Evaluation of the Efficacy and Safety of PTC299 in Hospitalized Subjects With COVID-19 (FITE19)
Phase: PHASE2
Conditions: Pneumonia, COVID-19, Coronavirus
Sponsor: PTC Therapeutics

V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 1  of 6 2  
C LI NI C A L P R O T O C O L  
E V A L U A TI O N O F T H E  E F FI C A C Y A N D S A F E T Y O F P T C 2 9 9 I N 
H O S PI T A LI Z E D S U B J E C T S WI T H C O VI D -1 9 ( FI T E 1 9)  
P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
0 2  J U N E  2 0 2 1  
V E R SI O N 7 . 0 
P T C T H E R A P E U TI C S, I N C.  
1 0 0 C O R P O R A T E C O U R T  
S O U T H P L AI N FI E L D, N J 0 7 0 8 0 U S A  
N otice of Pr o prietar y I nf or mati o n: T his d oc u me nt c o ntai ns c o nfi de ntial i nf or mati o n o w ne d b y or i n t he 
p oss essi o n/c o nt r ol of P T C T hera pe utics, I nc. E xce pt as ma y ot her wis e be per mitte d i n writi n g, b y acce pti n g or 
re vie wi n g t hes e materials, y o u a gree t hat t his i nf or mati o n s h o ul d n ot be dis cl os e d t o ot hers (e xce pt w here re q uire d b y 
a p plica ble la w) a n d s h o ul d n ot be us e d f or  u na ut h orize d p ur p os es. I n t he e ve nt of a n act ual or s us pecte d breac h of t his 
o bli gati o n, P T C T hera pe utics, I nc. s h o ul d be n otifie d pr o m ptl y .
N C T #: N C T 0 4 4 3 9 0 7 1

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P R O T O C O L I D E N TI FI E R S A N D S T U D Y P E R S O N N E L  
Pr oj ect C o d e  
P T C 2 9 9  
T h e r a p e utic Ar e a  
Vir ol o g y  
P T C T h e r a p e utics S u bst a nc e I d e ntifie r  
P T C 2 9 9  
N o n p r o priet ar y N a me  
E m v o d o dstat  
I N D N u m b er 
I N D 1 4 9 3 8 5 
E u d r a C T N u m b er  
2 0 2 0 -0 0 1 8 7 2 -1 3  
Pr ot oc ol N u m b er  
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Pr ot oc ol Ve rsi o n  
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Pr ot oc ol Ve rsi o n D ate  
0 2  J u ne 2 0 2 1  
Pr ot oc ol P h ase  
P hase 2/ 3  
Pr ot oc ol Title  
E val uati o n of t he effica c y a n d safet y of P T C 2 9 9 i n 
h os pitalize d s u bje cts wit h C O VI D -1 9  ( FI T E 1 9) 
P T C Cli nic al Le a d  
 
P T C M e dic al M o nit or  
 
P T C Bi ost atistici a n  
 
P T C St u d y M a n a ger  
 
 
 
 

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P T C T H E R A P E U TI C S P R O T O C O L A P P R O V A L SI G N A T U R E S  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
P T C T her a pe utics, I nc.  
 
D ate  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
P T C T her a pe utics, I nc.  
 
D ate  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
P T C T her a pe utics, I nc  
 
D ate  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
T he e Si g nat ure pa g e  is l ocate d o n t h e last p a ge. 

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P RI N CI P A L I N V E S TI G A T O R A G R E E M E N T A N D SI G N A T U R E  
 
I ha ve r ea d t he pr ot oc ol d oc u me nt a n d, o n be half of m y i nstit uti o n, a gre e t o c o m pl y wit h t he pr ot oc ol 
a n d all a p plic a ble re g ulati o ns.  
 
 
 
 
Pri n ci p al I n vesti g at or  
 
D ate  
 
 
 
I nstit uti o n: 
 
A d dr ess:  
 
Cit y:  
 
State/ Pr o vi nc e:  
 
C o u ntr y:  
 
P h o ne:  
 
Fa x:  
 
E -mail:  
 
 
 
 
 

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S Y N O P SI S  
St u d y N u m ber  
P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
N a me of 
I n vesti g ati o nal  
Pr o d uct  
E m v o d o dstat ( P T C 2 9 9 ) 
St u d y Title  
E val uati o n of t h e effic ac y a n d saf et y of P T C 2 9 9 i n h os pitali ze d 
s u bjects wit h C O VI D-1 9  ( FI T E 1 9) 
Pr o p ose d I n dic ati o n  Treat me nt of C O VI D -1 9  
N u m ber of St u d y 
Sites  
A p pr o xi matel y 5 0  
P h ase of Tri al  
P hase 2/ 3  
St u d y O bjecti ves  
Pri m ary St u dy O bjectiv e  
T o e val u ate t he cli nic al effica c y of P T C 2 9 9 c o m p are d wit h plac e b o 
assesse d b y ti me t o r es pirat or y i m pr o ve m e nt  i n a d ult s u bjects 
h os pitali ze d wit h C O VI D -1 9.  
Sec o n d ary St u dy O bjecti ves  
•  T o e val u ate t he cli nic al effica c y of P T C 2 9 9 c o m p are d wit h 
place b o, as assesse d b y res pirat or y f u ncti o n, i m m u ne 
res p o nse, le n gt h of h os pit ali zati o n, a n d m ort alit y. 
•  T o e val u ate t he safet y of P T C 2 9 9 as assesse d b y 
dr u g -relat e d a d verse e v e nts. 
St u d y E n d p oi nts  
Pri m ary E n d p oi nt  
•  Ti me fr o m ra n d o mizati o n t o res pir at or y i m pr o ve m e nt, 
defi ne d as peri p heral o x y g e n sat urati o n ( S p O 2) ≥9 4 %  o n 
r o o m air, s ustai n e d u ntil disc har g e fr o m t he h os pital  or t he 
e n d of t he st u d y ( Da y  2 8) .  
Sec o n d ary E n d p oi nts  
•  T he pr o p orti o n of s u bj ects re q uiri n g i n vasi v e ve ntilati o n at 
a n y p oi nt d uri n g t he st u d y  
•  T he pr o p orti o n of s u bj ects re q uiri n g s u p ple m e ntal o x y ge n 
or n o n -i n vasi ve ve ntil ati o n at a n y p oi nt d uri n g t h e st u d y i n 
s u bjects w h o di d n ot re q uire s u p ple me ntal o x y ge n at 
baseli ne  
•  Ti me fr o m ra n d o mizati o n t o def er vesce n ce i n s u bj ects 
prese nti n g wit h f e ver at e nr oll me nt (te m p erat ur e of 
≥3 7. 6 ℃ a xilla, ≥3 8. 0℃ oral, or ≥3 8. 6° C t y m p a nic or 
rectal)  
•  Ti me fr o m ra n d o mizati o n t o res pir at or y rate 
≤2 4  breat hs/ mi n ut e o n r o o m air  
•  Ti me fr o m ra n d o mizati o n t o c o u g h r e p orte d as mil d or 
a bse nt ( o n a scale of se vere, m o derate, mil d, a bse nt, i n 
t h ose wit h c o u g h at e nr oll me nt rate d se v ere or m o d erate) 

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•  Ti me fr o m ra n d o mizati o n t o d ys p nea r e p orte d as mil d or 
a bse nt ( o n a scale of se vere, m o derate, mil d, a bse nt, i n 
t h ose wit h d ys p nea at e nr oll me nt rate d as se vere or 
m o derat e)  
•  Atte n uati o n of i m m u ne res p o nses as i n di cate d b y:  
− re d ucti o n i n c yt o ki ne l e vels, p ote ntiall y i n cl u di n g 
i nterl e u ki n (I L)-2, I L -6, I L -7, I L -1 7, gra n ul oc yt e -
c ol o n y sti m ulati n g fact or, i nt erfer o n -γ i n d u ci bl e pr ot ei n 
1 0, m o n oc yte c he m o attra cta nt pr otei n 1, ma cr o p ha ge 
i nfla m mat or y pr otei n 1-α, a n d t u m or n ecr osis fact or -α  
− re d ucti o n i n le v els of ac ut e p hase pr ot ei ns, p ote ntiall y 
i ncl u di n g f erriti n, C -reacti ve pr otei n, D-di mer, a n d 
car dia c tr o p o ni n   
− n or mali zati o n i n t h e c o m ple te bl o o d c o u nt 
− c ha n ges i n ot h er la b orat or y para met ers p ote ntiall y 
i ncl u di n g d ecre ases i n lactat e de h y dr o ge n ase, 
pr ot hr o m bi n ti me, a n d al b u mi n  
•  Re d ucti o n i n viral l oa d  
•  D urati o n of h os pitaliz ati o n meas ure d i n d a ys  
•  M ortalit y at Da y 2 8  
•  O verall safet y pr ofile c hara cterize d b y t y pe, fre q ue n c y, 
se verit y, ti mi n g, a n d rel ati o ns hi p t o st u d y treat me nt of a n y 
a d verse e ve nts ( A Es) or la b orat or y a b n or maliti es.  
St u d y P o p ul ati o n  
H os pitaliz e d a d ult s u bjects wit h c o nfir me d p ne u m o nia, dia g n ose d wit h 
C O VI D -1 9, a n d n ot re q uiri n g me c ha nic al ve ntil ati o n.  
F or t he p ur p oses of e nr oll m e nt of s u bje cts i nt o t he st u d y, “ h os pitalize d 
patie nts” will i ncl u d e  a n y C O VI D -1 9 patie nt eit h er a d mitt e d or u n der 
o bser vati o n i n t he h os pit al f or a c o nti n u o us peri o d of 2 4 h o urs or m ore 
w h o ot her wise f ulfills t he eli gi bilit y  criteria.   
S a m ple Size  
A t otal of 3 2 6 e v e nts i n t h e st u d y will pr o vi de m or e t ha n 8 0 % of 
p o wer t o dete ct a ha zar d rati o of 1. 3 8 at t w o -si de d t y pe I err or of 0. 0 5. 
A p pr o xi matel y 3 8 0 s u bjects, i n t ot al, will be nee d e d.  
1 9 0 ra n d o miz e d t o P T C 2 9 9 a n d 1 9 0 r a n d o mi ze d t o place b o. 
E nr oll m e nt will be halte d w he n a p pr o xi matel y 4 0 s u bjects ( 2 0 i n eac h 
ar m) ha ve b ee n e nr olle d a n d a n i nt eri m a nal ysis of s afet y data will be 
c o n d ucte d w he n t h ose 4 0 s u bjects ha ve rec ei ve d 1 4 da ys of treat me nt 
a n d 1 4 da ys of f oll o w -u p . E nr oll me nt will c o nti n ue if t here ar e n o 
safet y c o nc er ns.  
Met h o d ol o g y/ St u d y 
Desi g n  
T his is a ra n d o mize d,  d o u ble -bli n d, plac e b o -co ntr oll e d, m ultice nter 
2 8  -da y st u d y  wit h safet y f oll o w -u p b y tele p h o ne c all at Da y 6 0 .  

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S u bjects will b e ra n d o mize d 1: 1 t o P T C 2 9 9 tr eat me nt or plac e b o , wit h 
a p pr o xi matel y 1 9 0 s u bj ects i n eac h c o h ort. T he r a n d o mizati o n will be 
stratifi e d b y a ge ( ≤6 2 vs > 6 2), re m desi vir use ( yes vs n o) , a n d 
de xa met has o ne use ( yes vs n o) . All s u bjects will als o recei v e sta n dar d 
of care ( S O C) defi ne d per l ocal writt e n p oli cies or g ui deli n es. T he use 
of ster oi ds  (e xce pt de xa m et has o ne), se nsiti ve C Y P 2 D 6  s u bstrates, 
C Y P 2 C i n d ucers, I L-6 ne utralizi n g a nti b o dies, I L -6 r ece pt or 
i n hi bit ors, a n d a n y i n vesti gati o nal t hera py  ar e pr o hi bite d.  
F oll o wi n g eli gi bilit y scre e ni n g a n d e nr oll me nt, s u bj e cts will re cei v e 
oral ta blets c o ntai ni n g P T C 2 9 9 or matc h i n g place b o 2 0 0 m g t wice 
dail y ( m or ni n g a n d e v e ni n g) o n Da ys 1 t o 7 a n d 5 0 m g o nce dail y 
( m or ni n g) o n Da ys  8 t o 1 4.  
A p pr o xi matel y 4 0 s u bjects ( 2 0 i n eac h ar m) will be e nr olle d i niti all y, 
e nr oll m e nt will t he n h alt, a n d a n i nteri m a nal ysis will be perf or m e d t o 
assess safet y. N o f or mal statistic al testi n g will be perf or me d at t he first 
i nteri m a nal ysis . A n i n de pe n de nt data a n d safet y m o nit ori n g b oar d 
(D S M B ) will re vie w a vaila bl e data  f or t he 4 0 s u bje cts. E nr oll me nt will 
c o nti n ue if t her e are n o safet y c o nc er ns.  I n a d diti o n t o t he D S M B, a n 
i n de pe n de nt He patic A d vis or y Safet y C o m mittee ( H A C ) will als o 
re vie w dat a relate d t o li ver e ve nts .  
A  sec o n d i nteri m a nal ysis is pla n ne d t o assess f utilit y. It will be 
perf or me d  w he n 5 0 % of res pirat or y i m pr o v e me nt e v e nts ha ve be e n 
reac he d, ie, 1 6 3  e ve nts ha ve be e n o bser ve d ( a p pr o xi matel y  
1 9 0  s u bjects).  
T he u n bli n d e d  i nt eri m a nal yses will be c o n d ucte d b y a n i n de pe n d e nt 
statisti cia n a n d t he r es ults will b e o nl y s hare d wit h t h e cl osed  sessi o n 
of  t he D S M B . D S M B will ma ke t he g o - or n o -g o  re c o m me n dati o ns 
a n d t he re c o m m e n dati o ns will be c o m m u ni cat e d wit h t he st u d y te a m. 
T he st u d y te a m will  be ke pt bli n d e d  f or res ults rel ate d t o t he i nteri m 
a nal ys es.  
S u bjects will b e assesse d dail y w hile h os pit ali ze d. All s u bjects will 
u n der g o effic ac y, safet y, a n d la b or at or y assess me nts as s u m mariz e d i n  
Ta ble  3 . T here will be a f oll o w -u p tele p h o ne call at D a y 6 0 t o assess 
A Es, seri o us A Es, a n d deat hs.  
F or s u bjects w h o are disc har ge d fr o m t he h os pital pri or t o Da y 2 8:  
•  If S p O2 is < 9 4 %, S p O2 meas ure me nts will be ta ke n dail y 
u ntil Da y 2 8  
•  S u bject -re p orte d assess me nts f or c o u g h a n d d ys p ne a will 
c o nti n ue t o Da y 2 8  
•  N o ot her assess me nts will t a ke pl ace e x ce pt f or t h ose 
s pecifie d at Da y 1 4, 2 8 a n d Da y 6 0 i n t he pr ot o c ol.  
All s u bjects will u n der g o t h e assess me nts s pecifie d f or Da y 1 4 a n d 
Da y 2 8, a n d parti ci pate i n t h e Da y 6 0  tele p h o ne call, e ve n if t h e y are 
disc har ge d fr o m t he h os pit al pri or t o Da y 2 8.  

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M ai n I ncl usi o n 
Criteri a  
1.  S u bject  ( or l e gall y a ut h orize d re pr ese ntati ve) is willi n g a n d 
a ble t o pr o vi de i nf or me d c o nse nt a n d c o m pl y wit h all pr ot oc ol 
re q uire m e nts. 
2.  A grees t o t he c olle cti o n of nas o p har y n g eal s wa bs a n d ve n o us 
bl o o d a n d all ot her pr ot oc ol -s pecifie d pr o ce d ures. 
3.  Male or n o n -pr e g na nt fe male a d ult ≥1 8 y ears of a ge at ti me of 
e nr oll m e nt.  
4.  H os pitaliz e d a n d has l a b orat or y -c o nfir me d i nfecti o n wit h 
S A R S -C o V -2.  
5.  S y m pt o m o nset was ≤1 4  da ys pri or t o S cree ni n g . 
6.  Has S p O 2 < 9 4 % o n r o o m air  
7.  Has at least o n e of res pirat or y r ate > 2 4 br eat hs/ mi n ut e or 
c o u g h 
8.  L u n g i n v ol ve me nt as c o nfir m e d b y ra di o gra p hic i nfiltrates 
o bser ve d o n i ma gi n g (c hest X -ra y, C T sc a n, or a n e q ui vale nt 
test)  
9.  W o me n of c hil d be ari n g p ote ntial (as defi n e d i n (C T F G 2 0 1 4 )) 
m ust ha ve a n e gati ve pre g na n c y test at scre e ni n g a n d a gree t o 
a bsti ne nc e or t he use at le ast o ne of t h e f oll o wi n g hi g hl y 
effecti ve f or ms of c o ntr ace pti o n (wit h a fail ure rate of < 1 % per 
year w he n use d c o nsiste ntl y a n d c orr ectl y) . C o ntra ce pti o n or 
a bsti ne nc e m ust be c o nti n u e d  f or t he d urati o n of t h e st u d y 
f oll o wi n g disc har g e fr o m t h e h os pital, a n d f or u p t o 5 0 da ys 
after t h e last d ose of st u d y dr u g : 
•  c o m bi ne d ( estr o ge n a n d pr o gest o g e n c o nt ai ni n g) h or m o nal 
c o ntrac e pti o n ass ociate d wit h i n hi biti o n of o v ulati o n:  
− oral  
− i ntra va gi nal 
− tra ns der mal 
•  pr o gest o ge n -o nl y h or m o n al c o ntrace pti o n ass oci ate d wit h 
i n hi biti o n of o v ulati o n: 
− oral  
− i njecta bl e 
− i m pla nta bl e 
•  i ntra ut eri ne d e vice 
•  i ntra ut eri ne h or m o ne-rel easi n g s yste m 
•  vasect o mize d p art ner  wit h c o nfir m e d az o os per mia  
All fe males will b e c o nsi dere d of c hil d b eari n g p ote ntial u nl ess 
t he y are p ost me n o pa usal (at l east 1 2 m o nt hs c o nsec uti ve 
a me n orr he a i n t h e a p pr o priate a g e gr o u p wit h o ut ot h er k n o w n 
or s us pecte d ca use) or ha v e bee n st erilize d s ur gi call y (e g, 
bilat eral t u bal li gati o n, h ystere ct o m y, bilateral o o p h orect o m y).  
1 0.  Me n se x uall y a cti v e wit h w o me n of c hil d be ari n g p ot e ntial w h o 
ha ve n ot ha d a vasect o m y m ust a gr ee t o u se a barri er met h o d 
of birt h c o ntr ol d uri n g t h e st u d y f oll o wi n g disc har ge fr o m t he 
h os pital a n d f or u p t o 5 0 da ys aft er t he l ast d ose of st u d y dr u g.  

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M ai n E xcl usi o n 
Criteri a  
1.  Re q uires me c ha ni cal ve ntil ati o n  
2.  C urre nt partici p ati o n i n a n y ot her inter v e nti o n al  st u d y  
3.  A la ni ne tr a nsa mi n ase/as part ate tra nsa mi nase l e vels ≥3 ti mes t h e 
u p per li mit of n or m al ( × U L N) or t ot al bilir u bi n ( T bili) ≥2 × U L N  
4.  L y m p h oc yt e c o u nt < 5 0 0 l y m p h oc ytes/ µ L or he m o gl o bi n 
< 1 1 . 0 g/ d L  
5.  Sta ge 4 se vere c hr o nic ki d n e y disease or r e q uiri n g di al ysis 
(ie, esti mat e d gl o m er ular filtrati o n rate < 3 0)  
6.  A n y ot her c o n diti o n, t hat i n t h e o pi ni o n of t he i n vesti gat or, 
ma y be c a use t o e xcl u de t h e s u bject fr o m t h e st u d y.  
7.  Use of ster oi ds  (e xce pt de x a met has o ne), se nsiti ve C Y P 2 D 6 
s u bstrates, C Y P 2 C i n d ucers, I L-6 ne utr ali zi n g a nti b o dies, I L -6 
rece pt or i n hi bit ors, or a n y i n vesti gati o n al t h era p y. 
8.  Pre g na nc y or breast fe e di n g.  
9.  A ntici pate d tr a nsfer t o a n ot h er h os pital w hic h is n ot a st u d y 
site wit hi n 7 2 h o urs. 
1 0.  K n o w n aller g y  t o P T C 2 9 9 or e x ci pi e nts  
P h ar m ac o ki netics  
At select sites, p har m ac o ki netics ( P K) will be assesse d after t he si n gl e 
d ose ( Da y 1) a n d re peat e d d osi n g Da y 7 a n d 1 4. Bl o o d sa m ples will b e 
c olle cte d o n Da ys 1 a n d 7 at pre-d ose ( 0), a n d 6  h o urs p ost -d ose a n d 
o n  Da y 1 4 at pre -d ose ( 0) a n d 4 h o urs p ost -d ose ( m or ni n g d ose o nl y).  
St u d y Tre at me nt  
P T C 2 9 9 or matc hi n g pla ce b o orall y a d mi nister e d ta blets at a d ose of 
2 0 0  m g t wice p er da y f or Da ys 1 t o 7 f oll o we d 5 0 m g orall y 
a d mi nist ere d o nc e dail y o n Da ys 8 t o 1 4.  
D ur ati o n of 
Tre at me nt  
S u bjects will r ecei ve tre at m e nt f or 1 4 da ys t h e n f oll o w -u p f or 1 4 da ys 
t o gi ve a t otal st u d y d urati o n of 2 8 da ys, wit h a safet y f oll o w-u p 
tele p h o n e call at Da y 6 0. 
S afet y M o nit ori n g  
S u bjects will b e m o nit ore d cl osel y f or A Es a n d la b o r at or y 
a b n or maliti es d uri n g t he st u d y. A n i n d e pe n de nt D S M B will m o nit or 
o n g oi n g res ults t o e ns ure s u bj ect well -bei n g a n d safet y as well as 
st u d y i nte grit y. T he D S M B will m a ke re c o m m e n dati o ns a b o ut earl y 
st u d y cl os ure or c ha n g es t o st u d y ar ms. A d diti o nall y,  an i n de pe n d e nt 
H A C  will o versee t he h e patic safet y of s u bj ects i n t h e st u d y. 
St atistic al Met h o ds  
T he pri m ar y e n d p oi nt is ti me fr o m ra n d o miz ati o n t o res pirat or y 
i m pr o ve m e nt, defi ne d as S p O 2 ≥9 4 % o n r o o m air  s ustai ne d u ntil 
disc har ge fr o m t he h os pit al or t he e n d of t he st u d y ( Da y 2 8) . 
Ka pla n -Meier pl ots of ti me t o res pir at or y i m pr o ve m e nt will b e 
prese nte d. Me di a n ti me t o res pir at or y i m pr o ve m e nt will be esti mate d 
via t he Ka pla n -Mei er pr o d uct li mit met h o d. A t w o -si de d 9 5 % 
c o nfi de nc e i nt er val ( CI)  f or t h e me dia n ti me t o res pir at or y 
i m pr o ve m e nt will be c o m p ute d f or P T C 2 9 9 a n d plac e b o  c o h orts base d 
o n a l o g -l o g tr a nsf or me d CI f or t he s ur vi v or f u n cti o n S(t). Ti me  t o 
res pirat or y i m pr o ve m e nt will be c o m p are d bet wee n treat m e nt gr o u ps 
usi n g stratifi e d l o g -ra n k test. 

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 1 0  of 6 2  
Hazar d rati o a n d c orres p o n di n g t w o -si de d 9 5 % CIs will be esti mate d 
usi n g a C o x pr o p orti o nal haz ar ds m o del, wit h treat m e nt ar m as a 
si n gle c o variat e, stratifie d b y t h e stratific ati o n f act ors. 
Res pirat or y i m pr o ve m e nt  rates at Da ys 7, 1 4, a n d 2 8 will als o be 
esti mate d usi n g Ka pl a n -Meier esti mates o n t he ti m e t o res pirat or y 
i m pr o ve m e nt c ur v e. Ass ociate d t w o -si de d 9 5 % CIs f or eac h tr eat me nt 
gr o u p a n d t he diff ere nce b et wee n t he 2  tr eat me nt gr o u ps will be 
calc ulat e d usi n g Gr ee n w o o d’s f or m ula f or varia n c e deri vati o n.  
S u bjects will b e ra n d o mize d 1: 1 t o P T C 2 9 9  or pl ace b o  (a p pr o xi matel y 
1 9 0 s u bjects i n e ac h c o h ort). T he ra n d o miz ati o n will be stratifie d b y 
a ge ( ≤6 2 vs > 6 2) , re m d esi vir use ( yes vs n o) , a n d de xa met h as o ne use 
( yes vs n o).  
T his is a gr o u p se q ue ntial d esi g n wit h 2 i nteri m a nal yses pla n ne d. T he 
first i nteri m a n al ysis will o nl y assess t he safet y a n d t he trial will n ot be 
st o p pe d f or f utilit y or s u peri orit y of effi cac y . It will be perf or me d after 
t he first 4 0 ra n d o miz e d s u bjects ha v e c o m plet e d Da y  2 8  or 
disc o nti n ue d d u e t o de at h , wit h dr e w  c o nse nt, or wer e l ost-t o-f oll o w-
u p .  
T he sec o n d i nteri m a nal ysis is t o assess f utilit y a n d will be perf or me d 
w he n 5 0 % of res pirat or y i m pr o ve me nt e ve nts ha ve b ee n rea c he d, 
ie, 1 6 3  e ve nts ha ve bee n o bser v e d ( a p pr o xi mat el y  1 9 0 s u bjects).  All 
s u bjects w h o ha ve c o m plete d t hr o u g h Da y 2 8, were disc har ge d wit h 
S p O 2 ≥9 4 % o n r o o m air , wit h dr e w  c o nse nt, die d , were l ost t o 
f oll o w-u p , or t o o k a n y C O VI D-1 9 resc ue t hera p y d uri n g t he st u d y will 
be i ncl u d e d i n t h e i nt eri m a nal ysis. S u bjects w h ose pri mar y e v e nt 
ca n n ot be d eter mi ne d at t he i nteri m c ut, ie, o n g oi n g s u bjects , will n ot 
be i ncl u d e d  i n t h e i nt eri m effica c y a nal ys is. S u bjects w h o die d , 
wit h dre w c o nse nt, were l ost t o f oll o w -u p, or t o o k a n y C O VI D -1 9 
resc ue t her a p y will be ce ns ore d at Da y 2 8. A stratifie d l o g -ra n k test 
will be perf or me d a n d t he haz ar d rati o (tre at m e nt vs place b o) will be 
c o m pare d wit h t he f utilit y b o u n dar y. T h e tr i al m a y b e st o p pe d f or 
f utilit y if t h e haz ar d rati o is less t ha n 1. 0 9 1. T h e f utilit y b o u n dar y is 
base d o n La n -De Mets beta s pe n di n g f u ncti o n ( n o n -bi n di n g o pti o n) 
wit h o verall bet a of 8 0 % . 
T he sa m pl e size was calc ul ate d b ase d o n t he pri mar y e n d p oi nt of ti me 
t o res pirat or y i m pr o ve me nt. It is a ntici pate d t h at t h e me dia n ti m e t o 
res pirat or y i m pr o ve m e nt f or t he plac e b o gr o u p is 1 1 da ys a n d P T C 2 9 9 
treat me nt will de crease it t o 8 da ys, a n i m pr o ve me nt of 3 -da ys. 
S u bjects will b e f oll o we d f or t he fi xe d a m o u nt of ti m e of 2 8 da ys fr o m 
ra n d o miz ati o n ( c orres p o n di n g t o t h e a ntici p ate d i m pr o ve me nt r ates of 
0. 8 2 9 a n d 0. 9 1 2 at Da y 2 8 f or pl ace b o  a n d P T C 2 9 9, res pecti v el y). 
A  t otal of 3 2 6 e v e nts will pr o vi de m or e t ha n 8 0 % of p o wer t o dete ct a 
hazar d rati o of 1. 3 8  at t w o-si de d t y pe I err or of 0. 0 5. A p pr o xi matel y 
3 8 0  s u bjects, i n t otal, will be n ee de d. 
De m o gra p hic a n d baseli ne c har act eristi cs, dis p ositi o n, a n d safet y will 
be s u m mari ze d descri pti vel y b y tre at m e nt gr o u p.  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 1 1  of 6 2  
T A B L E O F C O N T E N T S  
P R O T O C O L I D E N TI FI E R S A N D S T U D Y P E R S O N N E L  ...........................................................2  
P T C T H E R A P E U TI C S P R O T O C O L A P P R O V A L SI G N A T U R E S ..............................................3  
P RI N CI P A L I N V E S TI G A T O R A G R E E M E N T A N D SI G N A T U R E ............................................4  
S Y N O P SI S  ......................................................................................................................................5  
T A B L E O F C O N T E N T S  ...............................................................................................................1 1  
LI S T O F T A B L E S  .........................................................................................................................1 4  
LI S T O F FI G U R E S  .......................................................................................................................1 4  
LI S T O F A B B R E V I A TI O N S A N D D E FI NI TI O N S O F T E R M S ................................................1 5  
1.  
I N T R O D U C TI O N ......................................................................................................1 7  
1. 1.  
St u d y Rati o nale  ...........................................................................................................1 8  
1. 2.  
Ris k/ Be nefit Assess me nt  ............................................................................................1 9  
2.  
S T U D Y O BJ E C TI V E A N D E N D P OI N T S  ................................................................2 0  
2. 1.  
O bjecti v es  ...................................................................................................................2 0  
2. 1. 1.  
Pri mar y O bjecti ve  .......................................................................................................2 0  
2. 1. 2.  
Sec o n dar y O bjecti ves  .................................................................................................2 0  
2. 1. 3.  
E x pl orat or y O bj ecti ves  ...............................................................................................2 0  
2. 2.  
E n d p oi nts  ....................................................................................................................2 0  
2. 2. 1.  
Pri mar y E n d p oi nt  ........................................................................................................2 0  
2. 2. 2.  
Sec o n dar y E n d p oi nts  ..................................................................................................2 0  
2. 2. 3.  
E x pl orat or y E n d p oi nts  ................................................................................................2 1  
3.  
S T U D Y D E SI G N  .......................................................................................................2 1  
3. 1.  
O verall Desi g n  ............................................................................................................2 1  
3. 2.  
J ustificati o n of D ose ...................................................................................................2 2  
3. 3.  
E n d of St u d y Defi niti o n  ..............................................................................................2 6  
4.  
S T U D Y P O P U L A TI O N  .............................................................................................2 6  
4. 1.  
O ver vie w  .....................................................................................................................2 6  
4. 2.  
I ncl usi o n Crit eria ........................................................................................................2 6  
4. 3.  
E xcl usi o n Criteri a  .......................................................................................................2 7  
4. 4.  
Scree n Fail ur es  ............................................................................................................2 8  
4. 5.  
Strate gi es f or Recr uit me nt a n d Ret e nti o n  ...................................................................2 8  
5.  
S T U D Y I N T E R V E N TI O N  ........................................................................................2 8  
5. 1.  
St u d y I nter ve nti o n(s) A d mi nistrati o n  .........................................................................2 8  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 1 2  of 6 2  
5. 1. 1.  
St u d y I nter ve nti o n Descri pti o n  ...................................................................................2 8  
5. 1. 2.  
D osi n g a n d A d mi nistrati o n  .........................................................................................2 8  
5. 2.  
Pre parati o n/ Ha n dli n g/ St ora ge/ Acc o u nta bilit y  ............................................................2 8  
5. 2. 1.  
Acc o u nta bilit y  .............................................................................................................2 8  
5. 2. 2.  
F or m ul ati o n, A p pe ara nc e, Pac ka gi n g, a n d La b eli n g  ..................................................2 9  
5. 3.  
Meas ures t o Mi ni mi ze Bi as: Ra n d o mizati o n a n d Bli n di n g  ........................................2 9  
5. 3. 1.  
E mer ge n c y Pr oce d ure f or U n bli n di n g  ........................................................................2 9  
5. 4.  
St u d y I nter ve nti o n a n d C o m plia n ce  ...........................................................................2 9  
5. 5.  
C o nc o mit a nt T h era p y  .................................................................................................3 0  
6.  
S T U D Y I N T E R V E N TI O N DI S C O N TI N U A TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L  ..................................................................3 0  
6. 1.  
Disc o nti n uati o n of St u d y I nter v e nti o n  ........................................................................3 0  
6. 1. 1.  
Disc o nti n uati o n d ue t o A b n or m al Li ver F u ncti o n  ......................................................3 1  
6. 1. 2.  
Disc o nti n uati o n d ue t o A b n or m al Bl o o d Test Res ults  ...............................................3 1  
6. 2.  
Partici p a nt Disc o nti n uati o n/ Wit h dra wal fr o m t he St u d y ............................................3 2  
6. 3.  
L ost t o F oll o w -u p  .......................................................................................................3 2  
7.  
S T U D Y A S S E S S M E N T A N D P R O C E D U R E S  ........................................................3 3  
7. 1.  
Sc he d ule of E v e nts a n d St u d y Para meters  ..................................................................3 3  
7. 2.  
Effica c y Assess me nts  .................................................................................................3 6  
7. 3.  
P K a n d/ or Ot her Assess me nts  ....................................................................................3 7  
7. 4.  
Safet y Assess me nts  .....................................................................................................3 7  
7. 5.  
A d verse E ve nts a n d Seri o us A d verse E ve nts  .............................................................3 7  
7. 5. 1.  
Defi niti o n of A d verse E ve nts  .....................................................................................3 7  
7. 5. 2.  
Defi niti o n of Seri o us A d verse E ve nts  ........................................................................3 9  
7. 5. 3.  
A d verse E ve nts of S peci al I nter est  .............................................................................4 0  
7. 5. 4.  
U ne x pecte d A d verse E v e nts  .......................................................................................4 0  
7. 5. 5.  
Eliciti n g A d verse E ve nt I nf or m ati o n  ..........................................................................4 0  
7. 5. 6.  
Rec or di n g N o n‑s eri o us A Es a n d S A Es  ......................................................................4 0  
7. 5. 7.  
Descri bi n g A d verse E ve nt Relati o ns hi p t o St u d y Dr u g  .............................................4 1  
7. 5. 8.  
Gra di n g of Se v erit y of A d verse E v e nt  ........................................................................4 1  
7. 5. 9.  
A d verse E ve nt Re p orti n g  ............................................................................................4 2  
7. 5. 1 0.  
Seri o us A d verse E ve nt Re p orti n g  ...............................................................................4 2  
7. 5. 1 1.  
Re p orti n g Pre g na n c y  ..................................................................................................4 3  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 1 3  of 6 2  
7. 5. 1 2.  
P T C T hera pe utics A d verse E ve nt Re p orti n g Re q uir e me nt  ........................................4 4  
8.  
S T A TI S TI C A L C O N SI D E R A TI O N S  .......................................................................4 4  
8. 1.  
Statisti cal H y p ot h eses  .................................................................................................4 4  
8. 2.  
Sa m ple Siz e Deter mi nati o n  ........................................................................................4 4  
8. 3.  
P o p ulati o n f or A nal yses  ..............................................................................................4 5  
8. 4.  
Statisti cal A nal yses  .....................................................................................................4 5  
8. 4. 1.  
Ge ner al A p pr oac h  .......................................................................................................4 5  
8. 4. 2.  
A nal ysis of Pri mar y Effi cac y E n d p oi nts  ....................................................................4 5  
8. 4. 3.  
A nal ysis of Sec o n dar y Effi cac y E n d p oi nts  ................................................................4 6  
8. 4. 4.  
Safet y A nal yses  ..........................................................................................................4 7  
8. 4. 4. 1.  
S u bject Dis p ositi o n  .....................................................................................................4 7  
8. 4. 4. 2.  
Me dical Hist or y a n d Pri or Me dic ati o n  .......................................................................4 7  
8. 4. 4. 3.  
E xte nt of E x p os ure a n d Tre at m e nt C o m plia n ce  .........................................................4 7  
8. 4. 4. 4.  
A d verse E ve nts  ...........................................................................................................4 7  
8. 4. 4. 5.  
La b orat or y Par a meters  ................................................................................................4 7  
8. 4. 5.  
Baseli ne Descri pti v e Statistics  ....................................................................................4 7  
8. 4. 6.  
Pla n ne d I nteri m A nal yses  ...........................................................................................4 8  
8. 4. 7.  
S u b gr o u p A nal yses  .....................................................................................................4 8  
8. 4. 8.  
E x pl orat or y A nal yses  ..................................................................................................4 8  
9.  
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 A L 
C O N SI D E R A TI O N S  ..................................................................................................4 8  
9. 1.  
Re g ulat or y, Et hi cal, a n d St u d y O versi g ht C o nsi derati o ns  .........................................4 8  
9. 1. 1.  
I nf or me d C o nse nt Pr ocess ..........................................................................................4 8  
9. 1. 2.  
St u d y Disc o nti n uati o n a n d Cl os ure  ............................................................................4 9  
9. 1. 3.  
C o nfi de nti alit y a n d Pri va c y  ........................................................................................4 9  
9. 1. 4.  
F ut ure use of St or e d S peci me ns a n d Data  ..................................................................4 9  
9. 1. 5.  
Safet y O versi g ht  .........................................................................................................5 0  
9. 1. 5. 1.  
Data a n d Safet y M o nit ori n g B o ar d  .............................................................................5 0  
9. 1. 5. 2.  
He patic A d vis or y Safet y C o m mitt ee  ..........................................................................5 1  
9. 1. 6.  
Cli nic al M o nit ori n g  ....................................................................................................5 1  
9. 1. 7.  
Q ualit y Ass ura nce a n d Q ualit y C o ntr ol  ......................................................................5 2  
9. 1. 8.  
Data Ha n dli n g a n d Rec or d Kee pi n g  ...........................................................................5 2  
9. 1. 9.  
Pr ot oc ol De viati o ns  ....................................................................................................5 2  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 1 4  of 6 2  
9. 1. 1 0.  
P u blicati o n a n d Dat a S hari n g P oli c y  ..........................................................................5 3  
9. 2.  
Pr ot oc ol A me n d m e nt Hist or y  .....................................................................................5 4  
9. 2. 1.  
Versi o n 2. 0: 0 8 Ma y 2 0 2 0  ..........................................................................................5 4  
9. 2. 2.  
Versi o n 3. 0: 0 5 J u ne 2 0 2 0  ..........................................................................................5 6  
9. 2. 3.  
Versi o n 4. 0: 2 3 J ul y 2 0 2 0  ...........................................................................................5 7  
9. 2. 4.  
Versi o n 5. 0: 0 8 Oct o ber 2 0 2 0  .....................................................................................5 8  
9. 2. 5.  
Versi o n 6. 0: 1 8 Dece m b er 2 0 2 0  .................................................................................5 8  
9. 2. 6.  
Versi o n 7. 0: 0 2 J u ne 2 0 2 1  ..........................................................................................5 9  
1 0.  
R E F E R E N C E S  ...........................................................................................................6 0  
 
LI S T O F  T A B L E S  
Ta ble  1:  
S u m mar y of P K a n d P D Para meters  ...........................................................................2 3  
Ta ble  2:  
S u m mar y of P T C 2 9 9 P har ma c o ki netics i n He alt h y V ol u nteers w he n 
A d mi nistere d wit h t he C a ps ule F or m ul ati o n ( ~ 2. 5 x of t he Bi oa v ail a bilit y of 
t he Ta blet F or m ulati o n) ( St u d y P T C 2 9 9-O N C -0 0 2 -H V)  ...........................................2 5  
Ta ble  3:  
Sc he d ule of E v e nts  .....................................................................................................3 3  
Ta ble 4:  
La b orat or y Par a meters t o be Assesse d  .......................................................................3 6  
Ta ble  5:  
Relati o ns hi p of St u d y Dr u g t o A d verse E ve nt Rel ati o ns hi p  ......................................4 1  
Ta ble  6:  
Gra di n g of A d verse E ve nt Se verit y Gra de  .................................................................4 2  
Ta ble  7:  
I n vesti gat or Site Re q uire m e nts f or Re p orti n g A d vers e E ve nts ..................................4 2  
 
LI S T O F FI G U R E S  
Fi g ure  1:  
Plas ma D H O a n d P T C 2 9 9 C o nce ntrati o ns aft er a Si n gle Oral D ose of 
P T C 2 9 9  .......................................................................................................................2 3  
Fi g ure  2:  
P T C 2 9 9 I n hi bits D H O D H i n Patie nts wit h Ne ur ofi br o mat osis T y pe 2 
T u m ors  ........................................................................................................................2 4  
 
 

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 1 5  of 6 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 or 
S p e ci ali z e d T er m  
E x pl a n ati o n  
A E  
A d v er s e e v e nt  
A E SI  
A d v er s e e v e nt of s p e ci al i nt er e st  
A L P  
Al k ali n e p h o s p h at a s e  
A L T  
Al a ni n e tr a n s a mi n a s e  
A M L  
A c ut e m y el oi d l e u k e mi a  
a P T T  
A cti v at e d p arti al t hr o m b o pl a sti n ti m e  
A R D S  
A c ut e r e s pir at or y di str e s s s y n dr o m e  
A S T  
A s p art at e tr a n s a mi n a s e 
A U C  
Ar e a u n d er t h e c ur v e  
A U C 0 -l a st 
Ar e a u n d er t h e c ur v e fr o m ti m e 0 t o l a st m e a s ur e m e nt 
B C R P  
Br e a st c a n c er r e si st a n c e pr ot ei n 
BI D  
T hr e e ti m e s p er d a y  
β H C G  
b et a h u m a n c h ori o ni c g o n a d otr o pi n  
C B C  
C o m pl et e bl o o d c o u nt  
CI  
C o nfi d e n c e i nt er v al  
C m a x  
m a xi m u m o b s er v e d c o n c e ntr ati o n  
C O VI D -1 9  
C or o n a vir u s di s e a s e 2 0 1 9  
C P K  
Cr e ati n e p h o s p h o ki n a s e  
C R F  
C a s e r e p ort f or m  
C R O  
C o ntr a ct R e s e ar c h Or g a ni z ati o n  
C R P  
C -r e a cti v e pr ot ei n 
D H O  
Di h y dr o or ot at e  
D H O D H  
Di h y dr o or ot at e d e h y dr o g e n a s e  
DI LI  
Dr u g -i n d u c e d li v er i nj ur y 
D S M B  
D at a a n d s af et y m o nit ori n g b o ar d  
E C  
Et hi c s c o m mitt e e  
e C R F  
El e ctr o ni c c a s e r e p ort f or m  
G C P  
G o o d L a b or at or y Pr a cti c e  
G -C S F  
Gr a n ul o c yt e -c ol o n y sti m ul ati n g f a ct or  
G G T  
G a m m a -gl ut a m yl tr a n s p e pti d a s e  
E D C  
El e ctr o ni c d at a c a pt ur e s y st e m  
H A C  
H e p ati c a d vi s or y s af et y c o m mitt e e  
H V  
H e alt h y v ol u nt e er  
I C F 
I nf or m e d c o n s e nt f or m 
I C H 
I nt er n ati o n al C o u n cil f or H ar m o ni s ati o n  
I C U 
Int e n si v e c ar e u nit  
I L 
I nt erl e u ki n 
I N R 
I nt er n ati o n al n or m ali z e d r ati o 
I P-1 0  
I nt erf er o n g a m m a-i n d u c e d pr ot ei n 1 0 
I R B 
I n stit 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 F T s  
Li v er f u n cti o n t e st s  
L D H  
L a ct at e d e h y dr o g e n a s e  
M C P  
M o n o c yt e c h e m o attr a ct a nt pr ot ei n  
M e d D R A  
M e di c al Di cti o n ar y f or R e g ul at or y A cti viti e s  
MI P  
M a cr o p h a g e i nfl a m m at or y pr ot ei n  
P D  
P h ar m a c o d y n a mi c s  
P K  
P h ar m a c o ki n eti c  
P T C  
P T C T h er a p e uti c s  
Q D  
O n c e d ail y  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 1 6  of 6 2  
A b br e vi ati o n or 
S p e ci ali z e d T er m  
E x pl a n ati o n  
R SI  
R ef er e n c e S af et y I nf or m ati o n  
R N A  
Ri b o n u cl ei c a ci d  
S A E  
S e v er e a d v er s e e v e nt  
S A P  
St ati sti c al a n al y si s pl a n  
S O C  
St a n d ar d of c ar e  
S O P  
St a n d ar d O p er ati n g Pr o c e d ur e  
S p O 2  
P eri p h er al o x y g e n s at ur ati o n  
t1/ 2  
H alf -lif e 
T bili  
T ot al bilir u bi n  
T E A E s  
Tr e at m e nt -e m er g e nt a d v er s e e v e nt s  
TI D  
T hr e e ti m e s p er d a y  
T m a x  
Ti m e t o C m a x  
T N F -α  
T u m or n e cr o si s f a ct or -al p h a  
U L N  
U p p er li mit s of n or m al  
V E G F  
V a s c ul ar e n d ot h eli al gr o wt h f a ct or  
W B C  
W hit e bl o o d c ell  
W O C B P  
W o m e n of c hil d b e ari n g p ot e nti al  
 
 
 

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 1 7  of 6 2  
1.  
I N T R O D U C TI O N 
Si nce t he first patie nt wit h a p ne u m o nia of u n k n o w n ori gi n i n l ate De ce m ber 2 0 1 9 i n W u ha n 
Cit y, C hi na, a ne w c or o na vir us, desi g nate d S A R S -C o V -2, has res ulte d i n a r a pi dl y s prea di n g 
w orl d -wi de pa n de mic of res pirat or y ill ness ter m e d c or o na vir us disease 2 0 1 9 ( C O VI D-1 9). 
S A R S -C o V -2 is a p ositi ve se nse , ri b o n uclei c aci d ( R N A) vir us of z o o n otic ori gi n a n d is a 
me m ber of t he c or o na vir us fa mil y. D ue t o its n o velt y a n d t he a p p are nt lac k of p o p ul ati o n or 
gr o u p i m m u n it y, C O VI D-1 9 has bee n s prea di n g ra pi dl y i n ma n y c o u ntri es acr oss t he gl o be 
ca usi n g great har m t o h u ma n he alt h, ec o n o mic a cti vit y, a n d disr u pti n g t he s oci al fa bric o n ma n y 
le vels (W a n g 2 0 2 0a ). Si nce it was first descri be d i n N o ve m ber 2 0 1 9, C O VI D -1 9 has ra pi dl y 
s prea d acr oss t he gl o b e a n d milli o ns of pe o ple ha v e bec o me i nfecte d. 
All a ges are s usce pti bl e t o i nfe cti o n wit h S A R S -C o V -2 (C he n g 2 0 2 0 , Li 2 0 2 0 ). T h e cli nical 
feat ures of C O VI D-1 9 are varie d, r a n gi n g fr o m a n as y m pt o matic st ate t o ac ute res pirat or y 
distress s y n dr o me ( A R D S), m ulti -o r ga n d ysf u ncti o n, a n d deat h (C h e n 2 0 2 0a , H ua n g 2 0 2 0 , 
Li u  2 0 2 0a , W a n g 2 0 2 0 b ). Acc or di n g t o c urre nt a nal yses, a b o ut 8 0 % of t he c ases res ol ve wit h at 
h o me car e a n d s u p p orti n g t hera p y a n d 2 0 % r e q uire h os pitali zati o n of w hic h 2 5 % t o 3 0 % d e vel o p 
se vere res pirat or y c o m plicati o ns. T he o v erall fat alit y fr o m C O VI D -1 9 is esti mate d t o ra n ge fr o m 
1 % t o 5 % wit h a hi g h e r ris k of deat h i n t he el derl y a n d pers o ns wit h u n derl yi n g c o m or bi dities 
( 5 0 % t o 7 0 % of fatal cases) (C E B M 2 0 2 0 , C or o na vir us O ut brea k 2 0 2 0 ). 
C O VI D -1 9 ca n be br oa dl y di vi de d i nt o 3 sta g es (S hi 2 0 2 0 , Si d di qi 2 0 2 0 ): 
•  A n as y m pt o matic i n c u bati o n peri o d;  
•  N o n -se vere peri o d of earl y sta ge t y pifi e d b y ra pi d viral pr olif erati o n; 
•  Se vere res pirat or y s y m pt o m atic st a ge of t h e disease t y pifie d b y a rise i n i nfla m mat or y 
c yt o ki nes a n d t he i nfl ue nce of c o m or bi diti es o n dise ase pr o gressi o n a n d pr o g n osis.  
T he c o m m o n cli nic al feat ures of C O VI D -1 9 i ncl u de fe ver, c o u g h, s ore t hr oat, hea d ac he, f ati g u e, 
m yal gi a, a n d s h ort ness of breat h. I n a s u bset of patie nts, b y t he e n d of t h e first wee k, t he disease 
ca n pr o gress t o p ne u m o nia, res pirat or y fail ure, or ga n fail ure, a n d deat h. S A R S C o V -2 tar gets 
cili ate d cells t hat are s u bse q ue ntl y s he d. T he dise ase pr o gressi o n is als o ass ociat e d wit h e xtre me 
rise i n i nfl a m m at or y c yt o ki nes i n cl u di n g i nterl e u ki n (I L)-2, I L -7, I L -1 0, gra n ul o c yte -c ol o n y 
sti m ulati n g fa ct or ( G-C S F), i nterfer o n ga m ma -i n d uc e d pr otei n 1 0 (I P-1 0), m o n o c yte 
c he m oattra cta nt pr o tei n ( M C P) 1, ma cr o p ha ge i nfla m mat or y pr ot ei n ( MI P) 1 A, t u m or necr osis 
fact or al p ha ( T N F-α), a n d v asc ular e n d ot heli al gr o wt h fact or  ( V E G F) (C h e n 2 0 2 0a , 
H ua n g  2 0 2 0 ). B ot h I L-6 a n d I L -1 7 h a v e bee n i m plic ate d i n A R D S (Wa n g 2 0 2 0 b , X u 2 0 2 0 ). 
Le vels of I L -6 a p pear t o pla y a n i m p ort a nt r ol e i n C O VI D -1 9 disease se verit y as t here is str o n g 
e vi de nc e t hat I L -6 pea k le vels are ass oci ate d wit h se verit y of p ul m o nar y c o m pli cati o ns 
(R ussell  2 0 2 0 ). 
T he h y per -i n d u cti o n of pr o-i nfla m mat or y c yt o ki n es - als o referre d t o as a “c yt o ki ne st or m” or 
c yt o ki ne r ele ase s y n dr o me - is c o m m o n i n a c ute viral i nfecti o ns a n d ca n lea d t o tiss ue da ma ge 
a n d p ul m o nar y p at h ol o g y (Li u 2 0 2 0 b ). V E G F, w hi c h pla ys a r ole i n t he p at h o ge nesis of A R Ds, 
has als o bee n f o u n d t o b e i ncre ase d i n patie nts wit h C O VI D -1 9 (Li u 2 0 2 0 b ) T he vi ral l oa d of 
S A R S -C o V -2 detecte d i n t h e patie nt’s res pirat or y tra ct is p ositi v el y li n ke d t o l u n g disease 
se verit y (Li u 2 0 2 0 b ). 

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 1 8  of 6 2  
P T C 2 9 9  (e m v o d o dstat) is a n orall y a vaila ble i n hi bit or of d i h y dr o or otat e de h y dr o ge nase 
(D H O D H ), a ke y e nz y me i n d e n o v o p yri mi di ne n u cle oti d e s y nt hesis. I n hi biti o n of D H O D H 
res ults i n t he d e pleti o n of p yri mi di n e n ucle oti des i n r a pi dl y di vi di n g c ells, l ea di n g t o a G 1/ S 
p hase cell c ycle arrest a n d s u bse q ue nt diff ere ntiati o n or cell d eat h. T heref ore, b y li miti n g h ost 
p yri mi di n e n ucl e oti d e le v els, P T C 2 9 9 ca n arr est viral R N A re plicati o n, re d u ce viral l oa d, a n d 
re d uce c yt o ki ne release. 
C o m p o u n ds t hat i n hi bit D H O D H e nz y me a cti vit y ha ve bee n s h o w n t o ha ve br oa d -s pe ctr u m 
a nti vir al a cti vit y  (L u cas -H o ura ni 2 0 1 5 , M u nier -L e h ma n n 2 0 1 5 , Le wis 2 0 1 6 , Die dric hs -M o hri n g 
2 0 1 8 , L olli 2 0 1 8 , S y kes 2 0 1 8 , C he n 2 0 1 9 , Mei -ji a o 2 0 1 9, Xi o n g 2 0 2 0 ). T his is d ue t o t h e ce ntral 
r ole of D H O D H  i n p yri mi di ne n ucle oti de  s y nt hesis a n d t he hi g h ne e d f or ne w p yri mi di ne 
n ucle oti de s y nt hesis i n viral  R N A  re plicati o n. T he D H O D H i n hi bit ors are parti c ularl y acti ve 
a gai nst R N A vir uses of b ot h p ositi v e a n d ne g ati ve stra n d ge n o me p olarit y a n d ha ve s h o w n 
effica c y a gai nst c or o na vir uses a n d a n u m ber of ot her res pirat or y R N A vir uses (H off ma n n 2 0 1 1 , 
Wa n g 2 0 1 1 , L uc as -H o ura ni 2 0 1 3 , Orti z -Ria n o 2 0 1 4 , C he u n g 2 0 1 7 , L ucas -H o ura ni 2 0 1 7 , 
L ut hra  2 0 1 8 , Ya n g 2 0 1 8 , C h e n 2 0 1 9 , Xi o n g 2 0 2 0 ). As D H O DH i n hi bit ors tar get a h ost pr otei n, 
t he y are e x pect e d t o retai n a nti viral acti vit y a gai nst all strai ns of S A R S-C o V -2  a n d mi ni mize t he 
e mer ge n ce of viral resista n ce . 
I n a d diti o n t o t heir p ote ntial a nti viral effects, D H O D H i n hi bit ors als o s u p press t he e x cessi ve 
i m m u ne r es p o nse c o m m o n t o viral i nfecti o ns w hic h res ults fr o m i ncr ease d c yt o ki ne e x pr essi o n 
(c yt o ki ne st or m) (Xi o n g 2 0 2 0 ). T his h y pera cti v e i m m u ne res p o nse res ults i n a n e xtre me 
i nfla m mat or y r es p o nse, res ulti n g i n p ul m o n ar y a n d m ulti-or g a n d ysf u ncti o n a n d da m a ge, 
ulti m atel y le a di n g t o m ulti ple or g a n fail ur e. I n t he l u n g, t he i nfl a m m at or y res p o nse ca n lea d t o 
fatal p n e u m o ni a, p ul m o n ar y i nfiltrati o n a n d d o w n-strea m fi br osis t h at c a n res ult i n t he ne e d f or 
ve ntil at or y s u p p ort. L u n g i nfla m mati o n is t h e lea di n g ca use of m ort alit y i n S A R S -C o V -2 
i nfecti o n. T her ef ore, P T C 2 9 9 ma y n ot o nl y aff ect vir al re plicati o n, b ut ca n pr o vi de pr otecti o n 
a gai nst t h e h y peri nfla m mat or y pr oc ess t hat u n der pi ns  vir us -relate d m ortalit y. 
Pre -cli ni cal d ata i n dicate P T C 2 9 9 i n hi bits a r a n ge of R N A vir uses a n d s u p presses h y per c yt o ki ne 
e x pressi o n. P T C 2 9 9 has bee n e xte nsi vel y e val u ate d i n 9 c o m plete d cli ni cal st u dies ; 5 were i n 
o nc ol o g y ( n = 1 3 4) a n d 4 were i n healt h y v o l u nteers (n = 1 6 9 ). A f urt her st u d y i n o nc ol o g y p ati e nts 
is o n g oi n g. Acr oss t hese st u dies, P T C 2 9 9 was ge ner all y well -t ol erat e d o ver a ra n g e of d osi n g 
re gi me ns. 
1. 1.  
St u d y R ati o n ale  
T he rati o nal e t o assess P T C 2 9 9 f or t he tre at m e nt of C O VI D -1 9 is base d o n e x peri me ntall y 
vali date d e vi de nce of P T C 2 9 9’s a bilit y t o t ar get t w o ke y as pects of C O VI D -1 9 pat h o ge nesis: 
1)  i n hi biti o n of D H O D H re d uces S A R S-C o V -2 re plicati o n (Xi o n g 2 0 2 0 ) a n d 2) P T C 2 9 9 i n hi bits 
e xcessi ve c yt o ki ne pr o d ucti o n ass oci ate d wit h viral i nfecti o ns (Xi o n g 2 0 2 0 ). 
P T C 2 9 9, si milar t o ot her D H O D H i n hi bit ors, de m o nstrates br oa d -s pectr u m a nti viral acti vit y i n 
vitr o i n hi bit i n g b ot h p ositi v e - a n d ne g ati v e -se nse R N A vir uses ( P T C 2 9 9-2 0 2 0 -0 0 7, 
P T C 2 9 9 -2 0 2 0 -0 0 9, a n d P T C 2 9 9 -2 0 2 0 -0 1 1). Im p orta ntl y , P T C 2 9 9 i n hi bits S A R S -C o V -2  i n cell 
c ult ure m o dels ( data o n file).  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 1 9  of 6 2  
D H O D H  i n hi bit ors als o atte n uate c yt o ki ne st or ms t h at ca n si g nific a ntl y c o ntri b ute t o p ul m o nar y 
pat h ol o g y, or ga n f ail ur e, a n d deat h i n vir al i nf ecti o ns, s pecific all y wit h S A R S -C o V -2 
(Y os hi ka wa 2 0 0 9 , Xi o n g 2 0 2 0 ). Le vels of I L-2, I L -7, I L -1 0, G -C S F , I P-1 0, M C P -1, MI P -1 A, 
a n d T N F were f o u n d t o be hi g h er i n C O VI D -1 9 pati e nts i n t he i nte nsi v e care u nit ( I C U) t ha n i n 
t h ose pati e nts  n ot i n t he I C U , i n di cati n g t hat t hese c yt o ki nes ma y b e s pecific mar k ers of se vere 
disease  (H ua n g 2 0 2 0 ). T he eff ect of P T C 2 9 9 o n c yt o ki ne pr o d ucti o n was assesse d usi n g 
Bi o M A P pr ofili n g ( Bi o See k, n o w part of E ur ofi ns) . P T C 2 9 9 was f o u n d t o be a p ote nt i n hi bit or 
of i m m u n o m o d ulat or y a n d i nfl a m m ati o n -relat e d pr o cesses . C o m pare d wit h v e hicle c o ntr ol, 
P T C 2 9 9 res ulte d i n:  
•  Decreases i n i m m u n o m o d ulat or y-ass oci ate d pr otei ns: C D 4 0, s ol u ble (s)I g G, sI L -1 7 A, 
sI L-1 7 F, sI L -6, sI L -2, sI L -1 0  
•  Decreases i n i nfla m mati o n -r elate d pr ot ei ns: M C P-1, I L -8, a n d s T N F -α  
•  Decreases i n tiss ue re m o deli n g pr otei ns: M M P -1  a n d s V E G F  
T he str o n g rati o nal e s u p p orti n g t h e de vel o p me nt of P T C 2 9 9 f or t he tre at m e nt of C O VI D -1 9 is 
base d o n t he f oll o wi n g reas o ns:  
•  P T C 2 9 9 is a n i n hi bit or of cell ul ar D H O D H e nz y me acti vit y.  
− D H O D H i n hi bit ors ha ve be e n s h o w n t o i n hi bit S A R S -C o V -2 re plicati o n  
(Xi o n g  2 0 2 0 ). 
•  P T C 2 9 9 has de m o nstrat e d i n hi biti o n of S A R S -C o V -2 re plic ati o n i n vitr o  
•  P T C 2 9 9 i n hi bits a h ost cell -pr otei n, a n d si milar t o ot her h ost -tar geti n g a nti virals, has 
br oa d a nti viral acti vit y.  
− H ost -tar geti n g a nti virals ha ve a d va nt a ges o ver dir ect vir us-acti n g a nti virals as 
t he y are n ot vir us-s pecific –  he nc e t he y ca n re mai n  effecti v e e ve n if t he vir us 
m utat es, t h us mi ni mizi n g t he e mer g e nce of vir al resista nce.  
•  P T C 2 9 9 i n hi bits c yt o ki ne st or ms d ue t o vir al i nf ecti o n t hat c a n ca use tiss ue da ma g e, 
p ne u m o nia, a n d or ga n fail ure.  
− P T C 2 9 9 re d uces le v els of I L -6 al o n g wit h ot her c yt o ki nes; el e vat e d le vels of I L -6 
are p ositi v el y ass oci ate d wit h se verit y of p ul m o nar y c o m pli cati o ns  
T o date, t here are n o s pecific t h era pe utic a ge nts f or C O VI D -1 9 a n d c urre ntl y treat me nt is 
s u p p orti ve a n d base d o n s y m pt o mat ol o g y (C he n 2 0 2 0 b , Ji n 2 0 2 0). A t hera pe utic a ge nt t hat 
tar gets b ot h viral r e pli cati o n a n d t he h y p er-rea cti v e i m m u ne res p o nse w o ul d offer a hi g hl y 
desira ble treat me nt f or C O VI D -1 9 ma na g e me nt.  
1. 2.  
Ris k/ Be nefit Assess me nt  
E xte nsi ve cli nical k n o wle d ge e xists f or P T C 2 9 9 as it has bee n e val uate d i n > 3 0 0 s u bje cts i n 
9  c o m plete d cli ni cal st u dies. I n ge neral, t hr o u g h o ut t his pri or cli nical e x perie nce, P T C 2 9 9 was 
well -t ol erat e d wit h mi ni m al a n d m a na ge a ble si d e-eff ects. St u d y P T C 2 9 9 -VI R -0 1 5 -C O V 1 9 will 
ha ve a d ata a n d safet y m o nit ori n g b oar d  (D S M B ) t hat will cl osel y m o nit or t h e safet y of p atie nts. 
I n a d diti o n, a n i n de p e n de nt H e patic A d vis or y S afet y C o m mittee ( H A C) will  r e vie w all m ar kers 
of  p ossi ble  li ver t o xicit y. 

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 2 0  of 6 2  
T he C O VI D -1 9 pa n de mic is a lar ge , ac ut e u n met me dical n ee d. T h e mec h a nis m of a cti o n of 
P T C 2 9 9 a n d t he f i n di n gs t hat it: a) has  br oa d -s pectr u m a nti viral acti vit y a n d i n hi bits 
S A R S -C o V -2  re plicati o n; b ) r e d uces c yt o ki ne st or ms; a n d c) is well-t oler ate d i n dicate t h ere is a 
p ositi ve be n efit/ris k pr ofil e f or e val u ati n g t he dr u g i n patie nts wit h C O VI D -1 9.  
2.  
S T U D Y O B J E C TI V E A N D E N D P OI N T S  
2. 1.  
O bjecti ves  
2. 1. 1.  
Pri m ar y O bjecti v e  
T he pri m ar y o bje cti ve of t he st u d y is t o e val u ate t he cli ni cal effica c y of P T C 2 9 9 c o m p are d wit h 
place b o assesse d b y ti me t o res pirat or y i m pro ve me nt  i n a d ult s u bj ects h os pit ali ze d wit h 
C O VI D -1 9 . 
2. 1. 2.  
Sec o n d ar y O bjecti ves  
Sec o n dar y o bje cti v es of t he st u d y are as f oll o ws:  
•  T o e val u ate t he cli nic al effica c y of P T C 2 9 9 c o m p are d wit h plac e b o , as assesse d b y 
res pirat or y f u ncti o n, i m m u ne res p o nse, l e n gt h of h os pitalizati o n, a n d m ortalit y.  
•  T o e val u ate t he safet y of P T C 2 9 9 as assesse d b y dr u g relat e d a d verse e v e nts.  
2. 1. 3.  
E x pl or at or y O bjecti ves  
T here ar e n o e x pl orat or y o bje cti v es i n t his st u d y.  
2. 2.  
E n d p oi nts  
2. 2. 1.  
Pri m ar y E n d p oi nt  
T he pri m ar y e n d p oi nt is t he ti m e fr o m ra n d o mizati o n t o res pirat or y i m pr o ve me nt, defi ne d as 
peri p heral o x y ge n sat urati o n ( S p O 2) ≥9 4 % o n r o o m air  s ustai ne d u ntil disc har ge fr o m t he 
h os pital  or t h e e n d of t h e st u d y ( Da y 2 8). 
2. 2. 2.  
Sec o n d ar y E n d p oi nts  
Sec o n dar y e n d p oi nts of t he st u d y are as f oll o ws:  
•  T he pr o p orti o n of s u bj ects re q uiri n g i n vasi v e ve ntilati o n at a n y p oi nt d uri n g t he st u d y  
•  T he pr o p orti o n of s u bj ects re q uiri n g s u p ple m e ntal o x y ge n or n o n -i n vasi ve v e ntilati o n 
at a n y p oi nt d uri n g t h e st u d y i n s u bje cts w h o di d n ot re q uire s u p ple me nt al o x y ge n at 
baseli ne  
•  T i me fr o m ra n d o mizati o n t o def er vesce n ce i n s u bj ects prese nti n g wit h f e ver at 
e nr oll m e nt ( t e m perat ure of ≥3 7. 6℃ a xilla, ≥3 8. 0 ℃ oral, or ≥3 8. 6° C t y m pa ni c or 
rectal) 
•  Ti me fr o m ra n d o mizati o n t o res pir at or y rate ≤2 4 br e at hs/ mi n ute o n r o o m air  
•  Ti me fr o m ra n d o mizati o n t o c o u g h r e p orte d as mil d or a bse nt (o n a scale of se vere, 
m o derat e, mil d, a bse nt,  i n t h ose wit h c o u g h at e nr oll me nt rate d se vere or m o derate) 

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 2 1  of 6 2  
•  Ti me fr o m ra n d o mizati o n t o d ys p nea r e p orte d as mil d or a bse nt ( o n a scale of se vere, 
m o derat e, mil d, a bse nt, i n t h ose wit h d ys p nea at e nr oll me nt rat e d as se vere or 
m o derat e)  
•  Atte n uati o n of i m m u ne res p o nses as i n di cate d b y:  
− re d ucti o n i n c yt o ki ne l e vels, p ote ntiall y i n cl u di n g i nt erle u ki n (I L)-2, I L -6, I L -7, 
I L-1 7, G -C S F, I P -1 0, M C P -1, MI P 1 -α, a n d T N F -α  
− re d ucti o n i n le v els of ac ut e p hase pr ot ei ns, p ote ntiall y i ncl u di n g f erriti n, 
C -reacti ve pr ot ei n, D-di mer, a n d car diac tr o p o ni n   
− n or mali zati o n i n t h e c o m plete bl o o d c o u nt  
− c ha n ges i n o t h er la b orat or y para met ers p ote ntiall y i n cl u di n g de creases i n lact ate 
de h y dr o ge nase, pr ot hr o m bi n ti me, al b u mi n  
•  Re d ucti o n i n viral l oa d  
•  D urati o n of h os pitaliz ati o n m eas ure d i n d a ys  
•  M ortalit y at Da y 2 8  
•  O verall safet y pr ofile c hara cterize d b y t y pe, fre q ue n c y, se verit y, ti mi n g, a n d 
relati o ns hi p t o st u d y tr eat me nt of a n y a d verse e v e nts ( A Es) or la b orat or y 
a b n or maliti es.  
2. 2. 3.  
E x pl or at or y E n d p oi nts  
T here ar e n o e x pl orat or y e n d p oi nts i n t his st u d y.  
3.  
S T U D Y D E SI G N  
3. 1.  
O ver all Desi g n  
T his is a ra n d o mize d, d o u ble -bli n d, plac e b o -c o ntr oll e d, m ultice nter 2 8 -da y st u d y , wit h a safet y 
f oll o w-u p tel e p h o ne c all at Da y 6 0 .  
T he st u d y p o p ulati o n is h os pit ali ze d a d ult s u bje cts wit h c o nfir me d p ne u m o nia, dia g n ose d wit h 
C O VI D -1 9, a n d n ot re q uiri n g me c ha nic al ve ntil ati o n.  F or t he p ur p oses of e nr oll m e nt of s u bje cts 
i nt o t he st u d y, “ h os pitaliz e d patie nts” will i ncl u de a n y C O VI D-1 9 patie nt eit her a d mitte d or 
u n der o bser vati o n i n t he h os pital f or a c o nti n u o us peri o d of 2 4 h o urs or m ore w h o ot her wise 
f ulfills t h e eli gibilit y  crit eria.   
S u bjects will b e ra n d o mize d 1: 1 t o P T C 2 9 9 tr eat me nt or plac e b o  usi n g a c e ntral r a n d o mi zati o n 
pr ocess , wit h a p pr o xi m atel y 1 9 0  s u bjects i n eac h c o h ort. T he ra n d o miz ati o n will be stratifi e d b y 
a ge ( ≤6 2  vs > 6 2) , re m d esi vir use ( yes vs n o ), a n d de xa met h as o ne use ( yes vs n o).  All s u bjects 
will als o re cei v e s ta n dar d of c are  ( S O C), defi ne d as t he S O C per l ocal writte n p olicies or 
g ui deli n es. T he use of ster oi ds  (e xce pt d e xa m et has o ne), se nsiti ve C Y P 2 D 6 s u bstrates, C Y P 2 C 
i n d ucers, I L-6 ne utralizi n g a nti b o di es , I L-6 r ec e pt or i n hi bit ors , a n d a n y i n vesti gati o nal t hera pi es 
are pr o hi bite d.  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
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P a ge 2 2  of 6 2  
F oll o wi n g eli gi bilit y scre e ni n g a n d e nr oll me nt, s u bj e cts will re cei v e oral t a blets c o ntai ni n g 
P T C 2 9 9 or matc h i n g pla ce b o 2 0 0 m g t wice dail y ( BI D) ( m or ni n g a n d e ve ni n g) o n Da ys 1 t o 7 
a nd 5 0 m g o nce d ail y ( Q D)  i n t h e m or ni n g o n Da ys 8 t o 1 4.  
A p pr o xi matel y 4 0 s u bjects ( 2 0 i n eac h ar m) will be e nr olle d i niti all y, e nr oll me nt will t h e n halt, 
a n d a n i nt eri m a nal ysis will be perf or m e d t o assess safet y. N o f or mal statistical testi n g will b e 
perf or me d at t he i nteri m  a nal ysis . A n i n de pe n de nt data safet y m o nit ori n g b oar d (D S M B ) a n d a n 
i n de pe n de nt H A C will re vi e w a vail a ble d ata  f or t he 4 0 s u bjects. E nr oll me nt will c o nti n u e if 
t here ar e n o safet y c o n cer ns.  
A sec o n d i nteri m a nal ysis is pla n ne d t o assess f utilit y. It will be p erf or me d w he n 5 0 % of 
res pirat or y i m pr o ve m e nt e ve nts ha ve be e n rea c he d, ie, 1 63  e ve nts ha v e bee n o bser ve d 
(a p pr o xi matel y 1 9 0 s u bj ects). 
S u bjects will b e assesse d dail y w hile h os pit ali ze d. All s u bjects will u n der g o effica c y, safe t y, a n d 
la b orat or y assess me nts as s u m mari ze d  i n T a ble  3 . T here will b e a f oll o w -u p tele p h o n e call at 
Da y 6 0 t o assess A Es, S A Es, a n d deat hs.  
F or s u bjects w h o are disc har ge d fr o m t he h os pital pri or t o Da y 2 8:  
•  If S p O2 is < 9 4 %, S p O 2 meas ure me nts will be ta ke n dail y u ntil Da y 2 8  
•  S u bject -re p orte d assess me nts f or c o u g h a n d d ys p ne a will c o nti n ue t o Da y 2 8 
•  N o ot her assess me nts will t a ke pl ace e x ce pt f or t h ose s pecifi e d at Da y 1 4, 2 8 a n d Da y 
6 0 i n t he pr ot o c ol.  
All s u bjects will u n der g o t h e assess me nts s pecifie d f or Da y 1 4 ( E n d of Treat me nt) a n d Da y  2 8 
( E n d of St u d y), a n d partici p ate i n t he Da y 6 0  t ele p h o ne call, e ve n if t he y ar e disc har g e d fr o m  t h e 
h os pital pri or t o Da y 2 8.   
3. 2.  
J ustific ati o n of D ose  
I n a precli nic al st u d y, m o n ke ys were gi ve n a si n gle oral 1 0 m g/ k g ca ps ule d ose of P T C 2 9 9. 
P las ma le v els of D H O, t he s u bstrate f or D H O D H, i ncrease d after d osi n g, pea k e d at 2 4 h o urs a n d 
t he n decr ease d (Fi g ure  1 ). T h e e x p os ure f or P T C 2 9 9 was 2 2. 5 µ g *hr/ m L. T he attai n me nt of t he  
pea k D H O c o nce ntrati o n  was  dela y e d rel ati v e t o t h e pea k c o nc e ntrati o n of P T C 2 9 9 ( 2 4 h o urs vs. 
2 h o urs) ( Ta ble  1 ). T h ese data s u g gest t hat a n e x p os ure of a p pr o xi m atel y 2 2. 5 µ g *hr/ m L  will 
res ult i n si g nifica nt D H O D H i n hi biti o n. 

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P a ge 2 3  of 6 2  
Fi g ur e  1 : 
Pl a s m a D H O a n d P T C 2 9 9 C o n c e ntr ati o n s aft er a Si n gl e Or al D o s e of P T C 2 9 9  
0
5 0
1 0 0
1 5 0
2 0 0
0
1
2
3
4
0
1
2
3
P l a s m a D H O  ( g/ m L )
H o u r s
P T C 2 9 9 P l a s m a C o n c e n t r a ti o n  ( g/ m L )
D H O
P T C 2 9 9
 
A b br e vi ati o n s : D H O, di h y dr o or ot at e 
T a bl e  1 : 
S u m m ar y of P K a n d P D P ar a m et er s  
 
P T C 2 9 9  
D H O  
A U C 0 -l a st ( µ g*hr/ m L)  
2 2. 5  
7 1. 4  
C m a x  ( µ g/ m L) 
2. 5 1  
2. 4 8  
T m a x  ( hr p o st-d o s e)  
2  
2 4  
H alf -lif e ( hr) 
3 3  
1 0  
A b br e vi ati o n s : A U C, ar e a u n d er t h e c ur v e: D H O, di h y dr o or ot at e 
Cli nic al D at a  
T he a bilit y of P T C 2 9 9 t o i n hi bit D H O D H i n h u ma ns was e xa mi ne d i n t he P hase 2 cli nical st u d y 
P T C 2 9 9 -O N C -0 0 7 -N F 2 ( St u d y 0 0 7). St u d y 0 0 7 e val uate d P T C 2 9 9 m o n ot hera p y i n a d ult 
patie nts wit h ne ur ofi br o mat osis t y p e 2  ( N F 2). P T C 2 9 9 was a d mi nister e d at a d ose of 1 0 0 m g 
ca ps ule BI D  (c orres p o n di n g t o  2 5 0 m g BI D of t he t a blet  f or m ulati o n).  
T he ser u m l e vels of D H O  were bel o w t he l o wer li mit of q ua ntificati o n pri or t o d osi n g a n d w ere 
si g nifica ntl y ele vate d at eit h er 8 or 1 6 wee ks  (Fi g ure  2 A ), c o nsiste nt wit h i n hi biti o n of D H O D H 
b y  P T C 2 9 9. T he el e vati o n of D H O le vels  (a b o ut 1. 7 µg/ m L ) aft er P T C 2 9 9 t her a p y is si milar if 
n ot great er t o t h at o bser ve d i n a patie nt wit h Mi ll er s y n dr o me ( 0. 5 3 7 µ g/ m L)  (D ul e y 2 0 1 6 ). 
Miller s y n dr o me is ca use d  b y  a m utati o n i n t he D H O D H  ge ne res ulti n g i n a deficie nc y i n 
D H O D H e nz y me acti vit y, w hic h le a ds t o  el e vat e d ser u m D H O le vels (D ule y 2 0 1 6 ).  
T he acti vit y of P T C 2 9 9 as a D H O D H i n hi bit or was als o teste d b y assessi n g  t he effect o n t he 
pr o d ucti o n of t h e c yt o ki ne vasc ul ar e n d ot h eli al gr o wt h fact or (V E G F ). V E G F l e vels are k n o w n 
t o be a b n or m all y ele vate d i n N F 2  patie nts (Pl ot ki n 2 0 0 9 ). D H O D H i n hi bit ors ha ve be e n s h o w n 
t o s u p press V E G F e x pr essi o n (Die dric hs -M o hri n g 2 0 1 8 ). As s h o w n i n  
Fi g ure  2 B , ser u m V E G F l e vels were ele vate d pri or t o d osi n g b ut were n or maliz e d  after 8 we e ks 
of treat me nt t o le v els si milar t o t h ose re p orte d f or h e alt h y s u bje cts (Rai m o n d o 2 0 0 1 , K ut 2 0 0 7 ), 
a statisticall y si g nifica nt re d ucti o n .  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
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P a ge 2 4  of 6 2  
T he P T C 2 9 9 -de pe n d e nt c h a n ges i n D H O a n d V E G F le vels str o n gl y i n dic ate t he dr u g dire ctl y 
i n hi bits D H O D H i n t hese pati e nts a n d elicits a p pr o priate p h ar ma c o d y na mi c c ha n g es.  
T h e re d ucti o n of V E G F le vels  was ass ociate d wit h a plas ma c o n ce ntr ati o n of P T C 2 9 9 4  -h o urs 
p ost d ose of 1. 9 µ g / m L, w hic h  is k n o w n t o be cl ose t o Cma x . 
Fi g ur e  2 : 
P T C 2 9 9 I n hi bit s D H O D H i n P ati e nt s wit h N e ur ofi br o m at o si s T y p e 2 T u m or s  
 
L e g e n d : ( A) D H O s a m pl e s fr o m a t ot al of 4 p ati e nt s pr e- a n d p o st -d o si n g wit h P T C 2 9 9 d o si n g. ( B) V E G F pl a s m a 
l e v el s f or 1 1 p ati e nt s pr e- a n d p o st -P T C 2 9 9 d o si n g.  
S o ur c e : P a n el A ( D H): P T C 2 9 9-1 7 0 3 0  
Pre dicti o n b ase d o n i n vitr o S A R S -C o V -2 d at a  
A c o nce ntrati o n of 2 5 0 n M P T C 2 9 9 ( 1 1 7 n g/ m L) re d uce d S A R S -C o V -2 viral tit er b y 3 -l o gs i n 
me dia wit h 5 % ser u m ( P T C 2 9 9 -2 0 -0 1 2). T o mai ntai n le vels 1 0 -f ol d a b o ve t his c o nce ntr ati o n, or 
1 1 7 0 n g/ m L, f or 2 4 h o urs w o ul d res ult i n a n A U C 0 -2 4 h of 2 8. 1 µ g *hr/ m L . T his is a b o v e t he tar get 
le vel r e q uire d f or D H O D H i n hi biti o n of 2 2. 5 µ g*hr/ m L.  
D ose Re gi m e n Re q uire d t o  Re ac h A U C  S h o w n t o I n hi b it D H O D H 
Cli nic al St u d y P T C 2 9 9 -O N C -0 0 2 -H V e val uat e d t he P K a n d safet y of i ncreasi n g d oses of t he 
ca ps ule f or m ulati o n of P T C 2 9 9 i n he alt h y v ol u nteers ( N = 3 2; n = 2 4 recei v e d P T C 2 9 9 a n d n = 8 
recei v e d plac e b o).  
St u d y 0 0 2 ha d 2 sta ges; i n St a ge 1, d oses ra n ge d fr o m 0. 3 t o 1. 2 m g/ k g BI D, a n d i n Sta ge 2, a 
1. 6 m g/ k g d ose was a d mi nistere d TI D (Ta ble  2 ). Pati e nts recei ve d t h e ca ps ule f or m ulati o n of 
P T C 2 9 9 f or 7 da ys i n b ot h sta ges. T h e 1. 2 m g/ k g ca ps ule f or m ulati o n s h o ul d ha v e si milar 
e x p os ure t o t he  a b o ut 2 0 0 m g of t he ta blet f or m ulati o n base d o n relati ve bi oa vaila bilit y; t he 
ta blet f or m ul ati o n h as a p pr o xi matel y 4 0 % r elati ve bi oa vail a bilit y c o m pare d wit h t he c a ps ule. F or 
refere nce, Ta bl e  2  prese nts t h e a p pr o xi mat e d ose of t he ta bl et f or m ulati o n, w hic h will be use d i n 
P T C 2 9 9 -VI R -0 1 5 -C O V 1 9, f or eac h d ose of t he ca ps ule f or m ul ati o n a d mi nistere d i n St u d y 0 0 2.  
T he e x p os ure o bser ve d f oll o wi n g t he 1. 2 m g/ k g  BI D d ose at Da y 1 was 1 8 µ g *hr/ m L a n d at 
Da y  7 was 3 2. 9 µ g *hr/ m L  (Ta bl e  2 ). T he Da y 1 e x p os ure is si milar t o t he e x p os ure of 
2 2. 5  µ g *hr/ m L o bser ve d after a b o ut 2 4 h o urs i n t he r hes us m o n ke y e x peri me nt t hat de m o nstrat e d 
D H O D H i n hi biti o n. T h e C ma x  of P T C 2 9 9 was 2. 1 1 µ g/ m L, w hic h is si mil ar t o t h at ass oci ate d 
wit h D H O D H i n hi biti o n (ie, 1. 9 µ g/ m L) see n i n p ati e nts i n St u d y 0 0 7.  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
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Ba s ed o n t he bi ol o gic al data o utli ne d a b o v e, t he P T C 2 9 9 e x p os ure after d osi n g at 1. 2 m g/ k g BI D 
w o ul d res ult i n si g nifica nt re d ucti o n of D H O D H e nz y me acti vit y i n t h e cli nic.  
N o seri o us a d verse e ve nts were re p orte d i n St u d y 0 0 2.  
T a bl e  2 : 
S u m m ar y of P T C 2 9 9 P h ar m a c o ki n eti c s i n H e alt h y V ol u nt e er s w h e n A d mi ni st er e d 
wit h t h e C a p s ul e F or m ul ati o n ( ~ 2. 5 x of t h e Bi o a v ail a bilit y of t h e T a bl et 
F or m ul ati o n) ( St u d y P T C 2 9 9 -O N C -0 0 2 -H V)  
A b br e vi ati o n s : A U C0 -4 , ar e a u n d er t h e c o n c e ntr ati o n c ur v e fr o m h o ur 0 t o 4; Cm a x , m a xi m al c o n c e ntr ati o n; 
T 1/ 2 , h alf -lif e; Tm a x , ti m e t o m a xi m al c o n c e ntr ati o n 
a  St u d y 0 0 2 o nl y a d mi ni st er e d t h e c a p s ul e f or m ul ati o n of P T C 2 9 9. T h e v al u e s f or t h e t a bl et r e pr e s e nt t h e 
a p pr o xi m at e d o s e of t h e t a bl et f or m ul ati o n f or r ef er e n c e. T h e d o s e c al c ul ati o n s a s s u m e a b o ut a 7 0 k g b o d y w ei g ht.  
N ot e: T h e v al u e s i n b ol d s h o w t h e d o s e  t h at r e s ult s i n e x p o s ur e s t h at ar e si mil ar t o t h o s e m e a s ur e d i n 
St u d y  P T C 2 9 9 -O N C -0 0 7 -N F 2.  
Pr o p ose d d osi n g re gi m e n  
S u bjects will b e d ose d f or a t otal of 1 4 da ys a n d f oll o we d f or a n a d diti o nal 1 4 d a ys wit h o ut 
d osi n g. S u bjects will r ecei ve oral ta bl ets c o nt ai ni n g P T C 2 9 9 or matc h e d pla ce b o 2 0 0 m g BI D 
( m or ni n g a n d e v e ni n g) o n D a ys 1 t o 7 a n d 5 0 m g Q D o n Da ys 8 t o 1 4.  S u bjects 
will  s u bse q ue ntl y b e  f oll o we d fr o m Da y 1 5 t o 2 8, a n d t here will be a tele p h o n e call at Da y 6 0 t o 
assess A Es, S A Es, a n d deat hs .  
T he d osi n g re gi me n t a kes i nt o c o nsi derati o n t he t y pi cal pr o gressi o n of t h e disease i n cl u di n g t he 
disease c har acteristics i n p ati e nts w h o are h os pit ali ze d wit h C O VI D -1 9. T he d osi n g of 2 0 0 m g 
BI D f or t he first 7 da ys will r aise t h e e x p os ure of t he dr u g q uic kl y t o ac c o m m o date t he n ee d f or 
ra pi d o nset of P T C 2 9 9 a cti vit y. T h e d osi n g of 5 0 m g Q D f or t he sec o n d 7 da ys will pre ve nt t he  
e x p os ure fr o m s u bsta nti all y d ecreasi n g. I m p orta ntl y, cli ni cal e vi de n ce i n di cat es t hat t his d osi n g 
re gi me n s h o ul d b e well t olerate d. 
T he d os i n g re gi me n is base d o n e xte nsi ve cli nical, safet y, a n d cli ni cal p har mac ol o g y e x perie nc e 
wit h t he c a ps ule f or m ulati o n of P T C 2 9 9, w hic h was use d i n t he pri or s oli d t u m or cli nical st u dies. 
T he res ults fr o m cli nical st u d y P T C 2 9 9 -O N C -0 0 2 -H V ( St u d y 0 0 2) i n dicat e t hat 2 0 0 m g BI D 
d osi n g w o ul d raise t he e x p os ure of P T C 2 9 9 wit hi n 7 da ys t o t he a ntici pat e d t hera p e uti c ra n ge  
( 2 3 t o 3 3 µ g *h r/ m L). 
A p pr o xi m at e C orr e s p o n di n g D o s e a  
D o s e 
Fr e q u e n c y  
D a y  
P T C 2 9 9  
T a bl et ( m g)  
C a p s ul e ( m g/ k g)  
T m a x  
( h) 
T 1/ 2  
( h) 
C m a x  
( µ g/ m L) 
A U C 0 -4  
( µ g*hr/ m L)  
5 0  
0. 3  
BI D  
1  
4. 0  
N A  
0. 2 8  
4. 3 1  
1 2 5  
0. 6  
3. 0  
0. 7 1  
1 0. 1  
2 0 0  
1. 2  
3. 5  
1. 1 4  
1 8. 0  
2 8 0  
1. 6  
TI D  
3. 0  
1. 6 7  
3 7. 1  
5 0  
0. 3  
BI D  
7  
3. 5  
1 6 4  
0. 5 1  
8. 4 4  
1 2 5  
0. 6  
4. 0  
2 1 0  
1. 1 1  
1 8. 6  
2 0 0  
1. 2  
4. 0  
2 2 8  
2. 1 1  
3 2. 9  
2 8 0  
1. 6  
TI D  
3. 0  
2 2 5  
3. 5 3  
7 8. 6  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
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P T C 2 9 9 2 0 0 m g t a blet BI D f or 7 d ays is e x pecte d t o be t oler at e d i n p ati e nts.  
T he e x pe cte d e x p os ure fr o m t he pr o p ose d d osi n g r e gi me n is e x p ect e d t o be well -t ol erat e d, as t he 
c o m para ble e x p os ure i n St u d y 0 0 2 di d n ot c a use  S A Es. T he C ma x  aft er gi vi n g t he 2 0 0 m g ta bl et 
BI D f or 7 da ys is a ntici p ate d t o be a b o ut 2. 1 1 µ g/ m L a n d is n ot e x pe cte d t o ca use a n y saf et y 
c o ncer n, as si milar plas ma c o n ce ntr ati o ns were o bser ve d i n t he p ati e nts w h o were treate d wit h 
P T C 2 9 9 ca ps ule f or > 4 0 da ys.  
Safet y e ve nts wit h re gar d t o i ncre ases i n P T C 2 9 9 le v els d ue t o sat ur ati o n of eli mi nati o n are 
u nli kel y as eli mi nati o n of t h e dr u g will n ot be sat urat e d wit h 7 da ys of 2 0 0 m g t a blet BI D d osi n g 
f oll o we d b y 7 da ys of 5 0 m g t a blet Q D d osi n g. T his is s u p p orte d b y res ults fr o m St u d y 0 0 2 i n 
w hic h relati ve d ose li nearit y was o bser ve d fr o m 0. 3 m g/ k g t o 1. 2 m g/ k g BI D d oses of P T C 2 9 9 
ca ps ules (e q ui v ale n t t o 2 0 0 m g BI D ta blets). It is als o s u p p orte d b y t he o n g oi n g A M L 
o pe n -la bel, n o n-ra n d o mize d, p hase 1 b st u d y, P T C 2 9 9-H E M -0 0 1 -L E U i n w hic h t he st ea d y stat e 
was reac he d at a p pr o xi m atel y Da y 1 5 aft er a d mi nistr ati o n of a n 8 0 m g Q D l oa di n g d ose of t h e 
ta blet f or m ul ati o n of P T C 2 9 9 f or 7 d a ys f oll o we d b y a 4 0 m g Q D mai nt e na nc e d ose. 
3. 3.  
E n d of St u d y Defi niti o n  
T he st u d y will e n d w he n t he last s u bje ct has c o m plet e d t he fi n al assess me nt. 
4.  
S T U D Y P O P U L A TI O N  
4. 1.  
O ver vi e w  
T he st u d y p o p ulati o n is h os pit ali ze d a d ult s u bje cts wit h  c o nfir me d p ne u m o nia, dia g n ose d wit h 
C O VI D -1 9, a n d n ot re q uiri n g me c ha nic al ve ntil ati o n. A p pr o xi matel y 3 8 0 s u bjects will be 
ra n d o miz e d: 1 9 0 s u bje cts t o pl ace b o  a n d 1 9 0 s u bj ects t o P T C 2 9 9. 
4. 2.  
I ncl usi o n Criteri a 
Bef ore e nr oll me nt i n t h e st u d y, s u bjects m ust f ul fil all of t he f oll o wi n g criteria: 
1.  S u bject ( or l e gall y a ut h orize d re pr ese ntati ve) is willi n g a n d a ble t o pr o vi de i nf or me d 
c o nse nt a n d c o m pl y wit h all pr ot oc ol re q uire m e nts . 
2.  A grees t o t he c olle cti o n of nas o p har y n g eal s wa bs a n d ve n o us bl o o d a n d all ot her 
pr o t oc ol-s pecifie d pr oc e d ures. 
3.  Male or n o n -pre g na nt fe male a d ult ≥1 8 y ears of a ge at ti me of e nr oll m e nt.  
4.  H os pitaliz e d a n d has l a b orat or y -c o nfir me d i nfecti o n wit h S A R S -C o V -2.  
5.  S y m pt o m o nset was ≤1 4  da ys pri or t o S cree ni n g  
6.  Has S p O 2 < 9 4 % o n r o o m air  
7.  Has at least o n e of res pirat or y r ate > 2 4 br eat hs/ mi n ut e or c o u g h  
8.  L u n g i n v ol ve me nt as c o nfir m e d b y ra di o gra p hic i nfiltrates o bser ve d o n i ma gi n g (c hest 
X -ra y, C T sca n, or a n e q ui v ale nt test )  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
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9.  W o me n of c hil d be ari n g p ote ntial (as defi n e d i n (C T F G 2 0 1 4 )) m ust ha ve a ne gati ve 
pre g na nc y t est at scre e ni n g a n d a gree t o a bsti n e nce or t he use at least o n e of t he 
f oll o wi n g hi g hl y effecti ve f or ms of c o ntrac e pti o n  (wit h  a fail ure r ate of < 1 % p er year 
w he n use d c o nsiste ntl y a n d c orrectl y). C o ntr ace pti o n or a bsti ne nc e m ust be c o nti n ue d  f or 
t he d urati o n of t he st u d y f oll o wi n g disc h ar ge fr o m t h e hos pital , a n d f or u p t o 5 0  da ys 
after t h e last d ose of st u d y dr u g : 
•  c o m bi ne d ( estr o ge n a n d pr o gest o g e n c o nt ai ni n g) h or m o nal c o ntrac e pti o n ass oci ate d 
wit h i n hi biti o n of o v ul ati o n:  
− oral  
− i ntra va gi nal 
− tra ns der mal 
•  pr o gest o ge n -o nl y h or m o n al c o ntrace pti o n ass oci ate d wit h i n hi biti o n of o v ul ati o n:  
− oral  
− i njecta bl e 
− i m pla nta bl e 
•  i ntra ut eri ne d e vice 
•  i ntra ut eri ne h or m o ne-rel easi n g s yste m 
•  vasect o mize d p art ner  wit h c o nfir m e d az o os per mia  
All fe males will b e c o nsi dere d of c hil d b eari n g p ote ntial u nl ess t he y are p ost me n o pa usal 
(at le ast 1 2 m o nt hs c o nse c uti v e a me n orr h ea i n t he a p pr o priate a ge gr o u p wit h o ut ot her 
k n o w n or s us pecte d ca use) or ha ve b ee n sterili ze d s ur gicall y (e g , bilat eral t u b al li gati o n, 
h ysterect o m y, bil ateral o o p h orect o m y).  
1 0.  Me n se x uall y a cti v e wit h w o me n of c hil d be ari n g p ot e ntial w h o ha ve n ot h a d a vasect o m y 
m ust a gree t o use a barri er met h o d of birt h c o ntr ol d uri n g t he st u d y f oll o wi n g disc har g e 
fr o m t he h os pit al a n d f or u p t o 5 0 da ys after t he l ast d ose of st u d y dr u g.  
4. 3.  
E xcl us i o n Criteri a 
S u bjects will n ot be per mitte d t o e nr oll i n t he st u d y if a n y of t he f oll o wi n g criteria a p pl y:  
1.  Re q uires me c ha ni cal ve ntil ati o n  
2.  C urre nt partici p ati o n i n a n y ot her i nter v e nti o n al st u d y. 
3.  A la ni ne tr a nsa mi n ase/as part ate tra nsa mi nase l e vels ( A L T/ A S T) ≥3 ti mes t he u p p er li mit 
of n or mal  (× U L N)  or t ot al bilir u bi n ( T bili) ≥2 × U L N . 
4.  L y m p h oc yt e c o u nt < 5 0 0 l y m p h oc ytes/ µ L  or he m o gl o bi n < 1 1 . 0 g/ d L  
5.  Sta ge 4 se vere c hr o nic ki d n e y disease or r e q uiri n g di al ysis (ie, esti mate d gl o mer ul ar 
filtrati o n rate < 3 0) 
6.  A n y ot her c o n diti o n, t hat i n t h e o pi ni o n of t he i n vesti gat or, m a y be c a use t o e xcl u de t h e 
s u bject fr o m t he st u d y. 

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7.  Use of ster oi ds  (e xce pt de x a met has o ne), se nsiti ve C Y P 2 D 6 s u bstrates, C Y P 2 C i n d ucers,  
I L-6 ne utralizi n g a nti b o dies, I L -6 re ce pt or i n hi bit ors , or a ny i n vesti g ati o n al t h era p y . 
8.  Pre g na nc y or breast fe e di n g.  
9.  A ntici pate d tr a nsfer t o a n ot h er h os pital w hic h is n ot a st u d y site wit hi n 7 2 h o urs.  
1 0.  K n o w n aller g y t o P T C 2 9 9  or e x ci pi e nts . 
4. 4.  
Scree n F ail ures  
A n y s u bject t hat d oes n ot m eet i ncl usi o n or e x cl usi o n criteri a wit hi n t he d efi ne d scre e ni n g 
wi n d o w pri or t o ra n d o mi zati o n, will b e c o nsi dere d a scree n fail ure. Scree ni n g a n d ra n d o miz ati o n 
s h o ul d occ ur wit hi n a 1-da y peri o d. Scree n fail ures will be c a pt ure d i n t he electr o nic d ata ca pt ur e 
s yste m ( E D C). Scree n fail ures  ca n b e rescre e ne d after c o ns ultati o n wit h t h e Me dic al M o nit or.  
4. 5.  
Str ate gies f or Recr uit m e nt a n d Rete nti o n  
S u bjects will b e recr uite d via e xisti n g p o p ulati o ns wit h C O VI D -1 9  at i de ntifie d i n v esti gati o nal 
sites. 
5.  
S T U D Y I N T E R V E N TI O N  
5. 1.  
St u d y I nter ve nti o n(s) A d mi nistr ati o n 
5. 1. 1.  
St u d y Inter ve nti o n D escri pti o n  
P T C 2 9 9 or matc hi n g pla ce b o t a blets f or oral a d mi nistrati o n will be pr o vi de d i n t he 5 0 m g d osa g e 
stre n gt h. 
5. 1. 2.  
D osi n g a n d A d mi nistr ati o n  
P T C 2 9 9 or matc hi n g pla ce b o oral ta bl e ts will b e a d mi nister e d at a d ose of 2 0 0 m g BI D ( m or ni n g 
a n d e ve ni n g  at a p pr o xi mat el y 1 2 -h o ur i nter vals ) o n Da ys 1 t o 7 f oll o we d b y 5 0 m g Q D (i n t he 
m or ni n g)  o n Da ys 8 t o 1 4.  It is re c o m m e n de d t hat P T C 2 9 9 be a d mi nister e d wit h f o o d.  
Ta blets will be a d mi nistere d i n t he h os pital; s h o ul d a s u bject be disc har ge d pri or t o Da y 1 4 , 
ta blets will be dis pe nse d t o t a ke at h o me.  
5. 2.  
Pre p ar ati o n/ H a n dli n g/ St or a ge/ Ac c o u nt a bilit y  
5. 2. 1.  
Acc o u nt a bilit y  
St u d y pers o n nel m ust e ns ure t hat all st u d y dr u g s u p plies are k e pt i n a sec ure l o c ke d ar ea with 
access li mit e d t o a ut h orize d p ers o n nel. St u d y dr u g  m ust n ot be use d o utsi de t he c o nte xt of t his 
pr ot oc ol. U n der n o circ u mst a nces s h o ul d t he i n vesti g at or or site p ers o n nel s u p pl y st u d y dr u g t o 
ot her i n vesti gat ors or cli ni cs or all o w st u d y dr u g t o b e use d ot her t h a n as directe d b y t his 
pr ot oc ol.  
T he i n vesti gat or is res p o nsi ble f or kee pi n g ac c urat e r ec or ds of t he cli ni cal s u p plies recei ve d fr o m 
P T C or desi g nee, t h e a m o u nt dis pe nse d t o a n d ret ur n e d b y t he s u bje cts, a n d t h e a m o u nt 
re mai ni n g at t he c o ncl usi o n of t he trial. 

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U se d a n d u n use d cli ni cal s u p plies m ust be ret ur ne d t o P T C T hera pe utics ( P T C)  or its desi g nee 
after t h e st u d y is c o m plet e d. If t he Sta n d ar d O perati n g Pr oce d ure ( S O P) at a n y site st ates t hat t he 
dr u g ca n n ot  be r et ur ne d a n d m ust be dis p ose d of o nsite, P T C m ust r e vie w t h e S O P of t hat site 
pri or t o a n y fi n al dis p ositi o n d o ne b y sit e. Rec or ds d oc u me nti n g t he d ate of st u d y  me di cati o n 
destr ucti o n or s hi p pi n g, a n d a m o u nt destr o y e d or s hi p pe d s h o ul d be  ke pt.  
5. 2. 2.  
F or m ul ati o n, A p pe ar a nce, P ac k a gi n g, a n d L a beli n g  
P T C 2 9 9 a n d mat c hi n g pl ace b o ta blets f or oral a d mi nistrati o n will be pr o vi de d i n 5 0 m g d osa ge 
stre n gt h. 
Ta blets will be p ac ka ge d i n b ottles f or distri b uti o n t o i n vesti gati o nal sites.  
P T C 2 9 9 a n d mat c hi n g pl ace b o ta blets m ust be st ore d per t he l a bel ed st ora ge c o n diti o ns.  
5. 3.  
Me as ures t o Mi ni mi ze Bi as: R a n d o miz ati o n a n d Bli n di n g  
T he st u d y is perf or m e d i n a d o u ble -bli n d f as hi o n. T h e I n vesti gat or a n d st u d y staff (i ncl u di n g 
pr ocessi n g la b pers o n nel), t he s u bje cts, a n d t h e s p o ns or’s staff will re mai n bli n d e d t o t h e 
treat me nt u ntil st u d y cl os ure. T h e i n vesti g ati o n al dr u g a n d its matc hi n g plac e b o are 
i n disti n g uis ha ble a n d will be p ac ka ge d i n t he sa me wa y. 
T he ra n d o mizati o n c o de will be k e pt stri ctl y c o nfi de ntial. F urt h er det ails ar e pr o vi de d i n t he 
P har mac y Ma n ua l. 
S u bjects will b e ra n d o mize d 1: 1 t o eit her P T C 2 9 9  or place b o usi n g a ce ntral ra n d o miz ati o n 
pr ocess . T he ra n d o mizati o n will b e stratifie d b y a ge ( ≤6 2 vs > 6 2) , re m desi vir use ( y es vs n o ), 
a n d de xa m et has o ne use ( yes vs n o).  
5. 3. 1.  
E mer ge nc y P r oce d ure f or U n bli n di n g  
T he I n vesti g at or a n d t he st u d y staff m ust r e mai n bli n de d t o t he s u bj ect's tre at me nt assi g n me nt, 
e ve n if t h e s u bject ref uses t o partici p ate i n a n y st u d y pr oce d ures or e x peri e nces a n A E. T he 
i de ntit y of t he st u d y dr u g ma y be r e veal e d o nl y if t he s u bject e xp erie n ces a me dical e m er ge nc y 
w h ose ma na ge m e nt w o ul d be i m pr o ve d b y t h e k n o wle d ge of t h e bli n d e d treat me nt assi g n me nt.  
T he occ urr e nce of a n y c o de bre a k d uri n g t h e st u d y m ust be cl earl y j ustifi e d a n d e x pl ai ne d b y t he 
I n vesti gat or. B ef ore u n bli n di n g, e ver y att e m pt m ust be ma de b y t he I n vesti gat or t o disc uss t he 
i nte n de d c o de brea k wit h P T C. I n all cases, t h e s p o ns or m ust be i nf or me d as s o o n as p ossi ble 
bef ore or after t he c o d e brea k.  
A n y c o de brea k m ust b e d oc u me nte d i n a det ail e d re p ort wit h t he d ate a n d ti m e of t he c o de bre a k 
a n d si g ne d b y t he I n v esti gat or. T his re p ort is t o be attac he d t o t he s o urc e d oc u me nts a n d t he d ate 
a n d ti m e of c o de br ea k will b e d oc u m e nte d i n t he e C R F.  
5. 4.  
St u d y I nter ve nti o n a n d C o m pli a nce  
C o m plia n ce will be c alc ulate d as descri be d i n Se cti o n 8. 4. 4. 3 . 

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5. 5.  
C o nc o mit a nt T her a p y  
All s u bjects i n b ot h c o h orts will rec ei ve S O C, acc or di n g t o writt e n l oc al g ui d eli n es a n d practices.  
C o nc o mit a nt use of ster oi ds  (e xce pt d e xa m et has o ne), se nsiti ve C Y P 2 D 6 s u bstrates, C Y P 2 C 
i n d ucers, I L-6 ne utralizi n g a nti b o di es,  I L-6 rec e pt or i n hi bit ors , or a n y i n vesti g ati o n al t h era p y  
will n ot be p er mitte d.  
Ca uti o n s h o ul d be use d i n t he c o nc o mita nt a d mi nistr ati o n of bre ast ca nc er resista n ce pr ot ei n 
(B C R P ) s u bstrate dr u gs as i ntesti n al B C R P i n hi biti o n b y P T C 2 9 9 f oll o wi n g a 2 0 0 m g BI D d ose 
of P T C 2 9 9 ca n n ot be  e xcl u d e d ; g ui da n ce s h o ul d be s o u g ht fr o m t he st u d y Me dical M o nit or i n 
eac h c ase . 
A n atte m pt will b e ma d e t o rec or d all me di cati o ns ta ke n b y s u bjects 3 0 da ys pri or t o t he first 
d ose of st u d y dr u g a n d t hr o u g h Da y 2 8 . 
All c o nc o mita nt me dicati o ns ( prescri pti o n a n d o ver t he c o u nter), vita mi n a n d mi neral 
s u p ple me nts, a n d h er bs ta ke n d uri n g t he st u d y will b e d oc u me nte d o n t h e c o nc o mita nt 
me dic ati o n ele ctr o nic case re p ort f or m (e C R F). I nf or mati o n r ec or de d will i n cl u de start a n d st o p 
dates, d ose a n d r o ut e of a d mi ni strati o n, a n d i n dicati o n. 
6.  
S T U D Y I N T E R V E N TI O N DI S C O N TI N U A TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L  
6. 1.  
Disc o nti n u ati o n of St u d y I nter ve nti o n  
S u bjects will  r ecei ve st u d y tr eat m e nt u ntil tr eat me nt disc o nti n uati o n f or o ne of t he reas o ns liste d 
bel o w. H o we ver , s u bjects m a y disc o nti n ue st u d y tre at me nt or wit h dra w t h eir c o nse nt t o 
partici pat e i n t h e st u d y at a n y ti m e wit h o ut pr ej u di ce.  
T he f oll o wi n g c o n diti o ns re q uire s u bj ect disc o nti n uati o n fr o m all st u d y tr eat me nt:  
1.  At t heir o w n re q uest or at t h e re q uest of t h e ir l e gall y a ut h oriz e d re prese nt ati v e 
2.  If a s u bject e x perie n ces a n A E t h at is de e me d r elate d t o treat me nt wit h P T C 2 9 9 a n d i n 
t he In vesti g at or’s or t he S p o ns or’s me di cal j u d g me nt c o nti n uati o n of tr eat me nt w o ul d be 
detri m e ntal t o t h e s u bject  
3.  At t he s pecific re q uest of a re g ul at or y a g e nc y f or t er mi nati o n of tre at m e nt of a n 
i n di vi d ual s u bject or all s u bjects u n der t he pr ot o c ol 
4.  S u bject partici pati o n i n a n ot her cli nic al st u d y usi n g a n i n vesti gati o nal a ge nt or 
i n vesti gati o nal me dical de vic e 
5.  Ref usal of se x uall y acti ve fertil e s u bjects (e xcl u di n g s u bjects w h o ha ve be e n sterilize d) t o 
use me dic all y acce pte d m et h o ds of c o ntr ace pti o n  
6.  If a s u bject b ec o mes pre g n a nt 
7.  Si g nifica nt n o nc o m plia n ce wit h t he pr ot oc ol i n t h e o pi ni o n of t he i n vesti g at or or t h e 
s p o ns or 
8.  Di sease pr o gressi o n necessitati n g (i n t he o pi ni o n of t he i n vesti g at or) disc o nti n uati o n of 
st u d y treat me nt 

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S u bject s w h o disc o nti n u e st u d y tre at m e nt will be tre ate d at t he discreti o n of t he i n v esti gat or, 
i ncl u di n g, as a p pr o priate, a n y m e dic ati o ns .  
6. 1. 1.  
Disc o nti n u a ti o n d ue t o A b n or m al Li ver F u ncti o n  
S e veral s pecific meas ures will b e u n dert a ke n t o i de ntif y t he ris k of he p at ot o xicit y i n s u bje cts a n d 
ma na ge hi g h dr u g e x p os ure. T o a v oi d he pat ot o xi cit y, P T C has i m ple me nt e d a c o m pre he nsi ve 
m o nit ori n g of li ver f u n cti o n tests (L F Ts ), i ncl u di n g A L T, A S T, t otal bilir u bi n (T bili ), a n d 
al kali ne p h os p hat ase ( A L P ). D uri n g h os pitali zati o n, t he L F Ts  will b e m o nit ore d dail y d uri n g  
treat me nt a n d at Da y 2 8 . A n  H A C will c o m pr e he nsi vel y m o nit or all he patic a b n or maliti es a n d 
c o nti n uall y e v al uate he patic saf et y d uri n g t he st u d y.  
C o nsiste nt wit h  t h e F o o d a n d Dr u g A d mi nistrati o n Dr u g I n d uce d Li v er I nj ur y ( DI LI ) g ui da n ce  
(F D A 2 0 0 9 ), s u bjects will b e cl osel y m o nit or e d f or a n y of t he f oll o wi n g: 
•  A n y ser u m A L T or A S T Gra de ≥3 ( > 5 × U L N), re gar dless of baseli ne   
•  T bili ( > 2 × U L N), w het h er or n ot ser u m A L T or A S T val ues are ele vate d; if s uc h a n 
ele vati o n oc c urs, direct bilir u bi n  will b e me as ure d  
If a n y of t he a b o v e c o n diti o ns are m et, t h e f oll o wi n g ste ps will be t a ke n: 
•  Te m p oraril y s t o p d osi n g st u d y dr u g a n d r etest A L T, A S T, a n d T bili wit hi n 7 2 h o urs 
t o c o nfir m c ha n ges. S u bje cts wit h Gra de 3 li ver f u ncti o n a b n or m alities will be 
m o nit ore d u ntil t hese val ues ret ur n t o t he baseli ne.  
•  N otif y t he s p o ns or a n d me dical m o nit or (see als o Se cti o n 7. 5. 3  a n d Se cti o n  7. 5. 1 0 ) 
•  Res u me d osi n g wit h st u d y dr u g if t he retesti n g d o es n ot c o nfir m t he m a g nit u d e of t he 
a b n or malit y(i es) , after disc ussi o n wit h t he m e dic al m o nit or. 
•  E val uate A L T, A S T, T bili, a n d A L P dail y , u ntil st a ble or res ol ve d. 
•  C o nsi der f urt her w or k -u p i n c o ns ultati o n wit h t he m e dical m o nit or.  
Per ma ne nt d isc o nti n u ati o n of st u d y dr u g f or a b n or m al li v er f u ncti o n s h o ul d be c o nsi d ere d b y t he 
i n vesti gat or w he n a s u bje ct me ets o ne of t h e c o n diti o ns o utli ne d a b o v e or if t h e i n vesti gat or 
belie v es t hat it is i n b est i nt erest of t he s u bject.  Aft er eac h a b n or mal li ver f u ncti o n e v e nt t h at 
meets t h e criteria f or disc o nti n u ati o n , t he H A C will meet t o assess t he se verit y a n d ca usalit y of 
t he e ve nt a n d ge n erate a case r e p ort.  
6. 1. 2.  
Disc o nti n u ati o n d ue t o A b n or m al Bl o o d Test Res ults  
S u bjects will b e m o nit ore d f or a n e mia a n d l o w l y m p h oc yte c o u nt. If eit her of the f oll o wi n g 
occ urs:  
•  L y m p h oc yt e c o u nt < 5 0 0 l y m p h oc ytes/µ L  
•  He m o gl o bi n < 1 1 . 0 g/ d L ( 1 1 0  g/ L)  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 3 2  of 6 2  
T he n t he f oll o wi n g ste ps will be t a ke n: 
•  Te m p oraril y s t o p d osi n g st u d y dr u g a n d r etest l y m p h oc yte c o u nt a n d he m o gl o bi n 
wit hi n 7 2  h o urs t o c o nfir m c ha n g es.  
•  Res u me d osi n g wit h st u d y dr u g if t he retesti n g d o es n ot c o nfir m t he m a g nit u d e of t he 
a b n or malit y(i es).  
•  N otif y t he m e dic al m o nit or if t he ret esti n g c o nfir ms a b n or maliti es.  
P er ma ne nt d isc o nti n u ati o n of st u d y dr u g f or a b n or m al bl o o d  t est res ults s h o ul d be c o nsi dere d b y 
t he i n vesti gat or w he n a s u bject meets o ne of t he c o n diti o ns o utli ne d a b o v e or if t h e i n vesti gat or 
belie v es t hat it is i n b est i nt erest of t he s u bject.  
6. 2.  
P artici p a nt Disc o nti n u ati o n/ Wit h dr a w al fr o m t he St u d y  
I n all c ases of s u bject wit h dra wal or disc o nti n uati o n , t he reas o n f or wit h dr a wal m ust be r ec or de d 
i n t he e C R F a n d i n t he s u bj ect’s m e dic al rec or ds.  If t he reas o n is n ot k n o w n, t he s u bj ect m ust be 
f oll o we d t o est a blis h w het h er t he re as o n was d ue t o a n A E, a n d, if s o, t his m ust b e re p ort e d i n 
acc or da n ce wit h t h e pr oce d ur es i n S ecti o n 7. 5. 9 . 
All s u bjects will u n der g o assess me nts u ntil Da y 2 8 u nless t he y die, are l ost t o f oll o w -u p or 
wit h dra w c o nse nt. F or s u bjects w h o are disc har ge d fr o m t he h os pit al pri or t o Da y 2 8:  
•  If S p O2 is <9 4 %, S p O 2 meas ure me nts will be ta ke n dail y u ntil Da y 2 8  
•  S u bject -re p orte d assess me nts f or c o u g h a n d d ys p ne a will c o nti n ue t o Da y 2 8 
•  N o ot her assess me nts will t a ke pl ace e x ce pt f or t h ose s pecifi e d at Da y 1 4, 2 8 a n d Da y 
6 0 i n t he pr ot o c ol.  
T he in vesti gat or will m a ke e ver y eff ort t o c o nta ct s u bjects l ost t o f oll o w -u p. S u bje ct s w h o ha ve 
a n o n g oi n g A E at t he ti me of st u d y c o m pl eti o n will be f oll o we d u ntil t h e e ve nt res ol ves, or u ntil 
t he S p o ns or a n d t he I n vesti gat or a gree t h at f urt h er f oll o w-u p is n ot me dicall y ne cessar y.  
6. 3.  
L ost t o F oll o w -u p  
A su bject is c o nsi der e d l ost t o f oll o w -u p if t h e he or s he  lea ves t h e h os pital a n d d oes n ot 
c o m plete t h e st u d y a n d atte m pts t o c o nt act t he s u bje ct are u ns uc cessf ul. Eff orts m ust be ma de o n 
t he part of t he sit e t o av oi d a n y s u bject bei n g l ost t o f oll o w -u p d uri n g t he st u d y. B ef ore a n y 
s u bject is c o nsi d ere d l ost t o f oll o w -u p, a mi ni m u m of 2 d oc u me nt e d tele p h o ne c o ntact atte m pts 
a n d 1 certifie d letter wit hi n a wee k of t h e m ost re ce nt pla n ne d st u d y assess me nt m ust be se n t i n 
eff orts t o c o nt act t he s u bject. After bei n g c o nsi der e d l ost t o f oll o w -u p, a s u bj ect’s stat us ma y be 
c ha n ge d if t he s u bje ct ma k es c o nta ct at a l ater ti m e pr o vi de d t he trial is o n g oi n g.  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 3 3  of 6 2  
7.  
S T U D Y A S S E S S M E N T A N D P R O C E D U R E S  
7. 1.  
Sc he d ule of E ve nts a n d St u d y P ar a meters  
T a bl e  3 : 
S c h e d ul e of E v e nt s  
A s s e s s m e nt/ A cti vit y  
S cr e e ni n g  
D a y 
1  
Tr e at m e nt P eri o d  
F oll o w -u p  
N ot e s  
D a y s 
2 -6  
D a y 
7  
D a y s 
8 -1 3  
D a y 1 4/  
E O T  
D a y s 
1 5 -2 7  
D a y 2 8/  
E O S  
D a y 
6 0  ± 3  
S cr e e ni n g a n d D a y 1 s h o ul d o c c ur wit hi n a 
1 -d a y p eri o d; w h er e t h e y o c c ur o n t h e s a m e 
d a y, a s s e s s m e nt s n e e d n ot b e r e p e at e d. 
S u bj e ct s r e m ai ni n g i n h o s pit al will u n d er g o 
t h e a s s e s s m e nt s s p e cifi e d. All s u bj e ct s will 
u n d er g o t h e a s s e s s m e n t s s p e cifi e d f or 
D a y  1 4, D a y 2 8, a n d D a y 6 0 e v e n if t h e y ar e 
di s c h ar g e d fr o m t h e h o s pit al pri or t o 
D a y  2 8.  
I nf or m e d c o n s e nt 
X  
 
 
 
 
 
 
 
 
 
M e di c al hi st or y  
X  
 
 
 
 
 
 
 
 
 
W H O or di n al s c al e 
a s s e s s m e nt  
X  
 
 
 
 
 
 
 
 
(W H O 2 0 2 0 ) 
Pr e g n a n c y t e st  
X  
 
 
 
 
 
 
X  
X  
W O C B P o nl y. Pr e g n a n c y t e st c a n b e s er u m 
β H C G or uri n e.  T h e D a y 6 0 t e st s h o ul d b e 
t a k e n at h o m e a n d s elf-r e p ort e d d uri n g 
t el e p h o n e c o nt a ct. 
Vit al si g n s  
X  
X  
X  
X  
X  
X  
X  
X  
 
Vit al si g n s will i n cl u d e o x y g e n s at ur ati o n d ail y 
f or pri m ar y e n d p oi nt a s s e s s m e nt i n a d diti o n, 
t e m p er at ur e, r e s pir at or y r at e, a n d bl o o d 
pr e s s ur e will al s o b e a s s e s s e d . 
C o u g h a n d d y s p n e a 
a s s e s s m e nt s  
X  
X  
X  
X  
X  
X  
X  
X  
 
C o u g h a n d d y s p n e a ar e a s s e s s e d d ail y o n a 
p ati e nt r e p ort e d s c al e of s e v er e, m o d er at e, 
mil d, or a b s e nt.  
B o d y w ei g ht a n d h ei g ht  
X  
 
 
 
 
 
 
 
 
 
P h y si c al e x a mi n ati o n  
X  
X  
X  
X  
X  
X  
 
X  
 
F ull p h y si c al e x a mi n ati o n (i n cl u di n g a mi ni m u m 
of g e n er al a p p e ar a n c e, h e a d, e y e s, e ar s, n o s e, 
m o ut h, t hr o at, h e art, t h yr oi d, c h e st a n d l u n g s, 
a b d o m e n, e xtr e miti e s, n e ur o m u s c ul ar s y st e m, 
s ki n, a n d l y m p h n o d e s) will b e c o m pl et e d 
d uri n g s cr e e ni n g; at all ot h er ti m e p oi nt s t h e 
e x a mi n ati o n will b e t ar g et e d.  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 3 4  of 6 2  
A s s e s s m e nt/ A cti vit y  
S cr e e ni n g  
D a y 
1  
Tr e at m e nt P eri o d  
F oll o w -u p  
N ot e s  
D a y s 
2 -6  
D a y 
7  
D a y s 
8 -1 3  
D a y 1 4/  
E O T  
D a y s 
1 5 -2 7  
D a y 2 8/  
E O S  
D a y 
6 0  ± 3  
S cr e e ni n g a n d D a y 1 s h o ul d o c c ur wit hi n a 
1 -d a y p eri o d; w h er e t h e y o c c ur o n t h e s a m e 
d a y, a s s e s s m e nt s n e e d n ot b e r e p e at e d. 
S u bj e ct s r e m ai ni n g i n h o s pit al will u n d er g o 
t h e a s s e s s m e nt s s p e cifi e d. All s u bj e ct s will 
u n d er g o t h e a s s e s s m e n t s s p e cifi e d f or 
D a y  1 4, D a y 2 8, a n d D a y 6 0 e v e n if t h e y ar e 
di s c h ar g e d fr o m t h e h o s pit al pri or t o 
D a y  2 8.  
C h e st X -r a y  
X  
 
 
 
 
X  
 
 
 
X -ra y t a k e n wit hi n 2 4 h o ur s pri or t o S cr e e ni n g 
will b e a c c e pt e d.  C T s c a n will b e a c c e pt e d i n 
pl a c e of t h e X -ra y if t a k e n wit h 4 8 h o ur s pri or t o 
S cr e e ni n g . 
N a s o p h ar y n g e al s w a b  
 
X  
X  
X  
 
X  
 
X  
 
N a s o p h ar y n g e al s w a b will b e t a k e n o n D a y s 1, 
2, 4, 7, 1 4, a n d 2 8.  
H e m at ol o g y, 
c o a g ul ati o n, a n d cli ni c al 
c h e mi str y a s s e s s m e nt  
X  
X  
X  
X  
X  
X  
 
X  
 
A s s e s s m e nt s t a k e n wit hi n 2 4 h o ur s pri or t o  
S cr e e ni n g will b e a c c e pt e d.  
Uri n al y si s  
X  
X  
X  
X  
X  
X  
 
 
 
 
C o n c o mit a nt m e di c ati o n s  
X  
X  
X  
X  
X  
X  
X  
X  
 
 
St u d y dr u g 
a d mi ni str ati o n  
 
X  
X  
X  
X  
X  
 
 
 
St u d y dr u g will b e a d mi ni st er e d or all y at 
2 0 0  m g BI D o n D a y s 1 t o 7 f oll o w e d b y 5 0 m g 
Q D o n D a y s 8 t o 1 4. S h o ul d a s u bj e ct b e 
di s c h ar g e d pri or t o D a y 1 4, t a bl et s will b e 
di s p e n s e d t o t a k e at h o m e  a n d c o m pli a n c e will 
b e r e c or d e d at D a y  1 4 . 
Bl o o d dr a w f or P K  
 
X  
 
X  
 
X  
 
 
 
O n D a y s 1  a n d  7 , bl o o d s a m pl e s f or P K 
a s s e s s m e nt will b e c oll e ct e d pr e -d o s e  ( 0) a n d 
at 6  h o ur s p o st -d o s e a n d o n D a y 1 4 at pr e -
d o s e ( 0) a n d 4 h o ur s p o st -d o s e ( m or ni n g d o s e 
o nl y) . A n a d h o c P K a s s e s s m e nt  will b e 
p erf or m e d i n t h e c a s e of h e p at ot o xi cit y  ( s e e 
al s o S e cti o n 7. 3 ). 
Bl o o d dr a w f or c yt o ki n e 
a s s e s s m e nt  
 
X  
X  
X  
 
X  
 
X  
 
 
Bl o o d dr a w f or a c ut e 
p h a s e pr ot ei n 
a s s e s s m e nt  
 
X  
X  
X  
 
X  
 
X  
 
 
A nti b o d y tit er 
a s s e s s m e nt  
 
X  
 
 
 
 
 
X  
 
 

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 3 5  of 6 2  
A s s e s s m e nt/ A cti vit y  
S cr e e ni n g  
D a y 
1  
Tr e at m e nt P eri o d  
F oll o w -u p  
N ot e s  
D a y s 
2 -6  
D a y 
7  
D a y s 
8 -1 3  
D a y 1 4/  
E O T  
D a y s 
1 5 -2 7  
D a y 2 8/  
E O S  
D a y 
6 0  ± 3  
S cr e e ni n g a n d D a y 1 s h o ul d o c c ur wit hi n a 
1 -d a y p eri o d; w h er e t h e y o c c ur o n t h e s a m e 
d a y, a s s e s s m e nt s n e e d n ot b e r e p e at e d. 
S u bj e ct s r e m ai ni n g i n h o s pit al will u n d er g o 
t h e a s s e s s m e nt s s p e cifi e d. All s u bj e ct s will 
u n d er g o t h e a s s e s s m e n t s s p e cifi e d f or 
D a y  1 4, D a y 2 8, a n d D a y 6 0 e v e n if t h e y ar e 
di s c h ar g e d fr o m t h e h o s pit al pri or t o 
D a y  2 8.  
A d v er s e e v e nt s  
X  
X  
X  
X  
X  
X  
X  
X  
X  
At D a y 6 0, t h e vi sit will b e a t el e p h o n e c all t o 
r e c or d A E s, S A E s, a n d d e at h s f or all s u bj e ct s 
e x c e pt t h o s e w h o di e or ar e l o st t o f oll o w -u p  or 
wit h dr a w c o n s e nt . 
A b br e vi ati o n s:  β H C G, b et a h u m a n c h ori o ni c g o n a d otr o pi n; BI D, t wi c e d ail y; E O S, e n d of st u d y; E O T, e n d of tr e at m e nt; P K, p h ar m a c o ki n eti c; Q D, o n c e d ail y , 
W H O, W orl d H e alt h Or g a ni z ati o n; W O C B P, w o m e n of c hil d b e ari n g  p ot e nti al . 

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 3 6  of 6 2  
7. 2.  
Effic ac y Assess me nts  
All assess me nts will be i n li n e wit h t h e site’s C O VI D -1 9 assess me nt g ui deli n es.  
Fe ver ( b o d y te m p erat ure), r es pirat or y r ate, a n d S p O2 will be m o nit ore d r e g ularl y t hr o u g h o ut 
eac h da y d uri n g h os pitalizati o n. If a s u bj ect h as recei ve d a n a nti p yretic, assess me nt of fe v er 
s h o ul d occ ur ≥4 h o urs aft er a d mi nistrati o n of t he a nti p yretic. 
C o u g h se verit y a n d d ys p ne a will b e assesse d dail y vi a s u bject -r e p orte d scales as se vere, 
m o derat e, mil d, or a bse nt. 
F or s u bjects w h o are disc har ge d fr o m t he h os pital pri or t o Da y 2 8:  
•  If S p O2 is < 9 4 %, S p O 2 meas ure me nts will be ta ke n dail y u ntil Da y 2 8  
•  Patie nt -r e p orte d assess me nts f or c o u g h a n d d ys p nea will c o nti n ue t o Da y 2 8 
•  N o ot her assess me nts will t a ke pl ace e x ce pt f or t h ose s pecifi e d at Da y 1 4, 2 8 a n d Da y 
6 0 i n t he pr ot o c ol.  
F or a n y s u bje cts w h o are tr a nsferre d t o t h e I nte nsi v e Care U nit d uri n g t he st u d y, assess me nts per 
pr ot oc ol s h o ul d be p erf or me d w here v er reas o na bl y practi ca bl e.  
C ollecti o n of bl o o d, ser u m a n d nas o p har y n ge al s wa bs f or assess me nt of c yt o ki ne le vels, ac ute 
p hase pr otei ns, c o m plete bl o o d  c o u nt, ot her la b orat or y para meters, a n d viral l oa d will be 
perf or me d b y q ualifi e d a n d trai ne d pers o n nel d uri n g h os pitali zati o n, or aft er disc har ge at a 
me dic al fa cilit y as a gre e d b y t he me di cal m o nit or. L a b orat or y par a met ers assesse d will i ncl u de, 
b ut n ot  be li mite d t o, t h ose i n T a ble 4 . 
T a bl e 4 : 
L a b or at or y P ar a m et er s t o b e A s s e s s e d  
L a b or at or y A s s e s s m e nt s  
P ar a m et er s  
N a s o p h ar y n g e al  s w a b  
R P P a  
H e m at ol o g y  
C B C c o u nt wit h W B C diff er e nti al  
Cli ni c al C h e mi str y  
C o m pr e h e n si v e m et a b oli c p a n el t o i n cl u d e:  
•  
A S T  
•  
A L T  
•  
G G T  
•  
L D H  
•  
A L P  
•  
T bili  (dir e ct a n d i n dir e ct bilir u bi n , if a p pr o p ri at eb )  
•  
C P K  
•  
T ot al pr ot ei n  
•  
Al b u mi n  
C o a g ul ati o n  
a P T T  
P T/ I N R 
Uri n al y si s  
Bl o o d  
Bilir u bi n  
Gl u c o s e  
K et o n e s  
p H  
Pr ot ei n  
Pr e g n a n c y  ( W O C B P o nl y) 
Uri n e or S er u m β H C G [ R efl e cti v e fr o m C h e mi str y S a m pl e]  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 3 7  of 6 2  
L a b or at or y A s s e s s m e nt s  
P ar a m et er s  
Ot h er s  
C yt o ki n e s a  
A nti b o d y tit er s a  
A c ut e p h a s e pr ot ei n s  
•  
F erriti n  
•  
C R P  
•  
D -di m er  
C ar di a c tr o p o ni n  
A b br e vi ati o n s:  A L P, al k ali n e p h o s p h at a s e; A L T, al a ni n e a mi n otr a n sf er a s e; a P T T, a cti v at e d p arti al t hr o m b o pl a sti n 
ti m e; A S T, a s p art at e a mi n otr a n sf er a s e; β H C G, b et a h u m a n c h ori o ni c g o n a d otr o pi n ; C B C,  c o m pl et e bl o o d c o u nt; 
C R P, C -r e a cti v e pr ot ei n; C P K, cr e ati ni n e p h o s p h o ki na s e; G G T, g a m m a -gl ut a m yl tr a n s p e pti d a s e; I N R, int er n ati o n al 
n or m ali z e d r ati o; L D H, l a ct at e d e h y dr o g e n a s e; P T, pr ot hr o m bi n ti m e ; R P P,  r e s pir at or y p at h o g e n p a n el; T bili, t ot al 
bilir u bi n; W B C, w hit e bl o o d c ell; W O C B P, w o m e n of c hil d b e ari n g p ot e nti al.  
a  T o b e a n al y z e d at a c e ntr al l a b or at or y.  
b  Dir e ct a n d i n dir e ct bilir u bi n will b e m e a s ur e d if p art of t h e l o c al l a b or at or y u s u al a s s e s s m e nt  p a n el . In t h e c a s e of 
T bili > 2 x U L N  dir e ct bilir u bi n m u st b e a s s e s s e d ( S e cti o n  6. 1. 1 ).  
All la b orat or y para meters  s h o ul d be assesse d pri or t o d osi n g o n Da y 1.  
7. 3.  
P K a n d/ or Ot her Assess me nts  
A t select sites, P K will be assesse d aft er t he si n gl e d ose ( Da y 1) a n d re peat e d d osi n g Da y 7 a n d 
1 4. Bl o o d sa m ples will be c olle cte d o n Da ys 1  a n d 7  at pre-d ose ( 0), a n d 6 h o u rs p ost-d ose  a n d 
o n Da y 1 4 at pre -d ose ( 0) a n d 4 h o urs p ost -d ose  ( m or ni n g d ose o nl y). Plas ma c o nce ntrati o ns of 
P T C 2 9 9 a n d O -des met h yl P T C 2 9 9  will be e val u ate d f or a t le ast 1 2 e val ua ble p ati e nts w h o 
recei v e P T C 2 9 9. A nal yses will ta ke pl ace at a ce ntr al la b orat or y.  
F or t h ose s u bje cts disc har g e d fr o m t h e h os pital pri or t o Da y 7, P K sa m pli n g s h o ul d be o bt ai ne d 
o n t he last d a y of h os pitaliz ati o n, if p ossi ble. F or s u bjects disc h ar ge d pri or t o Da y  1 4, P K 
sa m ples o n Da y 1 4 s h o ul d be c olle cte d pre -d ose a n d at 4 h o urs p ost -d ose.  
A n a d h oc P K assess me nt will als o be p erf or me d i n t he case of he pat ot o xicit y , r e gar dl ess of 
w het her t he s u bj ect h as u n der g o ne ot her P K assess me nts . 
7. 4.  
S afet y Assess me nts  
S u bjects will b e m o nit ore d cl osel y f or A Es a n d la b or at or y a b n or m alities , i n cl u di n g assess me nt 
of vital si g ns,  d uri n g t he st u d y.  
F or A Es a n d la b or at or y a b n or malities, t h e i n vesti gat o r s h o ul d use his/ her j u d g m e nt i n 
deter mi ni n g w het h er t he e v e nt or a b n or malit y is cli ni call y si g nific a nt, w het h er dia g n osti c 
e val uati o n is warra nte d, a n d w het h er p ote ntial i nt err u pti o n of st u d y dr u g t her a p y is a p pr o pri ate. 
I n ge neral, life-t hreat e ni n g ( Gra de 4) or se v ere ( Gra d e 3) A E or la b orat or y a b n or malities s h o ul d 
be c o nsi dere d cli nicall y si g nifi ca nt, alt h o u g h r ec urre nt or persiste nt m o derate e ve nts ( Gra d e 2) 
ma y als o be c o nsi dere d cli ni call y si g nifi ca nt i n certai n circ u mst a nces. Refer e nce s h o ul d b e ma d e  
t o t he C T C A E Versi o n 5. 0 f or gr a di n g t h e se verit y of A Es a n d la b orat or y a b n or maliti es. 
7. 5.  
A d verse E ve nts a n d Seri o us A d verse E ve nts  
7. 5. 1.  
Defi niti o n of A d verse E ve nts  
A n a d verse e ve nt ( A E) is a n y u nt o war d me dical occ urre nce ass ociate d wit h t he use of a dr u g i n 
h u m a ns, w het her or n ot it is c o nsi d ere d rel ate d t o t he dr u g. A n A E ca n t heref ore b e a n y 

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u nfa v ora ble a n d u ni nt e n de d si g n (i ncl u di n g a n a b n or mal l a b orat or y fi n di n g), s y m pt o m, or 
disease i n a st u d y s u bj ect w h o is a d mi nist ere d st u d y dr u g i n t his st u d y.  
F or t his p r ot o c ol, u nt o war d me di cal o cc urre nc es t hat s h o ul d be re p orte d as A Es i ncl u de t he 
f oll o wi n g: 
•  All A Es d uri n g t he c o urse of treat me nt wit h st u d y dr u g a d mi nistr ati o n  
•  All A Es res ulti n g fr o m me di cati o n mis use, a b use, wit h dra wal, or o ver d ose, of st u d y 
dr u g  
•  All A E s res ulti n g fr o m me di cati o n err ors s uc h as dis pe nsi n g or a d mi nistrati o n err or 
o utsi de of w hat is descri be d i n t he pr ot oc ol  
•  A p pare ntl y u nrelat e d ill nesses, i ncl u di n g w orse ni n g of a pree xisti n g ill ness  
•  W orse ni n g of s y m pt o ms relat e d t o C O VI D -1 9  
•  I nj ur y or accide nts. N ote t hat if a me dical c o n diti o n is k n o w n t o ha ve ca use d t h e 
i nj ur y or ac ci de nt (a fall sec o n dar y t o diz zi ness), t he me dic al c o n diti o n ( dizzi ness) 
a n d t he a cci d e nt (fall) s h o ul d be re p orte d as 2 se par ate A Es. T he o ut c o me of t he 
acci d e nt ( hi p fra ct ur e se c o n dar y t o t he fall) s h o ul d b e rec or de d i n s o urce d oc u m e nts.  
•  A b n or malities i n p h ysi ol o gical testi n g or p h ysical e x a mi nati o n fi n di n gs t hat r e q uire 
cli ni cal i nter v e nti o n or f urt h er i n vesti gati o n ( be y o n d or deri n g a re p eat [c o nfir mat or y] 
test) 
•  La b orat or y a b n or malities t hat r e q uire cli nical i nt er ve nti o n or f urt her i n vesti g ati o n 
( be y o n d or deri n g a re p eat [ c o nfir m at or y] t est) u nless t he y are ass ociate d wit h a n 
alrea d y r e p orte d cli ni cal e ve nt. La b orat or y a b n or m alities ass oci ate d wit h a cli ni cal 
e ve nt s h o ul d be ca pt ur e d i n t he s o urc e d oc u m e nts. L a b orat or y a b n or malities n ot 
re q uiri n g cli ni cal i nter ve nti o n or f urt h er i n vesti gati o n will be c a pt ure d as part of 
o verall la b orat or y m o nit ori n g a n d s h o ul d n ot be re p orte d as A Es.  
•  A pree xisti n g c o n diti o n ( e g, aller gic r hi ni tis) m ust be n ote d o n t he a p pr o priate C R F 
f or scree ni n g b ut s h o ul d n ot be re p ort e d as a n A E u nless t he c o n diti o n w orse ns, or 
e pis o des i ncre ase i n fre q ue n c y d uri n g t h e A E re p orti n g peri o d. Dia g n osti c a n d 
t hera pe utic n o n-i n vasi ve a n d i n vasi ve pr o ce d ures, s u c h as s ur ger y, s h o ul d n ot be 
re p orte d as A Es. H o we ver, t he m e dic al c o n diti o n f or w hic h t he pr oc e d ure was 
perf or me d s h o ul d be r e p orte d if it m eets t h e defi niti o n of a n A E. F or e x a m pl e, a n 
ac ute a p pe n di citis t hat oc c urs d uri n g t he treat me nt wit h st u d y dr u g s h o ul d be re p orte d 
as t he A E a n d t h e res ulti n g a p pe n de ct o m y s h o ul d b e rec or de d i n t he s o urce 
d oc u me nts a n d e C R F. If a s ur gical pr oce d ure was pl a n ne d pri or t o e ntr y i nt o t he 
st u d y, a n d t he s ur ger y is n ot p erf or me d be ca use of a w orse ni n g of a baseli n e 
c o n diti o n, t his s h o ul d n ot be r e p orte d as a n A E. N ote t hat, as descri be d i n 
Secti o n  7. 5. 2  a n y h os pitalizati o n oc c urri n g as t he c o nse q ue nce of a n A E d uri n g t he 
st u d y peri o d s h o ul d be re p orte d as a n S A E.  
Eac h A E is t o b e cl assifie d as seri o us or n o n -seri o us b y t he i n vesti gat or usi n g me di cal a n d 
scie ntific j u d g me nt. 

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7. 5. 2.  
Defi niti o n of S eri o us  A d verse E ve nts  
A n S A E is a n u nt o war d me dic al occ urr e nce or effect ass ociate d wit h t he use of a st u d y dr u g at 
a n y d ose, re gar dl ess of w het her it is c o nsi d ere d t o b e relat e d t o t h e st u d y dr u g, w hic h res ults i n 
o ne of t he f oll o wi n g:  
•  D eat h. T his i n cl u des all deat hs o n treat me nt or wit hi n 3 0 da ys after l ast st u d y dr u g 
a d mi nistr ati o n, i ncl u di n g deat hs d ue t o disease pr o gr essi o n. A n y deat h occ urri n g later 
t ha n 3 0 da ys f oll o wi n g t he l ast d ose nee d n ot be re p orte d as a n S A E u nless it is a 
res ult of a n e v e nt t h at start e d wit hi n t he peri o d c o ver e d b y t he o n-st u d y defi niti o n. 
T he re p ort e d A E s h o ul d be t he e ve nt t hat ca use d t h e deat h. I n a d diti o n, a n y A E 
res ulti n g i n d eat h t hat o cc urs s u bse q ue ntl y t o t he A E re p orti n g peri o d a n d t h at t he 
i n vesti gat or assesses as p ossi bl y relat e d t o t he st u d y dr u g s h o ul d als o be re p ort e d as 
seri o us. 
•  A  life-t hre ate ni n g c o n diti o n. T his ref ers t o a n e v e nt i n w hic h t he s u bje ct was at ris k of 
deat h at t he ti m e of t he e v e nt. It d o es n ot i ncl u de a n e ve nt t h at, ha d it oc c urre d i n a 
m ore se vere f or m, h y p ot heticall y mi g ht ha v e ca use d deat h.  
•  H os pitaliz ati o n or pr ol o n gati o n of e xisti n g h os pitaliz ati o n (e x cl u di n g h os pitalizati o ns 
f or a d mi nistr ati o n of t he st u d y dr u g, pr oce d ur es re q uire d b y t he st u d y pr ot oc ol, or 
treat me nt-r elat e d dia g n ostic pr oc e d ures; ot h er pla n n e d h os pitalizati o ns; or 
h os pitali zati o ns relate d o nl y t o pr o gressi o n of diseas e). P r o gressi o n of disease 
res ulti n g i n tra nsfer t o I C U, m ec ha ni cal v e ntilati o n, or ot her me dicall y i m p orta nt 
e ve nt (at t he discreti o n of t he i n v esti gat or)  w o ul d be c o nsi dere d  S A Es. Treat me nts i n 
t he e m er ge nc y r o o m f or pr oce d ures s uc h as h y drati o n t hat d o n ot r e q uire a d mitti n g 
t he s u bject t o t h e h os pital a n d o bser vati o nal d ur ati o ns i n t he e m er ge nc y r o o m f or less 
t ha n 2 4 h o urs d o n ot fall i nt o t his cate g or y. 
•  P ersiste nt or si g nif i ca nt disa bilit y or i n ca pacit y or s u bsta ntial disr u pti o n of t he a bilit y 
t o c o n d uct n or mal life f u ncti o ns. 
•  A n y ot her me di call y i m p orta nt e v e nt t h at t h e i n vesti gat or or t he s p o ns or j u d ges t o b e 
seri o us or w hic h is defi ne d as seri o us b y t he re g ul at or y a ge nc y i n t he l o cal c o u ntr y. 
T hese are A Es t h at mi g ht n ot be i m me diatel y life -t hr eate ni n g or res ult i n deat h or 
h os pitali zati o n b ut mi g ht j e o par di ze t he s u bj ect or mi g ht re q uir e i nt er ve nti o n t o 
pre ve nt o ne of t he ot h er o utc o m es liste d a b o ve. Me di cal j u d g me nt s h o u l d b e 
e xercise d i n deci di n g w het her a n A E is seri o us base d o n a b o ve defi niti o n. E xa m ples 
of s uc h e ve nts are i nte nsi ve treat me nt i n a n e mer g e n c y r o o m or at h o me f or aller gi c 
br o nc h os pas m, bl o o d d yscrasias or c o n v ulsi o ns t hat d o n ot res ult i n h os pitalizati o n , 
or de vel o p m e nt of dr u g de pe n d e nc y or dr u g a b use.  
•  A pre g na nc y res ulti n g i n s p o nta n e o us a b orti o n, still birt h, ne o natal d eat h, or 
c o n ge nit al a n o mal y (i ncl u di n g t hat i n a n a b orte d fet us).  
N ote t hat a n y S A Es occ urri n g at a n y ti me u p t o Da y 6 0  s h o ul d be re p orte d t o t he s p o ns or if t h e 
i n vesti gat or bec o mes a ware of t h e m. 

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A d verse E ve nts of S peci al I nterest  
E ve nts t hat ma y b e i n di cati ve of he pat ot o xi cit y  (i ncl u di n g t he l o wer le vel Me d D R A ter m of 
h e pat ot o xicit y  or dr u g -i n d uce d h e pat ot o xicit y) ar e c onsi dere d a d verse e v e nts of s peci al i nterest 
( A E SIs) a n d will be re p ort e d o n a n e x pe dite d b asis. T hese i ncl u de: 
•  A L T i ncre ase Gra d e ≥3 ( > 5 × U L N)  
•  A S T i ncrease Gra de ≥3 ( > 5 × U L N)  
•  T bili  i ncre ase > 2 × U L N 
•  A L P ≥ 2 × U L N  
All i nsta nc es meeti n g t h e a b o ve criteria s h o ul d be r e p orte d wit hi n 2 4 h o urs  t o t he P T C 
T hera pe utics P har m ac o vi gila nc e De part me nt o n t he S A E f or m. If t he e ve nt is c o nsi dere d 
n o n -seri o us b y t he i n vesti gat or t he n t h e S A E f or m a n d A E C R F pa ge s h o ul d b e mar k e d as 
n o n -seri o us. Me dicall y si g nifi ca nt li ver e v e nts t hat are c o nsi dere d S A Es a n d c o nsist of mar ke d 
ele vati o ns of L F Ts a n d / or pr e -s pecifi e d A Es ma y als o be i ncl u de d i n e x pe dite d re p orti n g.  
7. 5. 4.  
U ne x pecte d A d verse E ve nts  
T he I n vesti g at or’s Br oc h ure  c o ntai ns t h e Refer e nce Safet y I nf or mati o n ( R SI) w hic h will be use d 
f or assessi n g e x pecte d ness. If a n e v e nt is n ot liste d i n t he R SI, it s h o ul d be c o nsi dere d 
u ne x pect e d or if t h e A E occ urs at a greater se verit y, s pecificit y or fre q ue n c y, it s h o ul d b e 
c o nsi dere d u ne x p ect e d.  
A n y he patic a b n or malities/ he pat ot o xi cit y ( h y p er bilir u bi ne mi a, as part ate a mi n otr a nsferase 
i ncrease, ala ni ne a mi n otra nsfer ase i ncr ease) of Gra d e ≥4 will b e c o nsi der e d u ne x pecte d.  
7. 5. 5.  
Eliciti n g A d verse E ve nt Inf or m ati o n  
T he i n vesti gat or is t o re p ort all dire ctl y o bser ve d A Es a n d all A Es s p o nta ne o usl y r e p orte d b y t he 
st u d y s u bject/ p are nt(s)/le gal g uar dia n/le g all y acc e pta ble re prese ntati ve. I n a d diti o n, e ac h st u d y 
s u bject/ p are nt(s)/le gal g u ar dia n/le g all y acc e pta ble re prese ntati ve will be q uesti o ne d a b o ut A Es at  
eac h sc he d ule d cli nic visit after st u d y dr u g a d mi nistr ati o n or d uri n g a n y tele p h o ne c o ntact wit h 
t he s u bject/ par e nt(s)/le g al g uar dia n/le gall y a cce pta bl e re prese nt ati ve. T he t y p e of q uesti o n as ke d 
s h o ul d be o pe n-e n de d, f or e x a m pl e, “ H o w h ave y o u bee n fe eli n g ? ” or a si milar t y pe of q uer y.  
7. 5. 6.  
Rec or di n g N o n ‑seri o us A Es a n d S A Es  
All A Es ( b ot h seri o us a n d n o n -seri o us) t hat occ ur i n s u bjects d uri n g t h e A E re p orti n g peri o d 
m ust be rec or d e d, w het her or n ot t he e v e nt is c o nsi d ere d dr u g  rel ate d. I n a d diti o n, a n y k n o w n 
u nt o war d e ve nt t hat o cc urs s u bse q ue nt l y t o t he A E r e p orti n g peri o d t hat t he i n vesti g at or assesses 
as p ossi bl y relat e d t o t h e i n vesti gati o nal dr u g/ pr o d u ct s h o ul d als o be re c or de d as a n A E.  
All A Es are t o be r ec or de d i n t he s o urce d o c u me nts a n d o n t he e C R F us i n g c o n cise m e dic al 
ter mi n ol o g y; w he ne v er p ossi ble, t er ms c o ntai ne d i n t he Me dical Dicti o nar y f or Re g ul at or y 
Acti vities ( Me d D R A) s h o ul d be e m pl o y e d. I n a d diti o n, t he f oll o wi n g i nf or mati o n s h o ul d be 
rec or de d: 
•  I n dicati o n of w het her t he e ve nt is seri o us or n on -seri o us (see Secti o n 7. 5. 2 ) 
•  Relati o ns hi p t o st u d y dr u g (see Se cti o n  7. 5. 7 ) 

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•  Se verit y of t h e e ve nt (see Secti o n  7. 5. 8 ) 
•  O nset date  
•  Res ol uti o n date, or date of deat h  
•  Acti o n ta k e n  
•  O utc o me of t h e e ve nt  
Classificati o n of t h e e ve nt as seri o us or n o n -seri o us deter mi nes t he r e p orti n g pr oc e d ures t o be 
f oll o we d. 
7. 5. 7.  
Descri bi n g A d verse E ve nt R el ati o ns hi p t o S t u d y D r u g 
T he i n vesti gat or s h o ul d pr o vi de a n assess me nt of t he relati o ns hi p of t he A E t o t he st u d y dr u g, 
ie, w het her t here is a reas o na bl e p ossi bilit y t hat t he st u d y dr u g ca use d t h e A E, usi n g t he 
c o nsi derati o ns o utli n e d i n  T a ble  5 . 
T a bl e  5 : 
R el ati o n s hi p of St u d y Dr u g t o A d v er s e E v e nt R el ati o n s hi p  
 
D e s cri pti o n  
Pr o b a bl e  
A cli ni c al e v e nt i n w hi c h a r el ati o n s hi p t o t h e st u d y dr u g s e e m s pr o b a bl e b e c a u s e of s u c h 
f a ct or s a s c o n si st e n c y wit h k n o w n eff e ct s of t h e dr u g; a cl e ar t e m p or al a s s o ci ati o n wit h 
t h e u s e of t h e dr u g; i m pr o v e m e nt u p o n wit h dr a w al of t h e dr u g; r e c urr e n c e u p o n 
r e-c h all e n g e wit h t h e dr u g; l a c k of alt er n ati v e e x pl a n ati o n s f or t h e e v e nt.  
P o s si bl e  
A cli ni c al e v e nt o c c urri n g c oi n ci d e nt wit h a d mi ni str ati o n of t h e st u d y dr u g a n d w hi c h m a y 
or m a y n ot b e e x pl ai n e d b y c o n c urr e nt di s e a s e or ot h er dr u g s or c h e mi c al s. I nf or m ati o n 
o n dr u g wit h dr a w al or r e -c h all e n g e m a y b e l a c ki n g.  
U nli k el y  
A cli ni c al e v e nt w it h a t e m p or al r el ati o n s hi p t o t h e st u d y dr u g e x p o s ur e t h at d o e s n ot 
pr e cl u d e c a u s alit y b ut f or w hi c h t h er e i s a cl e ar alt er n at e c a u s e t h at i s m or e li k el y t o h a v e 
c a u s e d t h e a d v er s e e v e nt t h a n st u d y dr u g. S u c h alt er n ati v e s i n cl u d e a c o n c o mit a ntl y 
a d mi ni st e r e d dr u g, t h e s u bj e ct’ s di s e a s e st at e, ot h er m e di c al c o n diti o n s, or 
e n vir o n m e nt al f a ct or s.  
U nr el at e d  
A cli ni c al e v e nt, f or w hi c h a r el ati o n s hi p t o t h e st u d y dr u g s e e m s i m pr o b a bl e b e c a u s e of 
f a ct or s s u c h a s i n c o n si st e n c y wit h k n o w n eff e ct s of t h e st u d y dr u g, l a c k of a t e m p or al 
a s s o ci ati o n wit h st u d y dr u g a d mi ni str ati o n, l a c k of a s s o ci ati o n of t h e e v e nt wit h st u d y 
dr u g wit h dr a w al or r e -c h all e n g e, a n d/ or pr e s e n c e of alt er n ati v e e x pl a n ati o n s f or t h e 
e v e nt. Alt er n ati v e e x pl a n ati o n s mi g ht i n cl u d e a k n o w n r el at i o n s hi p of t h e a d v er s e e v e nt 
t o a c o n c o mit a nt dr u g, m e di c al hi st or y of a si mil ar e v e nt, t h e s u bj e ct’ s di s e a s e st at e, 
ot h er m e di c al c o n diti o n s, or e n vir o n m e nt al f a ct or s.  
7. 5. 8.  
Gr a di n g of S e verit y of A d verse E v e nt  
T he se verit y of A E will b e gra de d usi n g t h e C o m m o n Ter mi n ol o g y Crit eria f or A d verse E v e nts 
( C T C A E) Versi o n 5. 0 (refer t o t h e st u d y ma n u al). F or eac h e pis o de, t he hi g hest se verit y gra de 
attai ne d s h o ul d be r e p orte d.  
If a C T C A E criteri o n d o es n ot e xist, t he i n vesti gat or s h o ul d use t he gra de or a djecti ves: Gra d e 1 
( mil d), Gra de 2 ( m o derat e), Gr a de 3 (se ver e), Gr a de 4 (life-t hr eat e ni n g), or Gr a de 5 (fatal) t o 
descri be t h e ma xi m u m i nte nsit y of t he A E. F or p ur p oses of c o nsiste nc y wit h t h e C T C A E, t h ese 
i nte nsit y gr a des are d efi ne d i n Ta bl e  6 . 

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Gr a di n g of A d v er s e E v e nt S e v erit y Gr a d e  
 
A dj e cti v e  
D e s cri pti o n  
Gr a d e 1  
Mil d  
Si g n or s y m pt o m i s pr e s e nt, b ut it i s e a sil y t ol er at e d, i s n ot e x p e ct e d t o 
h a v e a cli ni c all y si g nifi c a nt eff e ct o n t h e s u bj e ct’ s o v er all h e alt h a n d 
w ell -b ei n g, d o e s n ot i nt erf er e wit h t h e s u bj e ct’ s u s u al f u n cti o n, a n d i s 
n ot li k el y t o r e q uir e m e di c al att e n ti o n  
Gr a d e 2  
M o d er at e  
Si g n or s y m pt o m c a u s e s i nt erf er e n c e wit h u s u al a cti vit y or aff e ct s 
cli ni c al st at u s, a n d m a y r e q uir e m e di c al i nt er v e nti o n  
Gr a d e 3  
S e v er e  
Si g n or s y m pt o m i s i n c a p a cit ati n g or si g nifi c a ntl y aff e ct s cli ni c al st at u s 
a n d li k el y r e q uir e s m e di c al i nt er v e nti o n a n d/ or cl o s e f oll o w -u p  
Gr a d e 4  
Lif e -t hr e at e ni n g  
Si g n or s y m pt o m r e s ult s i n a p ot e nti al t hr e at t o lif e  
Gr a d e 5  
F at al  
Si g n or s y m pt o m r e s ult s i n d e at h  
7. 5. 9.  
A d verse E ve nt Re p orti n g  
In vesti gat or site re p orti n g re q uir e me nts f or A Es are s u m mari ze d i n  Ta bl e  7 . 
T a bl e  7 : 
I n v e sti g at or Sit e R e q uir e m e nt s f or R e p orti n g A d v er s e E v e nt s 
E v e nt  
R e c or d e d o n t h e e C R F  
R e p ort e d o n t h e S A E R e p ort F or m t o 
P T C P h ar m a c o vi gil a n c e Wit hi n 
2 4  H o ur s of A w ar e n e s s  
S eri o u s A E  
All  
All  
N o n -S eri o u s A E  
All  
N o n e  
E x p o s ur e t o t h e st u d y 
dr u g d uri n g pr e g n a n c y or 
br e a stf e e di n g, a n d 
o c c u p ati o n al e x p o s ur e  
All (r e g ar dl e s s of w h et h er 
a s s o ci at e d wit h a n A E), e x c e pt 
o c c u p ati o n al e x p o s ur e  
E x p o s ur e d uri n g pr e g n a n c y, e x p o s ur e 
vi a br e a stf e e di n g, o c c u p ati o n al e x p o s ur e 
(r e g ar dl e s s of w h et h er a s s o ci at e d wit h 
a n A E)  
A b br e vi ati o n s: A E, a d v er s e e v e nt; e C R F, el e ctr o ni c c a s e r e p ort f or m; S A E, s eri o u s a d v er s e e v e nt 
All A Es s h o ul d be f oll o we d u p b y t h e i n vesti gat or u ntil t h e y are r es ol ve d, or t he i n vesti g at or 
assesses t he m as c hr o nic or st a ble. T h e i n vesti gat or s h o ul d c o nsi der pr ot o c ol g ui d eli n es a n d use 
his/ her discreti o n i n or d eri n g  a d diti o nal tests as ne cessar y t o m o nit or t h e res ol uti o n of s uc h 
e ve nts. I n t he e ve nt of a d diti o n al i n v esti gati o ns, t he P T C T hera pe utics P har m ac o vi gila nc e 
De part me nt or desi g nee s h o ul d be i nf or m e d via e -mail or fa x. A s u bject wit h dra w n fr o m t he 
st u d y beca use of a n A E m ust be f oll o we d b y t he i n v esti gat or u ntil cli nical rec o ver y is c o m pl ete 
a n d la b orat or y res ults ha ve r et ur ne d t o n or mal, or u ntil pr o gressi o n has be e n sta biliz e d. 
F oll o w -u p m a y nee d t o c o nti n ue after t he s u bj ect h as disc o nti n ue d fr o m t he st u d y,  a n d a d diti o nal 
i n vesti gati o ns ma y b e re q uest e d b y t he m e dic al m o nit ori n g te a m. 
T he first da y of A E r e p orti n g will c oi n ci de wit h t he date of si g ni n g of I nf or me d C o nse nt.  
7. 5. 1 0.  
Seri o us A d verse E ve nt R e p orti n g  
All S A Es s h o ul d be re p orte d vi a t he “S A E R e p ort F or m ” t o P T C T h era pe utics wit hi n 2 4 h o urs of 
bec o mi n g a ware of t he e ve nt(s). I n a d diti o n, t he A E p orti o n of t he e C R F m ust als o be c o m pl ete d  
i n E D C. 
T he S A E re p ort f or m s h o ul d b e si g ne d b y t h e i n vesti gat or; h o we ver, if t he i n vesti gat or is u na bl e 
t o si g n at t h e time of t h e e ve nt or wit hi n 2 4 h o urs, t h e f or m s h o ul d be si g ne d b y t he cli ni cal staff 
me m ber r e p orti n g t he S A E (e g, t he st u d y c o or di nat or). T he S A E re p ort f or m m ust be fa xe d or 
e-maile d t o t he P T C T h era pe utics P har ma c o vi gila nc e De part m e nt or desi g ne e a n d t o t he sit e 
I nstit uti o n al Re vie w B oar d/ Et hi cs C o m mitte e I R B/ E C (if re q uire d b y l ocal re g ulati o ns) wit hi n 
2 4 h o urs.  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
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P a ge 4 3  of 6 2  
F oll o w -u p i nf or mati o n t o t h e S A E s h o ul d be cl earl y d oc u me nt e d wit h  “ F oll o w -u p” b o x c hec k e d 
a n d t he f oll o w -u p n u m ber i n t he S A E Re p ort F or m c o m plet e d a n d fa x e d or e-maile d t o t he sa me 
part y. All f oll o w -u p S A E re p ort f or ms f or t he e v e nt m ust be si g ne d b y t h e i n vesti gat or. A n y 
s o urce d oc u me nts (e g, pr o gress n otes, n urses’ n otes, la b orator y a n d dia g n ostic test res ults, 
disc har ge s u m m aries) pr o vi de d t o t he s p o ns or s h o ul d be re dacte d s o t hat t he s u bje ct’s na m e, 
a d dress, a n d ot her pers o nal i de ntit y i nf or mati o n are o bsc ure d. O nl y t he s u bje ct’s st u d y n u m ber 
a n d i nitials ar e t o be pr o vi de d (i n re gi o ns w here t he pr o visi o n of s uc h i nf or mati o n is per mitte d). 
T he i nf or m ati o n i n t he A E p orti o n of t he e C R F a n d t he S A E re p ort f or m(s) m ust m atc h or be 
rec o ncile d. W her e t he sa me data ar e c ollecte d, t he i nf or mati o n o n t he S A E Re p ort F or m m ust be 
c o m plete d i n a c o nsiste nt ma n ner.   
I n t he rare e ve nt t h at t h e i n vesti gat or d o es n ot bec o m e a ware of t he o cc urre n ce of a n S A E 
i m me diat el y (f or e xa m ple, if a s u bje ct i niti all y se e ks treat me nt else w here), t h e i n vesti gat or is t o 
re p ort t he e ve nt wit hin 2 4 h o urs after lear ni n g of it a n d t o d oc u me nt his/ her first a ware ness of t he 
A E.  
T he P T C T her a pe utics P har mac o vi gil a nce De p art m e nt c o nta ct i nf or mati o n f or re p orti n g S A Es is 
pr o vi de d bel o w. T his i nf or mati o n is als o pr o vi de d i n t he St u d y Ma n ual a n d i n t h e S A E re p ort 
f or m. 
P T C T her a pe utics S afet y D e p art me nt  
Atte nti o n: P h ar m ac o vi gil a nc e  
E -m ail:
F acsi mil e: 
 
7. 5. 1 1.  
Re p orti n g Pre g n a nc y  
P T C T hera pe utics s h o ul d be n otifi e d i n t h e e ve nt t hat a fe m ale s u bj ect i n t he st u d y, or a f e male 
part ner of a male s u bject i n t he st u d y, b ec o m es pre g na nt o n -st u d y or wit hi n 5 0 d a ys of t he l ast 
a d mi nistr ati o n of st u d y dr u g m ust be re p orte d o n a n electr o nic f or m “I n vesti g ati o n al a n d 
Mar kete d Pr o d ucts Pre g na n c y Re p ort F or m” (se e st u d y ma n ual f or details).  
T his m ust be d o ne w het her or n ot a n A E has occ urre d a n d wit hi n 2 4 h o urs of a ware ness of t he 
pre g na nc y. T h e i nf or mati o n s u b mitte d s h o ul d i ncl u d e t he a ntici pat e d date of birt h or pre g n a nc y 
ter mi n ati o n. 
Writt e n c o nse nt is re q uire d pri or t o c ollecti n g  a n d r e p orti n g a n y i nf or mati o n o n a fe male p art ner 
of a mal e s u bject i n t h e st u d y.  
If p ossi ble, t he i n v esti gat or s h o ul d f oll o w t h e s u bject, or t he pre g na nt fe male part ner of a mal e 
s u bject, u ntil c o m pleti o n of t h e pre g na nc y a n d n otif y t he me dical m o nit or o f t he o utc o me wit hi n 
5 da ys or as s pecifie d b el o w. T he i n v esti gat or will pr o vi de t his i nf or mati o n wit h ‘ F oll o w -u p”  
b o x c hec k e d a n d t he f oll o w -u p n u m b er c o m plete d o n t he Pre g na nc y R e p ort F or m (see t he st u d y 
ma n ual f or d etails).  
If t he o utc o me of t h e pre g na nc y meets t he criteria f or i m me diat e cl assificati o n as a n S A E 
(ie, pret er m t er mi nati o n, electi ve a b orti o n , i ntra uteri ne deat h,  or ot her) , t he i n vesti g at or s h o ul d 
f oll o w t he pr oc e d ures f or re p orti n g S A Es, ie, r e p ort t he e ve nt t o t he P T C T hera pe utics Safet y 
D e part me nt or desi g nee a n d f oll o w -u p b y s u b missi o n of a p pr o priat e A E e C R Fs 
(see Secti o n  7. 5. 1 0 ). 

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P a ge 4 4  of 6 2  
7. 5. 1 2.  
P T C T her a pe utics A d verse E ve nt Re p orti n g Re q uire me nt  
As t he s p o ns or of t he st u d y, P T C T hera pe utics is res p o nsi ble f or re p orti n g certai n safet y 
i nf or mati o n, partic ul arl y A E SIs,  S A Es a n d s u bject d eat hs rel ate d t o parti ci pati o n i n t he st u d y, t o 
eac h i n v esti gat or i n a n e x p e dit e d ma n n er. If n otificati o n of a n A E re q uiri n g e x pe dite d re p orti n g 
t o i n vesti g at ors is rec ei ve d, P T C T hera pe utics or its desi g nate d r e prese ntati ve will c o ntact ea c h 
i n vesti gati o nal site p arti ci pati n g i n t his st u d y b y e-m ail, fa x, a n d/ or o ver ni g ht mail s uc h t h at t h e 
i n vesti gat or can pr o m ptl y n otif y t h e site I R B/ E C per t heir l o cal r e q uire m e nts. T he i nitial 
e x pe dit e d safet y re p ort will b e pr o vi de d as re q uire d acc or di n g t o l oc al re g ul ati o ns (e g, wit hi n 
1 5  da ys) after t h e earliest date P T C T h era pe utics or a n a ge nt of P T C T h era pe utics (e g, a site 
m o nit or) be c o mes a ware of a n A E. T his a war e ness date is t h e dat e t he re g ulat or y r e p orti n g cl oc k 
be gi ns , a n d t he d ate is c o nsi dere d Da y 0.  
8.  
S T A TI S TI C A L C O N SI D E R A TI O N S  
A statistic al a n al ysis pla n ( S A P) will be pr e pare d a n d a p pr o ve d pri or t o t he first u n bli n de d 
i nteri m a nal ysis t o pr o vi de a m ore detaile d descri pti o n of t he nat ur e of t he a n al yses a n d t h e 
ma n ner i n w hi c h res ults will be c o m p iled. T he S A P will i ncl u de details of t he statisti cal m o dels 
t o be use d a n d t h e test st atistics t o be e m pl o ye d. 
8. 1.  
St atistic al H y p ot heses  
T he n ull h y p ot hesis f or t he pri mar y effica c y c o m p aris o n is t hat t he distri b uti o n of ti me t o 
res pirat or y i m pr o ve m e nt i n h os pitalize d s u bje cts wit h C O VI D-1 9 is t he  sa me bet wee n t he 
2  gr o u ps of P T C 2 9 9 a n d place b o . T he alter nati ve h y p ot hes is is t hat t he distri b uti o n of ti m e t o 
res pirat or y i m pr o ve m e nt bet we e n t he 2 treat me nt gr o u ps is n ot t he sa me. R eje cti n g t he n ull 
h y p ot hesis wit h s h orte ne d ti m e t o res pir at or y i m pr o v e me nt i n t he P T C 2 9 9, f or t he i nte nt-t o-treat 
(I T T) p o p ulati o n, will be c o nsi d ere d a s ucc essf ul de m o nstrati o n of effic ac y.  
8. 2.  
S a m ple Size Deter mi n ati o n  
T his is a gr o u p se q ue ntial d esi g n wit h 2 i nteri m a nal yses pla n ne d. T he first i nt eri m a n al ysis will 
o nl y assess t he safet y a n d t he trial will n ot be st o p p e d f or f utilit y or s u peri orit y  of effic ac y . It 
will be perf or me d after t he first 4 0 ra n d o mize d s u bj e cts ha ve c o m plete d Da y 2 8  or  disc o nti n ue d 
d ue t o deat h , wit h dr e w  c o nse nt, or were l ost-t o-f oll o w-u p .  
T he sec o n d i nteri m a nal ysis is t o assess f utilit y a n d will be perf or me d w he n 5 0 % of res pirat or y 
i m pr o ve m e nt e v e nts ha ve be e n rea c he d, ie, 1 6 3  e ve nts ha ve bee n o b ser v e d (a p pr o x i m atel y 
1 9 0  s u bjects). La n -De Mets beta s pe n di n g f u n cti o n ( n o n -bi n di n g o pti o n) is use d t o de fi n e t he 
b o u n dar y f or t he 2n d i nteri m f utilit y a nal ysis a n d t h e fi nal a n al ysis t o e ns ure t he o verall beta of 
8 0 % . T he sa m pl e size was calc ul ate d t o refl ect t he pri mar y e n d p oi nt of ti me fr o m ra n d o mizati o n 
t o res pirat or y i m pr o ve me nt, w hic h is defi ne d  as t he ti me fr o m r a n d o mi zati o n  t o res pirat or y 
i m pr o ve m e nt (S p O 2  ≥9 4 % i n r o o m air) , s ustai n e d u ntil disc h ar ge fr o m t he h os pit al  or t he e n d of 
t he st u d y ( D a y 2 8). Me dia n ti m e t o res pirat or y i m pr o ve me nt was n ot r ea dil y a vaila bl e fr o m t h e 
liter at ure. B ase d o n  ver y li mite d dat a, it is a nti ci pate d t hat t h e me dia n ti me t o res pirat or y 
i m pr o ve m e nt f or t h e plac e b o gr o u p is 1 1  da ys a n d P T C 2 9 9 treat me nt will d ecrease it t o 8  d a ys , 
a n i m pr o ve me nt of 3 -d a ys . S u bjects will be f oll o we d f or t he fi xe d a m o u nt of ti m e of 2 8 da ys 
fr o m ra n d o mi zati o n (c orres p o n di n g t o t he a ntici pat e d i m pr o ve m e nt rates of  0. 8 2 9  a n d 0.9 1 2  at 
Da y 2 8 f or place b o  a n d P T C 2 9 9, res pecti vel y ). A  t ot al of 3 2 6 e ve nts will pr o vi d e m ore t ha n 8 0 % 

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of p o w er t o dete ct a ha zar d  rati o of 1. 3 8  at t w o -si de d t y pe I err or of 0. 0 5. A p pr o xi matel y 
3 8 0  s u bjects, i n t otal, will be n ee de d. 
8. 3.  
P o p ul ati o n f or A n al yses  
I nte nt-t o-tre at (I T T) p o p ul ati o n: will i ncl u de all ra n d o mize d s u bj ects. T h e I T T p o p ulati o n will 
be use d i n all effi cac y a n al ysis a n d s u b je cts will b e gr o u pe d base d o n t he ar m t he y are 
ra n d o miz e d t o. I n t h e e ve nt t hat a s u bject rec ei ve d tr eat m e nt i n t he ar m differe nt fr o m t h e o ne t o 
w hic h he/s he was ra n d o mize d, t h e s u bject’s effic ac y data will be a n al yze d “as ra n d o mize d. ”  
S afet y p o p ul ati o n : will i ncl u de all r a n d o mi ze d s u bj ects w h o recei ve d at least o n e  d ose of st u d y 
dr u g . I n t he e ve nt t hat a s u bject rec ei ve d treat me nt i n t he ar m differe nt fr o m t he o n e t o w hic h 
he/s he was ra n d o mi ze d, t he s u bject’s safet y dat a will be a nal y ze d “as tr eat e d.” T h e  Safet y 
A nal ysis p o p ulati o n will be use d i n t he st atistical a nal yses f or safet y.   
P K  p o p ul ati o n:  will i ncl u de  safet y p o p ulati o n s u bje cts w h o ha d at l east o ne P K pr ofil e 
assess me nt.  
8. 4.  
St atistic al A n al yses  
8. 4. 1.  
Ge ner al A p pr o ac h  
F or c o nti n u o us varia bles, me dia n, m ea n, sta n dar d d e viati o n, mi ni m u m, m a xi m u m, a n d t h e 
n u m ber of s u bjects wit h n o n -missi n g data will be pr o vi de d f or ea c h treat me nt gr o u p . F or 
cate g orical varia bles, t he n u m ber ( per ce nt) of s u bj ects i n eac h c ate g or y will be pr o vi d e d.  
8. 4. 2.  
A n al ysis of P ri m ar y E ffic a c y E n d p oi nts  
T he pri m ar y e n d p oi nt is ti me fr o m ra n d o miz ati o n t o res pirat or y i m pr o ve m e nt, defi n e d as S p O 2 
≥9 4 % o n r o o m air  s ustai ne d u n til disc h ar ge fr o m t h e h os pital or t h e e n d of t h e st u d y ( Da y 2 8) . 
All h os pitalize d s u bj ects will be f oll o we d f ull y t o Da y 2 8 wit h effic ac y m eas ure me nts ta ke n 
dail y u nl ess t he y die, are l ost t o f oll o w -u p, or wit h dr a w c o nse nt. F or s u bj ects w h o are disc har ge d  
fr o m t he h os pit al pri or t o Da y 2 8 wit h o ut ac hie vi n g r es pirat or y i m pr o ve m e nt, S p O 2 
meas ure m e nts will b e ta ke n d ail y u ntil Da y 2 8 . All meas ure m e nts rec or de d will be use d f or 
effica c y a nal ysis.  
S u bjects w h o ac hi e ve d S p O 2 ≥9 4 % o n r o o m air a n d s ustai ne d t his t o Da y 2 8 or disc har ge 
wit h o ut ta ki n g a n y C O VI D -1 9 resc ue t hera py  d uri n g t he st u d y will b e c o nsi der e d as ac hi e vi n g 
t he res pirat or y i m pr o v e me nt e ve nt a n d t he e ve nt d ate will be t h e first date of ac hie vi n g S p O 2 
≥9 4 %. S u bjects will be c e ns o re d at Da y 2 8 if a n y of t he f oll o wi n g a p pl y : 
•  ra n d o miz e d b ut ha d n o f oll o w-u p  
•  t o o k a n y C O VI D -1 9 resc ue t hera py  d uri n g t he st u d y  
•  l ost t o f oll o w-u p pri or t o Da y 2 8  
•  die d pri or t o Da y 2 8  
•  wit h dr e w  c o nse nt pri or t o Da y 2 8  
•  ha d f ull f oll o w -u p wit h o ut a c hie vi n g  s ustai ne d S p O 2 ≥9 4 %.  

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Resc ue t her a p y is defi ne d as a n y a d diti o nal me dicati o n , e xcl usi ve of S O C, use d t o tr eat a 
w orse ni n g of C O VI D -1 9 s y m pt o ms a n d rec or de d as resc ue t her a p y o n t he e C R F.  
Ka pla n -Meier pl ots of ti me t o res pir at or y i m pr o ve m e nt will b e prese n t e d. Me dia n ti me t o 
res pirat or y i m pr o ve m e nt will be esti mat e d via t he K a pla n -Mei er  pr o d uct li mit met h o d. A  tw o -
si de d 9 5 % c o nfi de n ce i nter val ( CI ) f or t he m e dia n ti me t o res pir at or y i m pr o ve me nt will be 
c o m p ute d f or P T C 2 9 9  a n d pla ce b o c o h orts  base d o n a l o g -l o g tr a nsf or me d CI f or t he s ur vi v or 
f u ncti o n S(t). Ti me t o res pirat or y i m pr o ve me nt  will be c o m par e d bet wee n treat me nt gr o u ps 
usi n g stratifi e d l o g -ra n k test. 
Hazar d rati o a n d c orres p o n di n g t w o -si de d 9 5 % CIs will be esti mate d usi n g a C o x pr o p orti o nal 
hazar ds m o del, wit h tr eat m e nt ar m as a si n gl e c o vari ate, stratifi e d b y t he stratifi cati o n fact ors.  
Res pirat or y i m pr o ve m e nt  rates at D a ys 7 , 1 4, a n d 2 8 will als o be esti m ate d usi n g Ka pla n -Meier  
esti mates o n t he ti m e t o res pir at or y i m pr o v e me nt c ur ve. Ass ociate d t w o-si de d 9 5 % CIs f or ea c h 
treat me nt gr o u p a n d t he differe nc e bet we e n t he 2  tre at me nt gr o u ps will be cal c ulat e d usi n g 
Gree n w o o d’s f or m ul a f or varia n ce deri vati o n.  
8. 4. 3.  
A n al ysis of S ec o n d ar y E ffic ac y E n d p oi nts  
Si milar t o t he pri mar y e n d p oi nt, Ka pla n -Meier esti m ate, m e dia n a n d rate at D a ys 7, 1 4 , a n d 2 8 
will be prese nte d f or ti me fr o m r a n d o mi zati o n t o def er vesce nce (i n s u bjects prese nti n g wit h 
fe ver at e nr oll me nt), ti me fr o m ra n d o mizati o n t o r es pirat or y rate ≤2 4 br eat hs/ mi n ute o n r o o m air , 
ti me fr o m ra n d o mizati o n t o c o u g h re p orte d as mil d or a bse nt (i n t h ose wit h c o u g h at e nr oll me nt 
rate d se ver e or m o derate), a n d ti m e fr o m ra n d o miz ati o n t o d ys p nea re p orte d as mil d or a bse nt 
( o n a scale of se ver e, m o der ate, mil d, a bse nt, i n t h ose wit h d ys p nea at enr oll me nt  rate d as se vere 
or m o derat e) .  
T he pr o p orti o n of s u bj ects re q uiri n g i n vasi v e ve ntilati o n at a n y p oi nt d uri n g t he st u d y , s u bj ects 
re q uiri n g s u p ple me nt al o x y ge n or n o n-i n v asi ve ve ntilati o n at a n y p oi nt i n t he st u d y i n s u bj ects 
wit h o ut s u p ple m e ntal o x y ge n or n o n-i n v asi ve ve ntilati o n at b aseli n e, s u bjects wit h n or malizati o n 
of  t he c o m plet e bl o o d c o u nt, a n d t he n u m ber of s u bj ects w h o die d at t he e n d of t he st u d y will be 
s u m mariz e d b y fre q ue nc y a n d perc e nt.  
T he f oll o wi n g se c o n dar y e n d p oi nt s will be s u m mari ze d descri pti vel y 
•  Re d ucti o n i n c yt o ki ne l e vels, p ot e ntiall y i ncl u di n g I L -2, I L -6, I L -7, I L -1 7, G -C S F, 
I P-1 0, M C P 1, MI P 1 -α, a n d T N F -α,  
•  Re d ucti o n i n le v els of ac ute p hase pr ot ei ns, p ote ntiall y i ncl u di n g ferriti n a n d 
C -reacti ve pr ot ei n, D -di mer, a n d car diac tr o p o ni n,  
•  C ha n ges i n ot her la b orat or y para m eters i n cl u di n g lactate d e h y dr o ge nase, pr ot hr o m bi n 
ti me, al b u mi n,  
•  Re d ucti o n i n viral l oa d, a n d  
•  D urati o n of h os pitaliz ati o n meas ure d i n d a ys   

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8. 4. 4.  
S afet y A n al yses  
8. 4. 4. 1.  
S u bject Dis p ositi o n  
T he dis p ositi o n of s u bj ects, i n cl u di n g t he n u m b er of s u bjects scree n e d, t he n u m ber of 
ra n d o miz e d s u bjects, t he n u m ber of r a n d o mi ze d s u bj ects w h o recei ve d at least 1 d ose of st u d y 
dr u g, a n d t he n u m b er of s u bjects w h o pre mat urel y disc o nti n ue st u d y dr u g , as well as t he r eas o n 
f or t he pre m at ure ter mi n ati o n, will be ta b ul ate d.  
8. 4. 4. 2.  
Me dic al Hist ory a n d Pri or Me dic ati o n  
Me dical hist or y a n d pri or me dic ati o n i nf or mati o n will be s u m m ariz e d.  
8. 4. 4. 3.  
E xte nt  of E x p os ure a n d Tre at m e nt C o m pli a nce  
T he e xt e nt of e x p os ure t o st u d y me di cati o n is defi n e d as t he last d ose d ate mi n us t he first d ose 
date + 1 da y. C o m pli a nce will be assesse d i n ter ms of t he perc e nta ge of dr u g act u all y ta ke n 
relati ve t o t he a m o u nt t h at s h o ul d ha ve b ee n t a ke n d uri n g t he st u d y. E x p os ure a n d c o m plia nc e 
will be s u m m ari z e d descri pti vel y.  
8. 4. 4. 4.  
A dverse Eve nts  
S u m mar y i nf or m ati o n (t he n u m b er a n d perc e nt of s u bjects b y tr eat me nt) will be ta b ulate d f or:  
•  Treat me nt -e mer ge nt a d verse e ve nts ( T E A Es)  
•  Treat me nt -r elat e d A Es 
•  T E A Es b y se verit y  
•  S A Es  
•  A Es lea di n g t o disc o nti n u ati o n  
•  A E SIs  
S u m ma ries will be prese nte d b y tre at m e nt gr o u p a n d cate g orize d b y Me d D R A S yste m Or ga n 
Class a n d Preferre d Ter m. T he fr e q ue ncies of A Es dis pla ye d will b e t he cr u de rat es t hat 
re prese nt t h e n u m ber of s u bje cts e x perie nci n g A Es di vi de d b y t h e t ot al n u m b er of s u bjects. 
8. 4. 4. 5.  
L a b or at ory P ar a m eters  
C ha n ges i n cli nic al l a b orat or y t ests fr o m baseli ne (l ast meas ure m e nt pri or t o first d ose) a n d 
la b orat or y mar ke d a b n or maliti es usi n g pre-defi n e d a b n or malit y criteri a will b e descri pti vel y 
s u m mariz e d. 
8. 4. 5.  
B aseli ne D escri pti v e S t atistics 
De m o gra p hic a n d baseli ne c har act eristi cs of s u bjects (i ncl u di n g or di nal sc al e sc ore (W H O 2 0 2 0 ) 
will be s u m m ariz e d descri pti vel y b y mea ns a n d st a n dar d de viati o ns f or c o nti n u o us varia bl es, a n d 
fre q ue nc y distri b uti o n f or cate g orical vari a bles. S u m maries will be perf or me d base d o n all 
ra n d o miz e d s u bjects. 

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8. 4. 6.  
Pl a n ne d Interi m A n al yses  
T w o i nteri m a nal yses are pla n n e d. T he first  i nt eri m a nal ysis will be c o n d uct e d w he n 
a p pr o xi matel y 4 0 r a n d o mi ze d s u bjects ( 2 0 i n ea c h ar m) ha ve re cei ve d 1 4 d a ys of treat me nt a n d 
c o m plete d 1 4 da ys of f oll o w -u p  or disc o nti n ue d d u e t o deat h , wit h dr e w  c o nse nt, or were 
l ost-t o-f oll o w-u p . N o f or mal statistic al t esti n g will b e perf or me d at t he first i nt eri m a nal ysis . A n 
i n de pe n de nt dat a safet y m o nit ori n g b o ar d will r e vie w t he safet y data. E nr oll me nt will c o nti n u e if 
t here ar e n o safet y c o n cer ns. A sec o n d i nt eri m a nal ysis will be c o n d ucte d f or f utilit y . It will be 
perf or me d w he n 5 0 % of res pirat or y i m pr o v e me nt e v e nts ha ve be e n reac h e d, ie , 1 6 3  e ve nts ha v e 
bee n o bser ve d ( a p pr o xi mat el y  1 9 0 s u bje cts). Res pirat or y i m pr o ve me nt is defi ne d as S p O 2≥ 9 4 % 
i n r o o m air u ntil disc har ge fr o m t he h os pital or t h e e n d of st u d y  ( Da y 2 8). All s u bjects w h o ha ve 
c o m plete d t hr o u g h D a y 2 8 , were  disc har ge d wit h S p O 2 ≥9 4 % o n r o o m air , wit h dr e w c o nse nt, 
die d, were l ost t o f oll o w -u p, or t o o k a n y C O VI D -1 9 resc ue t her a py  d uri n g t he st u d y  will be 
i ncl u de d i n t he i nteri m a n al ysis . S u bjects w h ose pri mar y e ve nt ca n n ot be det er mi n e d at t he 
i nteri m c ut, ie, o n g oi n g s u bj ects , will n ot be i ncl u de d  i n t he i nteri m effi cac y a n al ysis. S u bjects 
w h o die d , wit h dre w c o nse nt, were l ost t o f oll o w-u p, or t o o k a n y C O VI D -1 9  resc ue t hera p y will 
be ce ns ore d at Da y 2 8. A stratifi e d l o g -ra n k test will be perf or me d a n d t he ha zar d rati o 
(treat me nt vs pl ace b o) will be c o m pare d wit h t he f utilit y b o u n dar y. T he trial ma y be st o p pe d f or 
f utilit y if t h e haz ar d rati o is less t ha n 1. 0 9 1. T h e f utilit y b ou n dar y is base d o n La n -De Mets bet a 
s pe n di n g f u ncti o n ( n o n-bi n di n g o pti o n) wit h o ver all beta of 8 0 % .  
T he u n bli n d e d i nt eri m a nal yses will be c o n d ucte d b y a n i n de pe n d e nt statisti cia n a n d t he res ults 
will be o nl y s har e d wit h t h e cl ose d sessi o n of t he D S M B. D S M B will ma ke t he g o - or n o -g o 
rec o m m e n dati o ns a n d o nl y t h e rec o m me n dati o ns will be c o m m u nic ate d wit h t he st u d y tea m. T he 
st u d y tea m will be k e pt bli n de d f or res ults relat e d t o t he i nt eri m a nal yses.  
8. 4. 7.  
S u b gr o u p  A n al yses  
S u b gr o u p a nal yses of t he pri mar y e n d p oi nt b y  baseli ne disease ris k fa ct ors  will be e x pl ore d as 
dee me d a p pr o priate. I n s uc h a nal yses,  a n u n-stratifie d l o g-ra n k test a n d t he h azar d rati o will be 
esti mate d usi n g t h e u nstratifie d C o x pr o p orti o nal h az ar ds m o del.  
8. 4. 8.  
E x pl or at or y A n al yses  
N ot a p plic a ble.  
9.  
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 A L 
C O N SI D E R A TI O N S  
9. 1.  
Re g ul at or y, Et hic al, a n d St u d y O versi g ht C o nsi der ati o ns  
9. 1. 1.  
I nf or me d C o nse nt P r ocess 
B y si g ni n g t he pr ot o c ol, t h e i n vesti gat or ass ures t hat i nf or me d c o nse nt will b e o btai ne d fr o m 
eac h s u bje ct  or l e gall y a ut h ori ze d re pr ese ntati ve  pri or t o st u d y e ntr y a n d t hat t he i nf or me d 
c o nse nt will b e o btai ne d i n acc or da n ce wit h c urre nt r e g ulati o ns.  

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T he i n vesti gat or or q u alifie d re prese ntati ve  will gi ve eac h s u bje ct or l e gall y a ut h ori ze d 
re prese ntati ve f ull an d a d e q uat e ver bal a n d writte n i nf or mati o n r e gar di n g t he o bje cti v es a n d 
pr oce d ures of t he st u d y a n d t he p ossi ble ris ks i n v ol v e d. A n i nf or me d c o nse nt d oc u me nt will b e 
pr o vi de d t o e ac h s u bje ct or le g all y a ut h ori ze d re pr ese ntati ve  i n a la n g u a ge i n w hic h t he su bje ct is 
fl ue nt, or tr a nslat e d, acc or di n g t o l o cal r e g ulati o ns. T his i nf or mati o n m ust be pr o vi de d t o t he 
s u bject or l e gall y a ut h orize d re pr ese ntati ve  pri or t o u n derta ki n g a n y st u d y rel ate d pr oc e d ure. 
A de q uate ti me s h o ul d b e pr o vi de d f or t h e s u bject or le g all y a ut h orize d re pr ese ntati ve  t o rea d t he 
i nf or me d c o nse nt, t o u n derst a n d t he ris ks a n d be n efits of partici p ati n g i n t he st u d y, a n d t o as k 
a n y q uesti o ns t hat t he s u bj ect ma y ha ve a b o ut t h e st u d y. T he s u bject or le g all y a ut h oriz e d 
re prese ntati ve s h o ul d b e a ble t o as k a d diti o nal q uesti o ns as a n d w he n nee de d d uri n g t he c o n d uct 
of t he st u d y. T he s u bj ect  or le gall y a ut h orize d r e pres e ntati ve ’s si g nat ur e o n t he i nf or me d c o nse nt 
f or m s h o ul d be o btai ne d at t he i n vesti gat or site i n t he prese nce of t h e i n vesti gat or or a q u alifie d 
re prese ntati ve (e g, s u b i n v esti gat or).  
Eac h s u bje ct will be gi v e n a c o p y of t h e si g ne d c o ns e nt/asse nt f or m. T he ori gi nal si g ne d 
i nf or me d c o nse nt f or ms will b e retai ne d b y t h e i n vesti gat or wit h t he st u d y r ec or ds. 
9. 1. 2.  
St u d y D isc o nti n u ati o n a n d C l os ure 
P T C T hera pe utics reser ves t h e ri g ht t o disc o nti n ue t h e st u d y pri or t o i n cl usi o n of t h e i nt e n de d 
n u m ber of s u bjects. T he i n v esti gat or, after c o ns ultati o n wit h t he m e dic al m o nit or, reser ves t h e 
ri g ht t o disc o nti n ue t he st u d y at t he i n vesti g at or sit e f or safet y reas o ns at a n y ti me. 
After a decisi o n t o t er mi nate t h e st u d y, i n vesti gat ors m ust c o nta ct all s u bje cts w h o are c o nti n ui n g 
t heir partici pati o n i n t h e st u d y a n d m ust d o s o wit hi n a ti m e peri o d set b y P T C T her a pe uti cs. As 
direct e d b y P T C T her a pe uti cs, all st u d y mat erials m ust be c oll ect e d,  a n d all el ectr o nic data e ntr y 
f or ms c o m plete d t o t he greatest e xte nt p ossi bl e. 
9. 1. 3.  
C o nfi de nti alit y a n d P ri v ac y  
Researc h rec or ds will be c olle cte d a n d st ore d i n a ma n ner t hat pr otects t he c o nfi d e nti alit y of 
s u bject i nf or mati o n. T he n a mes a n d i d e ntities of all r esearc h s u bje cts will b e ke pt i n strict 
c o nfi de nc e a n d will n ot a p pe ar o n e C R Fs, pa per C R Fs, or ot her re c or ds pr o vi de d t o or retai n e d 
b y P T C T hera pe utics ( or its a ut h oriz e d desi g ne e). T h e na mes a n d i de ntiti es of t he s u bjects nee d 
n ot be di v ul g e d; h o we ver, t he rec or ds m ust n e vert h el ess be i ns pecte d. T his will b e acc o m plis he d 
b y bla n ki n g o ut t he s u bje ct’s na m e a n d re pl aci n g t he na me wit h t he s u bje ct’s st u d y i de ntifi cati o n 
n u m ber o n a n y re c or d pr o vi de d t o or r etai ne d b y P T C T hera pe utics. T h e i nf or me d c o nse nt f or m 
m ust i ncl u d e a p pr o pri ate st ate m e nts e x pl ai ni n g t hese re q uire m e nts.  
B y si g ni n g t his pr ot oc ol, t he i n vesti g at or affir ms t o P T C T hera p e uti cs t hat t he i n vesti gat or will 
mai nt ai n, i n c o nfi de n ce, i nf or m ati o n f ur nis he d b y P T C T hera p e uti cs a n d will di v ul ge s uc h 
i nf or mati o n t o t h e I R B/I E C u n d er a n a p pr o pri ate u n d ersta n di n g of c o nfi de ntialit y wit h s uc h 
b oar d.  
9. 1. 4.  
F ut ure use of S t ore d S peci me ns a n d D at a  
As part of t he c urre nt st u d y  bl o o d, ser u m, uri n e, a n d nas o p har y n geal s wa bs wi ll b e c ollect e d.  
Sa m ple pr oc essi n g will be p erf or me d b y a la b orat or y u n der t he dir ecti o n of t he s p o ns or. 
Pr ocessi n g, a nal ysis, a n d st ora g e will b e perf or me d at a sec ure la b orat or y f acilit y t o pr ote ct t h e 
vali dit y of t he d ata a n d mai ntai n s u bj ect pri vac y.  

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Sa m ples will o nl y be use d f or t h e p ur p oses descri be d i n t his pr ot oc ol. La b or at ori es c o ntracte d t o 
perf or m t he a nal ysis o n be half of t he s p o ns or will n ot retai n ri g hts t o t he sa m ples be y o n d t h ose 
necessar y t o perf or m t he s pecifie d a nal ysis a n d will n ot tra n sfer or sell t h ose sa m ples. T he 
s p o ns or will n ot sell t h e sa m pl es t o a t hir d part y.  
Sa m ples will b e st ore d u ntil t h e c o m pleti o n of t he st u d y ( defi ne d as s u b missi o n of t h e cli nical 
st u d y re p ort t o t h e a p pr o pri ate re g ulat or y a ge ncies). At t he e n d of t h e st or a ge peri o d, sa m pl es 
will be destr o y e d. Sa m pl es ma y be st ore d l o n ger if a healt h a ut h orit y ( or me dici nal pr o d uct 
a p pr o val a g e nc y) has acti ve q u esti o ns a b o ut t he st u d y. I n t his s pecial cir c u msta nc e, t he sa m ples 
will be st ore d u ntil t he q uesti o ns ha ve bee n a d e q uatel y a d dresse d.  
N o s u bject -i de ntif yi n g i nf or mati o n (e g, i niti als, dat e of birt h, g o ver n m e nt i d e ntif yi n g n u m ber) 
will be ass oci ate d wit h a n y of t he bi ol o gic sa m pl es. All sa m ples will be si n gl e c o de d. T he 
s p o ns or will ta ke ste ps t o e ns ure t hat data are pr ot ect e d acc or di n gl y, a n d c o nfi de ntialit y is 
mai nt ai ne d as far as p ossi ble. Data fr o m s u bjects e nr olle d i n t his st u d y ma y b e a nal yze d 
w orl d -wi de , re gar dless of l oc ati o n of c oll ecti o n. 
T he s p o ns or a n d its re prese ntati ves a n d a ge nts ma y s hare c o de d d ata wit h  p ers o ns a n d 
or ga nizati o ns i n v ol v e d i n t h e c o n d uct or o v ersi g ht of t his researc h. T hese i ncl u de:  
•  C o ntract R esearc h Or ga ni zati o ns ( C R Os ) retai ne d b y t he s p o ns or 
•  I E Cs or I R Bs t hat ha ve r es p o nsi bilit y f or t his resear c h st u d y 
•  Nati o nal r e g ulat or y a ut h orities or  e q ui val e nt g o ver n me nt a g e nci es  
At t he e n d of t h e a nal ysis, res ults ma y be pr ese nte d i n a fi nal r e p ort w hic h c a n i ncl u de part or all 
of t he c o de d d ata, i n listi n g or s u m mar y f or m at. Ot her p u blicati o n (e g, i n peer -re vie we d 
scie ntific j o ur n als) or p u bli c prese ntati o n of t h e st u d y res ults will o nl y i ncl u d e s u m maries of t he 
p o p ulati o n i n t he st u d y, a n d n o i de ntifi e d i n di vi d ual res ults will be discl ose d.  
Gi ve n t he rese arc h nat ur e of t he la b orat or y a nal ysis, it will n ot be p ossi ble t o ret ur n i n di vi d u al 
data t o s u bj ects. T h e res ults t h at ma y b e ge ner ate d ar e n ot c urre ntl y a ntici pate d t o ha ve cli nical 
rele va n ce t o t he patie nts or t h eir fa mil y me m b ers. T h eref ore, t h ese res ults will n ot be discl ose d 
t o t he patie nts or t heir p h ysi cia ns. 
9. 1. 5.  
S afet y O versi g ht  
9. 1. 5. 1.  
D at a a n d S afety M o nit ori n g B o ar d  
E xter nal o versi g ht f or t his tri al will be pr o vi de d b y a D S M B. T he pri mar y res p o nsi bilit y of t h e 
D S M B is t o pr otect t he saf et y a n d welfare of s u bje cts partici p ati n g i n t his cli ni cal trial a n d t o 
e ns ure t he i nte grit y of t he cli ni cal trial.  T o m ai nt ai n t he bli n di n g a n d i nt e grit y of t he st u d y, 
pr oce d ures will b e i m ple me nte d t o e ns ure t he D S M B a n d i n de pe n d e nt statisti cia n ha v e s ole 
access t o u n bli n de d safet y data.  
S pecific all y, f or t his st u d y, t he D S M B will be r es p o nsi ble f or:  
•  E xa mi ni n g ac c u m ul ate d safet y dat a, P K, a n d c o m pli a nce data i n or der t o ma k e 
rec o m m e n dati o ns c o ncer ni n g c o nti n u ati o n, ter mi nati o n, or m o dific ati o n of t he trial 
base d o n t he safet y of t he i nter ve nti o ns u n der s t u d y 

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•  Re vie wi n g m aj or st u d y desi g n m o difi cati o ns pr o p ose d b y P T C T hera p e uti cs or t he 
i n vesti gat ors pri or t o i m ple me nt ati o n of t h ose m o difi cati o ns 
•  Re vie wi n g t h e ge ner al pr o gress of t he st u d y as re g ar ds accr ual, pr ot oc ol vi olati o ns, 
a n d st u d y c o n d uct  
T he D S M B  will re vie w t h e i nt eri m P K ( Da y 1 a n d 7) a n d safet y data w he n a p pr o xi mat el y 
4 0  s u bjects ha ve r ecei v e d 1 4 da ys of st u d y tre at m e nt. T he D S M B ma y re vie w t h e safet y data at 
ot her ti mes as warra nte d b y e mer gi n g res ults. Base d o n re vie w of t he safet y dat a, t he D S M B ca n 
rec o m m e n d c o nti n uati o n of t he st u d y u nc h a n ge d, st u d y i nterr u pti o n, st u d y ter mi nati o n, 
m o dific ati o n of t he trial, or alter a ti o n. F ull det ails of t he D S M B pr oce d ures, i ncl u di n g pri m ar y 
res p o nsi bilities, will b e d oc u m e nte d i n a D S M B C harter. 
9. 1. 5. 2.  
He p at i c A dvis ory S afet y C o m mittee  
A H A C c o m prise d of he pat ol o gists e x perie n ce d in t h e m o nit ori n g a n d i d e ntificati o n  of DI LI  wil l 
o versee t h e h e patic safet y of s u bj ects e nr olle d i n t he st u d y. T he H A C will me et re g ularl y t o 
assess t he se verit y a n d ca usalit y of all he pat ot o xi cit y e ve nts . F ull details of t he H A C pr oce d ures 
will be d oc u me nt e d i n t h e H A C C harter.  
9. 1. 6.  
Cli nic al M o nit o ri n g  
I n acc or da nc e wit h 2 1 C o de of Fe d eral R e g ulati o ns Part 3 1 2. 5 6 a n d/ or rele va nt  I nter nati o nal 
C o u ncil f or Har m o nisati o n  (I C H) g ui d eli nes, P T C T hera pe utics or a desi g ne e will p eri o di call y 
i ns pect all e C R Fs, st u d y d oc u m e nts, researc h f aciliti es, a n d cli nical la b orat or y facilities 
ass ociate d wit h t his st u d y at m ut u all y c o n ve nie nt ti m es, bef ore, d uri n g, a n d after c o m pleti o n of 
t he st u d y. As re q uire d b y a p plic a ble re g ulati o ns ( Res p o nsi bilities of S p o ns ors a n d I n vesti gat ors), 
t he m o nit ori n g visits pr o vi de P T C T h era pe utics wit h the o p p ort u nit y t o e v al uate t h e pr o gress of 
t he st u d y; verif y t he acc ura c y a n d c o m plete ness of d ata i n t he e C R Fs; e ns ure t hat all pr ot oc ol 
re q uire m e nts, rel e va nt re g ulati o ns, a n d i n vesti gat or’s o bli gati o ns are bei n g f ulfille d; a n d res ol ve 
a n y i nc o nsiste n cie s i n t he st u d y rec or ds. T his i ncl u d es i ns pecti o n of all d o c u me nts a n d rec or ds 
re q uire d t o b e mai ntai ne d b y t he i n vesti g at or, i n cl u di n g b ut n ot li mit e d t o m e dic al re c or ds 
( office, cli ni c, or h os pital) f or t he s u bje cts i n t his st u d y. T he na m es a n d i de ntities of all r esearc h 
s u bjects will b e ke pt i n strict c o nfi d e nce a n d will n ot a p pear o n e C R Fs or ot her r ec or ds pr o vi de d 
t o or retai ne d b y P T C T h era pe utics. T he i n vesti g at or/i nstit uti o n g uar a nte es direct acc ess t o 
s o urce d oc u me nts b y P T C T hera pe utics a n d a p pr o pri ate re g ulat or y a ut h orities. 
It is i m p ort a nt t h at t h e i n vesti gat or a n d rele v a nt i nstit uti o nal p ers o n nel ar e a vaila bl e d uri n g t h e 
m o nit ori n g visits a n d p ossi ble a u dits or i ns pe cti o ns a n d t hat s ufficie nt ti m e is de v ot e d t o t he 
pr ocess.  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 5 2  of 6 2  
9. 1. 7.  
Q u alit y A ss ur a nce a n d Q u alit y C o ntr ol  
T o e ns ure c o m plia n ce wit h G o o d Cli nical  Practice ( G C P) a n d all a p plica ble re g ul at or y 
re q uire m e nts, P T C, P T C’s re prese nt ati ves, a r e g ulat or y a ut h orit y or a n d I nstit uti o nal Re vi e w 
b oar d ma y c o n d u ct a q ualit y ass ura nce a u dit. Re as o ns f or q uali t y ass ura nc e a u dit ma y i n cl u de 
b ut are n ot li mite d t o  ra n d o m selecti o n, ge o gra p hic pr o xi mit y, s us pecte d G C P vi olati o n, hi g h 
e nr olli n g site, a n d r ec urri n g pr ot o c ol de viati o ns. T he p ur p ose of a S p o ns or a u dit or i ns pecti o n is 
t o s yste maticall y a n d i n de pe n de ntl y e x a mi n e all st u d y relat e d acti vities a n d d oc u me nts t o 
deter mi ne w het h er t hese a cti viti es were c o n d ucte d, a n d data were re c or de d, a n al yz e d, a n d 
acc uratel y re p orte d a cc or di n g t o t he pr ot oc ol, G o o d Cli nic al Practic e g ui deli nes of t he I C H, a n d 
a n y a p pli ca bl e re g ulat or y re q uir e me nts. T he i n v esti g at or s h o ul d c o nt act t he S p o ns or i m m e diatel y 
if c o nta cte d b y a re g ulat or y a ge n c y a b o ut a n i ns pecti o n. 
9. 1. 8.  
D at a H a n dli n g a n d R ec or d K ee pi n g 
T o e na bl e e val uati o ns a n d/ or a u dits fr o m re g ul at or y a ut h orities or P T C T her a pe utics, t he 
i n vesti gat or a gre es t o kee p a cc urate a n d c o m pl ete r e c or ds, i ncl u di n g t he i d e ntit y of all 
partici pati n g s u bjects (s ufficie nt i nf or mati o n t o li n k e C R Fs a n d cli ni c rec or ds/s o urc e 
d oc u me nts), all ori gi nal si g n e d i nf or me d c o nse nt f or ms, electr o nic c o pies (ie, C D -R O M, U S B, 
etc.) or pa p er c o pies of t h e dat a t hat ha ve b ee n c a pt ure d i n t he E D C f or eac h s u bje ct (e C R Fs), 
a n d detaile d r ec or ds of st u d y dr u g dis p ositi o n. All re c or ds a n d d oc u me nts pertai ni n g t o t he st u d y 
will be m ai nt ai ne d b y t he i n v esti gat or u ntil n otifi cati o n is recei v e d fr o m P T C T h era pe utics t hat 
t he rec or ds n o l o n g er nee d t o b e ret ai ne d. 
T he i n vesti gat or m ust o btai n writt e n per missi o n fr o m P T C T hera p e uti cs bef ore dis p osi n g of a n y 
rec or ds. T he i n v esti gat or will pr o m ptl y n otif y P T C T hera pe utics i n t h e e ve nt of acci de nt al l oss 
or destr ucti o n of a n y st u d y rec or ds. If t he i n vesti g at or rel ocates, retires, or f or a n y reas o n 
wit h dra ws fr o m t he st u d y, t h e st u d y rec or ds ma y b e tra nsferre d t o a n a cce pta bl e desi g ne e, s uc h 
as a n ot her i n v esti gat or, a n ot her i nstit uti o n, or t o P T C T hera pe utics as a p plica ble.  
9. 1. 9.  
Pr ot oc ol D e vi ati o ns  
A pr ot oc ol de vi ati o n is defi ne d as a n y i nte nti o nal or u ni nte nti o nal c ha n ge t o, or n o nc o m plia nc e 
wit h, t he a p pr o v e d pr ot oc ol pr oce d ures or re q uire m e nts. De viati o ns m a y res ult fr o m t he acti o n or 
i nacti o n of t he s u bj ect, i n vesti g at or, or site st aff. E xa m ples of de vi ati o ns i n cl u de, b ut are n ot 
li mite d t o: 
•  Fail ure t o a d here t o st u d y e xcl usi o n a n d i ncl usi o n criteria  
•  Fail ure t o c o m pl y wit h dis pe nsi n g or d osi n g re q uire me nts  
•  Use of me dica ti o ns t hat are s pecific all y pr o hi bit e d i n t he pr ot oc ol 
•  Misse d or o ut -of -wi n d o w visits  
•  Dr u g d osi n g n ot a d mi nist ere d wit hi n t he ti m e fra me s pecifie d i n t he pr ot oc ol  
•  Fail ure t o a d here t o test re q uire m e nts, i ncl u di n g vital si g ns, la b orat or y t ests, p h ysical 
e xa mi n ati o ns, P K bl o o d dra ws, me di cal hist or y, etc. - eit her tests n ot d o ne, i nc orrect 
tests d o ne, or n ot d o ne wit hi n t h e ti me fra me s pecifie d i n t he pr ot o c ol 

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 5 3  of 6 2  
•  Pr oce d u ral de viati o ns s uc h as i nc orrect st ora ge of st u d y dr u g, fail ure t o u p dat e t he 
inf or me d c o nse nt f or m  (I C F) w he n ne w ris ks bec o m e k n o w n, or fail ure t o o btai n 
I R B/I E C a p pr o vals f or t he pr ot o c ol a n d I C F re visi o ns  
Maj or  de viati o ns are a n y de viati o ns t hat i m p act  s u bj ect eli gi bilit y (ie, pr ot oc ol 
i ncl usi o n/ e xcl usi o n vi olati o ns), s u bject safet y or a s u bject’s a bilit y t o c o nti n ue i n t he cli nical 
trial. 
At t he o utset of t he st u d y, a pr o cess f or defi ni n g a n d ha n dli n g pr ot o c ol de viati o ns will be 
esta blis he d wit h t he C R O. T his will i n cl u de d eter mi ni n g w hic h de vi ati o ns will be desi g n ate d 
maj or ; t h us, re q uiri n g i m m e diate n otificati o n t o t he me dic al m o nit or a n d t he s p o ns or. 
Pr os pecti ve de viati o ns (e g, pr ot oc ol wai vers) are pr o hi bite d p er P T C p oli c y.  
T he i n vesti gat or is res p o nsi ble f or s eei n g t hat a n y k n o w n pr ot oc ol de vi ati o ns ar e rec or de d as 
a gree d.  
9. 1. 1 0.  
P u blic ati o n a n d D at a S h ari n g P olic y  
T he i nf or m ati o n d e vel o pe d d uri n g t he c o n d uct of t his cli nic al st u d y is c o nsi d ere d c o nfi de nti al b y 
P T C T hera pe utics. T his i nf or mati o n m a y be di scl ose d as dee me d n ecessar y b y 
P T C  T hera pe utics.  
P T C T hera pe utics i nte n ds t hat t he data fr o m t his st u d y will be prese nte d a n d p u blis he d. T he 
P T C  T hera pe utics staff u n d er t he dir ecti o n of t he P T C T hera pe utics C hi ef Me dical Officer or 
desi g nee i n c oll a b orati o n wit h t he i n vesti g at or will b e res p o nsi ble f or writi n g prese ntati o ns a n d 
ma n uscri pts f or p u blicati o n. I n vesti gat ors will n ot be all o we d t o p u blis h or prese nt t he data fr o m 
t his st u d y wit h o ut pri or a gree me nt wit h P T C T her a p e utics. 
T he i n vesti gat or is o bli ge d t o pr o vi de t he s p o ns or wit h c o m pl ete test res ults a n d all data d eri ve d 
b y t he i n vesti gat or fr o m t he st u d y. D uri n g t he st u d y, o nl y t he s p o ns or ma y m a ke st u d y 
i nf or mati o n a vaila ble t o ot her st u d y I n vesti g at ors or t o re g ulat or y a ge n cies, e xc e pt as re q uired b y 
la w or re g ulati o n. E x ce pt as ot h er wise all o wa ble i n t he C li ni cal S t u d y S ite A gree me nt, a n y 
p u blic discl os ure (i ncl u di n g p u blicl y accessi bl e we bsites) rel ate d t o t he pr ot oc ol or st u d y res ults, 
ot her t ha n st u d y r ecr uit me nt mat erials a n d/ or a d v ertise me nt s, is t he s ol e res p o nsi bilit y of t h e 
sp o ns or.  
T he s p o ns or ma y p u blis h a n y d ata a n d i nf or mati o n fr o m t he st u d y (i n cl u di n g d ata a n d 
i nf or mati o n ge ner ate d b y t h e i n vesti gat or) wit h o ut t h e c o nse nt of t h e I n vesti g at or. Ma n uscri pt 
a ut h ors hi p f or a n y pe er -re vie wed p u blic ati o n will a p pr o priatel y refl ect c o ntri b uti o ns t o t he 
pr o d ucti o n a n d r e vie w of t he d o c u me nt. All p u blicati o ns a n d prese ntati o ns m ust be pre p are d i n 
acc or da n ce wit h t his secti o n a n d t he Cli ni cal St u d y Site A gree me nt. I n t he e ve nt of a n y 
discre pa nc y b et wee n t h e pr ot oc ol a n d t h e Cli nical St u d y Site A gree m e nt, t h e Cli nical St u d y Site 
A gree me nt will pre v ail.  
Data fr o m all sit es partici pati n g i n t h e st u d y will b e p o ole d a n d a n al yz e d b y t he s p o ns or or t he 
s p o ns or’s desi g nee. T he first p u blicati o n of t he stu d y res ults s hall be ma de i n c o nj u n cti o n wit h 
t he res ults fr o m ot her st u d y sit es as a m ultice nter p u blicati o n. If a m ultice nter p u bli cati o n is n ot 
f ort hc o mi n g wit hi n 2 4 m o nt hs of c o m pl eti o n of t he st u d y at all sit es, t he I n vesti gat or ma y 
p u blis h or prese nt  t h e res ults ge n erate d at his or her site. 

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 5 4  of 6 2  
T he i n vesti gat or will pr o vi d e t he s p o ns or wit h a c o p y of a n y pr o p ose d p u blic ati o n or 
prese ntati o n f or re vie w a n d c o m m e nt at le ast 6 0 da ys pri or t o s uc h prese ntati o n or s u b missi o n 
f or p u blicati o n. T h e s p o ns or s hall i nf or m t he i n vesti gat or i n writi n g of a n y c h a n ges or deleti o ns 
i n s uc h prese ntati o n or p u blicati o n re q uir e d t o pr ot ect t he s p o ns or’s c o nfi de ntial a n d pr o priet ar y 
tec h ni cal i nf or mati o n a n d t o a d dress i nac c urat e dat a or i na p pr o priate i nter pret ati o ns i n t he 
c o nte xt of a n y p o ole d m ultice nter res ults. At t h e e x pirati o n of s uc h 6 0 -da y p eri o d, t he 
i n vesti gat or ma y pr o cee d wit h t he prese ntati o n or s u b missi o n f or p u blic ati o n u nless t he s p o ns or 
has n otifie d t he i nstit uti o n or t he i n vesti g at or i n writi n g t hat s uc h pr o p ose d p u blicati o n or 
prese ntati o n discl oses t h e s p o ns or’s c o nfi de ntial a n d pr o prietar y tec h nical i nf or mati o n. F urt her, 
u p o n t he re q uest of t he s p o ns or, t he i n v esti gat or will dela y t h e p u bli cati o n or prese ntati o n f or a n 
a d diti o n al 9 0 da ys t o p er mit t he s p o ns or t o t a ke nec essar y acti o ns t o pr ot ect its i nt ell ect ual 
pr o pert y i nt erests.  
9. 2.  
Pr ot oc ol A me n d me nt Hist or y  
V e rsi o n 1. 0: 1 7 A pril 2 0 2 0  
9. 2. 1.  
Versi o n 2. 0: 0 8  M a y 2 0 2 0   
O ver all re as o n f or Versi o n 2. 0:  T he o v erall reas o n f or Versi o n 2. 0 of t he pr ot oc ol was t o 
i nc or p orat e Healt h A ut h orit y fe e d bac k . 
It e m 
N o.  
Pr ot o c ol 
S e cti o n  
V er si o n 2/ U p d at e  
R e a s o n/ R ati o n al e  
1  
Pr ot o c ol  
T h e pr ot o c ol w a s u p d at e d t hr o u g h o ut t o r e pl a c e t h e 
S O C c o m p ari s o n ar m wit h pl a c e b o c o ntr ol. T h e v er si o n 
n u m b er a n d d at e w er e u p d at e d t hr o u g h o ut. 
E dit ori al a n d a d mi ni str ati v e r e vi si o n s ( e g, t y p o gr a p hi c al 
err or, p u n ct u ati o n, t e n s e s, a b br e vi ati o n s) w er e 
i n c or p or at e d t o pr o vi d e cl arit y. T h e s y n o p si s a n d 
s c h e d ul e of e v e nt s w er e  u p d at e d t o b e c o n si st e nt wit h 
c h a n g e s i n t h e pr ot o c ol.  
U p d at e  
2  
S e cti o n 1  
U p d at e d wit h l at e st s pr e a d of di s e a s e.  
U p d at e  
3  
S e cti o n 1. 1  
N e w n o n cli ni c al d at a w er e a d d e d  
U p d at e  
4  
S e cti o n 2. 1. 1  
T h e pri m ar y o bj e cti v e w a s u p d at e d t o b e t h e ti m e t o 
r e s pir at or y i m pr o v e m e nt. 
U p d at e  
5  
S e cti o n  2. 2. 1  
T h e pri m ar y e n d p oi nt w a s u p d at e d, c o n si st e nt wit h t h e 
n e w pri m ar y o bj e cti v e . 
U p d at e  
6  
S e cti o n 2. 2. 2  
F or t h o s e s e c o n d ar y e n d p oi nt s r e c or di n g ti m e t o 
i m pr o v e m e nt, it w a s cl arifi e d t h at t h e ti m e st art s at 
r a n d o mi z ati o n. Cl arifi c ati o n w a s a d d e d o n t h e c o u g h 
s e v erit y s c al e. D -di m er a n d c ar di a c tr o p o ni n w er e 
s p e cifi e d i n t h e li st of p ot e nti al a c ut e p h a s e pr ot e i n s t o 
b e a s s e s s e d.  
Cl arifi c ati o n  
7  
S e cti o n 3. 1  
T h e st u d y d e si g n w a s u p d at e d t o r efl e ct t h e c h a n g e t o a 
pl a c e b o -c o ntr oll e d, d o u bl e bli n d st u d y  a n d t o i n cl u d e 
str atifi c ati o n b y re m d e si vir, pr o hi biti o n of s e n siti v e 
C Y P 2 D 6 s u b str at e s a n d i n v e sti g ati o n al t h er a pi e s,  a n 
i n cr e a s e d s a m pl e si z e, a n d t h e a d diti o n of t h e D a y 6 0 
s af et y t el e p h o n e c all.  
U p d at e  
8  
S e cti o n 3. 2  
A d diti o n al cli ni c al e x p eri e n c e w a s a d d e d t o t h e d o s e 
j u stifi c ati o n. 
U p d at e  
9  
S e cti o n 4. 1  
T h e st u d y p o p ul ati o n si z e w a s i n cr e a s e d.  
U p d at e  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 5 5  of 6 2  
It e m 
N o.  
Pr ot o c ol 
S e cti o n  
V er si o n 2/ U p d at e  
R e a s o n/ R ati o n al e  
1 0  
S e cti o n 4. 2  
I n cl u si o n crit eri o n # 1 w a s a m e n d e d t o S u bj e ct ( or  l e g all y 
a ut h ori z e d r e pr e s e nt ati v e) i s willi n g a n d a bl e t o pr o vi d e 
i nf or m e d c o n s e nt a n d c o m pl y wit h all pr ot o c ol 
r e q uir e m e nt s 
“ Or e q ui v al e nt t e st” w a s a d d e d t o c h e st X -r a y or C T 
s c a n i n I n cl u si o n  crit eri o n # 9.  
U p t o 5 0 d a y s aft er l a st d o s e w a s a d d e d t o I n cl u si o n 
crit eri o n # 1 0  
Cl arifi c ati o n  
1 1  
S e cti o n 4. 3  
E x cl u si o n crit eri o n # 3 w a s c h a n g e d t o e x cl u d e s u bj e ct s 
wit h ≥3 × U L N A L T or A S T or ≥2 × U L N T bili.  
E x cl u si o n  crit eri o n # 4 w a s a d d e d t o e x cl u d e s u bj e ct s 
wit h l o w l y m p h o c yt e c o u nt or h e m o gl o bi n l e v el s.  
S e n siti v e C Y P 2 D 6 s u b str at e s a n d a n y i n v e sti g ati o n al 
t h er a p y w er e a d d e d t o pr o hi bit e d m e di ci n e s i n E x cl u si o n 
crit eri o n # 7.  
E x ci pi e nt s w er e i n cl u d e d i n E x cl u si o n crit eri o n # 1 0.  
U p d at e  
1 2  
S e cti o n 5. 1. 2  
A r e c o m m e n d ati o n t o t a k e P T C 2 9 9 wit h f o o d w a s 
a d d e d.  
U p d at e  
1 3  
S e cti o n 5. 3  
T h e s e cti o n w a s u p d at e d t o r efl e ct t h e c h a n g e i n st u d y 
d e si g n fr o m o p e n -l a b el t o d o u bl e bli n d a n d t o i n cl u d e 
t h e e m er g e n c y u n bli n di n g pr o c e d ur e.  
U p d at e  
1 4  
S e cti o n 5. 5  
S e n siti v e C Y P 2 D 6 s u b str at e s a n d i n v e sti g ati o n al 
t h er a pi e s w er e a d d e d t o t h e pr o hi bit e d c o n c o mit a nt 
m e di c ati o n.  
U p d at e  
1 5  
S e cti o n 6. 1  
Cl arifi c ati o n w a s a d d e d ar o u n d tr e at m e nt of s u bj e ct s 
aft er di s c o nti n u ati o n.  
Cl arifi c ati o n  
1 6  
S e cti o n 6. 1. 2  
St o p pi n g r ul e s w er e a d d e d f or l o w l y m p h o c yt e c o u nt s 
a n d l o w h e m o gl o bi n l e v el s.  
U p d at e  
1 7  
S e cti o n 7. 1  
A s af et y t el e p h o n e c all at D a y 6 0 w a s a d d e d a n d 
cl arifi c ati o n w a s a d d e d ar o u n d S cr e e ni n g a n d D a y  1 
o c c urri n g o n t h e s a m e d a y or 1 d a y a p art.  
U p d at e a n d 
cl arifi c ati o n  
1 8  
S e cti o n 7. 2  
D -di m er a n d c ar di a c tr o p o ni n w er e s p e cifi e d i n t h e li st of 
p ot e nti al l a b or at or y p ar a m et er s t o b e a s s e s s e d  
Cl arifi c ati o n  
1 9  
S e cti o n 7. 3  
T h e s e cti o n w a s u p d at e d t o s p e cif y t h at P K 
a s s e s s m e nt s will b e at s el e ct sit e s . Cl arifi c ati o n ar o u n d 
P K a s s e s s m e nt s f oll o wi n g di s c h ar g e fr o m t h e h o s pit al 
w a s a d d e d.  
U p d at e  
2 0  
S e cti o n 7. 4  
Cl arifi c ati o n w a s a d d e d t h at vit al si g n s ar e p art of s af et y 
a s s e s s m e nt s . 
Cl arifi c ati o n  
2 1  
S e cti o n 7. 5. 1  
E C G s w er e r e m o v e d  
U p d at e  
2 2  
S e cti o n 7. 5. 2  
U p d at e d t o ali g n wit h t h e n e w D a y 6 0 s af et y t el e p h o n e 
c all.  
U p d at e  
2 3  
S e cti o n 7. 5. 1 0  T e xt c o n c er ni n g  t h e S A E f or m w a s u p d at e d.  
U p d at e  
2 4  
S e cti o n 7. 5. 1 1  T e xt c o n c er ni n g t h e pr e g n a n c y f or m w a s u p d at e d.  
U p d at e  
2 5  
S e cti o n 8  
U p d at e s w er e m a d e t hr o u g h o ut c o n si st e nt wit h t h e 
u p d at e d e n d p oi nt s a n d a d diti o n of pl a c e b o, i n cl u di n g a n  
i n cr e a s e d s a m pl e si z e.  
U p d at e  
2 6  
S e cti o n 9. 1. 5  
F urt h er d et ail s of t h e D S M B w er e a d d e d.  
Cl arifi c ati o n  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 5 6  of 6 2  
9. 2. 2.  
Versi o n 3. 0: 0 5  J u ne 2 0 2 0  
O ver all re as o n f or Versi o n 3. 0: T he o v erall reas o n f or Versi o n 3. 0 of t he pr ot oc ol was t o 
i nc or p orat e fee d ba c k fr o m t h e F D A. 
It e m 
N o.  
Pr ot o c ol 
S e cti o n  
V er si o n 3 / U p d at e 
R e a s o n/ R ati o n al e  
1  
Pr ot o c ol  
T h e v er si o n n u m b er a n d d at e w er e u p d at e d t hr o u g h o ut.  
E dit ori al a n d a d mi ni str ati v e r e vi si o n s ( e g, t y p o gr a p hi c al 
err or, p u n ct u ati o n, t e n s e s, a b br e vi ati o n s) w er e 
i n c or p or at e d t o pr o vi d e cl arit y. T h e s y n o p si s a n d 
s c h e d ul e of e v e nt s w er e  u p d at e d t o b e c o n si st e nt wit h 
c h a n g e s i n t h e pr ot o c ol.  
U p d at e  
2  
S e cti o n s  1. 2  
a n d  6. 1. 1  
A n i n d e p e n d e nt H e p ati c A d vi s or y S af et y C o m mitt e e will 
m o nit or h e p ati c s af et y t hr o u g h o ut t h e st u d y a n d t h e 
pr ot o c ol w a s a m e n d e d a c c or di n gl y.  
U p d at e  
3  
S e cti o n s  
2. 2. 1 , 8. 2 , a n d 
8. 4. 2  
T h e pri m ar y e n d p oi nt w a s a m e n d e d t o t h e ti m e fr o m 
r a n d o mi z ati o n t o r e s pir at or y i m pr o v e m e nt, d efi n e d a s 
p eri p h er al o x y g e n s at ur ati o n ( S p O 2 ) ≥9 4 % o n r o o m air 
s u st ai n e d u ntil di s c h ar g e fr o m t h e h o s pit al or t h e e n d of 
t h e st u d y ( D a y 2 8) 
U p d at e  
4  
S e cti o n 3. 1  
T h e st u d y d e si g n w a s a m e n d e d t o r efl e ct c h a n g e s 
m a d e el s e w h er e, n a m el y e x cl u si o n of C Y P 2 C i n d u c er s , 
i n cl u si o n of t h e H A C, a n d a d diti o n of t h e i nt eri m a n al y si s 
f or f utilit y.  
U p d at e  
5  
S e cti o n s  4. 3  
a n d 5. 5  
C Y P 2 C i n d u c er s w er e a d d e d t o t h e e x cl u d e d t h er a pi e s 
i n e x cl u si o n crit eri o n # 7. 
U p d at e  
6  
S e cti o n 7. 1  
T h e s c h e d ul e of e v e nt s w a s u p d at e d t o i n cl u d e W H O 
or di n al s c al e a s s e s s m e nt at b a s eli n e,  dr u g c o m pli a n c e 
c h e c k o n D a y 1 4, a d diti o n al P K a s s e s s m e nt o n D a y 2 8 
a n d i n t h e c a s e of h e p at ot o xi cit y, a n d t o cl arif y w hi c h  
s u bj e ct s m u st att e n d  t h e D a y 6 0 t el e p h o n e c all.  
U p d at e a n d 
cl arifi c ati o n  
7  
S e cti o n 7. 2  
A nti b o d y tit er s w er e a d d e d t o t h e li st of l a b or at or y 
p ar a m et er s  
Cl arifi c ati o n  
8  
S e cti o n 7. 3  
A d diti o n al P K a s s e s s m e nt s o n D a y 2 8 a n d i n t h e c a s e 
of h e p at ot o xi cit y w er e a d d e d.  
U p d at e  
9  
S e cti o n 7. 5. 3  
A s e cti o n w a s a d d e d t o d efi n e a d v er s e e v e nt s of s p e ci al 
i nt er e st ( A E SI s).  
U p d at e  
1 0  
S e cti o n 7. 5. 1 2  A E SI s w er e a d d e d t o t h e e v e nt s t o b e r e p ort e d i n a n 
e x p e dit e d m a n n er.  
U p d at e  
1 1  
S e cti o n 8  
T h e st ati sti c al c o n si d er ati o n s s e cti o n s  w er e  u p d at e d t o 
i n cl u d e t h e u p d at e d pri m ar y e n d p oi nt, d et ail s of t h e  
s e c o n d i nt eri m a n al y si s f or  f utilit y, t h e r e s ulti n g s a m pl e 
si z e c h a n g e s , a n d t o i n cl u d e A E SI s . 
U p d at e  
1 2  
S e cti o n 8. 4. 5  
B a s eli n e cl a s sifi c ati o n o n t h e W H O or di n al s c al e w a s 
s p e cifi e d  
U p d at e  
1 3  
S e cti o n 
9. 1. 5. 2  
S e cti o n a d d e d t o d e s cri b e t h e H A C  
U p d at e  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 5 7  of 6 2  
9. 2. 3.  
Versi o n 4. 0: 2 3  J ul y 2 0 2 0  
O ver all re as o n f or Versi o n 4. 0:  T he o v erall reas o n f or Versi o n 4. 0 of t he pr ot oc ol was t o 
i nc or p orat e fee d ba c k fr o m Healt h A ut h orities . 
It e m 
N o.  
Pr ot o c ol 
S e cti o n  
V er si o n 4 / U p d at e 
R e a s o n/ R ati o n al e  
1  
Pr ot o c ol  
T h e v er si o n n u m b er a n d d at e w er e u p d at e d t hr o u g h o ut.  
E dit ori al a n d a d mi ni str ati v e r e vi si o n s ( e g, t y p o gr a p hi c al 
err or, p u n ct u ati o n, t e n s e s, a b br e vi ati o n s) w er e 
i n c or p or at e d t o pr o vi d e cl arit y. T h e s y n o p si s a n d 
s c h e d ul e of e v e nt s w er e  u p d at e d t o b e c o n si st e nt wit h 
c h a n g e s i n t h e pr ot o c ol.  
U p d at e  
2  
S y n o p si s  
T h e n u m b er of sit e s w a s i n cr e a s e d t o a p pr o xi m at el y 4 0  
U p d at e  
3  
S e cti o n 3. 1  
A d efi niti o n of h o s pit ali z ati o n w a s a d d e d.  
Cl arifi c ati o n  
4  
S e cti o n 3. 1  
a n d 4. 1  
A n err or i n t h e n u m b er of st u d y s u bj e ct s w a s c orr e ct e d  
Cl arifi c ati o n  
5  
S e cti o n s 3. 1 , 
5. 3 , a n d 8. 4. 7  
St r atifi c ati o n f a ct or s w er e a m e n d e d t o r e m o v e 
h y dr o x y c hl or o q ui n e a n d a d d d e x a m et h a s o n e.  
U p d at e  
6  
S e cti o n s 3. 1 , 
6. 2 , a n d 7. 2   
Cl arifi c ati o n w a s a d d e d r e g ar di n g o n g oi n g a s s e s s m e nt 
of s u bj e ct s di s c h ar g e d fr o m t h e h o s pit al b ef or e D a y 2 8.  
Cl arifi c ati o n  
7  
S e cti o n s  4. 2  
a n d  7. 2  
I n cl u si o n Crit eri o n # 5 w a s m o difi e d t o s p e cif y S cr e e ni n g 
n ot e nr oll m e nt  a n d I n cl u si o n Crit eri o n # 7 w a s m o difi e d 
f or u s e of a nti p yr eti c s.  
Cl arifi c ati o n  
8  
S e cti o n 4. 3  
E x cl u si o n Crit eri o n # 2 w a s a m e n d e d t o cl arif y t h at 
p arti ci p ati o n i n i nt er v e nti o n al st u di e s i s n ot p er mitt e d 
a n d E x cl u si o n Crit eri o n # 7 w a s a m e n d e d t o p er mit u s e  
of d e x a m et h a s o n e  
Cl arifi c ati o n a n d 
u p d at e  
9  
S e cti o n 5. 3  
T e xt r e g ar di n g t h e r a n d o mi z ati o n c o d e w a s r e m o v e d 
a n d r ef er e n c e w a s m a d e t o t h e P h ar m a c y M a n u al.  
Cl arifi c ati o n  
1 0  
S e cti o n 5. 5  
C o n c o mit a nt d e x a m et h a s o n e u s e w a s p er mitt e d a n d a 
c a uti o n ar y n ot e w a s a d d e d r e g ar di n g B C R P s u b str at e s.  
U p d at e  
1 1  
S e cti o n 6. 2  
Err o n e o u s t e xt r e g ar di n g r e pl a c e m e nt of dr o p o ut s w a s 
r e m o v e d. 
Cl arifi c ati o n  
1 2  
S e cti o n 7. 1  
A pr e g n a n c y t e st w a s a d d e d at D a y 6 0 a n d t h e 
n a s o p h ar y n g e al s w a b at S cr e e ni n g w a s r e m o v e d. 
Cl arifi c ati o n w a s a d d e d t h at C T s c a n s w o ul d b e 
a c c e pt a bl e i n t h e pl a c e of X -r a y s if t a k e n wit hi n 4 8 h o ur s 
b ef or e S cr e e ni n g a n d t h at l a b or at or y a s s e s s m e nt s 
t a k e n u p t o 2 4 h o ur s b ef or e S cr e e ni n g ar e a c c e pt a bl e.  
U p d at e a n d 
cl arifi c ati o n  
1 3  
S e cti o n 8. 4  
St ati sti c al m et h o d s w er e u p d at e d t o r efl e ct c h a n g e s 
el s e w h er e i n t h e pr ot o c ol  a n d f or cl arit y .  
U p d at e  
1 4  
S e cti o n 8. 4. 6  
T e xt r e g ar di n g r e c o m m e n d ati o n s fr o m t h e D S M B w a s 
cl arifi e d.  
Cl arifi c ati o n  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 5 8  of 6 2  
9. 2. 4.  
Versi o n 5. 0: 0 8  Oct o ber  2 0 2 0  
O ver all re as o n f or Versi o n 5. 0:  T he o v erall reas o n f or Versi o n 5 . 0 of t he pr ot oc ol was t o 
i nc or p orat e fee d ba c k fr o m st u d y sit es. 
It e m 
N o.  
Pr ot o c ol 
S e cti o n  
V er si o n 5 / U p d at e 
R e a s o n/ R ati o n al e  
1  
Pr ot o c ol  
T h e v er si o n n u m b er a n d d at e w er e u p d at e d t hr o u g h o ut.  
E dit ori al a n d a d mi ni str ati v e r e vi si o n s ( e g, t y p o gr a p hi c al 
err or, p u n ct u ati o n, t e n s e s, a b br e vi ati o n s) w er e 
i n c or p or at e d t o pr o vi d e cl arit y. T h e s y n o p si s w a s  
u p d at e d t o b e c o n si st e nt wit h c h a n g e s i n t h e pr ot o c ol.  
U p d at e  
2  
S e ct i o n 2. 2. 2  
a n d 8. 4. 3   
Cl arifi c ati o n w a s a d d e d t h at t h e s e c o n d ar y e n d p oi nt of 
ti m e fr o m r a n d o mi z ati o n t o d ef er v e s c e n c e a p pli e s o nl y 
t o s u bj e ct s wit h f e v er at e nr oll m e nt. 
Cl arifi c ati o n  
3  
S e cti o n 4. 2  
I n cl u si o n Crit eri o n # 7 , r e q uiri n g s u bj e ct s t o pr e s e nt wit h 
f e v er, w a s r e m o v e d. 
U p d at e  
4  
S e cti o n  4. 3  
E x cl u si o n Crit eri o n # 4 w a s m o difi e d t o e x cl u d e s u bj e ct s 
wit h l y m p h o c yt e c o u nt < 5 0 0  l y m p h o c yt e s/μ L  a n d a n y 
s u bj e ct wit h h e m o gl o bi n < 1 1 . 0 g/ d L  
U p d at e  
5  
S e cti o n 6. 1  
T h e t e xt w a s u p d at e d t o cl arif y t h at s u bj e ct s w o ul d b e 
di s c o nti n u e d fr o m st u d y tr e at m e nt, n ot t h e st u d y, i n c a s e 
of di s e a s e pr o gr e s si o n.  
Cl arifi c ati o n  
6  
S e cti o n  6. 1. 2  
L e v el s of l y m p h o c yt e s a n d h e m o gl o bi n i n di c ati n g 
a n e mi a or l o w l y m p h o c yt e c o u nt w er e r e d u c e d t o 
< 5 0 0  l y m p h o c yt e s/μ L a n d 1 1 g/ d L, r e s p e cti v el y.  
U p d at e  
9. 2. 5.  
Versi o n 6. 0: 1 8  Dece m ber  2 0 2 0  
O ver all re as o n f or Versi o n 6. 0:  T he o v erall reas o n f or Versi o n 6. 0 of t he pr ot oc ol was t o 
i nc or p orat e fee d ba c k fr o m st u d y sit es a n d Healt h A ut h oriti es . 
It e m 
N o.  
Pr ot o c ol 
S e cti o n  
V er si o n 6 / U p d at e 
R e a s o n/ R ati o n al e  
1  
Pr ot o c ol  
T h e v er si o n n u m b er a n d d at e w er e u p d at e d t hr o u g h o ut.  
E dit ori al a n d a d mi ni str ati v e r e vi si o n s ( e g, t y p o gr a p hi c al 
err or, p u n ct u ati o n, t e n s e s, a b br e vi ati o n s) w er e 
i n c or p or at e d t o pr o vi d e cl arit y. T h e s y n o p si s w a s  
u p d at e d t o b e c o n si st e nt wit h c h a n g e s i n t h e pr ot o c ol.  
U p d at e  
2  
S e cti o n  4. 2   
I n I n cl u si o n C rit eri o n # 5, t h e wi n d o w f or s y m pt o m o n s et 
pri or t o S cr e e ni n g w a s c h a n g e d fr o m 7 t o 1 0 d a y s.  
I n I n cl u si o n C rit eri o n # 9 t h e c o ntr a c e pti on  r e q uir e m e nt s 
a n d d efi niti o n of W O C B P w er e u p d at e d i n li n e wit h t h e 
CI T G g ui d eli n e s . 
U p d at e  
3  
S e cti o n  6. 1. 1  
a n d 
S e cti o n  6. 1. 2   
T e xt w a s a m e n d e d t o cl arif y  t h e di sti n cti o n b et w e e n 
t e m p or aril y st o p pi n g st u d y dr u g a n d p er m a n e nt 
di s c o nti n u ati o n , a n d t o e n s ur e n otifi c ati o n of t h e 
m e di c al m o nit or  i n c a s e of a b n or m al L F T s . 
Cl arifi c ati o n  
4  
S e cti o n  7. 1   
A wi n d o w of ± 3 d a y s w a s a d d e d t o t h e D a y 6 0 
t el e p h o n e c all. 
A pr e g n a n c y t e st w a s a d d e d at D a y 2 8 . 
C yt o ki n e a n d a c ut e p h a s e pr ot ei n bl o o d dr a w s w er e 
s e p ar at e d o nt o 2 diff er e nt r o w s f or cl arit y.  
F urt h er d efi niti o n of t h e p h y si c al e x a mi n ati o n w a s  
a d d e d.  
U p d at e  

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
Cli nic al Pr ot oc ol  
V 7 . 0 
P T C T her a pe utics - C o nfi de nti al  
P a ge 5 9  of 6 2  
It e m 
N o.  
Pr ot o c ol 
S e cti o n  
V er si o n 6 / U p d at e 
R e a s o n/ R ati o n al e  
5  
S e cti o n  7. 2   
T e xt w a s a m e n d e d t o cl arif y t h at t h e l a b or at or y 
a s s e s s m e nt s s h o ul d i n cl u d e all p ar a m et er s , w hi c h 
a n al y s e s o c c ur at a c e ntr al l a b or at or y , t o cl arif y 
a s s e s s m e nt of dir e ct a n d i n dir e ct bilir u bi n, a n d t h at all 
l a b or at or y p ar a m et er s s h o ul d b e a s s e s s e d at b a s eli n e.  
Cl arifi c ati o n  
6  
S e cti o n  7. 3   
T e xt w a s a d d e d t o c o nfir m t h at a n al y s e s will b e at 
c e ntr al l a b or at or y.  
Cl arifi c ati o n  
7  
S e cti o n  7. 5. 2  
Cl arifi c ati o n w a s a d d e d t h at tr a n sf er t o I C U, m e c h a ni c al 
v e ntil ati o n , or a n ot h er m e di c all y i m p ort a nt e v e nt ( at t h e 
di s cr eti o n of t h e i n v e sti g at or) a s a r e s ult of di s e a s e 
pr o gr e s si o n w o ul d b e cl a s sifi e d a s a n S A E.  
U p d at e  
8  
S e cti o n  8. 2  
a n d 
S e cti o n  8. 4. 6  
T e xt w a s a m e n d e d t o cl arif y t h at t h e fir st i nt eri m 
a n al y si s w o ul d b e aft er t h e fir st 4 0 s u bj e ct s r e a c h e d 
D a y 2 8 or di e d, wit h dr e w c o n s e nt, or w er e l o st t o f oll o w -
u p  a n d t o cl arif y t h o s e s u bj e ct s w h o w o ul d b e c e n s or e d.  
Cl arifi c ati o n  
9  
S e cti o n  8. 4. 2   
T e xt w a s a m e n d e d t o cl arif y t h at s u bj e ct s w o ul d b e 
f oll o w e d u nl e s s t h e y or di e d, wit h dr e w c o n s e nt, or w er e 
l o st t o f oll o w-u p ; t o cl arif y a c hi e v e m e nt of t h e pri m ar y 
e n d p oi nt;  a n d t o cl arif y t h o s e s u bj e ct s w h o w o ul d b e 
c e n s or e d . 
Cl arifi c ati o n  
1 0  
S e cti o n  8. 4. 3  
A s s e s s m e nt of o v er all s ur vi v al h a d b e e n err o n e o u sl y 
i n cl u d e d a n d w a s r e m o v e d.  
U p d at e  
1 1  
S e cti o n  8. 4. 4. 5   T h e b a s eli n e l a b or at or y a s s e s s m e nt w a s cl arifi e d a s 
b ei n g pri or t o fir st d o s e.  
Cl arifi c ati o n  
9. 2. 6.  
Versi o n 7 . 0: 0 2  J u ne 2 0 2 1   
O ver all re as o n f or Versi o n 7 . 0: T he o v erall reas o n f or Versi o n 7 . 0 of t he pr ot oc ol was t o 
i nc or p orat e fee d ba c k fr o m st u d y sit es a n d Healt h A ut h oriti es.  
Pr ot o c ol 
S e cti o n  
V er si o n 7 / U p d at e 
R e a s o n/ R ati o n al e  
Pr ot o c ol  
T h e n e w n o n pr o pri et ar y n a m e w a s a d d e d. T h e v er si o n n u m b er 
a n d d at e w er e u p d at e d t hr o u g h o ut.  E dit ori al a n d a d mi ni str ati v e 
r e vi si o n s ( e g, t y p o gr a p hi c al err or, p u n ct u ati o n, t e n s e s, 
a b br e vi ati o n s) w er e i n c or p or at e d t o pr o vi d e cl arit y. T h e 
s y n o p si s a n d S c h e d ul e of E v e nt s w er e u p d at e d t o b e c o n si st e nt 
wit h c h a n g e s i n t h e pr ot o c ol.  
U p d at e  
S y n o p si s  
T h e n u m b er of sit e s w a s i n cr e a s e d t o a p pr o xi m at el y 5 0 . 
U p d at e  
S e cti o n  4. 2   
I n cl u si o n crit eri o n # 5 w a s c h a n g e d t o all o w s y m pt o m o n s et ≤1 4 
d a y s.  
U p d at e  
S e cti o n  6. 1. 1   
T h e t e xt w a s a m e n d e d t o cl arif y t h at L F T m o nit ori n g i s d ail y 
d uri n g h o s pit ali z ati o n.  
Cl arifi c ati o n  
S e cti o n  7. 2   
D et ail s of w h at a s s e s s m e nt s t a k e pl a c e s h o ul d a s u bj e ct b e 
tr a n sf err e d t o t h e I C U w er e cl arifi e d.  
Cl arifi c ati o n  
S e cti o n  7. 3   
T h e P K a s s e s s m e nt s w er e r e d u c e d t o gi v e s p ar c e P K s a m pli n g.  U p d at e  
S e cti o n  7. 5. 4   
H e p ati c a b n or m aliti e s of Gr a d e ≥4 will b e c o n si d er e d 
u n e x p e ct e d a d v er s e e v e nt s.  
U p d at e  
S e cti o n  8. 4. 2   
R e s c u e t h er a p y w a s d efi n e d . 
U p d at e  
 

P T C 2 9 9 -VI R -0 1 5 -C O V 1 9  
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