Clinical Pharmacology of LT5001 Drug Product in Hemodialysis Patients With Uremic Pruritus to Assess the Safety, Local Tolerance and Pharmacokinetics
Phase: PHASE1
Conditions: Uremic Pruritus
Sponsor: Lumosa Therapeutics Co., Ltd.

Cli nic al St u d y Pr ot oc ol  
Cli nic al P h ar m ac ol o g y of L T 5 0 0 1  Dr u g Pr o d uct  i n He m o di al ysis P atie nts 
Wit h  Ure mic Pr urit us t o Assess t he S afet y, L oc al T oler a nce a n d 
P h ar m ac o ki netics  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
S p o ns or : 
L u m osa T hera p e utics C o., Lt d.  
4 t h F l o or, N o. 3 -2, Par k Street, Na n g a n g Dist., 
Tai pei 1 1 5 0 3,  
Tai wa n, R. O. C.  
Tele p h o ne: + 8 8 6 -2 -2 6 5 5 7 9 1 8  
Fa x: + 8 8 6 -2 -2 6 5 5 7 9 1 9  
C o nfi de nti alit y St ate me nt  
T his d oc u me nt a n d t he i nf or mati o n c o ntai ne d herei n or attac he d heret o (" C o nfi de ntial Material") are 
c o nfi de ntial a n d pr o prietar y t o L u m osa T hera pe utics C o., Lt d . T his C o nfi de ntial Material s h o ul d be vie we d 
o nl y b y t h o se i n di vi d uals or the pa rties t hat ha ve bee n gi ve n pri or a ut h orizati o n t o d o s o b y L u m osa 
T hera pe utics C o., Lt d  (" A ut h orize d Users"). T his C o nfi de ntial Material s h o ul d n ot be ma de a vaila ble i n 
a n y f or m t o a n y pers o n o r c o m pa n y, ot her t ha n t he A ut h orize d Users a n d t heir res pecti ve e m pl o yees or 
ass ociates o n a nee d -t o-k n o w basis, wit h o ut t he pri or wri tte n c o nse nt fr o m L u m osa T hera pe utics C o., Lt d . 

P r ot oc ol A p pr o v al –  S p o ns or S i g n at ure P a ge  
 
St u d y Title  
Cli nical P har mac ol o g y of L T 5 0 0 1 Dr u g Pr o d uct i n He m o dial ysis 
Patie nts Wit h Ure mic Pr urit us t o Assess t he Safet y, L ocal Tolera n ce a n d 
P har mac o ki netics  
Pr ot oc ol N u m ber  
L T 5 0 0 1 -1 0 1  
Pr ot oc ol Versi o n  
Versi o n 4 .3  
P r ot oc ol D ate  
0 4  Se p , 2 0 2 0  
 
P r ot oc ol re vie we d a n d a p pr o ve d b y L u m osa T hera pe utics C o., Lt d . 
 
 
 
 
 
 
Date ( D D -M m m -Y Y Y Y)  
 
 
 

P r ot oc ol A p pr o v al – I n vesti g at or S i g n at ure P a ge 
 
Decl ar ati o n of C urre nt G o o d Cli nic al Pr actice ( G C P)  C o m pli a nce St ate me nt  
 
•  I c o nfir me d t hat I h a ve caref ull y rea d a n d u n derst o o d t his pr ot oc ol a n d a gree t o c o n d u ct t his 
cli nical st u d y as o utli ne d i n t his pr ot oc ol, acc or di n g t o c urre nt G o o d Cli nical Practice a n d l ocal 
la ws a n d re q uire me nts. 
•  I will e ns ure t hat all s u bi n vesti gat ors a n d ot her staff me m bers rea d a n d u n derst o o d all as pects 
of t his pr ot oc ol.  
•  I h a ve recei ve d a n d rea d all st u d y-relate d i nf or m ati o n pr o vi de d t o me. 
•  T he o bjecti ves a n d c o nte nt of t his pr ot oc ol as well as t he res ults deri vi n g fr o m it will be treate d 
c o nfi de ntiall y, a n d will n ot be ma de a vaila ble t o t hir d parties wit h o ut pri or a ut h orizati o n b y 
S p o ns or.  
•  All ri g hts of p u blicati o n of t he res ults ma de b y t he S p o ns or, u nless ot her a gree me nts were ma de 
i n a se parate c o ntr act 
 
 
 
 
Si g nat ure of Pri nci pal I n vesti gat or 
 
Date ( D D -M m m -Y Y Y Y)  
 
 
 
 
Pri nte d Na me of Pri nci pal I n vesti gat or  
 
 
St u d y Title  
Cli nical P har mac ol o g y of L T 5 0 0 1 Dr u g Pr o d uct i n He m o dial ysis 
Patie nts Wit h Ure mic Pr urit us t o Assess t he Safet y, L ocal Tolera n ce a n d 
P har mac o ki netics  
Pr ot oc ol N u m ber  
L T 5 0 0 1 -1 0 1  
Pr ot oc ol Versi o n  
Versi o n 4 .3  
P r ot oc ol D ate  
0 4  Se p , 2 0 2 0  

L u m osa T hera pe utics C o., Lt d.  
 
P r ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date:  0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 4  
T A B L E O F C O N T E N T S  
LI S T O F T A B L E S  .........................................................................................................................7  
LI S T O F FI G U R E S  .......................................................................................................................7  
1  
S T U D Y S Y N O P SI S  .......................................................................................................8  
2  
S C H E D U L E O F A S S E S S M E N T S A N D P R O C E D U R E S  ......................................1 7  
LI S T O F A B B R E VI A TI O N S  .....................................................................................................2 2  
S T U D Y A D MI NI S T R A TI V E S T R U C T U R E  ...........................................................................2 3  
3  
I N T R O D U C TI O N A N D B A C K G R O U N D ...............................................................2 4  
3. 1  
I ntr o d ucti o n ..........................................................................................................2 4  
3. 2  
St u d y Dr u g B ac k gr o u n d  .....................................................................................2 4  
3. 3  
S u m m ar y of Fi n di n gs t o D ate  .............................................................................2 5  
3. 4  
St u d y R ati o n ale  ....................................................................................................2 5  
 
D ose Rati o nale  .......................................................................................................2 5  
 
St u d y Desi g n Rati o nale ..........................................................................................2 6  
3. 5  
H y p ot heses  ............................................................................................................2 7  
4  
O B J E C TI V E S  .............................................................................................................2 8  
4. 1  
Pri m ar y O bjecti ve –  P a rt A  ................................................................................2 8  
4. 2  
Pri m ar y O bjecti ve –  P a rt B  ................................................................................2 8  
5  
S T U D Y D E SI G N  .........................................................................................................2 9  
5. 1  
St u d y Desi g n a n d O ver vie w  ................................................................................2 9  
 
I nteri m Safet y/ P har mac o ki netic Data Re vie w ......................................................3 2  
 
D urati o n of St u d y  ...................................................................................................3 3  
 
Defi niti o n of St u d y C o m pleti o n .............................................................................3 3  
 
E n d of St u d y  ..........................................................................................................3 3  
6  
S E L E C TI O N A N D WI T H D R A W A L O F P A TI E N T S  ............................................3 4  
6. 1  
I ncl usi o n Criteri a .................................................................................................3 4  
6. 2  
E xcl usi o n Criteri a  ................................................................................................3 5  
6. 3  
Scree n  F ail ures  .....................................................................................................3 6  
6. 4  
P atie nt Wit h dr a w al  ..............................................................................................3 6  
6. 5  
E arl y Ter mi n ati o n of St u d y  ................................................................................3 7  
7  
T R E A T M E N T O F P A TI E N T S  .................................................................................3 8  
7. 1  
I de ntit y of St u d y Dr u gs .......................................................................................3 8  
7. 2  
Tre at me nts A d mi nistere d  ...................................................................................3 8  
7. 3  
Me t h o d of Assi g ni n g P atie nts t o Tre at me nt Gr o u ps ........................................3 8  
7. 4  
Me as ure me nts of Tre at me nt C o m pli a nce  .........................................................3 9  
7. 5  
St u d y Dr u g St or a ge, Acc o u nt a bilit y, a n d Rete nti o n  ........................................3 9  

L u m osa T hera pe utics C o., Lt d.  
 
P r ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date:  0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 5  
 
St ora ge C o n diti o ns  .................................................................................................3 9  
 
Dr u g Acc o u nta bilit y a n d Rete nti o n  .......................................................................3 9  
7. 6  
P ac k a gi n g a n d L a beli n g  ......................................................................................3 9  
 
St u d y Dr u g  .............................................................................................................3 9  
 
Bli n di n g o f Treat me nt Assi g n me nt ........................................................................4 0  
 
U n bli n di n g of Treat me nt Assi g n me nt  ...................................................................4 0  
7. 7  
C o nc o mit a nt Me dic ati o ns & Pr oce d ures/ Pr o hi bite d me dic ati o n/ Ot her 
Restricti o ns  ...........................................................................................................4 0  
 
C o nc o mita nt Me dicati o ns  ......................................................................................4 0  
 
C o nc o mita nt pr oce d ures  ........................................................................................4 1  
 
Pr o hi bite d me dicati o n  ............................................................................................4 1  
 
Ot her Restricti o ns  ..................................................................................................4 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  .....................................................4 2  
8. 1  
Di ar y r u n -i n ( 7-d a ys itc h N R S)  ...........................................................................4 2  
8. 2  
7 -d a ys Re pe ate d o pe n a p plic ati o n tests ( 7 -d a ys R O A T)  ..................................4 2  
8. 3  
Me dic al a n d S ur gic al Hist or y  .............................................................................4 2  
8. 4  
De m o gr a p hic C h ar acteristics  .............................................................................4 2  
8. 5  
P h ysic al Me as ure me nts  .......................................................................................4 2  
8. 6  
Itc h assess me nts ...................................................................................................4 3  
 
Dail y Assess me nt of t he itc h i nte nsit y b y t he patie nt  ............................................4 3  
 
Q uesti o n naire i nter vie we d b y i n vesti gat or or desi g nee .........................................4 3  
8. 7  
P h ar m ac o ki netic Assess m e nts  ............................................................................4 4  
 
Dr u g C o nce ntr ati o n Meas ure me nts  .......................................................................4 4  
 
P har mac o ki netic Para meters  ..................................................................................4 4  
8. 8  
S afet y Assess me nts  ...............................................................................................4 4  
 
A d verse E v e nts  ......................................................................................................4 4  
 
Cli nical La b orat or y Tests  .......................................................................................4 4  
 
Ot her Tests  .............................................................................................................4 7  
 
Vital Si g ns  ..............................................................................................................4 7  
 
P h ysical E xa mi nati o n .............................................................................................4 7  
 
A p plicati o n Site E xa mi nati o n  ................................................................................4 8  
 
A p pr o priate n ess of Safet y Assess me nts  ................................................................4 8  
9  
A D V E R S E E V E N T S  ...................................................................................................4 9  
9. 1  
Rec or di n g A d verse E ve nts  ..................................................................................4 9  
9. 2  
Assess m e nt of A d verse E ve nts  ............................................................................4 9  
 
Seri o us A d verse E v e nts  .........................................................................................5 0  
 
I nte nsit y..................................................................................................................5 0  
 
Relati o ns hi p t o St u d y Dr u g  ....................................................................................5 0  
9. 3  
Disc o nti n u ati o n d ue t o A d verse E ve nts  .............................................................5 1  
9. 4  
Re p orti n g Seri o us A d verse E ve nts  .....................................................................5 2  
9. 5  
Pre g n a nc y  .............................................................................................................5 2  
1 0  
S T A TI S TI C A L C O N SI D E R A TI O N S  ......................................................................5 3  
1 0. 1  
S a m ple Size C alc ul ati o n  ......................................................................................5 3  
1 0. 2  
A n al ysis P o p ul ati o ns  ............................................................................................5 3  

L u m osa T hera pe utics C o., Lt d.  
 
P r ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m b er: L T 5 0 0 1 -1 0 1  
 
Date:  0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 6  
1 0. 3  
R a n d o miz ati o n  .....................................................................................................5 3  
1 0. 4  
E n d p oi nts  ..............................................................................................................5 3  
 
Part A Pri mar y E n d p oi nt  ........................................................................................5 3  
 
Part A Sec o n dar y E n d p oi nts  ..................................................................................5 3  
 
Part B Pri mar y E n d p oi nt  ........................................................................................5 4  
 
Part B Sec o n dar y E n d p oi nts  ..................................................................................5 4  
1 0. 5  
P h ar m ac o ki netic A n al ysis P art A ( o nl y) ............................................................5 4  
1 0. 6  
S afet y A n al ysis  .....................................................................................................5 5  
1 0. 7  
Effic ac y A n al ysis  ..................................................................................................5 5  
1 0. 8  
Ot her  St atistic al C o nsi der ati o ns  .........................................................................5 6  
1 0. 9  
Dr o p o uts, Pre m at ure T er mi n ati o n, a n d Missi n g V al ues  .................................5 6  
1 0. 1 0  
I nteri m A n al ysis ...................................................................................................5 6  
1 1  
A C C E S S T O S O U R C E D A T A/ D O C U M E N T S  .......................................................5 7  
1 2  
Q U A LI T Y C O N T R O L A N D Q U A LI T Y A S S U R A N C E  ........................................5 8  
1 2. 1  
C o n d uct of St u d y ..................................................................................................5 8  
 
Pr ot oc ol De viati o ns  ................................................................................................5 8  
1 2. 2  
Pr ot oc ol A me n d me nts  .........................................................................................5 8  
1 2. 3  
M o nit ori n g of St u d y  .............................................................................................5 9  
1 3  
E T HI C S  ........................................................................................................................6 0  
1 3. 1  
I nstit uti o n al Re vie w B o ar d/I n de pe n de nt Et hics C o m mittee A p pr o v al  ..........6 0  
 
Et hics Re vie w Pri or t o St u d y  .................................................................................6 0  
 
Et hics Re vie w of Ot her D oc u me nts  .......................................................................6 0  
1 3. 2  
Writte n I nf or me d C o nse nt  ..................................................................................6 0  
1 4  
D A T A H A N D LI N G A N D R E C O R D K E E PI N G  .....................................................6 1  
1 4. 1  
D at a Re p orti n g a n d C ase Re p ort F o r ms  ...........................................................6 1  
 
Case Re p ort F or ms  .................................................................................................6 1  
 
L a b orat or y Data  .....................................................................................................6 1  
 
Rete nti o n of S o urce D oc u me nts  ............................................................................6 1  
1 4. 2  
Rete nti o n of Esse nti al D oc u me nts  ......................................................................6 1  
1 5  
A D MI NI S T R A TI V E I N F O R M A TI O N  ....................................................................6 2  
1 5. 1  
Fi n a nci n g a n d I ns ur a nce  .....................................................................................6 2  
1 5. 2  
P u blic ati o n P olic y .................................................................................................6 2  
1 6  
R E F E R E N C E S  ............................................................................................................6 3  
A P P E N DI X A  
N U M E RI C A L R A TI N G S C A L E  ..................................................................6 4  
A P P E N DI X B  
S KI N D E X -1 0 S C A L E  ....................................................................................6 5  
A P P E N DI X C  
5 -D I T C H S C A L E  ..........................................................................................6 6  
 
 

L u m osa T hera pe utics C o., Lt d.  
 
P r ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date:  0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 7  
LI S T O F T A B L E S  
Ta ble 2. 1 Sc he d ule of Assess me nts a n d pr oce d ures - Part A  .........................................................1 7  
Ta ble 2. 2 Sc he d ule of assess me nts a n d pr oce d ures - Part B  ..........................................................1 9  
Ta ble 2. 3  
P har mac o ki netic Sa m pli n g Sc he d ule –  Part A  ......................................................2 1  
Ta ble 3. 1  
H u ma n Starti n g D ose Calc ulati o n  .........................................................................2 6  
Ta ble 7. 1  
St u d y Dr u gs  ...........................................................................................................3 8  
Ta ble 8. 1  
Cli nical La b orat or y Tests *  ....................................................................................4 6  
Ta ble 8. 2 Gra di n g sc ore b y I nter nati o nal C o ntact Der matitis Researc h Gr o u p 
(I C D R G) ................................................................................................................4 8  
 
LI S T O F FI G U R E S  
Fi g ure 5. 1   St u d y Desi g n Sc he matic ( Part A)  ................................................................................3 1  
Fi g ure 5. 2  St u d y Desi g n Sc he matic ( Part B)  ................................................................................3 2  
 
 
 
 

L u m osa T hera pe utics C o., Lt d.  
 
P r ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date:  0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 8  
1  
S T U D Y S Y N O P SI S  
Pr ot oc ol 
N u m ber:  
L T 5 0 0 1 -1 0 1  
Title:  
Cli nical P har mac ol o g y of L T 5 0 0 1 Dr u g Pr o d uct i n He m o dial ysis Patie nts 
wit h Ure mic Pr urit us t o Assess t he Safet y, L ocal Tolera nce a n d 
P har mac o ki netics . 
S p o ns or:  
L u m osa T hera pe utics C o, Lt d  
St u d y P h ase:  
1 ( Part A) a n d 2 ( Part B)  
C o n diti o n : 
He m o dial ysis patie nts wit h m o derate -t o-s e vere pr urit us 
B ac k gr o u n d:  
Ure mic pr urit us ( U P) is a c o m m o n a n d distressi n g c o m plicati o n  
of e n d -sta ge re nal diseas e ( E S R D). A gl o bal cr oss -secti o nal st u d y of 1 8, 0 0 0 
he m o dial ysis patie nts re p orte d a 4 2 % pre val e nce of m o derate or e xtr e me U P, 
w hic h was str o n gl y ass o ciate d wit h slee p dist ur ba nce, d e pressi o n, i m pair e d 
q ualit y of life, a n d m ortalit y. Des pite hi g h pre vale nce a n d life -alteri n g 
c o m or bi dities, U P re mai ns lac k of effecti ve treat me nt. Treat me nts c urre ntl y 
use d f or ure mic pr urit us s uc h as a nti hista mi nes, ster oi ds, e m ollie nts, a n d 
p h ot ot hera p y ( U V B) h a v e n ot bee n i n vesti gate d ri g or o usl y, a n d n o dr u gs ha ve 
bee n a p pr o ve d f or t his i n dica ti o n b y t he F D A. 
R ati o n ale:  
 
 
 
 
 T his st u d y is t o e val uate t he s afet y, 
l ocal t olera nce a n d p har mac o ki netics of L T 5 0 0 1 dr u g pr o d uct i n patie nts wit h 
ure mic pr urit us.  
O bjecti ves:  
P art A:  
T o i n vesti gate t he safet y, l ocal t olera nce a n d p h ar mac o ki netics of 4 -wee k, 
m ulti ple der mal a p plicati o ns of L T 5 0 0 1 dr u g pr o d uct t o t he  h e m o dial ysis 
patie nts wit h ure mic pr urit us.   
P art B:  
T o i n vesti gate t he safet y, a n d efficac y of 8 -wee k, m ulti ple der mal a p plicati o ns 
of L T 5 0 0 1 dr u g pr o d u ct t o t he  he m o dial ysis patie nts wit h ure mic pr urit us.  

L u m osa T hera pe utics C o., Lt d.  
 
P r ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date:  0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 9  
 
 
E n d p oi nts:  
P art A:  
Pri m ar y E n d p oi nts  
•  
Nat ure a n d s e verit y of a d verse e v e nts ( A Es) a n d n u m ber of patie nts 
wit h A Es   
 
Sec o n d ar y E n d p oi nts  
•  
 
.   
•  
C ha n ge i n mea n W orst Itc hi n g I nt e nsit y fr o m baseli ne t o t he e n d of 
Wee k 4 usi n g N R S.  
•  
Re d ucti o n of itc h i nte nsit y as assesse d b y t he pr o p orti o n of patie nts 
re d uce d N R S fr o m baseli ne ( ≥ 2 p oi nts, ≥ 3 p oi nts, or ≥ 4 p oi nts) wit h 
res pect t o t he wee kl y mea n of t he dail y 2 4-h o ur W orst Itc hi n g I nte nsit y 
N R S sc ore fr o m bas eli ne t o t he e n d of Wee k 4.  
•  
I m pr o v e me nt i n itc h-relate d q ualit y of life as assesse d b y t he c ha ng e 
fr o m baseli ne i n 5-D It c h Scale sc ore at t he e n d of Wee k 4.  
•  
I m pr o v e me nt i n itc h-relate d q ualit y of life as assesse d b y t he c ha n g e 
fr o m baseli ne i n t otal S ki n de x-1 0 Scale s c ore at t he e n d of Wee k 4.  
 
P art B:  
Pri m ar y E n d p oi nts  
•  
C ha n ge fr o m bas eli ne t o e n d of Wee k 8 i n mea n Worst Itc hi n g I nte nsit y 
usi n g N R S.    
 
Sec o n d ar y E n d p oi nts  
•  
Re d ucti o n of itc h i nte nsit y as assesse d b y t he pr o p orti o n of patie nts 
re d uce d N R S fr o m baseli ne wit h res pect t o t he wee kl y mea n of t he 
dail y 2 4 -h o ur W orst Itc hi n g I nte nsit y N R S sc ore fr o m baseli ne t o e n d 
of Wee k 8.  
•  
I m pr o v e me nt i n itc h-relate d q ualit y of life as assesse d b y t he c ha n g e 
fr o m baseli ne i n 5-D It c h Scale sc ore t o t he e n d of Wee k 8.  
•  
I m pr o v e me nt i n itc h-relate d q ualit y of life as assesse d b y t he c ha n g e 
fr o m baseli ne i n t otal S ki n de x -1 0 Scale s c ore at t he e n d of Wee k 8.   
•  
Nat ure a n d s e verit y of a d verse e v e nts ( A Es) a n d n u m ber of patie nts 
wit h A Es.  

L u m osa T hera pe utics C o., Lt d.  
 
P r ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date:  0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 1 0  
S u bject 
P o p ul ati o n  
I ncl usi o n Criteri a 
 
1.  
Male or fe m ale 2 0 t o 7 5  years of a ge, i ncl usi ve, at t he ti me of si g ni n g 
i nf or me d c o nse nt. 
2.  
Patie nt m ust ha ve bee n recei vi n g i n -ce nter he m o dial ysis f or ≥ 3 m o nt hs 
a n d c urre ntl y o n a sc he d ule of 3 ti mes per wee k.  
3.  
Patie nt m ust ha ve ha d at least 2 urea re d ucti o n rati o ( U R R) 
meas ure me nts ≥ 6 5 %, at least 2 si n gle -p o ol Kt/ V meas ure me nts ≥ 1. 2, 
or 1 si n gle -p o ol Kt/ V meas ure me nt ≥ 1. 2 a n d 1 U R R meas ure me nt ≥ 
6 5 % o n differe nt dial ysis da ys wit hi n t he last 3 m o nt h peri o d pri or t o 
ran d o m izatio n . 
4.  
B o d y wei g ht ≥ 4 0 k g ( n ot t o e xcee d 1 1 5 k g) a n d B MI ≥ 1 8. 0 a n d ≤ 3 1. 0 
k g/ m 2 at scree ni n g  (after he m o dial ysis). 
5.  
H ist or y of pr urit us > 4 wee ks of d urati o n 
6.  
Fe males wit h c hil d beari n g p ote ntial ( defi ne d as w o me n ≤5 0 years of 
a ge wit h a hist or y of a m e n orr hea f or < 1 2 m o nt hs pri or t o st u d y e ntr y) 
m ust a gree t o use effecti ve met h o ds of c o ntrace pti o n fr o m scree ni n g 
t hr o u g h t he last d ose of st u d y dr u g. 
7.  
Males w h o are se x uall y acti ve a n d w h ose p art ners are fe males of 
c hil d beari n g p ote ntial m ust a gree t o use c o n d o ms fr o m scree ni n g 
t hr o u g h 9 0 da ys, w hic he ver is l o n ger, after a d mi nistrati o n of t he last 
d ose of st u d y dr u g, a n d t heir part ners m ust be willi n g t o use a hi g hl y 
effecti ve met h o d of c o ntrace pti o n fr o m scree ni n g t hr o u g h 9 0  da ys aft er 
a d mi nistrati o n of t he last d ose of st u d y dr u g.  
8.  
Male s m ust a gree t o n ot d o nate s per m fr o m scree ni n g t hr o u g h 9 0 da ys, 
w hic he ver is l o n ger, aft er a d mi nistrati o n of t he last d ose of st u d y dr u g.  
9.  
Patie nt m ust ha ve c o m plete d at least 6 da ys of W orst Itc hi n g I nte nsit y 
N R S w or ks heets i n t he 7 -da y Diar y r u n -i n p eri od a n d ha ve a mea n 
W orst Itc hi n g I nte nsit y N R S sc ore > 4 pri or t o r a n d o mizati o n.  
1 0.  Patie nts m ust be a ble t o c o m plete q uesti o n naires, u n dersta n d t he st u d y 
pr oce d ures, a n d c o m m u nicate effecti vel y wit h t he st u d y pers o n nel.  
 
E xcl usi o n Criteri a  
1.  
 
 
. 
2.  
Hist or y of maj or s ur ger y or tra u ma wit hi n 1 2  wee ks of scree ni n g i n t he 
j u d ge me nt of t he i n vesti gat or, or s ur gery pla n ne d d uri n g t he st u d y.  
3.  
 
 

L u m osa T hera pe utics C o., Lt d.  
 
P r ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date:  0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 1 2  
St u d y Desi g n:  
T he st u d y c o ntai ns t w o parts: part A will assess t h e safet y, t olera bilit y a n d 
P K wit h 4 -wee k treat me nt, part B will assess safet y a n d effi cac y f or 8 -wee k 
treat me nt. B ot h parts will a p pl y i n vesti gati o nal dr u g i n he m o dial ysis patie nts 
wit h m o derate t o se vere of ure mic pr urit us.  
 
P art A:  
T his st u d y  will be a ra n d o mize d, d o u ble-bli n d, place b o -c o ntr olle d  trial t o 
e nr oll 1 8  he m o dial ysis patie nts ( L T 5 0 0 1: Place b o = 2: 1) wit h m o derate t o 
se vere pr urit us bet wee n t he a ges of 2 0 t o 7 5  y ears ol d. T he st u d y will assess 
safet y, t olera bilit y a n d t he p har mac o ki netic pr ofil e of L T 5 0 0 1 dr u g pr o d uct 
w he n a p plie d t o s ki n f or 4 wee ks wit h ur e mic pr urit us. 
 
After pr o visi o n of writte n i nf or me d c o nse nt, eac h s u bject will be e val uate d 
f or st u d y eli gi bilit y d uri n g t he scree ni n g p eri o d, w hic h is wit hi n  2 8 da ys pri or 
t o recei vi n g t he st u d y dr u g ( Da y 1). D uri n g t his peri o d, p atie nts nee d t o dail y 
recor d t h e w orst itc h N R S i n t he patie nt diar y f or 7 da ys ( diar y r u n-i n). At 
least 6 of 7 dail y W orst Itc hi n g I nte nsit y N R S w or ks heet m ust be c o m plete d 
a n d mea n N R S sc ore > 4 t o q ualif y.  At scree ni n g, p h ysical e xa mi nati o n of t he 
s ki n will be c o n d ucte d as a f ull-b o d y s ki n assess me nt, w hic h w ill ser ve as 
s u bject’s bas eli ne s ki n c o n diti o n. Patie nt’s  baseli ne s ki n c o n diti o n will be 
use d as refere nce f or c o m paris o n i n t he a p plicati o n site e xa mi nati o n fr o m 
Visit 2 t o 8 i n Part A . After si g ni n g t he i nf or me d c o nse nt, p atie nts ma y 
c o nti n ue b ut s ustai n t he d osi n g re gi me n of  all pre vi o us a nti pr uritic  
prescri pti o n 
me dicati o n  i ncl u di n g 
oral 
a nti hista mi ne 
a ge nts 
a n d/ or 
cortic oster oi d d uri n g t h e st u d y. H o we v er, g a b a pe nti n, pre ga b ali n, t o pical 
a nti hista mi ne/  cortic oster oi d a ge nts, O T C a nti hista mi ne/ cortic oster oi d a ge nts 
f or a nti-pr urit us treat me nt is pr o hi bite d t hr o u g h o ut t he st u d y.  
 
Eli gi ble patie nts will be ra n d o mize d i nt o  L T 5 0 0 1 dr u g pr o d uct or  place b o  
treat me nt gr o u ps wit h 2: 1 rati o. 
 
 
 
Patie nt will be i nstr ucte d t o directl y a p pl y t he st u d y dr u g t o t he 
itc h area. A  fi n gerti p u nit of st u d y dr u g is rec o m me n de d t o treat a n area of 
s ki n t wice t he size of a n a d ult p al m.  
 
In t he first 7 da ys of st u d y treat me nt, p atie nt will als o nee d u n der g o a 7 -d a y 
re peat e d o p e n a p plicati o n tests ( 7 -d a y R O A T) . A 0. 5 fi n gerti p u nit of t he st u d y 
dr u g is rec o m me n de d t o a p ply  t o a 5 x 5 c m 2 fi xe d pre -mar k e d z o n e wit h o ut 
a n y s ki n lesi o ns n ear t h e a ntec u bital f oss a  t wice dail y in t h e m or ni n g a n d 
e ve ni n g  f or 7 d a ys. If s ki n lesi o ns occ urre d o n  t he a ntec u bital f ossa , acce pt t o 
c h o ose t he v o lar f orear m or ve ntral i n ner ar m wit h o ut s ki n lesi o n u n der t he 
j u d g me nt of i n vesti gat or t o perf or m R O A T (a v oi d t he area de pi cte d i n t h e 
Dr u g a d mi nistrati o n secti o n) .   
 

L u m osa T hera pe utics C o., Lt d.  
 
P r ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date:  0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 1 3  
Patie nts will nee d t o dail y rec or d t he itc h c o n diti o n i n t he patie nt diar y b y 
t he msel ves i ncl u di n g t he dail y 2 4-h o ur w orst itc h N R S , a p plicati o n ti me/ site 
of t he st u d y dr u g, ti me a n d i nte nsit y of t he itc h bet wee n t he m or ni n g a n d 
e ve ni n g d ose  a n d ret ur n t he diar y at e v er y visit.  Patie nt nee d t o ret ur n t he 
st u d y dr u g a n d the act ual d osi n g i n eac h patie nt will be deter mi ne d b y  s u btract 
t he wei g ht of eac h ret ur n e d st u d y dr u g s u btract fr o m t he i nitial wei g ht  ( T0).   
 
Cli nical la b orat or y tests will be o btai ne d at Da y 1, 1 5, 2 9. Bl o o d sa m ple f or 
p har mac o ki netics will be c ollecte d at pre -d ose,  4 8, 1 2 0, 1 6 8, 3 3 6, 5 0 4, a n d 
6 7 2 hrs p ost d osi n g. S u bj ects will ret ur n f or a f oll o w -u p visit t o c o m plete 
safet y e v al uati o ns f or a p pr o xi matel y 3 5 da ys after st u d y dr u g a d mi nistrati o n.  
 
I nteri m a n al ysis a n d D S M B: 
After Part A c o m pleti o n, t he i nteri m a nal ysis will pla n t o be d o ne.  
D S M B will re vie w i nteri m a nal ysis a n d gi ve c o m me nts o n safet y or a n y 
me dical c o ncer n t o d eter mi ne w het her t he st u d y c o nti n ue d or n ot. Als o, 
D S M B will gi ve c o m me nts f or L T 5 0 0 1 dr u g pr o d uct dail y d ose a n d re gi m e n.  
 
P art B:  
T his part of st u d y  will recr uit  9 0  he m o dial ysis patie nts ( L T 5 0 0 1: 
Place b o = 1: 1) wit h m o derate t o se vere pr urit us. T he st u d y will assess safet y, 
a n d efficac y of L T 5 0 0 1 dr u g pr o d uct w he n a p pli e d t o s ki n f or 8 wee ks wit h 
ure mic pr urit us.  
 
Eli gi ble patie nts will be ra n d o mize d i nt o L T 5 0 0 1 dr u g pr o d uct a n d place b o 
treat me nt gr o u ps wit h 1: 1 rati o. 
 
 T he d ail y d ose 
a n d 
rec o m me n d e d 
re gi me n 
ma y 
be 
a dj uste d 
base d 
o n 
D S M B 
rec o m me n dati o n. 
 
Patie nts will nee d t o dail y rec or d t he itc h c o n diti o n i n t he patie nt diar y b y 
t he msel ves i ncl u di n g t he dail y 2 4-h o ur w orst itc h N R S , a p plicati o n site of t he 
st u d y dr u g, ti me a n d i nt e nsit y of t he itc h b et wee n t he m or ni n g a n d e ve ni n g 
d ose  a n d ret ur n t he diar y at e ver y vis it. T h e y will visit at Da y 1, 8, 1 5, 2 2, 2 9, 
3 6, 4 3, 5 0, a n d 5 7 after dr u g a d mi nistrati o n.  
 
If a s u bject is wit h dra w n fr o m t he treat me nt peri o d of t he st u d y f or reas o ns 
n ot ass ociate d wit h safet y c o nsi derati o ns, ad diti o nal s u bjects ma y be e nr olle d 
if a d diti o nal data are necessar y t o esta blis h safet y a n d t olera bilit y.  
Esti m ate d 
St u d y 
D ur ati o n:  
P art A:  
A p pr o xi matel y 6 wee ks, i ncl u des 1 wee ks of s cree ni n g ( D iary R u n -i n), 4 
wee ks of treat me nt a n d 1 wee k f oll o w u p.  
P art B:  

L u m osa T hera pe utics C o., Lt d.  
 
P r ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date:  0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 1 5  
Dr u g 
A d mi nistr ati o n  
T o pical a d mi nistrati o n  
T he st u d y me dicati o n will be a p plie d direct l y t o t h e itc hi n g area as i nstr ucte d 
b y t he st u d y staff .  
A v oi d a p pl y L T 5 0 0 1 dr u g pr o d uct  ar o u n d t he e yes, m o ut h, n ose, m uc o us 
me m bra ne, ge nital, a nal r e gi o n, vasc ular access  f or he m o dial ysis a n d its 
s urr o u n di n g re gi o n ( 1 c m i n b ot h si des). D o n ot a p pl y t he st u d y me dicati o n 
o n t o t he vesicles , o pe n w o u n d , or o n t he area of er yt he ma , ras h, s welli n g, 
parest hesia , p ai n , des q ua mati o n , disc ol orati o n.  
S a m ple Size:  
P art A:  
A p pr o xi matel y 2 0 s u bjects will be scree ne d t o ac hie ve 1 8  s u bjects e nr oll e d  
( L T 5 0 0 1: Place b o = 1 2: 6).  
P art B:  
A p pr o xi matel y 1 0 0  s u bjects will be scree ne d t o ac hie ve 9 0 s u bjects e nr olle d  
( L T 5 0 0 1: Place b o =4 5 :4 5 ). 
St atistic al 
Met h o ds:  
S afet y A n al yses  
All safet y a nal yses will be perf or me d o n t he safet y a nal ysis set ( S A S). 
A d verse e ve nts will be c o de d b y S yste m Or ga n Class a n d Preferre d Ter m 
usi n g t he c urre nt v ersi o n of Me d D R A. I nci de nces of treat me nt -e mer ge nt A E s 
(T E A Es), ie, e ve nts t hat starte d after e x p os ure t o st u d y dr u g or w orse ne d i n 
se verit y after d osi n g, will be prese nte d b y d ose gr o u p. I nci de nces of T E A Es 
will als o be pres e nte d b y ma xi m u m se verit y a n d relati o ns hi p t o st u d y 
me dicati o n.  
Safet y data will be s u m marize d t hr o u g h a p pr o priat e data ta b ulati o n s, sta n dar d 
descri pti ve statistics, a n d gra p hical prese ntati o ns. F or eac h c o nti n u o us 
la b orat or y p ara meter, res ults will be cate g orize d as l o w, n or mal, or hi g h b as e d 
o n t he la b orat or y n or mal ra n ges. Fre q ue n cies a n d perce nta ges will be 
prese nte d b y d ose gr o u p f or s u bjects w h o ha d a s hift t o l o w a n d f or s u bjects 
w h o ha d a s hift t o hi g h fr o m baseli ne t o a n y p ost -d osi n g assess me nt.  
T he ass ociati o n of A Es, cli nical la b orat or y tests, vital si g n meas ure me nts wit h 
t he act ual d os i n g of st u d y dr u g or  s yste mic e x p os ure of L T 5 0 0 1 dr u g pr o d uct  
ma y als o be e x pl ore d. If a p pr o priate, statistical m o deli n g will be perf or me d t o 
f urt her c h aracteriz e t he ass ociati o ns me nti o ne d a b o ve. All o ut-of -ra n g e a n d 
cli nicall y si g nifica nt la b orat or y res ults will be i de ntifie d i n s u bject d ata  
listi n gs. T he n u m ber a n d perce nta ge of s u bjects i n eac h d os e gr o u p wit h 
n or mal a n d a b n or mal p h ysical e x a mi nati o n res ults will be prese nte d f or 
e val uati o ns at baseli ne a n d fi nal visit.  
F or eac h b o d y s yste m, c ha n ges i n t he s u bjects’ fi n di n gs fr o m baseli ne t o fi nal 
visit ( n o c ha n ge, n or mal t o a b n or mal, or a b n or mal t o n or mal) will be ta b ulate d 
f or eac h d ose gr o u p. 
 
P h ar m ac o ki netics A n al yses  

L u m osa T hera pe utics C o., Lt d.  
 
P r ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date:  0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 1 6  
P har mac o ki netics Para meters  
Fr o m t he c o nce ntrati o n -ti me data, t he f oll o wi n g bl o o d  P K para meters will be 
deter mi ne d, as d ata per mit:  
C tr o u g h 
L o west o bser ve d bl o o d c o nce ntrati o n pri or t o ne xt a p plicati o n  
All calc ulati o ns f or P K para me t ers will be base d o n act ual d osi n g a n d 
sa m pli n g ti mes rec or de d d uri n g t he st u d y. C o nsi deri n g t he act ual d os e 
recei v e d b y eac h p atie nt ma y var y, t he P K para meter will be a dj uste d b y 
di vi di n g t o t he act ual d ose of eac h patie nt    
A dj uste d P K para meter = C tr o ug h/ Act ual D ose   
I n a d diti o n, t he ori gi nal bl o o d P K para meter (wit h o ut d ose a dj ust me nt ) vers us 
ti me will als o be  a nal yze d . B l o o d c o nce ntrati o ns t hat are bel o w t he li mit of 
q ua ntificati o n ( B L Q) pri or t o t he first meas ura ble c o nce ntrati o n will be set t o 
zer o, B L Q v al ues t hat are bet wee n meas ura ble c o nce ntrati o ns will be s et t o 
missi n g, a n d B L Q val ues t hat occ ur at t he e n d of t he pr ofile (after t he last 
q ua ntifia ble c o nce ntrati o n) will be set t o missi n g.  
P har mac o ki netic para met ers will be liste d b y s u bject a n d treat me nt usi n g t he 
S A S, a n d s u m marize d b y treat me nt usi n g t he usi n g t he p har mac o ki netic 
a nal ysis set ( P K A S) a n d t he f oll o wi n g s u m mar y st atistics: n, arit h metic mea n, 
sta n dar d de viati o n ( S D), C V %, mi ni m u m, me dia n, a n d ma xi m u m. Ge o metric 
mea n a n d ge o m etric C V % will als o be prese nt e d f or all P K para meters.  
Scatter pl ots of i n di vi d u al a dj uste d P K para meters ( C tr o u g h/ Act ual D ose) a n d 
n o n -a djus ted  P K  p aramet ers (C tr o u g h) vers us ti me f or L T 5 0 0 1 dr u g pr o d uct will 
be pr o d uce d o n l o g -l o g scales usi n g t he P K A S. 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
 
Date: 0 4 Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 1 9  
T a ble 2 .2  Sc he d ule of assess me nts a n d pr oce d ures - P art B  
 
a  

L u m osa T hera pe utics C o., L t d. 
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
 
Date: 0 4 Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 2 0  

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 2 1  
T a ble 2 .3  
P h ar m ac o ki netic S a m pli n g Sc he d ule –  P art A  
Visit  
St u d y D a y  
Ti m e Rel ati ve  t o 1 st St u d y Dr u g A d mi nistr ati o n 
( H o ur) 
P h ar m ac o ki netic Bl o o d 
S a m ple  
0  
-2 8 t o -1  
N ot a p plica ble  
N ot a p plica ble  
1  
1  
0 ( pre d ose)  
X  
2  
3  
4 8 ± 4  (tr o u g h) 
X  
3  
6  
1 2 0 ± 4  (tr o u g h) 
X  
4  
8  
1 6 8 ± 4  (tr o u g h) 
X  
5  
1 5  
3 3 6 ± 4  (tr o u g h) 
X  
6  
2 2  
5 0 4 ± 4  (tr o u g h) 
X  
7  
2 9  
6 7 2 ± 4  (tr o u g h) 
X  
8  
3 6  
N ot a p plica ble  
N ot a p plica ble  
P har mac o ki netic  sa m ples will b e c ollecte d as cl ose t o t he n o mi nal ti me p oi nt as p os si ble. All o wa ble wi n d o ws f or 
P K  c ollecti o n will be ±  4  h o urs f or all tr o u g h sa m ples. 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 2 2  
LI S T O F A B B R E VI A TI O N S  
A b bre vi ati o n  
Defi niti o n  
U P  
ure mic pr urit us  
A E  
a d verse e ve nt 
B L Q  
bel o w t he li mit of q ua ntificati o n  
B MI  
b o d y mass i n de x  
B U N  
bl o o d urea nitr o ge n  
C F R  
C o de of Fe deral Re g ulati o ns  
C N S  
ce ntral ner v o us s yste m  
C R U  
cli nical researc h u nit 
C R O  
c o ntract researc h or ga nizati o n  
C tr o u g h 
l o west o bser ve d bl o o d c o nce ntrati o n pri or t o ne xt a p plicati o n  
D S M B  
data a n d safet y m o nit ori n g b oar d  
e C R F  
electr o nic case re p ort f or m  
E O S  
e n d -of -st u d y 
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
F U  
f oll o w-u p  
G C P  
G o o d Cli nical Practice  
H B V  
he p atitis B vir us  
H C V  
he p atitis C vir us  
HI V  
h u ma n i m m u n o deficie n c y vir us  
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 
I E C 
i n de pe n de nt et hics c o m mittee 
I R B 
i nstit uti o nal re vie w b oar d 
Itc h N R S 
itc h n u merical rati n g scale 
N O A E L  
n o o bser ve d a d verse effect li mit  
N R S  
n u merical rati n g scale  
Me d D R A  
Me dical Dicti o nar y f or Re g ulat or y Acti vities  
O T C  
o ver -t he-c o u nter 
P K  
p har mac o ki netic(s)  
S A E  
seri o us a d verse e v e nt 
S A S  
safet y a n al ysis set 
S D  
sta n dar d de viati o n 
S O P  
sta n dar d o perati n g pr oce d ure 
S R M  
st u d y refere nce ma n ual 
U L N  
u p per li mit of n or mal  

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 2 3  
S T U D Y A D MI NI S T R A TI V E S T R U C T U R E  
S p o ns or:  
L u m osa T hera p e utics C o., Lt d.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 2 7  
 
.  
3. 5  
H y p ot heses  
T he st u d y is t o deter mi ne t he safet y, l ocal t olera nce, P K , a n d e x pl or e t he p ote ntial efficac y of 4 -
wee k ( Part A) a n d t h e safet y a n d efficac y of 8 -wee k ( Part B) m ulti ple der mal a p plicati o ns of 
L T 5 0 0 1  dr u g  pr o d uct  i n t he he m o dial ysis patie nts wit h m o derate t o se vere U P. 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 2 8  
4  
O B J E C TI V E S  
4. 1  
Pri m ar y O bjecti ve  –  P a rt A  
•  T o i n vesti gate t he safet y, l ocal t olera bilit y,  a n d P K  of 4 -wee k, m ulti ple der mal a p plicati o ns 
of L T 5 0 0 1  dr u g pr o d uct  t o he m o dial ysis patie nts wit h U P . 
4. 2  
P ri m ar y O bjecti ve  –  P a rt B  
•  T o i n vesti gate t he safet y a n d effi cac y of 8-wee k , m ulti ple der mal a p plicati o ns of L T 5 0 0 1 
dr u g pr o d uct t o he m o dial ysis patie nts wit h U P . 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot o c ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 2 9  
5  
S T U D Y D E SI G N  
5. 1  
St u d y Desi g n a n d O ver vie w  
T his st u d y c o ntai ns 2  parts . B ot h st u d y parts will i ncl u de he m o dial ysis patie nts wit h m o derate t o 
se vere U P. Part A will assess t he safet y, t oler a bilit y, a n d P K of L T 5 0 0 1 dr u g pr o d uct  wit h 
4 -wee k  of dail y BI D t o pical d osi n g. Part B will assess safet y a n d effi cac y wit h 8 -wee k  of dail y  
t o pical d osi n g. T he ma xi m u m dail y d ose a n d rec o m me n de d re gi me n f or Part B will de pe n d o n 
D S M B c o m me nts.  
P art A:  
Part A  will be a ra n d o mi ze d, d o u ble -bli n d, a n d pl ace b o -c o ntr olle d . It will e nr oll 1 8  patie nts 
bet wee n 2 0  t o 7 5  years of a ge, i ncl usi ve. 
After pr o vi di n g  writte n i nf or me d c o nse nt, eac h patie nt will be e val uate d f or st u d y eli gi bilit y wit hi n 
2 8 da ys of Da y 1. D uri n g t his peri o d, patie nt nee d t o dail y rec or d t he w orst itc h N R S i n t he patie nt 
diar y f or 7 d a ys ( diar y r u n -i n). At least 6 of 7 dail y W orst Itc hi n g I nte nsit y N R S w or ks heet m ust 
be c o m plete d a n d m ea n N R S sc ore > 4 t o q u alif y.  At scree ni n g, p h ysical e xa mi nati o n of t he s ki n 
will be c o n d ucte d as a f ull -b o d y s ki n assess me nt, w hic h will ser ve as s u bject’s baseli ne s ki n 
c o n diti o n. P h ot o gra p h s of t he treat me nt area ma y be c o nsi dere d u n der t he i n vesti gat or’s j u d g me nt 
( o pti o nal). P atie nt’s  bas eli ne s ki n c o n diti o n will be use d as refere nce f or c o m paris o n i n t he 
a p plicati o n site e xa mi nati o n fr o m Visit 2 t o 8 i n Part A . After s i g ni n g t he i nf or me d c o nse nt, 
patie nts ma y c o nti n ue pre vi o us a nti pr uritic t hera p y  t hr o u g h o ut t he st u d y prescri be d b y t he 
p h ysicia n  ( u nless s p ecifi e d i n t he pr o hi bite d me di cati o n Secti o n 7. 7. 3 ).T h e d osi n g re gi me n of t he 
pre vi o us a nti pr uritic t hera p y ca n n ot be c ha n ge d.  G a ba pe nti n, pre g a bali n, t o pical a nti hista mi ne/ 
c ortic oster oi d a ge nts , O T C a nti hista mi ne/ c ortic oster oi d a ge nts are pr o hi bite d t hr o u g h o ut t he 
st u d y. E li gi ble patie nts will be ra n d o mize d i nt o 2 gr o u ps ( L T 5 0 0 1 dr u g pr o d uct  a n d Place b o ) at a 
rati o of 2: 1.  
 
 
T o pical d osi n g will occ ur f or 4 wee ks, c o nsisti n g of 5 6 t otal d oses t hr o u g h o ut t he treat me nt peri o d.  
Patie nt will be i nstr ucte d t o directl y a p pl y t he st u d y dr u g t o t he itc h area. A  fi n gerti p u nit of st u d y 
dr u g is rec o m me n de d t o treat a n area of s ki n t wice t he size of a n a d ult pal m.  
 
In t he first 7 da ys of st u d y treat me nt, patie nt will als o nee d u n der g o a 7 -d a y r e peat e d o pe n 
a p plicati o n tests ( R O A T) . A 0. 5 fi n gerti p u nit of t he st u d y dr u g  is rec o m m e n de d t o a p ply  t o a 
5 x 5 c m 2 fi xe d pre -mar k e d z o ne wit h o ut a n y s ki n lesi o ns near t he a ntec u bit al f ossa  t wice d ail y in 
t he m or ni n g a n d e ve ni n g f or 7 da ys. If s ki n lesi o n is occ urre d i n t he a ntec u bital f ossa , it is 
acce pta ble t o c h o ose t h e v olar f orear m or v e ntral i n ner ar m  wit h o ut s ki n lesi o n u n der t he 
j u d g me nt of i n vesti gat or t o perf or m R O A T (a v oi d t he area de picte d i n t he Secti o n 7. 2 
Treat me nts A d mi nistere d ). Patie nts will nee d t o dail y assess  t he itc h c o n diti o n at a fi xe d peri o d 
b y t he msel ves  a n d rec or d i n t he patie nt diar y i ncl u di n g t he dail y 2 4-h o ur w orst itc h N R S, 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 3 0  
a p plicati o n ti me/ site of t he st u d y dr u g, ti me a n d i nte nsit y of t he itc h bet wee n t he m or ni n g a n d 
e ve ni n g d ose a n d ret ur n t he diar y at e v er y visit.   
Patie nts will visit t he C R U f or d osi n g o n Da y 1, a n d f or pr oce d ures i n cl u di n g cli nical la b orat or y 
test sa m pli n gs, p h ysical e xa mi nati o ns, vital si g n assess me nts, itc h assess me nt ( S ki n de x -1 0 a n d 
5 D -itc h scale), a n d a p pli cati o n site assess me nts b y I C D R G scale ( der matitis, pr urit us, 
parest hesia, er yt he ma, dr y ness, vesicles, irritati o n, pa p ules, b ur ni n g)  acc or di n g t o  Ta ble 8 .2 , a n d 
P K bl o o d sa m ples will be perf or me d acc or di n g t o  Ta ble 2 .3 . A p plicati o n site  e val uati o n will be 
c o n d ucted  i n e ac h visit ( Visit 2 t o 8) i n Part A. P h ot o gra p hs of t he a p plicati o n site ma y be 
c o nsi dere d u n d er t he i n v esti gat or’s j u d g me nt ( o pti o nal).  Baseli ne s ki n c o n diti o n perf or me d at 
scree ni n g will be use d as refere nce f or c o m paris on.  
Patie nt will nee d t o ret ur n t he st u d y dr u g d uri n g 3 ti mes per wee k f oll o wi n g his/ her dial ysis 
sc he d ule. T h e act u al d osi n g i n eac h patie nt will be deter mi ne d b y s u btract t he wei g ht of eac h 
ret ur ne d st u d y dr u g fr o m t he i nitial wei g ht ( T0).   
Patie nts  will  ret ur n f or a f oll o w-u p visit t o c o m plete safet y e val uati o ns acc or di n g t o  Ta ble 2 .1 . 
A p plicati o n site assess me nts ( der matitis, pr urit us, parest hesia, er yt he ma, dr y ness, vesicles, 
irritati o n, pa p ules, b ur ni n g) b y I C D R G scale  acc or di n g t o  Ta ble 8 .2 , A E s, a n d c o nc o mita nt 
me dicati o ns a n d pr oce d ures will be rec or de d.  
P art B:  
Part B will be ra n d o mize d, d o u ble -bli n d, a n d place b o -c o ntr olle d. It will e nr oll 9 0  p atie nts  
bet wee n 2 0  t o 7 5  years of a ge, i ncl usi ve.  
After pr o vi di n g writte n i nf or me d c o ns e nt, eac h p atie nt will be e val uate d f or st u d y eli gi bilit y 
d uri n g scree ni n g ( wit hi n 2 8 da ys of Da y 1).  D uri n g t h is peri o d, patie nt nee d t o dail y rec or d t he 
w orst itc h N R S i n t he patie nt diar y f or 7 da ys ( diar y r u n -i n). At least 6  of 7 dail y W orst Itc hi n g 
I nte nsit y N RS w or ks heet m ust be c o m plete d a n d mea n N R S sc ore > 4 t o q ualif y.  At scree ni n g, 
p h ysical e xa mi nati o n of t he s ki n will be c o n d ucte d as a f ull -b o d y s ki n assess me nt, w hic h w ill 
ser ve as s u bject’s bas eli ne s ki n c o n diti o n. P h ot o gra p hs of t he treat me nt area ma y b e c o nsi dere d 
u n der t he i n vesti gat or’s j u d g me nt ( o pti o nal).  Patie nt’s  baseli ne s ki n c o n diti o n will be use d as 
refere nce f or c o m paris o n i n t he a p plicati o n site e x a mi nati o n fr o m Visit 2 t o 9  i n Part B . 
After si g ni n g t he i nf or me d c o nse nt, patie nts ma y  c o nti n ue all pre vi o us a nti pr uritic t hera p y 
prescri be d b y t h e p h ysici a n t hr o u g h o ut t he st u d y ( u nless s pecifie d i n t he pr o hi bite d me dicati o n 
Secti o n 7. 7. 3 ). T he d osi n g re gi me n of t he pre vi o us a nti pr uritic t hera p y ca n n ot be c ha n ge d.  
G a ba pe nti n, pre ga bali n, t o pical a nti hista mi ne/ c ortic oster oi d a ge nts, O T C a nti hista mi ne/ 
c ortic oster oi d a g e nts are pr o hi bite d t hr o u g h o ut t he st u d y. E ligi ble patie nts will be r a n d o mize d 
i nt o 2  gr o u ps ( L T 5 0 0 1  dr u g pr o d uct a n d Place b o ) at a rati o of 1: 1. T o pical d osi n g will occ ur f or 
8 wee ks. 
 
 
 T o pical d osi n g will occ ur f or 8  wee ks. Patie nts will nee d t o dail y assess  t he 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 3 1  
itc h c o n diti o n at a fi xe d peri o d b y t he msel ves  a n d rec or d i n t he p atie nt diar y i ncl u di n g t he dail y 
2 4 -h o ur w orst itc h N R S, a p plicati o n site / ti me of t he st u d y dr u g, ti me a n d i nte nsit y of t he itc h 
bet wee n t he m or ni n g a n d e ve ni n g d ose , a n d ret ur n t he diar y e ver y visit.   
Patie nts will visit t he C R U f or d osi n g o n Da y 1 a n d pr oce d ures i ncl u di n g cli ni cal la b orat or y test 
sa m pli n g, p h ysical e xa mi nati o ns, vital si g n assess me nts, a n d itc h assess me nt ( S ki n de x -1 0 a n d 
5 D -itc h scale), a n d a p pli cati o n site assess me nts ( der matitis, pr urit us, parest hesia, er yt he ma, 
dr y ness, vesicles, irritati o n, pa p ules, b ur ni n g)  b y I C D R G scale  acc or di n g t o Ta ble 8 .2 , A E s, a n d 
c o nc o mita nt me dicati o ns a n d pr oce d ures will be p erf or me d acc or d i n g t o Ta ble 2 .2 . A p plicati o n 
site e val uati o n will be c o n d ucte d i n eac h visit ( Visit 2 t o 9) i n Part B. P h ot o gra p hs of t he 
a p plicati o n site ma y be c o nsi dere d u n der t he i n vesti gat or’ s j u d g me nt ( o pti o nal). Baseli ne s ki n 
c o n diti o n perf or me d at scree ni n g will be us e d as refere nce f or c o m paris o n.  
Patie nt will nee d t o ret ur n t he st u d y dr u g d uri n g 3 ti mes per wee k f oll o wi n g his/ he r dial ysis 
sc he d ule. T h e act u al d osi n g i n eac h patie nt will be deter mi ne d b y  s u btract t he wei g ht of eac h 
ret ur ne d st u d y dr u g a n d s u btract fr o m t he i nitial wei g ht ( T0).   
 
Fi g ure 5 .1   St u d y Desi g n Sc he m atic ( P art A)  
 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 3 2  
 
 
 
Fi g ure 5 .2   St u d y Desi g n Sc he m atic ( P art B)  
 
 
I nteri m Safet y/ P har mac o ki netic Data Re vie w  
S u bject will recei ve a p plicati o n site e xa mi nati o n at eac h visit ( Part A: Visit 2  t o 8; Part B: Visit 2  
t o 9) assesse d b y  t he trai ne d st u d y tea m, u si n g I C D R G scale. If s u bject e x perie nce a ne w or 
w orse ni n g l ocalize d s ki n reacti o n i n t he treat me nt area, t h e s u bject s h o ul d r e p ort t o t he st u d y 
c o or di nat or a n d/ or i n v esti gat or d uri n g t he visit. Baseli ne s ki n c o n diti o n c o n d ucte d at scree ni n g 
i n t he p h ysical e xa mi nati o n sh o ul d be use d as a refere n ce f or c o m paris o n. All A Es s h o ul d be 
rec or de d i n t he e C R F   
 
If a s u bject e x peri e nce 1 ne wl y arise ac ute i nfla m mati o n of t he s ki n (e. g. p ai n, tra nsie nt 
er yt he ma, vesi c ulati o n, se vere s welli n g wit h b ullae, ulcerati o n , or e ve n b ot h) at t he a p plicati o n 
site, a n d is relate d (at least p ossi ble ) wit h st u d y dr u g, st u d y treat me nt is rec o m me n de d t o be  
i nterr u pte d. U p o n res ol uti o n of t he ac ute i nfl a m mati o n, s u bject ma y res u m e st u d y treat me nt 
u p o n i n vesti gat or’s j u d g me nt.    
 
After c o m pleti o n of 1 8  s u bjects  i n Part A, t he D S M B will c o n ve ne t o re vie w all safet y a n d P K 
data . Part B will o nl y occ ur if t he D S M B deter mi nes t hat t he c urre nt d ose was safe a n d well -
t olerate d. D oses f or Part B will be deci de d b y t he D S M B after t heir revie w of t he c u m ulati ve 
safet y data t ar gete d f or re vie w ( A Es, vital si g ns, cli nical la b orat or y res ults, p h ysical e xa mi nati o n 
res ults, itc h res ults, a n d a p plicati o n site e xa mi nati o n res ults) a n d a v aila ble P K data fr o m Part A. 
S p o ns or will ma ke t he fi nal deci si o n i n a n u n bli n de d fas hi o n. 
A n a d h oc D S M B meeti n g will be c o n ve ne d i n t he f oll o wi n g sit uati o ns:  
1.  
I n t he e ve nt of 4 s u bjects e x perie n ci n g dr u g rel ate d (at least p ossi ble) a d v erse e ve nts wit h at 
least m o derate i nte nsit y after t he 1 st d ose of st u d y dr u g  o r a n y I C D R G gra d e of R O A T ≥ 1 + 
f o u n d d uri n g t he first 7 d a ys of st u d y treat me nt, a d h oc D S M B meeti n g will be h el d t o 
re vie w t he s afet y dat a a n d rec o m me n d i n writi n g t o S p o ns or w het her t o c o nti n ue, m o dif y, 
or st o p t he cli nical st u d y o n t he basis of safet y  c o nsi derati o ns .  

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 3 3  
2.  
 I n t he e ve nt of ≥ 2 s u bjects e x perie n ci n g dr u g relate d (at least p ossi ble) a d verse e v e nts wit h 
at least m o derate i nte nsit y  i n t he first 6 s u bjects recei vi n g st u d y dr u g after t he 1 st d ose  o r 
a n y I C D R G gra d e of R O A T ≥ 1 + f o u n d d uri n g t h e first 7 da ys of st u d y treat me nt , a d h oc 
D S M B meeti n g will als o be  c o n ve n e d  t o disc uss  t he safet y e ve nts t o rec o m me n d S p o ns or 
w het her t o c o nti n ue , m o dif y, or s us pe nsi o n t he e nr oll me nt of t he st u d y . 
D S M B me m bers will i ncl u de e x perts i n t he diseas e u n der st u d y a n d bi ostatistics w h o are n ot 
partici pati n g i n t his st u d y a n d d o n ot ha ve affiliati o n wit h t he I n v esti gat ors or t he S p o ns or.  F ull 
details of t he r ole, re mit a n d me m bers hi p of t he D S M B will  be detaile d  i n a se parate D S M B 
C harter  
 
 
D urati o n of St u d y  
P art A:  
Patie nt  partici pati o n is e x pecte d t o last u p t o 6 3  da ys , i ncl u di n g a 2 8 -da y scree ni n g peri o d 
(c o nsisti n g of a 7 -da y diar y r u n -i n t o b uil d baseli ne itc h N R S) a n d a 3 6 -d a y o n st u d y peri o d 
(c o nsisti n g of 5 6  t otal d oses fr o m Da y 1 t o D a y 2 9 , a n d a 7  da y  f oll o w-u p/ E O S visit  at Da y 36 ). 
P art B:  
Patie nt  partici pati o n is e x pecte d t o last u p t o 8 5  da ys, i ncl u di n g a 2 8 -da y scree ni n g peri o d 
(c o nsisti n g of a 7-da y diar y r u n -i n t o b uil d baseli ne itc h N R S) a n d a 5 7 -d a y o n st u d y treat me nt 
peri o d . 
 
Defi niti o n of St u d y C o m pleti o n  
E n d -of -st u d y pr oce d ures will be perf or me d as s pecifie d i n t he sc he d ul e s of assess me nts (Ta ble 
2 .1  a n d Ta ble 2 .2 ); p atie nt s w h o wit h dra w  fr o m t he st u d y earl y will ha ve E O S  pr oce d ures 
perf or me d at t he ti me  or wit hi n 7 da ys  of disc o nti n uati o n. Patie nt s wit h o n g oi n g cli nicall y 
si g nifica nt cli nical or la b orat or y fi n di n gs will be f oll o we d u ntil t he fi n di n g is res ol ve d or 
me dicall y sta ble; reas o n a ble atte m pts will be ma de t o f oll o w -u p wit h patie nt s. T he patie nt ’s 
partici pati o n i n t he st u d y will e n d o nce all st u d y assess me nts a n d f oll o w -u p ha ve bee n 
c o m plete d.  
 
E n d of St u d y  
T he e n d of t he st u d y is d efi ne d as t he d ate w h e n t he last patie nt  has c o m pl ete d all st u d y 
pr oce d ures u p t o a n d i ncl u di n g t he E O S /earl y ter mi nati o n visit as s pecifie d i n t he sc he d ules of 
assess me nts (Ta ble 2 .1  a n d Ta ble 2 .2 ). 

L u m osa T he ra pe utics C o., Lt d. 
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 3 4  
6  
S E L E C TI O N A N D WI T H D R A W A L O F P A TI E N T S  
Patie nts m ust meet all t he f oll o wi n g i ncl usi o n criteria a n d n o n e of t he e xcl usi o n criteria i n or der 
t o be e nr olle d i n t his st u d y. Pr os pective 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 v ers or e xe m pti o ns, is n ot per mitte d.  
6. 1  
I ncl usi o n Criteri a 
Patie nt s m ust meet all i ncl usi o n criteria t o be eli gi ble f or st u d y partici pati o n. 
1.  Male or fe m ale 2 0  t o 7 5  years of a ge , i ncl usi ve, at t he ti me of si g ni n g i nf or me d c o nse nt . 
2.  Patie nt m ust ha ve bee n recei vi n g i n -ce nter he m o dial ysis f or ≥ 3 m o nt hs a n d c urre ntl y o n a 
sc he d ule of 3 ti mes per wee k. 
3.  Patie nt m ust ha ve ha d at least 2 urea re d ucti o n rati o ( U R R) meas ure m e nts ≥ 6 5 %, at least 2 
si n gle-p o ol Kt/ V meas ur e me nts ≥ 1. 2, or 1 si n gle -p o ol Kt/ V meas ure me nt ≥ 1. 2 a n d 1 U R R  
meas ure me nt ≥ 6 5 % o n differe nt dial ysis da ys wit hi n t he last 3 m o nt h peri o d pri or t o  
ran d o m izatio n . 
4.  B o d y wei g ht ≥ 4 0 k g ( n ot t o e xcee d 1 1 5 k g) a n d B MI ≥ 1 8. 0 a n d ≤ 3 1. 0 k g/ m 2 at scree ni n g 
(after he m o dial ysis). 
5.  H ist or y of pr urit us > 4 wee ks of d urati o n 
6.  Fe males  wit h c hil d beari n g p ote ntial ( defi ne d as w o me n ≤5 0 years of a ge wit h a hist or y of 
a me n orr hea f or < 1 2 m o nt hs pri or  t o st u d y e ntr y) m ust a gree t o use effecti ve met h o ds of 
c o ntrace pti o n fr o m scree ni n g t hr o u g h t he last d ose of st u d y dr u g.  
7.  M ales w h o are se x uall y acti ve a n d w h ose p art ners are fe males of c hil d beari n g p ote ntial m ust 
a gree t o us e c o n d o ms fr o m scree ni n g t hr o u g h 9 0 d a ys, w hic he ver is l o n ger,  after 
a d mi nistrati o n of t he last d ose of st u d y dr u g , a n d t heir part ners m ust be willi n g t o use a 
hi g hl y effecti ve m et h o d of c o ntrace pti o n fr o m scree ni n g t hr o u g h 9 0  da ys after  a d mi nistrati o n 
of t he last d ose of st u d y dr u g.  
8.  Males m ust a gree t o n ot d o nate s per m fr o m scree ni n g t hr o u g h  9 0  da ys, w hic he ver is l o n ger,  
after a d mi nistrati o n of t he last d ose of st u d y dr u g . 
9.  Patie nt  m ust ha ve c o m plete d at least 6 da ys of W orst Itc hi n g I nte nsit y N R S w or ks heets i n t he 
7 -da y Diar y r u n -i n Peri o d a n d ha ve a mea n W orst Itc hi n g I nte nsit y N R S sc ore > 4 pri or t o 
ra n d o mizati o n.  
1 0.  Patie nts m ust be a ble t o c o m plete q uesti o n naires, u n dersta n d t he st u d y pr oce d ures, a n d 
c o m m u nicate effecti vel y wit h t he st u d y pers o n nel.  
 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 3 5  
6. 2  
E xcl usi o n Criteri a  
Patie nts  will n ot be eli gi ble f or st u d y partici pati o n if t he y meet a n y of t h e e x cl usi o n criteria, or 
will be disc o nti n ue d at t he discreti o n of t he i n vesti gat or i n c o ns ultati o n wit h t he me dical m o nit or 
if t he y de vel o p a n y of t he e xcl usi o n criteria d uri n g t he st u d y. 
 
 
 
2.  
Hist or y of maj or s ur ger y or tra u ma wit hi n 1 2  wee ks  of scree ni n g i n t he j u d ge me nt of t he 
i n vesti gat or, or s ur ger y pla n ne d d uri n g t he st u d y. 
3.  
 
 
. 
4.  
Has ha d a si g nifica nt alterati o n i n dial ysis re gi me n wit hi n 2 wee ks of t he Scree ni n g Visit or 
a ntici pate d t o be recei vi n g n oct ur nal dial ysis, h o me he m o dial ysis treat me nt, or ki d ne y 
tra ns pla nt d uri n g t he st u d y. 
5.  
Has a n y k n o w n hist or y of aller gic reacti o n t o o pi oi ds.  
6.  
Hist or y of a latest p ositi ve ser ol o g y test f or H B V ( H Bs A g)  or  H C V (a nti -H C V)  wit hi n 1 
year pri or ra n d o mizati o n  c o nsiste nt wit h c urre nt i nfecti o n. C o nfir mat or y tests will be  
all o we d at t he discreti o n of t he i n vesti gat or t o r ule o ut false p ositi ves.  
7.  
Has a n y k n o w n hist or y of HI V.  
8.  
P ositi ve pre g na nc y test or is lactati n g. 
9.  
Has re q uir e d perit o neal dial ysis.  
1 0.  Ala ni ne a mi n otra nsf eras e a n d/ or as p artate a mi n otra nsferase c o nce ntrati o n > 2 x t he U L N, 
or t otal bilir u bi n > 1. 8 x U L N, or he m o gl o bi n c o nce ntrati o n < 9 g/ d L at t he Scree ni n g Visit.  
1 1.  Has ta ke n ot her i n vesti gati o nal dr u gs or partici pat e d i n a n y cli nical st u d y wit hi n 3 0  da ys or 
5  half -li ves (if k n o w n) of t he i n vesti gati o nal dr u g’s P K, P D, or bi ol o gical acti vit y (if 
k n o w n), w hic he v er is l o n ger, pri or t o first d ose of st u d y dr u g i n t his st u d y or is c urre ntl y 
partici pati n g i n a n ot her cli nical st u d y.  
1 2.  Has recei ve d a vacci nati o n wit hi n 3 da ys pri or t o a d mi nistrati o n of t he f irst d ose of st u d y 
dr u g.  
1 3.  Has pr urit us pr o ba bl y or defi nitel y attri b ute d t o a ca use ot her t ha n re n al disease or its 
c o m plicati o ns  s uc h as at o pic der matitis, c hr o nic urticarial, or h e patic pr urit us ca use d b y 
c hr o nic li ver disease .   
1 4.  Prese nce of s ki n i nfecti o n (as defi ne d b y t he i n vesti gat or) o n t he area t o be treate d.  

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 3 6  
1 5.  A n y ot her c o n diti o n or pri or t hera p y t hat, i n t he i n vesti gat or’s o pi ni o n, w o ul d ma ke t he 
patie nt u ns uita ble f or t he st u d y, or u na ble or u n willi n g t o c o m pl y wit h t he st u d y pr oce d ures  
1 6.  I n v ol ve d i n t he pl a n ni n g or c o n d uct of t his st u d y. 
1 7.  U n willi n g or u nli kel y t o c o m pl y wit h t he re q uire me nts of t he st u d y.  
6. 3  
S cree n F ail ures  
Patie nts  w h o are disc o nti n ue d fr o m t he st u d y pri or t o st u d y dr u g a d mi nistrati o n  will be 
c o nsi dere d scree n fail ures . T he patie nt ma y  b e re-scree n e d if t he patie nt  was n ot disc o nti n ue d 
fr o m t he st u d y d ue t o n o nc o m plia nce wit h t he pr ot oc ol, a n d als o t he in vesti gat or c o nsi der s t he 
patie nt s uita ble t o partici pate i n t he st u d y. If t he p atie nt  is re-scree n e d, t he patie nt  m ust be 
re-c o ns e nte d.  
Scree n fail ure dat a will  be rec or de d i n t he e C R F.  
6. 4  
P atie nt  Wit h dr a w al  
Patie nts  are free t o 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, a n d wit h o ut prej u dice t o 
f urt her tr eat me nt. T he i n vesti gat or ma y wit h dra w a patie nt  if, i n t he i n vestigat or’s j u d g me nt, 
c o nti n ue d partici pati o n w o ul d p ose u nacce pta ble ris k t o t he patie nt  or t o t he i nte grit y of t he st u d y 
data. All pr oce d ures f or earl y wit h dra wal m ust be c o m plete d. Reas o ns f or wit h dra wal ma y 
i ncl u de: 
•  A E  
•  L ost t o f oll o w -u p  
•  P h ysicia n decisi o n  
•  Pre g na nc y  
•  Pr ot oc ol de viati o n  
•  St u d y ter mi nate d b y S p o ns or  
•  Wit h dra wal b y patie nt  
•  Deat h  
•  N o nc o m plia nce wit h st u d y dr u g  or pr oce d ure  
•  Ot her  
If patie nts  w h o are wit h dra w n f or reas o ns ot her t h a n A Es , ad diti o nal patie nts ma y be e nr olle d if 
a d diti o nal data are necessar y t o esta blis h safet y a n d t olera bilit y.  
I n t he e ve nt of a patie nt ’s wit h dra wal, t he i n vesti g at or will pr o m ptl y n otif y t he me dical m o nit or 
a n d will ma ke e ver y eff ort t o c o m plete t he f oll o w-u p/ E O S  assess me nts. All wit h dra w n patie nts  
wit h o n g oi n g cli nicall y si g nifica nt cli nical or la b orat or y fi n di n gs will be f oll o we d u ntil t he 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 3 7  
fi n di n g is res ol ve d or me dicall y sta ble; reas o n a ble atte m pts will be ma de t o f oll o w-u p wit h 
patie nts . 
6. 5  
E arl y Ter mi n ati o n of St u d y  
T he st u d y ma y be  ter mi n ate d at a n y ti me b y t he S p o ns or if seri o us si de effects occ ur, if p ote ntial 
ris ks t o st u d y partici pa nts are i de ntifie d, if t h e i n vesti gat or d oes n ot a d here t o t he pr ot oc ol, or if, 
i n t he Sp o ns or’s j u d g me nt, t here are n o f urt h er be nefits t o be ac hie ve d fr o m t he st u d y. I n t he 
e ve nt t hat t he cli nical de vel o p me nt of t he st u d y dr u g is disc o nti n ue d, t he Sp o ns or s hall i nf or m all 
i n vesti gat ors/i nstit utio ns a n d re g ulat or y a ut h orities.  

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m b er: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 3 8  
7  
T R E A T M E N T O F P A TI E N T S  
7. 1  
I de ntit y of St u d y Dr u g s 
A descri pti o n  of t he st u d y dr u gs is prese nted i n  T a ble 7 .1 . 
T a ble 7 .1  
St u d y Dr u gs  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
7. 2  
Tre at me nts A d mi nistere d  
T he st u d y me dicati o n will be a p plie d direct l y t o t he itc hi n g area as i nstr ucte d b y t he st u d y staff . A  
fi n gerti p u nit of st u d y dr u g is rec o m me n de d t o treat a n area of s ki n t wice t he size of a n a d ult pal m. 
In t he first 7 da ys of st u d y treat me nt, patie nt will als o nee d t o a p pl y 0. 5 fi n gerti p u nit of t he st u d y 
dr u g t o a 5 x 5 c m 2 fi xe d pre-mar k e d z o ne wit h o ut a n y s ki n lesi o ns near t he a ntec u bital f ossa  BI D 
i n t he m or ni n g a n d e ve ni n g f or 7 da ys. If s ki n lesi o n is occ urre d i n t he a ntec u bital f ossa , it is 
acce pta ble t o c h o os e t he v olar f orear m or ve ntr al i n ner ar m  wit h o ut s ki n lesi o n u n der t he j u d g me nt 
of i n vesti gat or  t o perf or m R O A T (a v oi d t he area de picte d bel o w). 
A v oi d a p pl y L T 5 0 0 1 dr u g pr o d uct  ar o u n d t he e yes, m o ut h, n ose, m uc o us me m bra ne, ge nital, 
a nal re gi o n , vas c ular access f or he m o dial ysis a n d its s urr o u n di n g re gi o n ( 1 c m  i n b ot h si des). D o 
n ot a p pl y t he st u d y me dicati o n o n t o t he  vesicles , o pe n w o u n d , or o n t he area of er yt he ma, ras h, 
s welli n g, parest hesia , p ai n, des q ua mati o n , disc ol orati o n.  
P art A:  
L T 5 0 0 1  dr u g pr o d uct  will be  a p plie d BI D  i n t he m or ni n g a n d e ve ni n g per t he sc he d ule of 
assess me nt i n  Ta ble 
 
 
.  
P art B:  
T he d osi n g re gi me n will a dj ust acc or di n g t o D S M B s u g gesti o n after Part A c o m pleti o n. If 
D S M B has n o c o m me nt f or fre q u e nc y of treat me nt a d mi nistrati o n, t he d osi n g re gi me n will be 
ke pt t he sa me as Part A.  
 
. 
7. 3  
Met h o d of Assi g ni n g P atie nts  t o Tre at me nt Gr o u ps 
T he C R O s will pre pare t he ra n d o mizati o n sc h e me i n acc or da nce wit h its S O Ps a n d t he 
ra n d o mizati o n pla n, w hic h reflect G C P  sta n dar ds. Refer t o Secti o n  1 0 . 3 for a descri pti o n of 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 3 9  
ra n d o mizati o n met h o ds. Eli gi ble patie nts  will be assi g ne d t o a treat me nt gr o u p acc or di n g t o t he 
list of patie nt  ra n d o mizati o n assi g n me nts. 
7. 4  
Me as ure me nts of Tre at me nt C o m pli a nce  
St u d y dr u g s will be a d mi nistere d b y dele gate d a n d trai ne d staff  at t he C R U s. Details re gar di n g 
d osi n g, i ncl u di n g t he d ose a d mi nistere d a n d t h e date a n d ti me of d osi n g, will be rec or de d.  
7. 5  
St u d y Dr u g  St or a ge, Acc o u nt a bilit y, a n d Rete nti o n  
 
St ora ge C o n diti o ns  
T he i n vesti g at or will e ns ure t hat all t he st u d y dr u gs are st ore d a n d dis pe ns e d i n acc or da nce wit h 
t he re g ulati o ns fr o m t he re g ulat or y a ut h orit y c o n cer ni n g t he st ora ge a n d a d mi nistrati o n of 
i n vesti gati o nal dr u gs. 
L T 5 0 0 1  dr u g pr o d uct  will be st ore d at c o ntr olle d r o o m tem perat ure ( ≤ 2 5° C) i n t he ori gi nal 
pac ka gi n g.  
 
Dr u g Acc o u nta bilit y a n d Rete nti o n  
T he i n vesti gat or s m ust e ns ure t hat all st u d y dr u g s u p plies are ke pt i n a s ec ure l oc ke d area wit h 
access li mite d t o t h ose a ut h orize d b y t he i n vesti gat or. T he i n vesti gat or m ust m ai ntai n acc urate 
rec or ds of t he recei pt of all st u d y dr u g s hi p pe d b y L u m osa T hera p e utics C o., Lt d.  or t heir 
re pres e ntati ve, i ncl u di n g b ut n ot li mite d t o t he date recei ve d, l ot n u m ber, e x pirati o n date, a m o u nt 
recei v e d, a n d t he dis p ositi o n of all st u d y dr u g. C urre nt dis pe nsi n g rec or ds will als o be 
mai ntai ne d i ncl u di n g t he date a n d a m o u nt of st u d y dr u g dis pe nse d a n d t he p atie nt  recei vi n g t he 
dr u g. All re mai ni n g st u d y dr u g n ot re q uire d b y re g ulati o ns t o be hel d b y t he C R U m ust be 
ret ur ne d t o L u m osa T hera pe utics C o., Lt d.  or t heir re prese ntati ve i m me diat el y after t h e st u d y is 
c o m plete d.  
7. 6  
P ac k a gi n g a n d L a bel i n g 
 
St u d y Dr u g  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 4 0  
 
Bli n di n g of Treat me nt Assi g n me nt  
T he C R O  will mai ntai n t he ra n d o mizati o n c o d e i n a sec ure l ocati o n wit h c o ntr ols t o pre ve nt 
u na ut h orize d access , i ncl u di n g t he c om p uter pr o gra m writte n t o ge nerate t h e ra n d o mizati o n, 
ra n d o mizati o n c o des, pr o gra m l o g, see d n u m ber use d b y t he pr o gra m, c o p y of t he ra n d o mizati o n 
pla n al o n g wit h a p pr o val d oc u me ntati o n as a p pr o priate, a n d t he write -pr ot ecte d electr o nic 
st ora ge me di u m. 
T he  site a n d C R O will na me a n u n bli n de d statisticia n t o pr o vi de t he ra n d o mizati o n c o de.  
In v esti gat ors , p har macists , site staff, patie nts , C R O, a n d t he Sp o ns or  will re mai n bli n de d t o 
i n di vi d ual patie nts ’ treat me nt assi g n me nt f or t he d urati o n of t he st u d y u ntil t he st u d y u n bli n di n g 
has bee n a ut h orize d .  
I n or der t o preser ve t he bli n d, st u d y dr u g will be pre pare d a n d a d mi nistere d i n a ma n ner t hat 
mas ks t he c o nte nt f or b ot h t he patie nt  a n d staff m e m ber a d mi nisteri n g t he dr u g.  
 
U n bli n di n g  of Treat me nt Assi g n me nt  
7. 6. 3. 1  
U n bli n di n g f or A d verse E ve nt/ Safet y Reas o ns  
S h o ul d a n  S A E or ot her circ u msta nce re q uir e t hat t he bli n d be br o ke n t o e ns ure patie nt  safet y, 
t he i n vesti gat or m ust i m me diatel y n otif y t he me dical m o nit or . T he me dical m o nit or  will n otif y 
t he Sp o ns or as s o o n as p ossi ble a n d will release t he treat me nt assi g n me nt of t he patie nt  t o t he 
a p pr o priate p ers o n nel i n acc or da nce wit h t he a p pli ca ble st u d y-s pecific pr oce d ure. 
If t he treat me nt assi g n me nt is u n bli n de d b y t he site p har macist or a n y part y ot her t ha n C R O , t he 
i n vesti gat or m ust n otif y CR O i n writi n g a n d d oc u me nt t he c o urse of e ve nts i n t he s o urce rec or ds. 
A n y patie nt  f or w h o m t h e treat me nt c o de is pre m at urel y rel ease d will be wit h dra w n fr o m t he 
st u d y. 
7. 7  
C o nc o mit a nt Me dic ati o ns  & Pr oce d ures / Pr o hi bite d me dic ati o n/  Ot her 
Restricti o ns  
 
C o nc o mita nt Me dicati o ns  
C o nc o mita nt  me dicati o ns d uri n g t he st u d y will be d oc u me nte d o n t he c o n c o mita nt me dicati o n 
e C R F. I nf or m ati o n rec or de d will i ncl u de: start a n d st o p dates a n d ti mes, d ose a n d r o ute of 
a d mi nistrati o n, a n d i n dicati o n.  
•  
All o we d c o nc o mita nt me dicati o n  
C o nc o mita nt me dicati o ns or vacci n ati o ns ma y  be a d mi nistere d if t he y are prescri be d or 
c o nfir me d b y t he i n vesti gat or f or t he tr eat me nt of s pecific cli nical e ve nts. W he n p ossi ble, 
t he S p o ns or will be c o nsulte d bef ore a d mi nistrati o n of c o nc o mita nt me dicati o ns.  
M ai nte na nce m e dicati o ns as prescri be d b y t he patie nt’s p h ysicia ns are p er mitte d.   
•  
All o we d b ut nee d t o mai ntai n sta ble treat me nt r e gi me n  
After si g ni n g i nf or me d c o nse nt, s u bjects ma y  c o nti n ue pre vi o us a nti pr uritic t hera p y 
prescri be d b y t h eir p h ysicia n t hr o u g h o ut t he st u d y  ( u nless s pecifie d i n t he p r o hi bite d 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 4 1  
me dicati o n  Secti o n 7. 7. 3 ), i ncl u di n g b ut n ot li mite d t o oral a nti hista mi ne a ge nts a n d 
c ortic oster oi ds. T he a nti pr uritic re gi me n m ust mai ntai n sta ble  ( defi ne d as n o c ha n ge i n 
prescri pti o n ) t hr o u g h o ut t he st u d y.  
Me dicati o ns f or t he ma n a ge me nt of ser u m p h os p h or us, calci u m, or i P T H is rec o m me n de d 
t o mai ntai n sta ble u nless are per mitte d b y t he s u bject’s p h ysicia n f or t he treat me nt of 
s pecific cli nical e ve nts. .   
 
C o nc o mita nt pr oce d ures  
N o c o nc o mita nt pr oce d ures ot her t ha n dial ysis will be perf or me d d uri n g t he st u d y u nless 
a p pr o ve d b y t he i n vesti g at or. Me dicati o ns ta ke n f or a pr oce d ure will als o be i ncl u de d o n t he 
c o nc o mita nt me dicati o n e C R F, as well as t he pr oce d ure itself.  
 
Pr o hi bite d me dicati o n  
Ga ba pe nti n , pre ga bali n , a n d t o pical a nti histami ne/ c ortic oster oi ds  are pr o hi bite d t hr o u g h o ut t he 
st u d y. A d mi nistrati o n of O T C a nti hista mi ne a n d c ortic oster oi ds f or a nti pr uritic treat me nt are als o 
n ot all o we d.    
 
Ot her Restricti o ns  
Patie nt s will be i nstr ucte d t o a d here t o t he f oll o wi n g restricti o ns: 
•  Patie n ts are n ot per mitte d t o partici pate i n a n y ot her cli nical trial or d o n at e bl o o d or plas ma 
w hile partici pati n g i n t his cli nical trial.  

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 4 2  
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  
Patie nt s will u n der g o st u d y pr oce d ures a n d assess me nts at ti me p oi nts s pecifie d i n t he sc he d ule 
of assess me nts ( Ta bl e 2 .1 , Ta ble 2 .2 , a n d T a ble 2 .3 )  
8. 1  
D i ar y r u n-i n ( 7-d a ys itc h N R S)  
S u bject nee d t o rec or d t h e dail y w orst itc hi n g inte nsit y N R S f or 7 da ys i n t he patie nt diar y  at 
scree ni n g. At le ast 6 of 7 itc h N R S m ust be c o m plete d a n d t he mea n N R S sc ore > 4 t o  b e  
q ualif ie d f or partici pati o n i n t he st u d y . 
A fter si g ni n g i nf or me d c o nse nt, a patie nt diar y will be pr o vi de d t o t he s u bject f or t he Diar y r u n-
i n pr oce d ure at scree ni n g. Patie nt eli gi bilit y will be c o nfir me d after c o m pleti o n t he st u d y 
pr oce d ures s pecifi e d i n t he sc he d ule o f assess me nt. I n practice, t he or der of t he pr oce d ures 
s h o ul d be: ( 1) o btai n i nf or me d c o nse nt ( 2) re vie w i ncl usi o n a n d e xcl usi o n criteria  ( 3) Diar y r u n-
i n a n d all ot her assess me nts f or scree ni n g i n dicate d i n t he sc he d ule of assess me nts (Ta ble 2 .1 , 
Ta ble 2 .2 ) ( 4) c o nfir m eli gi bilit y ( 5)  ra n d o mizati o n.  
8. 2  
7 -d a ys R e pe ate d o pe n a p plic ati o n tests ( 7 -d a ys R O A T)  
I n t he first 7 da ys of st u d y treat me nt, s u bject will nee d  t o u n der g o a 7 -da y re peat e d o pe n 
a p plicati o n tests ( R O A T). A 0. 5 fi n gerti p u nit of t he st u d y dr u g is rec o m m e n de d t o a p ply  t o a 
5 x 5 c m 2 fi xe d pre -mar k e d z o ne wit h o ut a n y s ki n lesi o ns near t he a ntec u bit al f ossa  t wice d ail y i n 
t he m or ni n g a n d e ve ni n g f or 7 da ys. If s ki n lesi o n is occ urre d i n t he a ntec u bital f ossa , it is 
acce pta ble t o c h o ose  t h e v olar f orear m or v e ntral i n ner ar m  wit h o ut s ki n lesi o n u n der t he 
j u d g me nt of i n vesti gat or t o perf or m R O A T (a v oi d t he area de picte d i n t he Secti o n 7. 2 
Treat me nts A d mi niste re d). 
D uri n g t he 7 -da ys R O A T, t he pre -mar ke d z o n e a p plie d wit h t he st u d y dr u g will be e xa mi ne d a n d 
assesse d b y I C D R G scale i n eac h visit ( det ails i n Secti o n 8. 8. 6  A p plicati o n Site E xa mi nati o n ). I n 
t he e ve nt of I C D R G ≥ + t hat is c o nsi dere d cli nicall y si g nifica nt will be rec or de d as A E.  T h e 
i n vesti gat or ma y p h ot o gra p h t he s ki n c o n diti o n if t he i n vesti gat or c o nsi dere d hel pf ul f or t he 
safet y assess me nt i n t he D S M B meeti n g ( o pti o nal).  
8. 3  
Me dic al a n d S ur gic al Hist or y  
T he i n vesti gat or or desi g nee will c ollect a c o m plete me dical a n d  s ur gi cal hist or y wit hi n 3 m o nt hs 
pri or si g ni n g I C F at scree ni n g.  
8. 4  
De m o gr a p hic C h ar acteristics  
De m o gra p hic c haracteristics i ncl u di n g se x, a ge, race will be rec or de d  at scree ni n g . 
8. 5  
P h ysic al Me as ure me nts  
Hei g ht (c m) a n d b o d y wei g ht ( k g) (after he m o dial ysis) wit h o ut s h oes will be rec or de d.  B o d y 
mass i n de x will be calc ul ate d usi n g t he hei g ht o btai ne d at scree ni n g .  

L u m osa T hera pe utic s C o., Lt d. 
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 4 3  
8. 6  
Itc h assess me nts 
 
Dail y A ssess ment of t he itc h i nte nsit y b y t he patie nt  
S u bjecte d will be i nstr ucte d b y t he st u d y pers o n nel t o dail y self -rec or d t he it c h i nte nsit y b y N R S 
(A p pe n di x A ) i n t he p atie nt diar y i n a fi xe d peri o d. T he  foll o wi n g i nf or mati o n will nee d t o be 
d oc u me nte d d uri n g t he st u d y.   
Diar y r u n -i n ( 7 d a ys itc h N R S): 
•  T he dail y w orst itc h N R S  
Fr o m Da y 1 t o t he e n d of st u d y:  
•  T he ti me of t he dr u g a d mi nistrati o n  
•  T he a p plicati o n site of t h e dr u g  
•  T he dail y w orst itc h N R S  
•  T he ti me of t he itc h bef ore t he ne xt d ose  a d mi nistrati o n  
•  T he i nte nsit y of t he itc h bef ore t h e ne xt d ose  a d mi nistrati o n assesse d b y N R S  
 
Q uesti o n naire i nter vie we d b y i n vesti gat or or desi g nee 
T he S ki n de x -1 0 Scale a n d 5 -D Itc h scale are b ot h m ulti di me nsi o nal scales n ot o nl y access 
pr urit us i nte nsit y b ut meas ure t he i m pact of pr urit us o n patie nts. T he S ki n de x -1 0 e val u ate h o w 
t he patie nt’s itc h affects t hree i m p orta nt d o mai ns of q ualit y of life i ncl u di n g 3 d o mai ns ( disease, 
m o o d/e m oti o nal distress, a n d s ocial f u ncti o ni n g ) as n ote d i n i n A p pe n di x B . S u bjects  fille d o ne 
of se ve n b u b bles (“ 0 [ ne ver b ot here d], 1, 2, 3, 4, 5, a n d 6 [al wa ys b ot here d]”) f or eac h of t he 
q uesti o ns. T he t otal sc ore was t he s u m of t he n u meric val ue of eac h a ns were d q uesti o n  ra n gi n g 
fr o m 0 t o 6 0, wit h hi g her sc ores i n dicati n g w ors e itc h-relat e d q ualit y of life. T he 5 -D itc h scale 
i ncl u de 5 d o mai ns (t he d urati o n, de gree, directi o n, disa bilit y, a n d distri b uti o n) as n ote d i n 
A p pe n di x C , wit h a t otal sc ore ra n gi n g fr o m 5 ( n o itc hi n g) t o 2 5 ( ma xi m u m se verit y) . 
T he  S ki n de x -1 0 a n d 5 -D Itc h s cale will be p erf or me d w he n patie nts were i n t he dial ysis u nit. 
T he i n vesti gat or or desi g nee will c o n d uct  a face-t o-face i nter vie w t o assist t he s u bject c o m plete 
the S ki n de x -1 0 Scale a n d 5 -D Itc h scale. Bef ore t h e i nter vie w, th e i n vesti gat or or desi g nee will 
be trai ne d b y t he me di cal m o nit or t o e ns ure t he acc urac y a n d mai ntai n t he c o nsiste nc y  of t he 
i nter vie w acr oss i n di vi d uals. S u bjects will c o m plete t he q uesti o n naire wit h o ut i n p ut o n t he 
a ns wers fr o m t he st u d y tea m.  
T h e questi o n naire  i nter vie w will be c o n d uct e d e ver y 2 weeks  at da y 1 ( Visit 1), da y 1 5 ( Visit 5), 
a n d da y 2 9 ( Visit 7) i n Part A , a n d da y 1 ( Visit 1),  da y 1 5 ( Visit 3 ), da y 2 9 ( Visit 5 ), da y 4 3  
( Visit 7 ), da y 5 7  ( Visit 9 ) i n Part B as n ote d i n the sc he d ule of assess me nts (Ta ble 2 .1 , Ta bl e 
2 .2 ). 
I n practice, t he or d er of t he pr oce d ures is rec o m me n de d as f oll o ws b ut ma y be a dj uste d u p o n 
i n vesti gat or’s j u d ge me nt: ( 1) Bef ore dial ysis: vital si g ns, bl o o d sa m pli n g f or t he P K a n d 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 4 4  
la b orat or y tests ( 2) D uri n g dial ysis: S ki n de x -1 0 Scale a n d 5 -D Itc h scale (3) After dial ysis:  b o d y 
wei g ht, p h ysical e xa mi nati o n , a n d ot her safet y assess me nt pr oce d ures.  
 
8. 7  
P h ar m ac o ki netic Assess m e nts  
 
Dr u g C o nce ntr ati o n Meas ure me nts  
Bl o o d  P K  sa m ples will be c ollected i n Part A o nl y; at ti me p oi nts s pecifie d i n t he P K sa m pli n g 
sc he d ule (T a ble 2 .3 ). Bl o o d sa m ple c ollecti o n, pr o cessi n g, a n d s hi p pi n g details will be o utli ne d 
i n a se parate S R M . 
 
 
 
P har mac o ki netic Para meters  
T he f oll o wi n g P K para m eter will be deter mi ne d:  
All calc ulati o ns f or P K p ara meters will be base d o n act ual d osi n g a n d sa m pli n g ti mes rec or de d 
d uri n g t he st u d y. C o nsi deri n g t he act u al d ose recei ve d b y eac h p atie nt ma y var y, t he P K 
para meter will be a dj uste d b y di vi di n g t o t he act ual d ose of eac h patie nt : 
A dj uste d P K para meter =   C tr o u g h/ Act ual D ose 
T he act ual d osi n g i n e ac h patie nt will be deter mi ne d b y  s u btract t he wei g ht of eac h ret ur n e d 
st u d y dr u g a n d s u btract fr o m t he i nitial wei g ht ( T0). I n a d diti o n, t he ori gi nal bl o o d P K para meter 
wit h o ut d ose a dj ust me nt  (C tr o u g h) vers us ti me will als o be a nal yze d. 
8. 8  
S afet y Assess me nts  
 
A d verse E v e nts  
Patie nt s will be m o nit ore d f or A Es acc or di n g  t o S ecti o n 9 . 
 
Cli nical La b orat or y Tests  
A certifie d l a b orat or y will be utilize d t o pr ocess a n d pr o vi de res ults f or t he cli nical la b orat or y 
tests liste d i n Ta ble 8 .1 . Cli nical la b orat or y test will be c o n d ucte d e v er y 2 wee ks  as i n dicate d i n 
t he sc he d ule of assess me nts (Ta ble 2 .1 , Ta ble 2 .2 ). T h e assess me nt ti me f or s pecific tests s uc h as 
B U N,  intact P T H,  ser u m or u ri ne β-h C G , U R R, Kt/V is liste d i n Ta ble 8 .1 . 
T he baseli ne la b orat or y t est res ults f or cli nical assess me nt f or a p artic ular t est will be defi ne d as 
t he last meas ure me nt pri or t o t he first d ose of st u d y dr u g. Bl o o d c ollecti o n f or  cli nical la b orat or y 
tests  will be p erfor me d b ef ore di al ysis u nless s pecifie d i n t he B U N test  i n Ta ble 8 .1 .   
C tr o u g h 
T he l o west o bser ve d bl o o d c o nce ntr ati o n pri or t o ne xt a p plicati o n  

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 4 5  
D uri n g t he scree ni n g peri o d, if a patie nt  has a n o ut -of -ra n ge val u e f or a cli nical la b orat or y 
para meter t hat t he i n vesti gat or belie ves is n ot cli nicall y si g nifica nt or t he i n vesti gat or d oes  n ot 
belie ve is c orrect ( e g,  la b or s peci me n pr ocessi n g err or), b ut t he i n vesti gat or wa nts t o c o nfir m 
wit h a re peat la b orat or y t est, a si n gle re peat is all o we d  t o c o nfir m t he i nitial res ult. H o we ver, 
o nl y t he fi nal verifie d d ata c o nfir me d b y t h e i n vesti gat or nee d be rec or de d i n t he e C R F.  
A d diti o nal safet y la b orat or y tests ma y be c o n d uct e d as nee d e d b y t he i n vesti gat or t o e val uate 
patie nt  safet y. 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 4 7  
F or a n y l a b orat or y test v al ue o utsi de t he refere nce ra n ge t h at t he i n vesti gat or c o nsi ders cli nicall y 
si g nifica nt d uri n g t he o n -st u d y peri o d (ie, f oll o wi n g d ose a d mi nistrati o n), t he i n vesti gat or will : 
•  Re peat t he test t o ve rif y t he o ut-of -ra n ge v al ue a n d cli nical si g nifica nce  b ut o nl y t he fi nal 
verifie d dat a c o nfir me d b y t he i n vesti gat or nee d b e rec or de d i n t he e C R F.  
•  F oll o w t he o ut -of -ra n ge val ue u ntil t he val ue ret ur ns t o n or mal or baseli ne, or u ntil t he val ue 
is dee me d stable a n d n ot cli nicall y si g nifica nt b y t he i n vesti gat or . 
•  Rec or d as a n A E a n y la b orat or y test val ue t hat is c o nfir me d b y re peat a n d t he i n vesti gat or 
c o nsi ders cli nicall y si g nifica nt, re q uir es a p atie nt  t o be disc o nti n ue d fr o m t he st u d y, re q uires 
a patie nt  t o recei ve treat me nt, or re q uires a c h a n g e or disc o nti n uati o n of t he st u d y dr u g (if 
a p plica ble). 
 
Ot her Tests  
T he f oll o wi n g test hist or y will be re vie we d or perf or me d:  
•  Hist or y of latest ser ol o g y test (ie, H Bs A g, H C V a nti b o d y,  a n d a n y c o nfir m at or y tests 
perf or me d at t he discreti o n of t he i n vesti gat or )  
•  H ist or y of HI V 
•  Ser u m or u ri ne β-h C G  test (fe males o nl y) 
 
Vital Si g ns  
Vital si g ns assess me nts will i ncl u de te m perat ure ( ℃), res pirat or y rate ( breat hs per mi n ute), 
s yst olic a n d diast olic bl o o d press ure ( m m H g), a n d p ulse rate ( b p m). Vital si g ns  will be meas ure d 
after t he p atie nt  has bee n resti n g q uietl y i n a seate d p ositi o n f or at least 5 mi n utes.  A n y cli nicall y 
si g nifica nt a b n or mal vital si g n assess me nt re q uires at least o ne re p eat meas ure me nt  b ut o nl y  t he 
fi nal verifie d d ata c o nfir me d b y t he i n vesti gat or n ee d be rec or de d i n t he e C R F. 
A v ital si g ns a b n or malit y  t hat is c o nsi dere d cl i nicall y si g nifica nt i nitiall y a n d o n c o nfir mati o n, 
re q uires a p atie nt  t o be disc o nti n ue d fr o m t he st u d y, re q uires a p atie nt  t o recei ve treat me nt, or 
re q uires a c ha n g e or disc o nti n uati o n fr o m t he st u d y dr u g (if a p plica bl e) will be rec or de d as a n 
A E.  
 
P h ysical E xa mi nati o n  
At Scree ni n g, co m pr e he nsi ve p h ysical e xa mi nati o ns (e xcl u di n g ge nital, rectal, a n d breast 
e xa mi nati o ns  [ u nless i n dicate d) will be perf or me d. I n a d diti o n, p h ysical e xa mi nati o n of t he s ki n 
will be c o n d ucte d as a f ull -b o d y s ki n assess me nt, w hic h will ser ve as s u bject’s baseli ne s ki n 
c o n diti o n . A b n or mal fi n di n gs will be d oc u me nte d i n t he patie nt’s e C R F. T h e i n vesti gat or ma y 
c o nsi der p h ot o gra p h t he s ki n c o n diti o n of t he treat me nt area u p o n his/ her j u d ge me nt ( o pti o nal).  
S u bject’s  ba seli ne s ki n c o n diti o n will be use d as refere nce f or c o m paris o n i n t he a p plicati o n site 
e xa mi nati o n.   

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 4 8  
Tar gete d s y m pt o m -dri ve n  p h ysical e xa mi nati o ns will be perf or me d o n Da y 1, 3, 6, 8, 1 5, 2 2, a n d 
2 9 of eac h treat me nt p eri o d a n d at t he e n d -of -st u d y visit.  
A n a b n or mal p h ysical e x a mi nati o n fi n di n g t hat is c o nsi dere d cli nicall y si g nifica nt a n d re q uires 
t he patie nt t o be disc o nti n ue d fr o m t he st u d y, re q uires t he patie nt t o recei v e treat me nt, or 
re q uires a c ha n g e or disc o nti n uati o n of t he st u d y dr u g (if a p plica bl e) will be rec or de d as a n A E. 
 
A p p licati o n Site E xa mi nati o n  
A p plicati o n Site E xa mi nati o n will be c o n d ucte d at Visit 2  t o 8 i n Part A a n d Visit 2 t o 9 i n Part 
B  as i n dicate d i n sc he d ul e of assess me nt  (Ta ble 2 .1 , Ta ble 2 .2 ). A p plicati o n site  e val uati o n will 
be c o n d ucte d b y c o m pari n g t he  s ki n of t he ap plicati o n site wit h t he  baseli ne s ki n c o n diti o n i n 
eac h visit.  
T he a p plicati o n site  e val uati o n will i ncl u de der matitis, pr urit us, parest hesia, er yt he ma, dr y ness, 
vesicles, irritati o n, pa p ul es, b ur ni n g  assesse d b y I C D R G scale  (T a ble 8 .2 ). A n a b n or mal 
a p plicati o n site fi n di n g t hat is c o nsi dere d cli nicall y si g nifica nt will be rec or de d as A E.  T h e  
i n vesti gat or ma y c o nsi der  p h ot o gra p h t he s ki n c o n diti o n u n der t he c o nse nt of t he s u bject if t he 
i n vesti gat or c o nsi dere d h el pf ul  f or t he safet y assess me nt i n t he D S M B meeti n g ( o pti o nal).  
T a ble 8 .2  Gr a di n g sc ore b y I nter n ati o n al C o nt act Der m atitis Rese arc h Gr o u p (I C D R G)   
Gr a di n g  M or p h ol o g y  
I nter pret ati o n 
− 
N o reacti o n  
Ne gati ve  
± ?  
Er yt he ma o nl y, n o i nfiltrati o n  
D o u btf ul reacti o n  
+  
Er yt he ma, i nfiltrati o n, p ossi bl y discrete pa p ules  
Wea k p ositi ve reacti o n  
+ +  
Er yt he ma, i nfiltrati o n, pa p ules, vesicles  
Str o n g p ositi ve reacti o n  
+ + +  
Er yt he ma, i nfiltrati o n, c o nfl ue nt vesicles  
E xtre me p ositi ve reacti o ns  
Ir 
D iffere nt t y pes of reacti o ns (der matitis, 
parest hesia, dr y ness, b ur ni n g )  
Irrita nt reacti o n 
 
 
A p pr o priate n ess of Safet y Assess me nts  
Safet y e val uati o ns sele ct e d f or t his st u d y are t y pical of t h ose f or t his patie nt  p o p ulati o n a n d 
ut ilize wi del y acce pte d meas ures. 
 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 4 9  
9  
A D V E R S E E V E N T S  
A n A E is defi ne d as a n y u nt o war d me dical o cc urre nce i n a p atie nt  a d mi nistere d a p h ar mace utical 
pr o d uct d uri n g t he c o urs e of a cli nic al i n vesti gati o n. A n A E ca n t h eref ore be a n y u nfa v ora ble 
a n d u ni nte n de d si g n, s y m pt o m, or disease te m p orall y ass ociate d wit h  t he use of a st u d y dr u g , 
w het her or n ot t h o u g ht t o be relate d t o t he st u d y dr u g. 
Eac h A E will be c ollecte d fr o m t he si g ni n g of t he I C F u ntil t he f oll o w -u p/ en d -of -st u d y visit. 
A d verse e ve nts t hat are i de ntifie d at t he last assess me nt visit ( or t he earl y t e r mi nati o n visit) m ust 
be rec or de d o n t he A E e C R F wit h t he stat us of t he A E n ote d. All e ve nts t h at are o n g oi n g at t his 
ti me will be rec or de d as o n g oi n g o n t he e C R F. If t he I n v esti gat or i n dicates t he A E is “ pr o ba bl y”, 
“ p ossi bl y”, or “ defi nitel y” relate d t o t he st u d y dr u g, t he A E m ust be f oll o we d u ntil t he y are 
res ol ve d or me dicall y sta ble, or u ntil reas o na ble atte m pts t o deter mi ne res ol uti o n of t he e ve nt are 
e x ha uste d. T he i n v esti gat or s h o ul d use his/ her discreti o n i n or deri n g a d diti o nal tests as necess ar y 
t o m o nit or  t he res ol uti o n of s uc h e ve nts. 
T he pr oce d ures s p ecifie d i n Secti o n 9 . 4 are t o be f oll o we d f or re p orti n g S A Es.  
9. 1  
Rec or di n g A d verse E ve nts  
A d verse e ve nts are t o be rec or de d o n t he A E p a ge of t he e C R F. T he f oll o wi n g i nf or mati o n will 
be rec or de d:  
•  Assess me nt of w het he r or n ot t he A E is a n S A E (Secti o n 9 . 2. 1) 
•  Assess me nt of A E i nte nsit y ( Secti o n 9 . 2. 2) 
•  Assess me nt of A E relati o ns hi p t o st u d y dr u g (Secti o n 9 . 2. 3) 
•  Acti o n ta ke n - cate g ori ze d as d ose i ncreas e d or decreas e d , d ose n ot c ha n ge d, dr u g 
i nterr u pte d, dr u g wit h dr a w n, n ot a p plica ble, or u n k n o w n, as a p plica ble 
•  O utc o me - rec or de d as fatal, n ot rec o vere d/ n ot res ol ve d, rec o v ere d/r es ol ve d, 
rec o vere d/r es ol ve d wit h se q uelae, rec o v eri n g/res ol vi n g, or u n k n o w n, as a p plica ble  
9. 2  
Assess m e nt of A d verse E ve nts  
T he i n vesti gat or will assess eac h A E f or s eri o us n ess, i nte nsit y, a n d relati o ns hi p t o st u d y dr u g. 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 5 0  
 
Seri o us A d verse E v e nts  
T he i n vesti gat or is res p o nsi ble f or deter mi ni n g w het her a n A E meets t he d efi niti o n of a n S A E. 
A n S A E is a n y A E occ urri n g fr o m I C F si g ni n g t hr o u g h f oll o w-u p t hat res ults i n a n y of t he 
f oll o wi n g o utc o mes: 
•  Deat h  
•  A life -t hreate ni n g a d vers e dr u g e x perie nce  
•  I n p atie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n 
•  A ne w persiste nt or si g nifica nt disa bilit y/i nca pacit y  
•  A c o n ge nital a n o mal y/ birt h defect  
•  A n i m p orta nt me dical e v e nt(s)  
I m p ort a nt me dical e v e nts t hat ma y n ot res ult i n deat h, be life t hreate ni n g, or re q uire 
h os pitalizati o n ma y be c o nsi dere d a n S A E w he n, base d u p o n a p pr o priate me dical j u d g me nt, t he y 
ma y je o par dize t he patie nt  a n d ma y re q uir e me dical or s ur gical i nter v e nti o n t o pre ve nt a n y of t h e 
o utc o mes liste d i n t his defi niti o n.  E xa m ples of s uc h me dical e ve nts i ncl u de aller gic 
br o nc h os pas m re q uiri n g i nte nsi ve treat me nt i n a n e mer ge n c y r o o m or at h o me, bl o o d d yscrasias 
or c o n v ulsi o ns t hat d o n ot res ult i n i n patie nt h os pitalizati o n, or t he de v el o p me nt of dr u g 
de pe n de n c y or dr u g a b u s e. 
N ote: S A Es re q uire i m m e diate re p orti n g t o t he S p o ns or . Refer t o Secti o n  9. 4  f or details. 
 
I nte nsit y 
T he i nte nsit y of a n A E will be gra de d acc or d i n g t o t he f oll o wi n g defi niti o ns: 
•  Mil d: T he patie nt  e x perie nces a ware n ess of s y m pt o ms b ut t hese are easil y t olerate d or 
ma na ge d wit h o ut s pecifi c treat me nt . 
•  M o derate: T he p atie nt  e x perie nces disc o mf ort e n o u g h t o ca use i nterfere nce wit h us ual 
acti vit y, a n d/ o r t he c o n diti o n re q uires s pecifi c treat me nt. 
•  Se vere: T he p atie nt  is i nca pacitate d wit h i na bilit y t o w or k or d o us ual acti vit y, a n d/ or t he 
e ve nt re q uir es si g nifica nt treat me nt meas ures.  
 
Relati o ns hi p t o St u d y Dr u g  
T he relati o ns hi p of a n A E  t o t he st u d y dr u g s h o ul d be deter mi ne d b y t he i n vesti gat or acc or di n g 
t o t he f oll o wi n g criteria: 
•  U n relate d: T his c ate g or y a p plies t o t h ose A Es t hat are cl earl y a n d i nc o ntr o v erti bl y d ue t o 
e xtra ne o us ca uses ( diseas e, e n vir o n me nt, etc ). 
•  U nli kel y : T his cate g or y a p plies t o t h ose A Es t hat are j u d ge d t o be u nrelate d t o t he test 
dr u g/st u d y pr oce d ure g ut f or w hic h n o e xtra ne o us ca use ma y be f o u n d. A n A E ma y be 
c o nsi dere d u nli kel y t o be relate d t o i n vesti gati o nal pr o d uct/ pr oce d ure if or w he n it meets 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
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C O N FI D E N TI A L  
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2 of t he f oll o wi n g crit eri a:( 1) it d oes n ot f oll o w a reas o na bl e te m p oral se q u e nce fr o m 
a d mi nistrati o n of t he test dr u g/st u d y pr oce d ure; ( 2) it c o ul d rea dil y ha ve b ee n pr o d uce d 
b y t he patie nt’ s cli nical state, e n vir o n me ntal or t o xic fact ors, or ot her m o d es of t herap y 
a d mi nistere d  t o t he patie nt; ( 3) it d oes n ot f oll o w a k n o w n patter n of res p o nse t o t he test 
dr u g/st u d y pr oce d ure; or ( 4) it d oes n ot rea p p ear or w orse n w he n t he dr u g/st u d y 
pr oce d ure is re -a d mi nistere d.  
•  P ossi bl y: T his cate g or y a p plies t o t h ose A Es f or w hic h a c o n necti o n wit h t he test 
dr u g/st u d y pr oce d ure a d mi nistrati o n a p pears u nli kel y b ut ca n n ot be r ule d o ut wit h 
certai nt y. A n A E m a y be c o nsi dere d p ossi bl y relat e d if or w he n it meets 2 of t he 
f oll o wi n g criteria: ( 1) it f oll o ws a reas o n a ble te m p oral se q ue n ce fr o m a d mi nistrati o n of 
t he dr u g/st u d y pr oce d ure; ( 2) it c o ul d n ot rea dil y ha ve bee n pr o d uce d b y t he patie nt’s  
cli nical state, e n vir o n me ntal or t o xic fact ors, or ot her m o des of t hera p y a d mi nistere d t o 
t he patie nt ; or (s) it f oll o ws a k n o w n patter n of res p o nse t o t he test dr u g/st u d y pr oce d ure.  
•  Pr o ba bl y:  T his cate g or y  a p plies t o t h ose A Es t hat t he i n vesti gat or feels wit h a hi g h 
de gree of certai nt y are relate d t o t he test dr u g/st u d y pr oce d ure. A n A E m a y be c o nsi dere d 
pr o ba bl y relat e d if or w h e n it meets 3 of t he f oll o wi n g  criteria: ( 1) it f oll o ws a reas o na ble 
te m p oral se q ue n ce fr o m a d mi nistrati o n of t he dr u g/st u d y pr oce d ure; ( 2) it c o ul d n ot be 
reas o na bl y e x plai ne d b y t he k n o w n c haracteristics of t he patie nt’s cli nical state, 
e n vir o n me ntal or t o xic fact ors, or ot her m o des of t hera p y a d mi nistere d t o t he patie nt; ( 3) 
it disa p pears or decreases o n cessati o n or re d ucti o n i n d ose ( n ote t hat t here are e x ce pti o ns 
w here a n A E d oes n ot disa p pear u p o n dis c o nti n uati o n of t he dr u g, yet dr u g -relate d n ess 
clearl y e xists; f or e xa m pl e, as i n b o ne marr o w de pressi o n, fi xe d dr u g er u pti o ns, or tar di ve 
d ys ki nesia); or ( 4) it f oll o ws a k n o w n patter n of res p o nse t o t he test dr u g/st u d y 
pr oce d ure.  
•  Defi nitel y:  T his cate g or y a p plies t o t h ose A Es t hat t he in vesti gat or feels are 
i nc o ntr o verti bl y relate d t o test dr u g/st u d y pr oce d ure. A n A E ma y b e assi g n e d a n 
attri b uti o n of defi nitel y relate d if or w he n it meets all of t he f oll o wi n g criteria: ( 1) it 
f oll o ws a reas o n a ble te m p oral se q ue n ce fr o m a d mi nistrati o n of t he dr u g/st u d y pr oce d ure; 
( 2) it c o ul d n ot be reas o n a bl y e x plai ne d b y t he k n o w n c haracteristics of t he patie nt’s 
cli nical state, e n vir o n me nt or t o xic fact ors, or ot h er m o des of t hera p y a d mi nistere d t o t he 
patie nt ; ( 3) it disa p pears or decreases o n cessati o n or re d ucti o n i n d ose a n d re occ urs wit h 
re-e x pos ure t o t he dr u g (if re -c halle n ge o cc urs); a n d ( 4) it f oll o ws a k n o w n patter n of 
res p o nse t o t he test dr u g/st u d y pr oce d ure. 
9. 3  
Disc o nti n u ati o n d ue t o A d verse E ve nts  
A n y patie nt  w h o e x perie nces a n A E m a y be wit h dra w n at a n y ti me fr o m t he st u d y at t he 
discreti o n of t he i n vesti g at or. Patie nts  wit h dra w n fr o m t he st u d y d ue t o a n A E, w het her s eri o us 
or n o nseri o us, m a y be f oll o we d b y t he i n vesti gat or u ntil t he cli nical o utc o me of t he A E is 
deter mi ne d. T he A E(s) s h o ul d be n ote d o n t he a p pr o priate e C R Fs a n d t he patie nt ’s pr o gress 

L u m osa T hera pe utics C o., L t d. 
 
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C O N FI D E N TI A L  
Pa ge 5 2  
s h o ul d be f oll o we d u ntil t he A E is res ol ve d or me dicall y sta ble  as deter mi ne d b y t he i n vesti gat or . 
T he S p o ns or  m ust be n otifie d. If t he A E relate s t o o ver d ose of st u d y tr eat me nt, t he I n vesti gat or’s 
Br oc h ure s h o ul d be c o ns ulte d f or details of a n y s p ecific acti o ns t o be ta ke n.  
9. 4  
R e p orti n g Seri o us A d verse E ve nts  
I n t he e ve nt of a n y S A E re p orte d or o bs er ve d d uri n g t he st u d y, w het her or n ot attri b uta ble t o t he 
st u d y dr u g, site pers o n nel will rec or d a n d re p ort it t o t he S p o ns or  or desi g nee wit hi n 2 4 h o urs of 
occ urre nce or w he n t h e i n vesti gat or bec o mes a ware of t he e v e nt i n acc or da nce wit h pr oce d ures 
descri be d i n t he S R M . If t he i n vesti gat or re p orts t he S A E b y tele p h o ne, a writte n re p ort m ust 
f oll o w wit hi n 2 4 h o urs i ncl u di n g a f ull descri pti o n of t he e ve nt a n d s e q uelae i n t he f or mat 
detaile d i n t he S A E re p orti n g f or m . 
S A E Re p ort F or ms will be pr o vi de d t o t he C R U  t o assist i n c ollecti n g, or ga nizi n g, a n d re p orti n g 
S A Es a n d f oll o w -u p i nf or mati o n.  
All S A Es s h o ul d be f oll o we d t o t heir res ol uti o n, wit h d oc u me ntati o n pr o vi de d t o t he Sp o ns or o n  
a f oll o w-u p S A E Re p ort F or m.  
C o nt acts f or S A E R e p orti n g:  
 
 
 
9. 5  
Pre g n a nc y  
Pre g na ncies will be ca pt ure d if t he y occ ur i n fe male patie nts  fr o m t he ti me t he patie nt  is first 
e x p ose d t o t he st u d y dr u g u ntil 3 0  da ys af ter t he l ast e x p os ure or t h e last st u d y visit, w hic he ver 
occ urs later. Pre g na n cies i n t he s e x ual part ners of male patie nt s will be ca pt ure d fr o m t he ti me 
t he patie nt is first e x pose d t o t he st u d y dr u g u ntil 9 0  da ys after l ast e x p os ure t o t he st u d y dr u g.  
Fe male p atie nts  m ust be i nstr ucte d t o disc o nti n ue all st u d y dr u gs a n d i nf or m t he st u d y 
i n vesti gat or i m me diatel y if t he y bec o me pre g na nt d uri n g t he st u d y.  
T he i n vesti gat or m ust re p o rt a n y pre g n a nc y t o t he S p o ns or  or desi g nee  wit hi n 1  b usi ness da y of 
bec o mi n g a ware of t h e pre g na nc y p er pre g na nc y re p orti n g pr oce d ures des cri be d i n t he S R M . 
T he patie nt  m ust be i m me diatel y disc o nti n ue d fr o m f urt her treat me nt wit h st u d y dr u g. A n 
u nc o m plica te d pre g n a nc y will n ot be c o nsi dere d a n A E or S A E; h o we v er, all pre g na nci es will be 
f oll o we d t hr o u g h birt h a n d 3 m o nt hs p ost  deli ver y . 
A n y c o n ge nital a b n or m alities i n t he offs pri n g of a patie nt  w h o recei ve d st u d y dr u g will be 
re p orte d as a n S A E. T he o utc o me of a n y pre g na n c y a n d t he pres e nce or a bs e nce of a n y 
c o n ge nital a b n or malit y will be rec or de d i n t he s o urce d oc u m e ntati o n a n d re p orte d t o t he  
S p o ns or . 

L u m osa T hera pe utics C o., Lt d.  
 
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C O N FI D E N TI A L  
Pa ge 5 3  
1 0  
S T A TI S TI C A L C O N SI D E R A TI O N S  
T he statistical a nal ysis will be c o n d ucte d f oll o wi n g t he pri nci ples as s pecifi e d i n I C H T o pic E 9 
( C P M P/I C H/ 3 6 3/ 9 6). 
All statistical a nal yses will be descri be d i n a s e par ate statistical a nal ysis pla n.  
1 0. 1  
S a m ple Size C alc ul ati o n  
It is pla n ne d t o c o m plete 1 8 s u bjects i n Part A a n d 9 0 s u bjects i n Part B i n t his st u d y. T his 
sa m ple size is c h ose n  o n cli nical rat her t h a n statistical rati o nale. N o f or mal sa m ple size 
calc ulati o ns were perf or me d . T he sa m ple size is c o nsi dere d a de q uat e t o a d dress t he st u d y g oals. 
1 0. 2  
A n al ysis P o p ul ati o ns  
P har mac o k i netic a n al ysis set ( P K A S): T he P K A S set will i ncl u de patie nts w h o ha ve recei v e d at 
least 1 d ose of L T 5 0 0 1 dr u g pr o d uct  a n d h a ve at l east 1 meas ure d c o nce ntr ati o n of L T 5 0 0 1  dr u g 
pr o d uct  at a sc h e d ule d P K ti me p oi nt after d osi n g.  
Safet y a nal ysis set  ( S A S): T he S A S will i ncl u de all patie nts w h o recei ve at least 1 d ose of 
L T 5 0 0 1  dr u g pr o d uct  or place b o i n Parts A a n d B. Patie nts will be a nal yze d acc or di n g t o t he 
treat me nt t he y act uall y recei ve d. 
F ull a nal ysis set  ( F A S): T he F A S will i ncl u de all ra n d o mize d patie nts w h o recei v e at least 1 d ose 
of L T 5 0 0 1 dr u g pr o d uct or place b o.  
P er-P r ot oc ol ( P P): T he P P p o p ulati o n will c o m prise all F A S patie nts w h o c o m plete t he st u d y 
pr oce d ures wit h o ut a maj or pr ot oc ol de viati o n. T h e P P p o p ulati o n will als o be use d f or t h e 
a nal ysis of effi cac y.  
1 0. 3  
R a n d o miz ati o n  
Patie nt s will be ra n d o mize d i nt o t he st u d y o nce t he y ha ve c o m plete d scree ni n g a n d t he Da y -1 
pre d osi n g assess me nts a n d ha ve satisfie d all eli gi bilit y criteria. 
F or Part A, p atie nts  will be ra n d o mize d i n t o a 2:1  rati o t o recei ve L T 5 0 0 1 dr u g pr o d uct  or 
place b o. F or Pa rt B, patie nts will be ra n d o mize d i nt o a 1 :1  rati o t o recei ve L T 5 0 0 1 dr u g pr o d uct  
or place b o.  
1 0. 4  
E n d p oi nts  
 
Part A Pri mar y E n d p oi nt  
•  Nat ure a n d s e verit y of A Es a n d n u m ber of patie nts wit h A Es.  
 
Part A  Sec o n dar y E n d p oi nt s 
•  
 
 
•  C ha n ge i n mea n W orst Itc hi n g I nt e nsit y fr o m baseli ne t o t he e n d of Wee k 4 usi n g N R S.  

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
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C O N FI D E N TI A L  
Pa ge 5 4  
•  Re d ucti o n of itc h i nte nsit y as assess e d b y t he pr o p orti o n of patie nts re d uce d N R S fr o m 
baseli ne ( ≥ 2 p oi nts, ≥ 3 p oi nts, or ≥ 4 p oi nts) wit h res pect t o t he wee kl y mea n of t he 
dail y 2 4 -h o ur W orst Itc hi n g I nte nsit y N R S sc ore fr o m b aseli ne t o t he e n d of Wee k 4. 
•  I m pr o v e me nt i n itc h-relate d q uality of life as assesse d b y t he c ha n g e fr o m baseli ne i n 5 -D 
Itc h Sc ale sc ore t o t he e n d of Wee k 4. 
•  I m pr o v e me nt i n itc h-relate d q ualit y of life as assesse d b y t he c ha n g e fr o m baseli ne i n t he 
t otal S ki n de x-1 0 Scale sc ore t o t he e n d of Wee k 4. 
 
Part B Pri mar y E n d p oi nt  
•  C ha n ge fr o m bas eli ne t o e n d of Wee k 8 i n mea n W orst Itc hi n g I nte nsit y usi n g N R S. 
 
Part B Sec o n dar y E n d p oi nt s 
•  Re d ucti o n of itc h i nte nsit y as assesse d b y t he pr o p orti o n of patie nts re d uce d N R S fr o m 
baseli ne wit h res pect t o t he wee kl y mea n of t he d ail y 2 4 -h o ur W orst Itc hi n g I nte nsit y 
N R S sc ore fr o m bas eli ne t o e n d of Wee k 8 . 
•  I m pr o v e me nt i n itc h-relate d q ualit y of life as assesse d b y t he c ha n g e fr o m baseli ne i n 5-D 
Itc h Sc ale sc ore t o t he e n d of Wee k 8. 
•  I m pr o v e me nt i n itc h-relate d q ualit y of life as assesse d b y t he c ha n g e fr o m baseli ne i n 
t otal S ki n de x-1 0 Scale sc ore t o t he e n d of Wee k 8. 
•  Nat ure a n d s e verit y of A E s a n d n u m ber of patie nts wit h A Es. 
1 0. 5  
P h ar m ac o ki netic A n al ysis  P art A ( o nl y)  
T he f oll o wi n g P K para m eters  will be deter mi ne d f or L T 5 0 0 1  dr u g pr o d uct : 
All calc ulati o ns f or P K p ara meters will be base d o n act ual d osi n g a n d sa m pli n g ti mes rec or de d 
d uri n g t he st u d y. C o nsi deri n g t he act u al d ose recei ve d b y eac h p atie nt ma y var y, t he P K 
par a meter will be a dj uste d b y di vi di n g t o t he act ual d ose of eac h patie nt  
A dj uste d P K para meter = C tr o u g h/ Act ual D ose  
T he act ual d osi n g i n e ac h patie nt will be deter mi ne d b y s u btract t he wei g ht of eac h ret ur n e d 
st u d y dr u g fr o m t he i nitial wei g ht ( T0). I n a dditi o n, t he ori gi nal bl o o d P K para meter ( wit h o ut 
d ose a dj ust me nt) vers us ti me will als o be a nal yze d.  
P har mac o ki netic para met ers will be liste d b y s u bject a n d treat me nt usi n g t h e S A S, a n d 
s u m marize d b y treat me nt usi n g t he usi n g t he p har mac o ki netic a nal ysis set ( P K A S) a n d t he 
f oll o wi n g s u m mar y statistics: n, arit h metic mea n, sta n dar d de viati o n ( S D), C V %, mi ni m u m, 
me dia n, a n d ma xi m u m. Ge o metric mea n a n d ge o metric C V % will als o be prese nte d f or all P K 
para meters.  
C tr o u g h 
L o west o bser ve d bl o o d c o nce ntrati o n pri or t o ne xt a p plicati o n  

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
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Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 5 5  
Scatter pl ots of i n di vi d ual a dj uste d P K para mete rs ( Ctr o u g h/ Act ual D ose) a n d n o n-a dj uste d P K 
para meters ( C tr o u g h) vers us ti me f or L T 5 0 0 1 dr u g pr o d uct will be pr o d uce d o n l o g-l o g scales 
usi n g t he P K A S.  
1 0. 6  
S afet y A n al ysis  
All safet y a nal ysis will be perf or me d o n t he S A S  f or b ot h Part A a n d Part B. 
A d verse e ve nts will be c o de d b y S yste m Or ga n Class a n d Preferre d Ter m usi n g t he c urre nt 
versi o n of Me d D R A. I n ci de nces of T E A Es (ie, e v e nts t hat starte d aft er 1 st d ose of t he  st u d y dr u g 
or w orse n e d i n se verit y after 1 st d osi n g), wi ll be prese nte d b y d ose gr o u p. I ncide nces of T E A Es 
will als o be prese nte d b y ma xi m u m se verit y a n d relati o ns hi p t o st u d y me dicati o n.  
Safet y data will be s u m m arize d t hr o u g h a p pr o pri ate data ta b ulati o ns, sta n dar d descri pti ve 
statistics, a n d gra p hical prese ntati o ns. F or eac h c o nti n u o us la b orat or y para meter, res ults will be 
cate g oriz e d as l o w, n or m al, or hi g h base d o n t he l a b orat or y n or m al ra n g es. Fre q u e ncies a n d 
perce nt a ges will be prese nte d b y d ose gr o u p f or p atie nts  w h o ha d a s hift t o l o w a n d f or patie nts  
w h o ha d a s hift t o hi g h fr o m baseli ne t o a n y p ost-d osi n g assess me nt.  
T he ass ociati o n of A Es, cli nical la b orat or y tests, vital si g n meas ure me nts wit h t he  act ual d os i n g 
of t he st u d y dr u g or s yste mic e x p os ure of L T 5 0 0 1 dr u g pr o d uct ma y als o be e x pl ore d. If 
a p pr o priate, statistical m o deli n g will be perf or me d t o f urt her c h aracterize t he ass ociati o ns 
me nti o ne d a b o ve. All o ut -of -ra n ge a n d cli nicall y si g nifica nt la b orat or y res ults will be i de ntifie d 
i n patie nt  data listi n gs. T he n u m ber a n d p erce nta ge of patie nts  i n eac h d ose gr o u p wit h nor mal 
a n d a b n or mal p h ysic al e xa mi nati o n res ults will be prese nt e d f or e val uati o ns at baseli ne a n d fi n al 
visit.  
F or eac h b o d y s yste m, c h a n ges i n t he patie nts ’ fi n di n gs fr o m baseli ne t o fi nal visit ( n o c ha n ge, 
n or mal t o a b n or mal, or a b n or mal t o n or mal) will be ta b ulate d f or eac h d os e gr o u p.  
A p plicati o n site e xa mi nati o n  ( o bser ve d a n d c ha n g e fr o m baseli ne) will be s u m marize d b y ti me 
p oi nt usi n g a p pr o priate d escri pti ve statistics.  
T he n u m ber a n d p erce nta ge of patie nts  re p orti n g a n y treat me nt-e mer ge nt A E will be ta b ulate d 
b y s yste m or ga n class a n d preferre d t er m (c o d e d usi n g M e d D R A). Treat me nt-e mer ge nt A Es will 
be f urt her classifie d b y s e verit y a n d relati o ns hi p t o treat me nt.  
1 0. 7  
Effic ac y A n al ysis  
T he effi cac y of L T 5 0 0 1  dr u g pr o d uct  will be assesse d via t he f oll o wi n g:  
Part A:  
•  C ha n ge i n mea n W orst Itc hi n g I nt e nsit y usi n g N R S.  
•  Pr o p orti o n of patie nts re d uce d N R S fr o m baseli n e wit h res pect t o wee kl y mea n of t he 
dail y 2 4 -h o ur W orst Itc hi n g I nte nsit y N R S sc ore fr o m baseli ne t o t he e n d of W ee k 4.  
•  C ha n ge fr o m bas eli ne i n 5 -D Itc h Scal e sc ore at t h e e n d of Wee k 4.  

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 5 6  
•  C ha n ge fr o m bas eli ne i n t otal S ki n de x -1 0 Scale sc ore at t he e n d of Wee k 4.  
Part B:  
•  C ha n ge i n mea n W orst Itc hi n g I nt e nsit y usi n g N R S.  
•  Pr o p orti o n of patie nts re d uce d N R S fr o m baseli n e wit h res pect t o t he wee kl y mea n of t he 
dail y 2 4 -h o ur W orst Itc hi n g I nte nsit y N R S sc ore fr o m baseli ne t o t he e n d of Wee k 8.  
•  C ha n ge fr o m bas eli ne i n 5 -D Itc h Scal e sc ore at t h e e n d of Wee k 8.  
•  C ha n ge fr o m bas eli ne i n t otal S ki n de x -1 0 sc ore at t he e n d of Wee k 8.  
Mi xe d -effect m o del r e peate d meas ur es a nal ysis of c o varia n ce will be a p pli e d t o c o m pare t h e 
treat me nt gr o u ps f or effi cac y e n d p oi nts (i.e. c ha n ge of N R S, c ha n ge fr o m baseli ne i n 5-D Itc h 
Scale, c ha n g e fr o m b aseli ne i n t otal S ki n de x -1 0), wit h baseli ne itc h  a n d pri or a nti -itc h 
me dicati o n use as c o v ari ates , a n d patie nt as a ra n d o m effect.  
Pr o p orti o n of patie nts i m pr o ve d N R S fr o m baseli ne ( 2 -p oi nts, 3 -p oi nts, or 4 -p oi nts) was 
e val uate d at eac h ti me p oi nt c o m pare d bet w ee n tr eat me nt gr o u p usi n g l o gistic re gressi o n 
a nal ysis.  
1 0. 8  
Ot her S t atistic al C o nsi der ati o n s 
C o nti n u o us data will be s u m marize d usi n g descri pti ve statistics as n u m ber of o bser vati o ns, 
mea n, me dia n, sta n dar d de viati o n, mi ni m u m, a n d ma xi m u m. Cate g orical data will be 
s u m marize d b y n u m ber, fre q ue n c y, a n d perce nta ge.  
1 0. 9  
Dr o p o uts, Pre m at ure T er mi n ati o n, a n d Missi n g V al ues  
T he dr o p o uts, pre mat ure ter mi nati o n of st u d y me dicati o n, a n d wit h dra wal will be s u m marize d 
a n d a nal yz e d b y treat me nt gr o u ps. A listi n g of patie nts wit h wit h dra wal, as well as t h ose wit h 
pre mat u re t er mi nati o n of st u d y me dicati o n al o n g wit h t he date a n d reas o ns f or ter mi nati o n, will 
be pr o vi de d. Ge nerall y, t he last -o bser vati o n -carrie d -f or war d pr o ce d ure will be use d t o esti mate 
t he missi n g data f or efficac y vari a bles. N o i m p utati o n will be d o ne f or esti mati n g t he missi n g 
val ues f or safet y varia bles a n d ti me t o e ve nt data.  
1 0. 1 0  
I nteri m A n al ysis 
After c o m pleti o n of Part A, a n e val u ati o n of all safet y data will be perf or m e d. D S M B will 
re vie w i nteri m a n al ysis a n d gi ve c o m me nts o n safet y or a n y me dical c o ncern t o deter mi ne 
w het her t he st u d y c o nti n ue d or n ot. Als o, D S M B will gi ve c o m me nts f or L T 5 0 0 1 dr u g pr o d uct 
dail y d ose a n d re gi me n f or Part B.  S p o ns or will ma ke t he fi nal d ecisi o n i n a n u n bli n de d fas hi o n.  
 
 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 5 7  
1 1  
A C C E S S T O S O U R C E D A T A/ D O C U M E N T S  
T he i n vesti gat or will pr o vi de direct a ccess t o s o urce data a n d d oc u me nts f or i n di vi d uals 
c o n d ucti n g st u d y -relate d m o nit ori n g, a u dits, I E C r e vie w, a n d re g ulat or y re vie w. T he i n vesti gat or 
m ust i nf or m t he st u d y patie nt  t hat his/ her st u d y-relate d rec or ds ma y be revi e we d b y t he a b o ve 
i n di vi d uals wit h o ut vi olati n g t he patie nt ’s pri vac y of pers o nal healt h i nf or m ati o n i n c o m plia nce 
wit h H ealt h Ins ura n ce P orta bilit y a n d Acc o u nta bilit y Act of 1 9 9 6 re g ulati o ns. 
Atte nti o n is dra w n t o t he re g ulati o ns pr o m ul gate d b y t he F D A u n d er t he Free d o m of I nf or mati o n 
Act pr o vi di n g, i n part, t hat i nf or mati o n f ur nis he d t o  cli nical i n vesti gat ors a n d I E Cs will be ke pt 
c o nfi de ntial b y t he F D A o nl y if mai ntai ne d i n c o nfi de nce b y t he cli nical i n vesti gat or a n d I E C. 
B y si g ni n g t his pr ot oc ol,  the i n vesti gat or affir ms t o t he S p o ns or t hat t he i n vesti gat or will 
mai ntai n, i n c o nfi de nce, i nf or mati o n f ur nis he d t o hi m or her b y t he Sp o ns or a n d will di v ul ge 
s uc h i nf or mati o n t o t he I E C u n der a n a p pr o priate u n dersta n di n g of c o nfi de ntialit y wit h s uc h 
b oa r d. 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 5 8  
1 2  
Q U A LI T Y C O N T R O L A N D Q U A LI T Y A S S U R A N C E  
S p o ns or  or desi g nate d C R O will i m ple me nt a n d mai ntai n q ualit y c o ntr ol a n d q ualit y ass ura nce 
pr oce d ures wit h writte n S O Ps t o e ns ure t he st u d y is c o n d ucte d a n d dat a are ge nerate d, 
d oc u me nte d, a n d re p orte d i n c o m plia n ce wit h t he pr ot oc ol, G C P, a n d a p pl ica ble re g ulat or y 
re q uire me nts. 
1 2. 1  
C o n d uct of St u d y  
T his st u d y will be c o n d ucte d i n acc or da n ce wit h t he pr o visi o ns of t he Declarati o n of Helsi n ki 
a n d all re visi o ns t here of ( T o k y o 2 0 0 4), a n d i n acc or da nce wit h F D A C F R  ( § 3 1 2. 50 a n d § 3 1 2. 5 6) 
a n d t he I C H E 6 G ui deli n es o n G C P  ( C P M P/I C H/ 1 3 5/ 9 5). S pecificall y, t his st u d y is base d o n 
a de q uatel y p erf or m e d la b orat or y a n d a ni mal e x peri me ntati o n; t he st u d y will be c o n d ucte d u n der 
a pr ot oc ol re vi e we d b y a n I E C; t he st u d y will be c o n d ucte d  b y scie ntificall y a n d me dicall y 
q ualifie d pers o ns; t he be nefits of t he st u d y are i n pr o p orti o n t o t he ris ks; t he ri g hts a n d welf are of 
t he patie nts  will be res pecte d; t he p h ysicia ns c o n d ucti n g t he st u d y d o n ot fi n d t he hazar ds t o 
o ut wei g h t he p ote ntial be nefits; a n d eac h patie nt  will gi ve his or her writte n, i nf or me d c o nse nt 
bef ore a n y pr ot oc ol -dri ve n tests or e val uati o ns are perf or me d.  
T he i n vesti gat or ma y n ot de viate fr o m t he pr ot oc ol wit h o ut a f or mal pr ot oc ol a me n d me nt ha vi n g 
bee n esta blis he d a n d a p pr o v e d b y a n a p pr o priate I E C, e xce pt w he n n ecessar y t o eli mi nate 
i m me diate hazar ds t o t he patie nt  or w he n t he c ha n ge(s) i n v ol ve o nl y l o gistical or a d mi nistrati ve 
as pects of t he st u d y a n d are a p pr o ve d b y t he  S p o ns or . A n y de viati o n ma y res ult i n t he patie nt  
ha vi n g t o be wit h dra w n fr o m t he st u d y, a n d ma y re n der t hat patie nt  n o n e val ua ble.  
 
Pr ot oc ol De viati o ns  
A pr ot oc ol de viati o n is defi ne d as a n y i nte nti o nal or u ni nte nti o nal c ha n ge t o, or n o nc o m plia nce 
wit h, t he a p pr o ve d pr ot o c ol pr oce d ures or re q uire me nts. De viati o ns ma y res ult fr o m t he acti o n or 
i nacti o n of t he patie nt , i n vesti gat or, or site staff. 
At t he o utset of t he st u d y, a pr ocess f or defi ni n g a n d ha n dli n g pr ot oc ol de viati o ns will be 
esta blis he d. T his will i ncl u de deter mi ni n g w hic h vi olati o ns will be desi g nat e d “ ke y, ” re q uiri n g 
i m me diate n otificati o n t o L u m osa T hera p e utics C o., Lt d. T he i n vesti gat or is res p o nsi ble f or 
seei n g t hat a n y k n o w n pr ot oc ol de viati o ns are rec or de d a n d ha n dle d as a gree d.  
1 2. 2  
Pr ot oc ol A me n d me nts  
O nl y t he S p o ns or ma y m o dif y t he pr ot oc ol. A me n d me nts t o t he pr ot oc ol will be ma de o nl y after 
c o ns ultati o n a n d a gree me nt bet wee n t he Sp o ns or a n d t he i n vesti gat or. All a me n d me nts t hat ha ve 
a n i m pact o n patie nt  ris k or t he st u d y o bjecti ves, or re q uire re visi o n of t he I C F, m ust recei ve 
a p pr o val fr o m t he I E C pri or t o t heir i m ple me ntati o n.  

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 5 9  
1 2. 3  
M o nit ori n g of St u d y  
T he i n vesti gat or will per mit t he site m o nit or t o re vie w st u d y data as fre q ue ntl y as is dee me d 
necessar y t o e ns ur e data are bei n g rec or de d i n a n a de q uate m a n ner a n d pr ot oc ol a d here n ce is 
satisfact or y. 
T he i n vesti gat or will pr o vi de access t o me dical r ec or ds f or t he m o nit or t o verif y e C R F e ntries. 
T he i n vesti gat or is e x pecte d t o c o o perat e wit h t he Sp o ns or  or a desi g nee i n e ns uri n g t he st u d y 
a d heres t o G C P re q uire m e nts.  
T he i n vesti gat or ma y n ot recr uit pat ie nts i nt o t he st u d y u ntil t he Sp o ns or  or a desi g nee h as 
c o n d ucte d a site i nitiati o n visit  (i n-pers o n or via t elec o nfere n ce)  t o re vie w t he pr ot oc ol a n d e C R F 
i n detail. 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 6 0  
1 3  
E T HI C S  
1 3. 1  
I nstit uti o n al Re vie w B o ar d/I n de pe n de nt Et hics C o m mittee A p pr o v al  
 
Et hics Re vie w Pr i or t o St u d y 
T he i n vesti gat or will e ns ure t hat t he pr ot oc ol a n d I C F are re vi e we d a n d a p pr o ve d b y t he 
a p pr o priate I E C pri or t o t he start of a n y st u d y pr o ce d ures. T he I E C will be a p pr o priatel y 
c o nstit ute d a n d will perf or m its f u ncti o ns i n acc or da nce wit h F D A  re g ulati o ns, I C H G C P 
g ui deli nes, a n d l ocal r e q uire me nts as a p plica bl e.  
 
Et hics Re vie w of Ot her D oc u me nts  
T he I R B /I E C will a p pr o ve all p r ot oc ol a me n d me nts (e xce pt f or Sp o ns or -a p pr o ve d l o gistical or 
a d mi nistrati ve c ha n ges), writte n i nf or me d c o ns e nt d oc u me nts a n d d oc u me nt u p dates, patie nt  
recr uit me nt pr o ce d ures, writte n i nf or mati o n t o be pr o vi de d t o t he patie nts , a vaila ble safet y 
i nf or mati o n, i nf or mati o n a b o ut pa y me nt a n d c o m p e nsati o n a vaila ble t o pati e nts , t he 
i n vesti gat or’s c urri c ul u m vitae a n d/ or ot her e vi de nce of q ualifi cati o ns, a n d a n y ot her d oc u me nts 
re q ueste d b y t he I R B/I E C a n d re g ulat or y a ut h orit y as a p plica ble. 
1 3. 2  
Writte n I nf or me d C o nse nt  
T he nat ure a n d p ur p ose of t he  st u d y will be f ull y e x plai ne d t o eac h p atie nt . T he patie nts  m ust be 
gi ve n a m ple ti me a n d o p p ort u nit y t o i n q uire a b o ut details of t he st u d y, t o ha ve q uesti o ns 
a ns were d t o t heir satisfacti o n, a n d t o deci de w het h er t o partici pate. Writte n i nf or me d c o nse nt 
m u st be o btai ne d fr o m eac h patie nt  pri or t o a n y st u d y pr oce d ures bei n g perf or me d.  

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot o c ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 6 1  
1 4  
D A T A H A N D LI N G A N D R E C O R D K E E PI N G  
1 4. 1  
D at a Re p orti n g a n d C ase Re p ort F o r ms  
 
Case Re p ort F or ms  
T he i n vesti gat or will be pr o vi de d wit h e C R Fs, a n d will e ns ure all data fr o m patie nt  visi ts are 
pr o m ptl y e ntere d i nt o t he e C R Fs i n acc or da nce wit h t he s pecific i nstr ucti o ns gi ve n. T he 
i n vesti gat or m ust si g n t he e C R Fs t o verif y t he i nt e grit y of t he data rec or de d. 
 
La b orat or y Data  
A list of t he n or mal ra n g es f or all la b orat or y tests t o be u n derta ke n f or ms p art of t he 
d oc u me ntati o n t o be c ollate d pri or t o st u d y start. T he i n vesti gat or m ust mai ntai n s o urce 
d oc u me nts s uc h as la b orat or y re p orts a n d c o m plete hist or y a n d p h ysical e xa mi nati o n re p orts.  
 
Rete nti o n of S o urce D oc u me nts  
T he i n vesti gat or m ust m ai ntai n s o urce d oc u me nts s uc h as la b orat or y re p orts, x -ra ys, E C Gs, 
c o ns ultati o n re p orts, a n d c o m plete hist or y a n d p h ysical e xa mi nati o n re p orts.  
1 4. 2  
Rete nti o n of Esse nti al D oc u me nts  
T he st u d y esse ntial d oc u me nts m ust be mai ntai ne d as s pecifie d i n t he I C H g ui del i nes f or G C P 
a n d t he a p plica ble re g ulat or y re q uire me nts. T h e i n vesti gat or/i nstit uti o n s h o ul d ta ke meas ures t o 
pre ve nt a cci de ntal or pre mat ure destr ucti o n of t h ese d oc u me nts.  
Esse ntial d oc u me nts s h o ul d be retai ne d u ntil at least 2 years after t he l ast a p pr o val of a 
mar keti n g a p plicati o n i n a n I C H re gi o n a n d u ntil t here are n o p e n di n g or c o nte m plate d mar keti n g 
a p plicati o ns i n a n I C H re gi o n or u ntil at least 2 years ha ve ela pse d si nce t h e f or mal 
disc o nti n uati o n of cli nical de vel o p me nt of t he st u d y dr u g. T hese d o c u me nts s h o ul d be retai ne d 
f or a l o n ger p eri o d; h o we ver, if re q uire d b y t he a p plica ble re g ulat or y re q uir e me nts or b y a n 
a gree m e nt wit h t he S p o ns or. It is t he res p o nsi bilit y of t he S p o ns or  t o i nf or m t he 
i n vesti gat or/i nstit uti o n as t o w he n t hese d oc u me nts n o l o n ger nee d t o be ret ai ne d. 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 6 2  
1 5  
A D MI NI S T R A TI V E I N F O R M A TI O N  
1 5. 1  
Fi n a nci n g a n d I ns ur a nce  
Fi na nci n g a n d i ns ur a nce will be a d dresse d i n a s e parate a gree me nt bet wee n t he Sp o ns or  a n d t he 
i n vesti gat or. 
1 5. 2  
P u blic ati o n P olic y  
T he S p o ns or will retai n o w ners hi p of all data. All pr o p ose d p u blicati o ns base d o n t his st u d y will 
be patie nt  t o Sp o ns or’s a p pr o val re q uir e me nts.  

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 6 3  
1 6  
R E F E R E N C E S  
Pis o ni R L, Wi kstr o m B, El der SJ, et al. Pr urit us i n hae m o dial ysis patie nts: I nte r nati o nal r es ults 
fr o m t he Dial ysis O utc o mes a n d practice patter ns St u d y ( D O P P S). Ne p hr ol Dial Tra ns pl. 
2 0 0 6; 2 1( 1 2): 3 4 9 5 -3 5 0 5.  
 
 
 
 
 
 
 
 
  
Pereira M P, Stä n der S . Assess me nt of se verit y a n d b ur de n of pr urit us. Aller g ol I nt. 2 0 1 7 
Ja n; 6 6( 1): 3-7.  

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 6 4  
A P P E N DI X A  N u m eric al R ati n g Sc ale  
 
 
N u merical Rati n g Scale ( N R S), a n  u ni di me nsi o nal scale, w hic h ma y be t he m ost wi del y use d is a 
vali date d meas ur e me nt of U P i nte nsit y i n H D patie nts. T he i nte nsit y ca n be q uic kl y meas ure d wit h 
m o n o di me nsi o nal scales t hat are r o uti nel y use d i n cli nical care a n d R C Ts ( Pereira 2 0 1 7). Patie nts 
ca n be as ke d t o rate t heir itc h i nte nsit y fr o m 0 (“ n o itc h”) t o 1 0 (“ w orst i ma gi na ble itc h”) wit h t he 
N R S. Pr urit us i nte nsit y meas ure d usi n g N R S ca n b e cate g orize d i nt o n o ( 0 p oi nt), mil d ( 1 – 3 p oi nts), 
m o derate ( 4 – 6 p oi nts), se v ere ( 7– 8 p oi nts), a n d ver y se vere pr urit us ( ≥ 9 p oi nts).  
 

L u m osa T hera pe utics C o., Lt d.  
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 6 5  
A P P E N DI X B  
S ki n de x -1 0 Sc ale  
 
Patie nts fill o ne of se ve n b u b bles (“ 0 [ ne ver b ot h ere d], 1, 2, 3, 4, 5, a n d 6 [al wa ys b ot here d]”) f or 
eac h of t he q uesti o ns. T he t otal sc ore is t he s u m of t he n u meric val ue of eac h a ns were d q uesti o n. 
T he d o mai n sc ores a re s u ms of t he f oll o wi n g: disease d o mai n ( q u esti o ns 1 t o 3), m o o d/e m oti o nal 
distress d o mai n ( q uesti o n 4 t o 6), a n d s ocial f u ncti o ni n g d o mai n ( q uesti o ns 7  t o 1 0)  

L u m osa T he ra pe utics C o., Lt d. 
 
Pr ot oc ol: Versi o n: 4 .3  
Pr ot oc ol N u m ber: L T 5 0 0 1 -1 0 1  
 
Date: 0 4  Se p  2 0 2 0  
C O N FI D E N TI A L  
Pa ge 6 6  
A P P E N DI X C  5 -D Itc h Sc ale