A Phase 3, Multinational, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Study to Evaluate the Efficacy PK, Kinetics and Safety of Aramchol in Nonalcoholic Steatohepatitis (NASH) With Open-Label Part
Phase: PHASE3
Conditions: Nonalcoholic Steatohepatitis (NASH)
Sponsor: Galmed Research and Development, Ltd.

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1  of 1 2 7  
Cli nic al St u d y Pr ot oc ol  
A P h as e 3, M ulti n ati o n al, M ultic e nt er, R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr oll e d 
Cli nic al St u d y t o E v al u at e t h e Effic ac y  a n d S af et y of Ar a mc h ol i n S u bj ects wit h N o n alc o h olic 
St e at o h e p atitis  ( N A S H) wit h O p e n -L a b el P art t o E v al u at e t h e S af et y, P K a n d Tr e at m e nt 
R es p o ns e Ki n etics of Ar a mc h ol  
T h e A R M O R St u d y  
 
Pr ot oc ol N o: Ar a mc h ol -0 1 8  
E U D R A C T N o: 2 0 1 9 -0 0 2 0 7 3 -5 6   
I N D: 7 9, 2 0 0 
Cli nic al P h as e: 3  
Pr ot oc ol V ersi o n 4. 0 d at e d 2 3  N o v 2 0 2 0  
 
 
 
 
 
 
 
  
S p o ns or:  
G al m e d R es e arc h a n d D ev el o p m e nt,  Lt d. 
1 6 Z e’ e v Ti o m ki n St.  
T el A vi v, 6 5 7 8 3 1 7, I S R A EL  
T el: 9 7 2 -3 -6 9 3 8 4 4 8  
 
R es p o nsi bl e M e dic al Offic er:  
 
 
. 
 
C o -Pri nci p al I n v esti g at ors:  
 
 
 
 
 
 
 
 
 
1 4  
 
C o nfi d e nti alit y St at e m e nt  
T h e i nf or m ati o n c o nt ai n e d h er ei n c o nstit ut es c o nfi d e nti al a n d pr o pri et ar y i nf or m ati o n of 
G al m e d  R es e arc h a n d D ev el o p m e nt Lt d. (t h e S p o ns or). A ny u n a ut h oriz e d us e o r discl os ur e of s uc h 
i nf or m ati o n wit h o ut t h e pri or writt e n c o ns e nt of t h e S p o ns or is ex pr essly pr o hi bit e d. 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
2  of 1 2 7  
G C P St at e m e nt  
T his cli nic al st u d y will b e c o n d uct e d i n acc or d a nc e wit h t h e S p o ns or’s a n d/ or C o ntr act 
R es e arc h Or g a niz ati o n’s St a n d ar d O p er ati n g Pr oc e d ur es ( S O Ps), c urr e nt G o o d Cli nic al 
Pr actic e ( G C P), t h e pr o visi o ns of I C H (I nt er n ati o n al C o nf er e nc e o n H ar m o niz ati o n) 
G ui d eli n es, a p plic a bl e U S C o d e of F e d er al R e g ul ati o ns ( C F R) a n d E U Dir ectiv es.  
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
3  of 1 2 7  
T a bl e of C o nt e nts  
SI G N A T U R E P A G E  .............................................................................................................. 9  
I N V E S TI G A T O R’ S A G R E E M E N T ........................................................................................ 1 0  
1  
S Y N O P SI S  .................................................................................................................. 1 1  
2  
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 NS O F T E R M S ........................................... 3 7  
3  
I N T R O D U C TI O N ........................................................................................................ 4 0  
3. 1  
B ac k gr o u n d I nf or m ati o n  ...................................................................................... 4 0  
3. 1. 1  
N o n alc o h olic F att y Li v er Dis e as e ( N A FL D) a n d N o n alc o h olic St e at o h e p atitis 
( N A S H) ............................................................................................................ 4 0  
3. 2  
Ar a mc h ol  .............................................................................................................. 4 1  
3. 3  
K n o w n  a n d P ot e nti al Risks a n d B e n efits t o H u m a n S u bj ects  .............................. 4 2  
3. 4  
R ati o n al e f or St u d y D esi g n, D os e a n d P o p ul ati o n  ............................................... 4 3  
3. 4. 1  
St u d y R ati o n al e  .............................................................................................. 4 3  
3. 4. 2  
D os e R ati o n al e  ............................................................................................... 4 5  
3. 4. 3  
St u d y P o p ul ati o n R ati o n al e  ........................................................................... 4 6  
4  
S T U D Y O BJ E C TI V E S  .................................................................................................. 4 6  
4. 1  
Effic ac y E n d p oi nts  ................................................................................................ 4 6  
4. 1. 1  
O p e n -L a b el P art ............................................................................................. 4 6  
4. 1. 2  
R a n d o m iz e d, D o u bl e-Bli n d, Pl ac e b o -C o ntr oll e d P art  .................................... 4 7  
4. 2  
S af et y a n d T ol er a bilit y Ev al u ati o ns  ...................................................................... 4 9  
4. 3  
P h ar m ac o ki n etic E n d p oi nts  ................................................................................. 4 9  
5  
S T U D Y D E SI G N  ......................................................................................................... 4 9  
5. 1  
O v er vi e w a n d P l a n ............................................................................................... 4 9  
6  
S T U D Y P O P UL A TI O N  ................................................................................................ 5 2  
6. 1  
I ncl usi o n Crit eri a .................................................................................................. 5 2  
6. 2  
Excl us i o n Crit eri a .................................................................................................. 5 4  
7  
C O N C O MI T A N T M E DI C A TI O N S A N D S P E CI AL W A R NI N G S  ...................................... 5 6  
7. 1  
All o w e d C o nc o mit a nt M e dic ati o ns D uri n g t h e St u d y  ......................................... 5 6  
7. 2  
Dis all o w e d C o nc o mit a nt M e dic ati o ns D uri n g t h e St u d y  ..................................... 5 6  
7. 3  
Dr u g -Dr u g I nt er acti o ns  ........................................................................................ 5 7  
7. 4  
S p eci al W ar ni n gs a n d Pr ec a uti o ns f or Us e  .......................................................... 5 7  
7. 4. 1  
H e p atic I m p air m e nt  ....................................................................................... 5 7  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
4  of 1 2 7  
7. 4. 2  
R e n al I m p air m e nt  .......................................................................................... 5 7  
7. 5  
St o p pi n g Crit eri a  .................................................................................................. 5 8  
7. 5. 1  
Pr e g n a ncy  ....................................................................................................... 5 8  
7. 5. 2  
DILI M o nit ori n g a n d St o p pi n g R ul es  .............................................................. 5 9  
7. 5. 3  
St o p pi n g R ul es f or li v er -r el at e d e v e nts ......................................................... 6 3  
7. 6  
T hr o m b o e m b olis m  ............................................................................................... 6 4  
7. 7  
C h ol ecystitis  ......................................................................................................... 6 4  
8  
S T U D Y C O N D U C T  ..................................................................................................... 6 4  
8. 1  
St u d y P eri o d  ......................................................................................................... 6 4  
8. 2  
D et ail e d St u d y Pl a n  .............................................................................................. 6 5  
8. 2. 1  
Scr e e ni n g P eri o d  ............................................................................................ 7 1  
8. 2. 2  
B as eli n e Visit –  R a n d o miz ati o n  ...................................................................... 7 2  
8. 2. 3  
O p e n -L a b el P art- Sc h e d ul e d visits ( n ot i ncl u di n g E n d of St u d y visit) ............ 7 3  
8. 2. 4  
O p e n -L a b el P art - E n d -of -St u d y Visit  ............................................................. 7 5  
8. 2. 5  
R a n d o miz e d , D o u bl e-Bli n d, Pl ac e b o -C o ntr oll e d P art Sc h e d ul e d visits ( n ot 
i ncl u di n g E n d of St u d y visit) ........................................................................... 7 6  
8. 2. 6  
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr oll e d P art:  E n d -of -St u d y Visit a n d 7 -
Y e ar Visit  ........................................................................................................ 7 7  
8. 2. 7  
U nsc h e d ul e d Visit  .......................................................................................... 7 8  
8. 2. 8  
E arl y Disc o nti n u ati o n Visit - E T D/ E S D ( b ot h st u d y p arts; O p e n -L a b el P art a n d 
R a n d o miz e d, D o u bl e Bli n d, Pl ac e b o -C o ntr oll e d P art ) ................................... 7 9  
8. 3  
T e m p or ar y Disc o nti n u ati o n of St u d y Dr u g Tr e at m e nt  ........................................ 8 1  
8. 4  
I n v esti g ati o n al M e dici n al Pr o d ucts/ St u d y Dr u gs................................................. 8 1  
8. 4. 1  
Tr e at m e nt A d mi nistr ati o n  ............................................................................. 8 1  
8. 4. 2  
M et h o d of Assi g ni n g S u bj ects t o Tr e at m e nt Gr o u ps  .................................... 8 1  
8. 4. 3  
St u d y Bli n di n g a n d Bli n di n g Pl a n  ................................................................... 8 2  
8. 4. 4  
E m er g e ncy C o d e Br e a ki n g  ............................................................................. 8 4  
8. 4. 5  
D escri pti o n of I n v esti g ati o n al M e dici n al Pr o d ucts/ St u d y Dr u gs  ................... 8 4  
8. 4. 6  
P ac k a gi n g a n d L a b eli n g  .................................................................................. 8 5  
8. 4. 7  
S hi p pi n g & Distri b uti o n  .................................................................................. 8 5  
8. 4. 8  
St or a g e, Dis p e nsi n g a n d R et ur n ..................................................................... 8 6  
8. 4. 9  
V erific ati o n of Tr e at m e nt C o m pli a nc e a n d Acc o u nt a bilit y  ........................... 8 6  
8. 5  
C O VI D -1 9 C o nti n g e ncy m e as ur es  ........................................................................ 8 6  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
5  of 1 2 7  
8. 5. 1  
G e n er al  ........................................................................................................... 8 6  
8. 5. 2  
Alt er n ati v e L oc ati o n Visit  ............................................................................... 8 7  
8. 5. 3  
I nt er vi e w b y P h o n e or Vi d e o C o nf er e nc e ...................................................... 8 7  
8. 5. 4  
N ec ess ar y d at a c oll ecti o n r e q uir e m e nts  ....................................................... 8 7  
8. 5. 5  
St u d y e q ui p m e nt a n d m at eri als ..................................................................... 8 7  
8. 5. 6  
St u d y dr u g dis p e nsi n g a n d us e d dr u gs b ottl es c oll ecti o n  ............................. 8 8  
8. 5. 7  
L a b or at or y S p eci m e ns ................................................................................... 8 8  
8. 5. 8  
A d diti o n al c o nti n g e ncy m e as ur es  .................................................................. 8 8  
9  
A S S E S S M E N T S & P R O C E D U R E S  ............................................................................... 8 9  
9. 1  
Liv er Bi o ps y .......................................................................................................... 8 9  
9. 1. 1  
O p e n -L a b el P art ............................................................................................. 8 9  
9. 1. 2  
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr oll e d P art  .................................... 8 9  
9. 1. 3  
Li v er bi o ps y b as e d o n s us pici o n of dis e as e pr o gr essi o n ( B ot h  st u d y p arts, O p e n 
L a b el P art a n d R a n d o miz e d, D o u bl e Bli n d, Pl ac e b o C o ntr oll e d P art)  ........... 9 0  
9. 1. 4  
Li v er bi o ps y m e dic al a n d t ec h nic al s p ecifics  ................................................. 9 0  
9. 2  
Fi br osc a n  .............................................................................................................. 9 1  
9. 3  
A b d o mi n al Ultr as o u n d  ......................................................................................... 9 2  
9. 4  
M EL D sc or e  .......................................................................................................... 9 2  
9. 5  
Pr e -D efi n e d Cli nic al O utc o m e E v e nts  .................................................................. 9 2  
9. 6  
Lif est yl e h a bits ..................................................................................................... 9 3  
9. 7  
P h ar m ac o ki n etics  ................................................................................................. 9 3  
9. 8  
Bi o m ar k ers, M et a b ol o mics G e n e a n d Micr o bi o m e A n al ysis  ............................... 9 4  
9. 9  
S A F E T Y AS S E S S M E N T S  ......................................................................................... 9 4  
9. 9. 1  
A d v ers e E v e nts  ............................................................................................... 9 4  
9. 9. 2  
S af et y  L a b or at or y E v al u ati o ns ....................................................................... 9 4  
9. 9. 3  
Cli nic al L a b or at or y T ests  ................................................................................ 9 4  
9. 9. 4  
El ectr oc ar di o gr a m ( E C G)  ................................................................................ 9 5  
9. 9. 5  
Pr e g n a ncy T est  ............................................................................................... 9 6  
9. 9. 6  
Vit al Si g ns  ....................................................................................................... 9 6  
9. 9. 7  
P h ysic al Ex a mi n ati o ns  .................................................................................... 9 6  
9. 9. 8  
B o d y M e as ur e m e nts  ...................................................................................... 9 7  
1 0  S A F E T Y A N D P H A R M A C O VI GIL A N C E  ....................................................................... 9 7  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
6  of 1 2 7  
1 0. 1  A d v ers e E v e nt s ..................................................................................................... 9 8  
1 0. 1. 1  
D efi niti o n of a n A d v ers e E v e nts  ..................................................................... 9 8  
1 0. 1. 2  
R ec or di n g a n d R e p orti n g A d v ers e E v e nts ...................................................... 9 9  
1 0. 1. 3  
S e v erit y of a n A d v ers e Ev e nt  ......................................................................... 9 9  
1 0. 1. 4  
R el ati o ns hi p of a n A d v ers e E v e nt t o t h e St u d y Dr u g ................................... 1 0 0  
1 0. 1. 5  
S e ri o us A d v ers e E v e nts ................................................................................ 1 0 0  
1 0. 2  S af et y R e p orti n g t o I n v esti g at ors, I nstit uti o n al R e vi e w B o ar ds or I n d e p e n d e nt Et hics 
C o m mitt e es, a n d R e g ul at or y A ut h oriti es.  ......................................................... 1 0 1  
1 0. 3  Pr e g n a ncy R e p orts  ............................................................................................. 1 0 2  
1 1  S T A TI S TI C AL M E T H O D OL O G Y  ................................................................................ 1 0 2  
1 1. 1  O p e n -L a b el P art ................................................................................................. 1 0 2  
1 1. 2  R a n d o miz e d , D o u bl e-Bli n d, Pl ac e b o -C o ntr oll e d P art:  ....................................... 1 0 3  
1 1. 2. 1  
R a n d o miz ati o n  ............................................................................................. 1 0 4  
1 1. 2. 2  
St u d y Pri m ar y E n d p oi nts  .............................................................................. 1 0 4  
1 1. 2. 3  
Sc h e d ul e of St atistic al A n al ys es  ................................................................... 1 0 5  
1 1. 2. 4  
T y p e -I Err or a n d M ulti plicit y A dj ust m e nt .................................................... 1 0 5  
1 1. 2. 5  
S a m pl e Siz e R ati o n al e  .................................................................................. 1 0 5  
1 1. 2. 6  
M aj or D at a A n al ysis S ets  .............................................................................. 1 0 7  
1 1. 2. 7  
C o m p ar a bilit y of St u d y Gr o u ps at B as eli n e  ................................................. 1 0 8  
1 1. 2. 8  
Pri m ar y Esti m a n ds of I nt er est  ..................................................................... 1 0 8  
1 1. 2. 9  
Effic ac y E n d p oi nts a n d A n al ys es  .................................................................. 1 0 9  
1 1. 2. 1 0  
K e y S ec o n d ar y E n d p oi nt a n d A n al ysis  ......................................................... 1 1 1  
1 1. 2. 1 1  
Ex pl or at or y E n d p oi nts a n d A n al ys es  ........................................................... 1 1 1  
1 1. 2. 1 2  
St atistic al A n al ysis Pl a n (S A P) f or R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr oll e d 
P art  ............................................................................................................... 1 1 2  
1 1. 3  S af et y A n al ys es ( b ot h st u d y p arts; O p e n L a b el P art a n d R a n d o miz e d, D o u bl e Bli n d, 
Pl ac e b o C o ntr oll e d P art ) .................................................................................... 1 1 2  
1 1. 3. 1  
A d v ers e E v e nts  ............................................................................................. 1 1 2  
1 1. 3. 2  
L a b or at or y D at a ........................................................................................... 1 1 3  
1 1. 3. 3  
Vit al Si g ns  ..................................................................................................... 1 1 4  
1 1. 3. 4  
El ectr oc ar di o gr a m E C G  ................................................................................ 1 1 4  
1 1. 4  T ol er a bilit y Ass ess m e nts  .................................................................................... 1 1 4  
1 1. 5  St atistic al S oft w ar e  ............................................................................................ 1 1 4  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
7  of 1 2 7  
1 2  S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N AL C O N SI D E R A TI O N S  ............ 1 1 5  
1 2. 1  R e g ul at or y, Et hic al, a n d St u d y O v ersi g ht C o nsi d er ati o ns  ................................. 1 1 5  
1 2. 1. 1  
C o m pli a nc e  St at e m e nt  ................................................................................ 1 1 5  
1 2. 1. 2  
I n d e p e n d e nt Et hics  C o m mitt e e (I E C) / I nstit uti o n al R e vi e w B o ar d (I R B)  .... 1 1 6  
1 2. 1. 3  
I nf or m e d C o ns e nt  Pr o c ess  ......................................................................... 1 1 6  
1 2. 2  C o nfi d e nti alit y  .................................................................................................... 1 1 7  
1 2. 2. 1  
S u bj e ct C o nfi d e nti alit y ................................................................................. 1 1 8  
1 2. 3  St u d y  M o nit ori n g  ............................................................................................... 1 1 8  
1 2. 3. 1  
Pr ot oc ol D e vi ati o ns  ...................................................................................... 1 1 9  
1 2. 4  Q u alit y Ass ur a nc e a n d Q u alit y C o ntr ol  .............................................................. 1 1 9  
1 2. 5  A u dits a n d I ns p ecti o ns  ....................................................................................... 1 2 0  
1 2. 6  D at a H a n dli n g a n d R ec or d K e e pi n g  ................................................................... 1 2 1  
1 2. 6. 1  
D at a H a n dli n g a n d S o urc e D at a R ec or d e d o n t h e C as e R e p ort F or m  ......... 1 2 1  
1 2. 6. 2  
St u d y Disc o nti n u ati o n a n d Cl os ur e  .............................................................. 1 2 2  
1 2. 6. 3  
St u d y R ec or ds R et e nti o n  ............................................................................. 1 2 2  
1 2. 7  F ut ur e Us e of St or e d S p eci m e ns a n d D at a  ........................................................ 1 2 3  
1 2. 8  R e p orti n g a n d P u blic ati o n of R es ults  ................................................................. 1 2 3  
1 2. 9  Li a bilit y a n d I ns ur a nc e ....................................................................................... 1 2 3  
1 2. 1 0  V e n d ors  .............................................................................................................. 1 2 4  
1 3  R E F E R E N C E S  ........................................................................................................... 1 2 5  
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
8  of 1 2 7  
LI S T O F T A BL E S 
T a bl e 1:  
M o nit ori n g a n d st o p pi n g r ul es f or c h ol est atic DILI .................................................. 6 1  
T a bl e 2:  
C e ntr al l a b or at or y r ef er e nc e r a n g es r el at e d t o DILI m o nit ori n g  ............................. 6 3  
T a bl e 3:  
St u d y Pr oc e d ur es a n d Ass ess m e nts O p e n -L a b el P art .............................................. 6 6  
T a bl e 4:  
St u dy Pr oc e d ur es a n d Ass ess m e nts R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr oll e d P art  6 8  
T a bl e 5:  
B atc h F or m ul a  ........................................................................................................... 8 4  
T a bl e 6:  
Cli nic al L a b or at or y T ests  ........................................................................................... 9 5  
 
LI S T O F FI G U R ES  
Fi g ur e 1:  
O p e n -L a b el P art Sc h e m a .......................................................................................... 5 0  
Fi g ur e 2:  
D o u bl e -Bli n d, Pl ac e b o -C o ntr oll e d P art Sc h e m a  ....................................................... 5 1  
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 0  of 1 2 7  
G al m e d R es e arc h a n d D ev el o p m e nt Lt d  
A R M O R  St u d y  
Pr ot oc ol N o. Ar a mc h ol -0 1 8  
I N V E S TI G A T O R’ S A G R E E M E N T  
A P h as e 3, M ulti n ati o n al, M ultic e nt er, R a n d o miz e d,  D o u bl e -Bli n d, Pl ac e b o -C o ntr oll e d Cli nic al 
St u d y t o E v al u at e t h e Effic ac y  a n d S af et y of Ar a mc h ol i n S u bj ects wit h N o n alc o h olic 
St e at o h e p atitis  ( N A S H) wit h O p e n -L a b el P art t o E v al u at e t h e S af et y, P K a n d Tr e at m e nt 
R es p o ns e Ki n etics of Ar a mc h ol  ( T h e A R M O R St u dy). 
 
 
Pr ot oc ol V ersi o n 4. 0, d at e d 2 3  N o v 2 0 2 0  
 
I t h e u n d ersi g n e d, h a v e r e a d a n d u n d erst o o d t h e pr ot oc ol s p ecifi e d a b o v e a n d a gr e e o n its 
c o nt e nt. I a gr e e t o p erf or m a n d c o n d uct t h e st u dy as d escri b e d i n t h e pr ot oc ol a n d i n 
acc or d a nc e wit h t h e r el ev a nt l a ws a n d r e g ul ati o ns a n d st a n d ar ds o utli n e d i n t h e Cli nic al Tri al 
A gr e e m e nt.  
 
 
 
 
 
 
 
Pri nci p al I n v esti g at or’s n a m e  
 
I nstit uti o n n a m e   
 
 
 
 
 
 
 
 
I nstit uti o n a d dr ess  
 
 
 
 
 
 
 
 
Pri nci p al I n v esti g at or’s s i g n at ur e  
 
D at e  
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 1  of 1 2 7  
1  S Y N O P SI S  
St u d y Titl e  
A P h as e 3, M ulti n ati o n al, M ultic e nt er, R a n d o miz e d,  D o u bl e -Bli n d, Pl ac e b o -
C o ntr oll e d Cli nic al St u d y t o E v al u at e t h e Effic ac y  a n d S af et y of Ar a mc h ol i n 
S u bj ects wit h N o n alc o h olic St e at o h e p atitis  ( N A S H) wit h O p e n -L a b el P art t o 
E v al u at e t h e S af et y, P K a n d Tr e at m e nt R es p o ns e Ki n etics of Ar a mc h ol  ( T h e 
A R M O R St u d y)  
 
I N D N u m b er 
7 9 2 0 0  
E u dr a C T  
2 0 1 9 -0 0 2 0 7 3 -5 6  
Cli nic al P h as e  
P h as e  3  
I n v esti g ati o n al 
Dr u g  
Ar a mc h ol  
S p o ns or N a m e 
a n d A d dr ess:  
G al m e d  R es e arc h a n d D ev el o p m e nt L T D.  
1 6 Z e’ e v Ti o m ki n St.  
T el A vi v, 6 5 7 8 3 1 7  
I S R A EL 
T el:   9 7 2 -3 -6 9 3 8 4 4 8  
F ax:  9 7 2 -3 -6 9 3 8 4 4 7  
 
 
 
 
 
 
 
 
 
 
M ai n I n dic ati o n  
N o n alc o h olic St e at o h e p atitis  ( N A S H) 
St u d y O bj ecti v es  
O p e n -L a b el P art: 
•  T o e v al u at e  t h e s af et y a n d P K of t wic e d ail y a d mi nistr ati o n ( BI D) of 
Ar a mc h ol 3 0 0 m g i n s u bj ects wit h N A S H a n d li v er fi br osis . 
 
•  T o ex pl or e t h e ki n etics of hist ol o gic al o utc o m e m e as ur es a n d N o n -I n v asi v e 
T ests ( NI T s) ass oci at e d wit h N A S H a n d fi br osis f or t h e tr e at m e nt d ur ati o n 
of 2 4, 4 8 a n d 7 2 w e e ks . 
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art : 
T o e v al u at e t h e effic acy a n d s af et y of t wic e d ail y a d mi nistr ati o n ( BI D) of 
Ar a mc h ol 3 0 0 m g as c o m p ar e d t o pl ac e b o i n s u bj ects wit h N A S H a n d li v er 
fi br osis.   
St u d y P o p ul ati o n  
O p e n -L a b el P art : 
A t ot al of  1 5 0  a d ult s u bj ects wit h N A S H a n d fi br osis c o nfir m e d b y li v er 
hist ol o g y ( F 1 -F 3) 
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d-P art : 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 2  of 1 2 7  
A t ot al of 2 0 0 0  a d ult s u bj ects wit h N A S H a n d fi br osis c o nfir m e d b y li v er 
hist ol o g y  ( F 2-F 3)  w h o ar e o v er w ei g ht or o b es e a n d h a v e  pr e di a b et es  or ty p e 2 
di a b et es . 
St u d y Gr o u ps  
O p e n -L a b el P art: 
S u bj ects , i ncl u di n g t h os e alr e a d y r a n d o miz e d t o Ar a mc h ol 3 0 0 m g BI D or 
Pl ac e b o, will b e r a n d o miz e d i n a r ati o of 1: 1: 1 t o r ec ei v e Ar a mc h ol 3 0 0 m g BI D 
acc or di n g t o t h e b el o w gr o u pi n g :  
•  Gr o u p A: T h e p ost -b as eli n e li v er bi o ps y will b e c o n d uct e d at w e e k 2 4  
•  Gr o u p B: T h e p ost -b as eli n e  li v er bi o ps y will b e c o n d uct e d at w e e k 4 8  
•  Gr o u p C: T h e p ost -b as eli n e  li v er bi o ps y will b e c o n d uct e d at w e e k 7 2  
 
 
 
 
 
 
 
 
  
 
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art : 
S u bj ects will b e r a n d o miz e d i n a r ati o of 2: 1 t o r ec ei v e Ar a mc h ol 3 0 0 m g BI D or 
m atc hi n g pl ac e b o, r es p ecti v el y.  
 
St u d y D esi g n  
O p e n -L a b el P art: 
A t ot al of 1 5 0  s u bj ects i ncl u di n g t h os e alr e a d y r a n d o miz e d t o Ar a mc h ol 3 0 0 m g 
BI D or pl ac e b o, will b e r a n d o miz e d i n a r ati o of 1: 1: 1 t o r ec ei v e Ar a mc h ol 
3 0 0 m g BI D acc or di n g t o t h e b el o w  gr o u pi n g :  
•  Gr o u p A: T h e p ost -b as eli n e li v er bi o ps y will b e c o n d uct e d at w e e k 2 4  
•  Gr o u p B: T h e p ost -b as eli n e li v er bi o ps y will b e c o n d uct e d at w e e k 4 8  
•  Gr o u p C: T h e p ost -b as eli n e li v er bi o ps y will b e c o n d uct e d at w e e k 7 2  
I n or d er t o m or e c o m pr e h e nsi v el y ex pl or e t h e ki n etics of hist ol o gic al o utc o m e 
m e as ur es  ( e. g. ar e t h er e s u bj ects w h o  m a y n ot s h o w i m pr o v e m e nt i n 
hist ol o gic al  o utc o m e at w e e k 2 4, 4 8 or 7 2 b ut m a y i m pr o v e wit h l o n g er 
d ur ati o n of tr e at m e nt), a 2 n d p ost -b as eli n e  li v er bi o ps y s a m pl e will b e 
c oll ect e d f or s u bj ects w h os e p ost-b as eli n e li v er bi o ps y at w e e k 2 4 or 4 8 or 7 2 
d o es  n ot s h o w at l e a st 1 st a g e i m pr o v e m e nt i n fi br osis (fi br osis n o n -
r es p o n d ers). T h e 2n d  p ost -b as eli n e  li v er bi o ps y s a m pl e will b e c oll ect e d 1 y e ar 
l at er (i. e. at w e e ks 7 2 or 9 6 or 1 2 0  r es p ecti v el y 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 5  of 1 2 7  
D ur ati o n  
O p e n -L a b el P art: 
•  Scr e e ni n g:  u p t o 8  w e e ks  
Tr e at m e nt p eri o d:  T h e O p e n -L a b el P art will c o nti n u e f or t h e s a m e d ur ati o n as  
t h e R a n d o miz e d, D o u bl e-Bli n d, Pl ac e b o -C o ntr ol l e d P art. All s u bj ects i n t h e 
O p e n -L a b el P art will r ec ei v e Ar a mc h ol 3 0 0 m g BI D u ntil E n d of st u d y ( E o S).  
 
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art : 
•  Scr e e ni n g:  u p t o 8  w e e ks  
•  Tr e at m e nt p eri o d:  S u bj ects will r e m ai n o n t h e s a m e tr e at m e nt assi g n m e nt  
f or u p t o 7  y e ars.   
•  E n d of st u d y:  All 2 0 0 0 s u bj ects pl a n n e d t o b e r a n d o miz e d i nt o t his st u d y 
will r ec ei v e Ar a mc h ol or m atc hi n g pl ac e b o u ntil E n d -of -St u d y ( E o S) w hic h 
will occ ur at t h e ti m e w h e n a t ot al of 3 8 0 s u bj ects will  ex p eri e nc e at l e ast 
1  pr e -cli nic al e v e nt or at 5 y e ars fr o m l ast s u bj ect' r a n d o miz ati o n, 
w hic h e v er c o m es first . 
•  E xt e nsi o n st u d y : S u bj ects t h at c o m pl et e 7 y e ars i n t h e st u d y or t h at ar e 
o n g oi n g at E o S will b e pr o vi d e d t h e o pti o n t o r ec ei v e Ar a mc h ol tr e at m e nt 
i n a n o p e n-l a b el ext e nsi o n. T h e ext e nsi o n st u d y will b e d et ail e d u n d er a 
s e p ar at e pr ot oc ol. 
N u m b er of Sit es  
O p e n -L a b el P art: A p pr oxi m at el y 4 0  
 
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art : A p pr oxi m at el y 2 0 0  
 
N u m b er of 
S u bj ects  
O p e n -L a b el P art: A t ot al of 1 5 0 s u bj ects.  
 
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art : A t ot al of 2 0 0 0 s u bj ects .  
 
St u d y Dr u g 
A d mi nistr ati o n  
O p e n -L a b el P art: Ar a mc h ol 3 0 0 m g BI D  
 
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art : Ar a mc h ol 3 0 0 m g BI D or 
m atc hi n g pl ac e b o.  
 
St u d y V isits  
Sc h e d ul e of acti viti es f or b ot h st u d y P arts:  
Wit h t h e exc e pt i o n of t h e ti mi n g of t h e bi o psi es a n d a n al ysis of micr o bi o m e, 
a ll st u d y pr oc e d ur es of t h e O p e n -La b el P art will b e si mil ar t o t h e R a n d o miz e d, 
D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art . 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 6  of 1 2 7  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 7  of 1 2 7  
✓ 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 8  of 1 2 7  
✓ 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 9  of 1 2 7  
✓ 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
B ac k gr o u n d:  
N o n alc o h olic  st e at o h e p atitis ( N A S H) is a s u bs et of n o n alc o h olic f att y li v er 
dis e as e ( N A FL D), a br o a d t er m t h at e nc o m p ass es t h e e ntir e s p ectr u m of f att y 
li v er dis e as es i n i n di vi d u als wit h o ut si g nific a nt alc o h ol c o ns u m pti o n, r a n gi n g 
fr o m f att y li v er t o st e at o h e p atitis t o cirr h osis. N AS H is a hist ol o gic al d efi niti o n, 
r e q uiri n g t h e pr es e nc e of ≥5 % h e p atic st e at osis wit h i nfl a m m ati o n a n d 
h e p at oc yt e i nj ur y ( b all o o ni n g) wit h or wit h o ut fi br osis. N A S H pr o m ot es li v er 
fi br osis a n d s o m e p ati e nts pr o gr ess t o s e v er e h e p atic dis e as es, i ncl u di n g 
cirr h osis a n d li v er f ail ur e. P ati e nts w h o h a v e N A S H m a y als o d e v el o p 
h e p at oc ell ul ar c arci n o m a, a n d/ or r e q uir e li v er tr a ns pl a nt ati o n f or e n d -st a g e 
li v er dis e as e or h e p at oc ell ul ar c arci n o m a. 
N A S H is t h e s ec o n d l e a di n g c a us e of cirr h osis a m o n g a d u lts a w aiti n g li v er 
tr a ns pl a nt ati o n i n t h e U nit e d St at es, w hil e N A FL D is t h e t hir d m ost c o m m o n 
c a us e of h e p at oc ell ul ar c arci n o m a i n t h e U nit e d St at es. Li v er -r el at e d m ort alit y 
is i ncr e as e d 1 0-f ol d i n N A S H p ati e nts c o m p ar e d wit h t h e g e n er al p o p ul ati o n. 
A d diti o n all y, N A S H p ati e nts h a v e a n i ncr e as e d r at e of c ar di o v asc ul ar e v e nts 
a n d ar e at a hi g h er ris k of  c ar di o v asc ul ar m ort ality. 
Ar a mc h ol is a n o v el f att y aci d -bil e aci d c o nj u g at e t ar g et e d t o t h e li v er t h at 
i n d uc es b e n efici al m o d ul ati o n of i ntr a h e p atic li pi d m et a b olis m. I n n o n-cli nic al 
st u di es, t h e eff ect of Ar a mc h ol o n fi br osis w as s h o w n t o b e i n dir ect vi a 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
2 0  of 1 2 7  
r e d ucti o n of st e at osis a n d b all o o ni n g, a n d dir ect vi a r e d ucti o n of c oll a g e n 
pr o d ucti o n fr o m h u m a n h e p atic st ell at e c ells ( H S C). Ar a mc h ol ex erts its 
a nti -st e at otic a n d a nti-fi br otic eff ects vi a d o w n-r e g ul ati o n of St e ar o yl-C o A 
d es at ur as e -1 ( S C D 1) ex pr essi o n i n h e p at oc yt es a n d H S Cs, r es ulti n g i n u p 
r e g ul ati o n of A T P-bi n di n g c ass ett e tr a ns p ort er A B C A 1, i m pr o v e m e nt of f att y 
aci d oxi d ati o n wit h a c o nc o mit a nt r e d ucti o n i n t h e g e n er ati o n of oxi d ati v e 
str ess a n d r e d ucti o n i n c oll a g e n pr o d ucti o n. 
T w o P h as e 2 cli nic al st u di es d e m o nstr at e d pr eli mi n ar y b e n efit.  
T h e P h as e 2 a st u d y t est e d t w o d os es of Ar a mc h ol, 1 0 0 m g a n d 3 0 0 m g, a g ai nst 
pl ac e b o i n 6 0 s u bj ects wit h N A FL D. T h er e w as a st atistic all y-si g nific a nt 
d os e -r es p o ns e i n t h e r el ati v e c h a n g e i n li v er f at c o nt e nt b et w e e n t h e gr o u ps.  
I n t h e P h as e 2 b st u d y, 2 4 7 s u bj ects wit h bi o ps y-pr o v e n N A S H w h o w er e 
o v er w ei g ht or o b es e a n d h a d pr e di a b et es or T 2 D M , r ec ei v e d Ar a mc h ol 4 0 0 m g 
Q D  ( n = 1 0 1), Ar a mc h ol 6 0 0 m g Q D ( n = 9 8) or pl ac e b o ( n = 4 8) f or 5 2 w e e ks wit h 
p air e d M R S a n d bi o ps y. At b as eli n e a m aj orit y of st u d y p artici p a nts h a d  
a d v a nc e d dis e as e, 6 0 % wit h st a g e 2 or 3 fi br osis a n d 7 0 % wit h  N A FL D activit y 
sc or e (N A S ) ≥5.   
B ot h d os es of Ar a mc h ol r e d uc e d li v er f at vs pl ac e b o ( as m e as ur e d b y M R S) 
wit h a d os e -r es p o ns e f or a ≥5 % a bs ol ut e r e d ucti o n ( 6 0 0 m g > 4 0 0 m g > 
pl ac e b o). Ar a mc h ol 6 0 0 m g s h o w e d p ot e nti al effic ac y o n t h e 2 critic al 
hist ol o gic al e n d p oi nts f or a r e gistr ati o n al N A S H p h as e 3 st u d y: N A S H 
r es ol uti o n wit h o ut w ors e ni n g of fi br osis a n d fi br osis i m pr o v e m e nt wit h o ut 
w ors e ni n g of N A S H. Alt h o u g h li mit e d b y s a m pl e siz e a n d d ur ati o n, f e w er 
p ati e nts pr o gr ess e d t o cirr h osis i n t h e 6 0 0 m g ar m. B ot h Ar a mc h ol d os es 
si g nific a ntl y r e d uc e d al a ni n e a mi n otr a nsf er as e ( AL T ), as p art at e 
a mi n otr a nsf er as e (A S T ) a n d H b A 1c i n a d os e - r el at e d m a n n er. N o diff er e nc es 
i n b o d y w ei g ht w er e a p p ar e nt. 
I n t his o n e-y e ar st u d y i n p ati e nts wit h N A S H a n d c o m or bi diti es, b ot h d os es of 
Ar a mc h ol s h o w e d a f a v or a bl e s af et y a n d t ol er a bilit y pr ofil e. Al m ost 9 0 % of 
s u bj ects i n t h e acti v e-tr e at m e nt ar ms c o m pl et e d 5 2 w e e ks a n d 1 3 w e e ks of 
f oll o w-u p. N o d e at h w as r e p ort e d i n t h e st u d y. S eri o us a d v ers e e v e nts ( S A Es ) 
w er e r e p ort e d i n a p pr oxi m at el y 1 0 % i n e ac h tr e at m e nt gr o u p. S A Es w er e 
t y pic al f or t h e p ati e nt p o p ul ati o n. N o cl ust eri n g of e v e nt t y p es w as n ot e d i n 
t h e acti v e-tr e at m e nt ar ms. 
F oll o wi n g t h e d os e r es p o ns e p att er n d e m o nstr at e d, a n  eff ort w as m a d e t o 
i ncr e as e ex p os ur e a n d p ot e nti all y i ncr e as e effic acy.  A  s plit d os e m et h o d w as 
us e d a n d a P h as e 1 p h ar m ac o ki n etic ( P K) a n d s af et y st u d y w as c o n d uct e d, 
c o m p ari n g o nc e d ail y d osi n g of Ar a mc h ol 6 0 0 m g t o t wic e d ail y d osi n g o f 
Ar a mc h ol 3 0 0 m g. St u d y r es ults s h o w e d  t h at all s u bj ects h ad  a p pr oxi m at el y 
5 0 % hi g h er dr u g c o nc e ntr ati o ns wit h t h e 3 0 0 m g BI D r e gi m e n vs. 6 0 0 m g Q D .  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
2 1  of 1 2 7  
Si nc e d os e s plitti n g t o 3 0 0 m g BI D r es ults i n i ncr e as e d ex p os ur e pr o vi di n g a n 
o p p ort u nit y t o i ncr e as e effic ac y a n d i n li g ht of t h e g o o d s af et y pr ofil e 
o bs er v e d wit h Ar a mc h ol t o d at e , 3 0 0 m g BI D is t h e s el ect e d d os e f or cli nic al 
st u di es wit h Ar a mc h ol. 
 
R ati o n al e  
T h e c urr e nt st u d y is c o m p os e d of t w o p arts:  
A n O p e n -L a b el P art  t o ev al u at e t h e s af et y a n d P K of Ar a mc h ol 3 0 0 m g BI D i n 
s u bj ects wit h N A S H a n d li v er fi br osis a n d t o ex pl or e t h e ki n etics of hist ol o gic al 
o utc o m es a n d NI Ts ass oci at e d wit h N A S H a n d li v er fi br osis f or t h e tr e at m e nt 
d ur ati o n of 2 4, 4 8 a n d 7 2 w e e ks. T h e st u d y p o p ul ati o n i ncl u d es s u bj ects wit h 
N A S H a n d li v er fi br osis st a g e 1 -3, s u bj ects wit h N A S H w h o m a y or m a y n ot b e 
o v er w ei g ht a n d s u bj ects wit h N AS H w h o m a y or m a y n ot h a v e T 2 D M or b e 
pr e -di a b et ic. P K a n d s af et y d at a a n d i nf or m ati o n o n t h e ki n etics of hist ol ogic al 
o utc o m es a n d NI Ts fr o m t his O p e n -L a b el P art will b e s u m m ariz e d i n s u p p ort of 
r e g ul at or y s u b missi o ns. H o w e v er, hist ol o gic al o utc o m es a n d cli nic al e v e nts 
fr o m t h e O p e n -La b el P art will n ot b e c o nsi d er e d f or t h e Hist ol o g y -B as e d 
pri m ar y e n d p oi nt a n d t h e C li nic all y-B as e d pri m ary e n d p oi nt of t h e 
R a n d o miz e d, D o u bl e -B li n d, P l ac e b o-c o ntr oll e d p art of t h e st u d y. Cli nic al 
e v e nts will i nst e a d b e r e p ort e d as s af et y d at a.  
 
A R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr oll e d P art  t o e v al u at e t h e s af et y 
a n d effic acy of Ar a mc h ol 3 0 0 m g BI D t o s u p p ort r e g ul at or y a p pr o v al. T h e 
st u d y p o p ul ati o n f or t his p art i ncl u d es s u bj ects wit h N A S H a n d li v er fi br osis 
st a g e 2 a n d 3 w h o ar e o v er w ei g ht a n d ar e eit h er pr e -di a b etic or h a v e T 2 D M. 
T h e R a n d o miz e d, D o u bl e -bli n d, Pl ac e b o -C o ntr oll e d P art of t h e st u d y is 
g e n er all y c o nsist e nt wit h F D A G ui d a nc e f or I n d ustry –  N o ncirr h otic 
N o n alc o h olic St e at o h e p atitis wit h Liv er Fi br osis: D ev el o pi n g Dr u gs f or 
Tr e at m e nt ( D ec e m b er 2 0 1 8)  a n d  E M A  R efl ecti o n p a p er o n r e g ul at ory 
r e q uir e m e nts f or t h e d ev el o p m e nt of m e dici n al pr o d ucts f or c hr o nic 
n o ni nf ecti o us liv er dis e as es ( P B C, P S C, N A S H) ( N ov e m b er 2 0 1 8) , a n d is 
i nt e n d e d t o d e m o nstr at e t h e eff ecti v e n ess a n d s af et y of Ar a mc h ol t o s u p p ort 
r e g ul at or y a p pr o v al. 
 
 
 
 
 
 
 
  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
2 2  of 1 2 7  
✓ 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
✓ T h e o p e n l a b el p art of t h e st u d y will pr o vi d e a d diti o n al s af et y a n d P K  
i nf or m ati o n f or Ar a mc h ol 3 0 0 m g BI D i n s u bj ects wit h N AS H w hil e 
e nr oll m e nt i n t h e R a n d o miz e d, D o u bl e -bli n d, P l ac e b o-c o ntr oll e d P art of 
t h e st u d y is p e n di n g. L o n g-t er m s af et y d at a fr o m t his st u d y will ulti m at el y 
b e a v al u a bl e a d diti o n t o Ar a mc h ol s af et y d a t a b as e.   
T h e ki n etics of hist ol o gic al o utc o m es a n d NI Ts f or N A S H ass oci at e d wit h li v er 
fi br osis h a v e n ot b e e n w ell c h ar act eriz e d f or N A S H ( e. g. h o w e arl y c a n a 
b e n efici al eff ect o n fi br osis b e o bs er v e d, ar e t h er e s u bj ects t h at i m pr o v e wit h 
l o n g er d ur ati o n of t h er a p y etc.). P h as e 2 N A TI V E st u d y wit h l a ni fi br a n or, 
c o h ort 4 i n t h e P h as e 2 st u d y wit h al d af er mi n, B AL A N C E D  P h as e 2 a st u d y wit h 
efr uxif er mi n) s u g g est t h at f a v or a bl e eff ects m a y b e o bs er v e d as e arl y as at 
w e e k 1 6; ot h er st u di es h a v e r e p ort e d l o n g er ti m es t o o bs er v e d eff ect 
i ncl u di n g u p t o 9 6 w e e ks i n t h e PI V E N S st u d y wit h pi o glit az o n e. H o w e v er, n o 
st u d y, y et, h as ex a mi n e d wit hi n o n e cli nic al s etti n g t h e ki n etics of hist ol o gic al 
o utc o m e m e as ur es f or t h e diff er e nt tr e at m e nt d ur ati o n. T h e P h as e 2 b A R R E S T 
st u d y h a d a 5 2-w e e k e n d p oi nt f or w hic h f a v or a bl e eff ects w er e o bs er v e d. 
H o w e v er, it is n ot k n o w n h o w e arl y a tr e at m e nt eff ect m a y b e o bs er v e d a n d 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
2 3  of 1 2 7  
w h at t h e diff er e nc e m a y b e f or hist ol o gic al o utc o m es a n d NI Ts b et w e e n a 
tr e at m e nt d ur ati o n of 2 4, 4 8 or 7 2 we e ks. T h e O p e n -La b el P art will pr o vi d e 
d at a t o h el p c h ar act eriz e t h e ki n etics of hist ol o gic al o utc o m es a n d NI Ts f or 
Ar a mc h ol.  
I ncl usi o n Crit eri a 
T h e i ncl usi o n crit eri a f or t h e O p e n -La b el P art ar e  t h e s a m e as t h os e of t h e 
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art  wit h t h e exc e pti o n of  
fi br osis st a g e (t h e O p e n-L a b el P art all o ws e nr oll m e nt of s u bj ects wit h fi br osis 
st a g e 1), w ei g ht (t h e O p e n -L a b el P art all o ws e nr oll m e nt of s u bj ects w h o ar e 
n ot o v er w ei g ht)  a n d T y p e di a b et es m ellit us  (t h e O p e n-L a b el P art all o ws 
e nr oll m e nt of s u bj ects w h o ar e n ot pr e di a b et ic or s u bj ects w h o d o n ot h a v e 
t y p e 2 di a b et es m ellit us).  
1.  
M al e or f e m al e a g e 1 8 t o 7 5 y e ars (i ncl usi v e at first Scr e e ni n g visit)  
2.  
Hist ol o gic al c o nfir m ati o n of N A S H  o n a di a g n ostic li v er bi o ps y b y c e ntr al 
r e a di n g of t h e sli d es  
•  O p e n -L a b el P art: bi o ps y o bt ai n e d wit hi n 9  m o nt hs pri or t o 
r a n d o miz ati o n or d uri n g t h e scr e e ni n g p eri o d 
•  R a n d o miz e d, D o u bl e -Bli n d,  Pl ac e b o -C o ntr ol l e d P art : bi o ps y o bt ai n e d 
wit hi n 6 m o nt hs pri or t o r a n d o miz ati o n or d uri n g t h e scr e e ni n g 
p eri o d  
3.  
T ot al N A S S c or e 4 or m or e wit h at l e ast 1 i n e ac h c o m p o n e nt of t h e N A S 
S c or e (st e at osis ≥1 A N D i nfl a m m ati o n ≥1 A N D b all o o ni n g ≥1)  
4.  
Fi br osis St a g e m ust b e 2 or 3  
•  O p e n -L a b el P art m a y i ncl u d e u p t o 3 0 s u bj ects wit h fi br osis st a g e 1  
5.  
 
 
 
 
6.  
B o d y m ass i n d ex ( B MI)  
•  O p e n -L a b el P art: ≤ 4 0 k g/ m 2  
•  R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art:  b et w e e n 
2 5 k g/ m 2 a n d 4 0 k g/ m 2 
7.  
 
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
2 6  of 1 2 7  
•  
 
 
 
1 3.  K n o w n alc o h ol a n d/ or a ny ot h er dr u g a b us e or d e p e n d e nc e i n t h e l ast 
fi v e y e ars 
•  
 
 
1 4.  
 
 
 
 
 
 
 
 
1 7.  W ei g ht  l oss of m or e t h a n 5 % wit hi n 3 m o nt hs pri or t o scr e e ni n g 
1 8.  Hist or y of b ari atric s ur g er y wit hi n 5 y e ars of li v er bi o ps y o r pl a n n e d 
s ur g er y f or w ei g ht r e d ucti o n 
1 9.  Tr e at m e nt wit h dr u gs t h at m a y c a us e N A FL D wit hi n 1 2 m o nt hs pri or t o 
t h e bi o ps y 
 
 
 
2 0.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 5.  C urr e nt or pl a n n e d tr e at m e nt wit h i m m u n os u p pr essi v e dr u gs ( e. g. 
a d ali m u m a b, az at hi o pri n e a n d m et h otr ex at e)  
2 6.  E vi d e nc e of a n y ot h er u nst a bl e or u ntr e at e d cli nic all y si g nific a nt h e p atic, 
c ar di o v asc ul ar (i ncl u di n g a n y cli nic all y si g nific a nt c ar di o v asc ul ar e v e nts 
wit hi n 3 m o nt hs b ef or e scr e e ni n g), p ul m o n ar y, i m m u n ol o gic al, 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
2 7  of 1 2 7  
e n d ocri n e, h e m at ol o gic al, g astr oi nt esti n al, n e ur ol o gic al, n e o pl astic or 
ps yc hi atric dis e as e  
•  
 
 
 
 
2 7.  Hist or y or pr es e nc e of a ny dis e as e or c o n diti o n k n o w n t o i nt erf er e wit h 
t h e a bs or pti o n, distri b uti o n, m et a b olis m or excr eti o n of dr u gs i ncl u di n g 
bil e s alt m et a b olis m ( e. g. i nfl a m m at or y b o w el dis e as e (I B D); m aj or  
pr e vi o us or pl a n n e d  i nt esti n al o p er ati o n (il e al or i n v ol vi n g t h e ri g ht 
c ol o n); c hr o nic p a ncr e atitis; c eli ac dis e as e or pr e vi o us v a g ot o m y)  
2 8.  C hr o nic a nti bi otic tr e at m e nt ( e. g. rif axi mi n)  
2 9.  U nc o ntr oll e d h y p ert e nsi o n  
•  
 
 
 
3 0.  
 
 
  
 
 
 
 
 
 
 
  
 
  
 
 
 
 
  
 
 
 
3 8.  A n y ot h er c o n diti o n t h at i n t h e o pi ni o n of t h e In v esti g at or w arr a nts 
excl usi o n fr o m t h e st u d y  
3 9.  
 
  
Effic ac y 
E n d p oi nts  
O p e n -L a b el P art: 
Pri m ar y ki n etics E n d p oi nts:  
T h e pri m ar y e n d p oi nts ar e t h e ki n etics of t h e f oll o wi n g hist ol o gic al o utc o m e 
m e as ur es f or tr e at m e nt d ur ati o n of 2 4, 4 8 a n d 7 2 w e e ks a n d p ot e nti all y 
f oll o wi n g a 2n d p ost -b as eli n e bi o ps y at w e e ks 7 2 or 9 6 or 1 2 0 , r es p ecti v el y: 
•  I m pr o v e m e nt i n Fi br osis d efi n e d as t h e Pr o p orti o n ( %) of s u bj ects wit h 
i m pr o v e m e nt i n li v er fi br osis gr e at er t h a n or e q u al t o o n e st a g e ( N A S H 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
2 8  of 1 2 7  
C R N fi br osis sc or e) a n d n o w ors e ni n g of st e at o h e p atitis ( d efi n e d as n o 
i ncr e as e i n N A S f or b all o o ni n g, i nfl a m m ati on or st e at osis)  
•  R es ol uti o n of N A S H  d efi n e d as t h e Pr o p orti o n ( %) of s u bj ects wit h 
r es ol uti o n of N A S H ( d efi n e d b y b all o o ni n g of 0 a n d i nfl a m m ati o n 0 -1) a n d 
n o w ors e ni n g of li v er fi br osis o n N A S H C R N fi br osis sc or e ( ≥ 1 st a g e 
i ncr e as e). 
S ec o n d ar y ki n etics E n d p oi nt s: 
T h e s ec o n d ar y e n d p oi nts ar e  t h e ki n etics of t h e f oll o wi n g p ar a m et ers a n d NI Ts 
f or t h e tr e at m e nt d ur ati o n of 2 4, 4 8 a n d 7 2 w e e ks: 
•  AL T a n d A S T  
•  Gl yc e mic p ar a m et ers  
•  Li pi d p ar a m et ers 
•  Fi br osc a n  
•  Bi o m ar k ers i ncl u di n g b ut n ot li mit e d t o Pr o C 3 a n d EL F  
•  Micr o bi o m e  pr ofil e  
 
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art : 
Pri m ar y Effic ac y E n d p oi nts : 
T h e R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art  will utiliz e 2 pri m ar y 
effic ac y e n d p oi nts; Hist ol o g y -B as e d  pri m ar y e n d p oi nt  a n d Cli nic all y -B as e d  
pri m ar y e n d p oi nt . M e eti n g t h e Hist ol o g y -B as e d  pri m ar y e n d p oi nt will s er v e as 
t h e b asis f or t h e s u b missi o n of a m ar k eti n g a ut h oriz ati o n a p plic ati o n u n d er 
r e g ul at or y pr o visi o ns of acc el er at e d/c o n diti o n al a p pr o v al. M e eti n g t h e 
Cli nic all y -B as e d e n d p oi nt will pr o vi d e  c o nfir m ati o n of cli nic al b e n efit .  
T h e pri m ar y effic acy e n d p oi nts f or  t h e R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -
C o ntr ol l e d P art  ar e:  
•  
Hist ol o g y -B as e d : T h e Hist ol o g y-B as e d pri m ar y e n d p oi nt will b e d eri v e d 
fr o m t h e w e e k 7 2 bi o ps y of t h e i niti al 1 0 0 0 s u bj ects as c o m p ar e d t o 
b as eli n e bi o ps y a n d will us e:  
✓ R es ol uti o n of N A S H  d efi n e d as t h e Pr o p orti o n ( %) of s u bj ects wit h 
r es ol uti o n of N A S H (d efi n e d b y B all o o ni n g of 0 a n d i nfl a m m ati o n 0 -1) 
a n d n o w ors e ni n g of li v er fi br osis o n N A S H C R N fi br osis sc or e (≥ 1 
st a g e i ncr e as e). 
O R  
✓ I m pr o v e m e nt i n Fi br osis d efi n e d as t h e Pr o p orti o n ( %) of s u bj ects 
wit h i m pr o v e m e nt i n li v er fi br osis gr e at er t h a n or e q u al t o o n e st a g e 
( N A S H C R N fi br osis sc or e) a n d n o w ors e ni n g of st e at o h e p atitis 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
2 9  of 1 2 7  
( d efi n e d as n o i ncr e as e i n N A S f or b all o o ni n g, i nfl a m m ati o n or 
st e at osis) 
•  
Cli nic a ll y-B as e d : T h e Cli nic all y-B as e d pri m ar y e n d p oi nt is t h e ti m e t o first 
occ urr e nc e of a n y of t h e f oll o wi n g a dj u dic at e d e v e nts:   
✓ All -c a us e m ort alit y 
✓ Li v er tr a ns pl a nt 
✓ Hist ol o gic al pr o gr essi o n t o cirr h osis  
✓ M EL D sc or e > 1 5 if b as eli n e M EL D sc or e w as < 1 2  
✓ H os pit ali z ati o n d u e t o h e p atic d ec o m p e ns ati o n e v e nt(s) i ncl u di n g:  
- H e p atic e nc e p h al o p at h y gr a d e ≥2 ( as ass ess e d b y W est H a v e n 
sc al e) 
- V aric e al bl e e di n g  
- N e w o ns et ascit es r e q uiri n g tr e at m e nt  
- S p o nt a n e o us b act eri al p erit o nitis as ass ess e d b y eit h er p ositi v e c ell 
c ult ur e or c ell c o u nt  
E v e nts will b e a dj u dic at e d b y t h e i n d e p e n d e nt Cli nic al O utc o m e 
A dj u dic ati o n C o m mitt e e ( C O A C ). 
K e y S ec o n d ar y Effic ac y E n d p oi nt:  
•  
At E o S, I m pr o v e m e nt i n Fi br osis: 5 -Y e ar Pr o p orti o n ( %) of s u bj ects wit h 
i m pr o v e m e nt i n li v er fi br osis gr e at er t h a n or e q u al t o o n e st a g e ( N A S H 
C R N fi br osis sc or e) a n d n o w ors e ni n g of st e at o h e p atitis ( d efi n e d as n o 
i ncr e as e i n N A S f or b all o o ni n g, i nfl a m m ati o n or st e at osis) 
E x pl or at or y E n d p oi nts:  
•  
At t h e ti m e of t h e Hist ol o g y -B as e d a n al ysis:  
✓ P at h ol o gist  N A S H  r es ol uti o n ass ess m e nt:  W e e k  7 2 Pr o p orti o n ( %) of 
s u bj ects wit h N A S H  r es ol uti o n as  d efi n e d  b y  t h e p at h ol o gist  o v er all  
ass ess m e nt  of  c h a n g e fr o m pr es e nc e  of  d efi nit e  st e at o h e p atitis at  
b as eli n e  t o a bs e nc e  of  d efi nit e  st e at o h e p atitis ( wit h o ut w ors e ni n g  of  
fi br osis)  
✓ T w o -St a g e  I m pr o v e m e nt i n Fi br osis : W e e k 7 2 Pr o p orti o n ( %) of 
s u bj ects wit h i m pr o v e m e nt i n li v er fi br osis gr e at er t h a n or e q u al t o 
t w o st a g es a n d n o w ors e ni n g of N A S H ( d efi n e d as n o i ncr e as e i n N A S 
f or b all o o ni n g, i nfl a m m ati o n, or st e at osis). 
✓ N A S H  R es ol uti o n  A N D  I m pr o v e m e nt i n Fi br osis : W e e k 7 2 Pr o p orti o n 
( %) of s u bj ects wit h b ot h R es ol uti o n of N A S H a n d I m pr o v e m e nt i n 
Fi br osis.  
✓ Fi br osis  R es ol uti o n:  W e e k  7 2 Pr o p orti o n ( %) of s u bj ects wit h 
r es ol uti o n of fi br osis ( d efi n e d as fi br osis st a g e 0). 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
3 0  of 1 2 7  
✓ Fi br osis  Im pr o v e m e nt:  W e e k 7 2 Pr o p orti o n ( %) of s u bj ects wit h 
i m pr o v e m e nt i n li v er fi br osis gr e at er t h a n or e q u al t o o n e st a g e 
( N A S H C R N fi br osis sc or e) 
✓ Fi br osis  W ors e ni n g:  W e e k 7 2 Pr o p orti o n ( %) of s u bj ects wit h 
w ors e ni n g i n li v er fi br osis gr e at er t h a n or e q u al t o o n e st a g e ( N A S H 
C R N fi br osis sc or e)  
✓ B all o o ni n g 0: W e e k  7 2 Pr o p orti o n ( %) of s u bj ects wit h b all o o ni n g of 0  
✓ C h a n g e fr o m b as eli n e t o w e e k  7 2 i n AL T.  
✓ C h a n g e fr o m b as eli n e t o w e e k  7 2 i n Gl yc e mic p ar a m et ers (i ncl u di n g 
H b A 1c, f asti n g gl uc os e, f asti n g i ns uli n, C -p e pti d e, a n d H O M A - I R). 
✓ C h a n g e fr o m b as eli n e t o w e e k  7 2 i n A S T   
C h a n g e fr o m b as eli n e t o w e e k  7 2 i n li pi d p ar a m et ers (i ncl u di n g t ot al 
c h ol est er ol, L DL-C, a p o B, n o n - H DL c h ol est er ol, H DL c h ol est er ol, a n d 
tri gl yc eri d es)  
S af et y E v al u ati o n  S af et y a n d T ol er a bilit y  E v al u ati o ns  
1.  A d v ers e e v e nts a n d s eri o us a d v ers e e v e nts . 
2.  S af et y l a b or at or y e v al u ati o ns.  
3.  Vit als si g ns.  
4.  1 2 -L e a d E C G. 
5.  P h ysic al ex a mi n ati o ns.  
6.  Dr o p -o ut r at es.  
P h ar m ac o ki n etics  
E n d p oi nts  
Pl as m a c o nc e ntr ati o ns of Ar a mc h ol will b e s u bj ect e d t o p o p ul ati o n 
p h ar m ac o ki n etic a n al ysis usi n g N O N M E M  s oft w ar e. I n a d diti o n t o v ari a bility i n 
t h e w h ol e p o p ul ati o n t h at h a v e r ec ei v e d tr e at m e nt wit h Ar a mc h ol , t h e 
r el ati o ns hi ps b et w e e n t h e p o p ul ati o n P K pr ofil es a n d f act ors s uc h as 
d e m o gr a p h y, d ur ati o n of tr e at m e nt, c o nc o mit a nt m e dic ati o ns, s e v erit y of 
dis e as e a n d r es p o ns e t o tr e at m e nt will b e ex a mi n e d.  
St atistic al 
M et h o d ol o g y  
 
T his st u d y, w hic h c o nsist s of t w o p arts , is d esi g n e d as f oll o ws : 
•  O p e n -L a b el P art: T o ex pl or e t h e ki n etics of hist ol o gic al o utc o m e m e as ur es 
a n d N o n -I n v asi v e T ests ( NI Ts) ass oci at e d wit h N AS H a n d fi br osis f or t h e 
tr e at m e nt d ur ati o n of 2 4, 4 8 a n d 7 2 w e e ks. 
•  R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art : T o e v al u at e t h e 
effic ac y a n d s af et y of t wic e d ail y a d mi nistr ati o n ( BI D) of Ar a mc h ol 3 0 0 m g 
as c o m p ar e d t o pl ac e b o i n s u bj ects wit h N A S H a n d li v er fi br osis.   
O p e n -L a b el P art: 
A t ot al of 1 5 0  s u bj ects, i ncl u di n g t h os e alr e a d y r a n d o miz e d t o Ar a mc h ol 
3 0 0 m g BI D or pl ac e b o, will b e r a n d o miz e d i n a r ati o of 1: 1: 1 t o r ec ei v e 
Ar a mc h ol 3 0 0 m g BI D acc or di n g t o t h e b el o w gr o u pi n g :  
•  Gr o u p A: T h e p ost -b as eli n e li v er bi o ps y will b e c o n d uct e d at w e e k 2 4  
•  Gr o u p B: T h e p ost -b as eli n e li v er bi o ps y will b e c o n d uct e d at w e e k 4 8  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
3 1  of 1 2 7  
•  Gr o u p C: T h e p ost -b as eli n e li v er bi o ps y will b e c o n d uct e d at w e e k 7 2  
R a n d o miz ati o n i n t h e O p e n -La b el P art will e m pl oy a s e mi -mi ni mi z ati o n 
al g orit h m t o b al a nc e t h e 3 gr o u ps i n n u m b er of s u bj ects, distri b uti o n of 
s u bj ects acc or di n g t o fi br osis sc or e ( F 1, F 2 a n d F 3), pr es e nc e or a bs e nc e of 
T 2 D M , a n d pri or ex p os ur e t o Ar a mc h ol 3 0 0 m g BI D . F 1 s u bj ects will b e c a p p e d 
t o e nr oll n o m or e t h a n 3 0 s u bj ects. 
I n or d er t o m or e c o m pr e h e nsi v el y ex pl or e t h e ki n etics of hist ol o gic al o utc o m e 
m e as ur es acr oss tr e at m e nt d ur ati o n, a 2 n d p ost -b as eli n e  li v er bi o ps y s a m pl e 
will b e c oll ect e d f or s u bj ects w h os e p ost b as eli n e li v er bi o ps y at w e e k 2 4 or 4 8 
or 7 2 d o es n ot s h o w at l e ast 1 st a g e i m pr o v e m e nt i n fi br osis (fi br osis n o n -
r es p o n d ers).  T h e 2 n d p ost -b as eli n e  li v er bi o ps y s a m pl e will b e c oll ect e d 1 y e ar 
l at er (i. e. at w e e ks 7 2 or 9 6 or 1 2 0 r es p ecti v el y). 
T h e O p e n -L a b el P art will c o nti n u e f or t h e s a m e d ur a ti o n t h a n t h e R a n d o miz e d, 
D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art. All s u bj ects i n t h e O p e n -L a b el P art will 
r ec ei v e Ar a mc h ol 3 0 0 m g BI D u ntil E n d of st u d y ( E o S). 
R e vi e w a n d ass ess m e nt of d at a will b e c o n d uct e d acc or di n g t o a pr e -d efi n e d 
sc h e d ul e: 
•  T h e 1 st d at a  ass ess m e nt w hic h will b e li mit e d t o NI T s a n al ys es will occ ur at 
a ti m e w h e n a p pr oxi m at el y o n e t hir d of t h e st u dy p o p ul ati o n h as  
c o m pl et ed  2 4 w e e ks of tr e at m e nt . 
•  T h e 2 n d d at a ass ess m e nt will occ ur at a ti m e w h e n a p pr oxi m at el y o n e t hir d 
of t h e st u d y p o p ul ati o n h as u n d er g o n e t h e p ost -b as eli n e  li v er bi o ps y. 
Ass ess m e nts will i ncl u d e a n al ysis of hist ol o gic al e n d p oi nts a n d NI T s. 
•  T h e 3 r d d at a ass ess m e nt will occ ur at a ti m e w h e n a p pr oxi m at el y t w o -
t hir ds of t h e st u d y p o p ul ati o n h a v e u n d er g o n e  t h e p ost-b as eli n e  li v er 
bi o ps y . Ass ess m e nts will i ncl u d e a n al ysis of hist ol o gic al e n d p oi nts a n d NI Ts. 
•  T h e 4 t h d at a ass ess m e nt f or ass essi n g t h e ki n etics of t h e hist ol o gic al 
o utc o m e m e as ur es  a n d NI T s f or t h e d ur ati o n of 2 4,  4 8 a n d 7 2 w e e ks will b e 
c o n d uct e d at t h e ti m e w h e n all r a n d o miz e d s u bj ects h a v e u n d er g o n e  t h e 
p ost -b as eli n e li v er bi o psy . 
•  A p ot e nti all y 5 t h d at a ass ess m e nt f or f urt h er ass essi n g t h e ki n etics of t h e 
hist ol o gic al o utc o m e m e as ur es a n d NI T s f or tr e at m e nt d ur ati o n of 2 4, 4 8 
a n d 7 2 w e e ks a n d p ot e nti all y f oll o wi n g a 2 n d p ost -b as eli n e  bi o ps y at w e e ks 
7 2 or 9 6 or 1 2 0, r es p ectiv el y , will b e c o n d uct e d at t h e ti m e w h e n t h e l ast 
r a n d o miz e d s u bj ects h a v e u n d er w e nt t h e l ast p ost -b as eli n e li v er bi o ps y . 
T h e pl a n n e d s a m pl e siz e of a t ot al of 1 5 0 s u bj ects is c o nsi d er e d a p pr o pri at e f or 
ass essi n g t h e ki n etics  of hist ol o gic al o utc o m e m e as ur es a n d NI T s ass oci at e d 
wit h N AS H a n d fi br osis f or t h e tr e at m e nt d ur ati o n of 2 4, 4 8 a n d 7 2 w e e ks.  
T h e o v er all al p h a l e v el f or t h e O p e n -L a b el P art is 0. 05 usi n g 2 -t ail e d t ests. N o 
m ulti plicit y a dj ust m e nt is pl a n n e d as t his st u d y p art is ex pl or at or y i n n at ur e. 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
3 2  of 1 2 7  
St atistic al a n al ysis of effic ac y e n d p oi nts will us e t h e m o difi e d i nt e nt t o tr e at 
( mI T T) A n al ysis S et e m pl o yi n g v ari o us r e gr essi o n m o d els d esi g n e d t o ex pl or e 
t h e ki n etics of hist ol o gic al o utc o m e 
m e as ur es a n d NI T s as a f u ncti o n of  
tr e at m e nt d ur ati o n. 
A m or e d et ail e d St atistic al A n al ysis Pl a n ( S A P ) d e dic at e d f or t h e O p e n -L a b el P art 
will b e d e v el o p e d pri or t o t h e c o n d uct of t h e 1 st d at a e v al u ati o n . 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
3 3  of 1 2 7  
•  
 
Pri m ar y St u d y Effic ac y E n d p oi nts : 
T h e pri m ar y effic acy e n d p oi nts f or t his st u d y  ar e : 
•  
Hist ol o g y -B as e d : R es ol uti o n of N A S H  O R I m pr o v e m e nt i n Fi br osis 
•  
Cli nic all y -B as e d : Ti m e t o first occ urr e nc e of t h e a dj u dic at e d e v e nts  
Sc h e d ul e of St atistic al A n al ys es:  
St atistic al a n al ys es of effic ac y e n d p oi nts ar e pl a n n e d t o b e p erf or m e d at t w o 
st u d y mil est o n es: 
•  T h e Hist ol o g y -B as e d pri m ar y e n d p oi nt will b e a n al yz e d at t h e ti m e w h e n 
t h e i niti all y r a n d o miz e d 1 0 0 0  s u bj ects h a v e p erf or m e d t h e w e e k  7 2  visit or 
t er mi n at e d e arl y.  
•  T h e Cli nic all y -B as e d pri m ar y e n d p oi nt will b e a n alyz e d at E o S, w h e n all 
2 0 0 0 s u bj ects pl a n n e d t o b e r a n d o miz e d i nt o t his st u d y will r ec ei v e  
Ar a mc h ol or m atc hi n g  p l ac e b o u ntil E o S  w hic h  will  occ ur  at  t h e ti m e w h e n  
a  t ot al of  3 8 0  s u bj ects will  ex p eri e nc e  at  l e ast 1  pr e -s p ecifi e d cli nic al e v e nt  
or  at  5  y e ars  fr o m l ast s u bj ect r a n d o miz ati o n, w hic h e v er  c o m es first.  
Pri nci p al A n al ysis S et f or Effic ac y I nf er e nc e:  
T h e pri nci p al a n al ysis s et f or effic acy i nf er e nc e will b e t h e I nt e nti o n -t o-Tr e at 
(I T T) A n al ysis S et w hic h will i ncl u d e all r a n d o miz e d s u bj ects as f oll o ws: 
•  T h e Hist ol o g y -B as e d  pri m ar y e n d p oi nt will e m pl o y t h e Hist ol o g y -B as e d -I T T 
A n al ysis S et i ncl u di n g all i niti all y 1 0 0 0  r a n d o miz e d s u bj ects. 
•  T h e Cli nic all y -B as e d pri m ar y e n d p oi nt will e m pl o y t h e Cli nic all y -B as e d -I T T 
A n al ysis S et i ncl u di n g all r a n d o miz e d s u bj ects.  
T y p e -I Err or a n d M ulti plicit y A dj ust m e nt: 
T h e o v er all al p h a l e v el f or t his st u d y is 0. 0 5 usi n g 2 -t ail e d t ests. All si g nific a nc e 
t estin g f or t his st u d y will us e t w o -t ail e d t ests. 
T h e Hist ol o g y -B as e d pri m ar y e n d p oi nt will us e a n al p h a l e v el of 0. 0 2 a n d 
a dj ust m e nt f or m ulti plicit y f or t h e t w o alt er n ati v es  pr o p os e d ( R es ol uti o n of 
N A S H, or, I m pr o v e m e nt i n Fi br osis ) will us e t h e T r u nc at e d H oc h b er g’s  
pr oc e d ur e wit h g a m m a = 0. 1 . 
T h e Cli nic all y -B as e d pri m ar y e n d p oi nt will us e a n al p h a l e v el of 0. 0 3, or 0. 0 5 i n 
c as e t h at b ot h alt er n ati v es pr o p os e d f or Hist ol o gy -B as e d pri m ar y e n d p oi nt 
w er e m et ( n o k e y s ec o n d ar y e n d p oi nts ar e d efi n e d f or t h e Hist ol o g y -B as e d 
st u d y p art). T h e s ol e k e y sec o n d ar y e n d p oi nt f or t h e Cli nic all y -B as e d st u d y 
p art will us e t h e al p h a l ev el us e d f or t h e Cli nic all y -B as e d pri m ar y e n d p oi nt i n 
c as e t h at t h e l at er “ wi ns”.    

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
3 4  of 1 2 7  
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
  
  
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
3 5  of 1 2 7  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
3 6  of 1 2 7  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
3 7  of 1 2 7  
2  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  
A b br e vi ati o n  
T er m  
A D A  
A m eric a n di a b et es ass oci ati o n  
A E  
A d v ers e e v e nts  
AL T  
al a ni n e a mi n otr a nsf er as e ( S G P T)  
A S T  
as p art at e a mi n otr a nsf er as e ( S G O T)  
A T P  
A d e n osi n e tri p h os p h at e  
A U C  
ar e a u n d er t h e < pl as m a > dr u g c o nc e ntr ati o n b y ti m e c ur v e  
A U C 0 – t 
ar e a u n d er t h e < pl as m a > dr u g c o nc e ntr ati o n b y ti m e c ur v e f or 1 d osi n g 
i nt er v al of a m ulti pl e-d os e r e gi m e n  
B MI  
b o d y m ass i n d ex  
B U N  
bl o o d ur e a nitr o g e n  
C D M S  
cli nic al d at a m a n a g e m e nt s yst e m  
C F R  
C o d e of F e d er al R e g ul ati o ns  
C G R  
C o u ntr y g e o gr a p hic r e gi o n  
CI O M S  
C o u ncil f or I nt er n ati o n al Or g a niz ati o ns of M e dic al Sci e nc es  
C m ax  
m axi m u m o bs er v e d pl as m a dr u g c o nc e ntr ati o n  
C P K  
cr e ati n e p h os p h o ki n as e 
C R F  
c as e r e p ort f or m (r ef ers t o a n y m e di a us e d t o c oll ect st u d y d at a [ i. e., 
p a p er or el ectr o nic])  
C R O  
c o ntr act r es e arc h or g a niz ati o n  
C S  
C o m p o u n d S y m m etr y  
C S C  
Cli nic al S u p pl y C h ai n  
C S H  
H et er o g e n o us C o m p o u n d S y m m etr y  
C T F G  
Cli nic al Tri al F acilit ati o n Gr o u p  
DILI  
Dr u g -i n d uc e d li v er i nj ur y 
D M C  
D at a  M o nit ori n g C o m mitt e e  
E C G  
el ectr oc ar di o gr a p h y, el ectr oc ar di o gr a m  
E M A  
E ur o p e a n M e dici n es A g e ncy  
E o S  
E n d -of -St u d y  
E S D  
E arl y St u d y Disc o nti n u ati o n  
E T  
E arl y t er mi n ati o n  
E T D  
E arl y Tr e at m e nt Disc o nti n u ati o n  
E U  
E ur o p e a n U ni o n  
F A B A C  
F att y aci d -bil e aci d c o nj u g at es  
F A S  
f ull A n al ysis S et  
F C S  
F ull y C o n diti o n al S p ecific ati o n  
F D A  
U S F o o d a n d Dr u g A d mi nistr ati o n  
F M D  
Fl o w m e di at e d dil ati o n  
G C P  
G o o d Cli nic al Pr actic e  
G D P R  
G e n er al D at a Pr ot ecti o n R e g ul ati o n  
G G T  
g a m m a -gl ut a m yl tr a ns p e pti d as e  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
3 8  of 1 2 7  
A b br e vi ati o n  
T er m  
GI  
g astr oi nt esti n al  
G M P  
G o o d m a n uf act uri n g pr actic e  
H & E  
H e m at ox yli n & E osi n  
H C C  
h e p at oc ell ul ar c arci n o m a  
H C G  
h u m a n c h ori o nic g o n a d otr o pi n  
H DL  
Hi g h d e nsit y li p o pr ot ei n  
H D P E  
hi g h d e nsit y p ol y et h yl e n e  
HI V  
h u m a n i m m u n o d efici e ncy vir us  
H S C  
H e p atic st ell at e c ells  
I B 
I n v esti g at or's Br oc h ur e 
I B D 
I nfl a m m at or y b o w el dis e as e 
I C F 
I nf or m e d c o ns e nt f or m 
I C H 
I nt er n ati o n al C o nf er e nc e o n H ar m o nizati o n  
I E C 
I n d e p e n d e nt Et hics C o m mitt e e  
I M P 
i n v esti g ati o n al m e dic al pr o d uct 
I N R 
I nt er n ati o n al N or m aliz e d R ati o 
I R B 
I nstit uti o n al R e vi e w B o ar d 
I T T 
i nt e nt-t o-tr e at 
L D H 
l act at e d e h y dr o g e n as e 
L S M  
li v er stiff n ess m e as ur e m e nt  
M A C E  
M A D  
M aj or a d v ers e c ar di o v asc ul ar e v e nts  
M ulti pl e asc e n di n g d os e  
M A R  
Missi n g at r a n d o m  
m ax  
m axi m u m  
M D R D  
M o dific ati o n of Di et i n R e n al Dis e as e  
M e d D R A  
M e dic al Dicti o n ar y f or R e g ul at or y Acti viti es  
M EL D  
M o d el of e n d -st a g e li v er dis e as e 
M et S  
M et a b olic s y n dr o m e  
MI  
M ulti pl e I m p ut ati o ns  
ML  
M axi m u m -Li k eli h o o d 
M R S  
M a g n etic r es o n a nc e s p ectr osc o p y  
N A FL D  
N o n alc o h olic f att y li v er dis e as e  
N A S  
N A FL D acti vit y sc or e  
N A S H  
N o n alc o h olic st e at o h e p atitis  
N D A  
N e w dr u g a p plic ati o n  
NI T s 
N o n -I n v asi v e T ests  
N O A EL  
N o o bs er v e d a d v ers e eff ect l e v el  
N S AI D  
N o n -st er oi d al a nti-i nfl a m m at or y dr u gs 
O P T N  
Or g a n Pr oc ur e m e nt a n d Tr a ns pl a nt ati o n N et w or k  
O T C  
o v er -t h e-c o u nt er 
P B C  
Pri m ar y bili ar y c h ol a n gitis  
P B P K  
P h ysi ol o gic all y b as e d p h ar m ac o ki n etic  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
3 9  of 1 2 7  
A b br e vi ati o n  
T er m  
P C S  
P ot e nti al Cli nic al Si g nific a nc e  
P Gx  
p h ar m ac o g e n etic(s)  
PI  
Pri nci p al I n v esti g at or  
P K  
p h ar m ac o ki n etics  
P N PL A 3  
P at ati n -li k e p h os p h oli p as e d o m ai n-c o nt ai ni n g pr ot ei n 3 
P P  
P er -pr ot oc ol  
P S C  
Pri m ar y scl er osi n g c h ol a n gitis  
P T  
Pr ef err e d T er m  
Q A  
q u alit y ass ur a nc e  
Q C  
q u alit y c o ntr ol  
R B C  
r e d bl o o d c ell  
R E ML  
R estrict e d M axi m u m -Li k eli h o o d 
R T S M  
R a n d o miz ati o n & Tri al S u p pl y M a n a g e m e nt  
S A E  
S eri o us a d v ers e eff ects  
S A P  
St atistic al A n al ysis Pl a n  
S C D 1  
St e ar o yl C o e nz y m e A D es at ur as e 1  
S D  
st a n d ar d d e vi ati o n 
S D V  
s o urc e d oc u m e nt v erific ati o n  
S E  
st a n d ar d err or 
S O C  
s yst e m or g a n cl ass 
S O P  
st a n d ar d o p er ati n g pr oc e d ur e 
S P C  
S u m m ar y of Pr o d uct C h ar act eristics  
S U S A R  
s us p ect e d u n ex p ect e d s eri o us a d v ers e r e acti o n 
T 2 D M  
T y p e -2 di a b et es m ellit us  
T E A E  
Tr e at m e nt E m er g e nt A dv ers e E v e nts  
tm ax  
ti m e t o m axi m u m o bs er v e d dr u g c o nc e ntr ati o n 
T S H  
t h yr oi d sti m ul ati n g h or m o n e 
UL N  
u p p er li mit of t h e n or m al r a n g e  
U S( A)  
U nit e d St at es ( of A m eric a)  
U TI  
Uri n ar y tr act i nf ecti o n  
W B C  
w hit e bl o o d c ell  
W H O  
W orl d H e alt h Or g a niz ati o n  
W H O  Dr u g  
W orl d H e alt h Or g a niz ati o n ( W H O) dr u g dicti o n ary  
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
4 0  of 1 2 7  
3  I N T R O D U C TI O N 
3. 1  B ac k gr o u n d I nf or m ati o n  
3. 1. 1  
N o n alc o h olic F att y Li v er D is e as e ( N A FL D) a n d N o n alc o h olic S t e at o h e p atitis 
( N A S H) 
N o n alc o h olic  st e at o h e p atitis ( N A S H) is t h e pr o gr essi v e f or m of n o n alc o h olic f att y li v er dis e as e 
( N A FL D), a br o a d t er m t h at e nc o m p ass es t h e s p ectr u m of f att y li v er dis e as es r a n gi n g fr o m 
si m pl e st e at osis t o st e at o h e p atitis, fi br osis a n d cirr h osis i n i n di vi d u als wit h o ut s i g nific a nt 
alc o h ol c o ns u m pti o n or s ec o n d ar y c a us es of st e at osis. N A S H is a hist ol o gic al d efi niti o n, 
r e q uiri n g t h e pr es e nc e of ≥5 % h e p atic st e at osis wit h i nfl a m m ati o n a n d h e p at oc yt e i nj ur y 
( b all o o ni n g) wit h or wit h o ut fi br osis1. 
N A FL D is t h e m ost pr e v al e nt f or m of c hr o nic li v er dis e as e i n t h e w orl d, p ar all eli n g t h e 
e pi d e mic of o b esit y a n d o b esit y -r el at e d c o m plic ati o ns s uc h as t y p e 2 di a b et es m ellit us a n d 
m et a b olic s y n dr o m e 1, 2. A r ec e nt m et a-a n al ysis esti m at e d t h at a p pr oxi m at e l y 2 5 % of t h e 
w orl d’s p o p ul ati o n h as N A FL D 2 wit h a pr oj ect e d i ncr e as e o f 3 0 % b et w e e n 2 0 1 6 a n d 2 0 3 0 3. T h e 
pr e v al e nc e of N A S H is c h all e n gi n g t o ass ess b ec a us e of t h e bi o ps y -b as e d d efi niti o n. B as e d o n 
t h e pr e v al e nc e of N A S H a m o n g N A FL D p ati e nts w h o h a d li v er bi o ps i es, t h e pr e v al e nc e of N A S H 
i n t h e g e n er al p o p ul ati o n is esti m at e d at 1. 5 % -6. 4 5 % 2, wit h a pr oj ect e d i ncr e as e i n pr e v al e nc e 
of 1 5 % -5 6 % b et w e e n 2 0 1 6 a n d 2 0 3 0 3. F e at ur es of m et a b olic s y n dr o m e ar e n ot o nl y hi g hl y  
pr e v al e nt  i n p ati e nts wit h N A FL D, b ut als o i ncr e as e t h e ris k of d e v el o pi n g N A FL D. P ati e nts wit h 
t y p e 2 di a b et es h a v e a hi g h pr e v al e nc e of N A FL D, N A S H a n d a d v a nc e d st a g es of fi br osis 1.  
T h e n at ur al hist or y of N AFL D is ass oci at e d wit h li v er hist ol o g y at t h e ti m e of pr es e nt ati o n. 
P ati e nts wit h si m pl e st e at osis ar e li k el y t o  h a v e a b e ni g n c o urs e, w hil e a b o ut 3 0 -5 0 % of 
p ati e nts wit h N A S H d e v el o p pr o gr essi v e fi br osis, i ncr e asi n g t h eir  ris k f or cirr h osis a n d its 
c o m plic ati o ns 4, 5. B ot h dis e as e acti vit y ( q u a ntifi e d b y N A FL D acti vit y sc or e ( N A S)) a n d fi br osis 
st a g e aff ect t h e ris k f or pr o gr essi o n t o cirr h osis. Fi br osis is st a g e d fr o m 0-4 i n r el ati o n t o t h e 
ext e nt of t h e sc arri n g as f oll o ws: St a g e 1, z o n e 3 p erisi n us oi d al fi br osis; St a g e 2, as a b o v e wit h 
p ort al fi br osis; St a g e 3, as a b o v e wit h bri d gi n g fi br osis; a n d St a g e 4, cirr h osis ( N A S H/ C R N 
Br u nt/ Kl e i n er sc al e)6. T h e N A S H C R N fi br osis st a gi n g s yst e m h as b e e n v ali d at e d wit h r es p ect t o 
t h e i ntr a o bs er v er a n d i nt er o bs er v er c o nc or d a nc e a n d s e nsiti vit y t o c h a n g e7. T h e pr o gr essi o n 
fr o m N A S H wit h o ut fi br osis t hr o u g h v ari o us st a g es of fi br osis is n ot li n e ar; h o w e v er,  N A S H 
wit h fi br osis st a g es 2 a n d 3 h a s a si g nific a ntl y hi g h er ris k of pr o gr essi o n t o cirr h osis wit hi n a 
1 0‐ y e ar ti m e fr a m e a n d a n i ncr e as e d m ort alit y ris k c o m p ar e d t o l o w er st a g es ( 0‐ 1) of dis e as e 8. 
I n f act, t h e pr es e nc e of si g nific a nt fi br osis is t h e b est pr e dict or of li v er-r el at e d a n d all-c a us e 
m ort alit y i n N A S H 9 – 1 1. 
N A S H is r ec o g niz e d as a m aj or c a us e of c hr o nic liv er dis e as e l e a di n g t o cirr h osis, li v er 
tr a ns pl a nt ati o n a n d h e p at oc ell ul ar c arci n o m a ( H C C): N A S H is t h e s ec o n d l e a di n g eti ol o g y of 
cirr h osis a m o n g a d ults a w aiti n g li v er tr a ns pl a nt ati o n i n t h e U nit e d St at es, w hil e N A FL D is t h e 
t hir d m ost c o m m o n c a us e of H C C  i n t h e U nit e d St at es1. Li v er-r el at e d m ort alit y is i ncr e as e d 
1 0 -f ol d i n N A S H p ati e nts c o m p ar e d wit h t h e g e n er al p o p ul ati o n. A d diti o n all y, N A S H p ati e nts 
h a v e a n i ncr e as e d r at e of c ar di o v asc ul ar e v e nts a n d n e o pl asi a  a n d ar e at a hi g h er ris k f or 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
4 1  of 1 2 7  
c ar di o v asc ul ar-r el at e d m ort alit y1. Wit h t h e i ncr e asi n g pr e v al e nc e of m et a b olic s y n dr o m e a n d 
s u bs e q u e ntl y, N A FL D, N A S H, cirr h osis a n d c o m plic ati o ns, s u bst a nti al cli nic al a n d ec o n o mic 
b ur d e ns ar e i n e vit a bl e 1 2.  
T h er e ar e c urr e ntl y n o a p pr o v e d m e dic ati o ns f or N A S H a n d m a n a g e m e nt f oc us es o n lif est yl e 
m o dific ati o ns i ncl u di n g di et a n d ex ercis e. A 2 0 1 8 g ui d a nc e fr o m t h e A m eric a n Ass oci ati o n f or 
t h e St u d y of Li v er Dis e as es ai ms f or a r e d ucti o n i n b o d y w ei g ht of 3 %-5 % t o ac hi e v e 
i m pr o v e m e nt i n st e at osis a n d 7 %-1 0 % t o i m pr o v e t h e m aj orit y of hist o p at h ol o gic al f e at ur es of 
N A S H, i ncl u di n g fi br osis. T h e g ui d a nc e als o r ec o g niz es t h e us e of a n u m b er of m e dic ati o ns 
a v ail a bl e f or ot h er us es a n d tr e at m e nt m o d aliti es s uc h as Vit a mi n E , Pi o glit az o n e a n d b ari atric 
s ur g er y f or t h e i m pr o v e m e nt of li v er dis e as e i n p ati e nts wit h bi o ps y-pr o v e n N A S H a n d ﬁbr osis . 
3. 2  Ar a mc h ol  
Ar a mc h ol is a n o v el s y nt h etic s m all m ol ec ul e, a c o nj u g at e of t w o c o m p o n e nts; c h olic aci d ( bil e 
aci d) a n d ar ac hi dic aci d (s at ur at e d f att y aci d), li n k e d b y a st a bl e a mi d e gr o u p. Ar a mc h ol is t h e 
first i n a n e w p h ar m ac ol o gic al cl ass of f att y aci d-bil e aci d c o nj u g at es ( F A B A Cs).  
Ar a mc h ol aff ects St e ar o yl C o e nz y m e A D es at ur as e 1 ( S C D 1) , a k e y li v er e nz y m e i n v ol v e d i n 
r e g ul ati n g li pi d m et a b olis m. I n a ni m al m o d els of N A S H, it h as b e e n d e m o nstr at e d t h at 
Ar a mc h ol d o w n -r e g ul at es st e at osis, b all oo ni n g, i nfl a m m ati o n a n d fi br osis. T h e eff ect of 
Ar a mc h ol o n fi br osis is i n dir ect vi a r e d ucti o n of st e at osis a n d b all o o ni n g, a n d dir ect vi a 
r e d ucti o n of c oll a g e n pr o d ucti o n fr o m h u m a n h e p atic st ell at e c ells ( H S Cs). 
P h as e 1 st u di es s h o w e d a l ess t h a n d os e -pr o p orti o n al i ncr e as e i n t h e m e a n Ar a mc h ol 
ex p os ur e  ( 1. 6-f ol d b et w e e n 2 0 0 m g a n d 4 0 0 m g a n d a 1. 2-f ol d b et w e e n 4 0 0 m g a n d 6 0 0 m g 
m ulti pl e d os es), a n d a 2. 6 -f ol d ex p os ur e aft er a hi g h -f at hi g h-c al ori e m e al as c o m p ar e d t o a 
f ast st at e. Di vi di n g Ar a mc h ol t o t w o 3 0 0 m g d os es Q 1 2 h r es ult e d i n a n a v er a g e i ncr e as e of 
a p pr oxi m at el y 5 0 % i n t h e 2 4 -h o ur pl as m a c o nc e ntr ati o ns r el ati v e t o t h e l e v els f o u n d wit h a 
si n gl e d ail y d os e of 6 0 0 m g Q 2 4 h.  
I n t h e P h as e 2 a st u d y, a st atistic all y-si g nific a nt r e d ucti o n i n li v er f at c o m p ar e d t o pl ac e b o w as 
s e e n aft er 3 m o nt hs of tr e at m e nt. All A Es  i n t h e tr e at e d ar ms w er e mil d or m o d er at e a n d n o n e 
w er e s eri o us. N o n e of t h e p ati e nts wit h dr e w as a r es ult of A Es . 
I n t h e P h as e 2 b A R R E S T st u d y, 2 4 7 s u bj ects wit h bi o ps y-pr o v e n N A S H w h o w er e o v er w ei g ht or 
o b es e a n d h a d pr e di a b et es or t y p e 2 di a b et es m ellit us w er e r a n d o miz e d ( 2: 2: 1) t o r ec ei v e 
o nc e d ail y Ar a mc h ol 4 0 0 m g  ( n = 1 0 1), Ar a mc h ol 6 0 0 m g ( n = 9 8) or pl ac e b o ( n = 4 8). B as eli n e 
hist ol o g y of e nr oll e d p ati e nts d e m o nstr at e d a p o p ul ati o n wit h a d v a nc e d dis e as e, wit h 6 0 % 
h a vi n g st a g e 2 a n d 3 fi br osis a n d 7 0 %  h a vi n g N A S ≥5. S u bj ects u n d er w e nt b ot h M R S a n d a 
bi o ps y at B as eli n e a n d at W e e k 5 2 (t er mi n ati o n), w hic h w er e c e ntr all y -r e a d b y a n ass ess or 
bli n d e d t o tr e at m e nt all oc ati o n.  
Al m ost 9 0 % of s u bj e cts i n t h e acti v e-tr e at m e nt ar ms c o m pl et e d 6 5 w e e ks (5 2 w e e ks of 
tr e at m e nt a n d 1 3 w e e ks of  f oll o w-u p) i n t h e st u dy. T h e i nci d e nc e of e arl y t er mi n ati o n ( E T) d u e 
t o A Es w as v er y l o w a n d si mil ar acr oss st u d y ar ms. 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
4 2  of 1 2 7  
R es ults s h o w e d a st atistic all y -si g nific a nt r ed ucti o n i n li v er f at wit h Ar a mc h ol 4 0 0 m g ( p = 0. 0 4 5 0) 
b ut n ot wit h 6 0 0 m g ( p = 0. 0 6 5 5) c o m p ar e d t o t h e pl ac e b o ar m, d es pit e si mil arit y i n t h e 
m a g nit u d e of tr e at m e nt eff ect i n t h e 4 0 0 m g a n d 6 0 0 m g ar ms. A p ost -h oc a n al ysis s h o w e d 
st atistic all y-si g nific a nt ≥5 % a bsol ut e r e d ucti o n i n li v er f at i n 4 7 % of p ati e nts tr e at e d wit h 
Ar a mc h ol 6 0 0 m g vs . 2 4 % wit h pl ac e b o ( p < 0. 0 2 8) a n d 3 7 % wit h 4 0 0 m g, s u g g esti n g a 
d os e -r es p o ns e p att er n . 
Bi o ps y r es ults, k e y f or f urt h er ass ess m e nt i n a N AS H pi v ot al st u d y, s h o w e d t h at si g nific a ntl y  
m or e p ati e nts tr e at e d wit h Ar a mc h ol 6 0 0 m g vs. pl ac e b o ac hi e v e d N A S H r es ol uti o n wit h o ut 
w ors e ni n g of fi br osis ( 1 6. 7 % vs. 5. 0 %; p = 0. 0 5 1 4); a n d t h at a l ar g er pr o p orti o n of p ati e nts 
s h o w e d at l e ast a o n e p oi nt i m pr o v e m e nt i n fi br osis st a g e wit h o ut w ors e ni n g o f N A S H i n 
Ar a mc h ol 6 0 0 m g vs. pl ac e b o ( 2 9. 5 % vs. 1 7. 5 %; p = 0. 2 1 1 0). O nl y 1 p ati e nt ( 1. 3 %) pr o gr ess e d t o 
cirr h osis i n t h e Ar a mc h ol 6 0 0 m g ar m w h er e as  6 ( 7. 5 %) a n d 3 ( 7. 5 %)  p ati e nts r e ac h e d t his 
e n d p oi nt i n t h e 4 0 0 m g a n d pl ac e b o ar ms, r es p ecti v el y.  
B ot h d os es s i g nific a ntl y r e d uc e d al a ni n e a mi n otr a nsf er as e ( AL T ) ( p < 0. 0 0 1), as p art at e 
a mi n otr a nsf er as e (A S T ) ( p = 0. 0 0 2) a n d H b A 1c ( p < 0. 0 0 7) vs. pl ac e b o i n a d os e-d e p e n d e nt 
m a n n er.  
Ar a mc h ol c o nti n u e d t o s h o w a f a v or a bl e s af et y a n d t ol er a bilit y pr ofil e. N o d e at h w as r e p ort e d 
i n t h e st u d y. S A Es w er e r e p ort e d i n a p pr oxi m at ely 1 0 % of s u bj ects. E ac h S A E w as r e p ort e d f or 
a si n gl e s u bj ect, S A Es w er e t y pic al f or t h e p ati e nt p o p ul ati o n a n d n o  cl ust eri n g of e v e nt t y p es 
w as n ot e d i n t h e acti v e -tr e at m e nt ar ms. M ost A Es i n t h e st u d y w er e mil d a n d r ec o v er e d.  
F or a d et ail e d d escri pti o n  of t h e cli nic al a n d n o n -cli nic al d e v el o p m e nt pr o gr a m of Ar a mc h ol 
r ef er t o t h e c urr e nt I B. 
3. 3  K n o w n  a n d P ot e nti al Ris k s a n d B e n efits t o H u m a n S u bj ects 
Ar a mc h ol is a n o v el f att y aci d -bil e aci d c o nj u g at e t ar g et e d t o t h e li v er t h at i n d uc es b e n efici al 
m o d ul ati o n of i ntr a h e p atic li pi d m et a b olis m. I n n o n -cli nic al st u di es, t h e eff ect of Ar a mc h ol o n 
fi br osis w as s h o w n t o b e i n direct vi a r e d ucti o n of st e at osis a n d b all o o ni n g, a n d dir ect vi a 
r e d ucti o n of c oll a g e n pr o d ucti o n fr o m h u m a n H S C.  
I n t h e P h as e 2 b A R R E S T st u d y, Ar a mc h ol 6 0 0 m g o nc e d ail y s h o w e d p ot e nti al effic acy o n t h e 
t w o bi o ps y e n d p oi nts t h at m a y c urr e ntl y c o nstit ut e a pri m ar y e n d p oi nt f or a P h as e 3 st u d y; 
N A S H r es ol uti o n a n d n o fi br osis w ors e ni n g as w ell as I m pr o v e m e nt i n Fi br osis a n d n o N A S H 
w ors e ni n g .   
I n t his o n e -y e ar st u d y, i n p ati e nts wit h N AS H a n d c o m or bi diti es, b ot h d os es of Ar a mc h ol 
s h o w e d a f a v or a bl e s af ety a n d t ol er a bilit y pr ofil e. N o d e at h w as r e p ort e d i n t h e st u d y. S A Es 
w er e r e p ort e d i n a p pr oxi m at el y 1 0 % of s u bj ects. E ac h S A E w as r e p ort e d f or a si n gl e s u bj ect, 
a n d S A Es w er e  t y pic al f or t h e p ati e nt p o p ul ati o n. N o cl ust eri n g of e v e nt t y p es w as n ot e d i n t h e 
acti v e -tr e at m e nt ar ms. T h e l e a di n g c a us es f or E T w er e c o ns e nt wit h dr a w al a n d A Es. T h e 
i nci d e nc e of E T d u e t o A Es w as v er y l o w a n d si mil ar acr oss st u d y ar ms. 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
4 3  of 1 2 7  
M ost A Es i n t h e st u d y w er e mil d a n d r ec o v er e d. T h e pr o p orti o n of s e v er e e v e nts w as o v er all 
l o w i n all tr e at m e nt ar ms a n d n o diff er e nc es w er e n ot e d i n i nci d e nc e of s e v er e A Es b et w e e n 
ar ms.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 of Ar a mc h ol f or N A S H i n t his P h as e 3 
cli nic al st u d y. 
T h e st u d y d esi g n e m pl o ys ris k -miti g ati o n m e as ur es, wit h ext e nsi v e s af et y m o nit ori n g t h at 
i ncl u d es r ec or di n g a n d m o nit ori n g of a dv ers e e v e nts, s af et y l a b or at ori es, vit al si g ns a n d 
p h ysic al ex a mi n ati o ns as w ell as st o p pi n g r ul es a n d s p eci al w ar ni n gs a n d pr ec a uti o ns f or us e. 
T h e st u d y will b e f oll o w e d b y a D M C  t h at will ass ess t h e o n g oi n g s af et y d uri n g t h e st u d y as 
w ell as i n d e p e n d e nt a dj u dic ati o n c o m mitt e e s f or cli nic al o ut-c o m e e v e nts , p ossi bl e DILI e v e nts  
a n d m aj or a d v ers e c ar di o v asc ul ar e v e nts  ( M A C E). 
3. 4  R ati o n al e f or S t u d y D esi g n, D os e a n d P o p ul ati o n  
3. 4. 1  
St u d y  R ati o n al e  
T h e c urr e nt st u d y is c o m p os e d of t w o p arts:  
A n O p e n -L a b el P art  t o ev al u at e t h e s af et y a n d P K of Ar a mc h ol 3 0 0 m g BI D i n s u bj ects wit h 
N A S H a n d li v er fi br osis a n d t o ex pl or e t h e ki n etics of hist ol o gic al o utc o m es a n d NI Ts 
ass oci at e d wit h N A S H a n d li v er fi br o sis f or t h e tr e at m e nt d ur ati o n of 2 4, 4 8 a n d 7 2 w e e ks. T h e 
st u d y p o p ul ati o n i ncl u d es s u bj ects wit h N A S H a n d li v er fi br osis st a g e 1 -3, s u bj ects wit h N A S H 
w h o m a y or m a y n ot b e o v er w ei g ht a n d s u bj ects wit h N AS H w h o m a y or m a y n ot h a v e T 2 D M 
or b e pr e -di a b et ic. P K a n d s af et y d at a a n d i nf or m ati o n o n t h e ki n etics of hist ol o gic al o utc o m es 
a n d NI Ts fr o m t his O p e n -l a b el P art will b e s u m m ariz e d i n s u p p ort of r e g ul at or y s u b missi o ns. 
H o w e v er, hist ol o gic al o utc o m es a n d cli nic al e v e nts fr o m t h e O p e n -La b el P art will n ot b e 
c o nsi d er e d f or t h e Hist ol o g y -B as e d pri m ar y e n d p oi nt a n d t h e Cli nic all y -B as e d pri m ar y 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
4 4  of 1 2 7  
e n d p oi nt of t h e R a n d o miz e d, D o u bl e -B li n d, P l ac e b o-c o ntr oll e d p art of t h e st u d y. Cli nic al 
e v e nts will i nst e a d b e r e p ort e d as s af et y d at a.  
 
A R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr oll e d P art  t o e v al u at e t h e s af et y a n d effic acy of 
Ar a mc h ol 3 0 0 m g BI D t o s u p p ort r e g ul at or y a p pr o v al. T h e st u d y p o p ul at i o n f or t his p art 
i ncl u d es s u bj ects wit h N A S H a n d li v er fi br osis st a g e 2 a n d 3 w h o ar e o v er w ei g ht a n d ar e eit h er 
pr e -di a b etic or h a v e T 2 D M. T h e R a n d o miz e d, D o u bl e -bli n d, Pl ac e b o -C o ntr oll e d P art of t h e 
st u d y is g e n er all y c o nsist e nt wit h F D A G ui d a nc e f or I n d ustry –  N o ncirr h otic N o n alc o h olic 
St e at o h e p atitis wit h Liv er Fi br osis: D ev el o pi n g Dr u gs f or Tr e at m e nt ( D ec e m b er 2 0 1 8)  1 3  a n d 
E M A  R efl ecti o n p a p er o n r e g ul at ory r e q uir e m e nts f or t h e d ev el o p m e nt of m e dici n al pr o d ucts 
f or c hr o nic n o ni nf ecti o us liv er dis e as es ( P B C, P S C, N A S H) ( N ov e m b er 2 0 1 8)1 4, a n d is i nt e n d e d t o 
d e m o nstr at e t h e eff ecti v e n ess a n d s af et y of Ar a mc h ol t o s u p p ort r e g ul at or y a p pr o v al. 
C o nsist e nt wit h r e g ul at or y g ui d a nc e t h er e ar e t w o pri m ar y e n d p oi nts f or t his p art of t h e st u d y:  
✓ A Hist ol o g y -B as e d pri m ar y e n d p oi nt t h at will b e a n al yz e d aft er 1 0 0 0 s u bj ects h a v e 
c o m pl et e d 7 2 w e e ks. T h e Hist ol o g y -B as e d e n d p oi nt d at a will s er v e as t h e b asis f or t h e 
s u b missi o n of a m ar k eti n g a ut h oriz ati o n a pplic ati o n u n d er r e g ul at or y pr o visi o ns of 
acc el er at e d/c o n diti o n al a p pr o v al b as e d o n a s urr o g at e e n d p oi nt.  
✓ T h e Cli nic all y -B as e d pri m ar y e n d p oi nt t h at will b e a n al yz e d at E o S a n d will pr o vi d e 
c o nfir m ati o n of cli nic al b e n efit b as e d o n a cli nic al o utc o m es e n d p oi nt.  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
✓ T h e o p e n l a b el p art of t h e st u d y will pr o vi d e a d diti o n al s af et y a n d P K i nf or m ati o n f or 
Ar a mc h ol 3 0 0 m g BI D i n s u bj ects wit h N A S H w hil e e nr oll m e nt i n t h e R a n d o miz e d, D o u bl e -

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
4 5  of 1 2 7  
bli n d, P l ac e b o-c o ntr oll e d P art of t h e st u d y is p e n di n g.  L o n g-t er m s af et y d at a fr o m t his 
st u d y will ulti m at el y b e a v al u a bl e a d diti o n t o Ar a mc h ol s af et y d at a b as e.   
T h e ki n etics of hist ol o gic al o utc o m es a n d NI Ts f or N A S H ass oci at e d wit h li v er fi br osis h a v e n ot 
b e e n w ell c h ar act eriz e d f or N A S H ( e. g. h o w e arl y c a n a b e n efici al eff ect o n fi br osis b e 
o bs er v e d, ar e t h er e s u bj ects t h at i m pr o v e wit h l o n g er d ur ati o n of t h er a p y etc.). P h as e 2 
N A TI V E st u d y wit h l a ni fi br a n or1 6, c o h ort 4 i n t h e P h as e 2 st u d y wit h al d af er mi n 1 7, B AL A N C E D  
P h as e 2 a st u d y wit h efr uxif er mi n 1 8) s u g g est t h at f a v or a bl e eff ects m a y b e o bs er v e d as e arl y as 
at w e e k 1 6; ot h er st u di es h a v e r e p ort e d l o n g er ti m es t o o bs er v e d eff ect i ncl u di n g u p t o 9 6 
w e e ks i n t h e PI V E N S st u d y wit h pi o glit az o n e 1 9. H o w e v er, n o st u d y, y et, h as ex a mi n e d wit hi n 
o n e cli nic al s etti n g t h e ki n etics of hist ol o gic al o utc o m e m e as ur es f or t h e diff er e nt tr e at m e nt 
d ur ati o n. T h e P h as e 2 b A R R E S T st u d y h a d a 5 2 -w e e k e n d p oi nt f or w hic h f av or a bl e eff ects 
w er e o bs er v e d. H o w e v er, it is n ot k n o w n h o w e arl y a tr e at m e nt eff ect m ay b e o bs er v e d a n d 
w h at t h e diff er e nc e m a y b e f or hist ol o gic al o utc o m es a n d NI Ts b et w e e n a tr e at m e nt d ur ati o n 
of 2 4, 4 8 or 7 2 w e e ks. T h e O p e n -La b el P art will pr o vi d e d at a t o h el p c h ar act eriz e t h e ki n etics 
of hist ol o gic al o utc o m es a n d NI Ts f or Ar a mc h ol.  
 
3. 4. 2  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
4 6  of 1 2 7  
3. 4. 3  
St u d y P o p ul ati o n  R ati o n al e  
P ati e nts wit h st a g e 2 -3 fi br osis, w h o ar e o v er w ei g ht/ o b es e wit h pr e di a b et es or t y p e 2 
di a b et es ar e c o nsi d er e d at gr e at est ris k f or t h e n e g ati v e o utc o m es of N A S H. F e at ur es of 
m et a b olic s y n dr o m e ( M et S) ar e n ot o nl y hi g hl y pr e v al e nt i n p ati e nts  wit h N A FL D, b ut 
c o m p o n e nts of M et S als o i ncr e as e t h e ris k of d e v el o pi n g N A FL D. T his bi dir e cti o n al ass oci ati o n 
b et w e e n N A FL D a n d c o m p o n e nts of M et S h as b e e n w ell est a blis h e d. I n a d diti o n, t h e pr es e nc e 
of a n i ncr e asi n g n u m b er of m et a b olic dis e as es, s uc h as i ns uli n r esist a nc e, ty p e 2 di a b et es, 
h y p ert e nsi o n, d ysli pi d e mi a, a n d visc er al o b esit y, s e e m s t o i ncr e as e t h e ris k of pr o gr essi v e li v er 
dis e as e. T h er ef or e, p ati e nts wit h N A FL D a n d m ulti pl e ris k f act ors s uc h as ty p e 2 di a b et es a n d 
h y p ert e nsi o n ar e at t h e hi g h est ris k f or a d v ers e o utc o m es 1 
T h e R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art will e nr oll a d ult s u bj ects, 1 8 – 7 5 y e ars 
ol d, wit h N A S H  a n d fi br osis  ( F 2-F 3) c o nfir m e d b y li v er hist ol o g y  w h o ar e o v er w ei g ht or o b es e 
a n d h a v e  pr e di a b et es  or t y p e 2 di a b et es .  
T h e O p e n -l a b el P art i nt e n ds t o ass ess t h e s af et y, P K a n d tr e at m e nt r es p o ns e ki n etics of 
Ar a mc h ol 3 0 0 m g BI D i n a br o a d er p o p ul ati o n, i ncl u di n g s u bj ects wit h fi br osis st a g e 1, s u bj ects 
w h o ar e n ot o v er w ei g ht, a n d s u bj ects w h o d o n ot h a v e T 2 D M . 
I n b ot h st u d y p arts, pati e nts wit h cirr h osis,  a b n or m al s y nt h etic li v er f u ncti o n a n d hist or y or 
pr es e nc e of d ec o m p e ns at e d li v er dis e as e will n ot b e e nr oll e d t o t h e st u d y.  
 
4  S T U D Y O BJ E C TI V E S  
O p e n -L a b el P art: 
•  T o e v al u at e  t h e s af et y a n d P K of t wic e d ail y a d mi nistr ati o n ( BI D) of Ar a mc h ol 3 0 0 m g i n 
s u bj ects wit h N A S H a n d li v er fi br osis. 
•  T o ex pl or e t h e ki n etics of hist ol o gic al o utc o m e m e as ur es a n d N o n -I n v asi v e T ests ( NI Ts) 
ass oci at e d wit h N A S H a n d fi br osis f or t h e tr e at m e nt d ur ati o n of 2 4, 4 8 a n d 7 2 w e e ks . 
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art : 
T o e v al u at e  t h e effic acy a n d s af et y of t wic e d ail y a d mi nistr ati o n  ( BI D) of Ar a mc h ol 3 0 0 m g as 
c o m p ar e d t o pl ac e b o i n s u bj ects wit h N A S H  a n d li v er fi br osis . 
 
4. 1  Effic ac y E n d p oi nts  
4. 1. 1  
O p e n -L a b el P art 
Pri m ar y ki n etics E n d p oi nts:  
T h e pri m ar y e n d p oi nts ar e t h e ki n etics of t h e f oll o wi n g hist ol o gic al o utc o m e m e as ur es f or 
tr e at m e nt d ur ati o n of 2 4, 4 8 a n d 7 2 w e e ks a n d p ot e nti all y f oll o wi n g a 2 n d p ost -b as eli n e bi o ps y 
at w e e ks 7 2 or 9 6 or 1 2 0 , r es p ecti v el y: 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
4 7  of 1 2 7  
•  I m pr o v e m e nt i n Fi br osis d efi n e d as t h e Pr o p orti o n ( %) of s u bj ects wit h i m pr o v e m e nt i n 
li v er fi br osis gr e at er t h a n or e q u al t o o n e st a g e ( N A S H C R N fi br osis sc or e) a n d n o 
w ors e ni n g of st e at o h e p atitis ( d efi n e d as n o i ncr e as e i n N A S f or b all o o ni n g, i nfl a m m ati o n 
o r st e at osis) 
•  R es ol uti o n of N A S H  d efi n e d as t h e Pr o p orti o n ( %) of s u bj ects wit h r es ol uti o n of N A S H 
( d efi n e d b y b all o o ni n g of 0 a n d i nfl a m m ati o n 0 -1) a n d n o w ors e ni n g of li v er fi br osis o n 
N A S H C R N fi br osis sc or e ( ≥ 1 st a g e i ncr e as e).  
S ec o n d ar y ki n etics E n d p oi nt s: 
T h e s ec o n d ar y e n d p oi nts ar e  t h e ki n etics of t h e f oll o wi n g p ar a m et ers a n d NI Ts f or t h e 
tr e at m e nt d ur ati o n of 2 4, 4 8 a n d 7 2 w e e ks: 
•  AL T a n d A S T  
•  Gl yc e mic p ar a m et ers  
•  Li pi d p ar a m et ers 
•  Fi br osc a n  
•  Bi o m ar k ers i ncl u di n g b ut n ot li mit e d t o Pr o C 3 a n d EL F  
•  Micr o bi o m e pr ofil e  
 
4. 1. 2  
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art  
Pri m ar y Effic ac y E n d p oi nts   
T h e pri m ar y effic acy e n d p oi nts of t h e R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art  ar e:  
 
1.  Hist ol o g y -B as e d : T h e Hist ol o g y -B as e d pri m ar y e n d p oi nt will b e d eri v e d fr o m t h e w e e k 7 2  
bi o ps y of t h e i niti al 1 0 0 0 s u bj ects as c o m p ar e d t o b as eli n e bi o ps y a n d will us e : 
✓ R es ol uti o n of N A S H  d efi n e d as t h e Pr o p orti o n ( %) of s u bj ects wit h r es ol uti o n of N A S H 
(d efi n e d b y B all o o ni n g of 0 a n d i nfl a m m ati o n 0 -1) a n d n o w ors e ni n g of li v er fi br osis 
o n N A S H C R N fi br osis sc or e (≥ 1 st a g e i ncr e as e).  
O R  
✓ I m pr o v e m e nt i n Fi br osis d efi n e d as t h e Pr o p orti o n ( %) of s u bj ects wit h i m pr o v e m e nt 
i n li v er fi br osis gr e at er t h a n or e q u al t o o n e st a g e ( N A S H C R N fi br osis sc or e) a n d n o 
w ors e ni n g of st e at o h e p atitis ( d efi n e d as n o i ncr e as e i n N A S f or b all o o ni n g, 
i nfl a m m ati o n or st e at osis) 
 
2.    Cli nic all y -B as e d : T h e Cli nicall y -B as e d pri m ar y e n d p oi nt is ti m e t o first occ urr e nc e of a n y of 
t h e f oll o wi n g adj u dic at e d e v e nt s 
✓ All -c a us e m ort alit y 
✓ Li v er tr a ns pl a nt 
✓ H ist ol o gic al pr o gr essi o n t o cirr h osis 
✓ M EL D sc or e > 1 5  if b as eli n e M EL D sc or e w as < 1 2 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
4 8  of 1 2 7  
✓ H os pit aliz ati o n d u e t o h e p atic d ec o m p e ns ati o n e v e nt(s)  i ncl u di n g: 
- H e p atic e nc e p h al o p at h y gr a d e ≥2 ( as ass ess e d b y W est H a v e n sc al e)  
- V aric e al bl e e di n g  
- N e w o ns et ascit es r e q uiri n g tr e at m e nt  
- S p o nt a n e o us b act eri al p erit o nitis as ass ess e d b y eit h er p ositi v e c ell c ult ur e or c ell 
c o u nt 
E v e nts will b e a dj u dic at e d b y t h e i n d e p e n d e nt Cli nic al O utc o m e A dj u dic ati o n C o m mitt e e 
( C O A C).  
 
K e y S ec o n d ar y Effic ac y E n d p oi nts  
T h e k e y s ec o n d ar y effic acy e n d p oi nt f or t h e R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d 
P art  is:  
At E o S, I m pr o v e m e nt i n Fi br osis: 5 -Y e ar Pr o p o rti o n ( %) of s u bj ects wit h i m pr o v e m e nt i n li v er 
fi br osis gr e at er t h a n or e q u al t o o n e st a g e ( N A S H C R N fi br osis sc or e) a n d n o w ors e ni n g of 
st e at o h e p atitis ( d efi n e d as n o i ncr e as e i n N A S f or b all o o ni n g, i nfl a m m ati o n or st e at osis) . 
E x pl or at or y E n d p oi nts  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
4 9  of 1 2 7  
4. 2  S af et y  a n d T ol er a bilit y E v al u ati o ns   
1.  A d v ers e e v e nts a n d s eri o us a d v ers e e v e nts. 
2.  S af et y l a b or at or y e v al u ati o ns.  
3.  Vit als si g ns.  
4.  1 2 -L e a d E C G. 
5.  P h ysic al ex a mi n ati o ns.  
6.  Dr o p -o ut r at es.  
 
4. 3  P h ar m ac o ki n etic E n d p oi nts  
Pl as m a c o nc e ntr ati o ns of Ar a mc h ol will b e s u bj ect e d t o p o p ul ati o n p h ar m ac o ki n etic a n al ysis 
usi n g N O N M E M  s oft w ar e. I n a d diti o n t o v ari a bility i n t h e w h ol e p o p ul ati o n t h at h a v e r ec ei v e d 
tr e at me nt wit h Ar a mc h ol , t h e r el ati o ns hi ps b et w e e n t h e p o p ul ati o n P K  pr ofil es a n d f act ors 
s uc h as d e m o gr a p h y, d ur ati o n of tr e at m e nt, c o nc o mit a nt m e dic ati o ns, s e v erit y of dis e as e a n d 
r es p o ns e t o tr e at m e nt will b e ex a mi n e d. 
5  S T U D Y D E SI G N  
5. 1  O v er vi e w a n d P l a n 
T h e c urr e nt st u d y i ncl u d es t w o p arts:  
O p e n -L a b el P art: 
 
A t ot al of 1 5 0 s u bj ects i ncl u di n g t h os e alr e a d y r a n d o miz e d t o Ar a mc h ol 3 0 0 m g BI D or pl ac e b o, 
will b e r a n d o miz e d i n a r ati o of 1: 1: 1 t o r ec ei v e Ar a mc h ol 3 0 0 m g BI D acc or di n g t o t h e b el o w 
gr o u pi n g :  
•  Gr o u p A: T h e p ost -b as eli n e li v er bi o ps y will b e c o n d uct e d at w e e k 2 4  
•  Gr o u p B: T h e p ost -b as eli n e li v er bi o ps y will b e c o n d uct e d at w e e k 4 8  
•  Gr o u p C: T h e p ost -b as eli n e li v er bi o ps y will b e c o n d uct e d at w e e k 7 2  
I n or d er t o m or e c o m pr e h e nsi v el y ex pl or e t h e ki n etics of hist ol o gic al o utc o m e m e as ur es ( e. g. 
ar e t h er e s u bj ects w h o m a y n ot s h o w i m pr o v e m e nt i n o utc o m e at w e e k 2 4, 4 8 or 7 2 b ut m a y 
i m pr o v e wit h l o n g er d ur ati o n of tr e at m e nt), a 2n d p ost -b as eli n e li v er bi o psy s a m pl e will b e 
c oll ect e d f or s u bj ects w h os e  p ost -b as eli n e li v er bi o ps y at w e e k 2 4 or 4 8 or 7 2 d o es n ot s h o w 
at l e ast 1 st a g e i m pr o v e m e nt i n fi br osis (fi br osis n o n -r es p o n d ers). T h e 2n d p ost -b as eli n e li v er 
bi o ps y s a m pl e will b e c oll ect e d 1 y e ar l at er (i. e. at w e e ks 7 2 or 9 6 or 1 2 0 r es p ecti v el y  
S u bj ec ts alr e a d y r a n d o miz e d a n d o n g oi n g i n t h e R a n d o miz e d, D o u bl e-Bli n d, Pl ac e b o -
C o ntr oll e d P art i n t h e s el ect e d sit es p artici p ati n g i n t h e O p e n -L a b el p art will b e gi v e n t h e 
o pti o n t o s witc h t o t h e O p e n -L a b el P art.  
T h e O p e n -L a b el P art will c o nti n u e f or t h e s a m e  d ur ati o n t h a n t h e R a n d o miz e d, D o u bl e-Bli n d, 
Pl ac e b o -C o ntr ol l e d P art. All s u bj ects i n t h e O p e n -L a b el P art will r ec ei v e Ar a mc h ol 3 0 0 m g BI D 
u ntil E o S.  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
5 0  of 1 2 7  
 
 
T h e st u d y sc h e m a of t h e O p e n -L a b el P art is pr es e nt e d i n Fi g ur e 1  
 
Fi g ur e 1 : 
O p e n -L a b el P art Sc h e m a 
 
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art : 
 
A t ot al of 2 0 0 0  s u bj ects will b e r a n d o miz e d t o rec ei v e Ar a mc h ol or m atc hi n g pl ac e b o 
e m pl o yi n g a 2: 1 r a n d o miz ati o n sc h e m e , r es p ecti v el y. 
T h e R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art  c o nsists of 2 p h as es; a n i niti al p h as e 
wit h a Hist ol o g y -B as e d  e n d p oi nt, a n d a s u bs e q u e nt p h as e wit h a  Cli nic all y -B as e d e n d p oi nt. 
T hr o u g h o ut t h e d ur ati o n of b ot h st u d y p h as es, s u bj ects will b e tr e at e d wit h eit h er Ar a mc h ol 
or m atc hi n g pl ac e b o acc or di n g t o r a n d o miz ati o n sc h e m e g e n er at e d pri or t o st u d y i niti ati o n. 
T h e st u d y p h as es ar e:  
•  Hist ol o g y -B as e d  p h as e :  
T h e st atistic al a n al ysis of t h e Hist ol o g y -B as e d pri m ar y e n d p oi nt will b e c o n d uct e d w h e n 
t h e i niti all y r a n d o miz e d 1 0 0 0  s u bj ects h a v e c o m pl et e d t h e w e e k 7 2 visit or t er mi n at e d 
e arl y. T his a n al ysis will s er v e as t h e b asis f or s u b missi o n of a m ar k eti n g a ut h or iz ati o n 
a p plic ati o n u n d er r e g ul at or y pr o visi o ns of acc el er at e d/c o n diti o n al a p pr o v al.  
•  Cli nic all y -B as e d  p h as e :   

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
5 2  of 1 2 7  
6  S T U D Y P O P UL A TI O N  
T h e R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art will e nr oll a d ult s u bj ects, 1 8 – 7 5 y e ars 
ol d, wit h N A S H  a n d fi br osis  ( F 2-F 3) c o nfir m e d b y li v er hist ol o g y  w h o ar e o v er w ei g ht or o b es e 
a n d h a v e  pr e di a b et es  or t y p e 2 di a b et es .  
T h e O p e n -La b el P art  i nt e n ds t o ass ess t h e s af et y, P K a n d tr e at m e nt r es p o ns e ki n etics of 
Ar a mc h ol 3 0 0 m g BI D i n a br o a d er p o p ul ati o n, i ncl u di n g s u bj ects wit h fi br osis st a g e 1, s u bj ects 
w h o ar e n ot o v er w ei g ht, a n d s u bj ects w h o d o n ot h a v e T 2 D M . 
I n b ot h st u d y p arts, pati e nts wit h cirr h osis, a b n or m al s y nt h etic li v er f u ncti o n a n d hist or y or 
pr es e nc e of d ec o m p e ns at e d li v er dis e as e will n ot b e e nr oll e d t o t h e st u d y.  
6. 1  I ncl usi o n Crit eri a 
T h e i ncl usi o n crit eri a f or t h e O p e n -La b el P art ar e  t h e s a m e as  t h os e of t h e R a n d o miz e d, 
D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art  wit h t h e exc e pti o n of  fi br osis st a g e (t h e O p e n-L a b el 
P art all o ws e nr oll m e nt of s u bj ects wit h fi br osis st a g e 1) , w ei g ht (t h e O p e n -L a b el P art all o ws 
e nr oll m e nt of s u bj ects w h o ar e n ot o v er w ei g ht)  a n d T y p e -2 di a b et es m ellit us  (t h e O p e n-L a b el 
P art all o ws e nr oll m e nt of s u bj ects w h o  ar e n ot pr e di a b et ic or s u bj ects w h o d o n ot h a v e T y p e -2 
di a b et es m ellit us  
I n or d er t o b e eli gi bl e t o t h e st u d y, s u bj ects m ust  m e et  all t h e f oll o wi n g crit eri a:  
1.  
M al e or f e m al e a g e 1 8 t o 7 5 y e ars (i ncl usi v e at first Scr e e ni n g visit)  
2.  
Hist ol o gic al c o nfir m ati o n of N A S H  o n a di a g n ostic li v er bi o ps y b y c e ntr al r e a di n g of t h e 
sli d es  
 
 
 
 
 
 
3.  
T ot al N A S S c or e 4 or m or e wit h at l e ast 1 i n e ac h c o m p o n e nt of t h e N A S Sc or e (st e at osis 
≥1 A N D i nfl a m m ati o n ≥1 A N D b all o o ni n g ≥1)  
4.  
Fi br osis S t a g e m ust b e 2 or 3 
•  O p e n -L a b el P art o nl y : 3 0 s u bj ects wit h fi br osis st a g e 1 m a y b e i ncl u d e d  
5.  
 
 
 
6.  
B o d y m ass i n d ex ( B MI)  
•  O p e n -L a b el P art: ≤ 4 0 k g/ m 2 
•  R a n d o miz e d , D o u bl e-Bli n d, Pl ac e b o -C o ntr ol l e d P art : b et w e e n 2 5 k g/ m 2 a n d 4 0 
k g/ m 2 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
5 3  of 1 2 7  
7.  
 
 
 
 
8.  
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art  o nl y: T y p e 2 di a b et es m ellit us or 
pr e di a b et es: T y p e 2 di a b et es di a g n osis m ust  b e est a blis h e d a n d d oc u m e nt e d pri or t o 
scr e e ni n g. F or pr e di a b et es, u nl ess p h ar m ac ol o gic all y tr e at e d, t h e di a g n osis s h o ul d b e 
v erifi e d b y  scr e e ni n g r es ults ( b y c e ntr al l a b) acc or di n g t o t h e A m eric a n Di a b et es 
Ass oci ati o n crit eri a , w hic h r e q uir es at l e ast o n e of t h e f oll o wi n g 3  crit eri a: 
•  
 
 
 
 
 
 
9.  
F or s u bj ects wit h t y p e 2 di a b et es, gl yc e mi a m ust b e c o ntr oll e d 
 
1 0.  N e g ati v e bl o o d pr e g n a ncy t est at st u d y e ntr y f or f e m al es of c hil d b e ari n g p ot e nti al 
c o nfir m e d b y c e ntr al l a b or at or y 
1 1.  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
1 2.  A bl e t o u n d erst a n d t h e n at ur e of t h e st u d y a n d t o pr o vi d e si g n at ur e of t h e writt e n 
i nf or m e d c o ns e nt. 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
5 4  of 1 2 7  
6. 2  E xcl usi o n Crit eri a   
All excl usi o n crit eri a f or t h e O p e n -La b el P art ar e  t h e s a m e as  t h os e of t h e R a n d o miz e d, 
D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art . 
S u bj ect s will b e excl u d e d fr o m p artici p ati n g i n t his st u d y if t h e y m e et a n y of t h e f oll o wi n g 
crit eri a: 
1.  
H ist ol o gic all y d oc u m e nt e d li v er cirr h osis (fi br osis st a g e 4) 
2.  
I n a bilit y or u n willi n g n ess t o u n d er g o a li v er bi o psy 
3.  
A b n or m al s y nt h etic li v er f u ncti o n  
•  
 
 
 
 
 
 
 
4.  
AL T or A S T > 5 ×  u p p er li mit of n or m al ( UL N) ; acc or di n g t o c e ntr al l a b or at or y 
5.  
Pl at el et c o u nt < 1 5 0, 0 0 0 m m 3 
6.  
Al k ali n e p h os p h at as e ≥2 ×  UL N  
7.  
K n o w n or s us p ect e d h e p at oc ell ul ar c arci n o m a ( H C C)  
8.  
M o d el f or E n d -St a g e Li v er Dis e as e ( M EL D) sc or e > 1 2  usi n g O P T N f or m ul a   
9.  
Pri or hist or y of/ or pl a n n e d li v er tr a ns pl a nt ati o n  
1 0.  Pri or hist or y or pr es e nc e of d ec o m p e ns at e d li v er dis e as e  
1 1.  
 
 
1 2.  O t h er ( ac ut e or c hr o nic) c o existi n g li v er dis e as e b as e d o n m e dic al hist or y a n d/ or 
c e ntr aliz e d r e vi e w of li v er hist ol o g y 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
5 6  of 1 2 7  
i nfl a m m at or y b o w el dis e as e (I B D); m aj or pr e vi o us or pl a n n e d  i nt esti n al o p er ati o n (il e al 
or i n v ol vi n g t h e ri g ht c ol o n); c hr o nic p a ncr e atitis; c eli ac dis e as e or pr e vi o us v a g ot o m y) 
 
 
2 9.  U nc o ntr oll e d h y p ert e nsi o n  
•  
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
3 8.  A n y ot h er c o n diti o n t h at i n t h e o pi ni o n of t h e I n v esti g at or w arr a nts excl usi o n fr o m t h e 
st u d y 
3 9.  
 
 
 
7  C O N C O MI T A N T  M E DI C A TI O N S A N D S P E CI AL W A R NI N G S  
7. 1  All o w e d C o nc o mit a nt M e dic ati o ns  D uri n g t h e S t u d y 
A n y m e dic ati o ns, excl u di n g t h os e m e nti o n e d i n S ecti o n 7. 2  m a y b e gi v e n c o nc o mit a ntl y as 
n e e d e d f or t h e s u bj ect’s w elf ar e . A d mi nistr ati o n of all m e dic ati o ns, i ncl u di n g i n dic ati o n, d os e , 
st art a n d e n d d at e i ncl u di n g d os e m o dific ati o n, fr e q u e ncy, a n d ro ut e of a d mi nistr ati o n will b e 
r ec or d e d i n t h e s o urc e d oc u m e nt ati o n fil e a n d i n t h e el ectr o nic C as e R e p ort F or m ( e C R F). 
C o nc o mit a nt m e dic ati o ns will b e disc uss e d a n d d oc u m e nt e d at e ac h visit.  
•  
L oc al (i ncl u di n g i nj ecti o n, t o pic al a n d i n h al e d) st er oi ds ar e all o w e d 
 
7. 2  Dis all o w e d C o nc o mit a nt M e dic ati o ns  D uri n g t h e S t u d y 
I n v esti g ati o n al pr o d ucts ar e dis all o w e d d uri n g t h e st u d y . 
Alt er n ati v e tr e at m e nts s h o ul d n ot b e i niti at e d d uri n g st u d y.  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
5 7  of 1 2 7  
Dr u gs t h at ar e a p pr o v e d f or t h e tr e at m e nt of N A S H ( i n t h e e v e nt t h at dr u gs ar e a p pr o v e d 
d uri n g t h e c o urs e of t h e st u d y) ar e dis all o w e d d uri n g t h e st u d y. T h er ef or e,  s u bj ects i niti ati n g 
s uc h dr u gs s h o ul d b e disc o nti n u e d fr o m t h e st u dy. A li v er bi o ps y is r ec o m m e n d e d at e n d of 
st u d y u nl ess t h er e is a n av ail a bl e bi o ps y wit hi n th e p ast 6 m o nt hs . 
If d uri n g t h e st u d y a n y a p pr o v e d m e dic ati o n is st art e d t o tr e at N A S H, t h e 
i n dic ati o n m ust b e pr o p erl y d oc u m e nt e d o n t h e e C R F . 
 
T h e f oll o wi n g m e dic ati o ns if r e q uir e d ( a n d n o alt er n ati v e exists), will n e e d t o b e 
disc uss e d wit h t h e S p o ns or : 
•  
Dr u gs t h at m a y c a us e N AFL D ( e. g.  val pr oic aci d, ta m oxif e n , m et h otr ex at e , 
a mi o d ar o n e , c hr o nic tr e at m e nt wit h c ortic ost er oi ds, hi g h d os e estr o g e n a n d 
t etr ac ycli n e) 
•  
Gl uc a g o n -li k e p e pti d e-1  ( GL P-1) r ec e pt or a g o nists  
•  
T hi az oli di n e di o n es ( T Z Ds)  
•  
Vit a mi n E  
7. 3  Dr u g -Dr u g  Int er acti o ns  
A st u d y i n h e alt h y s u bj ects h as s h o w n n o e vi d e nc e of a n i nt er acti o n b et w e e n Ar a mc h ol 3 0 0 m g 
BI D a n d t h e pr o b e C Y P 3 A 4 s u bstr at e  mi d az ol a m or at or v ast ati n w hic h is als o m et a b oliz e d  b y 
t his is oz y m e.   
T h e p ot e nti al f or a n eff ect of Ar a m c h ol o n t h e a ntic o a g ul a nt acti vit y of w arf ari n h as n ot b e e n 
st u di e d; i n li g ht of its l o w t h er a p e utic i n d ex, s u bj ects r ec ei vi n g w arf ari n s h o ul d h a v e t h eir I N R 
m o nit or e d cl os el y d uri n g t h e  first f e w w e e ks of tr e at m e nt wit h st u d y dr u g. 
T h e eff ects of str o n g i n d uc ers of C Y P 3 A 4 o n c o nc e ntr ati o ns of Ar a mc h ol h a v e n ot b e e n 
st u di e d. T o e ns ur e a d e q u at e e x p os ur e t o Ar a mc h ol, c o -a d mi nistr ati o n of e nz y m e i n d uc ers 
s uc h as rif a m pici n, c ar b a m az e pi n e, p h e n yt oi n, e nz al ut a mi d e a n d St. J o h n’s w ort s h o ul d b e 
a v oi d e d.  
F or a d et ail e d d escri pti o n of D DI ass ess m e nt a n d st u di es r ef er t o t h e c urr e nt I B. 
7. 4  S p eci al W ar ni n gs a n d P r ec a uti o ns f or U s e 
7. 4. 1  
H e p atic Im p air m e nt  
S u bj ects wit h cirr h osis, a b n or m al s y nt h etic li v er f u ncti o n a n d hist or y or pr es e nc e of 
d ec o m p e ns at e d li v er dis e as e will n ot b e e nr oll e d t o t h e st u d y. Li v er f u ncti o n t ests will b e 
m o nit or e d d uri n g tr e at m e nt a n d crit eri a f or disc o nti n ui n g tr e at m e nt s h o ul d b e f oll o w e d  (s e e 
St o p pi n g R ul es,  S ecti o n 7. 5. 2  a n d 7. 5. 3 ) 
7. 4. 2  
R e n al Im p air m e nt  
S u bj ects wit h r e n al d ysf u ncti o n wit h  e G F R  < 4 5 ml/ mi n usi n g  t h e M D R D f or m ul a will n ot b e 
e nr oll e d t o t h e st u d y . G F R will b e m o nit or e d  d uri n g tr e at m e nt a n d disc o nti n u ati o n  m a y b e  
r e q uir e d. 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
5 8  of 1 2 7  
F or a d et ail e d d escri pti o n of s p eci al w ar ni n g s a n d pr ec a uti o n s r ef er t o t h e c urr e nt I B.  
7. 5  St o p pi n g C rit eri a 
A s u bj ect m a y disc o nti n u e p artici p ati o n i n t h e st u d y at a n y ti m e f or a n y r e as o n ( e. g. , A E , 
c o ns e nt wit h dr a w al). T h e In v esti g at or a n d/ or S p o ns or c a n wit h dr a w a s u bj ect fr o m t h e st u d y 
at a n y ti m e f or a n y r e as o n ( e. g. , pr ot oc ol d e vi ati o n, n o nc o m pli a nc e, A E ). 
7. 5. 1  
Pr e g n a nc y  
C urr e ntl y a v ail a bl e d at a fr o m n o n -cli nic al st u di es is n ot s uffici e nt t o r ul e o ut a p ot e nti al ris k o n 
pr e g n a ncy a n d a d e q u at e  a n d w ell -c o ntr oll e d st u di es h a v e  n ot b e e n c o n d uct e d i n pr e g n a nt or 
br e astf e e di n g w o m e n t o i nf or m dr u g -ass oci at e d ris ks. F urt h er m or e , t h e st u d y m a y r e q uir e 
pr oc e d ur es t h at ar e ass oci at e d wit h h ei g ht e n e d ris ks i n pr e g n a ncy  (i. e. bi o ps y). H e nc e, 
pr e g n a nc y s h o ul d b e a v oi d e d d uri n g st u d y  a n d 1 m o nt h aft er tr e at m e nt disc o nti n u ati o n .  
A n y s u bj ect w h o b ec o m es pr e g n a nt d uri n g t h e st u d y m ust n o t r ec ei v e a d diti o n al d os es of 
t h e st u d y dr u g a n d will b e wit h dr a w n fr o m t h e st u d y. 
A ll f e m al es of c hil d b e ari n g p ot e nti al s h o ul d pr actic e a hi g hl y eff ecti v e m et h o d of r eli a bl e 
c o ntr ac e pti o n at l e ast 1 m o nt h pri or t o r a n d o miz ati o n, t hr o u g h o ut t h e st u d y p eri od a n d f or 
1  m o nt h aft er tr e at m e nt disc o nti n u ati o n.  
A w o m a n is c o nsi d er e d of c hil d b e ari n g p ot e nti al if f ertil e, f oll o wi n g m e n arc h e a n d u ntil 
b ec o mi n g p ost -m e n o p a us al u nl ess p er m a n e ntl y st eril e. P er m a n e nt st erilis ati o n m et h o ds  
i ncl u d e h yst er ect o m y, bil at er al s al pi n g ect o m y a n d bil at er al o o p h or ect o my. A p ost m e n o p a us al 
st at e is d efi n e d as n o m e ns es f or 1 2 m o nt hs wit h o ut a n alt er n ati v e m e dic al c a us e.  
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
5 9  of 1 2 7  
F or d et ail e d d escri pti o n of  n o n -cli nic al r e pr o d ucti o n t oxicit y st u di es  r ef er t o t h e c urr e nt I B. 
7. 5. 2  
DILI M o nit ori n g a n d S t o p pi n g R ul es  
H e p at oc ell ul ar a n d c h ol est atic DILI s h o ul d b e m o nit or e d d uri n g t h e st u d y a n d s u bj ects s h o ul d 
b e  e d uc at e d t o r ec o g niz e s y m pt o ms a n d s e e k i m m e di at e m e dic al c ar e .  
W h e n t h e I n v esti g at or or sit e p ers o n n el, or t h e M e dic al M o nit or b ec o m es a w ar e of a c as e of 
s us pect e d DILI, or disc o nti n u ati o n d u e t o s us p ect e d DILI, all r el e v a nt p arti es (I n v esti g at or, 
M e dic al M o nit or, S p o ns or) ar e t o b e n otifi e d i m m e di at el y.  
7. 5. 2. 1  
H e p at oc ell ul ar DILI:  
G ui d eli n es r ef er t o s u bj ects wit h N or m al B as eli n e tr a ns a mi n as e a n d s u bj ects wit h E l e v at e d 
B as eli n e tr a ns a mi n as e. 
D efi niti o n of B as eli n e tr a ns a mi n as e ( AL T a n d A S T): 
•  B as eli n e v al u e is t h e a v er a g e of v al u es fr o m scr e e ni n g a n d b as eli n e visits (fr o m t h e 
c e ntr al l a b or at or y)  
A s u bj ect is d efi n e d t o h a v e a n El e v at e d  B as eli n e  w h e n t h e a v er a g e v al u es fr o m scr e e ni n g a n d 
b as eli n e visits of eit h er AL T a n d/ or A S T ar e  ≥1. 5  x UL N  
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
           
 
 
  
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
6 0  of 1 2 7  
 
 
 
 
 
 
 
 
 
 
 
* A “ n e w b as eli n e”: Tr a ns a mi n as e l e v els mi g ht d ecli n e d uri n g t h e st u d y. If t h e a v er a g e 
tr a ns a mi n as e val u e fr o m t h e t w o visits pri or t o t h e s us p ect e d DILI e v e nt is l o w er t h a n t h e 
ori gi n al el e v at e d b as eli n e v al u e ( a v er a g e fr o m scr e e ni n g a n d b as eli n e visits), t his v al u e s h o ul d 
b e s et as t h e n e w b as eli n e. If t h e n e w b as eli n e is wit hi n t h e n or m al r a n g e, g ui d el i n es f or 
n or m al b as eli n e v al u es s h o ul d b e f oll o w e d. 
F or s u bj ects u n d er cl os e o bs er v ati o n, li v er t ests s h o ul d b e r e p e at e d wit hi n 2‐ 5  d a ys a n d a n 
ass ess m e nt f or h e p atic sy m pt o ms s h o ul d b e p erf or m e d. T h e fr e q u e ncy of s u bs e q u e nt t esti n g 
( w e e kl y or bi w e e kl y) s ho ul d b e d et er mi n e d b as e d o n t h e s u bj ect’s cli nic al c o n diti o n. 
If cl os e m o nit ori n g is n ot p ossi bl e, st u d y dr u g s h o ul d b e disc o nti n u e d.  
If a s u bj ect m e ets t h e disc o nti n u ati o n crit eri o n, c o nti n u e m o nit ori n g u ntil t h e l a b or at or y 
el e v ati o ns/s y m pt o ms h av e r es ol v e d or st a biliz e d, or u ntil a d et er mi n ati o n of a c a us e u nr el at e d 
t o t h e st u d y dr u g is m a d e. 
7. 5. 2. 1. 1  
DILI W or k u p  
C o nfir m ati o n  
A n i ncr e as e of s er u m AL T or A S T t o > 3x UL N (if n or m al at b as eli n e) or i ncr e as e i n s er u m AL T or 
A S T t o  ≥2 x b aseli n e (if a b n or m al at b as eli n e) s h o ul d b e f oll o w e d b y r e p e at t esti n g wit hi n 4 8 t o 
7 2 h o urs of AL T, A S T, AL P, T BL, C P K a n d I N R t o c o nfir m t h e a b n or m aliti es a n d t o d et er mi n e if 
t h e y ar e i ncr e asi n g or d ecr e asi n g.  T h er e als o s h o ul d b e i n q uir y m a d e a b o ut s y m pt o ms. Bl o o d 
s a m pl es f or Ar a mc h ol P K s h o ul d als o b e o bt ai n e d. 
 
•  
 
 
 
 
 
 
 
 
 
 
 
 
   

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
6 1  of 1 2 7  
•  If cl os e m o nit ori n g is n ot p ossi bl e, st u d y dr u g s h o ul d b e i m m e di at el y disc o nti n u e d.  
 
Cl os e O bs er v ati o n  
•  R e p e ati n g li v er e nz y m e a n d s er u m bilir u bi n t ests t w o or t hr e e ti m es w e e kly. Fr e q u e ncy 
of r et esti n g c a n d ecr e a s e t o o nc e a w e e k or l ess if a b n or m aliti es st a biliz e or st u d y dr u g 
h as b e e n disc o nti n u e d a n d t h e s u bj ect is as y m pt o m atic.  
•  O bt ai ni n g a m or e d et ail e d hist or y of s y m pt o ms a n d pri or or c o nc urr e nt dis e as es.  
•  O bt ai ni n g a hist or y of c o nc o mit a nt dr u g us e (i ncl u di n g n o n pr escri pti o n m e dic ati o ns 
a n d h er b al a n d di et ar y s u p pl e m e nt pr e p ar ati o ns), alc o h ol us e, r ecr e ati o n al dr u g us e, 
a n d s p eci al di ets.  
•  R uli n g o ut ac ut e vir al h e p atitis t y p es A, B, C, D, a n d E; a ut oi m m u n e or alc o h olic 
h e p atitis; h y p oxic/isc h e mic h e p at o p at h y ; a n d bili ar y tr act dis e as e.  
•  O bt ai ni n g a hist or y of ex p os ur e t o e n vir o n m e nt al c h e mic al a g e nts.  
•  O bt ai ni n g a d diti o n al t ests t o e v al u at e li v er f u ncti o n, as a p pr o pri at e ( e. g., I N R, dir ect 
bilir u bi n). I n c as e o f disc o nti n u ati o n, st u d y dr u g c a n b e r est art e d o nl y if a n ot h er 
eti ol o g y is i d e ntifi e d a n d li v er e nz y m es h a v e r et ur n e d t o n or m al l e v els.  
If aft er  r e-c h all e n g e, a  s u bj ect ex p eri e nc es  DILI  (i. e., r ec urr e nt el e v ati o ns  of  t ot al bilir u bi n,  AL T,  
or  A S T ), irr es p ecti v e of  t h e m a g nit u d e  of  li v er e nz y m es  el e v ati o n,  t h e st u d y dr u g  s h o ul d b e  
disc o nti n u e d  p er m a n e ntl y . 
7. 5. 2. 2  
C h ol est atic DILI  
T a bl e 1 : 
M o nit ori n g a n d st o p pi n g r ul es f or c h ol est atic DILI  
  
E V E N T  
AL T / A S T l e v els 
T O T AL BILI R U BI N  
A C TI O N  
D o u bli n g of c o nj u g at e d or 
dir ect bilir u bi n ( C B or D B) - 
wit hi n n or m al v al u es  
Mil d el ev ati o ns * 
 
Mil d el ev ati o ns * 
 
P erf or m cl os e m o nit ori n g  
D o u bli n g of c o nj u g at e d or 
dir ect bilir u bi n ( C B or D B) –  
a b o v e n or m al v al u es  
 
Mil d el ev ati o ns * 
 
Mil d el ev ati o ns * 
 
I nt err u pt t h e 
tr e at m e nt, cl os ely 
m o nit or t h e p ati e nt a n d 
i niti at e p ot e nti al DILI 
e v al u ati o n.
 
Tr e at m e nt c a n o nl y b e 
i niti at e d if a n alt er n at e 
eti ol o gy f or li v er e nzy m e 
el e v ati o n is est a blis h e d.  
AL P/ G G T ≥ 2x UL N  (f or 
n or m al b as eli n e)  
 
 
 
P erf or m cl os e 
m o nit ori n g
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
6 2  of 1 2 7  
E V E N T  
AL T / A S T l e v els 
T O T AL BILI R U BI N  
A C TI O N  
AL P/ G G T ≥2x b as eli n e 
a n d > UL N (f or el e v at e d 
b as eli n e)  
 
AL P/ G G T ≥ 2x UL N  (f or 
n or m al b as eli n e)  
 
AL P/ G G T ≥2x b as eli n e 
a n d > UL N (f or el e v at e d 
b as eli n e)  
Mil d el ev ati o ns * 
Mil d el ev ati o ns * 
I nt err u pt t h e 
tr e at m e nt, cl os ely 
m o nit or t h e p ati e nt a n d 
i niti at e p ot e nti al DILI 
e v al u ati o n.
 
Tr e at m e nt c a n o nl y b e 
i niti at e d if a n alt er n at e 
eti ol o gy f or li v er e nzy m e 
el e v ati o n is est a blis h e d.  
T ot al  bilir u bi n  el ev ati o n  
a n d  sy m pt o ms c o nsist e nt 
wit h  cli nic al h e p atitis  (ri g ht 
u p p er  q u a dr a nt  p ai n  or  
t e n d er n ess, j a u n dic e, r as h, 
etc..)  
A ny  m a g nit u d e  
2 X UL N  
Disc o nti n u e  t h e 
tr e at m e nt, cl os ely 
m o nit or t h e p ati e nt a n d 
i niti at e p ot e nti al DILI 
e v al u ati o n.
 
Tr e at m e nt c a n 
o nl y b e i niti at e d if a n 
alt er n at e eti ol o gy f or liv er 
e nzy m e el e v ati o n is 
est a blis h e d.  If n o  c a us e is 
f o u n d, r e-c h all e n g e 
s h o ul d n ot  b e  i niti at e d.
 
*  Mil d el ev ati o n r ef ers t o C T C A E gr a d e 1:  
 - AL T/ A S T: > UL N - 3 x UL N if b as eli n e w as n or m al; 1. 5 - 3. 0 x b as eli n e if b as eli n e w as a b n or m al  
 - T ot al bilir u bi n: > UL N - 1. 5 x UL N if b as eli n e w as n or m al; > 1 - 1. 5 x b as eli n e if b as eli n e w as a b n or m al  
 
If aft er  r e-c h all e n g e, a  p ati e nt  ex p eri e nc es  DILI  (i. e., r ec urr e nt el e v ati o ns  of  t ot al bilir u bi n,  AL T,  
or  A S T ), irr es p ecti v e of  t h e m a g nit u d e  of  li v er e nz y m es  el e v ati o n),  t h e st u d y dr u g  s h o ul d b e  
disc o nti n u e d  p er m a n e ntl y . 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
6 4  of 1 2 7  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
8  S T U D Y C O N D U C T  
8. 1  St u d y P eri o d  
O p e n -L a b el P art: 
•  Scr e e ni n g:  u p t o 8  w e e ks  
•  Tr e at m e nt p eri o d:  T h e O p e n -L a b el P art will c o nti n u e f or t h e s a m e d ur ati o n t h a n t h e 
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr oll e d P art. All s u bj ects i n t h e O p e n -L a b el P art will 
r ec ei v e Ar a mc h ol 3 0 0 m g BI D u ntil E o S. 
 
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art : 
Scr e e ni n g : u p t o 8  w e e ks .  
Tr e at m e nt p eri o d : S u bj ects will r e m ai n o n t h e s a m e tr e at m e nt assi g n m e nt  f or u p t o 7 y e ars.  
E n d -of -St u d y : All 2 0 0 0 s u bj ects pl a n n e d t o b e r a n d o miz e d i nt o t his st u d y will r ec ei v e 
Ar a mc h ol or m atc hi n g pl ac e b o u ntil E o S w hic h will occ ur at t h e ti m e w h e n a t ot al of 
3 8 0  s u bj ects will ex p eri e nc e at l e ast 1 pr e -s p ecifi e d cli nic al e v e nt or at 5 y e ars fr o m l ast 
s u bj ect’s r a n d o miz ati o n, w hic h e v er c o m es first. 
B ot h st u d y p arts  ( O p e n L a b el P art a n d R a n d o miz e d, D o u bl e Bli n d, Pl ac e b o C o ntr oll e d P art): 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
6 5  of 1 2 7  
St u d y Visits:  All s u bj ects will att e n d t h e f oll o wi n g visits: Scr e e ni n g, B as eli n e, w e e ks 4, 8, 1 2, 
a n d e v er y 1 2 w e e ks t h er e after . 
Visit sc h e d uli n g f or s u bj ects w h o s witc h fr o m t h e R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -
C o ntr oll e d P art t o t h e O p e n -L a b el P art  is d e p e n d e nt o n pri or ex p os ur e t o Ar a mc h ol. S u bj ects 
t h at r ec ei v e d acti v e tr e at m e nt will c o nti n u e b as e d o n sc h e d ul e d visits. S u bj ects t h at r ec ei v e d 
pl ac e b o will st art t h e sc h e d ul e d visits fr o m a B as eli n e visit  
At t h e visit w h e n t h e  s witc h is p erf or m e d, su bj ects  will si g n a n e w I C F a n d c o m pl et e acti viti es  
as a p plic a bl e  ( e. g. l a b or at or y, i m a gi n g, st o ol s a m pl es).  
 
E arl y disc o nti n u ati o n  
T h er e ar e t w o t y p es of e arl y disc o nti n u ati o n : 
•  E arl y Tr e at m e nt Disc o nti n u ati o n ( E T D) : S u bj ect disc o nti n u es tr e at m e nt b ut c o n ti n u es 
wit h t h e sc h e d ul e d visits.  
•  E arl y St u d y  Disc o nti n u ati o n ( E S D) : S u bj ect disc o nti n u es st u d y.  
 
 
 
 
 
 
  
 
  
 
 
   
 
 
   
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art :  
•  W e e k 7 2  bi o ps y : m a y b e p erf or m e d fr o m 2 w e e ks pri or t o w e e k 7 2  visit  a n d u p t o 6 w e e ks  
aft er w e e k 7 2  
•  5 -y e ar bi o ps y : m a y b e p erf or m e d at  t h e 5 -y e ar  visit ±  8 w e e ks   
 
 
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
6 7  of 1 2 7  
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
C O N FI D E N TI AL  
6 9  of 1 2 7  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
7 1  of 1 2 7  
8. 2. 1  
S cr e e ni n g P eri o d   
T h e pr oc e d ur es s h o ul d pr oc e e d i n t h e f oll o wi n g or d er:  
•  I nf or m e d c o ns e nt: Pri or t o p erf or mi n g a n y st u d y acti viti es/ e v al u ati o ns, t h e s u bj ect 
m ust b e t h or o u g hl y i nf or m e d a b o ut all as p ects of t h e st u d y, i ncl u di n g t h e st u d y d esi g n 
wit h a Hist ol o g y -B as e d e n d p oi nt t h at m a y s er v e as t h e b asis f or s u b missi o n of a 
m ar k eti n g a ut h oriz ati o n a p plic ati o n  a n d c o nti n u ati o n wit h t h e s a m e tr e at m e nt 
assi g n m e nt t o a Cli nic all y-B as e d e n d p oi nt, sc h e d ul e d st u d y visits at t h e cli nic al sit e, 
t el e p h o n e c o nt acts a n d all acti viti es. T h e s u bj ect will als o b e i nf or m e d a b o ut t h e 
i m p ort a nc e of r e m ai ni n g i n t he st u d y  e v e n if st u dy m e dic ati o n is disc o nti n u e d. T h e 
writt e n I C F s h o ul d b e si g n e d a n d p ers o n all y d at e d b y t h e s u bj ect or b y t h e s u bj ect’s 
l e g all y acc e pt a bl e r e pr es e nt ati v e, a n d b y t h e p ers o n w h o c o n d uct e d t h e i nf or m e d 
c o ns e nt pr oc ess . A s e p ar at e c o ns e nt for m will b e si g n e d f or t h e bl o o d s a m pl e, w hic h 
will b e t a k e n f or g e n etic p ar a m et ers. Si g n e d c o pi es of t h e i nf or m e d c o ns e nt f or ms 
s h o ul d b e gi v e n t o t h e s u bj ect . 
•  S u bj ects w h o s witc h fr o m t h e R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr oll e d P art t o t h e 
O p e n -L a b el P art  ar e r e q uir e d t o  si g n a n e w I C F.  
•  Scr e e ni n g n u m b er all oc ati o n:   a u ni q u e scr e e ni n g n u m b er will b e all oc at e d t o a n y 
s u bj ect w h o si g n e d I C F usi n g t h e R a n d o miz ati o n a n d Tri al S u p pl y M a n a g e m e nt  (R T S M) 
s yst e m. 
•  T h e f oll o wi n g will b e ass ess e d / p erf or m e d: 
o  D e m o gr a p hics  
o  Alc o h ol a n d s m o ki n g st at us  
o  M e dic al hist or y  
o  Li v er dis e as e hist or y i ncl u di n g pri or tr e at m e nt ( dis e as e o ns et, pr e vi o us bi o ps y, 
pri or tr e at m e nt f or N A S H, p artici p ati o n i n ot h er N A S H cli nic al st u di es)  
o  C o nc o mit a nt m e dic ati o ns  
o  Di et ar y a n d lif est yl e h a bits as w ell as p h ysic al activit y r e gi m e n ( disc ussi o n a n d 
c o u ns eli n g a b o ut i m p ort a nc e of di et , w ei g ht m a n a g e m e nt a n d ex ercis e)  
o  P h ysic al ex a mi n ati o n  
o  B o d y m e as ur e m e nts i ncl u di n g h ei g ht, w ei g ht, w aist circ u mf er e nc e 
o  Vit al si g ns i ncl u di n g bl o o d pr ess ur e, h e art r at e, r es pir at or y r at e, a n d 
t e m p er at ur e 
o  El ectr oc ar di o gr a m  ( E C G) 
o  L a b or at or y s a m pl es 
F asti n g  ( 8 h o urs) is r e q uir e d b ef or e t h e visit 
o  C o m pl et e bl o o d c o u nt, S er u m bi oc h e mistr y, S er ol o g y ( H B V, H C V  a n d 
HI V), T h yr oi d f u ncti o n ( TS H, T 3 a n d T 4), R e n al f u ncti o n (cr e ati ni n e a n d 
e G F R), C P K, C o a g ul ati o n, Gl yc e mic p ar a m et ers, Uri n al ysis, S er u m β -h C G 
i n w o m e n of c hil d b e ari n g p ot e nti al 
o  M EL D will b e c alc ul at e d  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
7 2  of 1 2 7  
o  Bl o o d s a m pl es f or p ot e nti al bi o m ar k ers  (i ncl u di n g b ut n ot li mit e d t o 
Pr o C 3 a n d EL F) , m et a b ol o mics a n d b ett er u n d erst a n di n g of t h e 
m ec h a nis m of acti o n  will b e c oll ect e d.  
•  A b d o m i n al ultr as o u n d ( U S) t o ass ess t h e ri g ht u p p er q u a dr a nt ( R U Q) f or h e p at oc ell ul ar 
c arci n o m a ( H C C), c h ol elit hi asis, c h ol e d oc h olit hi as is, c h ol ecystitis, or pr es e nc e of ot h er 
h e p atic a b n or m aliti es  as w ell as si g ns of cirr h osis ( e. g. ascit es, s pl e n o m e g aly) . U S d o n e 
i n t h e 3  m o nt hs pri or t o scr e e ni n g is acc e pt a bl e.  
•  Fi br osc a n)  s h o ul d b e p erf or m e d u n d er pr o p er f asti n g a n d i n g o o d q u alit y . Fi br osc a n  i n 
t h e 4 w e e ks  pri or t o scr e e ni n g is acc e pt a bl e.   
•  Li v er bi o ps y 
o  Bi o ps y s h o ul d b e p erf or m e d as t h e fi n al eli gi bility ass ess m e nt st e p a n d o nl y 
aft er all pr e vi o us eli gi bilit y crit eri a w er e c o nfir m e d.  
o  O p e n -L a b el P art: Bi o psi es p erf or m e d i n t h e 9 m o nt hs pri or t o 
r a n d o miz ati o n ar e acc e pt a bl e a n d will b e s e nt f or c e ntr al r e a di n g. 
o  R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art:  B i o psi es p erf or m e d 
i n t h e 6  m o nt hs pri or t o r a n d o miz ati o n ar e acc e pt a bl e  a n d will b e s e nt 
f or c e ntr al r e a di n g 
o  Sli d es  will b e e v al u at e d by c e ntr al p at h ol o g y  r e a di n g 
o  C o a g ul ati o n r es ults s h o ul d b e wit hi n n or m al r a n g es b ef or e t h e b i o ps y is 
p erf or m e d . If t h e s u bj ect is t a ki n g a n y a ntic o a g ul a nt it s h o ul d b e disc o nti n u e d a 
s uffici e nt a m o u nt of ti m e b ef or e t h e bi o ps y t o a v oi d a n y u n d u e bl e e di n g . 
N o n -st er oi d al a nti-i nfl a m m at or y dr u gs ( N S AI Ds ) ar e  pr o hi bit e d f or 4 8 h o urs 
pri or t o t h e bi o ps y . 
 
•  T h e  s u bj ect will b e r e q u este d  t o r e p ort a n y A E st arti n g at I C F si g n at ur e d at e. 
•  A n y n e w cli nic all y si g nific a nt p h ysic al, cli nic al or l a b or at or y p ar a m et ers o bs er v e d d uri n g 
scr e e ni n g m ust b e d oc u m e nt e d as m e dic al hist or y. Aft er Scr e e ni n g, a n e w, or w ors e ni n g 
cli nic all y si g nific a nt p ar a m et er o bs er v e d m ust b e d oc u m e nt e d as a n A E i n t h e s ourc e 
d oc u m e nt ati o n fil e a n d i n t h e e C R F.  
At t h e visit w h e n t h e s witc h is p erf or m e d, s u bj ects will si g n a n e w I C F a n d c o m pl et e acti viti es 
as a p plic a bl e ( e. g. l a b or at or y, i m a gi n g, st o ol s a m pl es).  
 
 
 
 
 
 
 
 
 
   
8. 2. 2  
B as eli n e  V isit –  R a n d o miz ati o n   
•  Eli gi bilit y Crit eri a v erific ati o n ( e ns ur e n o c h a n g es occ urr e d si nc e scr e e ni n g visit)  
•  R a n d o miz ati o n n u m b er all oc ati o n b y R T S M  s yst e m 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
7 3  of 1 2 7  
•  T h e f oll o wi n g s h o ul d b e p erf or m e d /ass ess e d d uri n g t h e visit : 
•  P h ysic al ex a mi n ati o n  
•  B o d y m e as ur e m e nts i ncl u di n g w ei g ht, a n d w aist circ u mf er e nc e  
•  Vit al si g ns i ncl u di n g bl o o d  pr ess ur e, h e art r at e, r es pir at or y r at e, a n d t e m p er at ur e  
•  Di et ar y a n d lif est yl e c h a n g es as w ell as c h a n g e i n p h ysic al acti vit y r e gi m e n will b e 
ass ess e d, a n d s u bj ects will b e c o u ns el e d  
•  C o nc o mit a nt m e dic ati o n s 
•  A d v ers e E v e nts  
•  E C G  
•  L a b or at or y: 
F asti n g ( 8 h o urs) is r e q uir e d b ef or e t h e visit  
o  A uri n e p r e g n a ncy t est i n w o m e n of c hil d b e ari n g p ot e nti al  
o  C o m pl et e bl o o d c o u nt a n d s er u m bi oc h e mistr y,  R e n al f u ncti o n (cr e ati ni n e a n d 
e G F R), C o a g ul ati o n, C P K, Gl yc e mic p ar a m et ers    
o  M EL D will b e c alc ul at e d  usi n g t h e O P T N  f or m ul a/c alc ul at or 
( htt ps:// o pt n.tr a ns pl a nt. hrs a. g o v/r es o urc es/ all oc ati o n-c alc ul at ors/ m el d-
c alc ul at or/) 
o  Bl o o d s a m pl es f or p ot e nti al bi o m ar k ers  (i ncl u di n g b ut n ot li mit e d t o Pr o C 3 a n d 
EL F) , m et a b ol o mics a n d b ett er u n d erst a n di n g of m ec h a nis m of acti o n will b e 
c oll ect e d.  
o  Bl o o d s a m pl e f or g e n e a n al ysis will b e t a k e n fr o m s u bj ects pr o vi di n g c o ns e nt i n a 
d e dic at e d I C F  (s u bj ect t o l oc al r e g ul ati o ns a n d a p pr o v al), pr ef er a bl y at B as eli n e 
visit, b ut will b e acc e pt e d at a n y ot h er visit. S a m pl es will b e k e pt fr oz e n f or f ut ur e 
a n al ysis  
•  I n t h e O p e n -L a b el P art: St o ol s a m pl es f or a n al ysis of micr o bi o m e a n d b ett er 
u n d erst a n di n g o f m ec h a nis m of acti o n will b e c oll ect e d  
•  St u d y dr u g  dis p e nsi n g  acc or di n g t o t h e kit n u m b er pr o vi d e d b y R T S M s yst e m  
•  S u bj ects will b e all oc at e d t o tr e at m e nt gr o u ps d uri n g t h eir b as eli n e visits b as e d o n 
r a n d o miz ati o n list. T h e R T S M s yst e m will assi g n a u ni q u e  r a n d o miz ati o n n u m b er f or 
e ac h s u bj ect, i n a d diti o n t o t h e scr e e ni n g n u m b er pr e vi o usl y all oc at e d . 
•  T h e first d os e of st u d y dr u g will b e t a k e n o n sit e, a n d o nl y aft er all visit acti viti es h a v e 
b e e n p erf or m e d .  
 
F oll o wi n g B as eli n e visit,  t h e f oll o wi n g ass ess me nts will b e p erf or m e d d uri n g sc h e d ul e d visits 
at W e e k 4, 8, 1 2, a n d e v er y 1 2 w e e ks t h er e aft er . 
 
8. 2. 3  
O p e n -L a b el P art- S c h e d ul e d visits ( n ot i ncl u di n g E n d of St u d y visit) 
F oll o wi n g B as eli n e visit, t h e f oll o wi n g ass ess m e nts will b e p erf or m e d d uri n g sc h e d ul e d visits at 
W e e k 4, 8, 1 2, a n d e v er y 1 2 w e e ks t h er e aft er.  
T h e f oll o wi n g s h o ul d b e p erf or m e d/ ass ess e d  d uri n g t h e visit:  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
7 4  of 1 2 7  
•  P h ysic al ex a mi n ati o n  at w e e ks 2 4 a n d e v er y 2 4 w e e ks t h er e aft er 
•  B o d y m e as ur e m e nts i ncl u di n g w ei g ht a n d w aist circ u mf er e nc e at w e e k 1 2 a n d e v er y 
visit t h er e aft er   
•  Vit al si g ns i ncl u di n g bl o o d pr ess ur e, h e art r at e, r es pir at or y r at e, a n d t e m p er at ur e  
•  Di et ar y a n d lif est yl e c h a n g es  as w ell as c h a n g e i n p h ysic al act i vit y r e gi m e n will b e 
ass ess e d, a n d s u bj ects will b e c o u ns el e d  
•  C o nc o mit a nt m e dic ati o n s 
•  A d v ers e E v e nts  
•  E C G  
•  L a b or at or y: 
F asti n g ( 8 h o urs) is r e q uir e d b ef or e t h e visit  
o  A uri n e p r e g n a ncy t est i n w o m e n of c hil d b e ari n g p ot e nti al 
o  C o m pl et e bl o o d c o u nt a n d s er u m bi oc h e mistr y will b e m e as ur e d at e v ery st u d y 
visit  
o  R e n al f u ncti o n (cr e ati ni n e a n d e G F R) will b e m e as ur e d at e v er y st u d y visit  
o  C o a g ul ati o n at e v er y visit  
o  C P K will b e m e as ur e d at w e e k s 2 4  a n d e v er y 2 4 w e e ks t h er e aft er  
o  Gl yc e mic p ar a m et ers : f asti n g g l uc os e will b e m e as ur e d at e v er y st u d y visit. H b A 1c , 
C -p e pti d e, I ns uli n a n d H O M A-I R at w e e ks 1 2 ,2 4  a n d e v er y 2 4 w e e ks t h er e aft er  
o  T h yr oi d f u ncti o n ( T S H, T 3 a n d T 4)  will b e m e as ur e d  at w e e k 4 8  
o  M EL D will b e c alc ul at e d at w e e k 1 2, a n d at e v er y visit t h er e aft er  
o  Bl o o d s a m pl e f or P K will b e c oll ect e d  fr o m w e e k 4 u ntil 7 2  w e e ks a n d e v er y 2 4 
w e e ks  t h er e aft er 
o  Bl o o d s a m pl es f or p ot e nti al bi o m ar k ers  (i ncl u di n g Pr o C 3 a n d EL F), m et a b ol o mics 
a n d b ett er u n d erst a n di n g of m ec h a nis m of acti o n will b e c oll ect e d at w e e k  1 2,  2 4  
, 4 8 a n d e v er y 2 4 w e e ks t h er e aft er  
o  St o ol s a m pl es f or a n al ysis of micr o bi o m e a n d b ett er u n d erst a n di n g of m ec h a nis m  
of acti o n will b e c oll ect e d at w e e ks 4, 1 2, 2 4, 4 8, 7 2  
•  Dr u g acc o u nt a bilit y   
•  St u d y dr u g dis p e nsi n g  
•  A b d o mi n al  ultr as o u n d ( U S) a n d Fi br osc a n will b e p erf or m e d at w e e k 2 4 a n d e v er y 2 4 
w e e ks t h er e aft er   
o  A b d o mi n al  U S  is p erf or m e d t o ass ess f or si g ns of H C C  or ot h er R U Q n e w fi n di n gs 
as w ell as  si g ns of pr o gr essi o n t o cirr h osis  ( e. g. ascit es, s pl e n o m e g al y) 
o  Fi br osc a n is p erf or m e d as p art of t h e NI T s ass ess m e nt i n t h e st u d y. Sc a n s h o ul d 
m e et t h e mi ni m al q u alit y d efi niti o n (s u bj ect f asti n g f or a mi ni m u m of 3 h o urs a n d 
at l e ast 1 0 v ali d s h ots wit h I Q R ≤3 0 % of t h e v al u e of t h e m e di a n) 
o  Fi br osc a n  is als o p erf or m e d i n or d er t o i d e ntif y s u bj ects t h at m a y h a v e pr o gr ess e d 
t o cirr h osis. Ex a mi n ati o n  s h o ul d b e p erf or m e d u n d er pr o p er f asti n g c o n diti o ns a n d 
i n g o o d q u alit y. V al u es hi g hl y s u g g esti v e of pr o gr essi o n t o cirr h osis ( e. g. 
r ec o m m e n d e d hi g h s p ecificit y c ut-off f or Fi br osc a n L S M ≥1 6 k p) s h o ul d b e v erifi e d 
o n a r e p e at sc a n.  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
7 5  of 1 2 7  
It is r ec o m m e n d e d t o p erf or m li v er bi o ps y if t h er e is hi g h s us pici o n of pr o gr essi o n 
t o cirr h osis b as e d o n t h e a b d o mi n al U S or b as e d o n t h e f oll o wi n g ass ess m e nts 
(c o nfir m e d t hr o u g h r e p e at t esti n g wit hi n o n e m o nt h of i niti al t esti n g): Fi br osc a n  
r es ults a n d pl at el et c o u nt < 1 5 0, 0 0 0 m m 3 a n d  o n e s er u m fi br osis m ar k er i n dic ati v e 
of cirr h osis (f or ex a m pl e, Fi br o T est >  0. 7 5 or EL F > 1 1. 3  or FI B 4 > 2. 6 7 or N AFL D 
Fi br osis Sc or e > 0. 6 7 6) . 
 
•  Li v er Bi o ps y:   
o  T h e 2 n d sc h e d ul e d li v er bi o ps y will b e p erf or m e d b as e d o n r a n d o miz ati o n gr o u ps 
A, B, C at w e e k 2 4 or 4 8 or 7 2, r es p ecti v el y . 
T h e bi o ps y m a y b e p erf or m e d fr o m 2 w e e ks pri or t o t h e sc h e d ul e d bi o ps y u p t o 
6 w e e ks aft er t h e sc h e d ul ed  bi o ps y  
o  A 2 n d p ost -b as eli n e li v er bi o ps y s a m pl e will b e c oll ect e d f or s u bj ects w h os e p ost 
b as eli n e li v er bi o ps y at w e e k 2 4 or 4 8 or 7 2 d o es n ot s h o w at l e ast 1 st a g e 
i m pr o v e m e nt i n fi br osis (fi br osis n o n-r es p o n d ers).  T h e 2 n d p ost -b as eli n e li v er 
bi o ps y s a m pl e will b e c oll ect e d 1 y e ar l at er (i. e. at w e e ks 7 2 or 9 6 or 1 2 0 
r es p ecti v el y) 
 
C o a g ul ati o n r es ults  s h o ul d b e wit hi n n or m al r a n g es b ef or e t h e bi o ps y is p erf or m e d. If 
t h e st u d y s u bj ect is t a ki n g a n y a ntic o a g ul a nt it s h o ul d b e disc o nti n u e d a s uffici e nt 
a m o u nt of ti m e b e f or e t h e bi o ps y t o a v oi d a n y u n d u e bl e e di n g. N S AI Ds ar e pr o hi bit e d 
4 8 h o urs pri or t o t h e bi o ps y  
 
8. 2. 4  
O p e n -L a b el P art - E n d -of -St u d y Visit  
S u bj ects w h o ar e still i n t h e st u d y  at t h e ti m e t h e S p o ns or a n n o u nc e d E o S will b e r e q u est e d t o 
att e n d t his visit .   
T h e f oll o wi n g s h o ul d b e p erf or m e d/r e vi e w e d d uri n g t h e visit : 
•  P h ysic al ex a mi n ati o n  
•  Vit al si g ns i ncl u di n g bl o o d pr ess ur e, h e art r at e, r es pir at or y r at e a n d t e m p er at ur e  
•  B o d y m e as ur e m e nts i ncl u di n g w ei g ht a n d w aist circ u mf er e nc e  
•  C o nc o mit a nt m e dic ati o ns  
•  A d v ers e E v e nt s 
•  E C G  
•  Di et ar y a n d lif est yl e c h a n g es  as w ell as c h a n g e i n p h ysic al acti vit y r e gi m e n will b e 
ass ess e d, a n d s u bj ects will b e c o u ns el e d  
•  L a b or at or y: 
F asti n g ( 8 h o urs) is r e q uir e d b ef or e t h e visit  
o  A uri n e pr e g n a ncy t est i n w o m e n of c hil d b e ari n g p ot e nti al  
o  C o m pl et e bl o o d c o u nt a n d s er u m bi oc h e mistr y, R e n al f u ncti o n (cr e ati ni n e a n d 
e G F R), C o a g ul ati o n, T h yr oi d f u ncti o n ( T S H, T 3 a n d T 4), C P K, Gl yc e mic p ar a m et ers  
o  Bl o o d s a m pl e f or P K will b e c oll ect e d  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
7 6  of 1 2 7  
o  Bl o o d s a m pl es f or p ot e nti al bi o m ar k ers, m et a b ol o mics a n d b ett er u n d erst a n di n g 
of m ec h a nis m of acti o n  
•  Dr u g  acc o u nt a bilit y  
 
8. 2. 5  
R a n d o miz e d , D o u bl e-Bli n d, Pl ac e b o -C o ntr ol l e d P art S c h e d ul e d visits ( n ot 
i ncl u di n g E n d of St u d y visit) 
F oll o wi n g t h e B as eli n e visit, t h e f oll o wi n g ass ess m e nts will b e p erf or m e d d uri n g sc h e d ul e d 
visits  at W e e k 4, 8, 1 2, a n d e v er y 1 2 w e e ks t h er e aft er.  
T h e f oll o wi n g s h o ul d b e p erf or m e d/ ass ess e d  d uri n g t h e visit:  
•  P h ysic al ex a mi n ati o n  at w e e k s 2 4  a n d  e v er y  2 4 w e e ks t h er e aft er  
•  B o d y m e as ur e m e nts i ncl u di n g w ei g ht a n d w aist circ u mf er e nc e at w e e k 1 2 a n d e v er y 
visit t h er e aft er   
•  Vit al si g ns i ncl u di n g bl o o d pr ess ur e, h e art r at e, r es pir at or y r at e, a n d t e m p er at ur e  
•  Di et ar y a n d lif est yl e c h a n g es  as w ell as c h a n g e i n p h ysic al acti vit y r e gi m e n will b e 
ass ess e d, a n d s u bj ects will b e c o u ns el e d  
•  C o nc o mit a nt m e dic ati o n s 
•  A d v ers e E v e nts  
•  E C G  
•  L a b or at or y: 
F asti n g ( 8 h o urs) is r e q uir e d b ef or e t h e visit  
o  A uri n e p r e g n a ncy t est i n w o m e n of c hil d b e ari n g p ot e nti al 
o  C o m pl et e bl o o d c o u nt a n d s er u m bi oc h e mistr y will b e m e as ur e d at e v ery  st u d y 
visit  
o  R e n al f u ncti o n (cr e ati ni n e a n d e G F R) will b e m e as ur e d at e v er y st u d y visit  
o  C o a g ul ati o n at e v er y visit  
o  C P K will b e m e as ur e d at w e e k s 2 4  a n d e v er y 2 4 w e e ks t h er e aft er   
o  Gl yc e mic p ar a m et ers : f asti n g g l uc os e will b e m e as ur e d at e v er y st u d y visit. H b A 1c , 
C -p e pti d e, I ns uli n a n d H O M A-I R at w e e ks 1 2 ,2 4  a n d e v er y 2 4 w e e ks t h er e aft er   
o  T h yr oi d f u ncti o n ( T S H, T 3 a n d T 4)  will b e m e as ur e d  at w e e k 4 8  
o  M EL D will b e c alc ul at e d at w e e k 1 2, a n d at e v er y visit t h er e aft er  
o  Bl o o d s a m pl e f or P K will b e c oll ect e d  fr o m w e e k 4 u ntil 7 2  w e e ks a n d e v er y 2 4 
w e e ks  t h er e aft er 
o  Bl o o d s a m pl es f or p ot e nti al bi o m ar k ers  (i ncl u di n g Pr o C 3 a n d EL F), m et a b ol o mics 
a n d b ett er u n d er st a n di n g of m ec h a nis m of acti o n will b e c oll ect e d at w e e k  1 2  2 4 , 
4 8  a n d e v er y 2 4 w e e ks t h er e aft er  
•  Dr u g acc o u nt a bilit y   
•  S t u d y dr u g  dis p e nsi n g   
•  A b d o mi n al  ultr as o u n d ( U S) a n d Fi br osc a n will b e p erf or m e d at w e e k 2 4 a n d e v er y 2 4 
w e e ks t h er e aft er   
o  A b d o mi n al  U S  is p erf or m e d t o ass ess f or si g ns of H C C  or ot h er R U Q n e w fi n di n gs 
as w ell as  si g ns of pr o gr essi o n t o cirr h osis  ( e. g. ascit es, s pl e n o m e g al y) 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
7 7  of 1 2 7  
o  Fi br osc a n is p erf or m e d as p art of t h e NI T s ass ess m e nt i n t h e st u d y. Sc a n s h o ul d 
m e et t h e mi ni m al q u alit y d efi niti o n (s u bj ect f asti n g f or a mi ni m u m of 3 h o urs a n d 
at l e ast 1 0 v ali d s h ots wit h I Q R ≤3 0 % of t h e v al u e of t h e m e di a n)  
o  Fi br osc a n  is als o p erf or m e d i n or d er t o i d e ntif y s u bj ects t h at m a y h a v e pr o gr ess e d 
t o cirr h osis. Ex a mi n ati o n  s h o ul d b e p erf or m e d u nd er pr o p er f asti n g c o n diti o ns a n d 
i n g o o d q u alit y. V al u es hi g hl y s u g g esti v e of pr o gr essi o n t o cirr h osis ( e. g. 
r ec o m m e n d e d hi g h s p ecificit y c ut-off f or Fi br osc a n L S M ≥1 6 k p) s h o ul d b e v erifi e d 
o n a r e p e at sc a n.  
It is r ec o m m e n d e d t o p erf or m li v er bi o ps y if t h er e is hi g h s us pici o n of pr o gr essi o n 
t o cirr h osis b as e d o n t h e a b d o mi n al U S or b as e d o n t h e f oll o wi n g ass ess m e nts 
(c o nfir m e d t hr o u g h r e p e at t esti n g wit hi n o n e m o nt h of i niti al t esti n g): Fi br osc a n  
r es ults a n d pl at el et c o u nt < 1 5 0, 0 0 0 m m 3 a n d  o n e s er u m fi br osis m ar k er i n dic ati v e 
of cirr h osis (f or ex a m pl e, Fi br o T est >  0. 7 5 or EL F > 1 1. 3  or FI B 4 > 2. 6 7 or N AFL D 
Fi br osis Sc or e > 0. 6 7 6) . 
•  Li v er bi o ps y: 
o  7 2 -w e e k li v er bi o ps y m ay b e p erf or m e d fr o m 2 w e e ks pri or t o t h e w e e k 7 2 visit  
a n d u p t o 6 w e e ks aft er w e e k 7 2 .  
o  5 -y e ar li v er  bi o ps y  s h o ul d occ ur wit hi n 8 w e e ks  (pri or  t o or aft er ) of t h e 5-y e ar 
visit, u nl ess t h er e is a n av ail a bl e bi o ps y wit hi n t h e p ast y e ar. 
C o a g ul ati o n r es ults s h o ul d b e wit hi n n or m al r a n g es b ef or e t h e bi o p s y is p erf or m e d. If 
t h e st u d y s u bj ect is t a ki n g a n y a ntic o a g ul a nt it s h o ul d b e disc o nti n u e d a s uffici e nt 
a m o u nt of ti m e b ef or e t h e bi o ps y t o a v oi d a n y u n d u e bl e e di n g. N S AI Ds ar e pr o hi bit e d 
4 8 h o urs pri or t o t h e bi o ps y.  
 
 
8. 2. 6  
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art:  E n d -of -St u d y Visit  
a n d 7 -Y e ar Visit  
S u bj ects t h at c o m pl et e 7  y e ars i n t h e st u d y or t h at ar e o n g oi n g at t h e ti m e t h e S p o ns or 
a n n o u nc e d E o S will b e r e q u est e d t o att e n d t his visit  a n d will  b e pr o vi d e d t h e o pti o n t o r ec ei v e 
Ar a mc h ol tr e at m e nt i n a n o p e n -l a b el e d ext e nsi o n. T h e ext e nsi o n st u d y will b e d et ail e d  u n d er  
a s e p ar at e pr ot oc ol .  
T h e f oll o wi n g s h o ul d b e p erf or m e d/r e vi e w e d d uri n g t h e visit : 
•  P h ysic al ex a mi n ati o n  
•  Vit al si g ns i ncl u di n g bl o o d pr ess ur e, h e art r at e, r es pir a t or y r at e a n d t e m p er at ur e 
•  B o d y m e as ur e m e nts i ncl u di n g w ei g ht a n d w aist circ u mf er e nc e  
•  C o nc o mit a nt m e dic ati o n s 
•  A d v ers e E v e nts  
•  E C G  
•  Di et ar y a n d lif est yl e c h a n g es  as w ell as c h a n g e i n p h ysic al acti vit y r e gi m e n will b e ass ess e d, 
a n d s u bj ects will b e c o u ns el e d  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
7 8  of 1 2 7  
•  La b or at or y:  
F asti n g ( 8 h o urs) is r e q uir e d b ef or e t h e visit  
o  A uri n e p r e g n a ncy t est i n w o m e n of c hil d b e ari n g p ot e nti al 
o  C o m pl et e bl o o d c o u nt a n d s er u m bi oc h e mistr y, R e n al f u ncti o n (cr e ati ni n e a n d 
e G F R), C o a g ul ati o n, T h yr oi d f u ncti o n ( T S H, T 3 a n d T 4), C P K, Gl yc e mic 
p ar a m et ers  
o  Bl o o d s a m pl e f or P K will b e c oll ect e d  
o  Bl o o d s a m pl es f or p ot e nti al bi o m ar k ers, m et a b ol o mics a n d b ett er 
u n d erst a n di n g of m ec h a nis m of acti o n  
•  Dr u g  acc o u nt a bilit y  
•  Li v er bi o ps y will b e c o n d uct e d as f oll o ws  
o  I n c as e t h e S p o ns or a n n o u nc es E o S a n d t h e s u bj ect h as n ot r e ac h e d 5-y e ar visit, it is 
r ec o m m e n d e d t o p erf or m a li v er bi o ps y , u nl ess t h er e is a n a v ail a bl e bi o psy wit hi n 
t h e p ast y e ar . 
o  T h er e is n o sc h e d ul e d bi o ps y at y e ar 7 visit  
C o a g ul ati o n r es ults s h o ul d b e wit hi n n or m al r a n g es b ef or e t h e bi o ps y is p erf or m e d. If t h e  
st u d y s u bj ect is t a ki n g a ny a ntic o a g ul a nt it s h o ul d b e disc o n ti n u e d a s uffici e nt a m o u nt of 
ti m e b ef or e t h e bi o ps y t o a v oi d a n y u n d u e bl e e di n g. N S AI Ds ar e pr o hi bit e d 4 8 h o urs pri or 
t o t h e bi o ps y. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
7 9  of 1 2 7  
8. 2. 8  
E arl y Disc o nti n u ati o n V isit - E T D/ E S D  ( b ot h st u d y p arts; O p e n -L a b el P art 
a n d R a n d o miz e d, D o u bl e Bli n d, Pl ac e b o -C o ntr oll e d P art ) 
T h er e ar e t w o t y p es of disc o nti n u ati o n i n t h e st u dy : tr e at m e nt disc o nti n u ati o n (i. e. e arl y  
tr e at m e nt disc o nti n u ati o n ) a n d st u d y wit h dr a w al (i. e. e arl y st u d y disc o nti n u ati o n ). 
All eff orts s h o ul d b e m a d e f or s u bj ects t o c o nti n u e p artici p ati o n i n t h e st u d y , e v e n i n c as e 
tr e at m e nt is disc o nti n u e d. T his i ncl u d es als o s u bj ects w h o  disc o nti n u e tr e at m e nt d u e t o 
St o p pi n g R ul es f or Li v er -R el at e d E v e nts i ncl u di n g pr o gr essi o n t o cirr h osis.  
F or a n y  s u bj ect t h at st o ps st u d y tr e at m e nt, it s h o ul d b e ex pl ai n e d t h at t h ey c a n c o m pl et e all 
f ut ur e st u d y visits a n d r e m ai n i n t h e st u d y wit h o ut t a ki n g t h e st u d y dr u g. S u bj ects will p erf or m 
disc o nti n u ati o n pr oc e d ur es a n d will att e n d f ut ur e st u d y visits acc or di n g t o sc h e d ul e, wit h o ut 
dis p e nsi n g of st u d y dr u g. If t h e y d o n ot c h o os e t o c o m pl et e all sc h e d ul e d st u d y visits, s u bj ects 
will b e pr o vi d e d t h e o pt i o n of l ess fr e q u e nt visits a n d/ or t el ep h o n e c o nt act f or c oll ecti o n of 
critic al o utc o m e ass ess m e nt . A t a mi ni m u m, a d diti o n al o pti o ns f or a n n u al f oll o w-u p a n d 
p er missi o n t o acc ess t h e s u bj ect’s el ectr o nic/ m e dic al r ec or ds f or f oll o w -u p i nf or m ati o n s h o ul d 
b e off er e d.  
T h e r e as o n f or e arl y disc o nti n u ati o n will b e r ec or d e d o n t h e r el e v a nt e C RF ( E T D or E S D).   
Si nc e it is ex p ect e d t h at a s u bj ect m a y disc o nti n u e tr e at m e nt, c o nti n u e f oll o w u p b ut l at er 
wit h dr a w fr o m t h e st u d y, b ot h a n E T D a n d a n E S D visit m a y b e p erf or m e d a n d t h e 
c orr es p o n di n g r e as o n s h o ul d b e r ec or d e d f or e ac h. 
A s u bj ect m a y wit h dr a w or b e wit h dr a w n fr o m tr e at m e nt/ st u d y f or t h e f oll o wi n g r e as o ns: 
•  Wit h dr a w al b y s u bj ect  
o  T his c at e g or y m a y b e us e d f or a n y p ers o n al r e as o ns n ot r el at e d t o s af et y or l ac k of 
effic ac y f or N A S H or t o st u d y dr u g  
o  A s u bj ect m a y wit h dr a w c o ns e nt fr o m tr e at m e nt b ut c o nti n u e f oll o w u p i n t h e 
st u d y. Wit h dr a w al fr o m t h e st u d y is d efi n e d as s u bj ect wit h dr a w al of c o ns e nt t o 
c o ntri b ut e a n y a d diti o n al i nf or m ati o n 
•  P h ysici a n D ecisi o n  
•  Pr ot oc ol D e vi ati o n  
•  A d v ers e E v e nt  
•  L ac k of effic ac y f or N A S H 
o  L ac k of effic ac y s h o ul d b e d efi n e d c ar ef ull y aft er r uli n g o ut wit h dr a w al of c o ns e nt 
f or p ers o n al r e as o ns 
•  Pr e g n a ncy  
•  Pr ot oc ol -S p ecifi e d St o p pi n g r ul e f or Li v er-R el at e d E v e nts ( S ecti o n 7. 5. 3 ) 
•  L ost t o f oll o w-u p  
•  St u d y T er mi n at e d b y S p o ns or  
•  D e at h  
•  Ot h er  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
8 0  of 1 2 7  
R ef us al t o p erf or m a sc h e d ul e d  bi o ps y will n ot  r es ult i n wit h dr a w al fr o m tr e at m e nt/st u d y. 
A disc o nti n u ati o n visit s h o ul d b e p erf or m e d f or all s u bj ects w h o pr e m at ur el y disc o nti n u e 
tr e at m e nt w hic h i ncl u d es b ot h E T D ( e arl y tr e at m e nt disc o nti n u ati o n) a n d E S D ( e arl y st u d y 
disc o nti n u ati o n).  
Disc o nti n u ati o n  visit will b e p erf or m e d as s o o n as p ossi bl e aft er t h e l ast st u d y d os e.  
S u bj ects w h o disc o nti n u e fr o m t h e st u d y ( E S D) will p erf or m disc o nti n u ati o n pr oc e d ur es a n d 
e n d t h eir p artici p ati o n i n t h e st u d y.  
I n t h e f oll o wi n g c as es t h e s u bj ect will b e disc o nti n u e d fr o m t h e st u d y (E S D will b e r e q uir e d ): 
pr e g n a ncy, a s u bj ect t h at w as u n bli n d e d d u e t o e m er g e ncy ( S ecti o n 8. 4. 4 ) a n d a  s u bj ect t h at 
r ecei v es a n a p pr o v e d tr e at m e nt f or N A S H  (i n t h e e v e nt t h at dr u gs ar e a p pr o v e d d uri n g t h e 
c o urs e of t h e st u d y). 
E arl y disc o nti n u ati o n visit s ( E T D or E S D) will i ncl u d e t h e f oll o wi n g:  
•  P h ysic al ex a mi n ati o n  
•  Vit al si g ns i ncl u di n g bl o o d pr ess ur e, h e art r at e, r es pir a t or y r at e a n d t e m p er at ur e 
•  B o d y m e as ur e m e nts i ncl u di n g w ei g ht a n d w aist circ u mf er e nc e  
•  C o nc o mit a nt m e dic ati o n s 
•  A d v ers e e v e nts  
•  E C G  
•  Di et ar y a n d lif est yl e c h a n g es  as w ell as c h a n g e i n p h ysic al acti vit y r e gi m e n will b e ass ess e d, 
a n d s u bj ects will b e c o u ns el e d  
•  L a b or at or y: 
F asti n g ( 8 h o urs) is r e q uir e d b ef or e t h e visit  
o  A uri n e p r e g n a ncy t est i n w o m e n of c hil d b e ari n g p ot e nti al 
o  C o m pl et e bl o o d c o u nt a n d s er u m bi oc h e mistr y, R e n al f u ncti o n (cr e ati ni n e a n d 
e G F R), C o a g ul ati o n, T h yr oi d f u ncti o n ( T S H, T 3 a n d T 4), C P K, Gl y c e mic 
p ar a m et ers  
o  M EL D will b e c alc ul at e d  
o  Bl o o d s a m pl e f or P K will b e c oll ect e d  
o  Bl o o d s a m pl es f or p ot e nti al bi o m ar k ers  (i ncl u di n g Pr o C 3 a n d EL F), 
m et a b ol o mics a n d b ett er u n d erst a n di n g of m ec h a nis m of acti o n  
•  I n t h e O p e n -L a b el P art, st o ol s a m pl es will b e c oll ect e d if  e arl y disc o nti n u ati o n  is pri or t o 
w e e k 7 2 . 
Dr u g acc o u nt a bilit y  
•  Li v er bi o ps y at e arl y disc o nti n u ati o n : F or s u bj ects w h o disc o nti n u e tr e at m e nt b ut r e m ai n 
i n t h e st u d y a n d c o nti n u e t o b e f oll o w e d, c o n d uct a li v er bi o ps y eit h er at t h e tr e at m e nt 
disc o nti n u ati o n visit or, if c o ns e nt e d b y t h e s u bj ect, d uri n g t h e r e g ul arl y sc h e d ul e d st u d y 
visits.  
O p e n -L a b el P art: It is r ec o m m e n d e d t o p erf or m a li v er bi o ps y i n a s u bj ect t h at 
disc o nti n u es tr e at m e nt b et w e e n w e e k 2 4 t o w e e k 7 2 u nl ess t h e sc h e d ul e d bi o ps y h as 
alr e a d y b e e n p erf or m e d.  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
8 1  of 1 2 7  
 
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art : 
o  It is r ec o m m e n d e d t o p erf or m a li v er bi o ps y i n a s u bj ect t h at disc o nti n u es 
tr e at m e nt b et w e e n w e ek 
 
2 4 t o w e e k 7 2 u nl ess t h er e is a n a v ail a bl e bi o psy wit hi n 
t h e p ast 6 m o nt hs. 
o  It is r ec o m m e n d e d t o p erf or m a li v er bi o ps y i n a s u bj ect t h at disc o nti n u es 
tr e at m e nt b et w e e n 2 -y e ars t o 5 -y e ars, u nl ess  t h er e is a n a v ail a bl e bi o ps y wit hi n 
t h e p ast 6 m o nt hs. 
 
 
 
 
 
 
 
 
 
8. 4  I n v esti g ati o n al M e d ici n al P r o d ucts/ St u d y D r u gs 
8. 4. 1  
Tr e at m e nt A d mi nist r ati o n 
O p e n -L a b el P art: Ar a mc h ol 3 0 0 m g will b e t a k e n t wic e d ail y ( BI D) . 
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art : Ar a mc h ol 3 0 0 m g  or m atc hi n g pl ac e b o 
will b e t a k e n t wic e d ail y ( BI D) . 
T w o t a bl ets s h o ul d b e t ak e n b y m o ut h d ail y, o n e aft er br e a kf ast i n t h e m or ni n g a n d t h e ot h er 
aft er a m e al i n t h e e v e ni n g.     
8. 4. 2  
M et h o d of Assi g ni n g S u bj ects t o Tr e at m e nt Gr o u ps  
O p e n -L a b el P art: 
S u bj ects , i ncl u di n g t h os e alr e a d y r a n d o miz e d t o Ar a mc h ol 3 0 0 m g BI D or Pl ac e b o, will b e 
r a n d o miz e d i n a r ati o of 1: 1: 1 t o r ec ei v e Ar a mc h ol 3 0 0 m g BI D acc or di n g t o t h e b el o w 
gr o u pi n g :  
•  Gr o u p A: T h e p ost -b as eli n e li v er bi o ps y will b e c o n d uct e d at w e e k 2 4  
•  Gr o u p B: T h e p ost -b as eli n e  li v er bi o ps y will b e c o n d uct e d at w e e k 4 8  
•  Gr o u p C: T h e p ost -b as eli n e  li v er bi o ps y will b e c o n d uct e d at w e e k 7 2  
 
R a n d o miz ati o n i n t h e O p e n -La b el P art will e m pl oy a s e mi -mi ni miz ati o n al g orit h m t o b al a nc e 
t h e 3 gr o u ps i n n u m b er of s u bj ects, distri b uti o n of s u bj ects acc or di n g t o fi br osis sc or e ( F 1, F 2 
a n d F 3), pr es e nc e or a bs e nc e of T 2 D M , a n d pri or ex p os ur e t o Ar a mc h ol 3 0 0 m g BI D . F 1 
s u bj ects will b e c a p p e d t o e nr oll n o m or e t h a n 3 0 s u bj ects.  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
8 2  of 1 2 7  
S u bj ects alr e a d y r a n d o miz e d a n d i n t h e R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr oll e d P art i n 
t h e s el ect e d sit es p artici p ati n g i n t h e O p e n-L a b el p art will b e gi v e n t h e o pti o n t o s witc h t o t h e 
O p e n -L a b el P art .  
R a n d o miz ati o n i n t h e O p e n -l a b el P art will e m pl o y a s e mi-mi ni miz ati o n al g orit h m t o b al a nc e 
t h e 3 gr o u ps i n n u m b er of s u bj ects, distri b uti o n of s u bj ects acc or di n g t o fi br osis sc or e ( F 1, F 2 
a n d F 3), pr es e nc e or a bs e nc e of T 2 D M , a n d pri or ex p os ur e t o Ar a mc h ol 3 0 0 m g BI D . F 1 
s u bj ects will b e c a p p e d t o e nr oll n o m or e t h a n 3 0 s u bj ects.  
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art : 
A n eli gi bl e s u bj ect will r a n d o ml y b e all oc at e d t o tr e at m e nt wit h Ar a mc h ol or m atc hi n g pl ac e b o 
b as e d o n a r a n d o miz ati o n sc h e m e e m pl o yi n g a 2: 1 assi g n m e nt r ati o, r es p ecti v el y, usi n g 
p er m ut e d bl oc ks str atifi e d b y c o u ntr y/ g e o gr a p hic al r e gi o n ( C G R) a n d b y b as el i n e Fi br osis st a g e 
( F 2 or F 3).  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8. 4. 3  
St u d y Bli n di n g  a n d Bli n di n g Pl a n  
O p e n -L a b el P art:  
All s u bj ects will r ec ei v e Ar a mc h ol  3 0 0 m g BI D.  
 
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art : 
Ar a mc h ol  3 0 0 m g BI D or m atc hi n g pl ac e b o will b e a d mi nist er e d i n a bli n d e d m a n n er. T o 
m ai nt ai n t h e bli n d, Ar a mc h ol a n d m atc hi n g pl ac e b o c a ps ul es will h a v e i d e ntic al a p p e ar a nc e 
a n d will b e p ac k a g e d i n i d e ntic al b ottl es.  
P artici p ati n g s u bj ects, Inv esti g at ors, t h e Sp o ns or a n d a n y p ers o n n el i n v ol v e d i n s u bj ects’ 
ass ess m e nts, m o nit ori n g, a n al ysis a n d D at a M a n a g e m e nt  will b e  k e pt  bli n d e d t o t h e tr e at m e nt 
assi g n m e nt, excl u di n g t h e d esi g n at e d p ers o n n el i n cli nic al su p pl y v e n d or a n d t h e R T S M 
v e n d or.  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
8 3  of 1 2 7  
All  li v er bi o psi es will b e c e ntr all y e v al u at e d w hil e t h e ass ess or is bli n d e d t o tr e at m e nt 
assi g n m e nt  as w ell as t o ot h er p ar a m et ers i ncl u di n g sit e a n d s e q u e nc e or i n dic ati o n ( scr e e ni n g 
bi o ps y or w e e k 7 2  bi o psy or bi o ps y d u e t o s us pici o n t o pr o gr essi o n t o cirr h osis ). 
A dj u dic ati o n c o m mitt e e m e m b ers will b e bli n d e d t o tr e at m e nt assi g n m e nt.  
T h e  D M C  will  c o nsist of  i n d e p e n d e nt p h ysici a ns  wit h  ex p ertis e  i n li v er dis e as e  a n d  i nt er n al 
m e dici n e  a n d  a n  i n d e p e n d e nt bi ost atistici a n,  all  wit h  pri or  ex p eri e nc e  a n d  ex p ertis e  i n cli nic al 
tri als. A n  I n d e p e n d e nt U n bli n d e d  St atistici a n  will  pr e p ar e  t h e r e p orts f or r e vi e w b y  t h e D M C . 
U n bli n d e d s af et y r e p orts if r e q uir e d f or r e g ul at ory s u b missi o ns  as w ell as  r e p orti n g of 
S us p ect e d  U n ex p ect e d S eri o us A d v ers e R e acti o ns ( S U S A Rs) will  b e  h a n dl e d b y d e dic at e d 
p ers o n n el. F or t h es e p ur p os es, u n bli n di n g will b e p erf or m e d o n a n i n di vi d u al s u bj ect’s b asis . 
T h e S p o ns or will r e m ai n bli n d e d t o t h at i n di vi d u al s u bj ect’s tr e at m e nt assi g n m e nt.  
I n c as e of e m er g e ncy c o d e br e a ki n g, w h e n t h e st u d y dr u g assi g n m e nt is n e e d e d t o m a k e 
tr e at m e nt d ecisi o ns f or t h e s u bj ect, t h e In v esti g at or m a y u n bli n d t h e s u bj ect's dr u g 
assi g n m e nt. T h e u n bli n d e d s u bj ect will b e wit h dr a w n  fr o m t h e st u d y. I n s uc h c as es of 
e m er g e ncy u n bli n di n g, s u bj ect's tr e at m e nt assi g n m e n t will  n ot b e r e v e al e d  t o t h e S p o ns or. 
A n al ys is of t h e Hist ol o g y-B as e d pri m ar y e n d p oi nt will b e c o n d uct e d w h e n  1 0 0 0  s u bj ects 
c o m pl et e t h eir i niti al tr e at m e nt p eri o d of 7 2  w e eks ( or t er mi n at e d e arli er) . F or t h e p ur p os e of 
t h e c o n d uct of t h es e a n al ys es w hic h m a y b e f oll o w e d b y a m ar k eti n g a ut h oriz ati o n 
a p plic ati o n , t h e S p o ns or will est a blis h a s p eci al t as kf orc e fir e w all e d fr o m t h e st u d y t e a m. T h e 
t as kf orc e will b e l e d b y a  S p o ns or m a n a g e m e nt t e a m m e m b er n ot dir ectl y i n v ol v e d i n t h e 
o n g oi n g m a n a g e m e nt of t h e st u d y.  T o  m ai nt ai n t h e i nt e grit y of t h e fi n al p ost -W e e k 7 2  
a n al ys es, o nl y a mi ni m al n u m b er of p ers o n n el b el o n gi n g t o t his t as kf orc e will b e ex p os e d t o 
t h e s u bj ect -l e v el d at a, pri m aril y t o f acilit at e r e g ul at or y fili n gs a n d r e q uir e d p u blic discl os ur es.  
F urt h er m or e,  st u d y s u bj ects, In v esti g at ors, a n d t h e S p o ns or p ers o n n el i nv ol v e d i n t h e o n g oi n g 
st u d y m a n a g e m e nt a n d a n y p ers o n n el i n v ol v e d i n s u bj ects’ ass ess m e nts, m o nit ori n g, a n d D at a 
M a n a g e m e nt will r e m ai n bli n d e d t o tr e at m e nt assi g n m e nt . 
F oll o wi n g t h e c o n d uct of t h e Hist ol o g y -B as e d  mil est o n e a n al ys e s, m aj or fi n di n gs m a y b e 
p u blicl y diss e mi n at e d  b y t h e S p o ns or  i n acc or d a nc e  wit h  2 1  C F R  3 1 2. 7 . T o pr es er v e st u d y 
bli n di n g, tri al i nt e grit y, s u bj ect ’s a d h er e nc e a n d r et e nti o n, o nl y gr o u p e d l e v el s u m m ar y of 
r es ults of t h e Hist ol o g y-B as e d a n al ys es i ncl u di n g k e y s ec o n d ar y as w ell as p ot e nti all y 
ex pl or at or y e n d p oi nts pl a n n e d t o b e a n al yz e d at t his st u d y mil est o n e will b e diss e mi n at e d.  
S u m m ar y s af et y fi n di n gs will als o b e diss e mi n at e d.   
St u d y i nt e grit y a n d bli n di n g will n ot b e c o m pr o mis e d b y t h e p u blic diss e mi n ati o n of 
i nf or m ati o n d u e t o t h e f oll o wi n g m aj or r e as o ns: 1) t h e i n di vi d u al s u bj ect tr e at m e nt 
assi g n m e nt a n d d at a listi n gs will o nl y b e s h ar e d wit h t h e S p o ns or’s d e dic at e d t as kf o rc e a n d 
wit h r e g ul at or y a ut h oriti es. 2) T h e p u blicl y diss e mi n at e d i nf or m ati o n will b e o n a “b y gr o u p ” 
b asis. 3 ) T h e o bs er v e d pr o p orti o ns of Hist ol o g y -B as e d o utc o m es will n ot all o w d et er mi ni n g 
i n di vi d u al s u bj ect assi g n m e nt. 4) T h e o bs er v e d pr o p orti o ns of a d v ers e e v e nts  will n ot all o w 
d et er mi ni n g i n di vi d u al s u bj ect assi g n m e nt . 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
8 4  of 1 2 7  
A m or e d et ail e d St atistic al A n al ysis Pl a n ( S A P) c o v eri n g t h e a n al ys es of t h e Hist ol o g y -B as e d  
d at a as w ell as t h e Cli nic all y -B as e d d at a at E o S w as  s u b mitt e d pri or t o st u d y i niti ati o n. S AP 
a m e n d m e nt will  als o b e pr e p ar e d a n d s u b mitt e d pri or t o r e v e ali n g of t h e bli n d f or t h e a n al ysis 
of t h e Hist ol o g y -B as e d d at a.  
8. 4. 4  
E m er g e nc y C o d e Br e a ki n g  
O p e n -L a b el P art: N ot a p plic a bl e si nc e a ll s u bj ects will r ec ei v e Ar a mc h ol  3 0 0 m g BI D.  
 
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr ol l e d P art : 
I n c as e of a n y e m er g e ncy as p er t h e In v esti g at or crit eri a  or pr e g n a ncy, w h e n t h e st u d y dr u g 
assi g n m e nt is n e e d e d t o m a k e tr e at m e nt d ecisi o ns f or t h e s u bj ect , t h e Inv esti g at or m a y 
u n bli n d t h e s u bj ect's dr u g  assi g n m e nt. T h e u n bli n d e d s u bj ect will b e wit h dr a w n fr o m t h e 
st u d y. T h e s u bj ect s h o ul d r e m ai n i n t h e st u d y f or f oll o w -u p u ntil r es ol uti o n or st a biliz ati o n of 
t h e e v e nt. 
U n bli n di n g is p erf or m e d i n t h e I nt er acti v e W e b R es p o ns e S yst e m (I W R S). T h e pr oc ess i nc l u d es 
t h e f oll o wi n g st e ps: 
•  C o nfir mi n g t h e i d e ntit y of t h e s u bj ect  
•  C o nfir mi n g t h e u n bli n di n g r e q u est  
•  E nt eri n g t h e u n bli n di n g r e as o n  
•  E nt eri n g a p ass w or d  
 
 
   
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
8 5  of 1 2 7  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
8 6  of 1 2 7  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8. 5  C O VI D -1 9 C o nti n g e nc y m e as ur es  
8. 5. 1  
G e n er al  
D u e t o t h e C O VI D -1 9 p a n d e mic t h e st u d y s u bj ect m a y b e eit h er n ot all o w e d or u n willi n g t o 
att e n d a r e g ul arl y sc h e d ul e d st u d y visit or t h e visit m a y ot h er wis e n ot b e a bl e t o t a k e pl ac e at 
t h e st u d y sit e p er st a n d ar d pr actic e. I n t h at c as e c o nti n g e ncy m e as ur es d escri b e d i n S ecti o ns 
8. 5. 2 t hr o u g h 8. 5. 8  m a y p ot e nti all y b e a p pli e d acc or di n g t o t h e f oll o wi n g g e n er al g ui d a nc e:  
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
8 7  of 1 2 7  
•  L oc al r e g ul ati o ns a n d or di n a nc es p ert ai ni n g t o t h e C O VI D -1 9 p a n d e mic m ust al w a ys b e 
f oll o w e d a n d t h e s af et y of st u d y s u bj ects a n d r es e arc h t e a m m ust b e assur e d.  
•  E v er y eff ort m ust b e m a d e t o c o m pl et e t h e f ull sc o p e of t h e st u d y visit acti viti es a n d 
pr oc e d ur es. A n y d e vi ati o n fr o m t h e st a n d ar d pr actic e a n d pr oc e d ur es of i n p ers o n visit at 
t h e st u d y sit e a n d us e of t h e all o w e d c o nti n g e ncy m e as ur es, m ust b e cl e arly d oc u m e nt e d 
a n d fl a g g e d as C O VI D -1 9 r el at e d, a n d r e p ort e d t o t h e E C/I R B as a p plic a bl e.  
•  St u d y s u bj ects m ust b e i nf or m e d of a n y c h a n g e i n t h e st u d y c o n d uct t h at m a y b e 
i m pl e m e nt e d u n d er t h es e c o nti n g e ncy m e as ur es a n d v er b al a gr e e m e nt d oc u m e nt e d.  
•  T h e c o nti n g e ncy m e as ur es D O N O T A P PL Y t o Scr e e ni n g a n d B as eli n e visits.  
•  T h e c o nti n g e ncy m e as ur es s p ecifi e d h er e d o n ot c o ntr a dict a n y l oc al r ul es or r e g ul ati o ns  
8. 5. 2  
Alt er n ati v e L oc ati o n Visit  
I n c as e circ u mst a nc es r el at e d t o C O VI D-1 9 pr e v e nt h ol di n g t h e st u d y visit at  t h e st a n d ar d sit e 
l oc ati o n t h e PI m a y i d e ntif y a n alt er n ati v e l oc ati o n f or h ol di n g t h e st u d y visit ( e. g. pri v at e 
cli nic, o utsi d e of t h e h os pit al/st u d y f acilit y, s u bj ect h o m e) s o l o n g as t h e alt er n ati v e l oc ati o n 
pr o vi d es a n a p pr o pri at e e n vir o n m e nt f or a st u d y visit (i ncl u di n g pri v acy a n d a p pr o pri at e 
p h ysic al c o n diti o ns), t h e n ec ess ar y e q ui p m e nt, i ncl u di n g l a b or at or y a n d st u d y dr u g kits a n d 
p ers o n n el is a v ail a bl e a n d t h e st u d y s u bj ect a gr e es wit h t h e alt er n ati v e l oc ati o n.  
8. 5. 3  
I nt er vi e w b y P h o n e or Vi d e o C o nf er e nc e 
T h e PI m a y d eci d e t o h ol d t h e sc h e d ul e d s u bj ect i nt er vi e w b y p h o n e or vi d e o c o nf er e nc e 
i nst e a d of as a st a n d ar d i n p ers o n m e eti n g i n or d er  t o mi ni miz e t h e s oci al i nt er acti o n a n d ti m e 
r e q uir e d f or t h e act u al p h ysic al visit. At t h e b e gi n ni n g of t h e i nt er vi e w  t h e i d e ntific ati o n of t h e 
p artici p a nts m ust b e v erifi e d b y b ot h si d es pr es e nti n g t h e ms el v es b y f ull n a m e, a n d t h e 
exist e nc e of pr o p er pri v acy c o n diti o ns f or t h e s u bj ect m ust b e c o nfir m e d a n d d oc u m e nt e d. 
T h e i nt er vi e w m ust b e d oc u m e nt e d as a p h o n e/ vi d e o c o nf er e nc e i nt er vi e w i n t h e s u bj ect fil e.  
8. 5. 4  
N ec ess ar y d at a c oll ecti o n r e q uir e m e nts  
I n or d er f or a visit t o q u alif y as a st u d y visit a n d t o all o w a n e w dr u g kit t o b e dis p e ns e d as p art 
of t h e visit, t h e f oll o wi n g ess e nti al visit acti viti es m ust b e p erf or m e d:  
( a) S u bj ect i nt er vi e w  –  i ncl u di n g c h a n g es i n h e alt h c o n diti o n, a d v ers e e v e nts, c h a n g es i n 
m e dic ati o n, a n d c o nfir m ati o n of st u d y dr u g i nt a k e as p er i nstr ucti o ns.                                                                   
( b) S af et y l a b or at or y m e as ur e m e nts  - i ncl u di n g all t ests d efi n e d i n th e pr ot oc ol f or t h e 
s p ecific visit, wit h t h e exc e pti o n of bl o o d dr a ws f or P K. I n c as e t h e s p ecific pr oc essi n g a n d 
st or a g e r e q uir e m e nts f or P K t esti n g c a n n ot b e ass ur e d, t h e visit c a n still q u alif y as a st u d y visit 
e v e n if bl o o d f or P K is n ot t a k e n.  
8. 5. 5  
St u d y e q ui p m e nt a n d m at eri als  
St ori n g of st u d y r el at e d e q ui p m e nt a n d m at eri al (i. e. d oc u m e nt ati o n, st u d y dr u g kits, l a b 
s p eci m e ns, l a b kits, d e vic es, etc.) o utsi d e t h e st u dy sit e s h o ul d b e s h ort t er m a n d li mit e d t o 
w h at is dir ectl y r e q uir e d f or h ol di n g t h e st u d y visit at t h e alt er n ati v e l oc ati o n or s u bj ect h o m e. 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
8 8  of 1 2 7  
N o e q ui p m e nt or m at eri al s h o ul d b e st or e d at t h e s u bj ect's h o m e.  I n c as es w h er e e q ui p m e nt 
a n d m at eri als ar e k e pt o utsi d e t h e st u d y sit es, it m ust b e m ai nt ai n e d s ec ur el y a n d u n d er t h e 
r e q uir e d st or a g e c o n diti o ns. 
8. 5. 6  
St u d y dr u g dis p e nsi n g a n d us e d dr u gs b ottl es c oll ecti o n  
I n c as e st u d y visit is p erf or m e d at a n alt er n ati v e l oc ati o n, t h e f oll o wi n g a p pli es: 
•  St u d y dr u g dis p e nsi n g m ust o nl y t a k e pl ac e i n c as e t h e r e q uir e d d at a c oll ecti o n 
r e q uir e m e nts (s e e S ecti o n 8.5. 2) h a v e b e e n m et.  
•  All oc ati o n of st u d y dr u g kit b y t h e I R T s yst e m s h o ul d b e d o n e p er t h e st a n d ar d n or m all y 
f oll o w e d at t h e st u d y sit e. T h e all oc at e d kit m ust b e t a k e n u n d er a p pr o pri at e st or a g e 
c o n diti o ns t o t h e alt er n ati v e l oc ati o n a n d dis p e ns e d t o t h e s u bj ect d uri n g t h e st u d y visit.  
A st u d y dr u g kit m a y b e d eli v er e d t o t h e st u d y s u bj ect b y c o uri er b ut m ust n ot b e m ail e d.  
•  T h e all oc at e d kit m ust b e pr o p erl y d oc u m e nt e d at t h e sit e as p er st a n d ar d pr actic e a n d 
c o nfir m ati o n of d eli v er y/r ec ei pt is d oc u m e nt e d i n t h e s u bj ect fil e.  
•  Us e d st u d y dr u g b ottl es s h o ul d b e c oll ect e d if p ossi bl e, b ut i n c as e circ u mst a nc es d o n ot 
all o w, t h e s u bj ect s h o ul d b e i nstr uct e d t o k e e p t h e ol d us e d b ottl es a n d r et ur n t h e m at t h e 
e arli est f e asi bl e ti m e t o t h e alt er n ati v e l oc ati o n or st u d y sit e. If r et ur n e d t o a n alt er n ati v e 
l oc ati o n or d uri n g i n-h o m e visits, t h e PI a n d st u dy p ers o n n el or d el e g at e ar e r es p o nsi bl e 
f or e ns uri n g tr a ns p ort t o t h e sit e a n d f ull c o u nt of r et ur n e d st u d y dr u g at t h e st u d y sit e. 
 
8. 5. 7  
L a b or at or y S p eci m e ns 
I n c as e t h e st u d y visit is c o n d uct e d i n a n alt er n ati v e l oc ati o n: 
•  S af et y l a b or at or y s a m pl es s h o ul d b e pr oc ess e d f oll o wi n g st a n d ar d pr oc e d ur e b y t h e 
c e ntr al l a b or at or y if t h e c e ntr al l a b or at or y s er vic es ar e a v ail a bl e.  
•  I n c as e of disr u pti o n t o t h e c e ntr al la b or at or y o p er ati o n or t h e c o uri er s ervic e o p er ati o n, 
pr oc essi n g of t h e l a b or at or y s a m pl es b y a l oc al l a b or at or y is all o w e d.  
•  T est r es ults r e p ort e d b y t h e l oc al l a b or at or y s h o ul d b e r e vi e w e d b y t h e PI a n d t h e r es ults 
as w ell as t h e act u al r e vi e w of t h e r es ults, s h o ul d b e d oc u m e nt e d i n t h e s u bj ect fil e.  
•  L a b or at or y s p eci m e n c oll ect e d d uri n g a visit c o n d uct e d at a n alt er n ati v e l oc ati o n m ust 
f oll o w t h e st a n d ar d pr actic es of m ai nt e n a nc e, st or a g e, s hi p m e nt a n d d oc u m e nt ati o n. 
8. 5. 8  
A d diti o n al c o nti n g e nc y m e as ur es  
I n c ase of st a n d ar d pr ot oc ol -s p ecifi e d ti m e wi n d o ws c a n n ot b e m et t h e f oll o wi n g will a p pl y:  
•  Scr e e ni n g ti m e wi n d o w will b e ext e n d e d t o 1 2 w e e ks  
•  All o w a bl e ti m e wi n d o w f or t h e visits will b e ext e n d e d u p  t o ± 1 4 d a ys f or visits d uri n g 
t h e first 3 m o nt hs of tr e at m e nt, a n d u p t o 2 1 d a ys aft er t h e first 3 m o nt hs of t h e st u d y.  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
8 9  of 1 2 7  
9  A S S E S S M E N T S & P R O C E D U R E S  
9. 1  Li v er Bi o ps y 
9. 1. 1  
O p e n -L a b el P art 
I ncl u d es t h e f oll o wi n g li v er bi o psi es: 
•  B as eli n e li v er bi o ps y : P erf or m e d d uri n g scr e e ni n g ( bi o psi es p erf or m e d i n t h e 9  m o nt hs 
pri or t o r a n d o miz ati o n ar e acc e pt a bl e a n d will b e s e nt f or c e ntr al r e a di n g).  
•  A p ost -b as eli n e  sc h e d ul e d li v er bi o ps y : P erf or m e d b as e d o n r a n d o miz ati o n gr o u ps A, B, C 
at w e e k 2 4 or 4 8 or 7 2  r es p ecti v el y. T h e bi o ps y s h o ul d b e p erf or m e d  fr o m 2 w e e ks pri or t o 
t h e sc h e d ul e d bi o ps y a n d u p t o 6 w e e ks aft er t h e sc h e d ul ed  bi o ps y   
o  In or d er t o m or e c o m pr e h e nsi v el y ex pl or e t h e ki n etics of hist ol o gic al o utc o m e 
m e as ur es  ( e. g. ar e t h er e s u bj ects w h o  m a y n ot s h o w i m pr o v e m e nt i n o utc o m e at 
w e e k 2 4, 4 8 or 7 2 b ut m a y i m pr o v e wit h l o n g er d ur ati o n of tr e at m e nt), a 2 n d p ost -
b as eli n e  li v er bi o ps y s a m pl e will b e c oll ect e d f or s u bj ects w h os e p ost-b as eli n e li v er 
bi o ps y at w e e k 2 4 or 4 8 or 7 2 d o es  n ot s h o w at l e ast 1  st a g e i m pr o v e m e nt i n 
fi br osis (fi br osis n o n-r es p o n d ers). T h e 2n d p ost -b as eli n e  li v er bi o ps y s a m pl e will b e 
c oll ect e d 1 y e ar l at er  (i. e. at w e e ks 7 2 or 9 6 or 1 2 0  r es p ecti v el y 
•  
 
 
 
 
 
 
 
 
9. 1. 2  
R a n d o miz e d, D o u bl e -Bli n d, Pl ac e b o -C o ntr oll e d P art  
I ncl u d es t h e f oll o wi n g sc h e d ul e d li v er bi o psi es: 
•  B as el i n e li v er bi o ps y: P erf or m e d d uri n g scr e e ni n g ( bi o psi es p erf or m e d i n t h e 6  m o nt hs 
pri or t o r a n d o miz ati o n ar e acc e pt a bl e a n d will b e s e nt f or c e ntr al r e a di n g).  
•  7 2 w e e ks li v er bi o ps y: P erf or m e d fr o m 2 w e e k s pri or t o w e e k 7 2  visit  a n d u p t o 6  w e e ks 
aft er w e e k  7 2  
 
  
 
 
 
 
 
 
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
9 0  of 1 2 7  
 
 
 
 
 
 
 
 
 
 
                        
 
 
 
  
 
 
 
 
  
 
 
 
 
 
   
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
9 1  of 1 2 7  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
    
 
 
    
 
 
  
9. 2  Fi br osc a n  
Fi br osc a n will b e p erf or m e d at Scr e e ni n g , w e e k 2 4 a n d e v er y 2 4 w e e ks t h er e aft er  as at e arl y 
t er mi n ati o n/st u d y c o m pl eti o n. 
•  Scr e e ni n g Fi br osc a n: Fi br osc a n  d o n e  i n t h e 4 w e eks pri or t o scr e e ni n g is acc e pt a bl e 
•  Fi br osc a n is p erf or m e d as p art of t h e NI T s ass ess m e nt i n t h e st u d y  
•   Fi br osc a n  is als o us e d i n t h e st u d y as f oll o w -u p t o assist  i n i d e ntif yi n g s u bj ects w h o 
mi g ht r e q uir e d efi nit e di a g n osis b y bi o ps y . 
 
Fi br osc a n r ec o m m e n d ati o ns ar e as f oll o ws:  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
9 2  of 1 2 7  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
   
9. 3  
A b d o mi n al Ultr as o u n d  
A b d o mi n al ultr as o u n d will b e p erf or m e d at Scr e e ni n g, w e e k 2 4 a n d e v er y 2 4 w e e ks t h er e aft er 
as at e arl y t er mi n ati o n/st u d y c o m pl eti o n.  
•  Scr e e ni n g U S:  U S  d o n e i n t h e 3 m o nt hs pri or t o scr e e ni n g is acc e pt a bl e  
•  A b d o mi n al U S s h o ul d i ncl u d e  
o  R U Q  a b d o mi n al U S t o ass ess f or h e p at oc ell ul ar c arci n o m a ( H C C), c h ol elit hi asis, 
c h ol e d oc h olit hi asis, c hol ec ystitis, or pr es e nc e of ot h er h e p atic a b n or m aliti es.  
R es ults will b e r ec or d e d o n a d e dic at e d C R F p a g e  
o  A b d o mi n al U S is p erf or m e d t o ass ess f or si g ns of H C C or si g ns of pr o gr essi o n t o 
cirr h osis ( e. g. ascit es, s pl e n o m e g al y) 
9. 4  M EL D sc or e  
M EL D will b e c alc ul a t e d at scr e e ni n g, bas eli n e, w e e ks 1 2, a n d at e v er y st u d y visit t h er e aft er 
a n d at e arl y t er mi n ati o n/st u d y c o m pl eti o n.  
M EL D C alc ul ati o n will b e d o n e usi n g t h e O P T N f or m ul a/c alc ul at or w hic h r e q uir es t h e i n p ut of 
t h e f oll o wi n g l a b v al u es –  Bilir u bi n, S o di u m, C r e ati ni n e a n d I N R. 
( htt ps:// o pt n.tr a ns pl a nt. hrs a. g o v/r es o urc es/ all oc ati o n-c alc ul at ors/ m el d-c alc ul at or/) 
9. 5  Pr e -D efi n e d Cli nic al O utc o m e  E v e nts  
Pr e -d efi n e d cli nic al e v e nts f or t h e Cli nic all y -B as e d e n d p oi nt will b e a dj u dic at e d  b y a n 
i n d e p e n d e nt a dj u dic ati o n c o m mitt e e: 
•  All -c a us e m ort alit y 
•  Li v er tr a ns pl a nt 
•  H ist ol o gic al pr o gr essi o n t o cirr h osis 
•  M EL D sc or e > 1 5  if b as eli n e M EL D sc or e w as < 1 2 
•  H os pit aliz a ti o n d u e t o h e p atic d ec o m p e ns ati o n e v e nt(s) 
o  H e p atic e nc e p h al o p at h y gr a d e ≥2 ( as ass ess e d b y W est H a v e n sc al e)  
o  V aric e al bl e e di n g  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
9 3  of 1 2 7  
o  N e w o ns et ascit es r e q uiri n g tr e at m e nt  
o  S p o nt a n e o us b act eri al p erit o nitis as ass ess e d b y eit h er p ositi v e c ell c ult ur e or c ell 
c o u nt 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9. 7  P h ar m ac o ki n etics  
Bl o o d s a m pl e f or  a n al ysis of c o nc e ntr ati o ns of Ar a mc h ol a n d its m et a b olit es as w ell as f or  
p o p ul ati o n P K will b e c oll ect e d at all st u d y visits fr o m w e e k 4 u ntil w e e k  7 2  a n d e v er y 2 4 
w e e ks  t h er e aft er a n d at  e arl y t er mi n ati o n/st u d y c o m pl eti on . S u bj ects  att e n di n g a sit e visit i n 
t h e m or ni n g s h o ul d t a k e t h eir d os e as us u al i n t h e e v e ni n g b ef or e t h e visit a n d s h o ul d r ec or d 
t h e ti m e of d osi n g. T h e y  s h o ul d N O T t a k e t h eir d os e o n t h e m or ni n g of t h eir visit u ntil aft er t h e 
bl o o d s a m pl e f or P K h as b e e n dr a w n.  S u bj ects att e n di n g a sit e visit i n t h e aft er n o o n s h o ul d 
t a k e t h eir m or ni n g d os e as us u al a n d s h o ul d r ec or d t h e ti m e of d osi n g. 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
9 4  of 1 2 7  
T h e I n v esti g at or w ill r ec or d t h e ti mi n g t h e s u bj ect h as t a k e n t h e l ast t a bl et pri or t o bl o o d 
dr a wi n g a n d t h e ti m e of P K s a m pli n g.   
S a m pl es will b e us e d f or  p h ar m ac o ki n etic e n d p oi nts  a n al ysis  a n d s af et y if d e e m e d n ec ess ar y.  
9. 8  Bi o m ar k ers , M et a b ol o mics  G e n e a n d Micr o bi o m e A n al ys is 
•  Bl o o d s a m pl es f or p ot e nti al bi o m ar k ers  (i ncl u di n g b ut n ot li mit e d t o  Pr o C 3 a n d EL F) , 
m et a b ol o mics a n d b ett er u n d erst a n di n g of m ec h a nis m of acti o n will b e c oll ect e d at 
Scr e e ni n g, B as eli n e, w e eks 1 2, 2 4, 4 8 a n d e v er y 2 4 w e e ks  t h er e aft er a n d at  e arl y 
t er mi n ati o n/st u d y c o m pl eti o n.  
•  Bl o o d s a m pl e f or g e n e a n al ysis will b e t a k e n fr o m s u bj ects pr o vi di n g c o ns e nt i n a 
d e dic at e d i nf or m e d c o ns e nt f or m (I C F) (s u bj ect t o l oc al r e g ul ati o ns a n d a p pr o v al), 
pr ef er a bl y at B as eli n e visit, b ut will b e acc e pt e d at  a n y ot h er visit. S a m pl es will b e k e pt 
fr oz e n f or f ut ur e a n al ysis 
•  I n t h e O p e n -L a b el P art, st o ol s a m pl es f or a n al ysis of micr o bi o m e a n d b ett er u n d erst a n di n g 
of m ec h a nis m of acti o n  will b e c oll ect e d at B as eli n e, w e e ks  4,  1 2, 2 4, 4 8  a n d 7 2  a n d at 
e arl y t er mi n ati o n (if pri or t o w e e k 7 2 ). 
9. 9  S A F E T Y A S S E S S M E N T S  
9. 9. 1  
A d v ers e E v e nts  
A Es  will b e r ec or d e d as s o o n as t h e s u bj ect si g ns t h e I C F a n d t hr o u g h o ut t h e st u d y . A Es  s h o ul d 
b e r e vi e w e d a n d u p d at e d at e ac h visit .  
9. 9. 2  
S af et y L a b or at or y E v al u ati o ns  
S u bj ects s h o ul d f ast f or 8 h o urs pri or t o e ac h visit  t h at i ncl u d es l a b or at or y s a m pli n g. 
T h e c e ntr al l a b or at or y will b e  r es p o nsi bl e f or pr o vi di n g  pr eli mi n ar y a n d fi n al l a b or at or y 
r e p orts t o t h e sit es a n d f or s e n di n g “ al ert” v al u es t o b ot h t h e Pri nci p al I n v e sti g at or a n d 
S p o ns or or a d esi g n e e. T h e PI s h o ul d r e vi e w, c o m m e nt, si g n,  a n d d at e t h e fi n al l a b or at or y 
r e p orts. All o ut-of -r a n g e a n d “ al ert” l a b or at or y v al u es ar e t o b e e v al u at e d b y t h e PI f or cli nic al 
si g nific a nc e a n d cl assifi e d as:  
•  A b n or m al , n ot cli nic all y si g nific a nt  
•  A b n or m al cli nic all y si g nific a nt  
A n y cli nic all y si g nific a nt l a b or at or y p ar a m et ers o bs er v e d  at scr e e ni n g s h o ul d b e d oc u m e nt e d 
as m e dic al hist or y.  
A  n e w or w ors e ni n g cli nic all y si g nific a nt l a b or at ory  v al u e o bs er v e d at a n y ti m e aft e r scr e e ni n g 
s h o ul d b e f urt h er ass ess e d, m o nit or e d a n d  d oc u m e nt e d  as a n A E o n t h e A E e C R F . 
9. 9. 3  
Cli nic al L a b or at or y T ests  
Cli nic al l a b or at or y t ests ar e d et ail e d i n T a bl e 6 . T h e y will b e p erf or m e d acc or di n g t o t h e 
sc h e d ul e of acti viti es (S e e S ecti o n 8. 2 ). 
R ef er e nc e r a n g es f or all l a b or at or y p ar a m et ers ar e pr o vi d e d  i n t h e l a bor at or y m a n u al.  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
9 5  of 1 2 7  
 
T a bl e 6 : 
Cli nic al L a b or at or y T ests  
C at e g or y  
P ar a m et ers  
S er u m 
bi o ch e mistr y  
S o di u m, p ot assi u m, c hl ori d e, c alci u m, p h os p h or us, bl o o d ur e a nitr o g e n ( B U N), 
al b u mi n, bilir u bi n ( dir ect a n d t ot al), AL T, A S T, G G T, alk ali n e p h os p h at as e, 
c h ol est er ol (t ot al c h ol est er ol, L DL , a p o B, n o n - H DL c h ol est er ol  a n d H DL 
c h ol est er ol), tri glyc eri d es, hs -C R P  
H e m at ol o g y  
C o m pl et e bl o o d 
c o u nt ( C B C) 
H e m o gl o bi n, H e m at ocrit, R e d Bl o o d C ells c o u nt ( R B C), M C V, W hit e Bl o o d C ells 
c o u nt + diff er e nti al, N e utr o p hils, B as o p hils, E osi n o p hils, Ly m p h oc yt es, 
M o n ocyt es, Pl at el et c o u nt  
S er ol o g y  
H B V, H C V  (f or su bj ects p ositi v e f or h e p atitis C a nti b o di es , s ust ai n e d vir ol o gic 
r es p o ns e ( S V R) s h o ul d b e c o nfir m e d) a n d HI V  
R e n al f u ncti o n    
C r e ati ni n e, e G F R 
C P K  
Cr e ati n e ki n as e  
T h yr oi d f u ncti o n  
T S H, T 3 a n d T 4  
Uri n al ysis  
p H, Bl o o d, Gl uc os e, K et o n es, Er yt hr ocyt es, Pr ot ei n, S p ecific Gr avity ( U S G), 
Nitrit e, L e u k ocyt es, Bilir u bi n, Ur o bili n o g e n  
C o a g ul ati o n  
Fi bri n o g e n, pr ot hr o m bi n ti m e/I N R, a P T T  
Gl yc e mic  
P ar a m et ers  
F asti n g g l uc os e, H b A 1c, C -p e pti d e , I ns uli n a n d  H O M A -I R 
I nstr ucti o ns f or t h e pr e p ar ati o n, h a n dli n g, st or a g e, a n d s hi p m e nt of s p eci m e ns will b e d et ail e d 
i n t h e st u d y’s m a n u al of pr oc e d ur e. 
9. 9. 4  
El ectr oc ar di o gr a m ( E C G ) 
A st a n d ar d 1 2 -l e a d E C G will b e r ec or d e d at all st u d y visits. T h e  s u bj ect s h o ul d r est i n a 
r ec u m b e nt p ositi o n f or at l e ast 1 0 mi n ut es b ef or e t h e E C G  is t a k e n.  
T h e E C G will b e e v al u at e d b y t h e I n v esti g at or at  t h e ti m e of p erf or m a nc e  (si g n e d a n d d at e d) 
a n d t h e pri nt o ut s h o ul d b e k e pt i n t h e s o urc e d oc u m e nt ati o n fil e. A d diti o n all y, u ntil t h e 
S p o ns or i nstr ucts ot h er wis e , st arti n g fr o m t h e b as eli n e visit all E C Gs will als o b e s e nt t o a 
c e ntr al E C G l a b or at or y. T h e c e ntr aliz e d r e vi e w will b e d o n e b y a c ar di ol o g y s p eci alist w h o will 
pr o vi d e a n E C G r e p ort a n d n otific ati o ns t o t h e sit e. T h e r e p ort will pr o vi d e a n o v er all 
i nt er pr et ati o n of t h e E C G, fl a g gi n g cli nic all y r el e v a nt E CG a b n or m aliti es b as e d o n a pr e -d efi n e d 
s et of a b n or m alit y crit eri a. R e p orts wit h pr e -d efi n e d a b n or m aliti es will b e s e nt  t o b ot h t h e 
Pri nci p al I n v esti g at or  a n d S p o ns or or a d esi g n e e.  
If p ot e nti all y cli nic all y si g nific a nt fi n di n gs ar e d et ect e d b y t h e In v esti g at or  or b y t h e c e ntr al 
r e a di n g, a l oc al c ar di ol o gist s h o ul d b e c o ns ult e d. All c o m m u nic ati o ns a n d di a g n os es s h o ul d b e 
fil e d i n t h e s o urc e d oc u m e nt ati o n fil e.   

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
9 6  of 1 2 7  
A n y E C G fi n di n g t h at is j u d g e d b y t h e I n v esti g at or as a cli nic all y si g nific a nt c h a n g e c o m p ar e d 
wit h b as eli n e will b e c o nsi d er e d a n A E, r ec or d e d a n d m o nit or e d.  
T h e fi n al d ecisi o n w h et h er t h e E C G fi n di n gs ar e of cli nic al si g nific a nc e is t h e I n v esti g at or's 
r es p o nsi bilit y. 
9. 9. 5  
Pr e g n a nc y T est  
Pr e g n a ncy s h o ul d b e a v oi d e d d uri n g st u d y  a n d o n e m o nt h aft er disc o nti n ui n g tr e at m e nt.  A ll 
f e m al es of c hil d b e ari n g p ot e nti al m ust pr actic e a h i g hl y eff ecti v e m et h o d  of  c o ntr ac e pti o n 
t hr o u g h o ut t h e st u d y p eri o d a n d f or 1 m o nt h af t er tr e at m e nt disc o nti n u ati o n. M et h o ds t h at 
c a n ac hi e v e a f ail ur e r at e of l ess t h a n 1 % p er y e ar w h e n us e d c o nsist e ntl y a n d c orr ectl y ar e 
c o nsi d er e d as hi g hl y eff ecti v e birt h c o ntr ol. ; s e e Secti o n  6. 1 ). 
A n y s u bj ect w h o b ec o m es pr e g n a nt d uri n g t h e st u d y p eri o d m ust n ot r ec ei v e a d diti o n al d os es 
of st u d y dr u g.  
Pr e g n a ncy t est ( S er u m β-h C G)  will b e p erf or m e d f or w o m e n of c hil d b e ari n g p ot e nti al d uri n g 
t h e S cr e e ni n g visit. D uri n g t h e st u d y, a  uri n e pr e g n a ncy t est will b e p erf or m e d at e v er y st u d y 
visit  a n d  acc or di n g t o l oc al r e g ul ati o ns . 
A w o m a n t h at s us p ects pr e g n a ncy s h o ul d p erf or m a pr e g n a ncy t est, r e p ort r es ults t o t h e 
In v esti g at or a n d i n t h e ev e nt of p ositi v e r es ults, disc o nti n u e tr e at m e nt.  
R es ults of t h e pr e g n a ncy t est will b e d oc u m e nt e d o n  t h e pr e g n a ncy e C R F p a g e . 
9. 9. 6  
Vit al Si g ns  
Vit al si g ns will b e p erf or m e d at all sc h e d ul e d a n d u nsc h e d ul e d visits  . 
•  H e art r at e  
•  Bl o o d pr ess ur e (Di ast olic , S yst olic) 
•  T e m p er at ur e  
•  R es pir at or y r at e  
Bl o o d pr ess ur e a n d p uls e will b e r ec or d e d i n a sitti n g p ositi o n aft er r esti n g f or 5 mi n ut es . 
F or a n y a b n or m al vit a l si g n fi n di n g, f urt h er ass ess m e nt  s h o ul d b e p erf or m e d  as d e e m e d 
n ec ess ar y b y t h e I n v esti g at or. 
9. 9. 7  
P h ysic al E x a mi n ati o ns  
P h ysic al ex a mi n ati o ns  will b e p erf or m e d at Scr e e ni n g , B as eli n e, w e e k 2 4, 4 8, 7 2 a n d e v er y 2 4 
w e e ks  t h er e aft er as w ell as at e arl y t er mi n ati o n/st u d y c o m pl eti o n.  
•  G e n er al A p p e ar a nc e  
•  H e a d, E ars, E y es, N os e, T hr o at  
•  T h yr oi d  
•  C ar di o v asc ul ar  
•  R es pir at or y  
•  G astr oi nt esti n al  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
9 7  of 1 2 7  
•  S ki n  
•  M usc ul os k el et al  
•  N er v o us S yst e m  
•  L y m p h N o d es 
Cli nic all y si g nific a nt c h a n g es fr o m t h e i niti al p h ysic al fi n di n gs at scr e e ni n g o bs er v e d i n 
s u bs e q u e nt visits will b e c o nsi d er e d A Es a n d will b e d oc u m e nt e d o n t h e A E e C R F.  
9. 9. 8  
B o d y M e as ur e m e nts  
B o d y m e as ur e m e nts will b e  m e as ur e d at Scr e e ni n g, B as eli n e, w e e k 1 2 a n d at e v er y visit 
t h er e aft er as w ell as at e arl y t er mi n ati o n/st u d y c o m pl eti o n. 
•  B o d y W ei g ht  
•  W a ist Circ u mf er e nc e 
•  H ei g ht (m e as ur e d o nl y at S cr e e ni n g visit) 
 
1 0  S A F E T Y A N D P H A R M A C O VI GIL A N C E  
S af et y ass ess m e nts will c o nsist of e v al u ati n g r el e v a nt m e dic al hist or y, A E s a n d S A E s, 
l a b or at or y p ar a m et ers i ncl u di n g c h e mistr y, h e m at ol o g y a n d c o a g ul ati o n, vit al si g ns, E C G, 
p h ysic al ex a mi n ati o ns, a n d d oc u m e nt ati o n of all c o nc o mit a nt m e dic ati o ns a n d/ or t h er a pi es.  
T h e m et h o ds a n d ti mi n g of s af et y ass ess m e nts ar e pr o vi d e d i n S ecti o n  a n d will b e p erf or m e d 
i n acc or d a nc e wit h t h e sc h e d ul e i n T a bl e 3  a n d T a bl e 4  
T h e st u d y will cl os el y b e m o nit or e d b y a n i n d e p e n d e nt D at a M o nit ori n g C o m mitt e e ( D M C) 
acc or di n g t o a pr e -d efi n e d D M C c h art er.  T h e D M C will p eri o dic all y  m e et ( at l e ast e v er y 
3 -4  m o nt hs) t o ass ess t he st u d y pr o gr ess a n d c o n d uct, acc u m ul at e d s af et y d at a , a n d as 
a p pr o pri at e, p h ar m ac o ki n etic a n d effic acy d at a.  
T h e D M C  c a n m a k e r ec o m m e n d ati o ns r e g ar di n g st o p pi n g or m o dif yi n g t h e o v er all st u d y. T h e 
D M C  will c o n v e n e o n a r e g ul ar b asis a n d o n a n a d -h oc b asis  as o utli n e d i n t h e D M C  c h art er. 
T h e D M C  will b e c o m p os e d of i n d e p e n d e nt p h ysici a ns wit h ex p ertis e i n t h e li v er fi el d a n d 
ot h er r el e v a nt ex p erts . M e m b ers of t h e D M C  c a n n ot b e i n v esti g at ors i n t h e st u d y. A n ext er n al 
i n d e p e n d e nt u n bli n d e d st atistici a n will pr e p ar e t h e r e p orts f or r e vi e w b y t h e D M C . 
D uri n g t h e st u d y, p r e-d efi n e d cli nic al o utc o m e e v e nts , p ossi bl e DILI e v e nts  a n d m aj or a d v ers e  
c ar di o v asc ul ar e v e nts will b e a dj u dic at e d  b y i n d e p e n d e nt a dj u dic ati o n c o m mitt e e s. 
•  Cli nic al O utc o m e A dj u dic ati o n C o m mitt e e ( C O A C) will a dj u dic at e pr e d efi n e d cli nic al 
o utc o m e e v e nts ( all -c a us e m ort alit y, li v er tr a ns pl a nt, pr o gr essi o n t o cirr h osis, c h a n g e i n 
M EL D sc or e t o > 1 5 a n d h os pit aliz ati o n d u e t o h e p atic  d ec o m p e ns ati o n e v e nts)  
•  C ar di ac A dj u dic ati o n C o m mitt e e ( C A C)  will a dj u dic at e M aj or A d v ers e C ar di o v asc ul ar 
E v e nts (c ar di o v asc ul ar d e at h , n o n -f at al m y oc ar di al i nf arcti o n , n o n-f at al str o k e), 
h os pit aliz ati o n f or u nst a bl e a n gi n a or h e art f ail ur e, a n d all -c a us e m ort ality. E v e nt 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
9 8  of 1 2 7  
d efi niti o ns will b e b as e d o n t h e St a n d ar diz e d D efi niti o ns f or C ar di o v asc ul ar E n d p oi nt 
E v e nts i n Cli nic al Tri als 2 0, 2 1. 
•  H e p atic S af et y A dj u dic ati o n C o m mitt e e ( H S A C)  will a dj u dic at e h e p atic s af et y e v e nts 
i ncl u di n g c as es of sus p ect e d DILI as w ell as n o n -e n d p oi nt h e p atic/ h e p at o bili ar y S A Es  
T h e D M C will b e pr o vi d e d t h e o utc o m e of t h e a dj u dic ati o n . 
1 0. 1  A d v ers e E v e nt s 
1 0. 1. 1  
D efi niti o n of a n A d v ers e E v e nt s 
A n y u nt o w ar d m e dic al occ urr e nc e i n a p ati e nt or  cli nic al i n v esti g ati o n s u bj ect a d mi nis t er e d a 
p h ar m ac e utic al pr o d uct a n d w hic h d o es n ot n ec ess aril y h a v e a c a us al r el ati o ns hi p wit h t his 
tr e at m e nt. A n A E c a n t h er ef or e b e a n y u nf a v or a bl e a n d u ni nt e n d e d si g n (i ncl u di n g a n 
a b n or m al l a b or at or y fi n di n g), s y m pt o m, or dis e as e t e m p or all y ass oci at e d w it h t h e us e of a 
m e dici n al (i n v esti g ati o n al) pr o d uct, w h et h er or n ot r el at e d t o t h e m e dici n al (i n v esti g ati o n al) 
pr o d uct.  
T h e f oll o wi n g m e dic al e v e nts will b e c o nsi d er e d A Es:  
•  A n y n e w m e dic al c o n diti o n, si g n, s y m pt o m or dis e as e or a n y w ors e ni n g of pr e -existi n g 
c o n diti o n (i n s e v erit y or fr e q u e ncy) f oll o wi n g si g ni n g of I C F 
•  W ors e ni n g of a pr e -existi n g dis e as e s h o ul d b e r ec or d e d as a n A E  o nl y if t h e pr es e nt ati o n 
a n d/ or o utc o m e is m o r e s e v er e t h a n w o ul d n or m all y b e ex p ect e d fr o m t h e n or m al c o urs e 
of t h e dis e as e i n t his p ati e nt  
•  A n a b n or m al  r es ult of di a g n ostic pr oc e d ur es i ncl u di n g a b n or m al l a b or at or y fi n di n gs will b e 
c o nsi d er e d a n A E if a n y of t h e b el o w ar e m et: 
o  R es ults i n s u bj ect’s t em p or ar y or p er m a n e nt disc o nti n u ati o n of tr e at m e nt or 
wit h dr a w al b y t h e In v esti g at or  
o  Is ass oci at e d wit h cli nic al si g ns or s y m pt o ms 
o  Is c o nsi d er e d b y t h e p h ysici a n t o b e of cli nic al si g nific a nc e 
•  A n y pr oc e d ur al c o m plic ati o n  
T h e f oll o wi n g e v e nts will n ot b e c o nsi d er e d A Es: 
•  A c hr o nic c o n diti o n di a g n os e d d uri n g scr e e ni n g will b e r ec or d e d as m e dic al hist or y a n d n ot 
as a n A E  
•  Pr e -existi n g dis e as e, c o n diti o n or l a b or at or y a b n or m aliti es pr es e nt b ef or e st u d y e ntr y  (I C F 
si g n at ur e) t h at d o es n ot w ors e n d uri n g t h e st u d y 
•  Pr e -pl a n n e d el ecti v e h os pit al a d missi o n ( pl a n n e d pri or t o t h e st u d y e nr oll m e nt) f or 
tr e at m e nt or di a g n ostic pr oc e d ur e of a pr e-existi n g c o n diti o n, t h at h as n ot si g nific a ntl y 
w ors e n e d  
•  A bi o ps y p erf or m e d as p art of t h e st u d y is n ot c o nsi d er e d a n A E a n d h os p it aliz ati o n f or 
li v er bi o ps y, w h e n r e q uir e d as st a n d ar d of c ar e f or li v er bi o ps y, a n d wit h o ut c o m plic ati o ns 
is n ot c o nsi d er e d a n S A E 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
9 9  of 1 2 7  
•  M e dic al or s ur gic al pr oc e d ur es ar e n ot c o nsi d er e d A Es, r at h er, t h e c o n diti o n l e a di n g t o t h e 
pr oc e d ur e is t h e A E ( e. g. a n e mi a a n d n ot bl o o d tr a nsf usi o n, a p p e n dicitis a n d n ot 
a p p e n d ect o m y)  
•  A b n or m al l a b or at or y v al u es t h at i n t h e I n v esti g at or's o pi ni o n ar e n ot cli nic all y si g nific a nt 
a n d d o n ot r e q uir e a n y i nt er v e nti o n s h o ul d n ot b e r e p ort e d as A Es  
1 0. 1. 2  
R ec or di n g a n d R e p orti n g A d v ers e E v e nts  
A Es f all i nt o t h e c at e g ori es of “ n o ns eri o us” a n d “s eri o us”. All A E s m ust b e r ec or d e d o n s o urc e 
d oc u m e nts a n d e C R F fr o m t h e ti m e t h e s u bj ect h as si g n e d t h e i nf or m e d c o ns e nt u ntil t h e E o S 
or e arl y t er mi n ati o n ( E S D) visit , r e g ar dl ess of a p p ar e nt  c a us alit y fr o m us e of t h e st u d y dr u g. 
At e ac h visit, s u bj ects s h o ul d v ol u nt aril y r e p ort a n y A Es i n r es p o ns e t o g e n er al n o nl e a di n g 
q u esti o ns ( e. g., “ H o w h av e y o u b e e n f e eli n g si nc e y o ur l ast visit ?”). F or e ac h A E r e p ort e d b y 
s u bj ects, cli nic al sit e p ers o n n el s h o uld o bt ai n all r e q uir e d i nf or m ati o n t o c o m pl et e t h e e C R F.  
T h e A E t er m , d at e of o ns et , s e v erit y, s eri o us n ess, acti o n t a k e n, I n v esti g at or o pi ni o n of 
r el ati o ns hi p t o t h e st u d y dr u g, o utc o m e a n d d at e of r es ol uti o n will b e r ec or d e d i n s o urc e 
d oc u m e nts a n d e C R F f o ll o wi n g t h e In v esti g at or's ass ess m e nt. If a n o n g oi n g A E w ors e ns or 
i m pr o v es i n its s e v erit y, t h e m axi m u m s e v erit y t h at occ urr e d o v er t h e d ur ati o n of t h e e v e nt 
s h o ul d b e r ec or d e d i n e C R F. 
A E v er b ati m t er ms pr o vi d e d b y t h e I n v esti g at or will b e c o d e d usi n g t h e c urr e nt M e dic al 
Dicti o n ar y f or R e g ul at or y Acti viti es ( M e D R A) V ersi o n.  
A Es cl assifi e d as s eri o us m ust b e r ec or d e d o n t h e a p pr o pri at e S A E f or m a n d r e p ort e d usi n g t h e 
ex p e diti o us h a n dli n g of S A E pr oc e d ur es t o c o m pl y wit h r e g ul at or y r e q uir e m e nts (s e e 
S ecti o n  1 0. 1. 5. 3 ). 
1 0. 1. 3  
S e v erit y of a n A d v ers e E v e nt  
S e v erit y of A Es s h o ul d b e ass ess e d b y t h e I n v esti g at or acc or di n g t o C o m m o n T er mi n ol o g y 
Crit eri a f or A d v ers e E v e nts ( C T C A E) d efi niti o ns as f oll o ws :  
•  Gr a d e 1: Mil d ; as y m pt o m atic or mil d s y m pt o ms; cli nic al or di a g n ostic o bs er v ati o ns 
o nl y; i nt er v e nti o n n ot i n dic at e d.   
•  Gr a d e 2: M o d er at e ; mi ni m al, l oc al or n o ni n v asi v e i nt er v e nti o n i n dic at e d; li miti n g a g e  
a p pr o pri at e i nstr u m e nt al a cti viti es of d ail y li vi n g (A DL ; w hic h r efer s t o pr e p ari n g m e als, 
s h o p pi n g f or gr oc eri es or cl ot h es, usi n g t h e t el e p h o n e, m a n a gi n g m o n e y, etc .).  
•  Gr a d e 3 : S e v er e  or m e dic all y si g nific a nt b ut n ot i m m e di at el y lif e -t hr e at e ni n g; 
h os pit aliz ati o n or pr ol o n g ati o n of h os pit aliz ati o n i n dic at e d; dis a bli n g; li miti n g s elf-c ar e 
A DL  ( w hic h r ef ers t o b at hi n g, dr essi n g a n d u n dr essi n g, f e e di n g s elf, usi n g t h e t oil et, 
t a ki n g m e dic ati o ns, a n d n ot b e dri d d e n).  
•  Gr a d e 4 : Lif e t hr e at e ni n g c o ns e q u e nc es ; ur g e nt i nt er v e nti o n i n dic at e d.  
•  Gr a d e 5:  D e at h  r el at e d t o A E. 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 0 0  of 1 2 7  
A S e mi -c ol o n (;) i n dic at es ‘ or’ wit hi n t h e d escri pti o n of t h e gr a d e. 
S e v erit y is n ot s y n o n y m o us wit h s eri o us n ess. F or ex a m pl e, a s e v er e h e a d ac h e is n ot 
n ec ess aril y a n S A E.  H o w e v er, mil d c h est p ai n m ay r es ult i n a d a y’s h os pit aliz ati o n  t h us 
m e eti n g s eri o us crit eri a a n d w o ul d b e c o nsi d er e d a n S A E.  
1 0. 1. 4  
R el ati o ns hi p of a n A d v ers e E v e nt t o t h e St u d y Dr u g  
T h e r el ati o ns hi p of a n A E t o t h e st u d y dr u g s h o ul d b e ass ess e d b y t h e I n v esti g at or usi n g 
cli nic al e v al u ati o n a n d t h e f oll o wi n g cl assific ati o n a n d c o nsi d er ati o ns:  
N o r e as o n a bl e p ossi bilit y  - n ot r el at e d : T h er e is n ot a r e as o n a bl e p ossi bilit y t h at t h e 
a d mi nistr ati o n of t h e st u d y i nt er v e nti o n c a us e d t h e e v e nt or t h er e is n o t e m p or al r el ati o ns hi p 
b et w e e n t h e st u d y i nt erv e nti o n a n d e v e nt o ns et, or a n al t er n at e eti ol o g y h as b e e n 
est a blis h e d.  
R e as o n a bl e p ossi bilit y - r el at e d: T h e A E is k n o w n t o occ ur wit h t h e st u d y i nt er v e nti o n or t h er e 
is a r e as o n a bl e p ossi bility t h at t h e st u d y i nt er v e nti o n c a us e d t h e A E or t h er e is a t e m p or al 
r el ati o ns hi p b et w e e n t h e st ud y i nt er v e nti o n a n d e v e nt.  
R e as o n a bl e p ossi bilit y m e a ns t h at t h er e is e vi d e nc e t o s u g g est a c a us al r el ati o ns hi p b et w e e n 
t h e st u d y i nt er v e nti o n a n d t h e A E. 
1 0. 1. 5  
S e ri o us A d v ers e E v e nts 
1 0. 1. 5. 1  
D efi niti o n of a S eri o us A d v ers e E v e nt  
A n y u nt o w ar d m e dic al occ urr e nc e t h at:  
•  R es ults i n d e at h  
•  Is lif e-t hr e at e ni n g 
•  R e q uir es i n p ati e nt h os pit aliz ati o n or pr ol o n g ati o n of existi n g h os pit aliz ati o n  
•  R es ults i n p ersist e nt or si g nific a nt dis a bilit y/i nc a p acit y  
•  Is a c o n g e nit al a n o m al y/ birt h d ef ect 
•  A n i m p ort a nt m e dic al e v e nt w hic h r e q uir es m e dic al i nt er v e nti o n t o pr e v e nt a n y of t h e 
a b o v e o utc o m es  
T h e t er m " lif e-t hr e at e ni n g" r ef ers t o a n e v e nt i n w hic h t h e p ati e nt w as at ris k of d e at h at t h e 
ti m e of t h e e v e nt; it d o es n ot r ef er t o a n e v e nt w hic h h y p oth etic all y mi g ht h a v e c a us e d d e at h 
if it w er e m or e s e v er e. 
T h e t er m “ I n p ati e nt h os pit aliz ati o n” or pr ol o n g ati o n of existi n g h os pit aliz ati o n m e a ns t h at t h e 
e v e nt r e q uir e d at l e ast 2 4 h o urs h os pit aliz ati o n a n d/ or pr ol o n g ati o n of h os pit al st a y w er e 
r e q uir e d f or tr e at m e nt of A E, or t h at t h e y occ urr e d as a c o ns e q u e nc e of t h e e v e nt.  
T h e t er m “ I m p ort a nt m e dic al e v e nt” ar e t h os e w hic h m a y n ot b e i m m e di at el y lif e -t hr e at e ni n g 
b ut m a y j e o p ar diz e t h e s u bj ect a n d m a y r e q uir e i nt er v e nti o n t o pr e v e nt o n e of t h e ot h er 
s erio us o utc o m es list e d a b o v e. Ex a m pl es of s uc h e v e nts ar e i nt e nsi v e tr e at m e nt i n a n 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 0 1  of 1 2 7  
e m er g e ncy r o o m or at h o m e f or all er gic br o nc h os p as m; bl o o d d yscr asi as or c o n v ulsi o ns t h at 
d o n ot r es ult i n h os pit aliz ati o n.  
1 0. 1. 5. 2  
E x p ect e d n ess  
T h e ex p ect e d n ess of a n A E is d efi n e d i n acc or d a nc e wit h t h e R ef er e nc e S af et y I nf or m ati o n . F or 
a d et ail e d d escri pti o n  r ef er t o t h e c urr e nt I B. 
A n u n e x p ect e d  A E is a n A E f or w hic h t h e n at ur e or s e v erit y is n ot c o nsist e nt wit h t h e 
R ef er e nc e S af et y I nf or m ati o n . 
1 0. 1. 5. 3  
S A E R e p orti n g  
T h e S p o ns or is r e q uir ed t o ex p e dit e t o r e g ul at or y a ut h oriti es r e p orts of s p ecific S A Es t h at 
occ ur d uri n g t h e st u d y . S A Es m ust b e r e p ort e d t o t h e S p o ns or ( or its d esi g n e e) b y t h e 
In v esti g at or/sit e p ers o n n el  as s o o n as t h e y b ec o m e a w ar e of t h e e v e nt a n d n o l at er t h a n 
2 4  h o urs r e g ar dl ess of r el ati o ns hi p t o t h e st u d y dr u g.   
S A E r e p ort f or m c o m pl eti o n a n d r e p orti n g m ust n ot b e d el a y e d e v e n w h e n i nf or m ati o n is 
i nc o m pl et e at t h e ti m e of t h e i niti al r e p ort. 
A n y a d diti o n al (f oll o w -u p) i nf or m ati o n t h at b ec o m es a v ail a bl e aft er t h e i niti al r e p orti n g, 
s h o ul d b e f or w ar d e d i n a f oll o w-u p S A E r e p ort f or m b y t h e sit e p ers o n n el wit hi n 2 4 h o urs of 
t h e i nf or m ati o n b ec o mi n g a v ail a bl e. 
All S A Es s h o ul d b e r e p ort e d t o S p o ns or or its d esi g n e e f oll o wi n g t h e c o m pl eti o n g ui d eli n es 
pr o vi d e d wit h t h e st u d y S AE f or m. All S A Es s h o ul d b e f oll o w e d u ntil r es ol uti o n or st a biliz ati o n 
a n d all p ar a m et ers (i ncl u di n g l a b or at or y) r et ur n t o b as eli n e or u ntil t h e I nv esti g at or ass ess es 
t h e m as st a bl e or u ntil t h e p ati e nt is l ost t o f oll o w-u p. S A Es m ust b e c oll ect e d a n d r e p or t e d 
d uri n g t h e st u d y a n d u p t o 3 0 d a ys aft er st u d y c o m pl eti o n. T h e I n v esti g at or d o es n ot n e e d t o 
acti v el y  m o nit or s u bj ects f or A Es o nc e t h e st u d y h as e n d e d, b ut S A Es occ urri n g t o a p ati e nt 
s h o ul d b e r e p ort e d t o t h e S p o ns or, if t h e I n v esti g at or b ec o m es a w ar e of t h e m. S A Es occ urri n g 
a n y ti m e aft er t h e r e p orti n g p eri o d m ust b e pr o m ptl y r e p ort e d if a c a us al r el ati o ns hi p t o t h e 
st u d y dr u g is s us p ect e d.  
1 0. 2  S af et y R e p orti n g t o I n v esti g at ors, I nstit uti o n al R e vi e w B o ar ds or I n d e p e n d e nt 
Et hics C o m mitt e es, a n d R e g ul at or y A ut h oriti es.  
S p o ns or  or its d esi g n e e is r es p o nsi bl e f or r e p orti n g all a p plic a bl e S A Es t o R e g ul at or y 
a ut h oriti es, I n v esti g at ors, a n d I E Cs/IR B s, as a p plic a bl e, i n acc or d a nc e  wit h n ati o n al r e g ul ati o ns 
i n t h e c o u ntri es w h er e t h e st u d y is c o n d uct e d. 
S us p ect e d U n ex p ect e d S eri o us A d v ers e R e acti o ns ( S U S A Rs) s h o ul d b e r e p ort e d as ex p e dit e d 
s af et y r e p orts t o all p artici p ati n g In v esti g at ors, et hics c o m mitt e es, a n d a p plic a bl e r e g ul at or y 
a ut h oriti es i n acc or d a nc e wit h I C H g ui d eli n es a n d t h e l oc al r e g ul at or y r e q uir e m e nts. T h e 
S U S A Rs will b e s u b mitt e d wit hi n 7 d a ys f or f at al a n d lif e -t hr e at e ni n g e v e nts a n d wit hi n 1 5 d a ys 
f or ot h er S U S A Rs  e v e nts.  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 0 2  of 1 2 7  
T h e S p o ns or s h o ul d s u b mit all s af et y u p d at es  a n d p eri o dic r e p orts t o t h e r e g ul at or y 
a ut h oriti es, as r e q uir e d b y a p plic a bl e r e g ul at or y r e q uir e m e nts.  
I n v esti g at ors s h o ul d r e p ort t o t h eir l oc al I E C/I R B as dict at e d b y t h eir b o ar d’s p olici es a n d 
pr oc e d ur es.  
T h e bli n di n g will b e m ai nt ai n e d f or t h e t e a m w h o ar e i n v ol v e d dir ectl y i n t h e st u d y. F or S U S A R 
r e p orti n g, d e dic at e d p ers o n n el m a y br e a k t h e s u bj ect’s c o d e wit h o ut r e v e ali n g t h e bli n d t o t h e 
S p o ns or p er s o n n el, its d esi g n e e or sit e t e a m. 
1 0. 3  Pr e g n a nc y R e p orts  
A f e m al e cli nic al tri al s u bj ect m ust b e i nstr uct e d t o i nf or m t h e I n v esti g at or i m m e di at el y if s h e 
b ec o m es pr e g n a nt d uri n g t h e st u d y. Pr e g n a nci es occ urri n g u p t o 3 0 d a ys aft er tr e at m e nt 
disc o nti n u ati o n  m us t als o b e r e p ort e d t o t h e I n v esti g at or. 
T h e I n v esti g at or s h o ul d r e p ort all pr e g n a nci es t o S p o ns or  or its d esi g n e e wit hi n 2 4 h o urs of 
b ec o mi n g a w ar e of t h e m, usi n g a cli nic al tri al pr e g n a ncy r e p orti n g f or m.  
All pr e g n a ncy r e p orts will b e c a pt ur e d i n t h e s af e ty d at a b as e.  
If t h e s u bj ect r e q u ests t o k n o w w hic h tr e at m e nt s h e r ec ei v e d, t his i nf or m ati o n will b e 
pr o vi d e d t o h er  (s e e S ecti o n 8. 4. 4 ). 
T h e pr e g n a ncy s h o ul d b e f oll o w e d f or o utc o m e of t h e m ot h er a n d t h e c hil d, i ncl u di n g a n y 
pr e m at ur e t er mi n ati o ns, a n d all o utc o m es  s h o ul d b e r e p ort e d t o S p o ns or  or its d esi g n e e.   
 
1 1  S T A TI S TI C AL M E T H O D OL O G Y  
1 1. 1  O p e n -L a b el P art  
A t ot al of 1 5 0 s u bj ects, i ncl u di n g t h os e alr e a d y r a n d o miz e d t o Ar a mc h ol 3 0 0 m g BI D or 
pl ac e b o, will b e r a n d o miz e d i n a r ati o of 1: 1: 1 t o r ec ei v e Ar a mc h ol 3 0 0 m g BI D acc or di n g t o t h e 
b el o w gr o u pi n g :  
•  Gr o u p A: T h e p ost -b as eli n e li v er bi o ps y will b e c o n d uct e d a t w e e k 2 4 
•  Gr o u p B: T h e p ost -b as eli n e li v er bi o ps y will b e c o n d uct e d at w e e k 4 8  
•  Gr o u p C: T h e p ost -b as eli n e li v er bi o ps y will b e c o n d uct e d at w e e k 7 2  
R a n d o miz ati o n i n t h e O p e n -L a b el P art will e m pl oy a s e mi-mi ni miz ati o n al g orit h m t o b al a nc e 
t h e 3 gr o u ps i n n um b er of s u bj ects, distri b uti o n of s u bj ects acc or di n g t o fi br osis sc or e ( F 1, F 2 
a n d F 3), pr es e nc e or a bs e nc e of T 2 D M , a n d pri or ex p os ur e t o Ar a mc h ol 3 0 0 m g BI D . F 1 
s u bj ects will b e c a p p e d t o e nr oll n o m or e t h a n 3 0 s u bj ects.  
 
 
 
 
 
 
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 0 3  of 1 2 7  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
1 1. 2  R a n d o miz e d , D o u bl e-Bli n d, Pl ac e b o -C o ntr ol l e d P art:  
A t ot al of 2 0 0 0 s u bj ects will b e r a n d o miz e d i nt o t his st u d y i n a 2: 1 r ati o t o tr e at m e nt wit h 
Ar a mc h ol or wit h pl ac e b o, r es p ecti v el y.  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 0 4  of 1 2 7  
 
 
 
 
  
 
 
 
 
  
1 1. 2. 1  
R a n d o miz ati o n  
A n eli gi bl e s u bj ect will r a n d o ml y b e all oc at e d t o tr e at m e nt wit h Ar a mc h ol or m atc hi n g pl ac e b o 
b as e d o n a r a n d o miz ati o n sc h e m e e m pl o yi n g a 2: 1 assi g n m e nt r ati o, r es p ecti v el y, usi n g 
p er m ut e d bl oc ks str atifi e d b y c o u ntr y/ g e o gr a p hic al r e gi o n ( C G R) a n d b y b as eli n e Fi br osis st a g e 
( F 2 or F 3). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 1. 2. 2  
St u d y Pri m ar y E n d p oi nts  
T h e pri m ar y effic acy e n d p oi nts f or t his st u d y ar e:  
•  
Hist ol o g y -B as e d : T h e Hist ol o g y -B as e d pri m ar y  e n d p oi nt will b e d eri v e d fr o m t h e w e e k -7 2  
bi o ps y of t h e i niti al 1 0 0 0  s u bj ects as c o m p ar e d t o b as eli n e bi o ps y a n d will us e: 
✓ R es ol uti o n of N A S H  d efi n e d as t h e Pr o p orti o n ( %) of s u bj ects wit h r es ol uti o n of N A S H 
(d efi n e d b y B all o o ni n g of 0 a n d i nfl a m m ati o n 0 -1) a n d n o w ors e ni n g of li v er fi br osis 
o n N A S H C R N fi br osis sc or e (≥ 1 st a g e i ncr e as e).  
O R  
✓ I m pr o v e m e nt i n Fi br osis d efi n e d as t h e Pr o p orti o n ( %) of s u bj ects wit h i m pr o v e m e nt 
i n li v er fi br osis gr e at er t h a n or e q u al t o o n e st a g e ( N A S H C R N fi br osis sc or e) a n d n o 
w ors e ni n g of st e at o h e p atitis ( d efi n e d as n o i ncr e as e i n N A S f or b all o o ni n g, 
i nfl a m m ati o n or st e at osis) 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 0 5  of 1 2 7  
•  
Cli nic all y -B as e d : T h e Cli nic all y -B as e d pri m ar y e n d p oi nt is t h e ti m e t o first occ urr e nc e of 
a n y of t h e f oll o wi n g a dj u dic at e d e v e nts : 
✓ All -c a us e m ort alit y 
✓ Li v er tr a ns pl a nt 
✓ Hist ol o gic al pr o gr essi o n t o cirr h osis  
✓ M EL D sc or e > 1 5  if b as eli n e M EL D sc or e w as < 1 2 
✓ H os pit aliz ati o n d u e t o h e p atic d ec o m p e ns ati o n e v e nt(s) i ncl u di n g:  
- H e p atic e nc e p h al o p at h y gr a d e ≥2 ( as ass ess e d b y W est H a v e n sc al e) 
- V aric e al bl e e di n g  
- N e w o ns et ascit es r e q uiri n g tr e at m e nt  
- S p o nt a n e o us b act eri al p erit o nitis as ass ess e d b y eit h er p ositi v e c ell c ult ur e or c ell 
c o u nt 
E v e nts will b e a dj u dic at e d b y a n i n d e p e n d e nt a dj u dic ati o n c o m mitt e e.  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 0 6  of 1 2 7  
✓ 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
  
 
 
 
   
 
 
 
 
 
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 0 7  of 1 2 7  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 0 8  of 1 2 7  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 1. 2. 7  
C o m p ar a bilit y of St u d y Gr o u ps at B as eli n e  
D e m o gr a p hics a n d b as eli n e d at a will b e dis pl a y e d f or t h e I T T A n al ysi s S et. S u bj ects’ 
d e m o gr a p hics a n d b as eli n e c h ar act eristics, i ncl u di n g b as eli n e pr o g n ostic f act ors will 
d escri pti v el y b e ex a mi n e d t o ass ess t h e c o m p ar a bilit y of t h e tr e at m e nt gr o u ps. F or c o nti n u o us 
v ari a bl es, d escri pti v e st atistics ( n u m b er [ n], m e a n, st a n d a r d d e vi ati o n ( S D), st a n d ar d err or, 
m e di a n, mi ni m u m, a n d m axi m u m) will b e pr o vi d e d. F or c at e g oric al v ari a bl es, s u bj ect c o u nts 
a n d p erc e nt a g es will b e pr o vi d e d. C at e g ori es f or missi n g d at a will b e pr es e nt e d.  
S u m m ar y st atistics of t h es e p ar a m et ers will als o b e pr o vi d e d w h e n br o k e n d o w n b y C G R, a n d 
b y U S/ N o n -U S s u b -p o p ul ati o ns.  
1 1. 2. 8  
Pri m ar y Esti m a n ds of I nt er est  
1 1. 2. 8. 1  
W e e k -7 2 Hist ol o g y -B as e d Pri m ar y Esti m a n d  
T h e pri m ar y  Esti m a n d f or t h e W e e k -7 2  Hist ol o g y -B as e d st u d y p art will b e b as e d o n t h e 
eff ecti v e n ess ass u m pti o n ( d e -fact o) usi n g tr e at m e nt p olic y. T h e pri m ar y  Esti m a n d 
c o nstr ucti o n el e m e nts of t his Esti m a n d ar e:  
1.  P o p ul ati o n : S u bj ects wit h N o n alc o h olic St e at o h e p atitis ( N A S H) t h at w er e r a n d o miz e d t o t h e 
st u d y. 
2.  V ari a bl es of i nt er est : W e e k-7 2 ( -2 W e e ks, + 6 W e eks)  i n di vi d u al s u bj ect R es ol uti o n of N A S H,  
O R, I m pr o v e m e nt i n Fi br osis.  
3.  I nt er-c urr e nt e v e nts: S u bj ects t h at E S D d uri n g t h e Hist ol o g y -B as e d st u d y p art . T h e 
tr e at m e nt-p olic y Esti m a n d will b e us e d t o ass ess t h e b e n efit of Ar a mc h ol as c o m p ar e d t o 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 0 9  of 1 2 7  
pl ac e b o i n i niti all y r a n d o miz e d s u bj ects’ as act u all y o bs er v e d  r e g ar dl ess of t h e occ urr e nc e 
of E S D d uri n g t h e Hist ol o g y -B as e d st u d y p art.  
4.  P o p ul ati o n -l e v el s u m m ary: T h e b et w e e n gr o u ps diff er e nc e i n  t h e pr o p orti o n of s u bj ects 
wit h N A S H R es ol uti o n  A N D/ O R t h e b et w e e n gr o u ps diff er e nc e i n t h e pr o p orti o n of s u bj ects 
wit h I m pr o v e m e nt i n Fi br osis . 
T h e tr e at m e nt eff ect will b e attri b ut a bl e t o t h e s u bj ect’s wit h  N A S H  i niti ally r a n d o miz e d t o t h e 
st u d y a n d w h o h a d t h e b as eli n e a n d W e e k -7 2 li v er bi o psi es  r e g ar dl ess of E S D d uri n g t h e 
Hist ol o g y -B as e d st u d y p art . 
1 1. 2. 8. 2  
E o S Cli nic all y -B as e d Pri m ar y Esti m a n d  
T h e pri m ar y Esti m a n d f or t h e E o S Cli nic all y -B as e d  st u d y p art  will b e b as e d o n t h e eff ecti v e n ess 
ass u m pti o n ( d e -f act o) usi n g tr e at m e nt p olic y. T h e pri m ar y  Esti m a n d c o nstr ucti o n el e m e nts 
ar e:  
1.  P o p ul ati o n : S u bj ects wit h N o n alc o h olic St e at o h e p atitis ( N A S H)  t h at w er e r a n d o miz e d t o t h e 
st u d y. 
2.  V ari a bl es of i nt er est : Ti m e t o first occ urr e nc e of t h e a dj u dic at e d e v e nts.  
3.  I nt er-c urr e nt e v e nt: S u bj ects t h at w er e e arl y disc o nti n u e d fr o m t h e st u d y ( E S D). T h e 
tr e at m e nt-p olic y Esti m a n d will b e us e d t o ass ess t h e b e n efit of Ar a mc h ol as c o m p ar e d t o 
pl ac e b o i n i niti all y r a n d o miz e d s u b j ects’ as act u all y o bs er v e d  r e g ar dl ess of t h e occ urr e nc e 
of E S D . 
4.  P o p ul ati o n -l e v el s u m m ary: T h e diff er e nc e i n s ur viv al distri b uti o ns/ p erc e ntil es o bs er v e d i n 
t h e Ar a mc h ol ar m as c o m p ar e d t o  t h e Pl ac e b o Ar m. 
T h e tr e at m e nt eff ect will b e attri b ut a bl e t o t h e s u bj ect's  wit h N A S H i niti ally r a n d o miz e d t o t h e 
st u d y r e g ar dl ess of st u d y e arl y disc o nti n u ati o n. 
 
1 1. 2. 9  
Effic ac y E n d p oi nts a n d A n al ys es  
1 1. 2. 9. 1  
Pri m ar y E n d p oi nts a n d Pri nci p al A n al ysis of t h e St u d y 
Pri m ar y E n d p oi nts  
T h e st u d y i d e ntifi es t w o pri m ar y e n d p oi nts: T h e Hist ol o g y -B as e d e n d p oi nt a n d t h e 
Cli nic all y -B as e d e n d p oi nt. T h e pri nci p al a n al ysis s ets f or i nf er e nc e f or t h es e t w o pri m ar y 
e n d p oi nts will b e t h e c orr es p o n di n g I T T A n al ysis S ets. 
1 1. 2. 9. 2  
Pri nci p al A n al ysis of t h e Hist ol o g y -B as e d Pri m ar y E n d p oi nt  
Wit hi n t h e w or k -fr a m e of t h e W e e k -7 2 pri m ar y effic ac y e n d p oi nt,  t h e f oll o wi n g t w o 
alt er n ati v e o utc o m e m e as ur es will b e a n al yz e d, s e p ar at el y, f or ass essi n g t h e effic ac y of 
Ar a mc h ol as c o m p ar e d t o pl ac e b o : 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 1 0  of 1 2 7  
•  
R es ol uti o n of N A S H  
•  
I m pr o v e m e nt i n Fi br osis   
T h e b el o w d escri b e d pri nci p al a n al ysis will b e c o n d uct e d s e p ar at el y f or R es ol uti o n of N A S H 
a n d f or I m pr o v e m e nt i n Fi br osis.   
•  
T h e Hist ol o g y -B as e d I T T A n al ysis S et (Hist ol o g y -B as e d -I T T) will s er v e as t h e pri m ar y 
A n al ysis S et f or effic ac y ass ess m e nt of t h e Hi st ol o g y-B as e d pri m ar y e n d p oi nt f or  t h e 
pri m ar y Esti m a n d.  
•  
Missi n g w e e k 7 2 bi o ps y v al u es will b e h a n dl e d c o nc urr e ntl y b y d et er mi nistic r ul es ( e. g.  
s u bj ect w h o ex p eri e nc e cli nic al e v e nts b ef or e w e e k 7 2 will b e c o nsi d er e d tr e at m e nt 
f ail ur es) a n d b y m ulti pl e im p ut ati o ns pr oc e d ur es ( MI) .  
•  
T h e a n al ysis of t h e Hist ol o g y -B as e d pri m ar y e n d p oi nt will b e c o n d uct e d usi n g t h e i m p ut e d 
d at as ets a n d will e m pl o y t h e C oc hr a n -M a nt el -H a e nsz el ( C M H) t est ( S A S ®  P R O C F R E Q) 
str atifi e d b y b as eli n e Fi br osis st a g e ( F 2 or F 3), b as eli n e N A S sc or e ( < 6 or ≥6) , pr es e nc e or 
a bs e nc e of T 2 D M  at b as eli n e  a n d  c o u ntr y/ g e o gr a p hic al r e gi o n ( C G R) . 
•  
T h e Wils o n -Hilf ert y tr a nsf or m ati o n will b e us e d t o n or m aliz e t h e C M H t est st atistics a n d 
t h e R u bi n’s r ul e will b e a p pli e d f or c o m bi ni n g t h e r es ults t o o bt ai n t h e p-v al u e.  
•  
T h e m a g nit u d e of tr e at m e nt eff ect esti m at e a n d its 9 5 % CI will b e c alc ul at e d usi n g  t h e 
c o m bi n e d str atifi e d diff er e nc e i n pr o p orti o ns usi n g C M H w e i g hts. 
•  
M or e d et ails o n i m p ut ati o n m o d eli n g a n d s e nsiti vit y a n al ys es will b e pr o vi d e d  i n t h e 
St atistic al A n al ysis Pl a n (S A P) . 
 
1 1. 2. 9. 3  
Pri nci p al A n al ysis of t h e Cli nic all y -B as e d Pri m ar y E n d p oi nt  
T h e Cli nic all y -B as e d pri m ar y e n d p oi nt is t h e  ti m e t o first occ urr e nc e of a n y of t h e f oll o wi n g 
a dj u dic at e d e v e nt s:  
•  
All -c a us e m ort alit y 
•  
Li v er tr a ns pl a nt 
•  
Hist ol o gic al pr o gr essi o n t o cirr h osis  
•  
M EL D sc or e > 1 5  if b as eli n e M EL D sc or e w as < 1 2 
•  
H os pit aliz ati o n d u e t o h e p atic d ec o m p e ns ati o n e v e nt(s) i ncl u di n g:  
✓ H e p atic e nc e p h al o p at h y gr a d e ≥2 ( as ass ess e d b y W est H a v e n sc al e) 
✓ V aric e al bl e e di n g  
✓ N e w o ns et ascit es r e q uiri n g tr e at m e nt  
✓ S p o nt a n e o us b act eri al p erit o nitis as ass ess e d b y eit h er p ositi v e c ell c ult ur e or c ell 
c o u nt 
 
 
 
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 1 2  of 1 2 7  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
  
 
1 1. 3  S af et y A n al ys es  ( b ot h st u d y p arts; O p e n L a b el P art a n d R a n d o miz e d, D o u bl e 
Bli n d, Pl ac e b o C o n tr oll e d P art) 
S af et y a n al ys es will b e p erf or m e d f or t h e S af et y A n al ysis  S et ( S T)  a n d f or t h e ext e n d e d s af et y 
A n al ysis  S et ( e S T) .  
1 1. 3. 1  
A d v ers e E v e nts  
A n A E is a n y u nt o w ar d m e dic al occ urr e nc e i n a s u bj ect a d mi nist er e d a p h ar m ac e utic al 
pr o d uct, r e g ar dl ess of w h et h er it h as a c a us al r el ati o ns hi p wit h t his tr e at m e nt. I n t his st u d y, 
a n y A E occ urri n g aft er t h e s u bj ect h as si g n e d t h e I C F s h o ul d b e r ec or d e d a n d r e p ort e d as a n 
A E.  
T h e M e d D R A dicti o n ar y will b e us e d  t o st a n d ar diz e t h e t er ms us e d b y t h e I n v esti g at or t o 
d escri b e t h e A Es.  
T h e f oll o wi n g will b e i nc or p or at e d i nt o t h e a n al ysis of  a d v ers e e v e nts:  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 1 3  of 1 2 7  
•  
As a n al ysis of A Es c a n i nc or p or at e o nl y c o d e d A Es, it is m a n d at or y t h at at t h e ti m e of 
d at a b as e l oc k all A Es wil l b e c o d e d. 
•  
A d v ers e e v e nts a n al ys es will i ncl u d e o nl y t h e Tr e at m e nt E m er g e nt A d v ers e E v e nts 
( T E A Es), n a m el y, t h os e ev e nts w hic h st art e d o n t h e d a y of r a n d o miz ati o n or aft er w ar ds. 
A Es l ac ki n g st art d a y will b e c o nsi d er e d as T E A E.  
•  
A n al ys es of T E A Es will i ncl u d e t h e dis pl a y of c u m ul ati v e i nci d e nc e pr o p orti o ns  ( n o. of 
s u bj ects r e p orti n g at l e ast o n e T E A E p er c at e g or y), ex p os ur e a dj ust e d i nci d e nc e r at es  of 
t h e n u m b er of T E A Es, a n d esti m at e d diff er e nc es a n d c o nfi d e nc e i nt er v als f or all p air wis e 
tr e at m e nt ar m c o m paris o ns.  
T h e f oll o wi n g a n al ys es w hic h ar e pr e -pl a n n e d f or a d v ers e e v e nts  will i ncl u d e : 
•  
M ost fr e q u e nt T E A Es ( > 5 % of s u bj ects i n at l e ast o n e st u d y ar m) b y Pr ef err e d T er m ( P T).  
•  
T E A Es br o k e n d o w n b y Syst e m Or g a n Cl ass ( S O C) a n d b y S O C a n d P T acc or di n g t o M e d D R A 
dicti o n ar y.  
•  
S eri o us T E A Es b y M e d D R A S O C a n d P T, d at a listi n g as w ell as s u m m ar y t a bl e of S A Es 
br o k e n d o w n b y st u d y tri m est ers ( 9 0 d a ys e ac h).  
•  
T E A Es br o k e n d o w n b y s e v erit y.  
•  
T E A Es br o k e n d o w n b y r el ati o ns hi p t o st u d y dr u g.  
•  
T E A Es br o k e n d o w n b y acti o n t a k e n.  
•  
T E A Es br o k e n d o w n b y ev e nt o utc o m e.  
•  
T E A Es will b e pr o vi d e d br o k e n d o w n b y st u d y gr o u p a n d s u b gr o u ps . 
•  
A d v ers e E v e nts dicti o n ary us e d t o c o d e I n v esti g at or’s v er b ati m t er ms will als o b e 
pr o vi d e d.  
•  
I n di vi d u al s u bj ect listi n gs of T E A Es a n d n o n-T E A Es.  
1 1. 3. 2  
L a b or at or y D at a 
L a b or at or y t esti n g will b e p erf or m e d b y a c e ntr al l a b or at or y f acilit y a n d/ or affili at e d 
l a b or at ori es w hic h w or k u n d er t h e c e ntr al l a b or at or y r e g ul ati o ns usi n g t h e s a m e r ef er e nc e 
n or m al r a n g es.  
A n al ys es of s af et y c e ntr al l a b or at or y d at a will b e p erf or m e d i n t h e f oll o wi n g m a n n er:  
•  
A n al ys es  e v e nts as d efi n e d b el o w will i ncl u d e t h e dis pl a y of  c u m ul ati v e i nci d e nc e 
pr o p orti o ns ( n o. of s u bj ects r e p orti n g at l e ast o n e e v e nt  p er c at e g or y), ex p os ur e a dj us t e d 
i nci d e nc e r at es of t h e n u m b er of e v e nts , a n d esti m at e d diff er e nc es a n d c o nfi d e nc e 
i nt er v als f or all p air wis e tr e at m e nt ar m c o m p aris o ns: 
✓ P ost -r a n d o miz ati o n P ot e nti al Cli nic al Si g nific a nc e ( P C S) l a b v al u es will b e pr o vi d e d. 
✓ A b n or m al v al u es at a n y ti m e af t er r a n d o miz ati o n d a y, c alc ul at e d f or s u bj ects wit h 
n or m al v al u es at b as eli n e will b e pr o vi d e d. A n al ysis will i ncl u d e, p er t est e d 
p ar a m et er, t h os e s u bj ects wit h n or m al b as eli n e a n d at l e ast o n e p ost -r a n d o miz ati o n 
d a y m e as ur e m e nts.  
✓ T h e distri b uti o n of m axi m al v al u es of c e ntr al l a b or at or y A S T, AL T a n d t ot al bilir u bi n at 
a n y ti m e aft er r a n d o miz ati o n d a y i n t er m of t h e u p p er n or m al r a n g e m ulti pl es will b e 
pr o vi d e d f or s u bj ects wit h n or m al AS T, AL T a n d t ot al bilir u bi n at b as eli n e.  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 1 4  of 1 2 7  
•  
 Q u a ntit ati v e l a b or at or y m e as ur e m e nts will b e c at e g oriz e d wit h r ef er e nc e t o t h e n or m al 
r a n g es as L o w, N or m al or Hi g h. S hift a n al ysis of t h e c at e g oric al c h a n g e fr o m b as eli n e t o 
e ac h sc h e d ul e d visit a n d t o t h e l ast o bs er v e d v al u e will b e pr o vi d e d.  
•  
B ox -Pl ots of m e as ur e m e nts d o n e, fi g ur es o f m e a n v al u es ± S Es of c h a n g es fr o m b as eli n e as 
w ell as d escri pti v e st atistics f or all l a b or at or y q u a ntit ati v e p ar a m et ers a n d c h a n g es fr o m 
b as eli n e will b e pr o vi d e d b y sc h e d ul e d visits a n d tr e at m e nt gr o u ps.  
1 1. 3. 3  
Vit al Si g ns  
Vit al si g ns will b e a n al yz e d i n t h e f o ll o wi n g m a n n er : 
•  
C u m ul ati v e i nci d e nc e pr o p orti o ns ( n o. of s u bj ects r e p orti n g at l e ast o n e ev e nt ), ex p os ur e 
a dj ust e d i nci d e nc e r at es of t h e n u m b er of e v e nts , a n d esti m at e d diff er e nc es a n d 
c o nfi d e nc e i nt er v als f or all p air wis e tr e at m e nt ar m c o m p aris o ns  of p os t-r a n d o miz ati o n 
P ot e nti al Cli nic al Si g nific a nc e ( P C S) vit al si g ns v al u es will b e pr o vi d e d.  
•  
B ox -Pl ots of m e as ur e m e nts d o n e, fi g ur es of m e a n v al u es ± S Es as w ell as d escri pti v e 
st atistics f or all p ar a m et ers a n d c h a n g es fr o m b as eli n e will b e pr o vi d e d by sc h e d u l e d visits 
a n d tr e at m e nt gr o u ps.  
1 1. 3. 4  
El ectr oc ar di o gr a m E C G  
T h e st u d y Sit e I n v esti g at or cl assifi e d e ac h E C G as eit h er “ n or m al”, “ a b n or m al n ot cli nic all y 
si g nific a nt ( N C S)”, or “ a b n or m al cli nic all y si g nific a nt ( C S)”. 
A n al ys es of E C G e v al u ati o ns will b e p erf or m e d  i n t h e f oll o wi n g m a n n er: 
•  
C u m ul ati v e i nci d e nc e pr o p orti o ns ( n o. of s u bj ects r e p orti n g at l e ast o n e ev e nt ), ex p os ur e 
a dj ust e d i nci d e nc e r at es of t h e n u m b er of e v e nts , a n d esti m at e d diff er e nc es a n d 
c o nfi d e nc e i nt er v als f or all p air wis e tr e at m e nt ar m c o m p aris o ns of p ost -r a n d o miz ati o n 
P ot e nti al Cli nic al Si g nific a nc e ( P C S) E C G  v al u es will b e pr o vi d e d.  
•  
B ox -Pl ots of m e as ur e m e nts d o n e, fi g ur es of m e a n v al u es ± S Es as w ell as d escri pti v e 
st atistics f or all p ar a m et ers a n d c h a n g es fr o m b as eli n e will b e pr o vi d e d  by sc h e d ul e d visits 
a n d tr e at m e nt gr o u ps.  
1 1. 4  T ol er a bilit y Ass ess m e nts  
T ol er a bilit y ass ess m e nt will b e b as e d o n t h e n u m b er a n d p erc e nt ( %) of s u bj ects w h o e arl y 
disc o nti n u e d tr e at m e nt ( E T D) a n d e arl y disc o nti n u e d st u d y ( E S D) b y wit h dr a w al r e as o n will b e 
pr es e nt e d. Ti m e t o wit h dr a w al will als o b e pr es e nt e d b y K a pl a n -M ei er c ur v es.  
 
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 1 5  of 1 2 7  
1 2  S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N AL C O N SI D E R A TI O N S  
1 2. 1  R e g ul at or y, Et hic al, a n d St u d y O v ersi g ht C o nsi d er ati o ns  
1 2. 1. 1  
C o m pli a nc e  St at e m e nt  
T his st u d y will b e c o n d uct e d i n acc or d a nc e wit h t h e I nt er n ati o n al C o nf er e nc e o n 
H ar m o niz ati o n (I C H) G o o d Cli nic al Pr actic e ( G C P) C o ns oli d at e d G ui d eli n e E 6 ( R 2) a n d a n y 
a p plic a bl e n ati o n al a n d l oc al l a ws a n d r e g ul ati o ns ( e. g., Titl e  2 1 C o d e of F e d er al R e g ul ati o ns 
2 1 C F R P art 1 1, 5 0, 5 4, 5 6, 3 1 2, a n d  3 1 4, t h e H e alt h I ns ur a nc e P ort a bilit y a n d Acc o u nt a bilit y 
Act of 1 9 9 6 a n d c o difi e d at 4 5 C F R P art 1 6 0 & 1 6 4, E ur o p e a n U ni o n [ E U] Dir ecti v e 2 0/ E C or  
R e g ul ati o n E U N o. 5 3 6/ 2 0 1 4, as a p plic a bl e, 2 0 0 5/ 2 8/ E C  a n d R e g ul at i o n E U N o. 2 0 1 6/ 6 7 9) a n d 
a n y a n d all a p plic a bl e l a ws p ert ai ni n g t o pri v acy, s ec urit y, br e ac h n otific ati o n, or d at a 
pr ot ecti o n, or si mil ar l a ws, st at ut es, r ul es, or r e g ul ati o ns, as t h e s a m e m a y b e a m e n d e d fr o m 
ti m e t o ti m e, i ncl u di n g wit h o ut li mit ati o ns, t he G e n er al D at a Pr ot ecti o n R e g ul ati o n ( E U 
2 0 1 6/ 6 7 9) (“ G D P R”); a n d t h e H e alt h I nf or m ati o n P ort a bilit y a n d Acc o u nt a bilit y Act of 1 9 9 6 as 
a m e n d e d b y t h e H e alt h I nf or m ati o n T ec h n ol o g y f or Ec o n o mic a n d Cli nic al H e alt h Act ( Titl e XIII 
of t h e A m eric a n R ec o v ery a n d  R ei n v est m e nt Act of 2 0 0 9), a n d t h eir i m pl e m e nti n g r ul es a n d 
r e g ul ati o ns c o difi e d at 4 5 C. F. R. P arts 1 6 0 a n d 1 6 4. H e alt h I ns ur a nc e P ort a bilit y a n d 
Acc o u nt a bilit y Act (“ HI P A A”) (“D at a Pr ot ecti o n L a ws ”). A n y occ urr e nc e of n o nc o m pli a nc e will 
b e d oc u m e nt e d.  
T h e In v esti g at ors ar e r es p o nsi bl e f or p erf or mi n g t h e st u d y i n acc or d a nc e wit h t his pr ot oc ol 
a n d t h e a p plic a bl e D at a Pr ot ecti o n L a ws  r ef er e nc e d a b o v e f or c oll ecti n g, r ec or di n g, 
pr oc essi n g, tr a nsf erri n g a n d r e p orti n g t h e d at a acc ur at el y , s ec ur el y, a n d pr o p erl y. A gr e e m e nt 
of e ac h In v esti g at or t o c o n d uct a n d a d mi nist er t his st u d y i n acc or d a nc e wit h t h e pr ot oc ol will 
b e d oc u m e nt e d i n s e p ar at e st u d y a gr e e m e nts wit h t h e S p o ns or a n d ot h er f or ms as r e q uir e d 
b y n ati o n al a ut h oriti es.  
E ac h In v esti g at or is r e s p o nsi bl e f or e ns uri n g t h e pri v acy, h e alt h, a n d w elf ar e of t h e s u bj ects 
d uri n g a n d aft er t h e st u dy a n d m ust e ns ur e t h at tr ai n e d p ers o n n el ar e i m m e di at el y a v ail a bl e 
i n t h e e v e nt of a m e dic al e m er g e ncy. E ac h In v esti g at or a n d t h e a p plic a bl e st u d y st aff m ust b e 
f a mili ar wit h t h e b ac k gr o u n d t o, a n d r e q uir e m e nts of, t h e st u d y a n d wit h t h e pr o p erti es of t h e 
st u d y dr u g(s) as d escri b e d i n t h e I B a n d ot h er pr escri bi n g i nf or m ati o n.  
F urt h er, e ac h In v esti g at or s h all e ns ur e t h at all p ers o n al or s e nsiti v e d at a  ( as d efi n e d u n d er 
D at a Pr ot ecti o n L a ws),  r el at e d t o d at a s u bj ects (i. e., s u bj ects, e m pl o y e es, etc.) s h all b e 
c oll ect e d, pr oc ess e d, st or e d a n d tr a nsf err e d i n c o m pli a nc e wit h a p plic a bl e D at a Pr ot ecti o n 
L a ws, a n d as d et ail e d  h er ei n, i n t h e Cli nic al Tri al A gr e e m e nt, or as ot h er wis e i nstr uct e d b y t h e 
S p o ns or fr o m ti m e t o ti m e. N ot wit hst a n di n g t h e a b o v e, t h e In v esti g at or r es p o nsi bilit y t o 
c o m pl y wit h D at a Pr ot ecti o ns L a ws is i n d e p e n d e nt, r e g ar dl ess t o i nstr ucti o n pr o vi d e d or n ot 
b y t h e S p o ns or.  
T h e Pri nci p al I n v esti g at or h as t h e o v er all r es p o nsi bilit y f or t h e c o n d uct a n d a d mi nistr ati o n of 
t h e st u d y a n d f or c o nt acts wit h st u d y m a n a g e m e nt, wit h t h e I n d e p e n d e nt Et hics 
C o m mitt e e/I nstit uti o n al R e vi e w B o ar d (I E C/I R B), a n d wit h l oc al a ut h oriti es.  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 1 6  of 1 2 7  
1 2. 1. 2  
I n d e p e n d e nt Et hics  C o m mitt e e (I E C) / I nstit uti o n al R e vi e w B o ar d (I R B)  
T h e pr ot oc ol, I B, I C Fs, a ny i nf or m ati o n w hic h s h o ul d b e gi v e n t o t h e s u bj ect a n d a n y a d diti o n al 
r el e v a nt s u p p orti n g m at eri als r e q uir e d b y I C H G C P g ui d eli n es, D at a Pr ot ecti o n L a ws a n d t h e 
a p plic a bl e r e g ul a t or y a ut h oriti es, m ust b e s u b mitt e d t o t h e I n d e p e n d e nt Et hics C o m mitt e e/ 
I nstit uti o n al R e vi e w B o ar d (I E C/I R B) f or r e vi e w a n d a p pr o v al b ef or e t h e st u d y is i niti at e d. 
N o s u bj ect s h o ul d b e e nr oll e d t o t h e st u d y b ef or e t h e I E C/I R B iss u es its writt e n a p pr o v al/ 
f a v or a bl e o pi ni o n. 
I n c as e t h e S p o ns or will a m e n d t h e pr ot oc ol, t h e p r ot oc ol a m e n d m e nt m ust b e s u b mitt e d a n d 
a p pr o v e d b y t h e a p plic a bl e r e g ul at or y a ut h orit y a n d r el e v a nt I E C/I R B pri or t o i m pl e m e nt ati o n 
exc e pt w h e n n ec ess ar y t o eli mi n at e i m m e di at e s af et y c o nc er ns t o t h e s u bj ects or w h e n t h e 
c h a n g e(s) i n v ol v es o nl y l o gistic al or a d mi nistr ati v e as p ects of t h e tri al  
T h e In v esti g at or m ust f oll o w t h e i nt er n ati o n al a n d l oc al r e q uir e m e nts f or I E C/I R B s u b missi o n 
e. g. p eri o dic st at us r e p orts, S A Es, n otific ati o n of st u d y c o m pl eti o n a n d st u d y fi n al r e p ort.  
W h e n r e q uir e d, a n ext e nsi o n or r e n e w al of t h e I E C/I R B a p pr o v al m ust b e o bt ai n e d a n d 
f or w ar d e d t o S p o ns or or d esi g n e e.  
T h e I E Cs/I R Bs m ust s u p ply t h e S p o ns or wit h a list of t h e I E C/I R B m e m b ers hi p a n d a st at e m e nt 
t o c o nfir m t h at t h e I E C/I R B o p er at es i n acc or d a nc e wit h t h e I C H G C P g ui d eli n es a n d t h e 
a p plic a bl e l a ws, a n d r e g ul ati o ns  
1 2. 1. 3  
I nf or m e d C o ns e nt  Pr o c ess  
1 2. 1. 3. 1  
C o ns e nt/ A ss e nt a n d Ot h er I nf or m ati o n al D oc u m e nts 
Pr o vi d e d t o P artici p a nts  
T h e i nf or m e d c o ns e nt pr oc ess m ust b e i n acc o r d a nc e wit h t h e a p plic a bl e r e g ul at or y 
r e q uir e m e nts a n d m ust a d h er e t o G C P I C H g ui d eli n es , 2 1 C F R P art 5 0 F D A r e g ul ati o ns a n d 
et hic al pri nci pl es i n t h e D ecl ar ati o n of H elsi n ki , as w ell as D at a Pr ot ecti o n L a ws. 
Pri or t o st u d y i niti ati o n i n a n i n v esti g ati o n al  c e nt er, t h e PI m ust h a v e t h e I E Cs/I R Bs writt e n 
a p pr o v al or f a v or a bl e o pi ni o n of t h e writt e n I nf or m e d C o ns e nt F or ms ( m ai n I C F a n d G e n etic 
I C F) a n d a n y ot h er writt e n i nf or m ati o n t o b e pr o vi d e d t o s u bj ects. 
T h e writt e n a p pr o v al of t h e I E C/I R B, t o g et h er wit h t h e a p pr o v e d s u bj ects’ i nf or m ati o n a n d 
I C Fs, m ust b e fil e d i n t h e st u d y fil es. 
1 2. 1. 3. 2  
C o ns e nt Pr oc e d ur es a n d D oc u m e nt ati o n a n d S u bj ect’s Ri g hts 
wit h R e g ar ds t o Its D at a  
Fr e el y gi v e n , s p ecific, i nf or m e d a n d affir m ati v e  c o ns e nt s h o ul d b e o bt ai n e d fr o m  e v er y s u bj ect 
pri or t o a n y st u d y -s p ecific pr oc e d ur e t a k es pl ac e. 
T h e In v esti g at or, or a p ers o n d esi g n at e d b y t h e Inv esti g at or, s h o ul d f ull y i nf or m t h e  
s u bj ect or t h e s u bj ect's l e g all y acc e pt a bl e r e pr es e nt ati v e, of all p erti n e nt as p ects of t h e st u d y 
i ncl u di n g b ut n ot li mit e d t o t h e n at ur e of t h e st u dy, its p ur p os e, t h e pr oc e d ur es i n v ol v e d, t h e 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 1 7  of 1 2 7  
ex p ect e d d ur ati o n, t h e p ot e nti al ris ks a n d b e n efits i n v ol v e d a n d a n y disc o mf ort it m a y e nt ail.  
T h e s u bj ect will als o b e i nf or m e d a b o ut t h e i m p ort a nc e of r e m ai ni n g i n t h e st u d y e v e n if st u d y 
m e dic ati o n is disc o nti n u e d.  
T h e s u bj ect m ust b e f urt h er i nf or m e d t h at its d at a, i ncl u di n g p ers o n al d at a a n d h e alt h d at a,  
will  b e us e d i n acc or d a nc e wit h t h e D at a Pr ot ecti o n L a ws, i ncl u di n g wit h r e g ar ds t o its ri g hts 
wit h dr a w c o ns e nt  or r e q u est d el eti o n of p ers o n al or s e nsiti v e d at a . S p ecific all y, t h e s u bj ects 
s h all b e cl e arl y i nf or m e d of t h e li mit ati o ns s et f ort h o n d el eti o n ri g hts, a n d if a p plic a bl e, 
li mit ati o ns o n wit h dr a w c o ns e nt. 
T h e In v esti g at or will c o m m u nic at e wit h S p o ns or o n b e h alf of t h e s u bj ect , h o w e v er, t h e 
pr oc e d ur e f oll o w e d u p o n s uc h d at a s u bj ect r e q u est will b e h a n dl e d t o D at a Pr ot ecti o n L a ws  
a n d  t h e S p o ns or’s i nstr ucti o ns a n d g ui d a nc e. 
T h e In v esti g at or or its d esi g n e e, s h o ul d pr o vi d e t h e s u bj ect a m pl e ti m e a n d o p p ort u nit y t o 
i n q uir e a b o ut d et ails of t h e st u d y a n d t o d eci d e w h et h er or n ot t o p artici p at e i n t h e st u d y. All 
q u esti o ns a b o ut t h e st u dy s h o ul d b e a ns w er e d t o t h e s atisf acti o n of t h e s u bj ect or t h e 
s u bj ect's l e g all y acc e pt a bl e r e pr es e nt ati v e. T h e i nf or m e d c o ns e nt pr oc ess s h o ul d b e 
d oc u m e nt e d i n t h e s o urc e d oc u m e nts.  
C o pi es of t h e f ull y si g n e d a n d p ers o n all y d at e d I nf or m e d C o ns e nt F or ms (I C F) a n d a n y ot h er 
r el e v a nt writt e n i nf or m ati o n will b e gi v e n t o t h e s u bj ect a n d t h e ori gi n al I CFs will b e pr o p erl y 
m ai nt ai n e d at sit e.  
T h e writt e n I C F a n d a n y a p plic a bl e writt e n i nf or m ati o n will b e r e vis e d  w h e n e v er i m p ort a nt 
n e w i nf or m ati o n , r el e v a nt t o t h e s u bj ect’s willin g n ess t o c o nti n u e p artici p ati o n , b ec o m es 
a v ail a bl e . T his i ncl u d es r e g ul at or y acc el er at e d/c o n diti o n al a p pr o v al of A r a mc h ol i n t h e 
s u bj ects’ s p ecific c o u ntr y. I C Fs t e m pl at es s h all eit h er  b e  dr aft e d b y a p pr o v e d i n writi n g b y t h e 
S p o ns or. A n y r e vis e d writt e n I C F, a n d writt e n i nf or m ati o n will b e s u b mitt e d a n d a p pr o v e d b y 
t h e I E C/I R B b ef or e usi n g. T h e s u bj ect or t h e s u bj ect’s l e g all y acc e pt a bl e r e pr es e nt ati v e s h o ul d 
b e u p d at e d i n a ti m el y m a n n er a n d will b e as k e d t o r e vi e w a n d c o ns e nt t o t h e r e vis e d 
a p pr o v e d I C F.  
1 2. 2  C o nfi d e nti alit y  
All i nf or m ati o n s u p pli e d b y S p o ns or , or d esi g n e e o n its b e h alf, i n c o n n ecti o n wit h t his st u d y 
a n d n ot pr e vi o usl y p u blis h e d, is c o nsi d er e d c o nfi d e nti al i nf or m ati o n. T his i nf or m ati o n 
i ncl u d es, b ut is n ot li mit e d t o, t h e I n v esti g at ors' Br oc h ure, cli nic al pr ot oc ol, c as e r e p ort f or ms , 
S u bj ect’s D at a a n d ot h er sci e ntific d at a. A n y d at a c oll ect e d d uri n g t h e st u dy ar e als o 
c o nsi d er e d c o nfi d e nti al. T his c o nfi d e nti al i nf or m ati o n s h all r e m ai n t h e s ol e pr o p ert y of t h e 
S p o ns or, s h all n ot b e discl os e d t o ot h ers wit h o ut t h e writt e n c o ns e nt of S p o ns or , a n d s h all n ot 
b e us e d b y t h e r ec ei vi n g p art y exc e pt f or t h e p erf or m a nc e of t his st u d y.  
T h e i nf or m ati o n d e v el o p e d d uri n g t h e c o n d uct of t his cli nic al st u d y is als o c o nsi d er e d S p o ns or 
c o nfi d e nti al i nf or m ati o n a n d will b e us e d b y S p o ns or i n c o n n ecti o n wit h t h e d e v el o p m e nt of 
t h e dr u g. I n or d er t o e n a bl e S p o ns or t h e us e of t h e i nf or m ati o n d eri v e d fr o m t his cli nic al 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 1 8  of 1 2 7  
st u d y, t h e In v esti g at or is o bli g e d t o pr o vi d e all pr ot oc ol-s p ecifi e d d at a g e n er at e d i n t his st u d y 
t o S p o ns or . 
T h e S p o ns or is t h e s ol e o w n er of t h e ori gi n al c as e r e p ort f or ms c o m pl et e d as p art of t h e st u d y.  
By si g ni n g t h e cli nic al st u d y pr ot oc ol, t h e In v esti g at or a gr e es t h at t h e r es ults of t h e st u d y m a y 
b e us e d f or t h e p ur p os es of n ati o n al a n d i nt er n ati o n a l r e gistr ati o n, p u blic ati o n , a n d 
i nf or m ati o n f or m e dic al a n d p h ar m ac e utic al pr of essi o n als. T h e a ut h oriti es will b e n otifi e d of 
t h e In v esti g at or's n a m e, a d dr ess, q u alific ati o ns, a n d ext e nt of i n v ol v e m e nt.  
T h e i nf or m ati o n o bt ai n e d d uri n g t his st u d y m a y b e m a d e a v ail a bl e t o ot h er In v esti g at ors w h o 
ar e c o n d ucti n g si mil ar st u di es.  
It is a gr e e d t h at, c o nsist e nt wit h sci e ntific st a n d ar ds, p u blic ati o n of t h e r es ults of t h e st u d y 
s h all b e m a d e o nl y as p art of a p u blic ati o n of t h e r es ults o bt ai n e d b y all sit es p erf or mi n g t h e 
pr ot oc ol  u p o n pri or writt e n c o ns e nt fr o m t h e S p o ns or . 
1 2. 2. 1  S u bj ect  C o nfi d e nti alit y  
T h e  In v esti g at or m ust ass ur e t h at t h e s u bj ects' pri v acy a n d S u bj ect’s D at a c o nfi d e nti alit y a n d 
s ec urit y will b e strictl y m ai nt ai n e d. S u bj ects' D at a will b e i d e ntifi e d b y t h e assi g n e d s u bj ects' 
n u m b er  a n d i n acc or d a nc e wit h l oc al r e g ul ati o ns . 
T h e s u bj ect’s p er s o n al d at a (s uc h as n a m e, a d dr ess, c o nt act d et ails, i d e ntific ati o n n u m b er, 
etc.) s h all n ot b e s h ar e d or discl os e d, dir ectl y or i n dir ectl y, wit h t hir d p arti es, i ncl u di n g t h e 
S p o ns or , u nl ess t h e S p o ns or or its d esi g n e e ar e p h ysic all y at t h e sit e, or u nl ess re q uir e d u n d er 
a p plic a bl e l a w. I n t h e e v e nt t h at p ers o n al d at a is discl os e d , t h e I n v esti g at or s h all pr o m ptl y 
n otif y t h e S p o ns or. B ot h t h e S p o ns or a n d t h e In v esti g at or s h all h a n dl e s uc h discl os ur e 
acc or di n g t o a p plic a bl e l a ws, i ncl u di n g D at a Pr ot ecti o n L a ws.   
T h e In v esti g at or will m ai nt ai n a c o nfi d e nti al s u bj ect i d e ntific ati o n list t h at all o ws t h e 
u n a m bi g u o us i d e ntific ati o n of e ac h s u bj ect. T his list will b e s ec ur el y st or e d a n d will s er v e f or 
i nt er n al us e o nl y. At t h e e n d of t h e st u d y, all r ec or ds will c o nti n u e t o b e k e pt i n a s ec ur e 
l oc ati o n f or as l o n g a p eri o d as dict at e d b y t h e r evi e wi n g I R B, I nstit uti o n al p olici es, or Sp o ns or 
r e q uir e m ents.  
1 2. 3  St u d y  M o nit ori n g  
Cli nic al sit e m o nit ori n g is c o n d uct e d t o e ns ur e t h at t h e ri g hts a n d w ell -b ei n g of st u d y 
p artici p a nts ar e pr ot ect e d, t h at t h e r e p ort e d st u dy d at a is acc ur at e, c o m pl et e, a n d v erifi a bl e, 
a n d t h at t h e c o n d uct of t h e st u d y is i n c o m pli a nc e  wit h t h e c urr e ntl y a p pr ov e d 
pr ot oc ol/ a m e n d m e nt(s), wit h I nt er n ati o n al C o nf er e nc e  o n H ar m o niz ati o n G o o d  Cli nic al 
Pr actic e (I C H G C P), wit h a p plic a bl e r e g ul at or y r e q uir e m e nts a n d r el e v a nt Sp o ns or’s St a n d ar d 
O p er ati n g Pr oc e d ur es.  
T h e st u d y m o nit or is t h e pri mar y li ais o n b et w e e n t h e S p o ns or a n d t h e In v esti g at or. T h e m ai n 
r es p o nsi biliti es of t h e st u d y m o nit or ar e t o e ns ur e a d h er e nc e t o t h e pr ot oc ol, t o e ns ur e t h at 
i nf or m e d c o ns e nt is o bt ai n e d a n d r ec or d e d f or all  s u bj ects b ef or e t h e y p artici p at e  i n t h e st u d y 
a n d  t o v erif y t h at all st u dy d at a ar e c orr ectl y a n d c o m pl et el y r ec or d e d a n d r e p ort e d. 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 1 9  of 1 2 7  
T h e st u d y m o nit or will c o nt act t h e In v esti g at or a n d visit t h e i n v esti g ati o n al c e nt er at r e g ul ar 
i nt er v als t hr o u g h o ut t h e st u d y as d efi n e d b y t h e st u d y-s p ecific m o nit ori n g pla n. T h e st u d y 
m o nit or will b e p er mitt e d t o c h ec k a n d v erif y t h e v ari o us r ec or ds ( e C R Fs a n d ot h er p erti n e nt 
s o urc e d at a r ec or ds) r el ati n g t o t h e st u d y, t o v erify a d h er e nc e t o t h e pr ot oc ol a n d t o e ns ur e 
t h e c o m pl et e n ess, c o nsist e ncy, a n d acc ur ac y of t h e d at a b ei n g r ec or d e d. T h e m o nit ori n g  t y p e, 
fr e q u e ncy, d at a v erific ati o n ext e nt a n d ot h er m o nit ori n g acti viti es will b e d efi n e d i n t h e 
s p ecific st u d y m o nit ori n g pl a n. 
T h e PI or a d esi g n e e m ust m a k e a v ail a bl e all s o urc e d oc u m e nts  a n d r e g ul at or y d oc u m e nt ati o n 
t o S p o ns or or d esi g n e e a n d all a p plic a bl e r e g ul at or y a ut h oriti es. I n acc or d a nc e wit h I C H E 6, 
s o urc e d oc u m e nts i ncl u d e b ut ar e n ot li mit e d t o t h e f oll o wi n g: m e dic al r ec or ds; cli nic, offic e, 
or h os pit al c h arts, r ec or d e d d at a fr o m a ut o m at e d i nstr u m e nts s uc h as E C Gs, x -r a ys, a n d ot h er 
i m a gi n g r e p orts, l a b or at or y r e p orts, r ec or ds of t el e p h o n e c o nt acts, dr u g i n v e nt or y r ec or ds. 
S uffici e nt ti m e m ust b e all o w e d b y t h e sit e p ers o n n el f or t h e m o nit or t o r evi e w st u d y 
d oc u m e nts. T h e PI or a d esi g n e e  a n d ot h er r el e v a nt p ers o n n el s h o ul d b e av ail a bl e t o a ns w er 
q u esti o ns or r es ol v e q u eri es a n d t o pr o vi d e a n y missi n g i nf or m ati o n. T h e st u d y m o nit or will 
a d h er e t o t h e r e q uir e m e nts f or s u bj ects' c o nfi d e nti alit y a n d d at a s ec urit y i n a m a n n er at l e ast 
as strict as r e q uir e d h er ei n . 
1 2. 3. 1  
Pr ot oc ol D e vi ati o ns  
Pr ot oc ol d e vi ati o n is a n y n o nc o m pli a nc e wit h t h e cli nic al st u d y pr ot oc ol, I C H G C P  g ui d eli n es 
a n d t h e a p plic a bl e r e g ul at or y r e q uir e m e nts. T h e n o nc o m pli a nc e m a y b e eit h er o n t h e p art of 
t h e p artici p a nt, t h e In v esti g at or, or t h e st u d y sit e st aff.  If n o nc o m pli a nc e occ urs, c orr ecti v e 
acti o ns s h o ul d b e d e v el o p e d a n d i m pl e m e nt e d pr o m ptl y b y sit e st aff.  
E ac h pr ot oc ol d e vi ati o n s h o ul d b e r ec or d e d a n d m a n a g e d acc or di n g t o t h e m o nit ori n g pl a n.  
T h e pr ot oc ol d e vi ati o ns will b e r e p ort e d t o t h e a p plic a bl e I E C/I R B as r e q uir e d. 
T his st u d y will b e c o n d uct e d as s p ecifi e d i n t his pr ot oc ol exc e pt f or sit u ati o ns w h er e 
i m m e di at e i nt er v e nti o n is r e q uir e d t o eli mi n at e s af et y ris k b as e d o n t h e Inv esti g at or  or 
pr of essi o n al d esi g n e e j u d g m e nt.  
1 2. 4   Q u alit y Ass ur a nc e a n d Q u alit y C o ntr ol  
T h e S p o ns or a n d d esi g n e e will i m pl e m e nt a n d m ai nt ai n q u alit y ass ur a nc e a n d q u alit y c o ntr ol 
s yst e ms t o e ns ur e t h at t h e st u d y is c o n d uct e d a n d d at a ar e  g e n er at e d, d oc u m e nt e d a n d 
r e p ort e d i n c o m pli a nc e wit h t h e pr ot oc ol, G C P, a n d t h e a p plic a bl e r e g ul at or y r e q uir e m e nts. 
D at a M a n a g e m e nt is r es p o nsi bl e f or t h e acc ur ac y, q u alit y, c o m pl et e n ess, a n d i nt er n al 
c o nsist e ncy of t h e d at a fr o m t his st u d y. D at a h a n dli n g, i ncl u di n g d at a q u alit y ass ur a nc e, will 
c o m pl y wit h i nt er n ati o n al r e g ul at or y g ui d eli n es, i ncl u di n g I C H G C P g ui d eli n es  a n d D at a 
Pr ot ecti o n L a ws . D at a m a n a g e m e nt a n d c o ntr ol pr oc ess es s p ecific t o t his st u d y, al o n g wit h all 
st e ps a n d acti o ns t a k e n r e g ar di n g D at a M a n a g e m e nt a n d d at a q u alit y ass ur a nc e, will b e 
d escri b e d i n a d at a -m a n a g e m e nt pl a n.  
C as e r e p ort f or ms r ec ei v e d will b e pr oc ess e d a n d r e vi e w e d f or c o m pl et e n ess, c o nsist e ncy, a n d 
t h e pr es e nc e of m a n d at or y v al u es. A p plic a bl e t er ms will b e c o d e d acc or di n g t o t h e c o di n g 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 2 0  of 1 2 7  
c o n v e nti o ns f or t his st u dy. L o gic al c h ec ks will b e i m pl e m e nt e d t o e ns ur e d at a q u alit y a n d 
acc ur ac y. A n y n ec ess ar y c h a n g es will b e m a d e i n t h e cli nic al d at a b as e, a n d d at a r e vi e w a n d 
v ali d ati o n pr oc e d ur es will b e r e p e at e d as n e e d e d. D at a fr o m ext er n al s o urc es will b e 
r ec o ncil e d wit h t h e i nf or m ati o n a v ail a bl e i n t he C D M S  (cli nic al d at a m a n a g e m e nt s yst e m) . 
Discr e p a nci es f o u n d will b e q u eri e d.  
D at a c orr ecti o ns i n t h e C D M S will b e m a d e usi n g t h e C D M S u p d at e f u ncti o n. T h e s yst e m 
r e q uir es a r e as o n f or e ac h c h a n g e a n d k e e ps a c o m pl et e a u dit tr ail of t h e d at a v al u es, d at es 
a n d ti m es of m o dific ati o ns, a n d a ut h oriz e d el ectr o nic a p pr o v als of t h e c h a n g es . 
At t h e c o ncl usi o n of t h e st u d y, t h e C D M S a n d all ot h er st u d y d at a will b e l oc k e d t o f urt h er 
a d diti o ns or c orr ecti o ns. L oc ki n g t h e st u d y d at a r e pr es e nts t h e ac k n o wl e d g e m e nt t h at all d at a 
h a v e b e e n c a pt ur e d a n d c o nfir m e d as acc ur at e.  
All r ec or d e d d at a will  b e e nt er e d i nt o a p ass w or d  pr ot ect e d d at a b as e. All d at a e ntr y f or ms will 
b e acc ess e d a n d c o m pl et e d el ectr o nic all y t hr o u g h a p ass w or d -pr ot ect e d l o g -o n. All us er 
i nt er acti o n wit h t h e w e b-b as e d s yst e m, fr o m tr a ns mitti n g acc ess p ass w or ds t o e nt eri n g 
s e nsiti v e S u bj ect D at a, is d o n e usi n g t h e s ec ur e H T T P S pr ot oc ol. Fir e w alls will b e i m pl e m e nt e d 
t o e ns ur e t h at o nl y t h e mi ni m u m tr affic r e q uir e d f or n or m al o p er ati o ns is all o w e d t o tr a v ers e 
t h e n et w or k of w e b a n d d at a b as e s er v ers. T h e d at a b as e pr o d ucti o n s er v ers will b e h o us e d i n 
s ec ur e i nstit uti o n al d at a c e nt er f aciliti es a n d i ncl u d e f ail o v er pr ot ecti o n d esi g n e d t o mi ni miz e 
p ot e nti al f or s er v er d o w nti m e. Mi ni m al r e q uir e d p ers o n n el ar e all o w e d dir ect acc ess t o 
pr o d ucti o n f aciliti es. T h e st u d y d at a will r e m ai n s ec ur e a n d b e m axi m all y pr ot ect e d usi n g 
pr o d ucti o n  l e v el d at a c e nt er s er v ers, all, i n acc or d a nc e a n d wit h o ut d er o g ati n g fr o m t h e 
r e q uir e m e nts u n d er D at a Pr ot ecti o n L a ws 
1 2. 5  A u dits a n d I ns p ecti o ns  
T h e S p o ns or or d esi g n e e, r e g ul at or y a ut h oriti es a n d I E Cs/I R Bs m a y p erf o r m a u dits or 
i ns p ecti o ns t o t h e i n v esti g ati o n al c e nt ers t o e v al u at e st u d y c o n d uct a n d c o m pli a nc e wit h 
pr ot oc ol, S O Ps, I C H G C P g ui d eli n es, a n d a p plic a bl e r e g ul at or y r e q uir e m e nts. P artici p a nts' 
c o nfi d e nti alit y a n d pri v acy will b e strictl y h el d i n tr ust b y al l p arti es. 
T h e S p o ns or a n d/ or d esi g n e e will est a blis h a n a u dit pl a n a n d pr oc e d ur es f or st u d y a u dits. 
T h e In v esti g at or s h o ul d gr a nt dir ect acc ess t o s o urc e d at a/ d oc u m e nts, m e dic al r ec or ds 
(f oll o wi n g s u bj ects' si g n at ur e o n I C F), f aciliti es a n d a n y ot h er r es ourc es t h at ar e d e e m e d t o b e 
r el at e d t o t h e cli nic al st u d y f or m o nit ori n g, a u diti n g, I E C/I R B r e vi e w, a n d a p plic a bl e r e g ul at or y 
a ut h orit y i ns p ecti o n.  
T h e st u d y pr ot oc ol, d oc u m e nt ati o n, d at a, a n d all ot h er i nf or m ati o n g e n er at e d will b e h el d i n 
strict c o nfi d e nc e. N o i nf or m ati o n c o nc er ni n g t h e st u d y, or t h e d at a will b e r el e as e d t o a n y 
u n a ut h oriz e d t hir d p art y wit h o ut pri or writt e n a p pr o v al of t h e S p o ns or.  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 2 1  of 1 2 7  
1 2. 6   D at a H a n dli n g a n d R ec or d K e e pi n g  
1 2. 6. 1  
D at a  H a n dli n g  a n d  S o urc e D at a R ec or d e d o n t h e C as e R e p ort F or m  
D at a will b e c oll ect e d  a n d st or e d  usi n g el ectr o nic C R Fs t h at ar e s p ecific all y d esi g n e d f or t his 
st u d y a n d i n acc or d a nc e wit h a p plic a bl e l a w r e q uir e m e nts . 
S u bj ect’s p ers o n al d at a  a n d  r ec or ds ar e  strictl y c o nfi d e nti al a n d will b e c oll ect e d, h a n dl e d , 
pr oc ess e d  a n d  st or e d i n a s ec ur e m a n n er a n d i n f ull c o m pli a nc e wit h a p plic a bl e  D at a 
Pr ot ecti o n L a ws . 
T h e d at a c oll ect e d o n t h e C R Fs will b e st or e d i n a Cli nic al D at a M a n a g e m e nt S yst e m ( C D M S) 
t h at m e ets t h e t ec h nic al sci e ntific, r e g ul at or y, a n d l o gistic al r e q uir e m e nts of t h e st u d y, 
i ncl u di n g wit h o ut li mit ati o ns t h e t ec h nic al r e q uir e m e nts d escri b e d i n 2 1 C F R p art 1 1  as w ell as 
a p plic a bl e D at a Pr ot ecti o n L a ws,  pri or t o st ori n g  t h e st u d y d at a .  
Acc ess t o t h e  C D M S  will b e pr o vi d e d f oll o wi n g tr ai ni n g o n t h e s yst e m a n d a n y st ud y -s p ecific 
tr ai ni n g. S ol el y us ers wit h t h e n e e d t o k n o w will b e pr o vi d e d wit h i n di vi d u al s yst e m acc ess 
ri g hts, aft er t h e y c o m mit t h e ms el v es t o c o nfi d e nti alit y or a p pr o pri at e st at ut or y o bli g ati o n of 
c o nfi d e nti alit y i ncl u di n g wit h r e g ar ds t o t h e c o nfi d e nti a lit y of S u bj ect’s D at a, t h eir acc ess 
p er missi o ns, a n d p er mitt e d us e of S u bj ect’s D at a . 
D at a will b e c oll ect e d at t h e i n v esti g ati o n al c e nt er b y a p pr o pri at el y d esi g n at e d a n d tr ai n e d 
p ers o n n el, a n d C R Fs m ust b e c o m pl et e d f or e ac h s u bj ect w h o pr o vi d e d I C F i n acc or d a nc e wit h 
a p plic a bl e l a ws . S u bj ect  i d e ntit y, i ncl u di n g a n y i d e ntif yi n g d at a, s h o ul d n ot b e disc er ni bl e fr o m 
t h e d at a pr o vi d e d o n t h e CR F. D at a will b e v erifi e d usi n g t h e s o urc e d at a by t h e st u d y m o nit or 
a n d r e vi e w e d f or c o nsist e ncy b y D at a M a n a g e m e nt usi n g b ot h a ut o m at e d l o gic al c h ec ks a n d 
m a n u al r e vi e w. All d at a c oll ect e d will b e a p pr o v e d i n t h e s yst e m b y t h e Inv esti g at or at t h e 
i n v estig ati o n al c e nt er . T his a p pr o v al ac k n o wl e d g es t h e In v esti g at or’s r e vi e w a n d acc e pt a nc e of 
t h e d at a as b ei n g c o m pl et e a n d acc ur at e. 
All s u bj ect d at a m ust h a v e s u p p orti v e ori gi n al s o urc e d oc u m e nt ati o n i n t h e m e dic al r ec or ds, or 
e q ui v al e nt, b ef or e t h e y ar e tr a n scri b e d o nt o t h e C R F. D at a m a y n ot b e r ec or d e d dir ectl y o nt o 
t h e C R F a n d c o nsi d er e d as s o urc e d at a u nl ess t h e i n v esti g ati o n al c e nt er o bt ai ns writt e n 
d oc u m e nt ati o n fr o m t h e S p o ns or, b ef or e t h e b e gi n ni n g of t h e st u d y, i n dic ati n g w hic h d at a ar e 
p er mitt e d t o b e r ec or d e d dir ectl y o nt o t h e C R F.  
If d at a ar e pr oc ess e d fr o m ot h er t h a n s u bj ect cli nic al s o urc es ( e. g. c e ntr al l a b or at or y, 
bi o a n al ytic al l a b or at or y, c e ntr al r e a di n g c e nt er), t h e r es ults will b e s e nt t o t h e st u d y sit e, i n a 
s ec ur e a n d e ncr y pt e d m a n n er, w h er e t h e y will b e r et ai n e d a n d mi g ht b e tr a nscri b e d t o t h e 
C R F , if a p plic a bl e. T h es e d at a  s ets m a y als o b e s e nt el ectr o nic all y t o t h e S p o ns or ( a n d/ or 
or g a niz ati o n p erf or mi n g D at a M a n a g e m e nt) as p art of t h e  cli nic al d at a b as e. All d at a fr o m 
ot h er s o urc es will b e a v ail a bl e t o t h e In v esti g at or(s).  
F or s u bj ects w h o si g n t h e I C F a n d p erf or m scr e e ni n g pr oc e d ur es b ut d o n ot e nr oll i n t h e st u d y, 
f or a n y r e as o n, t h e r e q uir e d d at a will b e e nt er e d i nt o t h e C R F, acc or di n g t o t h e i nstr ucti o ns 
d et ail e d i n t h e e C R F c o m pl eti o n g ui d eli n es.  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 2 2  of 1 2 7  
A n y pr oc essi n g of S u bj ect’s D at a s h all b e s ol el y t o t h e ext e nt r e q uir e d a n d s u bj ect t o t h e 
i nf or m e d c o ns e nt pr o vi d e d, f or t h e p ur p os e of c o m pl yi n g wit h d at a mi ni miz ati o n pri nci pl es. 
N o a d diti o n al d at a s h all b e pr oc ess e d wit h o ut a p plic a bl e i nf or m e d c o ns e nt. F urt h er, S u bj ect 
D at a s h all b e us e d or s h ar e d s ol el y f or t h e p ur p os e of t h e st u d y, as s et f ort h h er ei n or 
ot h er wis e i nstr uct e d b y t h e S p o ns or i n writi n g a n d c o ns e nt e d b y t h e s u bj ect. Usi n g S u bj ect’s 
D at a f or a n y ot h er p ur p os es is strictl y f or bi d d e n . 
1 2. 6. 2  
St u d y Disc o nti n u ati o n a n d Cl os ur e  
All 2 0 0 0 s u bj ects pl a n n e d t o b e r a n d o miz e d i nt o t h e R a n d o miz e d D o u bl e -Bli n d, Pl ac e b o -
C o ntr ol l e d P art  will r ec eiv e Ar a mc h ol or m atc hi n g pl ac e b o u ntil E o S w hic h will b e a n n o u nc e d 
at t h e ti m e w h e n a t ot al of 3 8 0 s u bj ects will ex p eri e nc e at l e ast 1 pr e -s p ecifi e d clinic al e v e nt 
or at  5 y e ars fr o m l ast s u bj ect r a n d o miz ati o n, w hic h e v er c o m es first.  
T h e O p e n -L a b el P art will c o nti n u e f or t h e s a m e d ur ati o n as  t h e R a n d o miz e d, D o u bl e-Bli n d, 
Pl ac e b o -C o ntr ol l e d P art.  
All s u bj ects i n t h e O p e n -L a b el P art will r ec ei v e Ar a mc h ol  3 0 0 m g BI D u ntil E n d of st u d y ( E o S).  
Pr e m at ur e t er mi n ati o n or s us p e nsi o n of t his st u dy m a y occ ur d u e t o r e g ul at or y a ut h orit y 
d ecisi o n, I E C/I R B o pi ni o n, dr u g s af et y r e as o ns, a n d D M C  r ec o m m e n d ati o n or at t h e discr eti o n 
of t h e S p o ns or. T h e S p o ns or r et ai ns t h e ri g hts t o disc o nti n u e t h e d e v el o p m e nt of t h e 
i n v esti g ati o n al pr o d uct at a n y ti m e. 
If t h e st u d y is pr e m at ur el y t er mi n at e d, t h e S p o ns or will pr o m ptl y n otif y t h e In v esti g at ors a n d 
t h e r el e v a nt r e g ul at or y a ut h oriti es as r e q uir e d. T h e In v esti g at or s h o ul d pr o m ptl y n otif y t h e 
I E C/I R B a n d t h e st u d y p artici p a nts a n d ass ur e a p pr o pri at e t h er a p y a n d f oll o w -u p.  
1 2. 6. 2. 1  
D ecl ar ati o n of t h e E n d of t h e Cl i nic al Tri al 
F or cli nic al i n v esti g ati o n al c e nt ers, E o S d ecl ar ati o ns will b e i n acc or d a nc e  wit h l oc al 
r e g ul ati o ns. 
1 2. 6. 3  
St u d y R ec or ds R et e nti o n  
T h e I n v esti g at or or i nstit uti o n s h all r et ai n all ess e nti al st u d y d oc u m e nt ati o n a n d r ec or ds 
g e n er at e d b ef or e, d uri n g, a n d aft er t h e st u d y (“ St u d y R ec or ds”). T h e St u d y R ec or ds s h o ul d b e 
k e pt at t h e cli nic al sit e or a d esi g n at e d, s ec ur e d, off -sit e st or a g e f acilit y wit h li mit e d acc ess.  
T h e S p o ns or s p ecific ess e nti al d oc u m e nts a n d T h e St u d y R ec or ds s h o ul d b e r et ai n e d u ntil at  
l e ast 2 y e ars aft er t h e l ast a p pr o v al of a m ar k eti n g a p plic ati o n i n a n I C H r e gi o n a n d u ntil t h er e 
ar e n o p e n di n g or c o nt e m pl at e d m ar k eti n g a p plic ati o ns i n a n I C H r e gi o n or at l e ast 2 y e ars 
h a v e el a ps e d si nc e t h e f or m al disc o nti n u ati o n of cli nic al d e v el o p m e nt of t h e i n v esti g ati o n al 
pr o d uct. T h es e d oc u m e nts s h o ul d b e r et ai n e d f or a l o n g er p eri o d h o w e v er if r e q uir e d b y t h e 
a p plic a bl e r e g ul at or y r e q uir e m e nt(s) or if n e e d e d b y t h e Sp o ns or . 
If t h e I n v esti g at or b ec o m es u n a bl e t o c o nti n u e t o r et ai n S t u d y R ec or ds  for t h e r e q uir e d 
p eri o d, t h e S p o ns or s h o ul d b e pr os p ecti v el y n otifi e d, a n d t h e st u d y r ec or ds m ust b e 
tr a nsf err e d t o a d esi g n e e as a gr e e d b y t h e S p o ns or. 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 2 3  of 1 2 7  
1 2. 7  F ut ur e Us e of St or e d  S p eci m e ns a n d D at a  
T h e St u d y R ec or ds, a g gr e g at e d d at a  a n d st atistics as w ell as c ert ai n st u d y s u bj ects’ p ers o n al 
i nf or m ati o n a n d bi os p eci m e ns (s uc h as bl o o d s a m pl es or tiss u e bi o psi es)  c oll ect e d d uri n g t h e 
st u d y m a y b e st or e d a n d us e d f or f ut ur e r es e arc h. P ers o n al i nf or m ati o n a n d s a m pl es fr o m t his 
st u d y t h at will b e us e d f or f ut ur e r es e arc h m a y b e c o d e d (i ncl u d e t h e st u dy s u bj ect c o d e) or 
d e -i d e ntifi e d. If a n y f ut ur e r es e arc h r e q uir es us e of d e-i d e ntifi e d or a n o n y miz e d p ers o n al 
i nf or m ati o n or s a m pl es, all p ers o n al i d e ntifi ers will b e r e m o v e d fr o m t h e m, i ncl u di n g t h e st u d y 
c o d e, s o t h at t h e i nf or m ati o n or s a m pl es will b e c o nsi d er e d t o b e d e -i d e ntifi e d or a n o n y miz e d 
as d efi n e d u n d er  a p plic a bl e D at a P r ot ecti o n L a ws a n d c a n n ot b e li n k e d b ac k t o t h e s u bj ect.  
If r e q uir e d b y l a w, t h e I nv esti g at or s h all e ns ur e t h e s ubj ect c o ns e nts t o f ut ur e us e of t h eir 
s a m pl es a n d i nf or m ati o n t hr o u g h t h e I C F  
T h e af or es ai d c o d e d, d e -i d e ntifi e d or a n o n y miz e d s a m pl es a n d i nf or m ati o n m a y als o b e 
s h ar e d wit h t hir d p arti es wit h w h o m t h e S p o ns or c oll a b or at es e v e n if it exc e e ds t h e sc o p e of  
t h e cli nic al tri al.  
1 2. 8  R e p orti n g a n d P u blic ati o n of R es ults  
T h e S p o ns or is r es p o nsi bl e f or e ns uri n g t h at t h e p u blic h as acc ess t o t h e a p pr o pri at e 
i nf or m ati o n a b o ut t h e st u d y b y c o nf or mi n g t o l oc al a n d r e gi o n al r e q uir e m e nts f or r e gistr ati o n 
i n cli nic al tri al r e gistri es a n d p osti n g of r es ults. T his st u d y will b e r e gist er e d o n cli nic al tri als 
r e gistr y w e bsit es acc or di n g t o st a n d ar d pr oc e d ur es. 
T h e S p o ns or is r es p o nsi bl e f or pr e p ari n g a cli nic al st u d y r e p ort, i n c o o p er ati o n wit h t h e 
P ri nci p al In v esti g at or.  
N o d a t a t h at r es ult fr o m t h e st u d y a n d n o n e a n y of t h e i nf or m ati o n pr o vi d e d b y t h e S p o ns or  
t o t h e In v esti g at ors f or t h e p ur p os e of c o n d ucti n g t h e st u d y, will b e p u blis h e d or p ass e d o n t o 
a n y t hir d p art y, wit h o ut pri or writt e n c o ns e nt of t h e S p o ns or. P olici es r e g ar di n g t h e 
p u blic ati o n of t h e st u d y r es ults ar e d efi n e d i n t h e Cli nic al Tri al A gr e e m e nt.  
N o p at e nt a p plic ati o n(s) b as e d o n t h e r es ults of t h e st u d y m a y b e m a d e by t h e In v esti g at or or 
I nstit uti o n n or m a y assist a nc e b e gi v e n t o a n y t hir d p art y t o m a k e s uc h a n a p plic ati o n wit h o ut 
t h e writt e n a ut h oriz ati o n of t h e S p o ns or. 
1 2. 9   Li a bilit y a n d I ns ur a nc e 
T his cli nic al st u d y is i ns ur e d i n acc or d a nc e wit h t h e c orr es p o n di n g l oc al l e g al  pr o visi o ns.  
T h e p olic y c o v er a g e is s u bj ect t o t h e f ull p olic y t er ms, c o n diti o ns, ext e nsi o ns, a n d excl usi o ns.  
Excl u d e d fr o m t h e i ns ur a nc e c o v er ar e, i nt er ali a, d a m a g es t o h e alt h a n d w ors e ni n g of 
pr e vi o us existi n g dis e as e t h at w o ul d h a v e occ urr e d or c o nti n u e d if t h e s u bj ect h a d n ot t a k e n 
p art i n t h e cli nic al st u d y.  
T h e p olic y of Cli nic al Tri als I ns ur a nc e will b e pr o vi d e d t o t h e i n v esti g ati o n al c e nt ers b y t h e 
S p o ns or w h er e r e q uir e d.  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 2 4  of 1 2 7  
1 2. 1 0  V e n d ors  
C ert ai n st u d y acti viti es will b e p erf or m e d b y S p o ns or -d esi g n at e d  v e n d ors. T h es e m a y i ncl u d e, 
a m o n g ot h ers, a c o ntr act r es e arc h or g a niz ati o n, a c e ntr al l a b or at or y , bi o psy r e a di n g c e nt er , 
cli nic al s u p pl y m a n a g e m e nt, a n d d at a m a n a g e m e nt . T h e list of v e n d ors is a v ail a bl e i n t h e tri al 
m ast er fil e a n d will b e u p d at e d as n ec ess ar y.  
 
 

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 2 5  of 1 2 7  
1 3  R E F E R E N C E S  
1.  C h al as a ni N, Y o u n ossi Z, L a vi n e J E, et al. T h e di a g n osis a n d m a n a g e m e nt of n o n alc o h olic 
f att y li v er dis e as e: Pr actic e g ui d a nc e fr o m t h e A m eric a n Ass oci ati o n f or t h e St u d y of Li v er 
Dis e as es. H e p at ol o gy . 2 0 1 8; 6 7( 1): 3 2 8-3 5 7. d oi: 1 0. 1 0 0 2/ h e p. 2 9 3 6 7  
2.  Y o u n ossi  Z M, K o e ni g A B, A b d el atif D, F az el Y, H e nr y L, W y m er M. Gl o b al e pi d e mi ol o g y of 
n o n alc o h olic f att y li v er dis e as e — m et a -a n al ytic ass ess m e nt of pr e v al e nc e, i nci d e nc e, a n d 
o utc o m es. H e p at ol o gy . 2 0 1 6; 6 4( 1): 7 3– 8 4.  
3.  Est es C, A nst e e Q M, Ari as -L ost e M T, et al. M od eli n g N A FL D dis e as e b ur d e n i n C hi n a, 
Fr a nc e, G er m a n y, It al y, J a p a n, S p ai n, U nit e d Ki n g d o m, a n d U nit e d St at es f or t h e p eri o d 
2 0 1 6 -2 0 3 0. J H e p at ol. 2 0 1 8; 6 9( 4): 8 9 6-9 0 4. d oi: 1 0. 1 0 1 6/j.j h e p. 2 0 1 8. 0 5. 0 3 6  
4.  E ur o p e a n Ass oci ati o n f or t h e St u d y of t h e Li v er, E ur o p e a n Ass oci ati o n f or t h e St u d y of 
Di a b et es, E ur o p e a n Ass oci ati o n f or t h e St u d y of O b esit y. E A SL – E A S D – E A S O Cli nic al 
Pr actic e G ui d eli n es f or t h e m a n a g e m e nt of n o n -alc o h olic f att y li v er dis e as e. Di a b et ol o gi a . 
2 0 1 6; 5 9( 6): 1 1 2 1 – 1 1 4 0. d oi: D OI: 1 0. 1 0 0 7/s 0 0 1 2 5 -0 1 6 -3 9 0 2 -y 
5.  R atzi u V, G o o d m a n Z, S a n y al A. C urr e nt eff orts a n d tr e n ds i n t h e tr e at m e nt of N A S H. J 
H e p at ol . 2 0 1 5; 6 2( 1 S u p pl): S 6 5-7 5. d oi: 1 0. 1 0 1 6/j.j h e p. 2 0 1 5. 0 2. 0 4 1  
6.  Br u nt E M, J a n n e y C G, Di Bisc e gli e A M, N e usc h w a n d er -T etri B A, B ac o n B R. N o n alc o h olic 
st e at o h ep atitis: a pr o p os al f or gr a di n g a n d st a gi n g t h e hist ol o gic al l esi o ns. A m J 
G astr o e nt er ol . 1 9 9 9; 9 4( 9): 2 4 6 7-2 4 7 4. d oi: 1 0. 1 1 1 1/j. 1 5 7 2 -0 2 4 1. 1 9 9 9. 0 1 3 7 7.x  
7.  Si d di q ui M S, H arris o n S A, A b d el m al e k M F, et al. C as e d efi niti o ns f or i ncl usi o n a n d a n al ysis 
of e n d p oi nt s i n cli nic al tri als f or n o n alc o h olic st e at o h e p atitis t hr o u g h t h e l e ns of r e g ul at or y 
sci e nc e. H e p at ol o gy . 2 0 1 8; 6 7( 5): 2 0 0 1– 2 0 1 2.  
8.  Fil oz of C, C h o w S -C, Di mic k -S a nt os L, et al. Cli nic al e n d p oi nts a n d a d a pti v e cli nic al tri als i n 
pr ecirr h otic n o n alc o h olic st e at o h e p atitis: F acilit ati n g d e v el o p m e nt a p pr o ac h es f or a n 
e m er gi n g e pi d e mic. H e p at ol C o m m u n . 2 0 1 7; 1( 7): 5 7 7-5 8 5. d oi: 1 0. 1 0 0 2/ h e p 4. 1 0 7 9  
9.  A n g ul o P, Kl ei n er D E, D a m -L ars e n S, et al. Li v er Fi br osis, b ut N o Ot h er Hist ol o gic F e at ur es, 
Is Ass oci at e d Wit h L o n g-ter m O utc o m es of P ati e nts Wit h N o n alc o h olic F att y Li v er Dis e as e. 
G astr o e nt er ol o gy . 2 0 1 5; 1 4 9( 2): 3 8 9-3 9 7. e 1 0. d oi: 1 0. 1 0 5 3/j. g astr o. 2 0 1 5. 0 4. 0 4 3  
1 0.  D ul ai P S, Si n g h S, P at el J, et al. I ncr e as e d ris k of m ort alit y b y fi br osis st a g e i n n o n alc o h olic 
f att y li v er dis e as e: S yst e m atic r e vi e w a n d m et a-a n al ysis. H e p at ol o gy . 2 0 1 7; 6 5( 5): 1 5 5 7-
1 5 6 5. d oi: 1 0. 1 0 0 2/ h e p. 2 9 0 8 5  
1 1.  E kst e dt M, H a gstr ö m H, N asr P, et al. Fi br osis st a g e is t h e str o n g est pr e dict or f or dis e as e -
s p ecific m ort alit y i n N A FL D aft er u p t o 3 3 y e ars of f oll o w-u p. H e p at ol o gy . 2 0 1 5; 6 1( 5): 1 5 4 7-
1 5 5 4. d oi: 1 0. 1 0 0 2/ h e p. 2 7 3 6 8  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 2 6  of 1 2 7  
1 2.  Y o u n ossi Z, T ac k e F, Arr es e M, et al. Gl o b al P ers p ecti v es o n N o n -alc o h olic F att y  Li v er 
Dis e as e a n d N o n -alc o h olic St e at o h e p atitis. H e p at ol o gy . P u blis h e d o nli n e S e pt e m b er 4, 
2 0 1 8. d oi: 1 0. 1 0 0 2/ h e p. 3 0 2 5 1  
1 3.  N o ncirr h otic N o n alc o h olic St e at o h e p atitis Wit h Liv er Fi br osis: D e v el o pi n g Dr u gs f or 
Tr e at m e nt G ui d a nc e f or I n d ustr y - D R A F T G UI D A N C E. P u blis h e d o nli n e D ec e m b er 2 0 1 8. 
htt ps:// w w w.f d a. g o v/ d o w nl o a ds/ Dr u gs/ G ui d a nc e C o m pli a nc e R e g ul at or yI nf or m ati o n/ G ui d
a nc es/ U C M 6 2 7 3 7 6. p df  
1 4.  Dr aft r efl ecti o n p a p er o n r e g ul at or y r e q uir e m e nts f or t h e d e v el o p m e nt of m e dici n al 
pr o d ucts c hr o nic n o n -i nf ecti o us li v er dis e as es ( P B C, P S C, N A S H). E ur o p e a n M e dici n es 
A g e ncy. P u blis h e d S e pt e m b er 1 7, 2 0 1 8. Acc ess e d N o v e m b er 2 2, 2 0 2 0. 
htt ps:// w w w. e m a. e ur o p a. e u/ e n/ dr aft -r efl ecti o n-p a p er -r e g ul at or y-r e q uir e m e nts-
d e v el o p m e nt -m e dici n al -pr o d ucts -c hr o nic-n o n -i nf ecti o us 
1 5.  R es e arc h C f or D E a n d. F D A G ui d a nc e o n C o n d uct of Cli nic al Tri als of M e dic al Pr o d ucts 
d uri n g C O VI D -1 9 P u blic H e alt h E m er g e ncy. U. S. F o o d a n d Dr u g A d mi nistr ati o n. P u blis h e d 
S e pt e m b er 2 1, 2 0 2 0. Acc ess e d N o v e m b er 2 2, 2 0 2 0. htt ps:// w w w.f d a. g o v/r e g ul at or y -
i nf or m atio n/s e arc h -f d a-g ui d a nc e -d oc u m e nts/f d a -g ui d a nc e -c o n d uct-cli nic al-tri als-m e dic al -
pr o d ucts -d uri n g -c o vi d-1 9 -p u blic -h e alt h -e m er g e ncy  
1 6.  I N V E N TI V A Pr ess R el e as e : I n v e nti v a’s l a nifi br a n or m e ets t h e pri m ar y a n d k e y s ec o n d ar y 
e n d p oi nts i n t h e P h as e II b N A TI V E cli nic al tri al i n n o n -alc o h olic st e at o h e p atitis. P u blis h e d 
o nli n e J u n e 1 5, 2 0 2 0.  
1 7.  N G M Bi o A n n o u nc es P ositi v e I nt eri m R es ults fr o m O n g oi n g 2 4 -W e e k P h as e 2 St u d y 
E v al u ati n g Al d af er mi n ( N G M 2 8 2) i n P ati e nts wit h N A S H | N G M Bi o p h ar m ac e utic als, I nc. 
Acc ess e d N o v e m b er 1 3, 2 0 2 0. htt ps://ir. n g m bi o.c o m/ n e ws -r el e as es/ n e ws-r el e as e-
d et ails/ n g m -bi o -a n n o u nc es -p ositi v e -i nt eri m-r es ults-o n g oi n g -2 4 -w e e k -p h as e/  
1 8.  A k er o T h er a p e utics. A k er o A n n o u nc es Str o n gl y P ositi v e Hist ol o gic al D at a Acr oss 
All Efr uxif er mi n D os e Gr o u ps i n 1 6 -W e e k P h as e 2 a B AL A N C E D St u d y i n N A S H P ati e nts. 
P u blis h e d o nli n e J u n e 3 0, 2 0 2 0.  
1 9.  S a n y al AJ, C h al as a ni N, K o w dl e y K V, et al. Pi o glit az o n e, vit a mi n E, or pl ac e b o f or 
n o n alc o h olic st e at o h e p atitis. N E n gl J M e d . 2 0 1 0; 3 6 2( 1 8): 1 6 7 5-1 6 8 5. 
d oi: 1 0. 1 0 5 6/ N EJ M o a 0 9 0 7 9 2 9  
2 0.  T h y g es e n K, Al p ert J S, J aff e A S, et al. F o urt h u ni v ers al d efi niti o n of m y oc ar di al i nf arcti o n 
( 2 0 1 8). J o ur n al of t h e A m eric a n C oll e g e of C ar di ol o gy. 2 0 1 8; 7 2( 1 8): 2 2 3 1– 2 2 6 4.  
2 1.  Hic ks K ar e n A., Tc h e n g J a m es E., B oz k urt Bi y k e m, et al. 2 0 1 4 A C C/ A H A K e y D at a El e m e nts 
a n d D efi niti o ns f or C ar di o v asc ul ar E n d p oi nt E v e nts i n Cli nic al Tri als. Circ ul ati o n . 
2 0 1 5; 1 3 2( 4): 3 0 2 -3 6 1. d oi: 1 0. 1 1 6 1/ CI R. 0 0 0 0 0 0 0 0 0 0 0 0 0 1 5 6  

Pr ot oc ol N o. Ar a mc h ol -0 1 8  
 
 
A R M O R S t u dy                               
 
V ersi o n 4. 0 _ 2 3 N ov 2 0 2 0  
 
 
C O N FI D E N TI AL  
1 2 7  of 1 2 7  
2 2.  Ar a mc h ol -0 0 5 Cli nic al St u d y R e p ort; A P h as e II b, D o u bl e Bli n d, R a n d o miz e d C o ntr oll e d 
Cli nic al Tri al t o E v al u at e t h e Effic ac y a n d S af et y of T w o Ar a mc h ol D os es V ers us Pl ac e b o i n 
P ati e nts wit h N A S H. P u blis h e d o nli n e J a n u ar y 2 0 1 9.  
2 3.  Fri e d m a n SL, R atzi u V, H arris o n S A, et al. A r a n d o miz e d, pl ac e b o -c o ntr oll e d tri al of 
c e nicri vir oc f or tr e at m e nt of n o n alc o h olic st e at o h e p atitis wit h fi br osis. H e p at ol o gy . 
2 0 1 8; 6 7( 5): 1 7 5 4 – 1 7 6 7.  
2 4.  N e usc h w a n d er -T etri B A, L o o m b a R, S a n y al AJ, et al. F ar n es oi d X n ucl e ar r ec e pt or li g a n d 
o b etic h olic aci d f or n o n -cirr h otic, n o n-alc o h olic st e at o h e p atitis ( FLI N T): a m ultic e ntr e, 
r an d o mis e d, pl ac e b o -c o ntr oll e d tri al. L a nc et. 2 0 1 5; 3 8 5( 9 9 7 2): 9 5 6-9 6 5. 
d oi: 1 0. 1 0 1 6/ S 0 1 4 0 -6 7 3 6( 1 4) 6 1 9 3 3 -4  
2 5.  Y o u n ossi Z M, R atzi u V, L o o m b a R, et al. O b etic h olic aci d f or t h e tr e at m e nt of n o n -alc o h olic 
st e at o h e p atitis: i nt eri m a n al ysis fr o m a m ultic e ntr e, r a n d o mis e d, pl ac e b o -c o ntr oll e d p h as e 
3 tri al. T h e L a nc et . 2 0 1 9; 3 9 4( 1 0 2 1 5): 2 1 8 4– 2 1 9 6.  
2 6.  R atzi u V, H arris o n S A, Fr a nc q u e S, et al. El afi br a n or, a n A g o nist of t h e P er oxis o m e 
Pr olif er at or -Acti v at e d R ec e pt or -α a n d  -δ, I n d uc es R es ol uti o n of N o n alc o h olic 
St e at o h e p atitis Wit h o ut Fi br osis W ors e ni n g. G astr o e nt er ol o gy . 2 0 1 6; 1 5 0( 5): 1 1 4 7-1 1 5 9. e 5. 
d oi: 1 0. 1 0 5 3/j. g astr o. 2 0 1 6. 0 1. 0 3 8  
2 7.  CI RI U S T H E R A P E U TI C S Pr ess R el e as e: Ciri us T h er a p e utics A n n o u nc es R es ults fr o m P h as e 2 b 
N A S H St u d y S u p p orti n g A d v a nci n g t o P h as e 3 D ev el o p m e nt of M S D C -0 6 0 2 K; D at a 
Acc e pt e d f or L at e Br e a k er Pr es e nt ati o n at T h e Li v er M e eti n g. P u blis h e d o nli n e N o v e m b er 
8, 2 0 1 9.  
2 8.  G E N FI T Pr ess R el e as e :  G e nfit A n n o u nc es R es ults fr o m I nt eri m A n al ysis of R E S OL V E -I T 
P h as e 3 Tri al of El afi br a n or i n A d ults wit h N A S H a n d Fi br osis. P u blis h e d o nli n e M a y 1 1, 
2 0 2 0.  
2 9.  AJ M C N e wsr o o m R el e as e: N o v o N or dis k’s S e m a gl uti d e S h o ws Pr o mis e i n Tr e ati n g N A S H. 
P u blis h e d o nl i n e M a y 1 1, 2 0 2 0. 
3 0.  H arris o n S A, W o n g V W -S, O k a n o u e T, et al. S el o ns erti b f or p ati e nts wit h bri d gi n g fi br osis 
or c o m p e ns at e d cirr h osis d u e t o N A S H: r es ults fr o m r a n d o miz e d P h III S ℡
L A R tri als. 
J o ur n al of h e p at ol o gy. P u blis h e d o nli n e 2 0 2 0. 
3 1.  S a n y al AJ , H arris o n S A, R atzi u V, et al. T h e N at ur al Hist or y of A d v a nc e d Fi br osis D u e t o 
N o n alc o h olic St e at o h e p atitis: D at a Fr o m t h e Si mt uz u m a b Tri als. H e p at ol o gy . P u blis h e d 
o nli n e A pril 1 6, 2 0 1 9. d oi: 1 0. 1 0 0 2/ h e p. 3 0 6 6 4