Tocilizumab in Hospitalized Cancer Patients With Coronavirus 2019 (SARS-CoV-2) and Severe Complications of Coronavirus Disease 19 (COVID-19)
Phase: PHASE2
Conditions: Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm, Pneumonia, Pneumonitis, Severe Acute Respiratory Distress Syndrome, Symptomatic COVID-19 Infection Laboratory-Confirmed
Sponsor: National Cancer Institute (NCI)

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
i 
 
T o:  
Ca ncer T h era p y E v al uati o n Pr o gra m  
Fr o m:  
Ric har d F. Little, M. D.  
D ate:  
J u ne 4, 2 0 2 0 
Re:  
A me n d me nt 1 of  Pr ot oc ol # T R C -1 0 4 4 6: “ T ociliz u ma b i n H os pitalize d Ca n cer 
Patie nts wit h C or o na vir us 2 0 1 9 ( S A R S -C o V -2) a n d Se vere C o m plicati o ns of 
C or o na vir us Disease 1 9 ( C O VI D -1 9)  
Pr ot oc ol C h a n ges b y Pri nci p al I n vesti g at or:  
#  
Secti o n  
C o m me nts  
1.  
 
Title pa ge  
T he list of partici pati n g or ga nizati o ns has bee n u p date d.  
2.  
 4. 2  
T he e mail a d dress C T S U Re g Pref @cts u.c o cc g. or g  has bee n c orrecte d t o 
C T S U Re g P ref @c occ g. or g. 

 
 
N CI Pr ot oc ol #:  
T R C -1 0 4 4 6  
 
L oc al Pr ot oc ol #:  
T R C -1 0 4 4 6  
 
Cli nic al Tri als. g o v I de ntifier :  N C T 0 4 3 7 0 8 3 4  
 
T ociliz u m a b i n H os pit alize d C a ncer P atie nts wit h C or o n a vir us 2 0 1 9 ( S A R S -
C o V -2) a n d Se vere C o m plic ati o ns of C or o n a v ir us Dise ase 1 9 ( C O VI D-1 9)  
 
Tre at me nt Referr al Ce nter Pr ot oc ol  
T R C  1 0 4 4 6  
 
 
 
 
C o or di n ati n g Ce nter : 
Nati o nal Ca n cer I nstit ute ( N CI)  
 
 
 
 
R oc k ville, Mar yla n d  2 0 8 5 0  
 
Pri nci p al I n vesti g at or 
Ric har d F. Little, M D  
Di visi o n of Ca ncer Treat me nt a n d Dia g n osis  
 
 
 
 
Nati o nal Ca ncer I nstit ute  
 
 
 
 
R oc k ville, Mar yla n d  
 
 
 
 
P h o ne: 2 4 0 2 7 6 6 0 9 3  
 
 
 
 
E mail: littler @ mail. ni h. g o v  
 
C o -Pri nci p al I n vesti g at or Nirali S ha h, M D , M. H. Sc.  
Pe diatric O nc ol o g y Bra n c h  
 
 
 
 
Ce nter f or Ca n cer Res earc h  
 
 
 
 
Nati o nal Ca ncer I nstit ute  
 
 
 
 
P h o ne: 2 7 0 7 6 0 6 1 9 9  
 
 
 
 
E mail: s ha h n n @ mail. ni h. g o v 
 
I n vesti g at ors:  
 
Ji m D or os h o w, M D 
Direct or, Di visi o n of Ca n cer Treat me nt a n d Dia g n osis  
 
 
 
 
Nati o nal Ca ncer I nstit ute  
 
 
 
 
P h o ne: 2 4 0 7 8 2 3 3 2 0  
 
 
 
 
E mail: d or os h oj @ mail. ni h. g o v  
 
Matt he w J. B or o n, R P h  
Se ni or Cli nical Researc h P har macist  
P har mace utical Ma na g e me nt Bra nc h  
Ca ncer T h era p y E v al uati o n Pr o gra m  
 
 
 
 
Di visi o n of Ca ncer Treat me n t a n d Dia g n osis 
 
 
 
 
Nati o nal Ca ncer I nstit ute  
 
 
 
 
P h o ne: 2 4 0 2 7 6 6 5 7 5  
 
 
 
 
E mail: b or o n m @ mail. ni h. g o v  

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
2  
 
 
St atistici a n:    
 
B oris Frei dli n  
C hief, Bi ostatistics Bra nc h  
 
 
 
 
Bi o metric Researc h Pr o gra m  
Di visi o n of Ca ncer Treat me nt a n d Dia g n osis  
 
 
 
 
Nati o nal Ca ncer I nstit ute  
 
 
 
 
P h o ne: 2 4 0 2 7 6 6 0 2 4  
 
 
 
 
E mail : frei dli n b @cte p. nci. ni h. g o v 
 
Bi ore p osit or y:   
Bi o pat h ol o g y Ce nter ( B P C) at Nati o n wi de C hil dre n’s H os pital ( N C H)  
T he Researc h I nstit ute at Nati o n wi de C hil dre n's H os pital  
7 0 0 C hil dre n's Dri ve, W A 1 3 4 0  
C ol u m b us, O hi o 4 3 2 0 5  
P H: ( 8 0 0) 3 4 7 -2 4 8 6 F A X: ( 6 1 4) 7 2 2 -2 8 9 9  
E mail:  B P C Ba n k @ nati o n wi dec hil dre ns. or g  
 
 
N CI S u p ple d A ge nt:  T ociliz u ma b  (Acte mra ®, R O 4 8 7 7 5 3 3, N S C 8 2 0 0 1 3 ) 
 
 
P artici p ati n g Or g a niz ati o ns:  P artici p ati o n is li mite d t o t he f oll o wi n g U. S. selecte d N C T N, 
E T C T N, a n d N C O R P sites:  
 
G A 0 0 3  / Gra d y Healt h S yste m 
G A 0 0 5  / E m or y U ni versit y –  Wi ns hi p Ca ncer I nstit ute  
M A 0 3 7  / Bri g ha m a n d W o me n’s H os pital 
M A 0 3 8  / Bet h Israel Deac o ness Me dical Ce nter 
M D 0 0 4  / Nati o nal I nstit utes of Healt h Cli nical Ce nter 
N CI C C R  / N CI Ce nter f or Ca ncer R esearc h  
N V 0 1 7  / U ni versit y Me dical Ce nter of S o ut her n Ne va da 
N V 0 9 3  / S u m merli n H os pital Me dical Ce nter  
W A 0 0 4  / Valle y Me dical Ce nter 
N Y 0 4 3  / M o ntefi ore Me dical Ce nter –  Weiler H os pital  
N Y 0 4 5  / M o ntefi ore Me dical Ce nter –  M oses Ca m p us  
N Y 3 1 3  / M o ntefi ore Me dical Ce nter –  Ei nstei n Ca m p us  
N Y 3 2 7  / C hil dre n’s H os pital at M o ntefi ore 
O K 0 0 3  / U ni versit y of O kla h o ma Healt h Scie nces Ce nter 
 
 

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
3  
 
St u d y C o or di n at or : 
Re becca  E n os, M P H, A D N  
Nati o nal Ca ncer I nstit ute c o ntract or ( E m mes)  
P h o ne: 7 0 3 -8 5 1 -4 9 0 5  
N CI T R C 1 0 4 4 6 @ mail. ni h. g o v  
 
Res p o nsi ble D at a M a n a ger:   
Dia na V uli h  
T hera d e x O nc ol o g y  
6 0 9 -7 9 9 -7 5 8 0, x 3 0 7 0  
d v uli h @t he ra de x.c o m 
 
I N D S p o ns or:  D C T D, N CI    
 
Pr ot oc ol T y pe / Versi o n # / Versi o n D ate:  
Ori gi nal / A pril 1 6 , 2 0 2 0 
 
 
 
 
Re visi o n 1 / A pril 2 3, 2 0 2 0  
 
 
 
 
Re visi o n 2a / A pril 2 9, 2 0 2 0  
 
 
 
 
Re visi o n 2 b / Ma y 7, 2 0 2 0  
 
 
 
 
Re visi o n 2 c / Ma y 7 , 2 0 2 0 
 
 
 
 
Re visi o n 3 / Ma y 1 4, 2 0 2 0  
 
 
 
 
Re visi o n 4 / Ma y 2 6, 2 0 2 0  
A me n d me nt 1 / J u ne 4, 2 0 2 0  
 

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
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C A N C E R T RI A L S S U P P O R T U NI T ( C T S U) A D D R E S S A N D C O N T A C T 
I N F O R M A TI O N 
 
F or re g ul at or y 
re q uire me nts:  
F or p atie nt e nr oll me nts:  
F or st u d y d at a s u b missi o n:  
Re g ulat or y d oc u me ntati o n 
m ust be s u b mitte d t o t he 
C T S U via t he Re g ulat or y 
S u b missi o n P ortal.  
 ( Si g n i n at w w w.cts u. or g, 
a n d select t he Re g ulat or y > 
Re g ulat or y S u b missi o n.)  
 
I nstit uti o ns wit h patie nts 
waiti n g t hat are u na ble t o 
use t he P ortal s h o ul d alert 
t he C T S U Re g ulat or y Office 
i m me diatel y at 1-8 6 6 -6 5 1 -
2 8 7 8 t o recei ve f urt her 
i nstr ucti o n a n d s u p p ort. 
 
C o ntact t he C T S U 
Re g ulat or y Hel p Des k at 1 -
8 6 6 -6 5 1 -2 8 7 8 f or re g ulat or y 
assista nce. 
Refer t o t he patie nt 
e nr oll me nt secti o n of t he 
pr ot oc ol f or i nstr ucti o ns o n 
usi n g t he O nc ol o g y Patie nt 
E nr oll me nt Net w or k 
( O P E N). O P E N ca n be 
accesse d at 
htt ps:// w w w.cts u. or g/ O P E N _
S Y S T E M/  or 
htt ps:// O P E N.cts u. or g . 
 
C o ntact t he C T S U Hel p Des k 
w it h a n y O P E N-relate d 
q uesti o ns at 
cts uc o ntact @ westat.c o m . 
 
Data c ollecti o n f or t his st u d y will be 
d o ne e xcl usi vel y t hr o u g h Me di data 
Ra ve. Refer t o t he data s u b missi o n 
secti o n of t he pr ot oc ol f or f urt her 
i nstr ucti ons.  
 
T he m ost c urre nt v ersi o n of t he st u d y pr ot oc ol a n d all s u p p orti n g d oc u me nts m ust be 
d o w nl oa de d fr o m t he pr ot oc ol -s pecific p a ge l ocate d o n t he C T S U me m bers’ we bsite 
(htt ps:// w w w.cts u. or g ). Access t o t he C T S U me m bers’ we bsite is ma na g e d t hr o u g h t he Ca ncer 
T hera p y a n d E val uati o n Pr o gra m - I de ntit y a n d Access Ma n a ge me nt ( C T E P-I A M) re gistrati o n 
s yste m a n d re q uires l o g o n wit h C T E P-I A M user na me a n d pass w or d.  
F or cli nic al q uesti o ns ( i.e. p atie nt eli gi bilit y or tre at me nt -rel ate d),  see t he Pr ot oc ol C o ntacts, Pa ge 
2 . 
F or n o n -cli nic al q uesti o ns ( i.e. u nrel ate d t o p atie nt eli gi bilit y or cli nic al d at a s u b missi o n),  c o ntact 
t he C T S U Hel p Des k b y p h o ne or e-mail:   
C T S U Ge neral I nf or mati o n Li ne –  1 -8 8 8 -8 2 3 -5 9 2 3, or cts uc o ntact @ westat.c o m . All calls a n d 
c orres p o n de nce will be tria ge d t o t he a p pr o priate C T S U re prese ntati ve.  
T he C T S U we bsite is l oc ate d at  htt ps:// w w w.cts u. or g.  
 
 
 

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
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P R E CI S/ S Y N O P SI S  
 
T his si n gle -ar m trial is i nte n de d t o pr o vi de e x p a n d e d access t o t ociliz u ma b f or ca n cer patie nts 
wit h se vere C O VI D -1 9 p ul m o nar y c o m plicati o ns  a n d is i nte n de d t o ma ke t ociliz u ma b a vaila ble 
t o t h ose n ot a ble t o partici pate o n  t he ra n d o mize d p hase 3 trial s p o ns ore d b y H off ma n n -L a 
R oc he  c o m pari n g t ociliz u ma b t o place b o i n patie nts wit h se vere C O VI D -1 9 disease: “ A St u d y t o 
E val uate t he Safet y a n d Efficac y of T ociliz u ma b i n Patie nts Wit h Se vere C O VI D -1 9 P ne u m o nia 
( C O V A C T A)” (N C T 0 4 3 2 0 6 1 5 ).  T he pri mar y o bj ecti ve i n t he p hase 3 trial is t o c o m pare cli nical 
stat us assesse d usi n g a 7 -cate g or y or di nal scale at Da y 2 8 bet wee n ar ms.   
 
Si nce se vere C O VI D -1 9 p ul m o nar y disease a p p ears t o be me diate d b y c yt o ki ne releas e si milar t o 
t hat see n i n patie nts wit h c yt o ki ne release s y n dr o m e c o m plicati o ns of C A R-T t hera p y f or w hic h 
t ociliz u ma b is F D A a p pr o ve d, t his e x pa n de d access trial  is bei n g c o nd ucte d t o pr o vi de cli nical 
trial access t o t his p ote ntiall y life-sa vi n g t hera p y i n ca ncer patie nts a n d t o c ollect data o n cli nical 
o utc o mes .  T his trial will a d dress p ote ntial access dis parit y a m o n g a d ult a n d c hil dre n ca n cer 
patie nts t o t he ra n d o mize d p has e 3 trial c o m pare d t o t he bac k gr o u n d p o p ulati o n.  F D A 
w or ks h o ps c o n ve n e d wit h  Frie n ds of Ca n cer Res earc h, A merica n S ociet y of Cli nical O nc ol o g y, 
a n d t he A meric a n Ass oci ati o n f or Ca ncer Researc h ha ve artic ul ate d i m p orta nt pri nci ples f or 
m o der nizi n g eli gi bi lit y criteria t o cli nical trials a n d f or access t o cli nical trials, partic ularl y i n t he 
case of Africa n A meri ca ns m ulti ple m yel o ma dis parities. 1, 2  Rec o m me n dati o ns i ncl u de 
d e vel o p me nt of c o h ort st u dies t o parallel t he e x p eri me ntal ar m of pi v otal trials t o e n ha nce 
i ncl usi o n of  patie nts u n derre prese nt e d o n t he pi v otal trials o wi n g t o restricti ve eli gi bilit y criteria 
or ot her dis parities.   
 
T his e x pa n de d access trial  is res p o nsi ve t o t he F D A w or ks h o p rec o m me n d ati o ns i n t he f oll o wi n g 
wa ys:  
•  Ca ncer patie nts are at i ncrease d ris k of se vere C O VI D -1 9 yet will be u n derre pres e nte d o n  
t he pi v otal trial beca use of restricti ve eli gi bilit y criteria t hat will e xcl u de ma n y ca ncer 
patie nts, partic ularl y t h os e wit h he mat ol o gic mali g na ncies  
•  Africa n A merica n ca n cer patie nts  will be u n derre prese nte d o n t he pi v otal trial o wi n g t o 
b ot h treat me nt dis parit y iss ues a n d ca n cer patie nt eli gi bilit y restricti o ns  
•  C hil dre n of all races a n d et h nicities wit h ca ncer will be u n derre prese nte d o n t he pi v otal 
trial o wi n g t o t he a ge restricti o ns of t he pi v otal trial as well as restricti ve eli gi bilit y 
criteria t hat will li mit t h ose wit h ca ncer fr o m parti ci pati o n.  
•  T his trial will be c o n d ucte d o nl y i n sites w here C O V A C T A is n ot bei n g c o n d ucte d, wit h 
a n e m p hasis o n Mi n orit y E nr olli n g Sites of t he  Nati o nal Ca ncer I nstit ute C o m m u nit y 
O nc ol o g y Researc h Pr o gra m ( N C O R P), a n d t he Earl y T hera pe utics Cli nical Trials 
Net w or k a n d t h e Nati o nal Cli nical Trials Net w or k t o i ns ure e n ha nce d mi n orit y a n d 
pe diatric e nr oll me nt.   
•  T he trial will be c o n d uct e d as a c olla b orati o n bet wee n Ge ne ntec h a n d t he Nati o nal 
Ca ncer I nstit ute i n a ma n ner t hat is res p o nsi ve t o F D A w or ks h o p rec o m me n dati o ns t o 
e ns ure cli nic al trials access t o patie nts w h o are r o uti nel y n ot i ncl u de d i n pi v otal 
t hera pe utic i n d ustr y s p o ns ore d cli nical trials 
•  T his trial will pr o vi de critical cli nical o utc o me dat a f or patie nts w h o will n ot ha ve access 
t o t he C O V A C T A trial s o t hat if t he C O V A C T A trial is p ositi ve, t he cli nical o utc o mes 

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
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will be reas o na bl y d escri be d f or cli nical decisi o ns re gar di n g use of t ociliz u ma b i n ca ncer 
patie nts.  
 
Ke y eli gi bilit y criteria of t his trial a n d t he pi v otal C O V A C T A trial t hat will create cli nical trial 
access barri ers f or ca n cer patie nts, es peciall y Africa n A merica ns a n d c hil dre n wit h ca ncer a n d 
se vere C O VI D-1 9:  
 
Eli gi bilit y Criteri o n  
NI H Trial  
C O V A C T A Trial  
C o m me nts  
Ca ncer Di a g n osis  
Re q uire d  
Sile nt  
Res p o nsi ve t o F D A 
w or ks h o ps f or 
m o der nizi n g 
eli gi bilit y f or cli nical 
trials a n d a d dressi n g 
dis parit ies  
I m m u ne m o d ulat or y 
dr u gs  
All o we d  
N ot all o we d  
C O V A C T A trial will 
re n der m a n y ca n cer 
patie nts i neli gi ble.  
T ociliz u ma b has bee n 
s h o w n safe i n ca ncer 
patie nts wit h c yt o ki ne 
releas e s y n dr o me  
HI V  
I n cl u de d  
Sile nt  
Patie nts safel y treat e d 
wit h HI V a n d K S H V 
i n N CI cli nical trials; 
res p o nsi ve t o eff orts 
f or m o der nizi n g 
eli gi bilit y  
A ge  
≥ 2 years  
≥ 1 8 years  
T ociliz u ma b is 
a p pr o ve d f or use i n 
b ot h a d ults a n d 
c hil dre n t o treat 
c yt o ki ne release 
s y n dr o me ass ociate d 
wit h ca ncer t hera p y  
A N C  
n o l o wer li mit  
≥1 0 0 0/ mc L  
Ca ncer patie nts, s uc h 
as t h ose i n w h o m 
t ociliz u ma b is 
a p pr o ve d, oft e n ha ve 
A N C bel o w 5 0 0/ mc L 
a n d t he a ge nt ca n be 
gi ve n safel y i n t his 
setti n g; Be ni g n 
ne utr o pe nia c o m m o n 
i n Africa n A m erica ns 

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Platelets  
n o l o wer li mit  
≥5 0, 0 0 0/ mc L  
Ca ncer patie nts, s uc h 
as t h ose i n w h o m 
t ociliz u ma b is 
a p pr o ve d, oft e n ha ve 
platelets bel o w 
5 0, 0 0 0/ mc L a n d t he 
a ge nt ca n b e gi ve n 
safel y i n t his setti n g 
 
Bac k gr o u n d : C O VI D-1 9 is a hi g hl y c o nta gi o us n o vel pat h o ge n ca usi n g a gl o bal pa n de mic lea di n g 
t o hi g h rates of life-t hreat e ni n g or fatal c o m plicati o ns. Patie nts wit h ca ncer ma y be at partic ularl y 
hi g h -ris k t o de vel o p se vere c o m plicati o ns relate d t o C O VI D-1 9.  Miti gati o n strate gies are ur ge ntl y 
nee de d t o re d uce t h e se verit y of i nfecti o n t o re d uce t he b ur de n o n I C U le vel care a n d decrease t he 
case-fatalit y rate.  
 
O bjecti ves : T his Nati o nal Ca ncer I nstit ute cli nical trial will pr o vi de t ociliz u ma b t o se verel y ill 
C O VI D -1 9 ca ncer patie nts i n res p o nse t o t he Nati o nal E mer ge n c y as d eclare d b y t he Presi d e nt of 
t he U nite d States.  T he Ai m s are t o 1) distri b ute t ociliz u ma b t o h os pitals i n or der t o p ote ntiall y 
pre ve nt escalati o n of care a n d t o disc har ge s e vere C O VI D -1 9 cases fr o m i nte nsi ve care facilities 
as q uic kl y as p ossi ble i n or der t o kee p I C U be ds a vaila ble t o s uccessi ve wa ves of se vere C O VI D -
1 9 c ases, 2) t o e val uate cli nical o utc o mes  i n criti call y ill ca ncer patie nts wit h C O VI D -1 9 ill ness  
recei vi n g t ociliz u ma b.  
 
Eli gi bilit y : H os pitalize d ca ncer s u bjects >  2 y ears of a ge wit h cli nical ma nifestati o ns of C O VI D -
1 9 i nfecti o n a n d res pirat or y c o m pr o mise  ma y be eli gi ble t o recei ve t o ciliz u ma b.  
 
Desi g n : T his is a m ultice nter, si n gle-ar m, o pe n -la bel, i nter ve nti o nal st u d y wit h all e nr olle d 
s u bjects recei vi n g t ociliz u ma b. 
 
 
 
 

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S C H E M A:   
 
C o h orts A a n d B  ( o nl y Or di n al Sc ales 3 -6 are eli gi ble f or i niti al d ose o f t ociliz u m a b) 
C LI NI C A L S T A T U S O R DI N A L S C A L E  
S C A L E  
C O H O R T  
D E S C RI P TI O N  
1  
N/ A  
Disc h ar ge  
2  
A 1/ A 2  
N o n -I C U, h os pital war d, N O O 2 
3  
A 1/ A 2  
N o n -I C U, h os pital war d, o n O 2 
4  
A 1/ A 2  
I C U or n o n-I C U, re q uires n o n-i n vasi ve ve ntilat or y 
s u p p ort or hi g h fl o w O 2 
5  
B 1/ B 2  
I C U re q uires m ec ha nical or i m mi ne nt 
ve ntilati o n/i nt u bati o n  
6  
B 1/ B 2  
I C U re q uires E C M O a n d a d diti o nal O 2 s u p p ort a n d 
or ga n s u p p ort, e. g. v as o press ors, re n al re pl ace me nt 
t hera p y 
7  
N/ A  
De at h  
 
 
* * O pti mal res p o nse t o t o ciliz u ma b ma y n ot be see n u ntil 5 -6 h o urs after c o m pleti o n of t he 
i nitial i nf usi o n a n d will t y picall y ma nifest wit h res ol uti o n of/i m pr o ve me nt i n fe ver pri or t o 
ot her cli nical si g ns  
 
S u bjects wit h n o o bje cti ve i m pr o ve me nt after 2 d oses are u nli kel y t o be nefit fr o m f urt her 
a d mi nistrati o n of t ociliz u ma b a n d alter nati ve t hera pies s h o ul d be c o nsi dere d  
 
 
F or t h ose at or a b o ve 3 0 k g  (> ): 
C o h ort  
Cli nic al St at us 
Descri pti o n  
D osi n g f or I niti al D ose  
D osi n g f or Sec o n d  D ose *  
A 1  
3 -4  
( N ot o n mec ha nical ve ntilati o n 
at ti me of re gistrati o n a n d n o 
i m me diate pla n f or i nt u bati o n) 
4  m g/ k g  
8 m g/ k g  
( or di n al sc ale 2 m a y 
recei ve if cli nic all y 
i n dic ate d)*  

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9  
 
B 1  
5 -6  
( O n mec ha nical ve ntilati o n at 
ti me of e nr oll me nt or i m mi n e nt 
i nt u bati o n i n dicate d) 
8  m g/ k g  
8  m g/ k g  
F or t h ose bel o w 3 0 k g  ( <): 
C o h ort  
Cli nic al St at us 
Descri pti o n  
D osi n g f or I niti al D ose  
D osi n g f or Sec o n d  D ose *  
A 2  
3 -4  
( N ot o n mec ha nical ve ntilati o n 
at ti me of re gistrati o n a n d n o 
i m me diate pla n f or i nt u bati o n) 
6  m g/ k g  
1 2 m g/ k g  
( or di n al sc ale 2 m a y 
recei ve if cli nic all y 
i n dic ate d) * 
B 2  
5 -6  
( O n mec ha nical ve ntilati o n at 
ti me of e nr oll me nt or i m mi n e nt 
i nt u bati o n i n dicate d) 
1 2  m g/ k g  
1 2 m g/ k g  
•  Ma xi m al a d mi nistrate d  d ose , f or a si n gle d os e: 8 0 0 m g  re g ar dless of wei g ht  
•  O pti mal res p o nse t o t ociliz u ma b ma y n ot be s ee n u ntil 5 -6 h o urs aft er c o m pleti o n of t he 
i nitial i nf usi o n a n d will t y picall y ma nifest wit h res ol uti o n of/i m pr o ve me nt i n fe ver pri or t o 
ot her cli nical si g ns  
* A sec o n d d ose ma y b e gi ve n if t here is s ustai ne d or rec urre nt f e ver, n o decreas e or n ot m ore 
t ha n a 1-cate g or y i m pr o ve me nt o n t he 7-cate g or y or di nal scale ( o nl y sta bili zati o n or partial 
i m pr o ve me nt f oll o wi n g first d ose), or a ≥1-cate g or y w orse ni n g o n t he 7 -cat e g or y or di nal sc ale  
fr o m na dir.  T he s ec o n d d os e m a y be gi ve n bet wee n  8 h o urs a n d 7 d a ys fr o m c o m pleti o n of 
t he first d ose.  I n ma n y cases a s ec o n d d ose m a y n ot be necess ar y t o ac hi e ve o pti mal be nefit.   
 
 
 

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1 0  
 
T a ble of C o nte nts : 
 
P R E CI S/ S Y N O P SI S  ....................................................................................................................... 5  
S C H E M A:  ....................................................................................................................................... 8  
1.  
O BJ E C TI V E S  ........................................................................................................................ 1 2  
1. 1  
Pri mar y O bjecti ves  ......................................................................................................... 1 2  
1. 2  
Sec o n dar y O bj ecti ve  ...................................................................................................... 1 2  
1. 3  
E x pl or at or y O bjecti ves  ................................................................................................... 1 2  
2.  
B A C K G R O U N D a n d Rati o nale  ............................................................................................ 1 3  
2. 1  
C or o na vir us S A R S -C o V -2 a n d Se vere C or o na vir us Disease 1 9 ( C O VI D -1 9) as a 
Nati o nal P u blic Healt h E mer ge nc y  ........................................................................................... 1 3  
2. 2  
C O VI D -1 9 i n Ca ncer Patie nts  ........................................................................................ 1 5  
2. 3  
Se vere ac ute res pirat or y distress s y n dr o me ( A R D S) a n d c yt o ki ne rel ease s y n dr o me 
( C R S)  ........................................................................................................................................ 1 6  
2. 4  
T ociliz u ma b ( Pr o vi de d b y C T E P)  .................................................................................. 1 6  
2. 5  
St u d y Rati o nale a n d J ustificati o n f or t he Us e of T o ciliz u ma b  i n H os pitalize d Ca ncer 
Patie nts wit h C O VI D -1 9  ........................................................................................................... 1 8  
3.  
P A TI E N T S E L E C TI O N  ........................................................................................................ 1 9  
3. 1  
I n cl usi o n Criteria ............................................................................................................ 1 9  
3. 2  
E xcl usi o n Criteria  ........................................................................................................... 2 1  
4.  
R E GI S T R A TI O N P R O C E D U R E S  ....................................................................................... 2 1  
4. 1  
I n v esti gat or a n d Researc h Ass ociate Re gistrati o n wit h C T E P ...................................... 2 1  
4. 2  
Site Re gistrati o n  ............................................................................................................. 2 2  
4. 3  
Patie nt Re gistrati o n  ........................................................................................................ 2 5  
4. 4  
Ge neral G ui deli nes  ......................................................................................................... 2 6  
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  ............................................ 2 7  
5. 1  
S u m mar y Ta ble f or S peci me n C ollecti o n  ...................................................................... 2 7  
5. 2  
S peci me n Pr oc ure m e nt Kits a n d Sc he d uli n g  ................................................................. 2 7  
5. 3  
S peci me n Trac ki n g S yste m I nstr ucti o ns ........................................................................ 2 8  
5. 4  
S peci me n C ollecti o n  ...................................................................................................... 3 1  
5. 5  
S hi p pi n g S peci me ns fr o m Cli nical Site t o t he Bi o pat h ol o g y Ce nter ( B P C)  .................. 3 1  
5. 6  
Bi o mar ker Pla n  ............................................................................................................... 3 3  
5. 7  
E x pl orat or y/ A ncillar y C orrelati ve St u dies  ..................................................................... 3 5  
6.  
T R E A T M E N T P L A N ............................................................................................................ 3 5  
6. 1  
A ge nt A d mi ni strati o n ..................................................................................................... 3 5  

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1 1  
 
6. 2  
Treat me nt Sc he m a  .......................................................................................................... 3 7  
6. 3  
C o nc o mita nt Me dicati o ns/ T hera p y  ................................................................................ 3 7  
6. 4  
D urati o n of T hera p y  ....................................................................................................... 3 9  
6. 5  
D urati o n of F oll o w -U p  ................................................................................................... 3 9  
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  ................................................................... 4 0  
7. 1  
D osi n g Dela ys  ................................................................................................................ 4 0  
7. 2  
D osi n g M o dificati o ns  ..................................................................................................... 4 0  
8.  
P H A R M A C E U TI C A L I N F O R M A TI O N  ............................................................................. 4 0  
9.  
S T A TI S TI C A L C O N SI D E R A TI O N S  .................................................................................. 4 4  
9. 1  
St u d y Desi g n/ E n d p oi nts  ................................................................................................. 4 4  
9. 2  
Sa m ple Size/ Accr ual Rate  .............................................................................................. 4 4  
9. 3  
Stratificati o n Fact ors  ...................................................................................................... 4 5  
9. 4  
T o xicit y Re p orti n g a n d E xcl usi o ns  ................................................................................ 4 5  
9. 5  
Data C ollecti o n  ............................................................................................................... 4 7  
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  ........................... 4 7  
1 0. 1  C o m pre he nsi ve A d verse E ve nts a n d P ote ntial Ris ks Lists ( C A E P Rs)  .......................... 4 7  
1 0. 2  A d verse E v e nt C haracteristics  ....................................................................................... 4 9  
1 0. 3  E x pe dite d A d vers e E ve nt Re p orti n g  .............................................................................. 4 9  
1 0. 4  R o uti ne A d verse E ve nt Re p orti n g .................................................................................. 5 3  
1 0. 5  Pre g na nc y  ....................................................................................................................... 5 3  
1 1.  
S T U D Y C A L E N D A R  ...................................................................................................... 5 4  
1 2.  
M E A S U R E M E N T O F E F F E C T ....................................................................................... 5 7  
1 3.  
S T U D Y 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  ........................................................................................................................ 5 7  
1 3. 1  St u d y O versi g ht  .............................................................................................................. 5 7  
1 3. 2  Data Re p orti n g  ............................................................................................................... 5 7  
1 3. 3  Data Q ual it y P ortal ......................................................................................................... 5 8  
1 3. 4  C T E P M ultice nter G ui deli nes  ........................................................................................ 5 9  
1 3. 5  C olla b orati ve A gree me nts La n g ua ge  ............................................................................. 5 9  
1 4.  
R E F E R E N C E S  ................................................................................................................. 6 2  
A P P E N DI X A  
S U M M A R Y T A B L E F O R P A TI E N T D E M O G R A P HI C S A N D 
L A B O R A T O R Y V A L U E S T O B E R E C O R D E D O N T H E C R F  ............................................... 6 4  
 
 

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1 2  
 
1.  O B J E C TI V E S  
 
1. 1  
Pri m ar y O bjecti ves  
 
1. 1. 1  T o e n ha nce access t o t o ciliz u ma b f or patie nts w h o ca n n ot partici pat e i n  t he ra n d o mize d 
C O V A C T A Trial wit h s pecific e m p hasis o n patie nts wit h ca ncer, es p eci all y t h ose w h o 
bel o n g t o hi g h -ris k a n d mi n orit y p o p ulati o ns  a n d c hil dre n  a n d t o pr o vi de o bser vati o ns o n 
cli nical o utc o mes ass oci ate d wit h  t ociliz u ma b a d mi nistrati o n i n ca ncer patie nts wit h se vere 
C O VI D -1 9 diseas e . 
 
1. 2  
Sec o n d ar y O bjecti ve  
 
1. 2. 1  T o esti mate t he pr o p orti o n of patie nts w h ose l e v el of i nstit uti o nal care d oes n ot f urt her 
escalate f oll o wi n g a d mi nistrati o n of t ociliz u ma b  
 
1. 3  
E x pl or at or y O bjecti ves  
 
1. 3. 1  T o esti mate t he n u m ber of da ys I C U patie nts s pe nt i n t he I C U 
 
1. 3. 2  T o e val uate t he m ortalit y rate of p atie nts : 
 
1. 3. 2. 1  3 0 -da y a n d 6 0 -d a y m ortalit y i n patie nts i n t he I C U  
 
1. 3. 2. 2  E val uate  t he 1 4-, 3 0- a n d 6 0-da y m ortalit y rate f oll o wi n g i nf usi o n of t ociliz u ma b  
 
1. 3. 3  T o eval uate  o v erall s ur vi val  
 
1. 3. 4  T o d escri be t he pr o p orti o n of patie nts pr o gressi n g t o ve ntilat or s u p p ort after t ociliz u ma b 
t hera p y 
 
1. 3. 5  E val uate t he cli nic al c o urse  f oll o wi n g a d mi nistrati o n of t ociliz u ma b  
 
1. 3. 5. 1  T o e val uate t he d e vel o p me nt of a d diti o nal i nfecti o ns  
 
1. 3. 5. 2   
T o e val uate t he si d e effects f oll o wi n g t ociliz u ma b  
 
1. 3. 5. 3   
T o e val uate i m pact o n i nfla m mat or y mar kers  
 
1. 3. 6  E val uate t he d urati o n of ti me:  
 
1. 3. 6. 1  
T o  re m o val fr o m mec ha nical ve ntilat or s u p p ort 
 
1. 3. 6. 2  
T o  ste p-d o w n of  i nstit uti o nal care re q uir e me nts 
 
1. 3. 6. 3  
T o disc har ge fr o m t he I C U t o l o wer le vel 
 

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1 3  
 
1. 3. 6. 4  
T o h os pital Disc har ge  
 
1. 3. 6. 5  
T o res ol uti o n of cli nical s y m pt o ms 
 
1. 3. 6. 6  
T o ti me of  defer vesce nce  
 
1. 3. 6. 7  
T o n or malizati o n of dise ase -relate d la b orat or y a b n or malities 
 
1. 3. 7  E x pl orat or y Bi ol o gic c orrelates  
 
1. 3. 7. 1  
T o e val uate c yt o ki ne le vels pre a n d p ost -t ociliz u ma b, s pecificall y e val uati n g I L-6  
 
1. 3. 7. 2  
T o e val uate S A R S -C o V -2  viral l oa ds pre a n d p ost -t ociliz u ma b 
 
1. 3. 7. 3  
T o deter mi ne t he p h ar mac o ki netics of  t ociliz u ma b i n or der t o facilitate e x p os ure-
res p o nse a n al ysis 
 
1. 3. 7. 4  
T o c orrel ate cli nical o utc o mes wit h c ha n ges i n c yt o ki ne le vels a n d S A R S -C o V -2 
viral l oa ds  
 
2.  B A C K G R O U N D  A N D R A TI O N A L E  
 
2. 1  
C or o n a vir us S A R S -C o V -2  a n d Se vere C or o n a v ir us Dise ase 1 9 (C O VI D -1 9)  as a 
N ati o n al  P u blic He alt h E mer ge nc y  
 
S A R S -C o v -2 is a ra pi dl y s prea di n g pa n de mic c or o na vir us t hat ca us es a fe brile ill ness ter m e d 
C or o na v ir us Diseas e 1 9 ( C O VI D-1 9) a n d ca n i ncl u de a let h al ac ute res pir at or y s y n dr o me. 1  T h e 
i nitial cl uster of cases was re p orte d b y t he C hi nese g o ver n me nt o n Dece m ber 2 9, 2 0 1 9.  O n Ja n uar y 
3 0, 2 0 2 0 t he W or l d H ealt h Or ga niz ati o n declare d it a gl o bal healt h e mer g e nc y o wi n g t o its ra pi d 
gl o bal s prea d a n d c o ncer ns f or hi g h let halit y.  S A R S -C O V -2 is hi g hl y i nfecti o us b y cas ual c o nt act 
a n d is ass ociate d wit h a 2 -4 % m ortalit y i n affecte d pers o ns. 2 -4  T here is n o k n o w n effecti ve t h era p y.  
C O VI D -1 9 a p pears t o b e m ost da n g er o us t o t h e s ur vi val of t h ose a g e d 6 0 years a n d o ver wit h 
c hr o nic c o m or bi d c o n diti o ns, b ut se vere ill ness has bee n d oc u me nte d i n all a ge a n d healt h gr o u ps. 5  
F urt her m ore, i n ol der patie nts or i n t h ose w h o are i m m u n oc o m pr o mise d, t here ma y be a l o n ger 
d urati o n of ti me t hat t he vir us ca n c o nti n ue t o replicate bef ore t he b o d y’s o w n i m m u ne s yste m ca n 
res p o n d, lea di n g t o p ote ntiall y m ore se vere c o m plicati o ns.  T he d urati o n fr o m e x p os ure t o ill ness 
is less t ha n t w o w ee ks i n m ost cases, lea di n g t o ac ute de ma n ds o n healt h care res o urces.  C o m m o n 
s y m pt o ms at onset i ncl u de fe v er, c o u g h, a n d m y al gia or fati g ue.  U p t o 3 0 % of patie nts ma y 
de vel o p se vere c o m plicati o ns i ncl u di n g ac ute res pirat or y distress s y n dr o me,  re q uiri n g i nte nsi ve 
care s u p p ort.  A m o n g t his gr o u p  of criticall y ill patie nts, t he fatalit y rat e is hi g h a n d esti mate d 
bet wee n  2 0 -6 5 %. 3, 6  Se vere ac ute res pirat or y s y n dr o me ( S A R S) re prese nts m ost cases at t he e n d 
of life s pectr u m i n C O VI D -1 9 nat ural hist or y.  
 
2. 1. 1  Cli nical Prese ntati o n of Patie nts wit h C O VI D -1 9 I nfecti o n  
 
Base d o n a series of rece nt re p o rts o n C O VI D-1 9, t he prese ntati o n of C O VI D -1 9 ra n g es 

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1 4  
 
fr o m as y m pt o matic t o life-t hreat e ni n g, lea di n g t o fatal c o m plicati o ns.  Res pirat or y 
c o m plicati o ns are t he mai nsta y  of t he disease, ra n gi n g fr o m as y m pt o matic carri ers or mil d 
s y m pt o ms t o de vel o p me nt of acute res pirat or y distress s y n dr o me ( A R D S) a n d s u bse q ue nt 
res pirat or y a n d/ or m ulti-or ga n fail ure.  Alt h o u g h t he case fatalit y rate a m o n gst all patie nts 
wit h C O VI D -1 9 re mai ns l o w, 2 m ortalit y rates f or t h ose w h o are h os pitalize d or critic all y 
ill are asto nis hi n gl y hi g h. 3, 4  
 
A m o n gst 1 9 1 h os pitalize d patie nts fr o m o ne of t w o ce nters i n W u ha n, C hi na, 5 4 ( 2 8. 2 %) 
of patie nts die d fr o m c o m plicati o ns of C O VI D -1 9.  I n a si n gle-ce nter st u d y fr o m W u ha n, 
C hi na, 5 2 or 7 1 0 ( 7. 3 %) of patie nts wit h C O V I D-1 9 were critic all y ill.  A m o n gst t hese 
criticall y ill patie nts 3 2 of 5 2 ( 6 1. 5 %) i nfecti o n die d, wit h t he maj orit y of d eat hs occ urri n g 
wit hi n 1 -2 wee ks after a d missi o n t o t he I C U. 3 I n t his st u d y, n o n -s ur vi v ors were m ore li kel y 
t o be ol der, m ore li kel y t o de vel o p A R D S a n d nee de d mec ha ni cal ve ntilati o n.3  
 
Cli nical prese ntati o n al o n g wit h ra di o gr a p hic fi n di n gs 7 are ess e ntial i n i d e ntif yi n g t h ose 
patie nts at hi g h ris k fr o m de vel o pi n g se v ere C O VI D -1 9 p ne u m o nia.  Base d o n a si n gle 
center st u d y of 2 0 1 patie nts wit h C O VI D -1 9 i n W u ha n, C hi na fact ors ass ociate d wit h 
A R D S a n d deat h i n p atie nts wit h C O VI D -1 9 i ncl u de d ol der a ge, n e utr o p hilia, or ga n a n d 
c oa g ulati o n d ysf u ncti o n. 8  
 
2. 1. 2  C O VI D -1 9 I nfecti o n i n C hil dre n  
 
Preli mi nar y re p orts of C O VI D -1 9 i nfecti o n i n c hil dre n re p ort o n a ge nerall y mil der cli nical 
c o urse t ha n w hat has bee n see n i n a d ults. 9, 1 0  H o we ver, C O VI D -1 9 c o ul d ca use si g nifica nt 
m or bi dit y a n d m ortalit y, partic ularl y i n c hil dre n wit h pre -e xisti n g c o n diti o ns, t h ose w h o 
are i m m u n os u p presse d or ha ve c hr o nic car di o -p ul m o nar y disease.   I n dee d se vere cas es i n 
c hil dre n wit h C O VI D -1 9  ha ve bee n re p ort e d a n d i n t hese cases, feat ures of c yt o ki ne st or m 
ha ve bee n pres e nt , w hic h ca n prese nt wit h ver y ra pi d o nset.1 1  Miti gati o n strate gies t o 
pre ve nt se v erit y of dise ase i n c hil dre n at hi g h -ris k of m or bi dit y a n d m ortalit y fr o m 
C O VI D -1 9 are i n dicat e d.  
 
2. 1. 3  Treat me nt of Se v ere C O VI D -1 9 I nfecti o n  
 
T here are c urre ntl y n o c urati ve strat e gies f or tr eat me nt of C O VI D-1 9 a n d eff orts o n 
o pti mizi n g disease ma na ge me nt strate gies are bas e d o n esta blis he d treat me nt para di g ms of 
A R D S. 1 2  D ue t o t he ra pi d s prea d of S A R S -C o V -2 a n d t he i nci de nce of patie nts re q uiri n g 
h os pitalizati o ns or I C U le vel care , t he a bilit y t o 
meet t he i ncreasi n g de ma n d f or 
h os pitalizati o n a n d i nte nsi ve care u nit a d missi o ns is se verel y c halle n g e d. 1 3  Gi ve n t he hi g h -
ris k of m ortalit y partic ularl y f or t h ose re q uiri n g I C U le vel care, disease miti gati o n 
strate gies t o pre ve nt p atie nts fr o m re q uiri n g I C U le vel care or li miti n g d urati o n of 
i nt u bati o n i n t h ose at hi g hest-ris k of A R D S ma y i m pr o ve case-fatalit y rates a n d re d uce t h e 
b ur de n o n I C U le vel care all o wi n g m ore p atie nts t o be treate d.  Rece nt st u di es o n 
re m desi vir, a n u cle oti de a nal o g ue pr o dr u g t hat i n hi bits viral R N A p ol y merases wit h i n 
vitr o acti vit y a gai nst  S A R S -C o V -2, has s h o w n be nefit i n patie nts wit h C O VI D, 1 4 a n d ot her 
st u dies testi n g a nti-viral, a nti -malarial a n d a nti -c yt o ki ne directe d t hera pies are u n der wa y.  
 

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1 5  
 
 
2. 2  
C O VI D -1 9 i n C a ncer P atie nts  
 
As see n wit h ot her i nfecti o ns, p atie nts wit h ca ncer w h o bec o me i nfecte d wit h S A R S-C o V -2 are 
partic ularl y s usc e pti ble t o ha vi n g m ore se v ere c o m plicati o ns fr o m C O VI D -1 9 disease t ha n i n t h ose 
wi t h o ut a ca ncer dia g n osis.  I n a rece nt st u d y fr o m Dai a n d c ollea g ues, base d o n a m ulti-ce nter 
retr os pecti ve st u d y fr o m 1 4 h os pitals i n t he H u bei Pr o vi nce i n C hi na, patie nts wit h ca ncer a n d 
c o nc o mita nt C O VI D -1 9 ha d a hi g her i nci de nce of se vere e v e nts c o m par e d t o patie nts  wit h o ut 
ca ncer.1 5 S pecificall y, t he y c o m pare d o utc o mes fr o m 1 0 5 h os pitalize d patie nts wit h C O VI D -1 9 
a n d ca n cer t o 2 3 3 h os pitalize d patie nts wit h C O VI D -1 9 wit h o ut ca n cer.  T h eir fi n di n gs s u g geste d 
t hat patie nts wit h ca ncer te n de d t o ha ve m ore sev ere c o m plicati o ns relate d t o C O VI D -1 9 a n d t hat 
t his was partic ularl y n ot a ble i n t h ose wit h he mat ol o gic mali g na ncies, l u n g ca ncer, a n d met astatic 
disease.  F urt her m ore, i n t h ose w h o ha d rece nt i m m u n ot hera p y or ca ncer relate d s ur ger y, t here 
was a hi g h er ris k of nee di n g i nte nsi ve care a n d als o a hi g her deat h rate ( Fi g ur e 1).1 5  A n ot her st u d y 
fr o m Lia ng a n d c ollea g u es si milarl y f o u n d a hi g her ris k of se v ere e ve nts i n b ot h t h ose wit h ca ncer 
as well as i n ca n cer s ur vi v ors i n a li mite d s u bset of patie nts ( n = 1 8). 5  
 
 
Fi g ure 1. Se vere c o n diti o ns i n p atie nts wit h 
a n d wit h o ut c a ncer, a n d p atie nts wit h 
differe nt t y pes of c a ncer. Se vere c o n diti o ns 
i ncl u de deat h, I C U a d missi o n, ha vi n g 
se vere/critical s y m pt o ms ( Diffic ult y i n 
breat hi n g/ S h oc k/ Ac ute ki d ne y 
i nj ur y/ A R D S/ Arr h yt h mia/ M O D S) a n d usa g e of 
i n vasi ve mec ha nical ve ntilati o n. I C U =i nte nsi ve 
care u nit, A R D S = Ac ute Res pirat or y Distress 
S y n dr o me, M O D S = M ulti ple Or ga n D ysf u ncti o n 
S y n dr o me.  
T o p pa nel:  I nci de nce of se vere c o n diti o n a m o n g 
C O VI D -1 9 patie nts wit h ca ncer a n d wit h o ut 
ca ncer 
B ott o m pa nel:  I nci de nce of se vere c o n diti o n 
a m o n g C O VI D -1 9 patie nts wit h differe nt t y pes of 
ca ncer. 

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2. 3  
Se vere a c ute res pir at or y distress s y n dr o me ( A R D S) a n d c yt o ki ne rele ase s y n dr o me 
( C R S) 
 
C yt o ki ne re lease s y n dr o me ( C R S) is a s u pra-p h ysi ol o gic i nfla m mat or y pr ocess w hic h ca n b e see n 
i n t he c o nte xt of i nfla m m ati o n, i nfecti o n or i m m u ne acti vati o n. C R S as a ma nifestati o n has gai n e d 
si g nifica nt n ot oriet y i n rece nt y ears wit h t he a d v a nces i n cell ular t hera p y  a n d T-cell ass o ciate d 
C R S. 1 6  Ass ociate d wit h a h ost of m ulti -or ga n ma nifestati o ns, C R S ca n ra n ge fr o m mil d t o se v ere 
a n d t y picall y prese nts wit h t he o nset of fe v ers.  T h e cli nical pres e ntati o n ca n i ncl u de h y p ot e nsi o n, 
c oa g ul o pat h y, h y p o xia, a n d he p atic tra ns a mi nas es a m o n gst ot her feat ures a n d a nti -c yt o ki ne 
directe d t hera pies ha v e b ee n i m perati ve i n ma n a gi n g t he t o xicit y.  
 
Se vere ac ut e res pirat or y distress s y n dr o me ( A R D S) ca n be ass ociate d wit h c yt o ki ne release 
s y n dr o me ( C R S) or c yt o ki ne st or m, a n d t his is me diate d i n lar g e part b y i nterle u ki n -6 (I L -6). 1 7  I n 
C O VI D -1 9, hi g her plas ma le vels of c yt o ki nes i ncl u di n g I L -6, I L -2, I L -7, I L -1 0, gra n ul oc yte -
c ol o n y 
sti m ulati n g 
fact or 
( G -C S F), i nterfer o n -γ-i n d uci ble 
pr ot ei n 
(I P 1 0), 
m o n oc yte 
che m oattracta nt pr otei n ( M C P 1), macr o p ha ge i nfla m mat or y pr otei n 1 al p ha ( MI P -1 α), a n d T N F -
α were f o u n d i n I C U pati e nts c o nsiste nt wit h c yt o ki ne st or m. 6, 1 8  T he pres e ntati o n ass ociate d wit h 
se vere C O VI D-1 9 i nf ecti o n has i m plicate d t h e prese nce of a c yt o ki ne st or m t hat ma y b e a me na ble 
t o c yt o ki ne directe d t hera pies.1 9, 2 0  Treat me nt wit h met h yl pre d nis ol o ne decrease d t he ris k of deat h 
i n patie nts wit h A R D S i n o ne st u d y i n patie nts wit h C O VI D -1 9, 8 p ote ntiall y s u p p orti n g t he r ole 
of a nti -c yt o ki ne directe d t hera p y  i n a meli orati n g t he i mm u ne res p o nse t o C O VI D -1 9.  
 
2. 4  
T ociliz u m a b ( Pr o vi de d b y C T E P ) 
 
T ociliz u ma b is a rec o m bi na nt h u ma nize d m o n ocl o nal a nti b o d y directe d a g ai nst t he i nterle u ki n -6 
rece pt or (I L-6 R).  It bi n ds b ot h s ol u ble a n d m e m bra ne-b o u n d I L -6 R a n d i n hi bits I L -6 -me diate d 
si g nali ng t hr o u g h t hese rece pt ors.  It was i nitiall y F D A a p pr o ve d f or utilizati o n i n r he u mat oi d 
art hritis (i n 2 0 1 0) a n d j u ve nile i di o pat hic art hritis ( 2 0 1 1).  T ociliz u ma b is F D A a p pr o ve d f or 
c hil dre n a n d a d ults, starti n g at a n a ge >  2 years.  
 
Refer t o t he T o ciliz u ma b pac ka g e i nsert  f or d etails o n n o ncli nical a n d cli nical st u dies.  
 
2. 4. 1  T ociliz u ma b i n C A R T -cell Ass ociate d C R S  
 
Base d o n its utilizati o n i n treat me nt of C A R T -cell ass ociate d C R S, it recei v e d F D A 
a p pr o val i n t he treat me nt of se vere or life-t hreate ni n g C R S i n a d ults a n d i n pe diatric 
patie nts 2 years of a ge a n d ol der. 2 1 
 
T ociliz u ma b is a d mi nistere d i ntra ve n o usl y (I V) a n d d osi n g is wei g ht bas e d. 2 2  It ca n be 
use d al o ne or i n c o m bi nati o n wit h c ortic oster oi ds.  
 
T ociliz u ma b has als o bee n use d at l o wer d osi n g ( 4 m g/ k g) i n b ot h C R S a n d ot her 
r he u mat ol o gic diseases.  It is u n k n o w n w hat d ose of t ociliz u ma b w o ul d be effecti ve i n 
treati n g C R S ass ociate d wit h A R D S or S A R S.   
 

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2. 4. 2  Pre -e m pti ve Utilizati o n of T ociliz u ma b i n C R S  
 
Wit h i ncreasi n g utilizati o n of C A R T -cell t hera p y i n he mat ol o gic mali g na ncies, a n d a g oal 
t o a v oi d se vere t o xicities, t ociliz u ma b has bee n effecti vel y e m pl o ye d i n pre-e m pti ve 
strate gies t o re d uce t he s e verit y of C R S. 2 3  S peci ficall y i n patie nts wit h l o w-gra d e C R S, 
i nitiati o n of t ociliz u ma b has bee n effecti ve i n pre ve nti n g hi g her-gra d e C R S.  
 
2. 4. 3  T ociliz u ma b i n C O VI D -1 9  
 
T he le vels of t he c yt o ki nes a p pear t o b e ass oci ate d wit h disease se verit y a n d pr o g n osis.  
O n t his basis Xia oli n g X u a n d c ollea g ues tr eate d 2 1 se verel y ill patie nts wit h C O VI D -1 9 
wit h t he m o n ocl o nal a nti b o d y t ociliz u ma b, a n I L -6 rece pt or a nta g o nist t h at is U S F D A 
a p pr o ve d f or c yt o ki ne release s y n dr o me a n d se veral a ut oi m m u ne -relate d art hriti des. 2 4  All 
patie nts were o n  p utati ve C O VI D -1 9 t hera p e utics i ncl u di n g l o pi na vir, met h yl pre d nis ol o ne, 
o x y ge n a n d  ot her s u p p orti ve care meas ures at baseli ne.  Ei g htee n patie nts recei v e d 
t ociliz u ma b at a flat 4 0 0 m g I V d ose o nce a n d 3 patie nts recei ve d a sec o n d d ose at t he sa me 
d ose d ue t o fe ver wit hi n 1 2 h o urs.  T he cli nical s y m pt o ms i m pr o ve d i n all treate d patie nts.  
Ni netee n p atie nts ( 9 0. 5 %) ha v e b ee n dis c har ge d, i ncl u di n g t w o of t he m ost criticall y ill 
patie nts,  as of t he res ults bei n g ma de p u blicl y a vaila ble.  T h eref ore, it a p pears t h at 
t ociliz u ma b ca n effecti vel y treat se v ere C O VI D -1 9 -relate d S A R S b y bl oc ki n g t he I L-6 -
ass ociate d fe brile a n d i nfla m mat or y st or m res p o ns e.   A nec d otal re p orts fr o m off -la bel us e 
of t ociliz u ma b i n h os pitalize d patie nts s u g gest a rati o nal i n C O VI D -1 9 dis ease.  
 
A ra n d o mize d, d o u ble -bli n d, place b o -c o ntr olle d m ultice nter st u d y t o e val uate t he safet y 
a n d effi cac y of t ociliz u ma b i n h os pitalize d a d ults wit h se vere C O VI D -1 9 p ne u m o nia is 
acti vel y accr ui n g ( Cli nical Trials. g o v N C T 0 4 3 2 0 6 1 5 ).  I n t his st u d y, patie nts will be 
ra n d o mize d t o recei vi n g eit her place b o or a si n gle d ose of t ociliz u ma b 8 m g/ k g ( ma x d ose 8 0 0 
m g), wit h a n o pti o n t o recei ve o ne a d diti o nal d ose.  Ca ncer patie nts wit h he mat ol o gic 
mali g na nces or b o ne marr o w i n v ol ve me nt b y di sease ma y p ote ntiall y n ot be eli gi ble f or t he 
ra n d o mize d st u d y d ue t o  eli gi bilit y criteria base d o n ne utr o p hil a n d platelet c o u nts.  H o we ver, 
t his c o h ort of ca ncer patie nts is li kel y t o be m ost at ris k of se vere c o m plicati o ns fr o m C O VI D-
1 9 base d o n rece nt data. 1 5 
 
2. 4. 4  P har mac o ki netics of T o ciliz u ma b  
 
Alt h o u g h hi g her d oses of t ociliz u ma b ( 8 -1 2 m g/ k g) are t y picall y utilize d f or treat me nt of 
C A R T -cell relate d C R S, l o wer d osi n g ( 4 
m g/ k g) has effecti vel y bee n e m pl o ye d. 
F urt her m ore, it is u n k n o w n if l o wer d oses c o ul d be effecti ve f or  c yt o ki ne st or ms n ot relate d 
t o C A R T-cell t hera p y , w here c yt o ki ne le vels are si g nifica ntl y ele vate d.  T he d ose use d b y 
X u a n d c ollea g ues was a flat d ose of 4 0 0 m g, w hic h c o ul d wi del y c orres p o n d t o a d ose 
ra n ge fr o m 4-8 m g/ k g b ase d o n t he size of t h e patie nt (e. g., 4 0 0 m g = 6. 6 7 m g/ k g f or a 6 0 
k g a d ult).  
 
Base d o n p har mac o ki netic/ p har mac o d y n a mic data 2 5 a n d u n p u blis he d data ge nerate d b y 
Ge ne nte c h , a 4 m g/ k g I V d ose elicite d a si milar o nset a n d ma g nit u de of I L-6 p at h wa y 
i n hi biti o n as t he 8 m g/ k g d ose.  T he pri mar y differe nce was a s h orter d urati o n of i n hi biti o n 

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wit h t he 4 m g/ k g d ose c o m pare d t o t he hi g her d ose i n t he prese nce of hi g her le vels of 
I L-6 R; w hic h c o ul d be f urt her o pti mize d b y a sec o n d d ose of 4 m g/ k g if nee de d.  
 
2. 4. 5  Ris ks of T ociliz u ma b  
 
B ase d o n data i n patie nts wit h a ut oi m m u ne disease w here t ociliz u ma b is m ore c hr o nicall y 
use d , t he mai n ris k of t ociliz u ma b i ncl u des i nfecti o n.  As per t he pac ka ge i nsert, as t here 
is a hi g her i nci de nce of i nfecti o ns i n t he el derl y p o p ulati o n ( 6 5 years of a g e a n d ol der), i n 
ge neral, ca uti o n s h o ul d be use d w he n treati n g t he el derl y. 2 2  Alt h o u g h t ociliz u ma b is 
relati vel y c o ntr ai n dicate d i n t he setti n g of acti ve i nfecti o n, gi ve n t he hi g h m or bi dit y a n d 
m ortalit y rate of S A R S -C o V -1 9 a n d t he ass ociati o n of hi g her le vels of I L -6 i n t h ose 
patie nts w h o  ulti matel y g o o n t o ha v e fatal o utc o m es as a res ult of C O VI D -1 9, 4 t he a bilit y 
t o re d uce t he i nfla m mat or y res p o ns e t o i nfecti o n ma y ulti matel y i m pr o ve o utc o mes i n 
t h ose wit h S A R S.   
 
I n t he c o nte xt of C A R T-cell relate d t hera p y, t he i nfecti o n ris k i m parte d b y a fe w d oses of 
d oses of t ociliz u ma b a p pears t o be less t ha n t hat f or c hr o nic t hera p y gi ve n i n setti n gs s uc h 
as r he u mat oi d art hritis .  C o nsi deri n g t he patie nt p o p ulati o n recei vi n g C A R T -cells, t he vast 
maj orit y of w h o m ha ve  he mat ol o gic mali g na ncies , a b n or mal marr o w f u ncti o n, pre -
e xisti n g c yt o pe nias  (i ncl u di n g se vere ne utr o p e nia) a n d are i m m u n oc o m pr o mise d, 
utilizati o n of t ociliz u ma b f or 1 -2 d oses has n ot bee n defi niti vel y ass ociate d  wit h a n y 
i ncreas e d ris k of i nfecti o n.2 6, 2 7  A d diti o nall y , t ociliz u ma b a d mi nistere d at 8 m g/ k g e ver y 
t w o wee ks f or u p t o 6 d os es i n HI V-ass ociat e d Ka p osi  Sarc o ma Her pes Vir us -m ultice ntric 
Castle ma n disease  ( MC D)  w as safe a n d tr a nsie ntl y effecti ve i n re d u ci n g I L -6 me diate d 
cli nical se q uela e of  M C D 2 8   
 
 
2. 5  
St u d y R ati o n ale a n d J ustific ati o n f or t he Us e of T ociliz u m a b i n H os pit alize d C a ncer 
P atie nts wit h C O VI D -1 9  
 
T here are c urre ntl y n o acti ve t hera pies f or se vere C O VI D -1 9 disease.  Pr ol o n ge d i nte nsi ve care 
re q uire me nts create a s h orta ge of a d diti o nal ca p acit y f or n e w e mer gi n g cas es lea di n g t o i ncrease d 
m ortalit y a m o n g t h ose u na ble t o be a vaile d of p ote ntiall y life -sa vi n g s u p p orti ve care.  T his 
pr ot oc ol is i nte n de d t o pr o vi de t ociliz u ma b as a disease miti gati n g strate g y wit h p ote ntiall y 
lifesa vi n g be nefit t o C O VI D-1 9 ca ncer patie nts w h o ma y be at hi g her ris k of c o m plicati o ns fr o m 
C O VI D -1 9 .  If effecti ve, t he strate g y will pr o m ote a n esse ntial p u blic healt h res p o nse t o t he 
C O VI D -1 9 e pi de mic b y decreasi n g ti me s pe nt i n t he I C U b y ca ncer patie nts  at hi g h ris k of 
re q uiri n g pr ol o n ge d i nte nsi ve care s o t hat be ds are ma de a vaila ble t o n e xt wa ve of se v ere C O VI D-
1 9 patie nts  wi t h or wit h o ut ca ncer.  A d diti o nall y, if effecti ve, t ociliz u ma b ma y all o w m or e ti mel y  
i nitiati o n or c o nti n uati o n of ca ncer t hera p y f or t h ose wit h u n derlyi n g mali g na ncies .  F or a g gressi ve 
a n d pote ntiall y c urati ve ca ncers, t ociliz u ma b c o ul d pr o vi de a pat h f or n ot o nl y pre ve nti n g C O VI D -
1 9 m ortalit y, b ut als o f or all o wi n g a d mi nistrati o n of life -s a vi n g ca ncer t hera p y.  As s uccessi ve 
wa ves of criticall y ill patie nts are a d mitte d t o t he I C U, tr eate d, a n d release d, if t he strate g y is 
s uccessf ul, t he a bilit y of e xisti n g healt h care res o urces t o pr o vi de care t o e mer gi n g cas es ca n b e 
i m pr o ve d.    
 

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T he ra pi d gl o bal s prea d of C O VI D -1 9 has create d a se vere healt h a n d s oci o ec o n o mic dist ur ba nce 
i n t he U nite d States.  T he Presi de nt declare d a Nati o nal E mer ge nc y o n Marc h 1 3, 2 0 1 3 t o e n ha nce 
t he Nati o n’s res p o nse t o t his crisis.2 9  Ra pi d de vel o p me nt a n d la u nc h of i nter ve nti o nal cli nical 
trials m ust be i m me diatel y pri oritize d s o t hat p ot e ntial effecti ve tr eat me nts ca n be deli vere d t o 
patie nts w h o ha ve  life t hreate ni n g C O VI D -1 9 c o m plicati o ns.  Data fr o m s uc h trials ca n ra pi dl y 
i nf orm t he sci e ntific f o u n dati o n f or ot her ne w cli ni cal trials.  T his Nati o nal Ca ncer I nstit ute cli n ical 
trial t o pr o vi de t ociliz u ma b t o se verel y ill C O VI D-1 9 ca ncer patie nts is i n res p o nse t o t he Nati o nal 
E mer ge nc y as decl are d b y t he Presi de nt of t he U nite d St ates.  
 
T he p ur p ose of t his pr ot oc ol is  t o ra pi dl y distri b ute t ociliz u ma b t o a n d  c ollect res p o nse a n d t o xicit y 
data t o f urt her e val u ate t he p ote ntial effecti ve ness of t ociliz u ma b i n se vere cases of C O VI D -1 9 i n 
ca ncer patie nts base d o n t he earl y re p ort of its effecti ve ness.2 4  T his will als o be t he first trial of 
t ociliz u ma b o pe n t o e nr oll me nt of h os pitalize d c hil dre n wit h ca ncer a n d C O VI D -1 9 disease.  
 
F urt her m ore, bas e d o n t he esta blis he d p h ar mac o ki netics of t ociliz u ma b a n d lac k of i nf or mati o n 
o n w hat d ose of t ociliz u ma b is nee de d t o ac hie ve be nefit, t his trial will als o all o w f or t he 
assess me nt of t he efficac y of a l o wer d os e of t ociliz u ma b i n patie n ts w h o are less se verel y ill . 
 
2. 5. 1  Treat me nt  C o h orts  
 
Treat me nt is i nte n de d f or o nl y 2 d oses.  
  
D osi n g of T ociliz u ma b :  Please refer t o t he Precis . 
 
3.  P A TI E N T S E L E C TI O N  
 
3. 1  
 I ncl usi o n Criteri a  
 
Patie nts m ust meet t he f oll o wi n g criteria f or st u d y e ntr y:  
 
3. 1. 1  Ca ncer  Di a g n osis: S u bjects  m ust ha ve a n acti ve ca ncer di a g n osis or ha ve c o m plete d 
t hera p y wit hi n 1 2 m o nt hs of i nitiati o n of pr ot oc ol s pecifie d t hera p y.  T his i ncl u des:  
•  S u bjects wit h a ne w ca n cer dia g n osis w h o ha v e n ot yet i nit iate d ca ncer t hera p y . 
•  S u bjects o n acti ve or ha v e rece nt l y c o m plete d ca n cer-dir ecte d t h era p y i ncl u di n g 
c he m ot hera p y, ra diati o n t hera p y, i m m u n ot hera p y or h or m o nal t hera p y a m o n gst 
ot hers.  
o  M yel os u p pressi ve c h e m ot hera p y f or patie nts i n re missi o n ( e. g., a dj u va nt 
c he m ot hera p y f or breast ca ncer, A M L c o ns oli dati o n) is pr o hi bite d u ntil cli nical 
rec o ver y ( 1 or 2 o n t h e 7-cate g or y or di nal scale).  
•  S u bjects o n a n y i n vesti gati o nal t hera p y f or t heir u n derl yi n g ca ncer, i n vesti gati o nal 
C O VI D -1 9  a nti-vir al a ge nts, or c o n valesce nt ser u m ai me d at treati n g C O VI D -1 9 
disease are eli gi ble.   I n v esti gat ors are re mi n de d t o c hec k w het her t he ot h er 
i n vesti gati o nal st u d y(s) t he patie nt is partici pati n g o n s pecificall y e x cl u de t ociliz u ma b 
a n d t o a dj u dicate b es t cli nical ma na ge me nt d eci si o n f or t he s pecific patie nt.  
•  S u bjects w h o ha ve u n der g o ne he mat o p oietic ste m cell tra ns pla nt wit hi n t he past 1 2 
m o nt hs , or are c o nti n ue d o n G V H D t hera p y, are als o eli gi ble  

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3. 1. 2  C O VI D -1 9 Dia g n osis :  Patie nts h os pitalize d wit h C O VI D -1 9 p ne u m o nia c o nfir me d b y:  
•  Ra di o gra p hic fi n di n gs c o ncer ni n g f or C O VI D -1 9 p ne u m o nia A N D  
•  C o nfir mat or y S A R S -C o V 2  p ositi ve res ult usi n g a n y testi n g assa y, or ( wit h or wit h o ut 
a c o nfir mat or y t est) wit h s us pici o n of C O VI D -1 9 disease o wi n g t o bel o n gi n g t o a 
hi g h -ris k de m o gra p hic gr o u p or li vi n g a n d/ or w or ki n g i n hi g h-ris k setti n gs or wit h 
k n o w n e x p os ure  A N D  
•  S p O 2 o n r o o m  air ≤9 3 % or Pa O 2/ Fi O 2 < 3 0 0 m m H g  
 
3. 1. 3  A ge ≥ 2 years .   
 
3. 1. 4  Patie nts  m ust ha ve a de q u ate or ga n f u ncti o n as ass esse d b y t he treati n g i n vesti gat or t o 
a d mi nister t ociliz u ma b : 
•  A S T a n d A L T < 1 0 x i nstit uti o nal u p per li mit of n or mal  
•  Patie nts wit h l o w bl o o d c o u nts attri b uta ble t o ca ncer t hera p y or u n derl yi n g 
mali g na nc y are eli gi ble  
 
3. 1. 5  Patie nts ma y be o n ot her  t hera pies f or C O VI D-1 9 i ncl u di n g  i n vesti gati o nal a n d n ot 
li mite d t o c ortic oster oi ds, azit hr o m yci n , c hl or o q ui ne, h y dr o x yc hl or o q ui ne  
•  F or patie nts alr ea d y e nr olle d o n ot her i n vesti gati o nal st u dies f or C O VI D -1 9, st u d y 
i n vesti gat ors s h o ul d verif y t hat c o-e nr oll me nt o n t his st u d y is per missi ble as per t he 
eli gi bilit y of t he ot her st u d y.  
 
3. 1. 6  H u ma n i m m u n o deficie nc y vir us ( HI V) -i nfecte d patie nts are eli gi ble f or t his trial u nless 
t he y ha ve o p p ort u nistic c o m plicati o ns  of AI D S ot her t ha n t he ca ncer t he y ha ve.  
 
3. 1. 7  F or patie nts wit h e vi de n ce of c hr o ni c he patitis B vir us ( H B V) i nfecti o n, s h o ul d be o n  
s u p pressi ve t hera p y, if i n dicate d.   
 
3. 1. 8  Patie nts wit h a hist or y of he patitis  C vir us ( H C V) i nfecti o n s h o ul d be o n treat me nt  if 
i n dicate d. 
 
3. 1. 9  T he effects of T o ciliz u ma b  o n t he de vel o pi n g h u ma n fet us are u n k n o w n.   
•  Pre g na nc y:  Base d o n a ni mal data, ma y ca us e fet al har m.  T ociliz u ma b  ma y be gi ve n if i n 
t he p h ysicia n’s j u d g me nt t he patie nt’s life is t hreat e ne d wit h o ut p ote ntial effecti ve 
t hera p y  
o  W o me n of c hil d beari n g p ote ntial m ust a gree t o use birt h c o ntr ol or re m ai n 
a bsti ne nt f or t he d urati o n of t he st u d y a n d f or at least 2 8 da ys f oll o wi n g t he last 
d ose of t ociliz u ma b .  Pre g na nc y tests s h o ul d be d o ne base d o n  t he discreti o n of 
t he patie nt a n d p h ysicia n. 
o  N ursi n g M ot hers: Disc o nti n ue dr u g or n ursi n g ta ki n g i nt o  c o nsi derati o n 
i m p orta nce of dr u g t o m ot her. 
o  Me n m ust a gree t o r e mai n a bsti ne nt (refrai n fr o m heter ose x u al i nterc o urse) or use 
a c o n d o m, a n d a gree m e nt t o refrai n fr o m d o nati n g s per m, f or t he d urati o n of t he 
st u d y a n d f or at least 2 8 da ys f oll o wi n g t he last d ose of t ociliz u ma b. 

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
2 1  
 
 
3. 1. 1 0  A bilit y t o u n dersta n d a n d t he willi n g ness t o si g n a writte n i nf or me d c o ns e nt d oc u me nt.   
Partici pa nts wit h i m paire d decisi o n -ma ki n g ca p acit y (I D M C) w h o ha v e a le gall y -
a ut h orize d re pres e ntati ve ( L A R) a n d/ or fa mil y me m ber a vaila ble will als o be eli gi ble.  
 
3. 2  
E xcl usi o n Criteri a  
 
Patie nts w h o meet a n y of t he f oll o wi n g criteria will be e xcl u de d fr o m e nr oll me nt:  
 
3. 2. 1  Pri or or c o nc urre nt utilizati o n of I L -6 s pecific tar geti n g strate gies f or tr eat me nt of 
C O VI D -1 9 t hat s h o we d  n o  be nefit aft er ma xi m u m  d osi n g ; (patie nts  w h o ha ve o nl y 
recei v e d 1 pri or d ose  a n d t here was e vi de nce of p ote ntial be nefit  ma y be eli gi ble ). 
•  T his i ncl u des silt u xi ma b, t ociliz u ma b , a n d saril u ma b  
 
3. 2. 2  K n o w n h y perse nsiti vit y or hist or y  of  se vere aller gic reacti o n t o t ociliz u ma b  or ot her 
m o n ocl o nal a nti b o dies . 
 
3. 2. 3  A n y seri o us me dical c o n diti o n or acti ve u nc o ntr olle d i nfecti o ns ( besi des C O VI D -1 9) 
t hat, i n t he i n vesti gat or’s j u d ge me nt, precl u de t h e s u bject’s safe partici pati o n i n t he st u d y. 
•  E xa m ples: Acti ve T B i nfecti o n  
 
3. 2. 4  Acti ve  di vertic ulitis  beca use of se vere flairs i n disease lea di n g ris k of b o wel perf orati o n 
 
3. 2. 5  Patie nts i n w h o m, i n t he o pi ni o n of t he treati n g p h ysicia n, pr o gressi o n t o deat h is 
i m mi ne nt a n d i ne vita ble wit hi n t he ne xt 2 4 h o urs, irres pecti ve of t he pr o visi o n of 
treat me nts, will be e xcl u de d fr o m t he st u d y. 
 
3. 2. 6  Patie nts recei vi n g or pla n ni n g t o recei ve a n y i n vesti gati o nal a ge nts ot her t ha n 
t ociliz u ma b are i neli gi ble f or t his st u d y, wit h t he f oll o wi n g e xce pti o ns: 
•  I n v esti gati o nal a ge nts directe d at a patie nt’s u n derl yi n g ca ncer are all o we d. 
•  I n v estigati o nal S A R S -C o V -2 a nti -viral a ge nts  
•  C o n valesce nt ser u m directe d at C O VI D -1 9 diseas e  
 
4.  
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 C T E P 
 
Nati o nal Ca ncer I nstit ute ( N CI) p olic y re q uir e s all i n di vi d uals c o ntri b uti n g t o N CI -s p o ns ore d trials 
t o re gister a n d t o re ne w t heir re gistrati o n a n n uall y.  T o re gister, all i n di vi d uals m ust o btai n a 
Ca ncer T hera p y E v al uati o n Pr o gra m ( C T E P) I de ntit y a n d Access Ma n a ge me nt (I A M) acc o u nt at 
htt ps:// cte pc ore. nci. ni h. g o v/ia m .  I n a d diti o n, pers o ns wit h a re gistrati o n t y pe of I n vesti gat or 
(I V R), N o n-P h ysicia n I n vesti g at or ( N PI V R), or Ass ociate Pl us ( A P) ( i.e., cli nical site staff 
re q uiri n g write access t o O nc ol o g y Patie nt E nr oll me nt Net w or k ( O P E N), Ra ve, or acti n g as a 
pri mar y site c o ntact) m ust c o m plete t heir a n n ual re gistrati o n usi n g C T E P’s we b -bas e d Re gistrati o n 
a n d Cre de ntial Re p osit or y ( R C R) at htt ps://cte pc ore. nci. ni h. g o v/rcr .    
 

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
2 2  
 
R C R utilizes fi ve pers o n re gistrati o n t y pes.  
•  I V R:  M D, D O, or i nter n ati o nal e q ui vale nt, 
•  N PI V R:  a d v a nce d practice pr o vi ders ( e.g ., N P or P A) or gra d u ate le vel r es earc h ers (e.g ., 
P h D),  
•  A P:  cli nical site staff ( e.g ., R N or C R A) wit h data e ntr y access t o C T S U a p plicati o ns 
(e.g ., R oster U p dat e Ma n a ge me nt S yste m [ R U M S], O P E N, Ra ve,),  
•  Ass ociate ( A):  ot her cli nical site staff i n v ol ve d i n t he c o n d uct of N CI -s p o ns ore d trials, 
a n d 
•  Ass ociate Basic ( A B):  i n di vi d uals ( e.g ., p har mace utical c o m pa n y e m pl o yees) wit h 
li mite d access t o N CI-s u p p orte d s yste ms. 
 
R C R re q uires t he f oll o wi n g re gistrati o n d oc u me nts:  
 
D oc u me nt ati o n Re q uire d  
I V R 
N PI V R  
A P  
A  
A B  
F D A F or m 1 5 7 2  
✔
 
✔
 
 
 
 
Fi na ncial Discl os ure F or m  
✔
 
✔
 
✔
 
 
 
N CI Bi os ketc h (e d ucati o n, trai ni n g, e m pl o y me nt, lice nse, a n d 
certificati o n) 
✔
 
✔
 
✔
 
 
 
G C P trai ni n g  
✔
 
✔
 
✔
 
 
 
A ge nt S hi p me nt F or m (if a p plica ble)  
✔
 
 
 
 
 
C V ( o pti o nal)  
✔
 
✔
 
✔
 
 
 
 
A n acti ve C T E P -I A M us er acc o u nt a n d a p pr o priat e R C R re gistrati o n is re q uire d t o access all 
C T E P a n d Ca ncer Tri als S u p p ort U nit ( C T S U) we bsites a n d a p plicati o ns.  I n a d diti o n, I V Rs a n d 
N PI V Rs m ust list all cli nical practice sites a n d I nstit uti o nal Re vie w B oar ds (I R Bs) c o veri n g t heir 
practice sites o n t he F D A F or m 1 5 7 2 i n R C R t o all o w t he f oll o wi n g:  
 
•  A d diti o n t o a site r oster,  
•  Assi g n t he t reati n g, cre dit, c o nse nti n g, or dr u g s hi p me nt (I V R o nl y) tas ks i n O P E N, 
•  Act as t he site -pr ot o c ol Pri nci pal I n vesti gat or ( PI) o n t he I R B a p pr o val ; 
 
I n a d diti o n, all i n vesti gat ors act as t he Site-Pr ot oc ol PI, or c o ns e nti n g/treati n g/ dr u g s hi p me nt, 
m ust be r os tere d at t he e nr olli n g site wit h a partici pati n g or ga nizati o n (i.e., Allia nce).  
 
A d diti o nal i nf or mati o n is l ocate d o n t he C T E P we bsite at 
htt ps://cte p.ca ncer. g o v/i n vesti gat or Res o urces/ d efa ult. ht m .  F or q uesti o ns, please c o ntact t he 
R C R  Hel p Des k  b y e mail at R C R Hel p Des k @ ni h. g o v . 
 
4. 2  
Site Re gistr ati o n  
 
T his st u d y is s u p p orte d b y t he N CI C a ncer Trials S u p p ort U nit ( C T S U).  
 

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
2 3  
 
I R B A p pr o v al 
 
Sites m ust use t he  N CI Ce ntral I nstit uti o nal Re vie w B oar d ( N CI CI R B)  as t he I R B of rec or d  a n d 
m ust s u b mit t he St u d y S pecific W or ks heet f or L o cal C o nte xt ( S S W) t o t he CI R B usi n g 
I R B Ma na g er t o i n dicate t heir i nte nt t o o pe n t he st u d y l ocall y.  T he N CI CI R B’s a p pr o val of t he 
S S W is a ut o maticall y c o m m u nicate d t o t he C T S U Re g ulat or y Offi ce, b ut sites are re q uire d t o 
c o ntact t he C T S U Re g ulat or y Office at C T S U Re g Pref @c occ g. or g  t o esta blis h site prefere n ces f or 
a p pl yi n g N CI CI R B a p pr o vals acr oss t heir Si g nat or y Net w or k.  Site prefere nces ca n be s et at t he 
net w or k or pr ot o c ol le vel.  Q uesti o ns a b o ut esta blis hi n g site prefere nces ca n be a d dress e d t o t he 
C T S U Re g ulat or y Office b y e m aili n g t he e mail a d dress a b o ve or calli n g 1 -8 8 8 -6 5 1 -C T S U 
( 2 8 7 8). 
 
I n a d diti o n, t he Site-Pr ot oc ol PI ( i.e., t he i n vesti gat or o n t he I R B a p pr o val) m ust meet t he 
f oll o wi n g fi ve criteri a t o c o m plete pr ocessi n g of t he I R B a p pr o val r ec or d: 
•  H ol ds a n Acti ve C T E P s tat us, 
•  R ostere d at t he site o n t h e I R B a p pr o val ( O nly U S Sites m ay p artici p ate ) a n d o n at least 
o ne partici pati n g r oster,  
•  If usi n g N CI CI R B, r ostere d o n t he N CI CI R B Si g nat or y rec or d, 
•  I n cl u des t he I R B n u m ber of t he I R B pr o vi di n g a p pr o val i n t he F or m F D A 1 57 2 i n t he 
R C R pr ofile, a n d  
•  H ol ds t he a p pr o priate C T E P re gistrati o n t y pe f or t he pr ot oc ol.  
 
A d diti o n al Re q uire me nts  
 
A d diti o nal re q uire me nts t o o btai n a n a p pr o ve d sit e re gistrati o n stat us i ncl u de:  
•  O nl y U S Sites ma y partici pate  
•  A n acti ve Fe deral wi de Ass ura nce ( F W A) n u m ber,  
•  A n acti ve r oster affiliati o n wit h t he Lea d Pr ot oc ol Or ga nizati o n ( L P O) or a Partici pati n g 
Or ga nizati o n, a n d  
•  C o m plia nce wit h all pr ot oc ol -s pecific re q uir e me nts ( P S Rs). 
 
4. 2. 1  D o w nl oa di n g  Re g ulat or y D oc u me nts  
 
D o w nl oa d t he site re gistrati o n f or ms fr o m t he pr ot oc ol-s pecific p a ge l ocate d o n t he C T S U 
me m bers’ we bsite.  Per missi o n t o vie w a n d d o w nl oa d t his pr ot oc ol a n d its s u p p orti n g d oc u me nts 
is restricte d base d o n p ers o n a n d site r oster assi g n me nt.  T o partici pate, t he i nstit uti o n a n d its 
ass ociate d i n vesti gat ors a n d staff m ust be ass ociat e d wit h t he L P O or a Partici pati n g 
Or ga nizati o n o n t he pr ot oc ol.  
 
•  L o g o n t o t he C T S U me m bers’ we bsite ( htt ps:// w w w.cts u. or g ) usi n g y o ur C T E P -I A M 
user na me  a n d pass w or d,  
•  Clic k o n Pr ot oc ols i n t he u p per left of y o ur scree n 
o  E nter t he pr ot oc ol n u m ber i n t he searc h fiel d at t he t o p of t he pr ot oc ol tree, or 
o  Clic k o n t he B y Lea d Or ga nizati o n f ol der t o e x pa n d, t he n select N CI , a n d pr ot oc ol 
n u m ber T R C -1 0 4 4 6  

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
2 4  
 
•  Clic k o n  D oc u me nts , sele ct Site Re gistr ati o n , a n d d o w nl oa d a n d c o m plete t he f or ms 
pr o vi de d.  ( N ote:  F or sites u n der t he CI R B i nitiati ve, I R B data will l oa d a ut o maticall y t o 
t he C T S U as descri be d a b o ve.)  
 
4. 2. 2  Pr ot oc ol  S pecific Re q uir e me nts  F or T R C -1 0 4 4 6  Site Re gistrati o n  
 
•  S peci me n Trac ki n g S yste m Trai ni n g Re q uire me nt:  
o  All site staff pla n ni n g t o d o data e ntr y i n Ra ve f or T R C -1 0 4 4 6 (i.e., Ra ve C R A or 
Ra ve C R A ( La b A d mi n) r ole) m ust c o m plete t he o n -li ne s peci me n trac ki n g trai ni n g, 
w hic h is a d mi nistere d via t he C o m plia nce, Lear ni n g, a n d S O P S ol uti o ns ( C L A S S) 
s yste m.  
o  C o m plet i o n of t his trai ni n g is re q uire d f or i n di vi d ual Ra ve C R As/ Ra ve C R A 
( La b A d mi ns) t o recei ve Ra ve i n vitati o ns f or t he st u d y, i.e., t o be a ble t o access t he 
st u d y i n Ra ve a n d e nter d ata/ ma na ge s p eci me n trac ki n g. 
o  A Ra ve C R A/ Ra ve C R A ( La b A d mi n) at a site t h at re cei v es site re gistrati o n a p pr o val 
f or T R C-1 0 4 6 6 ( or is a d d e d t o t he site r oster after it has recei ve d a p pr o val) will 
recei v e a n a ut o mat e d e m ail fr o m C L A S S Hel p Des k @ westat.c o m  wit h t he trai ni n g 
assi g n me nt a n d i nstr ucti o ns f or accessi n g C L A S S.  
o  C o m pleti o n of t he trai ni n g will be a ut o maticall y c o m m u nicate d t o t he Re g ulat or y 
S u p p ort S yste m ( R S S) a n d t o Me di data Ra ve, a n d t he i n di vi d ual will recei ve a n 
i n vitati o n t o T R C-1 0 4 6 6 i n Ra ve. T here is n o nee d t o s u b mit a  tr ai ni n g c o m pleti o n 
certific ate t o  t he C T S U t hr o u g h t he Re g ul at ory S u b missi o n P ort al. 
o  T he trai ni n g is a o ne -ti m e o nl y re q uire m e nt per i n di vi d ual.  If a n i n di vi d ual has 
pre vi o usl y c o m plete d t he trai ni n g f or a n ot her E T C T N , N C T N or N C O R P S st u d y 
(eit her wit hin C L A S S, or via t he pr oce d ure i n place pri or t o C L A S S), t he trai ni n g 
d oes n ot nee d t o be c o m plete d a gai n.   H o we ver, ne w versi o ns of t he S peci m e n 
Trac ki n g S yste m ma y re q uire ne w trai ni n g.  
o  F or q uesti o ns a b o ut t he tr ai ni n g c o nte nt or t he trac ki n g s yste m itse lf, please c o ntact 
S T S S u p p ort at T hera de x f or t he trai ni n g ( S T S. S u p p ort @t hera de x. c o m , T h era de x 
p h o ne: 6 0 9 -7 9 9 -7 5 8 0).  
o  F or q uesti o ns or c o n cer ns a b o ut accessi n g t he trai ni n g i n C L A S S , please c o ntact t he 
C L A S S Hel p Des k C L A S S Hel p Des k @ westat.c o m . 
 
4. 2. 3  S u b mitti n g Re g ulat or y  D oc u me nts  
 
S u b mit re q uire d f or ms a n d d oc u me nts t o t he C T S U Re g ulat or y Offi ce via t he Re g ulat or y 
S u b missi o n P ortal o n t he C T S U we bsite.  
 
T o access t he Re g ulat or y S u b missi o n P ortal, l o g o n t o t he C T S U me m bers’ we bsite → 
Re g ulat or y → Re g ulat or y S u b missi o n.  
 
I nstit uti o ns wit h patie nts waiti n g t hat are u na bl e t o use t he Re g ulat or y S u b missi o n P ortal s h o ul d 
alert t he C T S U Re g ulat or y Offic e i m me diatel y at 1 -8 6 6 -6 5 1 -2 8 7 8 i n or der t o recei ve f urt her 
i nstr ucti o n a n d s u p p ort. 
 
 

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
2 5  
 
4. 2. 4  C hec ki n g Site Re gistrati o n  Stat us  
 
Y o u ca n verif y y o ur sit e’s re gistrati o n stat us o n t he me m bers’ si de of t he C T S U we bsite.  
 
•  L o g o n t o t he C T S U me m bers’ we bsite  
•  Clic k o n Re g ul at ory  at t he t o p of y o ur scree n  
•  Clic k o n Site Re gistr ati o n  
•  E nter y o ur 5 -c haracter C T E P I nstit uti o n C o de a n d clic k o n G o  
 
N ote:  T he stat us s h o w n o nl y reflects i nstit uti o nal c o m plia nce wit h site re gistrati o n re q uire me nts 
as o utli ne d a b o ve.  It d oes n ot reflect c o m plia n ce wit h pr ot oc ol re q uire me nts f or i n di vi d uals 
partici pati n g o n t he pr ot o c ol or t he e nr olli n g i n vesti gat or’s stat us wit h t he N CI or t heir affiliate d 
net w or ks.  
 
4. 3  
P atie nt Re gist r ati o n  
 
4. 3. 1  O P E N / I W R S  
 
T he O nc ol o g y Patie nt E nr oll me nt Net w or k ( O P E N) is a we b -base d re gistrati o n s yste m a vaila ble 
o n a 2 4/ 7 basis.  O P E N is i nte grate d wit h C T S U re g ulat or y a n d r oster data a n d wit h t he Lea d 
Pr ot oc ol Or ga nizati o n ( L P Os) re gistrati o n/ra n d o mizati o n s yste ms or T hera de x I nteracti ve We b 
Res p o nse S yste m (I W R S) f or retrie val of p atie nt r e gistrati o n/ra n d o mizati o n assi g n me nt.  O P E N 
will p o p ulate t he patie nt e nr oll me nt data i n N CI’s cli nical data ma na g e me nt s yste m, Me di data 
Ra ve.  
 
Re q uire me nts f or O P E N access:   
 
•  A vali d C T E P -I A M acc o u nt. 
•  Be o n a n L P O r oster, N C T N  i ncl u di n g C O G, N C O R P S or E T C T N  C orres p o n di n g r oster, 
or Partici pati n g Or ga niz ati o n r oster wit h t he r ole of Re gistrar.  Re gistrars m ust h ol d a 
mi ni m u m of a n A P re gistrati o n t y pe.  
•  Ha ve a n a p pr o ve d site re gistrati o n f or a pr ot oc ol pri or t o patie nt e nr oll me nt.  
 
T o assi g n a n I n vesti gat or (I V R) or N o n -P h ysicia n I n v esti gat or ( N PI V R) as t he treati n g, 
cre diti n g, c o nse nti n g, dr u g s hi p me nt (I V R o nl y), or recei vi n g i n vesti gat or f or a patie nt tra nsfer i n 
O P E N, t he I V R or N PI V R m ust list t he I R B n u m ber use d o n t he site’s I R B a p pr o val o n t heir 
F or m F D A 1 5 7 2 i n R C R.   
 
Pri or t o accessi n g O P E N, site staff s h o ul d verif y t he f oll o wi n g:  
 
•  Patie nt has met all eli gi bilit y criteria wit hi n t he pr ot oc ol state d ti mefra mes, a n d  
•  All patie nts ha ve si g ne d a n a p pr o pri ate c o nse nt f or m a n d HI P A A a ut h orizati o n  f or m (if 
a p plica ble).  
 
N ote:   T he O P E N  s yste m will pr o vi de t he site wit h a pri nta ble c o nfir mati o n of re gistrati o n a n d 
treat me nt i nf or mati o n.  Please pri nt t his c o nfir mati o n f or y o ur rec or ds.   

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
2 6  
 
 
A ccess O P E N at htt ps:// o pe n.cts u. or g  or fr o m t he O P E N li n k o n t he C T S U me m bers’ we bsite.  
F urt her i nstr u cti o nal i nf or mati o n is i n t he O P E N secti o n of t he C T S U we bsite at 
htt ps:// w w w.cts u. or g  or  htt ps:// o pe n.cts u. or g .  F or a n y a d diti o nal q uesti o ns, c o ntact t he C T S U 
Hel p Des k at 1 -8 8 8 -8 2 3 -5 9 2 3 or cts uc o ntact @ w estat.c o m . 
 
4. 3. 2  Re m ote I nf or me d C o nse nt Pr ocess  
 
Pati e nts m ust pr o vi de i nf or me d c o nse nt t o partici p ate i n t his st u d y. Re m ote c o nse nt pr oce d ures  
are f o u n d h ere:  
htt ps:// w w w. ncicir b. or g/c o nte nt/ nci -cir b-i nf or mati o n-a b o ut-c o vi d-1 9 . 
 
T his ma y be use d i n or der t o li mit c o ntact a n d pr o m ote s ocial dista nci n g i n res p o nse t o C O VI D -
1 9 c o ntai n me nt meas ur es. Bef ore usi n g t hese Re m ote C o nse nt Pr oce d ures, sites m ust u p date 
t heir St u d y S pecific W or ks heet ( S S W) or t he Si g n at or y I nstit uti o n W or ks heet ( SI W) wit h t he 
CI R B t o state Re m ote C o nse nt Pr oce d ures are use d at t heir site.  
 
 
4. 3. 3  S pecial I nstr ucti o ns f or P atie nt E nr oll me nt  
 
•  All bi os peci me ns c ollect e d f or t his trial m ust be s u b mitt e d usi n g t he Ra ve  S peci me n 
Trac ki n g S yste m ( S T S) u nless ot her wise n ote d.   
•  T he s yste m is accesse d t hr o u g h s pecial Ra ve us er r oles:  “ C R A S peci me n Trac ki n g” f or 
data e ntr y at t he tr eati n g i nstit uti o ns a n d “ Bi ore p osit or y” f or users recei vi n g t he 
s peci me ns f or pr ocessi n g a n d st ora ge at refere n ce la bs a n d t he Bi ore p osit or y.   
•  Please refer t o t he Me di d ata Acc o u nt Acti vati o n a n d St u d y I n vitati o n Acce pta nce li n k o n 
t he C T S U we bsite u n der t he Ra ve/ D Q P ta b. 
•  I m p ort a nt:  F ail ure t o c o m plete re q uire d fiel ds i n S T S m a y res ult i n a del a y i n 
s a m ple pr ocessi n g.  A n y case rei m b urse me nts ass ociate d  wit h sa m ple s u b missi o ns will 
n ot be cre dite d if s a m ples re q uiri n g S T S s u b missi o n are n ot l o g ge d i nt o S T S.  
 
Detaile d i nstr ucti o ns ca n be f o u n d i n Secti o n  5. 3 . 
 
4. 3. 4  O P E N/I W R S Q uesti o ns?  
 
F urt her i nstr ucti o nal i nf or mati o n o n O P E N is pr o vi de d o n t he O P E N li n k of t he C T S U we bsite 
at htt ps:// w w w.cts u. or g  or at htt ps:// o pe n.cts u. or g .  F or a n y a d diti o nal q uesti o ns c o ntac t t he 
C T S U Hel p Des k at 1 -8 8 8 -8 2 3 -5 9 2 3 or cts uc o nt act @ westat.c o m .  
 
4. 4  
Ge ner al G ui deli nes  
 
F oll o wi n g re gistrati o n, p atie nts s h o ul d be gi n pr ot oc ol treat me nt wit hi n fi ve da y s.  Iss ues t hat 
w o ul d ca use tr eat me nt dela y s s h o ul d be disc usse d wit h t he Pri nci pal I n v esti gat or.  If a p atie 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 patie nt’s re gistrati o n o n t he st u d y 
ma y be ca n cele d.  T h e St u d y C o or di nat or s h o ul d be n otifie d of ca ncellati o ns as s o o n as p o ssi ble. 
 

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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  
 
All bi os peci me ns are o pti o n al, b ut hi g hly e nc o ur a ge d bec a use of t heir p ote nti al scie ntific v al ue 
i n a d dressi n g t he C O VI D-1 9 p a n de mic  
 
5. 1  
S u m m ar y  T a ble f or S peci m e n C ollecti o n  
 
Ti m e P oi nt  
S peci m e n  
Se n d S peci m e ns T o:  
B aseli ne  ( at ti me of i niti al d ose) 
 
•  7 ml W h ole Bl o o d i n P ur ple t o p E D T A 
t u be  
Bi o pat h ol o g y Ce nter ( B P C)  
•  7 ml W h ole Bl o o d i n Gree n t o p s o di u m 
he pari n t u be  
Bi o pat h ol o g y Ce nter ( B P C)  
E ver y 1 2 h o urs  f o ur ti mes f oll o wi n g t he first d ose of t ociliz u m a b ( 1 2, 2 4, 3 6, 4 8 h o urs) 
 
•  7 ml W h ole Bl o o d i n P ur ple t o p E D T A 
t u be 
Bi o pat h ol o g y Ce nter ( B P C)  
•  7 ml W h ole Bl o o d i n Gree n t o p s o di u m 
he pari n t u be  
Bi o pat h ol o g y Ce nter ( B P C)  
7 2 h o urs after i niti al d ose  
 
•  7 ml W h ole Bl o o d i n P ur ple t o p E D T A 
t u be  
Bi o pat h ol o g y Ce nter ( B P C)  
•  7 ml W h ole Bl o o d i n Gree n t o p s o di u m 
he pari n t u be  
Bi o pat h ol o g y Ce nter ( B P C)  
7  d a ys  after i niti al d ose 1 
 
•  7 ml W h ole Bl o o d i n P ur ple t o p E D T A 
t u be 
Bi o pat h ol o g y Ce nter ( B P C)  
•  7 ml W h ole Bl o o d i n Gree n t o p s o di u m 
he pari n t u be  
Bi o pat h ol o g y Ce nter ( B P C)  
1If t he p atie nt is still h os pitalize d 
N ote:  F or pe diatric patie nts, all bl o o d c ollecti o ns are o pti o nal.  Baseli ne a n d 7 2 h o ur s peci me ns 
s h o ul d be pri oritize d f or c ollecti o n a n d 5 ml i n he pari nize d t u be is pri oritize d o ver E D T A t u be .  
F or t he e ver y 1 2 h o ur c ollecti o n sc he d ule, pe di atric patie nts s h o ul d o nl y ha ve t w o c ollecti o ns.  
 
 
5. 2  
S peci m e 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 m e nt Kits   
 
S hi p pi n g kits o nl y  are pr o vi de d f or t his st u d y.   I nstit uti o nal s u p plies m ust be use d f or all 
s peci me n c ollecti o n.  
 
S hi p pi n g kits ca n be or dere d o nli ne via t he Kit Ma na ge me nt s yste m: 
(htt ps://rica p ps. nati o n wi dec hil dre ns. or g/ Kit Ma n a ge me nt ).  
 

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Users at t he cli nic al sites will nee d t o set u p a n acc o u nt i n t he Kit Ma na ge me nt s yste m a n d select 
a s pecific cli nical trial pr ot oc ol t o re q uest a kit.  Please n ote t hat pr ot o c ol ma y i ncl u de m ore t ha n 
o ne t y pe of kit.  Eac h us er ma y or der f o ur kits per da y f or t his  pr ot oc ol.  Kits are s hi p pe d gr o u n d, 
s o please all o w 5-7 d a ys f or recei pt.  A c o m plete list of kit c o nte nts f or eac h kit t y pe is l ocate d 
o n t he Kit Ma na ge me nt s yste m we bsit e. 
 
5. 2. 2  Sc he d uli n g of S peci me n  C ollecti o ns  
 
Please a d here t o t he f oll o wi n g g ui deli nes w he n sc he d uli n g pr oce d ures t o c ollect bl o o d :  
 
•  Fres h bl o o d s peci me ns ma y be c ollecte d a n d s hi p p e d M o n da y t hr o u g h Fri d a y.  
 
5. 3  
S peci m e n Tr ac ki n g  S yste m I nstr ucti o ns  
 
5. 3. 1  S peci me n Trac ki n g S yste m O ver vie w a n d E nr oll me nt I nstr u cti o ns  
 
F or t he Ra v e S peci me n Trac ki n g S yste m  (S T S ), t he f oll o wi n g i nf or mati o n will be re q ueste d: 
•  Pr ot oc ol N u m ber  
•  C T E P I n vesti gat or I d e ntificati o n ( C T E P I D) 
o  I nstit uti o n a n d affiliate na me 
o  I n v esti gat or’s na me 
•  Eli gi bilit y Verificati o n:  Patie nts m ust meet all t he eli gi bilit y re q uire me nts liste d i n 
Secti o n 3 . 
•  A d diti o nal Re q uire me nts:  
o  Patie nts m ust pr o vi de a si g ne d a n d date d, writte n i nf or me d c o ns e nt f or m.  
 
U p o n e nr olli n g a patie nt, I W R S will c o m m u nicate wit h O P E N, assi g ni n g t w o se parate a n d 
u ni q ue i de ntificati o n n u m bers t o t he patie nt, a U ni versal patie nt I D ( U PI D) a n d a Treat me nt 
patie nt I D.  T he U PI D is ass ociate d wit h t he patie nt a n d use d eac h a n d e v er y ti me t he patie nt 
e n ga ges wit h t he p orti o n of t his pr ot oc ol  t hat uses t he Ra ve  S peci me n Trac ki n g S yste m .  T he 
U PI D c o ntai ns n o i nf or m ati o n or li n k t o t he treat me nt pr ot oc ol.  I W R S will mai ntai n a n 
ass ociati o n bet wee n t he U PI D f or bi o ba n ki n g a n d m olec ular c h aracterizati o n a n d a n y treat me nt 
pr ot oc ols t he patie nt partici pa tes i n, t here b y all o wi n g a nal ysis of t he m olec ular c haract erizati o n 
res ults wit h t he cli nical data.   
 
P lease n ote t hat t he S T S s oft ware creates p o p-u p wi n d o ws w he n re p orts are ge nerate d, s o y o u 
will nee d t o e na ble p o p -u ps wit hi n y o ur we b br o wser w hile usi n g t he s oft w are.   
 
F or q uesti o ns re g ar di n g t he S peci me n Trac ki n g S yste m, please c o ntact S T S S u p p ort at  
S T S. S u p p ort @t hera de x.c o m . 
 
A s hi p pi n g ma nifest m ust  be i ncl u de d wit h all sa m ple s u b missi o ns.  
 
5. 3. 2  S peci me n La beli n g  
 

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5. 3. 2. 1  Bl o o d S peci me n La bels   
 
I n cl u de t he f oll o wi n g o n bl o o d s peci me ns (i ncl u di n g w h ole bl o o d): 
•  Patie nt St u d y I D  
•  U ni versal Patie nt I D ( U PI D)  
•  S peci me n I D (a ut o maticall y ge nerate d b y Ra v e ) 
•  Ti me p oi nt  
•  S peci me n t y pe ( e. g., bl o o d, ser u m) 
•  C ollecti o n date (t o be a d de d b y ha n d)  
 
5. 3. 2. 2  E xa m ple of S peci me n L a bel  
 
T he f oll o wi n g i ma ge is a n e xa m ple of a tiss ue s p eci me n la bel pri nte d  o n a sta n dar d A ver y la bel 
t hat is 1” hi g h a n d 2. 6 2 5” wi de. 
 
  
 
T he Q R c o de i n t he a b o v e e xa m ple is f or t h e S peci me n I D s h o w n o n t he sec o n d li ne.   
N O T E:  T he Q R c o de la bel is c urre ntl y u n der de v el o p me nt at T hera de x as of 3 1 -A u g -2 0 1 8; 
t heref ore, la bels g e nerate d b y t he S T S f or t his st u d y ma y n ot i ncl u de a Q R c o de. 
 
T he sec o n d li ne ite m fr o m t he e n d i ncl u des f o ur d ata p oi nts j oi ne d t o get her:  
1.  Tiss ue o nl y: Pri mar y ( P), Metastatic ( M), N or mal ( N) tiss ue i n dicate d at t he 
be gi n ni n g of t he s peci me n I D; t his fiel d is bla n k if n ot rele va nt ( e.g ., f or bl o o d) 
2.  Bl oc k I D or bla n k if n ot r ele va nt  
3.  S PI D ( S ur gical Pat h ol o g y I D) or bla n k if n o n e  
4.  T he last al p ha -n u meric c o de is pr ot oc ol s pecific a n d is o nl y i ncl u de d if t he pr ot oc ol 
re q uires a n a d diti o nal s pecial c o d e classificati o n 
 
T he last li ne o n t he e xa m ple la bel is f or t he ha n d writte n date a n d o pti o nal ti me.  
 
5. 3. 3  O ver vie w of Pr ocess at Treati n g Site  
 
5. 3. 3. 1  O P E N Re gistrati o n  
 
All re gis trati o ns will be perf or me d usi n g t he O nc ol o g y Patie nt E nr oll me nt Net w or k ( O P E N) 
s yste m.  O P E N c o m m u nicates a ut o maticall y wit h t he I nt eracti ve We b R es p o nse S yste m (I W R S) 
w hic h ha n dles i de ntifier assi g n me nts, a n y st u d y ra n d o mizati o n, a n d a n y prescri be d sl ot 

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assi g n me nts.  If s peci me n a nal ysis is re q uire d t o deter mi ne eli gi bilit y, t he pr ot oc ol will be set u p 
wit h m ulti -ste p re gistrati o n. 
 
Re gistrati o n wit h o ut eli gi bilit y s peci me n a nal ysis:  
 
1.  Site e nters re gistrati o n data i nt o O P E N d uri n g o ne or m ore ste ps.  
2.  I W R S recei v es data fr o m O P E N, ge nerates t he Patie nt St u d y I D a n d t he U ni versal Patie nt 
I D, b ot h of w hic h are se nt bac k t o O P E N. 
3.  I W R S se n ds all a p plica bl e re gistrati o n data directl y t o Ra ve at t he e n d of t h e fi nal 
re gistrati o n ste p. 
 
A n y data e ntr y err ors ma de d uri n g e nr oll me nt s h o ul d be c orrecte d i n Ra ve.  
 
5. 3. 3. 2  Ra ve S peci me n Trac ki n g  Pr ocess Ste ps  
 
Ste p 1 :  C o m plete t he Hist ol o g y a n d Dise ase  f or m ( b ut d o n ot u pl oa d re p orts u ntil a s peci me n 
la bel ca n b e a p plie d t o t he m) a n d t he Baseli ne f or ms re gar di n g Pri o r T her a pies .  E nter t he 
i nitial cli nical s peci me n data:  
•  S peci m e n Tr ac ki n g E nr oll me nt C R F:  E nter Ti me P oi nt, S peci me n Cate g or y, 
S peci me n T y pe, a n d n u m ber of la bels nee de d (i ncl u de e xtra la bels t o a p pl y t o re p orts t o 
be u pl oa de d).  C R F g e nerates u ni q ue S peci me n I D.  
 
Ste p 2 :  Pri nt la bels usi n g re p ort i n E D C a n d c oll ect s peci me n. 
•  La bel s peci me n c o ntai ners a n d write c ollecti o n date o n eac h l a bel.  After c ollecti o n, st ore 
la bele d s peci me ns as des cri be d i n Secti o n 5. 4. 2.  
 
Ste p 3 :  C o m plete s peci me n data e ntr y. 
•  S peci m e n Tr a ns mitt al F or m:  E nter c ollecti o n date a n d ti me a n d ot her re q uire d 
s peci me n details. 
 
Ste p 4 :  W he n rea d y t o s hi p, e nter s hip me nt i nf or mati o n.  
•  S hi p pi n g St at us C R F:  E nter trac ki n g n u m ber, y o ur c o ntact i nf or m ati o n, reci pie nt, 
n u m ber of c o ntai n ers a n d s hi p date o nce f or t he first s peci me n i n a s hi p me nt.  
•  C o p y S hi p pi n g C R F:  Select a d diti o nal s peci me ns t o a d d t o a n e xisti n g s hi p me n t 
refere nce d b y t he trac ki n g n u m ber. 
 
Ste p 5 :  Pri nt s hi p pi n g list re p ort a n d pre pare t o s hi p.  
•  Pri nt t w o c o pies of t he s hi p pi n g list, o ne t o pr o vi de i n t he b o x, t he ot her f or y o ur o w n 
rec or ds. 
 
Ste p 6 :  Se n d e mail n otificati o n.  
•  F or o nl y o ne of t h e s peci m e ns i n t he s hi p me nt, clic k “ Se n d E mail Alert ” c h ec k b o x o n t he 
S hi p pi n g St at us C R F  t o e mail reci pie nt. 
 
Ste p 7:   S hi p t he s peci me n(s).  
 

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5. 4  
S peci m e n C ollecti o n  
 
5. 4. 1  Bl o o d C ollecti o n  
 
5. 4. 1. 1  C ollecti o n  of Bl o o d i n E D T A  T u bes f or W h ole Bl o o d Pr ocessi n g  
 
1.  La bel E D T A t u bes acc or di n g t o t he i nstr ucti o ns i n Secti o n 5. 3 . 2. 
2.  C ollect 7  m L bl o o d i n E D T A t u be(s) a n d ge ntl y i n vert t u be t o mi x.  
3.  S hi p o n da y of c ollecti o n ( w he ne v er p ossi ble) acc or di n g t o i nstr ucti o ns i n Secti o n 
5. 5 . 
4.  If bl o o d ca n n ot be s hi p pe d o n t he da y of c ollecti o n (e. g., a late s c he d ule d c ollecti o n), 
t he n refri g erat e u ntil s hi p me nt.  
 
5. 4. 1. 2  C ollecti o n of Bl o o d i n S o di u m He pari n  T u bes f or W h ole Bl o o d Pr ocessi n g  
 
1.  La bel S o di u m He pari n  t u bes acc or di n g t o t he i nstr ucti o ns i n Secti o n 5.3 . 2. 
2.  C ollect 7  m L bl o o d i n S o di u m He pari n  t u be(s) a n d ge ntl y i n vert t u be t o mi x. 
3.  S hi p o n da y of c ollecti o n ( w he ne v er p ossi ble) acc or di n g t o i nstr ucti o ns i n Secti o n 
5. 5 . 
4.  If bl o o d ca n n ot be s hi p pe d o n t he da y of c ollecti o n (e. g., a late s c he d ule d c ollecti o n), 
t he n refri g erat e u ntil s hi p me nt.  
 
5. 5  
S hi p pi n g S peci m e ns fr o m Cli nic al Site t o t he Bi o p at h ol o g y Ce nter ( B P C)  
 
5. 5. 1  Ge neral S hi p pi n g I nf or mati o n  
 
Fres h bl o o d s h o ul d be s hi p pe d as o ne s hi p me nt at a m bie nt te m perat ur e, w he ne ver p ossi ble.  I n 
wi nter m o nt hs, please i ncl u de e xtra i ns ulati o n, s uc h as b u b ble wra p, i nsi de t he s hi p pi n g 
c o ntai ner.  
 
5. 5. 2  S peci me n S hi p pi n g I nstr ucti o ns  
 
Fres h bl o o d ma y b e s hi p pe d o n M o n da y t hr o u g h Fri da y.  Pleas e select “ Sat ur da y Deli ver y” 
w he n s hi p pi n g fres h bl o o d o n a Fri d a y.  
 
5. 5. 2. 1  S hi p pi n g Bl o o d i n Si n gle -C ha m ber kit   
 
1.  Bef ore pac ka gi n g s peci me ns, veri fy t hat eac h s p eci me n is la bele d acc or di n g t o 
i nstr ucti o ns i n S ecti o n 5.3 .2  
2.  Place t he bl o o d c ollecti o n t u be(s) i nt o a zi p -l oc k ba g.   
3.  Place zi p -l oc k b a g i nt o a bi o hazar d e n vel o pe wit h a bs or be nt materi al.  E x pel as m uc h air 
as p ossi ble a n d seal t he e n vel o pe sec urel y.  
4.  Place t he bi o hazar d e n v el o pe i nt o a T y ve k e n vel o pe.  E x pel as m u c h air as p ossi ble a n d 
seal sec urel y. 
5.  Place t he s peci me n(s) a n d a c o p y of t he s hi p pi n g ma nifest i nt o a st ur d y s hi p pi n g 
c o ntai ner. I n wi nter m o nt hs, please use a n i ns ulate d c o ntai n er a n d i n cl u de e xtra 

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i ns ulati o n, s uc h as b u b ble wra p, i nsi de t he s hi p pi n g c o ntai ner t o pre ve nt s peci me ns fr o m 
freezi n g.  
6.  Cl ose t he c o ntai ner a n d t a pe s h ut.  
7.  Attac h a s hi p pi n g la bel pri nte d fr o m t he Kit Ma na ge me nt s yste m 
(htt ps://rica p ps. nati o n wi dec hil dre ns. or g/ Kit Ma n a ge me nt ) t o t he t o p of t he s hi p pi n g 
c o ntai ner.  
8.  Attac h a Bi ol o gical S u bsta nce Cate g or y B stic ker t o t he si de of t he c o ntai n er. 
9.  S hi p s peci me ns via o ver ni g ht c o urier t o t he a d dress bel o w.  Fe d E x Pri orit y O ver ni g ht is 
str o n gl y rec o m me n de d t o pre ve nt dela ys i n p ac ka g e recei pt 
 
 
5. 5. 3  S hi p pi n g A d dress  
 
S hi p t o t he a d dress bel o w.  S hi p fres h bl o o d s peci me ns t he sa me da y of s peci me n c ollecti o n.  D o 
n ot s hi p s peci me ns t he da y bef ore a h oli da y.  
 
Bi o pat h ol o g y Ce nter ( B P C) at Nati o n wi de C hil dre n’s H os pital ( N C H)  
T he Researc h I nstit ute at Nati o n wi de C hil dre n's H os pital  
7 0 0 C hil dre n's Dri ve, W A 1 3 4 0  
C ol u m b us, O hi o 4 3 2 0 5  
P H: ( 8 0 0) 3 4 7 -2 4 8 6 F A X: 6 1 4 -7 2 2 -2 8 9 7  
E mail:  B P C Ba n k @ nati o n wi dec hil dre ns. or g  
 
Fe d E x Pri orit y O ver ni g ht  ser vice is ver y str o n gl y preferre d.   
 
5. 5. 4  C o ntact I nf or mati o n f or Assista nce 
 
F or all q ueries, pleas e use t he c o nta ct i nf or mati o n bel o w:  
 
Bi o pat h ol o g y Ce nter ( B P C) at Nati o n wi de C hil dre n’s H os pital ( N C H)  
T he Researc h I nstit ute at Nat i o n wi de C hil dre n's H os pital 
7 0 0 C hil dre n's Dri ve, W A 1 3 4 0  
C ol u m b us, O hi o 4 3 2 0 5  
P H: ( 8 0 0) 3 4 7 -2 4 8 6 F A X: 6 1 4 -7 2 2 -2 8 9 7  
E mail:  B P C Ba n k @ nati o n wi dec hil dre ns. or g  

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5. 6  
Bi o m ar ker Pl a n   
 
List of Bi o m ar ker Ass a ys i n Or der of Pri orit y  
Pri orit y  Bi o m ar k er N a m e  
Ass a y  
( C LI A:  Y/ N) 
Use i n t he Tri al a n d 
P ur p ose  
S peci m e n s 
Teste d  
C ollecti o n Ti m e 
P oi nts  
M a n d at or y 
or 
O pti o n al  
Ass a y L a b or at or y  a n d 
L a b PI  
Bl o o d -b ase d Bi o m ar k ers  
1  
M S D V -ple x (a 
c o m bi nati o n of a 
Pr oi nfla m mat or y 
Pa nel 1 0 -ple x a n d 
2 ple x a n d 1 -ple x)  
I N F g a m ma, 
I L-1 0, I L -
1 2 p 7 0, I L -1 3, 
I L-1 beta, I L -2, 
I L-4, I L -6, I L -
8, T N F -al p ha, 
G M -C S F, I L -
1 5, MI P -1a  
C LI A:  N  
E x pl orat or y  
E val uati o n of 
C yt o ki ne St or m -
i n d uce d h y p o xic 
p ne u m o nitis, 
pr os pecti ve researc h  
Ser u m fr o m 
Bl o o d i n S o di u m 
He p ari n T u bes 
a n d E D T A T u bes  
Baseli ne  
 
E ver y 1 2 h o urs  
f or f o ur 
c ollecti o ns 
 
7 2 h o urs after 
i nitial treat me nt 
 
7 da ys after i nitial 
treat ment if still 
h os pitalize d  
O  
Fre deric k Nati o nal 
La bs  
J o h n I n glefiel d  
 j o n.i n glefiel d @ ni h. g o v 
 
2  
S A R S -C o V -2 Viral 
L oa d  
T B D  
 
C LI A N  
E x pl orat or y  
Ser u m fr o m 
Bl o o d i n S o di u m 
He p ari n T u bes 
a n d E D T A T u bes  
Baseli ne  
 
E ver y 1 2 h o urs  
f or f o ur 
c ollecti o ns 
 
7 2 h o urs after 
i nitial treat me nt 
 
7 da ys after i nitial 
treat me nt if still 
h os pitalize d  
O  
T B D  

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Pri orit y  Bi o m ar k er N a m e  
Ass a y  
( C LI A:  Y/ N) 
Use i n t he Tri al a n d 
P ur p ose  
S peci m e n s 
Teste d  
C ollecti o n Ti m e 
P oi nts  
M a n d at or y 
or 
O pti o n al  
Ass a y L a b or at or y  a n d 
L a b PI  
3  
T ociliz u ma b 
p har mac o ki netics  
T B D  
 
C LI A:  N  
E x pl orat or y  
Deter mi nati o n of 
t ociliz u ma b P K pr ofile 
f or e x p os ure/res p o nse 
a nal ysis 
Ser u m fr o m 
Bl o o d i n S o di u m 
He p ari n T u bes  
Baseli ne  
 
E ver y 1 2 h o urs  
f or f o ur 
c ollecti o ns 
 
7 2 h o urs after 
i nitial treat me nt 
 
7 da ys after i nitial 
treat me nt if still 
h os pitalize d  
O  
T B D  
 

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5. 7  
E x pl or at or y/ A ncill ar y C orrel ati ve St u dies  
 
5. 7. 1  M S D V -ple x (a c o m bi nati o n of a Pr oi nfla m mat or y Pa nel 1 0 -ple x a n d 2 ple x a n d 1 -ple x)  
 
5. 7. 1. 1  S peci me n(s) Recei pt a n d Pr ocessi n g at t he Bi o pat h ol o g y Ce nter   
 
W h ole bl o o d i n S o di u m He pari n a n d E D T A t u bes will be pr ocesse d i nt o ser u m, ali q u ote d a n d 
fr oze n pri or t o st ora ge pri or t o se n di n g t o t he la b orat or y f or a nal ysis.  
 
5. 7. 1. 2  Site(s) Perf or mi n g C orrel ati ve  St u d y  
 
T he M S D V -ple x pa n el will be r u n at t he Fre deric k Nati o nal La bs  u n d er t he directi o n of J o h n 
I n glefiel d a n d ot hers t o be na me d . 
 
5. 7. 2  S A R S -C o V -2 Viral L oa d  
 
5. 7. 2. 1  S peci me n(s) Recei pt a n d Pr ocessi n g at t he Bi o pat h ol o g y Ce nter   
 
W h ole bl o o d i n S o di u m He pari n a n d E D T A t u bes will be pr ocesse d i nt o ser u m, ali q u ote d a n d 
fr oze n pri or t o st ora ge pri or t o se n di n g t o t he la b orat or y f or a nal ysis.  
 
5. 7. 2. 2  Site(s) Perf or mi n g C orrel ati ve  St u d y  
 
T he S A R S -C o V -2 viral l oa d will be r u n at a La b orat or y t o be det er mi ne d.  
 
5. 7. 3  T ociliz u ma b P har mac o ki netics  
 
5. 7. 3. 1  S peci me n(s) Recei pt a n d Pr ocessi n g at t he Bi o pat h ol o g y Ce nter   
 
W h ole bl o o d i n S o di u m He pari n t u bes will be pr ocesse d  i nt o ser u m, ali q u ote d a n d fr o ze n pri or 
t o st ora ge pri or t o se n di n g t o t he la b orat or y f or an al ysis.  
 
5. 7. 3. 2  Site(s) Perf or mi n g C orrel ati ve  St u d y  
 
T he t ociliz u ma b p har mac o ki netics will be r u n at a La b orat or y t o be d eter mi ne d.  
 
 
6.  T R E A T M E N T  P L A N  
 
6. 1  
A ge nt A d mi nistr ati o n  
 
Treat me nt will be a d mi nistere d o n a n i n patie nt b asis.  Re p orte d a d verse e ve nts a n d p ote ntial 
ris ks are des cri be d i n Secti o n 1 0.  A p pr o priate d os e m o dificati o ns are d escri be d i n Secti o n 7.   
 

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D osi n g :  
•  S u bjects  will recei ve a first d ose of t ociliz u ma b as descri be d i n t he ta bl e bel o w. 
o  A si n gle d ose s h o ul d n ot e xcee d 8 0 0 m g  re gar dless of weig ht.   
o  Patie nts w h o are n ot i nt u bate d or will n ot be i m mi ne ntl y i nt u bate d will start at a 
l o wer d ose as p er T a ble 1, wit h t he p ote ntial t o d ose -escalate o n s u bse q ue nt d osi n g 
o  Data  pr o vi de d b y Ge n e ntec h c o nfir ms sI L -6 sat urati o n at 4 m g/ k g t h o u g h t he d urati o n 
is sli g htl y less t ha n f or t he 8 m g/ k g.  F or t h ose n ot re q uiri n g mec ha nical ve ntilati o n, 
t his l o wer d ose is cl oser t o w hat was use d i n t he W u ha n re p ort.  F or t h ose u n der 3 0 k g 
in wei g ht, t he 6 m g/ k g is e xtra p olat e d t o b e e q ui vale nt t o 4 m g/ k g i n h ea vier/lar ger 
patie nts.  Ot her wise t he d oses are as p er t h e t ociliz u ma b pac ka ge i nsert f or a d ults a n d 
c hil dre n.  
•  Res p o nse t o a first d ose of t ociliz u ma b s h o ul d be assesse d pri or t o pr o cee di n g wit h 
s u bse q ue nt d osi n g 
o  It ma y ta k e u p t o 6 h o urs f oll o wi n g t he c o m pleti o n of t he i nf usi o n t o see res p o nse t o 
t ociliz u ma b.  Us uall y t he first si g ns are wit h res ol uti o n or i m pr o ve me nt i n fe vers . 
•  A sec o n d d ose of t ociliz u ma b ma y be gi ve n  bet w ee n  8 h o urs a n d 7 da ys f oll o wi n g 
c o m pleti o n of  t he first i nf usi o n.  A sec o n d i nf usi o n c o ul d be c o nsi dere d f or t he f oll o wi n g 
reas o ns:  
o  S ustai ne d or rec urre nt f e ver  O R  
o  N o decrease or n ot m ore t ha n a 1 -cate g or y i m pr o ve me nt o n t he 7-cate g or y or di nal 
scale ( o nl y sta bilizati o n or partial i m pr o ve me nt f oll o wi n g first d ose) O R  
o  A ≥1 -cate g or y w ors e ni n g o n t he 7 -cate g or y or di nal scale  fr o m na dir 
 ( o nl y Or di n al Sc ales 3-6 are eli gi ble f or i niti al d ose of t ociliz u m a b)  
F or t h ose at or a b o ve 3 0 k g  (> ): 
C o h ort  
Cli nic al St at us 
Descri pti o n  
D osi n g f or I niti al D ose  
D osi n g f or Sec o n d  D ose *  
A 1  
3 -4  
( N ot o n mec ha nical ve ntilati o n 
at ti me of re gistrati o n a n d n o 
i m me diate pla n f or i nt u bati o n) 
4  m g/ k g  
8 m g/ k g  
( or di n al sc ale 2 m a y 
recei ve if cli nic all y 
i n dic ate d) * 
B 1  
5 -6  
( O n mec ha nical ve ntilati o n at 
ti me of e nr oll me nt or i m mi n e nt 
i nt u bati o n i n dicate d) 
8  m g/ k g  
8 m g/ k g  
F or t h ose bel o w 3 0 k g  ( <): 
C o h ort  
Cli nic al St at us 
Descri pti o n  
D osi n g f or I niti al D ose  
D osi n g f or Sec o n d  D ose *  
A 2  
3 -4  
( N ot o n mec ha nical ve ntilati o n 
at ti me of re gistrati o n a n d n o 
i m me diate pla n f or i nt u bati o n) 
6  m g/ k g  
1 2 m g/ k g  
( or di n al sc ale 2 m a y 
recei ve if cli nic all y 
i n dic ate d) * 
B 2  
5 -6  
( O n mec ha nical ve ntilati o n at 
ti me of e nr oll me nt or i m mi n e nt 
i nt u bati o n i n dicate d) 
1 2  m g/ k g  
1 2 m g/ k g  

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•  Ma xi m al a d mi nistrate d  d ose , f or a si n gle d os e: 8 0 0 m g  re g ar dless of wei g ht  
•  O pti mal res p o nse t o t ociliz u ma b ma y n ot be s ee n u ntil 5 -6 h o urs aft er c o m pleti o n of t he 
i nitial i nf usi o n a n d will t y picall y ma nifest wit h res ol uti o n of/i m pr o ve me nt i n fe ver pri or t o 
ot her cli nical si g ns  
* A sec o n d d ose ma y b e gi ve n if t here is s ustai ne d or rec urre nt f e ver, n o decreas e or n ot m ore 
t ha n a 1-cate g or y i m pr o ve me nt o n t he 7-cate g or y or di nal scale ( o nl y sta bili zati o n or partial 
i m pr o ve me nt f oll o wi n g first d ose), or a ≥1-cate g or y w orse ni n g o n t he 7 -cat e g or y or di nal sc ale  
fr o m na dir.  T he s ec o n d d os e m a y be gi ve n bet wee n  8 h o urs  a n d 7 d a ys  fr o m c o m pleti o n of 
t he first d ose.  I n ma n y cases a s ec o n d d ose m a y n ot be necess ar y t o ac hi e ve o pti mal be nefit.   
 
6. 2  
Tre at me nt Sc he m a  
 
 
* * O pti mal res p o nse t o t o ciliz u ma b ma y n ot be see n u ntil 5 -6 h o urs after c o m pleti o n of t he 
i nitial i nf usi o n a n d will t y picall y ma nifest wit h res ol uti o n of/i m pr o ve me nt i n fe ver pri or t o 
ot her cli nical si g ns  
 
S u bjects wit h n o o bje cti ve i m pr o ve me nt after 2 d oses are u nli kel y t o be nefit fr o m f urt her 
a d mi nistrati o n of t ociliz u ma b a n d alter nati ve t hera pies s h o ul d be c o nsi dere d . 
 
6. 3  
C o nc o mit a nt Me dic ati o ns/ T her a p y  
 
6. 3. 1  C o nc urre nt T hera p y  
 
S u bjects will recei ve c o nc urre nt sta n dar d of care t hera p y at t he discreti o n of t h e treati n g tea m.  
C ortic oster oi ds ma y be use d as cli nicall y i n dicate d i n t he treat me nt of S A R S/ A R D S.  
 
C o nc urre nt ca ncer t hera p y ca n be c o nti n ue d  at t he discreti o n of t he tr eati n g tea m , wit h t he 
f oll o wi n g e xcl usi o n: 
•  I nitiati o n of m yel os u p pr essi ve c h e m ot hera p y f or patie nts i n re missi o n ( e. g., a dj u va nt 
c he m ot hera p y f or breast ca ncer, A M L c o ns oli dati o n) is pr o hi bite d w hile o n st u d y u ntil 
cli nical rec o v er y (attai n me nt of 1 or 2 o n t he 7 -cate g or y or di nal scale)  
 
Patie nts recei vi n g ster oi ds as part of ca n cer t hera p y ca n c o nti n ue t o recei ve ster oi ds, b ut if a dela y 
i n ster oi ds ca n be i m ple me nte d t hat is prefera ble. 

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Treat me nt wit h a n y c o nc urre nt i n vesti gati o nal a ge nt is pr o hi bite d, e xce pt f or:  
•  I n v esti gati o nal S A R S-C o V -2 ( C O VI D -1 9) a nti -viral a ge nts  
•  C o n valesce nt ser u m  
•  A n y i n vesti gati o nal a nti -ca ncer t hera p y ai me d at treati n g t he u n derl yi n g disease  
 
Treat me nt wit h a n y a d diti o nal i n vesti gati o nal a ge nt direct e d at p ul m o nar y c o m plicati o ns of 
C O VI D -1 9 is pr o hi bite d t hr o u g h 1 4 da ys after t he last d ose of t ociliz u ma b f or t h ose w h o re mai n 
o n st u d y, wit h e xce pti o n f or treat me nt t hat ma y b e c o nsi dere d life -sa vi n g. 
 
6. 3. 2  I nfecti o n Pr o p h yla xis 
 
I nfecti o n pr o p h yla xis wit h a nti micr o bial t hera p y s h o ul d be i nitiate d as per t he i nstit uti o nal 
cli nical practice g ui deli n es.  Gi ve n t he ris k of vir al reacti vati o n wit h use of t ociliz u ma b, patie nts 
wit h a k n o w n hist or y of viral i nfecti o n s h o ul d be o n a p pr o priate a nti viral pr o p h yla xis as feasi ble.  
I ntr a ve n o us i m m u n o gl o b uli n ma y be utilize d as cli nicall y i n dicate d.  S ur veilla nce b l o o d a n d 
f u n gal c ult ures m ust be p erf or me d p er i nstit uti o nal g ui da nce i n ne utr o p e nic patie nts. 
 
6. 3. 3  He mat ol o gic S u p p ort  
 
Gr o wt h fact or s u p p ort ( e. g., G C S F /fil grasti m) ma y be use d as cli nicall y i n dicate d i n t he setti n g 
of se vere i nfecti o n.  
 
Usi n g dail y C B C s as a g ui de, t he patie nt will recei ve platelets a n d pac ke d re d bl o o d cells 
(P R B C s) as nee de d. Atte m pts will be ma de t o kee p he m o gl o bi n > 8. 0 g m/ dL , a n d platelet c o u nt 
> 1 0, 0 0 0/ m m 3 (f or afe bril e patie nts) a n d > 2 0, 0 0 0/ m m3  (f or fe brile patie nts). All bl o o d pr o d ucts 
s h o ul d be irra diate d. L e u k oc yte filters s h o ul d be utilize d f or all blo o d a n d platelet tra nsf usi o ns t o 
decrease se nsitiz ati o n t o tra nsf use d W B C s a n d d ecreas e t he ris k of C M V  i nfecti o n.  
 
I n p atie nts wit h s y m pt o matic c oa g ul o pat h y, atte m pts will be ma de t o kee p platelets 
> 5 0, 0 0 0/ m m 3 a n d fi bri n o ge n a b o ve t he l o wer li mit of n or mal.  
 
6. 3. 4  Cli nical Trials or Alter nati ve C O VI D -1 9 Directe d t hera pies  
 
Patie nts ma y be c o n c urre ntl y e nr olle d o n alterati ve cli nical tri als or be recei vi n g alter nati ve 
C O VI D -1 9 dir ecte d t hera pies, i ncl u di n g a nti -virals, azit hr o m yci n, c o n v alesce nt plas ma, or a nti -
malarials a m o n gst ot hers.  Patie nts ma y N O T be e nr olle d o n c o nc urre nt tria ls wit h I L -6 directe d 
t hera p y or be recei vi n g ot her I L -6 direct e d t hera pies. It is re q u este d t hat if patie nts are o n ot her 
cli nical trials, t h ose trials s h o ul d be c hec ke d f or s pecific pr o hi biti o n of t ociliz u ma b t hera p y.  I n 
t he case w here t he ot her cli nical trial i n w hic h t he patie nt is partici pati n g pr o hi bits t ociliz u ma b 
t hera p y, treati n g p h ysicia ns s h o ul d ma ke a decisi o n base d o n best j u d g me nt w het her t o e nr oll t he 
patie nt o n t his trial.  
 
6. 3. 5  C Y P 4 5 0 S u bstrates  
 
C yt oc hr o me P 4 5 0 e nz y m e s i n t he li ver are d o w n-re g ulate d b y i nfecti o n a n d i nfla m mati o n sti m uli 

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i ncl u di n g c yt o ki nes s uc h as I L-6.  I n hi biti o n of I L-6 si g nali n g i n patie nts treate d wit h t ociliz u ma b 
ma y rest or e C Y P 4 5 0 acti vities t o hi g her le vels t ha n t h ose i n t he a bs e nce of t ociliz u ma b, lea di n g 
t o i ncrease d meta b olis m of dr u gs t hat are C Y P 4 5 0 s u bstrates.  I n vitr o st u dies s h o we d t hat 
t ociliz u ma b has t he p ote ntial t o affect e x pressi o n of m ulti ple C Y P e nz y mes i ncl u di n g C Y P 1 A 2, 
C Y P 2 B 6, C Y P 2 C 9, C Y P 2 C 1 9, C Y P 2 D 6 a n d C Y P 3 A 4.  Its effect o n C Y P 2 C 8 or tra ns p orters is 
u n k n o w n.  I n vi v o st u dies wit h o me praz ol e, m eta b olize d b y C Y P 2 C 1 9 a n d C Y P 3 A 4, a n d 
si m vastati n, meta b olize d b y C Y P 3 A 4, s h o we d u p t o a 2 8 % a n d 5 7 % decreas e i n e x p os ure o ne 
wee k f oll o wi n g a si n gle d ose of t ociliz u ma b, res pecti vel y.  T he effect of t ociliz u ma b o n C Y P 
e nz y mes ma y b e cli nicall y rele va nt f or C Y P 4 5 0 s u bstrates wit h narr o w t hera pe utic i n de x, w here 
t he d ose is i n di vi d uall y a dj uste d.  U p o n i nitiati o n or  disc o nti n uati o n of t ociliz u ma b, i n patie nts 
bei n g treate d wit h t hese t y pe s of me dici nal pr o d ucts, perf or m t hera pe uti c m o nit ori n g of effect 
(e. g., w arfari n) or dr u g c o nce ntrati o n (e. g., c ycl os p ori ne or t he o p h ylli ne) a n d t he i n di vi d ual d ose 
of t he me dici nal pr o d uct a dj uste d as nee de d.  E x ercise ca uti o n w he n c o -a d mi nisteri n g t ociliz u ma b 
wit h C Y P 3 A 4 s u bstrate dr u gs 
w here d ecreas e i n effecti ve n ess is u n desira ble, 
e. g., oral 
c o ntrace pti ves,  l o vastati n, at or vastati n, etc.  T he effect of t ociliz u ma b o n C Y P 4 5 0 e nz y me acti vit y 
ma y persist f or se v eral w ee ks aft er st o p pi n g t hera p y . 
 
6. 4  
D ur ati o n of T her a p y  
 
I n t he a bse n ce of treat me nt dela ys d ue t o a d verse e ve nt(s), tr eat me nt ma y c o nti n ue f or u p t o 2 
d oses of  t ociliz u ma b or u ntil o ne of t he f oll o wi n g criteria a p plies:  
 
•  
C O VI D -1 9 diseas e pr o gressi o n  usi n g t he Cli nical Stat us Scale  
 
•  
I nterc urre nt ill ness t hat pre ve nts f urt h er a d mi nistrati o n of treat me nt 
 
•  
U nacce pta ble a d vers e e v e nt(s)  
 
•  
Patie nt deci des t o wi t h dr a w fr o m t he st u d y 
 
•  
Ge neral or s pecific c h a n ges i n t he patie nt's c o n diti o n re n der t he p atie nt u nacce pta bl e f or 
f urt her tr eat 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  
 
•  
Ter mi nati o n of t he st u d y b y s p o ns or  
 
•  
T he dr u g ma n ufact ur er ca n n o l o n ger pr o vi de t h e st u d y a ge 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 d ates m ust be d oc u me nte d i n t he Case Re p ort F or m ( C R F).  
 
6. 5  
D ur ati o n of F oll o w -U p  
 
Patie nts will be f oll o we d f or at least 6 0 da ys after t ociliz u ma b i nf usi o n ; atte m pts t o f oll o w u p f or 
u p t o a year will be ma d e .  A n y f oll o w -u ps occ urri n g after disc h ar ge fr o m h os pitalizati o n ma y 

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4 0  
 
occ ur via tel e p h o ne if all t o xicities ha ve res ol ve d.   Patie nts re m o ve d fr o m st u d y f or u nacce pta bl e 
a d verse e ve nt(s) will be f oll o we d u ntil res ol uti o n  or sta bilizati o n of t he a d v erse e v e nt.  
 
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 
 
7. 1  
D osi n g Del a ys  
 
•  D osi n g s h o ul d be hel d if s u bjects de vel o p a ne w s eri o us i nfecti o n f oll o wi n g 
t ociliz u ma b ( n ot i ncl u di n g S A R S-C o V -2) a n d n ot res u me d u ntil t he i nfecti o n is u n der 
c o ntr ol 
•  C o nsi der m o nit ori n g i n t he e ve nt  ne ur ot o xicit y ( e. g., ne w seiz ures, deliri u m) a n d 
p ote ntial dela y i n d osi n g .  C o nsi der i nitiati o n of c ortic oster oi ds f or t he treat me nt of 
ne ur ot o xicit y  
•  Patie nts wit h h y perse nsiti vit y reacti o ns t o t he first d ose of t ociliz u ma b s h o ul d n ot 
recei v e a sec o n d d ose. 
 
7. 2  
 D osi n g M o dific ati o ns  
 
•  N o d ose a dj ust me nt is re q uire d i n patie nts wit h mil d or m o derate re nal i m pair me nt .  T he 
safet y a n d effic ac y h a ve  n ot bee n well st u die d i n t h ose wit h he patic i m pair me nt.  
 
 
8.  P H A R M A C E U TI C A L  I N F O R M A TI O N 
 
8. 1. 1  T ociliz u ma b  ( N S C 8 2 0 0 1 3) 
 
Ot her N a mes:  Acte mra  
 
Cl assific ati o n:  m o n ocl o nal a nti b o d y i n hi bit or of I L -6 rece pt or  
 
M o de of Acti o n:   
T ociliz u ma b  bi n ds s pecificall y t o b ot h s ol u ble I L -6 R (sI L -6 R) a n d me m bra ne -b o u n d 
I L-6 R  
( mI L-6 R) a n d h as bee n s h o w n t o i n hi bit sI L -6 R a n d mI L -6 R
me diat e d si g nali n g.  
 
Descri pti o n :   
T ociliz u ma b is a rec o m bi na nt h u ma nize d, a nti -h u ma n m o n ocl o nal a nti b o d y of t he 
i m m u n o gl o b uli n G 1 (I g G 1) s u b-class dir ecte d a g ai nst t he s ol u ble a n d me m bra ne -b o u n d 
i nterle u ki n 6 rece pt or (I L-6 R).  
 
H o w S u p plie d:  
T ociliz u ma b is s u p plie d b y Ge ne ntec h a n d distri b ute d b y t he P har mace utical Ma na ge me nt 
Bra nc h, C T E P, D C T D, N CI as a preser vati ve -free, sterile, clear, c ol orless t o pale yell o w 
s ol uti o n i n 8 0 m g / 4 m L, 2 0 0 m g / 1 0 m L, a n d 4 0 0 m g / 2 0 m L vials f or f urt her di l uti o n 
pri or t o i ntra ve n o us i nf usi o n.  I n a d diti o n t o t ociliz u ma b, eac h vi al c o ntai ns, dis o di u m 
p h os p hate d o deca h y drat e/s o di u m di h y dr o ge n p h os p hate di h y drate b uffere d s ol uti o n, 

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
4 1  
 
p ol ys or bate 8 0, s ucr os e, a n d Water f or I njecti o n t o a dj ust t he c o nce ntr ati o n t o  2 0 m g/ m L.  
 
Pre p ar ati o n:    
Patie nt < 3 0 k g: pre pare i nf usi o n usi n g a 5 0 m L i nf usi o n ba g or b ottle  
Patie nt > 3 0 k g: pre pare i nf usi o n usi n g a 1 0 0 m L i nf usi o n ba g or b ottle  
 
1.  Wit h dra w a v ol u me of 0. 9 % or 0. 4 5 % S o di u m C hl ori de I njecti o n, U S P, e q ual t o t he 
v ol u m e of t he t ociliz u ma b i njecti o n re q uire d f or t he patie nt’s d ose fr o m t he i nf usi o n ba g.  
2.  Wit h dra w t he a m o u nt of t ociliz u ma b f or i ntra ve n o us i nf usi o n fr o m t he vial(s) a n d a d d 
sl o wl y i nt o t he 0. 9 % or 0. 4 5 % S o di u m C hl ori de I njecti o n, U S P i nf usi o n ba g or b ottle. T o 
mi x t he s ol uti o n, ge ntl y i n vert t he ba g t o a v oi d f oa mi n g.  
 
St or a ge:  
 
St ore i ntact vials refri g erate d at 2º C t o 8º C ( 3 6° F t o 4 6° F). D o n ot freeze. Pr otect t he 
vials fr o m li g ht b y st ora ge i n t he ori gi nal pac k a ge.  
 
If a st ora g e te m perat ure e xc ursi o n is i dentifie d, pr o m ptl y ret ur n t ociliz u ma b t o 2º C t o 8º C 
( 3 6° F t o 4 6° F) a n d q uara nti ne t he s u p plies.  Pr o vi de a detaile d re p ort of t h e e xc ursi o n 
(i ncl u di n g d oc u me ntati o n of te m perat ur e m o nit ori n g a n d d urati o n of t he e xc ursi o n) t o 
P M B After H o urs @ mail. ni h. g o v  f or deter mi nati o n of s uita bilit y. 
 
St a bilit y:   
Refer t o t he pac ka ge la bel f or e x pirati o n.  
 
Dil ute d t ociliz u ma b s ol uti o ns f or i nf usi o n usi n g 0. 9 % S o di u m C hl ori de I njecti o n , U S P ma y 
be st ore d at 2° t o 8° C ( 3 6° t o 4 6° F) or r o o m te m perat ure f or u p t o 2 4 h o urs a n d s h o ul d be 
pr otecte d fr o m li g ht. If n ot use d i m me diatel y f oll o wi n g pre parati o n, st ore pre pare d i nf usi o n 
ba gs i n t he refri gerat or.  
 
Dil ute d t ociliz u ma b s ol uti o ns f or i nf usi o n usi n g 0. 4 5 % S o di u m C hl ori de I njecti o n , U S P 
ma y be st ore d at 2° t o 8° C ( 3 6° t o 4 6° F) f or u p t o 2 4 h o urs or r o o m te m perat ure f or u p t o 4 
h o urs a n d s h o ul d be pr otecte d fr o m li g ht. If n ot use d i m me diatel y f oll o wi n g pr e parati o n, st ore 
pre pare d i nf usi o n ba gs i n t he refri gerat or.  
 
Dil ute d t ociliz u ma b s ol uti o ns are c o m pati ble wit h p ol y pr o p yle ne, p ol yet h yle ne a n d 
p ol y vi n yl c hl ori de i nf usi o n ba gs a n d p ol y pr o p yle ne, p ol yet h yle ne a n d glass i nf usi o n b ottles.  
 
C A U TI O N: 
T he si n gle -use 
d osa ge f or m c o ntai ns 
n o a nti bacterial 
preser vati ves. T heref ore, a n y u n use d pr o d uct re mai ni n g i n t he vial after t he 
d ose has bee n pre pare d m ust be discar de d.  
 
R o ute  of A d mi nistr ati o n:  i ntra ve n o us 
 
Met h o d of A d mi nistr ati o n:  
•  All o w t h e dil ute d t ociliz u ma b s ol uti o n t o reac h r o o m te m perat ure pri or t o i nf usi o n.  
•  A d mi nister i ntra ve n o usl y o ver 6 0 mi n utes. D o n ot a d mi nister as a n i ntra ve n o us p us h or b ol us.  

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
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4 2  
 
•  T ociliz u ma b s h o ul d n ot be i nf use d c o nc o mita ntl y i n t he sa me i ntra ve n o us li ne wit h ot her  
dr u gs. N o p h ysical or bi oc he mical c o m pati bilit y st u dies ha ve bee n c o n d ucte d t o e val uate t he 
c o-a d mi nistrati o n of t ociliz u ma b wit h ot her dr u gs.  
•  Pare nteral dr u g pr o d ucts s h o ul d be i ns pecte d vis uall y f or partic ulate matter a n d disc ol orati o n 
pri or t o a d mi nist rati o n, 
w he ne ver s ol uti o n a n d c o ntai ner per mit. If partic ulates a n d 
disc ol orati o ns are n ote d, t he pr o d uct s h o ul d n ot be use d.  
 
P ote nti al Dr u g I nter acti o ns:  
C yt oc hr o me P 4 5 0s i n t he li ver are d o w n -re g ulate d b y i nfecti o n a n d i nfla m mati o n sti m uli 
i ncl u di n g c yto ki nes s uc h as I L -6. I n hi biti o n of I L -6 si g nali n g i n patie nts treate d wit h 
t ociliz u ma b ma y rest ore C Y P 4 5 0 acti vities t o hi g her le vels t ha n t h ose i n t he a bse nce of 
t ociliz u ma b, lea di n g t o i ncreas e d meta b olis m of dr u gs t hat are C Y P 4 5 0 s u bstrates. I n 
vitr o st u dies s h o we d t hat t ociliz u ma b has t he p ote ntial t o affect e x pressi o n of m ulti ple 
C Y P e nz y mes i ncl u di n g C Y P 1 A 2, C Y P 2 B 6, C Y P 2 C 9, C Y P 2 C 1 9, C Y P 2 D 6 a n d 
C Y P 3 A 4. Its effect o n C Y P 2 C 8 or tra ns p orters is u n k n o w n. I n vi v o st u dies wit h 
o me praz ole, m eta b olize d b y C Y P 2 C 1 9 a n d C Y P 3 A 4, a n d si m vastati n, meta b olize d b y 
C Y P 3 A 4, s h o we d u p t o a 2 8 % a n d 5 7 % decrease i n e x p os ure o ne wee k f oll o wi n g a 
si n gle d ose of t ociliz u ma b, res pecti vel y. T h e effect of t ociliz u ma b o n C Y P e nz y mes ma y 
be cli nicall y rele v a nt f or C Y P 4 5 0 s u bstrates  wit h narr o w t hera pe utic i n d e x, w here t he 
d ose is i n di vi d uall y a dj uste d. U p o n i nitiati o n or  
disc o nti n uati o n of t ociliz u ma b, i n patie nts bei n g treate d wit h t hese t y pes of me dici nal 
pr o d ucts, perf or m t hera p e utic m o nit ori n g of effect (e. g., warfari n) or dr u g c o nce ntr ati o n 
(e. g., c ycl os p ori ne or t he o p h ylli ne) a n d t he i n di vi d ual d ose of t he me dici n al pr o d uct 
a dj uste d as nee d e d. E xercise ca uti o n w he n c o -a d mi nisteri n g t ociliz u ma b wit h C Y P 3 A 4 
s u bstrate dr u gs w here decreas e i n effecti ve n ess is u n desira ble, e. g., oral c o ntrace pti ves, 
l o vastati n, at or vastati n, etc. T he effect of t ociliz u ma b o n C Y P 4 5 0 e nz y me acti vit y ma y 
persist f or se veral w ee ks after st o p pi n g t hera p y. A v oi d c o nc o mita nt use wit h li ve 
vacci nes.  
 
P atie nt C are I m plic ati o ns:  
Male a n d fe male patie nts recei v i n g t ociliz u ma b s h o ul d mai ntai n a de q uate c o ntrace pti ve 
meas ures d uri n g a n d f or a mi ni m u m of 2 8 da ys after t he last d ose of t ociliz u ma b.  
 
A v ail a bilit y  
 
T ociliz u ma b  is a n i n vesti gati o nal a ge nt s u p plie d t o i n vesti gat ors b y t he Di visi o n of Ca ncer 
Treat me nt a n d Dia g n osis ( D C T D), N CI.  
 
T ociliz u ma b  is pr o vi de d t o t he N CI u n d er a C olla b orati ve A gree me nt bet w ee n t he 
P har mace utical C olla b orat or a n d t he D C T D, N CI (see Secti o n  1 3 .5 ). 
 
8. 1. 2  A ge nt Or deri n g a n d A ge nt  Acc o u nta bilit y  
 
8. 1. 2. 1  N CI -s u p plie d a ge nts ma y be re q uest e d b y eli gi ble partici pati n g  I n vesti gat ors ( or t heir 
a ut h orize d desi g n ee) at e ac h partici p ati n g i nstit uti o n.  T he C T E P -assi g ne d pr ot oc ol 
n u m ber m ust be use d f or or deri n g al l C T E P-s u p plie d i n vesti gati o nal a ge nts.  T he 

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4 3  
 
eli gi ble partici pati n g  i n vesti gat ors at eac h partici p ati n g i nstit uti o n m ust be re gistere d 
wit h C T E P, D C T D t hr o u g h a n a n n ual s u b missi o n of F D A F or m 1 5 7 2 ( Stat e me nt of 
I n v esti gat or), N CI Bi os k etc h , A ge nt S hi p me nt F or m , a n d Fi na ncial Discl os ure F or m 
( F D F).  If t here are se veral partici pati n g i n vesti gat ors at o ne i nstit uti o n, C T E P-s u p plie d 
i n vesti gati o nal a ge nts f or t he st u d y s h o ul d be or dere d u n der t h e na me of o n e lea d 
partici pati n g i n vesti gat or at t hat i nstit uti o n. 
 
T he C T E P P har mace utical Ma na ge me nt Bra nc h ( P M B ) will pr o vi de directi o n as t o 
w he n sites ca n or der P M B -s u p plie d a ge nts. 
 
S u b mit a ge nt re q uests t hr o u g h t he P M B O nli ne A ge nt Or der Pr ocessi n g ( O A O P) 
a p plicati o n.  Access t o O A O P re q uires t he esta blis h me nt of a C T E P I d e ntit y a n d 
Access M a na ge m e nt (I A M) acc o u nt a n d t he mai nte na nce of a n “acti ve” acc o u nt 
stat us, a “c urre nt” p ass w or d , a n d acti ve p ers o n re gistrati o n stat us.  F or q uesti o ns 
a b o ut dr u g or ders, tra nsf ers, ret ur ns, or acc o u nta bilit y, call or e mail P M B a n y ti me.  
Refer t o t he P M B’s we bsite  f or s pecifi c p olicies a n d g ui deli nes relate d t o a ge nt 
ma na ge me nt.   
 
8. 1. 2. 2  A ge nt I n ve nt or y Re c or ds  –  T he i n vesti gat or, or a res p o nsi ble part y desi g nat e d b y t he 
i n vesti gat or, m ust mai ntai n a caref ul rec or d of t h e recei pt, dis pe nsi n g a n d fi nal 
dis p ositi o n of all a ge nts recei ve d fr o m t he P M B usi n g t he a p pr o priate N CI 
I n v esti gati o nal A ge nt ( Dr u g) Acc o u nta bilit y Rec or d ( D A R F) a vaila bl e o n t he C T E P 
f or ms pa ge.  St ore a n d mai ntai n se parate N CI I n v esti gati o nal A ge nt Acc o u nta bilit y 
Rec or ds f or eac h a ge nt, stre n gt h, f or m ulati o n a n d or deri n g i n vesti gat or o n t his pr ot oc ol.  
 
8. 1. 3  I n v esti gat or Br oc h ure  A v aila bilit y  
 
T he c urre nt versi o ns of t he I Bs f or t he a ge nts will be accessi ble t o site i n vesti gat ors a n d researc h 
staff t hr o u g h t he P M B O A O P a p plicati o n.  Access t o O A O P re q uires t he esta blis h me nt of a 
C T E P I A M acc o u nt a n d t he mai nte na nce of a n “acti ve” acc o u nt stat us , a “c urre nt” pass w or d  a n d 
acti ve pers o n re gistrati o n stat us .  Q uesti o ns a b o ut I B access ma y be directe d t o t he P M B I B 
C o or di nat o r via e mail. 
 
8. 1. 4  Usef ul Li n ks a n d C o ntacts  
•  C T E P F or ms, Te m plates, D oc u me nts:  htt p://cte p.ca ncer. g o v/f or ms/  
•  N CI C T E P Re gistrati o n:  R C R Hel p Des k @ ni h. g o v  
•  P M B p olicies a n d g ui deli nes: 
htt p://cte p.ca ncer. g o v/ br a nc hes/ p m b/a ge nt _ ma na g e me nt. ht m   
•  
P M B O nli ne A ge nt Or der Pr ocessi n g ( O A O P) a p pl icati o n:  
htt ps ://cte pc ore. nci. ni h. g o v/ O A O P  
•  C T E P I de ntit y a n d Access Ma na ge me nt (I A M) acc o u nt: htt ps://cte pc ore. nci. ni h. g o v/ia m/   
•  C T E P I A M acc o u nt hel p:  cte pre g hel p @ cte p. nci. ni h. g o v   
•  I B C o or di nat or:  I B C o or di nat or @ mail. ni h. g o v  
•  P M B e mail:  P M B After H o urs @ mail. ni h. g o v  
•  P M B p h o ne a n d h o urs of ser vice: ( 2 4 0) 2 7 6 -6 5 7 5 M o n da y t hr o u g h Fri d a y bet wee n 8: 3 0 
a m a n d 4: 3 0 p m ( E T)  

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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 is a n i nter ve nti o nal st u d y t o e val uate cli nical o utc o mes  of tociliz u ma b  i n se vere C O VI D-1 9 
disease a n d t o d escri be  res o urce utilizati o n of i nte nsi ve healt h care res o urces o n a p atie nt le vel 
basis.  
 
T he pri mar y e n d p oi nt of t his st u d y is t he cli nical o utc o me of patie nts a d mi nistere d at least o ne 
d ose of t ociliz u ma b as  e val uate d per t he 7 -cate g or y disease se verit y or di nal scale prese nte d i n t he 
Sc he ma . 
 
9. 2  
S a m ple Size/ Accr u al  R ate  
 
T he accr ual rate t o t his trial is e x pecte d t o be bris k o wi n g t o t he ra pi d accelerati o n of C O VI D -1 9 
cases.  T he trial will treat u p t o a p pr o xi matel y 2 1 7 patie nts .  Eff orts t o e nr oll ar o u n d 2 0 pe diatric 
patie nts  t o t his trial will be ma de.  Eff orts t o i ncl u de i nstit uti o ns t hat ser ve p e diatric ca ncer 
p o p ulati o ns wit h C O VI D -1 9 a m o n g c hil dre n ha ve  bee n pri oritize d.  T he i n vesti gat ors will m o nit or 
e nr oll me nt of pe diatric patie nts a n d i ncl usi o n of a d diti o nal pe diatric sites will be u n derta ke n as 
feasi ble.  T here are t w o c o h orts:  c o h ort A ( n ot o n mec ha nical ve ntilati o n a n d n o i m mi ne nt ris k of 
re q uirin g it); c o h ort B ( o n or at i m mi ne nt ris k of mec ha nical ve ntilati o n) . 
   
Accr ual will be trac ke d, a n d o utc o mes e val uat e d b ot h c u m ulati vel y a n d als o b y t he f oll o wi n g a ge 
stratificati o n: Strat u m 1)  2  years -1 4  years ; Strat u m 2) 1 5 -3 9  years ; Strat u m  3) 4 0 -6 4  years;  Strat u m 
4) 6 5 years a n d o ver.  
 
T here will be n o accr ual halt w hile t he data fr o m t he i nitial patie nts is c ollecte d  a n d gat h ere d.  
T here will be re peate d ass ess me nt of cli nical o utc o mes  after e very  2 0 a d diti o nal patie nts per c o h ort 
are e nr olle d t o pr o vi de o n g oi n g safet y m o nit ori n g.  Accr ual will be h alte d if t here is e vi de n ce of  
har m  d ue t o t ociliz u ma b .  E vi de nce of h ar m will be e val uat e d t o i ncl u de t he f oll o wi n g:  
•  I n crease i n rare b ut seri o us a d verse e v e nts ass ociate d wit h t ociliz u ma b a d mi nistrati o n s uc h 
as e vi de nce t hat a na p h yl a xis is occ urri n g i n m ore t ha n 1 5 % of patie nts.  
•  I n C o h ort  A, if m ore t ha n 2 5 % of patie nts die wit hi n 4 8 h o urs, t he pr ot oc ol tea m will 
e val uate t he cases t o d eter mi ne w het her e nr oll me nt s h o ul d be pa use d .   
•  C o h ort  B is e x pecte d t o ha ve a p ot e ntiall y hi g h deat h rat e fr o m C O VI D -1 9 disease.  T h e 
pr ot oc ol tea m will m o nit or t he d eat hs t o e val uat e acc or di n g t o u n derl yi n g ca n cer t y pe 
( he mat ol o gic, t h oraci c, ot her s oli d t u m ors), w het her  t he u n derl yi n g ca use of deat h is relate d 
t o t he st u d y treat me nt rat her t ha n t o t he ca ncer t y p e, a n d se verit y of C O VI D -1 9 disease . 
 

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P L A N N E D E N R O L L M E N T R E P O R T  
R a ci al C at e g ori e s  
Et h ni c C at e g ori e s  
T ot al  
N ot Hi s p a ni c or L ati n o  
Hi s p a ni c or L ati n o  
 
F e m al e  
M al e  
F e m al e  
M al e  
 
A m eri c a n I n di a n/ Al a s k a 
N ati v e  
5  
5  
0  
0  
1 0  
A si a n  
4  
3  
0  
0  
7  
N ati v e H a w aii a n or 
Ot h er P a cifi c I sl a n d er  
2  
1  
0  
0  
3  
Bl a c k or Afri c a n 
A m eri c a n  
2 0  
1 8  
6  
6  
5 0  
W hit e  
7 5  
5 1  
1 3  
6  
1 4 5  
M or e T h a n O n e R a c e  
1  
1  
0  
0  
2  
T ot al  
1 0 7  
7 9  
1 9  
1 2  
2 1 7  
P H S 3 9 8 / P H S 2 5 9 0 ( Re v. 0 8/ 1 2 A p pr o ve d T hr o u g h 8/ 3 1/ 2 0 1 5)  
 
O M B N o. 0 9 2 5 -0 0 0 1/ 0 0 0 2  
 
 
9. 3  
Str atific ati o n F act ors  
 
Strat u m 1) 2 years -1 4 y ears; Strat u m 2) 1 5 -3 9 years; Strat u m 3) 4 0 -6 4 years; Strat u m 4) 6 5 years 
a n d o ver.  
 
9. 4  
T o xicit y Re p orti n g  a n d E xcl usi o ns  
 
9. 4. 1  E val uati 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 i nf usi o n wit h t ociliz u ma b.  
 
9. 4. 2  Cli nical O utc o me E val uati o n  
 
Patie nts will be e val uate d a n d sc ore d f or se v erit y of C O VI D -1 9 ill ness  at b aseli ne a n d o nce dail y 
f oll o wi n g t he first a d mi nistrati o n of t ociliz u ma b u ntil disc har ge fr o m t h e h os pital or Da y 6 0, 
w hic he ver is first.   F or t h e p ur p oses of t his pr ot oc ol , a res p o nse will be defi ne d as a p oi nt re d ucti o n 
i n s y m pt o ms as assesse d b y t he Cli nical Stat us Or di nal  at baseli ne a n d after t ocilizu ma b 
a d mi nistrati o n.  
 

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
4 6  
 
Base d o n t he res p o nse criteria o utli ne d i n Secti o ns 9. 4. 2. 1 a n d 9. 4. 2. 2  b el o w, s u bjects meeti n g t he 
defi niti o n of eit her c o m plete or partial res p o nse as t heir best res p o nse b y Da y 1 4 f oll o wi n g 
t ociliz u ma b a d mi nistrati o n will be c o nsi d ere d as ha vi n g be nefitte d fr o m t ociliz u ma b.    
 
Res p o nse deter mi nati o ns will be ma de dail y o ver t he c o urse of h os pitalizati o n .  T he ti me t o ac hie ve 
t he best res p o nse, as well as t he n u m ber of d oses recei ve d t o ac hie ve t he best res p o nse, will be 
ca pt ure d f or eac h tr eate d patie nt.  
 
A fi nal cli nical stat us res p o nse deter mi nati o n will als o be pr o vi de d at t he ti me t he patie nt is eit her: 
1) ali ve a n d disc h ar ge d fr o m t he h os pital; 2) has die d  or 3) meets off -st u d y criteria. 
 
All patie nts i ncl u de d i n t he st u d y m ust be assesse d f or res p o ns e t o treat me nt, e ve n if t here are 
maj or pr ot oc ol treat me nt de viati o ns.  Eac h patie nt will be assi g ne d t o o ne of t he f oll o wi n g 
c o h orts:   
•  C o h ort A  – n ot o n mec h a nical ve ntilati o n at ti me of re gistrati o n a n d n o i m m e diate pla n 
f or i nt u bati o n 
•  C o h ort B — O n mec ha ni cal ve ntilati o n  at ti me of re gistrati o n  or i m mi ne nt i nt u bati o n 
i n dicate d 
 
9. 4. 2. 1  Cli nical O utc o me e val uati o n C o h ort A  ( N O T o n mec ha nical ve ntilati o n) 
 
•  C o m plete res p o nse :  re d u cti o n i n se vere s y m pt o ms s uc h t hat t he y are n ot life-t hreate ni n g 
a n d re q uir e s y m pt o matic treat me nt o nl y (fe v er, na usea, fati g ue, h ea d ac he, m yal gias, 
malaise) a n d ca n be disc har ge d fr o m h os pital  
•  Partial res p o nse  i m pr o ve me nt i n cli nical stat us sc ore b y at least o n e p oi nt  b ut re q uires 
c o nti n ue d h os pitalizati o n  
•  Pr o gressi ve disease :  Cli nical sc ore c ha n g es t o a 5 or 6 (see Sc h e ma f or t he Cli nical 
Or di nal Scale )  
•  Deat h  
 
9. 4. 2. 2  Cli nical O utc o me  e val uati o n C o h ort B  ( o n mec ha nical ve ntilati o n ) 
 
•  C o m plete res p o nse :  re d u cti o n i n se vere s y m pt o ms s uc h t hat t he y are n ot life-t hreate ni n g 
a n d re q uir e s y m pt o matic treat me nt o nl y (fe v er, na usea, fati g ue, h ea d ac he, m yal gias, 
malaise) a n d ca n be disc har ge d fr o m h os pital  
•  Ve ntilat or C o m plete Res p o nse :  Re m o val fr o m mec ha nical ve ntilati o n a n d disc har ge 
fr o m I C U/I C U eli gi bilit y  
•  Partial res p o nse :  Disc har ge d fr o m I C U b ut re q uir es c o nti n ue d h os pitalizati o n 
•  Ve ntilat or Partial Res p o nse :  Re m o val fr o m mec h a nical ve ntilati o n a n d b ut re q uire n o n -
i n vasi ve ve ntilati o n or hi g h fl o w O 2 c o nti n ue d I C U s u p p ort/re mai ns I C U eli gi ble 
•  Pr o gressi ve disease :  N o decrease i n s u p p orti ve care dee m e d p ossi ble 
•  Deat h  
 
S u bjects w h o ha ve pr o gressi ve disease ( n o d ecrease i n s u p p orti ve care dee me d p ossi ble) or deat h 
fr o m C O VI D-1 9 will be c o nsi dere d as a Treat me nt fail ure   

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
4 7  
 
 
9. 4. 3  P o p ulati o n f or A nal ysis  
 
All  of t he patie nts w h o met t he eli gi bilit y criteria a n d are i nf use d wit h at least o ne d ose of 
t ociliz u ma b will be i ncl u de d i n t he cli nical o utc o me a nal ysis .  T h us, a n i n c orrect treat me nt 
sc he d ule or dr u g a d mi nistrati o n will n ot res ult i n e xcl usi o n fr o m t he a nal ysis of t he res p o nse 
rate.  Treat me nt fail ure will be defi ne d b y a n y pr o gressi ve diseas e or deat h as per t he res p o nse 
criteria i n se cti o n 1 2. 1 a n d 1 2. 2. F or t h ose s u bjects w h o are e nr olle d b ut n ot i nf use d, reas o ns f or 
n o n -i nf usi o n will be ca pt ure d as f easi ble.    
 
9. 5  
D at a C ollecti o n  
 
Data will be c ollect e d d uri n g t he treat me nt of t h ese patie nts as well as d uri n g t heir f oll o w -u p i n 
or der t o g ai n a d diti o nal i nf or mati o n c o ncer ni n g t h e efficac y a n d a d verse e v e n ts of t ociliz u ma b i n 
t his p o p ulati o n.  T he pri mar y i n dicat or of efficac y will be t he fre q ue nc y of res p o nse, le n gt h of  
ti me fr o m le vel of care t o ste p d ow n le vel of care, a n d s ur vi val.  Beca use l o n g ter m o utc o mes are 
of i nterest , f oll o w-u p of patie nts u ntil deat h is  i m p orta nt.   
 
A d diti o nall y, i nt u bati o n a n d ca use of deat h will als o be ca pt ure d i n s u p p ort of t he trial o bjecti ves.  
See A p pe n di x A f or a list of c ollecti o ns t hat s h o ul d be rec or de d i n t he Cas e Re p ort F or m ( C R F).  
 
 
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 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.  T h e f oll o wi n g list of A Es 
( Secti o n 1 0 . 1) a n d t he c h aract eristics of a n o bs er ve d A E ( Secti o ns 1 0 . 2 a n d 1 0 . 3) will deter mi ne 
w het her t he e ve nt r e q uires e x pe dite d  re p orti n g via t he C T E P A d verse E ve nt Re p orti n g S yste m 
( C T E P-A E R S)  i n a d diti o n t o r o uti ne re p orti n g. 
 
D ue t o t he narr o w safet y pr ofile of t ociliz u ma b c o m pare d  t o t he a d v erse e v e nts e x pecte d fr o m 
t he u n derl yi n g c o n diti o n of t he patie nts, c ollecti o n of a d verse e ve nt d ata will be li mite d t o: 
•  Gra de 5 a d vers e e ve nts ( deat hs)  
•  Gra de 1 -5 a d verse  e v e nts of s pecial i ntereste d liste d i n Secti o n 1 0. 3. 4  
•  A d diti o nal  seri o us or life-t hreate ni n g i nf ecti o n ( ot her t ha n C O VI D-1 9)  
•  A n y ot her gra d e 3 -4  a d verse e ve nt s c o nsi d ere d  rel ate d t o t ociliz u ma b per r o uti ne a n d 
seri o us re p orti n g g ui deli nes i n Secti o ns 1 0. 3. 3 a n d 1 0. 4 
 
1 0. 1  C o m pre he nsi ve A d verse E ve nts a n d P ote nti al Ris ks Lists ( C A E P Rs)  
 
1 0. 1. 1  C A E P R f or T ociliz u ma b ( Acte mra ®, R O 4 8 7 7 5 3 3, N S C 8 2 0 0 1 3)  
 
T he C o m pre h e nsi ve A d verse E ve nts a n d P ote ntial Ris ks list ( C A E P R) pr o vi des a si n gle list of re p orte d a n d/ or 
p ote ntial a d verse e ve nts ( A E) ass ociate d wit h a n a ge nt usi n g a u nif or m prese ntati o n of e ve nts b y b o d y s yste m. I n 
a d diti o n t o t he c o m pre h e nsi ve list, a s u bset, t he S pecific Pr ot oc ol E xce pti o ns t o E x pe dite d Re p orti n g ( S P E E R), 
a p pears i n a se p arate c ol u m n a n d is i de ntifie d wit h b ol d a n d italicize d te xt. T his s u bset of A Es ( S P E E R) is a list of 
e v e nts t hat are pr ot oc ol s pecific e x ce pti o ns t o e x pe dite d re p orti n g t o N CI (e xce pt as n ote d bel o w). Refer t o t he 
' C T E P, NCI G ui deli nes: A d verse E ve nt Re p orti n g  

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
4 8  
 
Re q uire me nts' htt p://cte p.ca ncer. g o v/ pr ot oc ol De vel o p me nt/electr o nic _a p plicati o ns/ d ocs/ae g ui deli nes. p df  f or f urt her 
clarificati o n  Fre q ue n cy is pr ovi de d b ase d o n 8 7 2 6 p atie nts . Bel o w is t he C A E P R f or T ociliz u ma b ( R O 4 8 7 7 5 3).  
 
N O T E : Re p ort A Es o n t he S P E E R O N L Y I F  t he y e xcee d t he gra de n ote d i n pare nt heses ne xt t o t he A E i n 
t he S P E E R. If t his C A E P R is part of a c o m bi nati o n pr ot oc ol usi n g m ulti ple i n vesti gati o nal a ge nts a n d has 
a n A E liste d o n differe nt S P E E Rs, use t he l o wer of t he gra des t o deter mi ne if e x pe dite d r e p orti n g is 
re q uire d. 
Versi o n 2. 0, A pril 1 4, 2 0 2 0 1  
 
 A d verse E ve nts wit h P ossi ble  
 Rel ati o ns hi p t o T ociliz u m a b ( R O 4 8 7 7 5 3 3)  
 ( C T C A E 5. 0 Ter m) 
[ n = 8 7 2 6] 
 
 
 S pecific Pr ot oc ol E xce pti o ns 
t o E x pe dite d Re p orti n g 
( S P E E R)  
 
Li k el y ( > 2 0 %)  
Less Li k el y ( < = 2 0 %) 
R are b ut Seri o us ( < 3 %)  
 
 
G A S T R OI N T E S TI N A L DI S O R D E R S  
  
 
 
Gastr oi ntesti nal dis or ders - Ot her 
(gastr oi ntesti nal perf orati o ns ) 
  
H E P A T O BI LI A R Y DI S O R D E R S  
  
 
 
He pat o biliar y dis or ders - Ot her 
( He pat o xicit y)2  
  
I M M U N E DI S O R D E R S 
  
 
 
A na p h yla xis  
  
I N F E C TI O N S A N D I N F E S T A TI O N S 
  
 
I nfecti o n3  
 
  
I N V E S TI G A TI O N S 
  
 
Ala ni n e a mi n otra nsferase i n creas e d   
  
 
As partate a mi n otra nsferase 
i n crease d 
 
  
 
Ne utr o p hil c o u nt decrease d  
 
  
 
1T his ta ble will be u p date d as t he t o xicit y pr ofile of t he a ge nt is re vise d.  U p dates will be distri b ute d t o all Pri nci pal 
I n vesti gat ors at t he ti me of re visi o n.  T he c urre nt versi o n ca n be o btai ne d b y c o ntacti n g 
PI O @ C T E P. N CI. NI H. G O V .  Y o ur na me, t he na me of t he i n vesti gat or, t he pr ot oc ol a n d t he a ge nt s h o ul d be 
i ncl u de d i n t he e-mail.  
 
2He p at o x ocit y i ncl u des dr u g i n d uce d li ver i nj ur y ( DI LI), ac ute li ver fail ure, he patitis, a n d ja u n dic e 
 
3I nfecti o n i ncl u des all 7 5 sites of i nfecti o n u n der t he I N F E C TI O N S A N D I N F E S T A TI O N S S O C.  
 
A d verse e v e nts re p orte d o n t ociliz u m a b ( R O 4 8 7 7 5 3) tri als, b ut f or w hic h t here is i ns ufficie nt e vi de nce t o 
s u g gest t h at t here w as a re as o n a ble p ossi bilit y t h at t ociliz u m a b ( R O 4 8 7 7 5 3) c a use d t he a d verse e ve nt : 
 
E N D O C RI N E DI S O R D E R S  - H y p ot h yr oi dis m  
G A S T R OI N T E S TI N A L DI S O R D E R S  - A b d o mi nal pai n; Gastric ulcer; Gastritis; M uc ositis oral  
G E N E R A L DI S O R D E R S A N D A D MI NI S T R A TI O N SI T E C O N DI TI O N S  - E de ma li m bs; I njecti o n site 
reacti o n 
I M M U N E S Y S T E M DI S O R D E R S- Aller gic reacti o n  
I N J U R Y, P OI S O NI N G A N D P R O C E D U R A L C O M P LI C A TI O N S - I nf usi o n relate d reacti o n 
I N V E S TI G A TI O N S - Bl o o d bilir u bi n i n cr e a s e d; C h ol e st er ol hi g h; Fi bri n o g e n d e cr e a s e d; Pl at el et c o u nt 
d e cr e a s e d; W ei g ht g ai n; W hit e bl o o d c ell d e cr e a s e d   
M E T A B O LI S M A N D N U T RI TI O N DI S O R D E R S  - H y pertri gl yceri de mia  
N E O P L A S M S B E NI G N, M A LI G N A N T A N D U N S P E CI FI E D (I N C L C Y S T S A N D P O L Y P S)  - Treat me nt 
relate d sec o n dar y mali g na nc y 
N E R V O U S S Y S T E M DI S O R D E R S  - Dizzi ness; Hea dac he  

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
4 9  
 
R E N A L A N D U RI N A R Y DI S O R D E R S  - Re nal a n d uri nar y dis or ders - Ot her, s pecif y ( ne p hr olit hiasis)  
R E S PI R A T O R Y, T H O R A CI C A N D M E DI A S TI N A L DI S O R D E R S  - C o u g h; D ys p nea  
S KI N A N D S U B C U T A N E O U S TI S S U E DI S O R D E R S  - Pr urit u s; R a s h m a c ul o -p a p ul ar; Urti c ari a; 
St e v e n s -J o h n s o n S y n dr o m e  
V A S C U L A R DI S O R D E R S  - H y perte nsi o n  
 
 
N ote : T ociliz u ma b ( R O 4 8 7 7 5 3) i n c o m bi nati o n wit h ot her a ge nts c o ul d ca use a n e xacer bati o n of a n y a d verse e v e nt 
c urre ntl y k n o w n t o be ca use d b y t he ot her a g e nt, or t he c o m bi nati o n ma y r es ult i n e ve nts ne ver pre vi o usl y 
ass ociate d wit h eit her a g e nt.  
 
1 0. 2  
A d verse E ve nt C h ar a cteristics  
 
•  C T C A E ter m ( A E descri pti o n) a n d gr a de:  T he descri pti o ns a n d gra di n g scales f o u n d 
i n t he re vise d N CI C o m m o n Ter mi n ol o g y Criteria f or A d verse E v e nts ( C T C A E) versi o n 
5. 0 will be utilize d f or A E re p orti n g.  All a p pr o pri ate treat me nt areas s h o ul d ha ve access 
t o a c o p y of t he C T C A E versi o n 5. 0.  A c op y of t h e C T C A E versi o n 5. 0 ca n be 
d o w nl oa de d fr o m t he C T E P we bsite 
htt p://cte p.ca ncer. g o v/ pr ot oc ol De vel o p me nt/electr o nic _a p plicati o ns/ctc. ht m . 
 
•  F or e x pe dite d re p orti n g p ur p oses o nl y:   
- 
A Es f or t he a g e nt  t hat are b ol d a n d it alicize d  i n t he C A E P R (i.e., t h ose liste d i n t he 
S P E E R c ol u m n, Secti o n 1 0. 1) s h o ul d be re p ort e d t hr o u g h C T E P -A E R S o nl y if t he 
gra de is a b o v e t he gra d e pr o vi de d i n t he S P E E R.  
- 
Ot her A Es f or t he pr ot oc ol  t hat d o n ot re q uire e x p e dite d re p orti n g are o utli ne d i n 
Secti o n 1 0. 3. 4.  
 
•  Attri b uti o n  of t he A E:  
- 
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 lik ely rel ate d t o t he st u d y tr eat me nt. 
- 
P ossi ble –  T he A E m ay b e 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 h e A E is cl e arly N O T rel ate d t o t he st u d y treat me nt. 
 
A d verse e ve nt ( A E) m o nit ori n g a n d re p orti n g f or t his trial is li mite d t o gra de 4 a n d 5 e v e nts t hat 
h a ve a n attri b uti o n of Pr o ba ble or Defi nite t o t ociliz u ma b.  
 
A d verse e ve nt d ata c ollecti o n a n d re p orti n g, w hic h are re q uir e d as p art of e ver y cli nical trial, are 
d o ne t o e ns ur e t he safet y of patie nts e nr olle d i n t he st u dies as well as t h ose w h o will e nr oll  i n 
f ut ure st u dies usi n g si mil ar a g e nts.  A E s are re p ort e d i n a r o uti ne m a n ner at sc he d ule d ti mes d uri n g 
t he trial usi n g Me di d ata Ra ve.  F or t his trial t h e  A d verse E ve nt C R F  is use d f or r o uti ne A E 
re p orti n g i n Ra ve. 
 
1 0. 3  E x pe dite d A d verse E ve nt Re p orti n g  
 
1 0. 3. 1  Ra ve -C T E P -A E R S I nte grati o n  
 
T he Ca ncer T hera p y E val uati o n P r o gra m A d verse E ve nt Re p orti n g S yste m ( C T E P-

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
5 0  
 
A E R S) i nte grati o n e na bl es e val uati o n of p ost -b aseli ne A E s e ntere d i n Ra v e t o deter mi ne 
w het her t he y re q uire e x p e dite d re p orti n g, a n d facilitates e ntr y i n C T E P -A E R S f or t h ose 
A Es re q uiri n g e x p e dite d re p orti n g.    
 
All A Es t hat occ ur after baseli ne are c ollect e d i n Me di data Ra ve usi n g t he A d verse E v e nt 
f or m, w hic h is a vaila ble f or e ntr y at eac h treat me nt or re p orti n g peri o d, a n d use d t o 
c ollect A Es t hat start d uri n g t he peri o d or persist fr o m t he pre v i o us re p orti n g peri o d.  T he 
Cli nical Researc h Ass o ciate ( C R A) will e nter A Es t hat occ ur pri or t o t he st art of 
treat me nt o n a bas eli ne f or m t hat is n ot i ncl u de d i n t he Ra ve -C T E P -A E R S i nte grati o n.  
A Es t hat occ ur pri or t o e nr oll me nt m ust be gi n a n d e n d o n t he b aseli ne A d verse E ve nt 
f or m a n d s h o ul d n ot be i ncl u de d o n t he sta n dar d A d verse E v e nts f or m t hat is a vaila ble at 
treat me nt u nless t here has bee n a n i ncreas e i n gra de.  
 
Pri or t o se n di n g A Es t hr o u g h t he r ules e val u ati o n pr ocess, site staff s h o ul d verif y t he 
f oll o wi n g o n t he A d verse E ve nt f or m i n Ra ve: 
 
•  T he re p orti n g peri o d (c o urse/c ycle) is c orrect, a n d  
•  A Es are rec or de d a n d c o m plete ( n o missi n g fiel ds) a n d t he f or m is q uer y-free 
(fiel ds a d de d t o t he f or m d uri n g st u d y b uil d d o n ot nee d t o be q uer y-free f or t he 
i nte grati o n call wit h C T E P-A E R S t o be a s uccess).  
 
T he C R A re p orts A Es i n Ra ve at t he ti me t he I n vesti gat or lear ns of t he e ve nt.   If t h e C R A 
m o difies a n A E, it m ust be re -s u b mitte d f or r ules e val uati o n. 
 
U p o n c o m pleti o n of A E e ntr y i n Me di data Ra ve, t he C R A s u b mits t he A E f or r ules 
e val uati o n b y c o m pleti n g t he E x pe dite d Re p orti n g E val uati o n f or m.  B ot h N CI a n d 
pr ot oc ol -s pecifi c re p orti n g r ules e val uat e t he A Es s u b mitte d f or e x pe dite d re p orti n g.   A 
re p ort is i nitiate d i n C T E P-A E R S usi n g i nf or mati o n e ntere d i n Me di d ata Ra ve f or A Es 
t hat meet re p orti n g r e q uire me nts.  T he C R A c o m pletes t he re p ort b y accessi n g C T E P -
A E R S via a direct li n k o n t he Me di data Ra ve E x p e dite d Re p orti n g E val uati o n f or m.  
 
I n t he rare occ urre nce t h at I nter net c o n necti vit y is l ost, a 2 4-h o ur n otifi cati o n is t o be 
ma de t o C T E P b y tele p h o ne at 3 0 1 -8 9 7 -7 4 9 7.  O nce I nter net c o n necti vit y is rest ore d , t he 
2 4 -h o ur n otificati o n t hat was p h o ne d i n m ust be e ntere d i m me diatel y i nt o C T E P -A E R S 
usi n g t he dee p li n k fr o m Me di data Ra ve.  
 
A d diti o nal i nf or mati o n a b o ut t he C T E P -A E R S i nte grati o n is a vaila ble o n t he C T S U 
we bsite:  
 
•  St u d y s pecific d oc u me nts:  Pr ot oc ols  > D oc u me nts > E d ucati o n a n d Pr o m oti o n, 
a n d   
•  E x pe dite d Safet y Re p orti n g R ules E val uati o n user g ui de:  Res o urces > C T S U 
O perati o ns I nf or mati o n > User G ui des.  
 
N CI re q uire m e nts f or S A E re p orti n g are a v aila ble o n t he C T E P we bsite:  
 

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
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•  N CI G ui d eli nes f or I n v est i gat ors:  A d verse E ve nt Re p orti n g Re q uire me nts is 
a vaila ble at 
htt ps://cte p.ca ncer. g o v/ pr ot oc ol De vel o p me nt/electr o nic _a p plicati o ns/ d ocs/a e g ui d
eli nes. p d f. 
 
1 0. 3. 2  Distri b uti o n of A d verse E ve nt Re p orts  
 
C T E P -A E R S  is pr o gra m me d f or a ut o matic electr o nic distri b uti o n of re p orts t o t he f oll o wi n g 
i n di vi d uals:  Pri nci pal I n vesti gat or a n d A d verse E ve nt C o or di nat or (s) (if a p plica ble) of t he 
C orres p o n di n g  Or ga ni zati o n  or Lea d Or ga nizati o n , t he l ocal treati n g p h ysicia n, a n d t he Re p orter 
a n d S u b mitter .  C T E P -A E R S  pr o vi des a c o p y feat ure f or ot her e -m ail reci pie nts.  
 
1 0. 3. 3  E x pe dite d Re p orti n g  G ui deli nes  
 
Use t he N CI pr ot oc ol n u m ber a n d t he pr ot o c ol -s p ecific patie nt I D assi g ne d d uri n g trial 
re gistrati o n o n all re p orts. 
 
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 as l o n g as t he de at h occ urre d wit hi n 3 0 d a ys after t he l ast a d mi nistr ati o n of t h e 
i n vesti g ati o n al a ge nt.  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. 
 
Deat h d ue t o  pr o gressi ve dise ase  fr o m C O VI D-1 9  s h o ul d be re p orte d as Gr a de 5 “I nfecti o ns 
a n d I nfestati o ns, Ot her, C O VI D -1 9 Dise ase pr o gressi o n. ”   E vi de nce t hat t he deat h was a 
ma nifestati o n of u n derl yi n g C O VI D -1 9 diseas e ( e. g., ra di ol o gical c ha n g es s u g gesti n g cli nical 
deteri orati o n ass o ciate d wit h a disease pr ocess) s h o ul d be s u b mitte d.  
 
Deat h d ue t o pr o gressi ve dise ase of c a ncer  s h o ul d be re p orte d as Gr a de 5  “ Disease 
pr o gressi o n” i n t he s yste m or ga n class ( S O C) “ Ge neral dis or ders a n d a d mi nistrati o n site 
c o n diti o ns.”  E vi de nce t h at t he deat h w as a ma nifestati o n of u n derl yi n g disease (e. g., 
ra di ol o gical c ha n g es s u g gesti n g t u m or gr o wt h or pr o gressi o n: cli nical deteri orati o n ass ociate d 
wit h a disease pr ocess) s h o ul d be s u b mitte d  
 
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 vesti g at ors M U S T  i m me diatel y re p ort t o t h e s p o ns or ( N CI) A N Y Seri o us A d verse E v e nts, as p er t h e bel o w ta ble  
( 2 1 C F R 3 1 2. 6 4) 
A n a d verse e ve nt is c o nsi dere d seri o us if it res ults i n A N Y  of t he f oll o wi n g o utc o mes:   
1)  
Deat h  
2)  
A life -t hreate ni n g a d verse e ve nt  
3)  
A n a d verse e ve nt t h at res ults i n i n patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n f or ≥ 2 4 h o urs.  
4)  
A p ersiste nt or si g nifica nt i nca pacit y or s u bsta ntial disr u pti o n of t he a bilit y t o c o n d uct n or mal life f u ncti o ns.  
5)  
A c o n ge nital a n o mal y/ birt h defect.  
6)  
I m p orta nt Me dical E ve nts (I M E) t h at ma y n ot res ult i n deat h, be life t hreate ni n g, or re q uire h os pitalizati o n ma y be 
c o nsi dere d seri o us w he n, base d u p o n me dical j u d g me nt, t h e y ma y je o par dize t he patie nt or s u bject a n d ma y re q uire 
me dical or s ur gical i nter ve nti o n t o pre ve nt o ne of t h e o utc o mes liste d i n t his defi 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 verse e ve nts t hat meet t h e a b o ve criteria M U S T be i m me diatel y re p orte d t o t he N CI via electr o nic 
s u b missi o n wit hi n t he ti mefra mes detaile d i n t he ta ble bel o w.  

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Rel ate d ness  
Gr a de 1 –  3 Ti m efr a m es  
Gr a de 4 Ti m efr a m es  
Gr a de 5 Ti m efr a m es  
U nrelate d  
U nli kel y  
N ot re q uire d  
N ot re q uire d  
2 4 -H o ur + 5 Cale n dar Da ys  
P ossi ble  
Pr o ba ble  
Defi nite  
N ot re q uire d  
2 4 -H o ur + 5 Cale n dar Da ys  
2 4 -H o ur + 5 Cale n dar Da ys  
E x pe dite d A E re p orti n g ti m eli nes a re defi ne d as:  
“ 2 4 -H o ur; 5 Cale n dar Da ys” - T he A E m ust i nitiall y be s u b mitte d electr o nicall y wit hi n 2 4 h o urs of lear ni n g of t he A E, 
f oll o we d b y a c o m plete e x pe dite d re p ort wit hi n 5 cale n dar da ys of t he i nitial 2 4 -h o ur re p ort.  
Seri o us a d verse e ve nts t hat occ ur m ore t h a n 3 0 da ys after t he last a d mi nistrati o n of i n vesti gati o nal a ge nt/i nter ve nti o n a n d h a ve 
a n attri b uti o n of p ossi ble, pr o ba ble, or defi nite re q uire re p orti n g as f oll o ws:  
E x pe dite d 2 4 -h o ur n otific ati o n f oll o we d b y c o m plete re p ort wit hi n 5 c ale n d ar d a ys f or:  
All Gra de 4 a n d Gra de 5 A Es  
 
1 0. 3. 4  A d verse E v e nts of S peci al  I nt erest 
 
At t he re q uest of t he p h ar mace utical c olla b orat or, t he f oll o wi n g e ve nts are of s pecial i nterest, a n d 
b ot h r o uti ne a n d e x pe dite d re p orti n g will be c ollecte d o n t his trial.  
T ociliz u ma b E ve nts of S pecial I nterest are:   
•  Seri o us  a n d/ or me dicall y si g nifica nt i nfecti o ns (e x cl u di n g C O VI D -1 9)  
•  M y ocar dial i nfarcti o n/ Ac ute c or o nar y s y n dr o me  
•  Me dicall y si g nifica nt blee di n g e ve nts  
•  Gastr oi ntesti nal perf orati o ns  
•  Mali g na ncies  (e x cl u di n g e xisti n g mali g na nc y t y pe) 
•  A na p h yla xis/ H y pers e nsiti vit y reacti o ns  
•  De m yeli nati n g dis or ders  
•  Str o ke  
•  Cases of p ote ntial dr u g -i n d uce d li ver i nj ur y ( DI LI) t hat i ncl u de a n el e vate d A L T or A S T 
i n c o m bi nati o n wit h eit her a n el e vate d bilir u bi n or cli nical ja u n dice, as defi ne d b y H y’s 
la w:  
o  Treat me nt -e mer ge nt A L T or A S T > 3 ×  U L N i n c o m bi nati o n wit h t otal bilir u bi n 
> 2 ×  U L N  
o  Treat me nt -e mer ge nt A L T or A S T > 3 ×  U L N i n c o m bi nati o n wit h cli nical 
ja u n dice  
* Data rel ate d t o a s us pe cte d tra ns missi o n of a n i nfecti o us a ge nt b y t he st u d y dr u g 
( S TI A M P), as defi n e d bel o w:  
A n y or ga nis m, vir us, or i nfecti o us particle (e. g., pri o n pr otei n tra ns mitti n g 
tra ns missi ble s p o n gif or m e nce p h al o pat h y), pat h o g e nic or n o n-p at h o ge nic, is 
c o nsi dere d a n i nfecti o us a ge nt.   A tra ns missi o n of a n i nfecti o us a g e nt ma y be 
s us pecte d fr o m cli nical s y m pt o ms or la b orat or y fi n di n gs t hat i n dicate a n i nfecti o n 
i n a patie nt e x p ose d t o a me dici nal pr o d uct.  T his ter m a p plies o nl y w he n a 
c o nta mi nati o n of t he st u d y dr u g is s us pecte d  

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1 0. 4  
R o uti ne A d verse E ve nt Re p orti n g  
 
A d verse E v e nts m ust  be re p orte d i n r o uti ne st u d y data s u b missi o ns  as f oll o ws :   
 
•  A d verse E v e nts of S peci al I nt erest per secti o n 1 0. 3. 4 re gar dl e ss of rel ate d ness: gra des 1-5  
•  Ot her r o uti ne a d v erse e v e nts rel ate d t o t ociliz u m a b : gra des 3-4  
•  All gra de 5 a d v erse e ve nts re gar dless of rel ate d ness  
 
Re mi n der:  A Es re p orte d e x pe diti o usl y t hr o u g h C T E P -A E R S  m ust als o  be re p orte d i n 
r o uti ne st u d y d at a s u b missi o ns.  
 
A d verse e ve nt data c ollecti o n a n d re p orti n g, w hic h are re q uire d as part of e ver y cli nical trial, are 
d o ne t o e ns ure t he s afet y of patie nts e nr olle d i n t he st u dies as well as t h ose w h o will e nr oll i n 
f ut ure st u dies usi n g si milar a ge nts.  A E s are re p orte d i n a r o uti ne ma n ner at sc he d ule d ti mes 
d uri n g t he trial usi n g Me di data Ra ve.  F or t his trial t he  A d verse E v e nt C R F  is use d f or r o uti ne 
A E re p orti n g i n Ra ve.  
 
1 0. 5  
Pre g n a nc y  
 
Alt h o u g h n ot a n a d verse e ve nt i n a n d of itself, pre g na nc y as w ell as its o utc o me m ust be 
d oc u me nte d via C T E P -A E R S .  I n a d diti o n, t he Pre g n a ncy I nf or m ati o n F or m  i ncl u de d wit hi n 
t he N CI G ui deli nes f or A d verse E ve nt Re p orti n g Re q uire me nts m ust be c o m plete d a nd 
s u b mitte d t o C T E P.  A n y pre g na nc y o cc 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 h e 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.  Pl ease see t he “ N CI 
G ui deli nes f or I n v esti gat ors: A d verse E v e nt Re p orti n g Re q uire me nts f or D C T D ( C T E P a n d CI P) 
a n d D C P I N Ds a n d I D Es ” (at htt p://cte p.ca n cer. g o v/ pr ot oc ol De vel o p me nt/a d verse _effects. ht m ) 
f or m ore det ails o n h o w t o re p ort pre g n a nc y a n d its o utc o me t o C T E P.  
 

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1 1.  S T U D Y C A L E N D A R  
 
R o uti ne e val uati o ns f or t he h os pitalize d patie nts c a n be use d f or t he bas eli ne  st u dies 
 
 
B aseli ne  
D a y 1  
E ver y 1 2 
H o urs  f o ur 
ti mes 
f oll o wi n g first 
d ose of 
t ociliz u m a b 
E ver y 2 4 
H o urs  u ntil 
h os pit al 
disc h ar ge  
7 2 h o urs after 
i niti al d ose 
7 d a ys after 
i niti al d osee 
Off 
Tre at me nt a 
T ociliz u m a b  
 
A , B 
 
 
 
 
 
I nf or me d c o nse nt 
X  
 
 
 
 
 
 
De m o gr a p hics  
X  
 
 
 
 
 
 
Me dic al hist or y  
X  
 
 
 
 
 
 
C o nc urre nt me ds  
X  
X ----------------------------------------------------------------------------X f 
 
P h ysic al e x a m  
X  
 
 
 
 
 
 
Vit al si g ns  
X  
 
 
X g  
 
 
 
Hei g ht  
X  
 
 
 
 
 
 
Wei g ht  
X  
 
 
 
 
 
 
B S A  
X  
 
 
 
 
 
 
B MI  
X  
 
 
 
 
 
 
Perf or m a nce st at us  
X  
 
 
 
 
 
 
C O VI D -1 9 testi n g  
X  
 
 
 
 
 
 
O x y ge n S at ur ati o n  
X  
 
 
X g  
 
 
 
C B C w/ diff, plts  
X  
 
X g 
X  
 
 
X g  

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Ser u m c he mistr y b  
X  
 
 
 
 
 
 
P T, P T T, I N R,  
X g 
 
X g 
 
 
 
X g  
fi bri n o ge n, D-di mer  
X g 
 
X g 
 
 
 
X g  
Ferr ati n  
X g 
 
X g 
 
 
 
X g  
C -re acti ve Pr otei n  
X g 
 
X g 
 
 
 
X g  
S M A 2 0  
X g 
 
X g 
 
 
 
X g  
A d verse e ve nt e v al u ati o n  
X  
X ----------------------------------------------------------------------------X  
 
C hest X -R a y ( A P a n d 
l ater al) ( as cli nic all y 
i n dic ate d)d  
X  
 
 
 
 
 
 
Pre g n a nc y test c 
X  
 
 
 
 
 
 
Bl o o d c ollecti o n  i n S o di u m 
He p ari n t u be f or c yt o ki ne 
rele ase s y n dr o me a n al ysis  
a n d S A R S -C o V -2 vir al l o a d d  
X d  
 
X d  
 
X d  
X d  
 
Bl o o d c ollecti o n i n S o di u m 
He p ari n t u be f or 
t ociliz u m a b P K a n al ysis 
X d 
 
X d 
 
X d 
X d 
 
Bl o o d c ollecti o n i n E D T A 
t u be f or a n d S A R S -C o V -2 
vir al l o a d d  
X d  
 
X d  
 
X d  
X d  
 
A , B: T ociliz u ma b :  D os e as assi g ne d  b y C o h ort ; I V.  A sec o n d d ose ma y  b e gi ve n bet wee n  8 h o urs a n d 7 da ys after t h e c o m pleti o n of 
t he first i nf usi o n, if t here is s ustai ne d or rec urre nt f e ver, n o decrease or n ot m ore t ha n a 1 -cate g or y i m pr o ve me nt o n t he 7-cat e g or y 
or di nal scale ( o nl y sta bili zati o n or partial i m pr o ve me nt f oll o wi n g first d ose), or  a ≥1-cate g or y w orse ni n g o n t he 7 -cate g or y or di nal 
scale fr o m n a dir. 
a: Off -tr eat me nt e v al uati o n . Vital stat us t o be assesse d at Da y 1 4, Da y 3 0 a n d Da y 6 0 after last d ose of tociliz u ma b . 
b : Al b u mi n, al kali ne p h os p hatase, t otal bilir u bi n, bicar b o nate, B U N, calci u m, c hl ori de, creati ni ne, gl uc ose, L D H, p h os p h or us, 
p otassi u m, t otal pr otei n, S G O T [ A S T], S G P T [ A L T], s o di u m.  
c: Pre g na nc y test f or w o me n of c hil d beari n g p ote nti al  at t he discreti o n of t he patie nt a n d p h ysicia n . 

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d : O pti o nal .  F or pe diatric p atie nts, all bl o o d c ollecti o ns are o pti o nal.  Baseli n e a n d 7 2 h o ur s peci me ns s h o ul d be pri oritize d f or 
c ollecti o n .  F or t he e ver y 1 2 h o ur c ollecti o n sc he d ule, pe diatric patie nts s h o ul d o nl y ha ve t w o c ollecti o ns  
e: If t he patie nt is still h os pitalize d 
f: F or patie nts i n t he I C U, d ail y me dicati o n rec or di n g is n ot necessar y. C ollect o nl y yes or n o f or t he d urati o n of t he I C U sta y: was o n 
vas o press ors, w as o n a nti bi otics, was o n a nti viral; was o n a ntic oa g ula nt . 
g : O pti o nal.  T he cli nical c are bl o o d dra ws will  be ca pt ure d fr o m t he r o uti ne bl o o d dra ws at m ost f or t h e ti mes i n dicate d.  Si nce t hese 
ca n be v er y ill patie nts, t he y ma y ha ve cli nical bl o o d dra ws m uc h m or e fre q ue ntl y t ha n liste d here.  

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1 2.  M E A S U R E M E N T O F E F F E C T  
 
Refer t o t he dise ase res p o nse criteria i n Secti o n 9. 4. 2 f or metrics of meas uri n g t he effect of 
t ociliz u ma b a d mi nistrati o n o n disease se v erit y. 
 
1 3.  S T U D Y 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  
 
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 
( A d vers e E ve nts: List a n d Re p orti n g Re q uire me nts). 
 
1 3. 1  
St u d y O versi g ht  
 
T his pr ot oc ol is m o nit ore d at se veral le vels, as des cri be d i n t his secti o n.  T h e Pr ot oc ol Pri nci pal 
I n v esti gat or is res p o nsi ble f or m o nit ori n g t he c o n d uct a n d pr o gress of t he cli nical trial, i ncl u di n g 
t he o n g oi n g re vie w of accr ual, patie nt -s p ecific cli nical a n d la b orat or y data, a n d r outi ne a n d 
seri o us a d vers e e v e nts ; re p orti n g of e x pe dite d a d verse e v e nts; a n d acc u m ulati o n of re p orte d 
a d verse e ve nts fr o m ot her trials testi n g t he sa me dr u g(s).  T he Pr ot oc ol Pri nci pal I n vesti gat or a n d 
statisticia n have  access t o t he data at all ti mes t hr o u g h t he C T M S we b -bas e d re p orti n g p ortal.   
 
All St u d y I n vesti gat ors at partici pati n g sites w h o re gister/e nr oll patie nts o n a gi v e n pr ot oc ol are 
res p o nsi ble f or ti mel y s u b missi o n of data via Me di data Ra ve a n d ti mel y re p orti n g of a d verse 
e ve nts f or t hat partic ular st u d y.  T his i ncl u des ti mel y re vie w of data c ollect e d o n t he electr o nic 
C R Fs s u b mitte d via Me di data Ra ve.  
 
All st u dies ar e als o re vi e we d i n acc or da n ce wit h t he e nr olli n g i nstit uti o n’s data safet y m o nit ori n g 
pla n.  
 
1 3. 2  D at a Re p orti n g  
 
Me di data Ra ve is a cli nical data ma na g e me nt s yste m bei n g use d f or d ata c ollecti o n f or t his 
trial/st u d y.  Access t o t he trial i n Ra ve is c o ntr olle d t hr o u g h t he C T E P -I A M s yste m a n d r ole 
assi g n me nts.  T o access Ra ve via i Me di data:  
 
•  
Site staff will nee d t o be re gistere d wit h C T E P a n d ha ve a v ali d a n d acti ve C T E P-I A M 
acc o u nt, a n d  
•  
Assi g ne d o ne of t he f oll o wi n g Ra ve r oles o n t he rele va nt Lea d Pr ot oc ol Or ga nizati o n 
( L P O) or Partici pati n g Or ga nizati o n r oster at t he e nr olli n g site:  Ra ve C R A, Ra ve Rea d 
O nl y, Ra ve C R A ( La b A d mi n), Ra ve S L A, or Ra ve I n v esti gat or.  Refer t o 
htt ps://cte p.ca ncer. g o v/i n vesti gat or Res o urces/ d efa ult. ht m  f or re gistrati o n t y pes a n d 
d oc u me ntati o n re q uir e d.  
o  T o h ol d Ra ve C R A or Ra ve C R A ( La b A d mi n) r ol e, site staff m ust h ol d a 
mi ni m u m of a n A P re gistrati o n t y pe,  
o  T o h ol d Ra ve I n vesti gat or r ole, t he i n di vi d ual m ust be re gistere d as a n N PI V R or 
I V R, a n d 

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o  T o h ol d Ra ve Rea d O nl y r ole, site staff m ust h ol d a n Ass ociates ( A) re gistrat i o n 
t y pe. 
 
U p o n i nitial site re gistrati o n a p pr o val f or t he st u d y i n Re g ulat or y S u p p ort S yste m ( R S S), all 
pers o ns wit h Ra ve r oles assi g ne d o n t he a p pr o priate r oster will be s e nt a st u d y i n vitati o n e -mail 
fr o m i Me di data.  T o acce pt t he i n vitati o n, site staff  m ust l o g i n t o t he Select L o gi n 
(htt ps://l o gi n.i me di data.c o m/selectl o gi n ) usi n g t heir C T E P-I A M us er na m e a n d pass w or d, a n d 
clic k o n t he acce pt  li n k i n t he u p per ri g ht-c or ner of t he i Me di data pa g e.   Site staff will n ot be 
a ble t o access t he st u d y i n Ra ve u ntil all re q uire d Me di data a n d st u d y s pecific trai ni n gs are 
c o m plete d.  Trai ni n gs will be i n t he f or m of electr o nic lear ni n gs (e Lear ni n gs), a n d ca n b e 
accesse d b y clic ki n g o n t he li n k i n t he u p per ri g ht pa ne of t he i Me di d ata scree n.  If a n e L ear ni n g 
is re q uire d a n d h as n ot yet bee n ta k e n, t he li n k t o t he e Lear ni n g will a p pear u n der t he st u d y na me 
i n i Me di data i nstea d of t he R ave E D C  li n k; o nce t he s uccessf ul c o m pleti o n of t he eLear ni n g has 
bee n rec or de d, access t o t he st u d y i n Ra ve will be gra nte d, a n d a R ave E D C  li n k will dis pla y 
u n der t he st u d y na me.  
 
Site staff t hat ha ve n ot pr e vi o usl y acti vate d t heir i Me di data/ Ra ve acc o u nt at t he ti me of i nitial 
site re gistrati o n a p pr o val for t he st u d y i n R S S will als o recei ve a se p arate i n vitati o n fr o m 
i Me di data t o acti vate t heir acc o u nt.  A cc o u nt acti vati o n i nstr ucti o ns are l ocate d o n t he C T S U 
we bsite i n t he Ra ve secti o n u n der t he Ra ve res o urce materi als ( Me di data Acc o u nt Acti vati o n a n d 
St u d y I n vitati o n Acce pta nce).  A d diti o nal i nf or mati o n o n i Me di data/ Ra ve is a vaila ble o n t he 
C T S U me m bers’ we bsite i n t he Data Ma na g e me nt >  Ra ve secti o n at w w w.cts u. or g/ R A V E/  or b y 
c o ntacti n g t he C T S U Hel p Des k at 1-8 8 8 -8 2 3 -5 9 2 3 or b y e -mail at cts uc o nt act @ westat. c o m .   
 
1 3. 2. 1  Met h o d  
 
T his st u d y will be m o nit ore d b y t he Cli nical Trials M o nit ori n g Ser vice ( C T M S).   Data will be 
s u b mitte d t o C T M S at least o nce e v er y t w o wee ks via Me di data Ra ve ( or ot her m o dalit y if 
a p pr o ve d b y C T E P).  I nf or mati o n o n C T M S re p orti n g is a vaila ble at 
htt p:// w w w.t hera de x.c o m/cli nical Tec h n ol o gies/? Nati o nal -Ca ncer -I nstit ute-N CI -1 1 .  O n-site 
a u dits will be c o n d ucte d t hree ti mes a n n uall y ( o ne a n n ual site visit a n d t w o data a u dits).  F or 
C T M S m o nit ore d st u dies, after users ha ve acti vate d t heir acc o u nts, ple ase c o ntact t he T hera de x 
Hel p Des k at ( 6 0 9) 6 1 9 -7 8 6 2  or b y e mail at C T M S S u p p ort @t hera de x.c o m  f or a d diti o nal s u p p ort 
wit h Ra ve a n d c o m pleti o n of C R Fs.   E nr oll me nts cre dite d t o a n N C T N Net w or k Gr o u p  
i ncl u di n g CO G a n d N C O R P will ha ve t he cases i n cl u de d as part of t he Net w or k Gr o u ps r o uti ne 
a u dits.  M ore fre q ue nt a u dits ma y be c o n d ucte d if warra nte d b y accr ual or d ue t o c o ncer ns 
re gar di n g d ata q ualit y or ti mel y s u b missi o n.   
 
 
1 3. 3  D at a Q u alit y P ort al  
 
T he Data Q u alit y P ortal ( D Q P) pr o vi des a ce ntral l ocati o n f or site staff t o ma na ge 
u na ns were d q ueri es a n d f or m deli n q ue ncies, m o nit or data q ualit y a n d ti meli ness, 
ge nerat e re p orts, a n d re vi e w metrics.  
 
T he D Q P is l ocate d o n t h e C T S U me m bers’ we bsite u n der  Dat a Ma na g e me nt.  T he Ra ve 

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
5 9  
 
H o me secti o n dis pla ys a ta ble pr o vi di n g s u m mar y c o u nts of T otal Deli n q ue ncies a n d 
T otal Q ueries.  D Q P Q ueries, D Q P Deli n q ue nt F or ms, a n d t he D Q P Re p orts m o d ules are 
a vaila ble t o access det ails a n d re p orts of u n a ns were d q ueri es, deli n q ue nt f or ms, a n d 
ti meli ness re p orts.  Re vie w t he D Q P m o d ules o n a re g ular b asis t o ma na ge s pecifie d 
q ueries a n d d eli n q ue nt f or ms.  
 
T he D Q P is accessi ble b y site staff t hat are r ostere d t o a site a n d ha v e access t o t he C T S U 
we bsite.   Staff t hat ha v e Ra ve st u d y access ca n access t he Ra ve st u d y dat a usi n g a direct 
li n k o n t he D Q P. 
 
T o lear n m ore a b o ut D Q P use a n d access, clic k o n t he Hel p ic o n dis pla ye d o n t he Ra ve 
H o me, D Q P Q ueri es, a n d D Q P Deli n q ue nt F or ms m o d ules.  
 
N ote:  S o me Ra ve pr ot oc ols ma y n ot ha ve deli n q ue nt f or m details or re p orts s pecifie d o n 
t he D Q P.  A pr ot oc ol m ust ha ve t he Cale n dar f u ncti o nalit y i m ple me nte d i n Ra ve b y t he 
Lea d Pr ot oc ol Or g a nizati o n ( L P O) f or d eli n q ue nt f or m details a n d re p orts t o be a vaila ble 
o n t he D Q P.   Site staff s h o ul d c o ntact t he L P O Dat a Ma na ger f or t h eir pr ot o c ol re gar di n g 
q uesti o ns a b o ut Ra ve Cale n dari n g f u n cti o nalit y.   
 
1 3. 4  
C T E P M ultice nter G ui deli nes  
 
N/ A  
 
1 3. 5  C oll a b or ati ve A gree me nts L a n g u a ge  
 
T he a ge nt(s) s u p plie d b y C T E P, D C T D, N CI use d i n t his pr ot oc ol is/are pr o vi de d t o t he N CI 
u n der a C olla b orati ve A gree me nt ( C R A D A, C T A, C S A) bet wee n t he P har mace utical 
C o m pa n y(ies) ( herei naft er referre d t o as “C olla b orat or(s) ”) a n d t h e N CI Di visi o n of Ca ncer 
Treat me nt a n d Dia g n osis.  T heref ore, t he f oll o wi n g o bli gati o ns/ g ui deli nes, i n a d diti o n t o t he 
pr o visi o ns i n t he “I nt ellect ual Pr o pert y O pti o n t o C olla b orat or”  
(htt p://cte p.ca ncer. g o v/i n d ustr y C olla b orati o ns 2/ i ntellect ual _ pr o pert y. ht m) c o ntai ne d wit hi n t he 
ter ms of a war d, a p pl y t o t he use of t he A ge nt(s) i n t his st u d y: 
 
1.  A ge nt(s) ma y n ot be us e d f or a n y p ur p os e o utsi de t he sc o pe of t his pr ot oc ol, n or ca n 
A ge nt(s) be tr a nsferre d or lice nse d t o a n y part y n ot pa rtici pati n g i n t he cli nical st u d y.  
C olla b orat or(s) dat a f or A ge nt(s) are c o nfi de ntial a n d pr o prietar y t o C olla b orat or(s) a n d s hall 
be mai ntai ne d as s uc h b y t he i n vesti gat ors.  T he pr ot oc ol d oc u me nts f or st u dies utilizi n g 
A ge nts c o ntai n c o nfi d e ntial i nf or m ati o n a n d s h o ul d n ot be s hare d or distri b ute d wit h o ut t he 
per missi o n of t he N CI.  If a c o p y of t his pr ot oc ol is re q ueste d b y a patie nt or patie nt’s fa mil y 
me m ber partici pati n g o n t he st u d y, t he i n di vi d ual s h o ul d si g n a c o nfi de ntialit y a gree me nt.  A 
s uita ble m o del a gree me nt ca n be d o w nl oa d e d fr o m: htt p://cte p.ca ncer. g o v . 
 
2.  F or a cli nical pr ot oc ol w here t here is a n i n vesti gati o nal A ge nt use d i n c o m bi nati o n wit h 
(a n) ot her A ge nt(s), eac h t he s u bject of differe nt C olla b orati ve A gree me nts, t he access t o a n d 
use of data b y eac h C olla b orat or s hall be as f oll o ws ( data pert ai ni n g t o s uc h c o m bi nati o n use 
s hall herei naft er be referre d t o as " M ulti-Part y Data ”): 

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
6 0  
 
 
a. N CI will pr o vi de all C olla b orat ors wit h pri or writte n n o tice re g ar di n g t he e xiste nce a n d 
nat ure of a n y a gree me nts g o ver ni n g t heir c olla b orati o n wit h N CI , t he desi g n of t he 
pr o p ose d c o m bi nati o n pr ot oc ol, a n d t he e xiste nce of a n y o bli gati o ns t hat w o ul d te n d t o 
restrict N CI's partici pati o n i n t he pr o p ose d c o m bi n ati o n pr ot oc ol. 
 
b.  Eac h C olla b orat or s h all a gree t o per mit use of t he M ulti -Part y Data fr o m t h e cli nical trial 
b y a n y ot her C olla b orat or s olel y t o t he e xte nt necessar y t o all o w sai d ot her C olla b orat or 
t o de vel o p, o btai n re g ulat or y a p pr o val or c o m mercialize its o w n A ge nt. 
 
c. A n y C olla b orat or ha vi n g t he ri g ht t o use t he M ulti -Part y Data fr o m t hese tri als m ust 
a gree i n writi n g pri or t o t he c o m me nce me nt of t he trials t hat it will use t he M ulti -Part y 
Data s olel y f or d e vel o p m e nt, re g ulat or y a p pr o val, a n d c o m merci alizati o n of its o w n 
A ge nt.  
 
3.  Cli nical Trial Data a n d R es ults a n d Ra w Data de v el o pe d u n der a C olla b orati ve A gree me nt 
will be ma de a vaila ble t o C olla b orat or(s), t he N CI, a n d t he F D A, as a p pr o priate a n d u nless 
a d diti o nal discl os ure is re q uire d b y la w or c o urt or der  as d escri be d i n  t he I P O pti o n t o 
C olla b orat or  (htt p://cte p.ca ncer. g o v/i n d ustr y C olla b orati o ns 2/i ntellect ual _ pr o pert y. ht m ).  
A d diti o nall y, all Cli nical Data a n d Res ults a n d Ra w Data will be c ollecte d , u se d a n d 
discl ose d c o nsiste nt wit h all a p plica ble fe deral stat utes a n d re g ulati o ns f or t he pr otecti o n of 
h u ma n s u bjects, i ncl u di n g, if a p plica ble, t he St a n d ar ds f or Priv acy of I n divi d u ally 
I de ntifi a ble He alt h I nf or m ati o n set f ort h i n 4 5 C. F. R. Part 1 6 4. 
 
4.  W he n a C olla b orat or wis hes t o i nitiate a data re q u est, t he re q uest s h o ul d first be se nt t o t he 
N CI, w h o will t he n n otif y t he a p pr o priat e i n vesti gat ors ( Gr o u p C hair f or C o o perati ve Gr o u p 
st u dies, or PI f or ot her st u dies) of C olla b orat or's wis h t o c o ntact t he m. 
 
5.  A n y data pr o vi de d t o C olla b orat or(s) f or P hase 3 st u dies m ust be i n acc or da nce wit h t he 
g ui deli nes a n d p olicies of t he res p o nsi ble Data M o nit ori n g C o m mittee ( D M C), if t here is a 
D M C f or t his cli nical trial.  
 
6.  A n y ma n uscri pts re p orti n g t he res ults of t his cli nical trial m ust be pr o vi de d t o C T E P b y t he 
Gr o u p office f or C o o perati ve Gr o u p st u dies or b y t he pri nci pal i n vesti gat or f or n o n -
C o o perati ve Gr o u p st u di es f or i m me diate deli ver y t o C olla b orat or(s) f or a d vis o r y re vie w a n d 
c o m me nt pri or t o s u b missi o n f or p u blicati o n.  C olla b orat or(s) will ha ve 3 0 da ys fr o m t he 
date of recei pt f or re vie w.  C olla b orat or s hall ha ve t he ri g ht t o re q uest t hat p u blicati o n be 
dela ye d f or u p t o a n a d diti o nal 3 0 da ys i n or der t o e ns ure t hat C olla b orat or’s c o nfi de ntial a n d 
pr o prietar y data, i n a d diti o n t o C olla b orat or(s)’s i ntellect ual p r o pert y ri g hts, are pr ot ecte d.  
C o pies of a bstracts m ust be pr o vi de d t o C T E P f or f or war di n g t o C olla b orat or(s) f or c o urtes y 
re vie w as s o o n as p ossi ble a n d prefera bl y at least t hree ( 3) da ys pri or t o s u b missi o n, b ut i n 
a n y case, pri or t o pres e ntati o n at t he meeti n g or p u blicati o n i n t he pr ocee di n gs.  Press 
releas es a n d ot her m e dia prese ntati o ns m ust als o be f or war de d t o C T E P pri or t o releas e.  
C o pies of a n y ma n uscri pt, a bstract a n d/ or press release/ me dia prese ntati o n s h o ul d be se nt t o:  
 
E mail:   ncicte p p u bs @ mail. ni h. g o v  

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
6 1  
 
 
T he Re g ulat or y Affairs Bra nc h will t he n distri b ute t he m t o C olla b orat or(s).  N o p u blicati o n, 
ma n uscri pt or ot her f or m of p u blic discl os ure s hall c o ntai n a n y of C olla b orat or ’s c o nfi d e ntial/ 
pr o prietar y i nf or mati o n.  
 
 
 

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
6 2  
 
1 4.  R E F E R E N C E S  
 
1.  
F D A. Ca n cer Cli nical Tri al Eli gi bilit y Criteri a: Patie nts wit h HI V, He p atitis B Vir us, or 
He patitis C Vir us I nfecti o ns G ui da nce f or I n d ustr y D R A F T G UI D A N C E. I n: E x celle nce O C o, 
( C B E R) Cf D Ea R C Cf B Ea R, e ds. Office of C o m m u nicati o ns, Di visi o n of Dr u g I nf or mati o n 
Ce nter f or Dr u g E val uati o n a n d Researc h  F o o d  a n d Dr u g A d mi nistrati o n  1 0 0 0 1 Ne w Ha m ps hir e 
A ve., Hilla n dale Bl d g., 4t h Fl o or  Sil ver S pri n g, M D 2 0 9 9 3 -0 0 0 2  P h o ne: 8 5 5 -5 4 3 -3 7 8 4 or 3 0 1 -
7 9 6 -3 4 0 0; Fa x: 3 0 1 -4 3 1 -6 3 5 3; E mail: dr u gi nf o @f da. h hs. g o v 
htt p:// w w w.f da. g o v/ Dr u gs/ G ui da nce C o m plia nce R e g ulat or yI nf or mati o n/ G ui da nces/ defa ult. ht m : 
F o o d a n d Dr u g A d mi nsitrati o n 2 0 1 9.  
2.  
F D A -A A C R -W or ks h o p. F D A -A A C R W or ks h o p T o E xa mi ne U n der -Re prese ntati o n of 
Africa n A merica ns i n M ulti ple M yel o ma  F D A -A A C R W or ks h o p T o E xa mi ne U n der -
Re prese ntati o n Of Africa n A merica ns I n M ulti ple M yel o ma  2 0 2 0 Fe br uar y 1 3; Wasi n gt o n 
htt ps:// w w w.aacr. or g/ pr ofessi o nals/ p olic y -a n d-a d v ocac y/r e g ulat or y -s cie nce-a n d-
p oli c y/e ve nts/ m ulti ple -m yel o ma -cli nical-tri als/: A merica n Ass o ciati o n f or Ca ncer Res earc h  
3.  
Z h u N, Z ha n g D, Wa n g W, et al. A N o v el C or o na vir us fr o m Patie nts wit h P ne u m o nia i n 
C hi na, 2 0 1 9. N E n gl J Me d 2 0 2 0; 3 8 2: 7 2 7 -3 3.  
4.  
G ua n WJ, Ni Z Y, H u Y, et al. Cli nical  C haracteristics of C or o na vir us Disease 2 0 1 9 i n 
C hi na. N E n gl J Me d 2 0 2 0.  
5.  
Ya n g X, Y u Y, X u J, et al. Cli nical c o urse a n d o ut c o mes of critic all y ill patie nts wit h 
S A R S -C o V -2 p ne u m o nia i n W u ha n, C hi na: a si n gle -ce ntere d, retr os pecti ve, o bser vati o nal st u d y . 
La ncet Res pir Me d 2 0 2 0.  
6.  
Z h o u F, Y u T, D u R, et al. Cli nical c o urse a n d ris k fact ors f or m ortalit y of a d ult 
i n patie nts wit h C O VI D-1 9 i n W u ha n, C hi na: a retr os pecti ve c o h ort st u d y. L a ncet 2 0 2 0.  
7.  
Lia n g W, G ua n W, C he n R, et al. Ca ncer patie nts i n S A R S -C o V -2 i nfecti o n: a 
nati o n wi de a nal ysis i n C hi na. La ncet O n c ol 2 0 2 0; 2 1: 3 3 5 -7.  
8.  
H ua n g C, Wa n g Y, Li X, et al. Cli nical feat ur es of patie nts i nfecte d wit h 2 0 1 9 n o vel 
c or o na vir us i n W u h a n, C hi na. La ncet 2 0 2 0; 3 9 5: 4 9 7 -5 0 6.  
9.  
S hi H, Ha n X, Jia n g N, et al. Ra di ol o gical fi n di n gs fr o m 8 1 patie nts wit h C O VI D -1 9 
p ne u m o nia i n W u ha n, C hi na: a descri pti ve st u d y. La ncet I nfect Dis 2 0 2 0.  
1 0.  
W u C, C he n X, Cai Y, et al. Ris k Fact ors Ass oci ate d Wit h Ac ute Res pir at or y Distress 
S y n dr o me a n d Deat h i n Patie nts Wit h C or o na vir us  Disease 2 0 1 9 P ne u m o nia i n W u ha n, C hi na. 
J A M A I nter n Me d 2 0 2 0. 
1 1.  
Li u W, Z ha n g Q, C he n J, et al. Detecti o n of C o vi d -1 9 i n C hil dre n i n Earl y Ja n uar y 2 0 2 0 
i n W u ha n, C hi na. N E n gl J Me d 2 0 2 0. 
1 2.  
L u X, Z ha n g L, D u H, et al. S A R S -C o V -2 I nfecti o n i n C hil dre n. N E n gl J Me d 2 0 2 0.  
1 3.  
S u n D, Li H, L u X X, et al. Cli nical feat ures of s e v ere pe di atric patie nts wit h c or o na vir us 
disease 2 0 1 9 i n W u ha n: a si n gle ce nter's o bser vati o nal st u d y. W orl d J Pe diatr 2 0 2 0.  
1 4.  
C u n ni n g ha m A C, G o h H P, K o h D. Treat me nt of C O VI D -1 9: o l d tric ks f or ne w 
c halle n ges. Crit Care 2 0 2 0; 2 4: 9 1.  
1 5.  
Sa n ger -K atz M, Kliff S, A P. T hese Places C o ul d R u n O ut of H os pital Be ds as 
C or o na vir us S prea ds. N e w Y or k Ti mes 2 0 2 0 Marc h 1 7, 2 0 2 0.  
1 6.  
Grei n J, O h ma gari N, S hi n D, et al. C o m passi o nate Use of Re m d es i vir f or Patie nts wit h 
Se vere C o vi d -1 9. N E n gl J Me d 2 0 2 0.  
1 7.  
Dai M -Y, Li u D, Li u M, et al. Patie nts wit h Ca ncer A p pear M ore V ul n era bl e t o S A R S -
C o V -2: A M ulti -Ce nter St u d y D uri n g t he C O VI D -1 9 O ut brea k. La n cet O nc ol o g y 2 0 2 0.  

N CI  Pr ot oc ol #:  T R C -1 0 4 4 6  
Versi o n Date:  J u n e 4, 2 0 2 0 
 
6 3  
 
1 8.  
Lee D W, Gar d ner R, P orter D L, et al. C urre nt c o nce pts i n t he dia g n osis a n d ma na ge me nt 
of c yt o ki ne rel ease s y n dr o me. Bl o o d 2 0 1 4; 1 2 4: 1 8 8 -9 5.  
1 9.  
Li Y, C he n M, Ca o H, Z h u Y, Z he n g J, Z h o u H. E xtra or di nar y G U -ri c h si n gle-stra n d 
R N A i de ntifie d fr o m S A R S c or o na vir us c o ntri b utes a n e xcessi ve i n nate i m m u ne res p o nse. 
Micr o bes a n d I nfecti o n 2 0 1 3; 1 5: 8 8 -9 5.  
2 0.  
C he n N, Z h o u M, D o n g X, et al. E pi de mi ol o gical a n d cli nical c haracteristics of 9 9 cas es 
of 2 0 1 9 n o vel c or o n a vir us p ne u m o nia i n W u ha n, C hi na: a descri pti ve st u d y. T he La ncet 
2 0 2 0; 3 9 5: 5 0 7 -1 3.  
2 1.  
C o nti P, R o nc o ni G, Caraffa A, et al. I n d u cti o n of pr o -i nfla m mat or y c yt o ki nes (I L-1 a n d 
I L-6) a n d l u n g i nfla m mati o n b y C or o na vir us -1 9 ( C O VI -1 9 or S A R S -C o V -2): a nti -i nfla m mat or y 
strate gies. J Bi ol Re g ul H o me ost A ge nts 2 0 2 0; 3 4. 
2 2.  
Me hta  P, Mc A ule y D F, Br o w n M, et al. C O VI D -1 9: c o nsi der c yt o ki ne st or m s y n dr o mes 
a n d i m m u n os u p pressi o n. La ncet 2 0 2 0.  
2 3.  
Le R Q, Li L, Y ua n W, et al. F D A A p pr o val S u m mar y: T ociliz u ma b f or Treat me nt of 
C hi meric A nti ge n Rece pt or T Cell -I n d uce d Se v ere or Life-T hrea t e ni n g C yt o ki ne Release 
S y n dr o me. O nc ol o gist 2 0 1 8; 2 3: 9 4 3 -7.  
2 4.  
F D A Pac k a ge I nsert T ociliz u ma b ( Act mera( R)).  
2 5.  
Gar d ner R A, Ce p pi F, Ri vers J, et al. Pree m pti ve miti gati o n of C D 1 9 C A R T -cell 
c yt o ki ne rele ase s y n dr o m e wit h o ut atte n uati o n of a ntile u ke mic ef ficac y. Bl o o d 2 0 1 9; 1 3 4: 2 1 4 9-
5 8.  
2 6.  
X u X, Ha n M, Li T, et al. Effecti ve Treat me nt of Se vere C O VI D -1 9 Patie nts wit h 
T ociliz u ma b. 
htt ps:// w w w. g o o gle.c o m/ url?sa =t &rct =j & q = &esrc =s &s o urce = we b &c d = 1 & ve d = 2a h U K E wj 0 8 O
T N nr H o A h U y g nI E H Yc _ Dl M Q Fj A Ae g QI A x A B & url = htt p % 3 A % 2 F % 2 F w w w.c hi na xi v. or g % 2 F
user % 2 F d o w nl oa d. ht m % 3 Fi d % 3 D 3 0 3 8 7 % 2 6filet y pe % 3 D p df & us g = A O v Va w 1 4 k Dz 5 m v kz Mss x
-dz P p V B C 2 0 2 0 . 
2 7.  
Gi bia ns k y L, Fre y N. Li n ki n g i nterle u ki n -6 rece pt or bl oc ka de wit h t ociliz u ma b a n d its 
he mat ol o gical effects usi n g a m o deli n g a p pr oac h. J P har mac o ki net P har m ac o d y n 2 0 1 2; 3 9: 5 -1 6.  
2 8.  
Par k J H, R o mer o F A, Ta ur Y, et al. C yt o ki ne Release S y n dr o me Gra d e as a Pre dicti ve 
Mar ker f or I nfecti o ns i n Patie nts Wit h Rela pse d or Refract or y B -Cell Ac ut e L y m p h o blastic 
Le u ke mia Treate d Wit h C hi meric A nti ge n Rece pt or T Cells. Cl i n I nfect Dis 2 0 1 8; 6 7: 5 3 3-4 0.  
2 9.  
Hill J A, Li D, Ha y K A, et al. I nfecti o us c o m plicati o ns of C D 1 9 -tar get e d c hi meric a nti ge n 
rece pt or-m o difie d T -cell i m m u n ot hera p y. Bl o o d 2 0 1 8; 1 3 1: 1 2 1 -3 0.  
3 0.  
Ra mas wa mi R, L urai n K, Peer CJ, et al. T ociliz u ma b i n Patie nts wit h S y m pt o matic 
Ka p osi sarc o m a Her pes vir us ( K S H V) - ass ociate d M ultice ntric Castle ma n disease. Bl o o d 2 0 2 0.  
3 1.  
Pr ocla mati o n o n Declari n g a Nati o nal E mer ge nc y C o ncer ni n g t he N o vel C or o na vir us 
Disease ( C O VI D -1 9) O ut brea k. T he W hite H o use, 2 0 2 0. at 
htt ps:// w w w. w hite h o use. g o v/ presi de ntial -acti o ns/ pr ocla mati o n -declari n g -n ati o nal -e mer g e nc y -
c o ncer ni n g -n o vel -c or o na vir us -disease -c o vi d-1 9 -o ut brea k/ .) 
3 2.  
T his ta ble will be u p date d as t he t o xicit y pr ofile of t he a ge nt is re vis e d.  U p dates will be 
distri b ute d t o all Pri nci pal I n vesti gat ors at t he ti me of re visi o n.  T he c urre nt versi o n ca n b e 
o btai ne d b y c o ntacti n g PI O @ C T E P. N CI. NI H. G O V .  Y o ur na me, t h e na m e of t he i n vesti gat or, 
t he pr ot oc ol a n d t he a g e nt s h o ul d be i ncl u de d i n t he e-mai l. 
 
 
 

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Versi o n Date:  J u n e 4, 2 0 2 0 
 
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A P P E N DI X A  
S U M M A R Y T A B L E F O R P A TI E N T D E M O G R A P HI C S A N D 
L A B O R A T O R Y V A L U E S T O B E R E C O R D E D O N T H E C R F  
 
Me dic al hist or y: (M a n d at or y ) 
Ca ncer dia g n osis (s oli d t u m or, le u ke mia, l y m p h o ma, a ut oi m m u ne, b o ne marr o w tr a ns pla nt,  
S oli d or ga n tra ns pla nt, i m m u n os u p presse d) 
Ca ncer sta g e if k n o w n  
A ge ( Strat u m : 1) 2 years -1 4 years; Strat u m 2) 1 5 -3 9 years; Strat u m 3) 4 0 -6 4 years;  Strat u m 4) 
6 5 years a n d o v er.  
Ne wl y dia g n osis vs rela pse d/refract or y  
Acti ve t hera p y vs c o m plete d t hera p y  
T y pe of rece nt  pri or t h era p y (c he m ot hera p y, s mall m olec ule, ra di ot hera p y, i m m u n ot hera p y, 
ot her)  
Tra nsfer fr o m a “ gr o u p” facilit y, n ursi n g h o me, re ha b, ot her  
Self -I de ntifie d G e n der ( male, fe male, n o n-bi nar y)  
Race Et h nicit y ( use sta n d ar d ta bles)  
 
He alt h hist or y ( O pti o n al):  
K n o w n c o ntact  
S m o ki n g  
O bese  
C hr o nic l u n g disease ( C O P D, Ast h ma, o bstr ucti ve slee p a p n ea, i nterstitial l u n g disease, c ystic 
fi br osis, p ul m o nar y h y perte nsi o n) 
C hr o nic heart dise ase ( C A D, C H F, atri al arr yt h mi a, ve ntric ular arr yt h mia)  
H y perte nsi o n  
D ia betes mellit us (a 1 C) 
 
C o n c o mit a nt me dic ati o ns : (O pti o n al)  
C o nc urre nt tri al e nr oll me nt a n d tre at me nt  ( O pti o n al) 
A nti h y perte nsi ves  
A nti -h y per gl yce mics  
A nti -HI V dr u gs  
Di uretics  
Stati n   
Br o hc h o dilat ors  
A ntic oa g ula nts  
A nti bi otics  
I m m u n os u p pr essa nts 
S u p ple me nt s, i ncl u di n g vita mi ns 
 
I ncl u de a n y C O VI D-1 9 directe d t her a p y (M a n d at or y ) 
Ster oi ds  
A ntic oa g ula nts  
HI V pr ote ase i n hi bit ors  
H y dr o x yc hl or o q ui ne  
C h l or oq ui ne  

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Re m desi vir  
T ociliz u ma b  
Saril u ma b  
Ot her  
 
Prese nti n g s y m pt o ms:  (M a n d at or y ) 
Re q uire me nt f or n o n -i n v asi ve O2 s u p ple me ntati o n  
Re q uire me nt f or mec ha ni cal ve ntilati o n i n t he E mer ge nc y De part me nt  
 
 
M o nit ori n g a n d rec or de d i n t he C R F:  (M a n d at or y at b aseli ne a n d w here i n dic ate d ; 
Re q ueste d  as i n dic ate d ) 
Vital Si g ns ( H R, R R, B P a n d te m perat ure, at b asel i ne a n d d ail y; O R per I C U or n o n-I C U   
r o uti ne 
Baseli ne Hei g ht, wei g ht, B S A, B MI  
O 2 sat urati o n, at baseli ne a n d e ver y 2 4 h o urs  u ntil disc har ge  fr o m h os pital  
O 2 re q uire m e nt, at baseli ne a n d e v er y 2 4 h o urs  u ntil disc har ge  fr o m h os pital  
I nt u bat e d ( yes/ n o), at bas eli ne a n d e v er y 2 4 h o urs u ntil disc har ge  fr o m h os pital  
C ollecti o n a n d re p orti n g of all gra de 3 -5 e ve nts attri b ute d t o t ociliz u ma b  
 
L a bs:  
At b aseli ne:  (M a n d at or y ) 
C B C wit h differe ntial  
A L T/ A S T  
 
O pti o n al:  
P T, P T T, I N R, fi bri n o ge n, D -di mer  
Ferriti n  
C -reacti ve pr otei n 
S M A 2 0 ( m o nit or M g a n d K fre q u e ntl y as cli nicall y i n dicate d)  
Gree n t o p s o di u m he pari n t u be (f or c yt o ki ne release s y n dr o me , S A R S-C o V -2 viral l oa d,  a n d 
t ociliz u ma b P K e val uati o n s) 
P ur ple t o p E D T A t u be (f or c yt o ki ne rel ease s y n dr o m e e val uati o n  a n d S A R S -C o V -2 viral l oa d ) 
 
E ver y 1 2 h o urs  f or f o ur c ollecti o ns after first d ose of t ociliz u ma b: (O pti o n al ) 
C B C wit h differe ntial  
P T, P T T, I N R, fi bri n o ge n, D -di mer  
Ferriti n  
C -reacti ve pr otei n 
S M A 2 0  
 
E ver y 1 2  h o urs  f or f o ur c ollecti o ns  after first d ose of t ociliz u ma b : (O pti o n al rese arc h bl o o d 
c ollecti o ns)  
Gree n t o p s o di u m he pari n t u be (f or c yt o ki ne release s y n dr o me S A R S -C o V -2 viral l oa d, a n d 
t ociliz u ma b P K e val uati o n s) 
P ur ple t o p E D T A t u be (f or c yt o ki ne rel ease s y n dr o me e val uati o n a n d S A R S -C o V -2 viral l oa d ) 

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Versi o n Date:  J u n e 4, 2 0 2 0 
 
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E ver y 2 4  h o urs  u ntil disc har ge fr o m h os pital : (M a n d at or y ) 
C B C wit h differe ntial  
 
7 2 H o urs after i niti al d ose of t ociliz u m a b : (O pti o n al rese arc h bl o o d c ollecti o ns)  
Gree n t o p s o di u m he pari n t u be (f or c yt o ki ne release s y n dr o me S A R S -C o V -2 viral l oa d,  a n d 
t ociliz u ma b P K e val uati o n s) 
P ur ple t o p E D T A t u be(f or c yt o ki ne rel ease s y n dr o me e val uati o n , a n d S A R S-C o V -2 viral l oa d ) 
 
7 D a ys after i niti al d ose of t ociliz u m a b (if still h os pit alize d) : (O pti o n al rese arc h bl o o d 
c ollecti o n s) 
Gree n t o p s o di u m he pari n t u be (f or c yt o ki ne release s y n dr o me , S A R S -C o V -2 viral l oa d, a n d 
t ociliz u ma b P K e val uati o n s) 
P ur ple t o p E D T A t u be (f or c yt o ki ne rel ease s y n dr o me e val uati o n , a n d S A R S-C o V -2 viral l oa d ) 
 
O pti o n al  
Off tre at me nt:   
C B C wit h differe ntial  
P T, P T T, I N R, fi bri n o ge n, D -di mer  
Ferriti n  
C -reacti ve pr otei n  
S M A 2 0  
 
O pti o n al  
I m a gi n g Re p ort : ( Descri pti ve or R a di ol o g y Re a di n g/ Re p ort) 
Baseli ne  
C X R, A P a n d lateral ( U n c ha n ge d, W orse n e d, I m pr o ve d)  
As cli nicall y i n dicate d  
 
Tre at me nt wit h t ociliz u m a b: (M a n d at or y ). Use 2 4 h o ur cl oc k  
Date a n d ti me of first d ose of t ociliz u ma b a n d a m o u nt a d mi nistere d  
Di d fe ver res ol ve wit hi n 6 h o urs of t ociliz u ma b a d mi nistrati o n?  
Di d res pirat or y s u p p ort d ecrease wit hi n 6 h o urs of t ociliz u ma b a d mi nistrati o n?  
Da te a n d ti me of s ec o n d d ose of t ociliz u ma b a n d a m o u nt a d mi nistere d?  
Di d fe ver res ol ve wit hi n 6 h o urs of 2 n d d ose of  t ociliz u ma b a d mi nistrati o n? 
Di d res pirat or y s u p p ort d ecrease wit hi n 6 h o urs of t ociliz u ma b a d mi nistrati o n?  
N O t ociliz u ma b a d mi nistere d  
 
Cli n ic al o utc o me E v al u ati o n:  
Res p o nse e v al u ati o n C o h ort A  ( N O T o n mec h a nic al ve ntil ati o n) 
•  C o m plete res p o nse :  re d u cti o n i n se vere s y m pt o ms s uc h t hat t he y are n ot life-
t hreate ni n g a n d re q uire s y m pt o matic treat me nt o nl y (fe ver, na usea, fati g ue, hea dac he, 
m yal gias, malaise) a n d ca n be disc har ge d fr o m h os pital  
•  Partial res p o nse :  I m pr o v e me nt i n cli nical stat us sc ore b y at least o ne p oi nt b ut 
re q uires c o nti n ue d h os pit alizati o n 

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Versi o n Date:  J u n e 4, 2 0 2 0 
 
6 7  
 
•  Pr o gressi ve disease :  Cli nical sc ore c ha n g es t o a  5 or 6  (see  Sc h e ma f or t he Cli nical 
Or di nal Scale ) 
•  Deat h  
 
S u bjects w h o ha ve pr o gressi ve disease ( n o decrease i n s u p p orti ve care dee me d p ossi ble) or deat h 
fr o m C O VI D-1 9 will be c o nsi dere d as a Treat me nt fail ure   
 
Cli nic al o utc o me e v al u ati o n C o h ort B  ( o n mec h a nic al ve ntil ati o n) 
•  C o m plete res p o nse :  re d u cti o n i n se vere s y m pt o ms s uc h t hat t he y are n ot life-
t hreate ni n g a n d re q uire s y m pt o matic treat me nt o nl y (fe ver, na usea, fati g ue, hea dac he, 
m yal gias, malaise)  a n d ca n be disc har ge d fr o m h os pi tal 
•  Ve ntilat or C o m plete Res p o nse : Re m o val fr o m mec ha nical v e ntilati o n a n d disc har ge 
fr o m I C U/I C U eli gi bilit y  
•  Partial res p o nse :  Disc har ge d fr o m I C U b ut re q uir es c o nti n ue d h os pitalizati o n 
•  Ve ntilat or Partial Res p o nse : Re m o val fr o m mec h a nical ve ntilati o n a n d b ut re q uire  
n o n -i n vasi ve ve ntilati o n or hi g h fl o w O2  c o nti n ue d I C U s u p p ort/re mai ns I C U eli gi ble  
•  Pr o gressi ve disease :  N o decrease i n s u p p orti ve care dee m e d p ossi ble 
•  D eat h  
 
S u bjects w h o ha ve pr o gressi ve disease ( n o decrease i n s u p p orti ve car e dee me d p ossi ble) or deat h 
fr o m C O VI D-1 9 will be c o nsi dere d as a Treat me nt fail ure