Randomized, Multi-arm Phase II Trial of Novel Agents for Treatment of High-risk COVID-19 Positive Patients
Phase: PHASE2
Conditions: COVID, Sars-CoV2
Sponsor: Susanne Arnold

Study Protocol and Statistical Analysis Plan 
 
 Study Title: Novel Agents for Treatment of High-risk COVID-19 Positive Patients  
Institution/Site:  
University of Kentucky 
Document (Approval/Update) Date: 
8/28/2020 
NCT Number: 
NCT04374019 
IRB Number 
58944 
Coversheet created: 
1/12/2022 
 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n, 
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
A me n d me nt 4 A u g us t 2 8, 2 0 2 0  
i 
M C C Pr ot oc ol #:  
M C C - 2 0-C O VI D - 0 1-P M C  
Cli n ic al Tri als. g o v I de ntifier:  N C T 0 4 3 7 4 0 1 9 3 
TI T L E:    M ulti -ar m p hase II trial f or i nitial assess me nt of n o vel a ge nts f or treat me nt of 
hi g h- ris k C O VI D 1 9 p ositi ve patie nts  
R O L E  
N A M E  
D E P A R T M E N T/ DI VI SI O N  
Pri nci p al 
I n vesti g at ors 
S usa n ne Ar n ol d, M D  
Mar ke y Ca ncer Ce nter, De part me nt of 
I nter nal Me dici ne, Me dical O nc ol o g y 
Ja mes Zac har y  P orterfiel d, M D, P h D   De part me nt of I nter nal Me dici ne, 
Di visi o n of I nfecti o us Diseases 
Jill K olesar, P har m D 
Mar ke y Ca ncer Ce nter, C o -Lea der D T 
Pr o gra m, a n d Pr ofess or, C olle ge of 
P har mac y  
Zi n M yi nt, M D  
Mar ke y Ca ncer Ce nter, De part me nt of 
I nter nal Me dici ne, Me dical O nc ol o g y 
Hei di Weiss, P h D  
Mar ke y Ca ncer Ce nter a n d 
Bi ostatistics a n d Bi oi nf or matics 
S hare d Res o urce Facilit y ( B B S R F), 
De part me nt of I nter nal Me dici ne  
D o n gli n Ya n, P h D  
Mar ke y Ca ncer Ce nter B B S R F, 
De part me nt of I nter nal Me dici ne  
T herese B oc kla ge, M D  
Mar ke y Ca nce r Ce nter Bi os peci me n 
Pr oc ure me nt a n d Tra nslati o nal 
Pat h ol o g y S R F, De part me nt of 
Pat h ol o g y a n d La b orat or y Me dici ne  
Elija h Ka ka ni, M D  
De part me nt of I nter nal Me dici ne, 
Di visi o n of H os pital Me dici ne  
Jare d Ha m mill, P h D 
C olle ge of P har mac y  
Fra n k R o ma nelli, P har m D  
C olle ge of P har mac y  
Alice T h or nt o n, M D  
De part me nt of I nter nal Me dici ne, 
Di visi o n of I nfecti o us Diseases  
Sc ott Berr y, P h D  
C olle ge of E n gi neeri n g, De part me nt 
of Mec ha nical E n gi neeri n g  
Aar o n Hessels o n, M D  
De part me nt of I nter nal Me dici ne, 
Di visi o n of Car di ol o g y  
Pra dee p  Yarra, M D  
De part me nt of I nter nal Me dici ne, 
Di visi o n of H os pital Me dici ne  
C olla b orat ors: 
Re becca D utc h, P h D  
I nteri m C hair, De part me nt of M olec ular 
& Cell ular Bi oc he mistr y  
P hil Ker n, M D  
De part me nt of I nter nal Me dici ne , 
E n d ocri n ol o g y a n d Ass ociate Pr o v ost f or 
Cli nical a n d Tra nslati o nal Scie nces  
Direct or, Ce nter f or Cli nical a n d 
Tra nslati o nal Scie nces  

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
ii 
 
 
I n vesti g ati o n al A ge nt(s):  I ver mecti n, ge neric; Ca m ostat  Mesilate ; Arte misia a n n ua, Artes u nate  
 
F u n di n g S o urce:  U ni versit y of Ke nt uc k y C olle ge of Me dici ne 
 
F D A I N D St at us: Ca m ostat Mesilate , I ver mecti n, Arte misia a n n ua, Artes u nate , I N D # 1 5 0 1 0 3  
 
Pr ot oc ol T y pe / Versi o n # / Versi o n D ate:   A me n d me nt / Versi o n 4 / A u g ust 2 8, 2 0 2 0  
  
   
 
C o ns ulta nts  
R o bert Di Pa ola, M D  
Dea n, C olle ge of Me dici ne  
R. Ki p G u y, P h D  
Dea n, C olle ge of P har mac y  
Vi ve k Ra n g ne kar, P h D  
Ass oci at e Dir ect or, M ar k e y C a ncer 
C e nt er a n d Pr ofess or of R a diati o n  
M e dici n e  

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
iii 
 
S U M M A R Y O F C H A N G E S  
M C C- 2 0 -C O VI D -P M C  
Pr ot oc ol: Re visi o n, v 4 
Versi o n Date: 1 8 A U G U S T 2 0 2 0  
 
# 
Secti o n  
C o m me nts  
1.  
 C o ver 
pa ge 
A d de d ne w a ge nt na me: Artes u nate, u p date date of re visi o n a n d versi o n n u m ber, 
clarifie d title; re vise d I N D stat us of eac h c o m p o u n d  
2.  
 
Sc he ma  U p date d fi g ure 
3.  
 T O C  
U p date d ta ble of c o nte nts 
4.  
 1. 1  
U p date d pri mar y  e n d p oi nt t o re m o ve refere nce t o h y dr o x yc hl or o q ui ne , clarifie d 
t he pri mar y p ur p ose of t his trial a n d clarifie d t he c ha n ge i n C O VI D- 7-P oi nt scale 
is less t ha n a 2-p oi nt decrease i n sc ore.  
5.  
 2. 4  
Re m o ve d bac k gr o u n d f or h y dr o x yc hl or o q ui ne a n d azit hr o m yci n a n d  u p date d 
secti o n n u m ber f or arte misia a n n ua 
6.  
 2. 5  
A d de d bac k gr o u n d f or artes u nate c o m p o u n d i ncl u di n g cli nical t o xic ol o g y a n d 
p har mac o ki netic e x perie nce  
7.  
 2. 6  
E x pa n de d rati o nale t o i ncl u de use of t he pic k -t he-wi n ne r trial desi g n a n d re m o ve d 
refere nce t o h y dr o x yc hl or o q ui ne a n d azit hr o m yci n  a n d a d de d a fi g ure f or t he 
C O VI D - 7 p oi nt or di nal scale a n d pri mar y e n d p oi nt. 
8.  
 3. 2  
Re m o ve d Q Tc e xcl usi o n a n d re m o ve d refere nce s t o h y dr o x yc hl or o q ui ne a n d 
azit hr o m yci n , as n o ne of t he c o m p o u n ds i n t his trial ha ve Q T pr ol o n gati o n. 
Clarifie d c o nc urre nt use d of C Y P 2 A 6 i n d ucers is e xcl u de d f or b ot h arte misia 
a n n ua a n d artes u nate 
9.  
 4. 9  
Clarifie d t he use of r o uti ne e xa mi nati o n, a d de d Da y 3 -4 a n d Da y 1 0 -1 1 safet y 
assess me nt  
1 0.  
 6. 1  
R e m o ve d refere nce t o h y dr o x yc hl or o q ui ne a n d azit hr o m yci n  t hr o u g h o ut a n d 
re gi me n descri pti o ns, a n d a d de d Re gi me n F artes u nate descri pti o n. 
Clarifie d t hat all ar ms will ha ve safet y r u n -i ns  
C ha n ge d t he  f oll o wi n g se nte nce: 
N O T E: if a patie nt de vel o ps a m y ocar dial i nfarcti o n or d oc u me nte d Q Tc > 5 0 0 
w hi le o n t he 1 4 da ys of dr u g, t he y s h o ul d be i m me diatel y ta ke n off st u d y 
me dicati o n a n d recei ve sta n dar d of care treat me nt per t heir treati n g p h ysicia n.  

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
i v 
 
# 
Secti o n  
C o m me nts  
T o:  
N O T E: if a patie nt de vel o ps a m y ocar dial i nfarcti o n or gra de 3 or 4 car diac 
arr yt h mia or d oc u me nte d Q Tc > 5 0 0 w hile o n t he 1 4 da ys of dr u g, t he y s h o ul d be 
i m me diatel y ta ke n off st u d y me dicati o n a n d recei ve sta n dar d of care treat me nt per 
t heir treati n g p h ysicia n. 
1 1.  
 8. 1  
Re m o ve d refere nce t o h y dr o x yc hl or o q ui ne a n d azit hr o m yci n as well as a d verse 
e ve nts listi n gs f or t hese dr u gs a n d a d de d artes u nate a n d its a d verse e ve nts listi n g  
1 2.  
 9. 1  
Clarifie d t hat less t ha n a 2 p oi nt D E C R E A S E i n C O VI D 7 -P OI N T O R DI N A L 
O U T C O M E S S C A L E  is a p ositi ve res ult a n d clarifie d t hat c o m paris o ns bet wee n 
ar ms or wit h a place b o is n ot perf or me d i n t his st u d y desi g n. 
1 3.  
 9. 2  
Clarifie d t he ti me fr o m baseli ne t o i m pr o ve me nt is b ot h Da y 1 4 a n d Da y 2 8  
1 4.  
 9. 3  
Clarifie d t he pri mar y e n d p oi nt a n d g oal of a decrease less t ha n 2 p oi nts i n C O VI D 
7- P OI N T O R DI N A L S C A L E  (cli nical sta bilit y) 
1 5.  
 9. 4  
Re m o ve d all refere nces t o h y dr o x yc hl or o q ui ne a n d azit hr o m yci n a n d clarifie d t he 
ra n d o mizati o n list pr ocess. 
1 6.  
 
9. 5 a n d 
9. 6 
Clarifie d t he defi niti o n of cli nical sta bilit y as a less t ha n 2 p oi nt decrease i n 
C O VI D scale.  
1 7.  
 1 0. 3  
U p date d e x pe dite d A E re p orti n g g ui deli nes  
1 8.  
 1 1  
A d de d p h o ne c o ntacts i n st u d y cale n dar f or Da y 3 or 4 a n d Da y 1 0 or 1 1 a n d 
clarifie d i n-pers o n vers us tele healt h e val uati o ns  
1 9.  
 1 2. 1  
Clarifie d le n gt h of f oll o w-u p  
2 0.  
 
A p p C  
Re m o ve d dr u g diaries f or H y dr o x yc hl or o q ui ne a n d Azit hr o m yci n, c orrecte d 
miss pelli n gs a n d a d de d Dr u g Diar y f or Artes u nate 
 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
v 
 
 
C O M M O N P R O T O C O L A B B R E VI A TI O N S  
 
A b 
A nti b o d y  
A E 
A d v er s e e v e nt  
A g 
A nti g e n  
A L T  
Al a ni n e tr a n s a mi n a s e t e st; al s o “ S G P T”  
A N C  
A b s ol ut e n e utr o p hil c o u nt  
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 A mi n otr a n sf er a s e t e st; al s o “ S G O T”  
A U C  
Ar e a u n d er t h e c ur v e  
BI D 
T wi c e a d a y; al s o, “ b.i. d.” , “ bi d”  
B MI 
B o d y m a s s i n d e x  
B P T P S R F  
Bi o s p e ci m e n Pr o c ur e m e nt a n d Tr a n sl ati o n al P at h ol o g y S h ar e d R e s o ur c e F a cilit y  
C B C  
C o m pl et e bl o o d c o u nt; s o m eti m e s s e e n “ wit h diff”, diff er e nti al  
C C T S  
C e nt er f or Cli ni c al a n d Tr a n sl ati o n al S ci e n c e  
C D C  
U. S. C e nt er s f or Di s e a s e C o ntr ol a n d Pr e v e nti o n  
C D M P  
Cli ni c al D at a M o nit ori n g Pl a n  
C F R  
C o d e of F e d er al R e g ul ati o n s  
c m 
C e nti m et er  
C M P  
C o m pr e h e n si v e m et a b oli c p a n el  
C o -I 
C o -i n v e sti g at or 
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 R  
C o m pl et e r e s p o n s e  
C R N/ C R A  
Cli ni c al r e s e ar c h n ur s e / cli ni c al r e s e ar c h a s s o ci at e  ( st u d y st aff) 
C R O  
M ar k e y’ s Cli ni c al R e s e ar c h Or g a ni z ati o n  
C R S O  
Cli ni c al R e s e ar c h S u p p ort Offi c e, U ni v er sit y of K e nt u c k y H e alt h c ar e  
C T  
C o m p ut e d t o m o gr a p h y  
C Y P  
C yt o c hr o m e P 4 5 0  
C Y P 3 A 4 
C yt o c hr o m e P 4 5 0 i s of or m 3 A 4  
D S M C 
D at a a n d  S af e t y M o nit ori n g C o m mitt e e, M ar k e y C a n c er C e nt er 
D S M P 
D at a a n d S af et y M o nit ori n g Pl a n  
e C R F  
El e ctr o ni c c a s e r e p ort f or m ( al s o C R F, c a s e r e p ort f or m)  
E D C  
El e ctr o ni c d at a c a pt ur e s y st e m  
E K G 
El e ctr o c ar di o gr a m t e st  
F D A  
U. S. F o o d a n d Dr u g A d mi ni str ati o n  
G F R  
Gl o m er ul ar filtr ati o n r at e  
HI P A A 
H e alt h I n s ur a n c e P ort a bilit y a n d A c c o u nt a bilit y A ct  
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 of G ui d eli n e s f or G o o d Cli ni c al Pr a cti c e 
I D E 
I n v e sti g ati o n al D e vi c e E x e m pti o n, p er t h e F D A 
I D S 
I n v e sti g ati o n al Dr u g Ser vi c e at U ni v er sit y of K e nt u c k y  
I H C 
I m m u n o hi st o c h e mi str y 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
vi 
 
S C H E M A  
II T 
I n v e sti g at or-i niti at e d tri al 
I N D 
I n v e sti g ati o n al N e w Dr u g, p er t h e F D A 
I R B 
I n stit uti o n al R e vi e w B o ar d 
I V 
I ntr a v e n o u s dr u g a d mi ni str ati o n  
k g 
Kil o gr a m  
L F T  
Li v er f u n cti o n t e st  
m
2  
S q u ar e m et er  
M A D 
M a xi m u m a d mi ni st er e d d o s e  
M C C  
M ar k e y C a n c er C e nt er  
m c L 
Mi cr olit er  
m g 
Milli gr a m  
m g/ d L  
Milli gr a m s p er d e cilit er  
m g/ k g 
Milli gr a m/ Kil o gr a m  
mi n  
Mi n ut e; al s o “ mi n.”  
ml 
Millilit er  
ml/ mi n  
Millilit er p er mi n ut e  
m m 
Milli m et er  
M T D 
M a xi m u m t ol er at e d d o s e 
N CI  
N ati o n al C a n c er I n stit ut e  
NI H  
N ati o n al I n stit ut e s of H e alt h  
N S AI D 
N o n -st er oi d al a nti -i nfl a m m at or y dr u g 
O S  
O v er all s ur vi v al  
PI 
Pri n ci p al i n v e sti g at or  
P K s 
P h ar m a c o ki n eti c s  
p lt s 
Pl at el et s  
P O 
B y m o ut h , or al a d mi ni str ati o n of dr u g 
P R M C 
Pr ot o c ol R e vi e w a n d M o nit ori n g C o m mitt e e, M ar k e y C a n c er C e nt er  
Q A  
Q u alit y a s s ur a n c e  
Q D  
O n e a d a y; al s o “ q. d.” , “ q d”  
Q T c  
C orr e ct e d Q T i nt er v al, i n E K G s  
R N A  
Ri b o n u cl ei c A ci d  
R N A - S e q 
Ri b o n u cl ei c A ci d s e q u e n ci n g  
S A E 
S eri o u s a d v er s e e v e nt  
S A R S 
S e v er e a c ut e r e s pir at or y s y n dr o m e  
S A R S- C o V -2  S e v er e a c ut e r e s pir at or y s y n dr o m e c or o n a vir u s 2  
S O P 
St a n d ar d o p er ati n g pr o c e d ur e  
S R F  
S h ar e d r e s o ur c e f a cilit y  
TI D  
T hr e e ti m e s a d a y; al s o, “ t.i. d.” , “ti d” 
μ m ol/ L  
Mi cr o m ol e/lit er  
U K  
U ni v er sit y of K e nt u c k y  
U L N  
I n stit uti o n al u p p er li mit of n or m al 
W B C 
W hit e bl o o d c ell s  

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
vii 
 
 
 
     

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
viii  
 
T A B L E O F C O N T E N T S  
 
1.  
O BJ E C TI V E S  ...................................................................................................................... 1 
1. 1  
Pri mar y O bjecti ve  .................................................................................................... 1 
1. 2  
Sec o n dar y O bjecti ves  ............................................................................................... 1 
1. 3  
E x pl orat or y O bjecti ves  ............................................................................................ 1 
2.  
B A C K G R O U N D  ................................................................................................................. 1 
2. 1  
S A R S -C o V - 2 Bac k gr o u n d ....................................................................................... 1 
2. 2  
I vermecti n  ................................................................................................................ 3 
2. 3  
Ca m ostat Mesilate  .................................................................................................... 3 
2. 4  
Arte misia a n n ua  ....................................................................................................... 4 
2. 5  
Artes u nate  ................................................................................................................ 5 
2. 6  
Rati o nale .................................................................................................................. 6 
2. 7  
C orrelati ve St u dies Bac k gr o u n d  .............................................................................. 7 
3.  
P A TI E N T S E L E C TI O N  ...................................................................................................... 8 
3. 1  
Eli gi bilit y Criteria  .................................................................................................... 8 
3. 2  
E xcl usi o n Criteria  .................................................................................................... 9 
3. 3  
I ncl usi o n of W o me n a n d Mi n orities ...................................................................... 1 1 
4.  
I N V E S TI G A T O R R E Q UI R E M E N T S A N D R E GI S T R A TI O N 
P R O C E D U R E S .................................................................................................................. 1 1 
4. 1  
I n vesti gat or a n d Researc h Ass ociate Re gistrati o n wit h M C C ............................... 1 1 
4. 2  
Cli nical Trial Re gistrati o n wit h cli nica ltrials. g o v a n d release of trial res ults ........ 1 1 
4. 3  
E nr oll me nt G ui deli nes  ........................................................................................... 1 1 
4. 4  
Dele gati o n of Tas ks L o g ( D T L) ............................................................................ 1 2  
4. 5  
I nf or me d C o nse nt................................................................................................... 1 2 
4. 6  
Recr uit me nt Pla ns:  ................................................................................................. 1 2 
4. 7  
Patie nt Scree ni n g O pti o ns  ...................................................................................... 1 3 
4. 8  
C o nse nt t o Treat me nt  ............................................................................................. 1 4 
4. 9  
Pati e nt Re gistrati o n t o Treat me nt  .......................................................................... 1 5 
4. 1 0  
Ge neral G ui deli nes ................................................................................................. 1 7  
5.  
BI O M A R K E R, C O R R E L A TI V E, A N D S P E CI A L S T U DI E S  ........................................ 1 7 
5. 1  
S u m mar y Ta ble f or S peci me n C ollecti o n  .............................................................. 1 7 
5. 2  
S peci me n Pr oc ure me nt Kits a n d Sc he d uli n g ......................................................... 1 8  
5. 3  
S peci me n C ollecti o n a n d Pr ocessi n g  ..................................................................... 1 8 
5. 4  
S hi p pi n g/ Dis pe nsi n g of S peci me ns ....................................................................... 2 0  
6.  
T R E A T M E N T P L A N  ........................................................................................................ 2 0 
6. 1  
A ge nt A d mi ni strati o n ............................................................................................. 2 0 
6. 2  
Defi niti o n of D ose- Li miti n g T o xicit y ( D L T) f or p hase I r u n i n p orti o ns of 
t his pr ot oc ol ........................................................................................................... 2 2 
6. 3  
D urati o n of T hera p y ............................................................................................... 2 2  
6. 4  
D ura ti o n of F oll o w-U p  .......................................................................................... 2 3 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
i x 
 
7.  
D O SI N G D E L A Y S/ D O S E M O DI FI C A TI O N S ................................................................ 2 3 
8.  
P H A R M A C E U TI C A L I N F O R M A TI O N  .......................................................................... 2 3 
8. 1  
Dr u g Or deri n g a n d Acc o u nta bilit y ........................................................................ 2 3  
9.  
S T A TI S TI C A L C O N SI D E R A TI O N S ............................................................................... 2 9 
9. 1  
St u d y Desi g n/ E n d p oi nts......................................................................................... 2 9  
9. 2  
Sec o n dar y E n d p oi nts ............................................................................................. 2 9  
9. 3  
Sa m ple  Size/ Accr ual Rate  ...................................................................................... 3 0 
9. 4  
Ra n d o mizati o n/ Stratificati o n Fact ors  .................................................................... 3 1 
9. 5  
Statistical A nal ysis Pla n  ......................................................................................... 3 2 
9. 6  
I nteri m A nal ysis ..................................................................................................... 3 2 
1 0.  
A D V E R S E E V E N T S:  LI S T A N D R E P O R TI N G R E Q UI R E M E N T S  ............................ 3 3 
1 0. 1  
E val uati o n of T o xicit y ........................................................................................... 3 3  
1 0. 2  
A d verse E ve nt C haracteristics  ............................................................................... 3 3 
1 0. 3  
M C C E x pe dite d A d verse E ve nt Re p orti n g G ui deli nes ......................................... 3 4  
1 0. 4  
E xce pti o ns t o A E re p orti n g .................................................................................... 3 6  
1 0. 5  
E x pe dite d Re p orti n g t o E xter nal A ge ncies ............................................................ 3 6  
1 0. 6  
E x pe dite d Re p orti n g t o t he F o o d a n d Dr u g A d mi nistrati o n ( F D A) ...................... 3 6  
1 0. 7  
E x pe dite d Re p orti n g t o H os pital Ris k Ma na ge me nt ............................................. 3 6  
1 0. 8  
R o uti ne A d verse E ve nt Re p orti n g ......................................................................... 3 6  
1 0. 9  
Pre g na nc y ............................................................................................................... 3 7  
1 1.  
S T U D Y C A L E N D A R  ....................................................................................................... 3 8 
1 2.  
M E A S U R E M E N T O F E F F E C T ........................................................................................ 3 9 
1 2. 1  
E val uati o n of Res p o nse .......................................................................................... 3 9  
1 2. 2  
Ot her Res p o nse Para meters  ................................................................................... 3 9 
1 3.  
S T U D Y A P P R O V A L, O V E R SI G H T A N D D A T A R E P O R TI N G / 
R E G U L A T O R Y R E Q UI R E M E N T S ................................................................................. 3 9 
1 3. 1  
Pr ot oc ol Re vie w a n d M o nit ori n g C o m mittee a n d I nstit uti o nal Re vie w 
B oar d Re vie w ......................................................................................................... 3 9  
1 3. 2  
Q ualit y Ass ura nce .................................................................................................. 3 9  
1 3. 3  
Data a n d Safet y M o nit ori n g C o m mittee  ................................................................ 4 0 
1 3. 4  
Data Re p orti n g ....................................................................................................... 4 0  
1 3. 5  
Data Ma na ge me nt  .................................................................................................. 4 1 
1 3. 6  
C o m plia nce wit h La ws a n d Re g ulati o ns................................................................ 4 1  
1 4.  
R E F E R E N C E S  .................................................................................................................. 4 1 
A P P E N DI X A: O B E SI T Y S C A L E  ............................................................................................... 4 6 
A P P E N DI X  B: C O VI D 7 -P OI N T O R DI N A L O U T C O M E S S C A L E .......................................... 4 7 
A P P E N DI X C: PI L L/ Pr o d uct DI A RI E S  ....................................................................................... 4 8 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
x 
 
A P P E N DI X D: Tele healt h Tria ge a n d Dri ve/ T hr o u g h Wal k -i n E nr oll me nt ................................. 6 1 
A P P E N DI X E: Get Well L o o p/ Ce ntralize d C O VI D -1 9 Tele healt h at U K ( C T U) 
Al g orit h m  ........................................................................................................................... 6 2 
A P P E N DI X F: C urr e nt recr uit me nt strate g y a n d Sc he matic f or I nta ke a n d 
C o nse nt f or Researc h at Researc h Desi g nate d Cli nic  ........................................................ 6 3 
A P P E N DI X G: T o xicit y Gra di n g Scales f or Deter mi ni n g Se verit y of A d verse 
E ve nts ................................................................................................................................. 6 5  
A P P E N DI X H: O R D E RI N G I N S T R U C TI O N S F O R A R M E, A R T E MI LI F E 
T E A O R C O F F E E  ............................................................................................................. 7 8 
 
 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 
 
1.  O B J E C TI V E S  
 
1. 1  
Pri m ar y O bjecti ve  
 
T o ra pi dl y e val uate  i nitial efficac y of m ulti ple p ote ntial i n hi bit ors of S A R S -C o V -2 viral 
re plicati o n i n C O VI D 1 9 p ositi ve patie nts wit h hi g h-ris k fact ors i n or der t o decrease cli nical 
deteri orati o n, as defi ne d as a less t ha n a 2- p oi nt de crease fr o m i nitial C O VI D 7 -P OI N T 
O R DI N A L O U T C O M E S S C A L E w it hi n 1 4 da ys fr o m st u d y e ntr y.  
 
1. 2  
Sec o n d ar y O bjecti ves  
 
1. 2. 1  T o assess t he decrease  i n viral l oa d at Da y 1 4. 
1. 2. 2  T o assess t he de vel o p me nt of se vere  res pirat or y or ot her or ga n fail ure i n t he st u d y 
p o p ulati o n   
1. 2. 3  T o assess  pr o gressi o n t o I C U care or ve ntilati o n i n n o n-criticall y ill h os pitalize d patie nts  
a n d o verall st u d y p o p ulati o n 
1. 2. 4  T o assess cleara nce of viral R N A  b y P C R testi n g  at da ys 1, 1 4, 2 8, a n d 4 0 da ys 
1. 2. 5  T o assess m ortalit y, cli nical stat us of s u bject at Da y 1 4, usi n g t he C O VI D 7- p oi nt or di nal 
o utc o mes scale,  a n d rate of se vere a d verse e ve nts defi ne d as gra de 3 n o n he mat ol o gic or 
greater b y D MI D T o xicit y Scale f or Deter mi ni n g Se verit y of A d verse E ve nts  
1. 2. 6  T o assess t he safet y , t olera bilit y a n d c o m plia nce wit h  eac h re gi me n . 
 
1. 3  
E x pl or at or y O bjecti ves 
 
1. 3. 1  
T o o bser ve a n d  rec or d t he i m pact of eac h dr u g c o m bi nati o n o n i nfla m mat or y mar kers 
( pr ocalcit o ni n, D-Di mer , hs-C R P ) a n d t heir p ote ntial pr o g n ostic/ pre dicti ve val ue 
1. 3. 2  
T o deter mi ne t he rate a n d ti mefra me of S A R S -C o V -2 ser oc o n versi o n as a mar ker of 
ac q uire d i m m u nit y via t he p rese nce of C O VI D- 1 9 a nti b o dies i n R N A ne gati ve patie nts 
as a mar ker of ac q uire d i m m u nit y usi n g eit her a ra pi d dia g n ostic test ( R D T) or e nz y me-
li n ke d i m m u n os or be nt assa y ( E LI S A) assa y. 
1. 3. 3  
T o deter mi ne if earl y detecti o n of ele vate d i nfla m mat or y c yt o ki nes are p re dicti ve of 
se vere i nfecti o n or se vere disease .  
1. 3. 4  
T o perf or m p ost- h oc c o variate a dj uste d a nal ysis f or p ote ntial pre-treat me nt, o utc o me-
pr o g n ostic c o variates s uc h as a ge, se x, de gree of ill ness, cli nical c he mistries, a n d ti mi n g 
of o nset of s y m pt o ms relati ve t o st u d y i ncl usi o n. 
1. 3. 5  
T o e val uate t he effect of C O VI D - 1 9 o n platelet f u ncti o n t o assess se vere c oa g ulati o n 
c o m plicati o ns  
1. 3. 6  
T o e val uate viral cleara nce at Da y 1 4, 2 8 a n d 4 0 
 
2.  B A C K G R O U N D  
 
2. 1  
S A R S -C o V - 2 B ac k gr o u n d 
 
C or o na vir us Disease 2 0 1 9 ( C O VI D- 1 9) is a hi g hl y c o nta gi o us disease, ca use d b y a n o vel 
e n vel o pe d R N A beta-c or o na vir us, als o k n o w n as 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). [ 1] T he first case of t his u n prece de nte d o ut brea k “ p ne u m o nia of u n k n o w n 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
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eti ol o g y” was re p orte d i n W u ha n Cit y, H u bei Pr o vi nce, C hi na o n Dece m ber 8 t h, 2 0 1 9 a n d 
re p orte d t o t he W orl d Healt h Or ga nizati o n ( W H O) o n Dece m ber 3 1st, 2 0 1 9. [ 2] W H O declare d a 
C O VI D - 1 9 gl o bal e mer ge nc y o n Ja n uar y 3 0, 2 0 2 0, a n d t he n cate g orize d t he o ut brea k as a 
pa n de mic o n Marc h 1 1, 2 0 2 0. [ 3] As of A pril 2 2, 2 0 2 0, m ore t ha n 2, 6 2 8, 8 9 4 c o nfir me d cases of 
C O VI D - 1 9 w orl d wi de a n d 1 8 2, 7 4 0 pe o ple gl o ball y ha ve die d fr o m C O VI D-1 9 si nce it e mer ge d 
i n C hi na, acc or di n g t o t he data fr o m J o h ns H o p ki ns U ni versit y.  
 
W hile t he maj orit y of patie nts wit h C O VI D - 1 9 de vel o p mil d or u nc o m plicate d ill ness, 
a p pr o xi matel y 2 0- 3 0 % of h os pitalize d patie nts ha ve re q uire d i nte nsi ve care s u p p ort a n d 5 % of 
t h ose ha ve m ulti- or ga n fail ure or s h oc k. T he case fatalit y rate ra n ges fr o m 1 t o 4% a n d it is 
hi g her a m o n g t h ose wit h pre- e xisti n g c o m or bi d c o n diti o ns s uc h as car di o vasc ular disease, 
dia betes mellit us, o besit y, c hr o nic res pirat or y disease, h y perte nsi o n a n d ca ncer. [ 4] T he vast 
maj orit y of patie nts prese nts wit h fe ver ( 8 3 -9 9 % ), c o u g h ( 5 9- 8 2 %), fati g ue ( 4 4- 7 0 %), a n ore xia 
( 4 0-8 4 %), s h ort ness of breat h ( 3 1 - 4 0 %), s p ut u m pr o d ucti o n ( 2 8- 3 3 %), m yal gias ( 1 1- 3 5 %). [ 2, 5-
9] Less t ha n 1 0 % of patie nts will prese nt wit h hea dac he, c o nf usi o n, r hi n orr hea, s ore t hr oat, 
he m o pt ysis, v o miti n g, or diarr hea. [ 2, 5, 6] A n os mia or a ge usia pr ocee di n g t he o nset of 
res pirat or y s y m pt o ms has bee n a nec d otall y re p orte d. [ 1 0]   
 
T he Ce nter f or Disease C o ntr ol a n d Pre ve nti o n ( C D C) fr o m C hi na di vi de d t he cli nical 
ma nifestati o ns of t he disease as bel o w: [ 4] 
 
•  Mil d t o m o derate disease ( 8 1 %): n o n- p ne u m o nia a n d mil d p ne u m o nia  
•  S e vere disease ( 1 4 %): d ys p nea, res pirat or y fre q ue nc y ≥3 0/ mi n, bl o o d o x y ge n sat urati o n 
( S p O 2) ≤ 9 3 %, Pa O 2/ Fi O 2 rati o or P/ F [t he rati o bet wee n t he bl o o d press ure of t he 
o x y ge n ( partial press ure of o x y ge n, Pa O 2) a n d t he perce nta ge of o x y ge n s u p plie d 
(fracti o n of i ns pire d o x y ge n, Fi O 2)] < 3 0 0, a n d/ or l u n g i nfiltrates > 5 0 % wit hi n 2 4 t o 4 8 
h o urs 
•  Critical disease ( 5 %): res pirat or y fail ure, se ptic s h oc k, a n d/ or m ulti ple or ga n d ysf u ncti o n 
or fail ure  
 
T o c o n d uct p o p ulati o n -base d s ur veilla nce f or la b orat or y -c o nfir me d C O VI D - 1 9 –ass ociate d 
h os pitalizati o ns i n t he U S, t he C O VI D- 1 9 – Ass ociate d H os pitalizati o n S ur veilla nce Net w or k 
( C O VI D- N E T) was create d a n d re p orte d earl y data o n h os pitalizati o n rates fr o m Marc h 2 0 2 0.  
T he h os pitalizati o n rate a m o n g patie nts d uri n g t his 4- we e k peri o d was 4. 6 per 1 0 0, 0 0 0 
p o p ulati o n. Rates were hi g hest ( 1 3. 8) a m o n g a d ults a ge d ≥6 5 years. A m o n g a s u bset of t h ose 
a d ults 1 7 8 ( 1 2 %) wit h data o n u n derl yi n g c o n diti o ns, a n d c o nsiste nt wit h re p orts fr o m ot her 
c o u ntries, t he vast maj orit y ( 8 9. 3 %) ha d o ne or m ore u n derl yi n g c o n diti o ns: h y perte nsi o n 
( 4 9. 7 %), o besit y ( 4 8. 3 %), c hr o nic l u n g disease ( 3 4. 6 %), dia betes mellit us ( 2 8. 3 %), a n d 
car di o vasc ular disease ( 2 7. 8 %). T his earl y data fr o m C O VI D -N E T s u g gest t hat C O VI D - 1 9 –
ass ociate d h os pitalizati o ns i n t he U ni te d States ( U S) are hi g hest a m o n g ol der a d ults, a n d nearl y 
9 0 % of pers o ns h os pitalize d ha ve o ne or m ore of t hese u n derl yi n g me dical c o n diti o ns. [ 1 1] 
Gi ve n t hat t hese u n derl yi n g me dical c o n diti o ns are ra m pa nt i n t he state of Ke nt uc k y, a f oc us o n 
pre ve nti n g pr o gressi o n t o h os pitalizati o n a m o n gst t h ose w h o are m ost v ul nera ble t o C O VI D 1 9 
is warra nte d.  
 
A d diti o nall y, t o date, t reat me nts f or C O VI D- 1 9 i n hi g h ris ks i n di vi d uals re mai n e x peri me ntal 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 
 
a n d thera pe utic strate gies t o deal wit h t he i nfecti o n are at best s u p p orti ve, wit h pre ve nti o n ai me d 
at re d uci n g tra ns missi o n i n t he c o m m u nit y a s t he best wea p o n. N o pr o ve n t hera pies ha ve bee n 
de m o nstrate d t o pre ve nt pr o gressi o n of C O VI D- 1 9 t o se vere ill ness  a n d t his is a critical u n met 
nee d f or hi g h ris k i n di vi d uals a n d warra nts st u d y.  Rece ntl y, t he  I nfecti o us Disease S ociet y of 
A merica has ma de  rec o m me n dati o ns f or t he treat me nt of patie nts wit h C O VI D- 1 9, f oc usi n g o n 
i n patie nt care, a n d rec o m me n di n g ra n d o mize d trials w here p ossi ble as t he best ste p t o i m pr o ve 
treat me nt o utc o mes a n d t o i ncrease o ur u n dersta n di n g of t his c or o na vir us pa n de mic.  [ 1 2] 
Disc o veries i n t his area ma y i nf or m cli nicia ns o n effecti ve treat me nt f or  l o w ris k i n di vi d uals w h o 
pr o gress t o se vere ill ness , as well.   
 
2. 2  
Iver mecti n  
 
I ver mecti n is a n F D A a p pr o ve d a nti-parasitic a ge nt t hat als o has acti vit y a gai nst a n u m ber of  
R N A vir uses, i ncl u di n g i nfl ue nza, e q ui ne e nce p halitis a n d West Nile.  I ver mecti n i n hi bits t he 
i nteracti o n bet wee n t he h u ma n i m m u n o deficie nc y vir us-1 ( HI V - 1) i nte grase pr otei n (I N) a n d t he 
i m p orti n (I M P) α/ β 1 heter o di mer res p o nsi ble f or I N n uclear i m p ort. Its br o a d acti vit y a gai nst 
R N A vir uses is t h o u g ht t o be beca use of t he vir us’s relia nce o n I M Pα /Β 1 d uri n g i nfecti o n.  A 
rece nt p u blicati o n t hat e val uates the a nti viral acti vit y of i ver mecti n t o war ds S A R S - C o V- 2, i n 
vitr o a n d de m o nstrates a 9 9. 8 % re d ucti o n in cell -ass ociate d viral R N A  after 2 h o urs. [ 1 3] 
 
T he I C 5 0 f or i ver mecti n vers us Sars -C o V - 2 is 2. 5 u M = 2 1 8 0 u g/ L.[ 1 4] T he A U C of t he 
I ver mecti n i n h u ma ns at t he a p pr o ve d d ose i n ( 2 0 0 mc g/ k g) is 1 1 3 2 u g/ L.  T he c o nce ntrati o ns i n 
l u n g are a ntici pate d t o be 3 x hi g her t ha n plas ma e x p os ure.  [ 1 5] T heref ore we a ntici pate t hat we 
will ac hie ve a de q uate p ul m o nar y c o nce ntrati o ns t o ha ve a nti viral effect.  Gi ve n its safet y pr ofile, 
we will use t he F D A a p pr o ve d d ose of i ver mecti n i n t his trial, as we are c o m bi ni n g it wit h H C Q.  
 
2. 3  
C a m ost at Mesil ate  
 
Rece ntl y, mec ha nistic st u dies ha ve el uci date d t hat a critical ste p f or S A R S -C o V - 2 viral e ntr y is 
t he pri mi n g of t he S A R S- C o V 2 s pi ke pr otei n, w hic h uses t he h u ma n seri ne pr otease T M P R S S 2. 
N ota bl y, c a m ostat mesilate  ( C A M), a p ote nt i n hi bit or of seri ne pr oteases, has bee n s h o w n t o 
bl oc k cell ular viral e ntr y of S A R S- C o V -2 i n pri mar y h u ma n air wa y e pit helial cells. [ 1 6]Ca m ostat 
bl oc k S A R S- C o V - 2 re plicati o n i n T M P R S S 2-e x pressi n g h u ma n cells, wit h a n a p pare nt E C 9 0 of 
3 µ M, a n d si g nifica ntl y lesse ns viral re pli cati o n at t hat le vel.[ 1 7]  Ca m ostat has bee n s h o w n t o 
bl oc k i nfecti o n wit h S A R S- C o V - 1 i n h u ma n cells wit h r o u g hl y e q ui vale nt p ote nc y.[ 1 8]  I n a 
m o use m o del of S A R S- C o V- 1 a d ose of t wice dail y at 3 0 m g/ k g, e q ui vale nt t o a 2 7 5 m g d ose i n 
a 7 0 k g h u ma n, pr o vi di n g a s ur vi val a d va nta ge.[ 1 9]   A d diti o nall y, ca m ostat  has bee n s h o w n t o 
atte n uate air wa y e pit helial s o di u m c ha n nel f u ncti o n a n d e n ha nce m uc ociliar y cleara nce w he n 
ne b ulize d i nt o t he trac hea of c o nsci o us s hee p.  [ 2 0] T his a nal ysis was e xte n de d t o c ystic fi br osis 
patie nts i n a s mall trial w here is was a d mi nistere d via a nasal s pra y p u m p a n d was s h o w n t o 
re d uce s o di u m tra ns p ort i n t he air wa y a n d was well t olerate d, s u g gesti n g t he p ossi bilit y t hat t his 
mi g ht i ncrease cle ara nce of i nfecti o us viri o ns. [ 2 1] Ca m ostat  is a p pr o ve d f or re missi o n of ac ute 
s y m pt o ms of c hr o nic pa ncreatitis a n d p ost - o perati ve es o p ha geal refl u x. A d diti o nall y , ca m ostat 
was a p pr o ve d i n t he U nite d States u n der I N D 1 0 9 0 3 5 f or t he relief of a b d o mi nal pai n ass ociate d 
wit h c hr o nic pa ncreatitis  a n d b y t he F D A f or  use a gai nst S A R S -C o V - 2 i n t his cli nical trial (I N D 
1 5 1 0 3). At t his ti me, t he cli nical i m pact of ca m ostat  o n C O VI D - 1 9 is n ot k n o w n, t h us, we pla n 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 
 
t o e xa mi ne w het her ca m ostat  ca n i m pr o ve patie nt o utc o mes. 
 
Ca m ostat is a p pr o ve d f or c hr o nic pa ncreatitis i n Ja pa n at a dail y d ose of 6 0 0 m g.  We are usi n g 
t he sa me d ose i n t his cli nical trial.  I n a m uri ne e x peri me nt, f oll o wi n g a let hal S A R S- C o V 
i nfecti o n, t he s ur vi val rate of ca m ostat treate d mice was 6 0 %.[ 1 9]  I n t his st u d y, mice were 
treate d at 3 0 m g/ k g f or 9 da ys.  A c orres p o n di n g d ose i n a 7 5 k g h u ma n w o ul d be 2 2 5 0 m g.  
Ca m ostat mes ilate was well t olerate d b y patie nts w he n a d mi nistere d t hree ti mes per da y at a d ose 
of 2 0 0 m g (t otal dail y d ose of 6 0 0 m g), a n d t his is t he a p pr o ve d d ose a n d sc he d ule i n Ja pa n f or 
c hr o nic pa ncreatitis. [ 2 2] Gi ve n t hat we are treati n g o ut patie nts, f or a 1 4- da y d urati o n, we 
a ntici pate  usi n g t he a p pr o ve d d ose i n Ja pa n is a reas o na ble starti n g p oi nt a n d we will c o nsi der a 
d ose escalati o n if t olera ble a n d t here are hi nts of efficac y.  
 
2. 4  
Arte misi a a n n u a  
 
Arte mis ia a n n ua, als o k n o w n as s weet w or m w o o d, is a b ota nical pr o d uct nati ve t o Asia b ut 
gr o ws i n ma n y c o u ntries, i ncl u di n g t he U nite d States. Arte misia  a n n ua has bee n use d f or 
ce nt uries as i nf usi o ns or p o w ders t o treat malaria. Arte misi ni n is e xtracte d fr o m Arte misia  
a n n ua, a n d artes u nate is t he n se mi -s y nt heticall y deri ve d fr o m arte misi ni n.[ 3 8]. Artes u nate is a 
hi g hl y effecti ve treat me nt f or malaria b ut is li mite d b y t he ra pi d de vel o p me nt of resista nce a n d 
m ust be use d i n c o m bi nati o n wit h ot her a nti malarials .[ 3 9]  I ntri g ui n gl y, Arte misia  a nn u a tea, 
w hic h c o ntai ns a mi xt ure of acti ve c o nstit ue nts, i ncl u di n g di h y dr oarte misi nic aci d, arte misi nic 
aci d, a n d arte misi ni n, ma y be m ore effecti ve t ha n artes u nate i n treati n g malaria. A ra n d o mize d, 
place b o -c o ntr olle d cli nical trial e nr olli n g 9 5 7 patie nt s wit h malaria c o m pare d Arte misia  a n n ua 
tea t o artes u nate-a m o dia q ui ne t hera p y. Patie nts were ra n d o mize d t o recei ve eit her artes u nate -
a m o dia q ui ne ta blets or Arte misia  a n n ua tea wit h 1. 6 g of t wi gs a n d lea ves / 0. 3 3 L e ver y 8 h o urs 
f or 7 da ys. Tea was pre pare d b y a d di n g 5 g of Arte misia  a n n ua drie d lea ves a n d t wi gs t o 1 liter 
of b oili n g water. T he pri mar y e n d p oi nt of t his trial was t he malaria c ure rate, wit h t he Arte misia  
a n n ua c ure rate of 9 6. 4 % at 2 8 da ys c o m pare d t o o nl y 3 4. 3 % i n t he artes u nate-a m o dia q ui ne ar m. 
[ 4 0]  Arte misia  a n n ua tea was als o well-t olerate d, wit h 5 % of s u bjects e x perie nci ng na usea or 
v o miti n g, alt h o u g h n o ne se vere e n o u g h t o disc o nti n ue t hera p y a n d n o ot her a d verse effects 
re p orte d. I n c o ntrast, 4 2. 8 % of patie nts i n t he artes u nate-a m o dia q ui ne ar m re p orte d a d verse 
effects, i ncl u di n g na usea, ast he nia, pr urit us, h y p o gl yce mia, a n d verti g o.   
 
T he a nti viral acti vit y of Arte misia  a n n ua a n d p ure Arte misi ni n a n n ua was teste d b y pretreati n g 
Ver o E 6 l u n g cells i nfecte d wit h S A R S- C o V - 2 o ver 1 2 0 mi n utes at a c o nce ntrati o n of 1 3 0 
pla q ue f or mi n g u nites per well. A q ue o us a n d et ha n olic e xtracts of Arte misi ni n a n n ua , a n d 
arte misi ni n c o nce ntrati o ns ra n gi n g fr o m 0- 2. 5 u g/ m L were i nc u bate d wit h vir us i nfecte d cells f o r 
1 5, 3 0, 6 0 a n d 1 2 0 mi n utes.  B ot h t he a q ue o us a n d et ha n olic e xtracts s h o we d s u bsta ntial acti vit y, 
a n d were a ble t o i n hi bit a p pr o xi matel y 5 0 % of viral re plicati o n at c o nce ntrati o ns of 1. 5 u g/ m L.  
B y c o m paris o n, p ure Arte misi ni n was n ot a ble t o i n hi bit t he vir us b y 5 0 % a n d n o E C 5 0 was a ble 
t o be calc ulate d.  T heref ore, t he e xtracts were a d va nce d f or f urt her cli nical testi n g.[ 4 1]  
T he d ose f or t his st u d y is base d o n e x perie nce wit h malaria, w here c hil dre n as y o u n g as 5 years 
of a ge recei ve d a d ose of tea ( 1. 6 g/ 0. 3 3 L) e ver y 8 h o urs f or 7 da ys wit h t he o nl y re p orte d 
a d verse effect t o be mil d na usea a n d v o miti n g.  N ota bl y, 1. 6 g of t wi gs a n d lea ves as use d i n t he 
malaria st u d y c orres p o n ds t o 2 2 1 m g of leaf al o ne.[ 4 2] W hile t here is a pa ucit y of e x perie nce 
wit h h u ma n p har mac o ki netic st u dies i n patie nts recei vi n g Arte misia  a n n ua tea,[ 4 0] i n rats, 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 
 
recei vi n g t he sa me d ose, t he c o nce ntrati o n of t he acti ve c o nstit ue nt, Arte misi ni n was 1 0 u g/ m L 
i n ser u m, a n d 5 u g/ m L i n t he l u n g after a si n gle d ose[ 4 3]   T he Arte misia  a n n ua decaf c offee 
p o ds a n d tea ba gs use d i n t his st u d y are c o m merciall y a vaila ble b ota nical pr o d ucts a n d s u p plie d 
b y Arte mi Life I nc. ( htt ps://arte milife.c o m/ h o me). Arte misia  a n n ua decaf c offee p o ds c o ntai n 4 5 0 
m g Arte misia  a n n ua leaf, a n d tea ba gs c o ntai n 2 2 5 m g Arte misia  a n n ua leaf.  T heref ore, we 
a ntici pate a de q uate c o nce ntrati o ns t o ac hie ve a nti viral acti vit y w hile mai ntai ni n g e xcelle nt 
t olera bilit y.  T he decaf c offee p o ds a n d tea ba gs c o ntai n F D A f o o d- gra de q ualit y i n gre die nts. 
Arte misia  a n n ua pla nts f or Ar te mi Life c offee a n d tea are gr o w n i n Ke nt uc k y. Arte mi Life c offee 
p o ds a n d tea ba gs are pr o d uce d a n d ma n ufact ure d i n t he U nite d States. 
 
2. 5  
Artes u n ate  
 
Arte misi ni n is e xtracte d fr o m Aa a n d artes u nate is t he n se mi -s y nt heticall y deri ve d fr o m 
arte misi ni n.[ 3 9] [ 4] .  Artes u nate is a hi g hl y effecti ve treat me nt f or malaria, b ut w hile hi g hl y 
effecti ve, artes u nate is li mite d b y t he ra pi d de vel o p me nt of resista nce a n d m ust be use d i n 
c o m bi nati o n wit h ot her a nti malarials.[ 4 0] [ 5]. T he us ual d ose of artes u nate i n a d ults f o r malaria 
is 2 0 0 m g o nce a da y f or 7 da ys a n d has bee n use d i n ca ncer st u dies at a d ose of 2 0 0 m g a da y 
f or u p t o 3 7 m o nt hs.[ 4 2]  T heref ore, i n t his st u d y we will a d mi nister 2 0 0 m g orall y dail y f or a 
t otal of 1 4 da ys.   
 
I n  a  ra n d o mize d  efficac y  a n d  safet y  trial  c o m pari n g  t w o  artes u nate  c o m bi nati o n  t hera pies, 
artes u nate  +  a m o dia q ui ne  ( A S A Q)  a n d  arte met her  +  l u mefa ntri ne  ( A L),  i n  c hil dre n  wit h  
u nc o m plicate d malaria, 2 2 7 s u bjects wit h a n a ge ra n ge of 6 m o nt hs t o 1 4 years were f oll o we d f or 
2 8 da ys after treat me nt, t he n m o nt hl y f or a year. [ 4 4] T he A S A Q gr o u p was treate d o nce dail y wit h 
1 0 m g / k g b o d y A Q a n d 4 m g/ k g A S f or 3 da ys. T he A L gr o u p was a d mi nistere d a si n gle d ose of 
2 0 m g arte met her a n d 1 2 0 m g l u mefa ntri ne o n t he first da y, t he n t w o d oses o n da y 2 a n d 3, wit h 
d osi n g at o ne ta blet/ d ose f or b o d y wei g ht of 5 -1 4 k g, t w o ta blets/ d ose f or b o d y wei g ht of 1 5 - 2 4 
k g, t hree ta blets/ d ose f or b o d y wei g ht of 2 5 -3 4 k g, or f o ur ta blets/ d ose wit h a b o d y wei g ht 3 5 k g 
or greater. B ot h A S A Q a n d A L were hi g hl y effecti ve wit h a de q uate cli nical a n d parasit ol o gical 
res p o nse rates of 9 7. 1 % a n d 9 8. 2 % at da y 1 4 f or t he A L a n d A S A Q gr o u ps, res pecti vel y. B ot h 
artes u nate c o m bi nati o n t hera pies were well t olerate d, wit h mil d na usea a n d v o miti n g t he m ost 
c o m m o n a d verse effects , wit h 2 7. 5 % a n d 1 2. 6 % of s u bjects re p orti n g eac h, res pecti vel y.[ 4 4]  
 
P har mac o ki netics of artes u nate was c o m plete d i n a m ultice nter trial wit h 4 7 2 Africa n pe diatric 
s u bjects wit h u nc o m plicate d malaria. One or t w o fi xe d -d ose ta blets of artes u nate - mefl o q ui ne ( 2 5 
m g/ 5 5 m g) were c o ns u me d dail y f or t hree da ys. D osi n g was base d o n a ge. S u bjects bet wee n 6 t o 
1 1  m o nt hs  were  a d mi nistere d  o ne  ta blet  dail y,  a n d  s u bjects  bet wee n  1 2  t o  5 9  m o nt hs  were 
a d mi nistere d t w o ta blets dail y. Bl o o d dra ws were c o m plete d o n 5 0 s u bjects f or P K a nal ysis. Bl o o d 
dra ws were perf or me d at re g ular i nter vals, i ncl u di n g pre d ose t o 6 hrs after first d ose, pre d ose t o 6 
hrs after t hir d d ose, 7 2 hrs after first d ose, o n da y 7, a n d o n o ne da y bet wee n da y 2 8 a n d da y 6 3. 
F or artes u nate t he A U C 0- 2 4, d a y 0 was 0. 3 4  n g/ L/ h, a n d t he  A U C 0- 2 4, da y 2 was 0. 2 3 n g/ L/ h. T he C ma x 
was 0. 5 2 n m ol/ m L, a n d t he ter mi nal half -life was 4 0 mi n. F or D H A, t he A U C 0- 2 4, da y 0 was 3. 3 0  
n g/ L/ h, a n d t he  A U C 0- 2 4, da y 2 was 2. 2 0 n g/ L/ h. T he C ma x was  3. 9 n m ol/ m L f or D H A, a n d t he 
ter mi nal half-life was 4 0 mi n [ 4 5]. 
 
Artes u nate has bee n re p orte d t o be well t olerate d i n c hil dre n wit h malaria. A ra n d o mize d efficac y 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
6 
 
a n d safet y trial c o m pari n g  artes u nate + a m o dia q ui ne  a n d arte met her + l u mefa ntri ne ( A L) was 
c o n d ucte d i n 2 2 7 s u bjects wit h malaria wit h a n a ge ra n ge of 6 m o nt hs t o 1 4 years. A d verse e ve nts 
were re p orte d t o be si milar bet wee n t he treat me nt gr o u ps. B ot h artes u nate c o m bi nati o n t hera pies 
were well t olerate d, wit h mil d na usea a n d v o miti n g t he m ost c o m m o n a d verse effects, wit h 2 7. 5 % 
a n d 1 2. 6 % of s u bjects re p orti n g eac h, res pecti vel y . H o we ver, a hi g her perce nta ge of s u bjects 
re p orte d na usea ( 4 0. 5 %) a n d v o miti n g ( 4 4. 8 %) bef ore be gi n ni n g treat me nt. 4. 3 % of s u bjects i n 
A S A Q gr o u p a n d 3. 6 % of s u bjects i n t he A L gr o u p  re p orte d fati g ue a n d e xcessi ve slee pi ness. 
Pr urit us was re p orte d f or 3 patie nts i n t he st u d y. 1 2 % of s u bjects i n t he A S A Q gr o u p a n d 8 % i n 
t he  A L  gr o u p  re p orte d  dizzi ness  a n d  se vere  a ne mia  was  re p orte d  i n  o ne  s u bject;  h o we ver,  
i n vesti gat ors deter mi ne d t hat b ot h s y m pt o ms were li kel y u nrelate d t o treat me nt. [ 4 4]  
 
A n ot her m ultice nter, ra n d o mize d st u d y c o m pare d fi xe d d ose artes u nate + a m o dia q ui ne o nce dail y 
( A S A Q 1) or t wice dail y (A S A Q 2 ) wit h arte met her + l u mefa ntri ne  ( A L) i n 9 4 1 patie nts wit h 
u nc o m plicate d malaria. T he mea n a ge f or t he A S A Q 1 gr o u p was 9. 5 years ( S D - 1 0. 8), f or t he 
A S A Q 2 gr o u p was 9. 1 years ( S D - 9. 8), a n d f or t he A L gr o u p was 9. 4 years ( S D - 1 0. 7). 2 9. 3 % of 
patie nts ha d at least o ne a d verse e ve nt, 2 0. 4 % were t h o u g ht t o be relate d t o treat me nt. M ost a d verse 
e ve nts ( 8 8. 5 %) were  c o nsi dere d  mil d  or  m o derate,  wit h  2 4. 4 %  e x perie nci n g  i ns o m nia  or  
s o m n ole nce a n d 1 6. 7 % gastr oi ntesti nal s y m pt o ms, wit h 1 3 % of s u bjects re p orte d t o ha ve v o miti n g 
wit hi n 3 0 mi n utes of treat me nt. 7 patie nts were re p o rte d t o ha ve a ne mia, wit h o ne patie nt re q uiri n g 
h os pitalizati o n b ut ulti matel y rec o vere d. T w o s u bjects die d d uri n g t he st u d y, b ut t he deat hs were 
n ot attri b ute d t o t he treat me nt. [ 4 6]  
 
2. 6  
R ati o n ale 
 
We pr o p ose t he use of a m ulti- ar m, p hase II “ pic k -t he-wi n ner” trial desi g n t o  all o w i nitial 
assess me nt of m ulti ple t hera pies i n parallel a n d selecti o n of pr o misi n g t hera pies wit h a de q uate 
pr o ba bilities after C O VI D 1 9 + testi n g  i n hi g h ris k, b ut n o n-criticall y ill i n di vi d uals. [ 4 7] Pri or t o 
m o vi n g a pr o misi n g t hera pe utic a ge nt f or war d i nt o lar ge ra n d o mize d trials of t his t hera p y vers us 
place b o, i n vesti gat ors nee d t o pr o vi de s u bsta ntial e vi de nce of effecti ve ness a n d a de q uate 
c haracterizati o n of safet y.  I n a d diti o n, we i nc or p orate ra pi d f utilit y a nal ysis w here eac h a ge nt is 
assesse d i n de pe n de ntl y usi n g Ba yesia n p osteri or  pr o ba bilit y calc ulati o ns. N O T E: t his is b ase d 
o n effic ac y n ot t o xicit y assess me nt.  T he t o xicit y assess me nt will be d o ne usi n g r u n -i ns f or 
s o me of t he ar ms.  T his selecti o n desi g n a p pr oac h al o n g wit h i nteri m assess me nts of efficac y,, 
use d ofte n i n ot her disci pli nes s uc h as o nc ol o g y, all o ws f or i nitial assess me nt of p ote ntial be nefit 
usi n g statistical pr o ba bilit y calc ulati o ns, bef ore desi g ni n g ra n d o mize d c o m parati ve trials t o a v oi d 
e x p osi n g lar ge n u m bers of s u bjects t o p ote ntiall y f ut ile a ge nts. T he “ pic k t he wi n ner” trial desi g n 
a n d Ba yesia n p osteri or pr o ba bilit y met h o ds all o w f or a n a da pti ve, pr o of- of- c o nce pt strate g y 
w hic h i nc or p orates pr os pecti vel y pla n ne d criteria t o st o p eac h ar m i n de pe n de ntl y f or f utilit y, [ 4 8] 
[ 4 9] wit h t he pr os pect of e x pa n di n g fr o m a pr o of- of-c o nce pt p hase t o a lar ger c o nfir mat or y trial , 
t y picall y a ra n d o mize d, place b o c o ntr olle d trial, if i nitial assess me nts are p ositi ve.  T he 
h y p ot hesis of t his st u d y is t hat t he a d diti o n of a ge nts t hat i n hi bit viral e ntr y or re plicati o n of 
S A R S -C o V - 2 vir us, will be de v oi d of a d diti o nal m o derate t o se vere t o xicit ies, will pre ve nt 
cli nical deteri orati o n  at 1 4 da ys , a n d will  i m pr o ve viral cleara nce at Da y 14 i n hi g h ris k 
i n di vi d uals. A d diti o nall y, we h y p ot hesize t hat cli nical o utc o mes i n C O VI D - 1 9 i nfecte d patie nts 
at hi g her ris k of p o or o utc o mes f oll o wi n g i nfecti o n will be i m pr o ve d c o m pare d t o t he e mer gi n g 
sta n dar ds w he n i ntr o d uce d as a n earl y i nter ve nti o n after dia g n osis .  

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
7 
 
 
 
C O VI D 7 - p oi nt Or di nal O utc o me Scale a n d Pri mar y E n d p oi nt 
2. 7  
C orrel ati ve St u dies B ac k gr o u n d  
 
2. 7. 1  S A R S -C o V - 2 Vir al L o a d  
Acti ve S A R S -C o V - 2 i nfecti o n is dia g n ose d b y q P C R i n u p per a n d l o wer res pirat or y s peci me ns 
o btai ne d b y nas o p har y n geal s wa bs.  T he i nitial, dia g n ostic test is perf or me d at baseli ne i n a 
C LI A la b orat or y a n d re q uire d f or dia g n ostic p ur p oses a n d f or st u d y e ntr y .  S u bse q ue nt sa m ples, 
t o a v oi d placi n g b ur de n o n cli nical res o urces, will be researc h le vel or o p har y n geal s wa bs or 
s p ut u m sa m ples a n d e val uate d i n t he K olesar la b orat or y b y a vali date d q P C R assa y.  I n a d diti o n, 
a n y resi d ual s peci me n fr o m nas o p har y n geal s wa bs t hat are c ollecte d f or r o uti ne care d ue t o a 
cli nical i n dicati o n t o retest usi n g a C LI A la b orat or y assa y  will be c ollecte d .  C orrelati ve testi n g 
will e xa mi ne t he li n ka ge of viral l oa d wit h ti me t o res ol uti o n a n d wit h cli nical stat us, as well as 
c orrelati o n bet wee n viral l oa d a n d ser o p ositi vit y, recr u desce nce, of disease a n d cli nical 
o utc o mes. 
 
2. 7. 2  S A R S -C o V - 2 A nti b o d y S er o p ositi vit y 
Defi niti ve met h o ds t o pr o ve a patie nt ha d bee n i nfecte d wit h S A R S- C o V -2 are c urre ntl y lac ki n g.  
Se veral gr o u ps wit hi n t he U K s y ste m are de vel o pi n g ser ol o g y tests t o detect S A R S-C o V - 2 
a nti b o dies.  Dr. Sc ott Berr y, a n Ass ociate Pr ofess or i n E n gi neeri n g at t he U ni versit y of Ke nt uc k y 
a n d C hief Scie ntific Officer of Salas Disc o ver y, is a n e x pert t he de vel o p me nt of p oi nt of care 
testi n g f or viral dia g n ostics.  He has a da pte d a n e mer gi n g tec h n ol o g y i n bi o mar ker 
is olati o n/ meas ure me nt, E xcl usi o n-base d Sa m ple Pre parati o n ( E S P), f or t he u n met cli nical nee d 
ass ociate d wit h p oi nt of care S A R S -C o V -2 meas ure me nt. [ 5 0] T his ser ol o g y test c o m bi nes t he 
se nsiti vit y a n d q ua ntitati ve nat ure of a n E LI S A wit h t he s pee d a n d si m plicit y of a lateral fl o w 
assa y (i.e., a ra pi d test) [ 5 1- 5 3]  Briefl y, E S P utilizes p hase i nterfaces (e. g., li q ui d/air b o u n daries) 
t o ra pi dl y a n d si m pl y ma ni p ulate a nal yte b o u n d t o para ma g netic particles ( P M Ps) wit hi n a b ul k 
sa m ple. E S P will be use d t o is olate S A R S -C o V -2 a nti b o d y fr o m a bl o o d sa m ple a n d t he n 
perf or m a strea mli ne d, E S P - base d i m m u n oassa y f or q ua ntitati o n S A R S - C o V- 2a nti b od y . 
I m p orta ntl y, E S P t hat has bee n s uccessf ull y i m ple me nte d as t he bac k b o ne of a ne w HI V assa y 
geare d t o war d de vel o pi n g c o u ntries, ill ustrati n g its a bilit y t o f u ncti o n o utsi de of s o p histicate d 
la bs.[ 5 4, 5 5]   
 
Me m bers of t he U ni versit y of Ke nt uc k y C U R E A llia nce i ncl u di n g Dr. Jerr y W o o d war d has 
e x pertise i n de vel o p me nt of i m m u ne pr ofili n g a n d i n c olla b orati o n wit h ot her me m bers of t he 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
8 
 
De part me nt of Micr o bi ol o g y, I m m u n ol o g y, a n d M olec ular Ge netics a n d ot her c olla b orat ors is 
de vel o pi n g a n i n -h o use ser ol o gical assa y t o test f or t he prese nce of a nti b o dies t o S A R S -C o V - 2 
i nfecti o n i n bl o o d a n d sali va w hic h will be critical t o o ur a bilit y t o u n dersta n d i m m u nit y t o t his 
vir us f oll o wi n g i nfecti o n. A d diti o nall y, his gr o u p will p urs ue c o m plete i m m u ne pr ofili n g of 
plas ma base d m o n o n uclear cells ( P B M Cs) w hic h is a n ass ociate d a n d critical part of e x pa n di n g 
o ur u n dersta n di n g of t he a da pti ve i m m u ne res p o nse t o t his n o vel vir us. 
 
2. 7. 3  I nfl a m m at or y C yt o ki nes 
Pri or st u dies ha ve de m o nstrate d t hat pr oi nfla m mat or y c yt o ki nes are ass ociate d wit h p ul m o nar y 
i nfiltrates a n d se vere i nfecti o n i n i n di vi d uals wit h S A R S, [ 5 6] M E R S - C o V  [ 5 7] a n d S A R S-
C o V - 2 [ 2] i nfecti o n.  We h y p ot hesize t hat i nfla m mat or y c yt o ki nes li ke T N F al p ha, I L- 1, I L- 2 
a n d I L- 6 will be ele vate d at baseli ne a n d da y 7 i n i n di vi d uals w h o g o o n t o de vel o p a se vere 
i nfecti o n w he n c o m pare d t o t h ose w h o d o n ot de vel o p a se vere i nfecti o n a n d t hat c yt o ki ne 
meas ure me nt ca n be a n earl y mar ker of se vere i nfecti o n, all o wi n g f or earlier i n ter ve nti o n i n 
t hese i n di vi d uals.  C yt o ki ne le vels will be meas ures b y t he E LI S A i n t he K olesar la b, b y Dr. Jill 
K olesar, as pre vi o usl y descri be d. [ 5 8]     
 
2. 7. 4  C o a g ul o p at h y i n C O VI D- 1 9 P atie nts 
Dr. Si d ne y W hite heart ( M olec ular a n d Cell ular Bi oc he mistr y) a n d Dr. Jere m y W o o d ( Me dici ne) 
ha ve de vel o pe d a c olla b orati o n t o st u d y t he c oa g ul o pat hies ass ociate d wit h C O VI D - 1 9 
patie nts.   S pecificall y, t heir f oc us is o n t he d ysf u ncti o n of n or mal he m ostatic c o ntr ol see n i n t he 
m ost se vere C O VI D -1 9 patie nts.   Re p orts fr o m C hi na, Ital y, a n d t he U S ha ve s h o w n a n i ncrease 
i n c oa g ul o pat hies i n C OVI D -1 9: prese nti n g as i ncrease d D -di mer, t hr o m b oc yt o pe nia, a n d 
t hr o m b otic micr oa n gi o pat h y.  T his cli nical ma nifestati o n has lea d I S T H a n d A S H t o rec o m me n d 
l o w m olec ular wei g ht he pari n i n cases w here C O VI D- 1 9 is se vere; h o we ver, t he u n derl yi n g 
ca uses of t his are u n k n o w n.  Drs. W hite heart a n d W o o d will use t heir s pecific e x pertise a n d 
batter y of f u ncti o nal assa ys t o st u d y t his c oa g ulati o n d ysf u ncti o n at b ot h t he c oa g ulati o n fact or 
a n d platelet le vel.   W h ole bl o o d is nee de d f or s o me of t he platelet-s pecific assa ys a n d plas ma 
will be retai ne d f or a nal ysis.   T he data ge nerate d will hel p deter mi ne w hat ca uses t he i ncrease d 
c oa g ulati o n a n d will g ui de h o w t o better ma na ge a ntic oa g ula nt t hera p y i n t he m ost se verel y 
affecte d patie nts.  
 
 
3.  P A TI E N T S E L E C TI O N  
 
3. 1  
Eli gi bilit y Criteri a  
 
3. 1. 1  A ge ≥1 8 years  
 
3. 1. 2  La b orat or y -c o nfir me d S A R S-C o V - 2 i nfecti o n wit hi n 7 da ys ( of pr o p ose d c o nse nt) or t he 
prese nce of  s y m pt o ms or p h ysical e xa mi nati o n si g ns pr o vi di n g hi g h pr o ba bilit y of 
C O VI D -1 9 disease des pite a ne gati ve C O VI D -1 9 test as deter mi ne d  b y I nfecti o us 
Disease s pecialist/ C O VI D -1 9 Tele healt h Treat me nt Tea m re vie w  
 
3. 1. 3  S u bjects m ust ha ve at least o ne of t he f oll o wi n g hi g h- ris k feat ures f or cli nical 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
9 
 
deteri orati o n:  
- 
H y perte nsi o n 
- 
Dia betes Mellit us  
- 
M o derate t o se vere C hr o nic O bstr ucti ve P ul m o nar y Disease , E m p h yse ma, C ystic 
Fi br osis,  or Ast h ma  
- 
Ca ncer  patie nts w h o ha ve recei ve d a n y i m m u n os u p pressi ve dr u gs wit hi n a year fr o m 
e nr oll me nt.  
- 
Sic kle cell disease  or  t halasse mia  
- 
A ge > 5 0 
- 
B MI > 3 0  
- 
Li vi n g i n a n ursi n g h o me or l o n g- ter m facilit y 
- 
U n derl yi n g seri o us heart c o n diti o n as deter mi ne d b y t he treati n g p h ysicia n 
- 
I m m u n oc o m pr o mise d s u bject as defi ne d b y t he treati n g p h ysicia n  or C O VI D - 1 9 
Tele healt h Treat me nt Tea m   
 
3. 1. 4  A bilit y t o pr o vi de i nf or me d c o nse nt b y t he patie nt or healt hcare pr o x y 
 
3. 1. 5  A bilit y t o ret ur n f or re peate d testi n g a n d o bser vati o n t o U K H C 
 
3. 1. 6  Patie nts m ust ha ve a de q uate or ga n a n d marr o w f u ncti o n meas ure d wit hi n t he last 3 0 da ys 
as defi ne d bel o w:  
 
− 
platelets    
 
≥1 0 0, 0 0 0/ mc L 
− 
A S T( S G O T)/ A L T( S G P T)    
≤3 × i nstit uti o nal U L N  
− 
creati ni ne   
 
≤ 1. 5 x i nstit uti o nal U L N 
O R  
− 
gl o mer ular filtrati o n rate ( G F R)  ≥4 5 m L/ mi n/ 1. 7 3 m 2 u nless data e xists s u p p orti n g 
safe use at l o wer ki d ne y f u ncti o n val ues, n o l o wer 
t ha n 3 0 m L/ mi n/ 1. 7 3 m2 (see A p pe n di x B).   
 
3. 1. 7  T he effects of t hera pe utic a ge nts use d i n t his trial o n t he de vel o pi n g h u ma n fet us are 
u n k n o w n.  Beca use t hera pe utic a ge nts use d i n t his trial ma y  be terat o ge nic, w o me n of 
c hil d- beari n g p ote ntial a n d me n m ust a gree t o use a de q uate c o ntrace pti o n ( h or m o nal or 
barrier met h o d of birt h c o ntr ol; a bsti ne nce) pri or t o st u d y e ntr y a n d f or t he d urati o n of 
st u d y partici pati o n.  S h o ul d a w o ma n bec o me pre g na nt or s us pect s he is pre g na nt w hile 
s he or her part ner is partici pati n g i n t his st u d y, s he s h o ul d i nf or m her treati n g p h ysicia n 
i m me diatel y.  Me n treate d or e nr olle d o n t his pr ot oc ol m ust als o a gree t o use a de q uate 
c o ntrace pti o n pri or t o t he st u d y, f or t he d urati o n of st u d y partici pati o n. 
 
3. 2  
E xcl usi o n Criteri a  
 
3. 2. 1  Se vere C O VI D - 1 9 is defi ne d b y o ne or m ore of t he f oll o wi n g: 
- 
bl o o d o x y ge n sat urati o n ≤ 9 0 %  
- 
partial press ure  of arterial o x y ge n t o fracti o n of i ns pire d o x y ge n rati o < 3 0 0 
- 
l u n g i nfiltrates > 5 0 % wit hi n 2 4 t o 4 8 h o urs 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 0 
 
3. 2. 2  Life -t hreate ni n g C O VI D- 1 9 is defi ne d as o ne or m ore of t he f oll o wi n g: 
- 
res pirat or y fail ure 
- 
se ptic s h oc k 
- 
m ulti ple or ga n d ysf u ncti o n or fail ure 
 
3. 2. 3  Wei g h t less t ha n 4 5 k g. 
 
3. 2. 4  Pre g na nt or breast -fee di n g fe males  
 
3. 2. 5  S u bjects o n dial ysis  or wit h creati ni ne cleara nce < 4 5 ml/ mi n  
 
3. 2. 6  E xisti n g D MI D T o xicit y Scale f or Deter mi ni n g Se verit y of A d verse E ve nts gra de 3 or greater 
he patic fail ure   
 
3. 2. 7  Pre vi o usl y d oc u me nte d m o derate or se vere  reti n o pat h y or mac ular de ge nerati o n 
 
3. 2. 8  U nc o ntr olle d Seiz ure dis or der  
 
 
3. 2. 9  K n o w n aller g y t o a rte misia a n n ua, artes u nate, i ver mecti n, ca m ostat  mesilate , or ot her 
a ge nts t o be use d i n t he trial.  
 
3. 2. 1 0  C urre ntl y recei vi n g a n y  st u d y me dicati o ns f or other i n dicati o ns     
 
3. 2. 1 1  C o nc urre nt use of me dicati o n t hat w o ul d ca use m o derate or se vere d ue t o dr u g- dr u g 
i nteracti o ns wit h st u d y me dicati o n.  
S pecificall y : 
•  Patie nts recei vi n g i ver mecti n ma y n ot be c o nc urre ntl y ta ki n g str o n g 
C Y P 3 A 4/ A B C B 1 i n hi bit ors ( Az ole a nt if u n gals i ncl u di n g v oric o naz ole, 
ket oc o naz ole, itrac o naz ole a n d p osac o naz ole; clarit hr o m yci n , telit hr o m yci n, 
nefaz o d o ne, sa q ui na vir, dar u na vir, or l o pi na vir, etc.) 
•  Patie nts recei vi n g Arte misi a a n n u a  te a or c offee  O R artes u n ate ma y n ot be 
c urre ntl y ta ki n g str o n g i n d ucers of C Y P 2 A 6, i ncl u di n g p he n o bar bital a n d 
rifa m pi n.[ 5 9]  
 
3. 2. 1 2  Recei pt i n t he 1 2 h o urs pri or t o e nr oll me nt, or pla n ne d a d mi nistrati o n d uri n g t he 1 4- da y 
st u d y peri o d t hat treati n g cli nicia ns feel ca n n ot be s u bstit ute d f or a n ot her me dicati o n, of 
a n y of t he f oll o wi n g: a mi o dar o ne; ci meti di ne; d ofetili de; p he n o bar bital; p he n yt oi n; or 
s otal ol. 
 
3. 2. 1 3  Ca ncer patie nts recei vi n g acti ve i m m u n os u p pressi ve treat me nt ca n n ot e nr olle d u nless 
t he y are o n a treat me nt h oli da y wit h n o a nti ne o plastic treat me nt wit h  3 wee ks  of 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 1 
 
e nr oll me nt. 
 
E nr oll me nt o n ot her e x peri me ntal t hera pies f or C O VI D 1 9  
3. 2. 1 4  I na bilit y t o recei ve e nteral me dicati o ns 
 
3. 2. 1 5  Patie nts wit h ps yc hiatric ill ness/s ocial sit uati o ns t hat w o ul d li mit c o m plia nce wit h st u d y 
re q uire me nts. 
 
3. 2. 1 6  A n y ot her c o n diti o n t hat i n t he o pi ni o n of t he treati n g p h ysicia n j ustifies e xcl usi o n fr o m 
t he st u d y.  
 
3. 3  
I ncl usi o n of W o me n a n d Mi n orities 
 
NI H p olic y re q uires t hat w o me n a n d me m bers of mi n orit y gr o u ps a n d t heir s u b p o p ulati o ns be 
i ncl u de d i n all NI H-s u p p orte d bi o me dical a n d be ha vi oral researc h pr ojects i n v ol vi n g NI H-
defi ne d cli nical researc h u nless a clear a n d c o m pelli n g rati o nale a n d j ustific ati o n esta blis hes t hat 
i ncl usi o n is i na p pr o priate wit h res pect t o t he healt h of t he s u bjects or t he p ur p ose of t he researc h.    
C ost is n ot a n acce pta ble reas o n f or e xcl usi o n e xce pt w he n t he st u d y w o ul d d u plicate data fr o m 
ot her s o urces.  W o me n of c hil d beari n g p ote ntial s h o ul d n ot be r o uti nel y e xcl u de d fr o m 
partici pati o n i n cli nical researc h.  Please see 
htt p:// gra nts. ni h. g o v/ gra nts/f u n di n g/ p hs 3 9 8/ p hs 3 9 8. p df . 
 
4.  I N V E S TI G A T O R R E Q UI R E M E N T S A N D R E GI S T R A TI O N P R O C E D U R E S 
 
4. 1  
I n vesti g at or a n d Rese arc h Ass oci ate Re gistr ati o n wit h M C C  
 
All i n vesti gat ors m ust be q ualifie d b y e d ucati o n, trai ni n g a n d e x perie nce t o ass u me 
res p o nsi bilit y f or t he pr o per c o n d uct of h u ma n s u bject researc h.  I n vesti gat ors are res p o nsi ble f or 
bei n g a ble t o pr o vi de e vi de nce of s uc h q ualificati o ns t hr o u g h u p- t o-date  c urric ul u m vitae a n d/ or 
ot her rele va nt d oc u me ntati o n a n d trai ni n g per i nstit uti o nal, state a n d fe deral g ui deli nes.  All 
i n vesti gat ors c o n d ucti n g M C C trials will c o m plete all re q uisite trai ni n g a n d re gistrati o ns per 
M C C S O Ps.  
 
4. 2  
Cli nic al Tri al Re gistr ati o n wit h cli nic altri als. g o v a n d rele ase of tri al res ults  
 
C o ntact t he M C C - C R O Re g ulat or y u nit at mccre g @ u k y.e d u if y o u nee d assista nce i n c o m pleti n g 
y o ur cli nicaltrials. g o v re gistrati o n . Res ults will be rele ase d o n cli nic altri als. g o v acc or di n g t he 
d at a g ui del i nes a n d re q uire me nts of cli nic altri als. g o v. 
 
4. 3  
E nr oll me nt G ui deli nes  
 
Eli gi ble patie nts will be i de ntifie d b y t he pri nci pal i n vesti gat or a n d c o-i n vesti gat ors of t his st u d y. 
P ote ntiall y eli gi ble patie nts will be scree ne d via m ulti ple testi n g sites as o utli ne d i n A p pe n di x F.  
Patie nts will be e val uate d at t he U ni versit y of Ke nt uc k y b y t he i n vesti gat ors a n d stu d y pers o n nel 
wit h o versi g ht b y t he Pri nci pal I n vesti gat or ( PI). U p o n o btai ni n g pr o per c o nse nt t o treat me nt, 
patie nts will be e nr olle d i nt o t he st u d y.   

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 2 
 
 
4. 4  
Dele g ati o n of T as ks L o g ( D T L)  
 
All M C C st u dies re q uire a Dele gati o n Tas k L o g w hic h is mai ntai ne d b y t he M C C Re g ulat or y 
U nit of t he Cli nical Researc h Office.  
I n or der t o be a d de d t o t he D T L f or a gi ve n st u d y, eac h staff me m ber m ust ha ve a p pr o priate 
trai ni n g t o c o n d uct assi g ne d d uties i ncl u di n g b ut n ot li mite d t o pr ot oc ol s pecific trai ni n g a n d 
re vie w of t he fi nal pr ot oc ol. 
 
4. 5  
I nf or me d C o nse nt 
 
T he g oal of t he i nf or me d c o nse nt pr ocess is t o pr o vi de pe o ple wit h s ufficie nt i nf or mati o n s o t he y 
ca n ma ke i nf or me d c h oices a b o ut w het her t o be gi n or c o nti n ue partici pati o n i n cli nical researc h.  
T he pr ocess i n v ol ves a d y na mic a n d c o nti n ui n g e xc ha n ge of i nf or mati o n bet wee n t he researc h 
tea m a n d t he partici pa nt t hr o u g h o ut t he researc h e x perie nce.  It i ncl u des disc ussi o n of t he st u d y's 
p ur p ose, researc h pr oce d ures, ris ks a n d p ote ntial be nefits, a n d t he v ol u ntar y nat ure of 
partici pati o n.  
 
T he i nf or me d c o nse nt d oc u me nt pr o vi des a s u m mar y of t he cli nical st u d y a n d t he i n di vi d ua l's 
ri g hts as a researc h partici pa nt.  T he d oc u me nt acts as a starti n g p oi nt f or t he necessar y e xc ha n ge 
of  i nf or mati o n  bet wee n  t he  i n vesti gat or  a n d  p ote ntial  researc h  partici pa nt.   Als o,  researc h  
partici pa nts a n d t heir fa milies ma y use t he c o nse nt d oc u me nt  as a n i nf or mati o n res o urce a n d 
refere nce t hr o u g h o ut partici pati o n i n t he trial.  T he i nf or me d c o nse nt d oc u me nt is ofte n c o nsi dere d 
t he f o u n dati o n of t he i nf or me d c o nse nt pr ocess; it d oes n ot, h o we ver, re prese nt t he e ntiret y of t he 
pr ocess.  N or is t he i nf or me d c o nse nt d oc u me nt a ris k -ma na ge me nt t o ol f or t he i n vesti gat or a n d/ or 
i nstit uti o n. 
 
T he i n vesti gat or m ust e x plai n t o eac h s u bject ( or le gall y a ut h orize d re prese ntati ve) t he nat ure of 
t he st u d y, its p ur p ose, t he pr oce d ures i n v ol ve d, t he e x pecte d d urati on, t he p ote ntial ris ks a n d 
be nefits i n v ol ve d a n d a n y disc o mf ort it ma y e ntail. Eac h s u bject m ust be i nf or me d t hat 
partici pati o n i n t he st u d y is v ol u ntar y a n d t hat he/s he ma y wit h dra w fr o m t he st u d y at a n y ti me 
a n d t hat wit h dra wal of c o nse nt will n ot affect his/ her s u bse q ue nt me dical treat me nt or 
relati o ns hi p wit h t he treati n g p h ysicia n. 
 
4. 6  
Recr uit me nt Pl a ns:  
 
I n p atie nt Recr uit me nt 
I n patie nts will be scree ne d b y t heir treati n g p h ysicia n tea m, i nf or me d of t he st u d y a n d if 
i ntereste d i n partici pati n g, will be a p pr oac he d b y st u d y staff f or re vie w of eli gi bilit y a n d 
i nf or me d c o nse nt. 
 
O ut p atie nt Recr uit me nt:  
•  I niti al st u dy prese nt ati o n: A p pe n dix D, E 
o  P h o ne or tele healt h c o ntact t o pr os pecti ve o ut patie nts w h o are bei n g referre d f or testi n g 
at t he U ni versit y of Ke nt uc k y 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 3 
 
 Prescree ni n g fr o m scree ni n g lists (secti o n 4. 5. 3)  
 Prese ntati o n of st u d y t o patie nt 
 Assess me nt of patie nt i nterest i n partici pati o n  
 Directi n g i ntereste d patie nts t o Researc h Desi g nate d Cli nic  or dri ve -t hr o u g h 
o  O R, wal k i n patie nt prese nti n g t o Resea rc h Desi g nate d Cli nic 
o  O R t o a tele healt h c o nse nt c o nfere nce  
 
•  Rese arc h Desi g n ate d Cli nic: U ni versit y of Ke nt uc k y a m b ulat or y care cli nics t hat are: 
o  Desi g nate d f or testi n g a n d ma na ge me nt of C O VI D- 1 9 a n d its c o m plicati o ns 
o  Pr o vi des testi n g, e val uati o n, a n d tre at me nt site a d heri n g t o c urre nt C D C a n d U ni versit y 
of Ke nt uc k y C O VI D- 1 9 g ui deli nes f or t he pr o visi o n of a m b ulat or y care  
o  I nte n de d t o e na ble recr uit me nt a n d partici pati o n i n researc h st u dies 
o  Has t he a bilit y t o o btai n t he nas o p har y n geal s wa bs, bl o o d sa m ples, electr ocar di o gra ms 
( E K Gs), a n d a d diti o nal st u d y relate d e val uati o ns re q uire d f or safet y/t olera bilit y a n d 
o utc o mes m o nit ori n g ass ociate d wit h t his st u d y 
 
•  St u dy i nt ake pr oce d ures: A p pe n dix F  
o  Researc h Desi g nate d Cli nic prese nts st u d y a n d o btai ns eit her c o nse nt or decli ne t o 
partici pate   
 E nr oll c o nse nti n g patie nts i n st u d y 
 Pr o vi de decli ni n g patie nts f ull sc o pe of r o uti ne care f or C O VI D- 1 9 patie nts 
 
4. 7  
P atie nt Scree ni n g  O pti o ns   
 
A ll i n di vi d uals w h o are teste d f or C O VI D -1 9, via a  dri ve t hr o u g h testi n g facility of t he 
U ni versit y of Ke nt uc k y, ot her testi n g sites sa ncti o ne d b y t he Ke nt uc k y De part me nt of Healt h, 
a n y o ut patie nt cli nic ass ociate d wit h U K H C, or a d mitte d t o U K H C i n patie nt h os pitals  will be 
eli gi ble f or scree ni n g .  If a scree ni n g c o nse nt is use d, i n di vid uals willi n g t o be scree ne d will 
c o nse nt t o t he f oll o wi n g: 
 
1)  
A gree t o all o w st u d y staff t o re vie w cli nical C O VI D 1 9 test res ults, baseli ne 
eli gi bilit y, la bs, via me dical rec or ds re vie w  
2)  
A gree t o be re-c o ntacte d f or st u d y partici pati o n a n d f ut ure c o ntact f or p ossi ble 
plas ma d o n or stat us. 
 
Researc h staff will re gister scree ne d patie nts i nt o a pass w or d pr otecte d Re d Ca p data base.   
 
Scree ni n g c a n be d o ne vi a o ne of t he f oll o wi n g w a ys: 
 
4. 7. 1  Face -t o-face scree ni n g o utsi de of cli nic or i n patie nt (i.e. dri ve t hr o u g h test facilit y, 
n ursi n g h o me setti n g, etc.).  I n t his setti n g, patie nts will be gi ve n a scree ni n g c o nse nt. 
 
4. 7. 2  Re m ote scree ni n g via referral fr o m t he U ni versit y of Ke nt uc k y o ut patie nt C O VI D - 1 9 
m o nit ori n g pr o gra ms, i ncl u di n g t he Get Well L o o p (a n a ut o mate d patie nt h ealt h 
m o nit ori n g t o ol, A p pe n di x E), ot her testi n g s yste ms or t hr o u g h p h o ne or tele healt h 
mec ha nis ms, w het her ce ntralize d or i n ass ociati o n wit h s pecific cli nics or cli nical 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 4 
 
e ntities, will be eli gi ble t o be as ke d if t he y are i ntereste d i n e nr oll me nt i n part ici pati n g i n 
researc h a n d will be electr o nicall y c o nse nte d via Re d Ca p a n d will be referre d t o researc h 
desi g nate d sites f or treat me nt c o nse nt a n d e val uati o n as a p pr o priate.  
 
4. 7. 3  Wai ver of c o nse nt f or scree ni n g – T he st u d y tea m will be pr o vi de d a list of all p e o ple 
testi n g p ositi ve f or C O VI D- 1 9 b y t he U ni versit y of Ke nt uc k y o ut patie nt C O VI D- 1 9 
m o nit ori n g pr o gra m  w h o ha ve a gree d t o be c o ntacte d f or t his researc h st u d y. Researc h 
staff will re vie w t his list of s u bjects, scree n f or t he hi g h ris k cate g ories w hic h w oul d 
ma ke t he m eli gi ble  a n d  c o ntact t he patie nt a n d offer partici pati o n i n t he trial via re m ote 
mea ns.   T h ose t hat meet e ntr y criteria, a n d a gree t o partici pate will t he n ha ve a n i nf or me d 
c o nse nt c o nfere nce wit h t he PI or c o -I, a C R A electr o nicall y (re m otel y, or i n pers o n) a n d 
e-si g n t he treat me nt c o nse nt via re m ote Re d Ca p c o nse nt pr ocess.  T he y will t he n be 
directe d t o t he researc h cli nic f or s peci me n c ollecti o n a n d cli nic visit.  
 
4. 7. 4  Direct scree ni n g  – Patie nt’s  treati n g p h ysicia n will be a p pr oac he d re gar di n g eli gi bilit y 
a n d a p pr o priate ness f or partici pati o n i n t his trial.   
  
4. 7. 5  Face -t o-face scree ni n g o utsi de of cli nic or i n patie nt will occ ur at t h ose testi n g sites w here 
pe o ple ca n be a p pr oac he d f or p ote ntial partici pati o n b ut ca n n ot be f ull y assesse d f or 
eli gi bilit y.  I n t hese cases, a scree ni n g c o nse nt will be use d  
 
4. 8  
C o nse nt t o Tre at me nt  
 
O nce a patie nt meets eli gi bilit y, a f or mal c o nse nt c o nfere nce will be u n derta ke n b y o ne of t he 
mea ns liste d bel o w.  
 
4. 8. 1  I n- pers o n c o nse nt: 
 
•  Researc h staff si g n t heir p orti o n of t he c o nse nt a n d t he c o nse nt f or m is gi ve n t o cli nical 
staff w h o deli ver t he c o nse nt t o t he patie nt as part of t heir cli nical d uties. 
•  Researc h staff will c o ntact t he s u bject or le gall y a ut h orize d re prese ntati ves (L A R ) b y 
tele p h o ne or vi de o p h o ne ( met h o d dictate d b y i nstit uti o nal p olic y) t o ha ve t he i nf or me d 
c o nse nt c o n versati o n. T his ste p c o nfir ms s u bject/ L A R i de ntity . 
•  If t he s u bject or L A R c o nse nts: 
o  S u bject or L A R si g ns t he c o nse nt f or m a n d t his si g nat ure is wit nesse d b y t w o 
i n di vi d uals w h o d oc u me nt t he si g ni n g of t he c o nse nt o n a pa per attestati o n f or m 
o utsi de t he r o o m.  
O R  
o  A pict ure of t he si g ne d c o nse nt is ma de, a n d e maile d t o t he st u d y staff. 
•  T he s u bject/ L A R retai ns t he c o nse nt f or m, a n d t he si g ne d attestati o n of c o nse nt or c o p y 
of t he p h ot o gra p h is st ore d i n t he researc h staff rec or ds. N o c o p y of t he c o nse nt is st ore d 
d ue t o t he p ote ntial f or tra ns missi o n of C O VI D 1 9 vir us 
 
4. 8. 2  Electr o nic C o nse nti n g 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 5 
 
•  Researc h staff e mail t he c o nse nt t o t he patie nt or L A R.  If t he patie nt or L A R is offsite, a 
sca n of t he c o nse nt f or m ca n be e maile d, fa xe d, or ot her wise electr o nicall y tra nsferre d t o 
t he L A R ( met h o d dictate d b y i nstit uti o nal p olic y) 
•  Researc h staff will c o ntact t he s u bject or L A R b y tele p h o ne or vi de o p h o ne ( met h o d 
dictate d b y i ns tit uti o nal p olic y) t o ha ve t he i nf or me d c o nse nt c o n versati o n. T his ste p 
c o nfir ms s u bject/ L A R i de ntity . 
o  If t he s u bject or L A R c o nse nts a R E D C A P s ur ve y l i n k ca n be se nt t o t heir 
pers o nal de vice a n d  t he e-c o nse nt Re d Ca p si g nat ure pr ocess is c o m plete d  a n d 
se nt t o st u d y-s pecific Re d Ca p st ora ge w here t he PI will c o-si g n t he f or m. T his 
f or m als o i n dicates t he na me of t he st u d y tea m me m ber t hat was i n v ol ve d i n t he 
c o nse nt pr ocess.  
o  If usi n g a st u d y- pr o vi de d de vice, t he s u bject rea ds t he c o nse nt a n d f oll o ws t he 
pr o m pts i n Re d Ca p a n d t he si g ne d c o nse nt is electr o nicall y tra ns mitte d t o t he 
st u d y-s pecific Re d Ca p st ora ge w here t he PI will c o-si g n t he f or m.  T his f or m als o 
i n dicates t he na me of t he st u d y tea m me m ber t hat was i n v ol ve d i n t he c o nse nt 
pr ocess. T he de vice is t he n disi nfecte d acc or di n g t o l ocal i nstit uti o nal practices.  
•  T he s u bject/ L A R re cei ves a n electr o nic c o p y of t he c o nse nt f or m t o t he e mail pr o vi de d, 
a n d t he e- si g ne d c o nse nt is st ore d i n Re d Ca p t he researc h staff rec or ds. 
 
4. 8. 3  Ver bal c o nse nt 
 
Beca use of t he nat ure of t his viral disease a n d t he p ossi bilit y of tra ns missi o n t hr o u g h direct 
c o ntact wit h t he s u bject, ver bal c o nse nt ma y als o be gi ve n b y t he s u bject if wit nesse d a n d 
c o nfir me d b y t w o st u d y staff. T he ver bal c o nse nt will be d oc u me nte d o n t he c o nse nt f or m a n d 
si g ne d b y t he t w o wit nesses.  
 
If t he s u bject ca n n ot rea d or si g n t he d oc u me nts, oral prese ntati o n ma y be ma de or si g nat ure 
gi ve n b y t he s u bject’s le gall y a p p oi nte d re prese ntati ve, if wit nesse d b y t w o pe o ple a n d 
d oc u me nti n g t hat t he patie nt c o ul d n ot rea d or si g n t he d oc u me nts. N o patie nt ca n e nter t he st u d y 
bef ore his/ her i nf or me d c o nse nt has bee n o btai ne d.  T he i nf or me d c o nse nt f or m is c o nsi dere d t o 
be part of t he pr ot oc ol, a n d m ust be s u b mitte d b y t he i n vesti gat or wit h t he pr ot oc ol at t he ti me of 
I R B re vie w. 
 
 
4. 9  
 P atie nt Re gistr ati o n t o Tre at me nt  
 
T o re gister a patie nt, t he f oll o wi n g i nf or mati o n  s h o ul d be re vie we d b y t he cli nical researc h n urse 
( C R N) / cli nical researc h ass ociate ( C R A) wit h t he st u d y p h ysicia n per M C C S O Ps  t o c o nfir m 
eli gi bilit y: 
•  C o p y of C O VI D 1 9  testi n g res ults 
•  M o bile E K G traci n g ( o ut patie nts) or sta n dar d E K G (i n patie nts) wit hi n 5 da ys of 
re gistrati o n t o assess Q Tc i nter val  
•  E li gi bilit y la bs, as well as c orrelati ve la bs t o be dra w n  
•  Eli gi bilit y C hec klist  
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 6 
 
O nce eli gi bilit y is c o nfir me d, t he C R N/ C R A  will c o m plete s u bject re gistrati o n i n t he O n C ore 
data base  ( mi ni m u m data f o ot pri nt) f or ra n d o mizati o n a n d c o m plete st u d y -re q uire d Re d Ca p data 
f or ms. T o c o m plete t he re gistrati o n pr ocess, t he C R N/ C R A  will : 
•  assi g n a patie nt st u d y n u m ber 
•  re gister t he patie nt o n t he st u d y i n O n C ore 
•  recei ve t he a ut o mate d treat me nt ar m assi g n me nt   
•  se n d a n e mail or ot her c o m m u nicati o n t o t he st u d y tea m of ar m  assi g n me nts. 
 
If a patie nt is dee me d i neli gi ble f or treat me nt t heir s peci me ns will be retai ne d i n t he C O VI D 1 9 
BI O B A N K  if t he s u bject has i n dicate d a gree me nt t o s peci me n c ollecti o n a n d l o n g-ter m st ora ge 
i n t he c o nse nt f or m. 
 
At t he Da y 1 visit  or i n patie nt t he f oll o wi n g will be c o m plete d 
1)  Si g n tre at me nt i nf or me d c o nse nt ( u nless pre vi ousl y e- c o nse nte d as a b o ve)   
2)  U n der g o bl o o d testi n g f or eli gi bilit y (i n s u bjects w h o ha ve n ot ha d assess me nt of 
scree ni n g la bs wit hi n t he last 3 0 da ys will re q uire bl o o d dra w) 
3)  C o m plete a n eli gi bilit y q uesti o n naire (a ge, c o nc urre nt diseases, c urre nt me dicati o ns, 
c o ntact i nf or mati o n) 
4)  U n der g o a m o bile E K G or sta n dar d E K G traci n g t o assess Q Tc i nter val ( wit hi n 5 da ys 
of re gistrati o n)  
5)  Distri b ute me dicati o ns, pill diar y , a n d i nstr ucti o ns 
6)  Baseli ne c orrelati ve bl o o d sa m ple 
7)  S p ut u m sa m ple , wit h O P s wa b (alter nati ve, if n o s p ut u m a vaila ble) 
8)  Sali va sa m ple  
9)  C O VI D -1 9 or di nal scale assess me nt  ( See A p pe n di x B) 
1 0)  Li mite d vis ual p h ysical e xa m u nless a m ore c o m plete e xa m is cli nicall y i n dicate d.  
 
Da y 3  or 4 p h o ne call t o assess cli nical stat us a n d elicit c o ncer ns or q uesti o ns.  
 
Da y 7 tele healt h ( +/- 4 da ys) is re q uire d f or all patie nts t o assess t o xicit y.  If a s u bject has a 
sta n dar d of care tele healt h visit d uri n g t his peri o d, t his is als o a n acce pta ble t o xicit y assess me nt.  
 
Da y 1 0 or 1 1 p h o ne call t o assess cli nical stat us a n d elicit c o ncer ns or q uesti o ns  
 
Da y 1 4 ( +/- 4 da ys) visit  will als o be c o m plete d i n cli nic or i n patie nt h os pital . 
1)  U n der g o bl o o d testi n g f or t o xicit y 
2)  C ollecti o n of me dicati o ns, pill diar y a n d i nstr ucti o ns 
3)  M o bile E K G traci n g ( o ut patie nts) or sta n dar d E K G (i n patie nts) t o assess Q Tc i nter val  
4)  C orrelati ve b l o o d sa m ple 
5)  S p ut u m sa m ple , wit h O P s wa b  (alter nati ve, if n o s p ut u m a vaila ble) 
6)  Sali va sa m ple ( o pti o nal)  
7)  Nas o p har y n geal s wa b ( o pti o nal a n d if i n dicate d f or sta n dar d of care) * 
8)  C O VI D -1 9 or di nal scale assess me nt  ( See A p pe n di x B) 
9)  T o xicit y assess me nt via tele healt h or p h o ne call ( +/ - 4 da ys) 
 
Da y 2 8 ( +/- 4 da ys) visit will als o be c o m plete d i n cli nic or i n patie nt h os pital . 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 7 
 
1)  C orrelati ve bl o o d sa m ple  
2)  S p ut u m sa m ple , wit h O P s wa b  (alter nati ve, if n o s p ut u m a vaila ble) 
3)  Sali va sa m ple  ( o pti o nal) 
4)  Nas o p har y n geal s wa b ( o pti o nal a n d if i n dicate d f or sta n dar d of care) * 
5)  Ser ol o g y testi n g *  
6)  C O VI D -1 9 or di nal scale assess me nt  ( See A p pe n di x B) 
7)  T o xicit y assess me nt via tele healt h or p h o ne call ( +/ - 4 da ys) 
 
Da y 4 0 ( +/- 4 da ys) visit . If ser ol o g y testi n g is ne gati ve or viral l oa d re mai ns p ositi ve, patie nts 
will be re q ueste d t o ret ur n f or a Da y 4 0 visit ( o pti o nal) will als o be c o m plete d via dri ve t hr o u g h 
( preferre d), cli nic or i n patie nt h os pital. 
1)  C orrel ati ve bl o o d sa m ple  
2)  S p ut u m sa m ple , wit h O P s wa b  (alter nati ve, if n o s p ut u m a vaila ble) 
3)  Sali va sa m ple  ( o pti o nal) 
4)  Nas o p har y n geal s wa b ( o pti o nal a n d if i n dicate d f or sta n dar d of care) *  
5)  Ser ol o g y testi n g ( o pti o nal a n d if i n dicate d f or sta n dar d of care) *  
6)  C O VI D -1 9 or di nal scale assess me nt  ( See A p pe n di x B) 
* T hese are c o nsi dere d sta n dar d of care tests 
 
4. 1 0  Ge ner al G ui deli nes  
 
F oll o wi n g re gistrati o n, patie nts s h o ul d be gi n pr ot oc ol treat me nt wit hi n 7 da ys.  Iss ues t hat w o ul d 
ca use treat me nt dela ys s h o ul d be disc usse d wit h t he Pri nci pal I n vesti gat or.  If a patie nt d oes n ot 
recei ve pr ot oc ol t hera p y f oll o wi n g re gistrati o n, t he PI a n d t he statisticia n m ust be c o ns ulte d as 
s o o n as p ossi ble.  
 
 
5.  BI O M A R K E R, C O R R E L A TI V E , A N D S P E CI A L S T U DI E S   
 
5. 1  
S u m m ar y T a ble f or S peci me n C ollecti o n  
 
Ti me P oi nt  
S peci me n  
Se n d S peci me ns T o:  
Arc hi v al  
 
•  Disc ar de d tiss ue or bl o o d s a m ples fr o m 
ori gi n al C O VI D 1 9 testi n g  
•  Resi d u als fr o m a ny of t he rese arc h 
s a m ples c ollecte d bel o w 
Ce nter f or Cli nic al a n d 
Tr a nsl ati o n al Scie nce 
( C C T S) C O VI D- 1 9 
Rese arc h Re gistry a n d 
S peci me n B a nk ( C R R S B)  
B aseli ne  –  D a y 1  
 
•  1 0 m L a n d 6 m L bl o o d i n E D T A ( p ur ple 
t o p) t u bes f or a nti b o dy testi n g, 
pr oc alcit o ni n, C R P a n d cyt oki nes   
•  5 m L bl o o d i n A C D ( yell o w t o p) t u be f or 
pl atelet f u ncti o n ass ays ( o pti o n al)  
•  8 m L bl o o d i n C P T t u be ( o pti o n al)   
Bi os peci me n Pr oc ure me nt 
a n d Tr a nsl ati o n al P at h ol o gy 
S h are d Res o urce F acility 
( B P T P S R F) or C C T S 
C R R S B   

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 8 
 
•  S p ut u m s a m ple ( M a n d at ory) or O P s w a b 
( alter n ative, if s p ut u m is u n av ail a ble) 
•  1 ml of s aliv a ( o pti o n al)  
D ay 1 4 ( +  / - 4  d ay)  
 
•  1 0 m L a n d 6 m L bl o o d i n E D T A ( p ur ple 
t o p) t u bes f or a nti b o dy testi n g, 
pr oc alcit o ni n, C R P a n d cyt oki nes   
•  5 m L bl o o d i n A C D ( yell o w t o p) t u be f or 
pl atelet f u ncti o n ass ays ( o pti o n al)  
•  8 m L bl o o d i n C P T t u be ( o pti o n al)   
•  S p ut u m s a m ple ( M a n d at ory) or O P s w a b 
( alter n ative, if s p ut u m is u n av ail a ble) 
•  1 ml of s aliv a ( o pti o n al ) 
B P T P S R F  or C C T S C R R S B  
D ay 2 8 ( +/- 4  d ay s) 
 
•  1 0 m L a n d 6 m L bl o o d i n E D T A ( p ur ple 
t o p) t u bes f or a nti b o dy testi n g, 
pr oc alcit o ni n, C R P a n d cyt oki nes 
•  5 m L bl o o d i n A C D ( yell o w t o p) t u be f or 
pl atelet f u ncti o n ass ays ( o pti o n al)  
•  8 m L bl o o d i n C P T t u be ( o pti o n al)   
•  S p ut u m s a m ple ( M a n d at ory) or O P s w a b 
( alter n ative, if s p ut u m is u n av ail a ble) 
•  1 ml of s aliv a ( o pti o n al ) 
B P T P S R F  or C C T S C R R S B  
D ay 4 0 ( +/- 4  d ay s) 
 
•  1 0 m L a n d 6 m L bl o o d i n E D T A ( p ur ple 
t o p) t u bes f or a nti b o dy testi n g, 
pr oc alcit o ni n, C R P a n d cyt oki nes   
•  5 m L bl o o d i n A C D ( yell o w t o p) t u be f or 
pl atelet f u ncti o n ass ays ( o pti o n al)  
•  8 m L bl o o d i n C P T t u be ( o pti o n al)   
•  S p ut u m s a m ple ( M a n d at ory) or O P s w a b 
( alter n ative, if s p ut u m is u n av ail a ble) 
•  1 ml of s aliv a ( o pti o n al ) 
B P T P S R F  or C C T S C R R S B  
 
 
5. 2  
S peci me n Pr oc ure me nt Kits a n d Sc he d uli n g  
 
5. 2. 1  S peci me n Pr oc ure me nt Kits  
 
S peci me n pr oc ure me nt kits will be s u p plie d b y t he Bi os peci me n Pr oc ure me nt a n d Tra nslati o nal 
Pat h ol o g y S hare d Res o urce Facilit y ( B P T P S R F).   
 
5. 3  
S peci me n C ollecti o n a n d Pr ocessi n g  
 
Resi d u al Cli nic al  S a m ples  ( bl o o d, s p ut u m, sali va, nas o p har y n geal a n d or o p har y n geal s wa b 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 9 
 
sa m ples): Resi d ual cli nical sa m ples will i ncl u de ser u m a n d plas ma ori gi nall y c ollecte d i n E D T A, 
citrate d or he pari nize d t u bes a n d s u bse q ue ntl y st ore d at - 2 0 0C i n 5 ml p o ur- off t u bes. 
S u b se q ue ntl y, t hese sa m ples will be tra nsferre d t o t he Mar ke y Ca ncer Ce nter Bi os peci me n 
Pr oc ure me nt a n d Tra nslati o nal Pat h ol o g y S hare d Res o urce Facilit y ( B P T P) or t he Ce nter f or 
Cli nical a n d Tra nslati o nal Scie nce ( C C T S) C O VI D -1 9 Researc h Re gistr y a n d S peci me n  Ba n k . 
B P T P  or C C T S  staff will l o g, a n d la bel a n d st ore t he resi d ual cli nical plas ma a n d ser u m 
s peci me ns at - 8 00C or l o wer. U p per res pirat or y tract sa m ples will i ncl u de resi d ual 
nas o p har y n geal a n d or o p har y n geal s wa b s peci me ns st ore d i n viral tra ns p ort me di a ( V T M) a n d 
i nitiall y fr oze n at - 7 00C. After tra ns p ort t o t he B P T P, t he staff will l o g, la bel a n d st ore t he 
s peci me ns at - 8 00C or l o wer.  
 
Rese arc h Peri p her al Bl o o d S a m ples  f or Pr oc alcit o ni n, D- Di mer , C yt o ki nes, 
Ser oc o n versi o n , a n d Pl atelet F u ncti o n: O ne 1 0- m L a n d o ne 6- m L E D T A ( p ur ple t o p) t u bes, 
o ne 5 m L bl o o d i n A C D ( yell o w t o p) t u be a n d o ne 8 m L bl o o d i n C P T t u be ( o pti o nal)  of bl o o d 
will be dra w n a n d i m me diatel y deli vere d  t o t he Mar ke y B P T P-S R F la b  or t he C C T S  C O VI D - 1 9 
Researc h Re gistr y a n d S peci me n Ba n k. E D T A a n d C P T t u bes will be p r ocesse d as s o o n as 
p ossi ble, b ut at m ost will occ ur wit hi n 2 4 h o urs of bl o o d dra w.  A C D t u bes will be deli vere d 
i m me diatel y t o t he W hite heart la b (see bel o w).  Bi o ba n k staff will freeze a 1 - m L ali q u ot of 
w h ole bl o o d, t he n ce ntrif u ge t he re mai n der at ~ 1, 2 0 0 R C F f or 1 2 mi n utes t o se parate a n d c ollect 
plas ma a n d b uff y c oat. Sa m ples will be l o g ge d a n d la bele d a n d ali q u ote d a n d st ore d fr oze n at –
8 0 0C or l o wer. Deli ver y a n d recei pt of refri gerate d bl o o d sa m ples will occ ur M o n da y t hr o u g h 
Fri da y. 
 
Rese arc h Or o p h ar y n ge al ( O P) , f or Vir al L o a d: O ne s wa b sa m ple will be c ollecte d per patie nt 
f oll o wi n g sta n dar d pr oce d ure at eac h st u d y ti me p oi nt, i m me diatel y place d i n viral tra ns p ort 
me dia a n d refri gerate d or st ore d at -8 0 0C or l o wer. Deli veries a n d recei pt of fr oze n or 
refri gerate d sa m ples will occ ur M o n da y t hr o u g h Fri da y. 
 
Rese arc h S p ut u m S a m ples  f or Vir al L o a d: O ne s p ut u m sa m ple per patie nt at eac h st u d y ti me 
p oi nt will be c ollecte d f oll o wi n g sta n dar d pr ot oc ol. T he s peci me ns will be deli vere d i m me diatel y 
t o t he B P T P la b. Sa m ples will be l o g ge d a n d la bele d a n d st ore d at - 8 00C or l o wer.  
 
Rese arc h S ali v a S a m ples:  O ne o pti o nal sali va sa m ple per patie nt at eac h st u d y ti me p oi nt will 
be c ollecte d f oll o wi n g sta n dar d pr ot oc ol. T he s peci me ns will be c ollecte d i n a sta n dar dize d kit 
a n d hel d at 4 0C u ntil deli ver y t o t he B P T P la b. Sa m ples will be l o g ge d a n d la bele d a n d deli vere d 
t o t he W o o d war d La b. 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 0 
 
 
 
Researc h s peci me n pr ocessi n g a n d deli ver y al g orit h m 
 
5. 4  
S hi p pi n g/ Dis pe nsi n g of S peci me ns  
Sa m ples will be tra ns p orte d t o t he M C C B P T P S R F or t he C C T S C O VI D -1 9 Researc h Re gistr y 
a n d S peci me n Ba n k f or pr ocessi n g a n d tra ns p ort t o t he a p pr o priate la bs as a b o ve.   
 
6.  T R E A T M E N T P L A N  
 
S u bjects will be a p pr oac he d at t he ti me of i nitial C O VI D- 1 9 testi n g or wit hi n 7 da ys of a p ositi ve 
test. Pri or t o a n y st u d y-re q uire d tests, s u bjects m ust first pr o vi de writte n i nf or me d c o nse nt t o 
partici pate i n t his st u d y.   
 
6. 1  
A ge nt A d mi nistr ati o n  
 
T he C U R E Allia nce  Dr u g Steeri n g C o m mittee  will ser ve as t he dr u g selecti o n c o m mittee t o 
i de ntif y t he a p pr o priate ne w dr u gs f or eac h ne w ar m of t his cli nical trial . Treat me nt will be 
a d mi nistere d o n a n o ut patie nt  or i n patie nt basis  pr o vi de d t hat e ntr y criteria are met. If e mer gi n g 
data i n dicates f utilit y of a me dicati o n i n o ne or m ore ar ms of o ur st u d y, a n d was teste d i n a 
si milar patie nt p o p ulati o n i n a ra n d o mize d cli nical trial or trials, t he st u d y dr u g selecti o n 
c o m mittee ma y rec o m me n d re m o val of t hat dr u g treat me nt ar m f or f utilit y wit h a p pr o val of t he 
st u d y tea m. O nce a f utilit y e n d p oi nt is met i n a n ar m, we will re place t hat ar m wit h t he ne xt 
a p pr o priate pr o p ose d ar m wit h a p pr o val of t he C U R E Allia nce Dr u g Steeri n g C o m mittee. 
All s u bjects recei ve st a n d ar d s u p p orti ve tre at me nt t hr o u g h o ut t heir i nfecti o n, w het her 
o ut p atie nt or d uri n g i n p a tie nt h os pit aliz ati o n.  Re p orte d a d verse e ve nts a n d p ote ntial ris ks are 
descri be d i n Secti o n 1 0.   
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 1 
 
Tr eat me nt re gi me ns will be e val uate d  a n d n o vel a ge nts selecte d b y t he steeri n g c o m mittee.  
S h o ul d dr u g s u p pl y bec o me u na vaila ble t hat ar m w o ul d pa use u ntil dr u g s u p pl y is a vaila ble. 
 
Re gi me n Descri pti o n - Ar m C  
A ge nt  
F or m ul ati o n 
Stre n gt h  
D aily  
D ose  
R o ute  
Sc he d ule  
I ver mecti n 
3 m g ta blet  
1 2 -1 5  m g  
Oral  
Wei g ht < 7 5 k g : 4 ta b s o n Da ys 1 a n d 2, 
( 1 2 m g t otal dail y d ose)  
Wei g ht > 7 5 k g: 5 ta b s o n Da ys 1 a n d 2, 
( 1 5 m g t otal dail y d ose)  
 
Re gi me n Descri pti o n - Ar m D  
A ge nt  
F or m ul ati o n 
Stre n gt h  
D aily  
D ose  
R o ute  
Sc he d ule  
Ca m ostat Mesilate   
1 0 0 m g ta blet  
6 0 0 m g  
Oral  
2  ta b TI D after a meal  ( 6 0 0 m g t otal 
dail y d ose) Da ys 1 -1 4  
 
Re gi me n Descri pti o n - Ar m E  
A ge nt  
F or m ul ati o n  
Stre n gt h  
D aily  
D ose  
R o ute  
Sc he d ule  
Arte misia  a n n ua tea 
or c offee  
Decaf c offee 
4 5 0 m g per p o d 
Tea 2 2 5 m g per 
ba g  
1 3 5 0 m g  
Oral  
O ne 8 oz bre we d tea (t w o ba gs) or o ne 
c offee p o d TI D Da ys 1- 1 4 
 
Re gi me n Descri pti o n - Ar m F  
A ge nt  
F or m ul ati o n 
Stre n gt h  
D ail y  
D ose  
R o ute  
Sc he d ule  
Artes u n ate  
1 0 0 m g  
2 0 0 m g  
Oral  
T w o ta bs o nce da y ( 2 0 0 m g t otal) Da ys 
1 -1 4  
 
 
Patie nts will be assi g ne d t o a treat me nt ar m acc or di n g t o t he ra n d o mizati o n pr ocess descri be d i n 
Secti o n 9 of t his pr ot oc ol  
 
Si nce t here are n o safet y data f or t he me dicati o n s t o be e val uate d o n all ar ms of t his st u d y i n t he 
mil d t o m o derate S A R S -C o V -2 i nfecte d p o p ulati o n, t he first si x patie nts o n eac h ar m will be 
e val uate d f or a n y gra de 3 or hi g her he mat ol o gic or n o n- he mat ol o gic t o xicit y f or 1 4 da ys .  Patie nts 
c o mi n g off st u d y bef ore t he first 1 4 da ys  f or reas o ns ot her t ha n t o xicit y will be re place d. If t w o or 
m ore of t he si x patie nts i n t his ar m of t he st u d y de vel o p u nacce pta ble t o xicit y, t he treat me nt f or 
t hat ar m w o ul d be c o nsi dere d u nsafe a n d st o p pe d. Patie nts e x hi biti n g ra pi d pr o gressi o n of C O VI D-
1 9 s y m pt o mat ol o g y re q uiri n g i nte nsi ve care h os pitalizati o n or i nt u bati o n will c o me off st u d y a n d 
will be c o nsi dere d fail ures i n ter ms as per t he pri mar y e n d p oi nts of t he st u d y b ut n or f or safet y a n d 
will be re place d if t hese cases occ urre d d uri n g t he p hase 1 p orti o n of t he st u d y. 
 
O nce t he p hase 1 p orti o n safet y r u n-i n has c o ncl u de d, t hat ar m will be o pe ne d f or p hase II accr ual.  

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 2 
 
P atie nts will be assi g ne d t o eac h ar m i n c o h orts of t hree at a ti me u ntil accr ual n u m bers f or eac h 
ar m are f ulfille d or disc o nti n ue d d ue t o safet y c o ncer ns occ urri n g be y o n d t he P hase 1 p orti o n.  
M o nt hl y p h o ne c o nfere nces a m o n g i n vesti gat ors d uri n g e nr oll me nt will ta ke place.   
 
Patie nts will u n der g o baseli ne m o bile E K G or sta n dar d E K G t o e val uate Q Tc i nter val o n Da y  1 
( or wit hi n 5 da ys of re gistrati o n if i n patie nt) a n d a re peat E K G at Da y 14 ( +/- 4 da ys).  A n y C hest 
X- ra y or C T sca n of t he c hest t hat is perf or me d f or r o uti ne care will be re vie we d b y t he PI f or 
eli gi bilit y a n d rec or de d o n case re p ort f or ms.  N O T E: if a patie nt de vel o ps a m y ocar dial i nfarcti o n  
or gra de 3 or 4 car diac arr yt h mia w hile o n t he 1 4 da ys of dr u g, t he y sh o ul d be i m me diatel y  ta ke n 
off st u d y me dicati o n a n d recei ve sta n dar d of care treat me nt per t heir treati n g p h ysicia n. 
 
Patie nts will be f oll o we d f or cli nical o utc o mes b y p h o ne c o ntact eac h wee k a n d h os pitalizati o ns, 
a n d all c o m plicati o ns will be rec or de d o n  a d verse e ve nt case re p ort f or ms.  
 
6. 2  
Defi niti o n of D ose -Li miti n g T o xicit y ( D L T) f or p h ase I r u n i n p orti o ns of t his 
pr ot oc ol  
 
A D L T is defi ne d as a n y of t he bel o w treat me nt e mer ge nt t o xicities wit h attri b uti o n  of 
defi nitel y, pr o ba bl y or p ossi bl y relate d t o o ne or m ore of t he st u d y dr u gs t hat occ ur d uri n g t he 
first 1 4 da ys of st u d y treat me nt.   T o xicities t hat occ ur after t he 1 4 da y treat me nt peri o d will be 
re p orte d t hr o u g h a d verse e ve nt re p orti n g o utli ne d i n secti o n 1 0. 0, b ut will n ot be c o u nte d as 
D L Ts .    
 
• 
G r a de 3 or hi g her n o n - he m at ol o gic or n o n -he m at ol o gic  t o xicit y at le ast p ossi bl y, 
pr o b a bl y or defi nitel y rel ate d t o st u d y me dic ati o n or pr oce d ures,  per  D MI D 
T o xicit y Sc ale f or Deter mi ni n g Se verit y of A d verse E ve nts  
 
6. 3  
D ur ati o n of T her a p y  
 
I n t he a bse nce of treat me nt dela ys d ue t o a d verse e ve nt(s), treat me nt is gi ve n u ntil o ne of t he 
f oll o wi n g criteria a p plies: 
 
•  
I nterc urre nt ill ness t hat pre ve nts f urt her a d mi nistrati o n of treat me nt 
 
•  
U nacce pta ble a d verse e ve nt(s)  
 
•  
Patie nt deci des t o wit h dra w fr o m t he st u d y  
 
•  
Ge neral or s pecific c ha n ges i n t he patie nt's c o n diti o n re n der t he patie nt u nacce pta ble f or 
f urt her treat me nt i n t he j u d g me nt of t he i n vesti gat or 
 
•  
Patie nt n o n -c o m plia nce 
 
•  
Pre g na nc y 
 
 
•  
T he dr u g ma n ufact urer ca n n o l o n ger pr o vi de t he st u d y a ge nt 
 
•  
A d missi o n t o t he I nte nsi ve Care U nit a n d/ or nee d f or mec ha nical ve ntilati o n. At t his 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 3 
 
ti me, t he treati n g p h ysicia n will ha ve t he a bilit y t o c o nti n ue st u d y dr u g, disc o nti n ue 
t hera p y, place t he patie nt o n a n ot her st u d y trial, or treat t he patie nt wit h alter nati ve 
t hera pies, per t heir cli nical j u d ge me nt. At t his p oi nt, t he patie nt will be f oll o we d b y t he 
st u d y tea m t o trac k o utc o mes a n d m o nit or f or a d verse e ve nts t hat mi g ht be attri b uta ble t o 
st u d y dr u g b ut t he dr u g will be c o nsi dere d t o ha ve faile d t he pri mar y e n d p oi nt 
 
T he reas o n(s) f or pr ot oc ol t hera p y disc o nti n uati o n, t he reas o n(s) f or st u d y re m o val, a n d t he 
c orres p o n di n g dates m ust be d oc u me nte d i n t he Case Re p ort F or m ( C R F). F or clarit y, “ off 
treat me nt” is t he date w he n all me dicati o n has bee n c o m plete d (i ncl u di n g t he n or mal o bser vati o n 
peri o d) or disc o nti n ue d d ue t o o ne of t he fact ors a b o ve, a n d n o f urt her treat me nt is pla n ne d. T his 
is t he date t he patie nt has bee n officiall y ta ke n off treat me nt. “ Off st u d y” is t he date after w hic h 
n o f urt her f oll o w- u p of t he patie nt will occ ur 
 
6. 4  
D ur ati o n of F oll o w- U p   
 
Patie nts will be f oll o we d f or u p t o 4 0 da ys fr o m t he be gi n ni n g of t hera p y or u ntil deat h, 
w hic he ver occ urs first.    
 
7.  D O SI N G D E L A Y S/ D O S E M O DI FI C A TI O N S  
 
N/ A . 
 
8.  P H A R M A C E U TI C A L  I N F O R M A TI O N 
 
A list of t he a d verse e ve nts a n d p ote ntial ris ks ass ociate d wit h t he i n vesti gati o nal or c o m mercial 
a ge nts a d mi nistere d i n t his st u d y ca n be f o u n d i n Secti o n 1 0. 1. 
 
8. 1  
Dr u g Or deri n g a n d Acc o u nt a bilit y  
 
8. 1. 1  Pr oc ure me nt of me dic ati o ns:  
Prescri pti o ns f or me dicati o ns  will be writte n b y t he site PI, q ualifie d C o -I ( p h ysicia n), or treati n g 
p h ysicia n as o utli ne d i n Secti o n 6. 0.  I D S will or der a n d dis pe nse i ver mecti n, ca m ostat mesilate , 
artes u nate  a n d ot her i n vesti gati o nal a ge nts if ne w ar ms are o pe ne d  d uri n g t he treat me nt p hase of 
t his trial. Dr u g acc o u nta bilit y will be mai ntai ne d o n a Nati o nal Ca ncer I nstit ute Dr u g 
Acc o u nta bilit y Re p ort F or m ( D A R F).  Arte misia  a n n ua, a nat ural pr o d uct/ b ota nical, will be 
or dere d directl y fr o m Baes ma n Distri b ut ors.  
 
8. 1. 2  St or a ge & Dr u g Acc o u nt a bility:  
T he U ni versit y of Ke nt uc k y I n vesti gati o nal Dr u g Ser vice p har macist  will e ns ure t hat all st u d y 
dr u g is st ore d i n a sec ure d, li mite d access st ora ge area, u n der rec o m me n de d st ora ge c o n diti o ns i n 
acc or da nce wit h a p plica ble la bel i n g a n d re g ulat or y re q uire me nts a n d as pr o vi de d b y t he se parate 
st u d y dr u g acc o u nta bilit y ma n ual. U n der n o circ u msta nces s h o ul d t he i n vesti gat or or ot her site 
pers o n nel s u p pl y st u d y dr u g t o ot her i n vesti gat ors, patie nts, or cli nics. A de q uate rec or ds 
d oc u me nti n g recei pts, use, ret ur n, l oss, or ot her dis p ositi o n of st u d y pr o vi de d dr u gs m ust be 
ke pt. T he U ni versit y of Ke nt uc k y I n vesti gati o nal Dr u g Ser vice will s u p pl y dr u g acc o u nta bilit y 
f or ms t hat will be use d, or ma y a p pr o ve use of sta n dar d i nstit uti o n f or ms. Dr u g acc o u nta bilit y 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 4 
 
a n d s u p pl y or der i nstr ucti o ns a n d f or ms will be pr o vi de d i n a se parate st u d y ma n ual. T he 
acc o u nta bilit y le d gers will be mai ntai ne d t o c o ntai n c urre nt a n d acc urate i n ve nt or y rec or ds a n d 
m ust be rea dil y a vaila ble f or i ns pecti o n. U nless o t her wise a ut h orize d b y t he s p o ns or, at t he e n d 
of t he cli nical trial all dr u g s u p plies u nall ocate d or u n use d b y sites or patie nts m ust be ret ur ne d t o 
t he U ni versit y of Ke nt uc k y I n vesti gati o nal Dr u g Ser vice ( U K I D S) f or fi nal acti o ns i n 
acc or da nce wit h s p o ns or i nstr ucti o ns.  
 
T he e xce pti o n t o t his practice will be t he nat ural pr o d uct, Arte misia  a n n ua tea or c offee w hic h is 
c o m merciall y a vaila ble a n d will be s u p plie d b y Arte milife, via its distri b ut or, Baes ma n 
d istri b ut ors (see A p pe n di x H f or i nstr ucti o ns) 
 
8. 1. 3  Iver mecti n 
 
Pr oc ure me nt  
T his me dicati o n will be dis pe nse d b y I D S ser vice.  
 
F or m ul ati o n  
3 m g ta blets  
 
Pre p ar ati o n, St or a ge a n d St a bility  
Please refer t o pac ka ge i nsert f or c o m plete pre parati o n a n d dis pe nsi n g i nstr ucti o ns. 
Dis pe nse  ei g ht 3 m g ta blets (f or patie nts  < 7 5 k g); te n 3 m g ta blets (f or patie nts > 7 5 k g)  
 
A d mi nistr ati o n  
Refer t o t he treat me nt secti o n  6. 1 f or s pecific a d mi nistrati o n i nstr ucti o ns.  
 
Patie nts  s h o ul d be i nstr ucte d t o ta ke: 4 ta bs o n Da ys 1 a n d 2, ( 1 2 m g t otal dail y d ose) f or wei g ht 
< 7 5 m g; or 5 ta b s o n Da ys 1 a n d 2, ( 1 5 m g t otal dail y d ose) f or wei g ht > 7 5 k g.  I ver mecti n 
s h o ul d be ta ke n o n a n e m pt y st o mac h. 
 
Dr u g I nter acti o ns  
I ncrease d Effect/ T o xicit y: C Y P 3 A 4 a n d A B C B 1 i n hi bit ors ma y i ncrease t hera pe utic 
c o nce ntrati o ns of i ver mecti n, a v oi d c o nc urre nt use of i ver mecti n a n d str o n g C Y P 3 A 4 or A B C B 1 
i n hi bit ors 
Decrease d Effect: I ver mecti n ma y decrease t he t hera pe utic effect of B C G a n d li ve vacci nes, 
a v oi d c o nc urre nt use  
 
Her b/ N utr ace utic al I nter acti o ns : N o ne  
 
P h ar m ac oki netics  
A bs or pti o n : Well a bs or be d, a d mi nister o n e m pt y st o mac h.  Hi g h fat meal i ncrease d 
bi oa vaila bilit y 2. 5 f ol d  
Distri b uti o n: V d: 3. 1- 2. 5 L/ k g, d oes n ot cr oss bl o o d brai n barrier  
Meta b olis m: He patic via  C Y P 3 A 4 ( maj or)  
Half -life eli mi nati o n:  
Ter mi nal: 1 8 h o urs  

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 5 
 
E xcreti o n: Less t ha n 1 % via feces a n d uri ne  
 
A dverse Eve nts  
C o ns ult t he pac ka ge i nsert f or t he m ost c urre nt a n d c o m plete i nf or mati o n.  
 
C o m m o n k n o w n p ote nti al t o xicities, > 1 0 %: N o ne 
 
Less c o m m o n k n o w n p ote nti al t o xicities, 1 % - 1 0 %:  
Tac h ycar dia ( 4 %)  
Peri p heral e de ma ( 3 %)  
Dizzi ness ( 3 %)  
Diarr hea ( 2 %)  
E osi n o p hilia ( 3 %) 
Ele vati o ns i n L F Ts ( 2 %) 
 
R are k n o w n p ote nti al t o xicities, < 1 % ( Li mite d t o i m p ort a nt or life -t hre ate ni n g): 
H y per bilir u bi ne mia  
H y perse nsiti vit y 
 
Pre g na nc y: T he here is i ns ufficie nt e vi de nce t o pr o ve safet y.   Base d o n t he a ni mal a n d h u ma n 
data i ver mecti n is la bele d cate g or y C i n t he U S ( a ni mal E F D fi n di n g, b ut o nl y at d oses als o t o xic 
t o t he pre g na nt fe male).  T h e ma n ufact urer c o nsi ders it c o ntrai n dicate d i n pre g na nc y. 
8. 1. 4   C a m ost at Mesil ate  
 
Pr oc ure me nt  
T his me dicati o n will be dis pe nse d b y I D S ser vice.  
 
F or m ul ati o n  
1 0 0 m g ta blets 
 
Pre p ar ati o n, St or a ge a n d St a bility  
T a blets s h o ul d be st ore d at r o o m te m perat ure.   
 
Dis pe nse 8 4, 1 0 0 m g ta blets  
 
A d mi nistr ati o n  
Refer t o t he treat me nt secti o n f or s pecific a d mi nistrati o n i nstr ucti o ns  
Patie nts s h o ul d be i nstr ucte d t o ta ke t w o 10 0 m g ta blet, t hree ti mes per da y (after meal)  Da ys 1 -
1 4. 
 
Dr u g I nter acti o ns  
I ncrease d Effect/ T o xicit y: N o k n o w n dr u g i nteracti o ns 
  
Decrease d Effect: N o k n o w n dr u g i nteracti o ns 
  
Her b/ N utr ace utic al I nter acti o ns : N o k n o w n dr u g i nteracti o ns 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 6 
 
  
P h ar m ac oki netics  
A bs or pti o n: well a bs or be d orall y 
Distri b uti o n: N ot esta blis he d  
Meta b olis m: Meta b oli ze d t o t w o maj or meta b olites: t he car b o x ylic aci d deri ve d fr o m clea va ge of 
t he car b o xa mi de ( F O Y- 2 5 1); a n d t he car b o x ylic aci d deri ve d fr o m clea va ge of t he i nter nal 
car b o x yester ( G B A).  B ot h are ra pi dl y eli mi nate d wit h eli mi nati o n half -li ves of r o u g hl y 1 
h o ur.  F O Y -2 5 1 retai ns acti vit y a gai nst t he pr otease tar get.  
Half -life eli mi nati o n: 1 7 0 mi n utes  
Ter mi nal: N ot re p orte d  
E xcreti o n: M ost of t he s u bsta nce is e xcrete d b y 5 t o 6 h o urs after d osi n g, t hr o u g h all r o utes 
i ncl u di n g fecal, uri ne, bile, etc.  A b o ut 2 0 % of a 2 0 0 m g d ose is e xcrete d i nt o t he uri ne as G B A 
a n d a b o ut 1 % is e xcrete d as F O Y- 2 5 1 
  
A dverse Eve nts  
C o m m o n k n o w n p ote nti al t o xicities, > 1 0 %:  
N o ne re p orte d 
 
Less c o m m o n k n o w n p ote nti al t o xicities, 1 % - 1 0 %:  
T hr o m b oc yt o pe nia 
H y p o kale mi a 
Li ver f u ncti o n a b n or malities 
Ja u n dice 
Itc hi n g or s ki n er u pti o n/ras h  
Ne p hr olit hiasis  
Dia betic ket oaci d osis  
A b d o mi nal pai n or bl oati n g 
Pa ncreatitis  
 
Pre g na nc y: T here is i ns ufficie nt e vi de nce t o pr o ve safet y  of ca m ostat mesilate i n pre g na nt 
fe males.   
 
8. 1. 5  Arte misi a a n n u a te a a n d c offee  
 
Pr oc ure me nt  
 
O ut p atie nts:  C offee a n d tea b ota nical pr o d ucts will be directl y s hi p pe d o ver ni g ht t o st u d y 
patie nts, w h o are o ut patie nts b y Baes ma n o n be half of Arte mi Life .  Patie nts wit h o ut a p o d c offee 
ma ker will als o recei ve a c offee  ma ker.  
 
T he distri b ut or  f or Arte misia  a n n ua is as f oll o ws: 
Baes ma n  Distri b ut ors  
4 4 7 7 Re y n ol ds dri ve 
Hilliar d , O hi o 4 3 0 2 6 
C o ntact: T baes ma n @ baes ma n.c o m   
S u bjects ra n d o mize d t o Ar m E will ha ve t heir i nf or mati o n e ntere d i nt o t he or deri n g p ortal of 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 7 
 
Baes ma n Distri b ut ors  we bsite.   
 
 
I n p atie nts: T his b ota nical pr o d uct will be dis pe nse d b y Arte milife  t o t he I D S p har mac y. 
 
F or m ul ati o n  
Decaf c offee: 4 5 0 m g per p o d 
Tea: 2 2 5 m g per ba d 
 
Pre p ar ati o n, St or a ge a n d St a bility  
Tea a n d c offee  s h o ul d be st ore d at r o o m te m perat ure.   
 
C offee: Dis pe nse 4 2, 4 5 0  m g p o ds 
Tea: Dis pe nse 8 4, 2 2 5 m g ba gs 
 
A d mi nistr ati o n  
Refer t o t he treat me nt secti o n f or s pecific a d mi nistrati o n i nstr ucti o ns  
Patie n ts s h o ul d be i nstr ucte d t o bre w 1 ( 4 5 0 m g) c offee p o d or 2 ( 2 2 5 m g) tea ba gs i n 8 oz of 
water t hree ti mes per da y Da ys 1 - 1 4. 
 
Dr u g I nter acti o ns  
I ncrease d Effect/ T o xicit y: N o k n o w n dr u g i nteracti o ns 
  
Decrease d Effect: C Y P 2 A 6 str o n g i n d ucers ma y re d uce t he effects of Arte misia  a n n ua 
  
Her b/ N utr ace utic al I nter acti o ns:  N o k n o w n i nteracti o ns 
  
P h ar m ac oki netics  
A bs or pti o n: well a bs or be d orall y 
Distri b uti o n: N ot esta blis he d  
Meta b olis m: Meta b olize d b y C Y P 2 A 6 
Hal f-life eli mi nati o n: 1 hr 
Ter mi nal: N ot re p orte d  
E xcreti o n: N ot k n o w n 
  
A dverse Eve nts  
C o m m o n k n o w n p ote nti al t o xicities, > 1 0 %:  
N o ne re p orte d 
 
Less c o m m o n k n o w n p ote nti al t o xicities, 1 % - 1 0 %:  
Na usea  
 
Pre g na nc y: Arte misia a n n ua  tea is use d f or t he treat me nt of malaria i n pre g na nt w o me n a n d is 
c o nsi dere d safe  
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 8 
 
8. 1. 6  Artes u n ate ( Ar m F) 
 
Pr oc ure me nt  
 
T his me dicati o n will be dis pe nse d b y I D S ser vice.  
 
F or m ul ati o n  
 
1 0 0 m g ta blet 
 
Pre p ar ati o n, St or a ge a n d St a bility  
Artes u nate  s h o ul d be st ore d at r o o m te m perat ure.   
 
Dis pe nse 2 8, 1 0 0 m g ta blets  
 
A d mi nistr ati o n  
Refer t o t he treat me nt secti o n  f or s pecific a d mi nistrati o n i nstr ucti o ns 
Patie n ts s h o ul d be i nstr ucte d t o ta ke 2 ta blets o nce a da y Da ys 1- 1 4. 
 
Dr u g I nter acti o ns  
I ncrease d Effect/ T o xicit y: N o k n o w n dr u g i nteracti o ns 
 
Decrease d Effect: C Y P 2 A 6 str o n g i n d ucers ma y re d uce t he effects of Aa  a n d artes u nate 
 
Her b/ N utr ace utic al I nter acti o ns:  N o k n o w n dr u g i nteracti o ns 
 
P h ar m ac oki netics  
A bs or pti o n: well a bs or be d orall y 
Distri b uti o n: N ot esta blis he d  
Meta b olis m: Meta b olize d b y C Y P 2 A 6  
Half -life eli mi nati o n: 1 hr 
Ter mi nal: N ot re p orte d  
E xcreti o n: N ot k n o w n 
 
A dverse Eve nts  
C o m m o n k n o w n p ote nti al t o xicities, > 1 0 %:  
Ne utr o pe nia  
A ne mia  
Na usea  
 
Less c o m m o n k n o w n p ote nti al t o xicities, 1 % - 1 0 %:  
Diarr hea  
 
Pre g na nc y: Artes u nate is use d f or t he treat me nt of malaria i n pre g na nt w o me n a n d is c o nsi dere d 
safe 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 9 
 
8. 1. 7  Usef ul Li n ks a n d C o ntacts 
•  
I D S we bsite :  htt ps://i dsc.s hare p oi ntsite. net . 
•  I D S e mail: I D S @ u k y.e d u 
•  I D S p h o ne a n d h o urs of ser vice: ( 8 5 9) 2 1 8- 5 5 6 2   
•  I D S Fa x: ( 8 5 9) 3 2 3- 4 7 6 5  
•  I D S h o urs M o n da y t hr o u g h Fri da y bet wee n 8: 3 0 a m a n d 4: 3 0 p m ( E T) 
 
 
9.  S T A TI S TI C A L C O N SI D E R A TI O N S  
 
9. 1  
St u d y Desi g n/ E n d p oi nts  
 
T his st u d y is a ra n d o mize d, m ulti- ar m phase II trial.  N o pr o ve n effecti ve t hera pies c urre ntl y 
e xist f or C O VI D 1 9 ( Sa n ders J et al. J A M A A pril 1 3, 2 0 2 0), t h us a selecti o n desi g n usi n g t he 
fre q ue ntist pic k-t he-wi n ner  desi g n will be e m pl o ye d as earl y scree ni n g f or pr o misi n g t hera pies. 
T he pri mar y o bjecti ve is t o ra pi dl y e val uate m ulti ple p ote ntial i n hi bit ors of S A R S-C o V -2 viral 
re plicati o n i n C O VI D 1 9 p ositi ve patie nts wit h hi g h-ris k fact ors i n or der t o decrease cli nical 
deteri orati o n, defi ne d as a less t ha n 2 p oi nt de crease i n i nitial C O VI D 7 -P OI N T O R DI N A L 
O U T C O M E S S C A L E wit hi n 1 4 da ys fr o m st u d y e ntr y ( pri mar y).  As a n e xa m ple, if a pers o n 
e nters t he st u d y at O R DI N A L S C A L E 6 a n d d oes n ot w orse n t o 4 or less, t hat is c o nsi dere d a 
s uccess. 
 
F or eac h ar m a  p hase I lea d i n p orti o n, si x patie nts per gr o u p will be f oll o we d i n or der t o 
e val uate d ose li miti n g t o xicities a n d preli mi nar y safet y.  If 2 of t he first 5 patie nts or if ≥2 of 6 
patie nts e x perie nce D L T, t he re gi me n will n ot be c o nsi dere d safe f or f urt her e val uati o n.  
 
T he trial will be p o were d base d o n t he pri mar y e n d p oi nt of t he rate of patie nts w h o will e x hi bit 
less t ha n 2 le vels of decrease i n C O VI D 7 -P OI N T O R DI N A L S C A L E fr o m baseli ne t o Da y 1 4 . 
T he g oal of selecti o n desi g ns is t o select wit h hi g h pr o ba bilit y s h o ul d a s u peri or treat me nt e xist. 
N ote t hat h y p ot hesis testi n g or c o m paris o ns bet wee n ar ms or wit h a place b o  is n ot perf or me d 
wit h t his desi g n a n d s u bse q ue nt trials are nee de d f or defi niti ve h y p ot hesis testi n g of t he 
pr o misi n g ar m.  
 
9. 2  
Sec o n d ar y E n d p oi nts  
 
Sec o n dar y e n d p oi nts relate d t o efficac y: 
•  Prese nce of  s y m pt o ms or p h ysical e xa mi nati o n si g ns relate d t o C O VI D -1 9 disease o n Da y 
1 4 i ncl u di n g: fe ver, s h ort ness of breat h, m uscle ac hes, s ore t hr oat, l oss of se nse of taste or 
s mell, etc. 
•  Prese nce  of  S A R S -C o V - 2 R N A  as  d etecte d  b y  p ol y merase  c hai n  reacti o n  ( P C R)  i n  
nas o p har y n geal sa m ples meas ure d mi ni mall y o n Da ys 1, 1 4 a n d 2 8 
•  Pr o p orti o n of patie nts wit h s y m pt o ms or p h ysical e xa mi nati o n si g ns relate d t o C O VI D- 1 9 
disease i ncl u di n g s h ort ness of breat h, m uscle ac hes, s ore t hr oat, l oss of se nse of taste or 
s mell, h os pital a d missi o n, le n gt h of sta y, s u p ple me ntal o x y ge n re q uire me nts, nee d f or 
mec ha nical ve ntilati o n,  i nte nsi ve care u nit a d missi o n, etc. 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 0 
 
•  Ti me t o i m pr o ve me nt a n d res ol uti o n of s y m pt o ms fr o m baseli ne t o Da y 1 4 a n d 2 8 
•  O x y ge n- free da ys t o Da y 2 8 
•  Ve ntilat or -free da ys t o Da y 2 8 
•  Vas o press or -free da ys t o Da y 2 8 
•  I C U-free da ys t o Da y 2 8 
•  H os pital-free da ys t o Da y 2 8 
 
Sec o n dar y e n d p oi nts relate d t o safet y a n d t olera bilit y u p t o Da y 2 8 
•  I nci de nce, se verit y, dr u g-relate d ness, a n d seri o us ness of a d verse e ve nts 
•  Pr o p orti o n of patie nts meeti n g H y’ s la w criteria 
•  Pr o p orti o n of patie nts wit h t he f oll o wi n g Li ver f u ncti o n tests ( L F T) c ha n ges:  
o  A n y A L T or A S T ≥ 5 x U L N  
o  A n y A S T or A L T ≥ 3 x U L N t o get her wit h t he a p peara nce of fati g ue, na usea, 
v o miti n g, ri g ht u p per q ua dra nt pai n or te n der ness, fe ver, ras h a n d/ or e osi n o p hilia 
(e osi n o p hil perce nt or c o u nt a b o ve t he U L N) 
o  Persiste nt A L T ≥ 3 x U L N f or a peri o d of m ore t ha n 4 wee ks.  
•  Pr o p orti o n of patie nts wit h si g nifica nt c ha n ges i n E C G fi n di n gs, i ncl u di n g heart rate, E C G 
i nter vals ( P R, Q Tc B, Q Tc F), c o n d ucti o n c ha n ges, or a b n or malities i ncl u di n g se vere Q Tc 
pr ol o n gati o n of > 5 0 0 ms. 
•  Pr o p orti o n of patie nts wit h seri o us aller gic a n d s ki n reacti o ns 
•  Pr o p orti o n of patie nts wit h se vere h y p o gl yce mia 
•  Pr o p orti o n of patie nts wit h reti n o pat h y or mac ular de ge nerati o n 
•  Pr o p orti o n of patie nts wit h seiz ure 
•  Pr o p orti o n of patie nts wit h ac ute pa ncreatitis  
•  Pr o p orti o n of patie nts wit h ac ute ki d ne y i nj ur y 
•  Pr o p orti o n of patie nts wit h recei pt of re nal re place me nt t hera p y 
•  Pr o p orti o n of patie nts wit h ne utr o pe nia, l y m p h o pe nia, a ne mia, or t hr o m b oc yt o pe nia 
•  All -ca use m ortalit y rate  
 
9. 3  
S a m ple Size/ Accr u al R ate  
 
T he ass u m pti o n is t hat tra nsiti o n rate f or deteri orati o n i n cli nical scale is e q ual t o 2 0 % f or t he 
hi g h- ris k patie nts t o be e nr olle d i n t his trial base d o n a rece nt M M W R re p ort fr o m t he C D C. T he 
g oal is t o deter mi ne if a n y of t he ca n di date treat me nts will e x hi bit a 5 0 % re d ucti o n i n 
deteri orati o n of cli nical stat us (i.e. deteri orati o n rate = 1 0 %).  T h us, baseli ne sta bilit y  in cli nical 
scale ( decrease less t ha n 2 p oi nts i n C O VI D 7-P OI N T O R DI N A L S C A L E) is ass u me d t o be 
8 0 % a n d a n i m pr o ve me nt t o 9 0 % of all patie nts re mai ni n g sta ble ( decrease less t ha n 2 p oi nts i n 
C O VI D 7 -P OI N T O R DI N A L S C A L E) is h y p ot hesize d. A sa m ple of 6 0 patients i n eac h ar m is 
pr o p ose d.  If t here is a clear s u peri or treat me nt as s h o w n i n sce nari os A a n d B bel o w, t here is at 
least a n 8 2 % selecti o n pr o ba bilit y.  If t he cli nical res p o nse rate acr oss ar ms are n ot ver y 
differe nt, t he pr o ba bilit y of selecti n g t he s uperi or treat me nt is at 7 0 % a n d is m uc h hi g her 
c o m pare d t o t he ot her treat me nts (sce nari o C); w hile t here is a n e q ual c ha nce of selecti n g ar ms 
t hat ha ve si milar s u peri or efficac y (sce nari o D).   
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 1 
 
 
 
I nteri m m o nit ori n g t o assess f utilit y or efficac y will be perf or me d d uri n g t he trial usi n g t he 
Ba yesia n p osteri or pr o ba bilit y ( See Secti o n 9. 6 ).   If a t otal of 6 0 patie nts is e nr olle d i n a n ar m, 
t he pr o p ose d sa m ple size will pr o vi de a n esti mate of cli nical s uccess rate wit h wi dt h of a t w o-
si de d 9 0 % c o nfi de nce i nter val ( CI) e q ual t o 0. 1 4 3 ass u mi n g a res p o nse rate = 0. 9 0; s pecificall y, 
a 9 0 % t w o-si de d e xact bi n o mial CI = 0. 8 1 – 0. 9 5.    
 
Base d o n t his c urre nt desi g n, we pla n t o e nr oll a ma xi m u m of 2 4 0 t otal patie nts .   
 
9. 4  
R a n d o mi z ati o n/ Str atific ati o n F act ors  
 
Bl oc ke d ra n d o mizati o n wit h e q ual all ocati o n will be utilize d wit h a dj ust me nt i n ra n d o mizati o n 
se q ue nce t o acc o u nt f or t he p ote ntial t o dr o p a n ar m. Bl oc k size is 2 ti mes t he n u m ber of 
treat me nt ar ms. Ra n d o mizati o n will be stratifie d b y o ut patie nt or i n patie nt sta t us at ti me of 
e nr oll me nt i nt o t he trial.  
 
Ra n d o mizati o n list s will be ge nerate d pri or t o st u d y e nr oll me nt a n d pr o vi de d t o t he I D S 
p har macist w h o will be i n c har ge of t he ra n d o mizati o n wit h t he ra n d o mizati o n c o or di nat or.  All 
ot her st u d y pers o n nel i ncl u di n g t he PIs will be bli n de d t o t he ra n d o mizati o n lists t o pre ve nt 
patie nt a n d i n vesti gat or bias . Patie nts w h o are eli gi ble f or ra n d o mizati o n will be assi g ne d t o a 
treat me nt ar m acc or di n g t o t he ra n d o mizati o n list.  
 
I n t he sce nari o w here a treat me nt ar m is ter mi nate d earl y or a ne w treat me nt is a d de d i nt o t he 
st u d y, a ne w ra n d o mizati o n list ma y be ge nerate d t o re place t he e xisti n g o ne. T he ra n d o mizati o n 
list will gi ve e ver y patie nt e q ual pr o ba bilit y t o eac h st u d y ar m t hat is c urre ntl y a vaila ble. 
 
T he ra n d o mizati o n list will be i nc or p orate d i nt o t he O n C ore Cli nical Trials Ma na g e me nt S yste m 
a n d accessi ble  t o t he I D S p har macist. T his is facilitate d b y t he O n C ore C T M S w hic h assi g ns 
differe nt access a n d restricti o n le vels de pe n di n g o n pers o n nel r ole i n t he st u d y. Treat me nt 
all ocati o n f or eac h patie nt is t h us perf or me d b y t he I D S p har macist after St u d y C o or di nat or 
c o nfir ms patie nt eli gi bilit y stat us.  
   

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 2 
 
9. 5  
St atistic al A n al ysis Pl a n  
 
T he pri mar y a nal ysis will i ncl u de esti mate of t he rate of sta bilit y i n cli nical  scale (less t ha n 2 
p oi nt decrease i n C O VI D 7- P OI N T O R DI N A L S C A L E)  f or eac h ar m al o n g wit h e xact bi n o mial 
9 0 % c o nfi de nce i nter val.  T his is base d o n t he first res p o nse i n cli nical scale after e nr oll me nt a n d 
ra n d o mizati o n i nt o t he trial. I n a d diti o n, t he Ba yesia n p osteri or pr o ba bilit y of t he res p o nse rate 
bei n g greater t ha n 9 0 % will be calc ulate d f or eac h ar m at t he e n d of t he trial. T he rates of 
de vel o p me nt of se vere res pirat or y or or ga n fail ure, cleara nce of viral R N A at da y 2 8 a n d 
m ortalit y will be s u m mar ize d i n eac h ar m. C ha n ges i n S A R S -C o V - 2 R N A as detecte d b y 
p ol y merase c hai n reacti o n ( P C R)  o ver ti me will be s u m marize d i n eac h treat me nt ar m a n d 
c o m pare d usi n g paire d tests or l o n git u di nal li near m o dels.  
 
Sec o n dar y e n d p oi nts relate d t o pr o p orti o n of o utc o mes as i n dicate d i n Secti o n 9. 2 will be 
esti mate d al o n g wit h e xact c o nfi de nce i nter vals w hile descri pti ve statistics i ncl u di n g me dia n, 
ra n ge, I Q R will be calc ulate d f or t he d urati o n i n da ys of efficac y o utc o mes.  S ur vi val a nal ysis 
met h o ds will be utilize d t o esti mate ti me t o e ve nt e n d p oi nts.   T he e x pl orat or y a n d c orrelati ve 
e n d p oi nts s uc h as i nfla m mat or y mar kers a n d c yt o ki ne le vels will be s u m marize d at baseli ne a n d 
f oll o w- u p ti me p oi nts.  C ha n ges fr o m baseli ne will be c o m pare d usi n g paire d test or l o n git u di nal 
li near mi xe d m o dels.  
 
Sec o n dar y a nal yses will i ncl u de esti mates of rate a n d c o nfi de nce i nter vals of sta bilit y i n cli nical 
scale (less t ha n 2 p oi nt decrease i n C O VI D 7-P OI N T O R DI N A L S C A L E) eit her fr o m t he 
o ut patie nt or i n patie nt c o nti n u u m usi n g s u b gr o u p a nal yses or l o gistic re gressi o n wit h a varia ble 
t o acc o u nt f or res p o nse stat us a m o n g o ut patie nts f or eac h ar m.    
 
All patie nts w h o recei ve d st u d y dr u gs will be i ncl u de d i n t he safet y a nal ysis. T he ma xi m u m 
gra de of t o xicit y f or eac h cate g or y of i nterest will be re c or de d f or eac h patie nt a n d s u m mar y 
res ults will be ta b ulate d b y cate g or y a n d gra de. We will descri be all seri o us ( ≥ gra de 3) t o xicit y 
e ve nts.  Fre q ue nc y a n d i nci de nce ta bles of t o xicit y a n d A Es will be ge nerate d i n eac h treat me nt 
ar m.  Li ke wise, pr o p orti o ns of s pecific safet y e n d p oi nts i n Secti o n 9. 2 will be s u m marize d.   
 
m- I T T p o p ulati o n is defi ne d as all patie nts w h o ha ve bee n ra n d o mize d a n d recei ve d at least o ne 
d ose of t he st u d y treat me nt. T he pri mar y a nal ysis will be base d o n t he m-I T T p o p ulati o n. 
 
Ha n dli n g of missi n g data: T he pri mar y e n d p oi nt is base d o n a si m ple 7- scale assess me nt a n d is 
u nli kel y t o be missi n g. Patie nts w h o are i n t he m-I T T p o p ulati o n b ut ha ve missi n g pri mar y 
e n d p oi nts will be classifie d as n o n -res p o n ders t o t he treat me nt. 
 
9. 6  
I nteri m A n al ysis 
 
T he ti mi n g of i nteri m a nal ysis will be base d o n rate of patie nt accr ual. A n i nitial i nteri m a nal ysis 
will be perf or me d after 1 0 patie nts are ra n d o mize d i n eac h ar m.  F utili t y a n d efficac y will be 
assesse d i n eac h treat me nt ar m b y calc ulati n g Ba yesia n p osteri or pr o ba bilities.  T he beta 
distri b uti o n f or t he efficac y/s uccess rate is utilize d wit h a n o n -i nf or mati ve Jeffre y’s pri or e q ual 
t o beta ( 0. 5, 0. 5).   S pecificall y, a f uti lit y rate ≤ 8 0 % will be ass u me d a n d t he pr o ba bilit y f or 
st o p pi n g f or f utilit y will be set at 7 0 %.  A n efficac y rate ≥ 9 0% will be ass u me d a n d a 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 3 
 
pr o ba bilit y f or earl y st o p pi n g f or efficac y set at 9 0 %.  Base d o n t hese ass u m pti o ns, t he f utilit y 
st o p pi n g b o u n dar y f or t he first 1 0 patie nts i n eac h ar m is set at ≤ 7 patie nts wit h cli nical sta bilit y 
(i.e. less t ha n 2 p oi nt decrease i n C O VI D 7-P OI N T O R DI N A L S C A L E ) i n a s pecific treat me nt 
ar m.  
 
T he Ba yesia n met h o d ol o g y all o ws fle xi bilit y i n t he ti mi n g a n d c o h ort si ze i n eac h ar m i n t he 
c o n d uct of eac h i nteri m a nal ysis.  T h us, de pe n di n g o n patie nt e nr oll me nt a n d c o h ort size i n eac h 
ar m, s u bse q ue nt i nteri m a nal yses will be perf or me d (e. g. after e ver y 1 0 a d diti o nal patie nts i n 
eac h ar m)  a n d a d diti o nal st o p pi n g b o u n ds will be calc ulate d.  Re al -ti me assess me nts of p atie nt 
res p o nse will be critic al a n d will be f acilit ate d by cl ose c o or di n ati o n of cli nic al a n d rese arc h 
te a ms.  
 
T he decisi o n m a ki n g pr ocess f or t his tri al s uc h as dr o p pi n g a n ar m or ot her c h a n ges o n 
h o w t o pr ocee d wit h t he tri al will be b ase d o n cli nic al a n d s afet y c o nsi der ati o ns al o n g wit h 
ne wl y de vel o pi n g i nf or m ati o n o n C O VI D 1 9 as well as g ui d a nce b y res ults of effic ac y 
esti m ates a n d i nteri m p osteri or pr o b a bilities.  
 
1 0.  A D V E R S E E V E N T S:  LI S T A N D R E P O R TI N G R E Q UI R E M E N T S  
 
A d verse e ve nt ( A E) m o nit ori n g a n d re p orti n g is a r o uti ne part of e ver y cli nical trial. A d verse 
e ve nts m ust be e val uate d b y t he i n vesti gat or, gra de d a n d assi g ne d a n attri b uti o n of relate d ness t o 
st u d y treat me nt.  T he c haracteristics of a n o bser ve d A E will deter mi ne w het her t he e ve nt 
re q uires e x pe dite d re p orti n g t o O verall PI, t he F D A, t he U K I R B, a n d M C C D S M C via i n 
a d diti o n  t o r o uti ne re p orti n g.  
  
1 0. 1  E v al u ati o n of T o xicit y 
 
All patie nts will be e val ua ble f or t o xicit y fr o m t he ti me of t heir first treat me nt wit h t he 
i n vesti gati o nal a ge nts descri be d a b o ve. 
 
1 0. 2  A d verse E ve nt C h ar acteristics  
 
A d verse e ve nts ( A Es ) will be s u m marize d b y prese nti n g, f or eac h ar m, t he n u m ber a n d 
perce nta ge of patie nts ha vi n g a n y A E, ha vi n g a n A E i n eac h Me d D R A pri mar y s yste m or ga n 
class ( A p pe n di x G) a n d ha vi n g eac h i n di vi d ual A E ( preferre d ter m) i ncl u di n g relate d ness.  
A d diti o nall y, a s u m mar y of a d verse e ve nts b y preferre d ter m a n d se verit y will be perf or me d 
usi n g t he w orst se verit y gra de.   
 
All A Es m ust be e val uate d a n d c o m me nte d o n b y t he I n vesti gat or a n d gra de d acc or di n g t o t he 
D MI D T o xicit y Scale f or Deter mi ni n g Se verit y of A d verse E ve nts ( A p pe n di x G ). 
 
All relate d A Es, A Es wit h o utc o me deat h, A Es lea di n g t o per ma ne nt disc o nti n uati o n of 
treat me nt, S A Es a n d relate d S A Es will be s u m marize d b y perce nta ges a n d fre q ue ncies a n d liste d 
i ncl u di n g t he I n vesti gat or ter m, t he preferre d ter m, start a n d e n d date of A E, d urati o n ( da ys), 
se verit y, dr u g relati o ns hi p, acti o n ta ke n a n d o utc o me. 
 
•  Attri b uti o n  of t he A E: 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 4 
 
- 
Defi nite – T he A E is cle arly rel ate d t o t he st u d y treat me nt. 
- 
Pr o ba ble – T he A E is likely rel ate d t o t he st u d y treat me nt. 
- 
P ossi ble – T he A E m ay be rel ate d  t o t he st u d y treat me nt. 
- 
U nli kel y – T he A E is d o u btf ully rel ate d t o t he st u d y treat me nt. 
- 
U nrelate d – T he A E is cle arly N O T rel ate d t o t he st u d y treat me nt. 
 
1 0. 3  M C C E x pe dite d A d verse E ve nt Re p orti n g  G ui deli nes  
 
I n vesti gat ors will re p ort S A Es t hat are p ossi bl y, pr o ba bl y or defi nitel y relate d t o st u d y dr u g or 
pr oce d ures directl y t o t he M C C D S M C per t he M C C D S M C S O P a n d t he U ni versit y of 
Ke nt u c k y I R B re p orti n g p olic y, as s pecifie d  bel o w.  Use t he M C C pr ot oc ol n u m ber a n d t he 
pr ot oc ol- s pecific patie nt I D assi g ne d d uri n g trial re gistrati o n o n all re p orts.  
 
I n a d diti o n t o re p orti n g t o I R B, M C C D S M C a n d t he PI, f or a ge nts u n der a n I N D, 
i n vesti gat ors will re p ort all me dicati o n relate d ( p ossi bl y, pr o ba bl y or defi nitel y relate d) S A Es 
t o t he F D A per re q uire d re p orti n g pr ocesses usi n g Me d Watc h  f or m 3 5 0 0.  I n s u m mar y: 
1.  D uri n g p hase I r u n i n peri o d, re p ort gra de 1- 5 a d verse e ve nts (A Es ) t hat are dr u g-relate d 
( p ossi bl y, pr o ba bl y or defi nitel y relate d) t o PI, I R B, D S M C i n a n e x pe dite d fas hi o n.  
F oll o wi n g p hase I r u n-i n peri o d f or eac h ar m, re p ort gra de 3- 5 S A Es t hat are dr u g relate d 
t o PI, I R B, D S M C.  After t he p hase I r u n-i n peri o d, gra de 1 a n d 2 A Es relate d t o F D A 
a p pr o ve d me dicati o ns or b ota nical pr o d ucts are o nl y re p orte d if deter mi ne d b y t he 
i n vesti gat or t o be cli nicall y si g nifica nt A Es. 
2.  Re p ort a n y u ne x pecte d fatal or life -t hreate ni n g s us pecte d a d verse reacti o ns t o t he F D A 
n o later t ha n 7 cale n dar da ys af ter i nitial recei pt of t he i nf or mati o n.  S u b mit 7- da y re p orts 
electr o nicall y i n e C T D f or mat via t he F D A Electr o nic S u b missi o ns Gate wa y ( E S G).  
3.  Re p ort a n y seri o us, u ne x pecte d s us pecte d a d verse reacti o ns or a cli nicall y i m p orta nt 
i ncrease i n t he rate of a seri o us s us pecte d a d verse reacti o n t o t he F D A electr o nicall y i n 
e C T D f or mat via t he E S G  a n d t o all i n vesti gat ors n o later t ha n 1 5 cale n dar da ys after 
deter mi ni n g t hat t he i nf or mati o n q ualifies f or re p orti n g.   
 
D o n ot re p ort C O VI D -1 9 A Es or ot her A Es t o t hese  e ntities u nless t he y are rel ate d t o st u d y 
me dic ati o n or pr oce d ures  as liste d a b o ve.  
 
N ote:  A de at h o n st u d y re q uires b ot h  r o uti ne a n d e x pe dite d re p orti n g , re g ar dless of 
c a us alit y.  Attri b uti o n t o tre at me nt or ot her c a use m ust be pr o vi de d.  
 
 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 5 
 
E x pe dite d Re p orti n g Re q uire me nts f or A d verse E ve nts t h at Occ ur o n Me dic ati o ns in 
St u d y Ar ms  u n der a n I N D/I D E wit hi n 3 0 D a ys of t he L ast A d mi nistr ati o n of t he 
I n vesti g ati o n al A ge nt/I nter ve nti o n 1, 2  
F D A R E P O R TI N G R E Q UI R E M E N T S F O R S E RI O U S A D V E R S E E V E N T S ( 2 1 C F R P art 3 1 2)  
N O T E:   I n v e sti g at or s M U S T  i m m e di at el y r e p ort A N Y S eri o u s A d v er s e E v e nt s, a s li st e d b el o w( 2 1 C F R 3 1 2. 6 4)  
A n a d v er s e e v e nt i s c o n si d er e d s eri o u s if it r e s ult s i n A N Y  of t h e f oll o wi n g o ut c o m e s:   
1)  
D e at h  
2)  
A lif e -t hr e at e ni n g a d v er s e e v e nt  
3)  
A n a d v er s e e v e nt t h at r e s ult s i n i n p ati e nt h o s pit ali z ati o n or pr ol o n g ati o n of e xi sti n g h o s pit ali z ati o n f or ≥ 2 4 
h o ur s  
4)  
A p er si st e nt or si g nifi c a nt i n c a p a cit y or s u b st a nti al di sr u pti o n of t h e a bilit y t o c o n d u ct n or m al lif e f u n cti o n s  
5)  
A c o n g e nit al a n o m al y/ bi rt h d ef e ct.  
6)  
I m p ort a nt M e di c al E v e nt s (I M E) t h at m a y n ot r e s ult i n d e at h, n or b e lif e -t hr e at e ni n g, n or r e q uir e 
h o s pit ali z ati o n m a y b e c o n si d er e d s eri o u s  w h e n, b a s e d u p o n m e di c al j u d g m e nt, t h e y m a y j e o p ar di z e t h e 
p ati e nt or s u bj e ct a n d m a y r e q uir e m e di c al or s ur gi c al i nt er v e nti o n t o pr e v e nt o n e of t h e o ut c o m e s li st e d i n 
t hi s d efi niti o n. ( F D A, 2 1 C F R 3 1 2. 3 2; I C H E 2 A a n d I C H E 6). 
 
A L L  S E RI O U S  a d v er s e e v e nt s t h at m e et t h e a b o v e crit eri a M U S T b e i m m e di at el y r e p ort e d vi a el e ctr o ni c 
s u b mi s si o n wi t hi n t h e ti m efr a m e s d et ail e d i n t h e t a bl e b el o w. 
H o s pit ali z ati o n  
Gr a d e 1 a n d Gr a d e 2 ( d efi nit e, p o s si bl y 
or pr o b a bl y r el at e d t o st u d y 
m e di c ati o n) Ti m efr a m e s  
Gr a d e 3 -5  ( d efi nit e, p o s si bl y, or 
pr o b a bl y r el at e d t o 
st u d y m e di c ati o n   
Ti m efr a m e s  
R e s ulti n g i n 
H o s pit ali z ati o n  
≥ 2 4 hr s  
1 0 C al e n d ar D a y s  
2 4 -H o ur ; 5 C al e n d ar D a y s  
N ot r e s ulti n g i n 
H o s pit ali z ati o n  
≥ 2 4 hr s  
N ot r e q uir e d  
N O T E:   Pr ot o c ol s p e cifi c e x c e pti o n s t o e x p e dit e d r e p orti n g of s eri o u s a d v er s e e v e nt s ar e f o u n d i n t h e S p e cifi c 
Pr ot o c ol E x c e pti o n s t o E x p e dit e d  R e p orti n g S e cti o n . 
E x p e dit e d A E r e p orti n g ti m eli n e s ar e d efi n e d a s:  
o  
“ 2 4-H o ur; 5 C al e n d ar D a y s” - T h e A E m u st i niti all y b e s u b mitt e d el e ctr o ni c all y wit hi n  2 4 h o ur s of l e ar ni n g 
of t h e A E, f oll o w e d b y a c o m pl et e e x p e dit e d r e p ort wit hi n 5 c al e n d ar d a y s of t h e i niti al 2 4 -h o ur r e p ort.  
o  
“ 1 0 C al e n d ar D a y s” - A c o m pl et e e x p e dit e d r e p ort o n t h e A E m u st b e s u b mitt e d el e ctr o ni c all y wit hi n 1 0 
c al e n d ar d a y s of l e ar ni n g of t h e A E.  
1 S eri o u s a d v er s e e v e nt s t h at o c c ur m or e t h a n 3 0 d a y s aft er t h e l a st a d mi ni str ati o n of i n v e sti g ati o n al 
a g e nt/i nt er v e nti o n a n d h a v e a n attri b uti o n of p o s si bl e, pr o b a bl e, or d efi nit e r e q uir e r e p orti n g a s f oll o w s:  
E x p e dit e d 2 4 -h o ur n otifi c ati o n f oll o w e d b y c o m pl et e r e p ort wit hi n 5 c al e n d ar d a y s f or:  
•  
All Gr a d e 3, 4, a n d Gr a d e 5 A E s  
E x p e dit e d 1 0 c al e n d ar d a y r e p ort s f or:  
Gr a d e 1 a n d 2 A E s r e s ulti n g i n h o s pit ali z ati o n or pr ol o n g ati o n of h o s pit ali z ati o n  
 
 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 6 
 
1 0. 4  E xce pti o ns  t o A E re p orti n g 
 
A d verse e ve nts relate d t o S A R S -C o V -2 i nfecti o n are e xe m pt fr o m a d verse e ve nt re p orti n g u nless 
t he i n vesti gat or c o nsi ders t he e ve nt t o be p ossi bl y, pr o ba bl y, or defi nitel y relate d  t o t he st u d y 
dr u g or st u d y pr oce d ures.  E xa m ples of C O VI D- 1 9 relate d A Es i ncl u de:  
•  Deat h n ot relate d t o t he st u d y pr oce d ures  
•  Ne ur ol o gical e ve nts 
o  Seiz ure  
•  Car di o vasc ular e ve nts  
o  Atrial or ve ntric ular arr h yt h mia  
o  Car diac arrest  
•  Res pirat or y e ve nts  
o  H y p o xe mia re q uiri n g s u p ple me ntal o x y ge n 
o  Ac ute res pirat or y distress s y n dr o me  
o  Recei pt of mec ha nical ve ntilati o n  
o  Recei pt of e xtra -c or p oreal me m bra ne o x y ge nati o n 
 
1 0. 5  E x pe dite d Re p orti n g t o E xter n al A ge ncies  
 
O verall PI will c o m pl y wit h t he p olicies of all e xter nal f u n di n g a ge ncies a n d t he U K  I R B 
re gar di n g e x pe dite d re p orti n g, as per t he U K I R B’s Ma n date d Re p orti n g t o E xter nal A ge ncies 
S O P C 4. 0 1 5 0.   
 
1 0. 6  E x pe dite d Re p orti n g t o t he F o o d a n d Dr u g A d mi nistr ati o n ( F D A)  
 
O verall PI, as st u d y s p o ns or, will be res p o nsi ble f or all c o m m u nicati o ns wit h t he F D A. T he 
O verall PI will re p ort t o t he F D A, re gar dless of t he site of occ urre nce, a n y seri o us a d verse e ve nt 
t hat meets t he F D A’s criteria f or e x pe dite d re p orti n g f oll o wi n g t he re p orti n g re q uire me nts a n d 
ti meli nes set b y t he F D A usi n g t he Me d Watc h  3 5 0 0 f or m b y o ne of t he f oll o wi n g mea ns: 
•  T o fa x re p ort: 1- 8 0 0- F D A( 3 3 2)- 0 1 7 8 
•  T o re p ort o nli ne: w w w.f da. g o v/ me d watc h/re p ort. ht m   
•  T o re p ort b y e mail:  nase ya. mi n or @f da. h hs. g o v.   
 
1 0. 7  E x pe dite d Re p orti n g t o H os pit al Ris k M a n a ge me nt  
 
Partici pati n g i n ves ti gat ors will re p ort t o t he U K Office of Ris k Ma na ge me nt a n y partici pa nt 
safet y re p orts or se nti nel e ve nts t hat re q uire re p orti n g acc or di n g t o i nstit uti o nal p olic y.  
 
1 0. 8  R o uti ne A d verse E ve nt Re p orti n g  
 
All A d verse E ve nts  t hat are defi nitel y, pr o ba bl y or p ossi bl y relate d t o st u d y treat me nt m ust  be 
re p orte d i n r o uti ne st u d y data s u b missi o ns wit h t he e xce pti o n of t h ose liste d i n Secti o n 1 0. 4.  
A Es re p orte d e x pe diti o usl y t o t he O ver all PI a n d D S M C m ust als o be re p orte d i n r o uti ne 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 7 
 
st u d y d at a s u b missi o ns. 
 
Gr a de 1 a n d 2 a d verse e ve nts rel ate d t o F D A a p pr o ve d me dic ati o ns use d i n t his tri al (i.e. 
h y dr o x yc hl or o q ui ne, azit hr o m yci n, i ver mecti n, arte misi a a n n u a) are o nl y re p orte d if 
deter mi ne d b y t he i n vesti g at or t o be cli nic all y si g nific a nt A Es. 
 
1 0. 9  Pre g n a nc y  
 
Pre g na nc y is c o nsi dere d a n u na ntici pate d e ve nt a n d pre g na nc y as well as its o utc o me m ust be 
d oc u me nte d a n d re p orte d t o o verall PI a n d D S M C a n d Office of Researc h I nte grit y, as well t he 
F D A a n d s p o ns or i n acc or di n g t o re p orti n g re q uire me nts.  A n y pre g na nc y occ urri n g i n a patie nt 
or patie nt’s part ner fr o m t he ti me of c o nse nt t o 9 0 da ys after t he last d ose of st u d y dr u g m ust be 
re p orte d a n d t he n f oll o we d f or o utc o me.  Ne w b or n i nfa nts s h o ul d be f oll o we d u ntil 3 0 da ys ol d.   
 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 8 
 
1 1.  S T U D Y C A L E N D A R  
 
 
Pre- 
St u d y  
Da y  1 
Da y 3 
or 4 
Da y 7  
+/ -2 
Da ys  
Da y 
1 0  or 
1 1  
Da y 1 4 
+/ - 4 
Da ys  
Da y 2 8  
+/ - 4 
Da ys  
Da y 4 0 * * *  
+/ - 4 Da ys  
I nvesti g ati o n al A ge nt (s) (secti o n 6. 0) 
 
A 
 
 
I nf or me d c o nse nt scree ni n g ( o pti o nal) 
X 
 
 
 
 
 
 
 
I nf or me d c o nse nt treat me nt 
 
X 
 
 
 
 
 
 
De m o gra p hics  
 
X 
 
 
 
 
 
 
Eli gi bilit y re vie w via me dical rec or d  
X 
 
 
 
 
 
 
 
Me dical hist or y  via me dical rec or d 
re vie w 
 
X 
 
 
 
X 
X 
X 
I n-pers o n e val uati o n  
 
X 
 
 
 
X 
 
 
Tele healt h c o ntact  
 
 
X a 
X a 
X a 
 
 
 
C o nc urre nt me ds  
 
X --------------------------------------------------X  
 
C B C w/ diff, plts * 
 
X  
 
 
 
X * 
 
 
Ser u m c he mistr y, ( C M P) * 
 
X  
 
 
 
X *  
 
 
E K G  f or Q Tc 
 
X b 
 
 
 
X 
X * * * *  
 
A d verse E ve nts  
 
X--------------------------------------------------- X 
 
Sta n dar d of Care Nas o p har y n geal, S wa b 
a n d S A R S -C o V -2 a nti b o d y testi n g, if 
cli nicall y i n dicate d ( o pti o nal)* * * *  
 
 
 
 
 
X * *  
X * *  
X * *  
S p ut u m s a m ple or O P s w a b ( alter n ative)  
 
X 
 
 
 
X 
X 
X 
Bl o o d s a m ple f or I nfl a m m at ory 
cyt oki nes, D-Di mer, C R P, a n d 
Pr oc alcit o ni n a n d ser oc o nversi o n ( 1 0 
m L a n d 6 m L p ur ple t o ps)  
 
X 
 
 
 
X 
X 
X 
Bl o o d s a m ple f or pl atelet st u dies ( 5 m L 
yell o w t o p) ( o pti o n al)  
 
X * *  
 
 
 
X * *  
X * *  
X * *  
C P T t u be ( 8 m L s peckle d t o p)( o pti o n al)  
 
X * *  
 
 
 
X * *  
X * *  
X * *  
S aliv a s a m ple ( o pti o n al)  
 
X * *  
 
 
 
X * *  
X * *  
X * *  
A - base d o n assi g ne d ar m  
* if n ot o btai ne d f or r o uti ne care (f or scree ni n g p hase, if n ot o btai ne d wit hi n t he pre vi o us 3 0 
da ys ; f or treat me nt p hase, if n ot o btai ne d f or r o uti ne care of C O VI D 1 9) 
* * o pti o nal  
* * * Da y 4 0 o nl y occ urs if patie nt’s ser ol o g y is ne gati ve a n d viral R N A is p osit i ve 
* * * * O nl y if i n dicate d f or r o uti ne care   
a p h o ne or tele healt h c o ntact if t he patie nt is a n o ut patie nt  
b E K G m ust b e o btai ne d wit hi n 5 da ys of re gistrati o n  
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 9 
 
1 2.  M E A S U R E M E N T O F E F F E C T 
 
1 2. 1  E v al u ati o n of Res p o nse 
 
S u bjects will be assesse d f or i nci de nce of c ha n ge i n C O VI D 7 -P OI N T O R DI N A L O U T C O M E S 
S C A L E fr o m t he ti me of dia g n osis t o Da y 1 4 ( pri mar y e n d p oi nt) a n d Da y 2 8 (sec o n dar y 
e n d p oi nt).  S u bject s p ut u m sa m ples will be assesse d f or viral R N A b y P C R o n Da y 1, 1 4, 2 8 
(a n d w here i n dicate d at Da y 4 0) i n t he K olesar la b.  Viral l oa ds will be e x presse d i n c o pies per 
m L a n d t he decli ne i n viral c o p y n u m ber will be assesse d bet wee n Da y 1, 1 4, 2 8 (a n d w here 
i n dicate d at Da y 4 0) usi n g S A S.   
 
1 2. 2  Ot her Res p o nse P ar a meters  
 
Partici pa nts’ me dical rec or ds will be use d t o assess t he de vel o p me nt of se vere res pirat or y or 
ot her or ga n fail ure i n t he st u d y p o p ulati o n at 4 0 da ys, as well as t o assess m ortalit y a n d rate of 
se vere a d verse e ve nts defi ne d as gra de 3 n o n he mat ol o gic or greater b y D MI D T o xicit y Scale f or 
Deter mi ni n g Se verit y of A d verse E ve nts.   
 
Safet y, t olera bilit y a n d c o m plia nce wit h of eac h re gi me n will be rec or de d o n case re p ort f or ms.  
 
 
1 3.  S T U D Y A P P R O V A L, O V E R SI G H T  A N D  D A T A R E P O R TI N G / R E G U L A T O R Y 
R E Q UI R E M E N T S  
 
1 3. 1  Pr ot oc ol Re vie w a n d M o nit ori n g C o m mittee a n d I nstit uti o n al  Re vie w B o ar d Re vie w 
 
Bef ore i m pl e me nti n g t his st u d y, t he pr ot oc ol m ust be re vie we d b y t he Mar ke y Ca ncer Ce nter’s 
Pr ot oc ol Re vie w a n d M o nit ori n g C o m mittee a n d t he pr ot oc ol, t he pr o p ose d i nf or me d c o nse nt 
f or m a n d ot her i nf or mati o n t o s u bjects, m ust be re vie we d b y t he U ni versit y of Ke nt uc k y 
I nstit uti o nal Re vie w B oar d (I R B). A si g ne d a n d date d U K I R B i nitial re vie w a p pr o val me m o 
m ust be mai ntai ne d i n t he Mar ke y Ca ncer Ce nter Cli nical Researc h Office ( M C C C R O) 
re g ulat or y bi n der. A n y a me n d me nts t o t he pr ot oc ol, ot her t ha n a d mi nistrati ve o nes, m ust be 
re vie we d a n d a p pr o ve d b y t he P R M C, st u d y s p o ns or a n d t he U K I R B.   
 
1 3. 2  Q u alit y Ass ur a nce   
 
T he M C C places t he hi g hest pri orit y o n e ns uri n g t he safet y of s u bjects partici pati n g i n cli nical 
trials a n d o n t he q ualit y of data o btai ne d fr o m cli nical a n d tra nslati o n researc h.  T he M C C 
Q ualit y Ass ura nce ( Q A) Office o versees t he mai nte na nce of q ualit y sta n dar ds i n cli nical ca ncer 
researc h t hr o u g h cli nical data m o nit ori n g of I n vesti gat or-I nitiate d Trials (II Ts) a n d r o uti ne 
a u dits. 
 
1 3. 2. 1  Data M o nit ori n g  
 
T he M C C Q A Office will c olla b orate wit h t he PI, Bi ostatisticia ns a n d Data Ma na ge me nt S pecialist 
i n creati n g a Cli nical Data M o nit ori n g Pla n ( C D M P) usi n g a ris k -base d a p pr oac h . T he C D M P will 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 0 
 
descri be t he sc o pe, c o m m u nicati o n pla n, a n d fre q ue nc y of m o nit ori n g visits. I n a d diti o n, descri be 
q uer y s u b missi o ns a n d res ol uti o ns, acti o n ite ms a n d m o nit ori n g re p orts.  
 
T he Q A m o nit or assi g ne d t o t he trial will perf or m t he m o nit ori n g tasks i n acc or da nce wit h t he 
pr ot oc ol- s pecific C D M P. T h e m o nit ori n g pr ocess will pr o vi de researc h staff a n d t he PI wit h t he 
o p p ort u nit y t o e val uate t he pr o gress of t he st u d y, verif y t he acc urac y a n d c o m plete ness of t he 
case re p ort f or ms, ass ure t hat all pr ot o c ol re q uire me nts, i ncl u di n g a p plica ble 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 pr o m pt res ol uti o n of a n y i nc o nsiste ncies i n t he 
st u d y rec or ds. 
 
1 3. 2. 2  A u dit 
 
T o e ns ure c o m plia nce wit h t he I nter nati o nal C o nfere nce o n Har m o nisati o n of G o o d Cli nical 
Practice  G ui deli nes a n d all a p plica ble re g ulat or y re q uire me nts, t he M C C A u dit C o m mittee will 
c o n d uct a q ualit y ass ura nce a u dit. A mi ni m u m of  1 0 % of patie nts e nr olle d i n t he st u d y ma y be 
selecte d f or re vie w. T he p ur p ose of a M C C a u dit is t o s yste maticall y a n d i n de pe n de ntl y e xa mi ne 
all st u d y-relate d acti vities a n d d oc u me nts t o deter mi ne w het her t hese acti vities were c o n d ucte d, 
a n d data were rec or de d,  a nal yze d, a n d acc uratel y re p orte d acc or di n g t o t he pr ot oc ol, G o o d Cli nical 
Practice  g ui deli nes  of  t he  I nter nati o nal  C o nfere nce  o n  Har m o nizati o n,  a n d  a n y  a p plica ble  
re g ulat or y re q uire me nts.  
 
1 3. 3  D at a a n d S afet y M o nit ori n g C o m mittee 
 
T he M C C Data a n d Safet y M o nit ori n g C o m mittee ( D S M C) will o versee t he c o n d uct of t his trial. 
T he M C C D S M C perf or ms r o uti ne real -ti me data m o nit ori n g a n d safet y re vie w of all trials, wit h 
a s pecial f oc us u p o n i n vesti gat or -i nitiate d trials (II Ts). T he M C C D S M C will c o n d uct re vie w of 
the  trial  o n  a  sc he d ule  deter mi ne d  b y t he  M C C  Pr ot oc ol  Re vie w  &  M o nit ori n g  C o m mittee  
( P R M C).  
 
T he M C C D S M C will m o nit or t he f oll o wi n g ele me nts of t he trial: a d verse e ve nt a nal ysis, seri o us 
a d verse  e ve nts,  pr ot oc ol  de viati o ns/ vi olati o ns,  a n d  accr ual.  I n  a d diti o n,  w he n  a p plica ble  t he 
D S M C  will re vie w Q A a u dits a n d m o nit ori n g re p orts, pre vi o us re vie ws b y t he D S M C, s u g geste d 
acti o ns b y ot her c o m mittees   (s uc h as t he I R B, U K Ris k Ma na ge me nt C o m mittee), a n d ot her 
para meters a n d o utc o mes as deter mi ne d b y t he D S M C. If a p pr o priate, t he D S M C will desi g nate 
a n d m o nit or c orrecti ve acti o n(s) base d o n re vie w o utc o me. T he M C C D S M C has t he a ut h orit y t o 
a me n d, te m p oraril y s us pe n d, or ter mi nate t he trial base d u p o n patie nt safet y or c o m plia nce matters.  
A d verse e ve nt lists, g ui deli nes, a n d i nstr ucti o ns f or A E re p orti n g ca n be f o u n d i n Secti o n 1 0. 0 
( A d verse E ve nts: List a n d Re p orti n g Re q uire me nts). 
 
1 3. 4  D at a Re p orti n g 
 
1 3. 4. 1  Met h o d 
 
T his st u d y will re q uire mi ni mal data  set s u b missi o n a n d re p orti n g via t he O n C ore E nter prise 
Researc h Cli nical Trials Ma na ge me nt S yste m. Case re p ort f or ms will be create d i n a Re d Ca p 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 1 
 
data base.   I nstr ucti o ns f or s u b mitti n g data is liste d i n st u d y-s pecific g ui da nce d oc u me nts. T hese 
g ui da nce d oc u me nts ma y i ncl u de a n y of t he f oll o wi n g, as a p pr o priate f or t he sc o pe of t he st u d y: 
e C R F C o m pleti o n G ui deli nes, Data Ma na ge me nt S pecificati o ns, S u bject C o ns ole G ui de, a n d 
Q uer y Res ol uti o n G ui de.  
 
1 3. 4. 2  Res p o nsi bilit y f or Data S u b missi o n 
 
T his trial will be m o nit ore d b y t he M C C Data a n d Safet y M o nit ori n g C o m mittee ( D S M C) o n a  
sc he d ule deter mi ne d b y t he Pr ot oc ol Re vie w a n d M o nit ori n g C o m mittee at t he i nitial P R M C 
re vie w.  St u d y staff are res p o nsi ble f or s u b mitti n g st u d y data a n d/ or data f or ms as per t he Mar ke y 
Ca ncer  Ce nter  S O Ps.   St u d y  staff  are  res p o nsi ble  f or  c o m pili n g  a n d  s u b mitti n g  data  f or  all 
partici pa nts a n d f or pr o vi di n g t he data t o t he Pri nci pal I n vesti gat or f or re vie w.   
 
1 3. 5  D at a M a n a ge me nt  
 
Data ma na ge me nt will be perf or me d b y cr oss -tea m me m bers at M C C.  T hese tea m me m bers will 
i ncl u de re prese ntati ves fr o m t he Bi ostatistics a n d Bi oi nf or matics S R F, a n d t he Q ualit y Ass ura nce 
Office.  T he y will w or k cl osel y wit h st u d y staff t o e ns ure ti mel y a n d acc urate data s u b missi o n.  A 
pr ot oc ol- s pecific  Data  Ma na ge me nt  Pla n  ( D M P)  will  be  a ut h ore d  b y  t he  bi ostatisticia n  a n d  
Pri n ci pal I n vesti gat or wit h eac h e x pecte d t o re vie w a n d a p pr o ve t he fi nalizati o n of t he D M P.  I n 
or der t o mai ntai n best cli nical practices i n data ma na ge me nt, t he D M P ma y i ncl u de, b ut n ot be 
li mite d t o: C R F/e C R F desi g n, data base b uil d a n d desi g n, data base trai ni n g, e dit c hec k/ vali dati o n 
s pecificati o ns,  st u d y  data base  testi n g/release,  data  a n d  pa per  w or kfl o w,  re p ort,  metrics,  
q uer y/ discre pa nc y ma na ge me nt, ma na ge me nt of e xter nal (i ncl u di n g la b) data, me dical c o di n g, 
S A E ha n dli n g/rec o nciliati o n, data tra nsfers a n d  data base l oc k. T he pr ot oc ol -s pecific D M P will 
a d diti o nall y defi ne t he sc he d ule at w hic h data will be accesse d b y data ma na ge me nt a n d st u d y 
statisticia n t o perf or m statistical pr o gra m mi n g f or c o n d uct of data q ualit y, data c o ntr ol, data 
ma na ge me nt, ge nerati o n of i nteri m re p orts a n d statistical a nal ysis. Cr oss -tea m me m bers will 
c olla b orate t o esta blis h pr oce d ures a n d ti meli nes f or q ualit y c o ntr ol, a u dits, q uer y res ol uti o n, 
a n n ual re p orts, i nteri m a nal ysis a n d fi nal data a nal ysis.  
 
1 3. 6  C o m pli a nce wit h L a ws a n d Re g ul ati o ns 
 
T he st u d y will be c o n d ucte d i n acc or da nce wit h U. S. F o o d a n d Dr u g A d mi nistrati o n ( F D A) a n d 
I nter nati o nal C o nfere nce o n Har m o ni zati o n (I C H) G ui deli nes f or G o o d Cli nical Practice ( G C P), 
t he Declarati o n of Helsi n ki, a n y a p plica ble l ocal healt h a ut h orit y, a n d I nstit uti o nal Re vie w B oar d 
(I R B) re q uire me nts.  T he PI or desi g nee will be res p o nsi ble f or o btai ni n g c o nti n ui n g a n d n ot less 
t ha n a n n ual I R B re-a p pr o val t hr o u g h o ut t he d urati o n of t he st u d y.  C o pies of t he I n vesti gat or’s 
a n n ual re p ort t o t he I R B a n d c o pies of t he I R B c o nti n ua nce of a p pr o val m ust mai ntai ne d b y t he 
M C C C R O.  T he PI or desi g nee is als o res p o nsi ble f or n otif yi n g t he Data a n d Safet y M o nit ori n g 
C o m mittee of t he M C C a n d t he U K I R B of a n y si g nifica nt a d verse e ve nts t hat are seri o us a n d/ or 
u ne x pecte d, as per S O P’s of t h ose e ntities  a n d c o m plia nce wit h pr ot oc ol re q uire me nts. D S M C 
will re vie w all a d verse e ve nts of t his II T as per its S O P.  
 
1 4.  R E F E R E N C E S  
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 2 
 
1.  
d el Ri o C, M al a ni P N. C O VI D -1 9 — N e w I nsi g hts o n a R a pi dl y C h a n gi n g E pi d e mic. 
J A M A 2 0 2 0.  
2.  
H u a n g C, W a n g Y, Li X et al. Cli nic al f e at ur es of p ati e nts i nf ect e d wit h 2 0 1 9 n o v el 
c or o n a vir us i n W u h a n, C hi n a. L a nc et 2 0 2 0; 3 9 5: 4 9 7 -5 0 6.  
3.  
S o hr a bi C, Als afi Z, O' N eill N et al. W orl d H e alt h Or g a niz ati o n d ecl ar es gl o b al 
e m er g e ncy: A r e vi e w of t h e 2 0 1 9 n o v el c or o n a vir us ( C O VI D -1 9). I nt J S ur g 2 0 2 0; 7 6: 7 1 -7 6.  
4.  
W u Z, Mc G o o g a n J M. C h ar act eristics of a n d I m p ort a nt L ess o ns Fr o m t h e C or o n a vir us 
Dis e as e 2 0 1 9 ( C O VI D -1 9) O ut br e a k i n C hi n a: S u m m ar y of a R e p ort of 7 2 3 1 4 C as es Fr o m t h e 
C hi n es e C e nt er f or Dis e as e C o ntr ol a n d Pr e v e nti o n. J A M A 2 0 2 0.  
5.  
G u a n W -j, Ni Z-y, H u Y et al. Cli nic al C h ar act eristics of C or o n a vir us Dis e as e 2 0 1 9 i n 
C hi n a. N e w E n gl a n d J o ur n al of M e dici n e 2 0 2 0.  
6.  
C h e n N, Z h o u M, D o n g X et al. E pi d e mi ol o gic al a n d cli nic al c h ar act eristics o f 9 9 c as es 
of 2 0 1 9 n ov el c or o n a vir us p n e u m o ni a i n W u h a n, C hi n a: a d escri pti v e st u d y. L a nc et 2 0 2 0; 3 9 5: 
5 0 7 -5 1 3.  
7.  
W a n g D, H u B, H u C et al. Cli nic al C h ar act eristics of 1 3 8 H os pit aliz e d P ati e nts Wit h 
2 0 1 9 N o v el C or o n a vir us -I nf ect e d P n e u m o ni a i n W u h a n, C hi na. J A M A 2 0 2 0.  
8.  
X u X W, W u X X, Ji a n g X G et al. Cli nic al fi n di n gs i n a gr o u p of p ati e nts i nf ect e d wit h 
t h e 2 0 1 9 n o v el c or o n a vir us ( S A R S-C ov -2) o utsi d e of W u h a n, C hi n a: r etr os p ecti v e c as e s eri es. 
B MJ 2 0 2 0; 3 6 8: m 6 0 6.  
9.  
W u C, C h e n X, C ai Y et al. Ris k F act or s Ass oci at e d Wit h Ac ut e R es pir at or y Distr ess 
S y n dr o m e a n d D e at h i n P ati e nts Wit h C or o n a vir us Dis e as e 2 0 1 9 P n e u m o ni a i n W u h a n, C hi n a. 
J A M A I nt er n al M e dici n e 2 0 2 0. 
1 0.  
Gi ac o m elli A, P ezz ati L, C o nti F et al. S elf -r e p ort e d olf act or y a n d t ast e dis or d ers i n 
S A R S- C o V -2 p ati e nts: a cr oss -s ecti o n al st u d y. Cli n I nf ect Dis 2 0 2 0. 
1 1.  
G ar g S KL, W hit a k er M, O’ H all or a n A, C u m mi n gs C. H os pit aliz ati o n R at es a n d 
C h ar act eristics of P at e nts H os pit aliz e d wit h L a b or at or y -C o nfir m e d C or o n a vir us Dis e as e 2 0 1 9 - 
C O VI D - N E T, 1 4 St at e s, M arc h 1-3 0, 2 0 2 0. M M W R M or b M ort al W kl y R e p 2 0 2 0.  
1 2.  
B hi mr aj A M R, S h u m a k er A H, L a v er g n e V, B a d e n L, C h e n g V C C, E d w ar ds K M, G a n d hi 
R, M ull er WJ, O’ H or o J C, S h o h a m S, M ur a d M H, M ust af a R A, S ult a n S, F alc k -Ytt er Y. I nf ecti o us 
Dis e as es S oci ety of A m eric a G ui d eli n es o n t h e Tr e at m e nt a n d M a n a g e m e nt of P ati e nts wit h 
C O VI D -1 9 I nf ecti o n. I n. 2 0 2 0.  
1 3.  
C al y L, Dr uc e J D, C att o n M G et al. T h e F D A -a p pr ov e d Dr u g Iv er m ecti n i n hi bits t h e 
r e plic ati o n of S A R S-C o V -2 i n vitr o. A nti vir al R es 2 0 2 0; 1 0 4 7 8 7.  
1 4.  
C al y L, Dr uc e  J D, C att o n M G et al. T h e F D A-a p pr ov e d dr u g i v er m ecti n i n hi bits t h e 
r e plic ati o n of S A R S-C o V -2 i n vitr o. A nti vir al R es 2 0 2 0; 1 7 8: 1 0 4 7 8 7.  
1 5.  
Lifsc hitz A, Vir k el G, S all ovitz J et al. C o m p ar ati v e distri b uti o n of i v er m ecti n a n d 
d or a m ecti n t o p ar asit e l oc ati o n tiss u es i n c attl e. V et P ar asit ol 2 0 0 0; 8 7: 3 2 7 -3 3 8.  
1 6.  
Y a m a y a M, S hi m ot ai Y, H at ac hi Y et al. T h e s eri n e pr ot e as e i n hi bit or c a m ost at 
i n hi bits i nfl u e nz a vir us r e plic ati o n a n d c yt o ki n e pr o d ucti o n i n pri m ar y c ult ur es of h u m a n 
tr ac h e al e pit h eli al c ells. P ulm P h ar m ac ol T h er 2 0 1 5; 3 3: 6 6 -7 4.  
1 7.  
H off m a n n M, Kl ei n e -W e b er H, Sc hr o e d er S et al. S A R S -C o V -2 C ell E ntr y D e p e n ds o n 
A C E 2 a n d T M P R S S 2 a n d Is Bl oc k e d b y a Cli nic all y Pr ov e n Pr ot e as e I n hi bit or. C ell 2 0 2 0; 1 8 1: 2 7 1 -
2 8 0. e 2 7 8.  

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 3 
 
1 8.  
K a w as e M, S hir at o K, v a n d er H o e k L et al. Si m ult a n e o us tr e at m e nt of h u m a n 
br o nc hi al e pit h eli al c ells wit h s eri n e a n d c yst ei n e pr ot e as e i n hi bit ors pr e v e nts s e v er e ac ut e 
r es pir at or y sy n dr o m e c or o n a vir us e ntr y. J Vir ol 2 0 1 2; 8 6: 6 5 3 7-6 5 4 5.  
1 9.  
Z h o u Y, V e d a nt h a m P, L u K et al. Pr ot e as e i n hi bit ors t ar g eti n g c or o n a vir us a n d 
fil ovir us e ntr y. A nti vir al R es 2 0 1 5; 1 1 6: 7 6-8 4.  
2 0.  
C o ot e K, At h ert o n -W ats o n H C, S u g ar R et al. C a m ost at att e n u at es air w a y e pit h eli al 
s o di u m c h a n n el f u ncti o n i n vi v o t hr o u g h t h e i n hi biti o n of a c h a n n el-activ ati n g pr ot e a s e. J 
P h ar m ac ol Ex p T h er 2 0 0 9; 3 2 9: 7 6 4 -7 7 4.  
2 1.  
R o w e S M, R e e v es G, H at h or n e H et al. R e d uc e d s o di u m tr a ns p ort wit h n as al 
a d mi nistr ati o n of t h e pr ost asi n i n hi bit or c a m ost at i n s u bj ects wit h c ystic fi br osis. C h est 2 0 1 3; 
1 4 4: 2 0 0 -2 0 7.  
2 2.  
S ai J K, S u y a m a M, K u b o k a w a Y et al. Effic acy of c a m ost at m esil at e a g ai nst d ys p e psi a 
ass oci at e d wit h n o n -alc o h olic mil d p a ncr e atic dis e as e. J o ur n al of G astr o e nt er ol o g y 2 0 1 0; 4 5: 
3 3 5 -3 4 1.  
2 3.  
P ar n h a m MJ, Er a k ovic H a b er V, Gi a m ar ell os -B o ur b o ulis EJ et al. Azit hr o m yci n: 
m ec h a nis ms of acti o n a n d t h eir r el e v a nc e f or cli nic al a p plic ati o ns. P h ar m ac ol T h er 2 0 1 4; 1 4 3: 
2 2 5 -2 4 5.  
2 4.  
G a o J, Ti a n Z, Y a n g X. Br e a kt hr o u g h: C hl or o q ui n e p h os p h at e h as s h o w n a p p ar e nt 
effic ac y i n tr e at m e nt of C O VI D -1 9 ass oci at e d p n e u m o ni a i n cli nic al st u d i es. Bi osci Tr e n ds 2 0 2 0; 
1 4: 7 2 -7 3.  
2 5.  
Vi nc e nt MJ, B er g er o n E, B e nj a n n et S et al. C hl or o q ui n e is a p ot e nt i n hi bit or of S A R S 
c or o n a vir us i nf ecti o n a n d s pr e a d. Vir ol J 2 0 0 5; 2: 6 9.  
2 6.  
K e y a erts E, Vij g e n L, M a es P et al. I n vitr o i n hi biti o n of s e v er e ac ut e r es pir at or y 
s y n dr o m e c or o n a vir us b y c hl or o q ui n e. Bi oc h e m Bi o p h ys R es C o m m u n 2 0 0 4; 3 2 3: 2 6 4 -2 6 8.  
2 7.  
D e v a ux C A, R ol ai n J M, C ols o n P, R a o ult D. N e w i nsi g hts o n t h e a nti vir al eff ects of 
c hl or o q ui n e a g ai nst c or o n a vir us: w h at t o ex p ect f or C O VI D -1 9 ? I nt J A nti m icr o b A g e nts 2 0 2 0; 
1 0 5 9 3 8.  
2 8.  
W a n g M, C a o R, Z h a n g L et al. R e m d esi vir a n d c hl or o q ui n e eff ecti v ely i n hi bit t h e 
r ec e ntl y e m er g e d n ov el c or o n a vir us ( 2 0 1 9-n C o V) i n vitr o. C ell R es e arc h 2 0 2 0; 3 0: 2 6 9 -2 7 1.  
2 9.  
H or b y P L M. R a n d o mis e d E v al u ati o n of C ovi d -1 9 T h er a p y: N C T 0 4 3 8 1 9 3 6: N o cli nic al 
b e n efit fr o m us e of h y dr ox yc hl or o q ui n e i n h os pit alis e d p ati e nts wit h C O VI D -1 9. I n. 2 0 2 0.  
3 0.  
R estr e p o A. U p d at e o n h y dr ox yc hl or o q ui n e, W H O. I n. 2 0 2 0.  
3 1.  
Hi nt o n D. L ett er R e v o ki n g t h e E m er g e nc y Us e A ut h oriz ati o n f or E m er g e nc y Us e of 
C hl or o q ui n e P h os p h at e a n d H y dr oxyc hl or o q ui n e S ulf at e a g ai nst C ovi d -1 9. I n S er vic es D o H a H 
( e d). F D A w e bsit e: 2 0 2 0. 
3 2.  
J u urli n k D N. S af et y c o nsi d er ati o ns wit h c hl or o q ui n e, h y dr ox yc hl or o q ui n e a n d 
azit hr o m yci n i n t h e m a n a g e m e nt of S A R S -C o V -2 i nf ecti o n.  C m aj 2 0 2 0.  
3 3.  
R et all ac k H, Di L ull o E, Ari as C et al. Zi k a vir us c ell tr o pis m i n t h e d e v el o pi n g h u m a n 
br ai n a n d i n hi biti o n b y azit hr o m yci n. Pr oc N atl Ac a d Sci U S A 2 0 1 6; 1 1 3: 1 4 4 0 8 -1 4 4 1 3.  
3 4.  
M a dri d P B, P a nc h al R G, W arr e n T K et al. E v al u ati o n of E b ol a V ir us I n hi bit ors f or Dr u g 
R e p ur p osi n g. A C S I nf ect Dis 2 0 1 5; 1: 3 1 7 -3 2 6.  

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 4 
 
3 5.  
B ac h ari er L B, G uil b ert T W, M a u g er D T et al. E arl y A d mi nistr ati o n of Azit hr o m yci n 
a n d Pr e v e nti o n of S e v er e L o w er R es pir at or y Tr act Ill n ess es i n Pr esc h o ol C hil dr e n Wit h a Hist or y 
of S uc h Ill n ess es: A R a n d o miz e d Cli nic al Tri al. J A M A 2 0 1 5; 3 1 4: 2 0 3 4 -2 0 4 4.  
3 6.  
G a utr et P, L a gi er J C, P ar ol a P et al. H y dr ox yc hl or o q ui n e a n d azit hr o m yci n as a 
tr e at m e nt of C O VI D-1 9: r es ults of a n o p e n -l a b el n o n-r a n d o miz e d cli nic al tri al. I nt J A nti micr o b 
A g e nts 2 0 2 0; 1 0 5 9 4 9.  
3 7.  
M oli n a J M, D el a u g err e C, G off JL et al. M e d M al I nf ect 2 0 2 0.  
3 8.   
K o nst at-K orz e n n y E, Asc e nci o -Ar a g o n J A, Ni ez e n -L u g o S, V az q u ez-L o p ez R. 
Art e misi ni n a n d Its S y nt h etic D eri v ati v es as a P ossi bl e T h er a p y f or C a nc er. M e d Sci ( B as el) 2 0 1 8; 
6.  
3 9.  
R aff eti n A, Br u n e el F, R o uss el C et al. Us e of art es u n at e i n n o n -m al ari al i n dic ati o ns. 
M e d M al I nf ect 2 0 1 8; 4 8: 2 3 8 -2 4 9.  
4 0.  
M u n y a n gi J, C or n et -V er n et L, I d u m b o M et al. Art e misi a a n n u a a n d Art e misi a afr a 
t e a i nf usi o ns vs. art es u n at e-a m o di a q ui n e ( A S A Q) i n tr e ati n g Pl as m o di u m f alci p ar u m m al ari a i n 
a l ar g e sc al e, d o u bl e bli n d, r a n d o miz e d cli nic al tri al. P h yt o m e dici n e 2 0 1 9; 5 7: 4 9 -5 6.  
4 1.  
Gil m or e K O, K; S e e b er g er, P H. Art e misi a a n n u a Pl a nt Extr acts ar e Acti v e A g ai nst 
S A R S -C o V -2 I n Vitr o"; s u b mitt e d f or p u blic ati o n. I n. 2 0 2 0.  
4 2.  
Ar or a M, S ax e n a P, C h o u d h ar y D K et al. D u al s y m bi osis b et w e e n Pirif or m os p or a 
i n dic a a n d Az ot o b act er c hr o oc occ u m e n h a nc es t h e art e misi ni n c o nt e nt i n Art e misi a a n n u a L. 
W orl d J Micr o bi ol Bi ot ec h n ol 2 0 1 6; 3 2: 1 9.  
4 3.  
D esr osi ers M R, Mittl e m a n A, W e at h ers PJ. Dri e d L e af Art e misi a A n n u a I m pr ov es 
Bi o a v ail a bilit y of Art e misi ni n vi a C yt oc hr o m e P 4 5 0 I n hi biti o n a n d E n h a nc es Art e misi ni n Effic acy 
D o w nstr e a m. Bi o m ol ec ul es 2 0 2 0; 1 0: 2 5 4.  
4 4.  
A dj ei G O, K urtz h als J AL, R o dri g u es O P et al. A m o di a q ui n e -art es u n at e vs art e m et h er -
l u m ef a ntri n e f or u nc o m plic at e d m al ari a i n G h a n ai a n c hil dr e n: a r a n d o miz e d effic ac y a n d s af et y 
tri al wit h o n e y e ar f oll o w-u p. M al ari a j o ur n al 2 0 0 8; 7: 1 2 7 -1 2 7.  
4 5.  
G ui di M, M erci er T, A o uri M et al. P o p ul ati o n p h ar m ac o ki n etics a n d 
p h ar m ac o d y n a mics of t h e art es u n at e – m efl o q ui n e fix e d d os e c o m bi n ati o n f or t h e tr e at m e nt of 
u nc o m plic at e d f alci p ar u m m al ari a i n Afric a n c hil dr e n. M al ari a J o ur n al 2 0 1 9; 1 8: 1 3 9.  
4 6.  
N di a y e JL, R a n dri a n ari v el oj osi a M, S a g ar a I et al. R a n d o miz e d, m ultic e ntr e 
as s ess m e nt of t h e effic ac y a n d s af ety of A S A Q – a fix e d -d os e art es u n at e -a m o di a q ui n e 
c o m bi n ati o n t h er a p y i n t h e tr e at m e nt of u nc o m plic at e d Pl as m o di u m f alci p ar u m m al ari a. 
M al ari a J o ur n al 2 0 0 9; 8: 1 2 5.  
4 7.  
C e nt er f or Dis e as e C o ntr ol: I nf or m ati o n f or H e alt hc ar e Pr of essi o n als: C O VI D -1 9 a n d 
U n d erl yi n g C o n diti o ns. I n. N ati o n al C e nt er f or I m m u niz ati o n a n d R es pir at or y Dis e as es ( N CI R D), 
Di visi o n of Vir al Dis e as es.  
4 8.  
M a h aj a n R, G u pt a K. A d a pti v e d esi g n cli nic al tri als: M et h o d ol o g y, c h all e n g es a n d 
pr os p ect. I n di a n j o ur n al of p h ar m ac ol o g y 2 0 1 0; 4 2: 2 0 1 -2 0 7.  
4 9.  
B a u er P, Ki es er M. C o m bi ni n g diff er e nt p h as es i n t h e d e v el o p m e nt of m e dic al 
tr e at m e nts wit hi n a si n gl e tri al. St at M e d 1 9 9 9; 1 8: 1 8 3 3-1 8 4 8.  
5 0.  
B erry S M, Si n g h C, L a n g J D et al. Str e a mli ni n g g e n e ex pr essi o n a n al ys is: i nt e gr ati o n 
of c o -c ult ur e a n d m R N A p urific ati o n. I nt e gr Bi ol ( C a m b) 2 0 1 4; 6: 2 2 4 -2 3 1.  

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 5 
 
5 1.  
B erry S M, Al ari d E T, B e e b e DJ. O n e -st e p p urific ati o n of n ucl eic aci d f or g e n e 
ex pr essi o n a n al ysis vi a I m misci bl e Filtr ati o n Assist e d b y S urf ac e T e nsi o n (I F A S T). L a b C hi p 2 0 1 1; 
1 1: 1 7 4 7 -1 7 5 3.  
5 2.  
B erry S M, P ezzi H M, Willi a ms E D et al. Usi n g Excl usi o n -B as e d S a m pl e Pr e p ar ati o n 
( E S P) t o R e d uc e Vir al L o a d Ass a y C ost. PL o S O n e 2 0 1 5; 1 0: e 0 1 4 3 6 3 1. 
5 3.  
C as a v a nt B P, G uc k e n b er g er DJ, B e e b e DJ, B err y S M. Effici e nt s a m pl e pr e p ar ati o n 
fr o m c o m pl ex bi ol o gic al s a m pl es usi n g a sli di n g li d f or i m m o biliz e d dr o pl et extr acti o ns. A n al 
C h e m 2 0 1 4; 8 6: 6 3 5 5 -6 3 6 2.  
5 4.  
S p er g er J M, Str ot m a n L N, W els h A et al. I nt e gr at e d A n al ysis of M ulti pl e Bi o m ar k ers 
fr o m Circ ul ati n g T u m or C ells E n a bl e d b y Excl usi o n -B as e d A n al yt e Is ol ati o n. Cli n C a nc er R es 
2 0 1 7; 2 3: 7 4 6 -7 5 6.  
5 5.  
Sc h e hr JL, Sc h ultz Z D, W arric k J W et al. Hi g h S p ecificity i n Circ ul ati n g T u m or C ell 
I d e ntific ati o n Is R e q uir e d f or Acc ur at e E v al u ati o n of Pr o gr a m m e d D e at h-Li g a n d 1. PL o S O n e 
2 0 1 6;  1 1: e 0 1 5 9 3 9 7.  
5 6.  
W o n g C K, L a m C W, W u A K et al. Pl as m a i nfl a m m at or y c yt oki n es a n d c h e m o ki n es i n 
s e v er e ac ut e r es pir at ory s y n dr o m e. Cli n Ex p I m m u n ol 2 0 0 4; 1 3 6: 9 5-1 0 3.  
5 7.  
M a h all a wi W H, K h a b o ur O F, Z h a n g Q et al. M E R S -C o V i nf ecti o n i n h u m a ns is 
ass oci at e d wit h a pr o -i nfl a m m at ory T h 1 a n d T h 1 7 c yt o ki n e pr ofil e. C yt o ki n e 2 0 1 8; 1 0 4: 8-1 3.  
5 8.  
G e e J R, S altzst ei n D R, Ki m K et al. A P h as e II R a n d o miz e d, D o u bl e -bli n d, Pr es ur gic al 
Tri al of P ol y p h e n o n E i n Bl a d d er C a nc er P ati e nts t o E v al u at e P h ar m ac o d y n a mics a n d Bl a d d er 
Tiss u e Bi o m ar k ers. C a nc er Pr e v R es ( P hil a) 2 0 1 7; 1 0: 2 9 8 -3 0 7.  
5 9.  
El e w a H, Wil b y KJ. A R e vi e w of P h ar m ac o g e n etics of A nti m al ari als a n d Ass oci at e d 
Cli nic al I m plic ati o ns. E ur J Dr u g M et a b P h ar m ac o ki n et 2 0 1 7; 4 2: 7 4 5 -7 5 6.  
 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 6 
 
A P P E N DI X A: O B E SI T Y S C A L E 
 
 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 7 
 
A P P E N DI X B:  C O VI D 7 -P OI N T O R DI N A L O U T C O M E S S C A L E  
htt p:// w w w. w h o.i nt/ bl ue pri nt/ pri orit y -diseases/ ke y -acti o n/ n o vel-c or o na vir us/e n/ 
 
C O VI D 7 -p oi nt or di n al o utc o mes sc ale:  
1.  Deat h  
2.  H os pitalize d o n i n vasi ve mec ha nical ve ntilati o n or E C M O  
3.  H os pitalize d o n n o n-i n vasi ve ve ntilati o n or hi g h fl o w nasal ca n n ula 
4.  H os pitalize d o n s u p ple me ntal o x y ge n 
5.  H os pitalize d n ot o n s u p ple me ntal o x y ge n 
6.  N ot h os pitalize d wit h li mitati o n i n acti vit y (c o nti n ue d s y m pt o ms)  
7.  N ot h os pitalize d wit h o ut li mitati o n i n acti vit y ( n o s y m pt o ms)  
 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 8 
 
A P P E N DI X C: PI L L / P R O D U C T DI A R I E S  
 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 9 
 
 
St u d y P artici p a nt Self -A d mi nistr ati o n St u d y Dr u g Di ar y  
 
Please rec or d h o w ma n y ta blets y o u ta ke, t he ti me y o u ta ke t he m a n d a n y c o m me nts bel o w a n d 
bri n g t he c o m plete d Diar y as well as y o ur st u d y dr u g s u p pl y, i ncl u di n g e m pt y b ottles, t o e ver y 
st u d y visit. T his will hel p us kee p trac k of y o ur st u d y dr u g a n d h o w well y o u are t olerati n g it. 
Ar m C 
 
P artici p a nt I de ntifier:   
  
 
Pr ot oc ol #: M C C -2 0 -C O VI D -0 1 -P M C  
D oct or:  J a mes Z a c h ar y P orterfiel d, M D   
  
 
D oct or: S us a n ne M ar kes ber y Ar n ol d, M D  
N urse: e nter n a me a n d p h o ne n u m ber  
 
 
 
Y o u will t a ke t he f oll o wi n g n u m ber of c a ps ules/t a blets e ac h ti me ( per d ose) as liste d i n t he t a ble 
bel o w:  
 
St u d y Dr u g N a me  
# of c a ps ules (t a blets) 
t o t a ke per ti me/ d ose  
# of 
ti mes/ d oses 
e ac h d a y  
A p pr o xi m ate ti me t o t a ke dr u g  
I ver mecti n 
_ _ t a blets/ 1 2 m g -1 5 m g  
                (circle o ne) 
O nce a d a y  
2 h o urs bef ore 
or 2 h o urs 
after a me al  
_ _: _ _ _ 
 a. m . 
 
 
 
D a y  
D ate  
N u m ber of I ver mecti n T a blets  
Ti me of D ose  
1  
 
_ _  
_ _ _ _: _ _ _ _  □ a. m. 
 □ D ose N ot Ta ke n  W h y: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
 
_ _  
_ _ _ _: _ _ _ _  □ a. m. 
 □ D ose N ot Ta ke n  W h y: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
Partici pa nt/ Care gi ver Si g nat ure: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
Date: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
F O R S T U D Y T E A M U S E O N L Y
Staff I nitials:
D ate Dis pe nse d:
Date Ret ur ne d:
# pills/ca ps/ta bs dis pe nse d:
# pills/ca ps/ta bs ret ur ne d:
# pills/ca ps/ta bs t hat s ho uld ha ve bee n ta ke n:
Discre pa nc y N otes:

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 0 
 
 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 1 
 
 
St u d y P artici p a nt Self -A d mi nistr ati o n St u d y Dr u g Di ar y  
 
Please rec or d h o w ma n y ta blets y o u ta ke, t he ti me y o u ta ke t he m a n d a n y c o m me nts bel o w a n d 
bri n g t he c o m plete d Diar y as well as y o ur st u d y dr u g s u p pl y, i ncl u di n g e m pt y b ottles, t o e ver y 
st u d y visit. T his will hel p us kee p trac k of y o ur st u d y dr u g a n d h o w well y o u are t olerati n g it.  
 
Ar m D  
 
Partici pa nt I de ntifier:     
  
 
Pr ot oc ol #: M C C -2 0 -C O VI D -0 1 -P M C   
D oct or:  Ja mes Zac har y P orterfiel d, M D   
 
 
D oct or: S usa n ne Mar kes ber y Ar n ol d, M D  
N urse: e nter n a me a n d p h o ne n u m ber  
  
  
  
  
 
 
 
Y o u will ta ke t he f oll o wi n g n u m ber of ca ps ules/ta blets  eac h ti me ( per d ose)  as liste d i n t he ta ble bel o w:  
 
St u d y Dr u g N a me  
# of c a ps ules 
(t a blets) t o t a ke per 
ti me/ d ose  
# of 
ti mes/ d oses 
e ac h d a y  
A p pr o xi m ate ti me t o t a ke dr u g  
Ca m ostat Mesilate  
2 ta blets  
3 ti mes per 
da y  
_ _: _ _ _ 
 a. m.    
_ _: _ _ _ 
 p. m.  
_ _: _ _ _ 
 p. m.  
 
 
 
 
D a y  
D ate  
N u m ber 
of  
C a m ost at 
Mesil ate    
1 0 0 m g  
Ti me of D ose  
N u m ber 
of  
C a m ost at 
Mesil ate    
1 0 0 m g  
Ti me of D ose  
N u m ber of  
C a m ost at 
Mesil ate  
t a blets 
Ti me of D ose  
1 
 
2 
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
3 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
4 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
5 
 
2  
_ _ _: _ _ _   □ a. m. 
2  
_ _ _: _ _ _   □ p . m. 
2  
_ _ _: _ _ _   □ p . m. 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 2 
 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
6 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
7 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
8 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
9 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 0 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 1 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 2 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 3 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 4 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
Partici pa nt/ Care gi ver Si g nat ure: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
Date: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 3 
 
 
 
F O R S T U D Y T E A M U S E O N L Y
Staff I nitials:
D ate Dis pe nse d:
Date Ret ur ne d:
# pills/ca ps/ta bs dis pe nse d:
# pills/ca ps/ta bs ret ur ne d:
# pills/ca ps/ta bs t hat s ho uld ha ve bee n ta ke n:
Discre pa nc y N otes:

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 4 
 
 
St u d y P artici p a nt Self -A d mi nistr ati o n St u d y B ot a nic al  Di ar y  
 
Please rec or d t he n u m ber of ti mes y o u dri n k t he Arte misia  a n n ua tea or c offee, t he ti me y o u ta ke 
t he m a n d a n y c o m me nts bel o w a n d bri n g t he c o m plete d Diar y as well as y o ur st u d y tea or c offee 
s u p pl y, t o y o ur ne xt st u d y visit. T his will hel p us kee p trac k of y o ur st u d y pr o d uct a n d h o w well 
y o u are t olerati n g it.   
 
Ar m E  
 
Partici pa nt I de ntifier:     
  
 
Pr ot oc ol #: M C C -2 0 -C O VI D -0 1 -P M C   
D oct or:  Ja mes Zac har y P orterfiel d, M D   
 
 
D oct or: S usa n ne Mar kes ber y Ar n ol d, M D  
N urse: e nter n a me a n d p h o ne n u m ber  
  
  
  
  
 
 
 
Y o u will ta ke t he f oll o wi n g n u m ber of ca ps ules/ta blets  eac h ti me ( per d ose)  as liste d i n t he ta ble bel o w:  
 
St u d y B ot a nic al 
Pr o d uct N a me  
d ose  
# of 
ti mes/ d oses 
e ac h d a y  
A p pr o xi m ate ti me t o t a ke te a or 
c offee  
Arte misia  a n n ua   
1 p o d or 2  tea ba gs 
3 ti mes per 
da y  
_ _: _ _ _ 
 a. m.    
_ _: _ _ _ 
 p. m.  
_ _: _ _ _ 
 p. m.  
 
 
 
 
D a y  
D ate  
N u m ber of  
Arte misi a  
a n n u a  te a 
b a g or p o d  
Ti me of D ose  
N u m ber of  
Arte misi a  
a n n u a  te a 
b a g or p o d  
Ti me of D ose  
N u m ber of  
Arte misi a  
a n n u a te a 
b a g or p o d  
Ti me of D ose  
1 
 
_ 
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
3 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
4 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 5 
 
5 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
6 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
7 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
8 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
9 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 0 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 1 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 2 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 3 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 4 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
Partici pa nt/ Care gi ver Si g nat ure: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
Date: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 6 
 
 
 
 
 
F O R S T U D Y T E A M U S E O N L Y
Staff I nitials:
D ate Dis pe nse d:
Date Ret ur ne d:
# pills/ca ps/ta bs dis pe nse d:
# pills/ca ps/ta bs ret ur ne d:
# pills/ca ps/ta bs t hat s ho uld ha ve bee n ta ke n:
Discre pa nc y N otes:

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 7 
 
 
St u d y P artici p a nt Self -A d mi nistr ati o n St u d y Dr u g Di ar y  
 
Please rec or d t he n u m ber of ti mes y o u dri n k t he Artes u nate tea or c offee, t he ti me y o u ta ke t he m 
a n d a n y c o m me nts bel o w a n d bri n g t he c o m plete d Diar y as well as y o ur st u d y tea or c offee 
s u p pl y, t o y o ur ne xt st u d y visit. T his will hel p us kee p trac k of y o ur st u d y dr u g a n d h o w well 
y o u are t olerati n g it.   
 
Ar m F  
 
Partici pa nt I de ntifier:     
  
 
Pr ot oc ol #: M C C -2 0 -C O VI D -0 1 -P M C   
D oct or:  Ja mes Zac har y P orterfiel d, M D   
 
 
D oct or: S usa n ne Mar kes ber y Ar n ol d, M D  
N urse: e nter n a me a n d p h o ne n u m ber  
  
  
  
  
 
 
 
Y o u will ta ke t he f oll o wi n g n u m ber of ca ps ules/ta blets  eac h ti me ( per d ose)  as liste d i n t he ta ble bel o w:  
 
St u d y Dr u g N a me  
d ose  
# of 
ti mes/ d oses 
e ac h d a y  
A p pr o xi m ate ti me t o t a ke dr u g  
Artes u nate   
1 p o d or 2 tea ba gs  
3 ti mes per 
da y  
_ _: _ _ _ 
 a. m.    
_ _: _ _ _ 
 p. m.  
_ _: _ _ _ 
 p. m.  
 
 
 
 
D a y  
D ate  
N u m ber 
of  
Artes u n
ate te a 
b a g or 
p o d  
Ti me of D ose  
N u m ber 
of  
Artes u n at
e te a b a g 
or p o d  
Ti me of D ose  
N u m ber of  
Artes u n ate 
te a b a g or 
p o d  
Ti me of D ose  
1 
 
_ 
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
3 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
4 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 8 
 
5 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
6 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
7 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
8 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
9 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 0 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 1 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 2 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 3 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 4 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
Partici pa nt/ Care gi ver Si g nat ure: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
Date: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 9 
 
 
 
 
 
F O R S T U D Y T E A M U S E O N L Y
Staff I nitials:
D ate Dis pe nse d:
Date Ret ur ne d:
# pills/ca ps/ta bs dis pe nse d:
# pills/ca ps/ta bs ret ur ne d:
# pills/ca ps/ta bs t hat s ho uld ha ve bee n ta ke n:
Discre pa nc y N otes:

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
6 0 
 
 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
6 1 
 
 
A P P E N DI X D: T E L E H E A L T H T RI A G E A N D D RI V E/ T H R O U G H W A L K -I N 
E N R O L L M E N T  
 
 
 
 
 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
6 2 
 
A P P E N DI X E: G E T W E L L L O O P/ C E N T R A LI Z E D C O VI D -1 9 T E L E H E A L T H A T U K 
( C T U) A L G O RI T H M 
 
 
 
 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
6 3 
 
A P P E N DI X F: C U R R E N T R E C R UI T M E N T S T R A T E G Y A N D S C H E M A TI C F O R 
I N T A K E A N D C O N S E N T F O R R E S E A R C H A T R E S E A R C H D E SI G N A T E D C LI NIC 
 
 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
6 4 
 
P A TI E N T F L O W F O R I N T A K E I N T O I D C LI NI C 
 
 
 
 
 

I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
6 5 
 
A P P E N DI X G : T O XI CI T Y G R A DI N G S C A L E S F O R D E T E R MI NI N G S E V E RI T Y O F 
A D V E R S E E V E N T S  
 
htt ps:// w w w. niai d. ni h. g o v/researc h/ d mi d -safet y-re p orti n g- p har mac o vi gila nce 
 
A D U L T T O XI CI T Y T A B L E S  
 
A B B R E VI A TI O N S : A b bre viati o ns utilize d i n t he Ta ble:  
 
U L N = U p per Li mit of N or mal L L N = L o wer Li mit of N or mal  
R x = T hera p y Re q = Re q uire d  
M o d = M o derate I V  = I ntra ve n o us  
A D L = Acti vities of Dail y Li vi n g Dec = Decrease d  
 
E S TI M A TI N G S E V E RI T Y G R A D E  
 
F or a b n or malities N O T f o u n d else w here i n t he T o xicit y Ta bles use t he scale bel o w t o esti mate 
gra de of se verit y:  
 
G R A D E 1 Mil d  
Tra nsie nt or mil d disc o mf ort (< 4 8 h o urs); n o me dical 
i nter ve nti o n/t hera p y re q uire d  
 
G R A D E 2 M o der ate  
Mil d t o m o derate li mitati o n i n acti vit y - s o me assista nce ma y be 
nee de d; n o or mi ni mal me dical i nter ve nti o n/t hera p y re q uire d  
 
G R A D E 3 Se vere  
Mar ke d li mitati o n i n acti vit y, s o me assista nce us uall y re q uire d; 
me dical i nter ve nti o n/t hera p y re q uire d, h os pitalizati o ns p ossi ble  
 
G R A D E 4 Life -t hre ate ni n g E xtre me li mitati o n i n acti vit y, si g nifica nt assista nce re q uire d; 
si g nifica nt me dical i nter ve nti o n/t hera p y re q uire d, h os pitalizati o n or 
h os pice care pr o ba ble  
 
S E RI O U S O R LI F E -T H R E A T E NI N G A Es  
 
A N Y cli nical e ve nt dee me d b y t he cli nicia n t o be seri o us or lif e-t hreate ni n g s h o ul d be 
c o nsi dere d a gra de 4 e ve nt. Cli nical e ve nts c o nsi dere d t o be seri o us or life- t hreate ni n g i ncl u de, 
b ut are n ot li mite d t o seiz ures, c o ma, teta n y, dia betic ket oaci d osis, disse mi nate d i ntra vasc ular 
c oa g ulati o n, diff use petec hiae, paral ysis, ac ute ps yc h osis, se vere de pressi o n.  

I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                                                                            
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
6 6 
 
 
H E M A T O L O G Y  
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
He m o gl o bi n  
9. 5 -1 0. 5  g/ d L  
8. 0 -9. 4  g/ d L  
6. 5 -7. 9  g/ d L  
< 6. 5  g/ d L  
A bs ol ute Ne utr o p hil 
C o u nt  
1 0 0 0 -1 5 0 0/ m m 3   
7 5 0 -9 9 9/ m m 3  
5 0 0 -7 4 9/ m m 3   
< 5 0 0/ m m 3   
Platelets  
7 5, 0 0 0 -9 9, 9 9 9/ m m 3   
5 0, 0 0 0 -7 4, 9 9 9/ m m 3 
2 0, 0 0 0 -4 9, 9 9 9/ m m 3 
< 2 0, 0 0 0/ m m 3  
W B Cs  
> 1 3, 0 0 0/ m m 3   
1 3, 0 0 0 -1 5, 0 0 0/ m m 3 
1 5, 0 0 0 -3 0, 0 0 0/ m m 3   
> 3 0, 0 0 0 or 
< 1, 0 0 0/ m m 3   
P ol y m or p h o n uclear 
Le uc oc ytes + Ba n d 
Cells  
> 8 0 %  
9 0 -9 5 %  
> 9 5 %  
----------  
A b n or mal Fi bri n o ge n  
L o w:  
1 0 0- 2 0 0 m g/ d L  
Hi g h:  
4 0 0- 6 0 0 m g/ d L  
L o w:  
< 1 0 0 m g/ d L  
Hi g h:  
> 6 0 0 m g/ d L  
L o w:  
< 5 0 m g/ d L  
----------  
Fi bri n o ge n 
ass ociate d wit h gr oss 
blee di n g or wit h 
disse mi nate d 
c oa g ulati o n  
Fi bri n S plit Pr o d uct  
2 0 -4 0  µ g/ m L  
4 1 -5 0  µ g/ m L  
5 1 -6 0  µ g/ m L  
> 6 0  µ g/ m L  
Pr ot hr o m bi n Ti me ( P T)  1. 0 1 -1. 2 5 ×  U L N  
1. 2 6 -1. 5  ×  U L N  
1. 5 1 -3. 0  ×  U L N  
> 3  ×  U L N  
Acti vate d Partial 
T hr o m b o plasti n ( A P P T)  
1. 0 1 -1. 6 6  ×  U L N  
1. 6 7 -2. 3 3  ×  U L N  
2. 3 4 -3  ×  U L N  
> 3  ×  U L N  
Met he m o gl o bi n  
5. 0 -9. 9 %  
1 0. 0 -1 4. 9 %  
1 5. 0 -1 9. 9 %  
> 2 0. 0 %  

I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                                                                            
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
6 7 
 
C H E MI S T RI E S  
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
H y p o natrae mia  
1 3 0 -1 3 5 m E q/ L  1 2 3 -1 2 9 m E q/ L  1 1 6 -1 2 2 m E q/ L  
< 1 1 6 m E q/ L or a b n or mal s o di u m 
wit h me ntal stat us c ha n ges or 
seiz ures  
H y per natrae mia  
1 4 6 -1 5 0 m E q/ L  1 5 1 -1 5 7 m E q/ L  1 5 8 -1 6 5 m E q/ L  
> 1 6 5 m E q/ L or a b n or mal s o di u m 
wit h me ntal stat us c ha n ges or 
seiz ures  
H y p o kalae mia  
3. 0 - 3. 4 m E q/ L  2. 5 - 2. 9 m E q/ L  2. 0 - 2. 4 m E q/ L  
or i nte nsi ve re place me nt 
t hera p y or h os pitalizati o n 
re q uire d  
< 2. 0 m E q/ L or a b n or mal p otassi u m 
wit h paresis, ile us or life -t hreate ni n g 
arr h yt h mia  
H y per kalae mia  
5. 6 - 6. 0 m E q/ L  6. 1 - 6. 5 m E q/ L  6. 6 - 7. 0 m E q/l  
> 7. 0 m E q/ L or a b n or mal p otassi u m 
wit h life -t hreate ni n g arr h yt h mia  
H y p o gl ycae mia  
5 5 -6 4 m g/ d L  
4 0 -5 4 m g/ d L  
3 0 -3 9 m g/ d L  
< 3 0 m g/ d L or a b n or mal gl uc ose wit h 
me ntal stat us c ha n ges or c o ma  
H y per gl ycae mia  
( n o n-fasti n g a n d n o 
pri or dia betes)  
1 1 6 - 1 6 0 
m g/ d L  
1 6 1 - 2 5 0 m g/ d L  2 5 1 - 5 0 0 m g/ d L  
> 5 0 0 m g/ d L or a b n or mal gl uc ose 
wit h ket oaci d osis  
or seiz ures  
H y p ocalcae mia  
(c orrecte d f or 
al b u mi n)  
8. 4 - 7. 8 m g/ d L  7. 7 - 7. 0 m g/ d L  6. 9 - 6. 1 m g/ d L  
< 6. 1 m g/ d L or a b n or mal calci u m 
wit h life t hreate ni n g arr h yt h mia or 
teta n y  
H y percalcae mia 
(c orrect f or 
al b u mi n)  
1 0. 6 - 1 1. 5 
m g/ d L  
1 1. 6 - 1 2. 5 
m g/ d L  
1 2. 6 - 1 3. 5 m g/ d L  
> 1 3. 5 m g/ d L or a b n or mal calci u m 
wit h life -t hreate ni n g arr h yt h mia  
H y p o ma g nesae mia  
1. 4 - 1. 2 m E q/ L  1. 1 - 0. 9 m E q/ L  0. 8 - 0. 6 m E q/ L  
< 0. 6 m E q/ L or a b n or mal ma g nesi u m 
wit h life -t hreate ni n g arr h yt h mia  
H y p o p h os p hatae mia  2. 0 - 2. 4 m g/ d L  1. 5 -1. 9 m g/ d L 
or  
re place me nt R x 
re q uire d  
1. 0 -1. 4 m g/ d L  
i nte nsi ve t hera p y  
or h os pitalizati o n re q uire d  
< 1. 0 m g/ d L or a b n or mal p h os p hate 
wit h life -t hreate ni n g arr h yt h mia  
H y per bilir u bi nae mia  1. 1 - 1. 5 x U L N  1. 6 - 2. 5 x U L N  2. 6 - 5 x U L N  
> 5 x U L N  
B U N  
1. 2 5 - 2. 5 x 
2. 6 - 5 x U L N  
5. 1 - 1 0 x U L N  
> 1 0 x U L N  

I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                                                                            
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
6 8 
 
C H E MI S T RI E S  
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
U L N  
H y per uricae mia 
( uric aci d)  
7. 5 –  1 0. 0 
m g/ d L  
1 0. 1 –  1 2. 0 
m g/ d L  
1 2. 1 –  1 5. 0 m g/ d L  
> 1 5. 0 m g/ d L  
Creati ni ne  
1. 1 - 1. 5 x U L N  1. 6 - 3. 0 x U L N  3. 1 - 6 x U L N  
> 6 x U L N or dial ysis re q uire d  
 
 
 
 
 
E N Z Y M E S  
 
 
 
 
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
A S T ( S G O T)  
1. 2 5 -2. 5  ×  U L N  2. 6 -5  ×  U L N  
5. 1 -1 0  ×  U L N  
> 1 0  ×  U L N  
A L T ( S G P T)  
1. 2 5 -2. 5  ×  U L N  2. 6 - 5  ×  U L N  
5. 1 -1 0  ×  U L N  
> 1 0  ×  U L N  
G G T  
1. 2 5 -2. 5  ×  U L N  2. 6 -5  ×  U L N  
5. 1 -1 0  ×  U L N  
> 1 0  ×  U L N  
Al kali ne 
P h os p hatase  
1. 2 5 -2. 
5  ×  U L N  
1. 6 -5  ×  U L N  
5. 1 -1 0  ×  U L N  
> 1 0  ×  U L N  
A m ylase  
1. 1 -1. 5  ×  U L N  
1. 6 -2. 0  ×  U L N  
2. 1 -5. 0  ×  U L N  
> 5. 1  ×  U L N  
Li pase  
1. 1 -1. 5  ×  U L N  
1. 6 -2. 0  ×  U L N  
2. 1 -5. 0  ×  U L N  
> 5. 1  ×  U L N  
 
U RI N A L Y SI S  
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
Pr otei n uria  
1 + or 2 0 0 m g - 1  g 
l oss/ da y  
2 -3 + or 1 -2  g 
l oss/ da y  
4 + or 2 -3. 5  g l oss/ da y  
ne p hr otic s y n dr o me or  
> 3. 5  g l oss/ da y  
He mat uria  
micr osc o pic o nl y  
< 1 0 r bc/ h pf  
gr oss, n o cl ots  
> 1 0 r bc/ h pf  
gr oss, wit h or wit h o ut 
cl ots, O R re d bl o o d 
cell casts  
o bstr ucti ve or re q uire d tra nsf usi o n  
 
 

I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                                                                            
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
6 9 
 
 
C A R DI O V A S C U L A R  
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
Car diac R h yt h m  
 
as y m pt o matic, 
tra nsie nt si g ns, 
n o R x re q uire d  
rec urre nt/ persiste nt; 
s y m pt o matic R x 
re q uire d  
u nsta ble d ysr h yt h mia; h os pitalizati o n 
a n d treat me nt re q uire d  
H y perte nsi o n  
tra nsie nt i ncrease 
> 2 0 m m/ H g; n o 
treat me nt  
rec urre nt, 
c hr o nic i ncrease 
> 2 0 m m/ H g. 
/treat me nt 
re q uire d  
ac ute treat me nt 
re q uire d; o ut patie nt 
treat me nt or 
h os pitalizati o n 
p ossi ble  
e n d or ga n da ma ge or h os pitalizati o n 
re q uire d  
H y p ote nsi o n  
tra nsie nt ort h ostatic 
h y p ote nsi o n wit h heart 
rate i ncrease d b y < 2 0 
beat/ mi n or decrease d 
b y < 1 0 m m H g s yst olic 
B P, N o treat me nt 
re q uire d  
s y m pt o ms d ue t o 
ort h ostatic 
h y p ote nsi o n or 
B P decrease d b y 
< 2 0 m m H g 
s yst olic; 
c orrecta ble wit h 
oral fl ui d 
treat me nt  
re q uires I V fl ui ds; n o 
h os pitalizati o n 
re q uire d  
mea n arterial press ure < 6 0 m m/ H g or 
e n d or ga n da ma ge or s h oc k; re q uires 
h os pitalizati o n a n d vas o press or 
treat me nt  
Pericar ditis  
mi ni mal eff usi o n  
mil d/ m o derate 
as y m pt o matic 
eff usi o n, n o 
treat me nt  
s y m pt o matic 
eff usi o n; pai n; E C G 
c ha n ges  
ta m p o na de; pericar di oce ntesis or 
s ur ger y re q uire d  
He m orr ha ge, 
Bl o o d L oss  
micr osc o pic/ occ ult  
mil d, n o 
tra nsf usi o n  
gr oss bl o o d l oss; 1 -2 
u nits tra nsf use d  
massi ve bl o o d l oss; > 3 u nits 
tra nsf use d  
Electr ocar di o gra m 
Q T c orrecte d 
i nter val pr ol o n ge d  
 
A vera ge Q Tc 
4 8 1 - 5 0 0 ms 
A vera ge Q Tc > = 5 0 1 
ms; > 6 0 ms c ha n ge 
fr o m baseli ne 
T orsa de de p oi ntes; p ol y m or p hic 
ve ntric ular tac h ycar dia; 
si g ns/s y m pt o ms of seri o us arr h yt h mia 
Si n us tac h ycar dia  As y m pt o matic, 
i nter ve nti o n n ot 
S y m pt o matic; 
n o n- ur ge nt 
S u pra ve ntric ular 
tac h ycar dia 
S y m pt o matic, ur ge nt i nter ve nti o n 
i n dicate d Life 

I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                                                                            
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i n dicate d 
me dical 
i nter ve nti o n 
i n dicate d Ur ge nt 
me dical 
i nter ve nti o n 
i n dicate d  
As y m pt o matic, 
i nter ve nti o n n ot 
i n dicate d N o n- ur ge nt 
me dical i nter ve nti o n 
i n dicate d -t hreate ni n g 
c o nse q ue nc es 
 
 

I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                                                                            
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R E S PI R A T O R Y   
 
 
 
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
C o u g h  
tra nsie nt- n o 
treat me nt  
persiste nt c o u g h; 
treat me nt res p o nsi ve  
Par o x ys mal c o u g h; 
u nc o ntr olle d wit h 
treat me nt  
 
Br o nc h os pas m, 
Ac ute  
tra nsie nt; n o 
treat me nt; 7 0 % - 
8 0 % F E V 1 of pea k 
fl o w  
re q uires treat me nt; 
n or malizes wit h 
br o nc h o dilat or; F E V 1 
5 0 % - 7 0 % ( of pea k 
fl o w)  
n o n or malizati o n wit h 
br o nc h o dilat or; F E V 1 2 5 % 
- 5 0 % of pea k fl o w; or 
retracti o ns prese nt  
c ya n osis: F E V 1 < 2 5 % of pea k  
fl o w or i nt u bati o n necessar y  
D ys p n oea  
d ys p n oea o n e xerti o n  d ys p n oea wit h n or mal 
acti vit y  
d ys p n oea at rest  
d ys p n oea re q uiri n g O x y ge n 
t hera p y  
A d ult res pirat or y 
distress  
s y n dr o me 
- 
- 
Prese nt wit h ra di ol o gic  
fi n di n gs; i nt u bati o n n ot 
i n dicate d 
Life -t hreate ni n g res pirat or y or 
he m o d y na mic c o m pr o mise; 
i nt u bati o n or ur ge nt 
i nter ve nti o n i n dicate d 
P ul m o nar y 
he m orr ha ge 
 
Mil d s y m pt o ms; 
i nter ve nti o n 
n ot i n dicate d 
M o derate s y m pt o ms; 
i n vasi ve 
i nter ve nti o n n ot 
i n dicate d 
 
Tra nsf usi o n i n dicate d;  
i n vasi ve i nter ve nti o n 
i n dicate d; h os pitalizati o n 
Life -t hreate ni n g 
c o nse q ue nces; i nt u bati o n or 
ur ge nt i nter ve nti o n i n dicate d  
P ne u m o nitis  
o x y ge n i n dicate d 
 
As y m pt o matic; 
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 
S y m pt o matic; me dical  
i nter ve nti o n i n dicate d; 
li miti n g i nstr u me ntal 
A D L  
Se vere s y m pt o ms; li miti n g 
self 
care A D L; 
Life -t hreate ni n g res pirat or y 
c o m pr o mise; ur ge nt 
i nter ve nti o n i n dicate d (e. g., 
trac he ot o m y or i nt u bati o n) 
L u n g i nfecti o n - 
 
M o derate s y m pt o ms; 
oral i nter ve nti o n 
i n dicate d (e. g., 
a nti bi otic, a ntif u n gal, 
or a nti viral)  
I V a nti bi otic, a ntif u n gal, or 
a nti viral i nter ve nti o n 
i n dicate d; i n vasi ve 
i nter ve nti o n i n dicate d 
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 

I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
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G A S T R OI N T E S TI N A L  
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
Na usea  
mil d or tra nsie nt; 
mai ntai ns reas o na ble 
i nta ke  
m o derate 
disc o mf ort; i nta ke 
decrease d 
si g nifica ntl y; s o me 
acti vit y li mite d  
n o si g nifica nt i nta ke; re q uires I V 
fl ui ds  
h os pitalizati o n re q uire d;  
V o miti n g  
1 e pis o de i n 2 4 h o urs  
2 -5 e pis o des i n 2 4 
h o urs  
> 6 e pis o des i n 2 4 h o urs or 
nee di n g I V fl ui ds  
p h ysi ol o gic c o nse q ue nces 
re q uiri n g h os pitalizati o n or 
re q uiri n g pare nteral n utriti o n  
C o nsti pati o n  re q uiri n g st o ol 
s ofte ner or dietar y 
m o dificati o n  
re q uiri n g la xati ves  
o bsti pati o n re q uiri n g ma n ual 
e vac uati o n or e ne ma  
o bstr ucti o n or t o xic 
me gac ol o n  
Diarr hea  
mil d or tra nsie nt; 3 -4 
l o ose st o ols/ da y or 
mil d diarr hea last < 1 
wee k  
m o derate or 
persiste nt; 5 - 7 l o ose 
st o ols/ da y or 
diarr hea lasti n g > 1 
wee k  
> 7 l o ose st o ols/ da y or bl o o d y 
diarr hea; or ort h ostatic 
h y p ote nsi o n or electr ol yte 
i m bala nce or > 2 L I V fl ui ds 
re q uire d  
h y p ote nsi ve s h oc k or 
p h ysi ol o gic c o nse q ue nces 
re q uiri n g h os pitalizati o n  
Oral 
Disc o mf ort/  
D ys p ha gia  
mil d disc o mf ort; n o 
diffic ult y s wall o wi n g  
s o me li mits o n 
eati n g/ dri n ki n g  
eati n g/tal ki n g ver y li mite d; 
u na ble t o s wall o w s oli d f o o ds  
u na ble t o dri n k fl ui ds; 
re q uires I V fl ui ds  

I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
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N E U R O L O GI C A L   
 
 
 
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
Ne ur o -Cere bellar  
sli g ht i nc o or di nati o n 
d ys dia d oc h o ki nesis  
i nte nti o n tre m or, 
d ys metria, sl urre d 
s peec h; n ysta g m us  
l oc o m ot or ata xia  
i nca pacitate d  
Ps yc hiatric  
mil d a n xiet y or 
de pressi o n  
m o derate a n xiet y or 
de pressi o n; t hera p y 
re q uire d; c ha n ge i n 
n or mal r o uti ne  
se vere m o o d c ha n ges 
re q uiri n g t hera p y; or 
s uici dal i deati o n; or 
a g gressi ve i deati o n  
ac ute ps yc h osis re q uiri n g 
h os pitalizati o n; or s uici dal 
gest ure/atte m pt or 
hall uci nati o ns  
M uscle Stre n gt h  
s u bjecti ve wea k ness / 
n o o bjecti ve 
s y m pt o ms/ si g ns  
mil d o bjecti ve 
si g ns/s y m pt o ms/ n o 
decrease i n f u ncti o n  
o bjecti ve wea k ness 
f u ncti o n li mite d  
paral ysis  
Parest hesia 
( b ur ni n g, ti n gli n g, 
etc.)  
mil d disc o mf ort; n o 
treat me nt re q uire d  
m o d erate disc o mf ort; 
n o n- narc otic a nal gesia 
re q uire d  
se vere disc o mf ort; or 
narc otic a nal gesia 
re q uire d wit h 
s y m pt o matic 
i m pr o ve me nt  
i nca pacitati n g; or n ot 
res p o nsi ve t o narc otic 
a nal gesia  
Ne ur o -se ns or y  
mil d i m pair me nt i n 
se nsati o n ( decrease d 
se nsati o n, e. g., 
vi brat or y, pi n pric k, 
h ot/c ol d i n great t oes) 
i n f ocal area or 
s y m metrical 
distri b uti o n; or c ha n ge 
i n taste, s mell, visi o n 
a n d/ or heari n g  
m o derate i m pair me nt 
( m o d decrease d 
se nsati o n, e. g., vi brat or y, 
pi n pric k, h ot/c ol d t o 
a n kles) a n d/ or j oi nt 
p ositi o n or mil d 
i m pair me nt t hat is n ot 
s y m metrical  
se vere i m pair me nt 
( decrease d or l oss of 
se nsati o n t o k nees or 
wrists) or l oss of 
se nsati o n of at least 
m o d de gree i n 
m ulti ple differe nt 
b o d y areas (i.e., u p pe r 
a n d l o wer e xtre mities)  
se ns or y l oss i n v ol ves li m bs 
a n d tr u n k; paral ysis; or 
seiz ures  

I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
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M U S C U L O S K E L E T A L   
 
 
 
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
Art hral gia (j oi nt pai n)  
mil d pai n n ot 
i nterferi n g wit h 
f u ncti o n  
m o derate pai n, a nal gesics 
a n d/ or pai n i nterferi n g 
wit h f u ncti o n b ut n ot wit h 
acti vities of dail y li vi n g  
se vere pai n; pai n a n d/ or 
a nal gesics i nterferi n g 
wit h acti vities of dail y 
li vi n g  
disa bli n g pai n  
Art hritis  
mil d pai n wit h 
i nfla m mati o n, 
er yt he ma or j oi nt 
s welli n g – b ut n ot 
i nterferi n g wit h 
f u ncti o n  
m o derate pai n wit h 
i nfla m mati o n, er yt he ma 
or j oi nt s welli n g – 
i nterferi n g wit h f u ncti o n, 
b ut n ot wit h acti vities of 
dail y li vi n g  
se vere pai n wit h 
i nfla m mati o n, eryt he ma 
or j oi nt s welli n g –a n d 
i nterferi n g wit h acti vities 
of dail y li vi n g  
per ma ne nt a n d/ or 
disa bli n g j oi nt 
destr ucti o n  
M yal gia  
m yal gia  wit h  n o  
li mitati o n of  
acti vit y  
m uscle te n der ness (at 
ot her t ha n i njecti o n site) 
or wit h m o derate 
i m pair me nt of activit y  
se vere m uscle te n der ness 
wit h mar ke d i m pair me nt 
of acti vit y  
fra n k m y o necr osis  

S KI N  
 
 
 
 
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
M uc oc uta ne o us  
er yt he ma; pr urit us  diff use, mac ul o 
pa p ular ras h, dr y 
des q ua mati o n  
vesic ulati o n or 
m oist 
des q ua mati o n or 
ulcerati o n  
e xf oliati ve der matitis, 
m uc o us me m bra ne 
i n v ol ve me nt or er yt he ma, 
m ultif or me or s us pecte d 
Ste ve ns-J o h ns o n or 
necr osis re q uiri n g 
s ur ger y  
I n d urati o n  
< 1 5  m m  
1 5 -3 0  m m  
> 3 0  m m  
 
Er yt he ma  
< 1 5  m m  
1 5 -3 0  m m  
> 3 0  m m  
 
E de ma  
< 1 5  m m  
1 5 -3 0  m m  
> 3 0  m m  
 
Ras h at I njecti o n 
Site  
< 1 5  m m  
1 5 -3 0  m m  
> 3 0  m m  
 
Pr urit us  
sli g ht itc hi n g at 
i njecti o n site  
m o derate itc hi n g 
at i njecti o n 
e xtre mit y  
itc hi n g o ver 
e ntire b o d y  
 
 
 

I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
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S Y S T E MI C  
 
 
 
 
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
Aller gic Reacti o n  pr urit us wit h o ut 
ras h  
l ocalize d urticaria  ge neralize d 
urticaria; 
a n gi oe de ma  
a na p h yla xis  
Hea dac he  
mil d, n o treat me nt 
re q uire d  
tra nsie nt, 
m o derate; 
treat me nt 
re q uire d  
se vere; res p o n ds 
t o i nitial narc otic 
t hera p y  
i ntracta ble; re q uires 
re peate d narc otic t hera p y  
Fe ver: oral  
3 7. 5 - 3 8. 5 C  
or  
1 0 0. 0 - 1 0 1. 5 F  
3 8. 6 - 3 9. 5 C or  
1 0 1. 6 - 1 0 2. 9 F  
3 9. 6 - 4 0. 5 C or  
1 0 3 - 1 0 5 F  
> 4 0 C  
or  
> 1 0 5 F  
Fati g ue  
n or mal acti vit y 
re d uce d < 4 8 
h o urs  
n or mal acti vit y 
decrease d 2 5 - 
5 0 % > 4 8 h o urs  
n or mal acti vit y 
decrease d > 5 0 % 
ca n’t w or k  
u na ble t o care f or self  
I nfectio ns  a n d 
i nfestati o ns - 
Ot her,  
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 
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 
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 e xisti n g 
h os pitalizati o n 
i n dicate d; 
li miti n g self-care 
A D L  
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 
Se psis  
- 
- 
Bl o o d c ult ure 
p ositi ve wit h 
si g ns or 
s y m pt o ms; 
treat me nt 
i n dicate d 
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 
Aller gic reacti o n  
 
S yste mic 
i nter ve nti o n n ot 
i n dicate d 
 
Oral i nter ve nti o n 
i n dicate d 
Br o nc h os pas m;  
h os pitalizati o n 
i n dicate d f or 
cli nical 
se q uelae; 
i ntra ve n o us 
i nter ve nti o n 
i n dicate d 
 
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 
 
A na p h yla xis   
 
- 
- 
S y m pt o matic 
br o nc h os pas m, 
wit h or wit h o ut 
urticaria;  
pare nteral 
i nter ve nti o n 
i n dicate d; 
aller g y-relate d 
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 
 

I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                        
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
 
e de ma/a n gi oe de
ma;  
h y p ote nsi o n 
 
 
 
 

I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
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A P P E N DI X H: O R D E RI N G  I N S T R U C TI ON S F O R A R M E, A R T E MI LI F E T E A O R C O F F E E  
 
 
T he i nf or mati o n f or s u p pl y of Arte misia  a n n ua is as f oll o ws:  
Baes ma n Distri b ut ors  
4 4 7 7 Re y n ol ds dri ve 
Hilliar d, O hi o 4 3 0 2 6 
C o ntact: T baes ma n @ baes ma n.c o m   
 
Rec or d of Re q uest f or Ar m E, M C C -C O VI D - 0 1-P M C cli nical trial  
 
O V E R NI G H T S HI P M E N T T O:  
Na me: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
A d dress: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
C o ntact P h o ne N u m ber: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
Dis pe nse:  
  C offee: Dis pe nse 4 2 p o ds ( 4 5 0 m g) 
  P o d c offee ma ker (if patie nt d oes n ot ha ve a p o d c offee ma ker)  
O R  
  Tea: Dis pe nse 8 4  tea ba gs (2 2 5 m g) 
 
Or dere d b y: 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _                          _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
St u d y C o or di nat or   
  
  
  
  
  
 
Date  
 
 
E nter data i nt o p ortal as descri be d bel o w.  
 

I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                        
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
 
S C R E E N S H O T S O F O R D E RI N G P O R T A L  
 
 

I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                        
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I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                        
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
 
 

I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                        
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