A Randomized, Double-blind, Dose-ranging, Placebo Controlled, Phase 2a Evaluation of the Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Participants With Acute Respiratory Distress Syndrome (ARDS) Associated With at Least Severe COVID-19 (INTEGRIS-ARDS)
Phase: PHASE2
Conditions: Acute Respiratory Distress Syndrome, SARS-CoV-2
Sponsor: Pliant Therapeutics, Inc.

PLN-74809-ARDS-204, 23 October 2020, Protocol Amendment 2 
Page 1 
PLIANT 
I K(I.AP( UlfLt. 
Study Title: 
Study Number: 
Study Phase: 
Product Name: 
IND Number: 
EudraCT Number: 
Indication: 
Sponsor: 
Sponsor Study 
Director: 
Document ID 
Original Protocol 
Amendment 1 
Amendment 2 
Clinical Trial Protocol 
PLN-74809-ARDS-204 
A randomized, double-blind. dose-ranging, placebo controlled, Phase 2a 
evaluation of the safety. tolerability, and pharmacokinetics of PLN-74809 
in paiticipants with acute respiratory distress syndrome (ARDS) associated 
with at least severe COVID-19 (INTEGRIS-ARDS) 
PLN-74809-ARDS-204 
2a 
PLN-74809-000 
150,181 
Not applicable 
Treannent of acute respiratory distress syndrome (ARDS) associated with 
at least severe COVID-19 
Pliant Therapeutics Inc. 
2 60 Littlefield A venue 
South San Francisco, CA 94080, USA 
Date 
24 June 2020 
31 July 2020 
23 October 2020 
Confidentiality Statement 
This document is the property of Pliant Therapeutics. The confidential inf01mation in this document 
may not be used, published or disclosed without the prior written consent of Pliant Therapeutics 
except to the extent required under applicable laws or regulations. 
Proprietaiy and Confidential 
Pliant TI1erapeutics, Inc. 

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 4 
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
7.  Cli nical dia g n osis of A R D S, as defi ne d b y Berli n criteria, i ncl u di n g:   
a. C hest i ma gi n g (ra di o gra p h y or C T sca n): bilateral o pacities n ot f ull y e x plai ne d b y 
eff usi o ns, l o bar/l u n g c olla pse, or n o d ules  
b.  Ori gi n of e de ma: res pirat or y fail ure n ot f ull y e x plai ne d b y car diac fail ure or fl ui d 
o verl oa d  
c. Ac ute h y p o xe mia defi ne d b y partial press ure of arterial o x y ge n ( Pa O 2)/ fracti o n of 
i ns pire d o x y ge n ( Fi O2): 
i. Mil d h y p o xe mia: 2 0 0 m m H g < Pa O
2/ Fi O2 ≤ 3 0 0 m m H g wit h p ositi ve 
e n d-e x pirat or y press ure ( P E E P) or c o nti n u o us p ositi ve air wa y press ure 
( C P A P) ≥ 5 c m H 2O 
ii. M o derate h y p o xe mia: 1 0 0 m m H g < Pa O
2/ Fi O2 ≤ 2 0 0 m m H g wit h 
P E E P ≥ 5 c m H 2O 
iii. Se vere h y p o xe mia: Pa O 2/ Fi O2 ≤ 1 0 0 m m H g wit h P E E P ≥ 5 c m H 2O 
N ote : If a relia ble esti mati o n of Fi O2 is n ot p ossi ble i n n o n-ve ntilate d partici pa nts, t h ose 
meeti n g i ncl usi o n Criteria 9 a n d 1 0 will be eli gi ble if all ot her criteria are met.  
8.  T he ra di ol o gical a n d h y p o xe mia i ncl usi o n criteria (i.e., 7a a n d 7c) m ust be met wit hi n t he 
sa me 2 4-h o ur peri o d. T he t i me of o nset of A R D S is defi ne d as t he ti me w he n t hese 
t w o criteria are met.  
9.  Recei vi n g s u p p ort f or ac ute l u n g i nj ur y/res pirat or y distress via s u p ple me ntal o x y ge n (e. g., 
hi g h fl o w nasal ca n n ula [ H F N C], face mas k [i.e., n o n -re breat her]), n o n-i n vasi ve ve ntilati o n, 
or via i nt u bati o n a n d mec ha nical ve ntilati o n.  
Me dical Hist or y a n d C o m or bi d C o n diti o ns  
1 0.  H os pitalize d wit h at least se vere C O VI D -1 9 
) 
a. P ositi ve testi n g b y sta n dar d re verse tra nscri pti o n p ol y merase c hai n reacti o n 
( R T-P C R) assa y ( or a n e q ui vale nt C O VI D -1 9 test a ut h orize d u n der E U A)  
b.  S y m pt o ms s u g gesti ve of se vere s yste mic ill ness wit h C O VI D -1 9, w hic h c o ul d 
i ncl u de a n y s y m pt o m of m o derate ill ness or s h ort ness of breat h at rest, or res pirat or y 
distress  
c. Cli nical si g ns i n dicati ve of se vere s yste mic ill ness wit h C O VI D -1 9, s uc h as 
res pirat or y rate ≥ 3 0 per mi n ute, heart rate ≥ 1 2 5 per mi n ute, o x y ge n sat urati o n 
( S p O2) ≤ 9 3 % o n r o o m air at sea le vel or Pa O2/ Fi O2 < 3 0 0 m m H g  
1 1.  Ser u m as partate a mi n otra nsferase ( A S T) c o nce ntrati o n ≤ 1 2 0 U/ L a n d ser u m a la ni ne 
a mi n otra nsferase ( A L T) c o nce ntrati o n ≤ 1 5 0 U/ L (a p pr o xi matel y 3 ×  U L N f or b ot h 
para meters)  
1 2.  Ser u m t otal bilir u bi n ≤ 1. 8 m g/ d L, i n t he a bse nce of Gil bert's s y n dr o me or he m ol ysis.  
1 3.  Platelet c o u nt ≥1 2 0, 0 0 0/ m m 3 
1 4.  Al b u mi n ≥ 3. 3 g/ d L  
1 5.  I nter nati o nal n or malized rati o (I N R) ≤1. 5 i n t he a bse nce of a ntic oa g ula nt t hera p y or ot her 
c oa g ul o pat hies  

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 7 
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
• Bi o mar kers: plas ma a n d ser u m sa m ples will be o btai ne d.  
  
St atistic al Met h o ds:  
T his is a safet y a n d P K st u d y, wit h e x pl orat or y e n d p oi nts; as s uc h, n o statistical h y p ot heses are 
b ei n g teste d.  
I n ge neral, data will be s u m marize d usi n g statistical s u m mar y met h o ds; gra p hic prese ntati o ns of 
data ma y als o be pre pare d.  
 

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 8 
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
T A B L E O F C O N T E N T S  
S Y N O P SI S  ................................................................................................................................. 2 
T A B L E O F C O N T E N T S  ........................................................................................................... 8 
LI S T O F I N -T E X T T A B L E S  .................................................................................................. 1 1 
LI S T O F I N -T E X T FI G U R E S ................................................................................................. 1 1 
LI S T O F A P P E N DI C E S  .......................................................................................................... 1 1 
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  .......................................... 1 2 
1  
I N T R O D U C TI O N ................................................................................................. 1 5 
1. 1  
Bac k gr o u n d ...................................................................................................... 1 5  
1. 2  
S u m mar y of Cli nical De vel o p me nt  ................................................................. 1 7 
1. 3  
Rati o nale f or St u d y  .......................................................................................... 1 8 
1. 4  
Be nefit -Ris k Assess me nt  ................................................................................. 1 9 
2  
S T U D Y O BJ E C TI V E S  .......................................................................................... 2 1 
2. 1  
Pri mar y O bjecti ve  ............................................................................................ 2 1 
2. 2  
Sec o n dar y O bjecti ve  ........................................................................................ 2 1 
2. 3  
E x pl orat or y O bjecti ves  .................................................................................... 2 1 
3  
I N V E S TI G A TI O N A L P L A N ................................................................................ 2 2 
3. 1  
O verall St u d y Desi g n a n d Pla n ........................................................................ 2 2  
3. 2  
Rati o nale f or St u d y Desi g n a n d C o ntr ol Gr o u p ............................................... 2 3  
3. 3  
St u d y D urati o n ................................................................................................. 2 4  
4  
S T U D Y P O P U L A TI O N A N D S E L E C TI O N  ........................................................ 2 5 
4. 1  
St u d y P o p ulati o n .............................................................................................. 2 5  
4. 1. 1  
I ncl usi o n Criteria ................................................................................. 2 5 
4. 1. 2  
E xcl usi o n Criteria  ................................................................................ 2 7 
5  
S T U D Y D R U G A N D A C C O U N T A BI LI T Y  ........................................................ 2 9 
5. 1  
Descri pti o n of St u d y Dr u g ............................................................................... 2 9  
5. 1. 1  
P L N - 7 4 8 0 9 ........................................................................................... 2 9 
5. 1. 2  
Place b o  ................................................................................................. 2 9 
5. 2  
Pac ka gi n g a n d La beli n g ................................................................................... 2 9  
5. 3  
St ora ge a n d Acc o u nta bilit y  .............................................................................. 2 9 
5. 4  
Treat me nt C o m plia nce  ..................................................................................... 2 9 
6  
S T U D Y T R E A T M E N T S  ....................................................................................... 3 0 
6. 1  
Descri pti o n of Treat me nts  ................................................................................ 3 0 
6. 2  
D ose M o dificati o ns a n d I nterr u pti o ns ............................................................. 3 0  
6. 3  
Selecti o n a n d Ti mi n g of D ose f or Eac h Partici pa nt ......................................... 3 0  
6. 4  
Met h o d of Assi g ni n g Partici pa nts t o Treat me nt Gr o u ps ................................. 3 0  
6. 5  
Bli n di n g............................................................................................................ 3 0  
6. 6  
C o nc o mita nt T hera p y....................................................................................... 3 1  

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 9 
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
6. 6. 1  
All o we d Me dicati o ns ........................................................................... 3 1  
6. 6. 2  
Disall o we d Me dicati o ns ....................................................................... 3 3 
6. 7  
Restricti o ns  ...................................................................................................... 3 4 
6. 7. 1  
Pri or T her a p y ....................................................................................... 3 4 
6. 7. 2  
Fl ui d a n d F o o d I nta ke .......................................................................... 3 4  
6. 7. 3  
Partici pa nt Acti vit y Restricti o ns  .......................................................... 3 4 
6. 7. 4  
C o ntrace pti o n ....................................................................................... 3 4  
7  
S T U D Y P R O C E D U R E S  ....................................................................................... 3 6 
7. 1  
I nf or me d C o nse nt............................................................................................. 3 6 
7. 2  
I ncl usi o n/ E xcl usi o n Criteria ............................................................................ 3 6 
7. 3  
De m o gra p hic I nf or mati o n  ................................................................................ 3 6 
7. 4  
Me dical Hist or y  ............................................................................................... 3 6 
7. 5  
Hei g ht a n d Wei g ht ........................................................................................... 3 6  
7. 6  
E x pl orat or y Efficac y Assess me nts  .................................................................. 3 7 
7. 6. 1  
 ............................................................................... 3 7 
7. 6. 2  
 ................................................. 3 7 
7. 6. 3  
 ................................... 3 7 
7. 7  
Pri or a n d C o nc o mita nt Me dicati o n Assess me nts  ............................................ 3 7 
7. 8  
P h ysical E xa mi nati o ns  ..................................................................................... 3 7 
7. 9  
Vital Si g ns  ........................................................................................................ 3 8 
7. 1 0  
 .......................................................................................... 3 8 
7. 1 1  
Cli ni cal La b orat or y Tests  ................................................................................. 3 8 
7. 1 1. 1  
La b orat or y Para meters  ......................................................................... 3 8 
7. 1 1. 2  
Sa m ple C ollecti o n, St ora ge, a n d S hi p pi n g .......................................... 4 0  
7. 1 2  
A d verse E ve nt Assess me nts  ............................................................................ 4 0 
7. 1 3  
P har mac o ki netic Assess me nts  ......................................................................... 4 0 
7. 1 4  
P har mac o d y na mic Assess me nts  ...................................................................... 4 1 
7. 1 5  
Dis pe nsi n g St u d y Dr u g  .................................................................................... 4 2 
7. 1 6  
Misse d Assess me nts ......................................................................................... 4 2 
7. 1 7  
A p pr o priate ness of Meas ure me nts  ................................................................... 4 2 
8  
A D V E R S E E V E N T S  ............................................................................................. 4 3 
8. 1  
Ti mi n g  .............................................................................................................. 4 3 
8. 2  
Defi niti o n of a n A d verse E ve nt ....................................................................... 4 3  
8. 3  
Se verit y of a n A d verse E ve nt .......................................................................... 4 4  
8. 4  
Ca usal Relati o ns hi p of a n A d verse E ve nt ........................................................ 4 4  
8. 5  
O utc o me ........................................................................................................... 4 5  
8. 6  
Pre g na nc y ......................................................................................................... 4 5  
8. 7  
Cli nical La b orat or y A d verse E ve nts  ................................................................ 4 5 

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 1 2  
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
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 A G  
al p ha- 1 aci d gl yc o pr otei n  
A E  
a d verse e ve nt  
A L P  
al kali ne p h os p hatase  
A L T  
ala ni ne a mi n otra nsferase  
A R D S  
ac ute res pirat or y distress s y n dr o me  
A S T  
as partate a mi n otra nsferase  
A U C 0- 2 4 
area u n der t he plas ma c o nce ntrati o n- ti me c ur ve fr o m ti me zer o t o 2 4 
h o urs  
 
 
B A L F  
br o nc h oal ve olar la va ge fl ui d  
 
 
C F R  
C o de of Fe deral Re g ulati o ns 
C O VI D -1 9  
c or o na vir us disease  
C P A P  
c o nti n u o us p ositi ve air wa y press ure  
C R O  
c o ntract researc h or ga nizati o n  
C T  
c o m p ute d t o m o gra p h y  
C T C A E  
C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts  
 
 
D DI  
dr u g- dr u g i nteracti o n  
 
 
D S M B  
Data Safet y M o nit ori n g B oar d  
 
 
e C R F  
electr o nic case re p ort f or m  
E C L S  
e xtrac or p oreal life s u p p ort 
E C M O  
e xtrac or p oreal me m bra ne o x y ge nati o n 
E D C  
electr o nic data ca pt ure  
E o T  
e n d of treat me nt 
E T  
earl y ter mi nati o n 
E U A  
E mer ge nc y Use A ut h orizati o n ( b y t he F D A) 

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 1 3  
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
F A C T T  
Fl ui ds a n d Cat heters Treat me nt Trial  
F D A  
F o o d a n d Dr u g A d mi nistrati o n 
Fi O 2 
fracti o n of i ns pire d o x y ge n 
F S H  
f ollicle-sti m ulati n g h or m o ne 
G C P  
G o o d Cli nical Practice  
G D P R  
Ge neral Data Pr otecti o n Re g ulati o n  
H F N C  
hi g h fl o w nasal ca n n ula 
H F O V  
hi g h -fre q ue nc y oscillat or y ve ntilati o n 
HI P A A  
Healt h I nf or mati o n P orta bilit y a n d Acc o u nta bilit y Act 
I C5 0, I C8 0 
5 0 %, 8 0 % i n hi bit or y c o nce ntrati o n  
I C F 
i nf or me d c o nse nt f or m 
I C H 
I nter nati o nal C o nfere nce o n Har m o nisati o n  
I C U 
i nte nsi ve care u nit 
I E C 
i n de pe n de nt et hics c o m mittee 
I L 
i nterle u ki n 
I N R 
i nter nati o nal n or malize d rati o 
I P F 
i di o pat hic p ul m o nar y fi br osis 
I R B 
i nstit uti o nal re vie w b oar d 
L A P  
late nc y-ass ociate d pe pti de  
M A T E 1  
m ulti dr u g t o xi n e xtr usi o n tra ns p orter 1  
Me d D R A  
Me dical Dicti o nar y f or Re g ulat or y Acti vities  
M E R S  
Mi d dle East Res pirat or y S y n dr o me  
N E  
nas oe nteric  
N G  
nas o gastric  
 
 
 
 
 
 
Pa C O 2 
partial press ure of arterial car b o n di o xi de  
Pa O 2 
partial press ure of arterial o x y ge n  

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 1 4  
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
P D  
p har mac o d y na mics(s) 
P E E P  
p ositi ve e n d- e x pirat or y press ure  
PI P E D A  
Pers o n nel I nf or mati o n Pr otecti o n a n d Electr o nic D oc u me nts Act  
P K  
p har mac o ki netic(s) 
P P B  
plas ma -pr otei n bi n di n g  
P S C  
pri mar y scler osi n g c h ola n gitis  
Q D  
o nce dail y 
 
 
R E B  
researc h et hics b oar d 
R T -P C R  
re verse tra nscri pti o n p ol y merase c hai n reacti o n 
S A E  
seri o us a d verse e ve nt 
S A P  
statistical a nal ysis pla n 
S A R S  
Se vere Ac ute Res pirat or y S y n dr o me  
S A R S -C o V - 2 
se vere ac ute res pirat or y s y n dr o me c or o na vir us 2 
S M A  
s m o ot h m uscle a nti b o d y 
S M A D  
fa mil y of pr otei ns si milar t o t he ge ne pr o d ucts of t he Dr os o p hila ge ne 
' m ot hers a gai nst deca pe nta ple gic' (M a d ) a n d t he C. ele g a ns  ge ne S m a  
 
 
S p O 2 
o x y ge n sat urati o n  
T E A E  
treat me nt-e mer ge nt a d verse e ve nt  
T G F -β  
tra nsf or mi n g gr o wt h fact or-beta  
U L N  
u p per li mit of n or mal  
W H O  
W orl d Healt h Or ga nizati o n 
 

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 1 5  
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
1  
I N T R O D U C TI O N 
1. 1  
B ac k gr o u n d 
Dise ase B ac k gr o u n d 
Plia nt T hera pe utics, I nc. ( Plia nt) is de vel o pi n g P L N - 7 4 8 0 9-0 0 0 ( hereafter referre d t o as 
P L N - 7 4 8 0 9) f or t he treat ment of ac ute res pirat or y distress s y n dr o me ( A R D S) ass ociate d wit h 
at least se vere c or o na vir us disease ( C O VI D -1 9). A R D S is a maj or ca use of m ortalit y i n 
patie nts i nfecte d wit h se vere ac ute res pirat or y s y n dr o me c or o na vir us 2 ( S A R S -C o V - 2), 
w hic h ca uses C O VI D - 1 9. I nfecti o n b y S A R S- C o V-2 ca n ca use a ra n ge of s y m pt o ms fr o m 
mil d fe ver a n d c o u g h t o se vere res pirat or y ill ness, i ncl u di n g A R D S, res pirat or y fail ure a n d 
deat h. A R D S is c haracterize d b y persiste nt p ul m o nar y e de ma w hic h is a res ult of i m paire d 
fl ui d a n d i o n tra ns p ort i n t he al ve olar s pace. 
I n a rece nt st u d y of 2 0 1 patie nts wit h c o nfir me d C O VI D-1 9 p ne u m o nia h os pitalize d at 
Ji n yi nta n H os pital i n W u ha n ( C hi na), ris k fact ors ass ociate d wit h t he de vel o p me nt of A R D S 
a n d pr o gressi o n fr o m A R D S t o deat h i ncl u de d ol der a ge, ne utr o p hilia, a n d or ga n a n d 
c oa g ulati o n d ysf u ncti o n (
). I n t his st u d y, t he me dia n a ge of patie nts was 5 1 years 
a n d 6 3. 7 % patie nts were me n. Ei g ht y-f o ur patie nts ( 4 1. 8 %) we nt o n t o de vel o p A R D S, a n d 
of t h ose 8 4 patie nts, 4 4 ( 5 2. 4 %) die d.  
I n a n o bser vati o nal data base i ncl u di n g 8 9 1 0 patie nts fr o m 1 6 9 h os pitals i n Asia, E ur o pe, a n d 
N ort h A merica, t he relati o ns hi p bet wee n car di o vasc ular disease a n d i n - h os pital deat h a m o n g 
h os pitalize d patie nts wit h C O VI D -1 9 was e val uate d.  T his i n vesti gati o n c o nfir me d pre vi o us 
re p orts of t he i n de pe n de nt relati o ns hi p of ol der a ge, u n derl yi n g car di o vasc ular disease 
(c or o nar y arter y disease, heart fail ure, a n d car diac arr h yt h mias), c urre nt s m o ki n g, a n d 
c hr o nic o bstr ucti ve p ul m o nar y disease wit h deat h d ue t o C O VI D- 1 9 (
). Alt h o u g h 
t he m ortalit y rate i n patie nts wit h A R D S a n d C O VI D- 1 9 was n ot re p orte d i n t his a nal ysis, 
ol der a ge a n d c o m or bi dities c o nti n ue t o be str o n gl y ass ociate d wit h i ncrease d ris k of deat h.  
Av ail a ble A R D S/ C O VI D - 1 9 T her a pies 
Vari o us s u p p orti ve t hera pies ha ve bee n f o u n d t o re d uce m ortalit y i n patie nts wit h A R D S; 
h o we ver, m ortalit y re mai ns hi g h at 2 0 % t o 4 0 % (
 
). Effecti ve s u p p orti ve t hera pies are l u n g- pr otecti ve mec ha nical ve ntilati o n a n d 
a fl ui d c o nser vati ve strate g y, al o n gsi de ne ur o m usc ular bl oc ka de a n d pr o ne p ositi o ni n g i n 
m o re se vere cases. L u n g- pr otecti ve ve ntilati o n, usi n g a ti dal v ol u me of 6 m L per k g of 
pre dicte d b o d y wei g ht a n d a platea u air wa y press ure of < 3 0 c m H 2O, has ha d a maj or effect 
i n re d uci n g m ortalit y fr o m A R D S. Ne ur o m usc ular bl oc ka de a n d pr o ne p ositi o ni n g ha ve 
f urt her re d uce d m ortalit y i n m ore se verel y h y p o xe mic A R D S patie nts; pr o ba bl y b y e xte n di n g 
t he t hera pe utic effects of l u n g pr otecti ve ve ntilati o n. I n a d diti o n, fl ui d-c o nser vati ve t hera p y 
has i ncrease d ve ntilat or -free da ys.  

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 1 6  
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
H o we ver, n o effecti ve p har mac ol o gical t hera pies ha ve bee n f o u n d t o i m pr o ve cli nical 
o utc o me i n A R D S (
). T he lac k of a vaila bilit y of dr u gs t o treat 
A R D S re mai ns a si g nifica nt me dical c halle n ge. Ma n y l ar ge m ultice nter cli nical trials wit h 
vari o us dr u g t hera pies, i ncl u di n g gl uc oc ortic oi ds ( met h yl pre d nis ol o ne), nitric o xi de, 
s urfacta nt, β2-a g o nists, stati ns (si m vastati n a n d r os u vastati n), a nti o xi da nts, ket oc o naz ole, 
lis of ylli ne, o me ga 3 s u p ple me ntati o n, acti vate d pr otei n C, li p os o mal pr osta gla n di n, 
gra n ul oc yte- macr o p ha ge sti m ulati n g fact or, si velestat, a n d fact or VIIai, ha ve faile d t o s h o w 
a n y clear be nefit.  
O ne p har mac ol o gical i nter ve nti o n has bee n all o we d u n der E mer ge nc y Use A ut h orizati o n 
( E U A) b y t he F o o d a n d Dr u g A d mi nistrati o n ( F D A): re m desi vir, f or treat me nt of s us pecte d 
or la b orat or y c o nfir me d C O VI D- 1 9 i n a d ults a n d c hil dre n h os pitalize d wit h se vere disease. 
P at h o p hysi ol o gy of A R D S 
A R D S is c haracterize d b y persiste nt p ul m o nar y e de ma, w hic h is a res ult of i m paire d fl ui d 
a n d i o n tra ns p ort i n t he al ve olar s pace. Tra nsf or mi n g gr o wt h fact or beta ( T G F- β) is a 
pl uri p ote nt c yt o ki ne wit h esta blis he d r oles i n A R D S a n d p ul m o nar y fi br osis (
 
). T G F-β le vels are si g nifica ntl y i ncrease d i n l u n g tiss ue a n d 
br o nc h oal ve olar la va ge fl ui d ( B A L F) fr o m A R D S patie nts a n d T G F -β is i m plicate d i n earl y 
l u n g i nj ur y as well as pr o m oti o n of t he fi br o pr oliferati ve p hase of A R D S (
 
). T hr o m bi n as well as i nterle u ki n (I L)-1 β, earl y me diat ors of ac ute l u n g i nj ur y, 
acti vate T G F -β i n a n α vβ 6 i nte gri n-s pecific ma n ner, pr o m oti n g e pit helial da ma ge, al ve olar 
lea k a n d c olla ge n s y nt hesis a n d fi br osis (
).  
I nte gri n αvβ 6, e x presse d o n l u n g e pit helial cells, bi n ds t o t he ar gi ni ne-gl yci ne -as partate 
se q ue nce of late nc y-ass ociate d pe pti de ( L A P) a n d u p o n sti m ulati o n b y a variet y of si g nals 
(e. g. pr otei nase-acti vate d rece pt or -1 a n d l ys o p h os p hati dic aci d) releases T G F -β fr o m t he 
late nt c o m ple x a n d i nitiates T G F-β dri ve n pr ocesses (
). I n t he l u n g, αvβ 6 is t he 
ke y re g ulat or of T G F- β acti vit y (
). I n healt h y l u n gs, αvβ 6 is e x presse d at l o w 
le vels a n d pri maril y f u ncti o ns t o s u p press al ve olar macr o p ha ge activati o n. I n l u n g i nj ur y i n 
mice a n d h u ma ns, t he e x pressi o n of α vβ 6 o n e pit helial cells a n d acti vati o n of T G F -β is 
dra maticall y i ncrease d a n d T G F -β dri ve n tiss ue i nj ur y a n d re pair effects d o mi nate w hile a nti -
i nfla m mat or y effects are o verc o me b y ot her pr o-i nfla m mat or y me diat ors. I n a d ults, αvβ 6 
e x pressi o n is li mite d t o e pit helial cells a n d is e x presse d at l o w le vels i n healt h y tiss ues, 
s u g gesti n g t hat p har mac ol o gical i n hi biti o n of α vβ 6 ma y pr o vi de a tiss ue-tar gete d a n d 
p ote ntiall y safer a p pr oac h f or T G F- β i n hi biti o n. 
Si milarl y, i nte gri n α vβ 1 is e x presse d b y l u n g fi br o blasts a n d, li ke αvβ 6 o n e pit helial cells, 
re g ulates T G F-β acti vit y t hr o u g h bi n di n g t o L A P a n d release of acti ve T G F -β (
). 
P har mac ol o gical i n hi biti o n of α vβ 1 atte n uates fi br osis i n t he ble o m yci n m o use m o del of 
p ul m o nar y fi br osis (
), i m plicati n g αvβ 1 i n T G F-β - dri ve n l u n g i nj ur y. I n A R D S a 
s u bset of patie nts de vel o p fi br otic disease t hat res ults i n re d uce d l u n g f u ncti o n after rec o ver y 
fr o m ac ute i nj ur y, i ncl u di n g a p pr o xi matel y 3 0 % of Mi d dle East Res pirat or y S y n dr o me 
( M E R S) a n d Se vere Ac ute Res pirat or y S y n dr o me ( S A R S) s ur vi v ors (
). W hile it 
is t o o earl y t o k n o w t he l o n g ter m i m pact of C O VI D- 1 9 A R D S o n l u n g healt h a n d f u ncti o n 

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 2 5  
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
4  
S T U D Y P O P U L A TI O N A N D S E L E C TI O N  
4. 1  
St u d y P o p ul ati o n  
Partici pa nts wit h A R D S ass ociate d wit h at least se vere C O VI D - 1 9 w h o meet wit h t he 
f oll o wi n g eli gi bilit y criteria ma y be e nr olle d. 
Treat me nt wit h i n vesti gati o nal C O VI D - 1 9 t hera pies a vaila ble u n der E U A b y t he F D A a n d/ or 
off-la bel use of a n y ot her dr u gs, de vices, or i nter ve nti o ns t hat mi g ht be use d t o ma na ge 
C O VI D - 1 9 ma y be all o we d, pe n di n g re vie w a n d a p pr o val b y t he Me dical M o nit or a n d 
S p o ns or St u d y Direct or. 
4. 1. 1  
I ncl usi o n Criteri a 
Eac h partici pa nt m ust meet al l t he f oll o wi n g criteria t o be e nr olle d i n t he st u d y. 
Ge neral a n d A d mi nistrati ve  
1.  A ges 1 8 years a n d ol der. 
2.  A ble t o pr o vi de c o nse nt eit her o n t heir o w n be half or t hr o u g h a le gall y a ut h orize d 
re prese ntati ve. 
3.  Fe male partici pa nts of c hil d beari n g p ote ntial ( o v ul ati n g or pre me n o pa usal a n d n ot 
s ur gicall y sterile) a n d male partici pa nts wit h se x ual part ners of c hil d beari n g p ote ntial 
m ust a gree t o use hi g hl y effecti ve met h o ds of birt h c o ntr ol d uri n g t heir partici pati o n i n 
t he st u d y a n d f or 3 0 da ys f or fe male partici pa nts a n d 9 0 da ys f or male partici pa nts a n d 
fe male part ners of male partici pa nts after t he last a d mi nistrati o n of st u d y dr u g. Hi g hl y 
effecti ve met h o ds of birt h c o ntr ol are defi ne d as t h ose wit h 9 9 % or greater efficac y (see 
Secti o n  6. 7. 4 ). 
4.  Fe male partici pa nts of n o nc hil d beari n g p ote ntial m ust be eit her s ur gicall y sterile ( defi ne d 
as h ysterect o m y, bilateral t u bal li gati o n, sal pi n gect o m y a n d/ or bilateral o o p h orect o m y at 
least 6 m o nt hs pri or t o scree ni n g) or p ost me n o pa usal ( defi ne d as 1 2 m o nt hs of 
s p o nta ne o us a me n orr hea wit h o ut a n alter nati ve me dical ca use or 6 m o nt hs of 
s p o nta ne o us a me n orr hea wit h ser u m f ollicle-sti m ulati n g h or m o ne [ F S H] le vels 
> 4 0 mI U/ m L)  
5.   A gree t o a bstai n fr o m s per m or e g g d o nati o n t hr o u g h 9 0 da ys or 3 0 da ys, res pecti vel y, 
after a d mi nistrati o n of t he last d ose of st u d y dr u g.  
6.   
 

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 2 6  
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
A R D S Dia g n osis  
7.  Cli nical dia g n osi s of A R D S, as defi ne d b y Berli n criteria (refer t o A p pe n di x 2 ), 
i ncl u di n g:  
a. C hest i ma gi n g (ra di o gra p h y or C T sca n) : bilateral o pacities n ot f ull y e x plai ne d b y 
eff usi o ns, l o bar/l u n g c olla pse, or n o d ules 
b.  Ori gi n of e de ma: res pirat or y fail ure n ot f ull y e x plai ne d b y car diac fail ure or fl ui d 
o verl oa d 
c. Ac ute h y p o xe mia defi ne d b y p artial press ure of arterial o x y ge n ( Pa O 2)/ fracti o n 
of i ns pire d o x y ge n ( Fi O 2): 
i. Mil d h y p o xe mia: 2 0 0 m m H g < Pa O
2/ Fi O2 ≤ 3 0 0 m m H g wit h 
p ositi ve e n d-e x pirat or y press ure ( P E E P) or c o nti n u o us p ositi ve air wa y 
press ure ( C P A P) ≥ 5 c m H 2O 
ii. M o derate h y p o xe mia: 1 0 0 m m H g < Pa O
2/ Fi O2 ≤ 2 0 0 m m H g wit h 
P E E P ≥5 c m H 2O 
iii. Se vere h y p o xe mia: Pa O 2/ Fi O2 ≤ 1 0 0 m m H g wit h P E E P ≥ 5 c m H 2O 
N ote : If a relia ble esti mati o n of Fi O2 is n ot p ossi ble i n n o n- ve ntilate d partici pa nts, t h ose 
meeti n g i ncl usi o n Criteria 9 a n d 1 0 will be eli gi ble if all ot her criteria are met.  
8.  T he ra di ol o gical a n d h y p o xe mia i ncl usi o n criter ia (i.e., 7a a n d 7c) m ust be met wit hi n t he 
sa me 2 4- h o ur peri o d. T he ti me of o nset of A R D S is defi ne d as t he ti me w he n t hese 
t w o criteria are met. 
9.  Recei vi n g s u p p ort f or ac ute l u n g i nj ur y/res pirat or y distress via s u p ple me ntal o x y ge n 
(e. g., hi g h fl o w nasal ca n n ula [ H F N C], face mas k [i.e., n o n-re breat her]), n o n-i n vasi ve 
ve ntilati o n, or via i nt u bati o n a n d mec ha nical ve ntilati o n.  
Me dical Hist or y a n d C o m or bi d C o n diti o ns 
1 0.  H os pitalize d wit h at least se vere C O VI D - 1 9 (
) 
a. P ositi ve testi n g b y sta n dar d re ve rse tra nscri pti o n p ol y merase c hai n reacti o n 
( R T-P C R) assa y ( or a n e q ui vale nt C O VI D - 1 9 test a ut h orize d u n der E U A) 
b.  S y m pt o ms s u g gesti ve of se vere s yste mic ill ness wit h C O VI D - 1 9, w hic h c o ul d 
i ncl u de a n y s y m pt o m of m o derate ill ness or s h ort ness of breat h at rest, or 
res pirat or y distress  
c. Cli nical si g ns i n dicati ve of se vere s yste mic ill ness wit h C O VI D - 1 9, s uc h as 
res pirat or y rate ≥ 3 0 per mi n ute, heart rate ≥ 1 2 5 per mi n ute, o x y ge n sat urati o n 
( S p O2) ≤ 9 3 % o n r o o m air at sea le vel or Pa O2/ Fi O2 < 3 0 0 m m H g 
1 1.  Ser u m as partate a mi n otra nsferase ( A S T) c o nce ntrati o n ≤ 1 2 0 U/ L a n d ser u m ala ni ne 
a mi n otra nsferase ( A L T) c o nce ntrati o n ≤ 1 5 0 U/ L (a p pr o xi matel y 3 × U L N f or b ot h 
para meters)  
1 2.  Ser u m t otal bilir u bi n ≤ 1. 8 m g/ d L, i n t he a bse nce of Gil bert's s y n dr o me or he m ol ysis  

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 3 5  
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
- 
Oral h or m o nal c o ntrace pti ves wit h less t ha n 1 year of use i n c o nj u ncti o n wit h 
c o n d o m 
• Se x ual part ner wit h s ur gical sterilizati o n (e. g., vasect o m y, t u bal li gati o n, h ysterect o m y 
a n d/ or bilateral o o p h orect o m y)  
Fe male partici pa nts w h o are usi n g h or m o nal c o ntrace pti ves m ust ha ve bee n usi n g t he 
h or m o nal c o ntrace pti ve f or at least 1 2  wee ks  bef ore scree ni n g. Partici pa nts m ust a gree t o 
a bstai n fr o m s per m or e g g d o nati o n f or at least 9 0  da ys or 3 0 da ys, res pecti vel y, after 
a d mi nistrati o n of t he last d ose of st u d y dr u g. 

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 3 9  
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
T a ble  2.  
L a b or at or y Tests, as Liste d, or per L oc al St a n d ar ds 
He m at ol o g y  
Ser u m C he mistr y  
- 
He mat ocrit ( Hct)  
- 
He m o gl o bi n ( H g b)  
- 
Mea n c or p usc ular he m o gl o bi n ( M C H)  
- 
Mea n c or p usc ular he m o gl o bi n 
c o nce ntrati o n ( M C H C)  
- 
Mea n c or p usc ular v ol u me ( M C V)  
- 
Platelet c o u nt  
- 
Re d bl o o d cell ( R B C) c o u nt  
- 
W hite bl o o d cell ( W B C) c o u nt wit h 
differe ntial  
- 
Ala ni ne a mi n otra nsferase ( A L T)  
- 
Al b u mi n ( A L B)  
- 
Al kali n e p h os p hatase ( A L P)  
- 
Al p ha - 1-aci d-gl uc o pr otei n ( A A G)  
- 
A m ylase (refle x li pase if a m ylase 
≥1. 5  × U L N)  
- 
As partate a mi n otra nsferase ( A S T)  
- 
Bilir u bi n (t otal a n d direct)  
- 
Bl o o d urea nitr o ge n ( B U N)  
- 
Calci u m ( Ca)  
- 
C hl ori de ( Cl)  
- 
Creati ni ne  
- 
Creati ne ki nase ( C K)  
- 
Ga m ma -gl uta m yl tra nsferase ( G G T)  
- 
Gl o b uli n  
- 
Gl uc ose  
- 
Lactate de h y dr o ge nase ( L D H)  
- 
P h os p h or us ( P)  
- 
P otassi u m ( K)  
- 
S o di u m ( Na)  
- 
T otal pr otei n  
- 
T otal c h olester ol  
- 
Tri gl yceri des  
- 
Tr o p o ni ns  
- 
Uric aci d  
C o a g ul ati o n  
- 
I nter nati o nal n or malize d rati o (I N R) 
Uri n al ysis  
- 
A p peara nce  
- 
Bilir u bi n  
- 
C ol or  
- 
Gl uc ose  
- 
Ket o nes  
- 
Micr osc o pic e xa mi nati o n of se di me nt  
- 
Nitrite  
- 
Occ ult bl o o d  
- 
p H  
- 
Pr otei n  
- 
S pecific gra vit y  
- 
Ur o bili n o ge n  
Ot her  
Scree ni n g O nl y  
- 
Ser u m h u ma n c h ori o nic g o na d otr o pi n 
( h C G) (fe males) 
- 
F ollicle -sti m ulati n g h or m o ne ( F S H) –  
t o c o nfir m p ost me n o pa usal stat us 
- 
He patitis A I g M a nti b o d y ( H A V -I g M 
A b)  
- 
He patitis B s urface a nti ge n ( H bs A g)  
- 
He patitis C vir us a nti b o d y ( H C V A b)  
- 
H u ma n i m m u n o deficie nc y vir us ( HI V)  
- 
S A R S - C o V-2 P C R ( or C O VI D -1 9 tests 
a ut h orize d u n der E U A)  
- 
Uri ne dr u g scree n, i ncl u di n g, b ut n ot 
li mite d t o: 
o  a m p heta mi nes  
o  bar bit urates  
o  be nz o diaze pi nes  
o  c ocai ne  
o  met ha d o ne  
o  p he nc ycli di ne  
o  o piates  
 

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 4 1  
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
7. 1 4  
P h ar m ac o d y n a mic Assess me nts  
Plas ma a n d ser u m bi o mar ker sa m ples will be o btai ne d as detaile d i n t he Sc he d ule of E ve nts 
(A p pe n di x 1 ).  
T he st u d y will test, i n a n e x pl orat or y ma n ner, a pa nel of bi o mar kers wit h p ote ntial t o assess 
dr u g effects. A ta ble of ke y e x pl orat or y bi o mar kers of i nterest a n d e vi de nce f or t heir 
pr o g n ostic or p har mac o d y na mic val ue is prese nte d i n Ta ble  3.  
I nf or mati o n o n t he c ollecti o n, pr ocessi n g, st ora ge, a n d s hi p pi n g of bi o mar ker sa m ples will be 
pr o vi de d i n a la b orat or y ma n ual.  
T a ble  3.  
Ke y E x pl or at or y Bi o m ar kers of I nterest a n d E vi de nce f or T heir 
Pr o g n ostic or P h ar m ac o d y n a mic V al ue  
C ate g or y  
Bi o m ar ker  
E vi de nce of Pr o g n ostic or P h ar m ac o d y n a mic V al ue 
( Refere nce) 
E pit helial 
Da ma ge  
Rece pt or f or a d va nce d 
gl ycati o n e n d -pr o d ucts 
( R A G E) 
Hi g her le vels i ncrease o d ds of A R D S dia g n osis i n at ris k 
patie nts (
) a n d pre dict m ortalit y i n A R D S 
patie nts wit h hi g h -ti dal v ol u me ve ntilati o n (
) 
Kre bs v o n de n L u n ge n -
6 
( K L-6)  
Hi g her le vels i n patie nts wit h A R D S t ha n ve ntilate d a n d 
healt h y c o ntr ols a n d, wit hi n A R D S patie nts, hi g her le vels i n 
n o n -s ur vi v ors t ha n s ur vi v ors (
) 
S urfacta nt pr otei n D  
( S P-D)  
Hi g her baseli ne le vels of S P -D were ass ociate d wit h w orse 
o utc o mes a n d i ncrease d m ortalit y i n A R D S (
) 
Fi bri n ol ysis  
Plas mi n o ge n acti vat or 
i n hi bit or 1 ( P AI-1)  
Hi g her baseli ne le vels of P AI -1 i n A R D S patie nts a n d 
pre dict or of m ortalit y (
) 
D- di mer  
Hi g her le vels of   D-di mer ma y pre dict i n -h os pital m ortalit y 
i n C O VI D-1 9 patie nts (
) 
I nfla m mati o n 
I nterle u ki n 6 (I L-6)  
Hi g her baseli ne le vels of I L -6 pre dict m ore se vere C O VI D -
1 9 a n d a si g nifica nt decrease i n I L -6 was o bser ve d i n 
rec o veri n g patie nts (
). Hi g her le vels were o bser ve d 
i n patie nts w h o die d vers us t h ose w h o were disc har ge d 
(
). 
I nterle u ki n 8 (I L-8)  
Hi g her le vels are a pre dict or of m ortal it y i n patie nts wit h 
A R D S (
) 
C- reacti ve pr otei n 
( C R P) 
Hi g her le vels o bser ve d i n patie nts wit h se vere C O VI D -1 9 
(
) a n d i n patie nts w h o die d vers us t h ose w h o 
were disc har ge d (
) 
Fi br osis  
Pr o C 3 ( T y pe III 
c olla ge n s y nt hesis 
ne oe pit o pe)  
Hi g her le vels of relate d N -ter mi nal pe pti de f or t y pe III 
pr oc olla ge n were o bser ve d i n ser u m of patie nts wit h bi o ps y -
c o nfir me d fi br o pr oliferati ve A R D S (
) 
  
 

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 4 3  
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
8  
A D V E R S E E V E N T S  
8. 1  
Ti mi n g  
I n t his st u d y, A Es will be c ollecte d fr o m t he ti me t he partici pa nt si g ns t he I C F u ntil t he Da y 
2 8 st u d y visit. 
8. 2  
Defi niti o n of a n A d verse E ve nt  
A n A E is a n y e ve nt, si de effect, or ot her u nt o war d me dical occ urre nce t hat occ urs i n 
c o nj u ncti o n wit h t he use of a st u d y dr u g i n h u ma ns, w het her or n ot c o nsi dere d t o ha ve a 
ca usal relati o ns hi p t o t his treat me nt. A n A E ca n, t heref ore, be a n y u nfa v ora ble a n d 
u ni nte n de d si g n (t hat c o ul d i ncl u de a cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n g), 
s y m pt o m, or disease te m p orall y ass ociate d wit h t he use of a st u d y dr u g, w het her or n ot 
c o nsi dere d relate d t o t he st u d y dr u g. E ve nts meeti n g t he defi niti o n of a n A E i ncl u de:  
• E xacer bati o n of a c hr o nic or i nter mitte nt pre -e xisti n g c o n diti o n i ncl u di n g eit her a n 
i ncrease i n fre q ue nc y a n d/ or i nte nsit y of t he c o n diti o n. 
• Ne w c o n diti o ns detecte d or dia g n ose d after st u d y dr u g a d mi nistrati o n e ve n t h o u g h it ma y 
ha ve bee n prese nt pri or t o t he start of t he st u d y. 
• Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d i nteracti o n.  
• Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d o ver d ose of eit her st u d y dr u g or 
a c o nc o mita nt me dicati o n ( o ver d ose per se will n ot be re p orte d as a n A E/ S A E). E ve nts 
t hat d o n ot meet t he defi niti o n of a n A E i ncl u de: 
- 
Me dical or s ur gical pr oce d ure (e. g., e n d osc o p y, a p pe n dect o m y); t he c o n diti o n t hat 
lea ds t o t he pr oce d ure is a n A E.  
- 
Sit uati o ns i n w hic h a n u nt o war d me dical occ urre nce di d n ot occ ur (e. g., s ocial a n d/ or 
c o n ve nie nce a d missi o n t o a h os pital).  
- 
A ntici pate d da y -t o-da y fl uct uati o ns of pree xisti n g disease(s) or c o n diti o n(s) prese nt 
or detecte d at t he start of t he st u d y t hat d o n ot w orse n.  
• If t here is e vi de nce of a n A E t hr o u g h re p ort or o bser vati o n, t he I n vesti gat or or desi g nee 
will e val uate f urt her a n d rec or d t he f oll o wi n g i nf or mati o n:  
- 
Ti me of o nset a n d res ol uti o n  
- 
Se verit y  
- 
Ca usalit y/relati o n  t o st u d y treat me nt 
- 
Acti o n ta ke n re gar di n g st u d y dr u g 
- 
O utc o me 

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 4 4  
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
8. 3  
Se verit y of a n A d verse E ve nt  
Gra di n g t he se verit y of A Es will use t he C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts 
( C T C A E) gra di n g s yste m, versi o n 5. 0 (
), as descri be d bel o w. T he cli nical 
si g nifica nce of t he A E is deter mi ne d b y t he I n vesti gat or. T he I n vesti gat or is e nc o ura ge d t o 
c o ns ult wit h t he Me dical M o nit or. F or A Es or la b orat or y a b n or malities n ot liste d i n t he 
C T C A E gra di n g s yste m, please use t he gra di n g scale as descri be d bel o w.  
Gra de 1 a 
Mil d; as y m pt o matic or mil d s y m pt o ms; cli nical or dia g n ostic o bser vati o ns o nl y; 
i nter ve nti o n n ot i n dicate d 
Gra de 2 a 
M o derate; mi ni mal, l ocal or n o ni n vasi ve i nter ve nti o n i n dicate d; li miti n g a ge -
a p pr o priate i nstr u me ntal A D L b 
Gra de 3 a 
Se vere or me dicall y si g nifica nt b ut n ot i m me diatel y life -t hreate ni n g; 
h os pitalizati o n or pr ol o n gati o n of h os pitalizati o n i n dicate d; disa bli n g; li miti n g 
self-care A D L c 
Gra de 4 a 
Life -t hreate ni n g c o nse q ue nces; ur ge nt i nter ve nti o n i n dicate d 
Gra de 5 a 
Deat h relate d t o A E  
a. A se mi -c ol o n i n dicates ‘ or’ wit hi n t he descri pti o n of t he gra de.  
b.  I nstr u me ntal acti vities of dail y li vi n g ( A D L) refer t o pre pari n g meals, s h o p pi n g f or gr oceries or 
cl ot hes, usi n g t he tele p h o ne, ma na gi n g m o ne y, etc. 
c. Self -care A D L refer t o bat hi n g, dressi n g a n d u n dressi n g, fee di n g self, usi n g t he t oilet, ta ki n g 
me dicati o ns, a n d n ot be dri d de n.  
 
8. 4  
C a us al Rel ati o ns hi p of a n A d verse E ve nt 
T he I n vesti gat or will assess t he relati o ns hi p bet wee n st u d y dr u g a n d t he occ urre nce of eac h 
A E. T he I n vesti gat or’s assess me nt of t he relati o ns hi p of eac h A E t o st u d y dr u g will be 
rec or de d i n t he s o urce d oc u me nts a n d o n t he e C R F. Alter nati ve ca uses, s uc h as me dical 
hist or y, c o nc o mita nt t he ra p y, or ot her ris k fact ors, a n d t he te m p oral relati o ns hi p of t he e ve nt 
t o t he st u d y dr u g s h o ul d be c o nsi dere d a n d i n vesti gate d, if a p pr o priate. T he relati o ns hi p or 
ass ociati o n of t he A E t o a st u d y dr u g ( P L N- 7 4 8 0 9 or place b o) s h o ul d be assesse d usi n g 
cli nical j u d g me nt a n d t he f oll o wi n g c o nsi derati o ns:  
N o:  
E vi de nce e xists t hat t he a d verse e ve nt has a n eti ol o g y ot her t ha n t he st u d y 
dr u g. F or S A Es, a n alter nati ve ca usalit y m ust be pr o vi de d (e. g., pree xisti n g 
c o n diti o n, u n derl yi n g disease, i nterc urre nt ill ness, or c o nc o mita nt 
me dicati o n).  
Yes:  A te m p oral relati o ns hi p e xists bet wee n t he A E o nset a n d a d mi nistrati o n of 
t he st u d y dr u g t hat ca n n ot be rea dil y e x plai ne d b y t he partici pa nt’s cli nical 
state or c o nc o mita nt t hera pies. F urt her m ore, t he A E a p pears wit h s o me 
de gree of certai nt y t o be relate d, base d o n t he k n o w n t hera pe utic a n d 
p har mac ol o gic acti o ns or A E pr ofile of t he st u d y dr u g. I n case of cessati o n 

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 4 6  
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
T he I n vesti gat or s h o ul d e xercise his/ her me dical a n d scie ntific j u d g me nt i n deci di n g w het her 
a n a b n or mal la b orat or y fi n di n g or ot her a b n or mal assess me nt is cli nicall y si g nifica nt. 
Us uall y, t he a b n or malit y s h o ul d be ass ociate d wit h a cli nicall y e vi de nt si g n or s y m pt o m or 
be li kel y t o res ult i n a n e vi de nt si g n or s y m pt o m i n t he near ter m t o be c o nsi dere d cli nicall y 
si g nifica nt. A cli nicall y si g nifica nt la b orat or y a b n or malit y i n t he a bse nce of cli nical 
s y m pt o ms ma y je o par dize t he partici pa nt a n d ma y re q uire i nter ve nti o n t o pre vent i m me diate 
c o nse q ue nces. F or e xa m ple, a mar ke dl y l o w ser u m gl uc ose c o nce ntrati o n ma y n ot be 
acc o m pa nie d b y c o ma or c o n v ulsi o ns yet be of a ma g nit u de t o re q uire gl uc ose a d mi nistrati o n 
t o pre ve nt s uc h se q uelae. 
8. 8  
Seri o us A d verse E ve nts  
8. 8. 1  
Defi niti o n of Seri o us A dverse Eve nts  
A n S A E is a n y u nt o war d me dical occ urre nce t hat at a n y d ose:  
• Is life-t hreate ni n g 
• Res ults i n deat h  
• Re q uires i n patie nt h os pitalizati o n (i.e., a d missi o n, o ver ni g ht sta y) or pr ol o n gs e xisti n g 
h os pitalizati o n  
• Res ults i n persiste nt or si g nifica nt disa bilit y/i nca pacit y  
• Is a c o n ge nital a n o mal y/ birt h defect 
A n A E is c o nsi dere d life-t hreate ni n g if, i n t he o pi ni o n of eit her t he I n vesti gat or or t he 
S p o ns or, its occ urre nce places t he partici pa nt at i m me diate ris k of deat h. It d oes n ot i ncl u de 
a n A E t hat, ha d it occ urre d i n a m ore se vere f or m, mi g ht ha ve ca use d deat h. 
I m p orta nt me dical e ve nts t hat are n ot o ne of t he a b o ve ma y be c o nsi dere d t o be S A Es b y t he 
I n vesti gat or w he n, base d u p o n a p pr o priate me dical j u d ge me nt, t he y are c o nsi dere d t o be 
cli nicall y si g nifica nt a n d ma y je o par dize t he partici pa nt or w he n me dical or s ur gical 
i nter ve nti o n ma y be re q uire d t o pre ve nt o ne of t he o utc o mes liste d a b o ve. ( E xa m ples of s uc h 
e ve nts i ncl u de aller gic br o nc h os pas m re q uiri n g i nte nsi ve treat me nt at a n e mer ge nc y r o o m or 
at h o me, bl o o d d yscrasias, c o n v ulsi o ns t hat d o n ot res ult i n i n patie nt h os pitalizati o n, or t he 
de vel o p me nt of dr u g de pe n de nc y or dr u g a b use.) 
8. 8. 2  
Re p orti n g Seri o us A dverse Eve nts  
T o meet t he re q uire me nts f or e x pe dite d re p orti n g of S A Es t hat meet s pecifi c re q uire me nts t o 
a p plica ble re g ulat or y a ut h orities a n d i nstit uti o nal re vie w b oar ds (I R Bs)/ i n de pe n de nt et hics 
c o m mittees (I E Cs)/ researc h et hics b oar ds ( R E Bs), all S A Es m ust be re p orte d t o t he S p o ns or 
wit hi n 2 4 h o urs fr o m t he ti me site pers o n nel first bec o me a ware of t he e ve nt. T his ma y 
i nitiall y be ac hie ve d b y tele p h o ne or b y c o m pleti n g a n S A E re p ort f or m a n d e maili n g t he 
f or m t o t he e mail a d dress, as pr o vi de d o n t he f or m.  

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 4 7  
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
I nitial n otificati o n of a n S A E b y tele p h o ne m ust be c o nfir me d i n writi n g wit hi n 2 4 h o urs 
fr o m t he ti me t he site pers o n nel first bec o me a ware of t he e ve nt usi n g t he S A E re p ort f or m as 
descri be d a b o ve. As f urt her i nf or mati o n re gar di n g t he S A E bec o mes a vaila ble, s uc h 
f oll o w- u p i nf or mati o n s h o ul d be d oc u me nte d o n a ne w S A E re p ort f or m, mar ke d as a 
f oll o w- u p re p ort, sca n ne d, a n d e maile d t o t he a d dress pr o vi de d. 
Wit h dra wal fr o m t he st u d y i n t he e ve nt of a n S A E a n d t he t hera pe utic meas ures t hat are 
ta ke n s hall be at t he discreti o n of t he I n vesti gat or. A f ull e x pla nati o n f or t he disc o nti n uati o n 
fr o m t he st u d y s h o ul d be ma de i n t he e C R F. 
T he re p orti n g of a n y S A Es t o a p plica ble re g ulat or y a ut h orities will be t he res p o nsi bilit y of 
t he S p o ns or i n c o m plia nce wit h a p plica ble c o u ntr y re g ulati o ns. All S A Es m ust be re p orte d t o 
t he I R B/I E C/ R E B b y t he I n vesti gat or i n acc or da nce wit h rele va nt re g ulati o ns. 

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 6 0  
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
1 3  Q U A LI T Y C O N T R O L A N D A S S U R A N C E  
D uri n g t he st u d y, t he S p o ns or a n d/ or re prese ntati ves of t he S p o ns or ma y visit t he site t o 
c o n d uct a n a u dit of t he st u d y. T he p ur p ose of t his visit will be t o deter mi ne t he I n vesti gat or’s 
a d here nce t o t he pr ot oc ol, a p plica ble re g ulati o ns, a n d t he S p o ns or’s pr oce d ures, i n a d diti o n 
t o assessi n g t he acc urac y of t he st u d y data. Pri or t o i nitiati n g t his a u dit, t he I n vesti gat or will 
be c o ntacte d b y t he S p o ns or t o arra n ge a c o n ve nie nt ti me f or t his visit. T he I n vesti gat or a n d 
staff are e x pecte d t o c o o perate wit h t he a u dit ors a n d t o all o w access t o all partici pa nt rec or ds 
s u p p orti n g t he e C R Fs a n d ot her st u d y-relate d d oc u me nts. 
At s o me p oi nt d uri n g t he de vel o p me nt pr o gra m f or t he st u d y dr u g, a re g ulat or y a ut h orit y 
ma y visit t he I n vesti gat or t o c o n d uct a n i ns pecti o n of t he st u d y a n d t he site. T he I n vesti gat or 
a n d staff are e x pecte d t o c o o perate wit h t he i ns pect ors a n d t o all o w access t o a ll s o urce 
d oc u me nts s u p p orti n g t he e C R Fs a n d ot her st u d y relate d d oc u me nts. T he I n vesti gat or m ust 
i m me diatel y n otif y t he S p o ns or w he n c o ntacte d b y a n y re g ulat or y a ut h orit y f or p ur p oses of 
c o n d ucti n g a n i ns pecti o n.  

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 6 1  
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
1 4  A D MI NI S T R A TI V E C O N SI D E R A TI O N S  
1 4. 1  
I nstit uti o n al Re vie w B o ar d, I n de pe n de nt Et hics C o m mittee A p pr o v al, or 
Rese arc h Et hics B o ar d A p pr o v al  
T he I n vesti gat or m ust i nf or m a n d o btai n a p pr o val fr o m t he I R B/I E C/ R E B f or t he c o n d uct of 
t he st u d y at na me d sites, f or t he pr ot oc ol, f or t he partici pa nt I C F a n d a n y other writte n 
i nf or mati o n t hat will be pr o vi de d t o t he partici pa nts, a n d a n y a d vertise me nts t hat will be 
use d. Writte n a p pr o val m ust be o btai ne d pri or t o recr uit me nt of partici pa nts i nt o t he st u d y 
a n d s hi p me nt of i n vesti gati o nal a ge nt.  
Pr o p ose d a me n d me nts t o  t he pr ot oc ol a n d af ore me nti o ne d d oc u me nts m ust be disc usse d 
a m o n g t he S p o ns or a n d c o ntract researc h or ga nizati o n ( C R O) pers o n nel, s u b mitte d t o t he 
I R B/I E C/ R E B f or a p pr o val, a n d t he n s u b mitte d t o re g ulat or y a ut h orities f or a p pr o val pri or t o 
i m ple me ntati o n. A me n d me nts ma y be i m ple me nte d o nl y after a c o p y of t he l ocal 
I R B/I E C/ R E B a p pr o val letter has bee n tra ns mitte d t o t he S p o ns or. A me n d me nts t hat are 
i nte n de d t o eli mi nate a n a p pare nt i m me diate hazar d t o partici pa nts ma y be i m ple me nte d pri or 
t o recei vi n g S p o ns or or I R B/I E C/ R E B a p pr o val. H o we ver, i n t his case, a p pr o val m ust be 
o btai ne d as s o o n as p ossi ble after i m ple me ntati o n.  
T he I n vesti gat or will be res p o nsi ble f or re p orti n g pr ot oc ol de viati o ns t o t he I R B/I E C/ R E B as 
re q uire d b y l ocal re q uire me nts. T he I n vesti gat or will be res p o nsi ble f or e ns uri n g t hat a n 
a n n ual u p date is se nt t o t he I R B/I E C/ R E B t o facilitate c o nti n ui n g re vie w of t he trial (if 
nee de d) a n d t hat t he I R B/I E C/ R E B is i nf or me d a b o ut t he e n d of t he st u d y. C o pies of t he 
u p date, s u bse q ue nt a p pr o vals, a n d fi nal letter m ust be se nt t o t he S p o ns or.  
1 4. 2  
Et hic al C o n d uct of t he St u d y  
T he st u d y will be c o n d ucte d i n acc or da nce wit h t he c urre nt versi o n of t he Declarati o n of 
Helsi n ki, c o ncer ni n g me dical researc h i n h u ma ns. T he st u d y will be c o n d ucte d i n a d here nce 
t o t he st u d y pr ot oc ol a n d G o o d Cli nical Practice ( G C P), as defi ne d i n Title 21 of t he U S 
C o de of Fe deral Re g ulati o ns ( C F R) Parts  5 0, 5 4 5 6, 3 1 2 a n d Part 1 1 a n d i n I nter nati o nal 
C o nfere nce o n Har m o nisati o n (I C H) E 6: G ui deli ne f or G o o d Cli nical Practice C o ns oli date d 
G ui deli nes (I C H -G C P), a n d a p plica ble re g ulat or y re q uire me nts.  
1 4. 3  
P artic i p a nt I nf or m ati o n a n d C o nse nt 
It is t he I n vesti gat or’s res p o nsi bilit y t o o btai n writte n i nf or me d c o nse nt fr o m t he partici pa nt, 
or t he partici pa nt's le gall y a ut h orize d re prese ntati ve, after a de q uate e x pla nati o n of t he 
o bjecti ves, met h o ds, a ntici pate d be nefi ts, a n d p ote ntial hazar ds of t he st u d y a n d bef ore a n y 
st u d y pr oce d ures c o m me nce.  
T he partici pa nt, or t he partici pa nt's le gall y a ut h orize d re prese ntati ve, s h o ul d be gi ve n a c o p y 
of t he I R B/I E C/ R E B -a p pr o ve d I C F i n his/ her nati ve la n g ua ge. T he i nf or me d c o nsent pr ocess 
s h o ul d be rec or de d i n t he s o urce d oc u me ntati o n. T he ori gi nal c o p y of t he si g ne d a n d date d 
I C F m ust be retai ne d i n t he i nstit uti o n’s rec or ds a n d be a vaila ble f or i ns pecti o n b y 

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 6 2  
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
re prese ntati ves of t he S p o ns or or re prese ntati ves fr o m re g ulat or y a ge ncies. T he partici pa nt, 
or t he partici pa nt's le gall y a ut h orize d re prese ntati ve, will be gi ve n a c o p y of t he si g ne d I C F. 
T he partici pa nt, or t he partici pa nt's le gall y a ut h orize d re prese ntati ve, will be i nf or me d t hat 
he/s he ca n freel y wit h dra w c o nse nt a n d st o p partici pati o n i n t he st u d y at a n y ti me wit h n o 
prej u dice t o f urt her treat me nt. It is t he partici pa nt’s, or t he partici pa nt's le gall y a ut h orize d 
re prese ntati ve res p o nsi bilit y t o c o m m u nicate t his decisi o n t o t he I n vesti gat or. 
1 4. 4  
P artici p a nt C o nfi de nti alit y  
T h e I n vesti gat or m ust e ns ure t hat t he partici pa nt’s pri vac y is mai ntai ne d. O n t he e C R F a n d 
ot her d oc u me nts t hat are s u b mitte d t o t he S p o ns or, partici pa nts will be i de ntifie d b y a 
partici pa nt st u d y n u m ber o nl y. D oc u me nts t hat are n ot s u b mitte d t o t he S p o ns or (e. g., si g ne d 
I C F) s h o ul d be ke pt i n a strictl y c o nfi de ntial file b y t he I n vesti gat or.  
T he I n vesti gat or s hall per mit a ut h orize d re prese ntati ves of t he S p o ns or, re g ulat or y a ge ncies, 
a n d I R Bs/I E Cs/ R E Bs t o re vie w t he p orti o n of t he partici pa nt’s me dical rec or d t hat is directl y 
relate d t o t he st u d y. As part of t he re q uire d c o nte nt of i nf or me d c o nse nt, t he partici pa nt m ust 
be i nf or me d t hat his/ her rec or ds will be re vie we d i n t his ma n ner.  
A p plica ble data pri vac y la ws a n d re g ulati o ns m ust be a d here d t o. T he I n ves ti gat or a n d t he 
S p o ns or are res p o nsi ble f or e ns uri n g t hat se nsiti ve i nf or mati o n is ha n dle d i n acc or da nce wit h 
l ocal re q uire me nts (e. g., Healt h I ns ura nce P orta bilit y a n d Acc o u nta bilit y Act [ HI P A A], 
Pers o n nel I nf or mati o n Pr otecti o n a n d Electr o nic D oc u me nts A ct [ PI P E D A], Ge neral Data 
Pr otecti o n Re g ulati o n [ G D P R]). A p pr o priate c o nse nt a n d a ut h orizati o ns f or use a n d 
discl os ure a n d/ or tra nsfer (if a p plica ble) of pr otecte d i nf or mati o n m ust be o btai ne d.  
1 4. 5  
St u d y M o nit ori n g  
T he I n vesti gat or m ust all o w t he St u d y M o nit or s t o peri o dicall y re vie w, at m ut uall y 
c o n ve nie nt ti mes, d uri n g t he st u d y a n d after t he st u d y has bee n c o m plete d, all e C R Fs a n d 
office, h os pital, a n d la b orat or y rec or ds t hat s u p p ort t he partici pati o n of eac h partici pa nt i n t he 
st u d y (s o urce data). T he e C R Fs a n d ot her d oc u me ntati o n t hat s u p p ort t he st u d y m ust be ke pt 
u p- t o-date b y t he I n vesti gat or a n d t he researc h staff at t he i n vesti gati ve site. T hese st u d y 
materials m ust be a vaila ble f or re vie w b y t he St u d y M o nit or a n d/ or ot her q ualifie d 
re prese ntati ves of t he S p o ns or, at eac h m o nit ori n g visit. 
It is t he m o nit or’s res p o nsi bilit y t o i ns pect t he e C R Fs at re g ular i nter vals t hr o u g h o ut t he trial 
t o verif y a d here nce t o t he pr ot oc ol; t he c o m plete ness, acc urac y a n d c o nsiste nc y of t he data; 
a n d a d here nce t o G C P g ui de li nes. 
T he I n vesti gat or a grees t o c o o perate wit h t he m o nit or t o e ns ure t hat a n y pr o ble ms detecte d 
d uri n g t he c o urse of t hese m o nit ori n g visits are res ol ve d.  

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3  Oct o ber  2 0 2 0, Pr ot oc ol A me n d me nt 2  
 Pa ge 6 4  
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
1 4. 9  
Fi n a nci al Discl os ure  
F i na ncial Discl os ure state me nts will be ha n dle d i n a se parate a gree me nt a part fr o m t he 
pr ot oc ol, ke pt o n file, a n d s u b mitte d as a p plica ble wit h a n y s u bse q ue nt lice nse a p plicati o n.   
1 4. 1 0  
P u blic ati o n a n d Discl os ure P olic y  
T he data ge nerate d i n t his cli nical st u d y are t he e xcl usi ve pr o pert y of t he S p o ns or a n d are 
c o nfi de ntial. A n y p u blicati o n of t he res ults of t his st u d y m ust be a ut h orize d b y t he S p o ns or. 
T he S p o ns or will ha ve t he o p p ort u nit y t o re vie w a n y p u blicati o ns t hat arise fr o m t he 
I n vesti gat ors bef ore s u b missi o n f or p u blicati o n. A n y s uc h re vie w a n d a p pr o val of 
p u blicati o ns relate d t o t he st u d y s hall be ma de p urs ua nt t o t he pr ocess a gree d bet wee n t he 
parties i n t he site’s cli nical trial a gree me nt wit h S p o ns or. A ut h ors hi p o n a n y p u blicati o n of 
t he res ults fr o m t his st u d y will be base d o n c o ntri b uti o ns t o st u d y desi g n, data ac q uisiti o n a n d 
a nal ysis, a n d i nter pretati o n of res ults.  

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3 Oct o ber 2 0 2 0 2 , Pr ot oc ol A me n d me nt 2 
Pa ge 7 1  
 
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
 
 
Da y 7: pre d ose, 3 h o urs ( ± 6 0 mi n), a n d 2 4 h o urs ( ± 6 0 mi n) p ost d ose  
 
Da y 1 4: pre d ose f or partici pa nts o n st u d y dr u g  
If t he partici pa nt is n o l o n ger bei n g treate d wit h st u d y dr u g, disc o nti n ues t he st u d y earl y, or is n ot treate d wit h st u d y dr u g o n Da y 1 4, a si n gle plas ma sa m ple 
f or P K s h o ul d be ta ke n at t he Da y 1 4/ E o T/ E T Visit if p ossi ble. Act ual P K sa m ple c ollecti o n ti me a n d d osi n g ti me will be rec orde d.  
  
j 
F or partici pa nts o n he m o dial ysis, t he st u d y dr u g will be a d mi nistere d after t he partici pa nt has c o m plete d t he he m o dial ysis.  
 
 

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3 Oct o ber 2 0 2 0 , Pr ot oc ol A me n d me nt 2 
 Pa ge 7 2   
 
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
A P P E N DI X 2. 
B E R LI N D E FI NI TI O N O F A R D S  
 
A R D S  
Ti mi n g  
Wit hi n 1 wee k of a k n o w n cli nical i ns ult or ne w or w orse ni n g res pirat or y 
s y m pt o ms 
C hest i ma gi n g a 
Bilateral o pacities – n ot f ull y e x plai ne d b y eff usi o ns, l o bar/l u n g c olla pse, or 
n o d ules  
Ori gi n of e de ma  
Res pirat or y fail ure n ot f ull y e x plai ne d b y car diac fail ure or fl ui d o verl oa d  
Nee d o bjecti ve assess me nt (e. g., ec h ocar di o gra p h y) t o e xcl u de h y dr ostatic 
e de ma if n o ris k fact or prese nt  
O x y ge nati o n b 
 
Mil d  
2 0 0 m m H g < Pa O 2/ Fi O2 ≤ 3 0 0 m m H g wit h P E E P or C P A P ≥5 c m H 2O c 
 
M o derate  
1 0 0 m m H g < Pa O 2/ Fi O2 ≤ 2 0 0 m m H g wit h P E E P ≥5 c m H 2O 
 
Se vere  
Pa O 2/ Fi O2 ≤ 1 0 0 m m H g wit h P E E P ≥ 5 c m H 2O 
C P A P = c o nti n u o us p ositi ve air wa y press ure; Fi O 2 = fracti o n of i ns pire d o x y ge n; Pa O 2 = partial press ure of 
arterial o x y ge n; P E E P = p ositi ve e n d -e x pirat or y press ure.  
a 
C hest ra di o gra p h or C T sca n  
b 
If altit u de is hi g her t ha n 1 0 0 0 m, t he c orrecti o n fact or s h o ul d be calc ulate d as foll o ws:  
[ Pa O2/ Fi O2 × ( bar o metric press ure/ 7 6 0)]  
c 
T his ma y be deli vere d n o ni n vasi vel y i n t he mil d A R D S gr o u p  
S o urce: 
 
 

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3 Oct o ber 2 0 2 0 , Pr ot oc ol A me n d me nt 2 
 Pa ge 7 3   
 
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
A P P E N DI X 3. 
V E N TI L A TI O N P R O T O C O L A N D F L UI D M A N A G E M E N T 
P R O T O C O L  
M ay be m o difie d per l oc al i nstit uti o n al st a n d ar ds 
A R D S Ve ntil ati o n Pr ot oc ol (
) 
L o w ti dal v ol u me ve ntilati o n i n patie nts wit h ac ute res pirat or y distress s y n dr o me  
I nitial Ve ntilat or Setti n gs 
Calc ulate pre dicte d b o d y wei g ht ( P B W) 
Male = 5 0 + 2. 3 [ hei g ht (i nc hes) – 6 0] or 5 0 + 0. 9 1 [ hei g ht (c m) – 1 5 2. 4] 
Fe male = 4 5. 5 + 2. 3 [ hei g ht (i nc hes) – 6 0] or 4 5. 5 0. 9 1 [ hei g ht (c m) – 1 5 2. 4] 
Set m o de t o v ol u me assista nt -c o ntr ol 
Set i nitial ti dal v ol u me t o 6 m L/ k g P B W  
Set i nitial ve ntilat or rate ≤ 3 5 breat hs/ mi n t o matc h baseli ne mi n ute ve ntilati o n  
S u bse q ue nt ti dal v ol u me a dj ust me nt 
Platea u press ure g oal: P plat ≤ 3 0 c m H 2O 
C hec k i ns pirat or y platea u press ure wit h 0. 5 sec o n d i ns pirat or y pa use at least e ver y 4 h o urs 
a n d after eac h c ha n ge i n P E E P or ti dal v ol u me 
If P plat > 3 0 c m H 2O, decrease ti dal v ol u me i n 1 m L/ k g P D W ste ps t o 5 or if 
necessar y t o 4 m L/ k g P W B  
If P plat < 2 5 c m H2O a n d ti dal v ol u me < 6 m L/ k g, i ncrease ti dal v ol u me b y 1 m L/ k g 
P B W u ntil P plat > 2 5 c m H 2O or t i dal v ol u me = 6 m L/ k g 
If breat h stac ki n g ( A ut o P E E P) or se vere d ys p nea occ urs, ti dal v ol u me ma y be 
i ncrease d t o 7 or 8 m L/ k g P D W if P plat re mai ns ≤ 3 0 c m H2O 
Arterial O x y ge nati o n a n d P E E P 
O x y ge nati o n g oal: Pa O 2 5 5 t o 8 0 m m H g or S p O2 8 8 % t o 9 5 % 
Use t hese Fi O 2/ P E E P c o m bi nati o ns t o ac hie ve o x y ge nati o n g oal: 
Fi O 2 
0. 3  
0. 4  
0. 5  
0. 6  
0. 7  
0. 8  
0. 9  
1. 0  
P E E P 
5 
5 t o 8  
8 t o 1 0  
1 0  
1 0 t o 1 4  
1 4  
1 4 t o 1 8  
1 8 t o 2 4  
P E E P s h o ul d be a p plie d starti n g wit h t he mi ni m u m val ue f or a gi ve n Fi O 2 
P plat: platea u press ure. Pa O 2: arterial o x y ge n te nsi o n. S p O2: o x y he m o gl o bi n sat urati o n. P E E P: p ositi ve e n d-
e x pirat or y press ure. Fi O 2: fracti o n of i ns pire d o x y ge n. 
A da pte d fr o m 
. 

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3 Oct o ber 2 0 2 0 , Pr ot oc ol A me n d me nt 2 
 Pa ge 7 4   
 
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
Fl ui d M a n a ge me nt Pr ot oc ol: F A C T T -Lite (
) 
Ce ntr al Ve n o us 
Press u re 
( Rec o m me n de d) 
P ul m o n ar y 
Arter y 
Occl usi o n 
Press u re 
( O pti o n al) 
Me a n Arteri al Press ure ≥ 6 0 m m H g  
a n d Off V as o press ors ≥ 1 2 h o urs  
Uri ne o ut p ut < 0. 5 m L/ k g/ h  
Uri ne o ut p ut ≥ 0. 5  m L/ k g/ h  
> 8  
> 1 2  
F ur ose mi de a; reassess i n 1 h 
F ur ose mi de a; reassess i n 4 h 
4 – 8 
8 – 1 2  
Gi ve fl ui d b ol us; reassess i n 1 h  
F ur ose mi de a; reassess i n 4 h 
< 4  
< 8  
Gi ve fl ui d b ol us; reassess i n 1 h  N o i nter ve nti o n; reassess i n 4 h  
 
Rec o m me n de d f ur ose mi de d osi n g = be gi n wit h 2 0 m g b ol us or 3 m g/ h i nf usi o n or last k n o w n effecti ve 
d ose. D o u ble eac h s u bse q ue nt d ose u ntil g oal ac hie ve d ( oli g uria re versal or i ntra vasc ular press ure ta r get) or 
ma xi m u m i nf usi o n rate of 2 4 m g/ h or 1 6 0 m g b ol us reac he d. D o n ot e xcee d 6 2 0 m g/ d. Als o, if patie nt has 
heart fail ure, c o nsi der treat me nt wit h d o b uta mi ne.  
 
I nitiate t his pr ot oc ol wit hi n 4 h o urs of ra n d o mizati o n i n e nr olle d partici pa nts a n d c o nti n ue 
u ntil u nassiste d breat hi n g or st u d y Da y 1 4, w hic he ver occ urs first. 
Pr ot oc ol Meta -r ules: 
1.  Disc o nti n ue mai nte na nce fl ui ds  
2.  C o nti n ue me dicati o ns a n d n utriti o n 
3.  Ma na ge electr ol ytes a n d bl o o d pr o d ucts per us ual practice  
4.  F or s h oc k, use a n y c o m bi nati o n of fl ui d b ol uses (rec o m me n de d fl ui d b ol us = 1 5 m L/ k g 
cr ystall oi d [r o u n d t o nearest 2 5 0 m L] or 1 u nit pac ke d re d cells or 2 5 g al b u mi n) a n d 
vas o press or(s) t o ac hie ve mea n arterial press ure ≥ 6 0 m m H g as fast as p ossi ble. Wea n 
vas o press ors as q uic kl y as t olerate d be gi n ni n g 4 h o urs after bl o o d press ure has sta bilize d  
5.  Wit h h ol d di uretic t hera p y i n re nal fail ure ( defi ne d as dial ysis de pe n de nce, oli g uria wit h 
ser u m creati ni ne > 3 m g/ d L, or oli g uria wit h ser u m creati ni ne 0 – 3 wit h ur i nar y i n dices 
i n dicati ve of ac ute ki d ne y i nj ur y) a n d u ntil 1 2 h o urs after last fl ui d b ol us or vas o press or 
gi ve n 
 
Please refer t o t he f oll o wi n g ta ble f or t he F A C T T C o nser vati ve Fl ui d Ma na ge me nt Pr ot oc ol.  

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3 Oct o ber 2 0 2 0 , Pr ot oc ol A me n d me nt 2 
 Pa ge 7 5   
 
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
S u p ple me nt al T a ble: Fl ui d a n d C at heter Tre at me nt Tri al ( F A C T T) C o nser v ati ve a n d 
Li ber al Fl ui d M a n a ge me nt Pr ot oc ols (
) 
Me as ure d i ntr a v asc ul ar 
press ure ( m m H g)  
M A P 
< 6 0  m m H g 
or a nee d f or 
a n y 
v as o press or  
M A P ≥ 6 0 m m H g wit h o ut v as o press ors  
(e xce pt d o p a mi ne ≤ 5 μ g/ k g/ mi n)  
C V P  
P A O P 
A ver a ge uri n ar y o ut p ut 
< 0. 5  m L/ k g/ h  
A ver a ge uri n ar y o ut p ut 
≥ 0. 5  m L/ k g/ h  
C o nser v ati ve  
Li ber al  
C o nser v ati ve  
Li ber al  
I neffecti ve 
Circ ul ati o n §  
Effecti ve 
Circ ul ati o n #  
I neffecti ve 
Circ ul ati o n §  
Effecti ve 
Circ ul ati o n #  
Ra n ge 1  
vas o press or 
fl ui d b ol us 
K V O I V  
D o b uta mi ne  
F ur ose mi de  
K V O I V  
F ur ose mi de  
K V O I V  
D o b uta mi ne  
F ur ose mi de  
K V O I V  
F ur ose mi de  
> 1 3  
> 1 8  
> 1 8  
> 2 4  
Ra n ge 2  
K V O I V  
D o b uta mi ne  
K V O I V  
F ur ose mi de  
K V O I V  
D o b uta mi ne  
K V O I V  
F ur ose mi de  
9 -1 3  
1 5 -1 8  
1 3 -1 8  
1 9 -2 4  
Ra n ge 3  
fl ui d b ol us 
vas o press or  
Fl ui d b ol us  
Fl ui d b ol us  
Fl ui d b ol us  
Li beral  
K V O I V  
4- 8 
1 0 -1 4  
8- 1 2  
1 4 -1 8  
C o nser vati ve  
F ur ose mi de  
Ra n ge 4  
Fl ui d b ol us  
Fl ui d b ol us  
Fl ui d b ol us  
Li beral  
Fl ui d b ol us  
< 4  
< 1 0  
< 8  
< 1 4  
C o nser vati ve  
K V O I V  
C V P = ce ntral ve n o us press ure; I V = i ntra ve n o us; K V O = kee p vei n o pe n; P A O P = p ul m o nar y arter y occl usi o n 
press ure  
§ I neffecti ve circ ulati o n: Car diac i n de x < 2. 5 L/ mi n/ m 2 or c ol d, m ottle d s ki n wit h ca pillar y -refilli n g ti me 
> 2 sec o n ds 
# Effecti ve circ ulati o n: Car diac i n de x ≥ 2. 5 L/ mi n/ m 2 or a bse nce of criteria f or i neffecti ve circ ulati o n  

P L N- 7 4 8 0 9 -A R D S -2 0 4, 2 3 Oct o ber 2 0 2 0 , Pr ot oc ol A me n d me nt 2 
 Pa ge 7 9   
 
Pr o prietar y a n d C o nfi de ntial  
 
Plia nt T hera pe utics, I nc.  
A P P E N DI X 7. 
I N V E S TI G A T O R SI G N A T U R E 
St u d y Title:  
A ra n d o mize d, d o u ble -bli n d, d ose -ra n gi n g, place b o-c o ntr olle d, P hase 2a 
e val uati o n of t he safet y, t olera bilit y, a n d p har mac o ki netics of P L N -
7 4 8 0 9 i n partici pa nts wit h ac ute res pirat or y distress s y n dr o me ( A R D S) 
ass ociate d wit h at least se v ere C O VI D -1 9 (I N T E G RI S -A R D S)  
St u d y N u m ber:  
P L N -7 4 8 0 9 -A R D S -2 0 4  
Fi nal Date:  
2 3 Oct o ber 2 0 2 0  
 
 
 
 
I ha ve rea d t he pr ot oc ol descri be d a b o ve. I a gree t o c o m pl y wit h all a p plica ble re g ulati o ns 
a n d t o c o n d uct t he st u d y as descri be d i n t he pr ot oc ol.  
 
 
Si g ne d:  
 
 
Date:    
 
 
Na me:     
  
  
  
  
  
 
 
Affiliati o n:   
  
  
  
  
  
 
 
Site N u m ber: