Conditions: Alopecia Areata
Allocation: RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 149
Healthy volunteers: no

Brief summary:
This study will evaluate the safety and efficacy of CTP-543 on hair loss in adults with chronic, moderate to severe alopecia areata.

Detailed description:
This is a double-blind, randomized, placebo-controlled multi-center study consisting of 3 cohorts to assess the safety and efficacy of CTP-543. Each Cohort will be initiated sequentially in ascending dose order. Participants will be randomized to either an active dose of CTP-543 or placebo for a 24-week treatment period.

Arms:
arm 1: Participants will receive CTP-543 4 mg tablets, twice daily for up to 24 weeks. arm 2: Participants will receive CTP-543 8 mg tablets, twice daily for up to 24 weeks. arm 3: Participants will receive CTP-543 12 mg tablets, twice daily for up to 24 weeks. arm 4: Participants will receive CTP-543 matched placebo tablets, twice daily for up to 24 weeks in Cohorts 1, 2, and 3.

Interventions: intervention 1: CTP-543 intervention 2: CTP-543 matching placebo
Intervention descriptions: intervention 1: Administered as tablets. intervention 2: Administered as tablets.

Protocol document:
Prot_000.pdf: 
 
Offi ci al  Titl e:   
A   D o u bl e -Bli n d,   R a n d o miz e d,   Pl a c e b o -C o ntr oll e d,   P ar all el   D os e   St u d y  to 
E v al u at e  th e  S af et y  a n d  Effi c a c y  o f  CT P -5 4 3 I n  A d ult  P ati e nts  Wit h  M o d er at e 
to  S e v er e  Al o p e ci a  Ar e at a  
N C T  N u m b er:  
 
N C T 0 3 1 3 7 3 8 1  
 
D o c u m e nt  D at e : 
 
Pr ot o c ol  V ersi o n  5 :  2 1 J a n u ar y 2 0 1 9 
 
 
 
 
 
 
 


C T P- 5 4 3 
 
2 1 J a n uar y 2 0 1 9 
Pr ot oc ol C P 5 4 3. 2 0 0 1, A me n d me nt 5   
 
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C O N FI D E N TI A L & P R O P RI E T A R Y   
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A D O U B L E - B LI N D, R A N D O MI Z E D, P L A C E B O- C O N T R O L L E D S T U D Y T O 
E V A L U A T E T H E S A F E T Y A N D E F FI C A C Y O F C T P- 5 4 3 I N A D U L T P A TI E N T S 
WI T H M O D E R A T E T O S E V E R E A L O P E CI A A R E A T A  
 
I N V E S TI G A TI O N A L P R O D U C T :  
 
C T P -5 4 3  
P R O T O C O L N U M B E R:  
 
C P 5 4 3. 2 0 0 1  
A M E N D M E N T 5 D A T E:  
A M E N D M E N T 4 D A T E:  
A M E N D M E N T 3 D A T E:  
A M E N D M E N T 2 D A T E:  
A M E N D M E N T 1 D A T E:  
O RI GI N A L P R O T O C O L : 
 
2 1  J a n u ar y 2 0 1 9  
1 7 A u g ust 2 0 1 8  
2 5 Se pte m ber  2 0 1 7  
0 5  J ul y 2 0 1 7 
1 4  Fe br uar y 2 0 1 7  
1 4 N o ve m ber  2 0 1 6  
E u dr a C T N U M B E R:  
 
N ot A p plica ble  
I N D N U M B E R: 
 
1 3 1, 4 2 3  
S P O N S O R N A M E / A D D R E S S:   
 
C o ncert P har mace uticals, I n c.  
9 9 Ha y de n A ve n ue, S uite 5 0 0  
Le xi n gt o n, M A 0 2 4 2 1  
 
C O N FI D E N TI A L  
T his pr ot o c ol is pr ovi d e d t o y o u as a n I nvesti g at or, p ote nti al I nvesti g at or, or c o ns ult a nt f or revie w by 
y o u, y o ur st aff, a n d et hics c o m mittee/i nstit uti o n al revie w b o ar d.  T he i nf or m ati o n c o nt ai ne d i n t his 
d oc u m e nt is re g ar de d as c o nfi d e nti al a n d, e xce pt t o t he e xte nt necess ary t o o bt ai n i nf or m e d c o nse nt, 
m ay n ot be discl ose d t o a n ot her p arty u n less s uc h discl os ure is re q uire d by l a w or re g ul ati o ns.  
Pers o ns t o w h o m t he i nf or m ati o n is discl ose d m ust be i nf or m e d t h at t he i nf or m ati o n is c o nfi d e nti al 
a n d m ay n ot be f urt her discl ose d by t he m.  
 


C T P- 5 4 3 
 
2 1 J a n uar y 2 0 1 9 
Pr ot oc ol C P 5 4 3. 2 0 0 1, A me n d me nt 5   
 
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M E DI C A L M O NI T O R / E M E R G E N C Y C O N T A C T I N F O R M A TI O N  
 
C o ntact I nf or mati o n  
Na me  
, M D 
Title  
 
A d dress  
 
 
 
P h o ne  
 
Facsi mile  
 
E mail  
 A N D  
  
 




C T P- 5 4 3 
 
2 1 J a n uar y 2 0 1 9 
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SI T E P RI N CI P A L I N V E S TI G A T O R SI G N A T U R E P A G E 
 
Pr ot oc ol N u m ber:  C P 5 4 3. 2 0 0 1 
 
 
 
  
 
Si g n at ure of Site Pri nci p al I n vesti g at or  
  
d d m m m y y y y  
 
 
Pri nte d N a me of Site Pri nci p al I n vesti g at or  
I nstit uti o n N a me:   
 
 
 
B y m y si g n at ure, I a gree t o pers o nall y s u p er vise t he c o n d uct of t his st u d y at m y st u d y 
site a n d t o e ns ure its c o n d uct is i n c o m plia nce wit h t he pr ot oc ol, i nf or me d c o nse nt, 
I n v esti gati o nal Re vie w B oar d pr oce d ures, i nstr ucti o ns fr o m C o ncert re pres e ntati ves, t he 
Declarati o n of Helsi n ki , I nter nati o nal C o nfere nce o n Har m o nizati o n G o o d Cli nical 
Practices G ui deli nes, a n d l ocal re g ulati o ns g o ver ni n g t he c o n d uct of cli nical st u dies.  
 
 


C T P- 5 4 3 
 
  
  
  
  
  
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S u m m ar y  of C h a n ges 
Secti o n  
Pre vi o us Te xt  
Ne w Te xt  
Re as o n f or 
Re visi o n  
S y n o psis/ M et h o d ol o g y  
 
Secti o n 7. 1/ St u d y Desi g n  
A c o h ort wit hi n t he st u d y is di vi de d i nt o 3 peri o ds: 
Scree ni n g, Treat me nt, a n d P ost -Treat me nt Safet y F oll o w -
U p.  T he Scree ni n g P eri o d ma y last u p t o 2 8 da ys pri or t o 
i nitiati o n of st u d y dr u g.  T he Treat me nt P eri o d is a 2 4-
we e k, d o u ble -bli n d, place b o -c o ntr o lle d peri o d t o defi n e 
effic ac y a n d safet y f or t h e st u d y.  T he P ost -Treat me nt 
Safet y F oll o w -u p P eri o d is t he fi n al 4 wee ks of eac h 
c o h ort t o assess safet y f oll o wi n g treat me nt c o m pleti o n.   
T he Scree ni n g P eri o d ma y last u p t o 2 8 da ys pri or t o i nitiati o n of s t u d y 
dr u g.  T he Treat me nt P eri o d is a 2 4 -wee k, d o u ble -bli n d, place b o -
c o ntr olle d peri o d t o defi n e efficac y a n d safet y f or t he st u d y.  T he P ost -
Treat me nt Safet y F oll o w -u p P eri o d is t he fi nal 4 wee ks of eac h c o h ort 
t o assess safet y f oll o wi n g treat me nt c o m pleti o n.  P atie nt s e nr olle d i n 
C o h ort 3 ( 1 2 m g BI D) will h a ve t he o pti o n t o c o nti n ue recei vi n g 
tre at me nt i n a n o pe n-l a bel e xte nsi o n st u d y f oll o wi n g t he tre at me nt 
peri o d.  If p atie nts  d o n ot wis h t o c o nti n ue i nt o t he o pe n -l a bel 
e xte nsi o n st u d y, t he y will c o m pl e te tre at me nt at Wee k 2 4 a n d 
ret ur n i n 4 w ee ks f or t he P ost -T re at me nt S afet y F oll o w -u p t o assess 
s afet y f oll o wi n g tre at me nt c o m pleti o n. 
 
S y n o psis/ St u d y Desi g n  
 
Secti o n 7. 1/ St u d y Desi g n  
 
 
A d de d O L E o pti o n 
t o C o h ort 3 St u d y 
Desi g n sc he matic  
S y n o psis/ St u d y  Desi g n  
 
Secti o n 7. 1/ St u d y Desi g n  
U p o n c o m pleti o n of treat me nt at Wee k 2 4, patie nts will 
st o p ta ki n g st u d y me dicati o n a n d e nter a 4 wee k P ost-
Treat me nt Safet y F oll o w -U p P eri o d.  P atie nts will be 
assess e d f or safet y t hr o u g h Wee k 2 8.        
F or C o h orts 1 a n d 2 , patie nts will st o p ta ki n g st u d y me dicati o n u p o n 
c o m pleti o n of tr e at me nt at Wee k 2 4 a n d e nter a 4 wee k P ost -
Treat me nt Safet y F oll o w -U p P eri o d.  P atie nts will be assesse d f or 
safet y t hr o u g h Wee k 2 8.  F or C o h ort 3, p atie nts will be eli gi ble t o 
eit her c o m pl et e tre at me nt at Wee k 2 4 a n d e xit t he st u d y at Wee k 
2 8 f oll o wi n g t he S afet y F oll o w -u p visit, or r oll -o ver i nt o a L o n g -
ter m O pe n-l a bel E xte nsi o n st u d y at Wee k 2 4.       
 
 
 
 


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C O N FI D E N TI A L & P R O P RI E T A R Y   
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Secti o n  
Pre vi o us Te xt  
Ne w Te xt  
Re as o n f or 
Re visi o n  
Secti o n 7. 1/ St u d y Desi g n  
F or eac h c o h ort, he mat ol o g y will be c o n d ucte d e ver y 2 
we e ks d uri n g t h e first 8 wee ks of t h e Treat me nt P eri o d, 
f oll o we d b y a n ass ess me nt e ver y 4 wee ks t h ereafter 
t hr o u g h c o m pleti o n of t h e P ost-Treat m e nt Safet y F oll o w-
U p P eri o d .  Li pi d le vels will be assesse d e ver y 1 2 wee ks 
t hr o u g h o ut t he Treat me nt P eri o d a n d at t he P ost-
Treat me nt Safet y F oll o w -U p Visit.  
F or eac h c o h ort, he mat ol o g y will be c o n d ucte d e ver y 2 wee ks d uri n g 
t h e first 8 wee ks of t h e Treat me nt P eri o d, f oll o we d b y a n assess me nt 
e ver y 4 wee ks t h ereafter t hr o u g h c o m pleti o n of t he st u d y.  Li pi d 
le vels will be assesse d e ver y 1 2 wee ks t hr o u g h o ut t he Treat me nt P eri o d 
a n d at t he P ost -Treat me nt Safet y F oll o w -U p Visit , if a p plic a ble. 
 
S y n o psis/ D ur ati o n of St u d y 
P artici p ati o n  
S u bjects  will partici pate i n t he st u d y f or a p pr o xi matel y 
3 2 wee ks, i n cl u di n g Scree ni n g a n d F oll o w -U p.  
P atie nts will partici p ate i n t he st u d y f or u p t o a p pr o xi matel y 3 2 wee ks 
if e xiti n g t he st u d y afte r t he 4-w ee k S af et y F oll o w -u p ( 4 -w ee k 
Scree ni n g, 2 4 -w ee k Tre at me n t, 4-w ee k S afet y F oll o w -u p) . F or 
C o h ort 3, u p o n c o m pleti o n of t he 2 4 -w ee k Tre at me nt Peri o d, 
p atie nts will be eli gi ble t o eit he r c o m plete tre at me nt a n d e xit t he 
st u d y f oll o wi n g t he 4-w ee k S afet y F oll o w -u p visit, or r oll -o ver i nt o 
a L o n g -ter m O pe n-l a bel E xtensi o n st u d y.   
C ha n ges s u bjects 
t o patie nts f or 
c o nsiste nc y;  
Sc he d ul e of Assess me nt  
N A  
1 3 T he S afet y F oll o w -U p Visit is i nte n de d f or t h ose p atie nts w h o d o 
n ot r oll o ve r i nt o t he o pe n -l a bel e xte nsi o n ( C o h ort 3) a n d f or 
p atie nts w h o h a ve bee n dis c o nti n ue d fr o m t he st u d y a n d c o m pl ete d 
t he E arl y Ter mi n ati o n Visit ( Wee k 2 4). 
F o ot n ote a d de d  
 


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1.   
S Y N O P SI S 
N a me of S p o ns or/ C o m p a n y:  
C o ncert P har mace uticals  
N a me of I n vesti g ati o n al Pr o d uct:  
C T P -5 4 3  
N a me of Acti ve I n gre die nt:  
D 8 - r u x oliti ni b; 1H -P yraz ole -1 -pr o pa ne nitrile, β -(c ycl o pe nt yl-2, 2, 3, 3, 4, 4, 5, 5 -d 8)-4 -( 7H -p yrr ol o[ 2, 3 -
d ] p yri mi di n-4 -yl) -, ( β R)-, p h os p hate 
Title of St u d y:  
A D o u ble -Bli n d,  Ra n d o mize d, Place b o -C o ntr olle d  St u d y t o E val uate t he Safet y a n d Efficac y of  
C T P -5 4 3 i n A d ult Patie nts wit h M o derate t o Se vere Al o pecia Areata  
St u d y ce nter(s):  M ulti ce nter st u d y; u p 1 4  sites 
St u die d peri o d ( ye ars):  
Esti mate d date first patie nt e nr olle d: A u g ust 2 0 1 7  
Esti mate d date last patie nt c o m plete d: J ul y 2 0 1 9  
P h ase of de vel o p me nt: 2  
 
O bjecti ves:  
T he o verall o bjecti ve s of t he st u d y are t o assess t he safet y a n d efficac y of a 2 4-wee k re gi me n of 
a d mi nistrati o n of C T P -5 4 3 i n a d ult patie nts wit h c hr o nic, m o derate t o se vere al o pecia areata.  
T he pri mar y o bjecti ve s are : 
 
T o assess t he effect of C T P -5 4 3 o n treati n g hair l oss  as meas ure d b y t he Severit y of Al o pecia 
T o ol ( S A L T);  
 
T o assess t he safet y of a d mi nistrati o n of C T P -5 4 3 i n a d ult patie nts wit h c hr o nic,  m o derate t o 
se vere al o pecia areata.  
T he e x pl orat or y o bj ecti ves are:  
 
T o assess t he c ha n ge i n al o pecia areata se verit y as meas ure d b y t he cli nic ia n Vis ual A nal o g 
Scale of Se verit y ( V A S -S) fr o m baseli ne;  
 
T o assess t he c ha n ge i n Cli nical  Gl o bal I m pressi o n of I m pr o ve me nt ( C GI -I) fr o m baseli ne; 
 
T o assess t he c ha n ge i n al o pecia areata se verit y as meas ure d b y t he patie nt V A S -S fr o m 
baseli ne;  
 
T o assess t he c ha n ge i n Patie nt Gl o bal I m pressi o n of I m pr o ve me nt ( P GI -I) fr o m baseli ne;  
 
T o assess t he c ha n ge i n patie nt re p orte d o utc o mes as meas ure d b y t he Al o pecia Areata 
S y m pt o m I m pact Scale ( A A SI S) a n d e x pl orat or y q uesti o ns fr o m baseli ne; 
 
T o e val uate t he plas ma c o nce ntrati o ns of C T P -5 4 3 i n a d ult patie nts wit h c hr o nic, m o derate  t o 
se vere al o pecia areata. 
Met h o d ol o g y:  
T his is a d o u ble -bli n d, ra n d o mize d, place b o -c o ntr olle d m ultice nter  st u d y t o e val uate t he safet y a n d 
efficac y of C T P -5 4 3 i n a d ult patie nts wit h c hr o nic,  m o derate t o se vere al o pecia areata.  Patie nts will 
be bet wee n 1 8 a n d 6 5 years of a ge a n d e x perie nci n g a n e pis o de of al o pecia areata  lasti n g at least 
6  m o nt hs a n d n ot e xcee di n g 1 0 years, wit h at least 5 0 % hair l oss as meas ure d b y t he S A L T at 


C T P- 5 4 3 
 
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Scree ni n g a n d Baseli ne, a n d are n ot c o nc urre ntl y bei n g treate d f or al o pecia areata or wit h ot her 
treat me nts t hat mi g ht affect hair re gr o wt h or i m m u ne res p o nse .  A p pr o xi matel y  5 0 % of al o pecia 
areata patie nts wit h al o pecia t otalis or u ni versalis, a n d a p pr o xi matel y 1 0 %  wit h o nl y al o pecia o p hiasis 
will be e nr olle d.  
T he st u d y c o nsists of u p t o 3  c o h orts i nitiate d se q ue ntiall y i n asce n di n g d ose or der. A n i n de pe n de nt 
data m o nit ori n g c o m mittee ( D M C) will deter mi ne if t here are a de q uate safet y data t o s u p p ort eac h 
s u bse q ue nt d ose c o h ort . Patie nts will n ot d ose escalate wit hi n a c o h ort a n d ma y o nl y partici pate i n 
o ne c o h ort .  
T he Scree ni n g Peri o d ma y  last u p t o 2 8 da ys pri or t o i nitiati o n of st u d y dr u g .  T he Treat me nt Peri o d 
is a 2 4 -wee k, d o u ble -bli n d, place b o -c o ntr olle d peri o d t o defi ne efficac y a n d safet y f or t he st u d y.  T he 
P ost -Treat me nt Safet y F oll o w -u p Peri o d is t he fi nal 4 wee ks of eac h c o h ort t o assess safet y f oll o wi n g 
treat me nt c o m pleti o n.  S u bject s e nr olle d i n C o h ort 3 ( 1 2 m g BI D) will ha ve t he o pti o n t o c o nti n ue 
recei vi n g treat me nt i n a n o pe n-la bel e xte nsi o n st u d y f oll o wi n g t he treat me nt peri o d.  If s u bj ects d o 
n ot wis h t o c o nti n ue i nt o t he o pe n -la bel e xte nsi o n st u d y, t he y will c o m plete treat me nt at Wee k 2 4 a n d 
ret ur n i n 4 wee ks f or t he P ost -Treat me nt Safet y F oll o w -u p t o assess safet y f oll o wi n g treat me nt 
c o m pleti o n . 
T he D M C will perf or m re g ular safet y assess me nt s f or eac h c o h ort base d o n re vie w of c ollecti ve 
safet y data. After t he last patie nt has c o m plete d t he Wee k 1 2  Visit, t he D M C will c o n ve ne t o re vie w 
acc u m ulate d safet y data t o assess if i nitiati o n of t he s u bse q ue nt c o h ort is s u p p orte d. T he D M C ma y 
a d vise treat me nt ar m cessati o n d ue t o i nt olera bilit y at a n y ti me.  
St u d y Desi g n   
 


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Patie nts will pr o vi de a p pr o priatel y o btai ne d i nf or me d c o nse nt pri or t o c o m pleti n g a n y scree ni n g 
pr oce d ures .  Patie nts meeti n g i nitial scree ni n g criteria will be eli gi ble t o c o nti n ue t o t he c o h ort Da y 1 
visit f or re vie w of eli gi bilit y a n d baseli ne assess me nts, i ncl u di n g S A L T assess me nt, p h ysi cal 
e xa mi nati o n, cli nical la b orat or y assess me nts, vital si g ns , a n d electr ocar di o gra m.  F or eac h c o h ort, 
patie nts meeti n g all i ncl usi o n criteria a n d n o ne of t he e xcl usi o n criteria will be ra n d o mize d t o C T P -
5 4 3 treat me nt  or place b o . T he first 2 c o h orts will be ra n d o mize d  i n a 2 : 1 rati o (acti ve: place b o) a n d 
t he t hir d c o h ort will be ra n d o mize d i n a 5: 1 rati o (acti ve: place b o)  i n or der t o pr o vi de a si milar n u m ber 
of patie nts acr oss t he C T P -5 4 3 a n d  place b o ( p o ole d) gr o u p s.  Ra n d o mizati o n will be stratifie d b y 
classificati o n of al o pecia areata s u bt y pe  i nt o o ne of t he f oll o wi n g t hree cate g ories: 1) al o pecia areata, 
2) al o pecia t otalis or  al o pecia u ni versalis, or  3)  al o pecia o p hiasis .  
T he d o u ble -bli n d, place b o -c o ntr olle d Treat me nt Peri o d f or eac h c o h ort will last 2 4  wee ks .  
Assess me nt of treat me nt res p o nse wit h S A L T f or efficac y will occ ur at 4, 8, 1 2, 1 6, 2 0 a n d 2 4 wee ks .  
A n i nteri m  a nal ysis of safet y  a n d efficac y will be perf or me d  w he n all patie nts i n t he 4 m g a n d t he 8 
m g c o h orts ha ve c o m plete d Wee k 2 4.  T he  fi nal efficac y a nal ysis will be c o n d ucte d w he n all patie nts 
i n t he 1 2 m g c o h ort ha ve c o m plete d Wee k 2 4.  
F or C o h orts 1 a n d 2 , patie nts will st o p ta ki n g st u d y me dicati o n u p o n c o m pleti o n of treat me nt at Wee k 
2 4 a n d e nter a 4 -wee k P ost -Treat me nt Safet y F oll o w -U p Peri o d .  Patie nts will be assesse d f or safet y 
t hr o u g h Wee k 2 8 .  F or C o h ort 3, patie nts will be eli gi ble t o eit her c o m plete treat me nt at Wee k 2 4 a n d 
e xit t he st u d y at Wee k 2 8 f oll o wi n g t he Safet y F oll o w -u p v isit, or r oll-o ver i nt o a L o n g -T er m O pe n -
la bel E xte nsi o n st u d y at Wee k 2 4.  
Patie nts e nr olle d i nt o eac h c o h ort will ta ke t he first d ose of st u d y dr u g i n t he cli nic o n Da y 1 a n d will 
be i nstr ucte d t o ta ke st u d y dr u g e ver y 1 2 h o urs f or t he d urati o n of t he Treat me nt Peri o d .  Patie nts 
s h o ul d d ose st u d y dr ug i n t he cli nic o n all St u d y Visit Da ys after cli nical la b orat or y bl o o d dra ws are 
c o m plete d. Bl o o d sa m ples f or p har mac o ki netic a n d p har mac o d y na mic assess me nt will be ta ke n 
peri o dicall y . Sc he d ule d assess me nt of patie nt a n d cli nicia n perce pti o n of disease severit y a n d 
i m pr o ve me nt will als o occ ur. Patie nt safet y will be m o nit ore d t hr o u g h o ut t he trial a n d s u p p orte d b y 
re g ular re vie w b y t he D M C.  He mat ol o g y para meters will be m o nit ore d cl osel y f or t he d urati o n of t he 
st u d y.  F or eac h c o h ort , he mat ol o g y will be co n d ucte d e ver y 2 wee ks  d uri n g t he first 8 wee ks of t he 
Treat me nt Peri o d , f oll o we d b y a n assess me nt e ver y 4 wee ks t hereafter t hr o u g h c o m pleti o n of t he 
st u d y.  Li pi d le vels will be assesse d e ver y 1 2 wee ks t hr o u g h o ut t he Treat me nt Peri o d a n d at t he P ost -
Treat me nt Safet y F oll o w -U p Visit , if a p plica ble.  Si g nifica nt c yt o pe nias or  ot her he mat ol o gic 
a b n or malities  will be ma na ge d b y se verit y t hr o u g h d ose i nterr u pti o n or disc o nti n uati o n,  a n d si g ns a n d 
s y m pt o ms of i nfecti o n will be cl osel y m o nit ore d a n d treate d pr o m ptl y.  Patie nts w h o e x perie nce 
i nt olera ble s y m pt o ms d uri n g treat me nt ma y disc o nti n ue t he st u d y at t he discreti o n of t he I n vesti gat or.  
Patie nts ma y wit h dra w c o nse nt at a n y ti me.  
N u m ber of p atie nts ( pl a n ne d):  
A p pr o xi matel y 1 5 0 patie nts are pla n ne d t o be e nr olle d  i n t he st u d y. T he first 2 c o h orts will be 
ra n d o mize d i n a 2: 1 rati o (acti ve: place b o) a n d t he t hir d c o h ort will be ra n d o mize d i n a 5: 1 rati o 
(acti ve: place b o) i n or der t o pr o vi de a si milar n u m ber of patie nts acr oss t he C T P -5 4 3 a n d place b o 
( po ole d) gr o u ps . 
Di a g n osis a n d m ai n criteri a f or i ncl usi o n:  
Patie n ts eli gi ble f or e nr oll me nt i n t he st u d y m ust meet all of t he f oll o wi n g i ncl usi o n criteria a n d n o ne 
of t he e xcl usi o n criteria.  
I ncl usi o n Criteri a:  
1.  Writte n i nf or me d c o nse nt, a n d a ut h orizati o n  f or release a n d use of pr otecte d healt h 
i nf or mati o n. 
2.  Bet wee n 1 8 a n d 6 5 years of a ge, i ncl usi ve, at t he ti me of i nf or me d c o nse nt . 


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3.  Defi niti ve d ia g n osis of al o pecia areata  wit h a c urre nt e pis o de  lasti n g at least 6 m o nt hs a n d n ot 
e xcee di n g 1 0  years  at t he ti me of Scree ni n g. T otal disease d urati o n greater t ha n 1 0 years is 
per mitte d.  
4.  At least 5 0 % scal p hair l oss, as defi ne d b y a S A L T sc ore ≥5 0, at Scree ni n g a n d Baseli ne .  
5.  If of re pr o d ucti ve a ge, willi n g a n d a ble t o use a me dicall y hi g hl y effecti ve f or m of birt h 
c o ntr ol d uri n g t he st u d y  a n d f or 3 0 da ys f oll o wi n g last d ose of st u d y me dicati o n .  E xa m ples 
of me dicall y hi g hl y effecti ve f or ms of birt h c o ntr ol are:  
a. S ur gical sterilit y ( via vasect o m y, h ysterect o m y or bilateral li gati o n) or 
p ost -me n o pa usal fe males  
b.  Se x ual p art ner is sterile, or of t he sa me se x  
c. I m pla nts of le v o n or gestrel i n fe males 
d.  Oral c o ntrace pti ve (c o m bi ne d or pr o gester o ne o nl y) i n fe males  
e. D o u ble -barrier met h o d (a n y c o m bi nati o n of p h ysical a n d c he mical met h o ds)  
f. I ntra uteri ne de vice i n fe males, or ot her met h o d wit h p u blis he d data s h o wi n g t hat t he 
l o west e x pecte d fail ure rate is less t ha n 1 % per year 
6.  Willi n g t o c o m pl y wit h t he st u d y visits a n d re q uire me nts of t he st u d y pr ot oc ol.  
E x cl usi o n Criteri a:  
1.  Hist or y or prese nce of hair tra ns pla nts . 
2.  Treat me nt wit h ot her  me dicati o n s or a ge nts wit hi n 1 m o nt h of S cree ni n g or d uri n g t he st u d y  
t hat ma y affect hair re gr o wt h or i m m u ne res p o nse, i ncl u di n g b ut n ot li mite d t o: 
c ortic oster oi ds a d mi nistere d orall y, b y i njecti o n, or a p plie d t o areas of s ki n affecte d b y 
al o pecia ; plat elet -ric h plas ma i njecti o ns; t o pical a p plicati o n t o affecte d areas of a nt hrali n, 
s q uaric aci d, di p he n ylc ycl o pr o pe n o ne , or mi n o xi dil.  
3.  Treat me nt wit h s yste mic i m m u n os u p pressi ve me dicati o ns i ncl u di n g b ut n ot li mite d t o 
met h otre xate, c ycl os p ori ne, a n d azat hi o pri ne; c hl or o q ui ne deri vati ves; Ja n us ki nase  i n hi bit ors 
(r u x oliti ni b, t ofaciti ni b, etc) or eta nerce pt wit hi n 3  m o nt hs of S cree ni n g or d uri n g t he st u d y ; 
or bi o l o gics (a dali m u ma b, atlizu ma b, ca na ki n u ma b, cert oliz u ma b,  f o nt oliz u ma b, g oli m u ma b, 
i nfli xi ma b, me p oliz u ma b, rit u xi ma b, sec u ki n u ma b, t ociliz u ma b, uste ki n u ma b) wit hi n 6 
m o nt hs of S cree ni n g or d uri n g t he st u d y . 
4.  Acti ve scal p i nfla m mati o n, ps oriasis, or se b orr h eic der matitis re q uiri n g t o pical treat me nt t o 
t he scal p, si g nifica nt tra u ma t o t he scal p, or u ntreate d acti nic kerat osis a n y w here o n t he b o d y 
at S cree ni n g a n d/ or B aseli ne . 
5.  K n o w n hist or y of m o derate t o se vere a n dr o ge nic al o pecia or fe male patter n hair l oss  pri or t o 
al o pecia areata . 
6.  U n willi n g t o mai ntai n a c o nsiste nt hair st yle , i ncl u di n g s ha m p o o a n d hair pr o d ucts (i ncl u di n g 
hair d ye, pr ocess, a n d ti mi n g t o hair a p p oi nt me nts ), a n d t o refrai n fr o m wea ves or e xte nsi o ns  
t hr o u g h o ut t he c o urse of t he st u d y, or s ha vi n g of scal p hair f or 2 wee ks prece di n g a S A L T 
assess me nt . 
7.  Use of a d hesi ve wi gs, ot her t ha n ba n de d peri meter wi gs, d uri n g t he st u d y . 
8.  Hist or y of a l y m p h o pr oliferati ve disease or mali g na nc y, ot her t ha n n o n -mela n o ma s ki n 
ca ncer or cer vical carci n o ma .  Patie n ts wit h 3 or m ore basal or s q ua m o us cell carci n o mas 
dia g n ose d i n t he past 2  years are e xcl u de d .  
9.  At y pical  ne vi or c uta ne o us lesi o ns t hat are s us pici o us f or mali g na nc y . 
1 0.  Hist or y of s oli d or ga n or he mat ol o gical tra ns pla ntati o n . 
1 1.  Fe ver or i nfecti o n wit hi n 2 wee ks pri or t o first d ose of st u d y dr u g . 


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1 2.  A b n or mal le vels of t h yr oi d sti m ulati n g h or m o ne at Scree ni n g, defi ne d as < 0. 9 x t he l o wer 
li mit of n or mal ( L L N) a n d > 1. 2 x t he u p per li mit of n or mal ( U L N) a n d, if ta ki n g t h yr oi d 
me dicati o n, a n i na bilit y t o mai ntai n le vels wit hi n t he n or mal ra n ge f or 6 m o nt hs pri or t o 
Scree ni n g or d uri n g t he st u d y.  
1 3.  Scree ni n g la bs o utsi de t he n or mal ra n ge f or para meters ass ociate d wit h p ote ntial ris k f or 
treat me nt u n der i n vesti gati o n.  T his will i ncl u de b ut is n ot li mite d t o : 
a. Platelets  ≤1 2 0 x 1 0 9/ L  
b.  A bs ol ute ne utr o p hil c o u nt  ≤1. 5 x 1 0 9/ L 
c. H e m o gl o bi n le vels ≤1 1 g/ d L  f or fe males, or he m o gl o bi n le vels ≤1 2. 5 g/ d L  f or males 
1 4.  Scree ni n g bl o o d gl uc ose le vels of he m o gl o bi n A 1c ≥6. 5 % ( 4 8 m m ol/ m ol).  
1 5.  A b n or mal li ver f u ncti o n at Scree ni n g, defi ne d as ≥1. 5  × U L N  of ser u m ala ni ne tra nsa mi nase, 
ser u m as partate tra nsa mi nase, ser u m al kali ne p h os p hatase, or t otal bilir u bi n ( u nless is olate d 
Gil bert’s s y n dr o me) . 
1 6.  A b n or mal re nal f u ncti o n (esti mate d gl o mer ular filtrati o n rate < 6 0 m L/ mi n/ 1. 7 3 m 2 usi n g t he 
M D R D e q u ati o n)  at Scree ni n g. 
1 7.  A n y acti ve i nfecti o n  at Scree ni n g, acti ve or pre vi o us He patitis B or C i nfecti o n, or k n o w n 
h u ma n i m m u n o deficie nc y vir us i nfecti o n.  
1 8.  Vacci nati o n wit h her pes z oster vacci ne or a n y li ve vir us vacci ne wit hi n 6 wee ks bef ore 
Scree ni n g  or d uri n g t he st u d y.  
1 9.  P ositi ve p urifie d pr otei n deri vati ve  test f or n o n -bacill us  Cal mette -G uéri n -vacci nate d patie nts, 
p ositi ve Q ua nti F E R O N ® -T B  G ol d test, or hist or y of i nc o m pletel y treate d or u ntreate d 
t u berc ul osis. 
2 0.  Hist or y of p r ol o n ge d Q T s y n dr o me or a Sc ree ni n g Q Tc i nter val wit h Fri dericia’s c orrecti o n 
( Q Tc F) > 4 5 0 msec f or males or Q Tc F >  4 7 0 msec f or fe males . 
2 1.  Hist or y of alc o h ol, me dicati o n, or illicit dr u g a b use wit hi n 1 year bef ore t he first d ose of 
st u d y dr u g. 
2 2.  Fe males w h o are n ursi n g, pre g na nt, or pla n ni n g t o bec o me pre g na nt w hile i n t he st u d y, a n d 
f or 3 0 da ys after last d ose of st u d y me dicati o n . 
2 3.  Partici pati o n i n a n ot her i n vesti gati o nal st u d y wit hi n t he greater of 4 wee ks or 5 half -li ves of 
a n i n vesti gati o nal me dicati o n pri or t o scree ni n g or d uri n g t he  st u d y. 
2 4.  Use of str o n g c yt oc hr o me P 4 5 0 3 A 4 ( C Y P 3 A 4) i n hi bit ors (s uc h as, b ut n ot li mite d t o 
clarit hr o m yci n, c o ni va pta n, gra pefr uit j uice, i n di na vir, itrac o naz ole, ket oc o naz ole, 
l o pi na vir/rit o na vir, mi befra dil, nefaz o d o ne, nelfi na vir, p osac o naz ole, sa q ui na vir, tela pre vir, 
telit hr o m yci n, v oric o naz ole, or fl uc o naz ole ) d ose d f or s yste mic e x p os ure. 
2 5.  Use of str o n g C Y P 3 A 4 i n d ucers (s uc h as, b ut n ot li mite d t o bar bit urates, car ba maze pi ne, 
efa vire nz, gl uc oc ortic oi ds, m o dafi nil, ne vira pi ne, o xcar baze pi ne, p he n o bar bital , p he n yt oi n, 
pi o glitaz o ne, rifa b uti n, rifa m pi n, St. J o h n’s W ort, or tr o glitaz o ne)  d ose d f or s yste mic 
e x p os ure . 
2 6.  D o nati o n of bl o o d wit hi n a m o nt h of first d ose of st u d y dr u g or at a n y p oi nt t hr o u g h o ut t he 
st u d y a n d f or 3 0 da ys after last d ose of st u d y me dicati o n. 
2 7.  Cli nicall y si g nifica nt me dical c o n diti o n , ps yc hiatric disease, or s ocial c o n diti o n, as 
deter mi ne d b y t he I n vesti gat or, t hat ma y u nfa v ora bl y alter t he ris k -be nefit of st u d y 
partici pati o n, a d versel y affect st u d y c o m plia nce , or c o nf o u n d i nter pretati o n o f st u d y res ults.  
 
 


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I n vesti g ati o n al pr o d uct, d os a ge a n d m o de of a d mi nistr ati o n:  
C T P -5 4 3 will be d ose d orall y as ta blets at d oses 4 m g, 8 m g, 1 2 m g, or matc hi n g place b o , e ver y 1 2 
h o urs  d uri n g t he Treat me nt Peri o d .   
Ref ere nce t her a p y, d os a ge a n d m o de of a d mi nistr ati o n:  
Matc hi n g place b o  
D ur ati o n of tre at me nt :  
Patie nts will recei ve u p t o 2 4 wee ks of st u d y dr u g.  
D ur ati o n of st u d y p artici p ati o n:  
Patie nts will partici pate i n t he st u d y f or u p t o a p pr o xi matel y 3 2 wee ks if e xiti n g t he st u d y after t he 4-
wee k Safet y F oll o w -u p ( 4 -wee k Scree ni n g, 2 4 -wee k Treat me nt, 4 -wee k Safet y F oll o w -u p). F or 
C o h ort 3, u p o n  c o m pleti o n of t he 2 4 -wee k Treat me nt Peri o d , patie nts will be eli gi ble t o eit her 
c o m plete treat me nt  a n d e xit t he st u d y f oll o wi n g t he 4-wee k Safet y F oll o w -u p visit, or r oll -o ver i nt o a 
L o n g -ter m O pe n -la bel E xte nsi o n st u d y.    
Criteri a f or e v al u ati o n:  
Effic acy:  
T he pri mar y efficac y e n d p oi nt will be t he pr o p orti o n of patie nt s ac hie vi n g at least a 5 0 % relati ve 
re d ucti o n i n S A L T sc ore fr o m baseli ne at Wee k 2 4.  
E x pl orat or y efficac y e n d p oi nts i ncl u de:  
 
Relati ve c ha n ge i n S A L T sc ores fr o m baseli ne ( mea n a n d perce nt) at Wee ks:  
o  4, 8, 1 2, 1 6, 2 0, a n d 2 4 i n t he Bli n de d Treat me nt Peri o d  
 
Relati ve c ha n ge i n al o pecia areata se verit y fr o m baseli ne as meas ure d b y t he cli nicia n’s 
V A S -S at Wee ks  1 2  a n d 2 4;  
 
C ha n ges i n al o pecia areata fr o m baseli ne usi n g t he cli nicia n rate d 7 -p oi nt Li kert scale C GI -I 
at Wee ks  1 2  a n d 2 4 ;  
 
Relati ve c ha n ge i n al o pecia areata se verit y fr o m baseli ne as meas ure d b y t he pa tie nt’s V A S-S 
at Wee ks  1 2  a n d 2 4;  
 
C ha n ges  i n al o pecia areata fr o m baseli ne usi n g t he patie nt rate d 7 -p oi nt Li kert scale P GI -I at 
Wee ks  1 2  a n d 2 4 ;  
 
Patie nt -re p orte d o utc o mes: C ha n ges i n s y m pt o ms fro m baseli ne as meas ure d b y A A SI S a n d 
e x pl orat or y q uesti o ns at Wee k 2 4  
P h ar m ac o ki netics:  
P har mac o ki netic sa m ples will be c ollecte d at t he f oll o wi n g ti me p oi nts t o e val uate plas ma 
c o nce ntrati o ns of C T P -5 4 3 a n d meta b olites.   
 
Da y 1  a n d Wee k 4 : 2 sa m ples at eac h visit; 1 sa m ple pre -d ose , a n d 1 sa m ple p ost -d ose at t he 
e n d of t he visit   
 
Wee k  2 : 1 sa m ple pre-d ose wit h t he safet y la b dra w  
 
Wee ks 8 , 2 4: 1 sa m ple at p ost -d ose at t he e n d of t he visit 
S afety:  
Safet y a n d t olera bilit y of C T P -5 4 3 will be assesse d b y e val uati n g a d verse e ve nts, vital si g ns, 
c o nc o mita nt me dicati o ns, cli nical la b orat or y , a n d electr ocar di o gra m res ults, as well as p h ysical 
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St atistic al met h o ds:  
S a m ple Size : 
T here are ver y fe w st u dies i n t he literat ure t o pr o vi de r elia ble esti mates of acti ve treat me nt or place b o 
res p o nse rates usi n g S A L T , or t he esti mate of varia nce ar o u n d t hese meas ures, i n patie nts wit h 
al o pecia areata .  P o wer calc ulati o ns ass u me a 2 -si de d test a n d si g nifica nce le vel of 0. 0 5 a n d are base d 
o n a n acti ve treat me nt res p o nse rate of 4 5 %  a n d a place b o res p o nse rate of 1 0 % . Base d o n esti mate d 
c o m pleti o n rates as of A me n d me nt 4, t his ra n d o mizati o n sc he me is e x pecte d t o pr o vi de a si milar 
n u m ber of patie nts i n t he 1 2 m g gr o u p a n d t he p o ole d place b o gr o u p.  A sa m ple size of 2 8 patie nts i n 
t he 1 2 m g gr o u p a n d 2 8 patie nts i n t he p o ole d place b o gr o u p will pr o vi de > 8 0 % p o wer f or t he c hi-
s q uare test. A p pr o xi matel y 15 0 patie nts will be ra n d o mize d i n or der t o pr o vi de 1 2 0  patie nts w h o 
c o m plete treat me nt.  
Effic acy A n alyses:  
 
T he Efficac y P o p ulati o n will i ncl u d e all patie nt s w h o recei ve st u d y dr u g a n d ha ve at least 
1  p ost -treat me nt S A L T assess me nt.  T he pri mar y efficac y e n d p oi nt will be t he pr o p orti o n of patie nts 
wit h a t least a 5 0 % relati ve re d ucti o n i n S A L T sc ore fr o m baseli ne at W ee k 2 4 .  T he place b o patie nts  
fr o m t he 3  c o h orts will be c o m bi ne d f or statistical c o m paris o ns t o eac h acti ve treat me nt gr o u p.  
Data will be s u m marize d b y acti ve treat me n t b y d ose le vel vers us place b o-treate d patie nt s (i.e., b y 
treat me nt gro u p) .  C o nti n u o us meas ures will be s u m marize d descri pti vel y ( mea n, sta n dar d de viati o n, 
me dia n , mi ni m u m val ue, a n d ma xi m u m val ue) a n d cate g orical meas ures will be prese nte d as n u m ber  
a n d perce nt a ge.   
All statistical tests will be 2 -si de d wit h a si g nifica nce val ue of 0. 0 5. T here will be n o a dj ust me nts f or 
m ulti ple c o m paris o ns.  
A n i nteri m a nal ysis of safet y a n d efficac y will be perf or me d w he n all patie nts i n t he 4 m g a n d t he 8 
m g c o h orts ha ve c o m plete d Wee k 2 4.  T he fi nal efficac y a na l ysis will be c o n d ucte d w he n all patie nts 
i n t he 1 2 m g c o h ort ha ve c o m plete d Wee k 2 4. A d diti o nal details f or  statistical met h o ds will be 
pr o vi de d  i n t he Statistical A nal ysis Pla n. 
P h ar m ac o ki netic A n alyses:  
T he P har mac o ki netic  P o p ulati o n will i ncl u de  all pa tie nts w h o recei ve st u d y dr u g a n d ha ve at least 
1  p har mac o ki netic  sa m ple ta ke n.  P las ma c o nce ntrati o ns will be s u m marize d b y descripti ve statistics 
as a p pr o priate  a n d will be liste d b y patie n t. 
S afety A n alyses:  
T he Safet y P o p ulati o n will i ncl u de  all patie n ts w h o recei ve st u d y dr u g i n t he Treat me nt Peri o d.  
A d verse e ve nts will be c o de d b y s yste m or ga n class a n d preferre d ter m wit h t he  Me dical Dicti o nar y 
f or Re g ulat or y Acti vities.  C o nc o mita nt me dicati o ns will be s u m marize d b y W orl d Healt h 
Or ga nizati o n Dr u g D icti o nar y A nat omical -T hera pe utic -C he mical  classificati o n a n d preferre d ter m.  
A d verse e ve nts, vital si g n meas ure me nts, p h ysical e xa mi nati o n fi n di n gs, electr ocar di o gra m, cli nical 
la b orat or y i nf or mati o n, a n d c o nc o mita nt me dicati o ns will be ta b ulate d a n d s u m marize d b y treat me nt 
a n d d ose le vel .  B y -patie nt listi n gs will be pr o vi de d f or a n y deat hs, seri o us a d verse e ve nts, a n d 
a d verse e ve nts  lea di n g t o disc o nti n uati o n of treat me nt.   
 
 
 


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C O N FI D E N TI A L & P R O P RI E T A R Y 
1 4  
 
T a ble 1 :   
Sc he d ule of E ve nts f or e ac h C o h ort 
 
Scree ni n g   
R a n d o miz ati o n  
Tre at me nt Peri o d  
S afet y    
F oll o w -U p  
D a y -2 8 t o D a y -1 1 2  
D a y 1 1  
We e k 2, 6  
( Visit 3, 5) 
We e k 4, 8  
( Visit 4, 6) 
Wee k 1 2  
( Visit 7) 
Wee k 1 6, 2 0  
( Visit 8, 9) 
Wee k 2 4
1 1 
( Visit 1 0) 
Wee k 2 8     
( Visit 1 1 )1 3 
E ve nt  
( Visit 1)  
( Visit 2) 
I nf or me d c o nse nt 
X  
 
 
 
 
 
 
 
Eli gi bilit y assess me nt  
X  
X  
 
 
 
 
 
 
De m o gra p hics  
X  
 
 
 
 
 
 
 
Me dical hist or y  
X  
X  
 
 
 
 
 
 
Ra n d o mizati o n  
 
X  
 
 
 
 
 
 
P h ysical e xa mi nati o n  
X  
X  
 
 
 
 
X  
X  
Brief p h ysical e xa mi nati o n  
 
 
 
X  
X  
X  
 
 
Hei g ht  
X  
 
 
 
 
 
 
 
Wei g ht  
X  
X  
 
X  
X  
X  
X  
X  
Pre g na nc y test 2 
X  
X  
 
X  
X  
X  
X  
 
T u berc ul osis  test 
X  
 
 
 
 
 
 
 
Cli nical la b orat or y testi n g 3, 8 
X 4 
X  
X  
X  
X  
X  
X  
X  
Li pi d assess me nt 5 
 
X  
 
 
X  
 
X  
X  
H B V a n d H C V test  
X  
 
 
 
 
 
 
 
P har mac o ki netic bl o o d sa m pli n g  
 
X 6 
X 6 
X 6 
 
 
X 6 
 
P har mac o d y na mic bl o o d sa m pli n g  
 
X 7 
X 7 
X 7 
 
 
X 7 
 
1 2 -lea d electr ocar di o gra m 
X  
X  
 
X  
X  
X  
X  
X  
Vital si g ns  
X  
X  
 
X  
X  
X  
X  
X  
Se verit y of Al o pecia T o ol  assess me nt 9 
X  
X  
 
X  
X  
X  
X  
 
P h ot o gra p hs  
X  
X  
 
X  
X  
X  
X  
 
Cli nicia n Vis ual A nal o g Scale –  Se verit y 9 
 
X  
 
 
X  
 
X  
 
Cli nicia n Gl o bal I m pressi o n of I m pr o ve me nt 9  
 
 
 
 
X  
 
X  
 
P atie nt Vis ual A nal o g Scale - Se verit y  
 
X  
 
 
X  
 
X  
 
P atie nt Gl o bal I m pressi o n of  I m pr o ve me nt 
 
 
 
 
X  
 
X  
 
A A SI S a n d e x pl orat or y q uesti o ns  
 
X  
 
 
 
 
X  
 
Dis pe nse st u d y dr u g  
 
X  
 
X  
X  
X  
 
 
St u d y dr u g acc o u nta bilit y  
 
 
 
X  
X  
X  
X  
 
A d verse e ve nts 1 0 
X  
X  
X  
X  
X  
X  
X  
X  
C o nc o mita nt me dicati o ns 1 0 
X  
X  
X  
X  
X  
X  
X  
X  


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A A S I S = Al o pecia Are ata S y m pt o m I m pact Scale ; H B V = he patitis B vir us; H C V = he patitis C vir us  
1 All s u bse q ue nt visits a n d wee k i n cre me nts s h o ul d be base d o n t he d ate of Visit 2. All   
v isit wi n d o ws are ± 3 da ys. 
2 Ser u m p re g na nc y test o nl y f or fe males of c hil dbeari n g p ote ntial.  
3 I ncl u des he mat ol o g y a n d ser u m c he mistr y.  
4 Will i ncl u de t h yr oi d sti m ulati n g h or m o ne a n d he m o gl o bi n A 1c at Scree ni n g o nl y. 
5 Incl u des t otal c h olester ol, l o w -de nsit y li p o pr otei n, hi g h -de nsit y li p o pr otei n, a n d tri gl yc eri d es. 
6 C ollecte d at Da y 1 a n d Wee k 4 ( pre -d ose , a n d p ost -d ose at e n d of visit), a n d Wee ks 2  ( pre-d ose 
wit h cli nical la bs) , a n d Wee ks 8, 2 4 ( p ost -d ose at e n d of visit).   
7 C ollecte d at Da y 1 a n d Wee k 2 ( pre -d ose wit h cli nical la bs), a n d Wee ks 4, 8, 2 4 ( p ost -d ose 
at e n d of visit). 8 C ollecte d pre -d ose.  
9 S h o ul d  be perf or me d b y t he sa me rater f or t he patie nt f or t he d urati o n of t he st u d y.  
1 0 C ollecti o n is o n g oi n g.  
1 1 Als o ser ves as t h e Earl y Ter mi nati o n Visit f or patie nt wit h dra wal.  
1 2  Ra n d o mizati o n/ Da y 1 ma y occ ur a n y ti me after Scree ni n g la b orat or y res ults are a vaila ble 
a n d re vie we d b y t h e I n vesti gat or.  
1 3 T he Safet y F oll o w -U p Visit is i nte n de d f or t h ose patie nts i n C o h ort 1 a n d C o h ort 2, a n d 
t h ose patie nts i n C o h ort 3 w h o d o  n ot r oll o ver i nt o t he O pe n -la bel E xte nsi o n. 
 


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1 6 
 
2.   
T A B L E O F C O N T E N T S, LI S T O F T A B L E S, A N D LI S T O F 
FI G U R E S  
 
1.  
S Y N O P SI S ................................................................................................................... 7  
2.  
T A B L E O F C O N T E N T S, LI S T O F T A B L E S, A N D LI S T O F FI G U R E S ............... 1 6  
3.  
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F T E R M S............................. 2 1  
4.  
I NT R O D U C TI O N ...................................................................................................... 2 2  
4. 1.  
O ver vie w of Al o peci a Areata ..................................................................................... 2 2  
4. 2.  
Sc ie ntific Rati o nale f or t he St u d y ............................................................................... 2 2 
4. 3.  
Pre cli nical I nf or mati o n f or C T P- 5 4 3 .......................................................................... 2 3  
4. 4.  
Cli nical I nf or mati o n .................................................................................................... 2 3  
4. 4. 1.  
P ha r mac o ki netics a n d Cli nical Safet y of R u x oliti ni b ................................................. 2 3 
4. 4. 2.  
Cli nical St u dies of C T P- 5 4 3 ....................................................................................... 2 4  
5.  
E T HI C S  ...................................................................................................................... 2 5 
5. 1.  
I nstit uti o nal Re vie w B oar d (I R B) ............................................................................... 2 5 
5. 2.  
Writte n I nf or m e d C o nse nt .......................................................................................... 2 5 
6.  
S T U D Y O BJ E C TI V E S .............................................................................................. 2 6  
6. 1.  
Pri ma r y O bj ecti ves ..................................................................................................... 2 6 
6. 2.  
E x pl ora t or y O bjecti ves ............................................................................................... 2 6 
7.  
O V E R A L L S T U D Y D E SI G N .................................................................................... 2 7  
7. 1.  
St u d y Desi g n ............................................................................................................... 2 7  
7. 2.  
N u m ber of  Patie nts a n d Sites ...................................................................................... 2 9 
7. 3.  
Met h o d of Treat me nt Assi g n me nt a n d Bli n di n g ........................................................ 2 9  
7. 4.  
Ra ti o nale f or St u d y Desi g n ......................................................................................... 2 9 
8.  
S E L E C TI O N A N D WI T H D R A W A L O F P A TI E N T S .............................................. 3 0  
8. 1.  
Pa tie nt I ncl usi o n Criteria ............................................................................................ 3 0 
8. 2.  
Pa tie nt E x cl usi o n Criteria ........................................................................................... 3 0 
8. 3.  
Pa tie nt Wit h dra wal Criteria ........................................................................................ 3 2 
8. 3. 1.  
Pa tie nt Wit h dra wal Pr oce d ures ................................................................................... 3 2 
8. 4.  
E mer ge nc y U n bli n di n g of Treat me nt Assi g n me nt ..................................................... 3 3  
8. 5.  
Criteria f or St u d y Ter mi nati o n ................................................................................... 3 3  
9.  
D E S C R I P TI O N O F S T U D Y T R E A T M E N T S .......................................................... 3 4  
9. 1.  
Descri pti o n of Treat me nts .......................................................................................... 3 4  


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9. 2.  
D ose- A dj ust me nt C riteri a ........................................................................................... 3 4 
9. 2. 1.  
D ose I nterr u pti o n Safet y Criteria a n d Ma n a ge me nt ................................................... 3 5  
9. 2. 2.  
P ha r mac o ki netic Criteria f or St o p pi n g D oses ............................................................ 3 6 
9. 3.  
Tre at me nt C o m plia nce ................................................................................................ 3 6  
9. 4.  
St u d y Dr u g Materials a n d Ma na ge me nt ..................................................................... 3 6  
9. 4. 1.  
P h ysical D escri pti o n of St u d y Dr u g ........................................................................... 3 6  
9. 4. 2.  
St u d y Dr u g Pac k a gi n g, La beli n g, a n d St ora ge ........................................................... 3 6  
9. 4. 3.  
St u d y Dr u g Pre p arati o n a n d A d mi nistrati o n .............................................................. 3 7  
9. 4. 4.  
St u d y Dr u g Ret ur n a n d Dis p osal ................................................................................ 3 7  
9. 4. 5.  
St u d y Dr u g Acc o u nta bilit y ......................................................................................... 3 7  
9. 5.  
C o nc o mita nt Me dicati o ns a n d Pr oce d ures ................................................................. 3 7  
1 0.  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S ...................................................... 3 9  
1 0. 1.  
De m o gra p hic C haract eristics a n d Me dical Hist or y .................................................... 3 9  
1 0. 2.  
Se verit y of Al o peci a T o ol ( S A L T) ............................................................................. 3 9  
1 0. 3.  
P h ot o g ra p hs ................................................................................................................ 4 0 
1 0. 4.  
Gl o bal I m pressi o n Scales ........................................................................................... 4 0 
1 0. 4. 1.  
Cli nica l Gl o bal I m pr essi o n of I m pr o ve me nt ( C GI-I) ................................................. 4 0 
1 0. 4. 2.  
Pati e nt Gl o bal I m pr essi o n of I m pr o ve me nt ( P GI- I) ................................................... 4 0 
1 0. 5.  
Patie nt Re p orte d O utc o m es: Al o pecia Areat a S y m pt o m I m pact Scale 
( A A SIS) a n d E x pl orat or y Q uesti o ns .......................................................................... 4 0  
1 0. 6.  
Vis ual A nal o g  Scale ( V A S) ........................................................................................ 4 1 
1 0. 6. 1.  
Cli nicia n V A S of Se verit y ( V A S- S)  ........................................................................... 4 1 
1 0. 6. 2.  
Pati e nt V A S of Se verit y ( V A S- S)  .............................................................................. 4 1 
1 0. 7.  
P har mac o ki netic Assess me nts .................................................................................... 4 1  
1 0. 8.  
Vital Si g ns, We i g ht, a n d Hei g ht ................................................................................. 4 1 
1 0. 9.  
P h ysical E x a mi nati o n ................................................................................................. 4 2  
1 0. 1 0.  
Electr oc ar di o gra m ....................................................................................................... 4 2 
1 0. 1 1.  
Cli nica l La b orat or y Assess me nts ............................................................................... 4 2 
1 0. 1 2.  
P har ma c o d y na mic Ass ess me nts ................................................................................. 4 3  
1 0. 1 3.  
U nsc he d ule d Visit ....................................................................................................... 4 4  
1 1.  
A D V E R S E E V E N T S.................................................................................................. 4 5  
1 1. 1. 1.  
Defi niti o n of  A d verse E v e nt ....................................................................................... 4 5 
1 1. 1. 2.  
E val uati o n of A d ve rse E ve nts .................................................................................... 4 5 
1 1. 1. 2. 1.  
Seri o us  A d verse E v e nt ................................................................................................ 4 5 


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1 1. 1. 2. 2.  
Se ve rit y/I nt e nsit y ........................................................................................................ 4 7 
1 1. 1. 2. 3.  
Relati o ns hi p t o St u d y Dr u g ........................................................................................ 4 7  
1 1. 1. 2. 4.  
D urati o n ...................................................................................................................... 4 8  
1 1. 1. 2. 5.  
Acti o n Ta ke n .............................................................................................................. 4 8  
1 1. 1. 2. 6.  
O utc o me ...................................................................................................................... 4 8 
1 1. 1. 3.  
F oll o w -U p  ................................................................................................................... 4 8 
1 1. 1. 4.  
Pre g n a nc y ................................................................................................................... 4 8  
1 1. 1. 5.  
Rec or di n g A d verse E ve nts ......................................................................................... 4 9  
1 1. 1. 6.  
Re p orti n g  A d verse E v e nts .......................................................................................... 4 9 
1 1. 1. 6. 1.  
Re p orti n g  Seri o us A d verse E ve nts ............................................................................. 4 9 
1 1. 1. 6. 2.  
Re p orti n g  Ur ge nt Safet y Iss u es .................................................................................. 4 9 
1 2.  
S T A TI S TI C A L M E T H O D S ....................................................................................... 5 1  
1 2. 1.  
Sa m ple Size Rati o nale ................................................................................................ 5 1  
1 2. 2.  
E n d p oi nts  .................................................................................................................... 5 1 
1 2. 2. 1.  
Effica c y ....................................................................................................................... 5 1  
1 2. 2. 2.  
P har ma c o ki netic ......................................................................................................... 5 2  
1 2. 2. 3.  
Safe t y .......................................................................................................................... 5 2 
1 2. 3.  
A nal ysis P o p ulati o ns .................................................................................................. 5 2  
1 2. 3. 1.  
Trea t me nt Peri o d ........................................................................................................ 5 2 
1 2. 4.  
A nal ys es ...................................................................................................................... 5 2  
1 2. 4. 1.  
Dis p ositi o n a n d Baseli ne C haracteristics .................................................................... 5 2  
1 2. 4. 2.  
Effica c y ....................................................................................................................... 5 3  
1 2. 4. 3.  
P har ma c o ki netics ........................................................................................................ 5 3  
1 2. 4. 4.  
St u d y  Dr u g E x p os ure .................................................................................................. 5 3 
1 2. 4. 5.  
P har ma c o d y na mics ..................................................................................................... 5 4  
1 2. 4. 6.  
Safe t y .......................................................................................................................... 5 4 
1 3.  
R E G U L A T O R Y C O N SI D E R A TI O N S...................................................................... 5 6  
1 3. 1.  
G o o d Cli nica l Practice ................................................................................................ 5 6  
1 3. 2.  
S p o ns or’s Res p o nsi bilities .......................................................................................... 5 6  
1 3. 3.  
I n vesti gat or’s Res p o nsi bilities .................................................................................... 5 7  
1 3. 4.  
Pr ot oc ol A me n d me nts ................................................................................................ 5 8  
1 3. 5.  
A u dits a n d I ns p ecti o ns ................................................................................................ 5 8  
1 3. 6.  
Q ualit y C o ntr ol a n d Q ualit y Ass ura n ce ...................................................................... 5 8  
1 4.  
D A T A  H A N D LI N G A N D R E C O R D K E E PI N G ....................................................... 6 0  


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1 4. 1.  
C o nfi de ntialit y ............................................................................................................ 6 0  
1 4. 2.  
Pa tie nt Data Pr otecti o n ............................................................................................... 6 0 
1 4. 3.  
Data C ol lecti o n ........................................................................................................... 6 0 
1 4. 4.  
Ca se Re p ort F or m C o m pleti o n ................................................................................... 6 1 
1 4. 5.  
Data ba se M a na ge me nt, Data Clarificati o n, a n d Q ualit y Ass ura nce ........................... 6 1  
1 4. 6.  
I ns pecti o n of Rec or ds ................................................................................................. 6 1  
1 4. 7.  
Re te nti o n of Rec or ds .................................................................................................. 6 2 
1 5.  
P U B LI C A TI O N P O LI C Y .......................................................................................... 6 3  
1 6.  
LI S T O F R E F E R E N C E S ............................................................................................ 6 4  
1 7.  
A P P E N DI C E S ............................................................................................................ 6 5  
1 7. 1.  
Se verit y of Al o peci a T o ol ( S A L T) ............................................................................. 6 5  
1 7. 2.  
Gl o bal I mpressi o n Scales ........................................................................................... 6 6  
1 7. 2. 1.  
Cli nica l Gl o bal I m pr essi o n Scale of I m pr o ve me nt .................................................... 6 6 
1 7. 2. 2.  
Pati e nt Gl o bal I m pr essi o n Scale of I m pr o ve me nt ...................................................... 6 7  
1 7. 3.  
Patie nt Re p orte d O utc o m es ........................................................................................ 6 8  
1 7. 3. 1.  
Al o pecia A reata S y m pt o m I m pact Scale ( A A SI S) ..................................................... 6 8 
1 7. 3. 2.  
E x pl orat or y Q uesti o ns ................................................................................................ 6 9  
1 7. 4.  
Vis ual A nal o g  Scales .................................................................................................. 7 0 
1 7. 4. 1.  
Cli nicia n Vis ual A nal o g Scale of Se verit y ................................................................. 7 0  
1 7. 4. 2.  
Patie nt Vis ual A nal o g Scale of Se verit y ..................................................................... 7 1  
 


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LI S T O F T A B L E S 
Ta ble 1:  
Sc he d ule of E ve nts f or eac h C o h ort ........................................................................... 1 4  
Ta ble 2:  
A b bre viati o ns a n d S peci alist Ter ms ........................................................................... 2 1  
Ta ble 3:  
Se lecte d He m at ol o gic T hres h ol ds f or D ose I nterr u pti o n ........................................... 3 5 
Ta ble 4:  
I n vesti gati o nal Pr o d uct ............................................................................................... 3 6  
Ta ble 5:  
Cli nical La b orat or y Assess me nts ............................................................................... 4 3  
 
LI S T O F F I G U R E S 
Fi g ure 1:  
St u d y Desi g n ............................................................................................................... 2 8  
 
  


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3.   
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F T E R M S 
T a ble 2:   
A b bre vi ati o ns a n d S peci alist T er ms  
A b bre vi ati o n or S peci alist Ter m   
E x pl a n ati o n  
A A SI S  
Al o pecia Areata S y m pt o m I m pact Scale  
BI D  
T wice dail y  d osi n g  
C F R  
C o de of Fe deral Re g ulati o ns  
C GI -I 
Cli nical  Gl o bal I m pressi o n of I m pr o ve me nt  
C T C A E  
C o m m o n ter mi n ol o g y criteria f or ad verse eve nt s 
C Y P 3 A 4  
C yt oc hr o me P 4 5 0 3 A 4  
D M C  
Data m o nit ori n g c o m mittee  
D M P  
Data Ma na ge me nt Pla n  
e C R F 
Electr o nic case re p ort f or m  
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
G C P  
G o o d Cli nical Practice  
HI V  
H u ma n I m m u n o deficie nc y Vir us  
I C F 
I nf or me d c o nse nt f or m 
I C H 
I nter nati o nal C o nfere nce o n Har m o nisati o n 
I R B 
I nstit uti o nal Re vie w B oar d 
J A K 
Ja n us ki nase 
L L N  
L o wer Li mit of N or mal  
M D R D  
M o dificati o n of Diet i n Re nal Disease  
Me d D R A  
Me dical Dicti o nar y f or Re g ulat or y Acti vities  
N D A  
Ne w Dr u g A p plicati o n  
P C S  
P ote ntiall y cli nicall y si g nifica nt  
P GI -I 
Patie nt Gl o bal I m pressi o n of I m pr o ve me nt  
Q Tc  
Q T i nter val c orrecte d f or heart rate  
Q Tc F  
Q T i nter val c orrecte d f or heart rate ( Fri dericia’s met h o d)  
S A L T  
Se verit y of Al o pecia T o ol  
S T A T  
Si g nal tra ns d ucers a n d acti vat ors of tra nscri pti o n  
T E A E  
Treat me nt -e mer ge nt a d verse e ve nts  
U L N  
U p per Li mit of N or mal  
V A S -S  
Vis ual A nal o g Scale of Se verit y  


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4.   
I N T R O DU C TI O N 
4. 1.   
O ver vie w of Al o peci a Are at a 
Al o pecia areat a is a n a ut oi m m u ne dis or der c haracterize d b y pat c hes of n o n-scarri n g al o peci a 
affecti n g s cal p a n d b o d y hair.  Al o pecia areata is cli nicall y heter o ge ne o us, affects me n a n d 
w o me n, a n d has a pre v ale nce rate of 0. 1 % t o 0. 2 % of t he U nite d States p o p ulati o n 
[Safa vi, 1 9 9 2 ]. T here is n o pre ve ntati ve t hera p y or c ure.  Al o pecia areata ofte n prese nts as a 
c yclical dis or der mar ke d b y u n pre dicta ble peri o ds of hair l oss a n d s p o nta ne o us re gr o wt h, a n d 
variati o n i n t he de gree or patter n of hair l oss gi ves rise t o differe nt s u bt y p es of al o pecia areata, 
s uc h as patc h y, o p hiasis, t otalis, or u ni versalis.  A p pr o xi matel y 7 % of patie nts ha ve se vere 
disease wit h al m ost c o m plete hair l oss a n d little or n o re gr o wt h [ Villasa nte Fric ke, 2 0 1 5 ].  O nset 
ca n oc c ur at a n y a ge a n d affects b ot h me n a n d w o me n o ver t he c o urse of t heir lifeti me. 
A p pr o xi matel y 8 0 % of al o pecia areat a patie nts e x perie nce t he first e pis o de of hair l oss b y 
4 0 years of a ge a n d 4 0 % b y 2 0 years of a ge [ Villasa nte F ric ke, 2 0 1 5].  Al o pecia areat a ca n h a ve 
a ps yc h ol o gical i m pac t wit h hi g h rates of d e pressi o n [Sella mi, 2 0 1 4 ] a n d a n xiet y re p orte d, 
partic ularl y i n c hil dre n a n d a d olesce nts [ Bil gic, 2 0 1 3 ], a n d t heref ore, ps yc h ol o gical c o u nseli n g is 
ofte n rec o m me n de d as p art of t he sta n dar d of care [ Al - M utairi, 2 0 1 1]. 
A ca use f or al o pecia areata has n ot yet b ee n i de ntifie d, t h o u g h as i n ot her a ut oi m m u ne dis or ders, 
ge n etic s usce pti bilit y a n d a wi de arra y of e n vir o n me ntal tri g gers ar e t h o u g ht t o be i n v ol ve d. 
Prese ntl y, treat me nts f or al o pecia areata i ncl u de m o deratel y effecti ve i ntral esi o nal c ortic oster oi d 
i njecti o ns or t o picals, or aest hetic dis g uises s uc h as ma ke u p a n d wi gs. Ot her treat me nts i ncl u de 
off-la bel us e of t o pical cl o betas ol pr o pi o nate ( Cl o be x ® ), a p pr o ved f or ps ori asis ( N D A 0 2 1 5 3 5), 
or pi mecr oli m us ( E li del®  crea m 1 %), a p pr o ve d f or at o pic der matitis ( N D A 0 2 1 3 0 2); h o we ver, 
eac h h as si g nificant a d verse reacti o ns ass ociat e d wit h its use, s uc h as C us hi n g’s s y n dr o me, 
h y per gl yce mi a, a n d dia betes mellit us f or Cl o be x, a n d a blac k b o x war ni n g of rare mali g n a ncies 
f or Eli del.  C urre ntl y, n o e xisti n g t hera pies f or al o pecia areat a ha ve b ee n a p pr o ve d b y t he U nite d 
States F o o d a n d Dr u g A d mi nistrati o n ( F D A), i n di cati n g a si g nifica nt u n met m e dical nee d.  
4. 2.   
Scie ntific R ati o n ale f or t he St u d y 
C o ncert has a p plie d its d e uteri u m c he mical e ntit y platf or m t o r u x oliti ni b (Ja kafi ® ), a s electi ve 
J a n us Ki nase (J A K) i n hi bit or t hat mo d ulates i m m u ne res p o nse t hr o u g h re d uce d i ntracell ular 
J A K 1 a n d J A K 2 si g nali n g. C T P- 5 4 3 is str uct urall y si milar t o r u x oliti ni b wit h t he e x ce pti o n of 
ei g ht de ut eri u m at o ms s u bstit ute d i n place of h y dr o ge n. C T P- 5 4 3 is bei n g de vel o pe d as a 
p ote ntial oral tre at me nt f or al o pecia areata.  
T he mec ha nis m of hair l oss i n al o pecia areata a p p ears t o be me di ate d b y c yt ot o xic T cell attac k 
of t he hair f ollicle after l oss of i m m u ne pri vile ge, re g ulate d b y u pstrea m J A K si g n ali n g [ Xi n g, 
2 0 1 4 ].  T heref ore, direct e d J A K i n hi biti o n ma y re prese nt a via bl e t hera p e utic a p pr oac h t o 
treati n g al o peci a areata.  
T he J A Ks are i ntracell ular t yr osi ne ki nases t hat pl a y a ce ntral r ole i n t he si g nali n g of c yt o ki n e 
a n d gr o wt h fact or rece pt ors [ G h oresc hi, 2 0 0 9 ].  C yt o ki ne-i n d uce d rece pt or c o nf or mati o n 
c ha n ges acti vate t he J A Ks a n d tri g ger p h os p h or ylati o n of t he 6- me m ber si g nal tra ns d ucers a n d 
acti vat ors of tr a nscri pti o n ( S T A T ) pr otei n tra ns cri pti o n fact or fa mil y.  U p o n p h os p h or ylati o n, 
S T A Ts di merize a n d tra nsl o cate t o t he n ucle us t o re g ul ate ge n e tra nscri pti o n.  T hera pies t hat 
i n hi bit c yt o ki n e si g n ali n g or d o w nstrea m J A K si g n ali n g ha v e de m o nstrat e d efficac y i n 
a ut oi m m u ne dis or ders s uc h as ps oriasis, ps oriatic art hritis, a n d  r he u mat oi d art hritis, a n d m ulti ple 




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patie nts wi t h p ol yc yt he mia vera. T h e war ni n gs a n d preca uti o ns secti o n of t he prescri bi n g 
i nf or mati o n f or J a kafi, m ost rece ntl y u p date d i n Dece m ber 2 0 1 7, i ncl u des t hr o m b oc yt o p e nia, 
a ne mia a n d n e utr o pe nia; ris k of i nfecti o n; n o n- mela n o ma s ki n ca ncer; li pi d ele vati o ns; a n d 
s y m pt o m e xacer bati o n f oll o wi n g i nterr u pti o n or disc o nti n uati o n [J a kafi, 2 0 1 7].  
Rec o m m e n dati o ns f or m a na ge me nt of c yt o pe nias i ncl u de d ose re d u cti o n or i nterr u pti o n, a n d 
m o nit ori n g of c o m plete bl o o d c o u nts e ver y 2 t o 4 wee ks u ntil sta bilize d, a n d as cli nicall y 
i n dicate d t hereafter.  Seri o us i nfecti o ns re p orte d i n cl u de t u berc ul osis, pr o gressi ve m ultif ocal 
le u k oe nce p h al o pat h y, her pes z oster, a n d he p atitis B; all si g ns a n d s y m pt o ms of i nfecti o n s h o ul d 
be ma na ge d pr o m ptl y. Peri o dic s ki n e x a mi nati o ns are rec o m me n d e d t o detect n o n- mela n o ma 
s ki n ca ncers i ncl u di n g b asal cell, s q ua m o us cell a n d Mer kel cell carci n o ma.  Li pi d ele vati o ns 
i ncl u di n g t otal c h olester ol, l o w- de nsit y li p o pr otei n, hi g h- de nsit y li p o pr otei n, a n d tri gl yceri des 
s h o ul d be assessed e v er y 8 t o 1 2 wee ks f or m o nit ori n g a n d treat me nt of h y p erli pi de mia.  
4. 4. 2.   
Cli nic al St u dies of C T P- 5 4 3 
T w o cli nica l st u dies wit h C T P- 5 4 3 i n healt h y v ol u nteers ha v e bee n c o m plet e d. St u d y 
C P 5 4 3. 1 0 0 1 wa s a p har mac o ki netic/ p har mac o d y na mic st u d y c o nsisti n g of a first- i n- h u ma n 
si n gle as ce n di n g d ose st u d y a n d a se q u e ntial m ulti ple asce n di n g d ose st u d y.  T he o bjecti ve of t he 
st u d y was t o ass ess safet y, t olera bilit y, p har mac o ki netics, a n d p har mac o d y n a mics of C T P- 5 4 3 i n 
healt h y v ol u nteers.  A t ot al of 8 2 s u bjects we re pla n ne d f or t he st u d y; 3 2 s u bjects i n 4 c o h orts 
ra n d o mized at a rati o of 3: 1 C T P- 5 4 3 t o place b o f or t he si n gle asce n di n g d ose part ( Part A), a n d 
t hereafter, 5 0 s u bjects i n 5 c o h orts ra n d o mize d at a rati o of 4: 1 C T P- 5 4 3 t o place b o f or t he 
m ulti ple asce n di n g d os e part ( Part B). T he d os es st u die d i n t he si n gle as ce n di n g d ose st u d y were 
8 m g, 1 6 m g, 3 2 m g , a n d 4 8 m g. T he d os es st u die d i n t he m ulti ple asce n di n g d ose st u d y were 8 
m g o nce dail y, 8 m g t wi ce dail y, 2 4 m g o n ce dail y, 3 2 m g o nce dail y, a n d 1 6 m g t wice d ail y, 
d ose d f or 7 c o ns ec uti ve d a ys. 
T he sec o n d cli nical st u d y C P 5 4 3. 1 0 0 2, als o perf or me d i n healt h y v ol u nteers was a si n gle d ose 
cr oss- o ver st u d y t o ass ess safet y a n d t olera bilit y a n d t o c o m pare t he met a b olite a n d 
p har mac o ki netic pr ofiles of C T P- 5 4 3 vers us r u x oliti ni b. A t otal of 1 2 s u bjects were e nr olle d i n 
t he st u d y; 2 gr o u ps of 6 s u bjects eac h were d ose d wit h eit her 1 5 m g of r u x oliti ni b ( 1 x 1 5 m g 
ta blet) or 1 6 m g of C T P- 5 4 3 ( 2 x 8 m g ta blets) i n peri o d 1 w h o t he n cr osse d o ver t o t he alter nate 
treat me nt f or p eri o d 2. A was h o ut peri o d of 3 d a ys occ urre d bet w ee n treat me nts.  
T o date, C T P- 5 4 3 ha s bee n ge nerall y well t olerate d.  N o deat hs or seri o us a d verse e v e nts ha ve 
occ urre d f oll o wi n g d osi n g wit h C T P- 5 4 3.    
 


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5.   
E T HI C S 
T he  pr oce d ures set o ut i n t his st u d y pr ot oc ol, pertai ni n g t o t he c o n d uct, e val uati o n a n d 
d oc u me ntati o n of t his st u d y, are desi g n e d t o e ns ure t hat t he S p o ns or a n d t h e I n vesti gat or a bi d e 
b y G o o d Cli nical Practice ( G C P), i ncl u di n g b ut n ot li mite d t o Title 2 1 C o de of Fe deral 
Re g ulati o ns ( C F R) Parts 5 0, 5 6, a n d 3 1 2, a n d t he I nter nati o nal C o nfere nce o n Har m o nisati o n 
(I C H) g ui deli nes a n d dir ecti ves.  C o m plia nce wit h t hese re g ulati o ns als o c o nstit utes c o m plia nce 
wit h t he et hical pri nci ples descri be d i n t he c urre nt re visi o n of t he Declarati o n of Helsi n ki a n d 
a p plicable l ocal re g ulat or y re q uire me nts a n d l a w.   
T he I n vesti gat or is r es p o nsi ble f or pr otecti n g t he ri g hts, safet y, a n d welfare of patie nts u n der 
his/ her care, a n d f or t he c o ntr ol of t he me dicati o ns u n der i n vesti gati o n.  All et hical, re g ulat or y, 
a n d le gal re q uire me nts m ust be met bef ore t h e first patie nt is e nr olle d i n t he st u d y. 
5. 1.   
I nstit uti o n al Re vie w B o ar d (I R B) 
T he I nstit uti o nal Re vie w B oar d (I R B) will meet all F D A re q uire me nts g o ver ni n g I R Bs acc or di n g 
t o C F R, Title 2 1, Part 5 6. T he I n vesti gat or ( or desi g nee) m ust s u b mit t his st u d y pr ot oc ol a n d a n y 
a me n d me nts, t he S p o ns or’ s a p pr o ve d i nf or me d c o nse nt f or m(s) (I C F), p atie nt i nf or mati o n 
s heets, patient recr uit me nt materials, a n d ot her a p pr o priate d oc u m e nts t o t he I R B f or re vi e w a n d 
a p pr o val. F oll o wi n g re vi e w of t he s u b mitte d materials a c o p y of t he writte n a n d date d 
a p pr o val/fa v ora ble o pi ni o n will be f or war d e d t o t he S p o ns or ( or desi g nee).  
A n y a d vertise me nts use d t o recr uit patie nts f or t h e st u d y will be re vi e we d b y t he S p o ns or a n d t h e 
I R B pri or t o use. 
5. 2.   
Writte n I nf or me d C o nse nt 
Pri or t o perf or mi n g a n y st u d y-relate d acti vities u n der t his pr ot oc ol, i ncl u di n g scree ni n g tests a n d 
assess me nts, writte n i nf or me d c o nse nt wit h t he a p pr o ve d I C F m ust be o btai ne d fr o m t he patie nt.  
T he I C F, as s pecifie d b y t he cli nical site’s I R B, m ust f oll o w t he Pr otecti o n of H u ma n S u bjects 
re g ulati o ns liste d i n t he C o de of Fe d eral Re g ul ati o ns, Title 2 1, Part 5 0. T he bac k gr o u n d of t he 
pr o p ose d st u d y, t h e pr oce d ures, t he b e nefits a n d ris ks of t he st u d y, a n d t hat st u d y partici p ati o n is 
v ol u ntar y m ust be e x plai ne d t o t he patie nt.  T he p atie nt m ust be gi ve n s ufficie nt ti me t o c o nsi der 
w het her t o partici pate i n t he st u d y.  
A c o p y of t he I C F, si g n e d a n d date d b y t he patie nt, m ust be gi ve n t o t he patie nt.  C o nfir mati o n of 
a patie nt’s i nf or me d c o ns e nt m ust als o be d oc u me nte d i n t he patie nt’s s o urce d oc u me nt ati o n 
pri or t o a n y testi n g u n d er t his pr ot oc ol, i ncl u di n g scree ni n g tests a n d assess me nts. T he ori gi n al 
si g ne d c o nse nt f or m will be retai ne d wit h t he st u d y rec or ds. 
All I C Fs us e d i n t his st u d y m ust be a p pr o ve d b y t h e a p pr o priate I R B a n d b y t he S p o ns or. T he 
I C F m ust n ot be altere d wit h o ut t he pri or a gree me nt of t he rel e va nt I R B a n d t he S p o ns or. 


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6.   
S T U D Y O B J E C TI V E S 
T he o verall o bjecti ves of t he st u d y are t o assess t h e safet y a n d efficac y of a 2 4- wee k re gi me n of 
a d mi nistrati o n of C T P- 5 4 3 i n a d ult patie nts wit h c hr o nic, m o derate t o se v ere al o p ecia areata. 
6. 1.   
Pri m ar y O bjecti ves 
T he pri mar y o bjecti ves are: 
 T o assess t he efficac y of C T P- 5 4 3 o n hair l oss as meas ure d b y t he Se verit y of 
Al o pecia T o ol ( S A L T); 
 T o assess t he safet y of a d mi nistrati o n of C T P- 5 4 3 i n a d ult patie nts wit h c hr o nic, 
m o derate t o se v ere al o pecia areata. 
6. 2.   
E x pl or at o r y O bjecti ves 
T he e x pl orat or y o bj ecti v es are: 
 T o assess t he c h a n ge i n p atie nt al o pecia areata se v erit y as meas ure d b y t he cli nicia n 
Vis ua l A nal o g Scale; 
 T o assess t he c h a n ge i n Cli nical Gl o bal I m pressi o n of I m pr o ve me nt ( C GI-I) fr o m 
baseli ne ; 
 T o assess t he c h a n ge i n al o pecia areata se verit y as meas ure d b y t he p atie nt Vis ual 
A nal o g S cale fr o m baseli ne; 
 T o assess t he c h a n ge i n Patie nt Gl o bal I m pressi o n of I m pr o ve me nt ( P GI- I) fr o m 
ba seli ne; 
 T o assess t he c h a n ge i n p atie nt re p orte d o ut c o mes as meas ure d b y t h e Al o p ecia 
Area ta S y m pt o m I m pact Scale ( A A SI S) a n d e x pl orat or y q uesti o ns fr o m baseli ne; 
 T o e val uate t he pl as ma c o nce ntrati o ns of C T P- 5 4 3 i n a d ult patie nts wit h c hr o nic, 
m o derate t o se v ere al o pecia areata. 


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7.   
O V E R A L L S T U D Y D E SI G N 
7. 1.   
St u d y Desi g n 
T his is a d o u ble- bli n d, ra n d o mize d, place b o-c o ntr olle d, m ultice nter st u d y t o e val uate t he safet y 
a n d effi cac y of C T P- 5 4 3 i n a d ult patie nts wit h c hr o nic, m o derate t o se v ere al o pecia areata.  
Patie nts will re q uire a defi niti ve dia g n osis of al o p ecia areat a b y t he I n vesti gat or base d o n cli nica l 
e val uati o n i nv ol vi n g p h ysical e x a mi nati o n a n d me dical hist or y. T h e patie nt’s al o pecia areata will 
be classifie d b y t he I n vesti gat or i nt o o ne of t hree cate g ories defi ne d f or t his st u d y: 
1)  Al o pecia are at a: patc h y t y p e h air l oss, 
2)  Al o pecia t otalis or u ni versalis: c o m plete hair l oss o n t he scal p wit h or wit h o ut b o d y hair 
l oss, 
3)  Al o pecia o p hiasis: ba n d-li ke hair l oss li mite d t o t he peri p her y of t he scal p al o n g t he bac k 
of t he hair li ne  i n t he occi pital re gi o n a n d p ossi bl y e xte n di n g o ver eac h ear i n te m p oral 
re gi o ns. 
P atients will be bet wee n 1 8 a n d 6 5 years of a ge a n d e x perie nci n g a c urre nt e pis o de of al o pecia 
areat a lasti n g at least 6 m o nt hs a n d n ot e xcee di n g 1 0 years. T otal disease d urati o n ma y e x cee d 
t he d urati o n of t he c urre nt e pis o de. Patie nts will re q uire at least 5 0 % h air l oss as meas ure d b y t h e 
S A L T ass ess me nt at Scree ni n g a n d Baseli ne, a n d s h o ul d n ot be treate d c o n c urre ntl y f or al o pecia 
areat a or wit h ot her tr eat me nts t hat mi g ht affect h air re gr o wt h.  A p pr o xi matel y 5 0 % of al o pecia 
areat a patie nts wit h al o pecia t otalis or u ni versalis, a n d a p pr o xi matel y 1 0 % wit h o nl y al o pecia 
o p hiasis, will be e nr olle d.  
T he st u d y c o nsists of u p t o 3 c o h orts i nitiate d se q ue ntiall y i n asce n di n g d ose or der. A n 
i n de pe n de nt data m o nit ori n g c o m mittee ( D M C) will deter mi ne if t here are a de q uate safet y data 
t o s u p p ort eac h s u bse q ue nt d ose c o h ort. Patie nts will n ot d ose escalate wit hi n a c o h ort a n d ma y 
o nl y partici p ate i n o ne c o h ort.   
T he Scre e ni n g Peri o d will last u p t o 2 8 da ys pri or t o i nitiati o n of st u d y dr u g.  T he Treat me nt 
Peri o d is t he  i nitial 2 4- wee k, d o u ble- bli n d, place b o-c o ntr olle d peri o d t o defi ne pri mar y efficac y 
a n d safet y f or t he st u d y. T he P ost- Treat me nt Safet y F oll o w- u p Peri o d is t he fi nal 4 wee ks of 
eac h c o h ort t o assess safet y f oll o wi n g treat me nt c o m pleti o n.  S u bjects e nr olle d i n C o h ort 3 ( 1 2 
m g BI D)  will ha ve t he o pti o n t o c o nti n ue recei vi n g treat me nt i n a n O pe n-la bel E xte nsi o n st u d y 
f oll o wi n g t he treat me nt p eri o d.  If s u bjects d o n ot wis h t o c o nti n ue i nt o t h e O pe n-la bel E xte nsi o n 
st u d y, t he y will c o m plete treat me nt at Wee k 2 4 a n d ret ur n i n 4 wee ks f or t h e P ost- Treat me nt 
Safet y F oll o w- u p t o ass ess safet y f oll o wi n g treat me nt c o m pleti o n.   
T he D M C will perf or m r e g ul ar safet y assess me nts f or eac h c o h ort b ase d o n re vie w of c ollecti ve 
safet y data. After t h e last patie nt i n a c o h ort has c o m plete d t he Wee k 1 2 Visit, t he D M C will 
c o n ve ne t o r e vie w acc u m ulate d safet y d ata t o assess if i nitiati o n of t he s u bse q ue nt c o h ort is 
s u p p orte d, as a p plica bl e. T he D M C ma y a d vise treat me nt ar m cess ati o n d ue t o i nt olera bilit y at 
a n y ti me.  


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Fi g ure  1:   
St u d y Desi g n 
 
 
Patie nts will pr o vi de a p pr o priatel y o btai ne d i nf or me d c o nse nt pri or t o c o m pleti n g a n y scree ni n g 
pr oce d ures.  Patie nts meeti n g i nitial scree ni n g criteria will be eli gi ble t o c o nti n ue t o t he c o h ort 
Da y 1 visit f or re vie w of eli gi bilit y a n d b aseli ne assess me nts, i ncl u di n g S A L T assess me nt, 
p h ysical e x a mi nati o n, cli nical la b orat or y assess me nts, vital si g ns, a n d electr ocar di o gra m.  T he 
first 2 c o h orts will be ra n d o mize d i n a 2: 1 rati o (acti ve: place b o) a n d t he t hir d c o h ort will be 
ra n d o mize d i n a 5: 1 rati o (acti ve: place b o) i n or d er t o pr o vi de a si milar n u m ber of patie nts acr oss 
t he C T P- 5 4 3 a n d p o ole d place b o ar ms.    Ra n d o mizati o n will be stratifie d b y cl assificati o n of 
al o pecia areata s u bt y p e i nt o o ne of t he f oll o wi n g t hree cate g ories: 1) al o pecia areata, 2) al o pe ci a 
t otalis or al o pecia u ni versalis, or 3) al o peci a o p hiasis.  
T he d o u ble- bli n d, place b o-c o ntr olle d Treat me nt Peri o d f or eac h c o h ort will last 2 4 wee ks.  
Assess me nt of tre at me nt res p o nse wit h S A L T f or efficac y will occ ur at 4, 8, 1 2, 1 6, 2 0 a n d 2 4 
wee ks.  All S A L T assess me nts will be perf or me d wit h a li ve p h ysical e xa mi nati o n of t he patie nt 
b y q ualifie d, trai ne d site pers o n nel. P h ot o gra p hs of t he scal p will be use d t o pr o vi de a vis ual 
rec or d at t he ti me of S A L T assess me nt, a n d p h ot o gra p hs of t he h a n ds a n d/ or e yes will be ta ke n 
t o d oc u me nt nail or e yelas h/e ye br o w i n v ol ve me nt i n t h ose patie nts f or w h o m it a p plies. T he 


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efficac y a n al ysis will be c o n d ucte d w h e n all patie nts i n t he hi g hest d ose c o h ort ha ve c o m plete d 
Wee k 2 4 of  d osi n g.  
F or C o h orts 1 a n d 2, pati e nts will st o p ta ki n g st u d y me dicati o n u p o n c o m pleti o n of treat me nt at 
Wee k 2 4, a n d e nter a 4 wee k P ost- Treat me nt Safet y F oll o w- U p Peri o d.  Patie nts will be assesse d 
f or safet y t hr o u g h Wee k 2 8.  F or C o h ort 3 ( 1 2 m g BI D), patie nts will be eli gi ble t o eit her 
c o m plete treat me nt at Wee k 2 4 a n d e xit t he st u d y at Wee k 2 8 f oll o wi n g t he Safet y F oll o w- u p 
visit, or r oll- o ver i nt o a L o n g-ter m E xte nsi o n st u d y at Wee k 2 4.  
Patie nts e nr olle d i nt o eac h c o h ort will ta ke t he first d ose of st u d y dr u g i n t h e cli nic o n Da y 1 a n d 
will be i nstr uc te d t o ta ke st u d y dr u g e v er y 1 2 h o urs wit h or wit h o ut f o o d, f or t he d urati o n of t he 
Treat m e nt Peri o d. Patie nts s h o ul d d ose st u d y dr u g i n t he cli nic o n all St u d y Visit Da ys after 
cli nical la b orat or y bl o o d dra ws are c o m plete d. Bl o o d sa m ples f or p har mac o ki netic a n d 
p har mac o d y n a mic assess me nt will be ta ke n peri o dicall y. Sc h e d ule d assess me nt of patie nt a n d 
cli nicia n perce pti o n of disease se v erit y a n d i m pr o ve me nt will als o occ ur. P atie nt safet y will be 
m o nit ore d t hr o u g h o ut t he st u d y b y t he I n v esti gat ors, a n d s u p p orte d b y re g ul ar re vi e w b y t he 
Me dical M o nit or, a n d D M C.  He mat ol o g y para m eters will be m o nit ore d cl osel y f or t he d urati o n 
of t he st u d y.  F or eac h c o h ort, he mat ol o g y will be c o n d ucte d e v er y 2 wee ks d uri n g t he first 8 
wee ks of t he Treat me nt Peri o d, f oll o we d b y a n ass ess me nt e ver y 4 wee ks t h ereafter t hr o u g h 
c o m pleti o n of t he st u d y.  Li pi d le vels will be ass esse d e ver y 1 2 wee ks t hr o u g h o ut t he Treat me nt 
Peri o d a n d at t he P ost- Treat me nt Safet y F oll o w- U p Visit, if a p plica ble.  Si g nifica nt c yt o pe nias 
or ot her he mat ol o gic a b n or maliti es will be ma na ge d b y s e verit y t hr o u g h d ose i nterr u pti o n or 
disc o nti n uati o n, a n d si g ns a n d s y m pt o ms of i nfecti o n will be cl osel y m o nit ore d a n d treate d 
pr o m ptl y.  Pa tie nts w h o e x perie nce i nt olera bl e s y m pt o ms d uri n g treat me nt ma y disc o nti n ue t he 
st u d y at t he discreti o n of t he I n v esti gat or.  Patie nts ma y wit h dra w c o ns e nt at a n y ti me. 
7. 2.   
N u m ber of P atie n ts a n d Sites 
A p pr o xi matel y 1 5 0 p atie nts are pla n ne d t o b e e nr olle d i n t he st u d y at u p t o 1 4 sites. T he first 2 
c o h orts will be ran d o mize d i n a 2: 1 rati o a n d t he t hir d c o h ort will be ra n d o mize d i n a 5: 1 rati o i n 
or der t o pr o vi de a si milar n u m ber of patie nts acr oss t he C T P- 5 4 3 a n d p o ole d place b o ar ms. 
7. 3.   
Met h o d of Tre at me nt Assi g n me nt a n d Bli n di n g 
Ra n d o mizati o n will be stratifie d b y classificati o n of al o pecia areata s u bt y p e i nt o o ne of t he 
f oll o wi n g t hree cate g ories: 1) al o pecia areata, 2) al o pecia t otalis or al o peci a u ni versalis, a n d 3) 
al o pecia o p hiasis. A p pr o xi matel y 5 0 % of al o pecia areata s u bjects wit h al o pecia t otalis or 
u ni versalis, a n d a p pr o xi matel y 1 0 % wit h o nl y al o pecia o p hiasis, will be e nr olle d. T he 
ran d o mizati o n sc he d ule will be ge n erat e d pri or t o st u d y start. 
All st u d y partici pa nts will be bli n de d t o st u d y dr u g assi g n me nt f or t he d urati o n of t he st u d y. 
Ta blets a n d pa c ka gi n g of C T P- 5 4 3 a n d place b o will be i de ntical i n a p peara nce. 
7. 4.   
R ati o n ale f or St u d y Desi g n 
D o u ble- bli n d, ra n d o mize d, place b o-c o ntr olle d st u dies are c o nsi dere d o pti mal f or o btai ni n g 
u n biase d esti mates of t he efficac y a n d s afet y of i n vesti gati o nal pr o d ucts.  T he 2 4- wee k d urati o n 
of t he Treat me nt Peri o d is a ntici pate d t o all o w s ufficie nt ti me f or i nitiati o n of hair gr o wt h wit h 
C T P- 5 4 3.  Asse ss me nt of treat me nt t hr o u g h 2 4 wee ks will pr o vi de a n i nitial assess me nt of t he 
safet y pr ofile ass ociate d wit h C T P- 5 4 3. 


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8.   
S E L E C TI O N A N D WI T H D R A W A L O F P A TI E N T S  
Patie nts eli gi ble f or e nr oll me nt i n t he st u d y m ust meet all of t he f oll o wi n g i ncl usi o n criteria a n d 
n o ne of t he e x cl usi o n criteria. 
8. 1.   
P atie n t I ncl usi o n Criteri a 
1.  Writte n i nf or me d c o nse nt, a n d a ut h orizati o n f or release a n d us e of pr otecte d healt h 
i nf or mati o n. 
2.  Bet wee n 1 8 a n d 6 5 years of a ge, i ncl usi ve, at t he ti me of i nf or me d c o ns e nt. 
3.  Defi niti ve dia g n osis of al o pecia areat a wit h a c urre nt e pis o de of at least 6 m o nt hs a n d n ot 
e x cee di n g 1 0 years at t he ti me of Scree ni n g. T otal disease d urati o n greater t ha n 1 0 years 
is per mitted. 
4.  At least 5 0 % scal p hair l oss, as defi ne d b y a S A L T sc ore ≥5 0, at Scree ni n g a n d Bas eli ne.  
5.  If of re pr o d ucti ve a ge, willi n g a n d a ble t o use a me dicall y hi g hl y effecti ve f or m of birt h 
c o ntr ol d uri n g t h e st u d y a n d f or 3 0 da ys f oll o wi n g last d ose of st u d y me di cati o n.  
E x a m ples of me dicall y hi g hl y effecti ve f or ms of birt h c o ntr ol are: 
a. S ur gical sterilit y ( via v as ect o m y, h ysterect o m y or bilateral li gati o n) or 
p ost- me n o pa usal fe m ales 
b.  Se x ual part ner is sterile, or of t he sa me se x 
c. I m plants of le v o n or gestr el i n fe males 
d.  Oral c o ntrace pti ve (c o m bi ne d or pr o gester o ne o nl y) i n fe males 
e. D o u ble- ba rrier met h o d ( a n y c o m bi nati o n of p h ysical a n d c he mic al met h o ds) 
f. I ntr a uteri ne de vice i n f e males, or ot her met h o d wit h p u blis he d data s h o wi n g t hat t he 
l o west e x pecte d fail ure rate is less t ha n 1 % per ye ar  
6.  Willi n g t o c o m pl y wit h t he st u d y visits a n d re q uire me nts of t he st u d y pr ot oc ol. 
8. 2.   
P a tie nt E xcl usi o n Criteri a 
1.  Hist or y or prese n ce of hair tra ns pla nts. 
2.  Treat me nt wit h ot her me dicati o ns or a ge nts wit hi n 1 m o nt h of Scree ni n g or d uri n g t h e 
st u d y t hat may affect hair re gr o wt h or i m m u ne res p o nse, i ncl u di n g, b ut n ot li mite d t o : 
c ortic oster oi ds a d mi nistere d orall y, b y i njecti o n, or a p plie d t o areas of s ki n affecte d b y 
al o pecia; platelet-ric h plas ma i njecti o ns; t o pical a p plicati o n t o affect e d areas of a nt hrali n, 
s q uaric aci d, di p he n yl c ycl o pr o pe n o ne, or mi n o xi dil.  
3.  Treat me nt wit h s yste mic i m m u n os u p pressi ve me dicati o ns i ncl u di n g b ut n ot li mite d t o 
met h otre x a te, c ycl os p ori ne, a n d azat hi o pri ne; c hl or o q ui ne deri vati ves; J A K i n hi bit ors 
(r u x olitini b, t ofaciti ni b, etc) or eta nerce pt wit hi n 3 m o nt hs of Scree ni n g or d uri n g t he 
st u d y; or bi ol o gi cs (a d ali m u ma b, atliz u ma b, ca na ki n u ma b, cert oliz u ma b, f o nt oliz u ma b, 
g oli m u ma b, i nfli xi ma b, me p oliz u ma b, rit u xi ma b, sec u ki n u ma b, t ociliz u ma b, 
uste ki n u ma b) wit hi n 6 m o nt hs of Scree ni n g or d uri n g t he st u d y. 
4.  Ac ti ve scal p i nfla m mati o n, ps oriasis, or se b orr h eic der matitis re q uiri n g t o pical tre at me nt 
t o t he scal p, si g nifica nt tra u ma t o t he scal p, or u ntreate d acti nic kerat osis a n y w h ere o n t he 
b o d y at Scree ni n g a n d/ or Baseli ne. 


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5.  K n o w n hist or y of m o derate t o se vere a n dr o ge nic al o pecia or fe male p atter n hair l oss 
pri or t o al o pecia areata. 
6.  U n willi n g t o mai ntai n a c o nsiste nt hair st yle, i ncl u di n g s ha m p o o a n d hair pr o d ucts 
(i ncl u di n g hair d ye, pr ocess, a n d ti mi n g t o hair a p p oi nt me nts), a n d t o refrai n fr o m wea v es 
or e xte nsi o ns t hr o u g h o ut t he c o urse of t he st u d y, or s ha vi n g of scal p h air f or at least 2 
we e ks pri or t o a S A L T assess me nt. 
7.  Use of a d h esi ve wi gs, ot her t ha n ba n d e d peri met er wi gs, d uri n g t h e st u d y. 
8.  Hist or y of a l y m p h o pr oliferati ve disease or mali g na nc y, ot her t ha n n o n- mela n o ma s ki n 
ca nc er or cer vical carci n o ma.  Patie nts wit h 3 or m ore basal or s q u a m o us cell carci n o mas 
dia g n ose d i n t he past 2 years are e x cl u de d.  
9.  At y pical ne vi or c uta ne o us lesi o ns t hat are s us pici o us f or mali g n a nc y. 
1 0.  Hist or y of s oli d or ga n or he mat ol o gical tra ns pla nt ati o n. 
1 1.  Fe ve r or i nfecti o n wit hi n 2 wee ks pri or t o first d ose of st u d y dr u g. 
1 2.  A b n or mal le vels of t h yr oi d sti m ulati n g h or m o ne at Scree ni n g, defi ne d as < 0. 9 x t he 
l o wer li mit of n or mal ( L L N) a n d > 1. 2 x t he u p per li mit of n or mal ( U L N) a n d, if ta ki n g 
t h yr oi d me dicati o n, a n i na bilit y t o mai ntai n le vels wit hi n t he n or mal ra n ge f or 6 m o nt hs 
pri or t o Scre e ni n g or d uri n g t he st u d y. 
1 3.  Scree ni n g la bs o utsi de t h e n or mal ra n ge f or p ara m eters ass oci ate d wit h p ote ntial ris k f or 
treat me nt u n der i n v esti gati o n. T his will i ncl u de b ut is n ot li mite d t o: 
a. Platelets ≤1 2 0 x 1 0 9/ L  
b.  A bs ol ute ne utr o p hil c o u nt ≤1. 5 x 1 0 9/ L 
c. He m o g l o bi n le vels ≤1 1 g/ d L f or fe mal es, or he m o gl o bi n le vels ≤1 2. 5 g/ d L f or 
males  
1 4.  S cree ni n g bl o o d gl uc ose le vels of he m o gl o bi n A 1c ≥6. 5 % ( 4 8 m m ol/ m ol). 
1 5.  A b n or mal li ver f u ncti o n at Scree ni n g, defi ne d as ≥1. 5 × U L N of ser u m ala ni ne 
tra nsa mi nase, ser u m as partate tra nsa mi nas e, ser u m al kali ne p h os p hatase, or  t otal bilir u bi n 
( u nless is olated Gil bert’s s y n dr o me). 
1 6.  A b n or mal re n al f u ncti o n (esti mate d gl o mer ular filtrati o n rate < 6 0 m L/ mi n/ 1. 7 3 m 2 usi n g 
t he M DR D e q uati o n) at Scree ni n g.  
1 7.  A n y acti ve i nfecti o n at Scree ni n g, acti ve or pre vi o us He patitis B or C i nfecti o n, or k n o w n 
h u ma n i m m u n o deficie nc y vir us i nfecti o n. 
1 8.  Vacci n ati o n wit h her pes z oster vacci ne or a n y li ve vir us vacci ne wit hi n 6 wee ks bef ore 
Scree ni n g or d uri n g t he st u d y.  
1 9.  P ositi ve p ur ifie d pr otei n deri vati ve test f or n o n- bacill us Cal mette- G uéri n- v acci nat e d 
patie nts, p ositi ve Q ua nti F E R O N ® -T B  G ol d test, or hist or y of i nc o m pletel y treate d or 
u ntreate d t u berc ul osis. 
2 0.  Hist or y  of pr ol o n ge d Q T s y n dr o me or a Scree ni n g Q Tc i nter val wit h Fri dericia’s 
c orrecti o n ( Q Tc F) > 4 5 0 msec f or males or Q Tc F > 4 7 0 msec f or fe mal es. 
2 1.  Hist or y of alc o h ol, me dicati o n, or illicit dr u g a b us e wit hi n 1 year bef ore t h e first d ose of 
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2 2.  Fe male s w h o are n ursi n g, pre g na nt, or pla n ni n g t o bec o me pre g na nt w hile i n t he st u d y, 
a n d f or 3 0 da ys after last d ose of st u d y m e dicati o n. 
2 3.  Partic i pati o n i n a n ot her i n vesti gati o nal st u d y wit hi n t he greater of 4 wee ks or 5 half-li ves 
of a n i n vesti gati o nal me dicati o n pri or t o scree ni n g or d uri n g t h e st u d y. 
2 4.  Use of str o n g C Y P 3 A 4 i n hi bit ors (s uc h as, b ut n ot li mite d t o clarit hr o m yci n, c o ni va pta n, 
gra pefr uit j uice, i n di na vir, itrac o naz ole, ket oc o naz ole, l o pi na vir/rit o na vir, mi befra dil, 
nefaz o d o ne, nelfi n a vir, p osac o naz ole, sa q ui na vir, tela pre vir, telit hr o m yci n, v oric o naz ole, 
or fl uc o naz ole ) d ose d f or s yste mic e x p os ure. 
2 5.  Use of str o n g C Y P 3 A 4 i n d ucers (s u c h as, b ut n ot li mite d t o bar bit urates, car ba maze pi ne, 
efa vir e nz, gl uc oc ortic oi ds, m o dafi nil, ne vira pi ne, o x car baze pi ne, p he n o bar bital, 
p he n yt oi n, pi o glitaz o ne, rifa b uti n, rifa m pi n, St. J o h n’s W ort, or tr o glitaz o ne) d ose d f or 
s yste mic e xp os ure. 
2 6.  D o nati o n of bl o o d wit hi n a m o nt h of first d ose of st u d y dr u g or at a n y p oi nt t hr o u g h o ut 
t he st u d y a n d f or 3 0 da ys after last d ose of st u d y me dicati o n. 
2 7.  Cli nica ll y si g nifica nt me dical c o n diti o n, ps yc hi atric disease, or s ocial c o n diti o ns, as 
deter mi ne d b y t he I n v esti gat or, t h at ma y u nfa v ora bl y alter t he ris k- be n efit of st u d y 
partici pati o n, a d verse l y affect st u d y c o m plia nce, or c o nf o u n d i nter pretati o n of st u d y 
res ults.  
8. 3.   
P atie nt Wit h dr a w al Criter i a 
All patie nts are free t o wit h dra w fr o m partici pati o n i n t he st u d y at a n y ti me, f or a n y reas o n, a n d 
wit h o ut prej u dice.  T he I n vesti gat or m ust wit h dra w a n y patie nt fr o m t he st u d y if t he p atie nt 
req uests t o st o p partici pati n g i n t he st u d y.  T he I n vesti gat or, S p o ns or, or its desi g nee ma y 
re m o ve a p atie nt fr o m t h e st u d y at a n y ti me a n d f or a n y reas o n.  I n a d diti o n, patie nts s h o ul d be 
wit h dra w n if t he y: 
 E x perie nce a n i nt olera ble a d verse e ve nt, i ncl u di n g b ut n ot li mite d t o, a n a d verse 
e ve nt ≥ Gra d e 4, i ncl u di n g b o ne m arr o w-rel ate d e ve nts, or a ≥ Gra de 3 c ar diac e ve nt, 
acc or di n g t o C T C A E v 4. 0 criteria 
 Re q uire a me dicati o n t hat is pr o hi bite d b y t he pr ot oc ol 
 D o n ot f oll o w g ui deli nes s pecifie d i n t he pr ot oc ol (ie, is n o nc o m plia nt wit h pr ot oc ol 
pr oce d ures or st u d y treat me nt a d mi nistrati o n) 
 A n y me di call y a p pr o priate reas o n or si g nifica nt pr ot oc ol vi olati o n, i n t he o pi ni o n of 
t he I n vesti gat or 
 Are l ost t o f oll o w u p 
Pati e nts w h o wit h dra w or are wit h dra w n fr o m t he st u d y will n ot be re place d. 
8. 3. 1.   
P ati e nt Wit h dr a w al Pr oce d ures 
A patie nt w h o pre mat urel y disc o nti n ues st u d y treat me nt/st u d y p artici pati o n s h o ul d ha ve all 
Wee k 2 4 assess me nts perf or me d as a n Earl y Ter mi nati o n Visit, a n d ret ur n f or t he Safet y F oll o w-
u p Visit. T he Safet y F oll o w- U p Visit ma y b e wai ve d b y t h e S p o ns or i n i nsta nces w here p atie nts 
ha ve disc o nti n ue d d osi n g pri or t o t he Earl y Ter mi nati o n Visit o n a case- b y -case b asis.  


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If a patie nt ter mi nates earl y fr o m t he st u d y, t he I n v esti gat or will rec or d t he reas o n(s) f or earl y 
ter mi nati o n o n t he rele va nt electr o nic case re p ort f or m (e C R F).  T he s pecifi c reas o n f or t he 
wit h dra wal s h o ul d be caref ull y d o c u me nte d o n t he e C R F.   
Patie nts w h o re q uire a d ose i nterr u pti o n lasti n g m ore t ha n 2 1 da ys s h o ul d be disc o nti n ue d fr o m 
t he st u d y. A d verse e ve nts res ulti n g i n patie nt earl y ter mi nati o n will be f oll o we d t o t he 
satisfact or y res ol uti o n a n d deter mi nati o n of o utc o me, as ascertai ne d b y t he I n v esti gat or (a n d/ or 
S p o ns or, or its desi g nee); See Secti o n 1 1. 1. 2 : A d verse E ve nts.  T h e data will be rec or de d o n t he 
a p pr o priate e C R F. 
8. 4.   
E mer ge nc y  U n bli n di n g of Tre at me nt Assi g n me nt 
I n t he cas e of a me di cal r e q uire me nt t o brea k t he bli n d t o deter mi ne a p pr o priate treat me nt f or a n 
a d verse e ve nt, u n bli n di n g of a patie nt’s treat me nt assi g n me nt ca n be ac hie ve d t hr o u g h t he st u d y-
s pecific I nteracti ve We b Res p o nse S yste m. If p ossi ble, t he I n v esti gat or s h o ul d disc uss t he 
circ u msta nces wit h t he Me dical M o nit or pri or t o accessi n g u n bli n di n g i nf or mati o n. I n t h e e ve nt 
of a bli n d brea k, t h e Me dical M o nit or will be n otifie d t hr o u g h t he electr o nic data ca pt ure s yste m. 
T he patie nt f or w h o m t he bli n d is br o ke n s h o ul d be s u bse q ue ntl y wit h dra w n fr o m t he st u d y. T he 
details re ga r di n g t he pr ocess of brea ki n g t h e bli n d are o utli ne d i n t he P har m ac y Ma n ual. 
8. 5.   
Criteri a f or St u d y Ter mi n ati o n 
If t he D M C deter mi nes t hat treat me nt wit h C T P- 5 4 3 p oses a n u nj ustifie d ris k t o patie nts, t he 
st u d y ma y be ter mi nate d. T he S p o ns or reser ves t h e ri g ht t o disc o nti n ue t he st u d y at a n y ti me f or 
cli nical or a d mi nistrati ve reas o ns.   
T he D M C will re vie w c ollecti ve safet y dat a f or eac h c o h ort at re g ular i nter vals t hr o u g h o ut t he 
st u d y. S h o ul d safet y si g n als arise t hat s u g gest treat me nt wit h C T P- 5 4 3 p oses a n u nj ustifie d ris k 
t o patie nts, ter mi nati o n of t he st u d y or m o dificati o n of d osi n g ar ms ma y occ ur u p o n S p o ns or 
re vie w of t h e D M C rec o m me n dati o n. T he D M C ma y call f or u nsc h e d ule d data re vie w meeti n gs 
at a n y time t o e ns ure a p pr o priate safet y m o nit ori n g.  
E ve nts t hat w o ul d tri g ger a n u nsc he d ule d re vie w ma y i ncl u d e, b ut are n ot li mite d t o:  
 Hi g h fre q ue n c y of d ose i nterr u pti o ns  
 Hi g h fre q ue n c y of, or a tr e n d i n, S A Es  
 Hi g h fre q ue n c y of Gra de 3/ 4 a d verse e ve nts 
 T re n d i n or ga n s yste m-s p ecific m o derate a n d/ or se vere a d v erse e ve nts  
 Hi g h fre q ue n c y of p atie nt wit h dra wal d ue t o a d v erse e ve nts 
T he S p o ns or will n otif y I n vesti gat ors of a n y rec o m me n dati o n of st u d y ter mi nati o n b y t he D M C. 
T he S p o ns or wil l n otif y I n vesti gat ors of rec o m me n dati o n f or st u d y m o dificati o n as necess ar y t o 
pr otect patie nt safet y i ncl u di n g a p pr o priate i nstr ucti o ns f or re m o vi n g p atie nts fr o m treat me nt, 
w hile mai ntai ni n g t he bli n d.  
A n y ter mi na ti o n re q uire d b y t he S p o ns or m ust be i m ple me nte d b y t h e I n vesti gat or, if i nstr uct e d 
t o d o s o, i n a ti me fra me t hat is c o m pati ble wit h t he patie nt’s well- b ei n g. 


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9.   
D E S C RI P TI O N O F S T U D Y T R E A T M E N T S 
9. 1.   
Descri pti o n of Tre at me nts 
F or eac h c o h ort, patie nts will be stratifie d b y al o pecia areata s u bt y pe a n d ra n d o mize d t o C T P-
5 4 3 or place b o i n a 2: 1 rati o f or C o h orts 1 a n d 2, a n d 5: 1 rati o f or C o h ort 3. 
  Treat me nts ar ms f or eac h c o h ort will i ncl u de: 
 C o h ort 1 
 C T P- 5 4 3 4 m g e ver y 1 2 h o urs 
 Place b o e ver y 1 2 h o urs 
If t he D M C re vi e w of safet y p ara met ers f or all patie nts i n C o h ort 1 ( 4 m g BI D) t hr o u g h 
Wee k 1 2 i n dicates n o safet y c o ncer ns, C o h ort 2 ( 8 m g BI D) will be i nitiate d. 
 C o h ort 2 
 C T P- 5 4 3 8 m g e ver y 1 2 h o urs 
 Place b o e ver y 1 2 h o urs 
 If t he D M C re vi e w of safet y p ara met ers f or all patie nts i n C o h ort 2 ( 8 m g BI D) 
t hr o u g h Wee k 1 2 i n dicates n o safet y c o ncer ns, C o h ort 3 ( 1 2 m g BI D) will be 
i nitiate d. 
 C o h ort 3 
 C T P- 5 4 3 1 2 m g e ver y 1 2 h o urs 
 Place b o e ver y 1 2 h o urs 
F or eac h c o h ort, patie nts will ta ke t he first d ose of st u d y dr u g i n t he cli nic o n Da y 1 of t he 
Treat me nt Peri o d a n d will be i nstr ucte d t o ta ke st u d y dr u g e ver y 1 2 h o urs f or t he d urati o n of t he 
peri o d. Patie nts s h o ul d d ose st u d y dr u g i n t he cli nic o n all St u d y Visit Da ys after cli nical 
la b orat or y bl o o d dra ws are c o m plete d.  
9. 2.   
D ose- A dj ust me nt Criteri a 
N o i n di vi d ualize d d ose a dj ust me nt is all o we d d uri n g t he Treat me nt Peri o d e x ce pt i n t he e ve nt of 
i nt olera bilit y, f or w hi c h a d ose i nterr u pti o n or st u d y disc o nti n uati o n ma y occ ur at t he discreti o n 
of t he I n ve sti gat or (see S ecti o n 9. 2. 1  bel o w f or details). 
T he  D M C will re vie w c ollecti ve safet y dat a t hr o u g h o ut t he st u d y i n acc or da nce wit h t he D M C 
C harter. If t h e D M C deter mi nes a c o h ort’s C T P- 5 4 3 treat me nt ar m s h o ul d be st o p pe d, patie nts 
recei vi n g tr eat me nt at t hat d ose will m o ve t o t he ne xt l o wer c o h ort’s C T P- 5 4 3 treat me nt ar m i n a 
bli n de d fas hi o n at t he patie nt’s ne xt visit, if a l o wer C T P- 5 4 3 treat me nt is a vaila ble. If a l o wer 
C T P- 5 4 3 treat me nt ar m is n ot a vaila ble, t he st u d y will ter mi nate. If a n i m m e diate hazar d is 
s us pecte d, patie nts wit h o ut a n i m mi ne nt visit ma y ha ve a n U nsc he d ule d Visit f or p ote ntial d ose 
a dj ust me nt t o mai ntai n t he bli n d. I n t he e ve nt of C T P- 5 4 3 treat me nt ar m cessati o n a n d c o h ort 
d ose a dj ust me nt t o a l o we r C T P- 5 4 3 treat me nt, t h e bli n d will be mai ntai ne d a n d i n di vi d ual 
patie nt treat me nt m o dificati o ns will n ot be discl ose d.  




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t he all o wa ble 2 1- d a y d os e i nterr u pti o n peri o d has ela pse d. I n t he case of se vere ne utr o pe nia 
( ne utr o p hil c o u nts less t ha n 0. 5 x 1 09/ L) patie nts s h o ul d disc o nti n ue t he st u d y a n d recei ve 
i nstr ucti o ns t o see k me dical hel p if t he y de v el o p fe ver or si g ns of i nfecti o n. Patie nts w h o 
disc o nti n ue t he st u d y  d ue t o lac k of acce pta bl e rec o ver y of para meters wit hi n t he 2 1- da y d ose 
i nterr u pti o n peri o d s h o ul d c o nti n ue t o be m o nit ore d as a p pr o priate t hr o u g h acce pta ble cli nical 
res ol uti o n. 
9. 2. 2.   
P h ar m a c o ki netic Crit eri a f or St o p pi n g D oses 
T here are n o p h ar mac o ki netic criteria f or st o p pi n g st u d y dr u g d oses. 
9. 3.   
Tre at me nt C o m pli a nce 
At eac h sc h e d ule d st u d y visit after ra n d o mizati o n, t he I n v esti gat or or desi g nee will i nter vie w t he 
patie nt re gar di n g tr eat m e nt c o m plia nce a n d c o m pare t he n u m ber of dis pe nse d vers us ret ur ne d 
st u d y dr u g ta blets. Patie nts s h o ul d stri ve f or 1 0 0 % c o m plia nce wit h t he dail y d osi n g sc he d ul e. 
Retrai ni n g o n tr eat me nt c o m plia nce s h o ul d occ ur f or patie nts wit h less t ha n 8 0 % c o m plia nce at 
a n y visit a n d t he S p o ns or s h o ul d be n otifie d.  
9. 4.   
St u d y Dr u g M ateri als a n d M a n a ge me nt 
Please c o ns ult t he P har m ac y Ma n ual f or a c o m plete descri pti o n of t he st u d y dr u g a n d 
re q uire me nts f or st ora ge, ha n dli n g, dis pe nsi n g, acc o u nta bilit y, ret ur ns a n d destr ucti o n. 
9. 4. 1.   
P h ysic al Des cri pti o n of St u d y Dr u g 
St u d y  dr u g will i ncl u de C T P- 5 4 3, a de uterat e d a n al o g of r u x oliti ni b, a n d matc hi n g place b o.  
Details re ga r di n g f or m ul ati o n a n d d osa ge are pres e nte d i n Ta ble 4  . 
T a ble 4:  
I n vesti g ati o n al Pr o d uct 
 
I n vesti g ati o n al Pr o d uct 
( C T P-5 4 3 or Pl ace b o)  
Pr o d uct N a me:  
C T P -5 4 3 or  
Matc hi n g place b o  
D os a ge F or m:  
T a blet 
D os a ge Stre n gt h of C T P -5 4 3  
4 m g, 8 m g , 1 2 m g  
R o ute of A d mi nistr ati o n  
Oral  
P h ysic al Descri pti o n  
W hite, ca ps ule -s ha pe d ta blets 
9. 4. 2.   
St u d y Dr u g P ac k a gi n g, L a beli n g, a n d St or a ge 
C T P- 5 4 3 acti ve a n d place b o ta blets will be pac k a ge d a n d la bel e d b y a n a p pr o priate l y q ualifie d 
ve n d or. Eac h patie nt will recei v e a d osi n g c ar d at eac h 4 wee k st u d y visit. Details of t he 
pac ka gi n g, la beli n g a n d dis pe nsi n g i nstr ucti o ns ca n be f o u n d i n t he P har mac y Ma n ual. 
T he la bel(s) f or t he i n vesti gati o nal pr o d uct a n d place b o will i ncl u de s p o ns or na me, a d dress a n d 
tele p h o ne n u m ber, t he pr ot oc ol n u m ber, i n vesti gati o nal pr o d uct na me, d osa ge f or m, a m o u nt of 
i n vesti gati o nal pr o d u ct per c o ntai ner, l ot n u m ber, u ni q ue d osi n g car d n u m b er, st ora ge 
c o n diti o ns, an d re q uire d ca uti o n state me nts a n d/ or re g ulat or y state me nts, as a p plica ble.  
A d diti o nal i nf or mati o n ma y b e i ncl u de d o n t he l a bel as a p plica ble per l ocal re g ulati o ns. 


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A de q uate s u p plie s of st u d y dr u g will be pr o vi de d t o eac h site. St u d y dr u g s h o ul d be st ore d i n t he 
ori gi nal pac ka ge bet wee n 1 5° C t o 2 5° C ( 5 9° F t o 7 7° F), as state d o n t he pr o d uct la bel, i n a 
sec ure, te m perat ure- m o nit ore d, l oc ke d area, u n der t he res p o nsi bilit y of t he I n vesti gat or or ot her 
a ut h orize d i n di vi d ual u ntil dis pe nse d t o t he pati e nts. 
St u d y dr u g dis pe nse d t o patie nts s h o ul d be st ore d i n t he ori gi nal pac ka ge at r o o m te m perat ure as 
state d o n t he pac ka ge la bel.  N o s pecial ha n dli n g pr oce d ures are re q uire d. 
9. 4. 3.   
St u d y Dr u g Pre p ar ati o n a n d A d mi nistr ati o n 
N o st u d y dr u g  pre parati o n is re q uire d. Patie nts will ta ke t he first d ose of st u d y dr u g i n t he cli nic 
o n Da y 1 a n d will be i nstr ucte d t o ta ke st u d y dr u g e ver y 1 2 h o urs f or t he d urati o n of t he 
Treat me nt Peri o d. Patie nts s h o ul d d ose st u d y dr u g i n t he cli nic o n all St u d y Visit Da ys after 
cli nical la b orat or y bl o o d dra ws are c o m plete d.  
St u d y dr u g s h o ul d be ta ke n at a p pr o xi matel y t he sa me ti mes eac h d a y, wit h water, a n d wit h or 
wit h o ut meals. Patie nts s h o ul d be i nstr ucte d t o ta k e st u d y dr u g as pres cri be d acc or di n g t o t he 
Wee k, Da y, a n d Ti me of da y d esi g nati o ns i n t he d osi n g car d. If a d ose is misse d, t he patie nt 
s h o ul d s ki p t he missed d ose a n d res u m e d osi n g at t he ne xt sc he d ule d d ose. T he patie nt s h o ul d 
n ot ta ke t w o d oses at t he sa me ti me. De viati o ns fr o m prescri be d d osi n g s h o ul d be disc usse d at 
eac h visi t f or ass ess me nt of c o m plia nce a n d retrai ni n g w he n n ecessar y. 
9. 4. 4.   
St u d y Dr u g Ret ur n a n d Dis p os al 
T he S p o ns or  ( or desi g nee) will re vie w wit h t he I n vesti gat or a n d rel e va nt site pers o n nel t he 
pr ocess f or st u d y tr eat me nt ret ur n, dis p osal, a n d/ or destr ucti o n, i ncl u di n g res p o nsi bilities f or t he 
site vers us t he S p o ns or ( or desi g n ee). S p ecific re q uire me nts f or destr u cti o n or ret ur n are d efi ne d 
i n t he P har mac y Man u al. 
9. 4. 5.   
St u d y Dr u g Acc o u nt a bilit y 
T o satisf y re g ulat or y re q uire me nts re gar di n g dr u g acc o u nta bilit y, all st u d y dr u g will be 
rec o ncile d i n f ull. T he I n vesti gat or or desi g nee m ust mai ntai n acc urate rec or ds of t he recei pt of 
st u d y dr u g, i ncl u di n g dat e recei ve d, l ot n u m ber, a m o u nt recei ve d, c o n diti o n of t he pac k a ge, a n d 
t he dis p ositi o n of st u d y dr u g. 
C urre nt dis pe nsi n g rec or ds will als o be mai ntai ne d, i ncl u di n g t he dat e a n d a m o u nt of me dicati o n 
dis pe nse d t o eac h i n di vi d ual patie nt.  Ret ur ne d st u d y dr u g rec or ds will be mai ntai ne d a n d fi nal 
st u d y dr u g rec o n ciliati o n will als o be rec or de d f or eac h p atie nt. 
9. 5.   
C o nc o mit a nt Me dic ati o ns a n d Pr oce d ures 
All me dicati o ns, i ncl u di n g o ver-t he-c o u nter t h era pies (e. g., vita mi ns, her bal, a n d n utriti o nal 
s u p ple me nts), ta ke n at t h e ti me of t he Scree ni n g Visit t hr o u g h t he F oll o w- U p Visit will be 
rec or ded i n t he patie nt’s s o urce d oc u m e ntati o n a n d d oc u me nte d i n t he e C R F. 
If ta ki n g t h yr oi d me dicati o n, t he patie nt m ust mai ntai n t h yr oi d sti m ulati o n h or m o ne le vels wit hi n 
t he n or mal ra n ge f or 6 m o nt hs pri or t o Scree ni n g a n d t hr o u g h o ut t he st u d y. 
A n y c o nc o mita nt me dicati o n dee me d necessar y f or t he well bei n g of t he s u bject ma y be gi ve n at 
t he discreti o n of t he I n v esti gat or. Us e of me dicati o ns t hat are pr o hi bite d per pr ot oc ol will re q uire 
patie nt wit h dra wal fr o m t he st u d y. 
T he f oll o wi n g tr eat me nts are n ot per mitte d d uri n g t he st u d y: 


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 Me dicati o ns t hat ma y affect hair re gr o wt h or i m m u ne res p o nse (s uc h as: 
cortic oster oi ds a d mi nistere d orall y, b y i njecti o n, or a p plie d t o areas of s ki n affecte d 
b y al o p ecia ; platelet-ric h i njecti o ns; t o pical a p plicati o n t o affecte d areas of a nt hrali n, 
s q uaric aci d, di p he n yl c ycl o pr o pe n o ne, or mi n o xi dil; 
 Treat me nt wit h s yste mic i m m u n os u p pressi ve me dicati o ns i ncl u di n g b ut n ot li mite d t o 
met h otre x a te, c ycl os p ori ne, a n d azat hi o pri ne; c hl or o q ui ne deri vati ves; J a n us ki nase 
i n hi bit ors (r u x oliti ni b, t ofaciti ni b, etc), et a nerce pt; or bi ol o gics (a dali m u ma b, 
atliz u ma b, ca na ki n u ma b, cert oliz u ma b, f o nt oliz u ma b, g oli m u ma b, i nfli xi ma b, 
me p oliz u ma b, rit u xi ma b, sec u ki n u ma b, t ociliz u ma b, uste ki n u ma b); 
 Use of str o n g C Y P 3 A 4 i n hi bit ors (s uc h as, b ut n ot li mite d t o clarit hr o m yci n, 
c o ni va pta n, gra p efr uit j ui ce, i n di na vir, itrac o naz ole, ket oc o naz ole, l o pi na vir/rit o na vir, 
mi befra dil, nefaz o d o ne, nelfi na vir, p osac o n az ole, sa q ui na vir, tela pre vir, 
telit hr o m yci n, v oric o n az ole, or fl uc o naz ole) d os e d f or s yst e mic e x p os ure; 
 Use of str o n g C Y P 3 A 4 i n d ucers (s u c h as, b ut n ot li mite d t o bar bit urates, 
car bam aze pi ne, efa vire nz, gl uc oc ortic oi ds, m o dafi nil, ne vira pi ne, o xcar baz e pi ne, 
p he n o bar bital, p he n yt oi n, pi o glitaz o ne, rifa b uti n, rifa m pi n, St. J o h n’s W ort, or 
tr o glitaz o ne) d ose d f or s yste mic e x p os ure. 


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1 0.   
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S 
T he sc he d ule of assess m e nts a n d pr oce d ures is prese nte d i n Ta ble 1  a n d s h o ul d be refere n ce d f or 
details re ga r di n g t he c ollecti o n of eac h assess me nt at eac h visit i n t he res pecti ve c o h ort peri o ds. 
1 0. 1 .  
De m o gr a p hic C h ar acteristics a n d Me dic al Hist or y 
De m o gra p hic c haracteristics (i.e., se x, et h nic ori gi n, date of birt h, a n d calc ulate d b o d y m ass 
i n de x) will be c oll ecte d at t he Scree ni n g Visit, bet wee n Da y - 2 8 a n d - 1, a n d detaile d o n t he 
e C R F.  
T he patie nt’s al o pecia areata will be classifi e d b y t he I n v esti gat or i nt o o ne of t hree cate g ories 
defi ne d f or t his st u d y: 
1)  Al o pecia areat a: patc h y t y p e h air l oss, 
2)  Al o pecia t otalis or u ni versalis: c o m plete hair l oss o n t he scal p wit h or wit h o ut b o d y hair 
l oss, 
3)  Al o pecia o p hiasis: ba n d-li ke hair l oss li mite d t o t he peri p her y of t he scal p al o n g t he bac k 
of t he hair li ne i n t he occi pital re gi o n a n d p ossi bl y e xte n di n g o ver eac h ear i n te m p oral 
re gi o ns. 
Ke y criteria t hat disti n g uis h al o pecia areata fr o m ot her f or ms of h air l oss ma y i ncl u d e a br u pt 
o nset of disease, a hist or y of rec urre n ce a n d s p o nta ne o us re missi o n, res p o nse t o t o pical or 
i ntralesi o nal ster oi d treat me nt, a n d distri b uti o n of hair l oss patter n. Care m ust be ta ke n d uri n g t he 
e val uati o n t o assess f or ot her ca us es of hair l oss s uc h as tric h otill o ma nia, or scarri n g al o peci a 
a n d ot her f or ms of n o n-s carri n g al o pecia. E vi d e nce of t hi n ni n g hair s h o ul d be disti n g uis he d fr o m 
patter n hair l oss or tel o ge n effl u vi u m a n d e vi de nce of i nfla m mati o n s h o ul d be i n vesti gat e d t o 
r ule o ut i nfecti o n, as a p pr o priate. 
T h or o u g h m e dical hist or y , i ncl u di n g c urre nt me di catio ns,  nail a n d facial hair i n v ol ve me nt, c o-
m or bi dities, seri o us i nfecti o n hist or y a n d e x p os ure ris k, i ncl u di n g HI V, as well as hist or y or 
vacci nati o n a gai nst her pes z oster will be c ollecte d at t he Scree ni n g Visit, a n d at t he 
Ra n d o miz ati o n Visit o n Da y 1  f or eac h c o h ort. 
Me dical hist or y s h o ul d b e t h or o u g hl y pr o be d f or p ote ntial e x p os ure t o seri o us i nfecti o ns s uc h as 
HI V, hist or y or vacci nati o n a gai nst her pes z oster or ot her rece nt li ve vir us vacci nati o ns, as w ell 
as ca ncer ris k d u e t o t he p ote ntial i m m u n os u p pressi ve pr o perties of C T P- 5 4 3 a n d k n o w n a d verse 
e ve nts ass ociate d wit h J A K i n hi bit ors. 
1 0. 2.   
Se verit y of Al o peci a T o ol ( S A L T) 
T he S A L T sc ore was i ntr o d uce d as part of i n vesti gati ve g ui d eli nes p u blis he d b y t h e Nati o nal 
Al o pecia Areata F o u n dati o n [ Olse n, 2 0 0 4 ].  T he S A L T is a m eas ure of hair a bse nce t h at 
q ua ntifies t he a m o u nt of scal p s urface wit h o ut hair i n a pre-s p ecifie d q u a dra nt of t he scal p (ri g ht 
si de, t o p, left si de, bac k), t hat is f urt her s u m me d after a p pl yi n g a q u a dra nt-s pecific m ulti plier 
i n dicati ve of scal p s urface area c o ntri b uti o n, t o pr o vi de a n o verall sc ore of t otal hair l oss. T he 
S A L T ass ess me nt will occ ur via li ve e x a mi nati o n of t he patie nt d uri n g cli nic visits.   
S A L T will be use d t o det er mi ne efficac y f or t he st u d y. T o re d uce varia bilit y, o ne rater s h o ul d 
perf or m t he S A L T assess me nt f or t he patie nt f or t he d urati o n of t he st u d y. All i n vesti gat ors usi n g 
t he S A L T s h o ul d be trai n e d pri or t o use. Please c o ns ult t he ass ociate d Site O perati o ns Ma n u al 


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f or a d diti o nal details re gar di n g S A L T sc ori n g a n d trai ni n g re q uire me nts f or t his st u d y. A n 
e x a m pl e of t he S A L T assess me nt t o ol is pr o vi de d i n  A p pe n di x 1 7. 1 .  
1 0. 3 .  
P h ot o gr a p hs 
P h ot o gra p hs will be ta k e n of eac h p atie nt’s scal p t o pr o vi de vis ual s u p p ort of Bas eli ne 
assess me nt of S A L T as well as p ote ntial c ha n ges i n S A L T sc ores t hr o u g h o ut t he st u d y . N o 
f or mal a nalyses of p h ot o gra p hs will occ ur. Scal p p h ot o gra p hs will c orres p o n d t o t he 4 defi ne d 
q ua dra nts of t he S A L T assess me nt a n d will be ta ke n w he n S A L T ass ess me nts are perf or me d. 
F or t h ose pati e nts wit h e ye a n d nail i n v ol ve me nt i n t heir al o pecia areata p he n ot y p e, a p h ot o gra p h 
of t he e ye s a n d ha n ds f or e yelas h/e ye br o w a n d n ail i n v ol ve me nt, res pecti vel y, will be ta ke n t o 
d oc u me nt p ote ntial c ha n ges t hr o u g h o ut t he st u d y  c o m pare d t o Baseli ne. N o f or mal a nal yses of 
p h ot o gra p hs will occ ur.  
1 0. 4.   
Gl o b al I m pressi o n Sc ales 
T he Gl o bal I m pressi o n S cales are meas ures c o m m o nl y use d i n cli nical trials t o all o w i nte grati o n 
of se veral s o urces of i nf or mati o n i nt o a si n gle rati n g of t he patie nt’s c o n diti o n. T he Gl o bal 
I m pr essi o n Scales e m pl o y a 7- p oi nt Li k ert scal e meas uri n g eit her disease state se verit y or 
i m pr o ve me nt after treat m e nt. T he al o pecia areata assess me nts s h o ul d c o nsi der t he c o n diti o n of 
t he patie nt at t he ti me of t he assess me nt c o m pare d t o Baseli ne.  
I n t his st u d y, t he Gl o bal I m pressi o n Scale of I mpr o ve me nt will be perf or me d b y b ot h t he 
cli nicia n an d t he patie nt at selecte d ti mes d uri n g t he st u d y as i n dicate d i n  Ta ble 1 . 
1 0. 4. 1.   
Cli nic al Gl o b al I m pressi o n of I m pr o ve me nt ( C GI-I) 
C o m pare d t o t he patie nt’s al o pecia areata pri or t o treat me nt at Baseli ne, t he patie nt’s c urre nt 
state of al o pecia areata will be assesse d acc or di n g t o t he I n v esti gat or’s percei ve d c ha n ge. T he 
I n v estigat or ma y select o ne of se ve n n u m eric c h oi ces re prese nti n g “ Ver y M uc h W orse” t o “ Ver y 
M uc h I m p r o ve d ”. T o re d uce vari a bilit y, o ne rater s h o ul d perf or m t he C GI-I assess me nt f or t he 
patie nt f or  t he d urati o n of t he st u d y. A n e x a m ple of t he C GI-I is pr o vi d e d i n A p pe n d i x 1 7. 2. 1 . 
1 0. 4. 2.   
P ati e nt Gl o b al I m pressi o n of I m pr o ve me nt ( P GI- I) 
C o m pare d t o t he patie nt’s al o pecia areata pri or t o treat me nt at Baseli ne, t he patie nt’s c urre nt 
state of al o pecia areata will be assesse d acc or di n g t o his/ her percei v e d c ha n ge. T he patie nt ma y 
select o ne of s e ve n n u meric c h oices re prese nti n g “ Ver y M uc h W orse” t o “ Ver y M uc h 
I m pr o v e d”. A n e x a m ple of t he P GI-I is pr o vi de d i n A p pe n di x 1 7. 2. 2 . 
1 0. 5 .  
P atie nt Re p orte d O utc o mes: Al o peci a Are at a S y m pt o m I m p act Sc ale 
( A A SI S) a n d E x pl or at or y Q uesti o ns 
T he A A SI S is a q uesti o n naire desi g ne d t o meas ure t he q ualit y of life, s y m pt o ms, a n d t heir 
i m pact f or patie nts wit h al o pecia areata [ Me n d oza, 2 0 1 3].  T hree di me nsi o ns relate d t o al o pecia 
areat a are assess e d: i m pact of al o peci a areata, hair l oss, a n d p h ysical s ki n s y m pt o ms. A n 
e x a m pl e of t he A A SI S is pr o vi de d i n A p pe n di x 1 7. 3. 1 .  
I n a d diti o n t o t he A A SI S, e x pl orat or y q uesti o ns will be use d t o atte m pt t o defi ne cli nicall y 
mea ni n gf ul o utc o mes f or patie nts wit h al o pecia areata. T he e x pl orat or y q u esti o ns are pr o vi de d i n 
A p pe n di x Secti o n 1 7. 3. 2 .  


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1 0. 6 .  
Vis u al A n al o g Sc ale ( V A S) 
T he vis ual a nal o g scale is a scale of c o nti n u o us meas ure i nitiall y de vel o pe d f or pai n t hat has 
bee n use d i n a variet y of cli nical setti n gs w here t h e e n d p oi nt of i nterest is b ase d o n a s u bjecti ve 
perce pti o n. T h e vis ual a n al o g scale is a disti nct 1 0 0 milli meter li ne a nc h ore d o n t he left e n d at 
f ull de gree of i m pair me nt a n d o n t he ri g ht e n d at n o de gree of i m pair me nt, w here i n dicati o n of 
t he de gree of i m pair me nt percei v e d at t he ti me of assess me nt is ca pt ure d b y mar ki n g t he 
a p pr o priate p osit i o n o n t he li ne bet wee n t he a n c h or p oi nts. T he meas ure d dista nce of t he mar k 
fr o m t he left a nc h or will be rec or de d i n milli meters.  
1 0. 6. 1.   
Cli nici a n V A S of Se verit y ( V A S- S)  
T he I n vesti gat or will c o m plete a V A S- S re gar di n g t he se v erit y of t he p atie nt’s al o pecia areata at 
t he ti me of c o m pleti o n as i n dicate d i n t he Sc he d ul e of E ve nts. T he l eft a n d ri g ht a nc h or p oi nts 
f or t he cli nician V A S- S are “ E xtre mel y A p pare nt” a n d “ N ot At All A p pare nt”, res pecti vel y. T o 
re d uce varia bilit y, o ne rater s h o ul d perf or m t he V A S- S assess me nt f or t he patie nt f or t he 
d urati o n of t he st u d y. A n e x a m ple of t he cli nicia n V A S- S is pr o vi de d i n A p pe n di x 1 7. 4. 1 .  
1 0. 6. 2.   
P ati e nt V A S  of Se verit y ( V A S-S)  
As s pecifie d i n t he Sc he d ule of E ve nts, patie nts will rate perce pti o n of his/ her al o pecia areata 
se verit y o n t he patie nt V A S- S. T he left a n d ri g ht a nc h or p oi nts f or t he patie nt’s al o peci a areata 
V A S - S are “ E xtre mel y A p pare nt” a n d “ N ot At All A p pare nt”, res pecti vel y. T he pati e nt V A S- S 
will meas ure  t he patie nt’s perce pti o n of his/ her al o pecia areat a at t he ti me of c o m pleti o n. A n 
e x a m pl e of t he patie nt V A S- S is pr o vi de d i n A p pe n di x 1 7. 4. 2 . 
1 0. 7.   
P h ar m ac o ki netic Assess me nts 
W h ole bl o o d ( 4 m L eac h) will be c ollecte d i n K
2E D T A vac utai n er c ollecti o n t u bes at t he 
f oll o wi n g ti me p oi nts t o e val uate plas ma c o nce ntrati o ns of C T P- 5 4 3 a n d meta b olites.   
 Da y 1 a n d Wee k 4 : 2 sa m ples at eac h visit; 1 sa m ple pre- d ose,  a n d 1 sa m ple p ost-
d ose at t he e n d of t h e visit  
 Wee k 2: 1 sa m ple pre- d ose wit h t he safet y la b dra w 
 Wee ks 8, 2 4: 1 sa m ple p ost- d ose at t he e n d of t h e visit 
T he  e x act ti me of bl o o d c ollecti o n as well as t he e x act ti me of t he prece di n g d ose will be 
rec or de d. T he Wee k 4 pre- d ose dra w is t he ti me p oi nt i nte n de d t o e xa mi ne stea d y-state tr o u g h 
le vels of st u d y dr u g, a n d t heref ore t he prece di n g d ose will n ot be o bser ve d i n t he cli nic. T o 
d oc u me nt t he prec e di n g d ose ti me, patie nts s h o ul d be i nstr ucte d t o rec or d t he last d osi n g ti me 
pri or t o t he Wee k 4 Visit i n t heir d osi n g car d. All atte m pts t o a d here t o t he p har mac o ki netic 
sc he d ule s h o ul d be ma de. H o we ver, t he i na bilit y t o f oll o w t he sc he d ule or t o o btai n/ pr ocess a 
sa m ple will n ot be c o nsi dere d a pr ot oc ol de viati o n.  
I nstr u cti o ns f or har vesti n g a n d pre pari n g plas ma s a m ples pri or t o freezi n g a n d a d diti o nal 
pr oce d ures f or bl o o d sa m ple c ollecti o n will be pr o vi de d i n se parat e st u d y la b orat or y ma n ual. 
1 0. 8 .  
Vit al Si g ns, Wei g ht, a n d Hei g ht 
Vital si g ns will be meas ure d aft er t he patie nt h as b ee n i n a s u pi ne or se mi-s u pi ne p ositi o n f or at 
least 5 mi n utes a n d will i ncl u de bl o o d press ure, p ulse rate, res pirat or y rate, a n d oral te m perat ure.   


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Wei g ht wil l be meas ure d per i nstit uti o n sta n dar d of care. Patie nts s h o ul d wear li g ht cl ot hi n g a n d 
re m o ve his/ her s h oes b ef ore wei g ht is meas ure d.  Hei g ht will be meas ure d per i nstit uti o n 
sta n dar d of care, after t he patie nt has re m o ve d his/ her s h oes. Hei g ht will o nl y be meas ure d at t he 
Scree ni n g Visit. Wei g ht a n d vital si g ns will be m eas ure d at eac h st u d y visit acc or di n g t o t he 
Sc he d ule of E ve nts. Wei g ht a n d hei g ht will be use d t o calc ulate t h e patie nt’s b o d y mass i n de x at 
Scree ni n g. Wei g ht a n d h ei g ht will be c o n v erte d as nee de d t o kil o gra ms a n d ce nti meters, 
res pectivel y, pri or t o statistical a nal yses. 
1 0. 9.   
P h ysic al E x a mi n ati o n 
A c o m plete p h ysical e xa mi nati o n will i ncl u de a n e x a mi nati o n of all maj or or ga n s yste ms, wit h 
a n e m p hasis o n assessi n g f or acti ve si g ns a n d s y m pt o ms of i nfecti o n i ncl u di n g t u berc ul osis, a n d 
will be perf or me d as i n dicate d i n t he Sc he d ul e of E ve nts. Brief p h ysical e x a mi nati o ns i ncl u di n g 
a b d o mi nal pal pati o n, a n d hea d, e yes, ears, n ose a n d t hr oat assess me nt i n a d diti o n t o assessi n g f or 
acti ve si g ns a n d s y m pt o ms of i nfecti o n, i ncl u di n g t u berc ul osis, will be perf or me d at all ot her 
i nter me diate visits as s pecifie d i n Ta ble 1 . Patie nts s h o ul d be i nstr ucte d t o n otif y t he cli nic of a n y 
si gns of i nfec ti o n bet wee n visits f or a p pr o priate m o nit ori n g a n d f oll o w- u p. 
1 0. 1 0.  
Electr oc ar di o gr a m 
T wel ve-lea d electr ocar di o gra ms will be perf or me d after t he p atie nt has reste d i n a s u pi ne or 
se mi-s u pine p ositi o n f or at least 5 mi n utes.  I n di vi d ual para met ers i ncl u di n g heart rate, P R, Q T, 
Q Tc F, Q R S, a n d R R i nter vals will be c ollecte d. R e peat el ectr ocar di o gra ms (if dee me d 
necessa r y) s h o ul d be p erf or me d at least 5 mi n utes a part. T he I n vesti gat or s h o ul d i n dicate re vie w 
of t he electr ocar di o gra m re p orts t hr o u g h o ut t he st u d y b y si g ni n g a n d dati n g eac h re p ort.   
1 0. 1 1.  
Cli nic al L a b or at or y Assess me nts 
Cli nical la b orat or y assess me nts are prese nte d i n Ta ble 5 . Cli nical la b orat or y sa m ples s h o ul d be 
c ollecte d at t he b e gi n ni n g of eac h cli nic visit a n d j ust pri or t o a d ose o n all St u d y Visit Da ys.  
T he res ults of c li nical la b orat or y tests c o n d uct e d at t he Scree ni n g Visit (a n d pri or t o d osi n g) 
m ust be assesse d b y t he I n vesti gat or t o d eter mi ne eac h p atie nt’s eli gi bilit y f or partici pati o n i n t he 
st u d y.  T he I n vesti gat or s h o ul d i n dicate re vie w of t he la b orat or y re p orts t hr o u g h o ut t he st u d y b y 
si g ni n g an d dati n g eac h re p ort.  
All cli nical la b orat or y res ults t hat fall o utsi de t he refere nce ra n ge will be i nter prete d b y t h e 
I n v esti gat or as A b n or mal, n ot cli nicall y si g nifica nt, or A b n or mal, cli nicall y si g nifica nt. 
La b orat or y res ults dee me d A b n or mal, cli nicall y si g nifica nt will be rec or de d as a n a d verse e v e nt 
i n t he e C R F a n d s h o ul d b e f ull y i n vesti gat e d a n d re peate d f or verificati o n.  Cli nicall y si g nifica nt 
la b orat or y a b n or malities i n dicati ve of he mat ol o gic or ot her effects re q uiri n g i nter ve nti o n s h o ul d 
be disc usse d wit h t he  Me dical M o nit or. A d diti o nal tests a n d e val uati o ns re q uire d t o esta blis h t he 
si g nifica n ce or eti ol o g y of a cli nicall y si g nifica nt a b n or mal res ult or t o m o nit or t he c o urse of a n 
a d verse e ve nt s h o ul d be o btai ne d w he n cli nicall y i n dicate d.  W he ne ver p ossi ble, t he eti ol o g y of 
t he cli nicall y si g nifica nt a b n or mal fi n di n gs will be d oc u me nte d o n t he e C R F.   
A n y si g nifica nt la b orat or y a b n or malities t hat are eit her seri o us or u ne x pect e d will be pr o m ptl y 
re p orte d t o t he S p o ns or.  A n y a d diti o nal rele va nt l a b orat or y res ults o btai ne d b y t he I n vesti gat or 
d uri n g t he c o urse of t his st u d y will be re p orte d t o t he S p o ns or or desi g n ee. 


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T a ble 5:  
Cli nic al L a b or at or y Assess me nts 
He m at o l o g y 
C he mistr y  
Ser u m Pre g n a nc y  
C o m plete bl o o d c o u nt  
A bs ol ute n e utr o p hil c o u nt  
A bs ol ute e osi n o p hil c o u nt  
Platelet c o u nt  
W hite bl o o d cell c o u nt wit h 
differe ntial  
A bs ol ute retic ul oc yte co u nt  
He m o gl o bi n A 1c  
Ala ni ne a mi n otra nsa mi nase  
Al b u mi n  
Al kali ne p h os p hatase  
A m ylase  
As partate a mi n otra nsa mi nase  
T otal bilir u bi n  
Direct bilir u bi n  
I n direct bilir u bi n 
Bl o o d urea nitr o ge n  
Calci u m  
Car b o n d i o xi de  
C hl ori de  
Creati ni ne  
Creati ne ki nase  
Gl uc ose  
Li pase  
T otal pr otei n  
P h os p h or us  
P otassi u m  
S o di u m  
Uric  Aci d  
H u ma n c h ori o nic g o na d otr o pi n  
(fe males of c hil d beari n g  p ote ntial 
o nl y)  
Ser ol o g y  
Li pi ds  
Ot her  
He p atitis B vir us   
He p atitis C vir us  
T otal c h olester ol  
L o w -de nsit y li p o pr otei n  
Hi g h -de nsit y li p o pr otei n  
T ri gl yceri des 
T u berc ul osis  
T h yr oi d sti m ulati n g h or m o ne  
1 0. 1 2.  
P h ar m ac o d y n a mic Assess me nts 
Bl o o d sa m ples will be c ollecte d f or p ote ntial f ut ure e x pl orati o n of t he p har mac o d y na mic 
pr o perties ass o ciate d wit h C T P- 5 4 3 d osi n g.  T w o milliliters of w h ole bl o o d will be c ollecte d i nt o 
a P A X gene ®  Bl o o d R N A t u be a n d 4 milliliters of w h ole bl o o d will be c oll ecte d i n a K 2E D T A 
vac utai ner c ollecti o n t u b e. P har mac o d y n a mic sa m ples will be c ollecte d at t he f oll o wi n g ti me 
p oi nts:   
 Da y 1: pre- d os e  
 Wee k 2 : pre- d ose wit h t he safet y la b dra w 
 Wee ks 4, 8, 2 4: p ost- d ose at t he e n d of t h e visit 
C ollecti o n of sa m ples s h o ul d be i n c o nj u ncti o n wit h safet y or p har mac o ki n etic bl o o d dra ws 
w he n p ossi ble. All atte m pts t o a d here t o t he p har ma c od y na mi c sc h e d ule s h o ul d be ma de. 
H o we ver, t he i na bilit y t o f oll o w t he sc he d ule or t o o btai n/ pr ocess a sa m ple will n ot be 
c o nsi dere d a pr ot oc ol de viati o n.  
Instr u cti o ns f or har vesti n g a n d pre pari n g sa m ples pri or t o st ori n g or freezi n g, a n d a d diti o nal 
pr oce d ure s f or bl o o d sa m ple c ollecti o n will be pr o vi de d i n a se parate st u d y la b orat or y ma n ual. 
I nf or mati o n o btai ne d fr o m t hese p ote ntial a nal yses w o ul d be li mite d t o J A K-si g n ali n g relate d 
i n vesti gati o ns o nl y an d w o ul d n ot be use d f or dia g n ostic p ur p os es, ge nerati o n of cell li nes, or 
c o m mercial uses, n or wo u l d res ults of i n di vi d ual patie nts be discl ose d. H o we ver, res ults of t he 


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bli n de d p ha r mac o d y n a mic st u dies data ma y be prese nte d or p u blis he d i n sci e ntific or me dical 
setti n gs. 
1 0. 1 3.  
U nsc he d ule d Visit 
I n a d diti o n t o re g ularl y s c he d ule d pr ot oc ol visits, a n U nsc he d ul e d Visit ma y be c o n d ucte d t o 
ens ure a p pr o priate s afet y m o nit ori n g or f oll o w- u p of t he patie nt, at t he discreti o n of t he 
I n v estigat or. F or e x a m ple, a n U nsc h e d ule d Visit ma y b e sc he d ule d t o m o nit or p ote ntial or act ual 
cli nicall y mea ni n gf ul safet y la b orat or y res ults, f or c o nfir mi n g h e mat ol o g y res ults t o s u p p ort d ose 
i nterr u ptio n or res u m pti o n of d osi n g t hereafter, f or s us pici o n of t u berc ul osis, or f or ot her cli nical 
si g ns, s ym pt o ms, or c o nsi derati o ns t hat warra nt a d diti o nal safet y f oll o w- u p . O nl y t h ose criteria 
re q uiri n g a d diti o nal m o nit ori n g s h o ul d be perf or me d at a n U nsc he d ule d Visit. A n U nsc he d ule d 
Visit will n ot re place re g ularl y s c he d ule d pr ot oc ol visits.  


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1 1.   
A D V E R S E E V E N T S 
1 1. 1. 1.   
Defi niti o n of A d verse E ve nt 
A n a d verse e ve nt is a n y u nt o war d me dical o cc urre nce t hat ma y a p pear or w orse n i n a patie nt 
d uri n g t he c o urse of a st u d y.  It ma y b e a ne w i nterc urre nt ill ness, a w orse ni n g c o n c o mita nt 
ill ness, a n i nj ur y, or a n y c o nc o mita nt i m pair me nt of t he patie nt’s healt h, i ncl u di n g la b orat or y test 
val ues, re gar dless of eti ol o g y.  A n y w orse ni n g (ie, a n y cli nicall y si g nifica nt a d verse c ha n ge i n 
t he fre q u e nc y or i nte nsit y of a pre-e xisti n g c o n diti o n) s h o ul d be c o nsi dere d a n a d verse e v e nt.  A 
dia g n osis or s y n dr o m e s h o ul d be rec or de d o n t he a d verse e v e nt pa ge of t he e C R F rat her t ha n t he 
i n di vi d ual si g ns or s y m pt o ms of t he dia g n osis or s y n dr o me. A w orse ni n g of t he c o n diti o n u n der 
st u d y, al o pecia areata, will n ot be re p orte d as a n a d verse e v e nt.  
All patie nts will be m o nit ore d f or a d verse e ve nts d uri n g t he st u d y.  Assess me nts ma y i ncl u de 
m o nit ori n g of t he f oll o wi n g para meters:  t he patie nt’s cli nical s y m pt o ms, la b orat or y, p h ysical 
e x a mi nati o n fi n di n gs, or fi n di n gs fr o m ot her tests a n d/ or pr oce d ures. 
A n a d verse e ve nt re p orte d afte r i nf or me d c o nse nt, b ut bef ore t he first d ose of st u d y dr u g (ie, 
Da y 1), will be c o nsi dere d a pretr eat me nt a d verse e ve nt a n d will be ca pt ure d o n t he e C R F.  
A d verse e ve nts will be c o nsi dere d treat me nt-e mer ge nt if t he o nset is after t he first d ose of st u d y 
dr u g.   
A n a b n or mal la b orat or y val ue is c o nsi dere d t o b e a n a d verse e v e nt if t he a b n or malit y: 
 res ults i n disc o nti n uati o n fr o m t he st u d y; 
 is j u d ge d b y t he I n v esti gat or t o be of si g nifica nt cli nical i m p orta nce re q uiri n g 
treat me nt, m o dificati o n/i nterr u pti o n of i n vesti gati o nal pr o d uct d ose, or a n y ot her 
t hera pe utic i nter ve nti o n 
Re gar dless of se v erit y gra de, o nl y la b orat or y a b n or malities t hat f ulfill a seri o us ness criteri o n 
nee d t o be d oc u m e nte d as a seri o us a d verse e v e nt.   
If a la b orat or y a b n or malit y is o ne c o m p o ne nt of a dia g n osis or s y n dr o me, t he n o nl y t he di a g n osis 
or s y n dr o me s h o ul d be rec or de d o n t he a d verse e v e nt e C R F.  If t he a b n or malit y was n ot a p art of 
a dia g n osis or s y n dr o me, t he n t he la b orat or y a b n or malit y s h o ul d be rec or de d as t he a d v erse 
e ve nt.  If p ossi ble, t he la b orat or y a b n or malit y s h o ul d be rec or de d as a me dical ter m a n d n ot 
si m pl y as a n a b n or mal la b orat or y res ult (e. g., rec or d t hr o m b oc yt o p e nia rat her t ha n decrease d 
platelets). 
1 1. 1. 2.   
E v al u ati o n of A d verse E ve nts 
A q ualifie d I n vesti gat or will e val uate all a d verse e ve nts as t o seri o us ness, se verit y/i nte nsit y, 
relati o ns hi p t o stu d y dr u g, d urati o n, acti o n ta ke n, a n d o utc o me.   
1 1. 1. 2. 1.  Ser i o us A d verse E ve nt  
A seri o us a d verse e v e nt is a n a d verse e ve nt, as per Title 2 1 C F R 3 1 2. 3 2 a n d I C H E 2 A.II. B t hat 
f ulfills t he f oll o wi n g crit eria: 
 Is fatal (res ults i n deat h); 


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 Is life-t hreate ni n g ( N ote: t he ter m "life-t hreate ni n g" refers t o a n e ve nt i n w hic h t he 
patie nt was at ris k of d eat h at t he ti me of t he e ve nt; it d oes n ot refer t o a n e ve nt t hat 
c o ul d h y p ot heticall y h a v e ca use d d eat h ha d it bee n m ore se vere); 
 Re q uires 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 
( h os pitalizatio n is defi ne d as a n i n patie nt a d missi o n, re gar dless of le n gt h of sta y); 
 Res ults i n persiste nt or si g nifica nt disa bilit y/i n ca p acit y (a s u bsta ntial disr u pti o n of t he 
patie nt's a bilit y t o c o n d uct n or mal life f u ncti o ns); 
 Is a c o n ge nital a n o mal y/ birt h defect; or 
 C o nst it utes a n i m p orta nt me dical e ve nt t hat ma y j e o par dize t he patie nt or ma y re q uire 
me dical or s ur gical i nter ve nti o n t o pre ve nt o ne of t he ot her o utc o mes liste d a b o ve. 
I m p ort a nt me dical e ve nts are defi ne d as t h ose o cc urre nces t hat ma y n ot be i m me diatel y 
life-t hreat e ni n g or res ult i n deat h, h os pitalizati o n, or disa bilit y, b ut ma y je o par dize t he patie nt or 
re q uire me di cal or s ur gical i nter ve nti o n t o pre ve nt o ne of t he ot her o ut c o mes liste d a b o ve.  
E x a m ples of s uc h me dical e ve nts i ncl u de aller gic br o nc h os pas m re q uiri n g i nte nsi ve treat me nt i n 
a n e mer ge nc y r o o m or at h o me, bl o o d d yscrasias or c o n v ulsi o ns t hat d o n ot res ult i n i n patie n t 
h os pitalizati o n.   
E ve nts n ot c o nsi dere d  t o be seri o us a d v erse e ve nts are h os pitalizati o ns f or: 
 A pr oce d ure f or pr ot oc ol/ disease-relate d i n vesti gati o ns (e. g., s a m pli n g f or l a b orat or y, 
p har mac o ki netic, a n d p h ar mac o d y n a mic tests).  H o we ver, h os pitalizati o n or 
pr ol o n ge d h os pitaliz ati o n f or a c o m plicati o n of s uc h pr oce d ures re mai ns a re p orta ble 
seri o us a d verse e v e nt. 
 H os pitalizati o n or pr ol o n gati o n of h os pitalizati o n f or tec h nical, practical, or s ocial 
reas o ns, in a bse n ce of a n a d verse e ve nt. 
 A pr oce d ure t hat is pla n n e d (i.e., pla n ne d pri or t o t he starti n g of treat me nt o n st u d y); 
m ust  be d oc u me nte d i n t he s o urce d o c u me nt a n d t he e C R F.  H os pitalizati o n or 
pr ol o n ge d h os pitalizati o n f or a c o m plicati o n re mai ns a re p orta bl e seri o us a d verse 
e ve nt. 
 A n electi ve tr eat m e nt of or a n electi ve pr oce d ure f or a pre-e xisti n g me dical c o n diti o n 
t hat d oes n ot w orse n.  
 E mer ge nc y o ut p atie nt treat me nt or o bser vati o n t hat d oes n ot res ult i n a d missi o n, 
u nless f ulfilli n g  ot her seri o us ness criteria a b o v e. 
If a n a d v erse e ve nt is c o nsi dere d seri o us, t he a d verse e ve nt e C R F m ust be c o m plete d. 
F or eac h seri o us a d verse e ve nt, t he I n vesti gat or will pr o vi de i nf or mati o n o n se verit y, start a n d 
st o p dates, relati o ns hi p t o i n vesti gati o nal pr o d uct, acti o n ta ke n re gar di n g i n vesti gati o nal pr o d u ct, 
a n d o utc o me. 
Q ueries pertai ni n g t o s eri o us a d verse e ve nts will be ha n dle d t hr o u g h t he electr o nic data ca pt ure 
s yste m or ot her a p pr o priate mea ns.  Ur ge nt q ueri es (e. g., missi n g ca usalit y ass ess me nt) ma y be 
ha n dle d b y tele p h o ne. 


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1 1. 1. 2. 2.  Se ve rit y/I nte nsit y 
F or b ot h a d verse e ve nts a n d seri o us a d verse e v e nts, t he I n v esti gat or m ust assess t he 
se verit y/i nte nsit y of t he e ve nt.  
T he Na ti o nal Ca ncer I nstit ute- C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts ( C T C A E) 
Versi o n 4. 0 s h o ul d be us e d t o gra de t he se verit y/i nte nsit y of all e v e nts.  T h ese criteria will be 
pr o vi de d i n t he Site O per ati o ns Ma n ual.  If a C T C A E criteri o n d oes n ot e xist, t he I n v esti gat or 
s h o ul d grad e t he se v erit y acc or di n g t o t he f oll o wi n g criteria:  
 Gra de 1 ( m il d): d oes n ot i nterfere wit h t he patie nt’s us ual f u ncti o n 
 Gra de 2 ( m o derat e) : i nterferes t o s o me e xte nt wit h patie nt's us ual f u n cti o n 
 Gra de 3 (se vere) : i nterferes si g nifica ntl y wit h pati e nt's us ual f u ncti o n 
 Gra de 4 (life-t hr eate ni n g): res ults i n a t hreat t o life or i n a n i nca p acitati n g disa bilit y 
 Gra de 5 ( deat h): res ults i n deat h 
T he ter m “se v ere” is ofte n use d t o descri be t he i nt e nsit y of a s pecifi c e ve nt (as i n mil d, m o derate 
or se vere m y o car dial i nfarcti o n); t he e ve nt itself, h o we ver, ma y be of relati vel y mi n or me dical 
si g nifica n ce (s uc h as se vere hea dac he).  T his criteri o n is n ot t he sa me as “s eri o us” w hic h is 
base d o n patie nt/e ve nt o utc o me or acti o n criteria ass ociate d wit h e ve nts t hat p ose a t hreat t o a 
patie nt’s life or f u n cti o ni n g.   
Seri o us ness, n ot se verit y, ser ves as a g ui de f or defi ni n g r e g ul at or y o bli gati o ns. 
1 1. 1. 2. 3.  Rel ati o ns hi p t o St u d y Dr u g 
Relati o ns hi p s h o ul d be assesse d a n d pr o vi de d f or e ver y a d v erse e ve nt/seri o us a d verse e ve nt 
base d o n c urre ntl y a vaila ble i nf or mati o n.  Relati o ns hi p is t o be reassesse d a n d pr o vi de d as 
a d diti o nal i nf or mati o n bec o mes a vaila ble.  A d verse e ve nts will be classifi e d b y t he I n vesti gat or 
as f oll o ws: 
Defi nitel y Rel ate d : T here is clear e vi de nce t o s u g gest a ca us al relati o ns hi p, a n d ot her p ossi ble 
c o ntri b uti n g fact ors ca n be r ule d o ut.  T he cli nical e ve nt, i ncl u di n g a n a b n or mal la b orat or y test 
res ult, occ urs i n a pl a usi ble ti me relati o ns hi p t o dr u g a d mi nistrati o n a n d ca n n ot be e x plai ne d b y 
c o nc urre nt disease or ot her dr u gs or c he micals.  T he e ve nt res ol ves or i m pr o ves u p o n wit h dra wal 
of dr u g ( de-c halle n ge).  T he e ve nt w o ul d be c o nsi dere d as d efi nitel y relate d t o t he st u d y dr u g 
u p o n res ults of a p ositi ve re-c h alle n ge pr oce d ure. 
Pr o b a bl y Rel at e d : T here is e vi de nce t o s u g gest a ca usal relati o ns hi p (e. g., t he e ve nt occ urre d 
wit hi n a rea s o na bl e ti me after a d mi nistrati o n of t he trial me dicati o n).  H o we ver, t he i nfl u e nce of 
ot her fact ors t hat ma y ha ve c o ntri b ute d t o t he e v e nt (e. g., t h e patie nt’s cli nical c o n diti o n, ot her 
c o nc urrent disease, c o nc o mita nt me dicati o ns or e ve nts) is u nli kel y, a n d t h e e ve nt f oll o ws a 
cli nicall y reas o na ble res p o nse u p o n wit h dra wal of dr u g ( de-c halle n ge).   
P ossi bl y Re l ate d: T h ere is e vi de nce t o s u g gest a ca usal relati o ns hi p (e. g., t he e ve nt occ urre d 
wit hi n a reas o na bl e ti me after a d mi nistrati o n of t he st u d y dr u g). H o we ver, t he i nfl ue nce of ot her 
fact ors ma y h a ve c o ntri b ute d t o t he e ve nt (e. g., t h e patie nt’s cli nical c o n diti o n, ot her c o nc urre nt 
disease, c o n c o mita nt me dicati o ns or e ve nts).  
U nli kel y Rel ate d : A cli nical e ve nt, i ncl u di n g a n a b n or mal la b orat or y test res ult, w h ose te m p oral 
relati o ns hi p t o dr u g a d mi nistrati o n ma kes a ca us al relati o ns hi p i m pr o ba ble (e. g., t he e v e nt di d 


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n ot occ ur wit hi n a r eas o n a ble ti me after a d mi nistrati o n of t he trial me dicati o n) a n d i n w hic h 
ot her dr u gs or c o n c urre nt or u n derl yi n g disease pr o vi de pla usi ble e x pla nati o ns (e. g., t he patie nt’s 
cli nical c o n diti o n, ot her c o nc o mita nt treat me nts). 
N ot rel at e d : T he a d verse e ve nt is c o m pletel y i n de pe n de nt of st u d y dr u g a d mi nistrati o n, a n d/ or 
e vi de nce e xists t hat t he e ve nt is defi nitel y relate d t o a n ot her eti ol o g y.  T here m ust be a n 
alter nati ve, defi niti ve eti ol o g y d oc u me nt e d b y t he cli nicia n. 
1 1. 1. 2. 4.  D ur ati o n 
F or all a d v erse e ve nts w het her or n ot c o nsi dere d s eri o us, t he I n vesti gat or will pr o vi de a rec or d of 
t he start a n d st o p dates of t he e ve nt. E ver y eff ort s h o ul d be ma de t o res ol ve all a d verse e ve nts 
wit h c o nti n ue d f oll o w- u p wit h t he patie nt u ntil a p pr o priate res ol uti o n ca n be ac hiev e d. If a n 
e ve nt is u nres ol ve d at t he e n d of t he st u d y it will be rec or de d as o n g oi n g.  
1 1. 1. 2. 5.  Acti o n T a ke n 
T he I n vesti gat or will rec or d t he acti o n ta ke n wit h i n vesti gati o nal pr o d uct as a res ult of a n 
a d verse e ve nt or s eri o us a d ve rse e ve nt o n t he e C R F, as a p plica ble (e. g., disc o nti n uati o n, or 
i nterr u ptio n of i n vesti gati o nal pr o d uct, as a p pr o pri ate) a n d rec or d if c o n c o mita nt a n d/ or 
a d diti o nal treat me nts were gi v e n f or t he e ve nt. 
1 1. 1. 2. 6.  O utc o me 
T he I n vesti gat or will rec or d t he o utc o me of a d verse e ve nts o n t he e C R F, as a p plica ble (e. g., 
rec o vered, rec o v ere d wit h se q uelae, n ot rec o v ere d, or deat h ( d ue t o t he a d v erse e v e nt).   
1 1. 1. 3.   
F oll o w- U p  
A d verse e ve nts assess e d as n ot relate d t o st u d y dr u g, i ncl u di n g cli nicall y si g nifica nt la b orat or y 
tests, electr ocar di o gra ms, or p h ysic al e xa mi nati o n fi n di n gs, m ust be f oll o we d u ntil t he e ve nt 
res ol ves, t he c o n diti o n sta bilizes, t he e ve nt is ot her wise e x plai ne d, or t he fi nal st u d y visit occ urs, 
w hic he ver c o mes first.     
A d verse e ve nts assess e d as relate d t o st u d y dr u g a n d seri o us a d verse e v e nts will be f oll o we d f or 
as l o n g as n ecessar y t o a de q uatel y e v al uate t he patie nt’s safet y, or u ntil t he e ve nt sta bilizes, is 
ot her wise e x plai ne d, deat h occ urs, or t he patie nt is l ost t o f oll o w u p.  If res ol ve d, a res ol uti o n 
date s h o ul d be pr o vi de d.  T he I n vesti gat or is res p o nsi ble f or e ns uri n g t hat f oll o w- u p i ncl u des a n y 
s u p ple me ntal i n vesti gati o ns i n dicate d t o el uci date t he nat ure a n d/ or ca us alit y of t he a d verse 
e ve nt.  T his ma y i ncl u de a d diti o nal cli nical la b orat or y testi n g or i n vesti gati o ns, e x a mi nati o ns, or 
c o ns ultati o n wit h ot her healt h care pr ofessi o nals as is practical.  
1 1. 1. 4.   
Pre g n a n c y  
T he S p o ns or m ust be i nf or me d wit hi n 2 4 h o urs u p o n lear ni n g t hat a patie nt, or male patie nt’s 
part ner, h as bec o me pre g na nt a n y ti me after t he first d ose of st u d y dr u g u ntil 3 0 da ys aft er t he 
last d ose of st u d y dr u g. T he Pre g na nc y N otificati o n e C R F s h o ul d be use d t o re p ort t he pre g na nc y 
t o t he S p o ns or or its desi g nee.  Patie nt pre g n a ncies ( or pre g n a nc y of a male patie nt’s part ner) 
m ust be f oll o we d u ntil ter mi nati o n of pre g na n c y or t he birt h of t he c hil d.  T he Pre g na nc y 
O utc o me e C R F s h o ul d b e use d t o re p ort i nf or mati o n re gar di n g t he stat us of t he i nfa nt. 


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If a fe male part ner of a m ale patie nt ta ki n g i n vesti gati o nal pr o d uct bec o m es pre g na nt, t he male 
patie nt ta ki n g t he i n vesti gati o nal pr o d uct s h o ul d n otif y t he I n v esti gat or, a n d t he pre g na nt fe male 
part ner s h o ul d be a d vise d t o call her healt hcare pr o vi der i m me diatel y. 
1 1. 1. 5.   
Rec or di n g A d verse E ve nts 
All a d verse e ve nts (re gar dless of seri o us ness or relati o ns hi p t o st u d y dr u g) i ncl u di n g t h ose fr o m 
t he ti me i nf or me d c o nse nt is o btai ne d t hr o u g h t o t he fi nal st u d y visit are t o be rec or de d i n t he 
e C R F.  Eac h i n di vi d ual a d verse e v e nt is t o be liste d as a se parate e ntr y.  T he I n vesti gat or will 
pr o vi de i nf or mati o n a b o ut date s of o nset a n d res ol uti o n, seri o us ness, se verit y, acti o n(s) ta ke n, 
o utc o me, a n d rel ati o ns hi p t o t he st u d y dr u g. All a d verse e v e nts s h o ul d be d oc u me nte d i n t he 
patie nt’s s o urc e d o c u me nts.  
1 1. 1. 6.   
Re p orti n g A d verse E ve nts 
T he I n vesti gat or m ust re p ort t o S p o ns or or its desi g nee all a d verse e v e nts t hat occ ur d uri n g t h e 
st u d y fr o m t he ti me writte n i nf or me d c o ns e nt is gi ve n u ntil t he fi nal st u d y visit or earl y 
ter mi nati o n, re gar dl ess of t heir relati o ns hi p t o t he st u d y dr u g. Seri o us a d v erse e ve nts a n d 
pre g na nc i es will be re p orte d fr o m t he ti me writte n i nf or me d c o nse nt is gi ve n t hr o u g h 3 0 d a ys 
be y o n d t h e last d ose of st u d y dr u g. 
1 1. 1. 6. 1.  Re p orti n g Seri o us A d verse E ve nts 
T he I n vesti gat or is r e q uir e d t o n otif y t he S p o ns or, a n d t he S p o ns or’s desi g n ate d Dr u g Safet y 
U nit wit hi n 2 4 h o urs after bec o mi n g a ware  of t he occ urre nce of a s eri o us a d verse e v e nt.  All 
seri o us a d verse e v e nts will be re p orte d t hr o u g h c o m pleti o n of t he a d verse e ve nt e C R F.  T he 
I n v estigat or will be res p o nsi ble f or re p orti n g seri o us a d verse e ve nts t o t he I R B. 
Me dic al M o nit or a n d E mer ge nc y C o nt act I nf or m ati o n: 
 
 
, M D 
Tele p h o ne:  
 
Facsi mile :  
 
E mail:  
 A N D 
  
 
S eri o us A d ver se E ve nt Re p orti n g C o nt act I nf or m ati o n: 
  
 Safet y Gr o u p E mail: 
 
  
Seri o us A d verse E v e nt Hel p Li ne: 
 
Seri o us A d verse E v e nt F a x Li n e: 
 
If a n I n v esti gat or bec o m es a ware of a seri o us a d v erse e v e nt wit hi n 3 0 da ys after t he l ast d ose of 
st u d y dr u g a n d it is c o nsi dere d b y hi m/ her t o be ca use d b y t h e st u d y dr u g wit h a reas o na bl e 
p ossi bilit y, t he e v e nt m ust be d oc u me nte d a n d re p orte d t hr o u g h c o m pleti o n of t he a d verse e v e nt 
e C R F. 
1 1. 1. 6. 2.  Re p orti n g Ur ge nt S afet y Iss ues 
If t he st u d y site staff bec o mes a ware of a n act ual or p ote ntial ur ge nt safet y iss ue, t he n t he 
S p o ns or a n d S p o ns or’s desi g nee ( Me di cal M o nit or) m ust be i m me diatel y c o ntacte d s o t hat 
a p pr o priate ur ge nt safet y meas ures ca n be a gree d u p o n.  A n ur ge nt safet y iss ue is defi ne d as:  


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 A n i m me diate hazar d t o t he healt h or safet y of patie nts partici pati n g i n a cli nical 
st u d y 
 A seri o us ris k t o h u ma n healt h or p ote ntiall y a seri o us ris k t o h u ma n healt h 
A n ur ge nt safet y iss ue ma y i n cl u de:  ( 1) iss ues wit h a n i n vesti gati o nal dr u g or c o m parat ors; 
( 2) st u d y pr oce d ures; ( 3) i nter-c urre nt ill ness (i ncl u di n g pa n d e mic i nfecti o ns); ( 4) c o nc o mita nt 
me dicati o ns;  ( 5) c o nc urre nt me dical c o n diti o ns; or ( 6) a n y ot her iss ues rel ate d t o t he safe 
c o n d uct of t he st u d y or t hat p ose a ris k t o st u d y p atie nts. 
I n e x ce pti o nal circ u msta nces of i m mi ne nt hazar d a n d i n or der t o safe g uar d t he healt h or safet y of 
i n di vi d uals, t he I n vesti gat ors ma y ta ke ur ge nt s afet y meas ures bef ore i nf or mi n g t he S p o ns or, b ut 
t he S p o ns or m ust be i nf or me d i m me diatel y after t he hazar d has res ol ve d.   


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1 2.   
S T A TI S TI C A L M E T H O D S 
1 2. 1.   
S a m ple Size R ati o n ale 
T here are v er y fe w st u dies i n t he literat ure t o pr o vi de relia ble esti mates of acti ve treat me nt or 
place b o res p o nse rates usi n g S A L T, or t he esti mate of varia nces ar o u n d t hese meas ures, i n 
patie nts wi t h al o pecia areata.  P o wer calc ulati o ns ass u me a 2-si de d c hi-s q u are test a n d 
si g nifica nce le vel of 0. 0 5 a n d are b ase d o n a n acti ve treat me nt res p o nse rate of 4 5 % a n d a 
place b o re s p o nse rate of 1 0 %.  
Alt h o u g h patie nts will be ra n d o mize d i n a n u n bala nce d rati o of acti ve dr u g t o place b o wit hi n 
eac h c o h ort, t he place b o patie nts fr o m t he 3 c o h orts will be c o m bi ne d f or statistical c o m paris o ns 
t o eac h acti ve treat me nt gr o u p. T h e first 2 c o h orts will be ra n d o mize d i n a 2: 1 rati o 
(acti ve: place b o) a n d t h e t hir d c o h ort will be ra n d o mize d i n a 5: 1 rati o (acti ve: place b o). Base d o n 
esti mate d c o m pleti o n rat es as of A me n d m e nt 4, t his ra n d o mizati o n sc he me is e x pecte d t o 
pr o vi de a si milar n u m ber of patie nts i n t he C T P- 5 4 3 a n d t he p o ole d place b o ar ms. T h us, p o wer 
calc ulati o ns f or t he c o m p aris o n t o place b o are b as e d o n a 1: 1 treat me nt rati o f or t he c o m paris o n 
of 1 2 m g t o pla ce b o. A s a m ple siz e of 2 8 patie nts i n t he 1 2 m g gr o u p a n d 2 8 patie nts i n t he 
p o ole d place b o gr o u p will pr o vi de > 8 0 % p o wer f or t he c hi-s q uare test. A p pr o xi matel y 1 5 0 
patie nts wi ll be ra n d o mize d i n or der t o pr o vi de 1 2 0 patie nts w h o c o m plete treat me nt.   
1 2. 2 .  
E n d p oi nts 
1 2. 2. 1.   
Effic ac y 
T he pri mar y efficac y e n d p oi nt will be t he pr o p orti o n of patie nts ac hie vi n g at least a 5 0 % relati ve 
re d ucti o n i n S A L T s c ore fr o m baseli ne at Wee k 2 4.   
E x pl orat or y  efficac y e n d p oi nts i ncl u de: 
 Relati ve c ha n ge i n S A L T sc ores fr o m baseli ne ( mea n a n d p erce nt) at Wee ks: 
o  4, 8, 1 2, 1 6, 2 0, a n d 2 4 i n t he Bli n de d Treat me nt Peri o d 
 Relati ve c ha n ge i n al o pecia areata se verit y fr o m b aseli ne as meas ure d b y t h e cli nicia n 
V A S - S at Wee ks 1 2 a n d 2 4; 
 C ha n ges i n al o pecia areata fr o m baseli ne usi n g t h e cli nicia n rat e d 7- p oi nt Li kert scale 
C GI- I at Wee ks 1 2 a n d 2 4 ; 
 Re lati ve c ha n ge i n al o pecia areata se verit y fr o m b aseli ne as meas ure d b y t h e patie nt 
V A S - S at Wee ks 1 2 a n d 2 4;  
 C ha n ges i n al o pecia areata fr o m baseli ne usi n g t h e patie nt rate d 7- p oi nt Li kert scale 
P GI -I at Wee ks 1 2 a n d 2 4 ;  
 Pa tie nt-re p orte d o utc o m es: C ha n ges i n s y m pt o ms fr o m baseli ne as m eas ure d b y 
A A SI S a n d e x pl orat or y q uesti o ns at Wee k 2 4 
A d diti o nal e x pl orat or y statistical a nal yses t o f urt h er assess f or treat me nt effect will be o utli ne d 
i n t he Statistical A nal ysis Pla n fi nalize d pri or t o data base l oc k f or t he Pri mar y Efficac y A n al ysis. 


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1 2. 2. 2.   
P h ar m a c o ki netic 
P har mac o ki netic sa m ples will be c ollecte d at t he f oll o wi n g ti me p oi nts t o e val uate plas ma 
c o nce ntr ati o ns of C T P- 5 4 3 a n d meta b olites.   
 Da y 1 a n d Wee k 4 : 2 sa m ples at eac h visit; 1 sa m ple pre- d ose, a n d 1 sa m p le p ost-
d ose at t he  e n d of t h e visit  
 Wee k 2: 1 sa m ple wit h t he safet y la b dra w 
 Wee ks 8, 2 4: 1 sa m ple p ost- d ose at t he e n d of t h e visit 
1 2. 2. 3.   
S afet y 
Safet y a n d t olera bilit y of C T P- 5 4 3 will be assesse d b y e v al uati n g a d verse e ve nts, vital si g ns, 
c o nc o mita nt me dicati o ns, cli nical la b orat or y, a n d electr ocar di o gra m res ults, as well as p h ysical 
e x a mi nati o ns. 
1 2. 3.   
A n al ysis P o p ul ati o ns 
1 2. 3. 1.   
Tre at me nt Peri o d 
T he Efficac y P o p ulati o n will i ncl u de all patie nts w h o recei ve st u d y dr u g a n d ha ve at least 
1 p ost-treat me nt S A L T assess me nt d uri n g t he Treat me nt Peri o d.   
T he P har ma c o ki n etic P o p ulati o n will i ncl u de all patie nts w h o recei ve st u d y dr u g a n d ha v e at 
least 1 p har mac o ki netic s a m ple ta ke n d uri n g t he Treat me nt Peri o d.  Patie nts w h o recei ve place b o 
will be e x cl u de d fr o m t he P har mac o ki netic P o p ul ati o n. 
T he Sa fet y P o p ulati o n will i ncl u de all patie nts w h o recei v e st u d y dr u g d uri n g t he Treat me nt 
Peri o d.   
T he P er Pr ot oc ol P o p ulati o n will i ncl u de all s u bj ects i n t he Efficac y P o p ulati o n w h o were d ose d 
acc or di n g t o pr ot o c ol a n d ha ve n o maj or pr ot o c ol de viati o ns.  
1 2. 4.   
A n al yses 
F or t he Treat me nt Peri o d, data will be s u m marize d b y acti ve treat me nt b y c o h ort d ose le vel 
vers us place b o-treate d patie nts (i.e., b y treat me nt gr o u p).  T he place b o pati e nts fr o m t he 3 
c o h orts will be co m bi ne d f or statisti cal c o m paris o ns t o eac h acti ve treat me nt gr o u p. All data f or 
a nal ysis will be liste d b y patie nt. 
C o nti n u o us meas ures will be s u m marize d descri pti vel y ( mea n, sta n dar d de viati o n, me dia n, 
mi ni m u m val ue, a n d ma xi m u m val ue) a n d cat e g orical meas ures will be pres e nte d as n u m ber a n d 
perce nt a ge.   
A d diti o nal details f or statistical met h o ds will be pr o vi de d i n t he Statistical A nal ysis Pla n. 
1 2. 4. 1.   
Dis p ositi o n a n d B aseli ne C h ar acteristics 
Dis p ositi o n will be s u m marize d b y ra n d o mize d treat me nt gr o u p. T he n u m ber a n d perce nta ge of 
patie nts, w h o a re ra n d o mize d, treate d, pre mat urel y disc o nti n ue d, a n d c o m plete t he st u d y will be 
s u m marized.  
Baseli ne c haracteristics will be s u m marize d b y treat me nt gr o u p. 


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T he n u m ber of pa tie nts i n eac h c o h ort’s treat me nt gr o u p will be s u m marize d f or eac h 
i n vesti gati ve site f or t he Treat me nt Peri o d.  Me di cal hist or y will be c o de d wit h t he Me dical 
Dicti o nar y f or Re g ul at or y Acti vities ( Me d D R A ) t er mi n ol o g y. C o nc o mita nt me dicati o ns will be 
s u m marized b y W orl d Healt h Or ga nizati o n Dr u g Dicti o nar y A nat o mical- T hera pe utic- C he mical 
classificati o n a n d preferre d ter m.   
1 2. 4. 2.   
Effic ac y 
All statistical tests will be 2-si de d wit h a si g nifica nce val ue of 0. 0 5. Testi n g will be perf or me d 
o nl y f or t h e Treat me nt Peri o d. 
A n i nteri m a nal ysis of safet y a n d efficac y will be perf or me d w he n all patie nts i n t he 4 m g a n d 
t he 8 m g c o h orts have c o m plete d Wee k 2 4.  T he fi nal efficac y a nal ysis will be c o n d ucte d w he n 
all patie nts i n t he 1 2 m g c o h ort ha ve c o m plete d Wee k 2 4. 
Pri m ar y Effic ac y E n d p oi nt 
T he pri mar y efficac y e n d p oi nt will be t he pr o p orti o n of patie nts ac hie vi n g at least a 5 0 % relati ve 
re d ucti o n i n S A L T s c ore fr o m baseli ne at Wee k 2 4.  Pair wise treat me nt gr o u p differe n ces fr o m 
place b o will be ass esse d wit h t he C oc hra n- Ma nt el- Hae nszel test usi n g t h e al o pecia areata 
s u bt y pe as t h e stratificati o n fact or.  
T here will be  n o a dj ust me nt f or m ulti ple treat me nt gr o u p c o m paris o ns i n t his d ose-ra n gi n g P hase 
2 st u d y. 
T he ha n dli n g of missi n g data will be s u m marize d i n t he Statistical A nal ysis Pla n. 
E x pl or at or y Effic ac y E n d p oi nts 
Treat me nt differe n ces f or relati ve c h a n ge i n S A L T sc ore fr o m baseli ne t o Wee ks 4, 8, 1 2, 1 6, 2 0, 
a n d 2 4 will be assesse d wit h a mi x e d-effect m o d el of re p eate d meas ures ( M M R M) m o del.  T he 
m o del will i ncl u de fi x e d fact ors f or treat me nt gr o u p, st u d y visit, a n d treat me nt b y st u d y visit 
i nteracti o n, wit h baseli ne S A L T sc ore as a c o v ariate.  A n u nstr uct ure d v aria nce-c o v aria n ce 
matri x will be use d. 
Treat me nt differe n ces f or t he Gl o bal I m pressi o n of I m pr o ve me nt a n d V A S scales will be 
assesse d wit h t he  C oc hra n- Ma ntel- Hae nszel test usi n g t he al o pecia areat a s u bt y pe as t he 
stratificati o n fact or. 
C ha n ge i n s y m pt o ms as meas ure d b y A A SI S a n d t he e x pl orat or y q u esti o ns fr o m baseli ne t o 
Wee k 2 4 will be assesse d wit h t he a nal ysis of c o varia nce wit h a fi xe d fact or f or treat me nt a n d 
ba seli ne val ue as a c o v ari ate. 
1 2. 4. 3.   
P h ar m a c o ki netics 
T he c ollecti o n stat us of p har mac o ki netic sa m ples will be liste d f or eac h visit wit h sc he d ule d 
p har mac o ki netic s a m pli n g. Plas ma c o n ce ntrati o ns of st u d y dr u g m a y be s u m marize d se paratel y, 
as a p pr o priat e. 
1 2. 4. 4.   
St u d y Dr u g E x p os ure 
St u d y dr u g e x p os ure will be s u m marize d f or eac h c o h ort’s Treat me nt Peri o d. T he n u m ber of 
da ys o n w hic h st u d y dr u g was d ose d will be s u m marize d f or eac h treat me nt gr o u p. 


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T he t otal n u m ber of da ys o n st u d y dr u g will e x cl u de d ose i nterr u pti o ns. T he t otal n u m ber of da ys 
of e x p os ure t o C T P- 5 4 3 will be s u m marize d wit h t he 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 n u m ber of da ys o n t he d ose. Dr u g c o m plia nce will als o be 
s u m marized. 
1 2. 4. 5.   
P h ar m a c o d y n a mi cs 
T he c ollecti o n stat us of p har mac o d y n a mic sa m ples will be liste d f or eac h visit wit h sc he d ule d 
p har mac o d y n a mic sa m pli n g. 
1 2. 4. 6.   
S afet y 
All safet y s u m maries will be descri pti ve wit h n o statistical h y p ot hesis testi n g a n d b ase d o n t he 
Safet y P o p ulati o n. Patie nts will be s u m marize d acc or di n g t o t he st u d y dr u g recei v e d (i.e., as 
treate d), s h o ul d it differ fr o m t he ra n d o mize d treat me nt ar m. All safet y e n d p oi nts will be liste d i n 
b y - p atie nt data listi n gs. 
A d verse e ve nts will be c o de d usi n g Me d D R A a n d s u m marize d b y s yste m or ga n class a n d 
preferre d t er m.  Cli nicall y si g nifica nt d eteri orati o ns i n p h ysical e xa mi nati o n fi n di n gs will be 
re p orte d a n d s u m marize d as a d verse e ve nts. 
La b orat or y v al ues will be c o n vert e d t o t he pr oject- defi ne d u nit of meas ure me nt, as a p plica ble, 
bef ore a nal ysis. A b n or m al, cli nicall y si g nifica nt la b orat or y v al ues will be re p orte d a n d 
s u m marized as a d verse e ve nts. 
A d verse E ve nts 
A n a d verse e ve nt re p orte d after i nf or me d c o nse nt, b ut bef ore t he first d ose of st u d y dr u g (i.e., 
Da y 1), wil l be c o nsi dere d a pre-tr eat me nt a d verse e ve nt.  Treat me nt-e mer ge nt a d verse e ve nts 
( T E A Es) will be defi ne d as a n y a d verse e v e nt t hat occ urs after a d mi nistrati o n of t he first d ose of 
st u d y dr u g u ntil Wee k 2 4 or t he Earl y Ter mi nati o n Visit.  T he n u m ber a n d perce nt a ge of patie nts 
w h o re p ort T E A Es will be s u m marize d b y s yste m or ga n class a n d preferre d ter m.  
Treat me nt e mer ge nt a d verse e ve nts will als o be s u m marize d b y i nte nsit y as well as relati o ns hi p 
t o st u d y dr u g.   
Patie nts w h o re p ort t he sa me preferre d ter m o n m ulti ple occasi o ns will be c o u nte d o nce f or t he 
preferre d t er m: u n der t he hi g hest se v erit y w he n s u m marize d b y se v erit y a n d u n der t he cl osest 
relati o ns hi p t o st u d y dr u g w he n s u m marize d b y relati o ns hi p.  If a patie nt re p orts m ulti ple 
preferre d t er ms f or a s yst e m or ga n class, t he patie nt will be c o u nte d o nl y o nce f or t h at s yste m 
or ga n class. 
Pr o p or ti o ns f or a d verse e ve nts that are ge n der-s pecific (e. g. , d ys me n orr hea) will be base d o n t he 
n u m ber of patie nts fr o m t hat ge n der. 
T he n u m ber a n d p erce nta ge of patie nts w h o e x perie nce T E A Es will be s u m marize d b y treat me nt 
gr o u p f or t he f oll o wi n g: 
 B y s yste m or ga n class a n d preferre d t er m 
 B y  se verit y/i nte nsit y, s yste m or ga n class, a n d preferre d t er m 
 B y rel ati o ns hi p t o st u d y dr u g, s yste m or ga n class, a n d preferre d ter m 
 Seri o us a d verse e ve nts b y s yste m or ga n class a n d preferre d t er m 


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 Seri o us a d verse e ve nts b y relati o ns hi p t o st u d y dr u g, s yste m or ga n class, a n d 
pre ferre d t er m 
 A d verse e ve nts res ulti n g i n disc o nti n uati o n of st u d y dr u g b y s yste m or ga n class a n d 
preferre d t er m 
 A d verse e ve nts t hat res ult i n st u d y dr u g d ose i nterr u pti o n b y s yste m or ga n class a n d 
preferr e d t er m 
B y - patie nt listi n gs will b e pr o vi de d f or a n y deat hs, seri o us a d verse e v e nts, a n d a d verse e v e nts 
lea di n g t o disc o nti n uati o n of treat me nt. Treat me nt-e mer ge nt a d verse e v e nts t hat res ult i n d ose 
i nterr u ptio n will als o be i de ntifie d.  
A d diti o nall y, treat me nt-e mer ge nt a d verse e v e nts will be s u m marize d b y ti me i nter val: 0 t o 1 2 
wee ks, a n d 1 2 t o 2 4 wee ks.  F or eac h ti me i nter val, a n i nci de nce ta bl e will s u m marize o nl y 
T E A Es wit h a n o nset dat e  wit hi n t he i nter val a n d a pre val e nce t a ble will s u m marize all T E A Es 
t hat ha ve a n o nset d ate wit hi n t he i nter val or c o nti n ue i nt o t he i nter val.  Differe n ces bet w ee n t he 
i nci de nce a n d pre v ale nce ta bles ca n pr o vi d e i nsi g ht i nt o t he d urati o n of T E A Es as well as t he 
rec urre nce of T E A Es. A preferre d t er m f or a n i n di vi d ual patie nt will be re p orte d i n m ulti ple ti me 
i nter vals if t here are m ulti ple a d verse e ve nt re p orts.  T he de n o mi nat or f or eac h ti me i nter val will 
be t he n u m ber of p atie nts w h o recei ve d at least 1 d ose of st u d y dr u g wit hi n t he i nter val.  
Cli nic al L a b or at or y 
Cli nical la b orat or y varia bles will be prese nte d i n 3 wa ys.  First, c ha n ge fr o m Baseli ne t o eac h 
sc he d ule d assess me nt will be s u m marize d descri pti vel y.  Baseli ne will be defi ne d as t he 
la b orat or y val u e o btai ne d bef ore t h e first d ose of st u d y dr u g o n Da y 1; if Da y 1 val u es are 
u na vaila ble, t he n v al ues o btai ne d at t he Scree ni n g Visit will be use d. 
Sec o n d, treat me nt-e mer ge nt p ote ntiall y cli nicall y si g nifica nt ( P C S) la b orat or y v al ues will be 
i de ntifie d.  P ote ntiall y cli nicall y si g nifica nt val ues are defi ne d as t h ose t h at meet Gra d e 3 or 
Gra de 4 t o xicit y criteria fr o m t he C T C A E criteria.  Treat me nt-e mer ge nt P C S la b orat or y val ues 
are t h ose i n w hic h t h e baseli ne val ue is n ot P C S a n d t he p ost- baseli ne val u e is P C S. T he n u m ber 
a n d percenta ge of patie nts wit h treat me nt-e mer ge nt P C S la b orat or y val ues will be s u m marize d 
b y treat me nt gr o u p f or eac h cli nical la b orat or y varia ble. 
T hir d, t he n u m ber a n d p erce nta ge of patie nts wit h A b n or mal, cli nicall y si g nifica nt la b orat or y 
val ues ( per I n vesti gat or j u d g me nt) will be s u m marize d b y treat me nt gr o u p f or eac h cli nical 
la b orat or y varia ble. 
Vit al Si g ns 
T he mea n c h a n ge fr o m b aseli ne t o eac h sc he d ul e d assess me nt will be s u m marize d descri pti vel y 
b y treat me nt gr o u p f or eac h vital si g n varia ble s pecifie d i n t his pr ot oc ol. 
Baseli ne will be defi ne d as t he last vital si g n val u e o btai ne d bef ore t he first d ose of st u d y dr u g o n 
Da y 1; if Da y 1 v al ues are u na vaila ble, t he n val ues o btai ne d at t he Scree ni n g Visit will be use d.  
Electr oc a r di o gr a m 
T he c ha n ge fr o m bas eli ne i n electr o car di o gra m i nter vals ( P R, Q T, Q Tc F, Q R S, a n d R R) t o eac h 
sc he d ule d assess me nt will be s u m marize d descri pti vel y b y treat me nt gr o u p. 
 


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1 3.   
R E G U L A T O R Y C O N SI D E R A TI O N S 
It is t he res p o nsi bilit y of t he cli nical site a n d staff t o n otif y t he S p o ns or a n d S p o ns or’s desi g n ee 
i m me diatel y u p o n bec o mi n g a ware of a seri o us breac h of G C P or of t he st u d y pr ot oc ol.  It is t he 
res p o nsi bility of t he S p o ns or or its desi g n ee t o n otif y a p pr o priate re g ulat or y a ut h orities of a n y 
seri o us breac h w hic h is li kel y t o effect, t o a si g nifica nt de gree, t he saf et y or me ntal i nte grit y of 
t he patie nts of t he st u d y or t he scie ntific val u e of t he st u d y.  
1 3. 1.   
G o o d Cli nic al Pr actice 
T he pr oce d ures set o ut i n t his st u d y pr ot oc ol pertai ni n g t o t he c o n d u ct, e val uati o n, a n d 
d oc u me ntati o n of t his st u d y are desi g n e d t o e ns ure t hat t he S p o ns or, its a ut h orize d 
re pres e ntati ve, a n d I n vesti gat or a bi d e b y G C P, as descri be d i n I C H G ui d eli ne E 6 a n d i n 
acc or da nce wit h t he ge neral et hical pri nci ples o utli ne d i n t he Declarati o n of Helsi n ki.  T he st u d y 
will recei ve a p pr o val fr o m t he I R B pri or t o c o m m e nce me nt.  T he I n vesti gat or will c o n d uct all 
as pects of t hi s st u d y i n acc or da n ce wit h a p plica bl e nati o nal, state, a n d l ocal la ws of t he perti n e nt 
re g ulat or y a ut h orities. 
1 3. 2.   
S p o ns or’s Res p o nsi bilities 
T he S p o ns or or its desi g n ee is res p o nsi ble f or t he f oll o wi n g: 
 Selecti n g q u alifie d I n vesti gat ors 
 Pr o vi di n g I n vesti gat ors wit h t he i nf or mati o n t he y nee d t o pr o perl y c o n d uct a n 
i n vesti gati o n 
 E ns uri n g pr o per m o nit ori n g of t he i n v esti gati o n 
 E ns uri n g t hat t he a p plica ble re g ulat or y a ut h orities, a n d all partici pati n g I n v esti gat or s 
are pr o perl y i nf or me d of si g nifica nt n e w i nf or mati o n re gar di n g a d verse e ve nts or 
ris ks ass ociate d wit h t he me dicati o n bei n g st u die d 
Bef ore a n i n v esti gati o nal site ca n e nter a patie nt i nt o t he st u d y, a re pres e ntati ve of t he S p o ns or 
will visit t he i n vesti gati o nal st u d y site t o: 
 Deter mi ne t he a de q uac y of t he facilities 
 Disc uss wit h t he I n v esti gat or(s) a n d ot h er pers o n nel t heir res p o nsi bilities wit h re gar d t o 
pr ot oc ol a d here nce, a n d t he res p o nsi bilities of t he S p o ns or or its re prese nt ati ves.  T his 
will be d oc u me nte d i n a Cli nical St u d y A gree m e nt bet wee n t he S p o ns or a n d t he 
I n v esti gat or. 
D uri n g t h e st u d y, a m o nit or fr o m C o ncert P har mace uticals or its re prese nt ati ve will ha ve re g ular 
c o ntacts wit h t he i n vesti gati o nal site, f or t he f oll o wi n g: 
 Pr o vi de i nf or mati o n a n d s u p p ort t o t he I n v esti gat or(s) 
 C o nfir m t hat facilities re mai n acce pta ble 
 C o nfir m t hat t he i n vesti gati o nal tea m is a d heri n g t o t he pr ot oc ol, t hat data are bei n g 
acc uratel y rec or de d i n t he case re p ort f or ms, a n d t hat i n vesti gati o nal pr o d uct 
acc o u nta bilit y c hec ks are bei n g p erf or me d 


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 Perf or m s o urce data verificati o n.  T his i ncl u des a c o m paris o n of t he data i n t he case 
re p ort f or ms wit h the pati e nt’s me dical rec or ds at t he h os pital or practice, a n d ot her 
rec or ds rele va nt t o t he st u d y.  T his will re q uire direct access t o all ori gi nal rec or ds f or 
eac h p atie nt (e. g., cli nic c harts). 
 Rec or d a n d re p ort a n y pr ot oc ol de viati o ns. 
 C o nfir m a d verse e ve nts a n d seri o us a d verse e v e nts ha ve bee n pr o perl y d o c u me nte d o n 
e C RFs a n d c o nfir m a n y s eri o us a d verse e v e nts ha ve bee n f or war de d t o t he S p o ns or a n d 
t h ose seri o us a d verse e v e nts t hat met criteria f or re p orti n g ha v e bee n f or war de d t o t he 
I R B. 
T he m o nit or will be a vaila ble bet wee n visits if t he I n v esti gat or(s) or ot her st aff nee ds 
i nf or mati o n or a d vice. 
As t he S p o ns or, C o ncert P har mace uticals has dele gat e d s o me res p o nsi bilities t o a desi g nee, or 
C o ntract Researc h Or ga nizati o n. 
1 3. 3.   
I n vesti g at or’s Res p o nsi bilities 
I n v esti gat or res p o nsi bilities are set o ut i n t he I C H G ui deli ne f or G C P a n d i n t he l ocal 
re g ulati o ns.  Eac h I n vesti gat or p artici pati n g i n t his st u d y is re q uire d t o mai ntai n c o m plete a n d 
acc urate st u d y d oc u me nt ati o n i n c o m plia nce wit h c urre nt G C P sta n dar ds a n d all a p plica ble l ocal 
re g ulati o ns relate d t o t he c o n d uct of a cli nical st u d y. 
T he Pri nci pal I n vesti gat or will e ns ure t hat all pers o ns assisti n g wit h t he st u d y are a d e q uatel y 
i nf or me d a b o ut t he pr ot o c ol, a n y a me n d me nts t o t he pr ot oc ol, t he st u d y dr u g, a n d t h eir 
st u d y-relate d d uties a n d f u ncti o ns.  T he Pri nci pal I n vesti gat or will mai ntai n a list of s u b-
I n v esti gat ors a n d ot her a p pr o priatel y q ualifie d p ers o ns t o w h o m he or s he h as dele gate d 
si g nifica nt st u d y-relate d d uties.  I n di vi d uals i neli gi ble fr o m c o n d ucti n g or w or ki n g o n cli nical 
st u dies, i ncl u di n g t h ose i neli gi ble as a res ult of de bar me nt u n der t h e Ge n eric Dr u g E nf orce me nt 
Act of 1 9 9 2, will n ot be all o we d t o c o n d uct or w or k o n st u dies s p o ns ore d b y C o ncert 
P har mace uticals.  T he I n vesti gat or is r e q uire d t o i m me diatel y discl ose t o t he S p o ns or i n writi n g, 
if a n y p ers o n i n v ol ve d i n t he c o n d uct of t he st u d y is de barre d p urs ua nt t o a heari n g b y t he F D A 
u n der t his a nti-fra u d l a w, or if a n y pr ocee di n g f or de bar me nt is pe n di n g, or is (t o t he best of t he 
I n v estigat or’s k n o wle d ge) t hreate ne d.  
T he I n vesti gat or is r es p o nsi ble f or kee pi n g a rec or d of all patie nts w h o si g n a n i nf or me d c o ns e nt 
d oc u me nt a n d are scree n e d f or e ntr y i nt o t he st u d y.  Patie nts w h o fail scree ni n g m ust ha ve t h e 
reas o n(s) rec or de d i n t he patie nt’s s o urce d o c u me nts. 
T he I n vesti gat or s h o ul d i nf or m t he I R B of a n y e v e nt li kel y t o affect t he s afet y of patie nts or t he 
c o nti n ue d c o n d uct of t he st u d y, i n partic ular a n y c ha n ge i n safet y.  A d diti o nall y, all u p dat es t o 
t he I n v esti gat or’s Br oc h ure will be se nt t o t he I R B.  A pr o gress re p ort will be se nt t o t he I R B a n d 
t he pr ot oc ol will be re vie we d a n n uall y (e. g., re-a p pr o ve d) or m ore fre q ue ntl y, as re q uire d b y t he 
I R B or l ocal re g ulati o ns.  
T he I n vesti gat or will mai ntai n a c o p y of all c orres p o n de nce wit h t he I R B, i ncl u di n g c o pi es of 
a p pr o ve d d oc u me nts.  T he I n vesti gat or will als o m ai ntai n a c o p y of t he I R B me m bers hi p list 
wit h occ u pati o n a n d q ualificati o n ( or a stat e me nt c o nfir mi n g c o m plia nce wit h G C P re q uire me nts 
f or c o m mittee c o m p ositi o n).   


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T he I n ve sti gat or will n otif y t he I R B of t he c o ncl usi o n of t he cli nical st u d y wit hi n 1 m o nt h of 
c o m pleti o n or ter mi nati o n of t he st u d y.  T he fi nal re p ort se nt t o t he I R B will als o be se nt t o t he 
S p o ns or al o n g wit h t he c o m plete d electr o nic case re p ort f or ms (e C R Fs) a n d all necessar y 
re g ulat or y d oc u m e nts, t here b y f ulfilli n g t he I n v esti gat or’s re g ulat or y res p o nsi bilit y. 
T he I n vesti gat or, or a desi g nate d m e m ber of t he I n vesti gat or’s staff, m ust b e a vaila ble d uri n g 
m o nit ori n g visits t o re vie w data, res ol v e q ueries a n d all o w direct access t o patie nt rec or ds (e. g., 
me dical rec or ds, offi ce c harts, h os pital c harts, a n d st u d y-relate d c h arts) f or s o urce dat a 
verificati o n.  T he I n vesti gat or m ust e ns ure ti mel y a n d acc ur ate c o m pleti o n of e C R Fs a n d q ueries. 
1 3. 4.   
Pr ot oc ol A me n d me nts 
A n y p er ma ne nt c ha n ge t o t he pr ot oc ol, w het her it is a n o verall c h a n ge or a c ha n ge f or s pecific 
st u d y ce nt er(s), m ust be ha n dle d as a pr ot oc ol a m e n d me nt.  All a me n d me nts t o t he pr ot oc ol will 
be writte n b y t he S p o ns or.  T he I n vesti gat or will n ot ma ke a n y c h a n ges t o t his pr ot oc ol wit h o ut 
pri or writte n c o nse nt fr o m t he S p o ns or a n d s u bse q ue nt a p pr o val b y t he I R B.  E xce pt f or 
a d mi nistrati ve a me n d me nts, I n vesti gat ors m ust a wait I R B a p pr o val of pr ot oc ol a me n d me nts 
bef ore i m ple me nti n g t he c ha n ge(s).  T he S p o ns or will e ns ure s u b missi o n of a n y pr ot oc ol 
a me n d me nts t o t he a p pr o priate re g ul at or y a ge n cies. 
A d mi nistrati ve a me n d me nts are defi n e d as ha vi n g n o effect o n t he safet y of t he researc h 
s u bjects, sc o pe of t he i n v esti gati o n, or q u alit y of t he st u d y.  H o we ver, a pr ot oc ol c ha n ge 
i nte n de d t o eli mi nate a n a p pare nt i m me diate h azar d t o patie nts s h o ul d be i m ple me nte d 
i m me diatel y, a n d t he I R B n otifie d wit hi n 5 da ys.   
W he n, i n t he j u d g me nt of t he c hair m a n of t he l ocal I R B, t he I n v esti gat ors, a n d/ or t he S p o ns or, 
t he a me n d me nt t o t he pr ot oc ol s u bsta ntiall y alters t he st u d y desi g n a n d/ or i ncreas es t he p ote ntial 
ris k t o t he patie nt, t he c urre ntl y a p pr o ve d writte n I C F will re q uire si milar m o dificati o n.  I n s uc h 
cases, re peat i nf or me d c o nse nt will be o btai ne d fr o m patie nts e nr olle d i n t he st u d y bef ore 
c o nti n ue d partici pati o n u n der t he ne w a me n d me nt. 
1 3. 5.   
A u dits a n d I ns pecti o ns 
T he S p o ns or’s Q ualit y Ass ura nce U nit ( or re prese ntati ve) ma y c o n d uct a u dits at t he st u d y site(s).  
A u dits will i ncl u de, b ut are n ot li mite d t o:  dr u g s u p pl y, pres e nce of re q uire d d oc u me nts, t he 
i nf or me d c o nse nt pr o cess, la b orat or y s peci me n pr ocessi n g, a n d c o m paris o n of e C R Fs wit h 
s o urce d oc u m e nts.  T he I n vesti gat or a grees t o c o o perate wit h a u dits c o n d u cte d at a reas o n a ble 
ti me a n d i n a reas o n a ble ma n ner. 
Re g ulat or y a ut h orities w orl d wi de ma y als o a u dit t he I n vesti gat or d uri n g or after t he st u d y.  T he 
I n v estigat or s h o ul d c o ntact t he S p o ns or i m me diatel y if t his occ urs, a n d m ust f ull y c o o perate wit h 
t he a u dits c o n d ucte d at a reas o na bl e ti me i n a reas o na ble ma n ner. 
T he I n vesti gat or is r e q uir e d t o ma ke all st u d y d o c u me ntati o n pr o m ptl y a vaila ble f or i ns pecti o n, 
re vie w or a u dit at t he st u d y site u p o n re q uest b y S p o ns or, its re prese nt ati ves, or a n y a p pr o priate 
re g ulat or y a ge ncies. 
1 3. 6.   
Q u alit y C o ntr ol a n d Q u alit y Ass ur a nce 
All as pects of t he st u d y will be caref ull y m o nit ore d b y t h e S p o ns or or its a ut h orize d 
re pres e ntati ve f or c o m plia nce wit h a p plica ble g o v er n me nt re g ul ati o ns wit h res pect t o c urre nt 
G C P a n d sta n dar d o perati n g pr oce d ures.   


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A q ualit y  c o ntr ol a n d q ualit y ass ura n ce pla n a d dressi n g as pects of t he st u d y t hat ma y i m pact data 
i nte grity or t he pr otecti o n of h u ma n s u bjects ma y be i nstit ute d f or t his st u d y.  All a u dit fi n di n gs 
will be s u m marize d a n d place d o n file wit h a p pr o priate d oc u me ntati o n of res p o nse/res ol uti o n. 


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1 4.   
D A T A H A N D LI N G A N D R E C O R D K E E PI N G 
1 4. 1.   
C o nfi de nti alit y 
All i nf or mati o n discl ose d or pr o vi de d b y t he S p o ns or ( or desi g nee), or ge nerate d or pr o d uce d 
d uri n g t he st u d y  i ncl u di n g, b ut n ot li mite d t o, t he pr ot oc ol, t he e C R Fs, t he I n v esti gat or’s 
Br oc h ure, a n d t he res ults o btai ne d d uri n g t h e c o urse of t he st u d y, are c o nfi de ntial.  T he 
I n v esti gat or or a n y p ers o n u n der his/ her a ut h orit y a grees t o k ee p c o nfi de ntial a n d n ot t o discl ose 
t he i nf or mati o n t o a ny t hir d part y wit h o ut t he pri or writte n a p pr o val of t h e S p o ns or. 
S u b missi o n of t his pr ot oc ol a n d a n y ot her n ecessar y d o c u me ntati o n t o t he I R B is e x pressl y 
per mitte d, I R B me m bers ha vi n g t he s a me o bli gati o n of c o nfi de ntialit y. A ut h orize d re g ulat or y 
officials a n d s p o ns or pe rs o n nel ( or desi g nee) will be all o we d f ull access t o i ns pect a n d c o p y t he 
rec or ds.  T h e c o pie d a n d i ns pecte d rec or ds will re mai n at t he site a n d will n ot be tra ns mitte d or 
re m o ve d fr o m t he site.  St u d y dr u g, p ati e nt b o dil y fl ui ds, a n d/ or ot her materials c ollecte d s hall be 
use d s olel y i n acc or da nce wit h t his pr ot oc ol, u nless ot her wise a gree d t o i n writi n g b y t he 
S p o ns or a n d res p o nsi ble et hics c o m mittee(s) or re g ulat or y a ut h orities. 
Patie nts’ na mes ma y, h o we ver, be ma de k n o w n t o a re g ulat or y a ge n c y or ot her a ut h orize d 
officials i n t he e ve nt of i ns pecti o ns.  D oc u me nts c o ntai ni n g t he f ull na me or ot her pers o nall y 
i de ntifia ble i nf or mati o n of t he patie nt are t o re mai n at t he site.  T his i nf or mati o n will n ot be 
tra nsferre d t o t he S p o ns or n or be c o nt ai ne d i n re g ulat or y fili n gs.   
1 4. 2.   
P atie nt D at a Pr otecti o n 
Pri or t o a n y testi n g u n der t his pr ot oc ol, i ncl u di n g scree ni n g tests a n d assess me nts, ca n di dates 
m ust als o pr o vi de all a ut h orizati o ns re q uire d b y l ocal la w (e. g., pr otecte d healt h i nf or mati o n 
a ut h orizati o n).  
Patie nts will be i de ntifie d o nl y b y u ni q ue patie nt n u m bers i n e C R Fs a n d ot her datasets ge nerate d 
f or t his st u dy.  T he p atie nt will n ot be i de ntifie d b y na m e i n t he e C R F, i n a n y st u d y sa m ples or 
st u d y rep orts. All data ge nerate d i n t his st u d y is f or researc h p ur p oses o nl y.  T he S p o ns or, its 
part ner(s) a n d desi g n ee(s), a n d vari o us g o v er n me nt healt h a ge ncies m a y i ns pect t he rec or ds of 
t his st u d y.  E v er y eff ort will be ma de t o kee p t he patie nt’s pers o nal me di cal data c o nfi de ntial.  
T he S p o ns or will pr otect i n di vi d ual patie nt i nf or mati o n t o t he f ullest e xte nt p ossi ble d uri n g t his 
st u d y.  At n o ti me will a patie nt bec o me i de ntifie d i n a n y p u blicati o n or prese ntati o n.  H o we ver, 
t he patie nt ma y ha ve t o b ec o me i de ntifie d i n t he e ve nt of a re g ulat or y a ut h orit y a u dit or 
i ns pecti o n i n or der t o verif y t he acc urac y of t he data.  Access t o patie nt i nf or mati o n is at t he 
discreti o n of t he S p o ns or a n d ca n n ot occ ur pri or t o data base l oc k or ot her s pecifie d e v e nts as 
deter mi ne d s olel y b y t he discreti o n of t he S p o ns or. 
1 4. 3.   
D at a C ollecti o n 
All data o btai ne d f or a nal ysis i n t he cli nical st u d y descri be d i n t his pr ot oc ol will use a n 
electr o nic d ata ca pt ure s yste m.  Data re p orte d i n t he e C R Fs s h o ul d be c o nsiste nt wit h a n d 
s u bsta ntiate d b y t he patie nt’s m e dical rec or d a n d ori gi nal s o urce d oc u m e nts.  A n y discre pa n cies 
m ust be e x plai ne d.   
Pri or t o t he start of t he st u d y, t he Pri nci pal I n vesti gat or will c o m plete a Dele gati o n of A ut h orit y 
f or m ( Site Si g nat ur e a n d Dele gati o n L o g), s h o wi n g t he si g nat ures a n d ha n d writte n i nitials of all 


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i n di vi d uals a n d t he delegati o n of res p o nsi bilities, s uc h as i de ntif yi n g t h os e i n di vi d uals w h o are 
a ut h orize d t o ma ke or c h a n ge e ntries o n e C R Fs. 
1 4. 4.   
C ase Re p ort F or m C o m pleti o n 
Data wit hi n t he e C R F will be m o nit ore d b y a Cli nical Researc h Ass ociat e acc or di n g t o t he 
M o nit ori n g Pla n.  Q ueries will be ge n erat e d base d o n discre pa n cies f o u n d w hile m o nit ori n g.  
Site pers o n nel will re vie w a n d res p o n d t o t hese q ueries a p pr o priatel y.  A d diti o nall y, t h e 
S p o ns or’s desi g n ee a n d t he S p o ns or ma y p eri o dicall y perf or m a g gre gate data re vie ws, w hic h 
c o ul d res ult i n q ueries bei n g ge n erate d f or site pers o n nel res ol uti o n.  T he c o m plete d e C R F f or 
eac h p atie nt m ust be si g n e d a n d date d b y t h e Pri nci pal I n v esti gat or t o si g nif y t hat t he Pri nci pal 
I n v esti gat or has re vie we d t he e C R F a n d certifies it t o be c o m plete a n d acc urate. 
1 4. 5.   
D at a b ase M a n a ge me nt, D at a Cl arific ati o n, a n d Q u alit y Ass ur a nce 
T he S p o ns or’s desi g nee (i.e., a desi g nate d C o ntract Researc h Or ga nizati o n) will be res p o nsi ble 
f or data ma na ge me nt.  Data Ma na ge me nt will de v el o p a Data Ma na ge m e nt Pla n ( D M P ) 
d oc u me nt, a n d pr o vi de it t o t he S p o ns or f or a p pr o val.  T he D M P d oc u me nt will defi ne all 
acti vities i n t he data c ollecti o n a n d clea ni n g pr ocess.  T he detaile d D M P will be base d o n t he 
pr ot oc ol, w or k sc o p e, c o ntract, a nal ysis pla ns, dat a-fl o ws, e C R Fs, d ata clea ni n g pr oce d ures, 
ot her s u p p orti n g d o c u me nts, a n d data ma na ge me nt sta n dar ds a n d practices. 
T he pr o gra m me d d ata vali dati o ns will be r u n t o c hec k f or d ata bas e c o m plete ness a n d 
c o nsiste nc y, a n d q ueries will be ge n erat e d u p o n d ata e ntr y or via re vie w b y a Cli nical D ata 
Ma na ge r after e ntr y.  T h e sites will res p o n d t o t he data q ueries i n a ti mel y ma n ner. 
Q ualit y c o ntr ol pr oce d ures will be c o n d ucte d pri or t o data base l o c k acc or di n g t o t he desi g nat e d 
C o ntract Resear c h Or ga nizati o n sta n dar d o perati n g pr oce d ures. 
W he n t he data base h as b ee n declare d t o b e c o m pl ete a n d acc urate, it will be l oc ke d.  A n y 
c ha n ges t o t he dat a base after t hat ti me will o nl y be ma de b y j oi nt writte n a gree me nt bet w ee n t he 
S p o ns or, Statisticia n, Data Ma na ger, a n d Q ualit y Ass ura nce A u dit or acc or di n g t o desi g nate d 
sta n dar d o perati n g pr oce d ures of t he C o ntract Researc h Or ga nizati o n. 
1 4. 6.   
I ns pecti o n of Rec or ds 
Acc or di n g t o t he I C H g ui deli nes f or G C P, t he S p o ns or or desi g nee m ust verif y d ata e nt ere d i n 
t he e C R F e ntries a gai nst t he s o urce d o c u me nts. T he o bjecti ve of s o urce d o c u me nt verificati o n is 
t o c o m pl y wit h G C P a n d i nter nati o nal re g ulat or y re q uire me nts a n d t o re d uce t he ris ks of fra u d.  
S o urce d oc u me nt verificati o n mea ns e ns uri n g t hat s o urce d oc u me nts are a n acc urate a n d 
c o nfir ma ble r eflecti o n of t he patie nt’s e val u ati o ns d uri n g partici pati o n i n t he st u d y a n d t hat all 
rele va nt i nf or m ati o n rec or de d i n t he s o urce d oc u m e nt is acc uratel y e ntere d i nt o t he e C R F. All 
s o urce d oc u me nts s h o ul d be c orrectl y la bele d a n d file d a n d ass ociat e d wit h a si n gle, verifia ble 
patie nt. 
All data re q uir e d f or t his st u d y s h o ul d be ca pt ure d i n s o urce n otes.  N o data o btai ne d b y t h e 
I n v estigat or or ot her st u d y pers o n nel s h o ul d be ca pt ure d directl y i n t he e C R F.  All s o urce 
d oc u me nts pertai ni n g t o t his st u d y will be mai ntai ne d b y t h e I n vesti gat or a n d ma de a vaila ble f or 
i ns pecti o n b y a ut h orize d pers o ns.  If electr o nic pr o gress n otes a n d ot her el ectr o nic s o urce 
d oc u me nts are n ot c o m plia nt wit h a p plica ble re g ul at or y g ui d a nce, t h e y are n ot c o nsi dere d a v ali d 
s o urce f or t his st u d y.  All patie nt pr o gress n otes m ust be date d a n d si g ne d at t he ti me of t he visit.  


C T P - 5 4 3 
 
2 1 J a n uar y 2 0 1 9 
Pr ot oc ol C P 5 4 3. 2 0 0 1, A me n d me nt 5   
 
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C O N FI D E N TI A L & P R O P RI E T A R Y   
6 2 
 
T he S p o ns or re ser ves t he ri g ht t o ter mi nate t he st u d y f or ref usal of t he I n vesti gat or t o s u p pl y 
ori gi nal s o urce  d oc u m e ntati o n f or t his cli nical st u d y. 
T he I n vesti gat or will n ot e i n a s o urce i n de pe n d e nt fr o m t he e C R F t he f oll o wi n g i nf or m ati o n: 
 I nf or mati o n t o c o nfir m t hat t he patie nt e xists ( e. g., i nitials, date of birt h, a n d se x); 
 C o nfir mati o n t hat t he patie nt satisfies t he i ncl usi o n/e xcl usi o n criteria; 
 C o nfir mati o n t hat t he patie nt is ta ki n g part i n t he cli nical st u d y; 
 C o nfir mati o n of t he i nf or me d c o nse nt pr ocess; 
 Visit date s a n d d oc u me nt ati o n of pr ot oc ol assess m e nts a n d pr oce d ures; 
 I nf or mati o n c o ncer ni n g all a d verse e v e nts; 
 Details o f c o nc o mita nt a n d i n vesti gati o nal me dicati o ns. 
S o urce  d oc u me nt verificati o n is n ot a s u bstit ute f or cli nical st u d y m o nit ori n g, t he p ur p ose of 
w hic h is t o e ns ure  t hat t h e pr ot oc ol has bee n f oll o we d c orrectl y, t he e C R F has bee n f ull y a n d 
acc uratel y c o m plete d, s o urce d oc u m e nt verificati o n has bee n carri e d o ut, a n d t he st u d y ti meli nes 
a n d e nr oll me nt g oals a n d re q uire me nts ha v e bee n met. 
1 4. 7.   
Rete nti o n of Rec or ds 
F or i n vesti gati o nal dr u g st u dies, cli nical I n v esti gat ors m ust retai n st u d y rec or ds f or a p eri o d of 
2 years f oll o wi n g t he dat e a mar k eti n g a p plicati o n is a p pr o ve d f or t h e dr u g f or t he i n dicati o n f or 
w hic h it is bei n g i n vesti gate d; or, if n o a p plicati o n is t o be file d or if t he a p plicati o n is n ot 
a p pr o ve d f or s uc h i n dicati o n, u ntil t w o years after t he i n vesti gati o n is disc o nti n ue d a n d F D A is 
n otifie d. 
T he I n vesti gat or m ust mai ntai n all st u d y d oc u me ntati o n as c o nfi de ntial, a n d ta ke meas ures t o 
pre ve nt acci de ntal or pre mat ure de str ucti o n of t h ese d oc u me nts. 
T he I n vesti gat or m ust n otif y t he S p o ns or pri or t o destr o yi n g a n y st u d y ess e ntial d oc u me nts. 
If t he I n vesti gat or can n o l o n ger e ns ure arc hi vi n g, he/s he s hall i nf or m t he S p o ns or.  T he rel e va nt 
rec or ds s h all be tra nsferre d t o a m ut uall y a gree d u p o n desi g n ee. 


C T P - 5 4 3 
 
2 1 J a n uar y 2 0 1 9 
Pr ot oc ol C P 5 4 3. 2 0 0 1, A me n d me nt 5   
 
C o ncert P har mace uticals, I n c. 
C O N FI D E N TI A L & P R O P RI E T A R Y   
6 3 
 
1 5.   
P U B LI C A TI O N P O LI C Y 
T he res ults of t his st u d y ma y b e p u blis he d i n a me dical p u blicati o n, j o ur nal, or a n ot her p u blic 
disse mi nati o n, or ma y be prese nte d at a me dical c o nfere n ce or us e d f or t eac hi n g p ur p oses.  
A d diti o nall y, t his st u d y a n d its res ults ma y be s u b mitte d f or i ncl usi o n i n all a p pr o priate healt h 
a ut h orit y st u d y re gistries, as well as p u blicati o n o n healt h a ut h orit y st u d y re gistr y we bsites, as 
re q uire d b y l ocal healt h a ut h orit y re g ul ati o ns.  Selecti o n of first a ut h ors hi p will be base d o n 
several c o nsi derati o ns, i n cl u di n g, b ut n ot li mite d t o st u d y partici p ati o n, c o ntri b uti o n t o t he 
pr ot oc ol de vel o p me nt, a n d a nal ysis a n d i n p ut i nt o t he ma n uscri pt, relat e d a bstracts, a n d 
prese ntati o ns i n a st u d y. 


C T P - 5 4 3 
 
2 1 J a n uar y 2 0 1 9 
Pr ot oc ol C P 5 4 3. 2 0 0 1, A me n d me nt 5   
 
C o ncert P har mace uticals, I n c. 
C O N FI D E N TI A L & P R O P RI E T A R Y   
6 4 
 
1 6.   
LI S T O F R E F E R E N C E S 
First A ut h or ( Ye ar)   
Cit ati o n  
Al -M utairi ( 2 0 1 1)  
Al -M utairi N , El di n O N.  Cli nical pr ofile a n d i m pact o n q ualit y of life: se ve n 
years e x perie nce wit h patie nts of al o pecia areata.  I n dia n J Der mat ol Ve nere ol 
Le pr ol. 2 0 1 1 J ul -A u g; 7 7( 4): 4 8 9 -9 3.  
Bil gic ( 2 0 1 3)  
Bil giç Ö, Bil giç A, Ba halı K, Ba hali A G, G ür ka n A, Yıl maz S. Ps yc hiatr ic 
s y m pt o mat ol o g y a n d healt h-relate d q ualit y of life i n c hil dre n a n d a d olesce nts 
wit h al o pecia areata. J E ur Aca d Der mat ol Ve nere ol. 2 0 1 4 N o v; 2 8( 1 1): 1 4 6 3 -
8.  
Crai gl o w ( 2 0 1 4)  
Crai gl o w B G , Ki n g BA. Killi n g t w o bir ds wit h o ne st o ne: oral t ofaciti ni b 
re verses al o pecia u ni versalis i n a patie nt wit h pla q ue ps oriasis. J I n vest 
Der mat ol. 2 0 1 4: 1 3 4( 1 2): 2 9 8 8 -2 9 9 0.  
Cris pi n ( 2 0 1 6)  
Cris pi n M K, K o J M, Crai gl o w B G, et al. Safet y a n d efficac y of t he J A K 
i n hi bit or t ofaciti ni b citrate i n patie nts wit h al o pecia areata. J CI I nsi g ht. 2 0 1 6 
Se p: 1( 1 5):e 8 9 7 6 6.  
G h oresc hi  (2 0 0 9 ) 
G h oresc hi  K., La ure nce A., O’ S hea JJ. Ja n us ki nases i n i m m u ne  cell 
si g nali n g. Im m u n ol Re v. 2 0 0 9; 2 2 8( 1): 2 7 3 -8 7.  
Harris ( 2 0 1 6)  
Harris J E, Ras hi g hi M, N g u ye n N, J a b bari A, Uleri o G, Cl y nes R, C hristia n o 
A M, Mac ka y -Wi g ga n J. J A m Aca d Der mat ol. 2 0 1 6: 7 4( 2): 3 7 0 -3 7 1.  
Ja bb ari ( 2 0 1 5) 
Ja b bari A, Dai Z, Xi n g L, et al.  Re versal of Al o pecia Areata F oll o wi n g 
Treat me nt wit h t he J A K 1/ 2 I n hi bit or Bariciti ni b. E Bi o Me dici ne. 2 0 1 5( 2): 
3 5 1 – 3 5 5.  
Ja kafi ( 2 0 17 ) 
Ja kafi prescri bi n g i nf or mati o n. I nc yte C or p orati o n. Wil mi n gt o n, D E. 2 0 1 7 . 
Mac ka y -Wi g ga n ( 2 0 1 6)  Mac ka y -Wi g ga n J, J a b bari A, N g u ye n N, et al. Oral r u x oliti ni b i n d uces hair 
re gr o wt h i n patie nts wit h m o derate-t o-se vere al o pecia areata. J CI I nsi g ht. 
2 0 1 6 Se p: 1( 1 5):e 8 9 7 9 0.  
Me n d oza ( 2 0 1 3)  
Me n d oza T R, Osei J S, S hi Q, D u vic M. De vel o p me nt of t he al o pecia areata 
s y m pt o m i m pact scale. J I n vesti g Der mat ol S y m p Pr oc. 2 0 1 3 Dec; 1 6( 1): S 5 1 -
2 . 
Olse n ( 2 0 0 4)  
Olse n E A , H or di ns k y M K, Price V H, et al. Al o pecia areata i n vesti gati o nal 
assess me nt g ui deli nes --Part II. Nati o nal Al o pecia Areata F o u n dati o n.  J A m 
Aca d Der mat ol. 2 0 0 4 Se p; 5 1( 3): 4 4 0 -7.  
Safa vi ( 1 9 9 2) 
Safa vi K. Pre vale nce of al o pecia areata i n t he First Nati o nal Healt h a n d 
N utriti o n E xa mi nati o n S ur ve y. Arc h Der mat ol. 1 9 9 2; 1 2 8( 5): 7 0 2 . 
Sella mi ( 2 0 1 4)  
Sella mi R, Mas m o u di J, O uali U, et al. T he relati o ns hi p bet wee n al o pecia 
areata a n d ale xit h y mia, a n xiet y a n d de pressi o n: a case -c o ntr ol st u d y. I n dia n J 
Der mat ol. 2 0 1 4 J ul; 5 9( 4): 4 2 1.  
S hi ( 2 0 1 1)  
S hi J G , C he n X, Mc Gee R F, et al. T he p har mac o ki netics, p har mac o d y na mics, 
a n d safet y of orall y d ose d I N C B 0 1 8 4 2 4 p h os p hate i n healt h y v ol u nteers. J 
Cli n P har mac ol. 2 0 1 1; 5 1: 1 6 4 4 -5 4.  
Villa sa nte Fric ke ( 2 0 1 5) Villa sa nte Fric ke A C, Mite va, M.  E pi de mi ol o g y a n d b ur de n of al o pecia 
areata: a syste matic re vie w. Cli n C os met I n vesti g Der mat ol. 
2 0 1 5  J ul 2 4; 8: 3 9 7 -4 0 3.  
Xi n g ( 2 0 1 4)  
Xi n g L, Dai Z, J a b bari A, et al. Al o pecia areata is dri ve n b y c yt ot o xic 
T  l y m p h oc ytes a n d is re verse d b y J A K i n hi biti o n. Nat Me d. 2 0 1 4 
Se p; 2 0( 9): 1 0 4 3 -9.  


















A me n d me nt 2   
0 5 J ul y 2 0 1 7   
• S t u d y d esi g n was c h a n ge d t o c o nsist of u p t o 2 
c o h orts i nitiate d se q ue ntiall y i n asce n di n g d ose 
or der.  A c o h ort wit hi n t he st u d y was di vi de d i nt o 3 
peri o ds: Scree ni n g, Treat me nt, a n d P ost -treat me nt 
Safet y F oll o w -u p.  T h e D ose A dj ust me nt Peri o d was 
re m o ve d. 
 
• Ti mi n g of D M C re vi e ws of c ollecti ve safet y data 
f or eac h co h ort clarifie d f or i nitial of s u bse q ue nt 
d osi n g co h orts.  
 
• Ra n d o mizati o n rati os f or eac h treat me nt ar m  
re vise d. 
 
• N u m ber of patie nts e nr olle d re vise d . 
 
• La n g ua ge s urr o u n di n g d ose a dj ust me nt peri o d 
re m o ve d. 
 
• Statistical met h o ds secti o n re vise d t o reflect 
a dj uste d p o wer calc ulati o ns.  
 
A me n d me nt 1   
1 4 Fe br uar y 2 0 1 7   
• In cl usi o n/e xcl usi o n criteria were re vise d f or 
patie nt safet y a n d/ or f or clarificati o n.  
 
• A d diti o nal la n g ua ge a d de d f or cl arificati o n 
s urr o u n di n g t h e para meters f or d ose i nterr u pti o n , 
re peat testi n g f or c o nfir m ati o n of la b orat or y v al ues, 
a n d re q uire me nts f or m o nit ori n g a n d d ose 
res u m pti o n. 
 
• Eac h patie nt’s me di cal hist or y was t o b e 
t h or o u g hl y pr o be d f or v acci nati o n a gai nst her pes 
z oster or ot her rece nt li ve vir us vacci nati o ns.  
 
Ori gi nal pr ot oc ol  1 4 N o ve m ber 2 0 1 6  
N ot a p plica ble ( N/ A)  
 
 

SAP_001.pdf: 
 
Offici al Titl e:  
A D o u bl e -Bli n d, R a n d o miz e d, Pl ac e b o -C o ntr oll e d, P ar all el D os e St u d y t o 
E v al u at e t h e S af et y a n d Effic ac y of C T P -5 4 3 I n A d ult P ati e nts Wit h M o d er at e 
t o S e v er e Al o p eci a Ar e at a 
N C T N u m b er:  
 
N C T 0 3 1 3 7 3 8 1  
 
D oc u m e nt  D at e : 
 
S A P  V ersi o n 2 : 07 M ay 2 0 1 9 
 
 
 
 
 
 
 




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T A B L E O F C O N T E N T S 
LI S T O F A B B R E VI A TI O N S ......................................... ................................................... 6 
LI S T O F I N- T E X T T A B L E S ........................................ .................................................... 8 
1.  
P U R P O S E O F T H E S T A TI S TI C A L A N A L Y SI S P L A N ...................... ...................... 9 
2.  
P R O T O C O L S U M M A R Y .............................................. ......................................... 1 0 
2. 1  
St u d y O bj e cti v e s............................................... .......................................... 1 0 
2. 1. 1  
Pri m ar y O bj e cti v e ............................................. ................................. 1 0 
2. 1. 2  
E x pl or at or y O b j e cti v e s ...................................................................... 1 0 
2. 2  
St u d y D e si g n .................................................. ............................................ 1 0 
2. 3  
St u d y P o p ul ati o n .............................................. .......................................... 1 2 
2. 4  
Tr e at m e nt R e gi m e n s ............................................ ...................................... 1 2 
2. 5  
Tr e at m e nt Gr o u p A s si g n m e nt s or R a n d o mi z ati o n .................. .................... 1 2 
2. 6  
S a m pl e Si z e D et e r mi n ati o n ........................................................................ 1 3 
3.  
G E N E R A L A N A L Y SI S A N D R E P O R TI N G C O N V E N TI O N S .................... ............. 1 4 
4.  
A N A L Y SI S P O P U L A TI O N S .................................................................................. 1 6  
4. 1  
Effi c a c y P o p ul ati o n ........................................... .......................................... 1 6 
4. 2  
P h ar m a c o ki n eti c P o p ul ati o n .................................... ................................... 1 6 
4. 3  
S af et y P o p ul ati o n ............................................. .......................................... 1 6 
4. 4  
P er Pr ot o c ol P o p ul ati o n .............................................................................. 1 6  
5.  
S T U D Y P A TI E N T S ................................................................................................ 1 7  
5. 1  
Di s p o siti o n of P ati e nt s ....................................... ......................................... 1 7 
5. 2  
Pr ot o c ol D e vi ati o n s ..................................................................................... 1 7 
6.  
D E M O G R A P HI C A N D O T H E R  B A S E LI N E C H A R A C T E RI S TI C S ........................ 1 8 
6. 1  
Pri or a n d C o n c o mit a nt M e di c at i o n s ............................................................ 1 9 
7.  
M E A S U R E M E N T S O F T R E A T M E N T C O M P LI A N C E .......................... ................. 2 0 
8.  
E F FI C A C Y E V A L U A TI O N ..................................................................................... 2 1  
8. 1  
Pri m ar y Effi c a c y  E n d p oi nt ........................................................................... 2 1 
8. 1. 1  
S e v erit y of Al o p e ci a T o ol ( S A L T) ....................................................... 2 1 
8. 2  
E x pl or at or y Effi c a c y E n d p o i nt s ................................................................... 2 1 
8. 2. 1  
Vi s u al A n al o g S c al e ( V A S)  ................................................................ 2 2 
Cli nicia n V A S of Se verit y ( V A S- S)  ............................................................ 22  
Patie nt V A S of Se verit y ( V A S- S)  ............................................................... 2 2 
8. 2. 2  
Cli ni c al Gl o b al I m pr e s si o n o f I m pr o v e m e nt ( C GI-I) ............................ 2 3 
8. 2. 3  
P ati e nt Gl o b al I m pr e s si o n of I m pr o v e m e nt ( P GI-I) .............. .............. 2 3 
8. 2. 4  
P ati e nt R e p ort e d O ut c o m e s: Al o p e ci a Ar e at a S y m pt o m I m p a ct S c al e  
( A A SI S) a n d E x pl or at or y Q u e sti o ns ............................. ..................... 2 3 
8. 3  
O v er vi e w of Effi c a c y  A n al y si s I s s u e s .......................................................... 2 3 
8. 3. 1  
H a n dli n g of Dr o p o ut s  or Mi s si n g D at a ............................................... 2 3 
8. 3. 2  
M ulti c e nt er St u di e s ........................................... ................................. 2 4 
8. 3. 3  
A s s e s s m e nt Vi sit  Wi n do w s ................................................................ 2 4  
8. 4  
A n al y si s M et h o d s .............................................. ......................................... 2 4 
8. 4. 1  
Pri m ar y Effi c a c y  A n al y si s .................................................................. 2 6 
8. 4. 2  
E x pl or at or y Effi c a c y A n al y s e s ................................. .......................... 2 7 
8. 5  
E x a mi n ati o n of S u b gr o u p s  .......................................................................... 2 8 


C o ncert P har mace uticals I nc. 
C O N FI D E N TI A L  
Statistical A nal ysis Pla n 
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S A F E T Y E V A L U A TI O N ............................................. ............................................ 2 9 
9. 1  
O v er vi e w of S af et y A n al y si s M et h o d s  ......................................................... 2 9 
9. 2  
A d v er s e E v e nt s ................................................ .......................................... 2 9 
9. 3  
Cli ni c al L a b or at or y E v al u a ti o n .................................................................... 3 1 
9. 4  
Vit al Si g n s, P h y si c al Fi n di n g s, a n d Ot h er O b s er v ati o n s R el at e d t o S af et y.. 3 2 
9. 4. 1  
Vit al Si g n s ................................................... ...................................... 3 2 
9. 4. 2  
E C G .................................................................................................. 3 2  
9. 4. 3  
P h y si c al E x a mi n ati o n s ......................................... ............................. 3 2 
1 0.  P H A R M A C O KI N E TI C E V A L U A TI O N .................................................................... 3 3  
1 0. 1  
P h ar m a c o ki n eti c a n d P h ar m a c o d y n a mi c M et h o d s ................... .................. 3 3 
1 1.  I N T E RI M A N A L Y S E S A N D D A T A M O NI T O RI N G ................................................. 3 4 
1 2.  C H A N G E S T O T H E A N A L Y S E S P L A N N E D I N T H E P R O T O C O L ............... ........ 3 5 
1 3.  R E F E R E N C E S ...................................................................................................... 3 6  
1 4.  LI S T O F P L A N N E D T A B L E S ........................................ ........................................ 3 7 
1 5.  LI S T O F P L A N N E D  FI G U R E S .............................................................................. 4 4 
1 6.  LI S T O F P L A N N E D D A T A LI S TI N G S ................................. .................................. 4 5 
1 7.  A P P E N DI C E S ........................................................................................................ 4 7 
1 7. 1  
St u d y Fl o w C h art .............................................. .......................................... 4 7 
1 7. 2  
S c h e d ul e of E v e nt s ..................................................................................... 4 8 
1 8.  A T T A C H M E N T S .................................................................................................... 5 0  
 


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LI S T O F A B B R E VI A TI O N S 
 
 
A b bre vi ati o n or 
S peci alist Ter m 
E x pl a n ati o n 
A A SI S 
Al o pecia Areata S y m pt o m I m pact Scale 
A E 
A d verse e ve nt 
A N C O V A 
A nal ysis of C o varia nce 
A T C 
A nat o mical- T hera pe utic- C he mical 
BI D 
T wice dail y d osi n g 
C GI-I 
Cli nical Gl o bal I m pressi o n of I m pr o ve me nt 
CI 
C o nfi de nce i nter val 
C M H 
C oc hra n- Ma ntel- Hae nszel T est 
C S R 
Cli nical st u d y re p ort 
C T C A E 
C o m m o n ter mi n ol o g y criteria f or a d verse e ve nts 
D M C 
Data m o nit ori n g c o m mittee 
E C G 
Electr ocar di o gra m 
e C R F 
Electr o nic case re p ort f or m 
H D L 
Hi g h- de nsit y li p o pr otei n 
I C H 
I nter nati o nal C o nfere nce o n Har m o nisati o n 
L D L 
L o w- de nsit y li p o pr otei n 
L O C F 
Last O bser vati o n Carrie d F or war d 
Me d D R A 
Me dical Dicti o nar y f or Re g ulat or y Acti vities 
M M R M 
Mi xe d-effects M o del of Re peate d Meas ures 
P D 
P har mac o d y na mic 
P GI-I 
Patie nt Gl o bal I m pressi o n of I m pr o ve me nt 
P K 
P har mac o ki netic 
Q T 
Q T i nter val  
Q T c F 
Q T i nter val c orrecte d f or heart rate ( Fri dericia’s met h o d)  
S A E 
Seri o us A d verse E ve nt 
S A L T 
Se verit y of Al o pecia T o ol 
S A P 
Statistical A nal ysis Pla n 
S D 
Sta n dar d de viati o n 
S O C 
S yste m or ga n class 


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T E A E 
Treat me nt-e mer ge nt a d verse e ve nts 
V A S- S 
Vis ual A nal o g Scale of Se verit y 
W H O 
W orl d Healt h Or ga nizati o n 
2 
C hi-s q uare d test 


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LI S T O F I N- T E X T T A B L E S 
T a bl e 8- 1  
Effi c a c y V ari a bl e s a n d A n al y si s M et h o d s ....................... ............... 2 5  
 
 


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1.  P U R P O S E O F T H E S T A TI S TI C A L A N A L Y SI S P L A N 
 
T his statistical a nal ysis pla n ( S A P) c o ntai ns detail e d i nf or mati o n t o ai d i n t he i m ple me ntati o n of 
t he statistical a nal ys es a n d re p orti n g of t he st u d y d ata f or use i n t he cli nical st u d y re p ort ( C S R) 
f or st u d y C P 5 4 3. 2 0 0 1.  T his S A P is bei n g writte n wit h d ue c o nsiderati o n of t he 
rec o m me n dati o ns o utli ne d i n t he most rece nt I nter nati o nal C o nfe re n ce o n Har m o nisati o n (I C H) 
E 9 G ui deli ne, e ntitle d G ui da nce f or I n d ustr y: Statistical Pri nc i ples f or Cli nical Trials, a n d t he 
m ost rece nt I C H E 3 G ui d eli ne, e ntitle d G ui da nce f or I n d ustr y: S tr u ct ure a n d C o nte nt of Cli nical 
St u d y R e p orts. 
T his S A P descri bes t he d ata sets  t hat will be use d f or a nal ysis, as w ell as patie nt c haracteristics, 
effic ac y, safet y, p har m ac o ki netic ( P K), p har mac o d y na mic ( P D), a n d cli nicia n-re p ort e d a n d 
patie nt-re p ort e d perce pti o n of disease se v erit y a n d i m pr o ve me nt para m eters.  T he details of t he 
s pecific statistical met h o ds state d i n t he pr ot oc ol will be pr ovi de d a n d a n y c ha n ges fr o m t he 
pr ot oc ol-s pecifi e d a nal ys es w ill be d oc u me nte d i n t he S A P pri or t o data bas e l oc k.  
P har mac o ki netic a n al yses are o utsi de t he sc o p e of t his d oc u me nt  a n d will be perf or me d a n d 
re p orte d se p aratel y.  If a d diti o nal a nal yses are re q uire d t o s up ple me nt t he pla n ne d a nal yses 
descri be d i n t his S A P after t he da ta b ase l oc k, t h e y ma y b e c o m plete d a n d will be descri be d i n t he 
C S R.  Ta ble, fi g ure, a n d listi n g s pecificati o ns are pr o vi de d as  a n attac h me nt i n a se parat e 
d oc u me nt. T he C P 5 4 3. 2 0 0 1 pr ot oc ol a me n d me nt 2. 0 was fi nalize d o n 0 5 J ul y 2 0 1 7.  T he 
p ur p ose of t his a me n d me nt was t o re vise f or a ne w se q ue ntial c o h ort st u d y desi g n, w here a 
parallel acti ve d ose c o m p aris o n w o ul d n o l o n ger b e c o n d ucte d.  A me n d me nt 3. 0, date d 2 5 
Se pte m ber 2 0 1 7, f urt her clarifies t his re vise d a p pr oac h.  A me n d me nt 4. 0, d ate d 1 7 A u g ust 2 0 1 8, 
i ncl u de d a n a d diti o nal C o h ort of s u bjects t o assess a 1 2 m g BI D d os e of C T P- 5 4 3 c o m pare d t o 
place b o.  T he s a m ple siz e calc ul ati o ns were u p d at e d t o reflect t he a d diti o nal patie nts e nr olle d.  
A me n d me nt 5. 0, date d 2 1 J a n uar y  2 0 1 9, i ncl u de d la n g u a ge f or allo wi n g eli gi ble patie nts w h o 
c o m plete d d osi n g f or 2 4 wee ks t o e nter a n o pe n-la bel e xte nsi o n st u d y of C T P- 5 4 3.  T his S A P is 
base d o n t he latest pr ot oc ol a me n d me nt. 


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2.  P R O T O C O L S U M M A R Y 
2. 1  St u d y O bj e cti v e s 
T he o verall o bjecti ves of t he st u d y are t o assess t h e safet y a n d efficac y of a 2 4- wee k re gi me n of 
a d mi nistrati o n of C T P- 5 4 3 i n a d ult patie nts wit h c hr o nic, m o der ate t o se v ere al o p ecia areata. 
 
2. 1. 1  Pri m ar y O bj e cti v e  
 T o assess t he effect of C T P- 5 4 3 o n treati n g h air l oss as meas ur e d b y t h e Se verit y of 
Al o pecia T o ol ( S A L T); 
 T o assess t he safet y of a d mi nistr ati o n of C T P- 5 4 3 i n a d ult pati e nts wit h c hr o nic, 
m o derate t o se v ere al o pe cia areata. 
 
2. 1. 2  E x pl or at or y O bj e cti v e s 
 T o assess t he c h a n ge i n al o pecia areata s e verit y as meas ure d b y  t he cli nicia n Vis ual 
A nal o g Scale of Se v erit y ( V A S- S) fr o m bas eli ne; 
 T o assess t he Cli nical Gl o bal I m pressi o n of I m pr o ve me nt ( C GI-I) ; 
 T o assess t he c h a n ge i n al o pecia areata s e verit y as meas ure d b y  t he patie nt V A S- S fr o m 
baseli ne; 
 T o assess t he Patie nt Gl o bal I m pressi o n of I m pr o v e me nt ( P GI-I);   
 T o assess t he c h a n ge i n p atie nt re p orte d o ut c o mes as meas ure d b y t h e Al o p ecia Areata 
S y m pt o m I m pa ct Scale ( A A SI S) a n d e x pl orat or y q uesti o ns fr o m bas eli ne.  
 
2. 2  St u d y D e si g n 
T his is a d o u ble- bli n d, ra n d o mize d, place b o-c o ntr olle d m ultice n ter st u d y t o e val uate t he s afet y 
a n d effi cac y of C T P- 5 4 3 i n a d ult patie nts wit h c hr o nic, m o derat e t o se v ere al o pecia areata.  
Patie nts will be bet wee n 1 8 a n d 6 5 years of a ge a n d e x perie nci n g a n e pis o d e of al o pecia areata 
lasti n g at least 6 m o nt hs a n d n ot e x cee di n g 1 0 years, wit h at least 5 0 % hair l oss as meas ure d b y 
t he S A L T at Scree ni n g a n d Baseli ne, a n d are n ot c o nc urre ntl y b ei n g treat e d f or al o pecia areata or 
wit h ot her treat me nts t hat mi g ht affect hair re gr o wt h or i m m u ne  res p o nse.  A p pr o xi matel y 5 0 % 
of al o pecia areata patie nts wit h al o pecia t otalis or u ni versalis, a n d a p pr o xi matel y 1 0 % wit h o nl y 
al o pecia o p hiasis will be e nr olle d.  
T he st u d y c o nsists of u p t o 3 c o h orts i nitiate d se q ue ntiall y i n  asce n di n g d ose or der. A n 
i n de pe n de nt data m o nit ori n g c o mmittee ( D M C) will deter mi ne if t here are a de q uate safet y data 
t o s u p p ort eac h s u bse q u e nt hi g her d os e c o h ort. Patie nts will n ot d ose escalate wit hi n a c o h ort a n d 
ma y o nl y partici pate i n o ne c o h ort.  


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T he Scree ni n g Peri o d ma y last u p t o 2 8 da ys pri or t o ra n d o mizat i o n a n d i nitiati o n of st u d y dr u g.  
T he Treat me nt Peri o d is t he i nitial 2 4- wee k, d o u bl e- bli n d, place b o-c o ntr oll e d peri o d t o defi n e 
effic ac y a n d s afet y of C T P- 5 4 3 c o m pare d t o place b o.  T he P ost- T reat me nt Safet y F oll o w- u p 
Peri o d is t he fi nal 4 wee ks of eac h c o h ort t o assess safet y f ol l o wi n g treat me nt c o m pleti o n.  
Patie nts e nr olle d i n C o h ort 3 ( 1 2 m g BI D) will ha ve t he o pti o n t o c o nti n ue recei vi n g tr eat me nt i n 
a n o pe n-la b el e xte nsi o n st u d y f oll o wi n g t he treat me nt peri o d.  If patie nts d o n ot wis h t o c o nti n ue 
i nt o t he o pe n-la bel e xte nsi o n st u d y, t h e y will c o m plete treat ment at Wee k 2 4 a n d ret ur n i n 4 
wee ks f or t he P ost- Treat me nt Sa fet y F oll o w- u p t o assess safet y f oll o wi n g treat me nt c o m pleti o n.    
T he D M C will perf or m r e g ul ar safet y assess me nts f or eac h c o h ort  b ase d o n re vie w of c ollecti ve 
safet y data. After t h e last patie nt has c o m plete d t h e Wee k 1 2 Visit wit hi n a c o h ort, t he D M C will 
c o n ve ne t o r e vie w acc u m ulate d safet y d ata t o assess if i nitiati o n of t he s u bse q ue nt c o h ort is 
s u p p orte d. T he D M C ma y a d vise treat me nt ar m cessati o n d ue t o i nt olera bilit y at a n y ti me. 
Patie nts will pr o vi de a p pr o priatel y o btai ne d i nf or me d c o nse nt p ri or t o c o m pleti n g a n y scree ni n g 
pr oce d ures.  Patie nts meeti n g scree ni n g criteria will be eli gi b le t o c o nti n ue t o t he Da y 1 visit f or 
re vie w of eli gi bilit y a n d baseli ne assess me nts, i ncl u di n g S A L T, p h ysical e x a mi nati o n, cli nical 
la b orat or y ass ess me nts, vital si g ns, a n d electr ocar di o gra m ( E C G).  F or eac h c o h ort, patie nts 
meeti n g all i ncl usi o n criteria a n d n o n e of t he e x cl usi o n criter ia will be ra n d o mize d t o C T P- 5 4 3 
treat me nt or place b o. T h e first 2 c o h orts will be ra n d o mize d i n a 2: 1 rati o (acti ve: place b o) a n d 
t he t hir d c o h ort will be ra n d o mize d i n a 5: 1 rati o (acti ve: place b o) i n or der t o pr o vi de a si milar 
n u m ber of patie nts a cr oss eac h C T P- 5 4 3 d ose a n d  o verall place b o ( p o ole d) gr o u p.  
Ra n d o mizati o n will be stratifie d b y classificati o n of al o pecia areata s u bt y p e i nt o o ne of t he 
f oll o wi n g t hree cate g ories: 1) al o pecia areata, 2) al o pecia t otalis or al o peci a u ni versalis, or 3) 
al o pecia o p hiasis.  
T he d o u ble- bli n d, place b o-c o ntr ol le d Treat me nt Peri o d f or eac h c o h ort will last 2 4 wee ks.  
Assess me nt of treat me nt res p o nse wit h S A L T f or efficac y will oc c ur at 4, 8, 1 2, 1 6, 2 0 a n d 2 4 
wee ks.  T he fi nal efficac y a n a l ysis will be c o n d ucte d w he n all patie nts i n t he 1 2 m g c o h ort ha ve 
c o m plete d Wee k 2 4. 
F or C o h orts 1 a n d 2, pati e nts will st o p ta ki n g st u d y me dicati o n  u p o n c o m pleti o n of treat me nt at 
Wee k 2 4 a n d e nter a 4- w ee k P ost- Tr eat me nt Safet y F oll o w- U p Peri o d.  Patie nts will be assesse d 
f or safet y t hr o u g h Wee k 2 8.  F or C o h ort 3, patie nts will eit her c o m plete treat me nt at Wee k 2 4 
a n d ha ve a Safet y F oll o w- u p visit at Wee k 2 8 pri or t o e xiti n g t he st u d y, or if eli gi ble, ma y e nr oll 
i nt o a n O pe n-la bel E xte nsi o n st u d y of C T P- 5 4 3 at t heir Wee k 2 4 visit. 
Patie nts e nr olle d i nt o eac h c o h ort  will ta ke t he first d ose of st u d y dr u g i n t h e cli nic o n Da y 1 a n d 
will be i nstr ucte d t o ta ke st u d y dr u g e v er y 1 2 h o urs f or t he d u rati o n of t he Treat me nt Peri o d.  
Patie nts will d ose st u d y dr u g i n t he cli nic o n all St u d y Visit Da ys after cli nic al la b orat or y bl o o d 
dra ws are c o m plete d. Bl o o d sa m ples f or p har mac o ki netic a n d p har mac o d y n a mic assess me nt will 
be ta ke n peri o dicall y. Sc he d ule d assess me nt of p atie nt a n d cli n icia n perce pti o n of disease 


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se verit y a n d i m pr o ve me nt will als o occ ur. Patie nt safet y will be m o nit ore d t hr o u g h o ut t he trial 
a n d s u p p orte d b y re g ular re vie w b y t he D M C.   
He mat ol o g y p ara m eters will be m o nit ore d cl osel y f or t he d urati o n of t h e st u d y.  F or eac h c o h ort, 
he mat ol o g y will be c o n d ucte d e ver y 2 wee ks d uri n g t he first 8 wee ks of t he Treat me nt Peri o d, 
f oll o we d b y a n ass ess me nt e ver y 4 wee ks t hereaft er t hr o u g h c o m pleti o n of t he st u d y.  Li pi d 
le vels will be assesse d e v er y 1 2 wee ks t hr o u g h o ut t he Treat me nt Peri o d a n d at t he P ost-
Treat me nt Safet y F oll o w- U p Visit, if a p plica ble.  Si g nifica nt c yt o pe ni as or ot her he mat ol o gic 
a b n or malities will be ma na ge d b y d ose i nterr u pti o n a n d si g ns a n d s y m pt o ms of i nfecti o n will be 
treate d pr o m ptl y.  Patie nts w h o e x perie nce i nt olera ble s y m pt o ms d uri n g treat me nt ma y 
disc o nti n ue t he st u d y at t he discreti o n of t he I n vesti gat or.  P atie nts ma y wit h dra w c o ns e nt at a n y 
ti me. 
2. 3  St u d y P o p ul ati o n 
T he st u d y p o p ulati o n will c o nsist of male a n d fe m ale patie nts o f a n y et h nicit y bet wee n 1 8 a n d 6 5 
years of a ge, i ncl usi ve, wit h dia g n osis of al o pecia areat a wit h a c urre nt e pis o de lasti n g at least 6 
m o nt hs a n d n ot e x cee di n g 1 0 years at t he ti me of Scree ni n g.  T o tal diseas e d urati o n great er t ha n 
1 0 years is per mitte d.  Patie nts m ust als o e x hi bit at least 5 0 %  scal p hair l oss, as defi ne d b y a 
S A L T ≥ 5 0, at Scree ni n g a n d Bas eli ne .  
A f ull list of t he i ncl usi o n a n d e x cl usi o n criteria ca n be f o u n d i n Secti o ns 8. 1 a n d 8. 2 i n t he 
C P 5 4 3. 2 0 0 1 Pr ot oc ol.   
2. 4  Tr e at m e nt R e gi m e n s 
C T P- 5 4 3 will be d ose d orall y as ta blets at d oses 4 m g, 8 m g, 1 2  m g, or mat c hi n g place b o, e ver y 
1 2 h o urs d uri n g t h e Treat me nt Peri o d.  D oses will be all ocate d t o eac h c o h ort as f oll o ws: 
 C o h ort 1: 4 m g ( 2: 1 C T P- 5 4 3 4 m g : place b o) 
 C o h ort 2: 8 m g ( 2: 1 C T P- 5 4 3 8 m g : place b o) 
 C o h ort 3: 1 2 m g ( 5: 1 C T P- 5 4 3 1 2 m g : place b o) 
2. 5  Tr e at m e nt Gr o u p A s si g n m e nt s or R a n d o mi z ati o n 
Patie nts meeti n g all i ncl usi o n criteria a n d n o n e of t he e x cl usi o n criteria will be ra n d o mize d t o 
C T P- 5 4 3 treat me nt or place b o.  T h e first 2 c o h orts will be ra n d o mize d i n a 2: 1 rati o 
(acti ve: place b o) a n d t h e t hir d co h ort will be ra n d o mize d i n a 5 : 1 rati o (acti ve: place b o) i n or der t o 
pr o vi de a si milar n u m ber of patie n ts acr oss eac h C T P- 5 4 3 d ose an d  t he o verall place b o ( p o ole d) 
gr o u p.  Ra n d o mizati o n will be str atifie d b y classificati o n of al o pecia areata s u bt y pe i nt o o n e of 
t he f oll o wi n g t hr ee cate g ories: 1) al o peci a areata, 2) al o pecia t otalis or al o pecia u ni versalis, or 3) 


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al o pecia o p hiasis. A p pr o xi matel y 5 0 % of al o pecia areata patie nt s wit h al o pecia t otalis or 
u ni versalis, a n d a p pr o xi matel y 1 0 % wit h o nl y al o pecia o p hiasis will be e nr olle d. 
2. 6  S a m pl e Si z e D et er mi n ati o n 
T here are v er y fe w st u dies i n t he literat ure t o pr o vi de relia ble esti mates of acti ve treat me nt or 
place b o res p o nse rates usi n g S A L T, or t he esti mate of vari a nces  ar o u n d t hese meas ures, i n 
patie nts wit h al o pecia areata.  P o wer calc ulati o ns ass u me a 2-s i de d c hi-s q u are d test a n d 
si g nifica n ce le v el of 0. 0 5 a n d are b ase d o n a n acti ve treat me nt r es p o nse rate of 4 5 % a n d a 
place b o res p o nse rate of 1 0 %.  
Alt h o u g h patie nts will be ra n d o mize d i n a n u n bala nce d rati o of acti ve dr u g t o place b o wit hi n 
eac h c o h ort, t he place b o patie nts fr o m t he 3 c o h orts will be c o m bi ne d f or statistical c o m paris o ns 
t o eac h acti ve treat me nt gr o u p. T h e first 2 c o h orts will be ra nd o mize d i n a 2: 1 rati o 
(acti ve: place b o) a n d t h e t hir d c o h ort will be ra n d o mize d i n a 5: 1 rati o (acti ve: place b o). Base d o n 
esti mate d c o m pleti o n rat es, t his  ra n d o mizati o n sc he me is e x pecte d t o pr o vi de a si milar n u m ber 
of patie nts i n eac h C T P- 5 4 3 d ose gr o u p a n d t he p o ole d place b o g r o u p. T h us, p o wer calc ulati o ns 
f or t he c o m paris o n t o place b o are bas e d o n a 1: 1 treat me nt rati o of eac h C T P- 5 4 3 d ose gr o u p t o 
place b o. P o wer calc ul ati o ns ass u me a 2-si de d test a n d si g nifica nce le vel of 0. 0 5 a n d are base d o n 
a n acti ve tr eat me nt res p o nse ra te of 4 5 % a n d a place b o res p o ns e rat e of 1 0 %. Bas e d o n esti mate d 
c o m pleti o n rates as of A me n d me nt 4, t his ra n d o mizati o n sc he me i s e x pecte d t o pr o vi de a si milar 
n u m ber of patie nts i n t he 1 2 m g gr o u p a n d t he p o ole d place b o gr o u p.  
A sa m ple siz e of 2 8 patie nts i n t he 1 2 m g gr o u p a n d 2 8 patie nts  i n t he p o ole d place b o gr o u p will 
pr o vi de > 8 0 % p o w er f or t he c hi-s q ua re d test w he n c o m pari n g eac h d ose gr o u p t o t he c o m bi ne d 
place b o gr o u p ( 2 8 acti ve, 2 8 place b o). A p pr o xi matel y 1 5 0 patie n ts will be ra n d o mize d i n or der 
t o pr o vi de 1 2 0 patie nts w h o c o m plete treat me nt.  


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C O N FI D E N TI A L  
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3.  G E N E R A L A N A L Y SI S A N D R E P O R TI N G C O N V E N TI O N S 
T he f oll o wi n g is a list of ge n eral a nal ysis a n d re p orti n g c o n v e nti o ns t o be a p plie d t o t his st u d y, 
u nless ot her wise s pecifie d. 
All data dis pla ys (t a bles, listi n gs, a n d fi g ures) will ha ve a h ea der s h o wi n g t he s p o ns or c o m pa n y 
na me, pr ot oc ol n u m ber, pa ge n u m ber , a n d dis pla y stat us (i.e. “ D R A F T” or “ FI N A L”), as w ell as 
a f o oter i n dicati n g p at h, file na me, a n d r u n d ate/ti me.  S u m mar y ta bles a n d data listi n gs will be 
s u m marize d b y treat me nt a n d o verall, as a p pr o pri ate. All data c ollecte d per- pr ot oc ol a n d all 
deri ve d varia bles will be liste d.   
Cate g orical varia bles will be s u m marize d usi n g c o u nts ( n) a n d p erce nta ges ( %) a n d will be 
prese nte d i n t he f or m “ n ( x x. x).” If a c o u nt is 0, 0 % will be s h o w n f or t he perce nt a ge. If a 
perce nt a ge is 1 0 0 %, 1 0 0 % will be s h o w n wit h n o deci mal place. T o e ns ure c o m plete ness, 
s u m maries f or cate g orical varia bles will i ncl u de all cate g ories, e ve n if n o p atie nts ha d a res p o nse 
i n a partic ular cate g or y. U nless ot her wise s pecifie d, t he de n o mi nat or f or eac h perce nta ge will be 
base d o n t he n u m ber of patie nts i n t he p o p ulati o n bei n g s u m marize d ( hea d er n).   If missi n g 
val ues are pres e nt, c o u nts will be s h o w n b ut will n ot be i ncl u d e d i n perce nta ge cal c ulati o ns. 
C o nti n u o us varia bles will be s u m marize d usi n g mea n, sta n dar d de viati o n ( S D), mi ni m u m, 
ma xi m u m, me dia n, a n d n u m ber of pati e nts. T he m ea n a n d me di a n wi ll be re p orte d t o a n 
a d diti o nal le vel of precisi o n t ha n t he ori gi n al o bser vati o ns, a n d t he S D will be re p ort e d t o t w o 
a d diti o nal le vels of precisi o n t ha n t he ori gi nal o bs er vati o ns. T he mi ni m u m a n d ma xi m u m will be 
t he sa me precisi o n as t he ori gi nal dat a. I n ge n eral, a n y calc ulate d val ues, s u c h as t h ose d ue t o 
u nit c o n versi o n, will be r o u n de d t o t he sa me n u m ber of deci mal places as t he ori gi n al data. 
All statistical tests will be 2- si de d wit h a si g nifica nce val ue of 0. 0 5.  Testi n g will be perf or me d 
o nl y f or t h e Treat me nt Peri o d.  Esti mates a n d c o nfi de nce i nter v als will be re p orte d t o 1 m ore 
deci mal t ha n t he ori gi nal data.  P- val ues will be re p orte d t o 3  deci mal places.  
S u m mar y ta bles a n d data listi n gs:  
 N o preli mi nar y r o u n di n g will be perf or me d; r o u n di n g will o nl y o cc ur after a nal ysis.  
 Data fr o m p atie nts e x cl u de d fr o m a n a nal ysis p o p ulati o n will be  prese nte d i n t he data 
listi n gs b ut will n ot be i ncl u de d i n t he calc ulati o n of s u m mar y statistics, w here 
a p plica ble. 
 Data fr o m eac h p atie nt will be se parate d b y a bla n k li ne. Wit hi n a data listi n g, if a 
descri pti ve ite m a p pears li ne  after li ne (e. g., re p etiti o n of a patie nt n u m ber, date, visit, 
etc.), o nl y t he first oc c urre nce will be dis pla ye d (e. g., i n Li sti n g of Vital Si g ns, patie nt 
n u m ber, date a n d visit will o nl y b e dis pla ye d o n first r o w w he n prese nti n g all para meters 


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c ollecte d at sa m e visit). Re petiti o n of act ual res ults or o utc o mes (e. g., A d verse E ve nts 
( A Es), la b res ults, vital si g n val u es, etc.) will n ot be c olla pse d.  
 Data listi n gs will be s orte d b y c o h ort wit hi n treat m e nt, patie n t, a n d wee k a n d/ or ti me of 
assess me nt, as a p plica bl e. 
 Place b o gr o u ps will be se parate d b y c o h ort wit hi n data listi n gs  a n d p o ole d wit hi n 
s u m mar y ta bl es. 
 W he n c ha n ge fr o m baseli ne is ca lc ulate d, baseli ne is t he last obser vati o n o btai ne d pri or 
t o d osi n g of t he st u d y dr u g. 
M oc k ta bles a n d dat a listi n gs will be pr o vi de d as attac h me nts t o t his a nal ysis pla n. Mi n or 
c ha n ges t o t he m oc ks aft er f or mal S A P a p pr o val will n ot necessi tate re-a p pr o val u nless c ha n ges 
t o t he te xt of t he S A P are re q uire d. 
All statistical deli vera bles will be pr o d uce d, vali d ate d, a n d r e vie we d f or acc urac y/ c o nsiste nc y i n 
acc or da nce wit h  
 sta n dar d o perati n g pr oce d ures a n d t h e  pr ocesses descri be d i n t he 
statistical vali dati o n pla n. 
S A S ® ( S A S I nstit ute, Car y, N ort h Car oli na) statistical s oft ware , v ersi o n 9. 4 or later, will be use d 
f or all a nal yses. A d vers e E ve nts a n d Me dical Hist or y will be c ode d i n Me dical Dicti o nar y f or 
Re g ulat or y Acti vities ( Me d D R A) Versi o n 1 9. 1. C o nc o mita nt me dica ti o ns will be c o de d i n 
W orl d Healt h Or ga niz ati o n ( W H O) Dr u g Versi o n E ( 2 0 1 6. 0 1) a n d A n at o mical- T hera pe utic-
C he mical ( A T C) classifi cati o n a n d preferre d ter m. 


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4.  A N A L Y SI S P O P U L A TI O N S 
A nal ysis p o p ulati o ns will be s u m marize d a n d liste d f or eac h pat ie nt, b y treat me nt a n d c o h ort. 
4. 1  Effi c a c y P o p ul ati o n 
T he Efficac y P o p ulati o n will i n cl u de all patie nts w h o recei ve st u d y dr u g a n d ha ve at least 1 p ost-
treat me nt S A L T assess m e nt d uri n g t he Treat me nt Peri o d.  Patie nts i n t he Efficac y P o p ulati o n 
will be a nal yze d acc or di n g t o t he ir ra n d o mize d treat me nt gr o u p.    
4. 2  P h ar m a c o ki n eti c P o p ul ati o n 
T he P har mac o ki n etic P o p ulati o n will i ncl u de all patie nts w h o re cei ve st u d y dr u g a n d ha v e at 
least 1 p har mac o ki netic s a m ple t a ke n d uri n g t he Treat me nt Peri od. Patie nts w h o recei ve place b o 
will be e x cl u de d fr o m t he P har mac o ki netic P o p ul ati o n. 
4. 3  S af et y P o p ul ati o n 
T he Safet y P o p ulati o n will i ncl u de all patie nts w h o recei v e st u d y dr u g d uri n g t he Treat me nt 
Peri o d.  Patie nts i n t he Safet y P o p ulati o n will be a nal yze d acc or di n g t o t he act ual tr eat me nt 
recei v e d d uri n g t he st u d y.  
4. 4  P er Pr ot o c ol P o p ul ati o n 
T he Per Pr ot oc ol P o p ulati o n will i n cl u de all patie nts i n t he Ef ficac y P o p ulati o n w h o were d os e d 
acc or di n g t o pr ot o c ol, ha ve a w ee k 2 4 S A L T sc ore, a n d ha v e n o m aj or pr ot oc ol de viati o ns. T he 
pr oce d ure f or d efi ni n g maj or pr ot oc ol de viati o ns is descri be d i n Secti o n  5. 2. 


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5.  S T U D Y P A TI E N T S 
 
5. 1  Di s p o siti o n of P ati e nt s 
Dis p ositi o n will be s u m mariz e d b y ra n d o mize d treat me nt gr o u p f o r all patie nts scree n e d i n t he 
st u d y. T he f oll o wi n g dis p ositi o n i nf or mati o n will be s u m marize d ( perce nt a ges base d o n t h e 
n u m ber ra n d o mize d, wit h t he e x ce pti o n of t he reas o ns f or disc o n ti n uati o n): 
 T he n u m ber of p atie nts scree n e d. 
 T he n u m ber of p atie nts r a n d o mize d. 
 T he n u m ber a n d p erce nta ge of patie nts treate d wit hi n t he Effica c y, P har mac o ki netic, 
Safet y, a n d Per Pr ot oc ol P o p ulati o ns. 
 T he n u m ber a n d p erce nta ge of patie nts w h o c o m pl ete d t he st u d y ( defi n e d as c o m pleti n g 
all st u d y visits) a n d w h o c o m plete d 2 4 wee ks of treat me nt. 
 T he n u m ber a n d p erce nta ge of patie nts w h o pre mat urel y disc o nti n ue d, a n d t he fre q u e nc y 
a n d perce nta ge of eac h disc o nti n uati o n reas o n. T h e de n o mi nat or f or t h e perce nta ge of 
eac h disc o nti n uati o n reas o n will be t he n u m ber of patie nts w h o disc o nti n ue d. 
Dis p ositi o n a n d patie nt visits  will als o be prese nte d f or eac h patie nt i n patie nt data listi n gs. 
Patie nt data listi n gs will lis t date of i nf or me d c o ns e nt, date of first/last treat me nt, date of e n d of 
st u d y/earl y t er mi nati o n, a n d reas o ns f or disc o nti n uati o n. A d diti o nall y, scree n fail ures p ost a n d 
pri or t o A me n d me nt 2 will be prese nte d i n se p arat e listi n gs.  A  Ka pla n M eier c ur ve of ti me t o 
last d ose will als o be prese nte d. 
5. 2  Pr ot o c ol D e vi ati o n s 
Pr ot oc ol de viati o ns will be c ol lecte d at b ot h t he site a n d patie nt le vel o n t h e Electr o nic case 
re p ort f or m ( e C R F).  A bli n de d data re vie w will be c o n d ucte d bef ore data base l oc k b y t he 
s p o ns or t o classif y pr ot o c ol de viati o ns as mi n or or maj or.  De viati o ns t hat ma y alter or c o nf o u n d 
i nter pretati o n of t he st u d y res ults will be classifie d as maj or de viati o ns. Pr ot oc ol de viati o ns will 
be s u m mariz e d b y d e viati o n cla ssificati o n a n d cate g or y f or all ra n d o mize d patie nts a n d liste d b y 
patie nt i n a data listi n g. Pr ot oc ol de viati o ns t hat are i de ntif ie d as maj or will be use d t o e xcl u de 
patie nts fr o m t he Per Pr ot oc ol p o p ulati o n. 


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6.  D E M O G R A P HI C A N D O T H E R B A S E LI N E C H A R A C T E RI S TI C S 
De m o gra p hic c haracteristics (i.e., se x, et h nic ori gi n, race, d ate of birt h, a n d calc ulate d b o d y m ass 
i n de x) will be c ollecte d at t he Scree ni n g Visit, bet wee n Da y - 28 a n d - 1, a n d detaile d o n t he 
e C R F.  
T he patie nt’s al o pe cia areata will be classifi e d b y t he I n v esti gat or i nt o o ne of t hree cate g ori es 
defi ne d f or t his st u d y: 
1)  
Al o pecia areat a: patc h y t y p e h air l oss, 
2)  
Al o pecia t otalis or u ni versalis: c o m plete hair l oss o n t he scal p wit h or wit h o ut b o d y 
hair l oss, 
3)  
Al o pecia o p hiasis: ba n d-li ke hair l oss li mite d t o t he peri p her y  of t he scal p al o n g t he 
bac k of t he h air li ne i n t he occi pital re gi o n a n d p ossi bl y e xte n di n g o ver eac h ear i n 
te m p oral re gi o ns. 
T he al o peci a t otalis a n d al o pecia u ni versalis cate g or y will be se parate d i nt o eac h i n di vi d ual 
s u bt y pe f or s u m maries. Al o pecia areat a cat e g or y at baseli ne defi ne d as t he c urre nt e pis o de a n d 
al o pecia areata cate g or y at disease o nset will be s u m marize d.  I n a d diti o n, baseli ne S A L T sc ore 
will be prese nte d as a bas eli ne  c haracteristic.  T he d urati o n of t he c urre nt e pis o de i n m o nt hs a n d 
t he d urati o n of diseas e i n m o nt hs will als o be s u m marize d.  
D urati o n of c urre nt e pis o de will  be calc ulat e d as: ( date of ra nd o mizati o n –  date of c urre nt 
e pis o de o nset + 1) / 3 0. 4 3 7 5. 
D urati o n of diseas e at o nset will be calc ulate d as: ( date of ra n d o mizati o n –  date of diseas e o nset 
+ 1) / 3 0. 4 3 7 5. 
All de m o gra p hics a n d b aseli ne c haracteristics will be s u m mari ze d f or all ra n d o mize d patie nts 
wit h descri pti ve statistics a n d liste d wit hi n a b y- p atie nt data  listi n g.  
T h or o u g h m e dical hist or y, i ncl u di n g c urre nt me di cati o ns, nail a n d facial hair i n v ol ve me nt, c o-
m or bi dities, as well as hist or y of v acci n ati o n a gai nst her pes z oster c ollecte d at t he Scree ni n g a n d 
Ra n d o mizati o n Visits, will  be s u m marize d a n d liste d. 
Me dical hist or y will be s u m mariz e d b y fre q ue n cies of S yste m Or ga n Class ( S O C) a n d preferre d 
ter m a n d will be c o de d usi n g Me d D RA Versi o n 1 9. 1.  All me dical hist or y f or eac h patie nt will 
be i ncl u de d i n a dat a listi n g. 
 


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6. 1  Pri or a n d C o n c o mit a nt M e di c ati o n s 
Pri or a n d c o nc o mita nt m e dicati o ns  will be s u m marize d b y W H O Dr ug A T C classificati o n le vel 
2 a n d preferre d ter m a n d liste d w it hi n a b y- patie nt data listi ng.  
Me dicati o ns are classifie d as pri or if starte d a n d st o p pe d pri o r t o t he first d ose date of st u d y dr u g 
or as c o nc o mita nt if use d o n or aft er t h e first d ose date of st u d y dr u g. C o nc o mita nt me dicati o ns 
will be rec or de d fr o m Scree ni n g t hr o u g h t he F oll o w- U p Visit at Wee k 2 8. 
Partial a n d c o m pletel y missi n g  dates will be i m p ute d f or t he p ur p oses of cl assif yi n g c o n c o mita nt 
me dicati o ns as f oll o ws: 
 Partial dates will be i m p ute d f ol l o wi n g t he s a me al g orit h m as in 9. 2 f or Treat me nt-
e mer ge nt a d v erse e ve nts ( T E A Es). 
 F or a n e ntirel y missi n g st art date (i. e. da y, m o nt h, a n d year a re missi n g), t h e start date 
will be set t o t he date of a d mi nistrati o n of st u d y dr u g u nless t h e st o p date is pri or t o t he 
date of a d mi nistrati o n of st u d y dr u g, i n w hic h case t he start date will be set t o t he st o p 
date. 
F or a n e ntirel y missi n g st o p date (i.e. da y, m o nt h, a n d year ar e missi n g), t h e me dicati o n will be 
treate d as o n g oi n g. 
 


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7.  M E A S U R E M E N T S O F T R E A T M E N T C O M P LI A N C E 
Patie nts will stri ve f or 1 0 0 % c o m plia nce wit h t he dail y d osi n g sc he d ul e. Treat me nt c o m plia nce 
will be s u m mariz e d as ti me o n tre at me nt as w ell as perce nt of p la n ne d d os e recei ve d f or eac h 
treat me nt gr o u p.  Ti me o n treat me nt will be defi n e d as date of last d ose i n t he treat me nt peri o d 
mi n us t he date of first d ose i n t he treat me nt peri o d + 1. Perce nt of pla n ne d d ose recei v e d will be 
calc ulate d f or t he e ntire treat me nt peri o d as f oll o ws: 
 
Ta blets E x pecte d is defi n e d as t h e ti me o n treat me nt m ulti plie d  b y t he e x pecte d n u m ber of acti ve 
d ose pills ta ke n dail y ( x 2 f or t he 4 m g c o h ort, x 2 f or t he 8 m g  c o h ort, a n d x 2 f or t he 1 2 m g 
c o h ort).  D ose i nterr u pti o ns will be i g n ore d i n t his calc ulati o n. Patie nt c o m plia nce a n d d osi n g 
e x ce pti o ns will be liste d i n b y- p atie nt data listi n gs.  
  
   
 
 


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8.  E F FI C A C Y E V A L U A TI O N 
8. 1  Pri m ar y Effi c a c y E n d p oi nt 
T he pri mar y effic ac y e n d p oi nt will be t he pr o p orti o n of res p o n d ers, defi ne d as patie nts ac hie vi n g 
at least a 5 0 % relati ve re d ucti o n in S A L T sc ore, fr o m baseli ne at Wee k 2 4.  
8. 1. 1  S e v erit y of Al o p e ci a T o ol ( S A L T) 
T he S A L T is a meas ur e of hair a bse n ce t hat q u a ntifies t he a m o u n t of scal p s urface wit h o ut hair 
i n a pre-s pecifie d q u a dra nt of t he scal p (ri g ht si de, t o p, left si de, bac k), t hat is f urt her s u m me d 
after a p pl yi n g a q ua dra nt-s pecif ic m ulti plier i n dicati ve of scal p s urface area c o ntri b uti o n, t o 
pr o vi de a n o verall sc ore of t otal hair l oss. T otal S A L T s c ore i s c o m p ute d as [(left q ua dra nt ra w 
sc ore x 0. 1 8) + (ri g ht q ua dra nt ra w s c ore x 0. 1 8) + (t o p q ua drant r a w sc ore x 0. 4 0) + ( bac k 
q ua dra nt r a w sc ore x 0. 2 4)]. T he S A L T assess me nt will occ ur via li ve e x a mi nati o n of t he patie nt 
d uri n g cli nic visits. 
As t he S A L T s c ore is b y nat ure a me as ure m e nt of t otal s urface w it h o ut hair, it is i m p orta nt t o 
n ote t hat i n t he c o nte xt of t his S A P, e n d p oi nts will f oll o w t hese defi niti o ns: 
 A bs ol ute c ha n ge = differe nce i n S A L T meas ure m e nts (f oll o w- u p S A L T sc ore 
mi n us baseli ne S A L T sc ore)   
 Relati ve c ha n ge = perce nt c ha n ge of t he f oll o w- u p S A L T sc ore, w here b aseli ne 
S A L T sc ore is t he de n o mi nat or (i.e. a bs ol ute c h a n ge di vi de d b y t h e baseli n e 
sc ore, m ulti plie d b y 1 0 0) 
 
8. 2  E x pl or at or y Effi c a c y E n d p oi nt s  
E x pl orat or y efficac y e n d p oi nts i ncl u de: 
 T he pr o p orti o n of res p o n ders at Wee ks 4, 8, 1 2, 1 6 a n d 2 0; 
 Pr o p orti o n of res p o n ders w h o ha ve  at least 7 5 %, 9 0 % a n d 1 0 0 % relati ve re d ucti o n i n 
S A L T sc ore fr o m baseli n e at Wee ks 4, 8, 1 2, 1 6, 2 0, a n d 2 4; 
 A bs ol ute c ha n ge i n S A L T sc ore s fr o m baseli ne at Wee ks 4, 8, 1 2, 1 6, 2 0, a n d 2 4 i n t he 
Bli n de d Treat me nt Peri o d; 
 Relati ve c ha n ge i n S A L T sc ores fr o m baseli ne at Wee ks 4, 8, 1 2,  1 6, 2 0, a n d 2 4 i n t he 
Bli n de d Treat me nt Peri o d; 
 A bs ol ute S A L T sc ores at Wee ks 4, 8, 1 2, 1 6, 2 0, a n d 2 4 i n t he B li n de d Treat me nt Peri o d; 
 Pr o p orti o n of patie nts ac hie vi n g a n a bs ol ute S A L T sc ore of ≤1 0, ≤2 0, a n d ≤2 5 at Wee ks 
4, 8, 1 2, 1 6, 2 0 a n d 2 4; 
  Perce nt c h a n ge i n al o pecia are ata se v erit y fr o m baseli ne as meas ure d b y t he cli nicia n 
V A S- S at W ee ks 1 2 a n d 2 4; 


C o ncert P har mace uticals I nc. 
C O N FI D E N TI A L  
Statistical A nal ysis Pla n 
Pr ot oc ol N o. C P 5 4 3. 2 0 0 1 
 
0 7 Ma y 2 0 1 9 
Versi o n:  2. 0  
 
P a ge 2 2 of 5 0 
 C ha n ges i n al o pecia areata fr o m baseli ne as meas ure d b y t he cli nicia n rate d 7- p oi nt 
Li kert scale C GI-I at W ee ks 1 2 a n d 2 4; 
 Pr o p orti o n of s u bjects w orse ni n g i n al o pecia areata fr o m baseli ne t o Wee ks 1 2 a n d 2 4 as 
meas ure d b y res p o nses of “ Ver y M uc h W orse” or “ M uc h W orse” o n t he cli nicia n rate d 
C GI-I; 
 Pr o p orti o n of s u bjects i m pr o vi n g fr o m baseli ne t o Wee ks 1 2 a n d 2 4 as meas ure d b y 
res p o nses of “ Ver y M u c h I m pr o v e d” or “ M uc h I m pr o v e d” o n t he clinicia n rate d C GI -I; 
 Perce nt c h a n ge i n al o pecia areata se v erit y fr o m baseli ne as mea s ure d b y t he patie nt V A S-
S at W ee ks 1 2 a n d 2 4;  
 C ha n ges i n al o pecia areata fr o m baseli ne as meas ure d b y t he patie nt r ate d 7- p oi nt Li kert 
scale P GI-I at W ee ks 1 2 a n d 2 4;   
 Pr o p orti o n of s u bjects w orse ni n g i n al o pecia areata fr o m baseli ne t o Wee ks 1 2 a n d 2 4 as 
meas ure d b y res p o nses of “ Ver y M uc h W orse” or “ M uc h W orse” o n t he patie nt rate d 
P GI-I; 
 Pr o p orti o n of s u bjects i m pr o vi n g fr o m baseli ne t o Wee ks 1 2 a n d 2 4 as meas ure d b y 
res p o nses of “ Ver y M u c h I m pr o v e d” or “ M uc h I m pr o ve d” o n t he patie nt rate d P GI-I; 
 Patie nt-re p orte d o utc o m es: C ha n ges i n s y m pt o ms fr o m baseli ne as  m eas ure d b y A A SI S 
a n d e x pl orat or y q u esti o ns at W ee k 2 4. 
 
 
8. 2. 1  Vi s u al A n al o g S c al e ( V A S) 
T he V A S is a scal e i nitiall y de vel o p e d f or p ai n t hat has bee n u s e d i n a vari et y of cli nical setti n gs 
w here t he e n d p oi nt of i nterest is base d o n p atie nt perce pti o n. T h e V A S is a disti nct 1 0 0 
milli meter li ne a nc h ore d o n t he  left e n d at f ull de gree of i m pair m e nt a n d o n t he ri g ht e n d at n o 
de gree of i m pair me nt, w here i n dicati o n of t h e de gree of i m pair m e nt percei ve d at t he ti me of 
assess me nt is ca pt ure d b y mar ki n g t he a p pr o pri ate p ositi o n o n t he li ne bet wee n t he a nc h or 
p oi nts. T he meas ure d dista nce of t he m ar k fr o m t he left a n c h or will be rec or de d i n milli meters. 
Si nce t he V A S was me as ure d ri g ht t o left i n ter ms o n i ncreasi n g i m pair me nt, t he V A S a nal ysis 
val ue will be calc ulate d b y ta ki n g 1 0 0 mi n us t he c ollecte d val u e. 
 
Cli nici a n V A S of Se verit y ( V A S- S) 
T he I n vesti gat or will c o m plete a V A S- S re gar di n g t he se v erit y of t he p atie nt’s al o pecia areata at 
t he ti me of c o m pleti o n as i n dicate d i n t he Sc he d ul e of E ve nts. T he l eft a n d ri g ht a nc h or p oi nts 
f or t he cli nicia n V A S-S are “ E xtre mel y A p pare nt” a n d “ N ot At All A p pare nt”, res pecti v el y.  
 
P ati e nt V A S of Se verit y ( V A S- S) 
Patie nts will rate perce pti o n of hi s/ her al o peci a areata se verit y o n t he patie nt V A S- S. T he left 
a n d ri g ht a nc h or p oi nts f or t he patie nt’s al o pecia areat a V A S -S are “ E xtre mel y A p pare nt” a n d 


C o ncert P har mace uticals I nc. 
C O N FI D E N TI A L  
Statistical A nal ysis Pla n 
Pr ot oc ol N o. C P 5 4 3. 2 0 0 1 
 
0 7 Ma y 2 0 1 9 
Versi o n:  2. 0  
 
P a ge 2 3 of 5 0 
“ N ot At All A p pare nt”, res pecti vel y. T he p atie nt V A S -S will meas ure t he patie nt’s perce pti o n of 
his/ her al o pecia areata at t he ti me of c o m pleti o n. 
 
8. 2. 2  Cli ni c al Gl o b al I m pr e s si o n of I m pr o v e m e nt ( C GI-I) 
C o m pare d t o t he patie nt’s al o pecia areata pri or t o treat me nt a t baseli ne, t h e patie nt’s c urre nt state 
of al o pecia areata will be assesse d acc or di n g t o t h e I n vesti gat or’s p ercei ve d c ha n ge. T h e 
I n v esti gat or ma y sele ct o ne of se ve n n u m eric c h oi ces fr o m 1 t o 7, wit h 1 re prese nti n g “ Ver y 
M uc h I m pr o ve d ” t o 7 re prese nti n g “ V er y M uc h W orse ”.  
 
8. 2. 3  P ati e nt Gl o b al I m pr e s si o n of I m pr o v e m e nt ( P GI-I) 
C o m pare d t o t he patie nt’s al o pecia areata pri or t o treat me nt at  b aseli ne, t h e patie nt’s c urre nt state 
of al o pecia areata will be assesse d acc or di n g t o his/ her percei ve d c h a n ge. T he pati e nt ma y select 
o ne of se ve n n u m eric c h oices fr o m 1 t o 7, wit h 1 re pres e nti n g “ Ver y M uc h I m pr o v e d” t o 7 
re pres e nti n g “ Ver y M uc h W orse”.  
  
 
8. 2. 4  P ati e nt R e p ort e d O ut c o m e s: Al o p e ci a Ar e at a S y m pt o m I m p a ct S c al e  
( A A SI S) a n d E x pl or at or y Q u e sti o n s 
T he A A SI S is a q uesti o n naire desi g ne d t o meas ure t he q ualit y of  life, s y m pt o ms, a n d t heir 
i m pact f or patie nts wit h al o pecia areata [Me n d oza 2 0 1 3 ].  T hree di me nsi o ns relate d t o al o pecia 
areat a are assess e d: i m pact of al o peci a areata, hair l oss, a n d p h ysic al s ki n s y m pt o ms.  All 
res p o nses will be s u m me d t o pr o d uce t he A A SI S sc ore.   
I n a d diti o n t o t he A A SI S, e x pl orat or y q uesti o ns will be use d t o atte m pt t o defi ne cli nicall y 
mea ni n gf ul o utc o mes f or patie nts wit h al o pecia areata.  
 
8. 3  O v er vi e w of Effi c a c y A n al y si s I s s u e s 
8. 3. 1  H a n dli n g of Dr o p o ut s or Mi s si n g D at a 
T he Last O bser vati o n Carrie d F or war d ( L O C F) a p pr oac h will be i m ple me nte d f or missi n g S A L T 
sc ore dat a, e. g., if t he S A L T score i n t he Wee k 1 6 visit wi n d o w  is missi n g, t he ne xt a n d cl osest 
a vaila ble o n-tr eat me nt S A L T s c ore m eas ure me nt bef ore t h e Wee k 1 6 visit wi n d o w will be use d 
f or all re mai ni n g S A L T assessme nts: Wee k 1 6, Wee k 2 0 a n d Wee k 2 4.  Missi n g baseli ne v al ues 
will n ot be carrie d f or w ar d. If a S A L T ass ess me nt is missi n g be t wee n t w o n o n- missi n g S A L T 


C o ncert P har mace uticals I nc. 
C O N FI D E N TI A L  
Statistical A nal ysis Pla n 
Pr ot oc ol N o. C P 5 4 3. 2 0 0 1 
 
0 7 Ma y 2 0 1 9 
Versi o n:  2. 0  
 
P a ge 2 4 of 5 0 
assess me nts visits, t he S A L T s c ore at t hat visit will be i nter p olate d usi n g t he mea n of t he cl osest 
pre- a n d p ost- assess me nts. 
If t he n u m ber of disc o nti n uati o ns d ue t o a d verse e ve nts is s u bsta ntial, ot her met h o ds will be 
e x pl ore d. 
8. 3. 2  M ulti c e nt er St u di e s 
Patie nts will be e nr olle d at u p t o 1 5 sites.  T o re d u ce vari a bi lit y, o ne rater s h o ul d perf or m eac h 
cli nicia n de pe n de nt assess me nt ( S A L T, V A S- S, a n d C GI-I) f or t he  patie nt f or t he d urati o n of t h e 
st u d y. All i n vesti gat ors usi n g t he S A L T will be trai ne d pri or to use.  
8. 3. 3  A s s e s s m e nt Vi sit Wi n d o w s 
T he visit sc he d ule f or all st u d y assess me nts is pr o vi de d i n a p pe n di x 1 7. 2. Patie nts will be 
c o nsi dere d c o m plete d f or effic ac y a n al ys es aft er Wee k 2 4 ( Visit  1 0).  F or C o h orts 1 a n d 2, 
patie nts will st o p ta ki n g st u d y me dicati o n u p o n c o m pleti o n of t reat me nt at Wee k 2 4 a n d e nter a 
4- wee k P ost- Treat me nt Safet y F oll o w- U p Peri o d.  F or C o h ort 3, p atie nts will eit her c o m plete 
treat me nt at Wee k 2 4 a n d ha ve a Safet y F oll o w- u p visit at Wee k 2 8 pri or t o e xiti n g t he st u d y, or 
if eli gi ble, ma y e nr oll i nt o a n O pe n-la bel E xte nsi o n st u d y of CT P- 5 4 3 at t h eir Wee k 2 4 visit. 
 F or sc h e d ule d visits, t here will be n o reassi g n m e nt of t he a nal ysis visit base d o n date, a n d all 
data will a p pear i n s u m mar y ta bles bas e d o n t he n o mi nal ti me p oi nt. 
U nsc he d ule d a n d re p eat safet y visits will be assi g ne d t o t he cl osest pri or pl a n ne d visit. If t he 
cl osest pla n ne d visit is alread y d oc u m e nte d, t he u nsc he d ule d or  re peat visit will o nl y b e liste d 
a n d will n ot be s u m mariz e d.  
 
8. 4  A n al y si s M et h o d s 
All statistical tests will be 2- si de d wit h a si g nifica nce val ue of 0. 0 5.  Testi n g will be bas e d o n t he 
Efficac y p o p ulati o n a n d perf or me d o nl y f or t he Treat me nt Peri o d .  A n a nal ysis of t he pri mar y 
effic ac y e n d p oi nt a n d e x pl orat or y S A L T e n d p oi nts will als o be p erf or me d f or t he Per Pr ot oc ol 
p o p ulati o n. T he fi nal efficac y a na l ysis will be c o n d ucte d w he n all patie nts i n t he 1 2 m g c o h ort 
ha ve c o m plete d Wee k 2 4.  T he p lace b o gr o u ps fr o m all 3 c o h orts will be p o ole d a n d c o m pare d 
t o eac h acti ve d ose ( 4 m g, 8 m g, a n d 1 2 m g) i n di vi d uall y.  Active d oses, 4 m g, 8 m g, a n d 1 2 m g, 
will als o be c o m pare d.  T here w ill be n o a dj ust me nt f or m ulti ple treat me nt gr o u p c o m paris o ns i n 
t his d ose-ra n gi n g P hase 2 st u d y. 
Ta ble 8- 1  gi ves a n o v er vi e w of t he a n al ysis met h o ds t hat will be use d f or eac h of t he efficac y 
varia bles.  


C o ncert P har mace uticals I nc. 
C O N FI D E N TI A L  
Statistical A nal ysis Pla n 
Pr ot oc ol N o. C P 5 4 3. 2 0 0 1 
 
0 7 Ma y 2 0 1 9 
Versi o n:  2. 0  
 
P a ge 2 5 of 5 0 
 
T a bl e 8- 1  
Effi c a c y V ari a bl e s a n d A n al y si s M et h o d s 
Effic ac y V ari a bles 
C ollecti o n Ti mes 
Met h o d  
Pri m ar y 
 
 
Res p o n der A nal ysis 
S A L T ( 5 0 % rel ati ve re d u cti o n) 
Baseli ne, Wee k 2 4 
 Test 
E x pl or at or y 
 
 
Res p o n der A nal ysis 
S A L T ( 5 0 % rel ati ve re d u cti o n) 
Baseli ne, Wee k 4, 8, 
1 2, 1 6, 2 0  
 Test 
Res p o n der A nal ysis 
S A L T  ( 7 5 %,  9 0 %,  a n d  1 0 0 % 
relati ve re d ucti o n) 
Baseli ne, Wee k 4, 8, 
1 2, 1 6, 2 0, 2 4  
 Test 
S A L T  ( ≤1 0, ≤2 0, ≤2 5  a bs ol ute 
sc ore) 
Baseli ne, Wee k 4, 8, 
1 2, 1 6, 2 0, 2 4 
 Test 
S A L T (a bs ol ute c ha n ge) 
Baseli ne, Wee k 4, 8, 
1 2, 1 6, 2 0, 2 4 
M M R M 
S A L T (relati ve c ha n ge) 
 
S A L T (a bs ol ute sc ore)  
Baseli ne, Wee k 4, 8, 
1 2, 1 6, 2 0, 2 4  
Baseli ne, Wee k 4, 8, 
1 2, 1 6, 2 0, 2 4  
M M R M 
 
M M R M  
Cli nicia n V A S- S ( perce nt c ha n ge) 
Baseli ne, Wee k 1 2, 2 4 
A N C O V A 
Patie nt V A S- S ( perce nt c ha n ge) 
Baseli ne, Wee k 1 2, 2 4 
A N C O V A 
C GI-I 
Wee k 1 2, 2 4 
 Test 
C GI-I Res p o n der ( “ V er y 
M uc h/ M uc h I m pr o ve d ” a n d  
“ M uc h/ Ver y M u c h W orse” ) 
Wee k 1 2, 2 4 
 Test 
P GI-I 
Wee k 1 2, 2 4 
 Test 
P GI-I Res p o n der ( “ V er y 
M uc h/ M uc h I m pr o ve d ” a n d  
“ M uc h/ Ver y M u c h W orse” ) 
Wee k 1 2, 2 4 
 Test 
A A SI S 
Baseli ne, Wee k 2 4 
Descri pti ve Statistics  
E x pl orat or y Q uesti o ns 
Baseli ne, Wee k 2 4 
Descri pti ve Statistics  
Res p o n der A nal ysis, E x pl orat or y 
Q uesti o ns, Satisfie d v. 
U nsatisfie d 
Baseli ne, Wee k 2 4 
 Test  
 = C hi- S q uare d T est; A N C O V A = a nal ysis of c o varia nce; C M H = C ochra n- Ma ntel- Hae nszel; M M R M 
=  mi xe d-effect m o del f or re peate d meas ures 


C o ncert P har mace uticals I nc. 
C O N FI D E N TI A L  
Statistical A nal ysis Pla n 
Pr ot oc ol N o. C P 5 4 3. 2 0 0 1 
 
0 7 Ma y 2 0 1 9 
Versi o n:  2. 0  
 
P a ge 2 6 of 5 0 
8. 4. 1  Pri m ar y Effi c a c y A n al y si s 
T he ai m of t his st u d y is t o de m o nstrate t hat i n ter ms of t he pr i mar y efficac y e n d p oi nt, 5 0 % 
relati ve re d ucti o n i n S A L T sc ore at Wee k 2 4, C T P- 5 4 3 is s u peri or t o t he place b o.  Pair wis e 
treat me nt gr o u p differe n ces will be assesse d wit h t he 
 test. 
T he acti ve tr eat me nt will be c o nsi dere d effecti ve if p ≤ 0. 0 5. 
N u m ber a n d p erce nta ge, as well as p- v al ues base d o n t he 
 test, will be re p orte d f or t he 
res p o n ders, d efi ne d as a patie nt meeti n g at least 5 0 % relati ve re d ucti o n i n S A L T sc ore at Wee k 
2 4.  A d diti o nall y, t he n u m ber a n d perce nt a ge of res p o n ders will  be re p orte d b y al o p ecia areata 
s u bt y pe.   
Res p o n ders will be pres e nte d gra p hicall y b y tr eat me nt gr o u p as a bar gra p h at 2 4 Wee ks a n d as a 
li ne gra p h acr oss ti me. 


C o ncert P har mace uticals I nc. 
C O N FI D E N TI A L  
Statistical A nal ysis Pla n 
Pr ot oc ol N o. C P 5 4 3. 2 0 0 1 
 
0 7 Ma y 2 0 1 9 
Versi o n:  2. 0  
 
P a ge 2 7 of 5 0 
8. 4. 2  E x pl or at or y Effi c a c y A n al y s e s 
Treat me nt differe n ces f or a bs ol ute sc ore, a bs ol ute c ha n ge, a n d relati ve c ha n ge i n S A L T s c ore 
fr o m baseli ne t o W ee ks 4, 8, 1 2, 1 6, 2 0, a n d 2 4 will be assessed wit h a mi x e d-effect m o del of 
re peat e d meas ur es ( M M R M).  T he m o del will i ncl u de fi x e d fact ors f or treat me nt gr o u p, st u d y 
visit, treat me nt b y st u d y visit i nteracti o n, a n d al o pecia areat a s u bt y p e, wit h baseli ne S A L T sc ore 
as a c o variate.  A n u nstr u ct ure d varia nce-c o v aria n ce matri x wil l be use d.  If c o n ver ge nce is n ot 
ac hie ve d, a n alter nati ve a ut oregressi ve c o varia n ce str uct ure wi ll be use d.  If t he M M R M m o del 
d oes n ot c o n ver ge, ot her c o varia n ce str uct ures will be e x pl ore d .  If c o n ver ge nce is still n ot met, 
o nl y descri pti ve statistics will be prese nte d. 
P oi nt esti mates a n d sta n dar d err ors will be prese nt e d f or eac h tr eat me nt gr o u p at eac h ti me p oi nt.   
P- val ues f or t he tr eat me nt b y  visit i nteracti o n will be prese nte d at Wee k 2 4 f or eac h acti ve 
treat me nt c o m pare d t o t he place b o. A c o m paris o n of t he acti ve dos es ( 4 m g vs. 8 m g, 4 m g vs. 
1 2 m g, 8 m g v. 1 2 m g) will be prese nte d as w ell. Treat me nts wil l be c o m p are d o verall a n d b y 
visit.  
Descri pti ve statistics will be re p ort e d f or t he S A L T sc ore at e ac h ti me p oi nt f or eac h treat me nt 
gr o u p a n d b y s u bt y p e.  B y- p atie nt data listi n g will als o be pre se nte d f or patie nt S A L T sc ores a n d 
c ollecti o n of S A L T p h ot o gra p hs.  T he  mea n of o bser ve d val u e, a bs ol ute c h a n ge, a n d relati ve 
c ha n ge S A L T s c ores al o n g wit h sta n dar d err ors f or eac h treat me n t gr o u p will be prese nte d usi n g 
li ne gra p hs.  
Res p o n ders, as defi ne d f or t he pri mar y e n d p oi nt, will be a nal yze d p er secti o n 8. 4. 1 f or Wee ks 4, 
8, 1 2, 1 6, a n d 2 0. A d diti o nall y, t he f oll o wi n g res p o n der gr o u ps  will be a n al yze d per secti o n 8. 4. 1 
at W ee ks 4, 8, 1 2, 1 6, 2 0, a n d 2 4: 1) patie nts w h o meet at leas t 7 5 %, 9 0 %, a n d 1 0 0 % rel ati ve 
c ha n ge; 2) p atie nts w h o meet a n a bs ol ute S A L T s c ore of ≤1 0, ≤2 0, or ≤2 5. 
T he perce nt c h a n ge i n cli nicia n a n d patie nt V A S- S fr o m baseli ne  will be assesse d usi n g t he 
a nal ysis of c o varia nce ( A N C O V A) f or Wee k 1 2 a n d 2 4 wit h fi x e d f act ors f or treat me nt, al o p ecia 
areat a s u bt y p e, a n d b aseli ne V A S- S. T he least s q u ares mea n sc or e esti mates wit h 9 5 % CI will be 
prese nte d al o n g wit h p- val ues f or eac h tr eat me nt c o m paris o n at eac h ti me p oi nt.  Descri pti ve 
statistics will als o be re p orte d b y treat me nt a n d s u bt y pe.   
A 
tre n d test will be use d t o a nal yze C GI-I a n d P GI-I bet w ee n tr eat me nt gr o u ps o verall. 
Res p o nses f or P GI-I a n d C GI-I cate g orize d as ac hie vi n g “ Ver y M u c h/ M uc h I m pr o v e d” or 
“ M uc h/ Ver y M u c h W orse” will als o be c o m pare d bet wee n tr eat me nt gr o u ps wit h t he 
 test. 
Descri pti ve statistics a n d b y- p atie nt data listi n gs will als o b e prese nte d f or t he 7 res p o nse 
cate g ories f or eac h assess me nt.  
Mea n a n d me a n c ha n ge fr o m baseli ne f or t otal A A SI S sc ore will b e re p ort e d.  N u m ber a n d 
perce nt a ge of s u bjects i n eac h res p o nse cate g or y of A A SI S will als o be s u m marize d. I n di vi d ual 
res p o nses will be liste d i n cate g ories of “ Se verit y” a n d “I nt erfere n ce”. 


C o ncert P har mace uticals I nc. 
C O N FI D E N TI A L  
Statistical A nal ysis Pla n 
Pr ot oc ol N o. C P 5 4 3. 2 0 0 1 
 
0 7 Ma y 2 0 1 9 
Versi o n:  2. 0  
 
P a ge 2 8 of 5 0 
T he e x pl orat or y q u esti o ns will be s u m marize d wit h descri pti ve s tatistics at baseli ne a n d Wee k 
2 4, a n d will be liste d i n t he b y- pa tie nt data listi n gs. Res p o nses will be cate g orize d as “ Satisfie d” 
(i ncl u di n g res p o nses of “ Ver y satisfie d ”  a n d “ Satisfie d”) a n d “ U nsatisfie d ” ( i ncl u di n g res p o nses 
of “ U nsatisfie d ”  a n d “ Ver y u ns atisfie d”)  a n d pres e nte d as a 2 x 2 s hift ta ble fr o m baseli ne t o 
Wee k 2 4, c o m pare d wit h a 
 Test b y c o h ort. 
8. 5  E x a mi n ati o n of S u b gr o u p s 
Descri pti ve statistics will be pr o vi de d b y al o pecia s u bt y pe. 
 
 


C o ncert P har mace uticals I nc. 
C O N FI D E N TI A L  
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9.  S A F E T Y E V A L U A TI O N 
9. 1  O v er vi e w of S af et y A n al y si s M et h o d s 
Safet y a n d t olera bilit y of C T P- 5 4 3 will be assesse d b y e v al uati n g t he f oll o wi n g f or t he Safet y 
P o p ulati o n: 
 A d verse e ve nts 
 Cli nical la b orat or y res ults 
 Vital si g ns 
 E C G res ults 
 C o nc o mita nt me dicati o ns 
 P h ysical e x a mi nati o ns 
All safet y s u m maries will be descri pti ve wit h n o statistical h y p ot hesis testi n g a n d b ase d o n t he 
Safet y P o p ulati o n. Patie nts will  be s u m marize d acc or di n g t o t he st u d y dr u g rec ei v e d (i.e., as 
treate d), s h o ul d it differ fr o m the ra n d o mize d treat me nt ar m. A ll safet y e n d p oi nts will be liste d i n 
b y- p atie nt data listi n gs. 
 
9. 2  A d v er s e E v e nt s 
A d verse e ve nts will be c o de d usi n g Me d D R A a n d s u m marize d b y s ys te m or ga n class a n d 
preferre d t er m.  Cli nicall y si g nifica nt d eteri or ati o ns i n p h ysical e xa mi nati o n fi n di n gs will be 
re p orte d a n d s u m mariz e d as a d vers e e ve nts. 
A n a d vers e e ve nt re p orte d after i nf or me d c o nse nt, b ut bef ore t h e first d ose of st u d y dr u g (i.e., 
Da y 1), will be c o nsi dere d a pre-tr eat me nt a d verse e ve nt.  Trea t me nt-e mer ge nt a d verse e ve nts 
will be defi ne d as a n y a d verse e v e nt t hat occ urs after a d mi nist rati o n of t he first d ose of st u d y 
dr u g.  T h e n u m ber a n d p erce nt a ge of patie nts w h o re p ort T E A Es w ill be s u m marize d b y s yste m 
or ga n class a n d preferre d ter m.  
Treat me nt e mer ge nt a d v erse e ve nts will als o be s u m marize d b y i n te nsit y as well as relati o ns hi p 
t o st u d y dr u g.   
Partial dates will be i m p ute d f or t he p ur p os es of defi ni n g T E A E s as f oll o ws: 
 F or a missi n g start da y w here t he m o nt h a n d year are prese nt, t he start d a y will be set t o 
t he first da y of t he m o nt h, u nless 1) t he first da y of t he m o nth is bef ore t he date of 


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a d mi nistrati o n of st u d y dr u g a n d t he m o nt h a n d year are t he sa m e as t he m o nt h a n d year 
of t he date of a d mi nistrati o n of  st u d y dr u g, a n d 2) t he e n d date is o n or after t he date of 
a d mi nistrati o n of st u d y dr u g or t he e n d d ate is c o m pletel y miss i n g, i n w hi c h case t h e start 
da y will be set t o t he first da y of a d mi nistrati o n of st u d y dr u g. 
 F or a missi n g start da y a n d m o nt h w here t he year is prese nt, t h e start da y a n d m o nt h will 
be set t o J a n uar y 1 st, u nless 1) J a n uar y 1st is bef ore t he date of a d mi nistrati o n of st u d y 
dr u g, a n d 2) t he e n d date is o n or aft er t he d ate of a d mi nistra ti o n of st u d y dr u g or t he e n d 
date is c o m pletel y missi n g, i n w hic h case t he st art da y a n d m o n t h will be set t o t hat of t he 
first date of a d mi nistrati o n of st u d y dr u g. 
 F or a missi n g e n d da y w here t he m o nt h a n d year are prese nt, t he e n d d a y will be set t o 
t he last da y of t he m o nt h, u nless t he m o nt h a n d ye ar are t he sa me as t he m o nt h a n d year 
of t he last c o ntact d ate f or t he patie nt, i n w hic h case t he e n d  da y will be set t o t hat of t he 
patie nt's last c o nt act date. 
 F or a missi n g e n d da y a n d m o nt h w here t he year is prese nt, t he e n d d a y a n d m o nt h will 
be set t o t he patie nt's last c o ntact date, u nless t h e year of t h e patie nt's last c o ntact date is 
greater t ha n t he e n d year, i n w hic h case t he e n d da y a n d m o nt h will be set t o Dece m b er 
3 1st. 
F or a n e ntirel y missi n g st o p date (i.e. da y, m o nt h, a n d year are missi n g), t h e T E A E will be 
treate d as o n g oi n g. 
Patie nts w h o re p ort t he s a me pref erre d ter m o n m ulti ple occasi o ns will be c o u nte d o nce f or t he 
preferre d t er m: u n der t he hi g hest se v erit y w he n s u m marize d b y s e v erit y a n d u n der t he cl osest 
relati o ns hi p t o st u d y dr u g w h e n s u m marize d b y relati o ns hi p.  Missi n g se v erit y or relati o ns hi p 
will n ot be i m p ute d.  If a patie nt re p orts m ulti ple preferre d ter ms f or a S O C, t he patie nt will be 
c o u nte d o nl y o n ce f or t hat S O C. 
T he n u m ber a n d p erce nta ge of patie nts w h o e x peri e nce T E A Es will be s u m marize d b y tr eat me nt 
gr o u p f or t he f oll o wi n g: 
 B y S O C a n d preferre d ter m 
 B y se verit y/i nte nsit y, S O C, a n d preferre d t er m 
 B y rel ati o ns hi p t o st u d y dr u g, S O C, a n d preferre d ter m 
 Seri o us a d verse e ve nts ( S A Es) b y S O C a n d preferre d ter m 
 S A Es b y relati o ns hi p t o st u d y dr u g, S O C a n d preferre d t er m 


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 A Es res ulti n g i n disc o nti n uati o n of st u d y dr u g b y S O C a n d prefe rre d t er m 
 A Es t hat res ult i n st u d y dr u g d os e i nterr u pti o n b y S O C a n d preferre d t er m 
 A Es t hat meet Gra d e 3- 4 C o m m o n ter mi n ol o g y criteria f or a d verse  e ve nts ( C T C A E) 
he mat ol o g y res ults b y s yste m or ga n class a n d preferre d t er m 
 A Es t hat meet Gra d e 3- 4 C T C A E ser u m c he mistr y res ults b y s yste m  or ga n class a n d 
preferre d t er m 
B y- patie nt listi n gs will b e pr o v i de d f or all A Es, S A Es, a n d A Es relate d t o t he st u d y dr u g, as well 
as A Es lea di n g t o st u d y dr u g wit h dra wal or deat h. A b y- patie nt listi n g will als o be create d f or 
a n y pre g na n cies t hat oc c ur.  T E A Es t hat res ult i n d ose i nterr u p ti o n will als o be i de ntifie d.  
A d diti o nall y, T E A Es will be s u m marize d b y ti me i nter val: 0 t o 1 2 wee ks, a n d 1 2 t o 2 4 wee ks.  
F or eac h ti me i nter v al, a n i nci d e nce ta ble will s u m marize o nl y T E A Es wit h a n o nset date wit hi n 
t he i nter val a n d a pre v ale nce ta ble will s u m marize all T E A Es t hat ha ve a n o nset date wit hi n t he 
i nter val or c o nti n ue i nt o t he i nterval.  Differe nces bet wee n t h e i n ci de nce a n d pre vale nc e ta bles 
ca n pr o vi de i nsi g ht i nt o t he d urati o n of T E A Es as well as t he rec urre nce of T E A Es. A preferre d 
ter m f or a n i n di vi d ual patie nt will be re p orte d i n m ulti ple ti me i nter vals if t here are m ulti ple 
a d verse e ve nt r e p orts.  T he de n o mi nat or f or eac h ti me i nter val will be t he n u m ber of patie nts 
w h o recei ve d at least 1 d ose of st u d y dr u g wit hi n t he i nter val.  T hese i n ci de nce a n d pre vale nce 
ta bles will be re peate d f or ke y he mat ol o g y a n d s er u m c he mistr y A Es cate g orize d as C T C A E 
Gra de 3- 4 res ults. 
 
9. 3  Cli ni c al L a b or at or y E v al u ati o n 
O bser ve d me as ure m e nts al o n g wit h c h a n ge fr o m baseli ne f or eac h s c he d ul e d assess me nt will be 
s u m marize d descri pti vel y b y treat me nt gr o u p a n d visit f or eac h cli nical la b orat or y para meter. 
He mat ol o g y p ara m eters f or patie nts t hat meet Gra de 3 or Gra de 4  t o xicit y criteria fr o m t he 
C T C A E v 4. 0 f or ne utr o p hils, platele ts, a n d he m o gl o bi n will be su m marize d f or eac h sc he d ul e d 
visit a n d o verall f or all p ost- ba seli ne visits. I n a d diti o n, hemat ol o g y para meters of i nterest t hat 
meet Gra d e 3 or Gra de 4 t o xicit y criteri a will be pl otte d as me a n val ues o v er ti me. Ser u m 
c he mistr y p ara m eters f or patie nts t hat meet Gra d e 3 or Gra d e 4 t o xicit y criteria fr o m t he C T C A E 
v 4. 0 f or t otal c h olester ol, l o w- de nsit y li p o pr otei n ( L D L) c h ole ster ol, hi g h- d e nsit y li p o pr otei n 
( H D L), a n d tri gl yceri des will be s u m marize d f or eac h sc he d ul e d visit a n d o verall f or all p ost-
baseli ne visits. 
La b orat or y v al ues will be c o n ve rt e d t o t he pr oject- defi ne d u nit of meas ure me nt, as a p plica ble, 
bef ore a nal ysis. If la b orat or y v al ues are rec or de d as a b o ve or bel o w a t hres h ol d (i.e. “ < 2”, “ > 3 0 ”, 


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etc.), t he y will be c o u nt e d as missi n g f or c o nti n u o us s u m maries.  A b n or mal, cli nicall y si g nifica nt 
la b orat or y val u es ( per I n vesti gat or j u d g me nt) will be re p ort e d a n d s u m mari ze d as A Es. 
All la b orat or y para meter res ults will be i ncl u de d i n b y- p atie nt  data listi n gs.  Refere n ce ra n ges f or 
eac h cli nical la b orat or y p ara mete r will als o be s u m marize d i n a data listi n g. 
 
9. 4  Vit al Si g n s, P h y si c al Fi n di n g s, a n d Ot h er O b s er v ati o n s R el at e d t o S af et y 
9. 4. 1  Vit al Si g n s 
Baseli ne will be defi ne d as t he  last vital si g n val u e o btai ne d bef ore t he first d ose of st u d y dr u g o n 
Da y 1; if Da y 1 v al ues are u na vaila ble, t he n val ues o btai ne d at  t he Scree ni n g Visit will be use d. 
O bser ve d vital si g n meas ure me nts al o n g wit h c ha n ge fr o m baseli n e f or eac h sc he d ule d 
assess me nt will be s u m mariz e d de scri pti vel y b y tr eat me nt gr o u p a n d visit f or eac h vital si g n 
varia ble s pecifie d i n t he pr ot oc ol ( S yst olic Bl o o d Press ure, Di ast olic Bl o o d Press ure, P ulse Rate, 
Res pirat or y Rate, a n d Oral Te m perat ure).  Vit al si g ns will als o  be prese nte d f or eac h patie nt i n a 
data listi n g. 
 
9. 4. 2  E C G 
O bser ve d O v erall E C G I nter pretati o ns will be s u m marize d as N or mal, A b n or mal a n d N ot 
Cli nicall y Si g nifica nt, or A b n or mal a n d Cli nicall y Si g nifica nt f or eac h sc he d ule d visit b y 
treat me nt gr o u p.  I n a d diti o n, o bser ve d a n d c ha n ge fr o m baseli ne meas ure m e nts of E C G 
i nter vals ( P R, Q T, Q Tc F, Q R S, a n d R R) f or eac h s c he d ule d ass essme nt will be s u m marize d 
descri pti vel y b y treat me nt gr o u p a n d visit as well as liste d wi t hi n a b y- p atie nt data listi n g. 
Patie nts recei vi n g st u d y dr u g will be i de ntifie d a n d s u m marize d  b y treat me nt gr o u p a n d visit, as 
well as o verall f or t he f oll o wi n g cli nicall y n ota ble cate g ories : 
 Q Tc F > baseli ne a n d > 4 5 0 msec 
 Q Tc F > baseli ne a n d > 4 8 0 msec 
 Q Tc F > baseli ne a n d > 5 0 0 msec 
 Q Tc F i ncrease fr o m b aseli ne > 3 0 msec 
 Q Tc F i ncrease fr o m b aseli ne > 6 0 msec 
 
9. 4. 3  P h y si c al E x a mi n ati o n s 
A listi n g of p h ysical e x a mi nati o ns will be pr o vi de d. Deteri orat i o ns fr o m b aseli ne o n p h ysical 
e x a mi nati o n will be c o de d as a d vers e e ve nts a n d s u m marize d as s uc h.  


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1 0.  P H A R M A C O KI N E TI C E V A L U A TI O N 
1 0. 1  P h ar m a c o ki n eti c a n d P h ar m a c o d y n a mi c M et h o d s 
T he c ollecti o n stat us of p har mac o ki netic a n d p har mac o d y na mic sa m ples will be liste d f or eac h 
visit wit h sc he d ule d sa m pli n g b y patie nt usi n g t h e Safet y P o p ul ati o n. Plas ma c o nce ntr ati o ns of 
st u d y dr u g ma y b e s u m mariz e d se paratel y, as a p pr o priate, f or t he P har mac o ki netic P o p ulati o n. 
 
 
 


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1 1.  I N T E RI M A N A L Y S E S A N D D A T A M O NI T O RI N G 
W he n S A L T data t hr o u g h Wee k 2 4 of t reat me nt was a vaila ble f or all pati e nts i n C o h ort 1 ( 4 m g) 
a n d C o h ort 2 ( 8 m g), a n i nteri m a nal ysis was perf or me d. T he p ur p os e was t o re vie w selecte d 
effic ac y a n d s afet y res ults i n t h ose 2 c o h orts f or pl a n ni n g p ur p oses re gar di n g t he cli nical 
de vel o p me nt of t he c o m p o u n d. W hile t he res ults s h o we d a g gre gate  c o m paris o ns bet wee n t he 
patie nts w h o recei ve d acti ve C T P- 5 4 3 a n d t h ose w h o recei v e d pla ce b o, all bli n de d st u d y 
pers o n nel re m ai ne d bli n de d t o treat me nt assi g n me nt. Si nce n o f u rt her e nr oll me nt occ urre d i n 
t hese 2 c o h orts, t here will be n o a dj ust me nt f or m ulti ple treatme nt gr o u p c o m paris o ns. See 
Secti o n 1 4 a n d 1 5 f or s u m mar y ta bl es a n d fi g ures t hat were ge ne rate d f or t his i nteri m a nal ysis. 
A Data M o nit ori n g C o m mittee will m o nit or safet y at r e g ular i nte r vals as d efi ne d i n t h e D M C 
C harter. Aft er t he last patie nt i n a c o h ort has c o m plete d t he W ee k 1 2 Visit, t he D M C will 
c o n ve ne t o r e vie w acc u m ulate d safet y d ata t o assess if i nitiati o n of t he s u bse q ue nt c o h ort is 
s u p p orte d, as a p plica bl e.  S pecificati o ns of data t o be s u p plied t o t he C o m mittee are o utsi de t he 
sc o pe of t his d oc u me nt. F urt her details are pr o vi d e d i n t he latest versi o n of t he D M C C harter. 
 


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1 2.  C H A N G E S T O T H E A N A L Y S E S P L A N N E D I N T H E P R O T O C O L 
T he f oll o wi n g alterati o ns were ma d e t o t he ori gi nal a nal ys es pla n ne d i n t he pr ot oc ol: 
 S A L T 5 0 % re d ucti o n a n al ysis c h a n ge d fr o m C oc hra n- Ma ntel- Hae nszel Test ( C M H) t o 
 test a n d will n ot be stratifie d b y Al o pecia Areata s u bt y pe. 
 V A S- S a nal ysis met h o d c ha n ge d fr o m C M H t o A N C O V A. 
 C GI-I a n d P GI-I a n al ysis met h o d c ha n ge d fr o m C M H test t o 
test. 
 A A SI S a n d E x pl orat or y Q uesti o n a nal ysis met h o d c ha n ge d fr o m A N C O V A t o 
descri pti ve statistics a n d 
 test, res pecti vel y. 
 Al o pecia Areata s u bt y p e use d as a fi x e d effect wit hi n t he M M R M.  
 T E A E defi niti o n m o difie d s o t hat all A Es t hat occ ur after st u d y d osi n g will be c o u nte d, 
rat her t ha n o nl y t h ose t hat occ ur u p t o Wee k 2 4 or t he Earl y Ter mi nati o n Visit. 
 


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1 3.  R E F E R E N C E S 
Me n d oza T R, Osei J S, S hi Q, D u vic M. De vel o p me nt of t he al o peci a areata s y m pt o m i m pact scale. J 
I n vesti g Der mat ol S y m p Pr oc. 2 0 1 3 Dec; 1 6( 1): S 5 1- 2. 
Olse n E A, H or di ns k y M K, Price V H, et al. Al o pecia areata i n vest i gati o nal assess me nt g ui deli nes-- Part II. 
Nati o nal Al o pecia Areata F o u n dati o n. J A m Aca d Der mat ol. 2 0 0 4 S e p; 5 1( 3): 4 4 0- 7. 


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1 4.  LI S T O F P L A N N E D T A B L E S 
 T a ble I D 
T a ble N o. 
Title 
P o p ul ati o n 
U ni q ue ? 
I nteri m 
A n al ysis 
D S _ T A A 
1 4. 1. 1 
S u m mar y of Patie nt 
Dis p ositi o n 
All 
Scree ne d 
Patie nts 
Y 
X 
D S _ T A B 
1 4. 1. 2 
S u m mar y of 
Pr ot oc ol De viati o ns 
All 
Ra n d o mize d 
Patie nts 
Y 
 
D M _ T A A 
1 4. 1. 3 
S u m mar y of 
De m o gra p hics 
All 
Ra n d o mize d 
Patie nts 
Y 
X 
D M _ T A B 
1 4. 1. 4 
S u m mar y of 
Baseli ne 
C haracteristics 
All 
Ra n d o mize d 
Patie nts 
Y 
X 
M H _ T A A 
1 4. 1. 5 
S u m mar y of 
Me dical Hist or y b y 
S yste m Or ga n 
Class a n d Preferre d 
Ter m 
Safet y 
P o p ulati o n 
Y 
 
E X _ T A A 
1 4. 1. 6. 1 
S u m mar y of St u d y 
Dr u g 
A d mi nistrati o n a n d 
C o m plia nce b y 
Treat me nt Gr o u p 
Safet y 
P o p ulati o n 
Y 
 
C M _ T A A 
1 4. 1. 7. 1 
S u m mar y of Pri or 
Me dicati o ns 
Safet y 
P o p ulati o n 
N 
 
C M _ T A B 
1 4. 1. 7. 2 
S u m mar y of 
C o nc o mita nt 
Me dicati o ns 
Safet y 
P o p ulati o n 
N 
 
E F _ T A A 
1 4. 2. 1. 1 
C hi- S q uare d 
A nal ysis of 
Res p o n ders at 
Wee k 2 4 
Efficac y 
P o p ulati o n 
Y 
X 
E F _ T A B 
1 4. 2. 1. 2 
C hi- S q uare d 
A nal ysis of 
Res p o n ders at 
Wee k 2 4 
Per Pr ot oc ol 
P o p ulati o n 
N 
 
E F _ T A C 
1 4. 2. 1. 3 
C hi- S q uare d 
A nal ysis of 
Res p o n ders b y 
Visit 
Efficac y 
P o p ulati o n 
N 
X 
E F _ T A D 
1 4. 2. 1. 4 
C hi- S q uare d 
A nal ysis of 
Per Pr ot oc ol 
P o p ulati o n 
N 
 


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Res p o n ders b y 
Visit 
E F _ T A T 
1 4. 2. 1. 5 
C hi- S q uare d 
A nal ysis of Patie nts 
Ac hie vi n g ≤1 0, 
≤2 0, or ≤2 5 
A bs ol ute Salt 
Sc ores b y Visit 
Efficac y 
P o p ulati o n 
N 
 
E F _ T A U 
1 4. 2. 1. 6 
C hi- S q uare d 
A nal ysis of Patie nts 
Ac hie vi n g ≤1 0, 
≤2 0, or ≤2 5 
A bs ol ute Salt 
Sc ores b y Visit 
Per Pr ot oc ol 
P o p ulati o n 
N 
 
E F _ T A E 
1 4. 2. 1. 7. 1 
S u m mar y of T otal 
S A L T Sc ores b y 
Treat me nt Gr o u p 
a n d Visit 
Efficac y 
P o p ulati o n 
Y 
X 
E F _ T AI 
1 4. 2. 1. 7. 2 
 
S u m mar y of T otal 
S A L T Sc ores of 
Res p o n ders at 
Wee k 2 4 b y 
Treat me nt Gr o u p 
Efficac y 
P o p ulati o n 
Y 
X 
E F _ T A F 
1 4. 2. 1. 8 
M M R M A nal ysis 
f or A bs ol ute 
C ha n ge i n S A L T 
Sc ores 
Efficac y 
P o p ulati o n 
Y 
X 
E F _ T A G 
1 4. 2. 1. 9 
M M R M A nal ysis 
f or A bs ol ute 
C ha n ge i n S A L T 
Sc ores 
Per Pr ot oc ol 
P o p ulati o n 
N 
 
E F _ T A H 
1 4. 2. 1. 1 0 
M M R M A nal ysis 
f or Relati ve 
C ha n ge i n S A L T 
Sc ores 
Efficac y 
P o p ulati o n 
N 
X 
E F _ T A S 
1 4. 2. 1. 1 1 
M M R M A nal ysis 
f or Relati ve 
C ha n ge i n S A L T 
Sc ores 
Per Pr ot oc ol 
P o p ulati o n 
N 
 
E F _ T A Y 
1 4. 2. 1. 1 2 
M M R M A nal ysis 
f or A bs ol ute S A L T 
Sc ores 
Efficac y 
P o p ulati o n 
N 
 
E F _ T A Z 
1 4. 2. 1. 1 3 
M M R M A nal ysis 
f or A bs ol ute S A L T 
Sc ores 
Per Pr ot oc ol 
P o p ulati o n 
N 
 


C o ncert P har mace uticals I nc. 
C O N FI D E N TI A L  
Statistical A nal ysis Pla n 
Pr ot oc ol N o. C P 5 4 3. 2 0 0 1 
 
0 7 Ma y 2 0 1 9 
Versi o n:  2. 0  
 
P a ge 3 9 of 5 0 
E F _ T AJ 
1 4. 2. 2. 1  
S u m mar y of 
Cli nicia n V A S- S 
( m m) 
Efficac y 
P o p ulati o n 
 
Y  
 
E F _ T A K 
1 4. 2. 2. 2 
S u m mar y of Patie nt 
V A S- S ( m m) 
Efficac y 
P o p ulati o n 
N 
 
E F _ T A L 
1 4. 2. 3. 1 
S u m mar y of C GI-I 
Efficac y 
P o p ulati o n 
Y 
 
E F _ T A M 
1 4. 2. 3. 2 
S u m mar y of C GI-I 
I m pr o v e me nt 
Efficac y 
P o p ulati o n 
Y 
 
E F _ T A N 
1 4. 2. 3. 3 
S u m mar y of C GI-I 
W orse ni n g 
Efficac y 
P o p ulati o n 
N 
 
E F _ T A O 
1 4. 2. 3. 4 
S u m mar y of P GI-I 
Efficac y 
P o p ulati o n 
N 
 
E F _ T A P 
1 4. 2. 3. 5 
S u m mar y of P GI-I 
I m pr o v e me nt 
Efficac y 
P o p ulati o n 
N 
 
E F _ T A Q 
1 4. 2. 3. 6 
S u m mar y of P GI-I 
W orse ni n g 
Efficac y 
P o p ulati o n 
N 
 
E F _ T A R 
1 4. 2. 4. 1 
S u m mar y of 
E x pl orat or y 
Q uesti o ns at Wee k 
2 4 
Efficac y 
P o p ulati o n 
Y 
 
E F _ T A V 
1 4. 2. 4. 2 
S hift fr o m Baseli ne 
t o Wee k 2 4 
E x pl orat or y 
Q uesti o ns 
Efficac y 
P o p ulati o n 
Y 
 
E F _ T A W 
1 4. 2. 5. 1 
S u m mar y of 
A A SI S Res p o nses 
Efficac y 
P o p ulati o n 
Y 
 
E F _ T A X 
1 4. 2. 5. 2 
Mea n a n d Mea n 
C ha n ge fr o m 
Baseli ne i n A A SI S 
Res p o nses 
Efficac y 
P o p ulati o n 
Y 
 
A E _ T A A 
1 4. 3. 1. 1  
S u m mar y of 
Treat me nt-
E mer ge nt A d verse 
E ve nts 
Safet y 
P o p ulati o n 
Y 
X 
A E _ T A B 
1 4. 3. 1. 2  
S u m mar y of 
Treat me nt-
E mer ge nt A d verse 
E ve nts b y S yste m 
Or ga n Class a n d 
Preferre d Ter m 
Safet y 
P o p ulati o n 
Y 
X 
A E _ T A C 
1 4. 3. 1. 3 
S u m mar y of  
Treat me nt-
E mer ge nt Seri o us 
A d verse E v e nts b y 
S yste m Or ga n 
Safet y 
P o p ulati o n 
N 
 


C o ncert P har mace uticals I nc. 
C O N FI D E N TI A L  
Statistical A nal ysis Pla n 
Pr ot oc ol N o. C P 5 4 3. 2 0 0 1 
 
0 7 Ma y 2 0 1 9 
Versi o n:  2. 0  
 
P a ge 4 0 of 5 0 
Class a n d Preferre d 
Ter m 
A E _ T A D 
1 4. 3. 1. 4 
S u m mar y of All 
Treat me nt-
E mer ge nt A d verse 
E ve nts Lea di n g t o 
Disc o nti n uati o n of 
St u d y Dr u g S yst e m 
Or ga n Class a n d 
Preferre d Ter m 
Safet y 
P o p ulati o n 
N 
 
A E _ T A E 
1 4. 3. 1. 5 
S u m mar y of 
Treat me nt-
E mer ge nt A d verse 
E ve nts Res ulti n g i n 
St u d y D ose 
I nterr u pti o n b y 
S yste m Or ga n 
Class a n d Preferre d 
Ter m 
Safet y 
P o p ulati o n 
N 
 
A E _ T A F 
1 4. 3. 1. 6 
S u m mar y of 
C T C A E Gra de 3- 4 
He mat ol o g y 
Treat me nt-
E mer ge nt A d verse 
E ve nts b y S yste m 
Or ga n Class a n d 
Preferre d Ter m 
Safet y 
P o p ulati o n 
N 
 
A E _ T A G 
1 4. 3. 1. 7 
S u m mar y of 
C T C A E Gra de 3- 4 
Ser u m C he mistr y 
Treat me nt-
E mer ge nt A d verse 
E ve nts b y S yste m 
Or ga n Class a n d 
Preferre d Ter m 
Safet y 
P o p ulati o n 
N 
 
A E _ T A H 
1 4. 3. 1. 8 
S u m mar y of 
Treat me nt-
E mer ge nt A d verse 
E ve nts b y 
Se verit y/I nt e nsit y, 
S yste m Or ga n 
Class, a n d 
Preferre d Ter m 
Safet y 
P o p ulati o n 
Y 
 
A E _ T AI 
1 4. 3. 1. 9 
S u m mar y of 
Treat me nt-
E mer ge nt A d verse 
Safet y 
P o p ulati o n 
Y 
 


C o ncert P har mace uticals I nc. 
C O N FI D E N TI A L  
Statistical A nal ysis Pla n 
Pr ot oc ol N o. C P 5 4 3. 2 0 0 1 
 
0 7 Ma y 2 0 1 9 
Versi o n:  2. 0  
 
P a ge 4 1 of 5 0 
E ve nts b y S yste m 
Or ga n Class a n d 
Preferre d Ter m: 
I n ci de nce b y Ti me 
I nter val 
A E _ T AJ 
1 4. 3. 1. 1 0 
S u m mar y of 
Treat me nt-
E mer ge nt A d verse 
E ve nts b y S yste m 
Or ga n Class a n d 
Preferre d Ter m: 
Pre vale nce b y Ti me 
I nter val 
Safet y 
P o p ulati o n 
N 
 
A E _ T A K 
1 4. 3. 1. 1 1 
S u m mar y of 
C T C A E Gra de 3- 4 
Treat me nt-
E mer ge nt 
He mat ol o g y 
A d verse E v e nts 
S yste m Or ga n 
Class a n d Preferre d 
Ter m: I nci de nce b y 
Ti me I nt er val 
Safet y 
P o p ulati o n 
N 
 
A E _ T A L 
1 4. 3. 1. 1 2 
S u m mar y of 
C T C A E Gra de 3- 4 
Treat me nt-
E mer ge nt 
He mat ol o g y 
A d verse E v e nts 
S yste m Or ga n 
Class a n d Preferre d 
Ter m: Pre vale nce 
b y Ti me I nt er val 
Safet y 
P o p ulati o n 
N 
 
A E _ T A M 
1 4. 3. 1. 1 3 
S u m mar y of 
C T C A E Gra de 3- 4 
Treat me nt-
E mer ge nt Ser u m 
C he mistr y A d verse 
E ve nts S yste m 
Or ga n Class a n d 
Preferre d Ter m: 
I n ci de nce b y Ti me 
I nter val 
Safet y 
P o p ulati o n 
N 
 
A E _ T A N 
1 4. 3. 1. 1 4 
S u m mar y of 
C T C A E Gra de 3- 4 
Treat me nt-
Safet y 
P o p ulati o n 
N 
 


C o ncert P har mace uticals I nc. 
C O N FI D E N TI A L  
Statistical A nal ysis Pla n 
Pr ot oc ol N o. C P 5 4 3. 2 0 0 1 
 
0 7 Ma y 2 0 1 9 
Versi o n:  2. 0  
 
P a ge 4 2 of 5 0 
E mer ge nt 
He mat ol o g y 
A d verse E v e nts b y 
S yste m Or ga n 
Class a n d Preferre d 
Ter m: Pre vale nce 
b y Ti me I nt er val 
A E _ T A O 
1 4. 3. 1. 1 5 
S u m mar y of 
Treat me nt-
E mer ge nt A d verse 
E ve nts b y 
Relati o ns hi p t o 
St u d y Dr u g, 
S yste m Or ga n 
Class, a n d 
Preferre d Ter m 
Safet y 
P o p ulati o n 
N 
 
A E _ T A P 
1 4. 3. 1. 1 6 
S u m mar y of 
Treat me nt-
E mer ge nt Seri o us 
A d verse E v e nts b y 
Relati o ns hi p t o 
St u d y Dr u g, 
S yste m Or ga n 
Class, a n d 
Preferre d Ter m 
Safet y 
P o p ulati o n 
N 
 
L B _ T A A 
1 4. 3. 4. 1. 1 
S u m mar y of All 
Cli nical La b orat or y 
Val ues: 
He mat ol o g y 
Safet y 
P o p ulati o n 
Y 
X 
L B _ T A B 
1 4. 3. 4. 1. 2 
S u m mar y of All 
Cli nical La b orat or y 
Val ues: Ser u m 
C he mistr y 
Safet y 
P o p ulati o n 
N 
 
L B _ T A C 
1 4. 3. 4. 2. 1 
S u m mar y of 
C T C A E Gra de 3- 4 
Ke y Cli nical 
La b orat or y Val ues: 
He mat ol o g y 
Safet y 
P o p ulati o n 
Y 
X 
L B _ T A D 
1 4. 3. 4. 2. 2 
S u m mar y of 
C T C A E Gra de 3- 4 
Ke y Cli nical 
La b orat or y Val ues: 
Ser u m C he mistr y 
Safet y 
P o p ulati o n 
N 
 
V S _ T A A 
1 4. 3. 5. 1 
Vital Si g ns 
S u m mar y 
Safet y 
P o p ulati o n 
Y 
 


C o ncert P har mace uticals I nc. 
C O N FI D E N TI A L  
Statistical A nal ysis Pla n 
Pr ot oc ol N o. C P 5 4 3. 2 0 0 1 
 
0 7 Ma y 2 0 1 9 
Versi o n:  2. 0  
 
P a ge 4 3 of 5 0 
E G _ T A A 
1 4. 3. 5. 2 
1 2- Lea d 
Electr ocar di o gra m 
S u m mar y 
Safet y 
P o p ulati o n 
N 
 
E G _ T A B 
1 4. 3. 5. 3 
S u m mar y of 
A b n or mal, 
Cli nicall y 
Si g nifica nt 1 2- Lea d 
Electr ocar di o gra m 
Val ues b y 
Treat me nt Gr o u p 
a n d Visit 
Safet y 
P o p ulati o n 
Y 
 
E G _ T A C 
1 4. 3. 5. 4 
S u m mar y of 
Cli nicall y N ota ble 
1 2- Lea d 
Electr ocar di o gra m 
Val ues b y 
Treat me nt Gr o u p 
a n d Visit 
Safet y 
P o p ulati o n 
Y 
 
 


C o ncert P har mace uticals I nc. 
C O N FI D E N TI A L  
Statistical A nal ysis Pla n 
Pr ot oc ol N o. C P 5 4 3. 2 0 0 1 
0 7 Ma y 2 0 1 9 
Versi o n:  2. 0  
P a ge 4 4 of 5 0 
1 5.  LI S T O F P L A N N E D FI G U R E S
 Fi g ure 
I D 
Fi g ure N o. 
Title 
P o p ul ati o n 
U ni q ue ? 
I nteri m 
A n al ysis 
D S _ F A A 
1 4. 1. 1 
Ka pla n- Mei er Pl ot f or 
Ti me  t o Last D os e 
Safet y 
P o p ulati o n 
Y 
E F _ F A A 
1 4. 2. 1. 1 
Res p o n ders b y 
Treat me nt at Wee k 2 4 
Efficac y 
P o p ulati o n 
Y 
X 
E F _ F A B 
1 4. 2. 1. 2 
Res p o n ders b y 
Treat me nt acr oss Ti me 
Efficac y 
P o p ulati o n 
Y 
X 
E F _ F A C 
1 4. 2. 1. 3 
Mea n S A L T Sc ores b y 
Treat me nt acr oss Ti me 
Efficac y 
P o p ulati o n 
Y 
X 
E F _ F A D 
1 4. 2. 1. 4 
Mea n A bs ol ute C ha n ge 
i n S A L T Sc ores b y 
Treat me nt acr oss Ti me 
Efficac y 
P o p ulati o n 
N 
X 
E F _ F A E 
1 4. 2. 1. 5 
Mea n Relati ve C ha n ge 
i n S A L T Sc ores b y 
Treat me nt acr oss Ti me 
Efficac y 
P o p ulati o n 
N 
X 
L B _ F A A 
1 4. 3. 4. 1. 1 
Ke y Cli nical La b orat or y 
Val ues: He mat ol o g y 
Para meters 
Safet y 
P o p ulati o n 
Y 


C o ncert P har mace uticals I nc. 
C O N FI D E N TI A L  
Statistical A nal ysis Pla n 
Pr ot oc ol N o. C P 5 4 3. 2 0 0 1 
 
0 7 Ma y 2 0 1 9 
Versi o n:  2. 0  
 
P a ge 4 5 of 5 0 
1 6.  LI S T O F P L A N N E D D A T A LI S TI N G S 
 
Listi n g I D 
Listi n g 
N o. 
 
Title 
 
P o p ul ati o n 
U ni q ue ? 
I nteri m 
A n al ysis 
R N _ L A A 
1 6. 1. 1 
Ra n d o mizati o n 
C o des 
All Ra n d o mize d 
Patie nts 
Y 
 
L B _ L A A 
1 6. 1. 1 0. 1 
Cli nical La b orat or y 
Refere n ce Ra n ge 
N/ A 
Y 
 
D S _ L A A 
1 6. 2. 1. 1 
Patie nt Dis p ositi o n 
All Ra n d o mize d 
Patie nts 
Y 
 
D S _ L A B 
1 6. 2. 1. 2 
Scree n Fail ures 
 
Y 
 
D S _ L A C 
1 6. 2. 1. 3 
Scree n Fail ures 
Pri or t o A me n d me nt 
2 
 
N 
 
D S _ L A D 
1 6. 2. 1. 4 
Patie nt Visits 
All Ra n d o miz e d 
Patie nts 
Y 
 
D S _ L A E 
1 6. 2. 2  
Pr ot oc ol De viati o ns 
All Ra n d o miz e d 
Patie nts 
Y 
 
D S _ L A F 
1 6. 2. 3 
A nal ysis Sets 
All Ra n d o mize d 
Patie nts 
Y 
 
D M _ L A A 
1 6. 2. 4. 1 
Patie nt 
De m o gra p hic a n d 
Baseli ne 
C haracteristics 
All Ra n d o mize d 
Patie nts  
Y 
 
D M _ L A B 
1 6. 2. 4. 2 
Al o pecia Areata 
Hist or y 
All Ra n d o mize d 
Patie nts 
Y 
 
M H _ L A A 
1 6. 2. 4. 3 
Me dical Hist or y 
Safet y P o p ulati o n 
Y 
 
C M _ L A A 
1 6. 2. 4. 4 
Pri or a n d 
C o nc o mita nt 
Me dicati o ns 
Safet y P o p ulati o n 
Y 
 
E X _ L A A 
1 6. 2. 5. 1 
Treat me nt 
C o m plia nce 
Safet y P o p ulati o n 
Y 
 
E X _ L A B 
1 6. 2. 5. 2 
D osi n g E x ce pti o ns 
Safet y P o p ulati o n 
Y 
 
E F _ L A A 
1 6. 2. 6. 1 
S A L T Sc ore 
Efficac y 
P o p ulati o n 
Y 
 
E F _ L A B 
1 6. 2. 6. 2 
S A L T P h ot o gra p hs 
Efficac y 
P o p ulati o n 
Y 
 
E F _ L A C 
1 6. 2. 6. 3 
Cli nicia n a n d 
Patie nt V A S- S 
Efficac y 
P o p ulati o n 
Y 
 
E F _ L A D 
1 6. 2. 6. 4 
C GI-I a n d P GI-I 
Efficac y 
P o p ulati o n 
Y 
 
E F _ L A E 
1 6. 2. 6. 5 
A A SI S 
Efficac y 
P o p ulati o n 
Y 
 


C o ncert P har mace uticals I nc. 
C O N FI D E N TI A L  
Statistical A nal ysis Pla n 
Pr ot oc ol N o. C P 5 4 3. 2 0 0 1 
 
0 7 Ma y 2 0 1 9 
Versi o n:  2. 0  
 
P a ge 4 6 of 5 0 
E F _ L A F 
1 6. 2. 6. 6 
E x pl orat or y 
Q uesti o ns 
Efficac y 
P o p ulati o n 
N 
 
A E _ L A A 
1 6. 2. 7. 1 
All A d verse E v e nts 
Safet y P o p ulati o n 
Y 
 
A E _ L A B 
1 6. 2. 7. 2 
Seri o us A d verse 
E ve nts 
Safet y P o p ulati o n 
N 
 
A E _ L A C 
1 6. 2. 7. 3 
A d verse E v e nts 
Relate d t o St u d y 
Dr u g 
Safet y P o p ulati o n 
N 
 
A E _ L A D 
1 6. 2. 7. 4 
A d verse E v e nts 
Lea di n g t o St u d y 
Dr u g 
Disc o nti n uati o n 
Safet y P o p ulati o n 
N 
 
A E _ L A E 
1 6. 2. 7. 5 
A d verse E v e nts 
Lea di n g t o St u d y 
Dr u g I nterr u pti o n  
Safet y P o p ulati o n 
N 
 
A E _ L A F 
1 6. 2. 7. 6 
A d verse E v e nts 
Lea di n g t o Deat h 
Safet y P o p ulati o n 
N 
 
A E _ L A G 
1 6. 2. 7. 7 
Pre g n a nc y 
Safet y P o p ulati o n 
N 
 
P E _ L A A 
1 6. 2. 8 
P h ysical 
E x a mi nati o ns 
Safet y P o p ulati o n 
Y 
 
L B _ L A B 
1 6. 2. 9. 1 
Cli nical La b orat or y 
Data: He mat ol o g y 
Safet y P o p ulati o n 
Y 
 
L B _ L A C 
1 6. 2. 9. 2 
Cli nical La b orat or y 
Data: Ser u m 
C he mistr y  
Safet y P o p ulati o n 
N 
 
V S _ L A A 
1 6. 2. 1 0. 1 
Vital Si g ns 
Safet y P o p ulati o n 
Y 
 
E G _ L A A 
1 6. 2. 1 0. 2 
1 2- Lea d 
Electr ocar di o gra m 
Safet y P o p ulati o n 
Y 
 
P K _ L A A 
1 6. 2. 1 0. 3 
P har mac o ki netic 
Bl o o d Sa m ples 
P har mac o ki netic 
P o p ulati o n 
Y 
 
P D _ L A A 
1 6. 2. 1 0. 4 
P har mac o d y na mic 
Bl o o d Sa m ples 
P har mac o ki netic 
P o p ulati o n 
Y 
 
 


C o ncert P har mace uticals I nc. 
C O N FI D E N TI A L  
Statistical A nal ysis Pla n 
Pr ot oc ol N o. C P 5 4 3. 2 0 0 1 
 
0 7 Ma y 2 0 1 9 
Versi o n:  2. 0  
 
P a ge 4 7 of 5 0 
1 7.  A P P E N DI C E S 
1 7. 1  St u d y Fl o w C h art 
 
 
 
 
 
 
 
 
 
 
 
 


 
Versi o n: 2. 0 
 
P a ge 4 8  of 5 0  
 
1 7. 2  S c h e d ul e of E v e nt s 
 
 
Scree ni n g  
R a n d o miz ati o n 
Tre at me nt Peri o d 
S afet y    
F oll o w- U p 
D a y - 2 8 t o D a y - 1 1 2 
D a y 1 1 
We e k 2, 6 
( Visit 3, 5) 
We e k 4, 8 
( Visit 4, 6) 
We e k 1 2 
( Visit 7) 
We e k 1 6, 2 0 
( Visit 8, 9) 
We e k 2 4
1 1 
( Visit 1 0) 
We e k 2 8    
( Visit 1 1)1 3 
E ve nt 
( Visit 1) 
( Visit 2) 
I nf or me d c o nse nt 
X 
 
 
 
 
 
 
 
Eli gi bilit y assess me nt 
X 
X 
 
 
 
 
 
 
De m o gra p hics 
X 
 
 
 
 
 
 
 
Me dical hist or y 
X 
X 
 
 
 
 
 
 
Ra n d o mizati o n 
 
X 
 
 
 
 
 
 
P h ysical e xa mi n ati o n 
X 
X 
 
 
 
 
X 
X 
Brief p h ysical e xa mi nati o n 
 
 
 
X 
X 
X 
 
 
Hei g ht  
X 
 
 
 
 
 
 
 
Wei g ht 
X 
X 
 
X 
X 
X 
X 
X 
Pre g na nc y test 2 
X 
X 
 
X 
X 
X 
X 
 
T u berc ul osis test 
X 
 
 
 
 
 
 
 
Cli nical la b orat or y testi n g 3, 8 
X 4 
X 
X 
X 
X 
X 
X 
X 
Li pi d assess me nt 5 
 
X 
 
 
X 
 
X 
X 
H B V a n d H C V test 
X 
 
 
 
 
 
 
 
P har mac o ki n etic bl o o d sa m pli n g 
 
X 6 
X 6 
X 6 
 
 
X 6 
 
P har mac o d y na mic bl o o d sa m pli n g 
 
X 7 
X 7 
X 7 
 
 
X 7 
 
1 2-lea d electr o car di o gra m 
X 
X 
 
X 
X 
X 
X 
X 
Vital si g ns 
X 
X 
 
X 
X 
X 
X 
X 
Se verit y of Al o pecia T o ol assess me nt 9 
X 
X 
 
X 
X 
X 
X 
 
P h ot o gra p hs 
X 
X 
 
X 
X 
X 
X 
 
Cli nicia n Vis ual A nal o g Scale –  Se verit y9 
 
X 
 
 
X 
 
X 
 
Cli nicia n Gl o bal I m pressi o n of I m pr o ve me nt 9 
 
 
 
 
X 
 
X 
 
P atie nt Vis ual A nal o g Scale - Se verit y 
 
X 
 
 
X 
 
X 
 
P atie nt Gl o bal I m pressi o n of I m pr o ve me nt 
 
 
 
 
X 
 
X 
 
A A SI S a n d e x pl orat or y q uesti o ns 
 
X 
 
 
 
 
X 
 
Dis pe nse st u d y dr u g 
 
X 
 
X 
X 
X 
 
 
St u d y dr u g acc o u nta bilit y 
 
 
 
X 
X 
X 
X 
 
A d verse e ve nts 1 0 
X 
X 
X 
X 
X 
X 
X 
X 
C o nc o mita nt me dicati o ns 1 0 
X 
X 
X 
X 
X 
X 
X 
X  


C o ncert P har mace uticals I nc. 
C O N FI D E N TI A L  
Statistical A nal ysis Pla n 
Pr ot oc ol N o. C P 5 4 3. 2 0 0 1 
 
0 7 Ma y 2 0 1 9 
Versi o n:  2. 0  
 
P a ge 4 9 of 5 0 
A A SI S = Al o pecia Are ata S y m pt o m I m pact Scale; H B V = h e patitis B vir us; H C V = he patitis C vir us 
1  All s u bse q ue nt visits a n d wee k i ncre me nts s h o ul d be base d o n the d ate of Visit 2. All    
v isit wi n d o ws are ± 3 da ys. 
2 Ser u m pre g na nc y test o nl y f or fe males of c hil d beari n g p ote ntial. 
3  I ncl u des he mat ol o g y a n d ser u m c he mistr y.  
4  Will i n cl u de t hyr oi d sti m ulati n g h or m o ne a n d he m o gl o bi n A 1c at Scree ni n g o nl y.  
5 Incl u des t otal c h olester ol, l o w- de nsit y li p o pr otei n, hi g h- de nsit y li p o pr otei n, a n d tri gl yc eri d es. 
6  C ollecte d at Da y 1 a n d Wee k 4 ( pre- d ose, a n d p ost- d ose at e n d of visit), a n d Wee ks 2 ( pre-d ose 
wit h cli nical la bs), a n d Wee ks 8, 2 4 ( p ost- d ose at e n d of visit ).  
7  C ollecte d at Da y 1 a n d Wee k 2 ( pre- d ose wit h cli nical la bs), an d Wee ks 4, 8, 2 4 ( p ost- d ose 
at e n d of visit). 8  C ollecte d pre- d ose. 
9 S h o ul d be perf or me d b y t h e sa me rater f or t he pati e nt f or t he d urati o n of t he st u d y. 
1 0 C ollecti o n is o n g oi n g. 
1 1 Als o ser ves as t h e Earl y Ter mi n ati o n Visit f or patie nt wit h dra w al. 
1 2  Ra n d o mizati o n/ Da y 1 ma y occ ur a n y ti me after Scree ni n g la b orator y res ults are a vaila ble 
a n d re vie we d b y t h e I n vesti gat or. 
1 3 T he Safet y F oll o w-U p Visit is i nte n de d f or t h ose patie nts i n C o h ort 1 a n d C o h ort 2, a n d 
t h ose patie nts i n C o h ort 3 w h o d o n ot r oll o ver i nt o t he O pe n-la bel E xte nsi o n. 


 
Versi o n: 2. 0 
 
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1 8.   A T T A C H M E N T S 
Attac h me nt A: “ C P 5 4 3. 2 0 0 1 –  T L F S hells” –  S hells f or Pla n ne d Ta bles, Fi g ures, a n d Listi n gs