o c o nti n ue t heir H R T d uri n g t he st u d y. 
Ot her wise, t he y m ust disc o nti n ue H R T t o all o w c o nfir mati o n of p ost me n o pa usal stat us bef ore st u d y 
e nr oll me nt.  
F or m ale p artici p a nts of re p r o d ucti ve p ote nti al b 
T he f oll o wi n g met h o ds d uri n g t he Pr ot oc ol -defi ne d ti mefra me i n Secti o n  5. 1  are hi g hl y effecti ve:  
•  Use of a male c o n d o m pl us part ner use of a n a d diti o nal  c o ntrace pti ve met h o d w he n ha vi n g pe nile -va gi nal 
i nterc o urse wit h a W O C B P w h o is n ot c urre ntl y pre g na nt 
•  Vasect o m y wit h me dical assess me nt of t he s ur gical s uccess ( verifie d b y site pers o n nel 's re vie w of t he 
partici pa nt 's me dical rec or ds) 
•  P er ma ne ntl y sterile  ( verifie d b y site pers o n nel's re vie w of t he partici pa nt's me dical rec or ds) 
•  Se x ual a bsti ne nce c 
− A bsti ne nce fr o m pe nile -va gi nal i nterc o urse  
T he f oll o wi n g are n ot  acce pta ble met h o ds of c o ntrace pti o n:  
•  P eri o dic a b sti ne nce (cale n dar, 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 met h o d  
•  Male c o n d o m wit h ca p, dia p hra g m, or s p o n ge wit h s per mici de  
•  Male a n d fe male c o n d o m use d t o get her  
N ote: Me n wit h a  pre g na nt or breastfee di n g part ner m ust a gr ee t o re mai n a bsti ne nt fr o m pe nile -va gi nal 
i nterc o urse or use a male c o n d o m d uri n g eac h e pis o de of pe nile pe netrati o n.  

I nc yte C or p orati o n 
P a ge 9 2  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
F or fe m ale p artici p a nts w h o are W O C B P  
T he f oll o wi n g met h o ds d uri n g t he Pr ot oc ol -defi ne d ti mefra me i n Secti o n 5. 1  t hat ca n ac hie ve a fail ure rate of less 
t ha n 1 % per year w he n use d c o nsiste ntl y a n d c orrectl y are c o nsi dere d as hi g hl y effective birt h c o ntr ol met h o ds:  
•  C o m bi ne d (estr o ge n a n d pr o gest o ge n c o ntai ni n g) h or m o nal c o ntrace pti o n ass ociate d wit h i n hi biti o n of 
o v ulati o n d 
− oral  
− i ntra va gi nal 
− tra ns der mal 
•  Pr o gest o ge n -o nl y h or m o nal c o ntrace pti o n a ss ociate d wit h i n hi biti o n of o v ulati o n d 
− oral  
− i nj ecta ble 
− i m pla nta blee 
•  I ntra uteri ne de vicee 
•  I ntra uteri ne h or m o ne-releasi n g s yste me 
•  Bilateral t u bal occl usi o n e 
•  Bilateral t u bal li gati o n e 
•  Vasect o mize d part ner e,f 
•  Se x ual a bsti ne nce c  
a D oc u me ntati o n ca n c o me fr o m t h e site p ers o n nel 's re vie w of t h e partici p a nt's me dical rec or ds, me dic al e xa mi n ati o n, or me dical 
hist or y i nter vie w.  
b If t h e male partici p a nt has a part ner of c hil d beari n g p ote ntial, t he part n er s h o ul d als o use c o ntrace pti ves.  
c I n t h e c o nte xt of t his g ui d a nce, se x ual a bsti n e nce is c o nsi dere d a hig hl y effecti ve met h o d o nl y if defi ne d as refrai ni n g fr o m 
heter ose x ual i nterc o urse d uri n g t he e ntire peri o d of ris k ass ociate d wit h t h e st u d y treat me nt. T he relia bilit y of se x ual a bst i n e nce 
nee ds t o be e val u ate d i n relati o n t o t h e d urati o n of t h e cli nical s t u d y a n d t h e preferre d a n d us ual lifest yle of t h e partici p a nt. 
d H or m o nal c o ntrace pti o n ma y be s usce pti ble t o i nteracti o n wit h t h e i n vesti gati o nal me dici nal pr o d uct, w hic h ma y re d uce t h e 
effic ac y of t h e c o ntrace pti o n met h o d . I n t his case, 2 met h o ds of c o ntrace pti o n s h o ul d be use d. 
e C o ntrace pti o n met h o ds t h at i n t he c o nte xt of t his g ui d a nce are c o nsi d ere d t o ha ve l o w user de pe n de nc y.  
f V asect o mize d part n er is a hi g hl y effecti ve met h o d of a v oi di n g pre g na nc y pr o vi d e d t h at part n er is t he s ole se x ual part n er of t he 
W O C B P st u d y partici p a nt a n d t hat t h e vasect o mize d part n er has recei v e d me dical ass ess me nt of t h e s ur gical s uccess.  
S o urce: Cli nical Trials Facilitati o n a n d C o or di nati o n Gr o u p 2 0 2 0 . 

I nc yte C or p orati o n 
P a ge 9 3  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
A P P E N DI X  B.  LI S T O F S T R O N G S Y S T E MI C C Y P 3 A 4 I N HI BI T O R S 
A N D S T R O N G/ M O D E R A T E S Y S T E MI C C Y P 3 A 4 
I N D U C E R S 
Str o n g S yste mic C Y P 3 A 4 I n hi bit ors 
Str o n g a n d M o der ate S yste mic C Y P 3 A 4 I n d ucers  
•  Ceriti ni b  
•  Clarit hr o m yci n  
•  C o bicistat  
•  Da n o pre vir  
•  Dasa b u vir  
•  El vite gra vir  
•  I delalisi b 
•  I n di na vir 
•  Itrac o naz ole 
•  Ket oc o naz ole  
•  L o pi na vir  
•  Nefaz o d o ne  
•  Nelfi na vir  
•  O m bitas vir  
•  Parita pre vir  
•  P osac o naz ole  
•  Rit o na vir a 
•  Sa q ui na vir  
•  T elit hr o m yci n  
•  Ti pra na vir  
•  Tr olea n d o m yci n  
•  V oric o naz ole  
•  Gra pefr uit/ gra pefr uit j uice  
•  Se ville ora n ges  
•  A pal uta mi de  
•  B ose nta n  
•  Car ba maze pi ne  
•  Ce n o ba mate  
•  Da brafe ni b  
•  Efa vire nz  
•  E nzal uta mi de  
•  Etra viri ne  
•  I v osi de ni b 
•  L orlati ni b  
•  L u macaft or  
•  Mit ota ne  
•  Pe xi darti ni b  
•  P he n o bar bital  
•  P he n yt oi n  
•  Pri mi d o ne  
•  Rifa m pici n/rifa m pi n  
•  Rifa pe nti ne  
•  S ot orasi b  
•  St J o h n 's w ort 
N ote : U p date d lists of C Y P 3 A 4 i n hi bit ors/i n d ucers ca n be f o u n d at t he F D A's Dr u g De vel o p me nt a n d Dr u g 
I nteracti o ns: T a ble of S u bstrates, I n hi bit ors a n d I n d ucers, availa ble at: htt ps:// w w w.f da. g o v/ dr u gs/ dr u g -
i nteracti o ns-la beli n g/ dr u g-de v el o p me nt -a n d -dr u g -i nteracti o ns-ta ble-s u bstrates-i n hi bit ors-a n d -i n d ucers 
a P a xl o vi d ™ is a c o a d mi nistrati o n of nir matrel vir a n d rit o na vir. 

I nc yte C or p orati o n 
P a ge 9 4  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
A P P E N DI X  C.  I N S T R U C TI O N T O P A R TICI P A N T S F O R H A N D LI N G  
S T U D Y D R U G  
T he partici pa nt m ust be i nstr ucte d i n t he ha n dli n g of st u d y dr u g as f oll o ws:  
•  St ore st u d y dr u g at r o o m te m perat ur e ( 1 5° C-3 0° C/ 5 9° F -8 6° F).  
•  Kee p st u d y dr u g i n a s afe place a n d o ut of reac h of c hil dre n.  
•  O nl y re m o ve t he n u m ber of ta blets nee d e d at t he ti me of a d mi nistrati o n.  
•  D o n ot re m o ve d oses i n a d va nce of t h e ne xt sc he d ule d a d mi nistrati o n.  
•  Ta ke st u d y dr u g o nce a d a y, at a b o ut t he sa me ti m e eac h da y.  
− O n site visit da ys, t he d ose will be ta ke n at t he st u d y site.  
•  Ma ke e ver y eff ort t o ta ke d oses o n sc he d ule.  
•  If a d ose of st u d y dr u g is misse d b y m ore t ha n 1 2 h o urs, t hat d ose s h o ul d be s ki p pe d, 
a n d t he ne xt sc he d ule d d ose s h o ul d be a d mi nistere d t he ne xt da y at t he us ual ti me.  
•  Ta ke st u d y dr u g, prefera bl y i n t he m or ni n g, wit h a f ull glass of water.  
− T he st u d y dr u g ca n b e ta ke n wit h or wit h o ut f o o d.  
•  Re p ort a n y misse d d oses/l ost ta blets.  
•  Bri n g all use d a n d u n us e d st u d y  dr u g blister pac ks  t o t he site at eac h visit. 
•  If v o miti n g occ urs aft er t a ki n g st u d y dr u g, d o n ot ta ke a n ot her d os e. If v o miti n g is 
persiste nt, c o ntact t he st u d y site.  

I nc yte C or p orati o n 
P a ge 9 5  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
A P P E N DI X  D.  M A N A G E M E N T O F P O T E N T I A L H Y'S L A W 
C A S E S/ P O T E N TI A L DI LI  
I N T R O D U C TI O N 
D uri n g t h e c o urs e of t he st u d y, t he i n vesti gat or will re mai n vi gila nt f or i n creases i n li ver 
bi oc he mistr y. T h e i n vesti gat or is r es p o nsi ble f or deter mi ni n g w het her a partici pa nt  meets 
p ote ntial H y 's la w criteri a at a n y p oi nt d uri n g t he st u d y. 
T he i n vesti gat or partici p ates, i n c o nj u ncti o n wit h I n c yt e cli nical pr oj ect a n d P har mac o vi gila nce 
re pres e ntati ves, i n t he re vie w a n d assess me nt of cases f ulfilli n g p ote ntial H y's la w criteria t o 
ascert ai n w het her t h ere is a n alter nati ve e x pla nati o n f or t he ele vati o ns i n li ver bi oc he mistr y ot her 
t ha n DI LI ca use d b y t he st u d y dr u g. 
T he i n vesti gat or f ulfills r e q uire me nts f or t h e rec or di n g of data pert ai ni n g t o p ote ntial or H y 's l a w 
cases a n d A E/ S A E re p orti n g acc or di n g t o t he o utc o me of t he re vi e w a n d assess me nt i n li ne wit h 
sta n dar d safet y re p orti n g pr ocesses. 
D E FI NI TI O N S  
F or t he p ur p os e of t his pr ocess, defi niti o ns are as f oll o ws:  
P ote ntial H y 's la w 
A n i ncreas e i n A S T or A L T > 3 × U L N a n d t otal bilir u bi n > 2 × U L N at t h e sa me ti me.  
H y 's la w 
A n i ncreas e i n A S T or A L T ≥ 3 × U L N a n d t otal bilir u bi n  > 2 × U L N, w h ere n o ot her reas o n ca n 
be f o u n d t o e x plai n t he c o m bi nati o n of i ncreases (e g, ele vat e d ser u m A L P/ G G T i n dicati n g 
c h olestasis, viral he patitis, a n ot her dr u g).  
A C TI O N S R E Q UI R E D I N C A S E S O F A S T O R A L T > 3 × U L N A N D C O N C U R R E N T 
T O T A L BI LI R U BI N ≥ 2 × U L N  
I de ntific ati o n a n d Deter mi n ati o n of P ote nti al H y's L a w 
T o i de ntif y cases of A S T or A L T > 3 × U L N a n d t otal bilir u bi n > 2 × U L N a n d c o nse q ue ntl y 
deter mi ne w het h er t he p artici pa nt meets p ote ntial H y 's la w criteria, pleas e f oll o w t he i nstr ucti o ns 
bel o w:  
•  Re vie w t he la b orat or y re p ort a n d if a partici pa nt h as A S T or A L T > 3 × U L N or t otal 
bilir u bi n > 2 × U L N at a n y visit:  
− Deter mi ne wit h o ut dela y w het her t he p artici pa nt  meets p ote ntial H y 's l a w criteria 
b y re vie wi n g la b orat or y re p orts fr o m all pre vi o us visit s. 
− E nter t he la b orat or y data i nt o t he la b orat or y e C R F as s o o n as p ossi ble.  

I nc yte C or p orati o n 
P a ge 9 6  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
P ote nti al H y 's L a w Criteri a N ot Met 
If t he partici p a nt  has n ot ha d A S T or A L T ≥ 3 × U L N a n d t otal bilir u bi n > 2 × U L N, irres pecti ve 
of A L P, ple ase f oll o w t h e i nstr ucti o n bel o w:  
•  Perf or m f oll o w -u p o n s u bse q ue nt la b orat or y res ults acc or di n g t o t he g ui da nce 
pr o vi de d i n E val uati o n of Alter nati ve Ca us es ( bel o w) . 
P ote nti al H y 's L a w Criteri a Met 
If t he partici p a nt has ha d A S T or A L T ≥ 3 × U L N a n d t otal bilir u bi n > 2 × U L N, irres p ecti ve of 
A L P, ple ase f oll o w t he i nstr ucti o n bel o w:  
•  Ha ve t he p artici pa nt  i nterr u pt st u d y dr u g. 
•  N otif y t he I nc yte st u d y te a m wit h o ut dela y.  
− T he i n vesti gat or or desi g nee s h o ul d c o ntact t he m e dical m o nit or t o disc uss a n d 
a gree u p o n a n a p pr oac h f or t he st u d y p artici pa nt 's f oll o w-u p a n d t he c o nti n u o us 
re vie w of data. 
•  M o nit or t he partici pa nt u ntil li ver bi oc he mistr y para meters, c oa g ulati o n, a n d 
a p pr o priate cli nical s y m pt o ms a n d si g ns ret ur n t o n or mal or baseli ne le vels, or as 
me dicall y i n dicate d.  
•  I n v esti gate t he eti ol o g y of t he e ve nt a n d perf or m a n y rele va nt dia g n ostic 
i n vesti gati o ns as disc usse d wit h t he me dical m o nit or. 
•  E nter t he la b orat or y data i nt o t he La b orat or y e C R F as s o o n as p ossi ble.  
•  If at a n y ti me (i n c o ns ult ati o n wit h t he me dical m o nit or) t he p ote ntial H y's la w case 
meets seri o us criteria, re p ort it as a n S A E usi n g st a n dar d re p orti n g pr oce d ures.  
R E VI E W A N D A S S E S S M E N T  
N o later t ha n 3 wee ks after t he bi oc he mistr y a b n or malit y is i nitiall y detecte d a n d t he criteria f or 
p ote ntial H y 's la w are met, t he me dical m o nit or a n d i n vesti gat or will disc uss a n d re vie w 
a vaila ble data a n d a gree o n w het her t here is a n alt er nati ve e x pla nati o n f or t he ele vati o ns i n li ver 
bi oc he mistr y ot her t ha n DI LI ca use d b y t he st u d y dr u g. P artici pa nt matter e x perts will be 
i ncl u de d i n t he re vie w as a ppr o priate.  
E v al u ati o n of Alter n ati ve C a uses  
I n or der t o gat h er a d diti o nal cli nical i nf or mati o n t o see k ot her p ossi ble ca uses of t he o bser ve d 
li ver test a b n or malities, t he f oll o wi n g alter nati ve eti ol o gies s h o ul d be c o nsi dere d, i ncl u di n g b ut 
n ot li mite d t o:  
•  Acti ve viral he p atitis  
•  Alc o h olic a n d a ut oi m m u ne he patitis  

I nc yte C or p orati o n 
P a ge 9 7  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
•  He pat o biliar y dis or ders  
− Biliar y tract disease, s u c h as mi grati o n of gallst o nes or i ntra he p atic lesi o ns, m ore 
ofte n ca us es c h olestatic i nj ur y i nitiall y a n d s h o ul d be i n vesti gat e d wit h 
gall bla d d er a n d  d u ctal i ma gi n g st u dies, es p eciall y if A L P/ G G T is i ncreas e d. 
Mali g na nt i nterr u pti o n of t he biliar y tr act als o s h o ul d be c o nsi dere d.  
•  C o nc o mita nt treat me nt  
•  Ot her ca us es s uc h as s yst e mic i nfecti o ns (e g, b act erial, f u n gal, viral), n o nal c o h olic 
steat o he patitis, a n d car di o vasc ular dise ases  
Acti o ns After Re vi e w a n d Assess me nt  
Acc or di n g t o t he o utc o m e of t he re vie w a n d assess me nt, please f oll o w t he i nstr ucti o ns bel o w:  
If t here is a n a gree d alter nati ve e x pla nati o n f or t he A S T or A L T a n d  t otal bilir u bi n ele vati o ns, a 
deter mi nati o n of w het h er t he alter nati ve e x pla nati o n is a n A E will be ma de a n d s u bse q ue ntl y 
w het her t he A E meets t h e criteri a f or a n S A E.  
•  If t he alter nati ve e x pla nati o n is n ot a n A E, rec or d t he alter nati ve e x pla nati o n o n t he 
a p pr o priate e C R F if p ossi ble.  
•  If t he alter nati ve e x pla nati o n is a n A E/ S A E, rec or d t he A E/ S A E i n t he e C R F 
acc or di n gl y a n d f oll o w t he sta n dar d st u d y pr ocesses.  
•  Ha ve t he p artici pa nt  res u me st u d y dr u g as per Pr ot oc ol g ui deli nes. 
If it is a gree d t h at t here is no e x pla nati o n t hat w o ul d e x plai n t he A S T or A L T a n d t otal bilir u bi n 
ele vati o ns:  
•  Ha ve t he p artici pa nt  per ma ne ntl y disc o nti n ue st u d y dr u g a n d perf or m E O T 
pr oce d ures.  
•  Re p ort a n S A E (re p ort ter m "H y 's la w"). 
− T he 'me dicall y i m p orta nt ' seri o us criteri o n s h o ul d be use d if n o ot her s eri o us 
criteria a p pl y.  
− As t here is n o alter nati ve e x pla nati o n f or t he H y 's la w case, a ca usalit y assess me nt 
of relate d m a y be assi g ne d.  
•  If t here is a n u na v oi da ble dela y of o ver 3 wee ks i n o btai ni n g t he i nf or m ati o n 
necessar y t o assess w h et her or n ot t he case meets t he criteria f or a H y 's l a w case, t he n 
it is ass u me d t hat t here is n o alter nati ve e x pla nati o n u ntil s uc h ti me as a n i nf or me d 
decisi o n ca n be m a de. Re p ort a n S A E (re p ort ter m "P ote ntial H y 's la w") a p pl yi n g 
seri o us criteria a n d causalit y assess me nt as per a b o ve.  

I nc yte C or p orati o n 
P a ge 9 8  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
A C TI O N S R E Q UI R E D F O R R E P E A T E PI S O D E S O F A S T O R A L T > 3 × U L N A N D/ O R 
T O T A L BI LI R U BI N > 2 × U L N  
T he re q uir e me nt t o c o n d uct f oll o w -u p, re vie w, a n d assess me nt of a re peat occ urre nce(s) of 
p ote ntial H y 's la w is b ase d o n t he nat ure of t h e alter nati ve ca us e i de ntifie d f or t he pre vi o us 
occ urre nce.  
If t he alter nati ve ca use f or t he pre vi o us occ urre nce of p ote ntial H y's l a w was n ot c hr o nic or 
pr o gressi n g mali g n a nt disease, ple ase f oll o w t he pr ocess f or p ote ntial H y 's la w re vie w a n d 
assess me nt as descri be d i n t his a p pe n di x.  
If t he alter nati ve ca use f or t he pre vi o us occ urre nce of p ote ntial H y's l a w was c hr o nic or 
pr o gressi n g mali g n a nt disease, ple ase f oll o w t he i nstr ucti o ns bel o w:  
•  Deter mi ne  w h et her t here has bee n a si g nifica nt c ha n ge * i n t he partici p a nt 's c o n diti o n. 
− If t here is n o si g nifica nt c ha n ge, n o acti o n is re q uire d. 
− If t here is a si g nifi ca nt c ha n ge, f oll o w t he pr ocess descri be d f or p ote ntial H y's la w 
re vie w a n d assess me nt as descri be d i n t his a p pe n di x. 
*  A 'si g nifica nt' c ha n ge i n t he partici pa nt 's c o n diti o n refers t o a cli nicall y rele va nt c ha n ge i n A L T, A S T, or t otal 
bilir u bi n or ass ociate d s y m pt o ms. T he deter mi nati o n of w het her t here has bee n a si g nifica nt c ha n ge will be at t he 
discreti o n of t he i n vesti gat or; t his ma y b e i n c o ns ultati o n wit h t he me dical m o nit or if t here is a n y u ncertai nt y.  
Si g nifica nt c ha n ges w o ul d i ncl u de ne w o nset or w orse ni n g j a u n dice, fati g ue, pr urit us, na usea, v o miti n g, 
pale -c ol ore d st o ols, a n d dar k uri ne. Cli nicall y rele va nt c ha n ges i n li ver f u ncti o n, t hat is, decrease i n s y nt hesis of 
al b u mi n a n d cl otti n g fact ors, w o ul d prese nt wit h e de ma, h y perc oa g ula bilit y, br uisi n g, a n d blee di n g.  

I nc yte C or p orati o n 
P a ge 9 9  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
A P P E N DI X  E.  C O VI D -1 9 P A N D E MI C MI TI G A TI O N S T R A T E GI E S A N D 
I N S T R U C TI O N S 
T he C O VI D -1 9 gl o b al pa n de mic is a n e v ol vi n g sit uati o n a n d pre se nts n u m er o us c halle n ges t o 
t he o n g oi n g c o n d u ct of cli nical trials. T he s p o ns or has iss ue d t he f oll o wi n g Pr ot oc ol 
c o nsi derati o ns t o e ns ure partici pa nt safet y is mai ntai ne d a n d a d e q uate be nefit/ris k a nal ys es are 
a p plie d relati ve t o t he c o m pleti o n of st u d y pr oce d ures a n d mai ntai ni n g t he i n vesti gati o nal 
pr o d uct s u p pl y c hai n.  
Rec o g nizi n g t h e fle xi bilit y re q uire d t o ma n a ge t he i m pact of t he pa n de mic o n t his cli nical trial, 
a d diti o nal details will be a d de d as nee de d t o r es pecti ve st u d y ma n uals a n d pr oject pla n 
d oc u me nts a n d c o m m u nicate d t o t he i n vesti gati ve sites as nee de d.  
N u m ber of St u d y P arti ci p a nts  
T he e v ol vi n g sit uati o n of t he pa n de mic ma y res ult i n a s u bsta ntial n u m ber of partici pa nts ' earl y 
wit h dra wal fr o m t he st u d y, w hic h c o ul d affect t he data i nte grit y of t he st u d y. Beca use of t his ris k 
a n d i n or der t o miti gate it, t he s p o ns or ma y deci de t o recr uit a d diti o nal parti ci pa nts i n t he st u d y, 
be y o n d t h e e x pecte d n u m ber.  
St u d y Visits  
Re m ote Site Visit G ui deli nes  
N ote: Re m ote visits are n ot a p plica ble i n c o u ntries w here re m ote visits are n ot per mitte d b y l ocal 
la w. 
T he e v ol vi n g sit uati o n of t he pa n de mic ma y re q uir e f urt her tra vel r estricti o ns a n d is olati o n 
re q uire me nts, or t h e i n vesti gat or's be n efit/ris k ass essme nt ma y d eter mi ne it t o be u nsafe f or 
partici pa nts t o atte n d st u d y visits at t he i n vesti gati o nal site. I n s u c h cas es, t he site staff ma y elect 
t o p urs ue t he f oll o wi n g: 
•  I n or der t o mi ni miz e partici pa nt ris k, st u d y visits ma y b e c o n d uct e d via tel e me dici ne 
m o dalities (tele p h o ne or vi de o calls). At a mi ni m u m, a re vie w of A Es, c o n c o mita nt 
me dicati o ns, a n d st u d y dr u g c o m plia nce m ust be c o m plete d.  
•  N o effic ac y assess me nts ca n be p erf or m e d via tele me dici ne ( vi de o call, p h o ne call, or 
via p h ot o gra p h y).  
•  La b orat or y s a m pli n g: i n or der t o s u p p ort i n vesti gat or o versi g ht of partici pa nt safet y 
a n d disease ma n a ge me nt, off -site la b orat or y sa m pli n g (i n acc or da nce wit h t he S o A; 
see Ta ble  3 ) ma y be all o we d as f oll o ws: 
− I nstr u ct t he partici p a nt t o u n der g o s o me la b orat or y tests at a l o cal ( near b y) 
h os pital la b orat or y or facilit y cl oser t o t he partici pa nt 's resi de nce rat h er t ha n at t he 
i n vesti gati o nal site. I n t his case, t he st u d y p h ysicia n will pr o vi de t he partici pa nt 
wit h t he list of para meters t o be c hec k e d. T hese t ests s h o ul d be perf or me d at 
certifie d la b orat ories a n d c o pies of res ults pr o vi de d t o t he site.  

I nc yte C or p orati o n 
P a ge 1 0 0  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
O n -site visits s h o ul d be c o n d ucte d w he n e ver feasi ble, i n a d diti o n t o t he ma n dat or y o n -site visits 
o utli ne d bel o w, e ve n if t he date t hat t he partici pa nt e ve nt uall y c o mes i nt o t he cli nic de viates 
fr o m t he visit wi n d o w. 
M a n d at or y O n -Site Visits  
T he visits o utli ne d bel o w m ust be pe rf or me d i n pers o n  i n or der t o ca pt ur e t he i n vesti gat or 's 
effic ac y ass ess me nts a n d t he P R Os, e ve n if t he date t hat t he partici pa nt e v e nt uall y c o mes i nt o t he 
cli nic de viates fr o m t he visit wi n d o w.  
N o effic ac y assess me nts ca n be p erf or m e d via tele me dici ne ( vi de o call, tele p h o ne call, or 
p h ot o gra p h y).  
T he vis it wi n d o w de viati o n m ust be d oc u me nte d, a n d t he s p o ns or's re prese ntati ve m ust be 
i nf or me d of w h e n it is belie ve d t hat t he partici pa nt ca n c o me i nt o t he cli nic. F urt her i nstr u cti o ns 
will be pr o vi de d if nee d e d.  
T he f oll o wi n g visits m ust be perf or m e d i n pers o n:  
•  Scree ni n g  
•  D a y 1  ( bas eli ne) visit  
•  Wee k 1 2  visit  
D uri n g t h e E X T peri o d, t he f oll o wi n g visits m ust be perf or me d i n pers o n  
•  Wee k 2 4 visit  
•  Wee k 3 6 visit  
I n vesti g ati o n al Me dici n al Pr o d uct Dis pe ns ati o n a n d Distri b uti o n 
I n or der t o e ns ure t he c o nti n uit y of pr o vi di n g t h eir partici pa nts ' cli nical s u p plies wit hi n t he 
c o nstrai nts i m parte d b y t he pa n de mic, t he site staff ca n deci de t o s u p pl y st u d y dr u g vi a s hi p me nt 
t o partici pa nts. 
If t he partici p a nt ca n n ot atte n d a visit at t he st u d y site, a de q uate s u p plies of st u d y dr u g 
deter mi ne d b y t he i n vesti gat or ca n b e s hi p pe d t o t he partici pa nt b y t he i n vesti gat or or 
a p pr o priatel y d ele gate d staff (e g, t h e st u d y p h ar m ac y staff) usi n g a t hir d -p art y s er vice if d ul y 
a ut h orize d b y t he p artici pa nt.  
T he st u d y site ma y us e t heir o w n preferre d c o urier, pr o vi de d t he c o uri er a d heres t o c ertai n 
sta n dar ds (e g, us e of pers o nal pr otecti o n e q ui p me nt, mai nte na nce of t e m perat ure -c o ntr olle d 
tra nsit e n vir o n me nt), or o ne ce ntr all y c o ntract e d b y t he s p o ns or. 
Cli nic al Tri al M o nit ori n g  
St u d y m o nit ori n g visits ma y b e p ost p o ne d d ue t o d oc u me nte d C O VI D -1 9 – relate d reas o ns; 
h o we ver, t he site m o nit or will c o nti n ue t o e m pl o y off -site m o nit ori n g practi ces s uc h as r o uti ne 
c o m m u nicati o n met h o ds (e g, p h o ne calls, e -mails, vi de o visits) wit h t he sites t o get i nf or mati o n 
o n trial pr o gress, partici pa nt stat us, a n d i nf or mati o n o n iss ue res ol uti o n. T he st u d y m o nit or ma y 
re m otel y re vie w data e ntere d i nt o t he E D C f or acc urac y a n d c o m plete ness. If all o we d b y l ocal 

I nc yte C or p orati o n 
P a ge 1 0 1  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
re g ulati o ns, re m ote s o ur ce data verificati o n ma y b e i mple me nte d wit h a gree me nt of t he pri nci p al 
i n vesti gat or a n d i nstit uti o n, as a p plica ble. 
If t he st u d y site m o nit or ca n n ot be o n-site t o perf or m t he fi nal dr u g acc o u nt a bilit y f or 
rec o nciliati o n p ur p oses a n d t he o perati o n ca n n ot be p ost p o ne d, it ma y b e perf or me d b y a 
p har macist fr o m t he h os pital p har mac y or b y t h e st u d y c o or di nat or/ data m a na ger wit h s uita ble 
trai ni n g. T h e st u d y dr u g ca n be ret ur ne d t o t he s p o ns or b y t he h os pital p har mac y directl y or 
destr o ye d i n acc or da n ce wit h l ocal practices, if a p plica ble, a n d wit h s p o ns or a p pr o val.  
Ot her C o nsi der ati o ns  
If necessar y, dir ect c o ntracts ca n b e esta blis he d wit h t hir d-part y l ocal p h ysicia ns t o c o n d uct 
acti vities relate d t o t he cli nical ma na ge me nt of p artici pa nts f or w h o m t he i n vesti gat or is 
res p o nsi ble a n d mai ntains o versi g ht. I n s u c h sit uati o ns, t he i n vesti gat or is r e q uire d t o pr o vi de t he 
l ocal p h ysici a n wit h a del e gati o n letter listi n g all d ele gate d acti vities. T he s p o ns or, t hr o u g h t h e 
st u d y i n vesti gat or or i nstit uti o n, will rei m b urse t he l ocal p h ysici a n f or t he t ests/ pr oce d ures 
c o n d ucte d o utsi de of t he S O C . 
•  I n case of nee d, p artici pa nts ma y refer t o t he l ocal healt h care pr o vi der. Partici pa nts will 
be re q uest e d t o o btai n certifie d c o pies of t he s o urce data at t he l ocal healt h facilit y wit h 
t he o utc o me of t he c o ntact a n d pr o vi de t h ose t o t h e i n vesti gat or f or a p pr o priate o versi g ht. 
T he i n vesti gat or/ dele gat e will be re q ueste d t o e nt er a n y rel e va nt i nf or mati o n i nt o t he 
E D C.  
•  S h o ul d C O VI D -1 9 – relat e d restricti o ns be l ocalize d a n d ha ve a n effect o n a li mite d 
n u m ber of sit es, t he affecte d sites ma y utilize direct c o ntracti n g of t hir d parties t o s u p p ort 
c o nti n u o us st u d y c o n d uct (e g, h o me n ursi n g ser vices, c o uriers, etc).  
Rei m b urse me nt of E xtr a or di n ar y E x pe nses  
T he s p o ns or will arra n ge t o rei m b urse partici p a nts f or a n y e xtra o r di nar y e x pe nses, kee pi n g 
a p pr o priate d o c u me ntati o n as e vi de nce (e g, tr a vel e x pe nses f or t he l ocal la b orat or y visit[s], t he 
c osts of l ocal [ near b y] l a b orat or y tests).  

I nc yte C or p orati o n 
P a ge 1 0 2  of 1 0 2  
Pr ot oc ol I N C B 5 4 7 0 7 -2 0 7  
Versi o n 1  
0 7 M A R  2 0 2 3  
V V -C LI N -0 2 2 4 5 3  
C O N FI D E N TI A L  
A P P E N DI X  F.  P R O T O C O L A M E N D M E N T S U M M A R Y O F C H A N G E S  
N ot a p plica ble.  

Si g nat ure Pa ge f or V V- C LI N- 0 2 2 4 5 3 v 2. 0
Si g nat ure Pa ge f or V V- C LI N- 0 2 2 4 5 3 v 2. 0
A p pr o val Tas k
A p pr o ver
 Bi ostatisticia n
0 7- Mar- 2 0 2 3 1 8: 2 8: 1 9 G M T + 0 0 0 0
A p pr o val Tas k
of I nfla m mati o n a n d
A ut oI m m u nit y Gr o u p
0 7- Mar- 2 0 2 3 1 8: 5 3: 4 8 G M T + 0 0 0 0
A p pr o val Tas k
I nfla m mati o n a n d
A ut oI m m u nit y
0 7- Mar- 2 0 2 3 2 0: 4 7: 4 9 G M T + 0 0 0 0
A p pr o val Tas k
r
 Cli nical O perati o ns
0 7- Mar- 2 0 2 3 2 1: 4 3: 4 0 G M T + 0 0 0 0
A p pr o val Tas k
A p pr o ver
 Cli nical Researc h Scie ntist
0 8- Mar- 2 0 2 3 1 3: 1 4: 2 6 G M T + 0 0 0 0
A p pr o val Tas k
 Gl o bal Pr o gra m Hea d
0 8- Mar- 2 0 2 3 1 5: 3 9: 0 4 G M T + 0 0 0 0