A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 2a Study to Assess the Efficacy and Safety of ME3183 Administered Orally in Subjects With Moderate to Severe Plaque Psoriasis
Phase: PHASE2
Conditions: Plaque Psoriasis
Sponsor: Meiji Pharma USA Inc.

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 1  of 8 9  
1  
FI N A L C LI NI C A L S T U D Y P R O T O C O L 
 
 
 
Pr ot oc ol Title:  A M ulti- ce nter, Ra n d o mize d, D o u ble- bli n d, Place b o-c o ntr olle d, Parallel Gr o u p, 
P hase 2a St u d y t o Assess t he Efficac y a n d Safet y of M E 3 1 8 3 A d mi nistere d Orall y i n S u bjects 
wit h M o derate t o Se vere Pla q ue Ps oriasis 
Pr ot oc ol N u m ber:  M E 3 1 8 3- 3 
 
I n vesti g ati o n al Ne w Dr u g (I N D) N u m ber: 
I N D 1 4 0 6 8 8 
N a me of I n vesti g ati o n al Pr o d uct: 
M E 3 1 8 3 
P h ase of De v el o p me nt: 
2a 
I n dic ati o n: 
Pla q ue ps oriasis 
S p o ns or: 
Meiji P har ma U S A I nc. ( herei n after c ollecti vel y referre d 
t o as Meiji) 
5 0 0 Fra n k W. B urr B o ule var d  
T ea nec k, NJ 0 7 6 6 6  
U S A  
T el:  + 1- 2 0 1- 7 7 7- 7 1 3 3 
Fa x: + 1- 2 0 1- 7 7 7- 7 1 3 4 
Pr ot oc ol Versi o n:  
Versi o n 2. 0 
Pr ot oc ol D ate: 
0 7 Dec 2 0 2 1 
 
- C O N FI D E N TI A L- 
T his d oc u me nt a n d its c o nte nts are t he pr o pert y of a n d c o nfi de ntial t o Meiji P har ma U S A I nc. A n y u na ut h orize d 
c o p yi n g or use of t his d oc u me nt is pr o hi bite d. 
 
 
 
••• 
m e 1 J 1 
M eiji P h ar m a U S A I n c. 

Meiji P har ma U S A I nc.
M E 3 1 8 3- 3
M E 3 1 8 3
Versi o n 2. 0 ( 0 7  Dec 2 0 2 1)
T his d oc u me nt is c o nfi de ntial.
P a ge 2 of 8 9
P R O T O C O L A P P R O V A L SI G N A T U R E S
Pr ot oc ol Title:
A  M ulti-ce nter,  Ra n d o mize d,  D o u ble- bli n d,  Place b o-c o ntr olle d,  
Parallel Gr o u p, P hase 2a St u d y t o  Assess t he Efficac y a n d Safet y 
of  M E 3 1 8 3  A d mi nistere d  Orall y  i n  S u bjects  wit h M o derate  t o  
Se vere Pla q ue Ps oriasis
Pr ot oc ol N u m ber:
M E 3 1 8 3- 3
T his st u d y will be c o n d u cte d i n c o m plia nce wit h t he cli nical st u d y pr ot oc ol (a n d 
a me n d me nts), I nter nati o nal C o u ncil f or Har m o nisati o n g ui deli nes f or c urre nt G o o d 
Cli nical Practice , a n d a p plica ble re g ulat or y re q uir e me nts.
S p o ns or Si g n at or y
Mei ji P har ma U S A I nc.
Si g nat ure
Date ( D D- M m m- Y Y Y Y)
, M D
Si g nat ure
Date ( D D- M m m- Y Y Y Y)
D e c 9, 2 0 2 1
Dec 9, 2 0 2 1
P P D
P P D
P P D
P P D
P P D
P P D
P P D

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 3  of 8 9  
I N V E S TI G A T O R SI G N A T U R E P A G E 
P r ot oc ol Title: 
A M ulti-ce nter, Ra n d o mize d, D o u ble- bli n d, Place b o-c o ntr olle d, Parallel Gr o u p, 
P hase 2a St u d y t o Assess t he Efficac y a n d Safet y of M E 3 1 8 3 A d mi nistere d 
Orall y i n S u bjects wit h M o derate t o Se vere Pla q ue Ps oriasis 
P r ot oc ol N u m ber: 
M E 3 1 8 3- 3 
C o nfi de nti alit y a n d C urre nt Cli nic al Pr actice ( G C P)/ E 6 C o m pli a nce St ate me nt 
 
I, t he u n dersi g ne d, ha ve re vie we d t his pr ot oc ol, i ncl u di n g a p pe n dices, a n d I will c o n d uct t he st u d y as 
descri be d i n c o m plia nce wit h t his pr ot oc ol (a n d a me n d me nts), G C P, a n d rele va nt I nter nati o nal 
C o u ncil f or Har m o nisati o n g ui deli nes. 
 
I a m t h or o u g hl y fa miliar wit h t he a p pr o priate use of t he st u d y dr u g, as descri be d i n t his pr ot oc ol a n d 
a n y ot her i nf or mati o n pr o vi de d b y Meiji P har ma U S A I nc. or Meiji Sei ka P har ma C o., Lt d. ( herei n 
after c ollecti vel y referre d t o as Meiji) i ncl u di n g, b ut n ot li mite d t o, t he c urre nt i n vesti gat or’s 
br oc h ure. 
 
O nce t he pr ot oc ol has bee n a p pr o ve d b y t he i n de pe n de nt et hics c o m mittee (I E C)/i nstit uti o nal re vie w 
b oar d (I R B), I will n ot m o dif y t his pr ot oc ol wit h o ut o btai ni n g pri or a p pr o val of Meiji a n d of t he 
I E C/I R B. I will s u b mit t he pr ot oc ol a me n d me nts a n d/ or a n y i nf or me d c o nse nt f or m m o dificati o ns t o 
Meiji a n d t he I E C/I R B, a n d a p pr o val will be o btai ne d bef ore a n y a me n d me nts are i m ple me nte d. 
 
I e ns ure t hat all pers o ns or part y assisti n g me wit h t he st u d y are a de q uatel y q ualifie d a n d i nf or me d 
a b o ut t he Meiji st u d y dr u g a n d of t heir dele gate d st u d y-relate d d uties a n d f u ncti o ns as descri be d i n 
t he pr ot oc ol. 
 
I e ns ure t hat s o urce d oc u me nts a n d st u d y rec or ds t hat i ncl u de all perti ne nt o bser vati o ns o n eac h of t he 
site’s s u bjects will be attri b uta ble, le gi ble, c o nte m p ora ne o us, ori gi nal, acc urate, a n d c o m plete. 
 
I u n dersta n d t hat all i nf or mati o n o btai n e d d uri n g t he c o n d uct of t he st u d y wit h re gar d t o t he s u bjects’ 
state of healt h will be re gar de d as c o nfi de ntial. N o s u bjects’ na mes will be discl ose d. All s u bjects will 
be i de ntifie d b y assi g ne d n u m bers o n all case re p ort f or ms, la b orat or y sa m ples, or s o urce d oc u me nts 
f or war de d t o t he S p o ns or. Cli nical i nf or mati o n ma y be re vie we d b y t he S p o ns or or its a ge nts or 
re g ulat or y a ge ncies. A gree me nt m ust be o btai ne d fr o m t he s u bj ect bef ore discl os ure of s u bject 
i nf or mati o n t o a t hir d- part y. 
 
I nf or mati o n de vel o pe d i n t his cli nical st u d y ma y be discl ose d b y Meiji t o ot her cli nical i n vesti gat ors, 
re g ulat or y a ge ncies, or ot her healt h a ut h orit y or g o ver n me nt a ge ncies as re q uire d. 
 
 
 
Pri nte d Na me 
 
I n vesti gat or Si g nat ure 
 
 
 
Title 
 
Date ( D D- M m m- Y Y Y Y) 
 
 
 
I nstit uti o n 
 
 
 
 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 4  of 8 9  
2  
S Y N O P SI S 
Title of St u d y: 
A M ulti-ce nter, Ra n d o mize d, D o u ble- bli n d , Place b o-c o ntr olle d, P arallel Gr o u p, 
P hase 2a St u d y t o Assess t he Efficac y a n d Safet y of M E 3 1 8 3 A d mi nistere d 
Orall y i n S u bj ects wit h M o derate t o Se vere Pla q ue Ps oriasis 
Pr ot oc ol N u m ber: 
M E 3 1 8 3- 3 
I n vesti g at ors/ St u d y Sites: 
A p pr o xi matel y 3 0 st u d y sites acr oss t he U nite d States a n d Ca na da will partici pate 
i n t his st u d y. 
P h ase of De v el o p me nt: 
P hase 2a  
O bjecti ves: 
Pri m ar y O bjecti ve 
 
T o e val uate t he efficac y of oral M E 3 1 8 3 c o m pare d wit h plac e b o at Wee k  1 6 
i n s u bj ects wit h m o derate t o s e vere pla q ue ps oriasis as meas ure d b y t he 
Ps oriasis Area a n d Se verit y I n de x ( P A SI) sc ore 
Sec o n d ar y O bjecti ves  
 
T o e val uate t he safet y a n d t olera bilit y of oral M E 3 1 8 3 i n s u bj ects wit h 
m o derate t o se vere pla q ue ps oriasis 
 
T o e val uate t he efficac y of oral M E 3 1 8 3 i n s u bj ects wit h m o derate t o se vere 
pla q ue ps oriasis at vari o us ti me p oi nts 
 
T o e val uate t he effect of oral M E 3 1 8 3 o n patie nt-re p orte d o utc o me ( P R O) 
meas ures i n s u bj ects wit h m o d er ate t o se vere pla q ue ps oriasis 
 
T o e val uate t he p har mac o ki netics ( P K) of M E 3 1 8 3 a n d its meta b olite 
( 
) i n s u bj ects wit h m o derate t o se vere pla q ue ps oriasis w h o are 
treate d wit h oral M E 3 1 8 3 
E x pl or at or y O bjecti ves  
St u d y E n d p oi nts: 
Pri m ar y E n d p oi nt 
T he pri mar y efficac y e n d p oi nt is t he pr o p orti o n of s u bj ects ac hie vi n g ≥ 7 5 % 
re d ucti o n fr o m Baseli ne i n t he P A SI sc ore ( P A SI- 7 5) at Wee k 1 6. 
Sec o n d ar y E n d p oi nts  
Safet y E n d p oi nts  
T he safet y e n d p oi nts  are as f oll o ws: 
 
T he i nci de nce, se verit y, a n d s e ri o us ness of a d verse e ve nts ( A Es) re p orte d 
o ver t he 1 6- wee k Treat me nt P eri o d a n d t he 4- wee k F oll o w- u p P eri o d 
 
C ha n ges fr o m Baseli ne i n cli nicall y si g nifica nt ( C S) p h ysical e xa mi nati o n 
fi n di n gs a n d vital si g n meas ur e me nts ( bl o o d press ure, heart rate, res pirat or y 
rate, b o d y te m perat ure, a n d b o d y wei g ht) o ver t he 1 6-wee k Treat me nt P eri o d 
a n d t he 4- wee k F oll o w- u p P eri o d 
 
C ha n ges fr o m Baseli ne i n electr oca r di o gra m ( E C G) fi n di n gs o ver t he 
1 6- wee k Treat me nt P eri o d a n d t he 4- wee k F oll o w- u p P eri o d 
 
C ha n ges fr o m Baseli ne i n safet y la b orat or y val ues ( he mat ol o g y, c oa g ulati o n, 
C CI
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 5  of 8 9  
bl o o d c he mistr y, a n d uri nal ysis) o ver t he 1 6- wee k Treat me nt P eri o d a n d t he 
4- wee k F oll o w- u p P eri o d 
Efficac y E n d p oi nts  
T he sec o n dar y efficac y e n d p oi nts are as f oll o ws: 
 
T he perce nt c ha n ge fr o m Baseli ne i n P A SI sc ore  at all visits fr o m Wee k 1 t o 
Wee k 1 6 
 
T he pr o p orti o n of s u bj ects ac hie vi n g P A SI- 5 0, P A SI- 7 5, P A SI- 9 0, P A SI- 1 0 0 
at all visits fr o m Wee k 1 t o Wee k 1 6 
 
Ti me t o P A SI- 5 0 a n d P A SI- 7 5 
 
T he pr o p orti o n of s u bj ects ac hie vi n g a Static P h ysicia ns Gl o bal 
Assess me nt (s P G A) sc ore of “ 0” (“clear”) or “ 1” (“al m ost cl ear ”) c o m bi ne d 
wit h 2- p oi nt re d ucti o n o n t he 5- p oi nt s P G A scale  at all visits fr o m Wee k 1 t o 
Wee k 1 6 
 
T he c ha n ge fr o m Baseli ne i n af fecte d b o d y s urface area ( B S A) at all visits 
fr o m Wee k 1 t o Wee k 1 6 
 
T he c ha n ge fr o m Baseli ne i n t he itc h n u merical rati n g scale ( N R S) at all 
visits fr o m Wee k 1 t o Wee k 1 6 
 
T he c ha n ge fr o m Baseli ne i n t he Der mat ol o g y Life Q ualit y I n de x ( D L QI) 
sc ore at all visits fr o m Wee k 1 t o Wee k 1 6 
 
P erce nta ge of s u bj ects wit h at least a 5- p oi nt re d ucti o n fr o m Baseli ne i n t he 
D L QI sc ore  at all visits fr o m Wee k 1 t o Wee k 1 6  
P h ar m ac o ki netic E n d p oi nt 
T he P K e n d p oi nt is t he tr o u g h plas ma c o nce ntrati o n of M E 3 1 8 3 a n d its 
meta b olite ( 
) . 
E x pl or at or y E n d p oi nts  
St u d y Desi g n: 
T his m ulti-ce nter, ra n d o mize d, d o u ble- bli n d, place b o-c o ntr olle d, parallel gr o u p, 
P hase 2a st u d y is desi g ne d t o assess t he efficac y a n d safet y of M E 3 1 8 3 
a d mi nistere d orall y i n s u bj ects wit h mo derate t o se vere pla q ue ps oriasis. T he 
st u d y c o nsists of a 4- wee k Scree ni n g P eri o d ( Da y - 2 8 t o Da y - 1), a 1 6- wee k 
d o u ble - bli n d Treat me nt P eri o d ( Da y 1 t o Da y 1 1 3), a n d a 4- wee k F oll o w- u p 
Peri o d ( Da y 1 1 4 t o Da y 1 4 1).  T he t otal d urati o n of st u d y partici pati o n f or eac h 
s u bj ect is a p pr o xi matel y 2 4 wee ks. 
N ote: T he st u d y dr u g is a d mi nistere d fr o m Da y 1 t o Da y 1 1 2 i n t he Treat me nt 
P eri o d a n d t he e n d of Treat me nt P eri o d assess me nts will be perf or me d o n 
Da y  1 1 3. 
T he d urati o n of t he F oll o w- u p P eri o d is fr o m Da y 1 1 4 t o Da y 1 4 1 a n d t he e n d of 
C CI
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 6  of 8 9  
F oll o w- u p P eri o d assess me nts will be perf or me d o n Da y 1 4 1. 
After  t he Scree ni n g P eri o d, a p pr o xi matel y 1 2 5 eli gi ble s u bj ects wit h a c o nfir me d 
dia g n osis of ps oriatic pla q ues, a B S A i n v ol ve me nt of ≥ 1 0 % (at Scree ni n g a n d 
B aseli ne ), a P A SI sc ore 1 2 t o 4 0 (at Scree ni n g a n d Baseli ne), a n d a n s P G A ≥ 3 (at 
Scree ni n g a n d Baseli ne ) will b e ra n d o ml y assi g ne d t o recei ve M E 3 1 8 3 (  m g 
t wice dail y [ BI D],   m g o nce dail y [ Q D],  
 m g BI D, or   m g Q D) or place b o 
i n a 1: 1: 1: 1: 1 rati o. T o pr o m ot e bala nce d all ocati o n, ra n d o mi zati o n will be 
stratifie d b y t he s u bj ect’s recei pt ( yes/ n o) of pre vi o us treat me nt wit h a bi ol o gic 
dr u g f or ps oriasis. Bi o- naï ve s u bj ects will be ra n d o mize d a b o ve 5 0 % of t he 
pla n ne d  t otal s u bj ect ra n d o mi zati o n. 
After  ra n d o mizati o n ( Da y 1), all s u bj ects will be e val uate d at B aseli ne a n d at 
Wee ks  1, 2, 4, 8, 1 2, 1 6, a n d 2 0. Efficac y assess me nts (ie, P A SI, B S A, s P G A, a n d 
P R O assess me nt s [ D L QI a n d t he itc h N R S]), will be assesse d at Baseli ne ( Da y 1) 
a n d at Wee ks 1, 2, 4, 8, 1 2, 1 6 , a n d 2 0. Bl o o d sa m ples f or P K assess me nt will be 
c ollecte d pre d ose at Wee ks 1, 4, 8 a n d 1 6. Bl o o d sa m ples f or  
 assess me nts will 
be c ollecte d  pre d ose at Baseli ne ( Da y 1), Wee ks 4 a n d 1 6. Safet y a n d t olera bilit y 
will b e assesse d b y p h ysical e xa m, m o nit ori n g f or A Es a n d seri o us A E ( S A Es ), 
de m o gra p hics, me dical hist or y, vital si g ns a n d safet y la b orat or y tests 
( he mat ol o g y, c oa g ulati o n, bl o o d c he mistr y, a n d uri nal ysis) at Baseli ne ( Da y 1) 
a n d W ee ks 1, 2, 4, 8, 1 2, 1 6, a n d 2 0. E C Gs will be assesse d at Baseli ne ( Da y 1) 
a n d W ee ks 4, 8, 1 2, 1 6, a n d 2 0. 
Selecti o n of S u bjects: 
I ncl usi o n Criteri a: 
1.  
S u bj ect is willi n g a n d a ble t o par tici pate i n t he st u d y a n d has rea d, 
u n derst o o d, a n d si g ne d t he i nf or me d c o nse nt f or m acc or di n g t o nati o nal 
re g ulati o ns. 
2.  
S u bj ect is a male or fe male a ge d 1 8 t o 7 5 years (i ncl usi ve) at t he ti me of 
c o nse nt (ie, Scre e ni n g). 
3.  
S u bj ect has a b o d y mass i n de x ≥ 1 8. 5 t o < 4 0 k g/ m2 at Scree ni n g. 
4.  
S u bj ect has a dia g n osis of pla q ue ps oriasis f or ≥ 2 4 wee ks pri or t o 
Scree ni n g. 
5.  
T he s u bj ect’s s y m pt o ms of pla q ue ps oriasis are sta ble i n t he o pi ni o n of t he 
i n vesti gat or. Sta ble is defi ne d as n o ac ute deteri orati o n (e g, p ust ulati o n or 
er yt hr o der ma) wit hi n 1 2 wee ks bef ore Scree ni n g a n d n o re b o u n d of pla q ue 
ps oriasis wit hi n 4 wee ks bef or e Scree ni n g. 
6.  
T he s u bj ect’s se verit y of disease meets all of t he f oll o wi n g criteria:  
 
Ps oriatic pla q ues m ust c o ver ≥ 1 0 % of B S A at Scree ni n g a n d 
Baseli ne 
 
P A SI sc ore 1 2 t o 4 0 at Scree ni n g a n d Baseli ne 
 
s P G A ≥ 3 at Scree ni n g a n d Baseli ne 
7.  
S u bj ect is dee me d b y i n vesti gat or t o be eli gi ble f or p h ot ot hera p y or s yste mic 
t hera p y. 
8.  
S u bj ect a grees t o a v oi d pr ol o n ge d e x p os ure t o s u nli g ht or us e of artificial 
s u n bat hi n g (e g, ta n ni n g b o ot hs) or ot her ultra vi olet li g ht s o urces d uri n g t he 
Treat me nt P eri o d. 
9.  
S u bj ect, if fe male a n d of c hil d beari n g p ote ntial, m ust ha ve a ne gati ve ser u m 
pre g na nc y test at Scree ni n g a n d ne gat i ve uri ne pre g na nc y test at B aseli ne. 
A n y w o me n of c hil d beari n g p ote ntial ( W O C B P) m ust a gree t o se x ual 
a bsti ne nce or t o use a hi g hl y effecti ve c o ntrace pti ve meas ure starti n g at 
Scree ni n g, c o nti n ui n g t hr o u g h o ut t he e ntire Treat me nt P eri o d, a n d f or at 
least 4 wee ks after ta ki n g t he l ast d ose of st u d y treat me nt. A fe male s u bj ect 
is c o nsi dere d t o be a W O C B P after me narc he a n d u ntil s he is i n a 
p ost me n o pa usal state f or 1 2 m o nt hs or ot her wise per ma ne ntl y sterile (f or 
w hic h acce pta ble met h o ds i ncl u de h ys terect o m y, bilateral sal pi n gect o m y, 
C CI
C CI
C CI
C CI
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 7  of 8 9  
a n d bilateral o o p h orect o m y).  
1 0.  S u bj ect, if a fertile male, a gre es t o se x ual a bsti ne nce or t o use a c o n d o m 
d uri n g se x ual acti vit y wit h t heir fe male part ner of c hil d beari n g p ote ntial 
starti n g at Scree ni n g, c o nti n ui n g t hr o u g h o ut t he e ntire Treat me nt P eri o d, a n d 
f or at least 4 wee ks after ta ki n g t he last d ose of st u d y treat me nt. A male 
s u bj ect is c o nsi dere d fertile aft er p u bert y u nless per ma ne ntl y sterile b y 
bilateral orc hi dect o m y. A d diti o nall y, if t h eir part ner is a W O C B P, t he n t heir 
part ner s h o ul d be a d vise d t o use a hi g hl y effecti ve c o ntrace pti ve meas ure 
d uri n g se x ual acti vit y starti n g at Scree ni n g, c o nti n ui n g t hr o u g h o ut t he e ntire 
Treat me nt P eri o d, a n d f or at least 4 wee ks after ta ki n g t he last d ose of st u d y 
treat me nt.  
1 1.  S u bj ect, if f e male, m ust a gree t o n ot d o nate, or retrie ve f or her o w n use, o va 
starti n g at Scree ni n g, c o nti n ui n g t hr o ug h o ut t he e ntire Treat me nt P eri o d, a n d 
f or at least 4 wee ks after ta ki n g t he last d ose of st u d y treat me nt. 
1 2.  S u bj ect, if male, m ust a gree t o n o t freeze or d o nate s per m starti n g at 
Scree ni n g, c o nti n ui n g t hr o u g h o ut t he e ntire Treat me nt P eri o d, a n d f or at 
least 4 wee ks after ta ki n g t he l ast d ose of st u d y treat me nt. 
E xcl usi o n Criteri a:  
1.  
S u bj ect has a dia g n osis of n o n- pla q ue  ps oriasis ( pre d o mi na ntl y g uttate, 
p ust ular, i n verse, or er yt hr o der mic) or dr u g-i n d uce d ps oriasis. 
2.  
S u bj ect has a n y u nsta ble or C S (as deter mi ne d b y t he i n vesti gat or) car diac, 
e n d ocri n ol o gic, gastr oe nter ol o gic, p ul mo nar y, ne ur ol o gic, ps yc hiatric (s uc h 
as maj or de pressi o n), he patic, re nal, he mat ol o gic, i m m u n ol o gic disease, or 
ot her disease (e g, u nc o ntr olle d dia betes) t hat w o ul d place t he s u bj ect at 
u nacce pta ble ris k if t he y were t o partici pate i n t he st u d y. 
3.  
S u bj ect has s uici dal i deati o n or be ha vi or i n t he past 1 2 m o nt hs as i n dicate d 
b y a p ositi ve res p o nse ( yes) t o q uesti o ns 3, 4, or 5 o n t he C ol u m bia- S uici de 
Se verit y Rati n g Scale c o m plet e d at Scree ni n g a n d/ or at Baseli ne. 
4.  
S u bj ect has a prese nt rec urre nt me dical c o n diti o n ass ociate d wit h si g nifica nt 
gastr oi ntesti nal e ve nts (e g, na usea, v o miti n g, c o nsti pati o n, a b d o mi nal pai n, 
diarr hea). 
5.  
S u bj ect has a n y c o n diti o n t hat w o ul d c o nf o u n d t he a bilit y t o i nter pret data 
fr o m t he st u d y (e g, ecze ma, at o pic der matitis, l u p us, i nfla m mat or y b o wel 
disease). 
6.  
S u bj ect has a n y de gree of d ys p ha gia t hat ma y i nterfere wit h t he oral d osi n g 
of t he st u d y treat me nt. 
7.  
S u bj ect has a hist or y of aller g y or h y perse nsiti vit y t o a n y c o m p o ne nt of t he 
st u d y treat me nts. 
8.  
S u bj ects w h o ha ve ha d a pri or la b orat or y c o nfir me d C O VI D- 1 9 test or ha ve 
bee n i n cl ose p h ysical c o ntact ( 6 feet or cl oser f or at least 1 5 mi n utes) wit h a 
pers o n w h o is k n o w n t o ha ve l a b orat or y c o nfir me d C O VI D- 1 9 or wit h 
a n y o ne w h o has a n y s y m pt o ms c o nsiste nt wit h C O VI D- 1 9 wit hi n t he past 
1 4 da ys at Scree ni n g or Baseli ne. 
9.  
S u bj ects e x perie nci n g a n y of t he f oll o wi n g s y m pt o ms at Scr ee ni n g or 
B aseli ne: 
 
Fe ver or c hills 
 
C o u g h 
 
S h ort ness of breat h or diffic ult y breat hi n g 
 
Fati g ue 
 
M uscle or b o d y ac hes 
 
Hea dac he 
 
Ne w l oss of taste or s mell 
 
S ore t hr oat 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 8  of 8 9  
 
C o n gesti o n or r u n n y n ose 
 
Na usea or v o miti n g 
 
Diarr hea 
1 0.  S u bj ect has acti ve or c hr o nic he patitis B vir us or he patitis C vir us ( H C V) 
i nfecti o n as per Scree ni n g viral ser ol o g y tests. E xce pti o n: If t he s u bj ect has 
recei ve d d oc u me nte d treat me nt w hic h was c urati ve f or H C V a n d tests 
ne gati ve f or H C V R N A at Scr ee ni n g, t he s u bj ect ma y be c o nsi dere d f or 
ra n d o mizati o n. 
1 1.  S u bj ect is p ositi ve f or t he HI V a nti b o dies ( HI V- 1 or HI V- 2) at Scree ni n g or 
has a hist or y of c o n ge nital or ac q uire d i m m u n o deficie nc y (e g, c o m m o n 
varia ble i m m u n o deficie nc y disease). 
1 2.  S u bj ect has a rece nt hist or y of dr u g, s u bsta nce, or alc o h ol a b use/ de pe n de nce 
wit hi n 1 year pri or t o Scree ni n g as deter mi ne d b y t he i n vesti gat or. 
1 3.  S u bj ect has a n acti ve i nfecti o n ( bac teria, viral, f u n gal, etc.) re q uiri n g 
treat me nt wit h s yste mic a nti bi otics wit hi n 4 wee ks of Scree ni n g. A n y 
treat me nt f or s uc h i nfecti o ns m ust be c o m plete d at least 4 wee ks pri or t o 
Scree ni n g. 
1 4.  S u bj ect has acti ve t u berc ul osis or hist or y of i nc o m pletel y tr eate d 
t u berc ul osis per me dical hist or y. 
1 5.  S u bj ect has a mali g na nc y or hist or y of mali g na nc y (e xce pt f or treate d 
[ie, c ure d] basal cell or s q ua m o us cell i n sit u s ki n carci n o mas a n d treate d 
[ie, c ure d] cer vical i ntrae pit helial ne o plasia or carci n o ma i n sit u of t he cer vi x 
wit h n o e vi de nce of rec urre nc e). 
1 6.  S u bj ect is pre g na nt or breastfe e di n g at Scree ni n g or at Baseli ne. 
1 7.  S u bj ect has a hist or y of lac k of efficac y (i na de q uate efficac y w he n use d i n 
a d e q uate d ose a n d d urati o n i n acc or da nce  wit h t he a p pr o ve d la bel) t o a n y 
bi ol o gical pr o d ucts f or ps oriasis. 
1 8.  S u bj ect has recei ve d 2 or m or e bi ol o gical pr o d ucts i n t he past f or t he 
treat me nt of ps oriasis. 
1 9.  S u bj ect has a hist or y of lac k of efficac y t o 2 or m ore n o n- bi ol o gic s yste mic 
t hera p y d ue t o i na de q uate effi cac y w he n a d mi nistere d i n a de q uate d ose a n d 
d urati o n i n acc or da nce wit h t heir la b el (a p pr o ve d i n t he s u bject’s c o u ntr y) 
f or ps oriasis. 
2 0.  S u bj ect has r ecei ve d a n y pri or treat me nt wit h a pre milast or a n y ot her 
p h os p h o diesterase 4 i n hi bit or. 
2 1.  S u bj ect has recei ve d uste ki n u ma b, sec u ki n u ma b, br o dal u ma b, i xe kiz u ma b, 
g usel k u ma b, risa n kiz u ma b, til dra kiz u ma b, or bria ki n u ma b ( or a n y ot her 
t hera pe utic a ge nt tar geti n g I L- 1 2, I L- 1 7, or I L- 2 3) wit hi n 2 4 wee ks of first 
a d mi nistrati o n of st u d y treat me nt. 
2 2.  S u bj ect has recei ve d T N F- α  i n hi bit or(s)/ bl oc ker(s) wit hi n 8 wee ks of first 
a d mi nistrati o n of st u d y treat me nt. 
2 3.  S u bj ect has recei ve d nataliz u ma b (a n i nte gri n rece pt or a nta g o nist) , or a ge nts 
t hat m o d ulate B cells or T cells (e g, ale mt uz u ma b, a batace pt, aleface pt) 
wit hi n 1 2 wee ks of first a d mi nistrati o n of st u d y treat me nt. 
2 4.  S u bj ect has recei ve d rit u xi ma b wit hi n 2 4 wee ks of first a d mi nistrati o n of 
st u d y treat me nt. 
2 5.  S u bj ect h as recei ve d a n y s yste mic i m m u n os u p pressa nts (e g, met h otre xate, 
azat hi o pri ne, c ycl os p ori ne, 6- t hi o g ua ni ne, merca pt o p uri ne, m yc o p he n olate 
m ofetil, h y dr o x y urea, tacr oli m us), a n y pr otei n ki nase i n hi bit or (e g, 
t ofaciti ni b, bariciti ni b, peficiti ni b, u pa daciti ni b), or a na ki nra wit hi n 4 wee ks 
of t he first a d mi nistrati o n of st u d y treat me nt. 
2 6.  S u bj ect has recei ve d p h ot ot hera p y (e g, ultra vi olet B i ncl u di n g narr o w ba n d 
ultra vi olet B, G oec ker ma n t hera p y, a n d e xci mer laser or ps orale n ultra vi olet 
A) or a n y s yste mic me dicati o ns/treat me n ts t hat c o ul d affect ps oriasis or 
s P G A e val uati o n (i ncl u di n g, b ut n ot li mite d t o, oral or i nj ecta ble 
c ortic oster oi ds, reti n oi ds, 1, 2 5- di h y dr o x y vita mi n D 3 a n d a nal o g ues, 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 9  of 8 9  
ps orale ns, s ulfasalazi ne, or f u maric aci d  deri vati ves) wit hi n 4 wee ks of t he 
first a d mi nistrati o n of st u d y tr eat me nt. 
2 7.  S u bj ect has ha d a rece nt i nitiati o n of a dr u g t hat is k n o w n t o p ote ntiall y 
ca use or e xacer bate ps oriasis (i nc l u di n g, b ut n ot li mite d t o, beta-bl oc kers, 
lit hi u m, a n d a nti- malarials) wit hi n t he 8 wee ks pri or t o t he first 
a d mi nistrati o n of st u d y treat me nt; a s u bj ect w h o has bee n o n a sta ble d ose 
f or at least 8 wee ks pri or t o t he first a d mi nistrati o n of st u d y treat me nt 
wit h o ut e xacer bati o n of ps oriasi s ma y be ra n d o mize d a n d d oes n ot nee d t o 
disc o nti n ue t hese me dicati o ns. 
2 8.  S u bj ect has use d t o pical me di cati o ns/treat me nts t hat c o ul d affect ps oriasis or 
s P G A e val uati o n (i ncl u di n g, b ut n ot li mite d t o, certai n c ortic oster oi ds, 
a nt hrali n, calci p otrie ne, t o pical vita mi n D deri vati ves, ret i n oi ds, tazar ote ne, 
met h o xsale n, tri met h yl ps orale n, pi mecr oli m us, tacr oli m us, or 
p h os p h o diesterase 4 i n hi bit or) wit hi n 2 wee ks of t he first a d mi nistrati o n of 
st u d y treat me nt. 
2 9.  S u bj ect has recei ve d a n i n vesti gati o nal dr u g f or bi ol o gic t hera p y wit hi n t he 
pre vi o us 2 4 wee ks pri or t o t he first a d mi nistrati o n of st u d y tr eat me nt or 
recei ve d a n y ot her n o n- bi ol o gic i n vesti gati o nal t hera p y/ dr u gs or de vice 
wit hi n 4 wee ks or 5 half-li ves ( w hic h e ver is l o n ger) pri or t o t he first 
a d mi nistrati o n of st u d y treat me nt. 
3 0.  S u bj ect has recei ve d a n y pri or treat me nt wit h M E 3 1 8 3. 
3 1.  S u bj ect has a n y of t he f oll o wi n g a b n or mal la b orat or y test fi n di n gs at 
Scree ni n g. 
 
A b n or mal he patic f u ncti o n 
o  
As partate a mi n otra nsa mi nase or ala ni ne 
a mi n otra nsa mi nase ≥ 2 × u p per li mit of n or mal or 
o  
Total bilir u bi n ≥ 2 × u p per li mit of n or mal, u nless t he 
s u bj ect has a dia g n osis of Gil b ert’s s y n dr o me  
 
W hite bl o o d cell c o u nt < 3 0 0 0/ m m
3 ( < 3. 0 × 1 09/ L) 
 
Ne utr o p hil c o u nt < 1 0 0 0/ m m 3 ( < 1. 0 × 1 09/ L) 
 
Platelet c o u nt < 1 0 0, 0 0 0/ μ L ( <  1 0 0 × 1 09/ L) 
 
He m o gl o bi n < 8. 0 g/ d L 
 
Creati ni ne cleara nce esti mate d b y C oc kcr oft- Ga ult f or m ula 
< 6 0 m L/ mi n 
 
He m o gl o bi n A 1c > 9. 0 % 
3 2.  S u bj ect has a C S a b n or malit y o n a 1 2-lea d E C G or c orrecte d Q Tc F 
> 4 5 0 msec at Scree ni n g or Baseli ne. 
3 3.  S u bj ect has a s yst olic bl o o d press ure ≥ 1 6 0 m m H g or a diast olic bl o o d 
press ure ≥ 1 0 0 m m H g ( base d o n at least 2 re peat meas ure me nts) at 
Scree ni n g. 
3 4.  Pris o ners or s u bj ects w h o ar e i ncarcerate d f or a n y reas o n. 
3 5.  S u bj ect has a n y ot her fact or c o nstit uti n g dis q ualificati o n f or st u d y i ncl usi o n 
i n t he j u d ge me nt of t he i n vesti gat or. 
Pl a n ne d S a m ple Size: 
A p pr o xi matel y 1 2 5 eli gi ble s u bj ects are p la n ne d t o be ra n d o mize d ( 2 5 s u bj ects 
per treat me nt gr o u p). Eli gi ble s u bj ects will be ce ntrall y ra n d o mize d i n a 1: 1: 1: 1: 1 
rati o t o 1 of t he f oll o wi n g treat me nt gr o u ps: 
 
Treat me nt Gr o u p 1: (  m g M E 3 1 8 3 BI D a d mi nistere d orall y): 
 ca ps ule 
of   m g M E 3 1 8 3 a n d   ca ps ules of matc hi n g place b o i n t he m or ni n g a n d 
e ve ni n g 
 
Treat me nt Gr o u p 2: (  m g M E 3 1 8 3 Q D a d mi nistere d orall y):   
ca ps ules of   m g M E 3 1 8 3 a n d   ca ps ule of matc hi n g place b o i n t he 
m or ni n g a n d   ca ps ules of matc hi n g place b o i n t he e ve ni n g 
 
Treat me nt Gr o u p 3: ( 
 m g M E 3 1 8 3 BI D a d mi nistere d orall y):   
ca ps ule of   m g M E 3 1 8 3 a n d   ca ps ule of  
 m g M E 3 1 8 3 a n d   ca ps ule 
C CI
C CI
C CI
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C CI
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C CI
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Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 1 0  of 8 9  
of matc hi n g place b o i n t he m or ni n g a n d e ve ni n g 
 
Treat me nt Gr o u p 4: (  m g M E 3 1 8 3 Q D a d mi nistere d orall y):   
ca ps ules of   m g M E 3 1 8 3 i n t he m or ni n g a n d   ca ps ules of matc hi n g 
place b o i n t he e ve ni n g 
 
Treat me nt Gr o u p 5 ( Place b o BI D a d mi ni stere d orall y):   ca ps ules of 
matc hi n g place b o i n t he m or ni n g a n d e ve ni n g 
T o p r o m ote bala nce d all ocati o n, ra n d o mizati o n will be stratifie d b y s u bj ect’s 
recei pt ( yes/ n o) of pre vi o us treat me nt wit h a bi ol o gic dr u g f or ps oriasis. Eac h 
treat me nt gr o u p will i ncl u de ra n d o mize d s u bj ects w h o 1) are bi o- naï ve a n d 2) 
recei ve d pre vi o us treat me nt wit h a bi ol o gic dr u g f or ps oriasis. After 
ra n d o mizati o n of s u bj ects has reac he d t he ma xi m u m perce nt a ge as deter mi ne d b y 
t he s p o ns or f or s u bj ects t hat ha ve recei ve d pre vi o us treat me nt wit h a bi ol o gic 
dr u g f or ps oriasis, ra n d o mizati o n i n t his gr o u p will be st o p pe d a n d t he st u d y sites 
will b e i nf or me d acc or di n gl y.  
St u d y Tre at me nts 
M E 3 1 8 3 (  m g,  
 m g,   m g, a n d   m g) a n d matc hi n g pl ace b o will be 
pre p are d usi n g t he f oll o wi n g  M E 3 1 8 3 a n d place b o ca ps ules: 
 
M E 3 1 8 3 Ca ps ule  
 m g 
 
M E 3 1 8 3 Ca ps ule   m g 
 
M E 3 1 8 3 Place b o Ca ps ule 
Tre at me nt D ur ati o n: 
T he treat me nt d urati o n f or a n i n di vi d ual s u bj ect will be 1 6 wee ks. Eac h s u bj ect 
will recei ve BI D treat me nt u n der fe d c o n diti o n ( wit hi n a p pr o xi matel y 3 0 mi n utes 
after a sta n dar d meal ) fr o m D a y 1 t o Da y 1 1 2. 
Effic ac y: 
Efficac y assess me nts (i ncl u di n g P R O assess me nts) will i ncl u de: 
 
P A SI sc ore 
 
B S A 
 
s P G A 
 
Itc h N R S 
 
D L QI 
S afet y: 
Safet y assess me nts will i ncl u d e: 
 
A E/ S A Es 
 
1 2-lea d E C Gs 
 
P h ysical e xa mi nati o ns (c o m pl ete/tar gete d) i ncl u di n g hei g ht a n d b o d y 
mass i n de x 
 
Vital si g ns 
o  
Bl o o d press ure (s yst olic a n d diast olic) 
o  
Heart rate 
o  
Res pirat or y rate 
o  
B o d y te m perat ure 
o  
B o d y wei g ht 
 
Safet y la b orat or y tests i ncl u di n g: 
o  
Viral ser ol o g y ( he patitis B vir us, H C V, a n d HI V) 
o  
He mat ol o g y a n d c oa g ulati o n 
o  
Bl o o d c he mistr y 
o  
Uri nal ysis 
o  
Pre g na nc y tests ( W O C B P o nl y; ser u m or uri ne β -h u ma n c h ori o nic 
g o na d otr o pi n) 
o  
Ser u m f ollicle-sti m ulati n g h or m o ne ( p ost me n o pa usal w o me n o nl y) 
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 1 1  of 8 9  
P h ar m ac o ki netics: 
Bl o o d sa m ples f or t he deter mi nati o n of t he c o nce ntrati o ns of M E 3 1 8 3 a n d its 
meta b olite ( 
) will be c ollecte d fr o m eac h s u bj ect i n eac h treat me nt gr o u p. 
T he P K bl o o d sa m ples will be ta ke n pre d ose at sc he d ule d visits u ntil Wee k  1 6. 
Ot her Assess me nts: 
Ot her assess me nts will i ncl u d e: 
 
Eli gi bilit y assess me nts: I nf or me d c o nse nt 
 
I ncl usi o n/e xcl usi o n criteria 
 
Der mat ol o gic a n d me dical hist or y 
 
Hist or y of pre vi o us treat me nt wit h a bi ol o gic dr u g f or ps oriasis 
 
C ol u m bia- S uici de Se verit y Rati n g Scale 
 
De m o gra p hics 
 
Pri or a n d c o nc o mita nt me dicati o ns/t hera pies or pr oce d ures 
 
Treat me nt c o m plia nce 
 
Me dical p h ot o gra p h y of t he tar get s ki n lesi o n (at selecte d sit es i n a selecte d 
n u m ber of s u bj ects f or d oc u me n tati o n a n d p u blicati o n p ur p oses o nl y) 
St atistic al M et h o ds a n d 
Pl a n ne d A n al yses:  
Deter mi n ati o n of S a m ple Size 
N o f or mal sa m ple size calc ulati o n was perf or me d.  
F or t he assess me nt of efficac y a n d safet y of M E 3 1 8 3 i n s u bj ects wit h m o derate t o 
se vere pla q ue ps oriasis i n t his pr o of- of-c o nce pt st u d y, a p pr o xi matel y 1 2 5 eli gi ble 
s u bj ects will be e nr olle d. T we nt y-fi ve s u bj ects will be ra nd o mize d t o eac h of t he 
f oll o wi n g treat me nt gr o u ps: M E 3 1 8 3  m g BI D, M E 3 1 8 3   m g Q D, M E 3 1 8 3 
 m g BI D; M E 3 1 8 3   m g Q D, a n d place b o. T he n u m ber of pla n ne d s u bj ects is 
c o nsi dere d a de q uate t o assess safet y a n d t o pr o vi de efficac y esti mates f or i n t his 
P hase 2a st u d y. T he e x pecte d dr o p- o ut rate is ass u me d t o be 1 0 %. 
A n al ysis Sets  
F ull A nal ysis  Set  
All s u bj ects w h o ha ve bee n ra n d o mize d , recei ve d at least 1 d ose of st u d y dr u g, 
a n d ha ve at least 1 e val ua ble p ost- Baseli ne ti me p oi nt f or pri mar y e n d p oi nt will 
be i ncl u de d i n t he f ull a nal ysis set ( F A S) . A nal yses i n t he F A S will be base d o n 
t he s u bj ect’s ra n d o mize d treat me nt gr o u p. 
Per Pr ot oc ol Set   
T he per pr ot oc ol set ( P P S) is a  s u bset of t he F A S; t he P P S will e xcl u de s u bj ects 
wit h pr ot oc ol de viati o ns t hat ma y si g nifica ntl y i m pact t he assess me nt of t he 
pri mar y o bj ecti ve of t he st u d y. A nal yses i n t he P P S will be base d o n t he st u d y 
treat me nt act uall y recei ve d b y eac h s u bj ect. All decisi o ns t o e xcl u d e s u bj ects 
fr o m t he P P S will be ma de pri or t o t he u n bli n di n g of t he st u d y. 
Safet y A nal ysis Set  
All ra n d o mize d s u bj ects w h o recei ve d at least 1  d ose of st u d y dr u g will be 
i ncl u de d i n t he safet y a nal ysis set. A nal yses i n t he safet y a nal ysis set will be 
base d o n t he st u d y treat me nt act uall y recei ve d b y eac h s u bj ect.  
P har mac o ki netic  A nal ysis Set 
T he P K a nal ysis set will c o nsist of all s u bj ects w h o were c orrectl y a d mi nistere d at 
C CI
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C CI
C CI
C CI
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Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 1 2  of 8 9  
least 1 M E 3 1 8 3 d ose a n d w here M E 3 1 8 3 or  
 c o nce ntrati o n data is 
a vaila ble wit h o ut a n y pr ot oc ol de viati o n i nterferi n g wit h t hese res ults. A nal yses 
i n t he P K a nal ysis set will be base d o n t he st u d y treat me nt act uall y recei ve d b y 
eac h s u bj ect. 
St atistic a l A n al yses 
Efficac y A nal yses  
U nless ot her wise s pecifie d, all efficac y a nal yses will be perf or me d usi n g t he F A S. 
T he a nal ysis of t he pri mar y efficac y e n d p oi nt will als o be perf or me d usi n g t he 
P P S.  
A nal ysis of t he Pri mar y Effica c y E n d p oi nt 
T he pr i mar y efficac y e n d p oi nt is t he pr o p orti o n of s u bj ects ac hie vi n g ≥ 7 5 % 
re d ucti o n fr o m Baseli ne i n t he P A SI sc ore at Wee k 1 6. F or eac h M E 3 1 8 3 
treat me nt gr o u p, t he differe nc e i n t he pr o p orti o n of s u bj ects ac hie vi n g t he 
differe nce i n P A SI - 7 5 ( M E 3 1 8 3 –  place b o) a n d its 9 5 % c o nfi de nce i nter val will 
be esti mate d a n d teste d f or s u peri or treat me nt effect usi n g t he C oc hra n-Ma ntel-
Hae nszel test at a 1 -si de d si g nifica nce le vel of α  = 0. 0 2 5. T he P A SI sc ore will be 
re p orte d f or eac h treat me nt gr o u p t o get her wit h t he 9 5 % c o nfi de nce i nter val f or 
mea n . 
A nal yses  of t he Sec o n dar y Efficac y E n d p oi nts 
T he pr o p orti o n of s u bj ects ac hie vi n g P A SI - 5 0, P A SI- 7 5, P A SI- 9 0, a n d P A SI-1 0 0, 
t he pr o p orti o n of s u bj ects wit h an s P G A sc ore of “ 0” or “ 1” c o m bi ne d wit h 2-
p oi nt  re d ucti o n o n t he 5- p oi nt s P G A scale, a n d t he pr o p orti o n of s u bj ects wit h at 
least a 5- p oi nt re d ucti o n fr o m Baseli ne i n t he D L QI sc ore will be a nal yze d si milar 
t o t he pri mar y e n d p oi nt a nal ysis. 
T he pr o p orti o n of s u bj ects ac hie vi n g P A SI - 5 0, P A SI- 7 5, P A SI- 9 0, a n d P A SI-1 0 0, 
t he pr o p orti o n of s u bj ects wit h an s P G A sc ore of “ 0” or “ 1” c o m bi ne d wit h 
2 - p oi nt re d ucti o n o n t he 5-p oi nt s P G A scale, a n d t he pr o p orti o n of s u bj ects wit h 
at least a 5 - p oi nt re d ucti o n fr o m Baseli ne i n t he D L QI sc ore will be s u m marize d 
b y treat me nt gr o u p a n d visit. T he perce nt c ha n ge fr o m Baseli ne i n P A SI sc ore  a n d 
c ha n ge fr o m Baseli ne i n affect e d B S A, t he itc h N R S, a n d t he D L QI sc ore will be 
s u m marize d b y treat me nt gr o u p a n d visit. T he perce nt c ha n ge fr o m Baseli ne i n 
P A SI  sc ore a n d t he c ha n ge fr o m Baseli ne i n t he affecte d B S A, t he D L QI sc ore, 
a n d t he itc h N R S will be a nal yze d usi n g a mi xe d-effect m o del f or re peate d 
meas ures  w he n a p plica ble. 
Ka pla n - Meier esti mate will be use d f or s u m marizi n g t he ti me t o P A SI-5 0 a n d 
P A SI - 7 5. T he l o g-ra n k test ma y be use d f or c o m pari n g t he ti me t o P A SI-5 0 a n d 
P A SI - 7 5 bet wee n eac h M E 3 1 8 3 treat me nt gr o u p a n d place b o. T he C o x 
pr o p orti o nal hazar d m o del ma y als o be use d f or a nal yzi n g t he ti me t o P A SI- 5 0 
C CI
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 1 3  of 8 9  
a n d P A SI- 7 5. T he ti me t o P A SI- 5 0 a n d P A SI- 7 5 will b e s u m marize d b y treat me nt 
gr o u p.  
A nal ys es of t he E x pl orat or y Efficac y E n d p oi nts 
Safe t y A nal yses 
All safet y a nal yses will be perf or me d usi n g t he safet y a nal ysis set. All rec or de d 
A E a n d S A Es will be liste d a n d ta b ulate d b y Me dical Dicti o nar y f or Re g ulat or y 
Acti vities ( versi o n 2 4. 1 or hi g her) s yste m or ga n class, preferre d ter m, a n d 
treat me nt gr o u p o ver t he 1 6- wee k Treat me nt P eri o d a n d t he 4- wee k F oll o w-u p 
Peri o d . 
Vital si g ns a n d safet y la b orat or y test res ults will be liste d a n d s u m marize d b y 
treat me nt gr o u p o ver t he 1 6- wee k Treat me nt P eri o d a n d t he 4- wee k F oll o w-u p 
Peri o d . S u m maries will be pr o vi de d usi n g descri pti ve statisti cs, i ncl u di n g mea n 
val ues a n d mea n c ha n ge fr o m Baseli ne val ues, as well as n u m bers of s u bj ects 
wit h val ues o utsi de li mits of t he n or mal ra n ge at eac h ti me p oi nt.  
A n y  C S p h ysical e xa mi nati o n fi n di n gs a n d safet y la b orat or y res ults will be 
s u m marize d. E C G rea di n gs will be e val uate d b y t he i n vesti gat or a n d 
a b n or malities, if prese nt, will be s u m marize d a n d liste d.  
T he cli nicall y n ote w ort h y Q T/ Q T c i nter val ( > 4 5 0, > 4 8 0, or > 5 0 0 msec) or 
cli nicall y n ote w ort h y c ha n ge fr o m Baseli ne ( > 3 0 or > 6 0 ms ec) will als o be 
s u m marize d usi n g descri pti ve statistics. 
S u m mar y ta bles will be pr o vi de d f or c o nc o mita nt me dicati o ns i nitiate d d uri n g t he 
st u d y peri o d. 
P har mac o ki netic  A nal ysis 
T he P K a nal ysis set will be us e d f or t he P K a nal ysis. Tr o u g h plas ma 
c o nce ntrati o ns of M E 3 1 8 3 a n d its meta b olite ( 
) will be s u m marize d 
descri pti vel y b y treat me nt gr o u p  i n t he ta bles, fi g ures, a n d listi n gs ( T F L). 
C CI
C CI
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 1 4  of 8 9  
3  
T A B L E O F C O N T E N T S 
1  
FI N A L C LI NI C A L S T U D Y P R O T O C O L 
1  
2  
S Y N O P SI S
 4  
3  
T A B L E O F C O N T E N T S 
1 4  
3. 1  
List of I n-te xt Ta bles .................................................................................................. 1 8  
3. 2  
List of I n-te xt Fi g ures ................................................................................................. 1 9  
4  
LI S T O F A B B R E VI A TI O N S 
2 0  
5  
I N T R O D U C TI O N
 2 2 
5. 1  
Bac k gr o u n d o n Pla q ue Ps oriasis ................................................................................ 2 2  
5. 2  
Bac k gr o u n d o n M E 3 1 8 3............................................................................................. 2 2  
5. 2. 1  
N o ncli nical St u dies ............................................................................................ 2 3  
5. 2. 2  
Cli nical St u dies .................................................................................................. 2 5  
5. 3  
Cli nical Ris ks/ Be nefits of M E 3 1 8 3 ............................................................................ 2 6  
5. 4  
St u d y R ati o nale .......................................................................................................... 2 7  
5. 5  
Rati o nale f or D ose Sel ecti o n ...................................................................................... 2 7  
6  
S T U D Y O BJ E C TI V E S A N D E N D P OI N T S 
2 9  
6. 1  
St u d y O bjecti ves ......................................................................................................... 2 9  
6. 1. 1  
Pri mar y O bj ecti ve .............................................................................................. 2 9  
6. 1. 2  
Sec o n dar y O bj ecti ves ......................................................................................... 2 9  
6. 1. 3  
E x pl orat or y O bjecti ves ...................................................................................... 2 9  
6. 2  
St u d y E n d p oi nts.......................................................................................................... 2 9  
6. 2. 1  
Pri mar y E n d p oi nt ............................................................................................... 2 9  
6. 2. 2  
Sec o n dar y E n d p oi nts .......................................................................................... 2 9  
6. 2. 3  
P har mac o ki netic E n d p oi nt ................................................................................. 3 0  
6. 2. 4  
E x pl orat or y E n d p oi nts ....................................................................................... 3 0  
7  
I N V E S TI G A TI O N A L P L A N 
3 2  
7. 1  
Descri pti o n of O v erall St u d y Desi g n a n d Pla n........................................................... 3 2  
7. 2  
Disc ussi o n of St u d y Desi g n........................................................................................ 3 4  
7. 3  
E n d of St u d y ............................................................................................................... 3 4  
7. 4  
Earl y Ter mi nati o n ....................................................................................................... 3 5  
8  
S E L E C TI O N O F S T U D Y P O P U L A TI O N 
3 6  
8. 1  
I n cl usi o n Criteria ........................................................................................................ 3 6 
8. 2  
E x cl usi o n Criteria ....................................................................................................... 3 7  
8. 3  
Rescree ni n g ................................................................................................................ 4 0  

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 1 5  of 8 9  
8. 4  
St u d y Wit h dra w al, Re m o val, a n d Re place me nt of S u bjects ...................................... 4 0  
8. 4. 1  
Pre g n a nc y ........................................................................................................... 4 2  
8. 4. 2  
L ost t o F oll o w- U p .............................................................................................. 4 2  
9  
T R E A T M E N T S
 4 3  
9. 1  
Details of St u d y Treat me nts ....................................................................................... 4 3  
9. 1. 1  
Descri pti o n of Acti ve St u d y Treat me nt ............................................................. 4 3  
9. 1. 2  
Descri pti o n of Place b o St u d y Treat me nt ........................................................... 4 3  
9. 1. 3  
Pac ka gi n g a n d La b eli n g ..................................................................................... 4 3  
9. 1. 4  
St u d y Dr u g St ora ge ............................................................................................ 4 4  
9. 1. 5  
St u d y Dr u g Rete nti o n ......................................................................................... 4 4  
9. 2  
D osa ge Sc he d ul e ........................................................................................................ 4 4  
9. 3  
Meas ures t o Mi ni mize Bias ........................................................................................ 4 5  
9. 3. 1  
Met h o d of St u d y Treat m e nt Assi g n me nt ........................................................... 4 5  
9. 3. 2  
Bli n di n g 4 5  
9. 4  
D osa ge M o dificati o n .................................................................................................. 4 6  
9. 5  
Treat me nt A cc o u nta bilit y a n d C o m plia nce ................................................................ 4 6  
9. 6  
Pri or a n d C o nc o mita nt T hera p y ................................................................................. 4 6  
9. 6. 1  
Pri or a n d C o nc o mita nt Me dicati o ns .................................................................. 4 6  
1 0  
S T U D Y P R O C E D U R E S 
4 8  
1 0. 1  I nf or me d C o nse nt ....................................................................................................... 5 4 
1 0. 2  St u d y Pr oce d ures ........................................................................................................ 5 4  
1 1  
E F FI C A C Y A S S E S S M E N T S 
5 5  
1 1. 1  Ps oriasis Area Se verit y I n de x ..................................................................................... 5 5  
1 1. 2  Static P h ysici a n’s Gl o bal Assess me nt  ........................................................................ 5 5 
1 1. 3  B o d y S urface Area ..................................................................................................... 5 5  
1 1. 4  P R O Assess me nt: Itc h N u merical Rati n g Scale ......................................................... 5 5  
1 1. 5  P R O Assess me nt: Der mat ol o g y Life Q ualit y I n d e x .................................................. 5 6  
1 2  
S A F E T Y A S S E S S M E N T S 
5 7  
1 2. 1  De m o gra p hics a n d Me di cal a n d Der mat ol o gical Hist or y .......................................... 5 7  
1 2. 2  Vital Si g ns .................................................................................................................. 5 7  
1 2. 3  C o m plete/ Tar gete d P h ysical E x a mi nati o n ................................................................. 5 8  
1 2. 4  Electr ocar di o gra ms ..................................................................................................... 5 8  
1 2. 5  Safet y La b orat or y Assess me nts .................................................................................. 5 8  
1 2. 6  A d verse E v e nts ........................................................................................................... 6 0  
1 2. 6. 1  
A d verse E v e nts .................................................................................................. 6 0  

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 1 6  of 8 9  
1 2. 6. 2  
Treat me nt- E mer ge nt A d verse E ve nts ................................................................ 6 2  
1 2. 6. 3  
Seri o us A d verse E v e nts ..................................................................................... 6 2  
1 2. 6. 4  
Seri o us A d verse E v e nt Re p orti n g ...................................................................... 6 3  
1 2. 6. 5  
S us pecte d U ne x pecte d S eri o us A d verse Reacti o ns ........................................... 6 4  
1 2. 6. 6  
Pre g n a nc y ........................................................................................................... 6 4  
1 2. 6. 7  
O ver d ose ............................................................................................................ 6 5  
1 3  
P H A R M A C O KI N E TI C S
 6 6  
1 3. 1  P har mac o ki netic Sa m pli n g ......................................................................................... 6 6  
1 3. 1. 1  
Bl o o d Sa m ples ................................................................................................... 6 6  
1 3. 2  P har mac o ki netic A n al yti cal Met h o d ol o g y ................................................................. 6 6  
1 4  
O T H E R A S S E S S M E N T S 
6 7  
6 7  
1 4. 2  Me dical P h ot o gra p h y of Affecte d S ki n Area ............................................................. 6 7  
1 4. 3  C ol u m bia- S uici de Se verit y Rati n g Scale ................................................................... 6 7  
1 5  
S T A TI S TI C A L A N A L Y SI S 
6 8  
1 5. 1  Deter mi nati o n of Sa m ple Siz e .................................................................................... 6 8  
1 5. 2  A nal ysis Sets .............................................................................................................. 6 8  
1 5. 3  Efficac y A nal yses ....................................................................................................... 6 9  
1 5. 3. 1  
A nal ysis of t h e Pri mar y Efficac y E n d p oi nt ....................................................... 6 9  
1 5. 3. 2  
A nal ys es of t he Sec o n dar y Efficac y E n d p oi nts ................................................. 6 9  
1 5. 3. 3  
A nal ys es of t he E x pl orat or y Efficac y E n d p oi nts ............................................... 7 0  
1 5. 4  Safet y A nal yses .......................................................................................................... 7 0  
1 5. 5  P har mac o ki netic A n al ysis .......................................................................................... 7 0  
7 1  
1 6  
S T U D Y M A N A G E M E N T 
7 2  
1 6. 1  A p pr o val a n d C o nse nt ................................................................................................ 7 2  
1 6. 1. 1  
Re g ulat or y G ui deli nes ........................................................................................ 7 2  
1 6. 1. 2  
I nstit uti o nal Re vie w B oar d/I n d e pe n d e nt Et hics C o m mittee .............................. 7 2 
1 6. 1. 3  
I nf or me d C o nse nt ............................................................................................... 7 2 
1 6. 2  Data Ha n dli n g ............................................................................................................. 7 3  
1 6. 3  S o urce D oc u m e nts ...................................................................................................... 7 3  
1 6. 4  Rec or d Rete nti o n ........................................................................................................ 7 4  
1 6. 5  M o nit ori n g .................................................................................................................. 7 4  
1 6. 6  Q ualit y C o ntr ol a n d Q u alit y Ass ura n ce ..................................................................... 7 4  
1 6. 7  Pr ot oc ol A me n d me nt a n d Pr ot oc ol De viati o n ............................................................ 7 5  
C CI
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 1 7  of 8 9  
1 6. 7. 1  
Pr ot oc ol A me n d me nt ......................................................................................... 7 5  
1 6. 7. 2  
Pr ot oc ol De viati o ns ............................................................................................ 7 5  
1 6. 8  Et hical C o nsi derati o ns ................................................................................................ 7 5  
1 6. 9  Fi na nci n g a n d I ns ura n ce ............................................................................................. 7 5  
1 6. 1 0  P u blicati o n P olic y/ Discl os ure of Data........................................................................ 7 6  
1 7  
R E F E R E N C E S
 7 7  
1 8  
A P P E N DI C E S
 7 8  
A P P E N DI X 1.  C O N T R A C E P TI O N G UI D E LI N E S 
7 9  
A P P E N DI X 2.  P R O HI BI T E D C O N C O MI T A N T M E DI C A TI O N S A N D P R O C E D U R E S 8 1  
A P P E N DI X 3.  P S O RI A SI S A R E A S E V E RI T Y I N D E X - W O R K S H E E T 
8 3  
A P P E N DI X 4.  5- P OI N T S T A TI C P H Y SI CI A N’ S G L O B A L A S S E S S M E N T  8 4
 
A P P E N DI X 5.  D E R M A T O L O G Y LI F E Q U A LI T Y I N D E X 
8 5  
A P P E N DI X 6.  C O L U M BI A- S UI CI D E S E V E RI T Y R A TI N G S C A L E 
8 7  
 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 1 8  of 8 9  
3. 1  
List of I n-te xt T a bles 
Ta ble 1.  Sc he d ule of Assess me nts ........................................................................................ 4 9  
Ta ble 2.  Safet y La b orat or y Assess me nts .............................................................................. 5 9  
Ta ble 3.  Classificati o n of A d verse E ve nts b y Se v erit y ......................................................... 6 1  
Ta ble 4.  Classificati o n of A d verse E ve nts b y Relati o ns hi p t o St u d y Dr u g .......................... 6 2  
 
 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 1 9  of 8 9  
3. 2  
List of I n-te xt Fi g ures 
Fi g ure 1.  St u d y Desi g n ........................................................................................................... 3 4  
 
 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 2 0  of 8 9  
4  
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 
A D R 
a d verse dr u g reacti o n 
A E 
a d verse e ve nt 
A U C 
area u n der plas ma c o nce ntrati o n-ti me c ur ve 
A U C 0- 2 4 hr 
area u n der t he plas ma c o nce ntrati o n-ti me  c ur ve fr o m ti me zer o t o 2 4 h o urs 
A U C 0- ∞ 
area u n der t he plas ma c o nce ntrati o n-ti me  c ur ve fr o m ti me zer o t o i nfi nit y 
BI D 
t wice dail y 
B MI 
b o d y mass i n de x 
B S A 
b o d y s urface area 
C F R 
C o de of Fe deral Re g ulati o ns 
C ma x  
ma xi m u m plas ma c o nce ntrati o n 
C S 
cli nicall y si g nifica nt 
C- S S R S 
C ol u m bia- S uici de Se verit y Rati n g Scale 
C tr o u g h 
tr o u g h plas ma c o nce ntrati o n 
D L QI 
Der mat ol o g y Life Q ualit y I n d e x 
e C R F 
electr o nic case re p ort f or m 
E C G 
electr ocar di o gra m 
E D C 
electr o nic data ca pt ure 
F A S 
f ull a nal ysis set 
F S H 
f ollicle-sti m ulati n g h or m o ne 
G C P 
G o o d Cli nical Practice 
GI 
gastr oi ntesti nal 
H B V 
he p atitis B vir us 
H C V 
he p atitis C vir us 
I B 
i n vesti gat or’s br oc h ure 
I C5 0 
half ma xi mal i n hi bit or y c o nce ntrati o n 
I C F 
i nf or me d c o nse nt f or m 
I C H 
I nter nati o nal C o u ncil f or Har m o nisati o n  
I E C 
i n de p e n de nt et hics c o m mittee 
I L 
i nterle u ki n 
I R B 
i nstit uti o nal re vie w b oar d 
I W R S 
i nteracti ve we b res p o nse s yste m 
M A D 
m ulti ple asce n di n g d ose 
N O A E L 
n o- o bser ve d-a d verse-effect-le vel 
N R S 
n u merical rati n g scale 
P A SI 
Ps oriasis Area a n d Se verit y I n de x 
C CI
C CI
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 2 1  of 8 9  
A b bre vi ati o n 
Defi niti o n 
P A SI- 5 0 
≥ 5 0 % re d ucti o n fr o m Baseli ne i n t he P A SI sc ore 
P A SI- 7 5 
≥ 7 5 % re d ucti o n fr o m Baseli ne i n t he P A SI sc ore 
P A SI- 9 0 
≥ 9 0 % re d ucti o n fr o m Baseli ne i n t he P A SI sc ore 
P A SI- 1 0 0 
1 0 0 % re d ucti o n fr o m Baseli ne i n t he P A SI sc ore 
P D E 4 
p h os p h o diesterase 4 
PI 
pri nci pal i n vesti gat or 
P K 
p har mac o ki netic 
P P S 
per pr ot oc ol set  
P R O 
patie nt-re p orte d o utc o me 
Q D 
o nce dail y 
Q O L 
q ualit y of life 
Q T c 
c orrecte d Q T i nter val 
Q T c F 
Q T i nter val c orrecte d usi n g Fri dericia’s f or m ula   
S A D 
si n gle asce n di n g d ose 
S A E 
seri o us a d verse e ve nt 
S A P 
statistical a nal ysis pla n 
s P G A 
Static P h ysicia n’s Gl o bal Ass ess me nt 
S U S A R 
s us pecte d u ne x pecte d serio us a d verse reacti o ns 
T E A E 
treat me nt-e mer ge nt a d verse e ve nt 
T N F- α  
t u m or necr osis fact or-al p ha 
T F L 
T a bles fi g ures a n d listi n gs  
W O C B P 
w o me n of c hil d beari n g p ote ntial 
U V 
ultra vi olet 
U V B 
ultra vi olet B 
 
C CI
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 2 2  of 8 9  
5  
I N T R O D U C TI O N 
5. 1  
B ac k gr o u n d o n Pl a q ue Ps ori asis 
Ps oriasis is a c hr o nic i m m u ne- me diate d i nfla m m at or y dis or der t hat affects a p pr o xi matel y 2 % t o 
3 % of t he p o p ulati o n, w hic h tra nslates t o 1 7 milli o n pe o ple i n N ort h A meri ca a n d E ur o pe a n d 
a p pr o xi matel y 1 7 0 milli o n pe o ple w orl d wi de.( 1 ) It is c haracterize d b y disfi g uri n g, scali n g, 
er yt h e mat o us pla q ues t hat ma y be p ai nf ul or of te n se verel y pr uritic a n d ma y ca use si g nifica nt 
q ualit y of life ( Q O L) iss u es. T he pla q ues are irre g ular, r o u n d t o o val i n s ha pe, a n d m ost ofte n 
l ocate d o n t he scal p, tr u n k, b utt oc ks, a n d li m bs, wit h a pre dilecti o n f or e xte ns or s urfaces s uc h as 
t he el b o ws a n d k nees.(2 ) 
Nearl y o ne- q uart er of p e o ple w orl d wi de wit h ps oria sis are c o nsi dere d t o h a ve m o derate t o se vere 
f or m of t he diseas e.(3 ) A s ur ve y of dat a fr o m N ati o nal Healt h a n d N utriti o n E x a mi nati o n i n t he 
U nite d States, c o ncl u de d t hat ps oriasis is i n de pe n de ntl y ass o ciate d wit h a n i ncreas e d ris k of 
m ortalit y, w hic h mi g ht be me diate d b y i ncrease d  pre vale nce of c o m or bi dities (car di o v asc ular, 
i nfecti o us, a n d ne o plastic dis or ders) i n ps oriatic patie nts.(4 ) 
Treat me nt o pti o ns f or ps oriasis i ncl u de t o pical treat me nts f or mil der diseas e, a n d s yste mic 
treat me nts f or m o derate t o se vere dise ase n ot s ufficie ntl y res p o nsi ve t o t o pical treat me nts. 
T o pical treat me nts i ncl u d e c ortic oster oi ds, a nt hrali n, s y nt hetic vita mi n D 3, a n d vita mi n A. 
S yste mic t hera pies i ncl u de p h ot ot hera p y, acitreti n, c ycl os p ori ne, met h otre x ate, a pre milast, a n d 
vari o us s yste mic bi ol o gic pr o d ucts. Acitreti n is a p ote nt terat o ge n t hat s h o ul d be a v oi de d i n 
w o me n of c hil d beari n g a ge a n d p ote ntial. C ycl os p ori ne w or ks ra pi dl y a n d is effecti ve i n t he 
maj orit y of patie nts, h o we ver, i m pair e d re n al f u nc ti o n, h y perte nsi o n, c o ncer ns a b o ut l y m p h o ma, 
a n d a p ote ntial i ncrease i n c uta ne o us mali g na nci es are k n o w n a d verse effects after l o n g-t er m 
treat me nt wit h c ycl os p ori ne. Met h otre x ate, alt h o ug h effecti ve i n t he maj orit y of patie nts, h as t h e 
p ote ntial f or he pat ot o xicit y.( 2 ) A pre milast is a n oral p h os p h o diesterase 4 ( P D E 4) i n hi bit or, 
a p pr o ve d f or m o derate t o se vere ps oriasis. De s pite t he a d va nce me nt i n der mat ol o g y, a n d t he 
i ntr o d ucti o n of ne wer bi ol o gical dr u gs, a pre milast is t he o nl y n o vel or al me dicati o n t hat has bee n 
i ntr o d uce d t o treat ps ori asis i n t he past 2 deca des.(5 ) F or its safet y pr ofile a n d eas y r o ute of 
a d mi nistrati o n, a pre milast ma y offer a n oral treat me n t o pti o n f or t h ose patie nts t hat disc o nti n ue 
treat me nts beca use of i n effecti ve n ess, i nt olera bilit y or i neli gi bilit y t o t he c urre ntl y a vaila ble 
dr u gs.( 6 ) H o we ver, t h e efficac y of a pre milast is n ot s o great c o m pare d t o ot her s yste mic 
t hera pies. T heref ore, a d diti o nal oral treat me nts f or ps oriasis t hat ca n pr o vi d e hi g h le vels of 
effic ac y, safet y a n d t olera bilit y re mai n a n u n met nee d. 
5. 2  
B ac k gr o u n d o n M E 3 1 8 3 
M E 3 1 8 3 ( 1- {[ 2-( 3, 6- Diaza bic ycl o [ 3. 1. 1] he pta n- 3- yl)- 7-( 1, 3-t hiaz ol- 2- yl)- 1, 3- be nz o x az ol- 4-
yl] o x y }- 1, 1- difl u or o- 2- met h yl pr o p a n- 2- ol) is a s y nt hesize d, s mall m olec ule, disc o vere d b y Meiji 
Sei ka P har ma C o., Lt d., t hat acts as a P D E 4 i n hi bit or. M E 3 1 8 3 s h o ws a hi g her p ote nc y of 
i n hi bit or y acti vit y f or P D E 4 a n d a hi g her p ot e nc y of i n hi biti o n a gai nst li p o p ol ysacc hari de-

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 2 3  of 8 9  
i n d uce d t u m or necr osis fact or-α  ( T N F-α ) pr o d u cti o n i n h u ma n bl o o d cells t ha n e xisti n g PD E 4 
i n hi bit ors a n d t h us is e x pecte d t o ha v e a hi g her cli nical effi cac y i n ps oriasis. Als o, fe w M E 3 1 8 3 
was detect e d i n t he rat br ai n after si n gle oral  a d mi nistrati o n, i n dicati n g l o w distri b uti o n of 
M E 3 1 8 3 i nt o t he brai n. T heref ore, M E 3 1 8 3 is e x pecte d t o s h o w less ce ntral ne ur ocir c uitr y 
ass ociate d a d v erse effect (e g, v o miti n g) t ha n ot h er P D E 4 i n hi bit ors. 
5. 2. 1  
N o ncli nic al St u dies 
M E 3 1 8 3 is a hi g hl y sele cti ve P D E 4 i n hi bit or, n o n-selecti ve a m o n g P D E 4 s u bt y pes: half 
ma xi mal i n hi bit or y c o nce ntrati o n (I C 5 0) at P D E 4 A 1 A of 1. 2 8 n m ol/ L, at P D E 4 B 1 of 2. 3 3 
n m ol/ L, a n d at P D E 4 D 2 of 1. 6 3 n m ol/ L. I n hi biti o n of P D E 4 aff or ds M E 3 1 8 3 p ote nt a nti-
i nfla m mat or y acti vit y. T he effi cac y of M E 3 1 8 3 was assesse d i n p har mac ol o g y st u dies, w hic h 
s u p p orts t he rati o nale f or assess me nt of M E 3 1 8 3 i n cli nical st u dies. M E 3 1 8 3 i n hi bite d vasc ular 
per mea bilit y i n a hista mi ne-i n d uce d m o use m o d el. I n a d diti o n, e val uati o n of M E 3 1 8 3 i n a 
c hr o nic o x az ol o ne-i n d uce d m o use m o del of der m at itis de m o nstrate d t hat oral treat me nt of 
M E 3 1 8 3 s u p presse d ear s welli n g wit h a dr u g  d os e pr o d uci n g me dia n effecti ve d ose ( E D5 0) of 
1. 4 3 m g/ k g. 
N o effects of M E 3 1 8 3 o n ce ntral ner v o us s yste m ( C N S) i n male mice at d ose le vels of 3, 1 0, a n d 
3 0 m g/ k g. A n i ncrease i n heart rate a n d a pr ol o n gati o n of c orrecte d Q T i nter val ( Q Tc) d urati o n 
(  
% l o n ger t ha n t he i n di vi d ual ti me- matc he d o w n c o ntr ol val ue) was o bser ve d i n   of 
4 m o n ke ys at 1 0 m g/ k g of M E 3 1 8 3. T he I C 5 0 f or t he h u ma n Et her-à- g o- g o- Relate d Ge ne 
( h E R G) was  
 n m ol/ L ( 
 n g/ m L). 
T he p h ot ot o xic p ote ntial of M E 3 1 8 3 was e v al uate d i n t he c ult ure d ma m malia n cells ( Bal b/c 3 T 3 
cells). T he I C 5 0 val ues f or cell via bilit y wit h a n d wit h o ut irra diati o n were deter mi ne d t o be 
 μ g/ m L  a n d  
 μ g/ m L, res pecti vel y, a n d t he p h ot o irritati o n fact or was  
 a n d less 
t ha n 5, t hat is t he p ositi ve criteri a defi ne d b y t h e I nter nati o nal C o u ncil f or 
Har m o nisati o n (I C H) S 1 0 g ui da n ce. T heref ore, M E 3 1 8 3 was cat e g orize d as ha vi n g n o 
p h ot ot o xicit y. 
T he plas ma p har m ac o ki n etic ( P K) pr ofiles of M E 3 1 8 3 were o bs er ve d i n mice, rats, d o gs, a n d 
m o n ke ys after oral a n d/ or i ntra ve n o us a d mi nist rati o n. Oral bi oa vaila bilit y i n rats, d o gs, a n d 
m o n ke ys w ere a p pr o xi matel y   t o  
%,  
%, a n d   t o  
%, res pecti vel y. M E 3 1 8 3 e x hi bite d 
n o n-li near a bs or pti o n a n d area u n d er t he pl as ma c o nce ntrati o n-ti me c ur ve ( A U C) i ncrease d 
greater t ha n d ose pr o p orti o nalit y i n mice, ra ts, a n d m o n ke ys. Plas ma pr otei n bi n di n g of M E 3 1 8 3 
ra n ge d fr o m  
% i n m o use, rat, d o g, m o n k e y a n d h u ma n, a n d n o a p pare nt differe n ces 
were o bs er ve d a m o n g t hese s peci es a n d c o n ce n tr ati o ns. M E 3 1 8 3 was n ota bl y sta ble i n h u ma n 
a n d a ni mal he pat o c yt es e x ce pt m o n ke y he p at oc yte s. T he reacti o n p he n ot y pi n g st u dies i n dicate d 
t hat t he f or mati o n of  
 was mai nl y me di ate d b y c yt oc hr o me 3 A 4/ 5. T he e x creti o n of 
M E 3 1 8 3 i nt o uri ne a n d bile was a p pr o xi matel y  
% of d oses after i ntra v e n o us a d mi nistrati o n t o 
rats. M E 3 1 8 3 at t he c o n ce ntrati o n of   μ m ol/ L s h o we d little t o  n o i n hi biti o n f or c yt oc hr o m e 1 A, 
2 B 6, 2 C 8, 2 C 9, 2 C 1 9, 2 D 6, a n d 3 A e nz y m e assa ys. 
 
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Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 2 4  of 8 9  
T he t o xicit y of M E 3 1 8 3 was assesse d i n mice a n d m o n ke ys wit h u p t o  - wee k a n d  - wee k of 
c o nsec uti ve o nce dail y oral d osi n g. I n mice a n d m o n ke ys, t h e t o xicit y pr ofile of M E 3 1 8 3 was 
i de ntifie d as arteritis a n d deteri orat e d cli nical c o n diti o n d ue t o t he se vere gastr oi ntesti nal m otilit y 
i n hi biti o n. Arteritis was o bser ve d i n m ulti ple or ga ns i n t he m ori b u n d a ni mals at hi g h d ose i n 
b ot h s pecies. I n t he  - wee k re peate d d ose t o xicit y st u d y, t here was n o differe nce of t o xicit y 
fi n di n gs bet w ee n mice a n d m o n ke ys; h o w e ver, it was c o nsi dere d t hat m o n ke ys were m ore 
se nsiti ve t o t o xicit y t ha n mice beca use t o xicit y fi n di n gs were o bser ve d at l o wer plas ma 
c o nce ntr ati o ns i n m o n ke ys. 
I n mice, t he mea n m a xi m u m plas ma c o nce ntr ati o n ( Cma x ) o n Da y 2 8 at n o- o bser ve d a d v erse 
effect le vel ( N O A E L) ( 3 m g/ k g/ da y) were  
 a n d  
 n g/ m L, a n d A U C 0- 2 4 h were  
 a n d 
 n g· hr/ m L i n male a n d fe male, res pecti vel y. 
I n m o n ke ys, Cma x  o n D a y 2 8 at N O A E L ( 1 m g/ k g/ da y) were  
 a n d  
 n g/ m L, a n d 
A U C 0- 2 4 h were  
 a n d  
 n g· hr/ m L i n male a n d fe male, res pecti vel y. T he t o xicit y of oral 
a d mi nistrati o n of M E 3 1 8 3 was e val uat e d i n mice  a n d m o n ke ys i n a 1 6- wee k re peat e d d ose 
t o xicit y st u d y f oll o we d b y a 4- wee k rec o ver y st u d y. T he t o xicities o bser ve d i n t his st u d y were 
si milar (i nfla m mati o n i ncl u di n g arteritis) t o t h ose o bser ve d i n t he 2 8- d a y re peate d d ose t o xicit y 
st u d y a n d t he N O A E L w as 3 m g/ k g/ da y i n b ot h mice a n d m o n ke ys. I n mice, arteritis a n d 
periarteritis were n ote d i n a dea d m o use at 1 0 m g/ k g/ da y. T h e A U C 0- 2 4 hr o n t he last d osi n g da y 
was  
 n g hr/ m L i n males a n d  
 m g hr/ m L i n fe males. I n m o n ke ys, n o arteritis was 
o bser ve d, a n d n o a ni mal die d or sacrific e d d u e t o m ori b u n dit y a n d t he a v era ge A U C 0- 2 4 hr o n t he 
last d osi n g da y w as  
 n g hr/ m L i n males a n d  
 n g hr/ m L i n fe m ales. 
T he effects of oral M E 3 1 8 3 o n e m br y o-fetal de vel o p me nt were st u die d i n a preli mi nar y st u d y i n 
pre g na nt mice. M E 3 1 8 3 was orall y a d mi nistere d o nce dail y ( Q D) t o pre g n a nt mice ( 8 t o 
1 0 da ms/ gr o u p) at d ose l e vels of 0 ( ve hicle), 1, 3, a n d 1 0 m g/ k g/ da y d uri n g t he peri o d fr o m 
i m pla ntati o n t o t he cl os ure of t he h ar d palat e (fr o m Da y 6 t o D a y 1 5 of gestati o n). T he N O A E L 
was c o nsi dere d t o be 1 0 m g/ k g/ da y of M E 3 1 8 3 f or ge neral t o xicit y a n d re pr o d ucti ve f u ncti o ns i n 
da ms a n d e m br y o-fetal d e vel o p me nt. N o test article-relat e d c ha n ges were n ote d i n t he n u m ber of 
li ve fet uses, fet al via bilit y rate, n u m ber of e mbr y o-fetal deat hs, p ost-i m pla ntati o n l oss rate, fetal 
b o d y w ei g ht, place ntal w ei g ht, se x rati o, or e xter n a l, place ntal, visceral, or s keletal fi n di n gs at 
a n y d os e le vel. At t he N O A E L, t he C ma x  of dr u g of M E 3 1 8 3 a vera ge d  
 n g/ m L a n d t he mea n 
A U C 0- 2 4 hr of M E 3 1 8 3 a vera ge d  
 n g· hr/ m L o n Da y 1 5 of gestati o n. 
F or c o m plete d etails o n t he n o ncli nical st u dies of M E 3 1 8 3, refer t o t he i n vesti gat or ’s 
br oc h ure (I B). 
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Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 2 5  of 8 9  
5. 2. 2  
Cli nic al St u dies 
T w o ( 2) P hase 1 st u dies i n healt h y a d ult s u bjects ( M E 3 1 8 3- 1 a n d M E 3 1 8 3- 2 st u dies) ha ve bee n 
c o n d ucte d a n d 1 2 6 i n di vi d uals w h o recei ve d st u d y treat me nt ( 9 6 s u bjects recei ve d M E 3 1 8 3 a n d 
3 0 s u bjects recei ve d place b o). M E 3 1 8 3 was t olera ble a n d safe i n healt h y a d ults u p t o 2 5 m g 
si n gle a d mi nistrati o n, a n d 1 0 m g t wice d ail y ( BI D) a n d 1 5 m g Q D f or 1 4 da ys m ulti ple 
a d mi nistrati o ns. Fre q ue ntl y re p orte d treat me n t-e m er ge nt a d verse e ve nts ( T E A Es), t he T E A Es 
re p orte d b y m or e t ha n 2 s u bjects, i n si n gle a dmi nistrati o n were diarr hea, hea dac h e, li pase 
i ncreas e d, tac h ycar dia, a n d na usea. T h e maj orit y of T E A Es i n si n gle asce n di n g d ose ( S A D) 
st u dies were cl assifie d as mil d. M ost of t he T E A Es were rec o v ere d/r es ol ve d wit hi n fe w da ys 
wit h o ut a n y me dicati o n. T he seri o us a d v erse e v e nt ( S A E) of se vere vas o v a gal n e ur ocar diac 
s y nc o p e occ urre d i n 1 2. 5 m g s u bject. W he n M E 3 1 8 3 were a d mi nistere d re peate dl y, t he 
fre q ue ntl y re p orte d T E A Es were; me dical de vice site reacti o n, hea dac h e, diarr hea, a b d o mi nal 
pai n, v o miti n g, na usea, h e mat oc hezia, bac k p ai n, art hral gia, pai n i n e xtre mit y, m yal gia, 
der matitis, decrease d a p p etite, a n d d ys m e n orr h ea.  T he maj orit y of T E A Es i n m ulti ple asce n di n g 
d ose ( M A D) st u d y w ere classifie d as mil d. All T E A Es were te m p oral a n d res ol ve d d uri n g t he 
d osi n g peri o d. N o S A E was occ urre d i n M A D st u d y.  
M E 3 1 8 3 was a d mi nistere d t o healt h y a d ult s u bjects i n eit her i n s us pe nsi o n ( 1 m g t o 1 2. 5 m g) or 
ca ps ule ( 1 2. 5 m g t o 2 5 m g) i n S A D st u dies. M E 3 1 8 3 was a bs or be d orall y i n b ot h f or m wit h pea k 
c o nce ntr ati o n rec or de d at a p pr o xi matel y 3. 5 h o urs t o 4 h o urs p ost d ose a n d was eli mi nate d 
sl o wl y wit h a n eli mi nati o n half-life (t 1/ 2) of a p pr o xi matel y 1 6 h o urs t o 2 4 h o urs. T he mea ns of 
C ma x  a n d A U C i ncreas e d sli g htl y greater t ha n a d ose pr o p orti o nalit y fr o m 1 m g t o 1 0 m g 
s us pe nsi o n, w hile C ma x  a n d A U C i ncreas e d al m ost d ose pr o p orti o nall y o v er t he d ose ra n ge of 
1 2. 5 m g t o 2 5 m g of ca ps ule a d mi nistrati o n. T he mea ns of C ma x  a n d A U C i n  
 
( meta b olite of M E 3 1 8 3) were a p pr o xi matel y fr o m 
% t o  
% c o m pare d wit h t h ose of M E 3 1 8 3 
at eac h d os e le vel. As t he d ose of M E 3 1 8 3 i ncreas es, t he rati o of C ma x  a n d A U C of  
 t o 
M E 3 1 8 3 te n de d t o decrease. T he me a n of c u m ulati ve uri nar y e x creti o n rate i n M E 3 1 8 3 was  % 
t o  % w hic h was q uite s mall.  
I n t he M A D st u d y, t he m ea ns of Cma x  a n d A U C i n creas e d o ver t h e d ose ra n ge of 2. 5 m g BI D t o 
1 0 m g BI D. T he mea n C ma x  i ncrease d b y 4- t o 5-f ol d wit h m ulti ple d osi n g fr o m Da y 1 t o Da y 1 4, 
i n all t he BI D d ose gr o u ps. T he mea n Cma x  i ncreas e d b y 2-f ol d wit h m ulti ple d osi n g fr o m Da y 1 
t o Da y 1 4, i n 1 5 m g Q D d ose gr o u p. T he mea n plas ma c o nce ntrati o n i n t he stea d y-state of 
M E 3 1 8 3 was ac hi e ve d ar o u n d Da y 3 t o Da y 4 i n all t he gr o u ps. 
P K pr ofiles of M E 3 1 8 3 a n d  
 were affecte d sli g htl y b y f o o d i nta k e. T he f o o d i nta ke 
decrease d t he s yste mic e x p os ures of M E 3 1 8 3 after si n gle d os e of M E 3 1 8 3. T he ti me t o pea k 
plas ma c o nce ntrati o n of M E 3 1 8 3 u n der fe d c o n diti o n was dela ye d b y a p pr o xi matel y 2 h o urs 
c o m pare d wit h t hat u n der fast e d c o n diti o n. T he o bser ve d ge o m etric mea ns were i n t he rati o 
(fe d/fast e d) of 6 5 % f or Cma x  a n d 8 2 % f or area u n d er t he plas ma c o nce ntr ati o n-ti me c ur ve fr o m 
ti me zer o t o i nfi nit y ( A U C0- ). T here was n o a p pare nt differe nce of t1/ 2 of M E 3 1 8 3 bet wee n 
faste d a n d fe d c o n diti o ns. 
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M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 2 6  of 8 9  
Refer t o t he I B f or f urt her details o n cli nical st u dies wit h M E 3 1 8 3. 
5. 3  
Cli nic al Ris ks/ Be nefits of M E 3 1 8 3 
M E 3 1 8 3 was t olera ble a n d safe i n he alt h y a d ults u p t o 2 5 m g si n gle a d mi nistrati o n a n d 1 0 m g 
BI D a n d 1 5 m g Q D f or 1 4 da ys m ulti ple a d mi nistrati o ns. T he fre q u e ntl y re p orte d a d verse dr u g 
reacti o ns ( A D Rs), t he A D Rs re p orte d b y m or e t ha n 2 s u bjects, i n si n gle a d mi nistrati o n were 
diarr hea, tac h ycar dia, a n d li pase i ncrease d. Maj ori t y of A D Rs w ere classifi e d as mil d. All e ve nts 
e x ce pt f or vas o va gal ne ur ocar di ac s y nc o p e were r ec o vere d/res ol ve d wit hi n fe w da ys wit h o ut a n y 
me dicati o ns. N o s u bjects disc o nti n ue d t he st u d y d ue t o A D Rs i n S A D st u dies. 
O ne s u bject i n 1 2. 5 m g s us pe nsi o n gr o u p e x perie nce d a n S A E of se vere v as o va gal ne ur ocar diac 
s y nc o p e d uri n g M E 3 1 8 3- 1 S A D st u d y. T he s u bject ha d a pri or hist or y of s y nc o pe a n d dizzi ness 
li kel y d ue t o ort h ostatic i nt olera nce. T he s u bject was teste d wit h t he tilt ta ble test a n d s h o we d a 
vas o va gal r es p o nse cle arl y, s u g gesti n g t he s u bject ha d a ris k fact or of s y n c o pe. 
W he n M E 3 1 8 3 was a d mi nistere d re p eate dl y, t he fre q ue ntl y re p ort e d A D Rs, t he A D Rs re p orte d 
b y m ore t h a n 2 s u bjects, were h ea dac he, diarr hea, a b d o mi nal pai n, v o miti n g, na us ea, a n d 
decrease d a p petite. T he n u m ber of A D Rs of di arr h ea i ncrease d wit h t he d ose. Na usea a n d 
v o miti n g were n ot e d i n hi g her d os es ( 1 0 m g BI D a n d 1 5 m g Q D). Diarr hea was n ote d i n t he 
earl y peri o d of d osi n g, ar o u n d Da y 1 t o Da y 2, i n all d ose gr o u ps. Hea dac h e be ga n fr o m ar o u n d 
Da y 7 i n l o wer d ose ( 2. 5 m g BI D or 5 m g BI D) a n d fr o m Da y 1 t o Da y 2 i n hi g her d ose gr o u ps 
( 1 0 m g BI D or 1 5 m g Q D). V o miti n g was o bser ve d fr o m Da y 7 s p ora dicall y, b ut res ol ve d d uri n g 
t he d osi n g peri o d. T he m aj orit y of A D Rs were classifie d as mil d. T here were 6 m o derate A D Rs 
of hea dac he, diarr hea, a b d o mi nal pai n, v o miti n g, na usea, a n d t ac h ycar dia i n 1 0 m g BI D, a n d 1 
m o derate v o miti n g i n 1 5 m g Q D d os e gr o u p. T here was n o se vere A D R i n M A D st u d y. All 
A D Rs were t e m p oral a n d were res ol ve d d uri n g t he d osi n g peri o d. I n 1 0 m g BI D d os e gr o u p, 2 
s u bjects wit h dre w c o ns e nt d ue t o a d verse e ve nts ( A Es). T he A D Rs o bser ve d i n t hese 2 s u bjects 
were h ea dac he, diarr hea, v o miti n g, feeli n g h ot, na usea, a b d o mi nal pai n, a n xiet y, a n d s ki n 
e xf oliati o n. T he e ve nts s uc h as na usea, v o miti n g a n d diarr hea, a n d h ea d ac he are k n o w n t o be 
si de effects of e xisti n g P D E 4 i n hi bit ors. 
T he p ote ntial ris ks of M E 3 1 8 3 ca n be esti mate d base d o n t he A E pr ofile of a pre milast (a P D E 4 
i n hi bit or) prese nte d i n t h e c o m merci al la beli n g. T he c o m m o n A Es i ncl u de diarr hea, na usea, 
v o miti n g, de pressi o n, wei g ht decreas e, u p per re s pirat or y tract i nfecti o n, nas o p har y n gitis, 
a b d o mi nal pai n u p per, a n d hea dac he ( Ot ezla pac k a ge i nsert, U S A, re vise d: 0 4/ 2 0 2 0). Als o, t he 
m ost c o m m o n si de effects of k n o w n oral P D E 4 i n hi bit ors are gastr oi ntesti n al ( GI) effects s uc h as 
na usea, v o miti n g, a n d diarr hea.( 7 ) A d diti o nall y, GI m otilit y dis or d er, i nfl a m mat or y fi n di n gs 
i ncl u di n g art eritis/ vasc ulitis, a n d Q Tc pr ol o n gati o n were re p orte d b ase d o n t he n o ncli nical 
st u dies. 
T he p ote ntial si de effects i de ntifie d i n M E 3 1 8 3 n o ncli n ical st u dies a n d als o i n st u dies i n v ol vi n g 
ot her oral P D E 4 i n hi bit ors will be caref ull y m o nit ore d i n t he c urre nt st u d y. T he GI m otilit y 
dis or der will be i de ntifie d b y m o nit ori n g t h e s u bjects f or a n y si g ns of a b d o mi nal disc o mf ort, 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 2 7  of 8 9  
a b d o mi nal diste nsi o n, a b d o mi nal pai n, na usea, v o miti n g, l oss of a p petite, a n d c o nsti pati o n. 
Besi des t he a b o ve, all s u bjects will be m o nit ore d f or a n y car di o vas c ular m a nifestati o ns usi n g 
vital si g ns a n d 1 2-le a d el ectr ocar di o gra ms ( E C Gs) . Dr u g class p ote ntial effects s uc h as w ei g ht 
l oss a n d maj or de pressi o n will be m o nit ore d d uri ng t his st u d y. Wei g ht will be meas ure d at 
sc he d ule d visits t hr o u g h o ut t he st u d y t o c hec k f or a n y p ot e ntial e xcessi ve wei g ht l oss. S u bjects 
wit h maj or de pressi o n or at ris k f or s uici de wi ll be e x cl u de d a n d s uici dal i deati o n will be 
assesse d at Scree ni n g a n d/ or Baseli ne b y C ol u m bia- S uici de Se verit y Rati n g Scal e ( C- S S R S). 
C o nsi deri n g t he a b o v e safet y pr ofile of M E 3 1 8 3, ca uti o n will be e x ercise d (i n vesti gat or’s 
j u d ge me nt) b ef ore ra n d o mizi n g s u bjects wit h a n y cli nicall y si g nifica nt ( C S) c o m or bi dities 
(car di o v asc ular, GI, ne ur ol o gical, etc.). See Secti o n 8  f or detaile d list of i ncl usi o n a n d e x cl usi o n 
criteria. 
5. 4  
St u d y R ati o n ale 
T his st u d y is desi g n e d t o assess t he efficac y, safet y, a n d t olera bilit y of M E 3 1 8 3 a d mi nistere d 
orall y f or 1 6 w ee ks i n s u bjects wit h m o derate t o  s e vere pl a q ue ps oriasis as a pr o of- of-c o n ce pt 
st u d y. P hase 1 st u dies wit h M E 3 1 8 3 s h o we d it was safe a n d ge nerall y well t olerate d i n healt h y 
s u bjects. T his is t he first st u dy i n t he tar get patie nt p o p ulati o n. 
Efficac y will be assesse d t hr o u g h a set of vali da te d meas ures f or pla q ue ps oriasis. I n a d diti o n, 
P K a n d 
 e v al uati o ns will be c o n d ucte d. T h e res ults of t he st u d y will 
i nf or m t he desi g n a n d t he d osi n g re gime ns of t he s u bse q ue nt st u d y. 
5. 5  
R ati o n ale f or D ose Sele cti o n 
F o ur differe nt d os e le vels (  m g BI D,   m g Q D,  
 m g BI D a n d   m g Q D) were selecte d as 
d osi n g re gi me ns f or t his st u d y. T he d os e re gi me ns were s electe d base d o n t he res ults of P hase 1 
st u dies w hic h ha ve bee n c o ncl u de d t hat M E 3 1 8 3 was safe a n d ge n erall y well t olerate d i n healt h y 
s u bjects. 
T he f oll o wi n g p oi nts were c o nsi dere d f or d os e sel ecti o n: 
 
T he d oses were sel ecte d wit hi n t he ra n ge of d oses teste d i n t he S A D a n d M A D c o h orts i n 
P hase 1 st u dies. 
 
T he n o ncli nical st u d y of M E 3 1 8 3 s h o we d t hat t he i n hi bit or y acti vit y of M E 3 1 8 3 t o T N F- α  
pr o d ucti o n was str o n ger at 3 1 ti mes t ha n t hat of a pre milast. Gi ve n t hat t he plas ma 
c o nce ntr ati o n, t hat is stea d y-stat e tr o u g h plas ma c o nce ntrati o n ( C tr o u g h) a n d A U C, of select e d 
d oses of M E 3 1 8 3 w o ul d be e x pecte d t o be c o m p ara ble t o t hera p e utic e x p os ure le vel 
a ntici pate d b y t he res ult of t he n o ncli nical st u d y. 
 
Hi g h d oses w ere select e d wit hi n t he t olera ble d ose ( 2 0 m g p er da y f or 1 4 da ys) i n P hase 1 
st u dies, t o assess t he near ma xi mall y t hera pe utic res p o nses. E x p os ure le vel, t hat is C ma x  a n d 
A U C per da y, of select e d d oses  were esti mate d n ot t o e x cee d t he e x p os ure le vel of 1 0 m g 
BI D. 
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Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 2 8  of 8 9  
 
Base d o n t h e P K pr ofile of M E 3 1 8 3 i n P hase 1 st u dies, a Q D d osi n g re gi me n was selecte d 
i n a d diti o n t o t he BI D d osi n g re gi me n. 
Refer t o t he I B f or c o m pl ete details f or s afet y a n d P K. 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 2 9  of 8 9  
6  
S T U D Y O B J E C TI V E S A N D E N D P OI N T S 
6. 1  
St u d y O bjecti ves 
6. 1. 1  
Pri m ar y O bjecti ve 
 T o e val uate t he effi cac y of oral M E 3 1 8 3 c o m par e d wit h place b o at Wee k 1 6 i n s u bjects 
wit h m o derate t o se vere pla q ue ps oriasis as  meas ure d b y t he Ps oriasis Area a n d Se verit y 
I n d e x ( P A SI) sc ore 
6. 1. 2  
Sec o n d ar y O bjecti ves 
 T o e val uate t he s afet y a n d t olera bilit y of oral M E 3 1 8 3 i n s u bjects wit h m o derate t o 
se vere pl a q ue ps oriasis 
 T o e val uate t he effi cac y of oral M E 3 1 8 3 i n s u bjects wit h m o derate t o se vere pla q ue 
ps oriasis at vari o us ti me p oi nts 
 T o e val uate t he effect of oral M E 3 1 8 3 o n patie nt-re p orte d o utc o me ( P R O) meas ures i n 
s u bjects wit h m o derate t o se vere pl a q ue ps oriasis 
 T o e val uate t he P K of M E 3 1 8 3 a n d its meta b olite ( 
) i n s u bjects wit h m o derate t o 
se vere pl a q ue ps oriasis w h o are tr eate d wit h oral M E 3 1 8 3 
6. 1. 3  
E x pl or at or y O bjecti ves 
6. 2  
St u d y E n d p oi nts 
6. 2. 1  
Pri m ar y E n d p oi nt 
T he pri mar y effic ac y e n d p oi nt is t he pr o p orti o n of s u bjects ac hie vi n g ≥ 7 5 % re d ucti o n fr o m 
Baseli ne i n t he P A SI sc ore ( P A SI- 7 5) at Wee k 1 6. 
6. 2. 2  
Sec o n d ar y E n d p oi nts 
6. 2. 2. 1  S afet y E n d p oi nts 
T he safet y e n d p oi nts are as f oll o ws: 
 T he i nci de nce, se verit y, a n d seri o us ness of A Es re p orte d o ver t he 1 6- wee k Treat me nt 
Peri o d a n d t he 4- w ee k F oll o w- u p Peri o d 
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Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 3 0  of 8 9  
 C ha n ges fr o m Baseli ne i n C S p h ysic al e xa mi nati o n fi n di n gs a n d vital si g n meas ure me nts 
( bl o o d press ure, h eart rat e, res pirat or y rate, b o d y t e m perat ur e, a n d b o d y wei g ht) o ver t he 
1 6- wee k Treat me nt Peri o d a n d t he 4- wee k F oll o w- u p Peri o d 
 C ha n ges fr o m Baseli ne i n E C G fi n di n gs o ver t he 1 6- wee k Treat me nt Peri o d a n d t he 
4- wee k F oll o w- u p Peri o d 
 C ha n ges fr o m Baseli ne i n safet y la b orat or y val ues ( he mat ol o g y, c oa g ulati o n, bl o o d 
c he mistr y, a n d uri nal ysis) o ver t he 1 6- wee k Treat me nt Peri o d a n d t he 4- wee k F oll o w- u p 
Peri o d 
6. 2. 2. 2  Effic ac y E n d p oi nts 
T he sec o n d ar y efficac y e n d p oi nts are as f oll o ws: 
 T he perce nt c h a n ge fr o m Baseli ne i n P A SI sc ore at all visits fr o m Wee k 1 t o Wee k 1 6 
 T he pr o p orti o n of s u bjects ac hie vi n g P A SI- 5 0, P A SI- 7 5, P A SI- 9 0, P A SI- 1 0 0 at all visits 
fr o m Wee k 1 t o Wee k 1 6 
 Ti me t o P A SI- 5 0 a n d P A SI- 7 5 
 T he pr o p orti o n of s u bjects ac hie vi n g a S tatic P h ysi cia ns Gl o bal Assess me nt (s P G A) 
sc ore of “ 0” (“cle ar”) or “ 1” (“al m ost clear ”) c o m bi ne d wit h 2- p oi nt re d ucti o n o n t he 
5- p oi nt s P G A scale at all visits fr o m Wee k 1 t o Wee k 1 6 
 T he c ha n ge fr o m Baseli n e i n affecte d b o d y s u rface area ( B S A) at all visits fr o m Wee k 1 
t o W ee k 1 6 
 T he c ha n ge fr o m Baseli n e i n t he itc h n u mer ical r ati n g scale ( N R S) at all visits fr o m 
Wee k 1 t o W ee k 1 6 
 T he c ha n ge fr o m Baseli n e i n t he Der mat ol o g y Lif e Q ualit y I n de x ( D L QI) sc ore at all 
visits fr o m W ee k 1 t o Wee k 1 6 
 Perce nta ge of s u bjects wit h at least a 5- p oi nt re d u cti o n fr o m Baseli ne i n t he D L QI sc ore 
at all visits fr o m W ee k 1 t o W ee k 1 6 
6. 2. 3  
P h ar m a c o ki netic E n d p oi nt 
T he P K e n d p oi nt is t he C tr o u g h of M E 3 1 8 3 a n d its meta b olite ( 
). 
6. 2. 4  
E x pl or at or y E n d p oi nts 
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Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 3 1  of 8 9  
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 3 2  of 8 9  
7  
I N V E S TI G A TI O N A L P L A N 
7. 1  
Descri pti o n of O ver all St u d y Desi g n a n d Pl a n 
T his m ulti-ce nter, ra n d o mize d, d o u ble- bli n d, place b o-c o ntr olle d, p arallel gr o u p, P hase 2a st u d y 
is desi g ne d t o ass ess t he effic ac y a n d s afet y of M E 3 1 8 3 a d mi nistere d orall y i n s u bjects wit h 
m o derate t o se v ere pla q u e ps oriasis. T he st u d y c o nsists of a 4- wee k Scree ni n g P eri o d ( Da y - 2 8 
t o Da y - 1), a 1 6- wee k d o u ble- bli n d Treat me nt Peri o d ( Da y 1 t o Da y 1 1 3), a n d a 4- wee k F oll o w-
u p Peri o d ( Da y 1 1 4 t o D a y 1 4 1). T he t otal d ur ati o n of st u d y partici pati o n f or eac h s u bj ect is 
a p pr o xi matel y 2 4 wee ks. 
N ote: T he st u d y dr u g is a d mi nistere d fr o m Da y 1 t o Da y 1 1 2 i n t he Treat me nt Peri o d a n d t he e n d 
of Treat me nt Peri o d assess me nts will be perf or me d o n Da y 1 1 3. 
T he d urati o n of t he F oll o w- u p Peri o d is fr o m Da y 1 1 4 t o Da y 1 4 1 a n d t he e n d of F oll o w- u p 
Peri o d assess me nts will be perf or me d o n Da y 1 4 1. 
A s uita ble n u m ber of s u bjects wit h m o derate t o se vere pla q ue ps oriasis will be scree ne d t o 
ra n d o mize a p pr o xi matel y 1 2 5 s u bjects acr oss a p pr o xi matel y 3 0 st u d y sites i n t he U nite d States 
a n d Ca na da. S u bjects will be  ce ntrall y ra n d o mize d ( 2 5 s u bjects per tr eat me nt gr o u p) i n a 
1: 1: 1: 1: 1 rati o t o 1 of t he f oll o wi n g treat me n t gr o u ps t o recei ve oral M E 3 1 8 3 or matc hi n g 
place b o f or a d urati o n of 1 6 wee ks. 
 Treat me nt Gr o u p 1:   m g M E 3 1 8 3 BI D a d mi nistere d orall y:   ca ps ule of   m g M E 3 1 8 3 
a n d   ca ps ules of matc hi n g pla ce b o i n t he m or ni n g a n d e ve ni n g 
 Treat me nt Gr o u p 2:   m g M E 3 1 8 3 Q D a d mi nistere d orall y:   ca ps ules of   m g M E 3 1 8 3 
a n d   ca ps ule of matc hi n g pla ce b o i n t he m or ni n g a n d 3 ca ps ules of matc hi n g place b o i n 
t he e ve ni n g 
 Treat me nt Gr o u p 3:  
 m g M E 3 1 8 3 BI D a d mi nistere d orall y:   ca ps ule of   m g 
M E 3 1 8 3 a n d   ca ps ule of  
 m g M E 3 1 8 3 a n d   ca ps ule of mat c hi n g pl ace b o i n t he 
m or ni n g a n d e ve ni n g 
 Treat me nt Gr o u p 4:   m g M E 3 1 8 3 Q D a d mi nistere d orall y:   ca ps ules of   m g M E 3 1 8 3 
i n t he m or ni n g a n d   ca ps ules of matc hi n g pl ace b o i n t he e ve ni n g 
 Treat me nt Gr o u p 5: M atc hi n g place b o BI D a d mi nistere d orall y:   ca ps ul es of matc hi n g 
place b o i n t he m or ni n g a n d e ve ni n g 
T o pr o m ote bala nce d all ocati o n, ra n d o mizati o n will be stratifie d b y s u bject’s recei pt ( yes/ n o) of 
pre vi o us treat me nt wit h bi ol o gic dr u g f or ps oriasis. Eac h treat me nt gr o u p will i ncl u de 
ra n d o mize d s u bjects w h o 1) are bi o- n aï ve a n d 2) recei ve d pre vi o us treat me nt wit h a bi ol o gic 
dr u g f or ps oriasis. Bi o- naï ve s u bjects will be ra n d o mize d a b o ve 5 0 % of t he pla n ne d t otal s u bject 
ra n d o mizati o n. After ra n d o mizati o n of s u bjects has reac he d t he m a xi m u m perce nt a ge as 
deter mi ne d b y t he s p o ns or base d o n e nr oll me nt rates f or s u bjects t hat ha ve recei v e d pre vi o us 
treat me nt wit h a bi ol o gi c dr u g f or ps oriasis, ran d o mizati o n i n t his gr o u p ma y b e st o p pe d a n d t he 
st u d y sites will be i nf or m e d acc or di n gl y. 
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Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 3 3  of 8 9  
Scree ni n g Peri o d ( Da y - 2 8 t o Da y - 1): 
A s uita ble n u m ber of s u bjects wit h m o derate t o se vere pla q ue ps oriasis will be scree ne d b ase d o n 
t he i ncl usi o n a n d e x cl usi o n criteria. 
Treat me nt Peri o d ( Da y 1 t o Da y 1 1 3): 
D uri n g t h e Treat me nt Peri o d, t he first d ose of t he st u d y dr u g will be a d mi nistere d i n t he e ve ni n g 
u p o n t he s u bject ret ur ni n g t o t heir h o me o n Da y 1 ( Visit 2) a n d t he last d ose will be self-
a d mi nistere d b y t he s u bject o n Da y 1 1 2 (t he da y be f ore Visit 8). S u bjects will self-a d mi nister t he 
st u d y dr u g at h o me w he n t he y are n ot visiti n g t he st u d y site f or cli nical visits (see Ta ble 1  f or all 
t he sc he d ule d visits). T he t otal n u m ber of ca ps ules nee de d f or at h o me a d mi nistrati o n will be 
dis pe nse d d uri n g eac h st u d y site visit. See Secti o n 9. 2  f or a d diti o nal details. 
All ra n d o mize d s u bjects will be e val uate d f or effi cac y, safet y a n d t olera bilit y, P K, a n d  
 
assess me nts at sc he d ule d visits  per Sc he d ule of Assess me nts (Ta ble 1 ). 
Efficac y assess me nts (ie, P A SI, B S A, s P G A, a n d P R O assess me nts [ D L QI a n d t he itc h N R S]) 
will be assesse d at sc h e d ule d visits as i n dicate d i n t he Sc he d ule of Ass ess me nts (see T a ble 1  f or 
all t he sc he d ule d visits). Refer t o Secti o n 1 1  f or m ore details o n efficac y assess me nts. 
Safet y a n d t olera bilit y will be assesse d b y p h ysical e x a m, m o nit ori n g f or A Es a n d S A Es, 
de m o gra p hics, me dic al hist or y, vital si g ns, E C G, a n d safet y la b orat or y tests ( he mat ol o g y, 
c oa g ulati o n, bl o o d c he mistr y, a n d uri nal ysis) at sc he d ule d visits as i n dicate d i n t he Sc he d ule of 
Assess me nts (see T a ble 1  f or all t he sc he d ul e d visits). C o m plete details o n t he safet y a n d 
t olera bilit y assess me nts are pr o vi de d i n Secti o n 1 2 . 
Refer t o Secti o n 1 3 a n d Secti o n 1 4. 1 f or P K a n d 
 assess me nts, res pecti vel y. 
F oll o w- u p Peri o d ( D a y 1 1 4 t o Da y 1 4 1): 
S u bjects will be f oll o we d u p t o 4 wee ks aft er t he l ast d ose of t he st u d y treat me nt. Refer t o 
Ta ble 1  f or a c o m plete list of assess me nts t o be p erf or me d d uri n g t he f oll o w- u p visit. 
Or der of Assess me nts D uri n g E ac h St u d y Site Visit: 
T he f oll o wi n g pri orit y or der s h o ul d be c o nsi dere d  w he n m ore t ha n 1 assess me nt is re q uire d at a 
partic ular ti me p oi nt, wit h P K a n d  
 bl o o d sa m pli n g perf or me d at t he s p ecifie d ti me: 
1.  1 2-lea d E C G 
2.  Vital si g ns 
3.  Bl o o d sa m pli n g f or safet y la b orat or y tests, P K, a n d  
 assess me nts 
4.  Efficac y assess me nts 
Fi g ure 1  prese nts t he st u d y desi g n. 
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Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 3 4  of 8 9  
Fi g ure 1.  
St u d y Desi g n 
 
A b bre viati o ns: Q D = o nce dail y; BI D = t wice dail y; N = a p pr o xi mate n u m ber of s u bj ects t o be ra n d o mize d. 
7. 2  
Disc ussi o n of St u d y Desi g n 
A d o u ble- bli n d, ra n d o mi ze d, place b o-c o ntr olle d st u d y is c o nsi dere d a g ol d-sta n dar d f or 
c o n d ucti n g a n y i nter ve nti o nal st u d y. T his desi g n will mi ni mize bias a n d pr o vi de refere n ce dat a 
(ie, data fr o m place b o treat me nt gr o u p) f or c o m paris o n of t he efficac y a n d safet y para meters of 
t he M E 3 1 8 3. 
Ps oriasis is a c hr o nic i m m u ne- me diate d i nfla m m at or y dis or der, w hi c h re q uires a c hr o ni c 
t hera p y. Pri mar y effic ac y assess me nts of ps oriasis cli nical st u dies are us u all y perf or me d at 1 2 or 
1 6 wee ks after i nitiati o n of st u d y tr eat me nt. T his is t heref ore c o nsi dere d a n acce pta ble treat me nt 
d urati o n t o o bser ve a C S res p o nse t hat all o ws f or discri mi nati n g a m o n g differe nt teste d d os es of 
M E 3 1 8 3. Pri mar y e val uati o ns of a pre milast, t he o nl y P D E 4 i n hi bit or c urre ntl y a p pr o ve d f or 
ps oriasis treat me nt, were als o c o n d ucte d at w ee k 1 6. A 1 6- wee k Treat me nt Peri o d was als o 
dee me d acce pta ble f or t h e place b o ar m beca use ps oriasis is n ot a life-t hreat e ni n g dise ase; i n cas e 
of u n beara ble flares, s u bj ects ca n disc o nti n ue earl y fr o m t he st u d y a n d recei ve a p pr o priat e 
treat me nt. 
7. 3  
E n d of St u d y 
A s u bject will ha ve f ulfille d t he re q uir e me nts  f or st u d y c o m pleti o n if/ w he n t he s u bject has 
c o m plete d all st u d y p eri o ds (ie, Scree ni n g Peri o d, Treat me nt Peri o d, a n d F oll o w- u p Peri o d) as 
i n dicate d i n t he Sche d ule of Assess me nts ( Ta ble 1 ). 
T he e n d of t he st u d y or st u d y c o m pleti o n will be t he last s u bject’s last visit f or a n y 
pr ot oc ol-relat e d acti vit y. 
S cr e e n i n g P eri o d 
( 4 w e e k s ) 
Tr e at m e nt P eri o d 
(1 6 w e e k s ) 
Gr o u p 1 : M E 3 1 8 3 
 m g BI D 
Gr o u p 2 : M E 3 1 8 3 
m g Q D 
F oll o w- u p P eri o d 
( 4 w e e k s ) 
Gr o u p 3 : M E 3 1 8 3 
 m ~ BI D 
I· 
Da y -2 8 
(W e e k - 4) 
Gr o u p 4 : M E 3 1 8 3
m ~ Q D 
Gr o u p 5 : Pl a c e b o 
·I 
Da y 1 
(W e e k 0) 
R a n d o mi z ati o n 
1: 1 : 1: 1: 1 
( N = 1 2 5 ) 
D a y 1 1 3 
(W e e k 1 6 ) 
) 
Da y 1 4 1 
(W e e k 2 0) 
C CI
C CI
C CI
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 3 5  of 8 9  
7. 4  
E arl y Ter mi n ati o n 
If a s u bject wit h dra ws or is ter mi nate d fr o m stu d y treat me nt pri or t o c o m pleti o n of all st u d y 
peri o ds, all data c ollecte d at Visit 8 ( Da y 1 1 3) s h o ul d be c ollecte d at t he ti me of earl y 
ter mi nati o n. T he s u bject will be as ke d t o ret ur n t o t he st u d y site 4 wee ks aft er t he last d ose of 
st u d y dr u g t o c o m plete t h e f oll o w- u p visit assess me nts (t h ose perf or me d o n Da y 1 4 1) as 
i n dicate d i n t he Sc he d ule of Assess me nts (Ta ble 1 ). 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 3 6  of 8 9  
8  
S E L E C TI O N O F S T U D Y P O P U L A TI O N 
Secti o n 7. 1  pr o vi des i nf or mati o n re gar di n g n u m ber of s u bjects pla n ne d t o b e ra n d o mize d. 
8. 1  
I ncl usi o n Criteri a 
I n di vi d uals m ust meet all of t he f oll o wi n g criteri a t o be i ncl u de d i n t he st u d y: 
1.  S u bject is willi n g a n d a bl e t o partici pate  i n t he st u d y a n d h as rea d, u n derst o o d, a n d 
si g ne d t he i nf or me d c o ns e nt f or m (I C F) acc or di n g t o nati o nal re g ulati o ns. 
2.  S u bject is a male or fe m ale a ge d 1 8 t o 7 5 years (i n cl usi ve) at t he ti me of c o nse nt (ie, 
Scree ni n g). 
3.  S u bject has a b o d y mass i n de x ( B MI) ≥ 1 8. 5 t o < 4 0 k g/ m2 at Scree ni n g. 
4.  S u bject has a dia g n osis of pla q ue ps oriasis f or ≥ 2 4 wee ks pri or t o Scree ni n g. 
5.  T he s u bject’s s y m pt o ms of pla q ue ps oriasis are st a ble i n t he o pi ni o n of t he i n vesti gat or. 
Sta ble is defi ne d as n o ac ute deteri or ati o n (e g, p ust ulati o n or er yt hr o der m a) wit hi n 1 2 
wee ks bef ore Scree ni n g a n d n o re b o u n d of pl a q ue ps oriasis wit hi n 4 wee ks bef ore 
Scree ni n g. 
6.  T he s u bject’s se v erit y of disease meets all of t h e f oll o wi n g criteria: 
 Ps oriatic pla q ues m ust c o ver ≥ 1 0 % of B S A at Scree ni n g a n d Baseli ne 
 P A SI sc ore 1 2 t o 4 0 at Scree ni n g a n d Baseli ne 
 s P G A ≥ 3 at Scree ni n g a n d Baseli ne 
7.  S u bject is dee me d b y i n vesti gat or t o b e eli gi ble f or p h ot ot hera p y or s yste mic t hera p y. 
8.  S u bject a grees t o a v oi d pr ol o n ge d e x p os ure t o s u nli g ht or us e of artificial s u n bat hi n g 
(e g, ta n ni n g b o ot hs) or ot her ultra vi olet ( U V) li g ht s o urces d uri n g t he Treat me nt Peri o d. 
9.  S u bject, if fe male a n d of c hil d beari n g p ote ntial, m ust ha ve a ne gati ve ser u m pre g n a nc y 
test at Scree ni n g a n d n e gati ve uri ne pre g na nc y t est at Baseli ne. A n y w o me n of 
c hil d beari n g p ote ntial ( W O C B P) m ust a gree t o  s e x ual a bsti ne nce or t o us e a hi g hl y 
effecti ve c o ntr ace pti ve meas ure starti n g at Scree ni n g, c o nti n ui n g t hr o u g h o ut t he e ntire 
Treat me nt Peri o d, a n d f or at least 4 wee ks aft e r ta ki n g t he last d ose of st u d y treat me nt. A 
fe male s u bject is c o nsi dere d t o be a W O C B P after me narc h e a n d u ntil s he is i n a 
p ost me n o pa usal state f or 1 2 m o nt hs or ot her wise p er ma ne ntl y steril e (f or w hic h 
acce pta ble met h o ds i ncl u de h ysterect o m y, bi lateral sal pi n gect o m y, a n d bilateral 
o o p h orect o m y). F or t he d efi niti o n a n d a c o m plete list of acce pt a ble c o ntr ace pti ve 
meas ures se e A P P E N DI X 1 . 
1 0.  S u bject, if a fertile mal e, a grees t o se x ual a bsti ne n ce or t o use a c o n d o m d uri n g se x ual 
acti vit y wit h t heir fe male part ner of c hil d beari n g p ote ntial starti n g at Scree ni n g, 
c o nti n ui n g t hr o u g h o ut t he e ntire Treat me nt Pe ri o d, a n d f or at least 4 wee ks after ta ki n g 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 3 7  of 8 9  
t he last d ose of st u d y tr eat me nt. A male s u bject is c o nsi dere d fertile after p u bert y u nl ess 
per ma ne ntl y sterile b y bilateral or c hi dect o m y. A d diti o nall y, if t h eir part n er is a W O C B P, 
t he n t heir part ner s h o ul d be a d vise d t o use a hi g hl y effecti ve c o ntr ace pti ve meas ure 
d uri n g se x ual acti vit y starti n g at Scree ni n g, c o nti n ui n g t hr o u g h o ut t he e ntire Treat me nt 
Peri o d, a n d f or at least 4 wee ks after ta ki n g  t he last d ose of st u d y tr eat me nt. F or t he 
defi niti o n a n d a c o m plete list of acce pta ble c o ntrace pti ve meas ures see A P P E N DI X 1 . 
1 1.  S u bject, if fe male, m ust a gree t o n ot d o nate, or retrie ve f or h er o w n use, o v a starti n g at 
Scree ni n g, c o nti n ui n g t hr o u g h o ut t he e ntire Treat me nt Peri o d, a n d f or at least 4 wee ks 
after ta ki n g t he last d os e of st u d y tr eat me nt. 
1 2.  S u bject, if male, m ust a gree t o n ot freez e or d o n ate s per m starti n g at Scree ni n g, 
c o nti n ui n g t hr o u g h o ut t he e ntire Treat me nt Pe ri o d, a n d f or at least 4 wee ks after ta ki n g 
t he last d ose of st u d y tr eat me nt. 
8. 2  
E xcl usi o n Criteri a 
I n di vi d uals me eti n g a n y of t he f oll o wi n g criteri a at S cree ni n g or Baseli ne (as a p pli ca ble) are 
i neli gi ble t o partici pat e i n t his st u d y: 
1.  S u bject has a dia g n osis of n o n- pla q ue ps ori asis ( pre d o mi na ntl y g uttate, p ust ular, 
i n verse, or er yt hr o der mic) or dr u g-i n d uce d ps oriasis. 
2.  S u bject has a n y u nsta ble or C S (as deter mi ne d b y t he i n vesti gat or) car diac, 
e n d ocri n ol o gic, gastr o e nter ol o gi c, p ul m o nar y, ne ur ol o gic, ps yc hiatric (s u c h as maj or 
de pressi o n), he p atic, re n al, he mat ol o gic, i m m u n ol o gic disease, or ot her disease (e g, 
u nc o ntr olle d dia betes) t h at w o ul d place t he s u bject at u nacce pta ble ris k if t he y were t o 
partici pate i n t he st u d y. 
3.  S u bject has s uici dal i deati o n or be ha vi or i n t he past 1 2 m o nt hs as i n dicate d b y a p ositi ve 
res p o nse ( yes) t o q uesti o ns 3, 4, or 5 o n t he C- S S R S c o m plete d at Scree ni n g a n d/ or at 
Baseli ne. 
4.  S u bject has a pres e nt rec urre nt me dical c o n diti o n ass ociate d wit h si g nifica nt GI e ve nts 
(e g, na usea, v o miti n g, c o nsti pati o n, a b d o mi nal pai n, diarr hea). 
5.  S u bject has a n y c o n diti o n t hat w o ul d c o nf o u n d t he a bilit y t o i nter pret data fr o m t he 
st u d y (e g, ecze ma, at o pic der matitis, l u p us, i nfla m mat or y b o wel disease). 
6.  S u bject has a n y de gree of d ys p h a gia t hat ma y i nterfere wit h t he oral d osi n g of t he st u d y 
treat me nt. 
7.  S u bject has a hist or y of aller g y or h y perse nsiti vit y t o a n y c o m p o ne nt of t he st u d y 
treat me nts. 
8.  S u bjects w h o ha ve ha d a pri or la b orat or y c o nfir me d C O VI D- 1 9 test or h a ve bee n i n 
cl ose p h ysi cal c o ntact ( 6 feet or cl oser f or at least 1 5 mi n utes) wit h a pers o n w h o is 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 3 8  of 8 9  
k n o w n t o ha ve la b orat or y c o nfir me d C O VI D- 1 9 or wit h a n y o ne w h o has a n y s y m pt o ms 
c o nsiste nt wit h C O VI D- 1 9 wit hi n t he past 1 4 da ys at Scree ni n g or Bas eli ne. 
9.  S u bjects e x perie nci n g a n y of t he f oll o wi n g s y m pt o ms at Scree ni n g or Baseli ne: 
 Fe ver or c hills 
 C o u g h 
 S h ort ness of breat h or diffic ult y breat hi n g 
 Fati g ue 
 M uscle or b o d y ac hes 
 Hea dac he 
 Ne w l oss of taste or s mell 
 S ore t hr oat 
 C o n gesti o n or r u n n y n os e 
 Na usea or v o miti n g 
 Diarr hea 
1 0.  S u bject has acti ve or c hr o nic he patitis B vir us ( H B V) or he patitis C vir us ( H C V) 
i nfecti o n as per Scree ni n g viral s er ol o g y tests. E x ce pti o n: If t he s u bject h as recei v e d 
d oc u me nte d treat me nt w hic h was c urati ve f or  H C V a n d tests ne gati ve f or H C V R N A at 
Scree ni n g, t he s u bject ma y b e c o nsi dere d f or ra n d o mizati o n. 
1 1.  S u bject is p ositi ve f or t he HI V a nti b o dies ( HI V- 1 or HI V- 2) at Scree ni n g or has a 
hist or y of c o n ge nital or ac q uire d i m m u n o deficie n c y (e g, c o m m o n varia ble 
i m m u n o deficie nc y diseas e). 
1 2.  S u bject has a rece nt hist or y of dr u g, s u bsta nce, or alc o h ol a b use/ de pe n de nce wit hi n 
1 year pri or t o Scree ni n g as deter mi ne d b y t he i n v esti gat or. 
1 3.  S u bject has a n acti ve i nfecti o n ( bacteria, vi ral, f u n gal, etc.) re q uiri n g treat m e nt wit h 
s yste mic a nti bi otics wit hi n 4 wee ks of Scree ni n g. A n y tr eat me nt f or s u c h i nfecti o ns 
m ust be c o m plete d at least 4 wee ks pri or t o Scree ni n g. 
1 4.  S u bject has acti ve t u berc ul osis or hist or y of i nc o m pletel y treate d t u berc ul osis per 
me dical hist or y. 
1 5.  S u bject has a mali g n a nc y or hist or y of m ali g n a nc y (e x ce pt f or treate d [ie, c ure d] basal 
cell or s q ua m o us cell i n sit u s ki n carci n o mas a n d treate d [ie, c ure d] cer vical 
i ntrae pit helial ne o plasia or carci n o ma i n sit u of t he cer vi x wit h n o e vi de nce of 
rec urre nce). 
1 6.  S u bject is pre g n a nt or breastfe e di n g at Scree ni n g or at Baseli ne. 
1 7.  S u bject has a hist or y of l ac k of efficac y (i n a de q uate efficac y w he n use d i n a de q uate 
d ose a n d d urati o n i n a cc or da nce wit h t he a p pr o ve d la bel) t o a n y bi ol o gi cal pr o d ucts f or 
ps oriasis. 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 3 9  of 8 9  
1 8.  S u bject has recei ve d 2 or m ore bi ol o gical  pr o d ucts i n t he past f or t he treat me nt of 
ps oriasis. 
1 9.  S u bject has a hist or y of l ac k of efficac y t o 2 or m ore n o n- bi ol o gic s yste mic t hera p y d u e 
t o i na de q uate efficac y w he n a d mi nistere d i n a de q uate d ose a n d d urati o n i n acc or da nce 
wit h t heir la bel ( a p pr o ve d i n t he s u bject’s c o u ntr y)  f or ps oriasis. 
2 0.  S u bject has recei ve d a n y pri or treat me nt wi t h a pre milast or a n y ot her P D E 4 i n hi bit or. 
2 1.  S u bject has recei ve d uste ki n u ma b, sec u ki n u ma b, br o dal u ma b, i x e kiz u ma b, g usel k u ma b, 
risa n kiz u ma b, til dra kiz u ma b, or bria ki n u ma b ( or a n y ot h er t hera pe utic a ge nt tar geti n g 
I L- 1 2, I L- 1 7, or I L- 2 3) wit hi n 2 4 wee ks of first a d mi nistrati o n of st u d y tr eat me nt. 
2 2.  S u bject has recei ve d T N F- α  i n hi bit or(s)/ bl oc ker(s) wit hi n 8 wee ks of first a d mi nistrati o n 
of st u d y tr eat me nt. 
2 3.  S u bject has recei ve d nat aliz u ma b (a n i nte gri n rece pt or a nta g o nist), or a ge nts t hat 
m o d ulate B cells or T cells (e g, ale mt uz u ma b, a batace pt, aleface pt) wit hi n 1 2 wee ks of 
first a d mi nistrati o n of st u d y treat me nt. 
2 4.  S u bject has recei ve d rit u xi ma b wit hi n 2 4 wee ks of first a d mi nistrati o n of st u d y 
treat me nt. 
2 5.  S u bject has recei ve d a n y s yste mic i m m u n os u p pressa nts (e g, met h otre x ate, azat hi o pri ne, 
c ycl os p ori ne, 6-t hi o g ua ni ne, merca pt o p uri ne , m yc o p he n olate m ofetil, h y dr o x y urea, 
tacr oli m us), a n y pr otei n ki nase i n hi bit or (eg, t ofaciti ni b, bariciti ni b, peficiti ni b, 
u pa daciti ni b), or a n a ki nr a wit hi n 4 wee ks of t h e first a d mi nistrati o n of st u d y treat me nt. 
2 6.  S u bject has recei ve d p h ot ot hera p y (e g, ultra vi olet B i ncl u di n g n arr o w ba n d ultra vi olet 
B, G oec ker m a n t hera p y, a n d e x ci mer laser or ps orale n ultra vi olet A) or a n y s yste mic 
me dicati o ns/treat me nts t hat c o ul d affect ps or iasis or s P G A e val uati o n (i ncl u di n g, b ut n ot 
li mite d t o, oral or i njecta ble c ortic oster oids, reti n oi ds, 1, 2 5- di h y dr o x y vita mi n D 3 a n d 
a nal o g ues, ps or ale ns, s ulfasalazi ne, or f u m aric aci d deri vati ves) wit hi n 4 wee ks of t he 
first a d mi nistrati o n of st u d y treat me nt. 
2 7.  S u bject has ha d a rece nt i nitiati o n of a dr u g t h at is k n o w n t o p ote ntiall y ca use or 
e x acer bate ps oriasis (i ncl u di n g, b ut n ot li mite d t o, b eta- bl oc kers, lit hi u m, a n d 
a nti- malarials) wit hi n t he 8 wee ks pri or t o t h e first a d mi nistrati o n of st u d y treat me nt; a 
s u bject w h o has bee n o n a sta ble d ose f or at least 8 wee ks pri or t o t he first 
a d mi nistrati o n of st u d y tr eat me nt wit h o ut e x acer bati o n of ps oriasis ma y b e ra n d o mize d 
a n d d oes n ot nee d t o disc o nti n ue t hese me dicati o ns. 
2 8.  S u bject has use d t o pical me dicati o ns/treat me nts t hat c o ul d affect ps oriasis or s P G A 
e val uati o n (i ncl u di n g, b ut n ot li mite d t o, c or tic oster oi ds, a nt hrali n, calci p otrie ne, t o pical 
vita mi n D deri vati ves, reti n oi ds, taza r ote ne, met h o xsale n, tri met h yl ps or ale n, 
pi mecr oli m us, tacr oli m us, or P D E 4 i n hi bit or) wit hi n 2 wee ks of t he first a d mi nistrati o n 
of st u d y tr eat me nt. 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 4 0  of 8 9  
2 9.  S u bject has recei ve d a n i n vesti gati o nal dr u g f or bi ol o gic t hera p y wit hi n t he pre vi o us 
2 4 wee ks pri or t o t he first a d mi nistrati o n of st u d y treat me nt or recei v e d a n y ot her 
n o n- bi ol o gic i n vesti gati o nal t hera p y/ dr u gs or de vi ce wit hi n 4 wee ks or 5 half-li ves 
( w hic he ver is l o n ger) pri or t o t he first a d mi nistrati o n of st u d y tr eat me nt. 
3 0.  S u bject has recei ve d a n y pri or treat me nt wit h M E 3 1 8 3. 
3 1.  S u bject has a n y of t he f oll o wi n g a b n or mal la b orat or y test fi n di n gs at Scree ni n g. 
 A b n or mal he patic f u ncti o n 
o  As partate a mi n otra nsa mi nase or al a ni ne a mi n otra nsa mi nase ≥ 2 × u p per li mit 
of n or mal or 
o  Total bilir u bi n ≥ 2 × u p per li mit of n or mal, u nless t he s u bject has a dia g n osis 
of Gil bert’s s y n dr o me  
 W hite bl o o d cell c o u nt < 3 0 0 0/ m m
3 ( < 3. 0 × 1 09/ L) 
 Ne utr o p hil c o u nt < 1 0 0 0/ m m 3 ( < 1. 0 × 1 09/ L) 
 Platelet c o u nt < 1 0 0, 0 0 0/ μ L ( <  1 0 0 × 1 09/ L) 
 He m o gl o bi n < 8. 0 g/ d L 
 Creati ni ne cleara n ce esti mate d b y C oc k cr oft- Ga ult f or m ula < 6 0 m L/ mi n 
 He m o gl o bi n A 1c > 9. 0 % 
3 2.  S u bject has a C S a b n or malit y o n a 1 2-l ea d E C G or Q Tc F > 4 5 0 mse c at Scree ni n g or 
Baseli ne. 
3 3.  S u bject has a s yst olic bl o o d press ure ≥ 1 6 0 m m H g or a diast olic bl o o d press ure 
≥ 1 0 0 m m H g ( bas e d o n at least 2 re peat meas ure me nts) at Scree ni n g. 
3 4.  Pris o ners or s u bjects w h o are i ncarcerat e d f or a n y reas o n. 
3 5.  S u bject has a n y ot her fact or c o nstit uti n g dis q ualificati o n f or st u d y i ncl usi o n i n t he 
j u d ge me nt of t h e i n vesti gat or. 
See A P P E N DI X 2  f or details o n t he me dicati o ns a n d pr oce d ures t hat are pr o hi bite d pri or t o 
ra n d o mizati o n a n d d uri n g t he c o urse of t he st u d y u nless ot her wise s pecifie d. 
8. 3  
Rescree ni n g 
I n di vi d uals w h o faile d t h e i nitial Scree ni n g ma y b e c o nsi dere d f or rescree ni n g u p t o 1 ti me, u p o n 
a p pr o val of S p o ns or a n d/ or Me dical M o nit or o n a case- b y-cas e basis. All assess me nts will be 
re peat e d w he n rescree ni n g. W he n re-testi n g wit hi n t he sa me 2 8- da y Scree ni n g Peri o d, o nl y t he 
e x cl usi o nar y la b orat or y t ests will be re peat e d o nce i n case t he e x cl usi o nar y la b orat or y res ult was 
n ot d ue t o a pat h ol o gi cal c o n diti o n a n d was occasi o nal (e x ce pt f or i n di vi d uals w h o ha ve p ositi ve 
viral ser ol o g y res ults). 
8. 4  
St u d y Wit h dr a w al, Re m o v al, a n d Re pl ace me nt of S u bjects 
Alt h o u g h t he i m p orta nce of c o m pleti n g t he e ntire cli n ical st u d y will be e x plai ne d t o t he s u bjects, 
a n y s u bject is free t o disc o nti n ue his/ her partici p ati o n i n t he st u d y at a n y ti me a n d f or w h ate ver 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 4 1  of 8 9  
reas o n, s pe cifie d or u ns p ecifie d, a n d wit h o ut a n y prej u dice. N o c o nstrai nts are t o be i m p ose d o n 
t he s u bject, a n d w he n a p pr o priate, a s u bject ma y be treate d wit h ot her c o n ve nti o nal t hera p y 
w he n cli nicall y i n dicate d. I n v esti gat ors or t he S p o ns or ca n als o wit h dr a w s u bjects fr o m t he 
cli nical st u d y if d ee me d t o be necessar y. 
If a s u bject disc o nti n ues st u d y treat me nt a n d/ or is wit h dra w n fr o m t he st u d y f or a n y reas o n, t he 
st u d y site m ust i m me diatel y n otif y t he M e dical M o nit or. T he date a n d t h e reas o n f or st u d y 
disc o nti n uati o n m ust be rec or de d o n t h e electr o nic case re p ort f or m (e C R F). S u bjects w h o d o n ot 
c o m plete or disc o nti n ue earl y fr o m t he st u d y tr eat me n t will be as ke d t o ret ur n t o t he st u d y site t o 
c o m plete assess me nts as i n dicate d i n t he Sc he d ule of Assess me nts ( Ta ble 1 ). 
I n t he e ve nt t hat a s u bj ect disc o nti n ues pre mat urel y fr o m t he st u d y tr eat me nt beca use of a T E A E 
or seri o us T E A E, h e/s he will be f oll o we d u p u ntil  it res ol ves (ret ur ns t o n or mal or Bas eli ne 
val ues) or sta biliz es, or u ntil it is j u d ge d b y t he i n vesti gat or t o n o l o n ger be C S. If a T E A E or 
S A E is ca usi n g a l o n g-ter m effect a n d c o ul d n ot be f oll o we d u ntil res ol uti o n, t he reas o n f or n ot 
f oll o wi n g u p a n y f urt her m ust be rec or de d i n t he s o urce d oc u m e nt. 
O nce a s u bject is wit h dra w n fr o m t he st u d y, t he s u bject ca n n ot r ee nter t h e st u d y. 
A s u bject ma y v ol u ntaril y wit h dra w or be wit h dra w n  fr o m t he st u d y treat m e nt or t he st u d y at a n y 
ti me f or reas o ns i ncl u di n g, b ut n ot li mite d t o, t he f oll o wi n g: 
 pr o gressi ve dise ase 
 u nacce pta ble t o xicit y or A E 
 Q T i nter val c orrecte d usi n g Fri deri cia’s f or m ula ( Q Tc F) > 5 0 0 msec 
 s u bject wit h dra wal of c o nse nt: at a n y ti me, a s u bject's partici pati o n i n t he st u d y ma y be 
ter mi nate d at his/ her re q uest or o n t he basis of t he i n vesti gat or’s cli nical j u d ge m e nt. T he 
reas o n f or s u bject wit h dr a wal will be n ote d i n t he e C R F 
 i nterc urre nt ill ness: a c o n diti o n, i nj ur y, or disease u nrelate d t o t he pri mar y dia g n osis t hat 
beca me a p pare nt d uri n g treat me nt a n d necessitate d t he s u bject ’s ter mi nati o n fr o m t he 
st u d y 
 ge n eral or s pecifi c c ha n ges i n t he s u bject's c o n diti o n t hat re n ders hi m/ her i neli gi ble f or 
f urt her tr eat me nt acc or di n g t o t he i ncl usi o n/e xcl usi o n criteria 
 s u bject fails t o a d here t o t he pr ot oc ol req uir e me nts (e g, dr u g n o nc o m plia n ce, fail ure t o 
ret ur n f or defi ne d n u m ber of visits, use d or re q uir e t o use a n y of t he pr o hi bite d 
c o nc o mita nt me dicati o n or pr oce d ures [see A P P E N DI X 2 ]) 
 l ost t o f oll o w- u p: t he s u bject st o p pe d c o mi n g f or visits, a n d st u d y p ers o n nel are u na bl e t o 
c o ntact t he s u bject 
 s u bject has a n y ot her fact or c o nstit uti n g dis q ualificati o n f or st u d y i ncl usi o n i n t he 
j u d ge me nt of t h e i n vesti gat or 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 4 2  of 8 9  
 pre g na nc y, as i n dicate d i n Secti o n 1 2. 6. 6 . 
A d diti o nall y, t he S p o ns or ma y st o p t he st u d y at a n y ti me f or safet y, re g ulat or y, le gal, or ot her 
reas o ns ali g ne d wit h G o o d Cli nical Practice ( G C P). T his st u d y ma y be t er mi nate d at t he 
discreti o n of t he S p o ns or or a n y re g ul at or y a ge n c y. A n i n vesti gat or m a y elect t o disc o nti n ue or 
st o p t he st u d y at his or her st u d y site f or a n y reas o n, i ncl u di n g safet y or l o w ra n d o mizati o n. 
Wit h dra w n s u bjects ma y n ot be re place d o nce ra n d o mize d. 
8. 4. 1  
Pre g n a nc y 
T he safet y of M E 3 1 8 3 i n pre g na nt or lactati n g w o me n has n ot bee n est a blis he d. 
S u bjects will be i nstr ucte d t hat a k n o w n or s us pecte d pre g na n c y occ urri n g d uri n g t he st u d y will 
be c o nfir me d b y s er u m testi n g a n d re p orte d t o t he i n vesti gat or. If a s u bject bec o mes pre g na nt, 
t he i n vesti gat or m ust wit h dra w t he s u bject fr o m t he st u d y tr eat me nt wit h o ut dela y. T h e s u bject 
m ust n ot recei ve a n y f urt her d oses of t he st u d y dr u g a n d will be as ke d t o r et ur n f or t he f oll o w- u p 
visit 4 wee ks after t h e last d ose of st u d y dr u g. T he i n vesti gat or s h o ul d als o be n otifie d of 
pre g na nc y o cc urri n g d uri n g t he st u d y b ut c o nfir m e d after c o m pleti o n of t h e st u d y. I n t h e e ve nt 
t hat a fe male s u bj ect or fe male part n er of a male su bject is s u bse q ue ntl y f o u n d t o be pre g na nt 
after i ncl usi o n i n t he st u d y, a n y pre g na nc y will be f oll o we d t o ter m, a n d t he stat us of m ot her a n d 
c hil d will be re p orte d t o t he S p o ns or ( or desi g nee) after deli ver y. See Secti o n 1 2. 6. 6  f or f urt her 
re p orti n g a n d m o nit ori n g details. 
T he i n vesti gat or s h o ul d n otif y t he S p o ns or ( or desi g nee) o n a Pre g na n c y Re p orti n g f or m wit hi n 
2 4 h o urs of k n o wle d ge of t he pre g n a nc y. F ull details of t he pre g na n c y will be rec or de d o n t he 
wit h dra wal pa ge (e xit f or m) of t he e C R F, or a n S A E re p ort will be c o m plete d if t he s u bject has 
c o m plete d t he st u d y. Pre g na n c y is n ot t o be c o nsi dere d a n A E; h o we v er, s p o nta ne o us 
miscarria ges, c o n ge nital a b n or malities, a n d a n y pre mat ure ter mi nati o n of pre g na nc y will be 
re p orte d as S A Es as descri be d i n Secti o n 1 2. 6. 6 . 
8. 4. 2  
L ost t o F oll o w- U p 
A s u bject will be c o nsi dere d l ost t o f oll o w- u p if he or s he re peat e dl y fails t o ret ur n f or sc he d ule d 
visits a n d is u na ble t o be c o ntacte d b y t he st u d y ce nter. 
Reas o na ble eff orts will b e ma de t o c o ntact s u bjects w h o are l ost t o f oll o w- u p. T hese eff orts m ust 
be d oc u me nte d i n t he s u bject’s s o urce d oc u me nt.  

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 4 3  of 8 9  
9  
T R E A T M E N T S 
9. 1  
Det ails of St u d y Tre at me nts 
M E 3 1 8 3 (  m g,  
 m g,   m g, a n d   m g) a n d a matc hi n g place b o will be pre pare d usi n g t he 
f oll o wi n g M E 3 1 8 3 a n d place b o ca ps ules: 
 M E 3 1 8 3 Ca ps ule  
 m g 
 M E 3 1 8 3 Ca ps ule   m g 
 M E 3 1 8 3 Place b o Ca ps ule 
Refer t o t he I B f or c o m pl ete details o n t he st u d y tr eat me nt. 
A desi g n ate d p har macist will dis pe nse t he st u d y dr u gs at eac h visit. A d diti o nal details o n 
dis pe nsi n g of t he st u d y dr u gs will be pr o vi de d i n t he p har mac y ma n ual. 
9. 1. 1  
Descri pti o n of Acti ve St u d y Tre at me nt 
M E 3 1 8 3 is a w hite cr ystalli ne p o w der t hat is f or m ulate d as ca ps ul es. 
9. 1. 2  
Descri pti o n of Pl ace b o St u d y Tre at me nt 
Place b o will be i de ntical i n a p peara nce t o acti ve st u d y treat me nt a n d c o nt ai ns t he sa me i nacti ve 
i n gre di e nts as t he acti ve f or m ulati o n b ut wit h o ut t he acti ve i n gre die nt. 
9. 1. 3  
P a c k a gi n g a n d L a beli n g 
T he i n vesti gati o nal st u d y dr u gs will be p ac ka ge d  a n d la bele d acc or di n g t o a p plica ble l ocal a n d 
re g ulat or y re q uire me nts. La b eli n g will f ulfill t he G o o d Ma n ufact uri n g Practice re q uire me nts a n d 
will c o m pl y wit h le gal re q uire me nts of eac h c o u ntr y. M E 3 1 8 3/ place b o ca ps ules are pac ka ge d i n 
press t hr o u g h pac k s h eet ( 2 1 ca ps ules p er s heet) a n d a c hil d-resista nt blister pac k. Blister pac ks 
will be dis pe nse d b y a desi g nate d p h ar macist  at eac h visit f or m or ni n g a n d e ve ni n g d oses. 
Cli nical s u p plies are t o be dis pe nse d o nl y i n acc or da nce wit h t he pr ot o c ol. St u d y dr u g la bels will 
n ot bear a n y stat e me nt t hat is false or mislea di n g i n a n y m a n ner or re prese nt t hat t he st u d y dr u g 
is safe or effecti ve f or t h e p ur p oses f or w hic h it is bei n g i n vesti gate d. La bels o n t he blister pac ks 
will c o ntai n t he f oll o wi n g o pe n-la bel i nf or m ati o n: 
 
Pr ot oc ol n u m ber 
 
Me dicati o n n u m ber 
 
E x pirati o n date 
 
I d e ntical batc h n u m b er 
 
C o nte nt: 2 1 ca ps ules/ s heet, 2 s heets/ c hil d-resista nt blister pac k  
 
St ora ge c o n diti o n:  
° C t o  ° C ( ° F t o  ° F) 
 
Directi o ns: F or oral use 
 
Ca uti o n: Ne w Dr u g –  I n v esti gati o nal Us e O nl y 
 
S p o ns or na me a n d a d dress 
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 4 4  of 8 9  
9. 1. 4  
St u d y Dr u g St or a ge 
All st u d y dr u g s u p plies m ust be st ore d at a m bie n t te m perat ure ( ° C t o  ° C [ 
° F t o  ° F]). 
St u d y dr u gs m ust be recei ve d b y a desi g nate d pers o n at t he st u d y site, ha n dl e d a n d st ore d s afel y 
a n d pr o perl y, a n d ke pt i n a sec ure d l ocati o n i n  acc or da nce wit h t he la bele d st ora ge c o n diti o ns. 
9. 1. 5  
St u d y Dr u g Rete nti o n 
St u d y dr u g m ust be retai ne d u ntil c o m pleti o n or ter mi nati o n of t he st u d y, a n d writte n 
a ut h orizati o n fr o m t he S p o ns or has bee n recei ve d. T he details re gar di n g t h e st u d y dr u g rete nti o n 
will be detaile d i n t he P har mac y M a n ual. All u n use d a n d use d st u d y dr u g s h o ul d be ret ur ne d t o 
t he distri b ut or, if s pecifie d b y S p o ns or. It is t he in vesti gat or’s res p o nsi bilit y t o e ns ure t hat t he 
S p o ns or has pr o vi de d writte n a ut h orizati o n pri or t o  ret ur n or destr ucti o n, a n d t hat a p pr o priate 
rec or ds of t he dis p osal are d oc u me nte d a n d mai ntai ne d. N o use d or u n us e d st u d y dr u g ma y b e 
dis p ose d u ntil f ull y acc o u nte d f or b y t he st u d y m o nit or. 
9. 2  
D os a ge Sc he d ule 
T he first d ose of t he st u d y dr u g will  be a d mi nistere d i n t he e ve ni n g ( u p o n ret ur ni n g t o t heir h o m e 
after t he Da y 1 [ Visit 2] assess me nts are c o m p lete d) wit hi n a p pr o xi matel y 3 0 mi n utes after a 
sta n dar d meal a n d t he last d ose will be self-a d mi nistere d b y t he s u bject at h o me o n Da y 1 1 2 (t he 
da y b ef ore Visit 8) wit hi n a p pr o xi mat el y 3 0 mi n utes  after a sta n dar d m eal. O n Da y 1, all s u bjects 
will recei ve t he st u d y dr u gs i n t he e v e ni n g. Fr o m Da y 2 t o Da y 1 1 2, all s u bjects will recei ve t he 
st u d y dr u gs i n t he m or ni n g a n d e ve ni n g. 
At H o me D osi n g: 
T he st u d y dr u g m ust be ta ke n i n t he m or ni n gs a n d e ve ni n gs a p pr o xi matel y 1 2 h o urs a part wit h 
water wit hi n a p pr o xi matel y 3 0 mi n utes after a st a n da r d meal. S u bjects will be a d vise d t o ta ke t he 
st u d y dr u g at a p pr o xi matel y t he s a me ti me eac h d a y wit h o ut fail. 
At St u d y Site: 
F or all t he st u d y site visits, s u bjects will arri ve  at t he st u d y site after fasti n g o ver ni g ht (e x ce pt 
water) f or at least 1 0 h o urs. All t he safet y la b orat or y tests, efficac y ass ess me nts, a n d P K a n d  
 
assess me nts ( per Sc he d ul e of Assess me nts; Ta ble 1 ) will be perf or me d u p o n arri val at t he st u d y 
site. Refer t o Secti o n 7. 1  f or t he or der i n w hic h t he assess me nts s h o ul d be perf or me d. S u bjects 
will be releas e d after all t he sc he d ule d assess me nts  are perf or me d a n d will be a d vise d t o ta ke t he 
m or ni n g d ose of t he st u d y dr u g u p o n ret ur ni n g t o t heir h o me a n d wit hi n a p pr o xi matel y 
3 0 mi n utes after a sta n d ar d meal. 
F or t he p ur p os es of P K a nal ysis, t he act ual date a n d ti me of t he a d mi nistrati o ns ( b ot h m or ni n g 
a n d e ve ni n g i n t he pre vi o us da y) a n d eac h bl o o d s a m ple c ollecti o n will be rec or de d o n t h e 
s u bject’s e C R F at all visits w here P K bl o o d sa m pl es are t o b e c ollecte d. 
S u bjects will be a d vise d t o ret ur n t he u n use d st u d y dr u g d uri n g eac h st u d y site visit f or 
c o m plia nce c h ec k. 
C CI
C CI
C CI
C CI
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 4 5  of 8 9  
S u bjects m ust st o p usi n g a n y p e r mitte d t o pical pre parati o ns 2 4 h o urs pri or t o sc he d ule d st u d y 
site visit starti n g fr o m Visit 2 ( Da y 1). See Secti o n 9. 6  f or a d diti o nal details. 
9. 3  
Me as ures t o Mi ni miz e Bi as 
9. 3. 1  
Met h o d of St u d y Tre at me nt Assi g n me nt 
Pri or t o d osi n g o n Da y 1, all t he eli gi ble s u bjects will be ra n d o ml y assi g n e d t o 1 of t he 
5 treat me nt gr o u ps i n a 1: 1: 1: 1: 1 rati o. S u bjec ts will be assi g ne d a ra n d o mi zati o n n u m ber 
t hr o u g h i nteracti ve w e b res p o nse s yst e m (I W R S), i n acc or da nce wit h t he ra n d o mizati o n c o de 
ge n erat e d b y t he a ut h oriz e d pers o n nel at 
. A n u n bli n de d, i n de pe n de nt st u d y 
statisticia n will be assi g n e d t o pr o d uce t he ra n d o mizati o n sc he d ule. At st u d y site, t he 
ra n d o mizati o n sc he d ule will o nl y b e accessi ble t o a ut h orize d p har mac y p ers o n nel. O nce a 
ra n d o mizati o n n u m ber is all ocate d t o 1 s u bject, it ma y n ot be assi g n e d t o a n ot her s u bject e ve n if 
t he f or mer disc o nti n ue d t he st u d y. 
T o pr o m ote bala nce d all ocati o n, ra n d o mizati o n will be  stratifie d b y t he s u bject’s recei pt ( yes/ n o) 
of pre vi o us treat me nt wit h a bi ol o gic dr u g f or ps oriasis. Bi o- naï ve s u bjects will be ra n d o mize d 
a b o ve 5 0 % of t h e pla n ne d t otal s u bject ra n d o mizati o n. 
9. 3. 2  
Bli n di n g 
T his is a d o u ble- bli n d st u d y. 
A n I W R S will be use d f or s u bject ra n d o mizati o n a n d a u ni q ue s u bject i de ntificati o n n u m ber will 
be assi g n e d a ut o maticall y. A cc or di n g t o t he ra n d o mizati o n sc he d ule as i n dicate d i n t he Sc he d ule 
of Assess me nts ( Ta ble 1 ), t he i n vesti gat or or desi g nee will o btai n t he st u d y dr u g kit n u m ber fr o m 
t he I W R S f or t he s u bject, a n d t he n u m ber will be pr o vi de d t o t he p har macist or desi g n ee at t he 
st u d y ce nt er w h o is res p o nsi ble f or ha n dli n g t h e st u d y dr u gs. T his p har macist or desi g n ee will 
dis pe nse t he st u d y dr u g t o t he s u bject base d o n t h e st u d y dr u g kit n u m ber ge n erat e d fr o m t he 
I W R S. A n u n bli n de d, i n de pe n de nt st u d y statisticia n will be assi g n e d t o pr o d uce t he 
ra n d o mizati o n sc he d ule. N o ot her st u d y site p ers o n nel, s u bjects, S p o ns or pers o n nel, or S p o ns or 
desi g nees will be u n bli n de d t o treat me nt assi g n me nt t hr o u g h o ut t he d urati o n of t he st u d y u nless 
u n bli n di n g is re q uire d. If a n i n vesti gat or bec o m es u n bli n de d t o a gi ve n s u bj ect’s st u d y treat me nt, 
t hat s u bject will be disc o nti n ue d fr o m t he st u d y u nless t here are et hical reas o ns f or t hat s u bject 
n ot t o be disc o nti n ue d; a p pr o val fr o m t he Me di cal M o nit or m ust be o btai ne d i n s uc h i nsta nces. 
I n t he e ve nt t hat e m er ge n c y u n bli n di n g is re q uir e d f or a gi ve n s u bject beca use of A Es or 
c o ncer ns f or t he s u bject’s safet y or well bei n g, t h e i n vesti gat or ma y brea k t he ra n d o mizati o n c o de 
f or t he s u bject via t he I W R S, b y w hic h s yste m t he u n bli n di n g will be ca pt ur e d. T he i n vesti gat or 
is res p o nsi ble f or n otif yi n g t he M e dical M o nit or a n d/ or S p o ns or of s uc h a n e ve nt as s o o n as 
p ossi ble. T he u n bli n di n g a n d its ca use w ill als o be d oc u me nte d i n t he e C R F. 
T he bi oa nal ytical la b orat or y will recei v e a c o p y  of t he ra n d o mizati o n sc he d ule f or P K a nal ysis, 
as t he S p o ns or d oes n ot i nte n d t o a nal yze t h e sa m ples fr o m t he place b o gr o u p. T he bli n di n g 
pr oce d ure will be d oc u m e nte d i n a se parate d oc u me nt. 
P P D

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 4 6  of 8 9  
9. 4  
D os a ge M o dific ati o n 
D ose m o dificati o ns are n ot per missi ble i n t his st u d y. 
9. 5  
Tre at me nt Acc o u nt a bilit y a n d C o m pli a nce 
All t he st u d y dr u gs will b e st ore d at a ce ntr al dr u g distri b uti o n ce nter mai ntai ne d b y  
 
 a n d will be distri b ute d t o i n di vi d ual st u d y sites as nee d e d. 
T he p har macist or desi g n ee will mai ntai n rec or ds of st u d y tr eat me nt deli vere d t o t he st u d y site, 
t he i n ve nt or y at t he st u d y site, t he distri b utio n t o a n d use b y eac h s u bject, a n d t he ret ur n of 
materials t o t he S p o ns or f or st ora ge or dis p osal. T hese rec or ds s h o ul d i ncl u de dates, q ua ntities, 
batc h/serial n u m bers, e x pirati o n dates, i n-cli nic te m perat ure l o g, a n d u ni q ue c o de n u m bers 
assi g ne d t o t he pr o d uct a n d st u d y s u bjects. 
At eac h visit after i nitiati o n of treat me nt, st u d y site pers o n nel will rec or d c o m plia nce of t he 
s u bject wit h t he s u bject’s assi g ne d re gi me n. S u bjects will be i nstr ucte d t o bri n g t heir 
u n use d/ partiall y us e d/e m pt y st u d y dr u g blister pac ks bac k f or i ns pe cti o n at eac h st u d y visit. 
S u bjects are t o be re mi n de d of t he i m p orta nc e of c o m plia nce wit h t heir assi g ne d re gi me n, wit h 
a n e m p hasis o n ta ki n g t heir st u d y dr u g o n sc he d ul e, mai ntai ni n g t he prescri be d i nter val bet wee n 
d oses , a n d d oc u me nti n g t he d ose eac h da y i n t he s u bject’s diar y. 
T he i n vesti gat ors or desi g nat e d st u d y p ers o n nel will mai ntai n rec or ds t hat a de q uatel y d oc u me nt 
t hat t he s u bjects were pr o vi de d wit h t he c orrect st u d y treat me nt blister pac ks a n d rec o n cile t he 
pr o d ucts recei ve d fr o m t he ce ntr al dr u g distri b uti n g ce nter. I n vesti gati o na l pr o d uct will n ot be 
ret ur ne d t o t he S p o ns or u ntil acc o u nta bilit y has b ee n f ull y m o nit ore d. 
St u d y dr u g blister pac ks m ust be ret ur ne d at eac h  visit, as c o m plia nce will be assesse d b y 
ca ps ule c o u nts. N o n c o m plia nce is defi ne d as ta ki n g less t ha n 7 0 % or great er t ha n t he pr ot o c ol-
s pecifie d n u m ber of d oses (ie, 2 d oses per da y) of st u d y dr u g d uri n g a n y o ut patie nt e val uati o n 
peri o d ( visit t o visit). Disc o nti n uati o n f or n o nc o m plia nce is at t he i n vesti gat or’s  discreti o n a n d is 
t o be n ote d i n t he e C R F. 
9. 6  
Pri or a n d C o nc o mit a nt T her a p y 
9. 6. 1  
Pri or a n d C o nc o mit a nt Me dic ati o ns 
Restricte d pri or t hera pies are pr o vi d e d i n Secti o n 8. 2  a n d a c o m plete list of pr o hi bite d 
c o nc o mita nt me dicati o ns a n d pr oce d ures pri or  t o ra n d o mizati o n a n d d uri n g t he c o urse of t h e 
st u d y is pr o vi de d i n A P P E N DI X 2 . 
All me dicati o ns a n d ot her treat me nts (i ncl u di n g  s u p ple me nts) ta ke n b y t he s u bject d uri n g t h e 
st u d y, i ncl u di n g t h os e treat me nts i nitiate d bef ore t he start of t he st u d y, m ust be rec or de d i n t he 
e C R F. 
Me dicati o ns ta ke n b y or a d mi nistere d t o t he s u bj ect f or t he ti me peri o d b ef ore Scree ni n g will be 
rec or de d i n t he e C R F. After t he Baseli ne visit, a n y c o nc o mita nt me dicati o n t hat is n ot restricte d 
P P D

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 4 7  of 8 9  
b y t he pr ot oc ol is acce pta ble. T he d osa ge re gi me n of a n y c hr o ni c me dicati o n s h o ul d re mai n 
u nc ha n ge d as m uc h as p ossi ble d uri n g t he st u d y. A n y me di cati o n or t hera p y t hat is ta ke n b y or 
a d mi nistere d t o t he s u bject pri or t o start of t h e st u d y or d uri n g t h e c o urse of t he st u d y m ust be 
rec or de d o n a p pr o priate pa ges of t he e C R F. T he e ntr y m ust i ncl u de t he d os e, u nit, re gi me n, 
r o ute, i n dicati o n, a n d dat es of use. F or a n y p er mitte d t o pical me dicati o ns ta ke n f or ps oriasis, t he 
area of t he b o d y t o w hic h t he y are a p plie d s h o ul d als o be rec or de d. 
T he f oll o wi n g t o pical t hera p y will be per mitte d: 
1.  L o w- p ote nc y or wea k c ortic oster oi ds ( Class 6 [e g, beta met has o ne v alerat e l oti o n, 
des o ni de crea m, a n d fl u o ci n ol o ne acet o ni de s ol uti o n] or Class 7 [e g, de x a met has o ne 
s o di u m p h os p hate crea m, h y dr oc ortis o ne acetate crea m, or met h yl pr e d nis ol o ne acetate 
crea m] i n t he U nite d States) will be all o we d as bac k gr o u n d t hera p y f or tr eat me nt of t he 
face, a xillae, a n d gr oi n i n acc or da nce wit h t he ma n ufact ur ers’ s u g gest e d usa ge d uri n g t he 
c o urse of t he st u d y. 
2.  C oal tar s ha m p o o a n d/ or salic ylic aci d scal p pre parati o ns o n scal p lesi o ns will be 
per mitte d t o use b y s u bjects wit h scal p ps oriasis. 
3.  A n u n me dicate d s ki n m oist urizer (e g, E u ceri n)  will be per mitte d f or b o d y l esi o ns o nl y. 
S u bjects will be a d vise d n ot t o use t he a b o ve t o pical pre p arati o ns wit hi n 2 4 h o urs pri or t o a n y 
st u d y site visit. 
S u bjects will als o be a d vise d t o pr otect a gai nst s u n e x p os ure t hr o u g h a v oi da nce of pr ol o n ge d 
e x p os ure t o s u n, use of pr otecti ve cl ot hi n g (l o n g slee ves, pa nts, hats, et c.), a n d use of s u nscree n 
fr o m at least 1 wee k pri or t o t he first a d mi nistrati o n of st u d y tr eat me nt u ntil t he f oll o w- u p visit at 
Wee k 2 0. 
S u bjects m ust a v oi d t he use of artifici al s u n bat hi n g (e g, ta n ni n g b o ot hs) or ot her U V li g ht 
s o urces d uri n g t he Treat me nt Peri o d. 
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 4 8  of 8 9  
1 0  S T U D Y P R O C E D U R E S 
Ta ble 1  o utli nes t he ti mi n g of pr oce d ures a n d ass ess me nts t o be perf or me d t hr o u g h o ut t he st u d y. 
Secti o n 1 2. 5  s pecifies safet y la b orat or y assess me nt sa m ples t o be o btai ne d. See Secti o ns 1 1,  1 2, 
a n d 1 3  f or a d diti o nal det ails re gar di n g efficac y assess me nts, safet y assess me nts, a n d P K 
assess me nts, res pecti vel y. Details of ot her ass ess me nts s uc h as 
 are pr o vi de d i n 
Secti o n 1 4 . 
I n case a ra n d o mize d s u bject is n ot a ble t o atte n d sc he d ule d st u d y visit o n-site d ue t o restricti o ns 
relate d t o S A R S- C o V- 2, a re m ote visit ma y be c o n d ucte d i nstea d (a p h o ne call or a tele visit). 
It is str o n gl y rec o m me n d e d t o c o n d uct t he st u d y assess me nts f or t he a p plica ble visit as per 
pr ot oc ol Sc he d ule of Ass ess me nts (see T a ble 1 ) as m uc h as p ossi ble. If p ossi ble a n d if l ocal 
re g ulati o ns all o w a n d t he s u bject a grees, trai ne d a n d a ut h orize d me m bers of t he site staff are 
e nc o ura ge d t o c ollect st u d y ass ess me nts, i ncl u di n g sa m ples f or sc h e d ule d la b orat or y tests at 
s u bject’s h ome or at a l ocal facilit y. Alter n ati vel y, t he s u bject c o ul d ha ve t he he mat ol o g y, 
c oa g ulati o n, c he mistr y, uri nal ysis, a n d pre g na n c y testi n g at a l ocal la b orat or y a n d t he la b orat or y 
re p orts will be pr o vi de d t o t he i n vesti gat or. T he l o cal la b orat or y res ults s h o ul d be e ntere d i n t he 
e C R F. 
S u bjects wit h si g ns a n d s y m pt o ms of i nfect i o n, i n cl u di n g S A R S- C o V- 2 i nf ecti o n s h o ul d 
i m me diatel y c o nta ct t he i n vesti gat or, w h o s h o ul d i nf or m t he Me dical M o nit or or desi g nee as 
s o o n as p ossi ble t o disc uss s u bject’s c o nti n uati on of st u d y tr eat me nt. I n cas e of s us pici o ns f or 
S A R S- C o V- 2 i nfecti o n, rele va nt testi n g s h o ul d b e perf or me d l o cal site pr oce d ures. I n case st u d y 
visits or assess me nts are n ot perf or me d f or reas o ns relate d t o S A R S- C o V- 2 restricti o ns, t his 
s h o ul d be d oc u me nte d i n t he s o urce d o c u me nts a n d e C R F. 
 
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 4 9  of 8 9  
T a ble 1.  
Sc he d ule of Assess me nts 
St u d y Pr oce d ures 
Scree ni n g 
Peri o d 
Tre at me nt Peri o d 
F oll o w- u p 
Peri o d b  
Scree ni n g  
( Visit 1) 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 a 
F oll o w- u p 
Visit  
( Visit 9) 
Wee k - 4 
Wee k 0 
Wee k 1 
Wee k 2
 
Wee k 4 
Wee k 8
 
Wee k 1 2 
Wee k 1 6 
Wee k 2 0 
D a ys -2 8 t o - 1 
D a y 1 
( B aseli ne) 
D a y 8 
( ± 1 d a y) 
D a y 1 5 
( ± 1 d a y) 
D a y 2 9  
( ± 3 d a ys) 
D a y 5 7 
( ± 3 d a ys) 
D a y 8 5 
( ± 3 d a ys) 
D a y 1 1 3 * 
( ± 3 d a ys) 
D a y 1 4 1 * * 
( ± 3 d a ys) 
Eli gi bilit y Assess me nts 
I nf or me d c o nse nt 
X 
- 
- 
- 
- 
- 
- 
- 
- 
I ncl usi o n/e xcl usi o n criteria 
X 
X 
- 
- 
- 
- 
- 
- 
- 
De m o gra p hics  
X 
- 
- 
- 
- 
- 
- 
- 
- 
Der mat ol o gic a n d me dical 
hist or y c 
X
 -
 -
 -
  -
  -
 -  
-
 -
 
Pri or a n d c o nc o mita nt 
me dicati o ns/t hera pies a n d 
pr oce d ures  
X
 X  
X  
X
 X
 X
 X  
X
 X
 
Hist or y of pre vi o us treat me nt 
wit h a  bi ol o gic dr u g f or 
ps oriasis  
-
 X 
-
 -
  -
  -
 - 
-
 -
 
C- S S R S 
X 
X 
- 
- 
- 
- 
- 
- 
- 
S afet y Assess me nts 
P h ysical e xa mi nati o n 
(c o m plete) 
X
 -
 -
 -
  -
  -
 -  
-
 -
 
P h ysical e xa mi nati o n 
(tar gete d) 
-
 X 
X  
X
 X
 X
 X  
X
 X
 
Hei g ht a n d wei g ht d 
X 
- 
- 
- 
- 
- 
- 
- 
- 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 5 0  of 8 9  
St u d y Pr oce d ures 
Scree ni n g 
Peri o d 
Tre at me nt Peri o d 
F oll o w- u p 
Peri o d b  
Scree ni n g  
( Visit 1) 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 a 
F oll o w- u p 
Visit  
( Visit 9) 
Wee k - 4 
Wee k 0 
Wee k 1 
Wee k 2
 
Wee k 4 
Wee k 8
 
Wee k 1 2 
Wee k 1 6 
Wee k 2 0 
D a ys -2 8 t o - 1 
D a y 1 
( B aseli ne) 
D a y 8 
( ± 1 d a y) 
D a y 1 5 
( ± 1 d a y) 
D a y 2 9  
( ± 3 d a ys) 
D a y 5 7 
( ± 3 d a ys) 
D a y 8 5 
( ± 3 d a ys) 
D a y 1 1 3 * 
( ± 3 d a ys) 
D a y 1 4 1 * * 
( ± 3 d a ys) 
Vital si g ns: bl o o d press ure 
(s yst olic a n d diast olic), heart 
rate, res pirat or y rate, b o d y 
te m perat ure, a n d b o d y wei g ht 
X
 X  
X  
X
 X
 X
 X  
X
 X
 
1 2-lea d E C Gs e 
X 
X 
- 
- 
X 
X 
X 
X 
X 
S afet y L a b or at or y Tests  
Viral ser ol o g y g 
X 
- 
- 
- 
- 
- 
- 
- 
- 
He mat ol o g y a n d 
C oa g ulati o n h 
X
 X i 
X  
X
 X
 X
 X  
X
 X
 
Bl o o d c he mistr y j 
X 
X i 
X 
X 
X 
X 
X 
X 
X 
Uri nal ysis  
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pre g na nc y test (ser u m 
β -h C G) 
( W O C B P o nl y) 
X k -
 -
 -
  -
  -
 -
 
-
 -
 
Pre g na nc y test ( uri ne β - h C G) 
( W O C B P o nl y) 
-
 Xl, m 
-
 -
 Xm  
Xm  
X m  
X m  
X m  
Ser u m F S H 
( p ost me n o pa usal w o me n 
o nl y)  
X
 -
 -
 -
  -
  -
 -  
-
 -
 
A E M o nit o ri n g 
M o nit or f or A Es a n d S A Es 
X 
X 
X 
X 
X 
X 
X 
X 
X 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 5 1  of 8 9  
St u d y Pr oce d ures 
Scree ni n g 
Peri o d 
Tre at me nt Peri o d 
F oll o w- u p 
Peri o d b  
Scree ni n g  
( Visit 1) 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 a 
F oll o w- u p 
Visit  
( Visit 9) 
Wee k - 4 
Wee k 0 
Wee k 1 
Wee k 2
 
Wee k 4 
Wee k 8
 
Wee k 1 2 
Wee k 1 6 
Wee k 2 0 
D a ys -2 8 t o - 1 
D a y 1 
( B aseli ne) 
D a y 8 
( ± 1 d a y) 
D a y 1 5 
( ± 1 d a y) 
D a y 2 9  
( ± 3 d a ys) 
D a y 5 7 
( ± 3 d a ys) 
D a y 8 5 
( ± 3 d a ys) 
D a y 1 1 3 * 
( ± 3 d a ys) 
D a y 1 4 1 * * 
( ± 3 d a ys) 
P h ar m ac o ki netic Assess me nts 
P K sa m ple ( bl o o d) n 
- 
- 
X 
- 
X 
X 
- 
X 
- 
Effic ac y Assess me nts 
P A SI sc ore 
X 
X o 
X 
X 
X 
X 
X 
X 
X 
B S A 
X 
X o 
X 
X 
X 
X 
X 
X 
X 
s P G A 
X 
X o 
X 
X 
X 
X 
X 
X 
X 
P R O 
assess me nts 
 
Itc h N R S 
- 
X 
X 
X 
X 
X 
X 
X 
X 
D L QI  -
 
X
 
X  
X
 X
 X
 X  
X
 X
 
Ot her Assess me nts 
Me dical p h ot o gra p h y (tar get 
s ki n lesi o n)p 
-
 X 
-
 X
  X
  -
 - 
X
 -
 
Cli nic al Dr u g S u p plies 
S u bj ect ra n d o mizati o n 
- 
X 
- 
- 
- 
- 
- 
- 
- 
Dis pe nse st u d y dr u g 
- 
X 
X 
X 
X 
X 
X 
- 
- 
A d mi nistrati o n of st u d y dr u g q  
- 
X 
X 
X 
X 
X 
X 
- 
- 
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 5 2  of 8 9  
St u d y Pr oce d ures 
Scree ni n g 
Peri o d 
Tre at me nt Peri o d 
F oll o w- u p 
Peri o d b  
Scree ni n g  
( Visit 1) 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 a 
F oll o w- u p 
Visit  
( Visit 9) 
Wee k - 4 
Wee k 0 
Wee k 1 
Wee k 2
 
Wee k 4 
Wee k 8
 
Wee k 1 2 
Wee k 1 6 
Wee k 2 0 
D a ys -2 8 t o - 1 
D a y 1 
( B aseli ne) 
D a y 8 
( ± 1 d a y) 
D a y 1 5 
( ± 1 d a y) 
D a y 2 9  
( ± 3 d a ys) 
D a y 5 7 
( ± 3 d a ys) 
D a y 8 5 
( ± 3 d a ys) 
D a y 1 1 3 * 
( ± 3 d a ys) 
D a y 1 4 1 * * 
( ± 3 d a ys) 
S u bj ect t o ret ur n bac k u n use d 
st u d y treat me nt f or 
c o m plia nce c hec k  
-
 -
 X 
X
 X
 X
 X  
X
 -
 
Sc he d ule t he date/ti me f or t he 
ne xt visit  
X
 X  
X  
X
 X
 X
 X  
X
 -
 
Disc har ge t he s u bj ect fr o m 
t he st u d y siter 
X
 X  
X  
X
 X
 X
 X  
X
 X
 
A b bre viati o ns: β - h C G = β - h u ma n c h ori o nic g o na d otr o pi n; A E = a d verse e ve nt; B MI = b o d y mass i n de x; B S A = b o d y s urface area; C- S S R S = C ol u m bia- S uici de 
Se verit y Rati n g Scale; D L QI = Der mat ol o g y Life Q ualit y I n de x;  E C G = electr ocar di o gra m; F S H = f ollicle-sti m ulati n g h or m o ne; H B V = he p atitis B vir us; 
H C V = he p atitis C vir us; P A SI = Ps oriasis Area a n d Se verit y I n de x; 
; P K = p har mac o ki netic; P R O = patie nt-rep orte d o utc o me; Q Tc F = 
Q T i nter val c orrecte d usi n g Fri dericia’s f or m ula ; S A E = seri o us a d verse e ve nt; s P G A = St atic P h ysicia ns Gl o bal Assess me nt; W O C B P = w o me n of c hil d beari n g 
p ote ntial; N R S = n u merical rati n g scale. 
* T he d urati o n of t he Treat me nt P eri o d is fr o m Da y 1 t o Da y 1 1 2 a n d t he e n d of Treat me nt P eri o d assess me nts will be perf or me d o n Da y 1 1 3. 
* * T he d urati o n of t he F oll o w- u p P eri o d is fr o m Da y 1 1 4 t o Da y 1 4 1 a n d t he e n d of F oll o w- u p P eri o d assess me nts will be p erf or me d o n Da y 1 4 1.  
a or Earl y T er mi nati o n Visit. 
b S u bj ects w h o disc o nti n ue d or wit h dr e w earl y fr o m st u d y tr eat me nt s h o ul d ret ur n after 4 wee ks of last d ose of st u d y tre at me nt for f oll o w- u p safet y assess me nts. 
c M ust i ncl u de hist or y of dr u g, s u bsta nce, or alc o h ol a b use/ de pe n dence wit hi n 1 year pri or t o Scree ni n g as deter mi ne d b y t he i n v esti gat or. 
d Rec or d hei g ht at Scree ni n g o nl y. 
e 1 2-lea d E C G m ust i ncl u de Q T c F meas ure me nt. 
g All s u bj ects m ust ha ve t he f oll o wi n g viral ser ol o g y tests c om plete d at Scree ni n g: a nti- H C V a nti b o d y, H B V s urface a nti ge n, H B V c ore a nti b o d y, HI V- 1 
a nti b o d y, a n d HI V- 2 a nti b o d y. If t he s u bj ect tests p ositi ve f or a n ti- H C V a nti b o d y, t he n H C V R N A via p ol y merase c hai n reacti o n sh o ul d be perf or me d t o 
c o nfir m or r ule o ut acti ve i nfe cti o n. If t he s u bj ect has recei v e d d oc u me nte d treat me nt w hi c h was c urati ve f or H C V a n d tests ne g ati ve f or H C V ri b o n ucleic 
aci d ( R N A) at Scree ni n g, t he s u bj ect ma y be c o nsi dere d f or e nr oll me nt. 
h I ncl u des c o m plete f ull a n d differe ntial bl o o d c o u nt, platelet c o u nt, he m o gl o bi n, he m o gl o bi n A 1c ( o nl y at Scree ni n g), fi bri n o ge n a n d pr ot hr o m bi n ti me. See 
Secti o n 1 2. 5 f or a c o m plete list of tests t o be perf or me d. 
i T o be o btai ne d pre d ose (s u bjects are re q uire d t o fast f or at least 1 0 h o urs pri or t o t he c ollecti o n of s peci me ns f or safet y l ab orat or y tests). 
j See Secti o n 1 2. 5  f or a list of tests t o be perf or me d. 
k All W O C B P m ust ha ve a ne gati ve ser u m pre g na nc y test at Scree ni n g t o be eli gi ble f or t he st u d y. 
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 5 3  of 8 9  
l All W O C B P m ust ha ve a ne gati ve uri ne pre g na ncy test pri or t o ra n d o mizati o n a n d d osi n g o n Da y 1. 
m  A ser u m pre g na nc y test s h o ul d be perf or me d f or c o nfir mati o n of a n y p ositi ve uri ne pre g na nc y test. T he s u bj ect will be wit h dra wn fr o m t he st u d y tre at me nt if 
t he c o nfir mat or y ser u m pre g na nc y test is p ositi ve. T he s u bj ect m ust n ot recei ve a n y f urt her d oses of t he st u d y dr u g a n d will be  as ke d t o ret ur n f or t he 
f oll o w- u p visit 4 wee ks after t he last d ose of st u d y dr u g. 
n T he P K a n d  
 bl o o d sa m pl es will be c ollecte d pre d ose at all sc he d ule d visits as per Sc he d ule of Assess me nts.  
o T o be perf or me d pri or t o ra n d o mizati o n. 
p Me dical p h ot o gra p h y of t he t ar get s ki n lesi o n will be o btai ne d at selecte d sites i n a select e d n u m ber of s u bj ects f or d oc u me ntati o n a n d p u blicati o n p ur p oses 
o nl y. 
q S u bj ects will ta ke t he first d ose of t he st u d y dr u g u p o n ret ur ni n g t o t heir h o me after all Da y 1 ( Visit 2) assess me nts are c o mplete d. 
r S u bj ects will be disc har ge d fr o m t he st u d y site after all t he p ost d ose st u d y pr oce d ur es are c o m plete d. 
 
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 5 4  of 8 9  
1 0. 1  I nf or me d C o nse nt 
I C Fs m ust be a p pr o ve d f or use b y t he re vie wi ng i nstit uti o nal re vie w b oar d/i n de pe n de nt et hics 
c o m mittee (I R B/I E C). Bef ore p erf or mi n g a n y st u d y-relate d pr oce d ures, t h e i n vesti gat or ( or 
desi g nee) will o btai n writte n i nf or me d c o nse nt fr o m t he s u bject. 
I n t he e ve nt t hat r escree ni n g occ urs, t he i n di vi d ual is re q uire d t o si g n a ne w I C F a n d m ust be 
assi g ne d a ne w s u bj ect i de ntificati o n n u m ber. 
1 0. 2  St u d y Pr oce d ures 
Assess me nts a n d t heir ti mi n g are t o be perf or m e d as o utli ne d i n t he Sc he d ule of Assess me nts 
(Ta ble 1 ). Secti o n 1 2. 5  s pecifies safet y la b orat or y assess me nt sa m ples t o be o btai ne d. 
Assess me nts a n d pr oce d ures sc he d ule d s h o ul d be perf or me d b ef ore a d mi ni strati o n of treat me nt 
u nless ot her wise i n dicate d i n t he Sc he d ule of Assess me nts ( Ta ble 1 ). 
Efficac y assess me nts are descri be d i n Secti o n 1 1  a n d i ncl u de P A SI, s P G A, B S A, itc h N R S, a n d 
D L QI sc ori n g. 
Safet y assess me nts are d escri be d i n Secti o n 1 2  a n d i ncl u de de m o gra p hics, me dical hist or y, vital 
si g ns (i ncl u di n g b o d y te m perat ure, b o d y wei g ht, res pirat or y rate, heart rate, a n d s yst olic a n d 
diast olic bl o o d press ure meas ure me nts), c o m plete /tar gete d p h ysical e x a mi nati o ns, E C Gs, safet y 
la b orat or y ass ess me nts ( he mat ol o g y, c oa g ulati o n, c he mistr y, uri nal ysis, viral ser ol o g y, 
pre g na nc y t ests, a n d ser u m f ollicle-sti m ulati n g h or m o ne tests), a n d A Es. 
P K a n d 
 sa m pli n g is descri be d i n Secti o n 1 3  a n d Secti o n 1 4. 1 , res pecti vel y. 
Ot her assess me nts s uc h as me dical p h ot o gra p h y of  affecte d s ki n area a n d C- S S R S are descri be d 
i n Secti o n 1 4. 2  a n d Secti o n 1 4. 3 , res pecti vel y. 
T he i n vesti gat or ma y, at his/ her discreti o n, ar ra n ge f or a s u bject t o ha ve a n u nsc he d ule d 
assess me nt, es peciall y i n t he case of A Es t hat re q uire f oll o w- u p or are c o nsi dere d b y t he 
i n vesti gat or t o be p ossi bl y relate d t o t he use of st u d y dr u g. T h e u nsc h e d ule d visit pa ge i n t he 
e C R F m ust be c o m plete d. 
St u d y dis c o nti n uati o n pr oce d ures are d escri b e d i n Secti o n  8. 4 . 
T he pr oce d ures t o be p erf or me d d uri n g eac h st u d y visit are pr o vi de d i n Sc he d ule of Assess me nts 
(Ta ble 1 ). 
A f oll o w- u p visit is perf or me d at t he cli nical st u d y site 4 wee ks after t he last d ose of st u d y dr u g. 
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 5 5  of 8 9  
1 1  E F FI C A C Y A S S E S S M E N T S 
T he Sc he d ule of Assess me nts ( Ta ble 1 ) o utli nes t he efficac y assess me nts t o be perf or m e d 
t hr o u g h o ut t he st u d y a n d t heir ti mi n g. 
O nl y trai n e d assess or q u alifie d pers o n nel at si te will c o n d uct efficac y ass ess me nts. T he sa me 
assess or s h o ul d perf or m all assess me nts t hr o u g h o ut t he st u d y at least wit hi n t he sa me s u bject 
w he n p ossi ble. 
1 1. 1  Ps ori asis Are a Se verit y I n de x 
P A SI will be deter mi ne d f or all s u bjects t hr o u g h o u t t he st u d y. T he P A SI sc ori n g t o ol is s h o w n i n 
A P P E N DI X 3 . 
T he P A SI is a m eas ur e of ps oriatic disease s e verit y ta ki n g i nt o acc o u nt q ualitati ve lesi o n 
c haracteristics (er yt he ma, i n d urati o n, a n d des q ua mati o n) a n d perce nta ge of affecte d s ki n s urface 
area o n d efi ne d a nat o mic al re gi o ns. T he P A SI is a vali date d i nstr u me nt t hat is m ost wi del y us e d 
f or meas ur e me nt of se v erit y of ps oriasis. 
P A SI sc ores ra n ge fr o m 0 t o 7 2, wit h hi g her sc ores reflecti n g greater diseas e se verit y.( 5 ) 
Er yt h e ma, i n d urati o n/t hic k ness, a n d scali n g are s c ore d o n a s cale of 0 ( n o ne) t o 4 ( ver y s e vere) 
o n 4 a nat o mic re gi o ns of t he b o d y: hea d, tr u n k, u p per li m bs, a n d l o wer li m bs. De gree of 
i n v ol ve me nt o n eac h of t he 4 a nat o mic re gi o ns is sc ore d o n a s cale of 0 ( n o i n v ol ve me nt) t o 
6 ( 9 0 % t o 1 0 0 % i n v ol ve me nt). T he t otal q ualitati ve sc ore (s u m of er yt h e ma, t hic k ness, a n d 
scali n g s c ores) is m ulti plie d b y t he d e gree of i n v ol ve me nt f or eac h a n at o mic re gi o n a n d t he n 
m ulti plie d b y a c o nsta nt. T he sc ores f or eac h a n at o mic re gi o n are c o m bi ne d t o yiel d t he fi nal 
P A SI sc ore (see Ta ble 1 ). 
1 1. 2  St atic P h ysici a n’s Gl o b al Assess me nt 
T he i n vesti gat or will rate t he se verit y of s u bject’s ps oriasis o n t he 5- p oi nt scale ra n gi n g 
fr o m 0 (cle ar) t o 4 (s e vere). 
T he s P G A is use d t o deter mi ne t he s u bject’s ps ori asis state o verall at a gi ve n ti me p oi nt. 
See A P P E N DI X 4  f or gra di n g criteria (see T a ble 1 ). 
1 1. 3  B o d y S urf ace Are a 
B S A is a meas ur e me nt of t he affecte d s ki n area. T he o verall B S A affect e d b y ps oriasis pla q ues is 
esti mate d base d o n t he p al m area of t he s u bject ’s ha n d (e ntire p al mar s urface or “ h a n d pri nt” 
i ncl u di n g t he fi n gers), w hic h e q uates t o a p pr o xi matel y 1 % of t otal B S A (see Ta ble 1 ). 
1 1. 4  P R O Ass ess me nt: It c h N u meric al R ati n g Sc ale 
Eac h s u bject will be as ke d t o c o m plete t he itc h N R S assess me nt: ma xi mal i nte nsit y of itc h 
d uri n g t he pre vi o us 2 4 h o urs, rate d o n a n i nte ger sc ale ra n gi n g fr o m 0 ( n o it c h at all) t o 1 0 ( w orst 
itc h i ma gi na ble) d uri n g t he sc he d ule d st u d y site visit (see Ta ble 1 ). 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 5 6  of 8 9  
1 1. 5  P R O Ass ess me nt: D er m at ol o g y Lif e Q u alit y I n de x 
T he D L QI is a si m ple, self-a d mi nistere d q uesti o n naire desi g ne d t o meas ure t he healt h-relate d 
Q O L of a n a d ult s ufferi n g fr o m a s ki n disease. It c o nsists of 1 0 q uesti o ns (eac h sc ore d fr o m 0 t o 
3) c o ncer ni n g s u bjects ’ perce pti o n of t h e i m pact of s ki n disease o n differe nt as pects of t heir 
healt h-rel ate d Q O L o v er t he last wee k. Ni ne  of t he 1 0 q uesti o ns ha ve 4 res p o nse o pti o ns: “ N ot at 
all”, “ A little”, “ A l ot”, a n d “ Ver y m uc h” wit h c orres p o n di n g s c ores of 0, 1, 2, 3 a n d 3, 
res pecti vel y. Q u esti o n 7 is a m ulti part ite m, t he first part ascertai ns w het her t he s ki n c o n diti o n 
pre ve nte d t he m fr o m eit h er w or ki n g or st u d yi n g (“ Y es” or “N o”), a n d t he s ec o n d part d eter mi nes 
t o w hat de gree t he s ki n c o n diti o n has bee n a pr o bl e m f or w or ki n g or st u d yi n g (“ A l ot”, “ A 
little”, “ N ot at all”). Ei g ht ite ms als o ha ve a “ N ot  rele va nt” o pti o n sc ore d “ 0,” w hic h i n dicates n o 
pr o ble m. I n di vi d ual ite m sc ores are c o m bi ne d t o gi ve  a t otal sc ore t hat ra n ges bet wee n 0 a n d 3 0. 
T he hi g h er t he sc ore, t he m ore Q O L is i m paire d. S ee A P P E N DI X 5  f or t he D L QI q uesti o n nair e. 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 5 7  of 8 9  
1 2  S A F E T Y A S S E S S M E N T S 
Safet y assess me nts ( d e m o gra p hics, me dical hist or y, vital si g ns, c o m plete d/tar gete d p h ysic al 
e x a mi nati o ns, E C Gs, safet y la b orat or y res ults [r o uti ne he mat ol o g y, c oa g ul ati o n, c he mistr y, a n d 
uri nal ysis, viral ser ol o g y, pre g na nc y t ests, a n d s er u m f ollicle-sti m ulati n g h or m o ne tests], a n d 
A Es [i ncl u di n g S A Es]) are t o be perf or me d at pr ot oc ol-s pecifie d visits, as s pecifie d i n t he 
Sc he d ule of Assess me nts ( Ta ble 1 ). 
1 2. 1  De m o gr a p hics a n d Me dic al a n d Der m at ol o gic al Hist or y 
De m o gra p hic d ata will be c ollecte d f or all s u bjects at Scree ni n g a n d rec or d e d i n t he e C R F. 
Me dical hist or y will be rec or de d at Scree ni n g.  I n v esti gat ors s h o ul d d oc u m e nt t he occ urre nce, 
si g ns, a n d s y m pt o ms of t he s u bject’s pree xisti n g c o n diti o ns, i ncl u di n g all pri or si g nifica nt 
ill nesses, fr o m birt h u ntil Scree ni n g. A d diti o nal pree xisti n g c o n diti o ns prese nt at t he ti me w he n 
i nf or me d c o nse nt is gi ve n a n d u p t o t he ti me of first d osi n g ( Visit 2) are t o be re gar de d as 
c o nc o mita nt. Me dical hist or y will als o i ncl u de a n y t o xicities or aller gies t o pre vi o us treat me nts, 
alc o h ol c o ns u m pti o n, a n d s m o ki n g hist or y. 
Me dical hist or y will als o i ncl u de hist or y of dr u g, s u bsta nce, or alc o h ol a b us e/ de pe n de n ce wit hi n 
1 year pri or t o Scree ni n g as deter mi ne d b y t he i n v esti gat or. 
Der mat ol o gical hist or y c ollecte d will als o i ncl u de date a n d/ or a ge of dia g n osis of ps oriasis, a n d 
all pri or treat me nts f or pla q ue ps oriasis. All t he pri or ps oriasis treat me nts s h o ul d be i ncl u de d 
u n der pri or a n d c o nc o mit a nt me dicati o ns pa ge i n t he e C R F. 
T he de gree of s ki n s urface i n v ol ve me nt, se verit y, a n d lesi o n c haracteristics (er yt he ma, s cali n g, 
a n d t hic k ness) are t o be d oc u me nte d at Scree ni n g. 
Ill nesses first occ urri n g or detecte d d uri n g t he st u d y a n d/ or w orse ni n g of a c o nc o mita nt ill ness 
d uri n g t he st u d y are t o be d oc u me nte d as A Es i n t he e C R F i n acc or da n ce wit h Secti o n 1 2. 6 . All 
c ha n ges n ot prese nt at Baseli ne or descri be d i n t he past me dical hist or y a n d i de ntifie d as 
cli nicall y n ote w ort h y m ust be rec or de d as A Es. 
1 2. 2  Vit al Si g ns 
Vital si g ns ( b o d y te m perat ure, b o d y w ei g ht, res pirat or y rat e, heart rate, a n d s yst olic a n d diast olic 
bl o o d press ure me as ure m e nts) will be e val uat e d at t he visits i n dicate d i n t he Sc he d ule of 
Assess me nts ( Ta ble 1 ). All vital si g ns will be meas ure d after t he s u bject h as bee n resti n g i n a 
sitti n g p ositi o n f or at least 1 0 mi n utes. Bl o o d press ure meas ure me nts are t o be ta ke n i n t he sa me 
ar m f or t he d urati o n of t h e st u d y. 
Vital si g n meas ur e me nts will be re peat e d if C S  or mac hi ne/e q ui p me nt err ors occ ur. O ut- of-ra n ge 
bl o o d press ure, res pirat or y rate, b o d y te m perat ure, b o d y wei g ht or heart rat e meas ur e me nts will 
be re peate d at t he i n v esti gat or’s discreti o n. A n y c o nfir me d, C S vital si g n meas ure me nts m ust be 
rec or de d as A Es. 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 5 8  of 8 9  
1 2. 3  C o m plete/ T ar gete d P h ysic al E x a mi n ati o n 
A c o m plete p h ysical e x a mi nati o n i ncl u di n g he i g ht a n d wei g ht will be perf or me d at 
Scree ni n g ( Visit 1). T he c o m plete p h ysi cal e xa mi nati o n s h o ul d i ncl u de t he f oll o wi n g s yste ms: 
hea d, e yes, ears, n ose a n d t hr oat; res pirat or y; car di o vasc ular; m usc ul os keletal; ne ur ol o gical; 
meta b olic/e n d ocri ne/ n utriti o nal; he mat o p oietic; aller g i es; a b d o mi nal; a n d ge neral a p peara n ce. 
P h ysical e x a mi nati o ns will be perf or me d b y a p h ysicia n. 
A tar gete d p h ysic al e x a mi nati o n t o verif y c o nti n ue d s u bject eli gi bilit y a n d t o f oll o w- u p 
re gar di n g a n y c ha n ge i n me dical hist or y will be perf or me d at t he visits i n dicate d i n t he Sc he d ule 
of Assess me nts ( Ta ble 1 ). 
S y m pt o m- dri ve n, tar gete d p h ysical e x a mi nati o ns will  be perf or me d as cli nicall y i n dicat e d at a n y 
st u d y visit. 
Hei g ht will be rec or de d at Scree ni n g o nl y. 
A n y C S p h ysi cal e x a mi nati o n fi n di n g s h o ul d be re p orte d as a n A E. 
1 2. 4  Electr oc a r di o gr a ms 
A 1 2-lea d, resti n g E C G will be o btai ne d at t he visits i n dicate d i n t he Sc he d ule of 
Assess me nts ( Ta ble 1 ). D uri n g t h e E C G, ve ntric ular rate ( b p m), P R ( msec), Q R S ( msec), 
Q T ( msec), a n d Q Tc F ( msec) meas ure me nts will b e o btai ne d. 
All t he E C Gs o btai ne d will be i nter prete d b y a n e x perie nce d si n gl e i n de pe n de nt bli n de d rea d er at 
t he ce ntral la b orat or y. 
At Scree ni n g, t he i n vesti gat or will e x a mi ne t he E C G traces f or si g ns of car diac diseas e t hat c o ul d 
e x cl u de t he s u bject fr o m t he st u d y ( Q Tc F > 4 5 0 msec). A n assess me nt of n or mal or a b n or mal 
will be rec or de d; if t he E C G is c o nsi dere d a b n or mal, t he a b n or malit y will be d oc u me nte d i n t he 
e C R F. E C Gs will be re peate d if C S a b n or malities are o bser ve d, or artifacts are prese nt. T he d ate 
a n d ti me of eac h E C G a n d its res ults will be  d oc u me nte d i n t he s o urce d o c u me nts a n d e C R F. 
A n y C S E C G a b n or malities m ust be rec or de d as A Es. 
1 2. 5  S afet y L a b or at or y Assess me nts 
Safet y l a b orat or y assess me nt sa m ples ( Ta ble 2 ) are t o be o btai ne d at desi g nate d visits as detaile d 
i n t he Sc he d ule of Assess me nts (Ta ble 1 ). 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 5 9  of 8 9  
T a ble 2.  
S afet y L a b or at or y Assess me nts 
He m at ol o g y 
Bl o o d C he mistr y 
Uri n al ysis ( Di pstic k) 
F ull a n d differe ntial bl o o d c o u nt 
Hct  
H b  
M C H  
M C H C  
M C V  
Platelet c o u nt  
R B C c o u nt 
W B C c o u nt  wit h differe ntial 
H b A 1c * 
 
Al b u mi n 
A L T  
A L P  
A S T  
B U N or urea  
Creati ni ne  
Creati ni ne cleara nce * * 
Creati ne ki nase a n d s u bt y pes 
Electr ol ytes ( s o di u m, 
p otassi u m, c hl ori de, calci u m, 
p h os p h or us ) 
G G T  
Gl uc ose  
L D H  
T otal bilir u bi n  
Direct bilir u bi n  
L D L  
H D L  
T otal c h olester ol  
Tri gl yceri des  
A m ylase  
Li pase  
C-reacti ve pr otei n 
A p peara nce 
p H  
Pr otei n  
Gl uc ose  
Ket o ne b o dies  
I n dicat ors of bl o o d a n d W B Cs 
S pecific gra vit y  
Ur o bili n o ge n  
 
Vir al Ser ol o g y * * * 
H B V  
H C V  
HI V 
 
C o a g ul ati o n 
Fi bri n o ge n  
P T 
 
 
Pre g n a nc y test: A ser u m β - h C G pre g na nc y test ( pre me n o pa usal w o me n o nl y) will be perf or me d o n all W O C B P at 
Scree ni n g.  A uri ne β - h C G will b e perf or me d at later ti me p oi nts as i n dicati o n i n t he Sc he d ule of Assess me nts. A 
ser u m pre g na nc y test s h o ul d be perf or me d f or c o nfir mati o n of a n y p ositi ve uri ne pre g na nc y test. 
Ser u m F S H le vels will be test e d f or all p ost me n o pa usal w o me n at Scree ni n g. 
A b bre viati o ns: A L P = al kali ne p h os p hatase; A L T = ala ni ne a mi n otra nsa mi nase; A S T = as partate 
a mi n otra nsa mi nase; B U N = bl o o d urea nitr o ge n; F S H = f olli cle-sti m ulati n g h or m o ne; G G T = ga m ma- gl uta m yl 
tra ns pe pti dase; H B V = he p atitis B vir us; H C V = he patitis C vir us; β - H C G = β - h u ma n c h ori o nic g o na d otr o pi n; 
H D L = hi g h- de nsit y li p o pr otei ns; H b = he m o gl o bi n; Hct = he mat ocrit; L D H = lactate de h y dr o ge nase; L D L = l o w-
de nsit y li p o pr otei ns; M C H = mea n c or p usc ular he m o gl o bi n; M C H C = mea n c or p usc ular he m o gl o bi n 
c o nce ntrati o n; M C V = mea n c or p usc ular v ol u me; P T = pr ot hr o m bi n ti me; R B C = re d bl o o d cell; W B C = w hite 
bl o o d cell; W O C B P = w o me n of c hil d beari n g p ote ntial. 
* At Scree ni n g o nl y. 
* * Esti mate d b y C oc kcr oft- Ga ult f or m ula < 6 0 m L/ mi n 
* * * All s u bj ects m ust ha ve t he f oll o wi n g viral ser ol o g y tests c o m plete d at Scree ni n g: a nti- H C V a nti b o d y, H B V 
s urface a nti ge n, H B V c ore a nti b o d y, HI V- 1 a nti b o d y, a n d HI V- 2 a nti b o d y. If t he s u bj ect tests p ositi ve f or a nti-
H C V a nti b o d y, t he n H C V R N A via p ol y merase c hai n reacti o n s h o ul d be perf or me d t o c o nfir m or r ule o ut 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 6 0  of 8 9  
acti ve i nfecti o n. If t he s u bj ect has recei ve d d oc u me n te d treat me nt w hic h was c urati ve f or H C V a n d tests 
ne gati ve f or H C V ri b o n ucleic aci d ( R N A) at Scree ni n g,  t he s u bj ect ma y be c o nsi dere d f or e nr oll me nt. 
Bl o o d f or la b orat or y ass ess me nts will be c ollec te d u n der fasti n g c o n diti o ns fr o m eac h s u bject 
bef ore t h e st u d y dr u g d osi n g. T he i n vesti gat or or q ualifie d st u d y p ers o n nel will c ollect t he 
sa m ples as re q uir e d. 
Bl o o d a n d uri ne s a m ples will be a nal yze d at a ce ntral la b orat or y facilit y. Uri ne sa m ples will be 
a nal yze d b y di pstic k, a n d a micr osc o pic a nal ysis  will be perf or me d if t he res ults of di pstic k 
i n dicate a b n or malities t o be f urt her i n v esti gated. F ull details of e q ui p me nt a n d pr oce d ures f or 
la b orat or y testi n g will be liste d i n t he la b orat or y m a n ual. 
All la b orat or y re p orts m ust be re vie we d, si g n e d, a n d date d b y t he i n vesti gat or. A le gi ble c o p y of 
all t he si g ne d la b orat or y re p orts m ust be file d wit h b ot h t he s u bject’s e C R F a n d me dical rec or d 
(s o urce d o c u me nt) f or t hat visit. T he i n vesti gat or m ust cate g orize all a b n or mal uri ne, 
he mat ol o g y, c oa g ulati o n, a n d c he mistr y la b orat or y val u es as eit her C S or n ot C S. A n y l a b orat or y 
test res ult c o nsi dere d b y t he i n vesti gat or t o be C S a b n or mal s h o ul d be co nsi dere d a n d re p orte d as 
a n A E ( C S A Es i ncl u de t h ose t hat re q uire a n i nter ve nti o n). C S a b n or mal val ues occ urri n g d uri n g 
t he st u d y will be f oll o we d u p u ntil re peat test res ults ret ur n t o n or mal, sta bilize, or are n o l o n ger 
a b n or mal C S. 
1 2. 6  A d verse E ve nts 
A Es will be c ollecte d fr o m t he ti me t he s u bject si g ns t he I C F t hr o u g h 4 wee ks after t h e last d ose 
of st u d y dr u g. All A Es m ust be rec or de d i n t he s u bject’s e C R F. T he S p o ns or a n d i n vesti gat or or 
q ualifie d st u d y p ers o n nel will re vie w a n d e v al uate A Es o n a n o n g oi n g b asis. 
1 2. 6. 1  
A d verse E ve nts 
A n A E is a n y s y m pt o m, p h ysical si g n, s y n dr o me, or disease t hat eit her e mer ges d uri n g t he st u d y 
or, if prese nt at Scree ni n g, w orse ns d uri n g t h e st u d y, re gar dl ess of t he s us p ecte d ca use of t h e 
e ve nt. All me dical a n d ps yc hi atric c o n diti o ns (e x ce pt t h ose relate d t o t he i n dicati o n u n der st u d y) 
prese nt at Scree ni n g will be d oc u me nte d i n t he me dical hist or y e C R F. C ha n ges i n t hes e 
c o n diti o ns a n d ne w s y m pt o ms, p h ysi cal si g ns, s y n dr o mes, or diseas es s h o ul d be n ote d o n t he A E 
e C R F d uri n g t he rest of t he st u d y. C S la b orat or y a b n or malities (e g, safet y l a b orat or y assess me nts 
or E C Gs) s h o ul d als o be rec or de d as A Es. S ur g ical pr oce d ures t hat were pl a n ne d bef ore t he 
s u bject ra n d o mize d i n t he st u d y are n ot c o nsi dere d A Es if t he c o n diti o ns were k n o w n bef ore 
st u d y i ncl usi o n; t he me dical c o n diti o n s h o ul d be re p orte d i n t he s u bject’s me dical hist or y. 
S u bjects will be i nstr ucte d t o re p ort A Es at eac h  st u d y visit. All A Es are t o be f oll o we d u p u ntil 
res ol uti o n or a sta ble cli nical e n d p oi nt is reac he d. 
Eac h A E is t o be d oc u m e nte d i n t he e C R F wit h  refere nce t o date of o nset, d ate of o utc o me, 
se verit y, relati o ns hi p t o st u d y dr u g, acti o n ta ke n wit h st u d y dr u g, treat me nt of e ve nt, a n d 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 6 1  of 8 9  
o utc o me. F urt her m ore, eac h A E is t o be cl assifi e d as bei n g s eri o us or n o n-s eri o us. C ha n ges i n 
A Es a n d res ol uti o n dates are t o be d o c u me nte d i n t he e C R F. 
F or t he p ur p os es of t his st u d y, t he peri o d of o bs er vati o n f or c ollecti o n of A Es e xte n ds fr o m t he 
ti me t he s u bject gi ves i nf or me d c o nse nt u ntil t he f oll o w- u p visit. F oll o w- u p of t he A E, e v e n after 
t he date of t hera p y disc o nti n uati o n, is re q uire d if t he A E persists u ntil t he e ve nt res ol ves or 
sta bilizes at a le vel acce pta ble t o t he i n vesti gat or. 
W he n c ha n ges i n t he se v erit y of a n A E o cc ur m ore fre q u e ntl y t h a n o nce a da y, t h e ma xi m u m 
se verit y f or t he e ve nt s h o ul d be n ote d. If t he se v erit y cate g or y c h a n ges o v er a n u m ber of da ys, 
t he n t h ose c ha n ges s h o ul d be rec or de d se p aratel y ( wit h disti nct o nset dates). 
A n y A Es of m o derate or se vere i n se v erit y s h o ul d be n otifie d t o t he S p o ns or or desi g nee 
i m me diatel y. 
S pecific g ui deli nes f or cl assif yi n g A Es b y s e verit y a n d relati o ns hi p t o st u d y dr u g are gi v e n i n 
Ta ble 3  a n d T a ble 4 . 
T a ble 3.  
Cl assific ati o n of A d verse E ve nts b y Se verit y 
MI L D : A n e ve nt t hat is easil y t olerate d b y t he s u bj ect, ca usi n g mi ni mal disc o mf ort a n d n ot i nterferi n g wit h 
e ver y da y acti vities. 
M O D E R A T E : A n e ve nt t hat is s ufficie ntl y disc o mf orti n g t o i nterfere wit h n or mal e ver y d a y acti vities. 
S E V E R E : A n e ve nt t hat pre v e nts n or mal e ver y da y acti vities. 
 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 6 2  of 8 9  
T a ble 4.  
Cl assific ati o n of A d verse E ve nts b y Rel ati o ns hi p t o St u d y Dr u g 
U N R E L A T E D : T his cate g or y a p plies t o t h ose A Es t hat are clearl y a n d i nc o ntr o verti bl y d ue t o e xtra ne o us 
ca uses ( disease, e n vir o n me nt, etc). 
U N LI K E L 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 b 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 st u d y dr u g if or w he n it 
meets 2 of t he f oll o wi n g criteria: ( 1) it d oes n ot f oll o w a reas o na ble te m p oral se q ue nce fr o m a d mi nistrati o n of 
t he test dr u g; ( 2) it c o ul d rea dil y ha ve bee n pr o d uce d b y t he s u bj ect’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 her a p y a d mi nistere d t o t he s u bj ect; ( 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; or ( 4) it d oes n ot rea p pear or w orse n w he n t he dr u g is re-a d mi nist ere d. 
P O S SI B L 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 a d mi nistrati o n 
a p pears u nli kel y b ut ca n n ot b e r ule d o ut wit h certai nt y.  A n A E ma y be c o nsi dere d p ossi bl y relate d if or w he n 
it meets 2 of t he f oll o wi n g crit eria: ( 1) it f oll o ws a reas o na bl e te m p oral se q ue nce fr o m a d mi nistrati o n of t he 
dr u g ; ( 2) it c o ul d n ot rea dil y ha ve bee n pr o d uce d b y t he s u bj ect’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 s u bj ect ; or ( 3) 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. 
P R O B A B L 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. A n A E ma y be c o nsi dere d pr o ba bl y relate d if or w he 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 nce fr o m a d mi nistrati o n of t he dr u g; ( 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 s u bj ect’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 her a p y a d mi nistere d t o t he s u bj ect; ( 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 xce pti o ns w he n a n A E d oes n ot disa p pear u p o n disc o nti n uati o n of t he 
dr u g , yet dr u g-relate d ness clearl y e xists; f or e xa m ple, 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 no w n patter n of res p o nse t o t he test dr u g. 
D E FI NI T E L 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 are i nc o ntr o verti bl y relate d t o test 
dr u g . A n A E ma y be assi g ne 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 na ble te m p oral se q ue nce fr o m a d mi nistrati o n of t he dr u g; ( 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 s u bj ect’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 her a p y a d mi nistere d t o t he s u bj ect; ( 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 rec urs wit h ree x p os ure t o dr u g (if rec halle n ge occ 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. 
A b bre viati o n: A E = a d verse e ve nt. 
F or t he p ur p os es of t his st u d y, a n y A Es classifie d as ‘ U nrelate d’ or ‘ U nli kel y’ will be c o nsi d ere d 
as ‘ N ot Relate d’ a n d ‘ P ossi bl y’, ‘ Pr o ba bl y’, or ‘ D efi nitel y’ as ‘ Relat e d’ t o t he st u d y treat me nt.  
1 2. 6. 2  
Tre at me nt- E mer ge nt A d verse E ve nts 
A T E A E will be a n A E t hat occ urre d d uri n g t he st u d y after t he first d ose of st u d y dr u g or t h at 
was pres e nt pri or t o d osi n g a n d e x acer bates aft er t he first d ose of st u d y dr u g. 
1 2. 6. 3  
Seri o us A d verse E ve nts 
A n S A E is a n y u nt o w ar d me dical occ urre n ce, i n t he vie w of eit her t he i n vesti gat or or S p o ns or, 
t hat: 
 res ults i n deat h, 
 is life-t hreate ni n g, 
 res ults i n i n patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n, 
 res ults i n persiste nt or si g nifica nt disa bilit y/i n ca pacit y, a n d/ or 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 6 3  of 8 9  
 is a c o n ge nital a n o mal y/ birt h defect. 
Ot her i m p orta nt me dical e ve nts t hat ma y n ot be i m me diatel y life-t hreate ni n g or res ult i n deat h or 
h os pitaliz ati o n, base d u p o n a p pr o priate m e dical j u d ge m e nt, are c o nsi dere d S A Es if t he y are 
t h o u g ht t o je o par dize t he s u bject a n d/ or re q uire medical or s ur gical i nter ve nti o n t o pre ve nt o ne of 
t he o utc o mes defi ni n g a n S A E. S A Es are criticall y i m p orta nt f or t he i de ntificati o n of si g nifi ca nt 
safet y pr o ble ms; t heref ore, it is i m p orta nt t o ta ke i nt o acc o u nt b ot h t he i n vesti gat or’s a n d t he 
S p o ns or’s assess me nt. If eit her t he S p o ns or or t he i n vest i gat or b elie ves t hat a n e ve nt is seri o us, 
t he e ve nt m ust be c o nsi d ere d seri o us a n d e v al uate d b y t he S p o ns or f or e x pe dite d re p orti n g. 
T he ma na ge m e nt of s u bject’s C O VI D- 1 9 data will be detaile d i n a C O VI D- 1 9 g ui da nce 
d oc u me nt. 
1 2. 6. 4  
Seri o us A d verse E ve nt Re p orti n g 
A n S A E occ urri n g fr o m t he ti me i nf or me d c o nse nt is o btai ne d, d uri n g t he st u d y, or wit hi n 
4 wee ks of st o p pi n g t he treat me nt m ust be re p orte d t o 
 
 a n d will be c o m m u nicate d t o t he S p o ns or. A n y s uc h S A E d ue t o a n y 
ca use, w h et her or n ot rel ate d t o t he st u d y dr u g, m ust be re p orte d wit hi n 2 4 h o urs of occ urre nce 
or w he n t he i n vesti g at or bec o mes a w are of t he e ve nt . N otificati o n ca n b e ma de usi n g t he 
de dicate d fa x li ne or e mail f or 
 b y fa x or 
e mail: 
If t he i n vesti gat or c o nt acts 
 b y tele p h o ne, 
t he n a writte n re p ort m ust f oll o w wit hi n 2 4 h o urs a n d is t o i ncl u de a f ull descri pti o n of t he e ve nt 
a n d se q uela e i n t he f or m at detaile d i n t he S A E re p orti n g f or m. 
T he e ve nt m ust als o be rec or de d o n t h e sta n dar d A E e C R F. Preli mi nar y re p orts of S A Es m ust be 
f oll o we d u p b y detaile d d escri pti o ns later o n, i ncl u di n g clear a n d a n o n y miz e d p h ot oc o pies of 
h os pital case re p orts, c o ns ulta nt re p orts, a ut o ps y re p orts, a n d ot her d o c u me nts w he n re q uest e d 
a n d a p plica ble. S A E re p orts m ust be ma de w het her or n ot t he i n vesti gat or c o nsi ders t he e ve nt t o 
be relate d t o t he st u d y dr u g. 
A p pr o priate re me dial me as ures s h o ul d be ta ke n t o treat t he S A E, a n d t he res p o nse s h o ul d be 
rec or de d. Cli nical, la b orat or y, a n d dia g n ostic meas ures s h o ul d be e m pl o ye d as nee de d t o 
deter mi ne t he eti ol o g y of t he pr o ble m. T he i n vesti gat or m ust re p ort all a d diti o nal f oll o w- u p 
e val uati o ns t o 
 wit hi n 2 4 h o urs of 
bec o mi n g a ware of t h e a d diti o nal i nf or mati o n or as s o o n as is practica ble. All S A Es will be 
f oll o we d u p u ntil t he i n vesti gat or a n d S p o ns or a gree t he e v e nt is satisfact oril y res ol ve d. 
P P D
P P D
P P D
P P D
P P D

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 6 4  of 8 9  
A n y S A E t hat is n ot res ol ve d b y t he e n d of t he st u d y or u p o n disc o nti n uati o n of t he s u bject’s 
partici pati o n i n t he st u d y is t o be f oll o we d u p u ntil it eit her res ol ves, sta bilizes, ret ur ns t o 
Baseli ne v al ues (if a Bas eli ne val ue is a vaila bl e ), or is s h o w n t o n ot be attri b uta ble t o t he st u d y 
dr u g or pr oce d ures. 
1 2. 6. 5  
S us pecte d U ne x pecte d Seri o us A d verse Re a cti o ns 
A Es t hat meet all of t he f oll o wi n g criteria will be classifie d as s us pecte d u ne x pecte d seri o us 
a d verse reacti o ns ( S U S A Rs) a n d re p ort e d t o t he a p pr o priate re g ulat or y a ut h orities i n acc or da nce 
wit h a p plica ble re g ul at or y re q uire me nts f or e x pe dite d re p orti n g: 
 seri o us 
 u ne x pecte d (ie, t he e v e nt is n ot c o nsiste nt wit h t he safet y i nf or mati o n i n t he c urre nt 
versi o n of t he I B) 
 t here is at least a reas o na ble p ossi bilit y t hat t h ere is a ca usal relati o ns hi p bet wee n t he 
e ve nt a n d t he st u d y treat me nt 
T he i n vesti gat or will assess w het her a n e v e nt is ca usall y relate d t o st u d y tr eat me nt. T he S p o ns or 
( or 
) will c o nsi der t he i n vesti gat or’s assess me nt a n d deter mi ne w het her t h e e ve nt 
meets t he criteri a f or b ei n g re p orta ble as a 7- d a y or 1 5- da y safet y re p ort. S U S A Rs t hat are fat al 
or life-t hreate ni n g m ust be re p ort e d t o t he re g ulat or y a ut h orities a n d t he I E C/I R Bs ( w here 
re q uire d) wit hi n 7 da ys after t he S p o ns or ( or 
) has first k n o wle d ge of t he m, wit h a 
f oll o w- u p re p ort s u b mitte d wit hi n a f urt her 8 cale n dar da ys. Ot her S U S A Rs m ust be re p orte d t o 
t he rele va nt re g ulat or y a ut h orities a n d t he I E C/I R Bs wit hi n 1 5 cale n dar da ys after t he S p o ns or 
( or 
) first h as k n o wle d ge of t h e m. 
T he S p o ns or ( or 
) is res p o nsi ble f or re p orti n g S U S A Rs, a n d a n y ot h er e v e nts 
re q uire d t o be re p ort e d i n a n e x pe dite d ma n ner t o t he re g ulat or y a ut h orities a n d f or i nf or mi n g 
i n vesti gat ors of re p ort a ble e ve nts, i n c o m plia nce wit h a p plica ble re g ul at or y re q uire me nts wit hi n 
s pecific ti mefra mes. I n v esti gat ors will n otif y t h e rele va nt I E C/I R Bs of re p orta ble e ve nts wit hi n 
t he a p plica ble ti mefra mes. 
1 2. 6. 6  
Pre g n a nc y 
W O C B P m ust ha ve a ne gati ve pre g na n c y test at Scree ni n g. Aft er a d mi nistrati o n of st u d y dr u g, 
a n y k n o w n cas es of pre g na nc y i n fe mal e s u bjects will be re p orte d u ntil t he s u bject c o m pletes or 
wit h dra ws fr o m t he st u d y. T he pre g n a nc y will be re p orte d i m me diatel y b y fa xi n g/e maili n g a 
c o m plete d pre g n a nc y re p ort t o t he S p o ns or ( or desi g nee) wit hi n 2 4 h o urs of k n o wle d ge of t he 
e ve nt. T he pre g na n c y will n ot be pr ocesse d as a n S A E; h o we v er, t he i n vesti gat or will f oll o w- u p 
wit h t he s u bject u ntil c o m pleti o n of t he pre g na n c y a n d m ust ass ess t he o utc o me i n t he s h ortest 
p ossi ble ti me b ut n ot m ore t ha n 3 0 da ys after c o m pleti o n of t he pre g na n c y. T he i n vesti gat or 
s h o ul d n otif y t he S p o ns or ( or desi g nee) of t h e pre g na n c y o utc o me b y s u b mitti n g a f oll o w- u p 
pre g na nc y re p ort. If t he o utc o me of t he pre g na nc y i n v ol ve d s p o nta ne o us or t hera pe utic a b orti o n 
(a n y c o n ge nital a n o mal y detecte d i n a n a b orte d fet us is t o be d oc u me nte d), still birt h, ne o natal 
P P D
P P D
P P D
P P D

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 6 5  of 8 9  
deat h, or c o n ge nital a n o mal y, t he i n vesti gat or will  re p ort t he e v e nt as a n S A E b y fa xi n g/e maili n g 
a c o m plete d pre g na nc y re p ort f or m t o t he S p o ns or  ( or desi g nee) wit hi n 2 4 h o urs of k n o wle d ge of 
t he e ve nt. 
If t he i n vesti gat or bec o m es a ware of a pre g n a nc y occ urri n g i n t he p art ner of a s u bject 
partici pati n g i n t he st u d y, t he pre g na n c y s h o ul d be re p orte d t o t he S p o ns or ( or desi g n ee) wit hi n 
2 4 h o urs of k n o wle d ge of t he e ve nt. D etails of t he pre g na nc y m ust o nl y be c ollecte d after 
o btai ni n g writte n c o ns e nt fr o m t he pre g n a nt part ner. A se parate pre g na nt part ner c o nse nt f or m 
will be use d t o o btai n t he c o nse nt fr o m pr e g na nt p art ner. T h e i n vesti gat or will arra n ge 
c o u nseli n g f or t he pre g na nt part ner b y a s p ecialist t o disc uss t he ris ks of c o nti n ui n g wit h t he 
pre g na nc y a n d t he p ossi ble effects o n t he fet us. T he pre g na nt p art ner will be f oll o we d t o ter m 
a n d t he o utc o me of t he pre g na nc y will be re p ort e d t o t he S p o ns or ( or desi g nee). 
U p o n disc o nti n uati o n fr o m t he st u d y, o nl y t h os e pr oce d ures t hat w o ul d n ot e x p ose t he s u bject t o 
u n d ue ris k will be perf or me d. T he i n vesti gat or s h o ul d als o be n otifie d of pre g na nc y o cc urri n g 
d uri n g t he st u d y b ut c o nfir me d after c o m pleti o n of t he st u d y. I n t he e ve nt t hat a s u bject is 
s u bse q ue ntl y f o u n d t o be pre g na nt after i ncl usi o n i n t he st u d y, a n y pre g na n c y will be f oll o we d t o 
ter m, a n d t he stat us of m ot her a n d c hil d will be re p orte d t o t he S p o ns or ( or desi g nee) after 
deli ver y as des cri be d i n Secti o n 1 2. 6. 4 . 
1 2. 6. 7  
O ver d ose 
F or t he p ur p os es of t his st u d y, o ver d ose is defi ne d as a n acci de ntal or i nte nti o nal use of a d ose 
hi g her t h a n t he pr ot oc ol rec o m me n de d d ose. I n case of o ver d ose, s u bjects will be m o nit ore d f or 
a n y si g ns or s y m pt o ms of a d vers e reacti o ns a n d a p pr o priate s y m pt o matic treat me nt be i nstit ute d 
i m me diatel y. 
T he i n vesti gat or m ust i m me diatel y n otif y t he S p o ns or ( or desi g nee) of a n y occ urre nce of 
o ver d ose wit h st u d y dr u g. 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 6 6  of 8 9  
1 3  P H A R M A C O KI N E TI C S 
1 3. 1  P h ar m a c o ki netic S a m pli n g 
1 3. 1. 1  
Bl o o d S a m ples 
Bl o o d sa m ples f or P K a n al ysis of M E 3 1 8 3 a n d its meta b olite ( 
) le vels will be c ollecte d 
pre d ose at t he ti me p oi nts i n dicate d  i n t he Sc he d ule of Assess me nts (Ta bl e 1 ). T he act ual date 
a n d ti me of t he st u d y dr u g a d mi nistrati o ns ( b ot h m or ni n g a n d e ve ni n g i n t he pre vi o us da y) a n d 
eac h bl o o d sa m ple c ollecti o n will be rec or de d o n t he s u bject’s e C R F . 
Details of P K bl o o d sa m ple c ollecti o n, pr ocessi n g, st ora ge, a n d s hi p pi n g pr oce d ures are pr o vi de d 
i n t he la b orat or y ma n u al. 
1 3. 2  P h ar m a c o ki netic A n al ytic al Met h o d ol o g y 
T he C tr o u g h of st u d y dr u g a n d its meta b olite ( 
) will be deter mi ne d fr o m t he plas ma 
sa m ples usi n g a v ali date d a nal yti cal met h o d. Det ails of t he met h o d vali dati o n a n d sa m ple 
a nal ysis will be i ncl u d e d wit h t he fi nal cli nical st u d y re p ort. 
A d diti o nal para meters ma y b e esti mate d a n d re p orte d, as a p pr o priate. 
C CI
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 6 7  of 8 9  
1 4  O T H E R A S S E S S M E N T S 
1 4. 2  Me dic al P h ot o gr a p h y of Affecte d S ki n Are a 
P h ot o gra p hs of t h e affect e d s ki n area (tar get s ki n  lesi o n) will be ta ke n at sel ecte d sites i n a 
selecte d n u m ber of s u bjects f or d oc u me ntati o n a n d/ or p u blicati o n p ur p oses o nl y. T he s u bject 
m ust si g n a se parate I C F f or p h ot o gra p hs t o be ta ke n. A t hir d- part y v e n d or ( desi g n ate d b y t he 
S p o ns or) will s u p pl y t h e p h ot o gra p h y e q ui p me nt t o t he selecte d sites al o n g wit h t he user ma n ual 
c o ntai ni n g c o ntact i nf or mati o n, q uic k refere nce g ui de, a n d s u p pl y re q uest f or ms. Sites will 
tra ns mit di gital i ma ges t o t he t hir d- part y ve n d or. 
1 4. 3  C ol u m bi a- S uici de Se verit y R ati n g Sc ale 
T he C- S S R S is a s uici dal i deati o n a n d be ha vi or rati n g scal e create d b y researc hers at C ol u m bia 
U ni versit y, U ni v ersit y of Pe n ns yl va nia, U ni versit y of Pitts b ur g h, a n d Ne w Y or k U ni versit y t o 
e val uate s uici de ris k. It is a d mi nistere d as a cli nical i nter vie w. 
S u bjects will be as ke d t o self-re p ort usi n g t he C- S S R S. S u bjects wit h acti ve s uici dal i deati o n or 
be ha vi or wit hi n t he past 1 2 m o nt hs base d o n “ yes ” res p o nse t o q u esti o n 3, 4, or 5 at Scree ni n g or 
Baseli ne will be e x cl u de d fr o m t he st u d y.  
See A P P E N DI X 6  f or t he detaile d q uesti o n nair e t o be a d mi nistere d t o eac h s u bject. 
 
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 6 8  of 8 9  
1 5  S T A TI S TI C A L A N A L Y SI S 
A S A P will be pre pare d after t he pr ot oc ol is a p pr o ve d. T his d oc u me nt will pr o vi de f urt her details 
re gar di n g t he d efi niti o n of a nal ysis varia bl es a n d a nal ysis met h o d ol o g y t o a d dress all st u d y 
o bjecti ves. T he S A P will ser ve as a c o m pli me nt t o t he pr ot oc ol a n d s u perse des it i n case of 
differe n ces. 
T he statistical e val uati o n will be perf or me d usi n g S A S ®  s oft ware v ersi o n 9. 4 or hi g h er 
( S A S®  I nstit ute, Car y, N C). All data will be liste d, a n d s u m mar y ta bles will be pr o vi de d. 
S u m mar y statistics will be prese nt e d b y treat m e nt gr o u p. F or c o nti n u o us varia bles, data will be 
s u m marize d wit h t he n u m ber of s u bjects ( N), mea n, sta n dar d de viati o n, me dia n, mi ni m u m, a n d 
ma xi m u m b y treat me nt gr o u p. F or cate g orical varia bles, data will be ta b ulat e d wit h t he n u m ber 
a n d perce nta ge of s u bjects f or eac h cat e g or y b y treat me nt gr o u p. 
1 5. 1  Deter mi n ati o n of S a m ple Size 
N o f or mal sa m ple siz e calc ulati o n was perf or me d.  
F or t he ass ess me nt of efficac y a n d s afet y of M E 3 1 8 3 i n s u bjects wit h m o derate t o se v ere pl a q ue 
ps oriasis i n t his pr o of- of- c o nce pt st u d y, a p pr o xi m atel y 1 2 5 eli gi ble s u bjects will be e nr olle d. 
T we nt y-fi ve s u bjects will be ra n d o mize d t o eac h of t he f oll o wi n g tr eat me nt gr o u ps: M E 3 1 8 3   
m g BI D, M E 3 1 8 3   m g Q D, M E 3 1 8 3  
 m g BI D; M E 3 1 8 3   m g Q D, a n d place b o. T he 
n u m ber of pla n ne d s u bjects is c o nsi dere d a d e q uat e t o assess safet y a n d t o pr o vi de effi cac y 
esti mates f or i n t his P hase 2a st u d y. T he e x pecte d dr o p- o ut rate is ass u me d t o be 1 0 %. 
1 5. 2  A n al ysis Sets 
F ull A n al ysis Set  
All s u bjects w h o ha ve bee n ra n d o mize d, recei ve d at least 1 d ose of st u d y dr u g, a n d h a ve at least 
1 e val ua ble p ost- Bas eli ne ti me p oi nt f or pri mar y e n d p oi nt will be i ncl u de d i n t he f ull a nal ysis 
set ( F A S). A n al ys es i n t he F A S will be bas e d o n t he s u bject’s ra n d o mize d treat me nt gr o u p.   
Per Pr ot oc ol Set  
T he per pr ot o c ol set ( P P S) is a s u bset of t he F A S; t he P P S will e x cl u de s u bjects wit h pr ot oc ol 
de viati o ns t hat ma y si g nifica ntl y i m pact t he assess me nt of t he pri mar y o bjecti ve of t he st u d y. 
A nal ys es i n t he P P S will be base d o n t he st u d y treat me nt act uall y recei ve d b y eac h s u bject. All 
decisi o ns t o e x cl u de s u bjects fr o m t he P P S will be ma de pri or t o t he u n bli n di n g of t he st u d y. 
C CI
C CI
C CI
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 6 9  of 8 9  
S afet y A n al ysis Set 
All ra n d o mize d s u bjects w h o recei ve d at least 1 d ose  of st u d y dr u g will be i ncl u de d i n t he safet y 
a nal ysis s et. A nal yses i n t he safet y a n al ysis set will be base d o n t he st u d y tr eat me nt act uall y 
recei v e d b y eac h s u bject. 
P h ar m a c o ki netic A n al ysis Set 
T he P K a nal ysis set will c o nsist of all s u bject s w h o were c orrectl y a d mi nistere d at least 1 
M E 3 1 8 3 d ose a n d w here M E 3 1 8 3 or  
 c o n ce ntrati o n data is a vaila ble wit h o ut a n y 
pr ot oc ol de viati o n i nterferi n g wit h t hese res ults. A n al yses i n t he P K a nal ysis set will be base d o n 
t he st u d y treat me nt act uall y recei ve d b y eac h s u bj ect. 
1 5. 3  Effic ac y A n al yses 
U nless ot her wise s pecifie d, all effic ac y a n al ys es will be perf or me d usi n g t h e F A S. T he a nal ysis 
of t he pri mar y effic ac y e n d p oi nt will als o be perf or me d usi n g t he P P S. 
1 5. 3. 1  
A n al ysis of t he Pri m a r y Effic ac y E n d p oi nt 
T he pri mar y effic ac y e n d p oi nt is t he pr o p orti o n of s u bjects ac hie vi n g ≥ 7 5 % re d ucti o n fr o m 
Baseli ne i n t he P A SI sc ore at W ee k 1 6. F or e ac h M E 3 1 8 3 treat me nt gr o u p, t he differe nce i n t he 
pr o p orti o n of s u bjects ac hie vi n g t he differe nce i n P A SI- 7 5 ( M E 3 1 8 3 –  pl ace b o) a n d its 9 5 % 
c o nfi de nce i nter val will be esti mate d a n d teste d f or s u peri or treat me nt effect usi n g t he C oc hra n-
Ma ntel- Hae nszel test at a 1-si de d si g nifica nce le vel of α  = 0. 0 2 5. T he P A SI sc ore will be 
re p orte d f or eac h treat me nt gr o u p t o get her wit h t he 9 5 % c o nfi d e nce i nter val f or mea n. 
1 5. 3. 2  
A n al yses of t he Sec o n d ar y Effic ac y E n d p oi nts 
T he pr o p orti o n of s u bjects ac hie vi n g P A SI- 5 0, P A SI- 7 5, P A SI- 9 0, a n d P A SI- 1 0 0, t he pr o p orti o n 
of s u bjects wit h a n s P G A sc ore of “ 0” or “ 1” c o m bi ne d wit h 2- p oi nt re d ucti o n o n t he 5- p oi nt 
s P G A scale, a n d t he pr o p orti o n of s u bjects wit h at least a 5- p oi nt re d u cti o n fr o m Bas eli ne i n t he 
D L QI sc ore will be a n al yz e d si milar t o as t he pri mar y e n d p oi nt a nal ysis. 
T he pr o p orti o n of s u bjects ac hie vi n g P A SI- 5 0, P A SI- 7 5, P A SI- 9 0, a n d P A SI- 1 0 0, t he pr o p orti o n 
of s u bjects wit h a n s P G A sc ore of “ 0” or “ 1” c o m bi ne d wit h 2- p oi nt re d ucti o n o n t he 5- p oi nt 
s P G A scale, a n d t he pr o p orti o n of s u bjects wit h at least a 5- p oi nt re d u cti o n fr o m Bas eli ne i n t he 
D L QI sc ore will be s u m mariz e d b y tr eat me nt gr o u p a n d visit. T he perce nt c ha n ge fr o m Baseli ne 
i n P A SI sc ore a n d c h a n ge fr o m Baseli ne i n affecte d B S A, t he itc h N R S, a n d t he D L QI sc ore will 
be s u m mariz e d b y tr eat m e nt gr o u p a n d visit. T he perce nt c ha n ge fr o m Bas eli ne i n P A SI sc ore 
C CI
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 7 0  of 8 9  
a n d t he c ha n ge fr o m Bas eli ne i n t he affecte d B S A, t he D L QI sc ore, a n d t h e itc h N R S will be 
a nal yze d usi n g a mi x e d-effect m o del f o r re p eate d meas ures w h e n a p plica bl e. 
Ka pla n- Mei er esti mate will be use d f or s u m marizi n g t he ti me t o P A SI- 5 0 a n d P A SI- 7 5. T h e 
l o g-ra n k test ma y be us e d f or c o m pari n g t he ti me t o P A SI- 5 0 a n d P A SI- 7 5 bet wee n eac h 
M E 3 1 8 3 treat me nt gr o u p a n d place b o. T h e C o x pr o p or ti o nal hazar d m o del ma y als o be use d f or 
a nal yzi n g t he ti me t o P A SI- 5 0 a n d P A SI- 7 5. T he ti me t o P A SI- 5 0 a n d P A SI- 7 5 will be 
s u m marize d b y treat me nt gr o u p. 
1 5. 3. 3  
A n al yses of t he E x pl or at or y Effic ac y E n d p oi nts 
1 5. 4  S afet y A n al yses 
All safet y a nal yses will be perf or me d usi n g t he safet y a nal ysis set. All rec or de d A E a n d S A Es 
will be liste d a n d ta b ulate d b y M e dical Dicti o nar y f or R e g ulat or y Acti vities ( versi o n 2 4. 1 or 
hi g her) s yste m or ga n class, preferre d ter m, a n d tr eat me nt gr o u p o ver t he 1 6- wee k Treat me nt 
Peri o d a n d t he 4- w ee k F oll o w- u p Peri o d. 
T he i nci de nce of T E A Es (e ve nts wit h o nset dates o n or after t h e first d ose of t he st u d y dr u g or 
t hat was prese nt pri or t o d osi n g a n d e x acer bat es after t he first d ose of st u d y dr u g) will be 
i ncl u de d i n i nci de nce ta bles. E ve nts wit h missi n g o nset dates will be i ncl u d e d as T E A Es. If a 
s u bject e x perie nces m or e t ha n 1 occ urre nce of t he sa me A E, t he occ urre nce wit h t he greatest 
se verit y a n d t he cl osest ass ociati o n wit h t he st u d y dr u g will be use d i n t he s u m mar y ta bl es. S A Es 
a n d A Es ca usi n g st u d y disc o nti n uati o n will be ta b ula te d. All A Es will be liste d b y s u bject, al o n g 
wit h i nf or mati o n re gar di n g o nset, d ur ati o n, relati o ns hi p a n d se verit y t o st u d y dr u g, s eri o us ness, 
acti o n ta ke n wit h st u d y dr u g, tr eat me nt of e ve nt, a n d o utc o me. 
Vital si g ns a n d safet y la b orat or y res ults will be  liste d a n d s u m marize d b y tr eat me nt gr o u p o ver 
t he 1 6- wee k Treat me nt Peri o d a n d t he 4- wee k F oll o w- u p Peri o d. S u m maries will be pr o vi de d 
usi n g descri pti ve statistics, i ncl u di n g mea n v al u es a n d mea n c h a n ge fr o m Baseli ne val ues, as 
well as n u m bers of s u bjects wit h val ues o utsi de  li mits of t he n or mal ra n ge at eac h ti me p oi nt. 
A n y C S p h ysi cal e x a mi nati o n fi n di n gs a n d safet y  la b orat or y res ults will be s u m marize d. E C G 
rea di n gs will be e v al uate d b y t he i n vesti gat or an d a b n or malities, if prese nt, will be s u m marize d 
a n d liste d. T he cli nicall y n ote w ort h y Q T/ Q Tc i nter val ( > 4 5 0, > 4 8 0, or > 5 0 0 msec) or cli nicall y 
n ote w ort h y c ha n ge fr o m Baseli ne ( > 3 0 or > 6 0 ms ec) will als o be s u m mari ze d usi n g descri pti ve 
statistics. 
S u m mar y ta bles will be pr o vi de d f or c o nc o mita n t me dicati o ns i nitiate d d uri n g t he st u d y peri o d. 
1 5. 5  P h ar m a c o ki netic A n al ysis 
T he P K a nal ysis set will be us e d f or t h e P K a nal ysis. T he C tr o u g h of M E 3 1 8 3 a n d its meta b olite 
( 
) will be s u m m arize d descri pti vel y b y tr eat me nt gr o u p i n t he T F L. 
C CI
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 7 1  of 8 9  
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 7 2  of 8 9  
1 6  S T U D Y M A N A G E M E N T 
1 6. 1  A p pr o v al a n d C o nse nt 
1 6. 1. 1  
Re g ul at or y G ui deli nes 
T his st u d y will be c o n d u cte d i n acc or da n ce wit h t he acce pte d versi o n of t h e Decl arati o n of 
Helsi n ki a n d/ or all rele v a nt re g ul ati o ns, as set f ort h i n Parts 5 0, 5 6, 3 1 2, S u b part D, of Title 2 1 of 
t he U S C o de of Fe d eral Re g ulati o ns ( C F R), i n c o m plia nce wit h I C H a n d G C P g ui deli nes a n d 
acc or di n g t o t he a p pr o pri ate re g ulat or y re q uir e me nts i n t he c o u ntries w here t he st u d y was 
c o n d ucte d. 
1 6. 1. 2  
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 
C o n d uct of t he st u d y m ust be a p pr o ve d b y a n a p pr o priatel y c o nstit ute d I E C/I R B. A p pr o val is 
re q uire d f or t he st u d y pr ot oc ol, pr ot oc ol a me n d me nts (if a p plica ble), I B, I C Fs, recr uit me nt 
material a n d s u bject i nf or mati o n s heets, a n d ot her s u bject-faci n g m aterial. Writte n a p pr o val of 
t he st u d y a n d all rele v a nt st u d y i nf or mati o n m ust be o btai ne d bef ore t he st u d y ce nter ca n be 
i nitiate d or t he st u d y dr u g is rel ease d t o t he i n vesti gat or. A n y necessar y e xte nsi o ns or re ne wals 
of I E C/I R B a p pr o val m ust be o btai ne d f or c h a n ges t o t he st u d y s uc h as a me n d me nts t o t he 
pr ot oc ol, t he I C F or ot h er st u d y d oc u m e ntati o n. T he writte n a p pr o val of t h e I E C/I R B t o get her 
wit h t he a p pr o ve d I C F m ust be file d i n t he st u d y files. 
T he i n vesti gat or will pr o m ptl y re p ort t o t he I E C/I R B a n y ne w i nf or mati o n t hat ma y a d versel y 
affect t he safet y of t he s u bjects or t he c o n d u ct of t he st u d y. T h e i n vesti gat or will s u b mit writte n 
s u m maries of t he st u d y st at us t o t he I E C/I R B as re q uire d. O n c o m pleti o n of t he st u d y, t he 
I E C/I R B will be n otifie d t hat t he st u d y has e n de d. 
1 6. 1. 3  
I nf or me d C o nse nt 
F or eac h st u d y s u bject, writte n i nf or me d c o nse nt will be o btai ne d bef ore a n y pr ot oc ol-relat e d 
acti vities. As part of t his pr oce d ure, t he pri nci p al i n vesti gat or ( PI) or d esi g n ee m ust e x plai n 
orall y a n d i n writi n g t h e nat ure of t he st u d y, its p ur p ose, pr oce d ures, e x pecte d d urati o n, 
alter nati ve t hera p y a v aila ble, a n d t he be n efits a n d ris ks i n v ol ve d i n st u d y p artici pati o n. T he 
s u bject s h o ul d be i nf or m e d t hat he/s he ma y wit h dra w fr o m t he st u d y at a n y ti me, a n d t he s u bject 
will recei ve all i nf or mati o n t hat is re q uire d b y l ocal re g ulati o ns a n d g ui deli nes f or I C H. T h e PI 
will pr o vi de t he S p o ns or or its re prese nt ati ve wit h a c o p y of t he I E C-/I R B-a p pr o ve d I C F b ef ore 
t he start of t he st u d y. 
T he I C F s h o ul d be re vise d w he ne ver t here are s u bsta ntial c ha n ges t o pr oce d ures or w h e n ne w 
i nf or mati o n bec o mes a v aila ble t hat ma y affect t he willi n g ness of t he s u bject t o partici pate. 
Re visi o ns t o t he c o nse nt f or m re q uir e d d uri n g t he st u d y m ust be a p pr o ve d b y t he S p o ns or, a n d a 
c o p y of t he re vise d c o nse nt f or m is pr o vi de d t o t he S p o ns or. F or a n y u p d ate d or re vise d f or ms, 
t he s u bjects m ust be re- c o nse nte d f or c o nti n ue d partici pati o n i n t he st u d y. 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 7 3  of 8 9  
A pre g na nt part ner c o nse nt f or m s h o ul d be o btai ne d bef ore c ollecti n g a n y data fr o m a fe male 
pre g na nt part ner of a mal e s u bject, if bec o mes pre g na nt d uri n g t he c o urse of t he st u d y or wit hi n 
4 wee ks of t he l ast d ose of st u d y dr u g. 
1 6. 2  D at a H a n dli n g 
A n y d ata t o be rec or de d directl y i n t he e C R Fs (t o be c o nsi dere d as s o urce d ata) will be i de ntifie d 
at t he start of t he st u d y. Data re p orte d i n t he e C R F t hat are deri v e d fr o m s o urce d oc u m e nts 
s h o ul d be c o nsiste nt wit h t he s o urce d o c u me nts, or t he discre p a ncies m ust be e x plai ne d. See als o 
Secti o n 1 6. 3 . 
Cli nical data will be e ntere d b y site pers o n nel  o n e C R Fs f or tra ns missi o n t o t he S p o ns or. Data o n 
e C R Fs tra ns mitte d via t he we b- b ase d dat a s yst e m m ust c orres p o n d t o a n d b e s u p p orte d b y s o urce 
d oc u me ntati o n mai ntai ne d at t he st u d y site, u nless t he st u d y site ma kes direct data e ntr y t o t he 
data bases f or w hic h n o ot her ori gi nal or s o urce d o c u me ntati o n is mai ntai ne d. I n s u c h cas es, t he 
st u d y site s h o ul d d oc u me nt w hic h e C R Fs are s u bject t o direct dat a e ntr y a n d s h o ul d ha ve i n 
place pr oce d ures t o o btai n a n d retai n c o pi es of t he i nf or mati o n s u b mitte d b y direct data e ntr y. 
All st u d y f or ms a n d rec or ds tra ns mitte d t o t he S p o ns or m ust o nl y i ncl u de c o de d i de ntifiers s u c h 
t hat directl y i d e ntif yi n g p ers o nal i nf or mati o n is n ot tra ns mitte d. T he pri mar y met h o d of d ata 
tra ns mittal is via t he sec ure, i nter net- b ase d electr o nic data ca pt ure ( E D C) s yste m mai ntai ne d b y 
. Access t o t he E D C s yste m is a vail a ble t o o nl y a ut h orize d users via t he st u d y’s 
i nter net we b site, w h ere a user u ni q ue assi g n e d us er na me a n d pass w or d are re q uire d f or access. 
A n y c ha n ges m a de t o dat a after c ollecti o n will be ma de t hr o u g h t he use of t he E D C s yste m. 
e C R Fs will be c o nsi dere d c o m plete w he n all missi n g a n d/ or i nc orrect data ha ve bee n res ol ve d. 
1 6. 3  S o urce D oc u me nts 
S o urce d oc u me nts are c o nsi dere d t o be all i nf or m a ti o n i n ori gi nal rec or ds a n d certifi e d c o pies of 
ori gi nal rec or ds of cli nic al fi n di n gs, o bser vati o ns, data, or ot her acti vities i n a cli nical st u d y 
necessar y f or t he rec o nstr ucti o n a n d e val u ati o n of t he st u d y. T he i n v esti gat or will pr o vi de direct 
access t o s o urce d o c u me nts a n d/ or s o urce d ata i n t he facilitati o n of st u d y-relate d m o nit ori n g, 
a u dits, re vie w b y I E Cs/I R Bs, a n d re g ul at or y i ns pecti o ns. 
T he i n vesti gat or/i nstit uti o n s h o ul d mai ntai n a de q uate a n d acc urate s o urce d oc u me nts a n d st u d y 
rec or ds t hat i ncl u d e all p erti ne nt o bser vati o ns o n eac h of t h e site’s st u d y s u bjects. S o urce dat a 
s h o ul d be attri b uta ble, le gi ble, c o nt e m p ora ne o us, ori gi nal, acc urate, a n d c o m plete. C ha n ges t o 
s o urce dat a s h o ul d be tracea ble, n ot o bsc ure t he ori gi nal e ntr y, a n d be e x plai ne d if necessar y. 
Re g ulat or y a ge n cies ma y re q uest a ccess t o all st u d y rec or ds, i ncl u di n g s o urce d oc u me nts, f or 
i ns pecti o n a n d c o p yi n g, i n kee pi n g wit h c o u ntr y re g ul ati o ns. T he i n vesti gat or s h o ul d 
i m me diatel y n otif y t he S p o ns or of a n y a n n o u n ce d or u na n n o u nce d re g ulat or y a ge nc y 
i ns pecti o ns. A n a u diti n g i ns pecti o n ma y als o be c o n d ucte d b y t he S p o ns or re pres e ntati ve or 
desi g nee. A n y as pect of t he st u d y ma y b e s u bject t o a u dit b y t he S p o ns or a n d/ or i ns pecti o n b y 
re g ulat or y a ut h orities or t he I R B/I E C. S uc h a u dits/i ns pecti o ns ma y ta ke place at t he S p o ns or’s 
P P D

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 7 4  of 8 9  
site(s), 
, or at t he cli nical sites, i ncl u di n g la b orat ories, p har macies a n d a n y ot her 
facilities use d f or t he st u d y. T he i n v esti gat or will per mit t he desi g n ate d S p o ns or re prese ntati ves 
a n d re g ulat or y b o di es t o ha ve direct access t o t he s o urce d oc u m e nts t o verif y d ata re pres e nte d i n 
t he E D C s yste m. 
1 6. 4  Rec or d R ete nti o n 
St u d y rec or ds a n d s o ur ce d oc u me nts m ust be pres er ve d f or at least 2 5 years after t he c o m pleti o n 
or disc o nti n uati o n of/ wit h dra wal fr o m t he st u d y, at least 2 years after t he dr u g b ei n g st u die d has 
recei v e d its last a p pr o val f or sale, or at least 2 years after t he dr u g de vel o p m e nt has st o p pe d, a n d 
i n acc or da nce wit h t he a p plica ble l ocal pri vac y la ws, w hic he ver is t he l o n ger ti me peri o d. 
T he i n vesti gat or a grees t o c o m pl y wit h all a p plica ble fe deral, state, a n d l o cal la ws a n d 
re g ulati o ns relati n g t o t he pri vac y of s u bject healt h i nf or mati o n, i ncl u di n g, b ut n ot li mite d t o, t he 
Sta n dar ds f or I n di vi d uall y I d e ntifia ble Healt h I nf or mati o n, 4 5 C F R, Parts 1 6 0 a n d 1 6 4 (t he 
Healt h I ns ura nce P orta bilit y Acc o u nta bilit y Act of 1 9 9 6 Pri vac y Re g ulati o n). T he i n vesti gat or 
s hall e ns ure t hat st u d y s u bjects a ut h orize t he use a n d discl os ure of pr otecte d healt h i nf or mati o n 
i n acc or da nce wit h Healt h I ns ura nce P orta bility Acc o u nta bilit y Act Pri vac y Re g ulati o n a n d i n a 
f or m satisfact or y t o t he S p o ns or. 
1 6. 5  M o nit ori n g 
T he st u d y will be m o nit ore d acc or di n g t o 
 m o nit ori n g pla n a p pr o ve d b y t he 
S p o ns or t o e ns ure t hat it is c o n d ucte d a n d d oc u m e nte d pr o perl y acc or di n g t o t he pr ot oc ol, G C P, 
a n d all a p plica ble re g ulat or y re q uire m e nts. 
M o nit ori n g visits, o n-site a n d re m ote a n d c o ntac ts will be ma de at a p pr o priate ti mes d uri n g t he 
st u d y. T he PI will ass ur e hi m/ her a n d a de q u ate site pers o n nel are a vaila ble t hr o u g h o ut t he st u d y 
t o c olla b orate wit h cli nic al m o nit ors. Cli nical m o nit ors m ust ha ve direct access t o s o urce 
d oc u me ntati o n t o c hec k t he c o m plete ness, clarit y, a n d c o nsiste nc y of t he d ata rec or de d i n t he 
e C R Fs f or eac h s u bject. 
T he i n vesti gat or will ma ke a vaila ble t o t he cl i nical m o nit or all s o urce d oc u me nts a n d me dical 
rec or ds n ecess ar y t o re vie w pr otoc ol a d here n ce a n d e C R Fs. I n a d diti o n, t he i n vesti gat or will 
w or k cl osel y wit h t he cli nical m o nit or a n d as ne e de d, pr o vi de t he m a p pr o priate e vi de nce t hat t he 
st u d y is bei n g c o n d uct e d i n acc or da nce wit h t he pr ot oc ol, a p plica ble re g ulati o ns, a n d G C P 
g ui deli nes. 
1 6. 6  Q u alit y C o ntr ol a n d Q u alit y Ass ur a nce 
T he S p o ns or or its desi g n ee will perf or m t he q ualit y  ass ura nce a n d q u alit y c o ntr ol acti vities of 
t his st u d y; h o w e ver, res p o nsi bilit y f or t h e acc urac y, c o m plet e ness, sec urit y, a n d relia bilit y of t he 
st u d y data prese nte d t o t h e S p o ns or lies wit h t he i n vesti gat or ge nerati n g t h e data. 
T he S p o ns or or its desi g n ee will arra n ge a u dits as part of t he i m ple me ntati o n of q ualit y 
ass ura nce t o e ns ure t hat t he st u d y is bei n g c o n d u ct e d i n c o m plia nce wit h t h e pr ot oc ol, sta n dar d 
P P D
P P D

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 7 5  of 8 9  
o perati n g pr oce d ures, G C P, a n d all a p plica ble re g ulat or y re q uire m e nts. A u dits will be 
i n de pe n de nt of a n d s e parate fr o m t he r o uti ne m o nit ori n g a n d q u alit y c o ntr ol f u ncti o ns. Q ualit y 
ass ura nce pr oce d ures will be perf or m e d at st u d y sites a n d d uri n g data ma n a ge m e nt t o ass ure t hat 
safet y a n d effic ac y d ata are a de q u ate a n d well d oc u me nte d. 
1 6. 7  Pr ot oc ol A me n d me nt a n d Pr ot oc ol D e vi ati o n 
1 6. 7. 1  
Pr ot oc ol A me n d me nt 
A me n d me nts t o t he pr ot oc ol t hat e ntail c orrecti o ns of t y p o gra p hical err ors, clarificati o ns of 
c o nf usi n g w or di n g, c h a n ges i n st u d y pers o n nel, a n d mi n or m o dificati o ns t hat ha ve n o effect o n 
t he safet y of s u bjects or t he c o n d uct of t he st u d y will be classe d as a d mi nistrati ve a me n d me nts 
a n d will be s u b mitte d t o t he I E C/I R B f or i nf or mati o n o nl y. T he S p o ns or will e ns ure t hat 
ac k n o wle d g me nt is r ecei ve d a n d file d. A me n d m e nts  t hat are class e d as s u bsta ntial a me n d me nts 
m ust be s u b mitte d t o t he a p pr o priate re g ulat or y a ut h orities a n d t he I E Cs/I R Bs f or a p pr o val a n d 
will n ot be i m ple me nte d at sites u ntil s uc h a p pr o v als are recei ve d ot her t ha n i n t he case of a n 
ur ge nt safet y me as ure. 
1 6. 7. 2  
Pr ot oc ol D e vi ati o ns 
S h o ul d a pr ot oc ol de viati o n occ ur, t he S p o ns or m ust be i nf or me d as s o o n as p ossi ble. Pr ot oc ol 
de viati o ns a n d/ or vi olati o ns a n d t he reas o ns t he y o cc urre d will be i ncl u de d i n t he cli nical st u d y 
re p ort. Re p orti n g of pr ot oc ol de viati o ns t o t he I R B/I E C a n d i n acc or da nce wit h a p plica ble 
re g ulat or y a ut h orit y ma n dates is a site res p o nsi bilit y. 
1 6. 8  Et hic al C o nsi der ati o ns 
T his st u d y will be c o n d u cte d i n acc or da n ce w it h t his pr ot oc ol, t he acce pte d versi o n of t he 
Declarati o n of Helsi n ki a n d/ or all rele va nt f e deral re g ulati o ns, as set f ort h i n Parts 5 0, 5 6, 3 1 2, 
S u b part D, of Title 2 1 of t he C F R; a n d i n c o m plia nce wit h I C H G C P E 6 g ui deli nes. 
I E Cs/I R Bs will re vie w a n d a p pr o ve t his pr ot oc ol a n d t he I C F. All s u bjects are re q uire d t o gi ve 
writte n i nf or me d c o ns e nt bef ore p artici pati o n i n t he st u d y. 
1 6. 9  Fi n a nci n g a n d I ns ur a nce 
Bef ore t he st u d y c o m me nces, t he S p o ns or ( or  its desi g nee) a n d t he i n vesti gat or ( or t he 
i nstit uti o n, as a p plica ble) will a gree o n c osts necessar y t o perf or m t he st u d y. T his a gree me nt will 
be d oc u me nte d i n a fi na n cial a gree me nt t hat will be si g ne d b y t he i n vesti gat or ( or t he i nstit uti o n 
si g nat or y) a n d t he S p o ns or ( or its desi g nee). 
T he i n vesti gat or is re q uir e d t o ha ve a d e q uate c urre nt i ns ura nce t o c o ver clai ms f or ne gli ge nce 
a n d/ or mal practice. T he S p o ns or will pr o vi de n o-e x cl usi o n i ns ura nce c o vera ge f or t he cli nical 
st u d y as r e q uire d b y n ati o nal re g ulati o ns. 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 7 6  of 8 9  
1 6. 1 0  P u blic ati o n P olic y/ Discl os ure of D at a 
B ot h t he use of data a n d t he p u blicati o n p olic y are detaile d wit hi n t he cli nical st u d y a gree m e nt. 
I ntelle ct ual pr o pert y ri g hts (a n d relate d m atters) ge nerat e d b y t he i n vesti gat or a n d ot hers 
perf or mi n g t he cli nic al st u d y will be s u bject t o t he ter ms of a cli nical st u d y a gree m e nt t hat will 
be a gree d bet w ee n t he i nstit uti o n a n d t he S p o ns or or t heir desi g nee. Wit h res pect t o s uc h ri g hts, 
t he S p o ns or or its desi g n ee will s olel y o w n all ri g hts a n d i nterests i n a n y materials, d ata, a n d 
i ntellect ual pr o pert y ri g hts de vel o pe d b y i n vesti gat ors a n d ot hers perf or mi n g t he cli nical st u d y 
descri be d i n t his pr ot oc ol, s u bject t o t he ter ms of a n y s uc h a gree me nt. T o facilitate s uc h 
o w ners hi p, i n vesti gat ors will be re q uire d t o assi g n all s uc h i n ve nti o ns eit her t o t heir i nstit uti o n or 
directl y t o t he S p o ns or or its desi g nee, as will  be s et f ort h i n t he cli nical st u d y a gree m e nt. 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 7 7  of 8 9  
1 7  R E F E R E N C E S 
1.  G ulli ver W P, Ra n dell S, G ulli ver S, et al. D o  Bi ol o gics Pr otect Patie nts Wit h Ps oriasis 
Fr o m M y ocar dial I nfarcti o n? A Retr os pecti ve C o h ort. J C uta n Me d S ur g 2 0 1 6 
N o v; 2 0( 6): 5 3 6- 5 4 1. d oi: 1 0. 1 1 7 7/ 1 2 0 3 4 7 5 4 1 6 6 5 0 4 3 0. E p u b 2 0 1 6 Ma y 1 0.  
2.  Me nter A, G ottlie b A, Fel d ma n S R, et al. G ui deli nes of care f or t he ma na ge me nt of 
ps oriasis a n d ps oriatic art hritis: Secti o n 1. O ve r vie w of ps oriasis a n d g ui deli nes of care 
f or t he treat me nt of ps ori asis wit h bi ol o gics. J A m Aca d Der mat ol 2 0 0 8 Ma y; 5 8( 5): 8 2 6-
5 0. d oi: 1 0. 1 0 1 6/j.jaa d. 2 0 0 8. 0 2. 0 3 9.  
3.  Nati o nal Ps oriasis F o u n d ati o n. htt ps:// w w w. ps ori asis. or g/c o nte nt/statistics. Last u p d ate d 
0 8 Oct 2 0 2 0. Accesse d 0 5 Oct 2 0 2 1. 
4.  Se me n o v Y R, Her b osa C M, R o gers A T, et al. Ps oriasis a n d m ortalit y i n t he U nite d 
States: Data fr o m t he Nati o nal Healt h a n d N utriti o n E x a mi nati o n S ur ve y J A m Aca d 
Der mat ol. 2 0 2 1 A u g; 8 5( 2): 3 9 6- 4 0 3. d oi: 1 0. 1 0 1 6/j.jaa d. 2 0 1 9. 0 8. 0 1 1. E p u b 2 0 1 9 A u g 1 2.  
5.  S ha vit E, S hear N H. A n u p date o n t he safet y of a pre milast f or t he treat me nt of pla q ue 
ps oriasis. E x pert O pi n Dr u g Saf. 2 0 2 0 A pr; 1 9( 4): 4 0 3- 4 0 8. d oi: 
1 0. 1 0 8 0/ 1 4 7 4 0 3 3 8. 2 0 2 0. 1 7 4 4 5 6 2. E p u b 2 0 2 0 Mar 2 1.  
6.  Datt ola A, Del D u ca E, S arace n o R, et al. Safet y e val uati o n of a pre milast f or t he 
treat me nt of ps oriasis. E x pert O pi n Dr u g Saf. 2 0 1 7 Mar; 1 6( 3): 3 8 1- 3 8 5. d oi: 
1 0. 1 0 8 0/ 1 4 7 4 0 3 3 8. 2 0 1 7. 1 2 8 8 7 1 4. E p u b 2 0 1 7 Fe b 7.  
7.  Fre dri kss o n T, Petterss o n U. Se vere ps or iasis -- oral t hera p y wit h a ne w reti n oi d. 
Der mat ol o gica. 1 9 7 8; 1 5 7( 4): 2 3 8- 2 4 4. d oi: 1 0. 1 1 5 9/ 0 0 0 2 5 0 8 3 9. 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 7 8  of 8 9  
1 8  A P P E N DI C E S 
A P P E N DI X 1 . C O N T R A C E P TI O N G UI D E LI N E S 
A P P E N DI X 2 . P R O HI BI T E D C O N C O MI T A N T M E DI C A TI O N S A N D P R O C E D U R E S 
A P P E N DI X 3 . P S O RI A SI S A R E A S E V E RI T Y I N D E X–  W O R K S H E E T 
A P P E N DI X 4 . 5- P OI N T S T A T C PH Y SI CI A N’ S G L O B A L A S S E S S M E N T 
A P P E N DI X 5 . D E R M A T O L O G Y LI F E Q U A LI T Y I N D E X  
A P P E N DI X 6 . C O L U M BI A- S UI CI D E S E V E RI T Y R A TI N G S C A L E 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 7 9  of 8 9  
A P P E N DI X 1.  
C O N T R A C E P TI O N G UI D E LI N E S 
W o me n of c hil d beari n g p ote ntial ( W O C B P) m ust use at least 1 hi g hl y effecti ve met h o d of 
c o ntrace pti o n d uri n g t h e starti n g at Scree ni n g, c o nti n ui n g t hr o u g h o ut t he e ntire Treat me nt 
Peri o d, a n d f or at least 4 wee ks after ta ki n g t he last d ose of st u d y tr eat me nt.  
Fertile me n w h os e se x ual part ners are W O C B P m ust practice se x ual a bsti n e nce or t o us e a 
c o n d o m d uri n g s e x ual acti vit y wit h t heir fe male p art ner of c hil d beari n g p ot e ntial starti n g at 
Scree ni n g, c o nti n ui n g t hr o u g h o ut t he e ntire Tr eat me nt Peri o d, a n d f or at least 4 wee ks after 
ta ki n g t he last d ose of st u d y treat me nt. A d diti o nall y, if t heir p art ner is a W O C B P, t he n t heir 
part ner s h o ul d be a d vise d t o use a hi g hl y effect i ve c o ntrace pti ve meas ure d uri n g se x ual acti vit y 
starti n g at Scree ni n g, c o nti n ui n g t hr o u g h o ut t he e ntire Treat me nt Peri o d, a n d f or at least 4 w ee ks 
after ta ki n g t he last d os e of st u d y tr eat me nt. 
A w o ma n is c o nsi dere d t o be a W O C B P (fertile) after me narc he a n d u ntil bec o mi n g 
p ost me n o pa usal, u nless s he is per ma ne ntl y ster ile. Per ma ne nt steriliz ati o n met h o ds i ncl u de 
h ysterect o m y, bilateral sal pi n gect o m y, a n d bi lateral o o p h orect o m y. A p ost me n o pa usal state is 
defi ne d as n o me ns es f or 1 2 m o nt hs wit h o ut a n alter nati ve me dical ca us e. A hi g h 
f ollicle-sti m ulati n g h or m o ne ( F S H) l e vel i n t he p ost me n o pa usal ra n ge m a y be use d t o c o nfir m a 
p ost me n o pa usal state i n w o me n n ot usi n g h or m o n al c o ntrace pti o n or h or m o nal re place me nt 
t hera p y. H o we ver, i n t he a bse nce of 1 2 m o nt hs of a me n orr hea, a si n gle F S H meas ure m e nt is 
i ns ufficie nt. 
A ma n is c o nsi dere d fertile after p u bert y u nless per ma ne ntl y st erile b y bilat eral or c hi dect o m y. 
Hi g hl y effecti ve met h o ds of c o ntrace pti o n are t h ose w hic h ha v e a fail ure rate of < 1 % ( w he n 
i m ple me nte d c o nsiste ntl y a n d c orrectl y) a n d i n cl u de: 
 c o m bi ne d (c o ntai ni n g estr o ge n a n d pr o gest o ge n) h or m o nal c o ntrace pti o n ass ociate d wit h 
i n hi biti o n of o v ulati o n (a d mi nistrati o n ma y be oral, i ntra va gi n al, or tra ns d er mal) 
 pr o gest o ge n- o nl y h or m o nal c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n 
(a d mi nistrati o n ma y b e oral, i njecta ble, or i m pla nt a ble) 
 i ntra uteri ne de vic e 
 i ntra uteri ne h or m o ne-rel easi n g s yst e m 
 bilateral t u bal li gati o n or occl usi o n 
 vasect o m y ( pr o vi de d t h at t he male has a me di cal assess me nt of s ur gical s uc cess) 
 se x ual a bsti ne nce ( defi ne d as refrai ni n g fr o m het er ose x ual i nterc o urse d uri n g t he e ntire 
peri o d of ris k i n relati o n t o t he d urati o n of t he cli nical st u d y, i n li ne wit h t he preferre d 
a n d us ual lifest yl e of t he s u bject) 
All s u bjects will be str o n gl y a d vise d t hat t he y ( or t he fe male p art n ers of male s u bjects) s h o ul d 
n ot bec o me pre g n a nt w hile o n-st u d y tr eat me nt or f or 4 wee ks after t h e last d ose. A fe mal e 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 8 0  of 8 9  
s u bject will be a d vise d t h at s he m ust re p ort i mme diatel y t o t he st u d y site f or pre g na nc y t esti n g 
a n d a p pr o pri ate ma na ge me nt i n t he e ve nt t hat s he ma y be pre g na nt. 
Refere n ce 
1.  [ H M A] Hea ds of Me dici nes A ge ncies. Cli nical Trial Facilitati o n Gr o u p pa ge. 
Rec o m me n dati o ns relate d t o c o ntrace pti o n a n d pre g n a nc y testi n g i n cli nical trials. 
htt ps:// w w w. h ma.e u/filea d mi n/ dateie n/ H u ma n _ Me dici nes/ 0 1-
A b o ut _ H M A/ W or ki n g _ Gr o u ps/ C T F G/ 2 0 2 0 _ 0 9 _ H M A _ C T F G _ C o ntrace pti o n _ g ui da nce _ Ver
si o n _ 1. 1 _ u p date d. p df. 1 5 Se p 2 0 1 4. Access e d 0 4 Oct 2 0 2 1. 
 
 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 8 1  of 8 9  
A P P E N DI X 2.  
P R O HI BI T E D C O N C O MI T A N T M E DI C A TI O N S A N D 
P R O C E D U R E S 
T he f oll o wi n g c o nc o mita nt me dicati o ns a n d pr oce d ures are pr o hi bite d pri or t o ra n d o mizati o n 
a n d d uri n g t he c o urs e of t he st u d y u nless ot her wise s pecifie d. 
1.  T o pical t hera p y: 
T o pical t hera p y u nl ess ot her wise s pecifie d (i ncl u di n g b ut n ot li mite d t o t o pical 
c ortic oster oi ds, t o pical r eti n oi d [taz or ote n e] or vita mi n D a nal o g ue pre parati o ns 
[calci p otrie ne a n d calcitri ol], tacr oli m us, pi mecr oli m us, met h o xsale n, tri met h yl ps oral e n, 
pi mecr oli m us or a nt hrali n/ dit hra n ol). T o pical t h era p y is pr o hi bite d fr o m 2 wee ks pri or t o t he 
first a d mi nistrati o n of st u d y treat me nt u ntil 4 wee ks after t he last d ose of st u d y treat me nt 
u nless ot her wise s pecifie d i n Secti o n 9. 6. 1 . 
2.  S yste mic t hera p y: 
S yste mic t hera p y i ncl u di n g b ut n ot li mite d t o oral or i njecta ble reti n oi ds, a pre milast ( or a n y 
ot her P D E 4 i n hi bit ors), acitreti n, met h otre x ate,  c ycl os p ori ne, c ortic oster oi ds, m yc o p h e n olate 
m ofetil, 6-t hi o g ua ni ne, h y dr o x y urea, t hi o g ua ni n e, sir oli m us, is otreti n oi n, s ulfasalazi ne, 
azat hi o pri ne, or f u mari c aci d esters are b e pr o hi bite d fr o m 4 wee ks pri or t o t he first 
a d mi nistrati o n of st u d y tr eat me nt u ntil 4 w ee ks after t he last d ose of st u d y treat me nt. 
3.  Bi ol o gic A ge nts: 
 
T u m or necr osis f act or ( T N F)- α  i n hi bit ors (cert oliz u ma b pe g ol, eta nerce pt, a dali m u ma b, 
i nfli xi ma b, a n d g oli m u ma b) are pr o hi bite d fr o m 8 wee ks pri or t o t he first a d mi nistrati o n 
of st u d y tr eat me nt u ntil 4 wee ks after t he last d ose of st u d y tr eat me nt. 
 T N F- α  i n hi bit or, rit u xi ma b, is pr o hi bite d fr o m 2 4 wee ks pri or t o t he first a d mi nistrati o n 
of st u d y tr eat me nt u ntil 4 wee ks after t he last d ose of st u d y tr eat me nt. 
 I nterle u ki n (I L)- 1 2/ 2 3 i n hi bit ors ( uste ki n u ma b or a n y ot h er t hera pe utic a ge nt tar geti n g 
I L- 1 2 or I L- 2 3) is pr o hi bite d fr o m 2 4 wee ks pri or t o t he first a d mi nistrati o n of st u d y 
treat me nt u ntil 4 wee ks after t he last d ose of st u d y treat me nt. 
 I L- 1 7 i n hi bit ors (sec u ki n u ma b, i x e kiz u ma b, br o dal u ma b, or a n y ot her t hera pe utic a ge nt 
tar geti n g I L- 1 7) are pr o hi bite d fr o m 2 4 wee ks pri or t o t he first a d mi nistrati o n of st u d y 
treat me nt u ntil 4 wee ks after t he last d ose of st u d y treat me nt. 
C CI

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 8 2  of 8 9  
 I L- 2 3 i n hi bit ors (til dra kiz u ma b, risa n kiz uma b, g usel k u ma b, or a n y ot her t h era pe utic 
a ge nt tar geti n g I L- 2 3) are pr o hi bite d fr o m 2 4 wee ks pri or t o t he first a d mi nistrati o n of 
st u d y treat me nt u ntil 4 wee ks aft er t he last d ose of st u d y treat me nt. 
 I L- 1 2 i n hi bit ors ( bria ki n u ma b or a n y ot her t h era p e utic a ge nt tar geti n g I L- 1 2) are 
pr o hi bite d fr o m 2 4 wee ks pri or t o t he first a d mi nistrati o n of st u d y treat me nt u ntil 4 wee ks 
after t he l ast d ose of st u d y treat me nt. 
 T-cell i n hi bit ors: ale mt uz u ma b, a batace pt, aleface pt - fr o m 1 2 wee ks pri or t o t he first 
a d mi nistrati o n of st u d y tr eat me nt u ntil 4 wee k s after t he last d ose of st u d y treat me nt. 
 I nte gri n rece pt or a nta g o nist: nataliz u ma b - fr o m 1 2 wee ks pri or t o t he first a d mi nistrati o n 
of st u d y tr eat me nt u ntil 4 wee ks after t he last d ose of st u d y tr eat me nt. 
4.  P h ot ot hera p y: 
Pr ol o n ge d e x p os ure t o ultra vi olet B (i ncl u di n g narr o w ba n d ultra vi olet B, G oec ker ma n 
t hera p y a n d e x ci mer laser) or ps orale n ultra vi olet A u nless ot her wise s pecifie d i n Secti o n 8. 2 
a n d Secti o n 9. 6. 1 . P h ot ot hera p y is pr o hi bite d fr o m 4 wee ks pri or t o t he first a d mi nistrati o n of 
st u d y treat me nt u ntil 4 wee ks aft er t he last d ose of st u d y treat me nt. 
5.  Use of a n y i n vesti gati o nal dr u g: 
I n v esti gati o nal dr u gs f or bi ol o gic t hera p y are pr o hi bite d fr o m 2 4 wee ks pri or t o Da y 1 u ntil 
4 wee ks after t he last d os e of st u d y treat me nt. All n o n- bi ol o gic i n vesti gati o nal 
dr u gs/t hera p y/ de vices are pr o hi bite d fr o m 4 wee ks ( or 5 half-li ves w hi c he v er is l o n ger) pri or 
t o Da y 1 u ntil aft er t he last d ose of st u d y tr eat me nt. 
6.  Pr ol o n ge d s u n e x p os ure or use of artificial s u n bat hi n g (e g, t a n ni n g b o ot hs) or ot her U V li g ht 
s o urces fr o m Da y 1 u ntil after t he l ast d ose of st u d y treat me nt (ie, Treat me nt Peri o d). 
7.  S u bject has ha d a rece nt i nitiati o n of a dr u g t h at is k n o w n t o p ote ntiall y ca use or e x acer bate 
ps oriasis (i ncl u di n g, b ut n ot li mite d t o, beta bl oc kers, lit hi u m, a n d a nti- malarials), wit hi n t he 
8 wee ks pri or t o t he first a d mi nistrati o n of st u d y tr eat me nt; a t h ose s u bject w h o ha ve has 
bee n o n a sta ble d os e f or at least 8 wee ks pri or t o t he first a d mi nistrati o n of st u d y treat me nt 
wit h o ut e x acer bati o n of ps oriasis ma y b e e nr olle d ra n d o mize d a n d d oes n ot nee d t o 
disc o nti n ue t hese me dicati o ns. 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 8 3  of 8 9  
A P P E N DI X 3.  
P S O RI A SI S A R E A S E V E RI T Y I N D E X - W O R K S H E E T 
 
Refere n ce 
1.  Britis h Ass ociati o n of Der mat ol o gists. Accesse d at htt p:// w w w. ba d. or g. u k/s hare d/ get-
file.as h x?i d = 1 6 5 4 &ite mt y p e = d oc u me nt. Accesse d o n 0 5 Oct 2 0 2 1. 
 
 
T h e P s ori a si s Ar e a a n d S e v erit y I n d e x ( P A SI) i s a q u a ntit ati v e r ati n g s c or e f or m e a s uri n g t h e 
s e v erit y of p s ori ati c l e si o n s b a s e d o n ar e a c o v er a g e a n d pl a q u e a p p e ar a n c e. 
Pl a q u e c h ar a ct eri sti c 
L e si o n s c or e 
H e a d 
U p p er Li m b s 
Tr u n k 
L o w er Li m b s 
Er yt h e m a 
0 = N o n e 
1 = Sl ig ht 
I n d u r ati o n/ T hi c k n e s s 
2 = M o d er at e 
3 = S e v er e 
S c ali n g 
4 = V er y s e v er e 
A d d t o g et h er e a c h of t h e 3 s c or e s f or e a c h b o d y r e gi o n t o gi v e 4 s e p ar at e s u m s ( A). 
L e si o n S c or e S u m ( A) 
P er c e nt a g e ar e a 
Ar e a s c or e 
H e a d 
U p p er Li m b s 
Tr u n k 
L o w er Li m b s 
aff e ct e d 
0 = 0 % 
Ar e a S c or e ( B) 
1 = 1 % - 9 % 
D e gr e e of i n v ol v e m e nt a s a 
2 = 1 0 % - 2 9 % 
p er c e nt a g e f or e a c h b o d y 
3 = 3 0 %
- 4 9% 
r e gi o n aff e ct e d ( s c or e e a c h 
4 = 5 0 %-
6 9 % 
r e gi o n wit h s c or e b et w e e n 
5 = 7 0 %
- 8 9% 
0- 6) 
6 = 9 0 %- 1
0 0 % 
M ult i pl y L e s io n S c or e S u m ( A) b y Ar e a S c or e ( B), f or e a c h b o d y re gi o n , t o gi v e 4 i n di vi d u al s u bt ot al s ( C). 
S u bt ot al s ( C) 
M ulti pl y e a c h of t h e S u bt ot al s ( C) b y a m o u nt of b o d y s urf a c e ar e a r e pr e s e nt e d b y t h at r e gi o n, i. e. x 0. 1 f or h e a d , x 
0. 2 f or u p p er b o d y , x 0. 3 f or tr u nk, a n d x 0. 4 f or l o w er li m b s. 
B o d y S urf a c e Ar e a 
X 0. 1 
X 0. 2 
X 0. 3 
x 0. 4 
T ot al s ( D) 
A d d t o g et h er e a c h of t h e s c or e s f or e a c h b o d y r e gi o n t o g i ve t h e fi n al P A SI S c or e . 
P A SI S c or e = 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 8 4  of 8 9  
A P P E N DI X 4.  
5- P OI N T S T A TI C  P H Y SI CI A N’ S G L O B A L A S S E S S M E N T  
F or t he d eter mi nati o n of Static P h ysici a n’s Gl o bal Assess me nt ( s P G A), t he de gree of o verall 
lesi o n se verit y will be e v al uate d usi n g t h e cat e g ories bel o w: 
0 = Clear: N o si g ns of ps oriasis. P ost-i nfla m mat or y h y per pi g me ntati o n ma y be prese nt 
1 = Al m ost clear: N or m al t o pi n k c ol orati o n of l esi o ns; n o t hic ke ni n g; n o t o mi ni mal f ocal 
scali n g. 
2 = Mil d: Pi n k t o li g ht re d c ol orati o n; j ust de tecta ble t o mil d t hic ke ni n g; pre d o mi na ntl y fi n e 
scali n g 
3 = M o derate: D ull bri g ht re d, clearl y disti n g uis ha ble er yt h e ma; clearl y disti n g uis ha ble t o 
m o derate t hic ke ni n g; m o derate s cali n g 
4  =  Se vere:  Bri g ht  t o  dee p  d ar k  re d  c ol ora ti o n;  se vere  t hic k e ni n g  wit h  har d  e d ges;  
se vere/ c oars e scali n g c o v eri n g al m ost all or all lesi o ns 
Refere n ce 
1.  La n gl e y R G, Fel d ma n S R, N yira d y J, et al. T he 5- p oi nt I n v esti gat or’s Gl o bal Assess me nt 
(I G A) Scale: A m o difie d t o ol f or e val uati n g plaq ue ps oriasis se verit y i n cli nical trials. J 
Der mat ol o g Treat 2 0 1 5 Fe b; 2 6( 1): 2 3- 3 1. d oi: 1 0. 3 1 0 9/ 0 9 5 4 6 6 3 4. 2 0 1 3. 8 6 5 0 0 9. 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 8 5  of 8 9  
A P P E N DI X 5.  
D E R M A T O L O G Y LI F E Q U A LI T Y I N D E X  
T he ai m of t his q uesti o n naire is t o meas ure h o w m uc h y o ur s ki n pr o ble m has affecte d y o ur life 
O V E R T H E L A S T W E E K. Please tic k ( √) o ne b o x f or eac h q uesti o n. 
1.  O ver t he last wee k, h o w itc h y, s ore, p ai nf ul or sti n gi n g has y o ur 
s ki n bee n? 
Ver y m uc h 
 
A l ot 
 
A little  
 
N ot at all 
 
2.  O ver t he last wee k, h o w e m b a rr asse d  or self-c o nsci o us ha ve y o u 
bee n beca use of y o ur s ki n? 
Ver y m uc h 
 
A l ot 
 
A little  
 
N ot at all 
 
3.  O ver t he last wee k, h o w m uc h has y o ur s ki n i nterfere d wit h y o u 
g oi n g s h o p pi n g or l o o ki n g aft er y o ur h o me  or g ar de n ? 
Ver y m uc h 
 
A l ot 
 
A little 
 
N ot at all 
 
N ot rele va nt 
 
4.  O ver t he last wee k, h o w m uc h has y o ur s ki n i nfl ue nce d t he 
cl ot hes  y o u wear? 
Ver y m uc h 
 
A l ot 
 
A little 
 
N ot at all 
 
N ot rele va nt 
 
5.  O ver t he last wee k, h o w m uc h has y o ur s ki n affecte d a n y s o ci al or 
leis ure acti vities? 
Ver y m uc h 
 
A l ot 
 
A little 
 
N ot at all 
 
N ot rele va nt 
 
6.  O ver t he last wee k, h o w m uc h has y o ur s ki n ma de it diffic ult f or 
y o u t o d o a n y s p ort? 
Ver y m uc h 
 
A l ot 
 
A little 
 
N ot at all 
 
N ot rele va nt 
 
7.  O ver t he last wee k, has y o ur s ki n pre ve nte d y o u fr o m w or ki n g  or 
st u d yi n g? 
 
 
 
If “ N o ”, o ver t he last wee k h o w m uc h has y o ur s ki n bee n a 
pr o ble m at w or k  or st u d yi n g? 
Yes 
 
N o 
 
N ot Rele va nt 
 
 
 
A l ot 
 
A little 
 
N ot at all 
 
8.  O ver t he last wee k, h o w m uc h has y o ur s ki n create d pr o ble ms 
wit h y o ur p art ner  or a n y of y o ur cl ose frie n ds  or rel ati ves ? 
Ver y m uc h 
 
A l ot 
 
A little 
 
N ot at all 
 
N ot rele va nt 
 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 8 6  of 8 9  
9.  O ver t he last wee k, h o w m uc h has y o ur s ki n ca use d a n y se x u al 
diffic ulties ? 
Ver y m uc h 
 
A l ot 
 
A little 
 
N ot at all 
 
N ot rele va nt 
 
1 0.  O ver t he last wee k, h o w m uc h of a pr o ble m has t he tre at me nt f or 
y o ur s ki n bee n, f or e xa m ple, b y ma ki n g y o ur h o me mess y, or b y 
ta ki n g u p ti me? 
Ver y m uc h 
 
A l ot 
 
A little 
 
N ot at all 
 
N ot rele va nt 
 
Please c hec k y o u ha ve a ns were d E V E R Y q uesti o n. T ha n k y o u. 
Refere n ce 
1.  Fi nla y A Y, K h a n G K. D er mat ol o g y Life Q ualit y I n d e x ( D L QI): a si m ple practical 
meas ure f or r o uti ne cli ni cal use. Cli n E x p Der mat ol. 1 9 9 4 Ma y; 1 9( 3): 2 1 0- 2 1 6. d oi: 
1 0. 1 1 1 1/j. 1 3 6 5- 2 2 3 0. 1 9 9 4.t b 0 1 1 6 7. x. 
 
 

Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 8 7  of 8 9  
A P P E N DI X 6.  
C O L U M BI A- S UI CI D E S E V E RI T Y R A TI N G S C A L E 
 ( Scree ni n g Versi o n) 
 
S UI CI D A L I D EA TI O N 
. ~ <Jl. U! 3'.ti 0 1ts l mr d 2. Q' b ot n ar a m, g ali v e , p 1 ·o c ef', <I l o "S uici d al B e h m,'i or - S B Cli o n Q't hs m m ver · t o q u m!i oJ J' 1 i s ').. w -. 
as;k q nesti 0 1f!i J, 4 a n d 5. Jft hs = 
t o q =ti o n 1 t m d! O F 2 is ·>' 6 S ".. c o m plete "l n J 6 n Si qfl d e: atit m - ~,mti o n b el o w. 
1. V.l S Jl t o b e D e, a;d 
S u bjw d ,;:rrl c.rliilil ~ l:! Jtr o p. ~r. a b i::·.:l 1 1 ·u,;:is:!l m, 
. di. a d! c a :?'.lot a t'n.·;. UI) ~ ', ca lll Ul! ~ D :flll i W"'-:P . uJ. d D Dt ll"l.! o r.:.rp. 
H• 
~yo-:. w w i s Ait 4J o;f Wll e & a 4 ,0:rilff J'.l: ~I J L N11 c.:. o•l. d'lf'ltt slu p ,1 uti 1t o J M." d- e q! 
2.. N o n- S p e cifi c A cl:i n S oici. d al T h o u ~li. ts 
G.. nar >I , ·""""'JI O < m < 1 1 u!'.:! g bts a h -.,,.,,!!, t o o ,rl <111.11 ", il &' = cit • - {•- ~,. Ml ~ ;'J »r, gf,.t a.!\ o uf .ir!lr n g m_ > =!f") v.•ffi11111t 11u!· g bt, " "'' " Y' t o kill 
c:ri;,:;. c J C Hi!i «-t: a. N d m ~ 1
~ 
0 1 pl m. 
.lf• < J"" M a d. 1 1. all},1,'I Li U J i/t o" Pl!i o/ killi nl) 'O J Z <l,lft 
3 .. 
l\ c me S ui ci d al l de111:ion wi t h A n y M e t h o ds ( N at P i a) wi tll a ul m i nt t o, A d 
Sli. b.j;,:t 
D.rlilili ~ tttt m p.tli l ?f"-.·.!i. cif,;. ; md! m. 'ii 1:lv:! -~ g m o.f a.t ]. Qliiit C D ;. m ai h o d ,a m = ~ t h,;. ;u ~.,;s..'illllili D.i: ;:,i. ai o d. T hi 3' j s di ffi u-. mt t hl.!I Zi <i p ari nt; p W 1! 1 Ml"l h r.:iJ:::.;;,, 
:Fl" "• " " mrl ml d mili ~ o ut ("'- $-, 1 h o-:!!, ht a f =t h o d t o l:ill ... 1n .-:zt .. 1 • r; p or uic pil m ~ I n,: ·_a. , P " "' " " ..- ha,..,,. d ... 7. Ml / h ort g h.f < >!, o ut ~ - , g 
a n -, < h R /', Mil ll <l! UD W < o s p «rfi c pf a,r a s t o w h "- 1 ~,.r,,,.. ar h a w 1 ' 1" 1 d a dli al,!)i ti, ,r L. .. a ni, ,..,,. _ 1. 1~ 
g o 1 1 F o u gl, 1 1rtlr r L " 
s .. • J"" M 3,..,, u,;,, J; m g d....,, 1,.,,. J"" M .. ~r u at/ti s ? 
4. Art n- e S ui:cid al l de 1 11:i o:a. wi t h S o m e I:att,nt t o A ct , mt b o nt S p e ocif u: Pl a n 
.. '\ct: n·• , u: d d zl w u p.;, of ki! G ns .,,.,. tlf m d ,ii!,j;,ct N p o:rt, h a. ms S. Olllll u,.;;;,e,t t o 
= •- =-~ 1 1 u,-:, d,ta, ., <f p a n d . t o " 1 
w ,l h o,, gfJ n l >ut 1 
,r kf a,;t n y,. TII ' 1 0/d o < 0.,: >'il w.r g a.!\ o ut WJI L
" 
H.t a 
t: J h 1' 1i 1 lir dtlr a e di ~! .I PJi 1t ur dlrr 2 drt 1 J 1 1ti'L'ffil ~ o/t 1. C.irr g. 0 1 1.ilt c. J!I J! 
5. Ar n n S ui:ci dal . l de 1 11:i o:a. wit h S p e c m c P i n 
a n d! I nfe-nt 
~;, d kil m s ol > O wlf,ritl, d mili of pl u f u!.l y orf' Ul:iill:, ..- orl: ~ o ut w 
, 1 1");,,:l h >, = m: mt o c att y ii o ut. 
H a 
t: y o, 1, 1 st art c.i t o- l FOf'I r O Sll or r Ft H. kc.i t 0 1t.l t, h iltit nf s o/J.,,. t o EI 1 1 0 1t. J"fil/! .D,, J
WI i nt c, 1 1 4{ 0 " N J, 1 n 1 Ul u s pl a J J! 
u, y o, , d <s ai: 
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Il'•ff EN 5Ifl ' O FI D E 4 II ON 
1iit 1 J' 0il o wm g J Mi Uit 1:; :;h o. L i d Q.fl T at ~ a 1with l'(l ~f'I t o ! nfl m os t J; Q lWfl tJiJJtl ,efi a) aif o n (iA ·., J .j fr om ll' Q. M'<t wi tii 1 b,r m g t h o .lms t St/ HI T ~ · 
a n d J {l g,'n g Ih a . mo.rt U Tl 'fllfl}. . b.li: a b O. L1 ru!1"1 h s h a 1" <ll j ~ 1 m g t.!i, Jtt,H  H L, rri. da i 
M Oi5I St n w e I d ~ ati o n: 
F :r,t qoi,: n q • 
H o ' ' If/ JI.II} li m M ht n' e ')- 0,ll li d dt e s e l h: o,1 1 g h h ? 
m u,,.jj w, o:, o o " " "' " k 
( 2l 0.ll C O " " "'' " U) 2- ~u .. C!I W O oi 
('I\ D, ci h ·or zl m. o,;; t ,i!,; 1,.,- o u, r,,,,, 1 m1.o ... ~l, ,,l a v 
DIi uti o n 
W 7 1 m J' O U ht n ' 8 t ht 1 iJ 1o u g J 1 n, ! 1 1 1 11 1 l o n g d o t h e y l a st ? 
( 1) f mli n;;- :Ii;..-,..,.,,a, ., = - =•• 
( 2) .,,. jj w, l i b a mf = 
~ftl > o li: m o 
m 1- 4i b o m 11'a.l\ ot oflic:; o 
C o: a b -ol b b .ilit y 
( 4) 4,t h o;.:,-,., "i =,t of d o }" 
(l) ~!'!la, jj w, S 
mi n 1 p or, ;,i. a.1 <1 r O OII O!llll!t1 < 
C o, 1 1 ·l df c. m )" all st o p dri n ki n g a b o ut kilii n g J- a 1 1r seif or =ti n g l o ,di e if }' O U ll' altl t o ? 
( 1) i Ea,i'! y a bt.,, a oa nt:r ol w u p. 1, 
() c,,, c ~ l1l w.:, g],t, v.till, •l ot af,di.i m.c ul.i y 
( 2J C "' <: C O >lra ,li o·;. hts..-itlilitlt.,d:if E.c:,lt y 
( SJ U ~ b lol a 0 < 1atr ol ~;, 
( 3 1 c,.,, r olllr oH h•·:; d,t, v.ill , o m• d di c u! 1'{ 
C O) I Do o • l > Dt ar. = 1t o < ~! >lrll l ili o u,.; 1,l 3 
~ t a un ts 
A n t h er e t hi n gs- a n _),' Olt 8 ,or t myt hizrg ( e.t ~ ,f e mi! J;, nli g:i o n ,p ai n ' ,Q/ d e o d 1j - t h at sl o p p' el 1 } 1t mft o m tR u n z n e t o die, ,or a·~./izr g o n 
t h. o u g hts ,of ,c o m. milti n g s ui ci d e'! 
( 1) I D•lllr. Nni , d\; m ulll 1 y •tl!f;' o d }" 0 1 1 :!r o e • m o c:;rti,,,;; , wc o d o 
( 2) I D•lll m ni , :f ~t bl 7 ,,af;' O d )"<111 
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R e:as o:ns f or I d\e3ti o n 
('l} D.-:Ilr n >at S o ort li hL'r ,di.di ,, at ,t o p )'1111 
(l) ll•lll m ni , d <f u m l)· 
" "I •i•. P y o u 
WI D o a, n < >l c u l/\· 
W h at s ort of n m o m di d y o .1 1 /l' Ql!tij or t hi n ki n g a b o 1 1 1 = mr g 1 0 , di e or killi n, g }' OllI:tt q ? W a, it t o e n d di e p oi n or st o p t h ei ·1 1•' 1 } 
}'0. 1 1, v e nfllli n g (i n ,o J hfl T m 1r d s } " Oil r o ul d n't g o , o n firi n g will! llili p ai n ' ,or h o, v } ' O U w er ef ~ dilr g') or 1 1•. n, it t o g a t me nti o 1 1, 
7 eJ e n g e ,or a r; 1 M s e.ti o nft o 1 1 1 ot h ~ n ''! Or b o d 1'! 
( 1) C o mi; J.-: >l:, t o !,al att..,,;i,,i , ,,.,-or s• or a ,.., oli. oi, £re m ot!i = 
( 2) M. o-• ~· t o e'- 1 z. T mll. Dnn:. :! 1 1\" ~ 
l:t' a .r m.cti mJ. 
oi b.• rs 
( 3) E q u.ally t o ~ wt at m: m u:! 
n; .~;, O J" ii. mz,c:;ti.l:z. D! fr e: m a dt; a-; 
U 1 d .t o on d .1',;, p tl, o ~,i n 
C ? O OI I R.c:i drtl Fi n ni'ti ui N'.11 ' 3f' M ci' AJ 1 1-: 1 _,, 
m e;. fae 
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U!. T UJ g ·wt 1 h cl:,;, p,l m G r . l u z,;- ]!, EJ U. W  W ri! :f.;,;~ 
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Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 8 8  of 8 9  
 
S Li'I CI D. H. B E H  H I O R 
( C h « Jr. all t h at a p pl y. ~ o l o w g ai !II.,,., or e S <' p ar atfl ,n'f' ntt ; 1 1'lli 5t mfr. a b ollt ai'i pti ) 
A et n a] Atf e- m p t: 
.\\ p:111ilIItf:a117 1.,;!.f-crr _i uri o--li ~a · o oc.:. M!. n v d ."r.t.ii h ;rt 
a _. _,, H!: m;s v.isa::i -a Ill ar a T ~SJ Tl'i of a:ct.. B,; h 1. ~ or 1 1,; Zrli b::i p u.t 1n. O'. sb,.t o:f !.1i m a & d . t o lci 1l 1 1 E W!. 4!: £ I n ~-rat 
d: o o• " at ! m ~ l a b o 1 0 0 ¾ . Ifll u a-• i, wr y i m o m•'c! o ~ a d:' o a.,. ori,. o d llri'! h. t:l » a.ct. ll wlil c ai > b o < =rti. d: or o d , m. a m w , o:iici. d,i all <, u pt. Tll er e ' a « ~ n ot 
h. a w. t o b e a ny illft, 1 7)' or h a 1 1 1 1.j u,t ui or a m a.t:i• l : arillj m y <r.i w: c.If ? O < = Pllil• tri! ~ "· hi:l• ~ i <. izi m o::. 1 h·t: = !J L'lllt.- o b u o,i a iaj 11 1 y .r o ml'i,, 
tl £is.ili C GI L S idi m. d! mat'.i!I Df.t . 
!l n! =f: os i!a N nl: ;;, 
, if.,, i n,:!i,., m,J d a ni o, mt• nt .'v.·· n, di o , ii m a y ~ i nf = v d clillic-tlly £re m . t » 
ci a r o r ci m: m,.,t u,r. F o,- • =:::;, l o, • hi, _;;l,ly loll w 
a 1'1 ti at i, ct. arlr " at.,. ac-cid...i: "° n ~ ol h w i m o m b ul , 1 Dci d o <a m 
• i n! or. d (•,! ,. g-.lll wt t o h o 
ju, u pi':!\;; & o m w m di! w of a. ! 4f, fl o o .'>i o i: y). .. ' U, 1 1, ff 
S Dlll Dll a. o d mii os mr ui. t  m di o , b u t t h.y i.bau.,,_;;],t ui, t .,:b at 1. b o y ,dr d C01lld! b o lo1hal,_ mt o. m m.a y' b o i zlf = d. 
in:-e jl Oil 1 1'/ Jlil e II illi ci d e att ml pl ? 
i n:- e J' o, 1, 1· ,d o n e t mJ'l h i n g l o h a Tl!'I J' o.r m- efr. 
a w. )' Oil d o n e t mJ'l h i n g dt m 9't' T O W 1, h er e y o u · ,c o u! _ d h a w. di M ? 
W b. at ifi d y o 1 1 d o ? 
Di d J,•o u _ _ _ ,tJJ a' i my r o e ml J-- o ur lif e:' 
Di d j,' o.r.r ·n' Jllli' r o, ifi e ( et-' OI' a li 1 1l e)' w h. m J' Oll _ _ ? 
W e ~ J-"' 1 1l tl} m g l o ,mil } ' Mir lift 1, h :e n '}' Oll _ _ :' 
Or di d } "Oil t h m k ii l ~t:I J p o'Ili h 1 e J O U ' c m d d h.t n-e di e d fr o: m _ _ ? 
P ut X Y ,s n 
o:r 
Lif tii m.t o 
C 
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,'l.tt. m pt• 
Or ,tfiil. y o, u d o it p rm!!l} f or ot h' n r e. o st m s h vi J h Mlt Ai ·ar mtf'lf 1i. o n of kill m g- J OJ. 1 1' 5.rtlf (likei t o lll m·ei SI Tess,fr,eJ b ~ , gtil ~, m pl 2i h} '. 
or g et 3 0 m!'i hi n e <Ifi e · 1 0 , l ur p p e J Jj'! / E.;!f-,:laj;.:zri o us B o b.ad o, 'lril h =I ,- ~ mt. n . 
i!fy ••• d. ~ s-: n.l, 
H :.s s u b' e d e 
i n.N o n - S ui. ci ul: Se, Jf-l n ' uri o u s B e h :.,io .-1' 
I nte-rr o p.te d .Atte m p t: 
W h. m tl:to l""" D D. ,, ill:-- ~:;,:l ( by ; m o::l,t d• ci K =J,t m c o) :fr o m• ~ : h o p o m w 1 'r ,ril.f Cuij u ci <·,; > <1 (if w otji,r tl ut, a,."'f » al at m n pt 1'- o w' d h <n-,, 
O O C u m ? ~ . 
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Sl!.o« >'iin,;; : P <i n o n h a , p 
p o'. z m d t o 1'' L"ll ,, olf, !) 1 1 > i, t a h ?I a, n y l o)· , o m o a a a ri L,.,, <r i, "' m o h. o w ? "'.- u:;,:l :& o m :~ 
ir' _,.;;; a. • c, o I m.)· p ull t:l » iri! ~r . 
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it,, .,, • mi:::.;,t J· =i;i n g: P = o ?l ll p:tl.,,; dl l a j:= p. i, g, ·• b ~ u d t u. O D. .i,,..,, fr o m t. d,;; H.,, gi n,;; , ~ = h a• =••• "101IJl.d! 
n o d ·t u; h a, .! Wl -
, =.;,:l m 
'- "!,•· ll r n,,- p o,:I & o m d.l o ~ ... 
t h. er e b u n a ri m e w h . m J' Oll s J a m d t o d o s oI P 1 el hi n e t o e n d y 1 1 1 1 ·r ijft ,b.1, 1 1 r o m e e n e or sr J'lf J el hi n g st o p p e d ;, a u ,'fll!,/ 1 1r e y o .r.r 
,u: m a Jl} di d t m' J,'l hillf! ? 
!lf yii!,. d\ ncc.l: ,ac: 
A! b or!e d Aff ml p t: 
W h. m p; " " " b o,gia. , t x, 
, o •'l o p• -a w. ml .~ 
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~ p lo, or o i:ill!ill u- t o i m o mif- O;.:l ' nllllI F-''· 0 >: C <IJI C lllll. 1 ui o i n,fa·.i,f 
' C C 9' . h.i m.,~ n o!!; m,t.. dl of ~- ~ b y "' m ~ g .i. ... 
aJ t ~ b u n Q ri m e w h . m j ' Ull s J a n e d t o d o S OI N'lfl hi n e t o U} ' fl 1 ,t 1 n d J O U ' T 1f/e b ut J Oll 5t o p p e d Jl} U 'T St- U' b- ef o n J' Oll 1 1 £'/ll al g ili d 
a 1t yt hi n g-? 
!!f'y wir. . d\; s m J 
Pr ,e p: 1 nt or y . Ad s . o:r B d :ni oi: : 
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d • ,-.,..,li oali « n <1 r ~'-
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c::o '!l w <I (• -s . l > u: yi: o g:fll p urcli o.ia,;; • ~ ) « :f,: v p ari u g f ur• " "'• d ml:l, b y •·.:iic ui ~ (• · S , p. ui g l:!li n g, • =:,-, .,'ritil > g • illlri &. D 1 1 ~ ). 
ai:- e J.' Oll fll k e n, . mJ st e p s t w; a·r d s m a kilr e a s uf uit k 0 1t e: m p 1 ,or pr q NIIi n g r o kill y o .u T S e Q'( Sll dl a:s c oll el: mr e pilli , e, m m e a· r u 1 1, 
firizr e i'ill u a! J! e: ~ oll m}' or wr:i 1 mz II s ui ci d ~ n o t e ? 
i!fy ••• d. ~s-:n.1: 
: S D ki. d:il i Bel u.l'i. 1 1:r: 
S ufa:i d d b a b\ii c:r l D. 5, ?J:ri!i ~i ,d ur ~ th.11 < a ~iil D M at p ml D d r? 
4 n s w u for Actr, a:l Atte m p ts O n ~, 
Aet n a] Le i h: dit)'l'M e di , n D a. m :ag, : 
(I _ N a Jl b.)' Sic- <.l <1: m!.ogo er 
i!I Wl Oe ;:, h:, <ir,il d = a !  O ( ~
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l. '.' <fa m p h :, <iral ,da. m.a ~• ( ~
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m. a d E-:il 2 1 ~. ar.: k:ri 
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of .c:r >ja n- 0 0 >• ¥ 
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m,ti,. c m b o\ F'- " "'111.@:ril y mt <ll.' > n ·• <lll 1I r,, q ui:. ~ ( ~, !-- < o o c: », a, o m
, b. 
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d >i ~• l > m: u, o,i ·.,-2 0 ¾ a! b e <!y; u/J G n.;,. •o l: c o a d eo,. , mi, · =tii >l o 1it d <i p, ; m > jar ,da. m.a!!i t o• 1·ilal . _,..•).. 
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mi, ~ C'llt zl b u.t ? Ul!;.:l • =1 
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Meiji P har ma U S A I nc. 
M E 3 1 8 3- 3 
M E 3 1 8 3 
Versi o n 2. 0 ( 0 7 Dec 2 0 2 1) 
T his d oc u me nt is c o nfi de ntial. 
 
P a ge 8 9  of 8 9  
Refere n ce 
1. P os ner K, Bre nt D, L u cas C, et al. C ol u m bi a- S uici de Se verit y Rati n g Scale ( C- S S R S). 2 0 0 8 
T he Researc h F o u n dati o n f or Me ntal H y gie ne, I n c. Versi o n 1 4 J a n 2 0 0 9. Access e d date 
2 7 Se p 2 0 2 1 at htt ps://cssrs.c ol u m bia.e d u/ w p -c o nt e nt/ u pl oa ds/ C- S S R S 1- 1 4- 0 9- Scree ni n g. p df