Clinical trial NCT05268016
Conditions: Plaque Psoriasis
Sponsor: Meiji Pharma USA Inc.
Start date: 2022-03-24; Completion date: 2023-05-31
Enrollment: 132 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to assess the efficacy and safety of ME3183 administered orally for moderate to severe plaque psoriasis in adults.

Detailed description:

Arms: arm 1: Specified dose of ME3183 capsule for 16 weeks arm 2: Specified dose of ME3183 capsule for 16 weeks arm 3: Specified dose of ME3183 capsule for 16 weeks arm 4: Specified dose of ME3183 capsule for 16 weeks arm 5: Placebo capsule of ME3183 for 16 weeks
Interventions: intervention 1: ME3183 intervention 2: Placebo
Intervention descriptions: intervention 1: ME3183 capsule intervention 2: Placebo capsule

Protocol documents:
Prot_000.pdf: 
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 
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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 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
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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 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
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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
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 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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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 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  
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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 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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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 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 
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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. 
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u, y o, , d <s ai: 
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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 • 
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m u,,.jj w, o:, o o " " "' " k 
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('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 
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( 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 
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( 4) 4,t h o;.:,-,., "i =,t of d o }" 
(l) ~!'!la, jj w, S 
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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 
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~ 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'! 
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R e:as o:ns f or I d\e3ti o n 
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}'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 = 
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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-; 
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Meiji P har ma U S A I nc. 
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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  
 
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( 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 ) 
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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 . 
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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 
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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 ? 
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Di d j,' o.r.r ·n' Jllli' r o, ifi e ( et-' OI' a li 1 1l e)' w h. m J' Oll _ _ ? 
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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 _ _ ? 
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o:r 
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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, 
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O O C u m ? ~ . 
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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 
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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-? 
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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: 
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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, : 
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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 
 

SAP_001.pdf: 
 
 
This document is confidential. 
SAP Version: Final V3.0 11-Jul-2023 
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020 
Filing requirements: TMF 
Page 1 of 64 
Statistical Analysis Plan for Interventional Studies 
 
SAP Text Version Number: Final v3.0 
SAP Text Date: 11-Jul-2023 
 
Sponsor Name: Meiji Pharma USA Inc. 
 
Protocol Number: ME3183-3 
Protocol Title:  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 
 
Protocol Version and Date:  
Version 1.0 (08-Oct-2021) 
Version 2.0 (07-Dec-2021) 
 
 Project Code: 7028898  
 
Authors: 
 
 
 
 
 
 
 
 
Notice of Confidential and Proprietary Information: 
The information contained in this document is confidential belonging to Meiji Pharma USA. Acceptance of 
this document constitutes agreement by the recipient that no information contained herein will be 
published or disclosed without prior written authorization from an official of Meiji Pharma USA. However, 
this document may be disclosed to appropriate Institutional Review Board and Ethics Committees or duly 
authorized representatives of a national regulatory authority under the condition that they are requested 
to keep it confidential. In the event of an actual or suspected breach of this obligation, 
 
should be notified promptly. 
 
 
 
 
 
 
 
 


Statistical Analysis Plan for Interventional Studies 
Sponsor: Meiji Pharma USA Inc.; Protocol No.: ME3183-3 
 
This document is confidential. 
SAP Version: Final V3.0 11-Jul-2023 
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020 
Filing requirements: TMF 
Page 2 of 64 
Revision History 
Version # 
Date 
(DD-Mmm-YYYY) 
Document Owner 
Revision Summary 
v0.1 
18-Mar-2022 
Initial Release Version  
v0.2 
19-Apr-2022 
Revised draft addressing sponsor comments. 
v1.0 
13-Jun-2022 
Finalized version. 
v1.1 
07-Jun-2023 
Updated version with the following main updates:  
- screened set and randomized set are added in the 
analysis sets; clarifications are provided regarding 
defining safety analysis sets in the event of drug mis-
dispensation; pharmacokinetic set and 
 
 are updated to account for drug mis-
dispensation.  
- estimands are updated for secondary efficacy points to 
allow for imputation (LOCF and NRI) for sPGA related 
secondary endpoint.  
- imputation rules for missing start dates are updated  
- additional analyses are added in the section of 
secondary efficacy endpoints and analysis 
- additional analysis of TEAEs by time of onset is added 
- additional outputs are added in the Index of Tables  
 
v2.0 
26-Jun-2023 
Finalized version. 
v3.0 
11-Jul-2023 
Finalized version. 


Statistical Analysis Plan for Interventional Studies
Sponsor: Meiji Pharma USA Inc.; Protocol No.: ME3183-3
This document is confidential.
SAP Version: Final V3.0 11-Jul-2023
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020
Filing requirements: TMF
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I confirm that I have reviewed this document and agree with the content.
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Statistical Analysis Plan for Interventional Studies
Sponsor: Meiji Pharma USA Inc.; Protocol No.: ME3183-3
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SAP Version: Final V3.0 11-Jul-2023
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Table of Contents
Revision History..........................................................................................................................2
Approvals ..................................................................................................................................3
Glossary of Abbreviations...................................................................................................8
Purpose............................................................................................................................11
Study Objectives ..............................................................................................................12
Study Details/Design ........................................................................................................13
Endpoints .........................................................................................................................25
Analysis Sets....................................................................................................................27


Statistical Analysis Plan for Interventional Studies
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Estimands ........................................................................................................................30
General Aspects for Statistical Analysis ...........................................................................33
Demographic, Other Baseline Characteristics and Medication .........................................36
Efficacy ............................................................................................................................40


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Pharmacokinetics.............................................................................................................43
45
Safety...............................................................................................................................46
Changes from Analysis Planned in Protocol.....................................................................49
Reference List ..................................................................................................................50
Programming Considerations ...........................................................................................51


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Quality Control .................................................................................................................56
Index of Tables.................................................................................................................57
Index of Figures................................................................................................................61
Index of Listings ...............................................................................................................62
Shells ...............................................................................................................................63
Appendices ......................................................................................................................64


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Glossary of Abbreviations
Abbreviation
Description
AE
Adverse Event
AIC
Akaike¶s Information Criteria
ATC
Anatomical Therapeutic Chemical
BDRM
Blind Data Review Meeting 
BID
Twice Daily
BLQ
Below the Limit of Quantification
BMI
Body Mass Index
BSA
Body Surface Area
CI
Confidence Interval
CMH
Cochran-Mantel-Haenszel 
CS
Clinically Significant
C-SSRS
Columbia-Suicide Severity Rating Scale
CTMS
Clinical Trial Management System 
Ctrough
Trough Plasma Concentration
CV
Coefficient of Variation
DLQI
Dermatology Life Quality Index
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
FAS
Full Analysis Set
FSH
Follicle-Stimulating Hormone
GCP
Good Clinical Practice
GI
Gastrointestinal
HBV
Hepatitis B Virus
HCV
Hepatitis C Virus
HIV
Human Immunodeficiency Virus
IB
Investigator¶s Brochure
ICF
Informed Consent Form
ICH
International Council for Harmonisation
ID
Subject Identification


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Abbreviation 
Description 
IL 
Interleukin 
IWRS 
Interactive Web Response System 
LLT 
Lower Level Term 
LOCF 
Last Observation Carried Forward 
LS 
Least-square 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
Mixed-effect Model for Repeated Measures 
NRI 
Non-responder Imputation 
NRS 
Numerical Rating Scale 
PASI 
Psoriasis Area and Severity Index 
PASI-50 
 50% Reduction from Baseline in the PASI score 
PASI-75 
 75% Reduction from Baseline in the PASI score 
PASI-90 
 90% Reduction from Baseline in the PASI score 
PASI-100 
100% Reduction from Baseline in the PASI score 
PDE4 
Phosphodiesterase 4 
PK 
Pharmacokinetic  
PP 
Patient Privacy 
PPS 
Per Protocol Set 
PRO 
Patient-reported Outcome 
PT 
Preferred Term 
QD 
Once Daily 
QTc 
Corrected QT Interval 
QTcF 
QT Interval Corrected using Fridericia¶s Formula 
REML 
Restricted Maximum Likelihood  
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
sPGA 
Static Physician¶s Global Assessment 


Statistical Analysis Plan for Interventional Studies 
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Abbreviation 
Description 
TEAE 
Treatment-Emergent Adverse Event 
TFL 
Tables, Figures and Listings 
TNF-  
Tumor Necrosis Factor-alpha 
UV 
Ultraviolet 
UVB 
Ultraviolet B 
WHO 
World Health Organization  
WOCBP 
Women of Childbearing Potential 


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Purpose
The purpose of this statistical analysis plan (SAP) is to ensure that the data listings, summary tables and 
figures which will be produced, and the statistical methodologies which will be used, are complete and 
appropriate to allow valid conclusions regarding the study objectives.
Responsibilities
will perform the statistical analyses and is responsible for the production and quality 
control of all tables, figures, and listings.
Timings of Analyses
The primary analysis of safety, efficacy and pharmacokinetics/
is planned after all 
subjects complete the final study visit (Visit 8 at Week 16) or terminate early from the study. Database will 
be completely cleaned and locked prior to the primary analysis. No interim analyses are planned for the 
study. 


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Study Objectives
Primary Objective
To evaluate the efficacy of oral ME3183 compared with placebo at Week 16 in subjects with 
moderate to severe plaque psoriasis as measured by the Psoriasis Area and Severity Index (PASI) 
score
Secondary Objectives
To evaluate the safety and tolerability of oral ME3183 in subjects with moderate to severe plaque 
psoriasis
To evaluate the efficacy of oral ME3183 in subjects with moderate to severe plaque psoriasis at 
various time points
To evaluate the effect of oral ME3183 on patient-reported outcome (PRO) measures in subjects 
with moderate to severe plaque psoriasis
To evaluate the pharmacokinetic (PK) of ME3183 and its metabolite (
) in subjects with 
moderate to severe plaque psoriasis who are treated with oral ME3183 
Exploratory Objectives 


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Study Details/Design
Brief Description
This multi-center, randomized, double-blind, placebo-controlled, parallel group, Phase 2a study is 
designed to assess the efficacy and safety of ME3183 administered orally in subjects with moderate to 
severe plaque psoriasis. The study consists of a 4-week Screening Period (Day -28 to Day -1), a 16-week 
double-blind Treatment Period (Day 1 to Day 113), and a 4-week Follow-up Period (Day 114 to Day 141). 
The total duration of study participation for each subject is approximately 24 weeks.
Note: The study drug is administered from Day 1 to Day 112 in the Treatment Period and the end of 
Treatment Period assessments will be performed on Day 113.
The duration of the Follow-up Period is from Day 114 to Day 141 and the end of Follow-up Period 
assessments will be performed on Day 141.
A suitable number of subjects with moderate to severe plaque psoriasis will be screened to randomize 
approximately 125 subjects across approximately 30 study sites in the United States and Canada. 
Subjects will be centrally randomized (25 subjects per treatment group) in a 1:1:1:1:1 ratio to 1 of the 
following treatment groups to receive oral ME3183 or matching placebo for a duration of 16 weeks.
 Treatment Group 1:  mg ME3183 BID administered orally:  capsule of  mg ME3183 and  
capsules of matching placebo in the morning and evening
 Treatment Group 2: 
 mg ME3183 QD administered orally:  capsules of  mg ME3183 and  
capsule of matching placebo in the morning and  capsules of matching placebo in the evening
 Treatment Group 3: 
 mg ME3183 BID administered orally:  capsule of  mg ME3183 and  
capsule of 
 mg ME3183 and  capsule of matching placebo in the morning and evening
 Treatment Group 4: 
 mg ME3183 QD administered orally:  capsules of  mg ME3183 in the 
morning and  capsules of matching placebo in the evening
 Treatment Group 5: Matching placebo BID administered orally:  capsules of matching placebo in 
the morning and evening


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Figure 1. Study Design
Abbreviations: QD = once daily; BID = twice daily; N = approximate number of subjects to be randomized. 
Subject Selection
Inclusion Criteria
Individuals must meet all of the following criteria to be included in the study:
1. Subject is willing and able to participate in the study and has read, understood, and signed the 
informed consent form (ICF) according to national regulations.
2. Subject is a male or female aged 18 to 75 years (inclusive) at the time of consent (i.e., Screening).
3. Subject has a body mass index (BMI)  18.5 to 40 kg/m2 at Screening.
4. Subject has a diagnosis of plaque psoriasis for  24 weeks prior to Screening.
5. The subject¶s symptoms of plaque psoriasis are stable in the opinion of the investigator. Stable is 
defined as no acute deterioration (e.g., pustulation or erythroderma) within 12 weeks before Screening 
and no rebound of plaque psoriasis within 4 weeks before Screening.
6. The subject¶s severity of disease meets all of the following criteria:
Psoriatic plaques must cover  10% of body surface area (BSA) at Screening and Baseline
PASI score 12 to 40 at Screening and Baseline
Static Physician¶s Global Assessment (sPGA  3) at Screening and Baseline
7. Subject is deemed by investigator to be eligible for phototherapy or systemic therapy.
8. Subject agrees to avoid prolonged exposure to sunlight or use of artificial sunbathing (e.g., tanning 


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booths) or other ultraviolet (UV) light sources during the Treatment Period.
9. Subject, if female and of childbearing potential, must have a negative serum pregnancy test at 
Screening and negative urine pregnancy test at Baseline. Any women of childbearing potential 
(WOCBP) must agree to sexual abstinence or to use a highly effective contraceptive measure starting 
at Screening, continuing throughout the entire Treatment Period, and for at least 4 weeks after taking 
the last dose of study treatment. A female subject is considered to be a WOCBP after menarche and 
until she is in a postmenopausal state for 12 months or otherwise permanently sterile (for which
acceptable methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy). For 
the definition and a complete list of acceptable contraceptive measures see protocol APPENDIX 1.
10. Subject, if a fertile male, agrees to sexual abstinence or to use a condom during sexual activity 
with their female partner of childbearing potential starting at Screening, continuing throughout the 
entire Treatment Period, and for at least 4 weeks after taking the last dose of study treatment. A male 
subject is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. 
Additionally, if their partner is a WOCBP, then their partner should be advised to use a highly effective 
contraceptive measure during sexual activity starting at Screening, continuing throughout the entire 
Treatment Period, and for at least 4 weeks after taking the last dose of study treatment. For the 
definition and a complete list of acceptable contraceptive measures see protocol APPENDIX 1.
11. Subject, if female, must agree to not donate, or retrieve for her own use, ova starting at Screening, 
continuing throughout the entire Treatment Period, and for at least 4 weeks after taking the last dose 
of study treatment.
12. Subject, if male, must agree to not freeze or donate sperm starting at Screening, continuing 
throughout the entire Treatment Period, and for at least 4 weeks after taking the last dose of study 
treatment.
Exclusion Criteria
Individuals meeting any of the following criteria at Screening or Baseline (as applicable) are ineligible to 
participate in this study:
1. Subject has a diagnosis of non-plaque psoriasis (predominantly guttate, pustular, inverse, or 
erythrodermic) or drug-induced psoriasis.
2. Subject has any unstable or clinically significant (CS) (as determined by the investigator) cardiac, 
endocrinologic, gastroenterologic, pulmonary, neurologic, psychiatric (such as major depression), 
hepatic, renal, hematologic, immunologic disease, or other disease (e.g., uncontrolled diabetes) that 
would place the subject at unacceptable risk if they were to participate in the study.
3. Subject has suicidal ideation or behavior in the past 12 months as indicated by a positive response 
(yes) to questions 3, 4, or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) completed at 
Screening and/or at Baseline.
4. Subject has a present recurrent medical condition associated with significant gastrointestinal (GI)
events (e.g., nausea, vomiting, constipation, abdominal pain, diarrhea).
5. Subject has any condition that would confound the ability to interpret data from the study (e.g., 
eczema, atopic dermatitis, lupus, inflammatory bowel disease).


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6. Subject has any degree of dysphagia that may interfere with the oral dosing of the study treatment. 
7. Subject has a history of allergy or hypersensitivity to any component of the study treatments. 
8. Subjects who have had a prior laboratory confirmed COVID-19 test or have been in close physical 
contact (6 feet or closer for at least 15 minutes) with a person who is known to have laboratory 
confirmed COVID-19 or with anyone who has any symptoms consistent with COVID-19 within the past 
14 days at Screening or Baseline. 
9. Subjects experiencing any of the following symptoms at Screening or Baseline: 
 
Fever or chills 
 
Cough 
 
Shortness of breath or difficulty breathing 
 
Fatigue 
 
Muscle or body aches 
 
Headache 
 
New loss of taste or smell 
 
Sore throat 
 
Congestion or runny nose 
 
Nausea or vomiting 
 
Diarrhea 
10. Subject has active or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection as per 
Screening viral serology tests. Exception: If the subject has received documented treatment which was 
curative for HCV and tests negative for HCV RNA at Screening, the subject may be considered for 
randomization. 
11. Subject is positive for the Human Immunodeficiency Virus (HIV) antibodies (HIV-1 or HIV-2) at 
Screening or has a history of congenital or acquired immunodeficiency (e.g., common variable 
immunodeficiency disease). 
12. Subject has a recent history of drug, substance, or alcohol abuse/dependence within 1 year prior 
to Screening as determined by the investigator. 
13. Subject has an active infection (bacteria, viral, fungal, etc.) requiring treatment with systemic 
antibiotics within 4 weeks of Screening. Any treatment for such infections must be completed at least 4 
weeks prior to Screening. 
14. Subject has active tuberculosis or history of incompletely treated tuberculosis per medical history. 
15. Subject has a malignancy or history of malignancy (except for treated [i.e., cured] basal cell or 


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squamous cell in situ skin carcinomas and treated [i.e., cured] cervical intraepithelial neoplasia or 
carcinoma in situ of the cervix with no evidence of recurrence). 
16. Subject is pregnant or breastfeeding at Screening or at Baseline. 
17. Subject has a history of lack of efficacy (inadequate efficacy when used in adequate dose and 
duration in accordance with the approved label) to any biological products for psoriasis. 18. Subject 
has received 2 or more biological products in the past for the treatment of psoriasis. 
19. Subject has a history of lack of efficacy to 2 or more non-biologic systemic therapy due to 
inadequate efficacy when administered in adequate dose and duration in accordance with their label 
(approved in the subject¶s country) for psoriasis. 
20. Subject has received any prior treatment with apremilast or any other Phosphodiesterase 4 
(PDE4) inhibitor. 
21. Subject has received ustekinumab, secukinumab, brodalumab, ixekizumab, guselkumab, 
risankizumab, tildrakizumab, or briakinumab (or any other therapeutic agent targeting Interleukin-12 
[IL-12], IL-17, or IL-23) within 24 weeks of first administration of study treatment. 
22. Subject has received Tumor Necrosis Factor-alpha (TNF- ) inhibitor(s)/blocker(s) within 8 weeks 
of first administration of study treatment. 
23. Subject has received natalizumab (an integrin receptor antagonist), or agents that modulate B cells 
or T cells (e.g., alemtuzumab, abatacept, alefacept) within 12 weeks of first administration of study 
treatment. 
24. Subject has received rituximab within 24 weeks of first administration of study treatment. 
25. Subject has received any systemic immunosuppressants (e.g., methotrexate, azathioprine, 
cyclosporine, 6-thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, tacrolimus), any 
protein kinase inhibitor (e.g., tofacitinib, baricitinib, peficitinib, upadacitinib), or anakinra within 4 weeks 
of the first administration of study treatment. 
26. Subject has received phototherapy (e.g., ultraviolet B including narrow band ultraviolet B, 
Goeckerman therapy, and excimer laser or psoralen ultraviolet A) or any systemic 
medications/treatments that could affect psoriasis or sPGA evaluation (including, but not limited to, 
oral or injectable corticosteroids, retinoids, 1,25-dihydroxy vitamin D3 and analogues, psoralens, 
sulfasalazine, or fumaric acid derivatives) within 4 weeks of the first administration of study treatment. 
27. Subject has had a recent initiation of a drug that is known to potentially cause or exacerbate 
psoriasis (including, but not limited to, beta-blockers, lithium, and anti-malarials) within the 8 weeks 
prior to the first administration of study treatment; a subject who has been on a stable dose for at least 
8 weeks prior to the first administration of study treatment without exacerbation of psoriasis may be 
randomized and does not need to discontinue these medications. 
28. Subject has used topical medications/treatments that could affect psoriasis or sPGA evaluation 
(including, but not limited to, corticosteroids, anthralin, calcipotriene, topical vitamin D derivatives, 
retinoids, tazarotene, methoxsalen, trimethylpsoralen, pimecrolimus, tacrolimus, or PDE4 inhibitor) 
within 2 weeks of the first administration of study treatment. 


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29. Subject has received an investigational drug for biologic therapy within the previous 24 weeks prior 
to the first administration of study treatment or received any other non-biologic investigational 
therapy/drugs or device within 4 weeks or 5 half-lives (whichever is longer) prior to the first 
administration of study treatment. 
30. Subject has received any prior treatment with ME3183. 
31. Subject has any of the following abnormal laboratory test findings at Screening. 
Abnormal hepatic function
o Aspartate aminotransaminase or alanine aminotransaminase
2×upper limit of normal or
o Total bilirubin 
2×upper limit of normal, unless the subject has a diagnosis of Gilbert¶s 
syndrome
White blood cell count <3000/mm3(<3.0×109/L)
Neutrophil count <1000/mm3(<1.0×109/L)
Platelet count <100,000/ L (<100×109/L)
Hemoglobin <8.0 g/dL
Creatinine clearance estimated by Cockcroft-Gault formula <60mL/min
Hemoglobin A1c >9.0%
32. Subject has a CS abnormality on a 12-lead Electrocardiogram (ECG) or QTcF > 450 msec at 
Screening or Baseline. 
33. Subject has a systolic blood pressure  160 mmHg or a diastolic blood pressure  100 mmHg 
(based on at least 2 repeat measurements) at Screening. 
34. Prisoners or subjects who are incarcerated for any reason. 
35. Subject has any other factor constituting disqualification for study inclusion in the judgement of the 
investigator. 
Determination of Sample Size
No formal sample size calculation was performed.
For the assessment of efficacy and safety of ME3183 in subjects with moderate to severe plaque 
psoriasis in this proof-of-concept study, approximately 125 eligible subjects will be enrolled. Twenty-five 
subjects will be randomized to each of the following treatment groups: ME3183  mg BID, ME3183 
 mg 
QD, ME3183 
 mg BID; ME3183 
 mg QD, and placebo. The number of planned subjects is 
considered adequate to assess safety and to provide efficacy estimates for in this Phase 2a study. The 
expected drop-out rate is assumed to be 10%.


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Treatment Assignment and Blinding
Method of Study Treatment Assignment
Prior to dosing on Day 1, all the eligible subjects will be randomly assigned to 1 of the 5 treatment groups 
in a 1:1:1:1:1 ratio. Subjects will be assigned a randomization number through interactive web response 
system (IWRS), in accordance with the randomization code generated by the authorized personnel at 
designated by 
. An unblinded, independent study statistician will be assigned to produce 
the randomization schedule. Once a randomization number is allocated to 1 subject, same number may 
not be assigned to another subject even if the former discontinued the study. 
To promote balanced allocation, randomization will be stratified by the subject¶s receipt (yes/no) of 
previous treatment with a biologic drug for psoriasis. Bio-naïve subjects will be randomized above 50% of 
the planned total subject randomization.
Blinding
This is a double-blind study. 
An IWRS will be used for subject randomization and a unique subject identification number will be 
assigned automatically. According to the randomization schedule as indicated in the Schedule of 
Assessments (Table 1), the investigator or designee will obtain the study drug kit number from the IWRS 
for the subject, and the number will be provided to the pharmacist or designee at the study center who is 
responsible for handling the study drugs. This pharmacist or designee will dispense the study drug to the 
subject based on the study drug kit number generated from the IWRS. An unblinded, independent study 
statistician will be assigned to produce the randomization schedule. No other study site personnel, 
subjects, Sponsor personnel, or Sponsor designees will be unblinded to treatment assignment throughout 
the duration of the study unless unblinding is required. If an investigator becomes unblinded to a given 
subject¶s study treatment, that subject will be discontinued from the study unless there are ethical reasons 
for that subject not to be discontinued; approval from the Medical Monitor must be obtained in such 
instances. 
In the event that emergency unblinding is required for a given subject because of adverse events (AEs) or 
concerns for the subject¶s safety or wellbeing, the investigator may break the randomization code for the 
subject via the IWRS, by which system the unblinding will be captured. The investigator is responsible for 
notifying the Medical Monitor and/or Sponsor of such an event as soon as possible. The unblinding and 
its cause will also be documented in the electronic case report form (eCRF). 
The bioanalytical laboratory will receive a copy of the randomization schedule for PK analysis, as the 
Sponsor does not intend to analyze the samples from the placebo group. The blinding procedure will be 
documented in a separate document.
Administration of Study Medication
ME3183 (  mg, 
 mg, 
 mg, and 
 mg) and a matching placebo will be prepared using the following 
ME3183 and placebo capsules:
ME3183 Capsule 
 mg
ME3183 Capsule  mg


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ME3183 Placebo Capsule
Refer to the investigator¶s brochure (IB) for complete details on the study treatment.
A designated pharmacist will dispense the study drugs at each visit. Additional details on dispensing of 
the study drugs will be provided in the pharmacy manual.
Study Procedures and Flowchart
Table 1 outlines the timing of procedures and assessments to be performed throughout the study. 
Protocol Section 12.5 specifies safety laboratory assessment samples to be obtained. See Protocol 
Sections 11, 12, and 13 for additional details regarding efficacy assessments, safety assessments, and 
PK assessments, respectively. Details of other assessments such as 
 are provided in 
Protocol Section 14.
In case a randomized subject is not able to attend scheduled study visit on-site due to restrictions related 
to SARS-CoV-2, a remote visit may be conducted instead (a phone call or a televisit).
It is strongly recommended to conduct the study assessments for the applicable visit as per protocol 
Schedule of Assessments (see Table 1) as much as possible. If possible and if local regulations allow 
and the subject agrees, trained and authorized members of the site staff are encouraged to collect study 
assessments, including samples for scheduled laboratory tests at subject¶s home or at a local facility. 
Alternatively, the subject could have the hematology, coagulation, chemistry, urinalysis, and pregnancy 
testing at a local laboratory and the laboratory reports will be provided to the investigator. The local 
laboratory results should be entered in the eCRF.
Subjects with signs and symptoms of infection, including SARS-CoV-2 infection should immediately 
contact the investigator, who should inform the Medical Monitor or designee as soon as possible to 
discuss subject¶s continuation of study treatment. In case of suspicions for SARS-CoV-2 infection, 
relevant testing should be performed local site procedures. In case study visits or assessments are not 
performed for reasons related to SARS-CoV-2 restrictions, this should be documented in the source 
documents and eCRF.


 
 
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Table 1. Schedule of Assessments 
Study Procedures  
 
Screening 
Period  
Treatment Period 
Follow-up 
Periodb  
Screening 
(Visit 1)  
Visit 2  
Visit 3  
Visit 4  
Visit 5  
Visit 6  
Visit 7  
Visit 8a  
Follow-up 
Visit  
(Visit 9)  
Week -4  
Week 0  
Week 1  
Week 2  
Week 4  
Week 8  
Week 12  
Week 16  
Week 20  
Days -28 to -1  
Day 1 
(Baseline)  
Day 8 
(±1 day)  
Day 15 
(±1 day)  
Day 29 
(±3 days)  
Day 57 
(±3 days)  
Day 85 
(±3 days)  
Day 113* 
(±3 days)  
Day 141** 
(±3 days)  
Eligibility Assessments 
Informed consent  
X 
- 
- 
- 
- 
- 
- 
- 
- 
Inclusion/exclusion criteria  
X 
X 
- 
- 
- 
- 
- 
- 
- 
Demographics  
X 
- 
- 
- 
- 
- 
- 
- 
- 
Dermatologic and medical 
historyc  
X 
- 
- 
- 
- 
- 
- 
- 
- 
Prior and concomitant 
medications/therapies and 
procedures  
X 
X 
X 
X 
X 
X 
X 
X 
X 
History of previous 
treatment with a biologic 
drug for psoriasis  
- 
X 
- 
- 
- 
- 
- 
- 
- 
C-SSRS  
X 
X 
- 
- 
- 
- 
- 
- 
- 
Safety Assessments  
Physical examination 
(complete)  
X 
- 
- 
- 
- 
- 
- 
- 
- 
Physical examination 
(targeted)  
- 
X 
X 
X 
X 
X 
X 
X 
X 
Height and weightd  
X 
- 
- 
- 
- 
- 
- 
- 
- 
blood pressure (systolic and 
diastolic), heart rate, 
respiratory rate, body 
temperature, and body 
weight  
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECGse  
X 
X 
- 
- 
X 
X 
X 
X 
X 


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Study Procedures  
 
Screening 
Period  
Treatment Period 
Follow-up 
Periodb  
Screening 
(Visit 1)  
Visit 2  
Visit 3  
Visit 4  
Visit 5  
Visit 6  
Visit 7  
Visit 8a  
Follow-up 
Visit  
(Visit 9)  
Week -4  
Week 0  
Week 1  
Week 2  
Week 4  
Week 8  
Week 12  
Week 16  
Week 20  
Days -28 to -1  
Day 1 
(Baseline)  
Day 8 
(±1 day)  
Day 15 
(±1 day)  
Day 29 
(±3 days)  
Day 57 
(±3 days)  
Day 85 
(±3 days)  
Day 113* 
(±3 days)  
Day 141** 
(±3 days)  
Safety Laboratory Tests  
Viral serologyg  
X 
- 
- 
- 
- 
- 
- 
- 
- 
Hematology and 
Coagulationh  
X 
Xi 
X 
X 
X 
X 
X 
X 
X 
Blood chemistryj  
X 
Xi 
X 
X 
X 
X 
X 
X 
X 
Urinalysis  
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy test (serum -
hCG) (WOCBP only)  
Xk 
- 
- 
- 
- 
- 
- 
- 
- 
Pregnancy test (urine -
hCG) (WOCBP only)  
- 
Xl, m 
- 
- 
Xm 
Xm 
Xm 
Xm 
Xm 
Serum FSH 
(postmenopausal women 
only)  
X 
- 
- 
- 
- 
- 
- 
- 
- 
AE Monitoring  
Monitor for AEs and SAEs  
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pharmacokinetic Assessments  
PK sample (blood)n  
- 
- 
X 
- 
X 
X 
- 
X 
- 
Efficacy Assessments 
 
PASI score  
X 
Xo 
X 
X 
X 
X 
X 
X 
X 
BSA  
X 
Xo 
X 
X 
X 
X 
X 
X 
X 
sPGA  
X 
Xo 
X 
X 
X 
X 
X 
X 
X 
PRO 
assessments  
Itch NRS  
- 
X 
X 
X 
X 
X 
X 
X 
X 
DLQI 
- 
X 
X 
X 
X 
X 
X 
X 
X 
Other Assessments  


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Study Procedures  
 
Screening 
Period  
Treatment Period 
Follow-up 
Periodb  
Screening 
(Visit 1)  
Visit 2  
Visit 3  
Visit 4  
Visit 5  
Visit 6  
Visit 7  
Visit 8a  
Follow-up 
Visit  
(Visit 9)  
Week -4  
Week 0  
Week 1  
Week 2  
Week 4  
Week 8  
Week 12  
Week 16  
Week 20  
Days -28 to -1  
Day 1 
(Baseline)  
Day 8 
(±1 day)  
Day 15 
(±1 day)  
Day 29 
(±3 days)  
Day 57 
(±3 days)  
Day 85 
(±3 days)  
Day 113* 
(±3 days)  
Day 141** 
(±3 days)  
Medical photography (target 
skin lesion)p  
- 
X 
- 
X 
X 
- 
- 
X 
- 
Clinical Drug Supplies  
Subject randomization  
- 
X 
- 
- 
- 
- 
- 
- 
- 
Dispense study drug  
- 
X 
X 
X 
X 
X 
X 
- 
- 
Administration of study 
drugq  
- 
X 
X 
X 
X 
X 
X 
- 
- 
Subject to return back 
unused study treatment for 
compliance check  
- 
- 
X 
X 
X 
X 
X 
X 
- 
Schedule the date/time for 
the next visit  
X 
X 
X 
X 
X 
X 
X 
X 
- 
Discharge the subject from 
the study siter  
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: -hCG = -human chorionic gonadotropin; AE = adverse event; BMI = body mass index; BSA = body surface area; C-SSRS = Columbia-
Suicide Severity Rating Scale; DLQI = Dermatology Life Quality Index; ECG = electrocardiogram; FSH = follicle-stimulating hormone; HBV = hepatitis 
B virus; HCV = hepatitis C virus; PASI=Psoriasis Area and Severity Index; 
; PK=pharmacokinetic; PRO=patient-reported 
outcome; QTcF = QT interval corrected using Fridericia¶s formula; SAE = serious adverse event; sPGA = Static Physicians Global Assessment; WOCBP 
= women of childbearing potential; NRS = numerical rating scale.  
* The duration of the Treatment Period is from Day 1 to Day 112 and the end of Treatment Period assessments will be performed on Day 113.  
** The duration of the Follow-up Period is from Day 114 to Day 141 and the end of Follow-up Period assessments will be performed on Day 141.  
a or Early Termination Visit.  
b Subjects who discontinued or withdrew early from study treatment should return after 4 weeks of last dose of study treatment for follow-up safety assessments.  
c Must include history of drug, substance, or alcohol abuse/dependence within 1 year prior to Screening as determined by the investigator.  
d Record height at Screening only.  
e 12-lead ECG must include QTcF measurement.  
g All subjects must have the following viral serology tests completed at Screening: anti-HCV antibody, HBV surface antigen, HBV core antibody, HIV-1 
antibody, and HIV-2 antibody. If the subject tests positive for anti-HCV antibody, then HCV RNA via polymerase chain reaction should be performed to confirm 


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or rule out active infection. If the subject has received documented treatment which was curative for HCV and tests negative for HCV ribonucleic acid (RNA) at 
Screening, the subject may be considered for enrollment.  
h Includes complete full and differential blood count, platelet count, hemoglobin, hemoglobin A1c (only at Screening), fibrinogen and prothrombin time. See 
Protocol Section 12.5 for a complete list of tests to be performed.  
i To be obtained predose (subjects are required to fast for at least 10 hours prior to the collection of specimens for safety laboratory tests).  
j See Protocol Section 12.5 for a list of tests to be performed.  
k All WOCBP must have a negative serum pregnancy test at Screening to be eligible for the study. 
l All WOCBP must have a negative urine pregnancy test prior to randomization and dosing on Day 1.  
m A serum pregnancy test should be performed for confirmation of any positive urine pregnancy test. The subject will be withdrawn from the study treatment if 
the confirmatory serum pregnancy test is positive. The subject must not receive any further doses of the study drug and will be asked to return for the follow-up 
visit 4 weeks after the last dose of study drug.  
n The PK and 
 blood samples will be collected predose at all scheduled visits as per Schedule of Assessments.  
o To be performed prior to randomization.  
p Medical photography of the target skin lesion will be obtained at selected sites in a selected number of subjects for documentation and publication purposes 
only.  
q Subjects will take the first dose of the study drug upon returning to their home after all Day 1 (Visit 2) assessments are completed.  
r Subjects will be discharged from the study site after all the postdose study procedures are completed.


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Endpoints  
Primary Efficacy Endpoint
The primary efficacy endpoint is the proportion of subjects achieving  75% reduction from baseline in the 
PASI score (PASI-75) at Week 16. 
Secondary Efficacy Endpoints
The percent change from baseline in PASI score at all visits from Week 1 to Week 16 
The proportion of subjects achieving PASI-50, PASI-75, PASI-90, PASI-100 at all visits from 
Week 1 to Week 16 
Time to PASI-50 and PASI-75 
The proportion of subjects achieving a Static Physicians Global Assessment (sPGA) score of ³0´ 
(³clear´) or ³1´ (³almost clear´) combined with 2-point reduction on the 5-point sPGA scale at all 
visits from Week 1 to Week 16 
The change from baseline in affected body surface area (BSA) at all visits from Week 1 to Week 
16 
The change from baseline in the itch numerical rating scale (NRS) at all visits from Week 1 to 
Week 16 
The change from baseline in the Dermatology Life Quality Index (DLQI) score at all visits from 
Week 1 to Week 16 
Percentage of subjects with at least a 5-point reduction from baseline in the DLQI score at all 
visits from Week 1 to Week 16 
Exploratory Endpoints


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Pharmacokinetic Endpoints
The PK endpoint is the trough plasma concentration (Ctrough) of ME3183 and its metabolite (
).
Safety Endpoints
The safety endpoints are as follows:
The incidence, severity, and seriousness of AEs reported over the 16-week Treatment Period and 
the 4-week Follow-up Period
Changes from baseline in CS physical examination findings and vital sign measurements (blood 
pressure, heart rate, respiratory rate, body temperature, and body weight) over the 16-week 
Treatment Period and the 4-week Follow-up Period
Changes from baseline in ECG findings over the 16-week Treatment Period and the 4-week 
Follow-up Period
Changes from baseline in safety laboratory values (hematology, coagulation, blood chemistry, 
and urinalysis) over the 16-week Treatment Period and the 4-week Follow-up Period


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Analysis Sets
Screened Set
All subjects who have signed ICFs will be included in the screened set. 
Randomized Set 
All subjects who have signed ICFs and have received a randomization number within the IWRS will be 
included in the randomized set.
Safety Analysis Set 
All randomized subjects who received at least 1 dose of study drug will be included in the safety analysis 
set. Analyses in the safety analysis set will be based on the study treatment actually received by each 
subject. 
In the event of drug mis-dispensation, the following guidelines will be followed: 
For subjects randomized to the placebo group but received any active study drug, they will be 
included in the active treatment group corresponding to the largest number of kits dispensed. 
For subjects randomized to any one of the four active treatment groups, they will be included in 
the active treatment corresponding to the largest number of kits dispensed.
The Safety Analysis Set will be used for all analyses of safety endpoints. 
Full Analysis Set 
All subjects who have been randomized, received at least 1 dose of study drug, and have at least 1 
evaluable post-baseline time point for primary endpoint will be included in the full analysis set (FAS). 
Analyses in the FAS will be based on the subject¶s randomized treatment group. 
The FAS will be used for all analyses of efficacy endpoints.
Per Protocol Set 
The per protocol set (PPS) is a subset of the FAS; the PPS will exclude subjects with protocol deviations 
that may significantly impact the assessment of the primary objective of the study. Analyses in the PPS 
will be based on the study treatment actually received by each subject. All decisions to exclude subjects 
from the PPS will be made prior to the unblinding of the study. 
Pharmacokinetic Set
The PK analysis set will consist of all subjects who were correctly administered at least 1 ME3183 dose 
and where ME3183 or 
 concentration data is available without any protocol deviation interfering 
with these results. Analyses in the PK analysis set will be based on the study treatment actually received 
by each subject. In the event of drug mis-dispensation when a subject has received more than one active 
study drug, the subject will be excluded from the PK analysis set.
PK concentrations are listed for all subjects in PK analysis set. 


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Protocol Deviations
All subject data will be reviewed for the occurrence of protocol deviations. Identified protocol deviations 
will be recorded into the Clinical Trial Management System (CTMS) by the Site Monitor. The detail on the 
types of Protocol deviation criteria is made in the BDRM Preparation Plan. Final decisions of subjects to 
be included in the PPS will be made at the BDRM. All deviations will be categorized as major or minor. 
Significant protocol deviations are defined as those with major severity.
Deviation type will be recorded as one of the following categories:
Concomitant Medication / Administration of prohibited medication
Inclusion or Exclusion Criteria
Informed Consent / ICF not signed or signed late
Informed Consent / Other
Investigational Product / Incorrect IP kit given to subject
Investigational Product / IP
Investigational Product / IP Storage
Investigational Product / Other
Met Withdrawal Criteria but was not Withdrawn
Randomization / Mis-stratification
Randomization / Multiple Randomizations
Randomization / Other
Randomization / Randomized not Treated
Randomization / Treated and not Randomized
SAE not reported or reported late
Study Procedure / Missed procedure


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Study Procedure / Other 
 
Study Procedure / Site Staff Authorization, Delegation, Training 
 
Study Procedure / Subject compliance 
 
Study Procedure / Unmasking (not per protocol) 
 
Study Procedure / Visit Missing 
 
Visit Window 


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Estimands
Estimand for Primary Efficacy Endpoint
The main estimand for the primary efficacy endpoint µproportion of subjects achieving  75% reduction 
from baseline in the PASI score (PASI-75) at Week 16¶ is defined as follows: 
Population: Subjects with moderate to severe plaque psoriasis defined by the study 
inclusion/exclusion criteria in Section 4.2. The analysis population for the primary efficacy 
endpoint will be full analysis set as defined in Section 6.2 and per protocol set as defined in 
Section 6.3. 
Variable: Binary variable indicating whether the subject has achieved  75% reduction from 
baseline in the PASI score (PASI-75) at Week 16.
Population-level summary: Numbers and proportions of subjects achieving  75% reduction from 
baseline in the PASI score (PASI-75) at Week 16, and differences in these proportions between 
each ME3183 treatment group and placebo group.
Intercurrent events: 
o
Withdrawals or early terminations will be handled using hypothetical strategy, where Last 
Observation Carried Forward (LOCF) and Non-responder Imputation (NRI) will be applied
as sensitivity analyses in addition to complete-case analysis.
o
All other intercurrent events will be handled using treatment policy strategy. 
Estimands for Secondary Efficacy Endpoints
The estimands for secondary efficacy endpoints are defined as below: 
Population: Subjects with moderate to severe plaque psoriasis defined by the study 
inclusion/exclusion criteria in Section 4.2. The analysis population for the secondary efficacy 
endpoints will be full analysis set as defined in Section 6.2. 
Variables: 
o
Continuous variables measuring the percent changes from baseline in PASI score at all 
visits from Week 1 to Week 16
o
Binary variables indicating whether the subject has achieved  50%, 75%, 90% and 
100% reduction from baseline in the PASI score at all visits from Week 1 to Week 16
o
Time to event variable measuring the time from baseline to the time achieving  50% and 
75% reduction in PASI score in days respectively, censored by the date of last PASI 
assessment date for subjects who never achieves  50% or 75% reduction
o
Binary variables indicating whether the subject has achieved a sPGA score of ³0´ (³clear´) 
or ³1´ (³almost clear´) combined with a 2-point reduction on the 5-point sPGA scale at all 
visits from Week 1 and Week 16
o
Continuous variables measuring the changes from baseline in BSA at all visits from 
Week 1 to Week 16
o
Continuous variables measuring the changes from baseline in NRS at all visits from 
Week 1 to Week 16
o
Continuous variables measuring the changes from baseline in DLQI score at all visits 
from Week 1 to Week 16


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o
Binary variables indicating whether a subject achieves at least a 5-point reduction from 
baseline in the DLQI score at all visits from Week 1 to Week 16
Population-level summary: 
o
Binary variables will be summarized using numbers and proportions of subjects achieving 
that outcome of interest, then differences in the proportions between each ME3183 
treatment group and placebo group will be calculated. 
o
Continuous variables will be summarized using descriptive statistics by treatment group 
and overall. Mixed-effect model for repeated measures will be used to estimate the least-
square (LS) mean differences between each ME3183 treatment group and placebo 
group. 
o
Time to event variables will be summarized using medians and 95% CIs, Kaplan-Meier 
estimates, and hazard ratios estimated Cox proportional hazard models. 
Intercurrent events: 
o
Withdrawals or early terminations will be handled via while-on-treatment policy, where no 
missing data will be imputed, except for analyses listed below where intercurrent events
will be handled via hypothetical strategy and missing data will be imputed using LOCF 
and NRI methods in addition to complete case analysis: percent change from baseline for 
PASI scores at all visits from Week 1 to Week 16, the numbers and percentages of 
subjects achieving  50%, 75%, 90% and 100% reduction from baseline in the PASI 
score at all visits from Week 1 to Week 16, the numbers and percentages of subjects 
achieving an sPGA score of ³0´ (³clear´) or ³1´ (³almost clear´) and a 2-point reduction 
from baseline.
Estimands for Secondary Safety Endpoints
The estimands for the secondary safety endpoints are defined as below: 
Population: Subjects with moderate to severe plaque psoriasis defined by the study 
inclusion/exclusion criteria in Section 4.2. The analysis population for the secondary safety
endpoints will be the safety analysis set as defined in Section 6.1. 
Variables: 
o
Binary variables indicating whether a subject experiences any AEs over the 16-week 
treatment period and the 4-week follow-up period, along with information regarding 
severity and seriousness
o
Continuous variables measuring the change from baseline in CS physical examination 
findings and vital sign measurements (blood pressure, heart rate, respiratory rate, body 
temperature, and body weight) over the 16-week treatment period and the 4-week follow-
up period
o
Continuous variables measuring the change from baseline in ECG findings over the 16-
week treatment period and the 4-week follow-up period
o
Binary variable indicating whether the subject has any abnormal ECG findings at all visits 
over the 16-week treatment period and the 4-week follow-up period
o
Continuous variables measuring the change from baseline in safety laboratory values 
(hematology, coagulation, blood chemistry and urinalysis) over the 16-week treatment 
period and the 4-week follow-up period
o
Binary variables indicating whether subject has any abnormal safety laboratory findings 
(hematology, coagulation, blood chemistry and urinalysis) over the 16-week treatment 
period and the 4-week follow-up period


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Population-level summary:  
o 
Binary variables will be summarized using numbers and proportions of subjects achieving 
that outcome of interest.  
o 
Continuous variables will be summarized using descriptive statistics.  
 
Intercurrent events:  
o 
Withdrawals or early terminations will be handled via while-on-treatment policy, where no 
missing data will be imputed.  
 


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General Aspects for Statistical Analysis
General Methods
Unless otherwise specified, summaries will be presented for each treatment group and overall.
Continuous variables will be summarized using the number of subjects (N), mean, standard 
deviation (SD), median, minimum, and maximum. Categorical variables will be tabulated with the 
number and percentage of subjects for each category.
All relevant subject data will be included in listings. All subject data will be included in listings. The 
listings will be generally sorted by treatment and subject identification (ID), unless otherwise 
specified.
Key Definitions
Age will be collected in the eCRF and the derivation is defined as follows:
Age = year of informed consent ± year of birth
BMI will be calculated using weight at baseline and height at screening using the formula below:
BMI (kg/m2) = weight (kg) / [height (m)]2
Baseline
Baseline is defined as the last non-missing assessment before the date/time of first dose of any 
study drug and includes assessments taken on Day 1, unless otherwise specified.
For PK analysis, the baseline values are those collected predose at all scheduled visits per 
Schedule of Assessments in Table 1.
Change from baseline 
The change from baseline will be calculated for each post-baseline assessment as:
Change from baseline = Post-baseline value ± baseline value
Percent change from baseline 
The percent change from baseline will be calculated for each post-baseline assessments as:
Percent change from baseline =
(Post-baseline value ± baseline value) * 100 / baseline value
Missing Data
For the purposes of assessing treatment emergence for AEs or classifying medications into 
prior/concomitant, the following algorithms will be used for partially missing dates. However, the 
assessment times (start date, stop date) without imputation will be presented in the listings.
For start dates of events: 


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Only the year is reported: 
o
If the participant did not receive any study drug (i.e., study intervention start date is 
missing), then start date will be set to µJanuary 1¶
o
If the participant received the study drug (i.e., study intervention start date is not missing): 
If the year of the start date is identical to that of the study intervention start date
and the stop date contains a full date and earlier than the study intervention start 
date, then start date will be set to µJanuary 1¶, otherwise the start date will be set 
to the study intervention start date. 
If the year of the start date is not identical to that of the study intervention start 
date, then the start date will be set to µJanuary 1¶. 
Only the month and year are reported: 
o
If the participant did not receive any study drug, then the start date will be set to the 1st
day of the month. 
o
If the participant received any study drug: 
If the month and year are identical to the month and year of the study 
intervention start date, and the stop date contains a full date earlier than the 
study intervention start date, then the start date is set to the 1st day of the month, 
otherwise set start date to the study intervention start date. 
If the month and year are not identical to the month and year of the study 
intervention start date, the start date will be set to the 1st day of the month.
For stop dates of events: 
Only the year is reported: if the last visit is in the reported year, the date of last visit will be used as 
the stop date; otherwise, ¶31 December¶ will be used as the stop date. 
Only the month and year are reported: if the last visit is in the reported month and year, the date of 
last visit will be used as the stop date; otherwise, the last day of the reported month and year will 
be used as the stop date.
If an AE has the start date completely missing, this AE will be considered as treatment-emergent, unless 
the stop date is before first dose of randomized study drug.
If a medication has the stop date completely missing, this medication will be considered as ongoing and 
concomitant.
There is no imputation for missing values in the safety analysis. The imputation of efficacy data is 
described in Section 10. 
Visit Windows
The visits recorded in database will be used for all analyses. There is no plan to re-assign visits based on 
actual visit dates.


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Pooling of Centers
This study will be conducted at approximately 28 sites. All data will be combined for summaries and 
analyses.
Subgroups
Selected analysis will be carried out further stratified by prior receipt of any biologics for psoriasis (bio-
naïve vs non-bio-naïve, where bio-naïve is defined as not receiving any biologics for psoriasis previously 
and non-bio-naïve is defined otherwise), including primary efficacy analysis and selective secondary 
efficacy analysis for PASI scores (actual values, percent change from baseline at post-baseline visits, 
proportions of subjects achieving PASI-50, PASI-75, PASI-90 and PASI-100 at post-baseline visits). 


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Demographic, Other Baseline Characteristics and Medication
Subject Disposition and Withdrawals
This section describes subject disposition for both subject study status and the subject analysis 
populations. 
The number of subjects screened, the number and percentage of subjects randomized and not 
randomized among all subjects screened, and the reasons for not being enrolled will be summarized. The 
above percentages will be calculated using the number of subjects screened as the denominator. 
The number of subjects randomized and the number and percentage of subjects included in the safety 
analysis population, FAS, PPS, PK analysis set and 
will be summarized by 
treatment group and overall. Subjects withdrawing early and primary reason for withdrawal will be 
summarized. The above percentages will be calculated using the number of subjects enrolled as the 
denominator. The completion status and the reason for discontinuation will be listed.
A frequency table will be provided to summarize the number and percentages of randomized subjects 
excluded from the Safety Analysis Set, FAS, PPS, PK Set and 
. Additionally, reasons for 
exclusion will be summarized for each analysis set, where numbers and percentages for each 
 
category will be displayed. All percentages are based on the number of subjects randomized within each 
treatment group and overall. Listings of subjects excluded from the analysis populations, with the reasons 
for exclusions, will be provided. 
Protocol Deviation
Major protocol deviations, as determined in the Blind Data Review Meeting (BDRM) prior to database 
lock, may result in the removal of a subject from the PPS.  
The number and percentage of subjects with at least one major protocol deviation by type of deviation 
category will be presented by treatment group and overall. In addition, all protocol deviations (including 
both major and minor deviations) will be provided in a by-subject listing.
Demographic and Baseline Characteristics
Demographics and baseline characteristics will be summarized descriptively by treatment group and 
overall using Safety Analysis Set, FAS and PPS. The comparability of the treatment groups for each 
relevant characteristic will be assessed descriptively in table format; no statistical hypothesis tests will be 
performed on these characteristics.  
For summaries (number and percentage) of categorical variables in demographics and baseline disease 
characteristics, a ³missing´ or ³not applicable´ level may be added (in addition to the levels specified 
below) to account for missing or not applicable data as appropriate.
Demographics and Baseline Characteristics
Summary statistics will be provided by treatment group and overall for the following variables:
Age (years)
Sex (Male, Female)
Child bearing potential for female subjects only (No, Yes)


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Race (White, Black or African American, Asian, Native Hawaiian or Pacific Islander, American 
Indian or Alaska Native)
Ethnicity (Hispanic or Latino, Not Hispanic or Latino)
Height (cm) at screening. Conversion to cm: Height (in inch) * 2.64
Weight (kg) at baseline. Conversion to kg: Weight (in lbs.) * 0.4536
BMI (kg/m2) 
Previously Treated with Any Biologics for Psoriasis (Yes, No)
Allergy or Toxicity of Previous Treatment (Yes, No)  
History of Substance Abuse (Yes, No)
Smoking
o
Yes (Light, Moderate, Heavy, Other)
o
No (Past Smoker, Never Smoker)
Alcohol Intake
o
Yes (Beer, Wine, Spirits, Other)
o
No
Baseline Clinical Characteristics
Baseline clinical characteristics will be summarized descriptively by treatment group and overall and will 
include the following:
Age at initial diagnosis of psoriasis (years)
Duration of plaque psoriasis (from date of initial diagnosis to the date of informed consent; year, 
presented with one decimal of accuracy)
Type of psoriasis at initial diagnosis (Plaque, Guttate, Pustular, Inverse, Erythrodermic, Nail 
psoriasis, Psoriatic arthritis, Not known)
Severity of psoriasis at initial diagnosis (Mild, Moderate, Severe, Unknown)
Prior treatment for psoriasis (Yes, No)
Any associated types of psoriasis other than plaque at screening (Yes, No)
Other associated types of psoriasis at screening (Guttate, Pustular, Inverse, Erythrodermic, Nail 
psoriasis)
Medical History 
Medical history terms will be coded using the Medical Dictionary for Regulatory Activities (MedDRA)
dictionary Version 24.1 or later. A frequency table (with number and percentage) of medical history will be 
presented by treatment group and overall in terms of system organ class (SOC) and preferred term (PT)
for the Safety Analysis Set.
Prior and Concomitant Medications and Procedures
Medications will be coded using the World Health Organization (WHO) Drug Dictionary Version 
September 2021 or later, and subject incidence will be tabulated by Anatomic Therapeutic Class (ATC) 
Level 2 and preferred term (PT) for the Safety Analysis Set. The systemic medication of psoriasis will be 
summarized and listed separately.
Prior procedures will be collected with medical history, coded using MedDRA Version 24.1 or later and 
summarized by SOC and PT for the Safety Analysis Set.


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See Section 8.3 for handling of partial dates for medications/procedures, in the case where it is not 
possible to define a medication/procedures as prior, concomitant, or post treatment.
Prior medications/procedures are the medications/procedures which started and stopped prior to 
the first dose of study drug.
Concomitant medications/procedures are medications/procedures which started prior to, on or 
after the first dose of study drug and before or on the date of last dose of study drug.
Post medications/procedures are medications/procedures which started after the last dose of 
study drug.
Prior Treatment for Psoriasis
Prior systemic treatment for psoriasis is collected from the eCRF page ³Prior Systemic Treatment for 
Psoriasis´. The medications will be coded using WHO Drug Dictionary version September 2021 or later 
and summarized by ATC and PT for the Safety Analysis Set.
Extent of Exposure
Treatment duration will be summarized by treatment and overall using the Safety Analysis Set. 
Subject data listings of study drug dispensation records will be provided.
Treatment duration (in days) is calculated as the date of the last dose of study drug ± the date of the first 
dose of study drug + 1. 
The specific definitions of the first dose and last dose dates of study drug are given below:
First dose date: The date of the first dose of study drug that is dispensed at Week 0/Visit 2 
obtained from the study drug exposure eCRF page. 
Last dose date: The date of the last dose of study drug obtained from the end of treatment eCRF
page for subjects who have completed the treatment or discontinued early.
Summary statistics for treatment duration (in days), as well as a frequency summary of treatment duration 
categories (<7 days, 7 - <14 days, 14 - <28 days, 28 - <56 days, 56 - <84 days, 84 ±
112 days, > 112 
days), will be provided.
Treatment Compliance 
As part of the routine recording of the amount of study drug taken by each subject, the numbers of 
capsules dispensed and returned, as well as the number of planned and actual capsules taken will be 
recorded at each visit during treatment period, starting at Visit 2. 
The overall study drug compliance is collected from eCRF page ³Study Drug Accountability´. The 
derivation is defined as below:
Overall compliance (percent): calculated as actual number of actual capsules taken / planned 
number of actual capsules taken x 100%
Treatment compliance will not be calculated for subjects (if existent) who have only the tablet dispensed
record at Week 0/Visit 2 and no other drug accountability records. A frequency summary of compliance 


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will also be presented with the following categories: < 70%, 70% -  85%, 85% - 100%, and >100% by 
treatment group and overall. 


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Efficacy
Unless otherwise specified, all efficacy analyses will be performed using the FAS. The analysis of the 
primary efficacy endpoint and selective analysis for the secondary endpoints will also be performed using 
the PPS.
Primary Efficacy Endpoint and Analysis
The primary efficacy endpoint is the proportion of subjects achieving  75% reduction from baseline in the 
PASI score at Week 16. Baseline is defined as the PASI score on Day 1 pre-dose.
For each ME3183 treatment group, the difference in the proportion of subjects achieving the difference in 
PASI-75 (ME3183 ± placebo) and its 95% confidence interval (CI) will be estimated and tested for 
superior treatment effect using the Cochran-Mantel-Haenszel (CMH) test with prior receipt of any 
biologics for psoriasis (bio-naïve vs non-bio-naïve) as adjustment factor at a 1-sided significance level of 
 = 0.025. 
Analysis will be conducted using observed data at Week 16 only (complete-case analysis). In the 
presence of missing data, additional sensitivity analysis will be conducted using both LOCF and NRI. 
Under LOCF, the last non-missing PASI score will be carried forward to Week 16, based on which the 
subject will be considered as responder or non-responder and summarized accordingly. Under NRI, 
subjects with missing PASI scores at Week 16 will be considered non-responders.
Subgroup analysis will be carried out stratified by the prior receipt of any biologics for psoriasis (bio-naïve 
vs non-bio-naïve), where Fisher¶s exact test will be used instead of CMH for superiority. 
Secondary Efficacy Endpoints and Analyses
The binary variables for secondary endpoints include the following:
The proportion of subjects achieving PASI-50, PASI-75, PASI-90, PASI-100 at all visits from 
Week 1 to Week 16 
The proportion of subjects achieving an sPGA score of ³0´ (³clear´) or ³1´ (³almost clear´) 
combined with 2-point reduction on the 5-point sPGA scale at all visits from Week 1 to Week 16 
The proportion of subjects with at least a 5-point reduction from baseline in the DLQI score at all 
visits from Week 1 to Week 16 
The binary secondary endpoints will be analyzed using similar methods as described in Section 10.1.
Analysis of PASI-related secondary endpoints will be based on both FAS and PPS using complete case 
analysis, LOCF and NRI. In addition, analysis will be performed stratified by receipt of any biologics for 
psoriasis based on FAS. Analysis of the secondary endpoint of achieving an sPGA score of ³0´ (³clear´) 
or ³1´ (³almost clear´) combined with a 2-point reduction on the 5-point sPGA scale will be based on both 
FAS and PPS using complete analysis, LOCF and NRI. Analysis of the secondary endpoint of at least 5-
point reduction from baseline in the DLQI score will be based on both FAS and PPS using complete case 
analysis only. 
The continuous variables for secondary endpoints include the following:


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The percent change from baseline in PASI score at all visits from Week 1 to Week 16 
 
The change from baseline in affected BSA at all visits from Week 1 to Week 16  
 
The change from baseline in the itch NRS at all visits from Week 1 to Week 16  
 
The change from baseline in the DLQI score at all visits from Week 1 to Week 16  
Descriptive statistics for the continuous secondary endpoints described above will be provided at each 
schedule visit by treatment group. Additionally, the secondary continuous efficacy endpoints (including 
percent changes for PASI, changes for DLQI, BSA and NRS) will be analyzed using a mixed-effect model 
for repeated measures (MMRM) with the change or percent change from baseline as the response 
variable, treatment group, visit, treatment-by-visit interaction as fixed effects, and the baseline value as a 
covariate. An unstructured covariance matrix will be used to model the correlation among repeated 
measurements. The Kenward-Roger adjustment will be used with restricted maximum likelihood (REML) 
to make proper statistical inference. The LS mean differences between ME3183 treatment groups and 
placebo at each scheduled visits along with the 2-sided 95% CIs and 2-sided p-values will be estimated 
from the MMRM model. In the event that MMRM with unstructured covariance matrix fails to converge, 
alternative covariance structures will be explored, including Toeplitz, heterogeneous Toeplitz, variance 
components, compound symmetry, heterogeneous compound symmetry, autoregressive and 
heterogeneous autoregressive covariance matrices, where the optimal covariance matrix structure will be 
selected based on Akaike¶s Information Criteria (AIC), where smaller values of AIC indicate better overall 
fit. MMRMs will be estimated for the secondary continuous efficacy endpoints using complete case 
analysis only.  
Kaplan-Meier method will be used for summarizing the time to the first response of PASI-50 and PASI-75 
in days. The time to the first response of PASI-50 and PASI-75 is defined as the number of days from the 
first dose of the study drug to the first response. If a subject does not achieve PASI-50 and PASI-75, the 
variable will be censored on the last PASI assessment date. Median time to response and 95% CI will be 
provided, when estimable. The CI will be based on log-log transformation. The reverse Kaplan-Meier 
plots of PASI-50 and PASI-75 will be presented by treatment group. The comparison of the time to PASI-
50 and PASI-75 between each ME3183 treatment group and placebo will be performed using the log-rank 
test.   
The Cox proportional hazard model will be used for analyzing the time to PASI-50 and PASI-75, where 
time to the first response of PASI-50 or PASI-75 will be used as outcome variables and treatment group 
will be included as covariates. Estimated hazard ratios along with 95% CIs and p-values between each 
ME3183 treatment group and placebo will be provided.  
For the secondary endpoints of proportions of subjects achieving PASI-50, PASI-75, PASI-90, PASI-100 
at all visits from Week 1 to Week 16 and percent change in PASI scores from baseline at all visits from 
Week 1 to Week 16, any missing PASI scores arising from intercurrent events will be imputed via LOCF 
and NRI, similar to the methods described in Section 10.1 for the primary efficacy endpoints, in addition to 
the complete case analysis. 
For PASI and DLQI, in addition to the total score, the region specific PASI scores (head, upper limbs, 
trunk, lower limbs) and the numerical responses for each of the ten questions in DLQI questionnaire will 
be summarized descriptively at each study visit for the actual values and changes from baseline for all 
post-baseline visits. 


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Exploratory Efficacy Endpoints and Analyses


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Pharmacokinetics
The PK analysis set will be used for the PK analysis. 
PK Sampling Schedule 
Blood samples for quantitation of ME3183 and its metabolite (
) will be collected at the time points 
indicated in Section 4.6 Table 1 Schedule of Assessment. The actual date and time of each blood sample 
collection will be recorded in the subject¶s eCRF and will be reported in the PK listing. The plasma 
samples will then be sent for bioanalysis using a validated method. 
Plasma PK Endpoint
The Ctrough in plasma of ME3183 and its metabolite (
) will be summarized descriptively by 
treatment group in the Tables, Figures and Listings (TFLs).
Presentation of Concentration Data
Handling of Missing Data 
Missing concentration data for all subjects who are administered study drug will be considered as non-
informative missing and will not be imputed. No concentration estimates will be provided for missing 
sample values. 
For individual plasma concentration vs. time curves, the following rules will apply:
Concentration values below the limit of quantification (BLQ) of the corresponding analyte 
(ME3183 or 
) in samples will be treated as zero, with the exception of calculation of 
geometric mean and geometric coefficient of variation% (CV%), for which these assessments will 
be excluded. 
Listing and Presentation of Individual PK Data
The following presentations of individual PK concentrations will be produced: 
-
Listing of PK sampling times including nominal and actual time elapsed from dose with the 
deviation from the nominal time and measured concentrations of the drug. 
Individual Ctrough concentrations in linear scale for all subjects by treatment combined on one graph and 
plotted for each day.
PK Parameters Derivation
No PK parameters derivation is planned for ME3183 and its metabolite (
) concentrations.
PK Parameters Summarization
For summarization of PK data for ME3183 and its metabolite (
), the following data handling 
measures will be employed: 
-
The mean/median value at a time point where 1 or more samples have BLQ values will be 
reported even if the mean/median value is BLQ. 
-
Zero mean or median values will be included in summary tables. 
-
SD will not be displayed if more than 30% of values are missing or BLQ. 


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-
Tables of summary statistics for concentration-time data will be reported as per below table. 
The following summary presentations of mean PK concentrations for ME3183 and its metabolite 
(
) will be produced: 
-
Table of PK concentrations summarized by nominal time for each treatment separately. 
-
Mean Ctrough profiles in linear scale for both treatments vs. nominal time. 
Variable
Summarized with:
plasma concentration at 
each time point
n, number and % BLQ, arithmetic mean, SD, coefficient of variance
(CV) %, Geometric mean and CV%, minimum, median and
maximum
CV% = SD/mean in %.
%BLQ = 100 * (total number of subjects who have BLQ values/total number of exposed subjects
within treatment group, with a PK assessment at each time point).
Planned Statistical Models for PK Parameters and Concentrations
No formal statistical analysis is planned for ME3183 and its metabolite (
) concentrations.
Interim Analyses
No formal interim analysis is planned.
Deviation from Analyses Planned in Protocol
Not applicable.


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Safety
All safety analyses will be performed using the safety analysis set. 
Adverse Events 
An AE is any symptom, physical sign, syndrome, or disease that either emerges during the study or, if 
present at Screening, worsens during the study, regardless of the suspected cause of the event. AEs will 
be collected from the time the subject signs the ICF through 4 weeks after the last dose of study drug.
AEs will be coded according to the MedDRA Version 24.1 or higher. Unless otherwise specified, AEs will 
be summarized by SOC and PT by treatment group and overall, with SOCs presented in the standard 
international order and PTs within SOCs presented in descending order of subject incidence.
Adverse events are summarized by subject incidence rates. In any tabulation, a subject contributes only 
once to the count for a given SOC or PT. If a subject experiences more than 1 occurrence of the same 
AE, the occurrence with the greatest severity and the closest association with the study drug will be used 
in the summary tables.
For the purposes of this study, any AEs classified as µUnrelated¶ or µUnlikely¶ will be considered as µNot 
Related¶ and µPossibly¶, µProbably¶, or µDefinitely¶ as µRelated¶ to the study treatment. Missing relationship 
will be considered related to study product.
All AEs will be listed by subject, along with information regarding onset, duration, relationship and severity 
to study drug, seriousness, action taken with study drug, and outcome.
Treatment-Emergent Adverse Events
A Treatment-Emergent Adverse Event (TEAE) is an AE that occurred during the study after the first dose 
of study drug or that was present prior to dosing and exacerbates after the first dose of study drug. 
If the treatment-emergent status of an AE is unclear due to a missing/incomplete start date, it will be 
considered treatment-emergent. Date imputation rules for missing AE start dates are described in Section 
8.3.
Overall summary of AEs
An overall summary of the following AE categories will be provided for all subjects in the Safety Analysis 
Set:
Any AEs
Any TEAEs
Any drug-related TEAEs
Any severe TEAEs
Any serious TEAEs
Any serious drug-related TEAEs
Any TEAEs leading to treatment discontinuations
Any serious TEAEs leading to treatment discontinuation
Any TEAEs leading to death
Any deaths


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TEAEs by Maximum Severity/Relationship
All TEAEs will be summarized by maximum severity (mild, moderate, severe, and, if needed, missing). If 
a subject reports multiple occurrences of a specific event within a specific analysis period, the subject will 
be counted only once by the maximum severity. If the severity is missing for one or more but not all of the 
occurrences of the same event, the maximum severity of the remaining occurrences with non-missing 
severities will be used. If the severity is missing for all of the occurrences, the subject will be counted only 
once in the ³missing´ category of severity.
Similarly, all TEAEs will be summarized by maximum relationship to the study drug (unrelated, unlikely, 
possibly, probably, definitely related, and missing if needed). If a subject reports multiple occurrences of a 
specific event within a specific analysis period, the subject will be counted only once by the maximum 
relationship. If the relationship is missing for one or more but not all of the occurrences of the same event, 
the maximum relationship of the remaining occurrences with non-missing relationships will be used. If the 
relationship is missing for all of the occurrences, the subject will be counted only once in the ³missing´ 
category of relationship to the study drug.
TEAEs by Time of Onset
All TEAEs will be summarized by time of onset (Day 1 ± 3, Day 4 ± 7, Day 8 ± 14, Day 15 ± 21, Day 22 ±
28, Day 29 ± 56, Day 57 ± 84, Day 85 ± 113, Day 114+), where an overall summary of the numbers and
percentages of subjects with any TEAEs within a particular time of onset period will be calculated along 
with further breakdown by SOC and PT.
Laboratory Evaluations
Laboratory tests include the following:
Viral serology (HBV, HCV, and HIV) 
Hematology and coagulation 
Blood chemistry 
Urinalysis (Dipstick)
Pregnancy tests (WOCBP only; serum or urine -human chorionic gonadotropin) 
Serum follicle-stimulating hormone (FSH) (postmenopausal women only) 
Summary statistics of actual values and changes from baseline will be provided for each laboratory 
parameters by treatment group at each study visit if the results of the laboratory are continuous.
Frequencies tables, including numbers and percentages of subjects with normal and abnormal (low vs 
high), will be presented for laboratory parameters with categorical results by treatment group at each 
study visit. Shift tables will also be provided displaying the numbers and percentages of subjects with 
normal and abnormal results compared with the results at baseline.
Viral serology and pregnancy test results will be summarized in listings only. Subject data listings of all 
laboratory data will be provided.
Vital Signs 
Vital signs (body temperature, body weight, respiratory rate, heart rate, systolic and diastolic blood 
pressure measurements) will be evaluated at the visits indicated in the Schedule of Assessments (Table 
1). Summary statistics for actual values and changes from baseline in vital signs will be provided for each 


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vital sign parameter at each scheduled visit by treatment group and overall. A subject data listing of all 
vital sign data will be provided.
ECG
A 12-lead, resting ECG will be obtained at the visits indicated in the Schedule of Assessments (Table 1).
Summary statistics for actual values and changes from baseline will be provided for each of the ECG 
parameters at each scheduled visits, including ventricular rate (bpm), PR (msec), QRS (msec), QT 
(msec), and QTcF (msec) measurements will be obtained. A frequency table with number of percentage 
of patients with normal, abnormal and clinically significant abnormal ECG results will be provided. The 
clinically noteworthy QT/QTc interval (>450, >480, or >500 msec) or clinically noteworthy change from 
baseline (>30 or >60 msec) will also be summarized using frequency tables by treatment group at each 
scheduled visit.
Physical Examination
A complete physical examination including height and weight will be performed at Screening (Visit 1). A 
targeted physical examination to verify continued subject eligibility and to follow-up regarding any change 
in medical history will be performed at the study visits indicated in Schedule of Assessments (Table 1). 
Symptom-driven, targeted physical examinations will be performed as clinically indicated at any study 
visit. Any CS physical examination finding should be reported as an AE. All physical examination data will 
be summarized in data listings. 


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Changes from Analysis Planned in Protocol
There are no changes from analysis planned in the study protocol. 


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Reference List
None. 


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Programming Considerations
All TFLs, and statistical analyses will be generated using SAS Version 9.4 (SAS Institute Inc., Cary, 
NC, USA). Computer-generated TFL outputs will adhere to the following specifications.
General Considerations
One SAS program can create several outputs, or a separate SAS program will be created for each 
output.
One output file can contain several outputs or each output will be stored in a separate file.
Output files will be delivered in Word format or portable document format pdf.
Numbering of TFLs will follow International Council for Harmonisation (ICH) E3 guidance.
Table, Figure, and Listing Format
General
All TFLs will be produced in landscape format on <American letter size / A4 paper size>, unless 
otherwise specified.
All TFLs will be produced using the Courier New font, size 8 which is the smallest acceptable point 
size for the Regulatory Authorities.
The data displays for TFLs will have a minimum blank 1-inch margin on all 4 sides.
Headers and footers for figures will be in Courier New font, size 8 which is the smallest acceptable 
point size for the Regulatory Authorities.
Legends will be used for all figures with more than one variable, group, or item displayed.
TFLs will be in black and white (no color), unless otherwise specified.
Specialized text styles, such as bolding, italics, borders, shading, and superscripted and 
subscripted text, will not be used in the TFLs, unless otherwise specified. On some occasions, 
superscripts 1, 2, or 3 may be used.
Only standard keyboard characters will be used in the TFLs. Special characters, such as non-
printable control characters, printer-specific, or font-specific characters, will not be used. 
Hexadecimal-derived characters will be used, where possible, if they are appropriate to help display 
math symbols (e.g., ). Certain subscripts and superscripts (e.g., cm2, Cmax) will be employed on 
a case-by-case basis.
Mixed case will be used for all titles, footnotes, column headers, and programmer-supplied formats, 
as appropriate.
Headers
All outputs will have the following header at the top left of each page: 
Meiji Pharma USA Inc.


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Protocol ME3183-3 (
Study Number 7028898)
Draft/Final Run: <ddmmmyyyy>
All outputs will have Page n of N at the top or bottom right corner of each page. TFLs are internally 
paginated in relation to the total length (i.e., the page number will appear sequentially as page n of 
N, where N is the total number of pages in the table).
The date the output was generated will appear along with the program name as a footer on each 
page.
Display Titles
Each TFL will be identified by the designation and a numeral (i.e., Table 14.1.1). A decimal system 
(x.y and x.y.z) are used to identify TFLs with related contents. The title will be centered. The 
analysis set will be identified on the line immediately following the title and will be enclosed in 
parenthesis. The title and table designation will be single spaced. A solid line spanning the margins 
will separate the display titles from the Column headers. There will be one blank line between the 
last title and the solid line.
Table x.y.z
First Line of Title
Second Line of Title if Needed
(ITT Analysis Set)
Column Headers
Column headings will be displayed immediately below the solid line described above in initial 
upper-case characters. 
In the case of efficacy tables, the variable (or characteristic) column is on the far left followed by the 
treatment group columns and total column (if applicable). P-values may be presented under the 
total column or in separate p-value column (if applicable). Within-treatment comparisons may have 
p-values presented in a row beneath the summary statistics for that treatment.
For numeric variables, include µunit¶ in column or row heading when appropriate.
Analysis set sizes will be presented for each treatment group in the column heading as (N=xx) (or 
in the row headings, if applicable). This is distinct from the µn¶ used for the descriptive statistics 
representing the number of subjects in the analysis set.
The order of treatments in the tables and listings will be Placebo first in the case of placebo 
controlled studies and Active comparators first in the case of active comparator trials, followed by a 
total column (if applicable).
Body of the Data Display
16.2.5.1.
General Conventions
Data in columns of a table or listing are formatted as follows:


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 Alphanumeric values will be left-justified; 
 Whole numbers (e.g., counts) will be right-justified; and 
 Numbers containing fractional portions will be decimal aligned. 
16.2.5.2. 
Table Conventions 
 Units will be included where available. 
 For categorical parameters, all categories will be presented in the table, even if n=0 for all 
treatment groups in a given category. For example, the frequency distribution for symptom severity 
would appear as: 
Severity 
Rating 
N 
severe 
0 
moderate 
8 
mild 
3 
 
Where percentages are presented in these tables, zero percentages will not be presented and so counts 
of 0 will be presented as 0 and not as 0 (0%). 
 An Unknown or Missing category will be added to each parameter for which information is not 
available for 1 or more subjects. 
 Unless otherwise specified, the estimated mean and median for a set of values will be printed out 
to 1 more significant digit than the original values, and standard deviations will be printed out to 2 
more significant digits than the original values. The minimum and maximum will report the same 
significant digits as the original values. For example, systolic blood pressure will be presented as 
follows: 
N 
 XX 
Mean 
XXX.X 
Std Dev 
   X.XX 
Median 
XXX.X 
Minimum 
XXX 
Maximum 
XXX 
 
 P-values will be output in the format: µ0.xxx¶, where xxx is the value rounded to 3 decimal places. 
Every p-value less than 0.001 will be presented as <0.001. If the p-value are less than 0.0001, then 
present as <0.0001. If the p-value is returned as >0.999, then present as >0.999. 
 Percentage values will be printed to one decimal place, in parentheses with no spaces, one space 
after the count (e.g., 7 (12.8%), 13 (5.4%)). Unless otherwise noted, for all percentages, the 
number of subjects in the analysis set for the treatment group who have an observation will be the 
denominator. Percentages after zero counts will not be displayed and percentages equating to 
100% will be presented as 100%, without decimal places. 


Statistical Analysis Plan for Interventional Studies
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SAP Version: Final V3.0 11-Jul-2023
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Tabular display of data for medical history, prior/concomitant medications, and all tabular displays 
of adverse event data will be presented by the body system, treatment class, or SOC with the 
highest occurrence overall in decreasing order, assuming all terms are coded. Within the body 
system, drug class and SOC, medical history (by preferred term), drugs (by ATC1 code), and 
adverse events (by preferred term) will be displayed in decreasing order. If incidence for more than 
1 term is identical, they will then be sorted alphabetically. Missing descriptive statistics or p-values 
which cannot be estimated will be reported as µ-¶.
The percentage of subjects will normally be calculated as a proportion of the number of subjects 
assessed in the relevant treatment group (or overall) for the analysis set presented. However, 
careful consideration is required in many instances due to the complicated nature of selecting the 
denominator, usually the appropriate number of subjects exposed. Details will be described in 
footnotes or programming notes, as necessary.
For categorical summaries (number and percentage of subjects) where a subject can be included 
in more than one category, a footnote or programming note will be added describing whether the 
subject is included in the summary statistics for all relevant categories or just 1 category as well as 
the selection criteria.
Where a category with a subheading (such as SOC) has to be split over more than one page, 
output the subheading followed by µ(cont)¶ at the top of each subsequent page. The overall 
summary statistics for the subheading should only be output on the first relevant page.
16.2.5.3.
Listing Conventions
Listings will be sorted for presentation in order of treatment groups as above, subject number, 
visit/collection day, and visit/collection time.
Missing data will be represented on subject listings as either a hyphen (µ-¶) with a corresponding 
footnote (µ- = unknown or not evaluated¶), or as µN/A¶, with the footnote µN/A = not applicable¶, 
whichever is appropriate.
Dates will be printed in SAS DATE9.format (µDD_MMM_YYYY¶: 01JUL2000). Missing portions of 
dates will be represented on subject listings as dashes (--JUL2000). Dates that are missing 
because they are not applicable for the subject will be output as µN/A¶, unless otherwise specified.
All observed time values will be presented using a 24-hour clock HH:MM or HH:MM:SS format 
(e.g., 11:26:45, or 11:26). Time will only be reported if it was measured as part of the study.
Units will be included where available.
16.2.5.4.
Figure Conventions
Unless otherwise specified, for all figures, study visits will be displayed on the X-axis and endpoint 
(e.g., treatment mean change from baseline) values will be displayed on the Y-axis.
Footnotes
A solid line spanning the margins will separate the body of the data display from the footnotes. 


Statistical Analysis Plan for Interventional Studies 
Sponsor: Meiji Pharma USA Inc.; Protocol No.: ME3183-3 
 
This document is confidential. 
SAP Version: Final V3.0 11-Jul-2023 
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 All footnotes will be left justified with single-line spacing immediately below the solid line 
underneath the data display. 
 Footnotes will always begin with µNote:¶ if an informational footnote, or 1, 2, 3, etc. if a reference 
footnote. Each new footnote will start on a new line, where possible. 
 Subject specific footnotes are avoided, where possible. 
 Footnotes will be used sparingly and add value to the TFL. If more than six lines of footnotes are 
planned, then a cover page is strongly recommended to be used to display footnotes, and only 
those essential to comprehension of the data will be repeated on each page. 
 The last line of the footnote section will be a standard source line that indicates the name of the 
program used to produce the data display, the date the program was run, and the listing source 
(i.e., µProgram : myprogram.sas  Listing source: 16.x.y.z¶). 
 Sources and/or cross-references in footnotes will use the keyword prefix (Listing or Table) for each 
type of reference and will be separated by a comma when multiple cross-references of the same 
type are displayed where the prefix will be displayed in plural forms. When multiple types of 
references are involved, they would be separated by ³;´. 
Example 
Listing source: Table 14.2.4.1; Listings 16.2.4.1.1, 16.2.4.1.2, 16.2.4.2.1 


Statistical Analysis Plan for Interventional Studies
Sponsor: Meiji Pharma USA Inc.; Protocol No.: ME3183-3
This document is confidential.
SAP Version: Final V3.0 11-Jul-2023
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Quality Control
SAS programs are developed to produce output such as analysis data sets, summary tables, data 
listings, figures or statistical analyses. An overview of the development of programs is detailed in 
 
 Developing Statistical Programs SOP (3907).
Developing Statistical Programs SOP (3907), Conducting the Transfer of Biostatistical 
Deliverables SOP (3908) and the SAS Programming and Validation Plan describes the quality control 
procedures that are performed for all SAS programs and output. Quality control is defined here as the 
operational techniques and activities undertaken to verify that the SAS programs produce the output by 
checking for their logic, efficiency and commenting and by review of the produced output.


Statistical Analysis Plan for Interventional Studies
Sponsor: Meiji Pharma USA Inc.; Protocol No.: ME3183-3
This document is confidential.
SAP Version: Final V3.0 11-Jul-2023
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020
Filing requirements: TMF
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Index of Tables
Table Number
Name
Analysis Set
14.1.1.1
Number of Subjects Enrolled and Study Termination
(Screened/Randomized Set)
14.1.2.1
Major Protocol Deviations
(Randomized Set)
14.1.2.2
Reasons for Exclusions from Analysis Sets
(Randomized Set)
14.1.3.1.1
Subject Demographic and Baseline Characteristics
(Randomized Set)
14.1.3.1.2
Subject Demographic and Baseline Characteristics
(Safety Analysis Set)
14.1.3.1.3
Subject Demographic and Baseline Characteristics
(Full Analysis Set)
14.1.3.1.4
Subject Demographic and Baseline Characteristics
(Per Protocol Set)
14.1.3.2.1
Baseline Disease Characteristics
(Randomized Set)
14.1.3.2.2
Baseline Disease Characteristics
(Safety Analysis Set)
14.1.3.2.3
Baseline Disease Characteristics
(Full Analysis Set)
14.1.3.2.4
Baseline Disease Characteristics
(Per Protocol Set)
14.1.3.3
Medical History
(Safety Analysis Set)
14.1.4.1.1
Prior Medications
(Safety Analysis Set)
14.1.4.1.2
Concomitant Medications
(Safety Analysis Set)
14.1.4.2.1
Prior Medical/Surgical Procedures
(Safety Analysis Set)
14.1.4.2.2
Concomitant Medical/Surgical Procedures
(Safety Analysis Set)
14.1.4.3
Prior Biologics or Systemic Treatment for Psoriasis
(Safety Analysis Set)
14.1.5
Extent of Exposure
(Safety Analysis Set)
14.1.6
Treatment Compliance
(Safety Analysis Set)
14.2.1.1.1.1
Proportion of Subjects Achieving PASI-75 at Week 
16, Complete Case Analysis
(Full Analysis Set)
14.2.1.1.1.2
Proportion of Subjects Achieving PASI-75 at Week 
16 Stratified by Receipt of Any Biologics for 
Psoriasis, Complete Case Analysis
(Full Analysis Set)
14.2.1.1.2.1
Proportion of Subjects Achieving PASI-75 at Week 
16, LOCF
(Full Analysis Set)
14.2.1.1.2.2
Proportion of Subjects Achieving PASI-75 at Week 
16 Stratified by Receipt of Any Biologics for 
Psoriasis, LOCF
(Full Analysis Set)
14.2.1.1.3.1
Proportion of Subjects Achieving PASI-75 at Week 
16, NRI
(Full Analysis Set)
14.2.1.1.3.2
Proportion of Subjects Achieving PASI-75 at Week 
16 Stratified by Receipt of Any Biologics for 
Psoriasis, NRI
(Full Analysis Set)
14.2.1.2.1.1
Proportion of Subjects Achieving PASI-75 at Week 
16, Complete Case Analysis
(Per Protocol Set)
14.2.1.2.1.2
Proportion of Subjects Achieving PASI-75 at Week 
16 Stratified by Receipt of Any Biologics for 
Psoriasis
(Per Protocol Set)
14.2.1.2.2.1
Proportion of Subjects Achieving PASI-75 at Week 
16, LOCF
(Per Protocol Set)
14.2.1.2.2.2
Proportion of Subjects Achieving PASI-75 at Week 
16 Stratified by Receipt of Any Biologics for 
Psoriasis, LOCF
(Per Protocol Set)


Statistical Analysis Plan for Interventional Studies 
Sponsor: Meiji Pharma USA Inc.; Protocol No.: ME3183-3 
 
This document is confidential. 
SAP Version: Final V3.0 11-Jul-2023 
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Table Number 
Name 
Analysis Set 
14.2.1.2.3.1 
Proportion of Subjects Achieving PASI-75 at Week 
16, NRI 
(Per Protocol Set) 
14.2.1.2.3.2 
Proportion of Subjects Achieving PASI-75 at Week 
16 Stratified by Receipt of Any Biologics for 
Psoriasis, NRI 
(Per Protocol Set) 
14.2.2.1.1.1 
Summary of PASI by Visit: Actual Values, Percent 
Changes, Proportions of Subjects Achieving PASI-
50, PASI-75, PASI-90 and PASI-100, Complete 
Case Analysis 
(Full Analysis Set) 
14.2.2.1.1.2 
Summary of PASI by Visit: Actual Values, Percent 
Changes, Proportions of Subjects Achieving PASI-
50, PASI-75, PASI-90 and PASI-100 Stratified by 
Receipt of Any Biologics for Psoriasis, Complete 
Case Analysis 
(Full Analysis Set) 
14.2.2.1.2.1 
Summary of PASI by Visit: Actual Values, Percent 
Changes, Proportions of Subjects Achieving PASI-
50, PASI-75, PASI-90 and PASI-100, LOCF 
(Full Analysis Set) 
14.2.2.1.2.2 
Summary of PASI by Visit: Actual Values, Percent 
Changes, Proportions of Subjects Achieving PASI-
50, PASI-75, PASI-90 and PASI-100 Stratified by 
Receipt of Any Biologics for Psoriasis, LOCF 
(Full Analysis Set) 
14.2.2.1.3.1 
Summary of PASI by Visit: Proportions of Subjects 
Achieving PASI-50, PASI-75, PASI-90 and PASI-
100, NRI 
(Full Analysis Set) 
14.2.2.1.3.2 
Summary of PASI by Visit: Proportions of Subjects 
Achieving PASI-50, PASI-75, PASI-90 and PASI-
100 Stratified by Receipt of Any Biologics for 
Psoriasis, NRI 
(Full Analysis Set) 
14.2.2.2.1 
Summary of PASI by Visit: Actual Values, Percent 
Changes, Proportions of Subjects Achieving PASI-
50, PASI-75, PASI-90 and PASI-100, Complete 
Case Analysis 
(Per Protocol Set) 
14.2.2.2.2 
Summary of PASI by Visit: Actual Values, Percent 
Changes, Proportions of Subjects Achieving PASI-
50, PASI-75, PASI-90 and PASI-100, LOCF 
(Per Protocol Set) 
14.2.2.2.3 
Summary of PASI by Visit: Proportions of Subjects 
Achieving PASI-50, PASI-75, PASI-90 and PASI100, 
NRI 
(Per Protocol Set) 
14.2.3.1.1 
Proportion of Subjects with an sPGA Score of 0 or 1 
and a 2-Point Reduction from Baseline, Complete 
Case Analysis 
(Full Analysis Set) 
14.2.3.1.2 
Proportion of Subjects with an sPGA Score of 0 or 1 
and a 2-Point Reduction from Baseline, LOCF 
(Full Analysis Set) 
14.2.3.1.3 
Proportion of Subjects with an sPGA Score of 0 or 1 
and a 2-Point Reduction from Baseline, NRI 
(Full Analysis Set) 
14.2.3.2.1 
Proportion of Subjects with an sPGA Score of 0 or 1 
and a 2-Point Reduction from Baseline, Complete 
Case Analysis 
(Per Protocol Set) 
14.2.3.2.2 
Proportion of Subjects with an sPGA Score of 0 or 1 
and a 2-Point Reduction from Baseline, LOCF 
(Per Protocol Set) 


Statistical Analysis Plan for Interventional Studies 
Sponsor: Meiji Pharma USA Inc.; Protocol No.: ME3183-3 
 
This document is confidential. 
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Table Number 
Name 
Analysis Set 
14.2.3.2.3 
Proportion of Subjects with an sPGA Score of 0 or 1 
and a 2-Point Reduction from Baseline, NRI 
(Per Protocol Set) 
14.2.4.1.1 
Summary of DLQI by Visit: Actual Values, Changes 
from Baseline, Proportion of Subjects with at Least a 
5-Point Reduction from Baseline 
(Full Analysis Set) 
14.2.4.1.2 
Summary of DLQI by Visit: Actual Values, Changes 
from Baseline, Proportion of Subjects with at Least a 
5-Point Reduction from Baseline 
(Per Protocol Set) 
14.2.4.2 
DLQI: MMRM for Changes 
(Full Analysis Set) 
14.2.5 
PASI: MMRM for Percent Changes from Baseline, 
Complete Case Analysis 
(Full Analysis Set) 
14.2.6.1 
BSA: Summary of Visit Values and Changes from 
Baseline by Visit 
(Full Analysis Set) 
14.2.6.2 
BSA: MMRM for Changes 
(Full Analysis Set) 
14.2.7.1.1 
NRS: Summary of Visit Values and Changes from 
Baseline by Visit 
(Full Analysis Set) 
14.2.7.1.2 
NRS: Summary of Visit Values and Changes from 
Baseline by Visit 
(Per Protocol Set) 
14.2.7.2 
NRS: MMRM for Changes 
(Full Analysis Set) 
14.2.8.1.1 
Summary of Time to the First Response of PASI-50 
(Full Analysis Set) 
14.2.8.1.3 
Cox Proportional Hazard Model for Time to the First 
Response of PASI-50 
(Full Analysis Set) 
14.2.8.2.1 
Summary of Time to the First Response of PASI-75 
(Full Analysis Set) 
14.2.8.2.3 
Cox Proportional Hazard Model for Time to the First 
Response of PASI-75 
(Full Analysis Set) 
14.2.11.1 
Summary of Trough Plasma Concentrations (<unit>) 
of ME3183 and 
 by Visit 
(PK Analysis Set) 
14.3.1.1 
Overall Summary of Adverse Events 
(Safety Analysis Set) 
14.3.1.2 
Treatment-Emergent Adverse Events by System 
Organ Class and Preferred Term 
(Safety Analysis Set) 
14.3.1.3 
Treatment-Emergent Adverse Events by System 
Organ Class, Preferred Term and Maximum Severity 
(Safety Analysis Set) 
14.3.1.4 
Treatment-Emergent Adverse Events by System 
Organ Class, Preferred Term and Maximum 
Relationship 
(Safety Analysis Set) 
14.3.1.5 
Treatment-related Treatment-Emergent Adverse 
Events by System Organ Class and Preferred Term 
(Safety Analysis Set) 
14.3.1.6 
Serious Treatment-Emergent Adverse Events by 
System Organ Class and Preferred Term 
(Safety Analysis Set) 
14.3.1.7 
Treatment-Emergent Adverse Events Leading to 
Permanent Discontinuation of Study Drug by System 
Organ Class and Preferred Term 
(Safety Analysis Set) 
14.3.1.8 
Treatment-Emergent Adverse Events by Time of 
Onset, System Organ Class and Preferred Term 
(Safety Analysis Set) 


Statistical Analysis Plan for Interventional Studies 
Sponsor: Meiji Pharma USA Inc.; Protocol No.: ME3183-3 
 
This document is confidential. 
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Table Number 
Name 
Analysis Set 
14.3.2.1 
Serious Treatment-Emergent Adverse Events, 
Listing 
(Safety Analysis Set) 
14.3.2.2 
Treatment-Emergent Adverse Events Leading to 
permanent Discontinuation of Study Drug, Listing 
(Safety Analysis Set) 
14.3.4.1.1.1 
Hematology and Coagulation: Summary by Visit and 
Change from Baseline 
(Safety Analysis Set) 
14.3.4.1.1.2 
Hematology and Coagulation: Proportion of 
Abnormal Results by Study Visit 
(Safety Analysis Set) 
14.3.4.1.2.1 
Blood Chemistry: Summary by Visit and Change 
from Baseline 
(Safety Analysis Set) 
14.3.4.1.2.2 
Blood Chemistry: Proportion of Abnormal Results by 
Study Visit 
(Safety Analysis Set) 
14.3.4.1.3 
Urinalysis: Proportion of Abnormal Results by Study 
Visit 
(Safety Analysis Set) 
14.3.4.2 
Summary of Vital Signs by Visit and Change from 
Baseline 
(Safety Analysis Set) 
14.3.4.3.1 
12-Lead ECG: Summary by Visit and Change from 
Baseline 
(Safety Analysis Set) 
14.3.4.3.2 
12-Lead ECG: Summary of Overall ECG 
Interpretation by Visit 
(Safety Analysis Set) 
14.3.4.3.3 
12-Lead ECG: Summary of Noteworthy Changes of 
QT/QTc Interval by Visit 
(Safety Analysis Set) 


Statistical Analysis Plan for Interventional Studies
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Index of Figures
Figure Number
Name
Analysis Set
14.2.8.1.2
Reverse Kaplan-Meier Plot of Time to the First 
Response of PASI-50
(Full Analysis Set)
14.2.8.2.2
Reverse Kaplan-Meier Plot of Time to the First 
Response of PASI-75
(Full Analysis Set)
14.2.11.2
Linear Mean (± SD) Plasma Ctrough 
Concentrations (<unit>) of ME3183 and 
(PK Analysis Set)


Statistical Analysis Plan for Interventional Studies
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Index of Listings
Listing Number
Name
Analysis Set
16.2.1.1
Subject Disposition
(Screened Set)
16.2.1.2
Screen Failures
(Screened Set)
16.2.2
Subjects with Any Protocol Deviations
(Screened Set)
16.2.3
Subjects Excluded from Analysis Sets
(Screened Set)
16.2.4.1
Demographics and Baseline Characteristics
(Full Analysis Set)
16.2.4.2
Baseline Disease Characteristics
(Full Analysis Set)
16.2.4.3
Medical History
(Full Analysis Set)
16.2.4.4.1
Prior and Concomitant Medications
(Full Analysis Set)
16.2.4.4.2
Prior and Concomitant Medical/Surgical 
Procedures
(Full Analysis Set)
16.2.4.4.3
Prior Systemic Treatment for Psoriasis
(Full Analysis Set)
16.2.5.1
Study Drug Administration
(Full Analysis Set)
16.2.5.2
Study Drug Compliance
(Full Analysis Set)
16.2.6.1
Psoriasis Area and Severity Index (PSAI)
(Full Analysis Set)
16.2.6.2
Static Physician's Global Assessment (sPGA)
(Full Analysis Set)
16.2.6.3
Dermatology Life Quality Index (DLQI)
(Full Analysis Set)
16.2.6.4
Body Surface Area (BSA)
(Full Analysis Set)
16.2.6.5
Numerical Rating Scale (NRS)
(Full Analysis Set)
16.2.7.1
Treatment-Emergent Adverse Events
(Full Analysis Set)
16.2.7.2
Non-Treatment-Emergent Adverse Events
(Full Analysis Set)
16.2.8.1.1
Laboratory Reference Ranges
16.2.8.1.2
Hematology and Coagulation
(Full Analysis Set)
16.2.8.1.3
Blood Chemistry
(Full Analysis Set)
16.2.8.1.4
Urinalysis (Dipstick)
(Full Analysis Set)
16.2.8.2.1
Vital Signs
(Full Analysis Set)
16.2.8.2.2
Electrocardiogram (ECG)
(Full Analysis Set)
16.2.8.2.3
Physical Examination
(Full Analysis Set)
16.2.8.2.4
Serology at Screening
(Full Analysis Set)
16.2.8.2.5
Serum Pregnancy Test and FSH at Screening
(Full Analysis Set)
16.2.8.2.6
Urine Pregnancy Test
(Full Analysis Set)
16.2.8.2.7
Individual Ctrough Concentrations
(Full Analysis Set)


Statistical Analysis Plan for Interventional Studies
Sponsor: Meiji Pharma USA Inc.; Protocol No.: ME3183-3
This document is confidential.
SAP Version: Final V3.0 11-Jul-2023
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Shells
Tables, Figures and Listings mock shells are documented in a separate document.


Statistical Analysis Plan for Interventional Studies
Sponsor: Meiji Pharma USA Inc.; Protocol No.: ME3183-3
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SAP Version: Final V3.0 11-Jul-2023
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Filing requirements: TMF
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Appendices
None.