Immunogenicity of a Third Dose of Either the Moderna COVID-19 Vaccine or Pfizer-BioNTech COVID-19 Vaccine in Kidney Transplant Recipients Who Failed to Respond After Two Previous Doses
Phase: PHASE2
Conditions: Kidney Transplant Recipients
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

 
C o nfi d e nti al  
P a g e 1  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
C O VI D 1 9 -T B -0 2  
I m m u n o g e nicit y of a t hir d d os e of eit h er t h e M o d er n a C O VI D-1 9 v acci n e or  Pfiz er -
Bi o N T ec h  C O VI D -1 9 v acci n e i n ki d n e y tr a ns pl a nt r eci pi e nts w h o f ail e d t o r es p o n d 
aft er t w o pr e vi o us d os es  
V ersi o n 3. 0  / J a n u ary 1 4 , 2 0 22  
I N D # 2 7 2 1 5  
N ati o n al Cli nic al Tri al ( N C T) # 0 4 9 6 9 2 6 3   
I N D S p o ns or: T h e N ati o n al I nstit ut e of All er g y a n d I nf ecti o us Dis e as es ( NI AI D)  
NI AI D F u n di n g M ec h a nis m : C o o p er ativ e A gr e e m e nt  
I n v esti g ati o n al A g e nts: M o d er n a C O VI D -1 9 V acci n e , Pfiz er -Bi o N T ec h  C O VI D -1 9 V acci n e  
Pr ot oc ol C h air  
Gr a nt e e Pri nci p al I n v esti g at or  
D orr y S e g e v, M D, P h D  
Pr of ess or  of S ur g er y  
J o h ns H o p ki ns U ni v ersit y (J H U) 
Tr a ns pl a nt S ur g er y  
Sc h o ol of M e dici n e  
 
 
 
 
 
M ec h a nistic I n v esti g at or  
 
 
 
 
 
 
 
 
 
 
M ec h a nistic I n v esti g at or  
 
 
 
 
 
 
 
 
 
Sit e Pri nci p al I n v esti g at or   
 
 
 
 
 
 
 
 
 
  
Bi ost atistici a n  
 
 
 
 
 
 
 
 
 
 
NI AI D M e dic al M o nit or  
 
  
 
 
  
  
 
NI AI D R e g ul at or y Offic er  
 
 
 
 
 
 
 
NI AI D Pr oj ect M a n a g er  
 
 
 
 
 
  
 
NI AI D Cli nic al R es e arc h P h ar m acist  
 
 
 
 
 
  
     
    
 

 
C o nfi d e nti al  
P a g e 2  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
C o nfi d e nti alit y St at e m e nt  
T h e i nf or m ati o n c o nt ai n e d wit hi n t his d oc u m e nt is n ot t o b e discl os e d i n a ny w ay wit h o ut t h e pri or p er missi o n of t h e Di visi o n 
of All er g y, I m m u n ol o g y, a n d Tr a ns pl a nt ati o n, N ati o n al I nsit ut ut es of All er g y a n d I nf ecti o us Dis e as es, N ati o n al I nstit ut es of 
H e alt h . 
 
 
 
 
 
 
 

 
C o nfi d e nti al  
P a g e 4  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
Pr ot oc ol S y n o psis  
Titl e  
I m m u n o g e nicity of a t hir d d os e of eit h er t h e M o d er n a C O VI D-1 9 v acci n e or 
Pfiz er -Bi o N T ec h C O VI D -1 9 v acci n e i n ki d n e y tr a ns pl a nt r eci pi e nts w h o f ail e d t o 
r es p o n d t o t w o pr e vi o us d os es. 
S h ort Titl e  
C O VI D Pr ot ecti o n Aft er Tr a ns pl a nt  Pil ot  ( C P A T-P ) St u d y  
Cli nic al P h as e  
P h as e II  
N u m b er of Sit es  
Si n gl e C e nt er (J o h ns H o p ki ns U niv ersity)  
I N D S p o ns or / N u m b er   
NI AI D/ I N D #  2 7 2 1 5  
St u d y O bj ecti v es  
T o elicit a n a nti b o d y r es p o ns e t o v acci n ati o n a g ai nst S A R S -C o V -2 i n ki d n e y 
tr a ns pl a nt r eci pi e nts w h o h av e f ail e d t o r es p o n d t o t w o d os es of eit h er t h e 
M o d er n a C O VI D -1 9 v acci n e or Pfiz er -Bi o N T ec h C O VI D -1 9 v acci n e.  
St u d y D esi g n  
A n o p e n l a b el, n o n -r a n d o miz e d pil ot st u d y i n ki d n e y tr a ns pl a nt r eci pi e nts w h o 
r ec eiv e d t w o d os es of eit h er m R N A C O VI D-1 9 v acci n e a n d h av e a  n e g ativ e ( < 0. 8 
U/ mL)  or l o w (tit er < 5 0 U/ mL ) S A R S-C o V -2 a nti b o d y r es p o ns e usi n g t h e  R oc h e 
El ecs ys ®  a nti -R B D ass ay.  Eli gi bl e p artici p a nts will r ec ei v e a t hir d d os e of t h e 
s a m e m R N A v acci n e as t h e pri or t w o d os es.  
Pri m ar y E n d p oi nt  
T h e pri m ar y e n d p oi nt is t h e pr o p orti o n of p artici p a nts w h o ac hi e v e a n a nti b o d y 
r es p o ns e > 5 0 U/ mL m e as ur e d at 3 0 d ays aft er t h e t hir d d os e of v acci n e usi n g 
t h e R oc h e El ecs ys a nti -R B D ass ay . A ll s u bj ects wit h d et ect a bl e a nti b o d y will i n 
a d diti o n h av e n e utr alizi n g a nti b o d y tit ers  a n d f urt h er q u a ntific ati o n a n d 
c h ar act eriz ati o n of a nti b o d y usi n g t h e b est av ail a bl e ass ay . 
S af et y, S ec o n d ar y , a n d 
E x pl or at or y E n d p oi nt(s)  
S ec o n d ar y S af et y E n d p oi nts:  
• 
L oc al a n d s yst e mic v acci n e r e act o g e nicity a n d/ or all er g y  
• 
S eri o us a d v ers e e v e nts occ urri n g d uri n g t h e 3 0 d ays f oll o wi n g t h e t hir d 
d os e of v acci n e  
• 
Tr e at e d ac ut e c ell -m e di at e d a n d/ or a nti b o d y -m e di at e d all o gr aft 
r ej ecti o n (cli nic al or bi o ps y-pr o v e n) wit hi n 6 0 d ays f oll o wi n g t h e t hir d 
d os e of v acci n e  
• 
D e v el o p m e nt of d e n o v o d o n or -s p ecific a nti-HL A a nti b o d y  wit hi n 9 0  
d ays of t h e v acci n e  
• 
Gr aft l oss  wit hi n 6 0 d ays of t h e v acci n e  
• 
D e at h wit hi n 6 0 d ays of t h e v acci n e  
E x pl or at or y M ec h a nistic I m m u n o g e nicit y E n d p oi nts :  
• 
R a n g e of a nti b o d y r es p o ns es a n d ot h er m e as ur es of i m m u n ol o gic 
pr ot ecti o n  
• 
A nti -S 1 a n d a nti -R B D s er ol o g y  
•
A d diti o n al s er ol o gic al p a n els a n d c orr el at es of n e utr alizi n g a nti b o d y 
• 
N e utr alizi n g a nti b o d y ass ays  

 
C o nfi d e nti al  
P a g e 5  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
• 
S A R S -C o V -2 vir ol o g y, di a g n ostics, a n d s e q u e nci n g, i ncl u di n g n ov el 
v ari a nts of c o nc er n  
• 
A nti g e n -s p ecific B c ell r es p o ns e  
• 
A nti g e n -s p ecific T c ell r es p o ns e 
• 
E vi d e nc e of i m m u n e activ ati o n  a n d m et a b olic pr ofil e  b y tr a nscri pt o mics 
a n d c yt o ki n e si g n ali n g  
• 
D ur a bility of d e n o v o d o n or -s p ecific a nti-HL A a nti b o d y  
Accr u al O bj ecti v e  
T h e st u d y will e nr oll u p t o 2 0 0 p artici p a nts w h o h av e a n e g ativ e ( < 0. 8  U/ mL)  or 
l o w (< 5 0  U / mL) tit er a nti b o d y b y t h e R oc h e El ecs ys ® ass ay , wit h a mi ni m u m of 
5 0 a n d u p t o 1 0 0 p artici p a nts i n e ac h str atu m  ( n o n-r es p o n d er vs l o w r es p o n d er). 
St u d y D ur ati o n  
Accr u al: 4 w e e ks   
V acci n ati o n a n d F oll o w -u p: 8 -1 2 m o nt hs   
T ot al D ur ati o n: a mi ni m u m of 8  m o nt hs  a n d u p t o 1 3 m o nt hs  
Tr e at m e nt D escri pti o n   
A t hir d d os e  of t h e s a m e m R N A pl atf or m C O VI D -1 9 v acci n e  as pr e vi o usly 
r ec eiv e d ( 1 0 0 mc g M o d er n a or 3 0 mc g Pfiz er-Bi o N T ec h)  
I ncl usi o n Crit eri a 
I n divi d u als m ust m e et all t h e f oll o wi n g crit eri a t o b e eli gi bl e:  
1. 
A bl e t o u n d erst a n d a n d pr o vi d e i nf or m e d c o ns e nt.  
2. 
I n divi d u al  1 8 y e ars of a g e.  
3. 
R eci pi e nt of ki d n e y tr a ns pl a nt 1 2 m o nt hs pri or t o e nr oll m e nt, wit h o ut 
tr e at e d all o gr aft r ej ecti o n i n t h e 6 m o nt hs pr ec e di n g e nr oll m e nt. 
4. 
R ec ei v e d 2 d os es of eit h er t h e  M o d er n a C O VI D -1 9 v acci n e or Pfiz er -
Bi o N T ec h C O VI D -1 9 v acci n e  as s p ecifi e d i n t h e r es p ectiv e F D A E U As, > 3 0 
d ays a n d < 8 m o nt hs pri or t o st u d y e ntr y.  
5.
N e g ativ e  (tit er < 0. 8 U/ mL) or l o w ( a nti b o di es d et ect e d at tit er <  5 0 U/ mL ) 
r es p o ns e t o t h e v acci ne at >  3 0 d ays fr o m d os e 2 of t h e M o d er n a C O VI D -1 9 
v acci n e or t h e Pfiz er Bi o N T ec h v acci n e, usi n g t h e R oc h e El ecs ys ® a nti-R B D 
ass ay.  
E xcl usi o n Crit eri a  
 
I n divi d u als w h o m e et a n y of t h e f oll o wi n g crit eri a will n ot b e eli gi bl e: 
1. 
R eci pi e nt of a n y n u m b er of d os es of a n y C O VI D v acci n e pr o d uct ot h er t h a n 
t h e M o d er n a C O VI D-1 9 v acci n e or t h e Pfiz er -Bi o N T ec h C O VI D -1 9 v acci n e.  
2. 
K n o w n hist or y of s e v er e all er gic r e acti o n t o a n y c o m p o n e nt of eit h er t h e 
M o d er n a C O VI D -1 9 v acci n e or Pfiz er -Bi o N T ec h C O VI D -1 9 v acci n e.  
3. 
T hr o m b otic e v e nts, m y oc ar ditis, or p eric ar ditis t e m p or ally ass oci at e d wit h 
pri or d os e of C O VI D -1 9 v acci n e.  
4. 
A n y c h a n g e i n tr a ns pl a nt i m m u n os u p pr essi o n r e gi m e n ( dr u g or d os e) i n 
r es p o ns e t o s us p ect e d or pr o v e n r ej ecti o n wit hi n t h e l ast 6 m o nt hs.  
5. 
Si g nific a nt gr aft d ysf u ncti o n (s e e St u d y D efi niti o ns f or f urt h er d et ails).  
6. 
R ec ei pt of a n y c ell ul ar d e pl eti n g a g e nt ( e. g. A T G,  Rit u x i m a b, Al e mt uz u m a b,  
Cycl o p h os p h a mi d e) wit hi n 1 2 m o nt hs pr ec e di n g e nr oll m e nt.   
7. 
R ec ei vi n g s yst e mic i m m u n o m o d ul at or y m e dic ati o n(s) f or a n y c o n diti o n 
ot h er t h a n tr a ns pl a nt.  
8. 
A n y u ntr e at e d activ e i nf ecti o n.  

 
C o nfi d e nti al  
P a g e 6  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
9. 
I nf ecti o n wit h HI V. 
1 0. M ai nt e n a nc e i m m u n os u p pr essiv e r e gi m e n t h at i ncl u d es b el at ac e pt or 
a b at ac e pt.  
1 1. R ec e nt ( wit hi n o n e y e ar) or o n g oi n g tr e at m e nt f or m ali g n a nc y.  
1 2. A n y p ast or c urr e nt m e dic al pr o bl e ms, tr e at m e nts, or fi n di n gs w hic h, i n t h e 
o pi ni o n of t h e i n v esti g at or, m ay p os e a d diti o n al ris ks fr o m p artici p ati o n i n 
t h e st u d y, m ay i nt erf er e wit h t h e c a n di d at e’s a bilit y t o c o m ply wit h st u d y 
r e q uir e m e nts or m ay i m p act t h e q u ality or i nt er pr et ati o n of t h e d at a 
o bt ai n e d fr o m t h e st u d y.  
P a usi n g  R ul es  
If t h e f oll o wi n g occ ur, e nr oll m e nt m ay b e t e m p or arily halt e d a n d a n ex p e dit e d 
D S M B r evi e w t ak e pl ac e:  
R e act o g e nicit y : T w o Gr a d e 4 or hi g h er r e act o g e nic a d v ers e e v e nt s ( A Es) t h at ar e 
d efi nit el y or p ossi bly r el at e d t o t h e v acci n e   
All er g y : Fiv e p artici p a nts i n t h e first 1 0 0 p artici p a nts v acci n at e d, or 5 % of all 
p artici p a nts t h er e aft er ex p eri e nci n g a Gr a d e 3 s yst e mic all er gic  r e acti o n t h at is 
d efi nit el y or p ossi bly r el at e d t o t h e v acci n e   
 

 
C o nfi d e nti al  
P a g e 7  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
St u d y C o nt acts: P artici p ati n g C e nt ers   
 
S I T E P RI N CI P AL IN V E S TI G A T O R  
Willi a m W er b el, M D  
J o h ns H o p ki ns U niv ersit y 
 
 
 
 
 
 
 
  

 
C o nfi d e nti al  
P a g e 8  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
  
T a bl e of C o nt e nts  
Pr ot oc ol Sy n o psis  ............................................................................................................................................... 4  
Gl oss ary of A b br evi ati o ns  ................................................................................................................................ 1 3  
St u dy D efi niti o ns P a g e ...................................................................................................................................... 1 4  
1.  
B ac k gr o u n d a n d R ati o n al e  ....................................................................................................................... 1 6  
1. 1  
B a c k gr o u n d a n d Sci e ntific R ati o n al e  ................................................................................................ 1 6  
1. 2  
Pr ecli nic al Ex p eri e nc e  ....................................................................................................................... 1 7  
1. 3  
Cli nic al St u di es  .................................................................................................................................. 1 8  
2.  
St u dy Hy p ot h es es/ O bj ectiv es  .................................................................................................................. 1 9  
2. 1  
Hy p ot h es es  ....................................................................................................................................... 1 9  
2. 2  
Pri m ary O bj ectiv e(s)  ......................................................................................................................... 1 9  
2. 3  
S ec o n d ary S af et y O bj ectiv e(s)  .......................................................................................................... 1 9  
2. 4  
S ec o n d ary I m m u n o g e nicit y O bj ectiv es  ............................................................................................ 1 9  
2. 5  
Ex pl or at ory M ec h a nistic O bj ectiv es  ................................................................................................. 1 9  
3.  
St u dy D esi g n  ............................................................................................................................................. 2 0  
3. 1  
D escri pti o n of St u dy D esi g n  ............................................................................................................. 2 0  
3. 2  
Pri m ary E n d p oi nt  .............................................................................................................................. 2 0  
3. 3  
S ec o n d ary E n d p oi nts  ........................................................................................................................ 2 0  
3. 3. 1  
S ec o n d ary S af et y E n d p oi nts  ......................................................................................................... 2 0  
3. 3. 2  
Ex pl or at ory M ec h a nistic I m m u n o g e nicit y E n d p oi nts  .................................................................. 2 1  
4.  
S el ecti o n of P artici p a nts a n d Cli nic al Sit es/L a b or at ori es  ......................................................................... 2 2  
4. 1  
R ati o n al e f or St u dy P o p ul ati o n  ........................................................................................................ 2 2  
4. 2  
I ncl usi o n Crit eri a............................................................................................................................... 2 2  
4. 3  
Excl us i o n Crit eri a .............................................................................................................................. 2 2  
4. 4  
S el ecti o n of Cli nic al Sit es  .................................................................................................................. 2 3  
4. 4. 1  
S el ecti o n of Cli nic al Sit e  ............................................................................................................... 2 3  
5.  
K n o w n a n d P ot e nti al Risks a n d B e n efits t o P artici p a nts  ......................................................................... 2 4  
Risks of t h e I nv esti g ati o n al Pr o d ucts as cit e d i n t h e F ull F D A E U A Pr esc ri bi n g I nf or m ati o n ....................... 2 4  
5. 1. 1  
Risks of M o d er n a C O VI D -1 9 V acci n e  ............................................................................................ 2 4  
5. 1. 2  
Risks of Pfiz er -Bi o N T ec h C O VI D -1 9 V acci n e  ................................................................................. 2 4  

 
C o nfi d e nti al  
P a g e 9  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
5. 1. 3  
Risks of M o d er n a C O VI D -1 9 V acci n e a n d Pfiz er -Bi o N T ec h V acci n es i n a d ults as cit e d i n M e dic al 
Lit er at ur e ...................................................................................................................................................... 2 4  
5. 1. 4  
P ot e nti al Risks t o St u dy P o p ul ati o n  ............................................................................................. 2 4  
5. 2  
Risks of Ot h er Pr ot oc ol S p ecifi e d M e dic ati o ns  ................................................................................ 2 5  
5. 3  
Risks of St u dy Pr oc e d ur es  ................................................................................................................ 2 5  
5. 3. 1  
Risk of Bl o o d Dr a w  ....................................................................................................................... 2 5  
5. 3. 2  
Risks Ass oci at e d wit h N as o p h ary n g e al S w a b C oll ecti o n  ............................................................. 2 5  
5. 3. 3  
Risk of I nt er n et B as e d D at a C oll ecti o n  ......................................................................................... 2 5  
5. 4  
P ot e nti al B e n efits  ............................................................................................................................. 2 5  
6.  
I nv esti g ati o n al A g e nts .............................................................................................................................. 2 6  
6. 1  
I nv esti g ati o n al A g e nt # 1: M o d er n a C O VI D-1 9 V acci n e ................................................................ 2 6  
6. 1. 1  
F or m ul ati o n, P ac k a gi n g, a n d L a b eli n g ...................................................................................... 2 6  
6. 1. 2  
D os a g e, Pr e p ar ati o n, a n d A d mi nistr ati o n  ................................................................................ 2 6  
6. 2  
I nv esti g ati o n al A g e nt # 2: Pfiz er-Bi o N T ec h C O VI D -1 9 V acci n e  ......................................................... 2 6  
6. 2. 1  
F or m ul ati o n, P ac k a gi n g, a n d L a b eli n g ...................................................................................... 2 6  
6. 2. 2  
D os a g e, Pr e p ar ati o n, a n d A d mi nistr ati o n  ................................................................................ 2 7  
6. 3  
Dr u g Acc o u nt a bilit y  .......................................................................................................................... 2 7  
6. 4  
Ass ess m e nt of P artici p a nt C o m pli a nc e wit h I nv esti g ati o n al A g e nt  ................................................. 2 7  
6. 5  
T oxicit y Pr ev e nti o n a n d M a n a g e m e nt  ............................................................................................. 2 7  
6. 6  
Pr e m at ur e Disc o nti n u ati o n of I nv esti g ati o n al A g e nt ....................................................................... 2 8  
7.  
Ot h er M e dic ati o ns .................................................................................................................................... 2 9  
7. 1  
C o nc o mit a nt M e dic ati o ns  ................................................................................................................ 2 9  
7. 1. 1  
Pr ot oc ol -m a n d at e d  ...................................................................................................................... 2 9  
7. 1. 2  
Ot h er p er mitt e d c o nc o mit a nt m e dic ati o ns  ................................................................................. 2 9  
7. 2  
Pr o p hyl actic M e dic ati o ns  ................................................................................................................. 2 9  
7. 3  
Pr o hi bit e d M e dic ati o ns  .................................................................................................................... 2 9  
7. 4  
R e sc u e M e dic ati o ns.......................................................................................................................... 2 9  
8.  
St u dy Pr oc e d ur es  ..................................................................................................................................... 3 0  
8. 1  
E nr oll m e nt  ........................................................................................................................................ 3 0  
8. 2  
Scr e e ni n g Visi t .................................................................................................................................. 3 0  
8. 3  
St u dy Visits or St u dy Ass ess m e nts  ................................................................................................... 3 0  
8. 3. 1  
V acci n ati o n Visit ( D ay 0)  ............................................................................................................... 3 0  

 
C o nfi d e nti al  
P a g e 1 0  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
8. 3. 2  
F oll o w -u p Visits  ............................................................................................................................ 3 0  
8. 4  
U nsc h e d ul e d Visits  ........................................................................................................................... 3 1  
8. 5  
Visit Wi n d o ws  ................................................................................................................................... 3 1  
9.  
M ec h a nistic Ass a ys  ................................................................................................................................... 3 2  
9. 1  
I ntr o d ucti o n ...................................................................................................................................... 3 2  
9. 2  
O bj ectiv e 1:  T o q u a ntify s pi k e pr ot ei n pr o d ucti o n i n s er u m or pl as m a aft er v acci n ati o n.  ............ 3 3  
9. 3  
O bj ectiv e 2: T o pr ovi d e a d et ail e d ki n etic c h ar act eriz ati o n of t h e v acci n e i n d uc e d a nti b o d y 
r e p ert oir e (s p ecificit y, is ot y p e, tit er, n e utr aliz ati o n c a p acit y). ................................................................... 3 3  
9. 4  
O bj ectiv e 3: T o p erf or m a ki n etic p h e n ot y pic a n d f u ncti o n al a n al ysis of a nti g e n s p ecific B m e m 
(fr e q u e nc y, a nti g e n s p ecificit y, s urf ac e m ark ers, m et a b ol o mics, g e n e ex pr essi o n p att er ns, si n gl e c ell 
s e q u e nci n g) a n d P C. ..................................................................................................................................... 3 3  
9. 5  
O b j ectiv e 4: T o p erf or m a ki n etic, a n al ysis of a nti g e n s p ecific C D 4 + a n d C D 8 + T c ells (fr e q u e nc y, 
e pit o p e s p ecificit y, s urf ac e m ark ers, m et a b ol o mics, g e n e ex pr essi o n p att er ns si n gl e c ell s e q u e nci n g).  .. 3 3  
9. 6  
O bj ectiv e 5: T o ass ess p h e n ot y pic, f u ncti o n al a n d g e n e ex pr essi o n p att er ns of i n n at e i m m u n e D C, 
m o n oc yt e/ m acr o p h a g e a n d N K c ell s u bs ets i n p eri p h er al bl o o d.  ............................................................... 3 4  
9. 7  
O bj ectiv e 6: Ex pl or ati o n of m ol ec ul ar bi o m ark ers of e arl y r es p o n d ers t o v acci n ati o n  .................. 3 4  
1 0.  
Bi os p eci m e n St or a g e  ............................................................................................................................ 3 5  
1 1.  
Crit eri a f or P artici p a nt a n d St u dy C o m pl eti o n a n d Pr e m at ur e St u dy T er mi n ati o n ............................. 3 6  
1 1. 1  
P artici p a nt C o m pl eti o n  .................................................................................................................... 3 6  
1 1. 2  
P artici p a nt St o p pi n g R ul es a n d Wit h dr a w al Crit eri a  ....................................................................... 3 6  
1 1. 3  
P artici p a nt R e pl ac e m e nt  .................................................................................................................. 3 6  
1 1. 4  
F oll o w-u p aft er E arl y St u dy Wit h dr a w al  .......................................................................................... 3 6  
1 2.  
S af et y M o nit ori n g a n d R e p orti n g  ......................................................................................................... 3 7  
1 2. 1  
O v ervi e w ........................................................................................................................................... 3 7  
1 2. 2  
D efi niti o ns  ........................................................................................................................................ 3 7  
1 2. 2. 1  
A dv ers e E v e nt ( A E)  ....................................................................................................................... 3 7  
1 2. 2. 2  
S olicit e d A dv ers e E v e nts  .............................................................................................................. 3 7  
1 2. 2. 3  
U ns olicit e d A dv ers e E v e nts  .......................................................................................................... 3 8  
1 2. 2. 3. 1  
S us p ect e d A dv ers e R e acti o n (S A R)  .......................................................................................... 3 8  
1 2. 2. 4  
U n ex p ect e d A dv ers e E v e nt  .......................................................................................................... 3 8  
1 2 . 2. 5 
S eri o us A dv ers e E v e nt ( S A E)  ........................................................................................................ 3 8  
1 2. 3  
Gr a di n g a n d Attri b uti o n of A dv ers e E v e nts  ..................................................................................... 3 9  
1 2. 3. 1  
Gr a di n g Crit eri a  ............................................................................................................................ 3 9  

 
C o nfi d e nti al  
P a g e 1 1  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
1 2. 3. 2  
Attri b uti o n D efi niti o ns  ................................................................................................................. 3 9  
1 2. 4  
C oll ecti o n a n d R ec or di n g of A dv ers e E v e nts .................................................................................... 4 0  
1 2. 4. 1  
C oll ecti o n P eri o d  .......................................................................................................................... 4 0  
1 2. 4. 2  
C oll ecti n g A dv ers e E v e nts  ............................................................................................................ 4 0  
1 2. 4. 3  
R ec or di n g A dv ers e E v e nts  ............................................................................................................ 4 1  
1 2. 5  
R e p orti n g of S eri o us A dv ers e E v e nts a n d A dv ers e E v e nts  .............................................................. 4 1  
1 2. 5. 1  
R e p orti n g of S eri o us A dv ers e E v e nts t o D AI T/ NI AI D  ................................................................... 4 1  
1 2. 5. 2  
R e p orti n g t o H e alt h A ut h orit y  ...................................................................................................... 4 1  
1 2. 5. 2. 1  
A n n u al R e p orti n g  ...................................................................................................................... 4 1  
1 2. 5. 2. 2  
Ex p e dit e d S af et y R e p orti n g  ...................................................................................................... 4 2  
1 2. 5. 3  
R e p orti n g of A dv ers e E v e nts t o I R Bs/I E Cs  .................................................................................... 4 2  
1 2. 5. 4  
M a n d at ory r e p orti n g t o V acci n e A dv ers e E v e nt R e p orti n g Syst e m  ............................................ 4 2  
1 2. 6  
R e p orti n g of Ot h er S af et y I nf or m ati o n ............................................................................................ 4 3  
1 2. 7  
R e vi e w of S af et y I nf or m ati o n  ........................................................................................................... 4 3  
1 2. 7. 1  
M e dic al M o nit or R evi e w  .............................................................................................................. 4 3  
1 2. 7. 2  
D S M B R evi e w  ............................................................................................................................... 4 3  
1 2. 7. 2. 1  
Pl a n n e d D S M B R evi e ws  ............................................................................................................ 4 3  
1 2. 7. 2. 2  
A d h oc D S M B R evi e ws  .............................................................................................................. 4 3  
1 2. 7 . 2. 2. 1 
T e m p or ary S us p e nsi o n of e nr oll m e nt f or a d h oc D S M B S af et y R evi e w  .............................. 4 4  
1 3.  
St atistic al C o nsi d er ati o ns a n d A n al ytic al Pl a n  ..................................................................................... 4 5  
1 3. 1  
O v ervi e w ........................................................................................................................................... 4 5  
1 3. 2  
E n d p oi nts  .......................................................................................................................................... 4 5  
1 3. 3  
M e as ur es t o Mi ni miz e Bi as  .............................................................................................................. 4 5  
1 3. 4  
A n al ysis Pl a n  ..................................................................................................................................... 4 5  
1 3. 4. 1  
A n al ysis P o p ul ati o ns  ..................................................................................................................... 4 5  
1 3. 4. 2  
Pri m ary A n al ysis of Pri m ary E n d p oi nt  .......................................................................................... 4 5  
1 3. 4. 3  
S u p p ortiv e A n al ys es of t h e Pri m ary E n d p oi nt  ............................................................................. 4 6  
1 3. 4. 4  
A n al ys es of S ec o n d ary a n d Ot h er E n d p oi nts  ............................................................................... 4 6  
1 3. 4. 5  
D escri ptiv e A n al ys es  ..................................................................................................................... 4 6  
1 3. 5  
I nt eri m A n al ys es ............................................................................................................................... 4 6  
1 3. 6  
St atistic al Hy p ot h es es  ...................................................................................................................... 4 6  
1 3. 7  
S a m pl e Siz e C o nsi d er ati o ns  .............................................................................................................. 4 6  

 
C o nfi d e nti al  
P a g e 1 2  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
1 4.  
I d e ntific ati o n a n d Acc ess t o S o urc e D at a ............................................................................................. 4 8  
1 4. 1  
S o urc e D at a  ...................................................................................................................................... 4 8  
1 4. 2  
Acc ess t o S o urc e D at a  ...................................................................................................................... 4 8  
1 5.  
Q u alit y Ass ur a nc e a n d Q u alit y C o ntr ol  ................................................................................................ 4 9  
1 6.  
Pr ot oc ol D evi ati o ns  .............................................................................................................................. 5 0  
1 6. 1  
Pr ot o c ol D evi ati o n D efi niti o ns  ......................................................................................................... 5 0  
1 6. 2  
R e p orti n g a n d M a n a gi n g Pr ot oc ol D evi ati o ns  ................................................................................. 5 0  
1 7.  
Et hic al C o nsi d er ati o ns a n d C o m pli a nc e wit h G o o d Cli nic al Pr actic e  ................................................... 5 1  
1 7. 1  
St at e m e nt of C o m pli a nc e  ................................................................................................................. 5 1  
1 7. 2  
I nf or m e d C o ns e nt Pr oc ess ............................................................................................................... 5 1  
1 7. 3  
Pri v ac y a n d C o nfi d e nti alit y  ............................................................................................................... 5 1  
1 8.  
P u blic ati o n P olic y  ................................................................................................................................. 5 2  
1 9.  
R ef er e nc es  ............................................................................................................................................ 5 3  
A p p e n dix 1: Sc h e d ul e of E v e nts  ....................................................................................................................... 5 7  
 

 
C o nfi d e nti al  
P a g e 1 3  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
Gl oss ar y of A b br e vi ati o ns  
A T G  
A nti -t h y m oc yt e gl o b uli n  
C F R  
C o d e of F e d er al R e g ul ati o ns  
C O P  
C orr el at e of Pr ot ecti o n  
C R F  
C as e R e p ort F or m  
C T C A E  
C o m m o n T er mi n ol o g y Crit eri a f or A dv ers e E v e nts  
D AI T  
Divisi o n of All er g y, I m m u n ol o g y, a n d Tr a ns pl a nt ati o n  
E U A  
E m er g e nc y Us e A ut h oriz ati o n  
D S M B  
D at a S af et y M o nit ori n g B o ar d  
F D A  
F o o d a n d Dr u g A d mi nistr ati o n  
G C P  
G o o d Cli nic al Pr actic e  
I C H 
I nt er n ati o n al C o nf er e nc e o n H ar m o niz ati o n  
I N D 
I nv esti g ati o n al N e w Dr u g 
I R B 
I nstit uti o n al R e vi e w B o ar d 
M O P  
M a n u al of Pr oc e d ur es  
NI AI D  
N ati o n al I nstit ut e of All er g y a n d I nf ecti o us Dis e as e s 
PI  
Pri nci p al I nv esti g at or  
S A E  
S eri o us A dv ers e E v e nt  
S A P  
St atistic al A n al ysis Pl a n  
S A R  
S us p ect e d A dv ers e R e acti o n  
S O P  
St a n d ar d O p er ati n g Pr oc e d ur e  
S O T  
S oli d Or g a n Tr a ns pl a nt  
S U S A R  
S eri o us U n ex p ect e d S us p ect e d A dv ers e R e acti o n  
 

 
C o nfi d e nti al  
P a g e 1 4  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
St u d y D efi niti o ns P a g e  
Ac ut e C ell ul ar -M e di at e d 
R ej ecti o n  
A cli nic al a n d hist ol o gic e v e nt t h at m e ets t h e B a nff 2 0 1 5 crit eri a f or ac ut e 
c ell ul ar r ej ecti o n. 
A nti b o d y -M e di at e d 
R ej ecti o n  
A cli nic al a n d hist ol o gic e v e nt t h at m e ets t h e B a nff 2 0 1 5 crit eri a f or 
a nti b o d y m e di at e d r ej ecti o n.  
Bi o psy -Pr ov e n R ej ecti o n   
Hist ol o gic e vi d e nc e of r ej ecti o n o n bi o psy m e eti n g B a nff 2 0 1 5 crit eri a.  
D o n or S p ecific A nti b o di es  
( D S A) 
A nti b o di es dir ect e d  d o n or  h u m a n l e u k oc yt e a nti g e n s ( HL A). I d e ntific ati o n 
of D S A will c arri e d o ut at a c e ntr al l a b or at ory; s e e l a b m a n u al.   
Gr aft F ail ur e ( Ki d n e y)  
A n y of t h e f oll o wi n g e v e nts: r e n al di alysis  of m or e t h a n 3 m o nt hs 
d ur ati o n ; listi n g f or r e-tr a ns pl a nt ati o n; d e at h wit h f u ncti o ni n g gr aft . 
L ost t o F oll o w-u p   
Missi n g  s e q u e nti al visits i ncl u di n g t h e fi n al visit.   
M e dic al M o nit or  
T h e p hysici a n w h o is r es p o nsi bl e f or S p o ns or ov ersi g ht of s af et y as p ects of 
t he  tri al. T h e m e dic al m o nit or will d et er mi n e t h e attri b uti o n of S eri o us 
A dv ers e E v e nts aft er c o nsi d eri n g all i nv esti g at or i n p ut.  
N e g ati v e A nti b o d y 
R es p o ns e  
A m e as ur e m e nt of < 0. 8 U/ mL usi n g t h e R oc h e El ecsys ®  S A R S -C o V -2 
a nti -R B D I g g ass a y.  
NI AI D Pr oj ect M a n a g er  
NI AI D assi g n e d pr oj ect m a n a g er w h o is r es p o nsi bl e f or all d a y t o d a y 
pr ot oc ol r el at e d iss u es, i ncl u di n g v ersi o n c o ntr ol, c o ns e nt r evi e w, etc.  
Pri nci p al I nv esti g at or   
T h e p hysici a n r es p o nsi bl e f or s u p ervisi n g t h e c o n d uct of t h e 
cli nic al i nv esti g ati o n a n d t o pr ot ect i n g t h e ri g hts, s af et y, a n d w elf ar e of 
p artici p a nts c o nsist e nt wit h 2 1 C F R P art 3 1 2.  
P artici p a nt Pr e m at ur e 
T er mi n ati o n  
P artici p a nt s w h o ar e l ost t o f oll o w u p, wit h dr a w c o ns e nt, or di e d uri n g t h e 
st u dy.  D at a a n d s p eci m e ns will n o l o n g er b e ex p ect e d fr o m p artici p a nt s 
w h o ar e t er mi n at e d fr o m t h e st u dy.  
Pr o gr a m Offic er  
NI AI D offici al w h o ov ers e es t h e p r o gr a m m atic a n d b u d g et ary as p ects of 
t h e gr a nt. 
L o w A nti b o d y R es p o ns e  
( e ntry crit eri o n)  
A m e as ur e m e nt of < 5 0 U/ mL  usi n g t h e R oc h e El ecsys ®  S A R S -C o V -2 a nti -
R B D I g g ass a y.  
Pr ot oc ol M a n d at e d 
Pr oc e d ur es  
A pr oc e d ur e or i nt erv e nti o n t h at is a st u dy r e q uir e m e nt at t h e s p ecifi e d 
ti m e p oi nt i n t h e pr ot oc ol. 
R e g ul at ory Aff airs Offic er   
NI AI D -assi g n e d offic er r es p o nsi bl e f or r e g ul at ory as p ects of t h e st u dy.  
Si g nific a nt Gr aft 
D ysf u ncti o n  
Esti m at e d Gl o m er ul ar Filtr ati o n R at e l ess t h a n 3 0 mL/ mi n/ 1. 7 3 m 2. 
Sit e Pri nci p al I nv esti g at or   
L e a d i nv esti g at or list e d o n t h e F D A F or m 1 5 7 2  at a p artic ul ar cli nic al sit e 
w h o is r es p o nsi bl e f or t h e c o n d uct of t h e st u dy at t h at sit e. 
St u dy T h er a py  
T h e i nv esti g ati o n al pr o d uct is a t hir d d os e of eit h er t h e M o d er n a C O VI D -
1 9 V acci n e or Pfiz er -Bi o N T ec h C O VI D -1 9 v acci n e.  

 
C o nfi d e nti al  
P a g e 1 5  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
Tr e at e d R ej ecti o n   
A n y cli nic al e v e nt, wit h or wit h o ut s u p p orti n g e vi d e nc e fr o m a bi o psy, 
w hic h t h e tr e ati n g p hysici a n di a g n os is as  “rej ecti o n” A N D f or w hic h t h e 
p ati e nt is tr e at e d wit h st er oi ds, l ytic t h er a py, or a n i ncr e as e i n d os e or 
n u m b er of i m m u n os u p pr essiv e m e dic ati o ns.  

 
C o nfi d e nti al  
P a g e 1 6  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
1. 
B ac k gr o u n d a n d R ati o n al e   
1. 1 
B ac k gr o u n d  a n d Sci e ntific R ati o n al e  
C O VI D -1 9 dis pr o p orti o n at el y aff ects v ul n er a bl e p o p ul ati o ns, i ncl u di n g t h os e wit h i m p air e d i m m u n e 
d ef e ns es. O r g a n tr a ns pl a nt r eci pi e nts ar e p artic ul arl y at risk as a r es ult of b ot h t h e n e e d f or  lif e-l o n g 
i m m u n os u p pr essiv e t h er a py t o pr ev e nt r ej ecti o n a n d a hi g h pr ev al e nc e of ot h er risk f act ors f or s ev er e 
C O VI D -1 9 i ncl u di n g c ar di ov asc ul ar dis e as e, h y p ert e nsi o n, a n d di a b et e s. T h e c o ns e q u e nc es of C O VI D -1 9  ar e  
s e v er e i n or g a n tr a ns pl a nt r eci pi e nts; i n o n e st u dy of a l ar g e ( n = 4 8 2) c o h ort of p ati e nts w h o h a d a 
c o nfir m e d di a g n osis of C O VI D-1 9 b y p ol y m er as e c h ai n r e acti o n, 7 8 % w er e h os pit aliz e d, a n d of t h os e, 3 9 % 
r e q uir e d I C U c ar e a n d 3 1 % r e q uir e d m ec h a nic al v e ntil ati o n.  M ort alit y at 2 8 d a ys fr o m di a g n osis w as 1 7. 8 % 
ov er all a n d 2 0. 5 % a m o n g t h os e w h o w er e h os pit aliz e d. Risk f act ors f or m ort alit y i ncl u d e d a g e > 6 5 y e ars, 
c o n g esti v e h e art f ail ur e, c hr o nic l u n g dis e as e a n d o b esit y. 1 -5  
S A R S -C o V -2 v acci n es ar e hi g hly i m m u n o g e nic a n d eff ectiv e i n t h e g e n er al p o p ul ati o n . Tr a ns pl a nt r eci pi e nts 
w e r e excl u d e d fr o m l a n d m ark tri als , b ut it h as b ec o m e e vi d e nt d uri n g t h e p ost-E U A ex p eri e nc e t h at t h e 
r es p o ns e t o v acci n ati o n is s u bst a nti ally l o w er a m o n g or g a n tr a ns pl a nt r eci pi e nts as c o m p ar e d t o t h e 
g e n er al p o p ul ati o n: i n  a c o h ort of 4 3 6 tr a ns pl a nt r eci pi e nts w h o h a d r ec eiv e d t w o d os es of eit h er t h e  
M o d er n a C O VI D -1 9 v acci n e or t h e Pfiz er -Bi o N T ec h C O VI D -1 9 V acci n e, a  p ositiv e a nti -s pik e r es p o ns e w as 
d et ect a bl e i n o nly 1 7 % aft er t h e first d os e a n d  3 0 -6 0 % aft er t w o d os es  i n m ulti pl e st u di es. Ass oci ati o ns wit h 
s u b o pti m al v acci n e r es p o ns e i ncl u d e tr e at m e nt wit h a nti m et a b olit e t h er a pi es  s uc h as m yc o p h e n ol at e or 
az at hi o pri n e , w hic h ar e k n o w n t o i m p air l y m p h oc yt e f u ncti o n a n d r es p o ns e t o n e w a nti g e ns  (s uc h as 
i nfl u e nz a v acci n ati o n).1 0 -1 4  
It is critic al t o u n d erst an d risk str atific ati o n f or v acci n e f ail ur e giv e n m o u nti n g r e p orts of s eri o us 
br e a kt hr o u g h i nf ecti o ns i n f ull y v acci n at e d S O T r eci pi e nts. 3 5 P ersist e nt k n o wl e d g e g a ps i ncl u d e 
c h ar act eriz ati o n of h u m or al v acci n e r es p o ns es ( e. g., l ev el a n d d ur a bilit y of n e utr a lizi n g a nti b o d y, i ncl u di n g 
v ers us n ov el v ari a nts), B c ell m e m ory r es p o ns es, a n d a nti g e n -s p ecific T c ell r es p o ns es i n tr a ns pl a nt 
r eci pi e nts.1 5, 1 6 Str at e gi es t o i m pr ov e v acci n e r es p o ns e t o vir al a nti g e ns i n i m m u n oc o m pr o mis e d p ers o ns ar e 
l ar g el y b as e d o n ex p e ri e nc es wit h i nfl u e nz a a n d h e p atitis B v acci n es; t h es e i ncl u d e  a d mi nistr ati o n of  
a d diti o n al v acci n ati o ns, hi g h er a nti g e n d osi n g, a n d  mixi n g of v acci n e pl atf or ms s uc h as t h os e c o nt ai ni n g 
i m m u n osti m ul at ory a dj uv a nts.1 7 , 1 8 D ev el o p m e nt of a str at e g y f or eliciti n g a n a nti b o d y r es p o ns e t o C O VI D 
v acci n es i n tr a ns pl a nt r eci pi e nts is c o m pl ex as t h e p h ar m ac ol o gic i m m u n os u p pr essi o n t h at pr ev e nts 
r es p o ns e t o t h e v acci n e als o pr ev e nts r ej ecti o n of a lif e-s ust ai ni n g all o gr aft. P ot e nti al i nt erv e nti o ns i ncl u d e 
a d mi nistr ati o n of a t hir d d os e of v acci n e; alt er n at e v acci n e str at e gi es i ncl u di n g hi g h er d os es of v acci n e or 
t h e us e of a dj uv a nt e d v acci n es; a n d, m ost hi g h risk, tr a nsi e nt m o dific ati o n of a p ati e nt’s 
i m m u n os u p pr essiv e r e gi m e n b ef or e a n d aft er v acci n e a d mi nistr ati o n. A d ecisi o n al g orit h m f or a n i n divi d u al 
p ati e nt m ust c o nsi d er t h e lik eli h o o d of s ucc ess of a l o w risk i nt erv e nti o n (i. e. a t hir d d os e of v acci n e), t h e 
t y p e of tr a ns pl a nt ( e. g. ki d n e y, h e art or l u n g), t h e lik eli h o o d a n d c o ns e q u e nc es of all o gr aft r ej ecti o n if t h e 
p ati e nt’s i m m u n os u p pr essiv e r e gi m e n is m o difi e d ( e. g. t h e l o w lik eli h o o d of p er m a n e nt i nj ury aft er a n 
e pis o d e of liv er r ej ecti o n  v ers us t h e hi g h li k eli h o o d of p er m a n e nt i nj ury aft er a n e pis o d e of l u n g r ej ecti o n), 
a n d t h e i n divi d u al’s risk f or s ev er e dis e as e or d e at h fr o m C O VI D -1 9 if t h e y r e m ai n wit h o ut a nti b o d y 
pr ot ecti o n.  

 
C o nfi d e nti al  
P a g e 1 7  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
As a first st e p i n a d dr essi n g t his pr o bl e m, t his st u dy will  i nv esti g at e t h e eff ect of a t hir d d os e of m R N A 
v acci n ati o n i n  i m m u n ol o gic all y st a bl e ki d n e y tr a ns pl a nt r eci pi e nts wh o d e m o nstr at e a n e g ativ e ( < 0. 8 U/ mL)  
or l o w  (< 5 0 U/ mL) i m m u n e r es p o ns e t o t h e t w o-d os e s eri es.  A nti -S 1/ R B D l ev els ar e w ell c orr el at e d wit h 
n e utr alizi n g a nti b o d y v ers us S A R S -C o V -2 a n d v acci n e s er o -pr ot ecti o n. 3 7, 3 8 T h e pr ecis e c ut off t h at c o n n ot es 
pr ot ecti o n i n is n ot f ull y est a blis h e d.  T hr es h ol ds r a n gi n g fr o m 1 5 u nits/ mL 3-1 4 4 u nits/ mL 4 0 h av e b e e n 
c orr el at e d wit h liv e vir us n e utr aliz ati o n i n p ri or st u di es of c o nv al esc e nts.  A n a n alysis of v acci n e effic ac y 
acr oss tri als i n dic at es a l ev el 2 -4 -f ol d hi g h er f or v acci n e-ev ok e d n e utr aliz ati o n (c o m p ar e d t o c o nv al esc e nts) 
b est c orr el at es wit h v acci n e effic ac y. 4 1  T h us , f or scr e e ni n g p ur p os es, a l ev el of  5 0 u nits/ mL o n t his 
c o m m erci al ass a y w o ul d b e a pr a g m atic c ut off r e pr es e nti n g a c o ns erv ativ e l o w er b o u n d u n d er w hic h 
pr ot ecti o n is u nlik el y.   
R es p o ns e t o t h e t hir d d os e  f or t h e pri m ary e n d p oi nt will b e e v al u at e d usi n g t h e M S D m ulti pl ex ass a y a n d  
will b e c orr el at e d wit h cli nic al a n d i m m u n ol o gic  i m m u n o p h e n ot y pi n g i ncl u di n g ext e nsiv e ev al u ati o n of 
c ell ul ar i m m u nit y. O ur g o al is t o i d e ntify pr e -v acci n ati o n cli nic al a n d/ or l a b or at ory c h ar act eristics t h at h el p 
disti n g uis h t h os e w h o c a n b e n efit fr o m a t hir d d os e  of m R N A v acci n e v ers us t h os e w h o r e q uir e a m or e 
c o m pl ex a p pr o ac h. O ur fi n di n gs will i nf or m a s u bs e q u e nt a d a ptiv e tri al of hi g h er -risk i nt erv e nti o ns, s uc h as 
mix e d pl atf or m v acci n e d osi n g or i m m u n os u p pr essiv e m o d ul ati o n , t o i n d uc e v acci n e r es p o ns e.  
R ati o n al e f or S el ecti o n of I n v esti g ati o n al Pr o d uct or I nt er v e nti o n  
T his si n gl e -ar m tri al will a d mi nist er a t hir d d os e of m R N A v acci n ati o n t o S O T r eci pi e nts w h o d e m o nstr at e 
l o w or n e g ati v e  a nti -s pik e a nti b o d y r es p o ns e aft er c o m pl eti o n of t w o d os e s of eit h er t h e M o d er n a C O VI D-
1 9 V acci n e or t h e Pfiz er -Bi o N T ec h V acci n e, as d escri b e d i n t h eir r es p ectiv e F o o d a n d Dr u g A d mi nistr ati o n 
(F D A) E m er g e nc y Us e A ut h oriz ati o ns (E U As ). T h es e v acci n es h av e pr ov e n s af e a n d hi g hly i m m u n o g e nic i n 
t h e g e n er al p o p ul ati o n, wit h p ublic ati o n of l ar g e P h as e III tri als d at a s u p p orti n g F D A E U A. 1 9, 2 0 T his t hir d - 
d os e v acci n e i nt erv e nti o n w as c h os e n d u e t o d e m o nstr at e d s af et y of t h e t w o -d os e s eri es i n S O T r eci pi e nts 
(s e e 1. 4) a n d ex p eri e nc e wit h t h e effic ac y of a d diti o n al d osi n g str at e gi e s d os es of ot h er v acci n e s ( e. g., 
h e p atitis a n d i nfl u e nz a v acci n es) 1 7, 1 8 i n i m m u n oc o m pr o mis e d p e o pl e. B as e d o n t h e r es ults of t his pil ot tri al, 
f ut ur e st u di es will i nc or p or at e ot h er p ot e nti ally riski er str at e gi es f or t h os e w h o f ail t o r es p o n d t o a t hir d 
d os e of m R N A v acci n e , s uc h as mix e d pl atf or m or a dj uv a nt e d d os es. Us e of v acci n e pr o d ucts t h at h av e 
ac hi e v e d E m er g e nc y Us e A ut h oriz ati o n st at us a n d h av e pr o gr ess e d t hr o u g h P h as e III tri als, s uc h as t h e 
J o h ns o n & J o h ns o n A d. C O V 2. 2 6 v acci n e, w o ul d b e a p pr o pri ate i nt erv e nti o ns i n t his s etti n g.   T h e a dj u v a nt e d 
vir us-lik e n a n o p articl e ( VL P) v acci n e N V X-C o V 2 3 7 3 mi g ht als o b e c o nsi d er e d giv e n t h at  ot h er a dj uv a nt e d 
s u b u nit v acci n es, s uc h as t h e r ec o m bi n a nt v aric ell a z ost er ( S hi n grix), h e p atitis B ( H E PLI S A V-B), a n d  H P V 
( G ar d asil) v acci n es, h av e b e e n a d mi nist er e d s af el y a n d wit h g o o d eff ect i n tr a ns pl a nt r eci pi e nts. 1 7, 1 8, 2 1 -2 3  
1. 2 
Pr ecli nic al E x p eri e nc e  
St u di es p erf or m e d i n m uri n e m o d els i n t h e 1 9 7 0s a n d 1 9 8 0s s h o w e d t h at t h e r e p e at e d i m m u niz ati o n of u p 
t o 4 d os es c o nti n u es t o h av e a p ositiv e i m p act o n t h e tit er, is ot y p e, a n d affi nit y of t h e i n d uc e d a nti b o d y 
r es p o ns es.2 4, 2 5  Si mil arl y pr ecli nic al m uri n e d at a i n dic at e t h at i m m u niz ati o n sc h e d ul es t h at i ncl u d e t hir d 
d os es m ark e dly i ncr e as e t h e fr e q u e nc y a n d f u ncti o n al p r o p erti es of a nti g e n s p ecific T c ell i m m u n e 
r es p o ns es.2 6  

 
C o nfi d e nti al  
P a g e 1 8  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
T h er e ar e n o s p ecific pr ecli nic al st u di es a d dr essi n g w h et h er a n d h o w t h es e eff ects of i m m u niz ati o n 
sc h e d ul e o n v acci n e-i n d uc e d i m m u nit y ar e aff ect e d  by  t h e i m m u n os u p pr ess a nt m e dic ati o ns us e d i n 
tr a nspl a nt ati o n . 
1. 3 
Cli nic al St u di es  
T h e M o d er n a a n d Pfiz er -Bi o N T ec h v acci n es ar e k n o w n t o h av e exc ell e nt i m m u n o g e nicit y i n t h e g e n er al 
a d ult p o p ul ati o n , e v e n a g ai nst s o m e of t h e r ec e ntl y i d e ntifi e d S A R S-C o V -2 v ari a nts. 2 7 , 2 8 T h e v acci n e s ar e  
w ell -t ol er at e d, wit h mostl y mil d -t o-m o d er at e l oc al a n d s yst e mic r e act o g e nicit y  t h at is m or e pr o n o u nc e d 
aft er t h e s ec o n d d os e .2 9, 3 0 H o w ev er, or g a n tr a ns pl a nt  r eci pi e nts h av e r ec e ntl y b e e n s h o w n t o h av e m uc h 
l ess r eli a bl e a n d r o b ust r es p o ns e s t o t h e v acci n es.1 0, 1 2 I n a l ar g e ( N = 6 5 8) pr os p ectiv e c o h ort st u dy  of U. S. 
tr a ns pl a nt r eci pi e nts, o nly 1 5 % of p ati e nts h a d a  p ositiv e  a nti -s pik e/ R B D r es p o ns e aft er a  first d os e of 
eit h er t h e M o d er n a or t h e Pfiz er v acci n e, wit h i m pr ov e m e nt t o o nly 5 4 % b y f o ur w e e ks aft er t h e s ec o n d 
d os e of v acci n e . P ati e nts w h o h a d a  p ositiv e  r es p o ns e aft er t h e first d os e of v acci n e h a d hi g h er tit ers of 
a nti b o d y aft er d os e t w o as c o m p ar e d wit h t h os e w h o h a d a n e g ativ e  r es p o ns e aft er d os e o n e b ut di d h a v e 
a m e as ur a bl e r es p o ns e aft er d os e t w o.  I n t h os e wit h a p ositiv e  a nti b o d y r es p o ns e  aft er d os e t w o , a nti b o d y 
l e v els w er e s u bst a nti ally l o w er t h a n i n i m m u n oc o m p et e nt v acci n e r eci pi e nts.  Ass oci ati o ns wit h l ac k of 
v acci n e r es p o ns e i ncl u d e d ol d er a g e, us e of a nti m et a b olit e t h er a pi es, hist ory of ki d n e y tr a ns pl a nt ati o n  
(v ers us ot h er or g a n tr a ns pl a nt), m or e r ec e nt tr a ns pl a nt ati o n, a n d r ec ei pt of t h e Pfiz er-Bi o N T ec h v acci n e 
(v ers us t h e M o d er n a mR N A -1 2 7 3 v acci n e ). I n a Fr e nc h st u dy of 1 0 1 ki d n e y tr a ns pl a nt r eci pi e nts m ai nt ai n e d 
o n  b el at ac e pt -b as e d i m m u n os u p pr essi o n, o nly  6 % of p ati e nts h a d m e as ur a bl e a nti -s pik e a nti b o di es aft er 2 
d os es of t h e Pfiz er-Bi o N T ec h v acci n e. I n t h at st u dy, S A R S -C o V -2 -s p ecific T -c ell r es p o ns es b y Eli S p ot w er e  
pr es e nt i n o nly 3 0 % of t h os e t est e d ( N = 2 3) aft er t w o d os es of v acci n e. 3 2 

 
C o nfi d e nti al  
P a g e 1 9  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
2. 
St u d y H y p ot h es es /O bj ecti v es  
2. 1 
H y p ot h es es  
A s u bs et ( 2 5 %) of ki d n e y tr a ns pl a nt r eci pi e nts w h o h a d a n e g ativ e or  l o w r es p o ns e t o t w o d os es of t h e 
M o d er n a C O VI D -1 9 v acci n e or Pfiz er -Bi o N T ec h C O VI D -1 9 v acci n e will ac hi ev e a n i ncr e as e i n S A R S -C o V -2 
a nti b o d y tit ers f oll o wi n g a t hir d d os e of t h e s a m e m R N A v acci n e.   
P ati e nt c h ar act eristics ass oci at e d wit h r es p o ns e t o a t hir d d os e of v acci n e ( e. g. pri or v acci n e r es p o ns e , 
i m m u n os u p pr essiv e r e gi m e n,  a n d i m m u n ol o gic c h ar act eristics ) will b e i d e ntifi e d.  
2. 2 
Pri m ar y O bj ecti v e (s) 
T h e pri m ary o bj ectiv e of t his st u dy is t o elicit a n i ncr e as e i n S A R S -C o V -2 a nti b o d y tit ers t o gr e at er t h a n 5 0 
U/ mL i n k i d n e y tr a ns pl a nt r eci pi e nts w h o di d n ot ac hi ev e t his l ev el of a nti b o d y aft er t w o d os es of eit h er t h e 
M o d er n a C O VI D -1 9 v acci n e or Pfiz er -Bi o N T ec h  C O VI D -1 9 v acci n e . A nti b o d y r es p o ns e will b e e v al u at e d 3 0 
d ays f oll o wi n g t h e i nv esti g ati o n al d os e of v acci n e usi n g t h e R oc h e El ecsys  a nti -R B D ass a y . All p artici p a nts 
wit h m e as ur a bl e  S A R S -C o V -2 a nti b o d y tit ers will als o h av e n e utr alizi n g a nti b o d y tit ers a n d f urt h er 
q u a ntific ati o n  a n d c h ar act eriz ati o n  of a nti b o d y usi n g t h e b est av ail a bl e ass a y .  
2. 3 
S ec o n d ar y S af et y O bj ecti v e(s)   
• 
T o d et er mi n e t h e i nci d e nc e of a dv ers e ev e nts  ( A Es) a n d s eri o us a dv ers e ev e nts  (S A Es), i ncl u di n g 
r e act o g e nicit y, f oll o wi n g t h e t hir d d os e of C O VI D -1 9 v acci n e . 
• 
T o d et er mi n e t h e i nci d e nc e of all oi m m u n e ev e nts ( e. g., ki d n e y r ej ecti o n a n d d ev el o p m e nt of d e 
n ov o D S A) f oll o wi n g t h e t hir d d os e of v acci n e.  
2. 4 
S ec o n d ar y I m m u n o g e nicit y O bj ecti v es  
• 
C orr el ati o ns of a nti b o d y r es p o ns e wit h i m m u n os u p pr essiv e r e gi m e n  a n d  cli nic al a n d i m m u n ol o gic 
p h e n ot y p e . 
• 
T o d et er mi n e w h et h er r es p o ns e t o a t hir d d os e of eit h er m R N A v acci n e diff ers b et w e e n t h os e 
p artici p a nts w h o h a d a n e g ativ e  r es p o ns e t o t h e first tw o d os es a n d t h os e t h at h a d a l o w r es p o ns e 
aft er t h e first t w o d os es.  
• 
T o ass ess w h et h er r es p o ns e t o t hir d d os e of C O VI D -1 9 v acci n e  is ass oci at e d wit h cli nic al p h e n ot y p e 
( e. g., a g e, or g a n t y p e, ti m e p ost-tr a ns pl a nt, i m m u n os u p pr essiv e r e gi m e n).  
• 
T o e v al u at e  d ur a bilit y of r es p o ns e ov er 1 -y e ar i n t h os e w h o h av e a n a nti b o d y r es p o ns e  t o t h e t hir d 
d os e of v acci n e.  
2. 5 
E x pl or at or y  M ec h a nistic  O bj ecti v es  
• 
T o i d e ntify i m m u n ol o gic c orr el at es of v acci n e r es p o ns e.  
• 
T o e v al u at e i m m u n e activ ati o n i n r es p o ns e t o t h e v acci n e.  

 
C o nfi d e nti al  
P a g e 2 0  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
3. 
St u d y D esi g n  
3. 1 
D escri pti o n of St u d y D esi g n   
T his is a n  o p e n l a b el, n o n -r a n d o miz e d pil ot st u dy i n ki d n e y tr a ns pl a nt r eci pi e nts w h o r ec eiv e d t w o d os es of  
eit h er  t h e M o d er n a C O VI D-1 9 v acci n e  or t h e Pfiz er -Bi o N T ec h  C O VI D -1 9 v acci n e  a n d h av e a  n e g ativ e ( < 0. 8 
U/ mL)  or l o w (tit er < 5 0 U/ mL ) S A R S-C o V -2 a nti b o d y r es p o ns e. T h e st u dy will e nr oll u p t o 2 0 0 p artici p a nts 
wit h a mi ni m u m of 5 0 a n d u p t o 1 0 0 p artici p a nts i n e ac h str atu m  ( n o n-r es p o n d er vs l o w r es p o n d er). 
Eli gi bl e p artici p a nts will r ec eiv e a t hir d d os e of t h e s a m e m R N A C O VI D-1 9  v acci n e as t h e y r ec eiv e d 
pr e vi o usl y.  
 
Fi g ur e 1 .  St u d y D esi g n Di a gr a m  
3. 2 
Pri m ar y E n d p oi nt  
T h e pri m ary e n d p oi nt is t h e pr o p orti o n of p artici p a nts w h o  ac hi ev e a n  a nti b o d y r es p o ns e  > 5 0 U/ mL  
m e as ur e d at 3 0 d a ys aft er t h e t hir d d os e of v acci n e usi n g t h e R oc h e El ecsys a nti -R B D ass a y.  All s u bj ects 
wit h d et ect a bl e a nti b o d y will i n a d diti o n h av e n e utr alizi n g a nti b o d y tit ers a n d f urt h er q u a ntific ati o n  a n d 
c h ar act eriz ati o n of a nti b o d y usi n g t h e b e st av ail a bl e ass a y.  
3. 3 
S ec o n d ar y E n d p oi nt s 
3. 3. 1 
S ec o n d ar y S af et y E n d p oi nts  
• 
L oc al a n d syst e mic v acci n e r e act o g e nicit y a n d/ or all er g y  
• 
S eri o us a dv ers e ev e nts occ urri n g d uri n g t h e 3 0 d a ys f oll o wi n g t h e t hir d d os e of v acci n e  
Scr e e ni n g C o ns e nt a n d Eli gi bilit y E v al u ati o n
(L o w or n e g ati v e a nti b o d y aft er pri m ar y v acci n e 
s eri es, st a bl e all o gr aft f u ncti o n > 1 y e ar fr o m 
tr a ns pl a nt, n o r ec e nt r ej ecti o n or c h a n g es i n 
i m m u n os u p pr essi o n)
St u d y C o ns e nt, t h e n a d mi nistr ati o n of a 
si n gl e st a n d ar d d os e of M o d er n a of 
Pfiz er C O VI D -1 9 V acci n e (s a m e v acci n e 
as pr e vi o usl y a d mi nist er e d)
3 0 -d a y visit f or pri m ar y e n d p oi nt 
e v al u ati o n  
F oll o w -u p f or 1 2 m o nt hs aft er 
v acci n e a d mi nistr ati o n

 
C o nfi d e nti al  
P a g e 2 1  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
• 
Tr e at e d ac ut e c ell -m e di at e d a n d/ or a nti b o d y -m e di at e d all o gr aft r ej ecti o n (cli nic al or bi o psy -
pr ov e n) wit hi n 6 0 d a ys f oll o wi n g t h e t hir d d os e of v acci n e  
• 
D e v el o p m e nt of d e n ov o d o n or -s p ecific a nti-HL A a nti b o d y wit hi n 9 0 d ays of t h e v acci n e  
• 
Gr aft l oss  wit hi n 6 0 d a ys of t h e v acci n e  
• 
D e at h wit hi n 6 0 d a ys of t h e v acci n e  
3. 3. 2 
E x pl or at or y M ec h a nistic  I m m u n o g e nicit y E n d p oi nts 
• 
R a n g e of a nti b o d y r es p o ns es a n d ot h er m e as ur es of i m m u n ol o gic pr ot ecti o n  
• 
A nti -S 1 a n d a nti -R B D s er ol o g y  
• 
A d diti o n al s er ol o gic al p a n els a n d c orr el at es of n e utr alizi n g a nti b o d y  
• 
N e u tr alizi n g a nti b o d y ass a ys 
• 
S A R S -C o V -2 vir ol o g y, di a g n ostics, a n d s e q u e nci n g , i ncl u di n g n ov el v ari a nts of c o nc er n  
• 
A nti g e n -s p ecific B c ell r es p o ns e  
• 
A nti g e n -s p ecific T c ell r es p o ns e 
• 
E vi d e nc e of im m u n e activ ati o n  a n d m et a b olic pr ofil e  b y tr a nscri pt o mics  a n d c yt oki n e si g n ali n g  
• 
D ur a bilit y of d e n ov o d o n or -s p ecific a nti-HL A a nti b o d y  

 
C o nfi d e nti al  
P a g e 2 2  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
4. 
S el ecti o n of P artici p a nts a n d Cli nic al Sit es/L a b or at ori es  
4. 1 
R ati o n al e f or St u d y P o p ul ati o n  
P artici p a nts w h o r ec eiv e d t w o pri or d os es of m R N A v acci n e b ut h av e a n e g ativ e t est f or a nti b o d y or h a v e 
v ery l o w a nti b o d y tit ers ( < 5 0 U/ mL ) will b e e nr oll e d i n t his st u dy. T his gr o u p of p ati e nts is at hi g h risk f or 
s e v er e C O VI D-1 9 dis e as e d u e t o p h ar m ac ol o gic i m m u n os u p pr essi o n a n d a hi g h pr ev al e nc e of n o n -
tr a ns pl a nt risk f act ors s uc h as o b esit y a n d di a b et es.  
4. 2 
I ncl usi o n Crit eri a 
I n divi d u als w h o m e et all t h e f oll o wi n g crit eri a ar e eli gi bl e f or e nr oll m e nt as st u dy p artici p a nts:  
1.
A bl e t o u n d erst a n d a n d pr ovi d e  i nf or m e d c o ns e nt.  
2.
I n divi d u al  1 8 y e ars of a g e.  
3.
R eci pi e nt of ki d n e y tr a ns pl a nt 1 2 m o nt hs pri or t o e nr oll m e nt, wit h o ut tr e at e d all o gr aft r ej ecti o n i n 
t h e 6 m o nt hs pr ec e di n g e nr oll m e nt. 
4.
R ec ei v e d 2 d os es of eit h er t h e  M o d er n a C O VI D -1 9 v acci n e or Pfiz er -Bi o N T ec h C O VI D -1 9 v acci n e  as 
s p ecifi e d i n t h e r es p ectiv e F D A E U A s, > 3 0 d a ys a n d < 8  m o nt hs  pri or t o st u dy e ntry . 
5.
N e g ati v e  (tit er < 0. 8 U/ mL) or l o w ( a nti b o di es d et ect e d at tit er <  5 0 U/ mL ) r es p o ns e t o t h e v acci n e at >  
3 0 d a ys fr o m d os e 2 of t h e M o d er n a C O VI D -1 9 v acci n e or t h e Pfiz er Bi o N T ec h v acci n e, usi n g t h e R oc h e 
El ecsys ® a nti -R B D ass a y.  
4. 3 
E xcl usi o n Crit eri a  
I n divi d u als w h o m e et a n y of t h es e crit eri a ar e n ot eli gi bl e f or e nr oll m e nt as st u dy p artici p a nts:  
1.
R eci pi e nt of  a ny n u m b er of d os es of a ny C O VI D v acci n e pr o d uct ot h er t h a n t h e M o d er n a C O VI D -1 9 
v acci n e or t h e Pfiz er -Bi o N T ec h C O VI D -1 9 v acci n e.  
2.
K n o w n hist ory of s ev er e all er gic r e acti o n t o a n y c o m p o n e nt of eit h er t h e M o d er n a C O VI D -1 9 v acci n e or 
Pfiz er -Bi o N T ec h C O VI D -1 9  v acci n e.  
3.
T hr o m b otic e v e nts, m y oc ar ditis, or p eric ar ditis  t e m p or all y ass oci at e d wit h pri or d os e of C O VI D-1 9 
v acci n e . 
4.
A n y c h a n g e i n tr a ns pl a nt i m m u n os u p pr essi o n r e gi m e n ( dr u g or d os e) i n r es p o ns e t o s us p ect e d or 
pr ov e n r ej ecti o n wit hi n t h e l ast 6 m o nt hs.  
5.
S i g nific a nt gr aft d ysf u ncti o n (s e e St u dy D efi niti o ns f or f urt h er d et ails). 
6.
R ec ei pt of a n y c ell ul ar d e pl eti n g a g e nt ( e. g. A T G,  Rit uxi m a b, Al e mt uz u m a b,  C ycl o p h os p h a mi d e) wit hi n 
1 2 m o nt hs pr ec e di n g e nr oll m e nt.   
7.
R ec ei vi n g syst e mic i m m u n o m o d ul at ory m e dic ati o n (s) f or a n y c o n diti o n ot h er t h a n tr a ns pl a nt.  
8.
A n y u ntr e at e d activ e i nf ecti o n  i ncl u di n g B K vir e mi a > 1 04  c o pi es. 
9.
I nf ecti o n wit h HI V. 
1 0. M ai nt e n a nc e i m m u n os u p pr essiv e r e gi m e n t h at i ncl u d es b el at ac e pt or a b at ac e pt.  
1 1. R ec e nt ( wit hi n o n e y e ar) or o n g oi n g tr e at m e nt f or m ali g n a nc y.  
1 2. A n y p ast or c urr e nt m e dic al pr o bl e ms, tr e at m e nts, or fi n di n gs w hic h, i n t h e o pi ni o n of t h e i nv esti g at or, 
m a y p os e a d diti o n al risks fr o m p artici p ati o n i n t h e st u dy, m a y i nt erf er e wit h t h e c a n di d at e’s a bilit y t o 
c o m ply wit h st u dy r e q uir e m e nts or m ay i m p act t h e q u alit y or i nt er pr et ati o n of t h e d at a o bt ai n e d fr o m 
t h e st u dy. 

 
C o nfi d e nti al  
P a g e 2 3  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
4. 4 
S el ecti o n of Cli nic al Sit es  
4. 4. 1 
S el ecti o n of Cli nic al Sit e  
T his is a si n gl e sit e st u dy t h at will b e c arri e d o ut at t h e J o h ns H o p ki ns  U niv ersit y . V acci n e 
a d mi nistr ati o n will t a k e pl ac e at t h e B a yvi e w Cli nic al R es e arc h U nit ( C R U) a n d Br o a d w a y A d ult 
O ut p ati e nt C li nic al R es e arc h U nit ( C R U) . C R U p ers o n n el ar e tr ai n e d i n a n d c urr e ntl y e n g a g e d i n 
C O VI D -1 9 v acci n e  a d mi nistr ati o n  i n ot h er cli nic al r es e arc h st u di es. J o h ns H o p ki ns h as a l ar g e c o h ort 
of ki d n e y tr a ns pl a nt r eci pi e nts, w h o h av e r ec eiv e d t h e 2 -d os e C O VI D -1 9 m R N A v acci n e s eri es.  
 
 

 
C o nfi d e nti al  
P a g e 2 4  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
5. 
K n o w n a n d P ot e nti al Ris ks a n d B e n efits t o P artici p a nts  
I nf or m ati o n r el at e d t o a d mi nistr ati o n of a t hir d d os e of v acci n e t o i m m u n oc o m pr o mis e d tr a ns pl a nt 
r eci pi e nts is sc arc e a n d a n ec d ot al. T h e risks cit e d b el o w r efl ect t h e ex p eri e nc e i n 
i m m u n oc o m p et e nt p ers ons r ec eivi n g 2 d os es of t h e  M o d er n a or Pfiz er -Bi o N T ec h  v acci n e.  
5. 1 
Ris ks of t h e I n v esti g ati o n al Pr o d ucts  as cit e d i n t h e F ull F D A E U A Pr escri bi n g I nf or m ati o n   
5. 1. 1 
Ris ks of M o d er n a C O VI D -1 9 V acci n e   
T h e m ost c o m m o n si d e eff ects r e p ort e d i ncl u d e i nj ecti o n sit e r e acti o ns ( p ai n, r e d n ess a n d 
s w elli n g), axill ary s w elli n g/t e n d er n ess, f ati g u e, h e a d ac h e, m y al gi a, art hr al gi a, c hills, a n d 
n a us e a/v o miti n g . S ev er e all er gic r e acti o ns, i ncl u di n g a n a p hyl axis, h av e b e e n r e p ort e d f oll o wi n g t h e 
a d mi nistr at i o n d uri n g m ass v acci n ati o n o utsi d e of cli nic al tri als. S ev er e all er gic r e acti o n s i ncl u d e d 
diffic ult y br e at hi n g, s w elli n g of t h e f ac e a n d t hr o at, r as h , dizzi n ess , a n d w e a k n ess.  
5. 1. 2 
Ris ks of Pfiz er -Bi o N T ec h  C O VI D -1 9 V acci n e  
T h e m ost c o m m o n si d e eff ects r e p ort e d i ncl u d e n o n -s ev er e all er gic r e acti o ns (r as h, itc hi n g, hiv es 
a n d f aci al s w elli n g), i nj ecti o n sit e r e acti o ns ( p ai n, r e d n ess a n d s w elli n g), f ati g u e, h e a d ac h e, m y al gi a, 
art hr al gi a, c hills, f ev er, l y m p h a d e n o p at h y, v o miti n g, di arr h e a, ar m p ai n a n d g e n er al m al ais e. S e v er e 
all er gic r e acti o ns t h at i ncl u d e diffic ult y br e at hi n g, s w elli n g of t h e f ac e a n d t hr o at, r as h a n d dizzi n ess 
or w e a k n ess h av e b e e n r e p ort e d p ost a ut h oriz ati o n b ut ar e l ess c o m m o n.   
5. 1. 3 
Ris ks o f M o d er n a C O VI D-1 9 V acci n e a n d Pfiz er -Bi o N T ec h V acci n e s in a d ults  as cit e d i n M e dic al 
Lit er at ur e 
T h e M o d er n a C O VI D -1 9 V acci n e a n d Pfiz er -Bi o N T ec h C O VI D -1 9 V acci n e ar e b ei n g a d mi nist er e d 
u n d er a n E m er g e nc y Us e A ut h oriz ati o n. A dv ers e E v e nts t h at occ ur o utsi d e of cli nic al tri als as a 
r es ult of t h e m ass v acci n ati o n eff ort ar e r e p ort e d t o e ac h m a n uf act ur er a n d i ncl u d e d i n a F act 
S h e et f or H e alt hc ar e Pr ovi d ers. 3 3, 3 4  
I n a r ec e nt c o h ort of 7 4 1 or g a n tr a ns pl a nt r eci pi e nts w h o r ec eiv e d t w o d os es of eit h er t h e 
M o d er n a or Pfiz er -Bi o N T ec h  v acci n e, r e act o g e nicit y w as si mil ar t o w h at h as b e e n r e p ort e d i n 
i m m u n oc o m p et e nt p e o pl e: p ai n at i nj ecti o n sit e, f ati g u e, a n d h e a d ac h e w er e c o m m o n. S ev er e 
r e act o g e nicit y ( d efi n e d as pr ev e nti n g d ail y activit y) occ urr e d i n 1-2 % of st u dy p artici p a nts. Syst e mic 
r e acto g e nicit y w as m or e c o m m o n aft e r t h e s ec o n d d os e of v acci n e. T h er e w as a n i ncr e as e d risk of 
l oc al r e act o g e nicit y a m o n g r eci pi e nts w h o w er e m ai nt ai n e d o n a n  im m u n os u p pr essiv e r e gi m e n  
t h at i ncl u de d  c ortic ost er oi ds or m T O R i n hi bit ors, a n d als o a m o n g t h os e w h o r ec eiv e d t h e M o d er n a 
v acci n e.  T h er e w er e n o c as es of a n a p h yl axis.  T h er e w as o n e c as e of ac ut e all o gr aft r ej ecti o n aft er 
t h e s ec o n d d os e of v acci n e.3 6 
5. 1. 4 
P ot e nti al Ris ks t o St u d y P o p ul ati o n  
T h er e m a y b e a n i ncr e as e d risk of l o w -t o-m o d er at e r e act o g e nicit y t o tri al p artici p a nts w h o r ec ei v e 
a t hir d d os e of v acci n e. B as e d o n c urr e ntl y av ail a bl e i nf or m ati o n, t h e risk  of s eri o us all er gic e v e nts 
is lik el y t o b e extr e m el y l o w, e q u al t o  or l ess t h a n h as b e e n s e e n i n t h e i m m u n oc o m p et e nt 
p o p ul ati o n.  T h er e is n o e vi d e nc e t h at t h e C O VI D -1 9 v acci n e will r es ult i n n e w all oi m m u n e ev e nts, 
a n d n o n e ar e ex p ect e d . 

 
C o nfi d e nti al  
P a g e 2 5  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
5. 2 
Ris ks of Ot h er Pr ot oc ol S p ecifi e d M e dic ati o ns  
T h er e ar e n o ot h er pr ot oc ol s p ecifi e d m e dic ati o ns.  
5. 3 
Ri s ks of St u d y Pr oc e d ur es  
5. 3. 1 
Ris k of Bl o o d Dr a w  
C oll ecti o n of bl o o d m a y c a us e sli g ht disc o mf ort, p ai n, bl e e di n g or br uisi n g at t h e i nj ecti o n sit e.  
R ar el y, f ai nti n g or i nf ecti o n m a y occ ur.  
5. 3. 2 
Ris ks Ass oci at e d wit h N as o p h ar y n g e al  S w a b C oll ecti o n  
N as al s w a b c oll ect i o n m a y c a us e l oc aliz e d disc o mf ort. R ar el y, mil d e pist axis m ay occ ur.   
5. 3. 3 
Ris k of I nt er n et B as e d D at a C oll ecti o n  
D at a fr o m t his st u dy will b e e nt er e d i nt o a c o m p ut eriz e d d at a b as e t hr o u g h a s ec ur e d w e b sit e.  All 
i nf or m ati o n will b e s av e d a n d tr a ns mitt e d i n a c o d e d f or m.  O nl y a ut h oriz e d p ers o n n el r e q uiri n g a 
p ass w or d will b e p er mitt e d t o e nt er d at a.  T h er e is risk, alt h o u g h mi ni m al, of u n a ut h oriz e d p ers o ns 
o bt ai ni n g c o nfi d e nti al i nf or m ati o n.  
5. 4 
P ot e nti al B e n efits  
T h er e m a y b e n o b e n efit t o p artici p a nts i n t his st u dy. If a p artici p a nt ac hi ev es  a pr ot ectiv e l ev el of a nti b o d y 
a g ai nst S A R S -C o V -2 as a r es ult of p artici p ati n g i n t his st u d y, t h er e will li k el y b e ass oci at e d b e n efit. H o w e v er, 
w h et h er a n y p artici p a nt will ac hi ev e t his is u nk n o w n. T h e r es ults of t his st u dy  will i nf or m l ar g er sc al e 
st u di es d esi g n e d t o pr o m ot e v acci n e r es p o ns e i n tr a ns pl a nt r eci pi e nts.   

 
C o nfi d e nti al  
P a g e 2 6  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
6. 
I n v esti g ati o n al A g e nts 
6. 1 
I n v esti g ati o n al A g e nt # 1: M o d er n a C O VI D-1 9 V acci n e  
T h e M o d er n a C O VI D -1 9 V acci n e is a ut h oriz e d f or us e u n d er F D A E U A f or activ e i m m u niz ati o n t o pr ev e nt 
C O VI D -1 9 c a us e d b y S A R S -C o V -2 i n i n divi d u als 1 8 y e ars of a g e a n d ol d er.  T h e F D A E U A s p ecifi es a 2 -d os e 
s eri es a n d t his st u dy will i ncl u d e a t hir d d os e, w hich is n ot c urr e ntl y i ncl u d e d i n t h e F D A E U A.  
6. 1. 1 
F or m ul ati o n, P ac k a gi n g, a n d L a b eli n g  
M o d er n a C O VI D -1 9 V acci n e is pr ovi d e d as a w hit e t o off -w hit e s us p e nsi o n f or i ntr a m usc ul ar 
i nj ecti o n. E ac h 0. 5 mL d os e of M o d er n a C O VI D-1 9 V acci n e c o nt ai ns 1 0 0 mc g of n ucl e osi d e -m o difi e d 
m ess e n g er R N A ( m o d R N A) e nc o di n g t h e pr e -f usi o n st a biliz e d S pik e gl yc o pr ot ei n ( S) of S A R S-C o V -2 
vir us.  
E ac h d os e of t h e M o d er n a C O VI D -1 9 V acci n e als o c o nt ai ns t h e f oll o wi n g i n gr e di e nts: a t ot al li pi d 
c o nt e nt of 1. 9 3 m g ( S M -1 0 2, P E G 2 0 0 0 di myrist oyl gl yc er ol [ D M G], c h ol est er ol, a n d D S P C), 0. 3 1 m g 
tr o m et h a mi n e, 1. 1 8 m g tr o m et ha mi n e h y dr oc hl ori d e, 0. 0 4 3 m g ac etic aci d, 0. 1 2 m g s o di u m 
ac et at e, a n d 4 3. 5 m g s ucr os e.  
M o d er n a C O VI D -1 9 V acci n e will b e s u p pli e d i n c art o ns c o nt ai ni n g 1 0 m ulti pl e -d os e vi als p er c art o n 
( 1 0 d os es p er vi al); t h e vi al st o p p ers ar e n ot m a d e wit h n at ur al r u b b er l at ex.    
M o d er n a C O VI D -1 9 V acci n e s h o ul d b e st or e d fr oz e n b et w e e n -2 5° t o -1 5° C ( -1 3° t o 5° F) i n t h e 
ori gi n al c art o n t o pr ot ect fr o m li g ht. Pr o d uct s h o ul d n ot b e st or e d o n dry ic e or b el o w -4 0° C.  
6. 1. 2 
D os a g e, Pr e p ar ati o n, a n d A d mi nistr ati o n  
T h e M o d er n a C O VI D -1 9 V acci n e m ulti pl e -d os e vi al c o nt ai ns a fr oz e n s us p e nsi o n t h at d o es n ot 
c o nt ai n a pr es erv ativ e a n d m ust b e t h a w e d pri or t o a d mi nistr ati o n, p er t h e F ull F D A E U A 
Pr escri bi n g I nf or m ati o n .3 3 A d diti o n al d et ails ar e i ncl u d e d i n t h e P h ar m ac y M a n u al.  
T h e b o ost e r d os e l ev el i n t his tri al will b e 1 0 0 mc g ( 0. 5 mL ) M o d er n a C O VI D -1 9 V acci n e 
a d mi nist er e d i ntr a m usc ul arl y i n t h e d elt oi d.  V acci n e a d mi nistr ati o n d et ails will f oll o w F D A E U A f act 
s h e et i nstr ucti o n a n d b e r ec or d e d o n a c as e r e p ort f or m.  
6. 2 
I n v esti g ati o n al A g e nt # 2: Pfiz er -Bi o N T ec h  C O VI D -1 9 V acci n e  
T h e Pfiz er -Bi o N T ec h  C O VI D -1 9 V acci n e is a ut h oriz e d f or us e u n d er F D A E U A f or activ e i m m u niz ati o n t o 
pr e v e nt C O VI D -1 9 c a us e d b y S A R S -C o V -2 i n i n divi d u als 1 6 y e ars of a g e a n d ol d er.  T his pr ot oc ol is c urr e ntl y 
o nly e nr ol li n g p artici p a nts 1 8 y e ars of a g e a n d ol d er.  
6. 2. 1 
F or m ul ati o n, P ac k a gi n g, a n d L a b eli n g  
T h e Pfiz er -Bi o N T ec h  C O VI D -1 9 V acci n e is s u p pli e d as a fr oz e n s us p e nsi o n i n m ulti pl e -d os e vi als; 
e ac h vi al m ust b e dil ut e d wit h 1. 8 mL of st eril e n o n -b act eri ost atic 0. 9 % S o di u m C hl ori d e I nj ecti o n, 
U S P pri or t o us e t o f or m t h e v acci n e. E ac h d os e of t h e Pfiz er -Bi o N T ec h  C O VI D -1 9 V acci n e c o nt ai ns 
3 0 mc g of a m o d R N A e nc o di n g t h e vir al s pik e ( S) gl yc o pr ot ei n of S A R S -C o V -2.  
E ac h d os e of t h e Pfiz er -Bi o N T ec h -Bi o N T ec h C O VI D -1 9 V acci n e als o i ncl u d es t h e f oll o wi n g 
i n gr e di e nts: li pi ds ( 0. 4 3 m g ( 4-h y dr ox y b ut yl) az a n e diyl) bis( h ex a n e -6, 1 -diyl) bis( 2 -h ex yl d ec a n o at e), 

 
C o nfi d e nti al  
P a g e 2 7  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
0. 0 5 m g 2[ P E G -2 0 0 0] -N, N -dit etr a d ec yl ac et a mi d e, 0. 0 9 m g 1, 2 -dist e ar oyl -s n-gl yc er o -3 -
p h os p h oc h oli n e, a n d 0. 2 m g c h ol est er ol), 0. 0 1 m g p ot assi u m c hl ori d e, 0. 0 1 m g m o n o b asic 
p ot assi u m p h os p h at e, 0. 3 6 m g s o di u m c hl ori d e, 0. 0 7 m g di b asic s o di u m p h os p h at e di h y dr at e, a n d 
6 m g s ucr os e. T h e dil u e nt ( 0. 9 % S o di u m C hl ori d e I nj ecti o n, US P) c o ntri b ut es a n a d diti o n al 2. 1 6 m g 
s o di u m c hl ori d e p er d os e. 
T h e Pfiz er -Bi o N T ec h  C O VI D -1 9 V acci n e d o es n ot c o nt ai n pr es erv ativ e. T h e vi al st o p p ers ar e n ot 
m a d e wit h n at ur al r u b b er l at ex.  
Pfiz er -Bi o N T ec h  C O VI D -1 9 V acci n e will b e s u p pli e d i n c art o ns c o nt ai ni n g 2 5 m ulti pl e -d os e vi als p er 
c art o n ( 6 d os es p er vi al) i n t h er m al c o nt ai n ers wit h dry ic e. O nc e r ec eiv e d, t h e vi al c art o ns m ust b e 
r e m ov e d i m m e di at el y fr o m t h e t h er m al c o nt ai n er a n d st or e d i n a n ultr a-l o w t e m p er at ur e fr e ez er 
b et w e e n -8 0 °C t o -6 0 °C ( -1 1 2 °F t o -7 6 °F). Vi als m ust b e k e pt fr oz e n b et w e e n -8 0 ° C t o -6 0 °C  
(-1 1 2 °F t o -7 6 °F) a n d pr ot ect e d fr o m li g ht u ntil r e a d y t o us e.  
6. 2. 2 
D os a g e, Pr e p ar ati o n, a n d A d mi nistr ati o n  
T h e Pfiz er -Bi o N T ec h  C O VI D -1 9 V acci n e m ulti pl e -d os e vi al c o nt ai ns a v ol u m e of 0. 4 5 mL s u p pli e d as 
a fr oz e n s us p e nsi o n t h at d o es n ot c o nt ai n p r es erv ativ e. E ac h vi al m ust b e t h a w e d pri or t o dil uti o n 
wit h 1. 8 mL of st eril e n o n -b act eri ost atic 0. 9 % S o di u m C hl ori d e I nj ecti o n, US P a n d v acci n e 
a d mi nistr ati o n, p er t h e F ull F D A E U A Pr escri bi n g I nf or m ati o n .3 4 A d diti o n al d et ails ar e i ncl u d e d i n 
t h e P h ar m acy M a n u al.  
T h e d os e l ev el i n t his tri al is 3 0 mc g ( 0. 3 mL ) Pfiz er -Bi o N T ec h C O VI D -1 9 V acci n e a d mi nist er e d 
i ntr a m usc ul arl y i n t h e d elt oi d. V acci n e a d mi nistr ati o n d et ails will f oll o w F D A E U A f act s h e et 
i nstr ucti o n a n d b e r ec or d e d o n t h e V acci n e A d mi nistr ati o n e C R F. T h e Pfiz er -Bi o N T ec h  C O VI D 
v acci n e is a d mi nist er e d i ntr a m usc ul arl y as a si n gl e (t hir d) d os e t o st u dy p artici p a nts.  
6. 3 
Dr u g Acc o u nt a bilit y  
U n d er Titl e 2 1 of t h e C o d e of F e d er al R e g ul ati o ns ( 2 1 C F R § 3 1 2. 6 2) t h e i nv esti g at or will  m ai nt ai n a d e q u at e 
r ec or ds of t h e dis p ositi o n of t h e i nv esti g ati o n al a g e nt, i ncl u di n g t h e d at e a n d q u a ntit y of t h e dr u g r ec ei v e d, 
t o w h o m t h e dr u g w as dis p e ns e d ( p artici p a nt-by -p artici p a nt acc o u nti n g), a n d a d et ail e d acc o u nti n g of a n y 
dr u g acci d e nt all y or d eli b er at el y d estr oy e d.  
R ec or ds f or r ec ei pt, st or a g e, us e, a n d dis p ositi o n will b e m ai nt ai n e d by t h e st u dy sit e.  A dr u g -dis p e nsi n g 
l o g will b e k e pt c urr e nt f or e ac h p artici p a nt.  T his l o g will c o nt ai n t h e i d e ntific ati o n of e ac h p artici p a nt a n d 
t h e d at e a n d q u a ntit y of dr u g dis p ens e d.  
All r ec or ds r e g ar di n g t h e dis p ositi o n of t h e i nv esti g ati o n al pr o d uct will b e av ail a bl e f or i ns p ecti o n.  
6. 4 
Ass ess m e nt of P artici p a nt C o m pli a nc e wit h I n v esti g ati o n al A g e nt  
N ot A p plic a bl e ; o n e ti m e d os e a d mi nistr ati o n of C O VI D-1 9 v acci n e.  
6. 5 
T o xicit y Pr e v e nt i o n a n d M a n a g e m e nt 
T h e v acci n e will b e a d mi nist er e d  b y q u alifi e d p ers o n n el  i n d e dic at e d o bs erv ati o n r o o ms. P artici p a nts will b e 
m o nit or e d f or all er gic r e acti o ns or ot h er i nt ol er a nc e f or 3 0 mi n ut es f oll o wi n g v acci n e a d mi nistr ati o n. 
A p pr o pri at e m e dic ati o ns t o a d dr ess all er gic r e acti o ns will b e s u p pli e d b y t h e i nv esti g ati o n al p h ar m ac y (i. e., 

 
C o nfi d e nti al  
P a g e 2 8  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
e pi n e p hri n e, a nti -hist a mi n er gic m e dic ati o ns) a n d t h er e is acc ess t o l oc al r a pi d r es p o ns e t e a m s u p p ort i n 
c as e of s eri o us a dv ers e ev e nts.  
6. 6 
Pr e m at ur e Disc o nti n u ati o n of I n v esti g ati o n al A g e nt  
N ot A p plic a bl e  

 
C o nfi d e nti al  
P a g e 2 9  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
7. 
Ot h er M e dic ati o ns  
7. 1 
C o nc o mit a nt M e dic ati o ns  
7. 1. 1 
Pr ot oc ol -m a n d at e d  
N o n e   
7. 1. 2 
Ot h er p er mitt e d c o nc o mit a nt m e dic ati o ns  
Tr a ns pl a nt i m m u n os u p pr essi o n as d et er mi n e d b y t h e tr e ati n g tr a ns pl a nt p hysici a n m a y i ncl u d e 
t acr oli m us or c ycl os p ori n e, c ortic ost er oi ds, M M F a n d/ or az at hi o pri n e.  
7. 2 
Pr o p h yl actic M e dic ati o ns  
I nf ecti o us dis e as e pr o p hyl axis will b e d et er mi n e d b y t h e tr e ati n g tr a ns pl a nt p hysici a n.  
7. 3 
Pr o hi bit e d M e dic ati o ns  
T h er e ar e n o pr o hi bit e d m e dic ati o ns . 
7. 4 
R esc u e M e dic ati o ns  
N ot a p plic a bl e  

 
C o nfi d e nti al  
P a g e 3 0  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
8. 
St u d y Pr oc e d ur es  
8. 1 
E nr oll m e nt  
P ot e nti al st u dy p artici p a nts m ay b e i d e ntifi e d b y m e dic al c h art r evi e w  a n d i niti ally c o nt act e d b y a m e m b er 
of t h e st u dy t e a m i n p ers o n or ov er t h e p h o n e. D uri n g t his i niti al c o nt act, t h e p ot e nt i al p artici p a nt will b e 
pr ovi d e d i nf or m ati o n o n t h e st u dy a n d ask e d a b o ut t h eir i nt er est i n st u dy p artici p ati o n. If t h e y el ect t o 
c o nti n u e, t h e y will b e a p pr o pri at el y c o ns e nt e d a n d m ov e t o t h e scr e e ni n g p orti o n of t h e st u dy.   
D uri n g t h e c o ns e nt pr oc ess, p ot e nti al p artici p a nts will r ec eiv e a c o ncis e a n d f oc us e d pr es e nt ati o n of k e y 
i nf or m ati o n a b o ut t h e cli nic al tri al, v er b ally a n d wit h a writt e n c o ns e nt f or m. T h e r es e arc h st u dy will b e 
ex pl ai n e d i n l a y t er ms t o e ac h p ot e nti al r es e arc h p artici p a nt. T h e p ot e n ti al p artici p a nt will si g n a n i nf or m e d 
c o ns e nt f or m b ef or e u n d er g oi n g a n y st u dy pr oc e d ur es. 
8. 2 
Scr e e ni n g  Visit  
T h e p ur p os e of t h e scr e e ni n g p eri o d is t o c o nfir m eli gi bilit y pri or t o t h e st u dy i nt erv e n ti o n. D uri n g t h e 
scr e e ni n g p eri o d f or st u dy eli gi bilit y, t h e st u dy p ers o n n el will r evi e w t h e p artici p a nt’s m e dic al r ec or d f or 
pr e vi o us a n d c urr e nt m e dic al hist ory .  
T h e f oll o wi n g pr oc e d ur es, ass ess m e nts, a n d l a b or at ory m e as ur es will b e c o n d uct e d t o d et er mi n e 
p artici p a nt eli gi bilit y : 
1.
R e vi e w m e dic al h ist ory a n d i m m u n os u p pr essi o n t o c o nfir m eli gi bilit y. 
2.
Bl o o d dr a w n l oc all y f or a nti -R B D I g g ( usi n g R oc h e El ecsys ® ass a y).  A pri or r es ult m ay b e us e d f or 
eli gi bilit y if it w as o bt ai n e d at l e ast 3 0 d ays f oll o wi n g t h e s ec o n d C O VI D -1 9 v acci n e 
a d mi nistr ati o n.  
8. 3 
St u d y Visits or St u d y Ass ess m e nts  
8. 3. 1 
V acci n ati o n Visit  ( D a y 0)  
P artici p a nts w h o m e et i ncl usi o n a n d d o n ot m e et a n y excl usi o n crit eri a will b e sc h e d ul e d f or a 
v acci n ati o n visit. B as eli n e bl o o d , n as o p h ary n g e al , a n d uri n e s a m pl es will b e c oll ect e d p er t h e 
Sc h e d ul e of E v e nts i n A p p e n dix 1.  
F oll o wi n g s a m pl e c oll ecti o n, t h e p artici p a nt will pr oc e e d t o t h e a d mi nistr ati o n l oc ati o n a n d r ec ei v e 
t h eir t hir d d os e of C O VI D-1 9 v acci n e (s e e S ecti o n 6. 1 f or v acci n e d et ails). P artici p a nts will b e 
o bs erv e d f or 3 0 mi n ut es p ost v acci n e a d mi nistr ati o n.  
8. 3. 2 
F oll o w-u p Visits  
F oll o w-u p will occ ur o n D ay s 3, 7, 1 4, 3 0  ( m o nt h 1), 9 0 ( m o nt h 3), 1 8 0 ( m o nt h 6), 2 1 0 ( m o nt h 9) 
a n d 3 6 5 (y e ar 1) f oll o wi n g v acci n e a d mi nistr ati o n. T h e D a y 3 0 visit is t h e pri m ary e n d p oi nt visit.  
D uri n g t h es e visits, p artici p a nts will b e ask e d a b o ut t h eir g e n er al h e alt h, a ny n e w e v e nts, 
i m m u n os u p pr essi o n m e dic ati o n c h a n g es a n d t h eir tr a ns pl a nt e d ki d n e y .  
I n a d diti o n, bl o o d will b e c oll ect e d f or ass ess m e nts t o b e r u n i n t h e cli nic al a n d r es e arc h 
l a b or at ori es p er t h e Sc h e d ul e of E v e nts i n A p p e n dix 1. N as o p h ary n g e al s w a b f or S A R S -C o V -2 P C R 
t esti n g will b e c oll ect e d at b as eli n e a n d D a ys 3 0, 9 0 ( m o nt h 3), 1 8 0 ( m o nt h 6), 2 1 0 ( m o nt h 9) , 3 6 5 

 
C o nfi d e nti al  
P a g e 3 1  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
(y e ar 1) f oll o wi n g v acci n e a d mi nistr ati o n, a n d i n a n y c as e of s us p ect e d C O VI D-1 9 i nf ecti o n . 
P artici p a nts will b e i nstr uct e d t o c o nt act t h e st u dy t e a m if t h e y r ec eiv e a n y C O VI D -1 9 t esti n g at a n 
o utsi d e l a b d uri n g t h e c o urs e of t h e st u dy. All i nst a nc es of C O VI D -1 9 i nf ecti o n will b e r e p ort e d o n a 
c as e r e p ort f orm.  
8. 3. 3 
S us p ect e d or C o nfir m e d C as es of C O VI D -1 9 I nf ecti o n  
If p artici p a nts s us p ect t h e y h av e c o ntr act e d C O VI D-1 9 i nf ecti o n, t h e y will b e dir ect e d t o f oll o w-u p 
wit h t h eir l oc al tr a ns pl a nt p hysici a n or pri m ary c ar e pr ovi d er t o o bt ai n t h e a p pr o pri at e cli nic al c ar e. 
I nf or m ati o n r el at e d t o t h eir ill n ess will b e c oll ect e d f or t h e st u dy a n d r e p ort e d i n t h e cli nic al 
d at a b as e.  
8. 3. 4 
5 -M o nt h C O VI D -1 9 B o ost er  
T h e C D C  c urr e ntl y r ec o m m e n ds a C O VI D -1 9 b o ost er at 5 m o nt hs f oll o wi n g c o m pl eti o n of t h e pri m ary s eri es 
( 3 d os es f or i mm u n oc o m pr o mis e d p ati e nts). T h e st u dy t e a m will r e m ot el y c o nt act p artici p a nts m o nt hly, 
b e gi n ni n g 5 m o nt hs f oll o wi n g t h eir st u dy d os e of v acci n e t o e nc o ur a g e t h e m t o g et a C O VI D -1 9 b o ost er 
d os e a n d i nf or m t h e st u dy t e a m w h e n t his occ urs.  
P artici p a nts w h o r ec eiv e t h e 5 -m o nt h  C O VI D -1 9 b o ost er  will  b e f oll o w e d o n a s e p ar at e sc h e d ul e ( A p p e n dix 
2 ) at 3 0 d a ys a n d 9 0 d a ys f oll o wi n g t h e 5-m o nt h b o ost er . D at a will b e c oll ect e d r e g ar di n g t h eir b o ost er 
d os e of v acci n e a n d r es e arc h s p eci m e ns ( bl o o d, n as al s w a bs) will b e c oll ect e d at t h es e ti m e p oi nts.  T h eir 
p artici p ati o n will b e c o m pl et e at 9 0 d a ys p ost -b o ost er  or st u dy M o nt h 1 2, w hic h ev er occ urs first . 
P art ici p a nts w h o d o n ot r ec eiv e a 5 -m o nt h C O VI D -1 9 b o ost er b y M o nt h 1 1 will r e m ai n o n t h eir ori gi n al 
st u dy sc h e d ul e p er A p p e n dix 1 .  
8. 4 
U nsc h e d ul e d Visits  
If t h er e is a c h a n g e i n i m m u n os u p pr essiv e m e dic ati o ns, n e w m e dic al  ev e nts or a di a g n osis of r ej ecti o n  
b et w e e n r e g ul arl y sc h e d ul e d visits, p artici p a nts will b e i nstr uct e d t o c o nt act st u dy p ers o n n el a n d m a y b e 
ask e d t o r et ur n t o t h e st u dy sit e f or a n “ u nsc h e d ul e d” visit.  
8. 5 
Visit Wi n d o ws  
St u dy visits s h o ul d t a k e pl ac e wit hi n t h e ti m e li mits s p ecifi e d b el o w: t h e d esi g n at e d visit wi n d o ws (i. e. +/- n 
d a ys)  f or e ac h sc h e d ul e d visit ar e als o i n dic at e d o n t h e T a bl e of E v e nts.   
Visits 1 -2 ( D ay 3, D a y 7)  
+/ - 1 d a y  
Visits 3 -4 ( D ay 1 4, D a y 3 0 ) 
+/ - 3 d a ys  
Visits 5 -7 ( D ay 9 0, D a y 1 8 0, D a y 3 6 5)  
+/ - 2 w e e ks  

 
C o nfi d e nti al  
P a g e 3 2  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
9. 
M ec h a nistic Ass a ys  
9. 1 
I ntr o d ucti o n 
Eff ecti v e v acci n ati o ns i n d uc e p ot e nt pr ot ectiv e h u m or al a n d c ell ul ar i m m u nit y a n d pr o m ot e d ev el o p m e nt 
of r o b ust T a n d B c ell m e m ory, t o g et h er pr ev e nti n g i nf ecti o n a n d acc el er ati n g vir al cl e ar a nc e f oll o wi n g 
p at h o g e n ex p os ur e.  C urr e nt c o nc e pts ar e t h at v acc i n ati o n r es ults i n activ ati o n of b ot h T c ells a n d B c ells.  
V acci n e a nti g e n -activ at e d B c ells c a n diff er e nti at e i nt o l o w affi nit y I g G - or I g M -s ecr eti n g pl as m a c ells ( P Cs). 
Alt er n ati v el y, v acci n e a nti g e n -activ at e d B c ells c a n i nt er act wit h a nti g e n -activ at e d  C D 4 0 + C D 4 + ( T h 1) h el p er 
T c ells t o u n d er g o a n is ot y p e s witc h a n d e nt er g er mi n al c e nt er ( G C) r e acti o ns w h er ei n t h e y u n d er g o affi nit y 
m at ur ati o n.  P ositiv e s el ecti o n of t h e hi g h est affi nit y B c ells i n t h e G C r e q uir es c o g n at e i nt er acti o ns wit h 
a nti g e n s p ecif ic IL-2 1 -pr o d uci n g f ollic ul ar h el p er C D 4 + T c ells ( Tf h). T h e p ositiv el y s el ect e d hi g h affi nit y B 
c ells t h e n c a n diff er e nti at e i nt o l o n g liv e d a nti b o d y -s ecr eti n g P Cs, c a n b ec o m e m e m ory B c ells ( B m e m), or 
c a n r e e nt er t h e G C t o u n d er g o f urt h er affi nit y m at ur a ti o n. Cr uci al f e at ur es of t h e a nti b o d y r e p ert oir e 
r el e v a nt t o p at h o g e n cl e ar a nc e i ncl u d e a nti b o d y s p ecificit y, affi nit y, tit er, is ot y p e cl ass, a n d gl yc osyl ati o n 
p att er ns, a m o n g ot h ers. A nti g e n -r e activ e C D 4 + a n d C D 8 + T c ells t h at ex p a n d a n d diff er e nti at e f oll o wi n g 
v acci n ati o n ar e als o cr uci al m e di at ors of p at h o g e n cl e ar a nc e i n d e p e n d e nt of t h eir f u ncti o ns as h el p er c ells 
f or eff ecti v e h u m or al i m m u n e r es p o ns es.  I m p ort a nt c h ar act eristics of t h es e i n d uc e d T c ell r es p o ns es 
i ncl u d e e pit o p e s p ecificit y, c yt oki n e secr eti o n p att er ns, a n d c yt ot oxic f u ncti o n, a m o n g ot h ers. Eff ecti v e 
a nti -p at h o g e n i m m u nit y als o i nv olv es activ ati o n of i n n at e i m m u n e c ells, i ncl u di n g d e n dritic c ells, 
m acr o p h a g es, a n d n at ur al kill er c ells t h at c a n i nt er act wit h a n e n h a nc e t h e a d a ptiv e i m m u n e r es p o ns es a n d 
h av e b e e n r ec e ntl y s h o w n t o ex hi bit c ell ul ar a n d m ol ec ul ar f e at ur es c o nsist e nt wit h m e m ory.  
As n ot e d i n t h e b ac k gr o u n d s ecti o n, e m er gi n g e vi d e nc e i n dic at es t h at t h e ov er w h el mi n g m aj orit y of 
tr a ns pl a nt r eci pi e nts t a ki n g i m m u n os u p pr ess a nt m edic ati o ns d o n ot pr o d uc e eff ectiv e a nti b o d y r es p o ns es 
t o S A RS -C o V -2  s pik e pr ot ei n m R N A v acci n ati o ns. W h et h er t h es e p ati e nts d ev el o p a n d m ai nt ai n pr ot ecti v e T 
c ell r es p o ns es aft er  t h e s a m e v acci n es is n ot k n o w n. A d et ail e d ki n etic a n al ysis of i n n at e a n d a d a ptiv e 
i m m u nit y f oll o wi n g S A R S-C o V -2  m R N A v acci n ati o n, p artic ul arl y c o m p ari n g r es p o n d ers t o n o n -r es p o n d ers, is 
t h us ess e nti al i n or d er t o i nt er pr et t h e cli nic al tri al o utc o m e a n d t o g ui d e d esi g n of f oll o w u p st u di es ai m e d 
at ov erc o mi n g i d e ntifi e d d ef ects.  M or e ov er,  if it w er e p ossi bl e t o i d e ntify a n e arl y p ost v acci n e m ol ec ul ar 
si g n at ur e t h at c orr el at es wit h v acci n e s ucc ess vs f ail ur e, s uc h a bi o m ark er c o ul d b e us e d t o g ui d e 
s u bs e q u e nt str at e gi es ai m e d at e n h a nci n g i n d ucti o n pr ot ectiv e i m m u nit y i n e ac h tr a n s pl a nt p ati e nt. 
T h us, t h e ov er all g o als of t h e pr o p os e d m ec h a nistic st u di es ar e t o a) c h ar act eriz e t h e v acci n e -i n d uc e d 
i n n at e a n d a d a ptiv e i m m u n e r es p o ns es i n e ac h st u dy s u bj ect, b) d efi n e t h e d ur a bilit y of t h e r es p o ns es ov er 
1 -y e ar p ost v acci n ati o n, c) pr ovi d e i nsi g ht i nt o i m m u n e m ec h a nis ms t h at pr ev e nt f or m ati o n a n d/ or 
d ur a bilit y of t h e i n d uc e d r es p o ns es, d) i d e ntify m ol ec ul ar m ark ers of s ucc essf ul v acci n ati o n.  
T o t his e n d w e will s eri all y c oll ect s er u m, pl as m a a n d P B M C s a m pl es ov er t h e e ntir e st u dy p eri o d. Usi n g 
t h es e s a m pl es w e will a) q u a ntify s pi k e pr ot ei n pr o d ucti o n i n s er u m, b) pr ovi d e a d et ail e d ki n etic 
c h ar act eriz ati o n of t h e v acci n e i n d uc e d a nti b o d y r e p ert oir e (s p ecificit y, is ot y p e, tit er, n e utr aliz ati o n 
c a p acit y), c) p erf or m a ki n etic p h e n ot y pic  a n d f u ncti o n al a n alysis of a nti g e n s p ecific B m e m (fr e q u e nc y, 
a nti g e n s p ecificit y, s urf ac e m ark ers, m et a b ol o mics, g e n e ex pr essi o n p att er ns, si n gl e c ell s e q u e nci n g) a n d 
P C, d) p erf or m a ki n etic, a n al ysis of a nti g e n s p ecific C D 4 + a n d C D 8 + T c ells (fr e q u e nc y,  e pit o p e s p ecificit y, 
s urf ac e m ark ers, m et a b ol o mics, g e n e ex pr essi o n p att er ns si n gl e c ell s e q u e nci n g), e)  ass ess p h e n ot y pic, 

 
C o nfi d e nti al  
P a g e 3 3  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
f u ncti o n al a n d g e n e ex pr essi o n p att er ns of i n n at e i m m u n e D C, m o n oc yt e/ m acr o p h a g e a n d N K c ell s u bs ets 
i n p eri p h er al bl o o d, a n d f) p erf or m g e n o mic pr ofili n g of p eri p h er al bl o o d c ells t h at will pr ovi d e a bi o m ark er 
f or a n eff ecti v e r es p o ns e. 
9. 2 
O bj ecti v e 1:  T o q u a ntif y s pi k e pr ot ei n pr o d ucti o n i n s er u m  or pl as m a  aft er v acci n ati o n.  
Tr a nsi e nt ex pr essi o n of a m o difi e d s pik e pr ot ei n usi n g m R N A v acci n es ( M o d er n a a n d Pfiz er -Bi o N T ec h ) h as 
b e e n cr uci al i n gl o b al eff ort t o c o ntr ol t h e S A R S -C o V -2 p a n d e mic.  T his pl atf or m off ers t h e fl exi bilit y f or 
r a pi d m o dific ati o n t o c o ntr ol v ari a nts.  Giv e n t h e r e q uir e m e nt f or eff ectiv e pr ot ei n ex pr essi o n of 
i m m u n og e n t h e extr e m el y p o or r es p o ns es f or tr a ns pl a nt r eci pi e nts, p artic ul arl y t h os e o n myc o p h e n ol at e 
m of etil r ais es t h e q u esti o n w h et h er t h e a nti -m et a b olit e pr o p erti es of M M F m ay i m p air t h e tr a nsi e nt 
ex pr essi o n of s pik e p o or r es p o ns e of tr a ns pl a nt p ati e nts a n d t h er e b y c o ntri b ut e t o t h e i m p air e d r es p o ns e 
of tr a ns pl a nt p ati e nts.  Usi n g a r ec e ntl y d ev el o p e d ultr as e nsitiv e m ol ec ul ar ass a y t o d et ect s pik e pr ot ei n i n 
s er u m w e will ass ess ex pr essi o n at b as eli n e a n d 3 d a ys p ost v acci n ati o n.  
9. 3 
O bj ecti v e 2: T o pr o vi d e a d et ail e d ki n etic c h ar act eriz ati o n of t h e v acci n e i n d uc e d a nti b o d y 
r e p ert oir e (s p ecificit y, is ot y p e, tit er, n e utr aliz ati o n c a p acit y). 
W hil e r el ati v e c o ntri b uti o ns of v acci n e i n d uc e d h u m or al a n d T c ell i m m u nit y i n t h e pr ot ecti o n fr o m s e v er e 
S A R S -C o V -2 dis e as e a r e n ot f ull y u n d erst o o d, t h e d ev el o p m e nt of a critic al l ev el of S A R S -C o V -2  A b ar e 
e m er gi n g as a c orr el at e of pr ot ecti o n. A d et ail e d  u n d erst a n di n g of t h e pr ofil e of A b r es p o ns es i n tr a ns pl a nt 
r eci pi e nts aft er v acci n ati o n is cr uci al st e p t o w ar d u n d erst a n di n g w h at p o p ul ati o n b e n efits fr o m a n 
a d diti o n al d os e of v acci n e.  T h e pri m ary e n d p oi nt of t his st u dy f oc us es o n t h e c a n di d at e c orr el at e of 
pr ot ecti o n M S D 3 -pl ex ( S -2 P, R B D a n d N pr ot ei n + B S A) ass a y .   T his o bj ectiv e will pr ovi d e a d e e p er 
m ec h a nistic c h ar act eri z ati o n of t o s u p p ort h y p ot h esis g e n er ati n g o bs erv ati o ns t o u n d erst a n d t h e 
m ec h a nis ms u n d erl yi n g v acci n e f ail ur e a n d t o i d e ntify c a n di d at e h u m or al bi o m ark ers t o pr e dict v acci n e 
r es p o ns e. T his i ncl u d es s urr o g at e a n d liv e vir us n e utr aliz ati o n tit ers i ncl u di n g  v ers us n ov el v ari a nts of 
c o nc er n. 
9. 4 
O bj ecti v e 3: T o p erf or m a ki n etic p h e n ot y pic a n d f u ncti o n al a n al ysis of a nti g e n s p ecific B m e m 
(fr e q u e nc y, a nti g e n s p ecificit y, s urf ac e m ar k ers, m et a b ol o mics, g e n e e x pr essi o n p att er ns, si n gl e 
c ell s e q u e nci n g) a n d P C.  
T o i d e ntify a n d c h ar act eriz e S A R S -C o V -2 m e m ory B c ells w e will us e fl u or esc e ntl y l a b el e d m ulti m eriz e d 
pr o b es f or t ar g ets of t h e v acci n e (s pik e r ec e pt or -bi n di n g a n d ect o d o m ai n) a n d as w ell as n o n -v acci n e 
ex pr ess e d S A R S -C o V -2 a nti g e ns ( e. g.  N ucl e oc a psi d). T h e m a g nit u d e a n d diff er e nti ati o n of a nti -s p ecific I g M + 
a n d I g G + m e m ory B c ells will b e ass ess e d at e ac h ti m e p oi nt.  W e will us e fl o w c yt o m etry, C y T O F, si n gl e B 
c ell m ulti-o mics (c ell s urf ac e CI T E -s e q pr ofili n g usi n g t a g g e d a nti b o d y a n d m ulti m eriz e d pr o b es f or v acci n e 
t ar g ets), tr a nscri pt o mics, a n d B c ell r ec e pt or V DJ r e p ert oir e a n alysis t o c h ar act eriz e a nti g e n s p ecific B c ells.  
W e will p erf or m i n vitr o ELI S P O T ass a ys t o d et er mi n e fr e q u e nci es of a nti g e n s p ecific P Cs i n p eri p h er al 
bl o o d.  
9. 5 
O bj ecti v e 4: T o p erf or m a ki n etic, a n al ysis of a nti g e n s p ecific C D 4 + a n d C D 8 + T c ells (fr e q u e nc y, 
e pit o p e s p ecificit y, s urf ac e m ar k ers, m et a b ol o mics, g e n e e x pr essi o n p att er ns si n gl e c ell 
s e q u e nci n g). 
W hil e t h e r e q uir e m e nts f or s ust ai n e d pr ot ecti o n a g ai nst S A R S -C o V -2 ar e n ot y et k n o w n, eff ectiv e c o ntr ol of 
vir al p at h o g e ns oft e n d e p e n ds o n t h e d ev el o p m e nt of b ot h h u m or al a n d c ell ul ar i m m u nit y.   

 
C o nfi d e nti al  
P a g e 3 4  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
W e will ass ess t h e str e n gt h, br e a dt h a n d c h ar act er of t h e a nti -s pik e T c ell r es p o ns e i n st u dy p artici p a nts 
usi n g fl o w -c yt o m etry b as e d, ELI SP O T, a n d si n gl e c ell -m ulti -o mics ass a ys.  A nti g e n -s p ecific c ells will b e 
i nt err o g at e d usi n g a r a pi dl y ev olvi n g s et of p e pti d e a n d M H C m ulti m er r e a g e nts usi n g fl o w-c yt o m etry, 
C y T O F, a n d or ELI S P O T r e a d o uts. F or fl o w -b as e d a n al ysis w e will utiliz e 1) a nti g e n  s p ecific f u ncti o n al ass a ys 
( acti v ati o n-i n d uc e d m ark er ( AI M), i ntr ac ell ul ar c yt oki n e s ecr eti o n ass a ys a n d n ov el T c ell m et a b olic pr ofili n g 
ass a ys a n d, 2) p h e n ot y pic c h ar act eriz ati o n of s pik e -s p ecific T c ells M H C-p e pti d e m ulti m er st ai ni n g.  W e will 
us e si n g l e T c ell m ulti-o mics (c ell s urf ac e CI T E -s e q pr ofili n g usi n g t a g g e d a nti b o d y a n d t etr a m ers, 
tr a nscri pt o mics, a n d T c ell r ec e pt or V DJ r e p ert oir e a n alysis.  
Ex pl or at ory a n alysis of ass oci at e d of t h es e d e e p i m m u n e pr ofili n g ass ess m e nts wit h pr ot ectiv e i m m u nit y  
will b e p erf or m e d.  
9. 6 
O bj ecti v e 5: T o ass ess p h e n ot y pic, f u ncti o n al a n d g e n e e x pr essi o n p att er ns of i n n at e i m m u n e D C, 
m o n oc yt e/ m acr o p h a g e a n d N K c ell s u bs ets i n p eri p h er al bl o o d.  
W e will c h ar act eriz e t h e ki n etics of p eri p h er al bl o o d i m m u n e l a n dsc a p e of m o n o n ucl e ar l e u k oc yt e li n e a g e 
a n d p h e n ot y pic m ark ers t o br o a dl y ass ess t h e i m m u n ol o gic al c ell ul ar pr ofil e of tr a ns pl a nt r eci pi e nts b ef or e 
a n d aft er v acci n ati o n, f oc usi n g o n t h e a bs ol ut e a n d r el ati v e fr e q u e nc y of T, B, N K a n d A P C s u bs ets.  
W e will c h ar act eriz e t h es e c ells t y p es i n p eri p h er al bl o o d usi n g fl o w c yt o m etry a n d or C y T O F ass a ys.  W e 
will t est f u ncti o n usi n g i n vitr o ass a ys t h at i ncl u d e i n vitr o sti m ul ati o n of D C s u bs ets wit h TL R li g a n ds 
(c yt oki n e a n d s urf ac e m ark er r e a d o uts as m e as ur es of activ ati o n), i n vitr o sti m ul ati o n of m acr o p h a g es wit h 
L P S (c yt oki n e r e a d o uts as a m e as ur e of tr ai n e d i m m u nit y, w hic h w o ul d t h e n b e f oll o w e d u p wit h e pi g e n etic 
a n alys es), i n vitr o f u ncti o n al a n al ys es of N K c ells.  
9. 7 
O bj ecti v e 6: E x pl or ati o n of m ol ec ul ar bi o m ar k ers of e arl y r es p o n d ers t o v acci n ati o n  
W e will c oll ect s eri al  bl o o d  s a m pl es f or R N A pr ofili n g ( R N As e q) a n d/ or pr ot e o mics  i n a d diti o n t o 
c h ar act eriz ati o n of c yt oki n e si g n ali n g e arl y aft er v acci n e i nt erv e nti o n . 
 

 
C o nfi d e nti al  
P a g e 3 5  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
1 0. 
Bi os p eci m e n  St or a g e  
Bi ol o gic al s p eci m e ns o bt ai n e d u n d er t his pr ot oc ol m a y b e us e d i n f ut ur e ass a ys t o r e e v al u at e bi ol o gic al 
r es p o ns es as a d diti o n al r es e arc h t ests ar e d ev el o p e d ov er ti m e.  T h es e m a y i ncl u d e, b ut ar e n ot li mit e d  t o, 
t ests ex a mi ni n g as p ects of h ost i m m u n ol o g y, c ell bi ol o g y, or h u m a n g e n etics as it r el at es t o a n y of t h es e 
as p ects. A p pr o pri at e i nf or m e d c o ns e nt will b e o bt ai n e d f or b ot h t h e c oll ecti o n a n d st or a g e  of s a m pl es.  T h e 
s p eci m e ns fr o m t h es e ev al u ati o ns will b e l a b el e d wit h a c o d e d I D a n d m a y b e st or e d b e y o n d t h e f u n di n g 
p eri o d.  

 
C o nfi d e nti al  
P a g e 3 6  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
1 1. 
Crit eri a f or P artici p a nt a n d St u d y C o m pl eti o n a n d Pr e m at ur e St u d y T er mi n ati o n  
1 1. 1 
P artici p a nt C o m pl eti o n  
All p artici p a nts will b e f oll o w e d f or 1 2 m o nt hs p ost v acci n e a d mi nistr ati o n.  
1 1. 2 
P art ici p a nt St o p pi n g R ul es  a n d Wit h dr a w al Crit eri a  
P artici p a nts m ay b e pr e m at ur el y t er mi n at e d fr o m t h e st u dy f or t h e f oll o wi n g r e as o ns:  
1.
T h e p artici p a nt el ects t o wit h dr a w c o ns e nt fr o m all f ut ur e st u dy activiti es, i ncl u di n g f oll o w -u p.  
2.
T h e p artici p a nt is “l ost t o f oll o w -u p” (i. e., n o f urt h er f oll o w -u p is p ossi bl e b ec a us e att e m pts t o 
r e est a blis h c o nt act wit h t h e p artici p a nt h av e f ail e d).  
3.
T h e p artici p a nt di es.  
4.
T h e I nv esti g at or n o l o n g er b eli ev es p artici p ati o n is i n t h e b est i nt er est of t h e p artici p a nt. 
1 1. 3 
P artici p a nt R e pl ac e m e nt  
P artici p a nts w h o wit h dr a w or ar e wit h dr a w n will n ot  b e r e pl ac e d . 
1 1. 4 
F oll o w-u p aft er E arl y St u d y Wit h dr a w al  
If a  p artici p a nt is wit h dr a w n  fr o m t h e st u dy f or a n y r e as o n, t h e p artici p a nt m ay b e ask e d t o c o m pl et e a fi n al 
visit a n d/ or fi n al ass ess m e nts.  
1 2. 5. 
St u d y P a usi n g  R ul es  
T h e t hir d v acci n e d os es will b e a d mi nist er e d ov er a v ery s h ort p eri o d at t h e b e gi n ni n g of t h e st u dy, a n d 
t h er e ar e n o f urt h er i nt erv e nti o ns. T h er e will t h er ef or e b e a v ery bri ef wi n d o w  f or t h e i m pl e m e nt ati o n of 
p a usi n g r ul es. P a usi n g r ul es will o nly r e m ai n  i n eff ect u ntil all st u dy p artici p a nts h av e r ec eiv e d t h eir t hir d 
d os e of v acci n e.  
If t h e f oll o wi n g occ ur, e nr oll m e nt m a y b e t e m p or aril y h alt e d a n d a n e x p e dit e d D S M B r e vi e w t a k e pl ac e: 
R e act o g e nicit y:  T w o Gr a d e 4 or hi g h er  r e act o g e nic a dv ers e ev e nts ( A Es) t h at ar e d efi nit el y or p ossi bl y 
r el at e d t o t h e v acci n e  
All er g y:  Fi v e p artici p a nts i n t h e first 1 0 0 p artici p a nts v acci n at e d, or 5 % of all p artici p a nts t h er e aft er 
ex p eri e nci n g a Gr a d e 3 syst e mic all er gic r e acti o n t h at is d efi nit el y or p ossi bl y r el at e d t o t h e v acci n e   
 

 
C o nfi d e nti al  
P a g e 3 7  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
1 2. 
S af et y M o nit ori n g  a n d R e p orti n g  
1 2. 1 
O v er vi e w  
T his s ecti o n d efi n es t h e t y p es of s af et y d at a t h at will b e c oll ect e d u n d er t his pr ot oc ol a n d o utli n es t h e 
pr oc e d ur es f or a p pr o pri at el y c oll ecti n g, gr a di n g, r ec or di n g, a n d r e p orti n g t h os e  d at a. A dv ers e ev e nts t h at 
ar e cl assifi e d as s eri o us acc or di n g t o t h e d efi niti o n of h e alt h a ut h oriti es m ust b e r e p ort e d pr o m ptl y ( p er 
S ecti o n 1 2 . 5, R e p orti n g of S eri o us A dv ers e E v e nts a n d A d v ers e E v e nts ) t o t h e s p o ns or, D AI T/ NI AI D. 
A p pr o pri at e n otific ati o ns will  als o b e m a d e t o sit e pri nci p al i nv esti g at ors, I nstit uti o n al R e vi e w B o ar ds (I R Bs), 
a n d h e alt h a ut h oriti es.  
I nf or m ati o n i n t his s ecti o n c o m pli es wit h I C H G ui d eli n e E 2 A: Cli nic al S af et y D at a M a n a g e m e nt: D efi niti o ns 
a n d St a n d ar ds f or Ex p e dit e d R e p orti n g, I C H G ui d eli n e E -6: G ui d eli n e f or G o o d Cli nic al Pr actic e, 2 1 C F R P arts 
3 1 2 a n d 3 2 0, a n d a p pli es t h e st a n d ar ds s et f ort h i n t h e N ati o n al C a nc er I nstit ut e ( N CI), C o m m o n 
T er mi n ol o g y Crit eri a f or A dv ers e E v e nts ( C T C A E), V ersi o n [e nt er 5 . 0 or c orr ect v ersi o n a p plic a bl e t o tri al] : 
htt p://ct e p.c a nc er. g ov/r e p orti n g/ctc. ht ml . 
1 2. 2 
D efi niti o ns  
1 2. 2. 1
A d v ers e E v e nt ( A E)  
A n y u nt o w ar d or u nf av or a bl e m e dic al occ urr e nc e ass oci at e d wit h t h e s u bj ect’s p artici p ati o n i n t h e 
r es e arc h, w h et h er or n ot c o nsi d er e d r el at e d t o t h e s u bj ect’s p artici p ati o n i n t h e r es e arc h ( m o difi e d 
fr o m t h e d efi niti o n of a dv ers e ev e nts i n t h e 1 9 9 6 I nt er n ati o n al C o nf er e nc e o n H ar m o niz ati o n E-6 
G ui d eli n e s f or G o o d Cli nic al Pr actic e) (fr o m O H R P " G ui d a nc e o n R e vi e wi n g a n d R e p orti n g 
U n a ntici p at e d Pr o bl e ms I nv olvi n g Risks t o S u bj ects or Ot h er s a n d A dv ers e E v e nts ( 1/ 1 5/ 0 7)" 
htt p: / / w w w. h hs. g o v / o hr p / p oli c y / a d v e v nt g ui d. ht ml # Q 2  )  
F or t his st u dy, a n a d v ers e ev e nt will i ncl u d e t h e f oll o wi n g ass oci at e d wit h t h e t hir d d os e of v acci n e 
a n d st u dy m a n d at e d pr oc e d ur es.   
V acci n e A d mi nistr ati o n ( M o d er n a C O VI D -1 9 V acci n e or Pfiz er -Bi o N T ec h C O VI D -1 9 V acci n e)  
• 
All A Es occ urri n g wit hi n 3 0  d ays f oll o wi n g v acci n e a d mi nistr ati o n a n d S A Es u p t o 6 
m o nt hs p ost v acci n e a d mi nistr ati o n.  
St u dy m a n d at e d pr oc e d ur es:  
• 
A n y A E occ urri n g wit hi n 2 4 h o urs of a pr ot oc ol m a n d at e d bl o o d dr a w  
• 
A n y A E occ urri n g wit hi n 2 4  h o urs of a pr ot oc ol m a n d at e d n as o p h ary n g e al s w a b  
1 2. 2. 2
S olicit e d A d v ers e E v e nts  
F or t h e p ur p os es of t his st u dy, t h e f oll o wi n g s p ecific l oc al a n d syst e mic r e act o g e nicit y e v e nts, as 
w ell as sy m pt o ms of a p ot e nti al all er gic r e acti o n, will b e s olicit e d fr o m t h e p ar tici p a nt t hr o u g h a 
r e m ot e c o nt act o n D ay 7 p ost -v acci n ati o n . A n y ot h er a dv ers e ev e nts r e p ort e d d uri n g t h e c o urs e of 
t his r e m ot e c o nt act will b e r e p ort e d o n t h e A E e C R F. St u dy cli nici a ns will f oll o w all a dv ers e ev e nts 
t o r es ol uti o n. 

 
C o nfi d e nti al  
P a g e 3 8  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
• 
Loc al r e acti o ns at t h e i nj ecti o n sit e i ncl u di n g eryt h e m a/r e d n ess, s w elli n g/i n d ur ati o n ( h ar d n ess), 
a n d p ai n.  
• 
S yst e mic r e acti o ns i ncl u di n g f ev er, my al gi a, art hr al gi a, f ati g u e, h e a d ac h e, n a us e a, v o miti n g, 
di arr h e a, a n d c hills.  
• 
P ot e nti al all er gic r e acti o n, w hic h i ncl u d es t h e f oll o wi n g s y m pt o ms : 
• 
Ski n: hiv es, s w elli n g ot h er t h a n i nj ecti o n sit e, itc hi n g, r e d n ess ot h er t h a n i nj ecti o n sit e, r as h  
• 
R es pir at ory: w h e ezi n g, s h ort n ess of br e at h, c o u g hi n g, ti g ht n ess i n t h e t hr o at or c h est, s n e ezi n g, 
n as al st uffi n ess or c o n g esti o n  
• 
G astr oi nt esti n al:  tr o u bl e s w all o wi n g, a b d o mi n al cr a m ps, di arr h e a, n a us e a, v o miti n g 
• 
Dizzi n ess or li g ht h e a d e d n ess  
1 2. 2. 3
U ns olicit e d A d v ers e E v e nts  
P artici p a nts will b e i nstr uct e d t o c o nt act t h e st u dy sit e a n d r e p ort a n y a dv ers e ev e nts u p t o 3 0 d ays 
p ost v acci n e a d mi nistr ati o n. T h is will i ncl u d e a n y d el a y e d o ns et l oc al r e acti o ns.  
1 2. 2. 3. 1
S us p ect e d A d v ers e R e acti o n ( S A R)  
A n y a dv ers e ev e nt f or w hic h t h er e is a r e as o n a bl e p ossi bilit y t h at t h e S A R S -C o V -2 v acci n e c a us e d 
t h e a dv ers e ev e nt. F or t h e p ur p os es of s af et y r e p orti n g, ‘r e as o n a bl e p ossi bilit y’ m e a ns t h er e is 
e vi d e nc e t o s u g g est a c a us al r el ati o ns hi p b et w e e n t h e dr u g a n d t h e a dv ers e ev e nt. A s us p ect e d 
a dv ers e r e acti o n i m pli es a l ess er d e gr e e of c ert ai nt y a b o ut c a us alit y t h a n a dv ers e r e acti o n, w hic h 
m e a ns a n y a dv ers e ev e nt  c a us e d b y a dr u g ( 2 1 C F R 3 1 2. 3 2( a)).  
1 2. 2. 4
U n e x p ect e d A d v ers e E v e nt   
A n a dv ers e ev e nt or s us p ect e d a dv ers e r e acti o n is c o nsi d er e d  “ u n ex p ect e d” if it is n ot list e d i n t h e 
P ac k a g e I ns ert or F D A E m er g e nc y Us e A ut h oriz ati o n  or is n ot list e d at t h e s p ecificit y, s ev erit y or 
r at e of occ urr e nc e t h at h as b e e n o bs erv e d; or  is n ot c o nsist e nt wit h t h e risk i nf or m ati o n d escri b e d 
i n t h e g e n er al i nv esti g ati o n al pl a n or els e w h er e i n t h e I N D.  
 “ U n ex p ect e d” als o r ef ers t o a dv ers e ev e nts or s us p ect e d a dv ers e r e act i o ns t h at ar e m e nti o n e d i n 
t h e I nv esti g at or Br oc h ur e or p ac k a g e i ns ert as occ urri n g wit h a cl ass of dr u gs or as a ntici p at e d fr o m 
t h e p h ar m ac ol o gic al pr o p erti es of t h e dr u g, b ut ar e n ot s p ecific all y m e nti o n e d as occ urri n g wit h 
t h e p artic ul ar dr u g u n d er i nv esti g ati o n ( 2 1 C F R 3 1 2. 3 2( a) ] 
1 2. 2. 5
S eri o us A d v ers e E v e nt ( S A E)  
A n a dv ers e ev e nt  or s us p ect e d a dv ers e r e acti o n is c o nsi d er e d “s eri o us” if, i n t h e vi e w of eit h er t h e 
i nv esti g at or or S p o ns or D AI T/ NI AI D , it r es ults i n a ny of t h e f oll o wi n g o utc o m es ( 2 1 C F R 3 1 2. 3 2( a)): 
1.
D e at h.  
2.
A lif e -t hr e at e ni n g e v e nt: A n A E or S A R is c o nsi d er e d “lif e-t hr eat e ni n g” if, i n t h e vi e w of eit h er 
t h e i nv esti g at or or S p o ns or [ a d d D AI T/ NI AI D or ot h er S p o ns or, if a p plic a bl e], its occ urr e nc e 
pl ac es t h e s u bj ect at i m m e di at e risk of d e at h. It d o es n ot i ncl u d e a n A E or S A R t h at, h a d it 
occ urr e d i n a m or e s ev er e f or m, mi g ht  h av e c a us e d d e at h.  
3.
I n p ati e nt h os pit aliz ati o n or pr ol o n g ati o n of existi n g h os pit aliz ati o n. 
4.
P ersist e nt or si g nific a nt i nc a p acit y or s u bst a nti al disr u pti o n of t h e a bilit y t o c o n d uct n or m al lif e 
f u ncti o ns. 

 
C o nfi d e nti al  
P a g e 3 9  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
5.
C o n g e nit al a n o m aly or b irt h d ef ect.  
6.
I m p ort a nt m e dical e v e nts t h at m ay n ot r es ult i n d e at h, b e lif e t hr e at e ni n g, or r e q uir e 
h os pit aliz ati o n m a y b e c o nsi d er e d s eri o us w h e n, b as e d u p o n a p pr o pri at e m e dic al j u d g m e nt, 
t h e y m a y j e o p ar diz e t h e s u bj ect a n d m ay r e q uir e m e dic al or s ur gic al i nt erv e nti o n t o pr e v e nt 
o n e  of t h e o utc o m es list e d a b ov e.  
El ecti v e h os pit aliz ati o ns or h os pit al a d missi o ns f or t h e p ur p os e of c o n d uct of pr ot oc ol m a n d at e d 
pr oc e d ur es ar e n ot t o b e r e p ort e d as a n S A E u nl ess h os pit aliz ati o n is pr ol o n g e d d u e t o 
c o m plic ati o ns. 
1 2. 3 
Gr a di n g a n d Attri b uti o n of  A d v ers e E v e nts  
1 2. 3. 1
Gr a di n g Crit eri a  
T h e st u dy sit e will gr a d e t h e s ev erit y of a dv ers e ev e nts ex p eri e nc e d b y t h e st u dy s u bj ects acc or di n g 
t o t h e crit eri a s et f ort h i n t h e N ati o n al C a nc er I nstit ut e’s C o m m o n T er mi n ol o g y  Crit eri a f or A d v ers e 
E v e nts ( C T C A E)  V ersi o n 5. 0 . T his d oc u m e nt (r ef err e d t o  h er ei n as t h e N CI -C T C A E m a n u al) pr ovi d es a 
c o m m o n l a n g u a g e t o d escri b e l ev els of s ev erit y, t o a n al yz e a n d i nt er pr et d at a, a n d t o artic ul at e t h e 
cli nic al si g nific a nc e of all a dv ers e ev e nts. T h e N CI -C T C A E h as b e e n r evi e w e d b y t h e  NI AI D M e dic al 
M o nit or a n d P r ot oc ol C h air a n d h as b e e n d e e m e d a p pr o pri at e f or t h e s u bj ect p o p ul ati o n t o b e 
st u di e d i n t his pr ot oc ol.  
A d v ers e ev e nts will b e gr a d e d o n a sc al e fr o m 1 t o 5 acc or di n g t o t h e f oll o wi n g st a n d ar ds i n t h e 
N CI -C T C A E m a n u al:  
Gr a d e 1  = Mil d; asy m pt o m atic or mil d sy m pt o ms; cli nic al or di a g n ostic o bs erv ati o ns o nly; 
i nt erv e nti o n n ot i n dic at e d.  
Gr a d e 2  = M o d er at e; mi ni m al, l oc al or n o ni nv asiv e i nt erv e nti o n i n dic at e d; li miti n g a g e a p pr o pri at e  
i nstr u m e nt al activiti es of d ail y livi n g ( A DL: I nstr u m e nt al A DL r ef er t o pr e p ari n g m e als, s h o p pi n g f or 
gr oc eri es or cl ot h es, usi n g t h e t el e p h o n e, m a n a gi n g m o n e y, etc. )  
Gr a d e 3  = S ev er e or m e dic all y si g nific a nt b ut n ot i m m e di at el y lif e -t hr e at e ni n g; h os pit aliz ati o n or 
pr ol o n g ati o n of h os pit aliz ati o n i n dic at e d; dis a bli n g; li miti n g s elf-c ar e activiti es of d ail y livi n g   
( A DL: S elf-c ar e A DL r ef er t o b at hi n g, dr essi n g a n d u n dr essi n g, f e e di n g s elf, usi n g t h e t oil et,  
t a ki n g m e dic ati o ns, a n d n ot b e dri d d e n.)  
Gr a d e 4  = Lif e-t hr e at e ni n g c o ns e q u e nc es; ur g e nt i nt erv e nti o n i n dic at e d.  
Gr a d e 5  = D e at h r el at e d t o A E.  
F or  gr a di n g a n a b n or m al v al u e or r es ult of  a cli nic al or l a b or at ory e v al u ati o n (i ncl u di n g, b ut n ot 
li mit e d t o, a r a di o gr a p h, a n ultr as o u n d, a n el ectr oc ar di o gr a m etc. ), a tr e at m e nt -e m er g e nt a d v ers e 
e v e nt is d efi n e d as a n i ncr e as e i n gr a d e fr o m b as eli n e or fr o m t h e l ast p ost -b as eli n e v al u e t h at 
d o es n’t m e et gr a di n g crit eri a. C h a n g es i n gr a d e fr o m scr e e ni n g t o b as eli n e  will als o b e r ec or d e d as 
a dv ers e ev e nts  b ut  ar e n ot tr e at m e nt -e m er g e nt. If a s p ecific e v e nt or r es ult fr o m a giv e n cli nic al or 
l a b or at ory e v al u ati o n is n ot i ncl u d e d i n t h e N CI-C T C A E m a n u al, t h e n a n a b n or m al r es ult w o ul d b e 
c o nsi d er e d a n a dv ers e ev e nt if c h a n g es i n t h er a py or m o nit ori n g ar e i m pl e m e nt e d  as a r es ult of t h e 
e v e nt/r es ult . 
1 2. 3. 2
Attri b uti o n D efi niti o ns  

 
C o nfi d e nti al  
P a g e 4 0  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
T h e r el ati o ns hi p, or attri b uti o n, of a n a dv ers e ev e nt t o t h e st u dy t h er a py r e gi m e n or st u dy 
pr oc e d ur e(s) will i niti all y b e d et er mi n e d b y t h e sit e i nv esti g at or a n d r ec or d e d o n t h e a p pr o pri at e 
A E / S A E e C R F .  Fi n al d et er mi n ati o n of attri b uti o n f or s af et y r e p orti n g will b e d et er mi n e d b y 
D AI T/ NI AI D .  T h e r el ati o ns hi p of a n a dv ers e ev e nt t o st u dy t h er a py r e gi m e n or pr oc e d ur es will b e 
d et er mi n e d usi n g t h e d escri pt ors a n d d efi niti o ns pr ovi d e d i n T a bl e 1 2 . 3. 2.  
F or  a d diti o n al i nf or m ati o n a n d a pri nt a bl e v ersi o n of t h e N CI -C T C A E m a n u al, c o ns ult t h e N CI -C T C A E 
w e b sit e: htt p://ct e p.c a nc er. g ov/r e p orti n g/ctc. ht ml . 
        
T a bl e 1 2. 3. 2 Attri b uti o n of A d v ers e E v e nts  
C o d e   
D escri pt or   
R el ati o ns hi p (t o pri m ar y i n v esti g ati o n al pr o d uct 
a n d/ or ot h er c o nc urr e nt m a n d at e d st u d y t h er a p y  or 
st u d y pr oc e d ur e) 
U N R EL A T E D C A T E G O R Y  
1   
N ot 
R el at e d  
T h e a dv er s e ev e nt is cl e arl y n ot r el at e d:  t h er e is 
i ns uffici e nt e vi d e nc e t o s u g g est a c a us al r el ati o ns hi p. 
 R EL A T E D C A T E G O RI E S  
2   
P ossi bl y 
R el at e d  
T h e a dv ers e ev e nt h as a r e as o n a bl e p ossi bilit y t o b e 
r el at e d; t h er e is e vi d e nc e t o s u g g est a c a us al 
r el ati o ns hi p. 
3   
R el at e d   
T h e a dv ers e ev e nt is cl e arl y r el at e d.  
 
1 2. 4 
C oll ecti o n a n d R ec or di n g of A d v ers e E v e nts  
1 2. 4. 1
C oll ecti o n P eri o d  
A d v ers e E v e nts t e m p or all y ass oci at e d ( 2 4 h o urs) wit h t h e r es e arc h bl o o d dr a ws a n d 
n as o p h ary n g e al s w a bs will b e c oll ect e d fr o m t h e ti m e of t h e scr e e ni n g visit u ntil a s u bj ect  
c o m pl et es st u dy p artici p ati o n . 
A d v ers e E v e nts as d efi n e d i n S ecti o n 1 2. 2. 1 will b e c oll ect e d f or 3 0 d a ys f oll o wi n g C O VI D -1 9 v acci n e 
a d mi nistr ati o n. S eri o us A dv ers e E v e nts will b e c oll ect e d f or 6 m o nt hs f oll o wi n g v acci n e 
a d mi nistr ati o n.  
1 2. 4. 2
C oll ecti n g A d v ers e  E v e nts  
A d v ers e e v e nts (i ncl u di n g S A Es) m a y b e disc ov er e d t hr o u g h a ny of t h es e m et h o ds:  
• 
O bs ervi n g t h e s u bj ect.  
• 
I nt ervi e wi n g t h e s u bj ect [ e.g., usi n g a c h ec klist, str uct ur e d q u esti o ni n g, di ary, etc.]. 
• 
R ec ei vi n g a n u ns olicit e d c o m pl ai nt fr o m t h e s u bj ect. 
• 
I n a d diti o n, a n a b n or m al v al u e or r es ult fr o m a cli nic al or l a b or at ory e v al u ati o n c a n als o i n dic at e a n 
a dv ers e  ev e nt, as d efi n e d i n S ecti o n 1 2 . 3, Gr a di n g a n d Attri b uti o n of  A d v ers e E v e nts.  

 
C o nfi d e nti al  
P a g e 4 1  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
1 2. 4. 3
R ec or di n g A d v ers e E v e nts  
T hr o u g h o ut t h e st u dy, t h e i nv esti g at or will r ec or d a dv ers e ev e nts a n d s eri o us a dv ers e ev e nts as 
d escri b e d pr evi o usl y ( S ecti o n 1 2 . 2, D efi niti o ns) o n t h e a p pr o pri at e  el ectr o nic c as e r e p ort f or m  
r e g ar dl ess of t h e r el ati o ns hi p t o st u dy t h er a py r e gi m e n or st u dy pr oc e d ur e.  
O nc e r ec or d e d, a n A E/ S A E will b e f oll o w e d u ntil it r es olv es wit h or wit h o ut s e q u el a e, or u ntil t h e 
e n d of st u dy p artici p ati o n, or u ntil 3 0 d a ys aft er t h e s u bj ect pr e m at ur el y wit h d r a ws ( wit h o ut 
wit h dr a wi n g c o ns e nt)/ or is wit h dr a w n fr o m t h e st u dy, w hic h ev er occ urs first.  
1 2. 5 
R e p orti n g of S eri o us A d v ers e E v e nts  a n d A d v ers e E v e nts  
1 2. 5. 1
R e p orti n g of S eri o us A d v ers e E v e nts t o D AI T/ NI AI D  
T his s ecti o n d escri b es t h e r es p o nsi biliti es of t h e sit e i nv e sti g at or t o r e p ort s eri o us a dv ers e ev e nts 
t o t h e s p o ns or vi a t h e A E/ S A E e C R F. Ti m el y r e p orti n g of a dv ers e ev e nts is r e q uir e d b y 2 1 C F R a n d 
I C H E 6 g ui d eli n es.  
Sit e i nv esti g at ors will  r e p ort all s eri o us a dv ers e ev e nts (s e e S ecti o n 1 2. 2. 3, S eri o us A d v ers e E v e nt) , 
r e g ar dl ess of r el ati o ns hi p or ex p ect e d n ess wit hi n 2 4 h o urs of disc ov eri n g t h e e v e nt.  
F or s eri o us a dv ers e ev e nts, all r e q u est e d i nf or m ati o n o n t h e A E/ S A E  e C R F  pr ovi d e d.  H o w ev er, 
u n a v ail a bl e d et ails of t h e e v e nt will  n ot d el ay s u b missi o n of t h e k n o w n i nf or m ati o n. As a d diti o n al 
d et ails b ec o m e av ail a bl e, t h e A E/ S A E e C R F will  b e u p d at e d a n d s u b mitt e d.  I niti al S A E e C R Fs s h o ul d 
i ncl u d e as m uc h i nf or m ati o n as p ossi bl e, b ut at a mi ni m u m: 
• 
A E t er m  
• 
R el ati o ns hi p t o st u dy v acci n ati o n  
• 
R el ati o ns hi p t o st u dy pr oc e d ur e  
• 
R e as o n w h y t h e e v e nt is s eri o us  
• 
S u p pl e m e nt ary e C R F p a g es t h at ar e c urr e nt at t h e ti m e of t h e S A E  r e p orti n g e. g. m e dic al 
hist ory a n d v acci n e a d mi nistr ati o n  
1 2. 5. 2
R e p orti n g t o H e alt h A ut h orit y  
Aft er a n a dv ers e ev e nt r e q uiri n g 2 4 h o ur r e p orti n g ( p er S ecti o n 1 2 . 5. 1, R e p orti n g of S eri o us A d v ers e 
E v e nts t o S p o ns or ) is s u b mitt e d b y t h e sit e i nv esti g at or a n d ass es s e d b y D AI T/ NI AI D , t h er e ar e t w o 
o pti o ns f or D AI T/ NI AI D  t o r e p ort t h e a dv ers e ev e nt t o t h e a p pr o pri at e h e alt h a ut h oriti es: 
1 2. 5. 2. 1
A n n u al R e p orti n g  
D AI T/ NI AI D  will i ncl u d e i n t h e a n n u al st u dy r e p ort t o h e alt h a ut h oriti es all a dv ers e ev e nts 
cl assifi e d as:  
o 
S eri o us, ex p ect e d, s us p ect e d a dv ers e r e acti o ns (s e e S ecti o n 1 2 . 2. 1. 1, S us p ect e d A d v ers e 
R e acti o n, a n d S ecti o n 1 2 . 2. 2, U n ex p ect e d A d v ers e Ev e nt ). 
o 
S eri o us a n d n ot a s us p ect e d a dv ers e r e acti o n (s e e S ecti o n 1 2 . 2. 2, S us p ect e d A d v ers e 
R e acti o n ). 
o 
Pr e g n a nci es.  
N ot e t h at all a d v ers e e v e nts ( n ot j ust t h os e r e q uiri n g 2 4 -h o ur r e p orti n g) will b e r e p ort e d i n t h e 
A n n u al I N D R e p ort . 

 
C o nfi d e nti al  
P a g e 4 2  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
1 2. 5. 2. 2
E x p e dit e d S af et y R e p orti n g  
T his o pti o n, wit h 2 p ossi bl e c at e g ori es, a p pli es if t h e a dv ers e ev e nt is cl assifi e d as o n e of t h e 
f oll o wi n g: 
C at e g or y 1 :  S eri o us a n d u n e x p ect e d s us p ect e d a d v ers e r e acti o n  [S U S A R]  (s e e S ecti o n 1 2. 2. 1. 1, 
S us p ect e d A d v ers e R e acti o n a n d S ecti o n 1 2 . 2, U n ex p ect e d A d v ers e E v e nt  a n d 2 1 C F R 
3 1 2. 3 2(c)( 1)i).  
T h e s p o ns or s h all r e p ort a n y s us p ect e d a dv ers e r e actio n t h at is b ot h s eri o us a n d u n ex p ect e d.  T h e 
s p o ns or s h all r e p ort a n a dv ers e ev e nt as a s us p ect e d a dv ers e r e acti o n o nly if t h er e is e vi d e nc e t o 
s u g g est a c a us al r el ati o ns hi p b et w e e n t h e st u dy dr u g a n d t h e a dv ers e ev e nt, s uc h as:  
1.
A si n gl e occ urr e nc e of a n e v e nt t h at is u nc o m m o n a n d k n o w n t o b e str o n gl y ass oci at e d 
wit h dr u g ex p os ur e ( e. g., a n gi o e d e m a, h e p atic i nj ury, or St ev e ns -J o h ns o n Sy n dr o m e); 
2.
O n e or m or e occ u rr e nc es of a n ev e nt t h at is n ot c o m m o nly ass oci at e d wit h dr u g 
ex p os ur e, b ut is ot h er wis e u nc o m m o n i n t h e p o p ul ati o n ex p os e d t o t h e dr u g ( e. g., t e n d o n 
r u pt ur e); 
3.
A n a g gr e g at e a n alysis of s p ecific e v e nts o bs erv e d i n a cli nic al tri al (s uc h as k n o w n 
c o ns e q u e nc es of t h e u n d erl yi n g dis e as e or c o n diti o n u n d er i nv esti g ati o n or ot h er e v e nts 
t h at c o m m o nly occ ur i n t h e st u dy p o p ul ati o n i n d e p e n d e nt of dr u g t h er a py) t h at i n dic at es 
t h os e ev e nts occur m or e fr e q u e ntl y i n t h e dr u g  tr e at m e nt gr o u p t h a n i n a c o nc urr e nt or 
hist oric al c o ntr ol gr o u p.  
 
C at e g or y 2 : A n y fi n di n gs fr o m st u di es t h at s u g g ests a si g nific a nt h u m a n ris k   
T h e s p o ns or s h all r e p ort a n y fi n di ngs fr o m ot h er e pi d e mi ol o gic al st u di es, a n alys es of a dv ers e 
e v e nts  wit hi n t h e c urr e nt st u dy or p o ol e d a n al ysis acr oss cli nic al st u di es or a ni m al or i n vitr o t esti n g 
( e. g. m ut a g e nicit y, t er at o g e nicity, c arci n o g e nicit y) t h at s u g g est a si g nific a nt risk i n h u m a ns ex p os e d 
t o t he dr u g t h at w o ul d r es ult i n a s af et y-r el at e d c h a n g e i n t h e pr ot oc ol, i nf or m e d co ns e nt, 
i nv esti g at or br oc h ur e or p ac k a g e i ns ert or ot h er a s p ects of t h e ov er all c o n d uct of t h e st u dy.   
 
D AI T/ NI AI D  s h all n otify t h e  F D A a n d all p artici p ati n g i nv esti g at ors of e x p e dit e d S af et y R e p orts 
wit hi n 1 5 c al e n d ar d ays; u n ex p ect e d f at al or i m m e di at el y lif e -t hr e at e ni n g s us p ect e d a dv ers e 
r e acti o n(s) s h all b e r e p ort e d as s o o n as p ossi bl e or wit hi n 7 c al e n d ar d a ys.  
1 2. 5. 3
R e p orti n g of A d v ers e E v e nts t o I R Bs/I E Cs  
All i nv esti g at ors s h all r e p ort a dv ers e ev e nts, i ncl u di n g ex p e dit e d r e p orts, i n a ti m el y f as hi o n t o t h eir 
r es p ectiv e I R Bs/I E Cs i n acc or d a nc e wit h a p plic a bl e re g ul ati o ns a n d g ui d eli n es. All S af et y R e p orts t o 
t h e F D A s h all b e distri b ut e d b y D AI T/ NI AI D or d esi g n e e t o all p artici p at i n g i nstit uti o ns f or sit e 
I R B/I E C s u b missi o n. 
1 2. 5. 4
M a n d at or y r e p orti n g t o V acci n e A d v ers e E v e nt R e p orti n g S yst e m  
P er t h e F D A E U A f or t h e Pfiz er -Bi o N T ec h C O VI D -1 9 V acci n e a n d t h e F D A E U A f or t h e M o d er n a 
C O VI D -1 9 V acci n e, t h e sit e i nv estig at or, or d esi g n e e,  is r es p o nsi bl e f or m a n d at ory r e p orti n g of t h e 
f oll o wi n g t o t h e V acci n e A dv ers e E v e nt R e p orti n g Syst e m ( V A E R S): 

 
C o nfi d e nti al  
P a g e 4 3  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
• 
v acci n e a d mi nistr ati o n err ors w h et h er or n ot ass oci at e d wit h a n a dv ers e ev e nt,  
• 
s eri o us a dv ers e ev e nts (irr es p ectiv e of attri b uti o n t o v acci n ati o n),  
• 
cas es of M ultisyst e m I nfl a m m at ory S y n dr o m e i n a d ults, a n d  
• 
c as es of C O VI D-1 9 t h at r es ult i n h os pit aliz ati o n or d e at h.  
T h e sit e i nv esti g at or, or d esi g n e e, is als o r es p o nsi bl e f or r ec or di n g v acci n ati o n i nf or m ati o n i n t h e 
st at e/l oc al j uris dicti o n’s I m m u niz ati on S urv eill a nc e Syst e m or ot h er d esi g n at e d syst e m.   
1 2. 6 
R e p orti n g of Ot h er S af et y I nf or m ati o n  
A n i n v esti g at or s h all pr o m ptl y n otify t h e sit e I R B as w ell as t h e S A C C C  w h e n a n “ u n a ntici p at e d pr o bl e m 
i nv olvi n g risks t o s u bj ects or ot h ers” is i d e ntifi e d, w hic h is n ot ot h er wis e r e p ort a bl e as a n a dv ers e ev e nt.  
1 2. 7 
R e vi e w of S af et y I nf or m ati o n  
1 2. 7. 1
M e dic al M o nit or R e vi e w  
T h e NI AI D  M e dic al M o nit or s h all r ec eiv e m o nt hly r e p orts fr o m t h e S A C C C  c o m pili n g n e w a n d 
acc u m ul ati n g i nf or m ati o n o n A Es  a n d S A Es  r ec or d e d by t h e st u dy sit e(s) o n a p pr o pri at e e C R Fs.  
I n a d diti o n, t h e M e dic al M o nit or s h all r evi e w a n d m a k e d ecisi o ns o n t h e dis p ositi o n of t h e S A E a n d 
pr e g n a nc y r e p orts r ec eiv e d by t h e S A C C C ( S e e S ecti o ns 1 2 . 5. 1, R e p orti n g of S eri o us A dv ers e E v e nts 
t o S p o ns or, a n d 1 2 . 6, Pr e g n a nc y R e porti n g).   
1 2. 7. 2
D S M B R e vi e w   
1 2. 7. 2. 1
Pl a n n e d D S M B R e vi e ws  
T h e D at a a n d S af et y M o nit ori n g B o ar d ( D S M B) s h all r evi e w s af et y d at a o n e m o nt h aft er all st u dy 
p artici p a nts h av e r ec eiv e d st u dy v acci n e, u nl ess a s af et y e v e nt r e q uir es e arli er r evi e w.  T h e y will 
r e vi e w t h e st u dy a g ai n w h e n t h e d at a b as e is l oc k e d aft er t h e l ast p ati e nt’s l ast visit.  I nt eri m 
D S M B r evi e ws m ay occ ur at a n y ti m e at t h e discr eti o n of t h e m e dic al m o nit or or t h e pr ot oc ol 
c h air. D at a f or t h e pl a n n e d s af et y r evi e ws will i ncl u d e, at a mi ni m u m, a listi n g of all r e p ort e d A Es 
a n d S A Es.   
T h e D S M B will b e i nf or m e d of a ny  Ex p e dit e d S af et y R e p ort s wit hi n o n e w e e k of s u b mitti n g s uc h 
r e p orts t o t he  F D A. . 
1 2. 7. 2. 2
A d h oc  D S M B R e vi e ws  
I n a d diti o n t o t h e pr e-sc h e d ul e d dat a r evi e ws a n d pl a n n e d s af et y m o nit ori n g, t h e D S M B m a y b e 
c all e d u p o n f or a d h oc  r evi e ws. T h e D S M B will  r evi e w a n y ev e nt t h at p ot e nti ally i m p acts s af et y at 
t h e r e q u est of t h e pr ot oc ol c h air or D AI T/ NI AI D. I n a d diti o n, t h e f oll o wi n g e v e nts will tri g g er a n  a d 
h oc  c o m pr e h e nsiv e D S M B S af et y R evi e w:  
o 
A n y d e at h t h at occ urs i n t h e st u dy w hic h is p ossi bl y or d efi nit el y r el at e d t o st u dy tr e at m e nt 
r e gi m e n. 
o 
A P a usi n g R ul e ( o utli n e d i n S ecti o n 1 1. 2) is m et.  

 
C o nfi d e nti al  
P a g e 4 4  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
Aft er r evi e w of t h e d at a, t h e D S M B will m a k e r ec o m m e n d ati o ns  r e g ar di n g st u dy c o n d uct a n d/ or 
c o nti n u ati o n. 
1 2. 7. 2. 2. 1 
T e m p or ar y  S us p e nsi o n  of e nr oll m e nt  f or a d h oc D S M B S af et y R e vi e w  
S e e S ecti o n 1 1. 2 f or P artici p a nt St o p pi n g R ul es  a n d Wit h dr a w al Crit eri a  

 
C o nfi d e nti al  
P a g e 4 5  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
1 3. 
St atistic al C o nsi d er ati o ns a n d A n al ytic al Pl a n  
1 3. 1 
O v er vi e w  
T h e g o al of t h e st u dy is t o ass ess a nti b o d y r es p o ns e t o a t hir d d os e of v acci n e a g ai nst S A R S-C o V -2 i n ki d n e y 
tr a ns pl a nt r eci pi e nts w h o h av e f ail e d t o r es p o n d t o t w o d os es of eit h er t h e M o d er n a C O VI D-1 9 v acci n e or 
Pfiz er -Bi o N T ec h C O VI D -1 9 v acci n e. T h e st u dy p o p ul ati o n will c o nsist of ki d n e y tr a ns pl a nt r eci pi e nts w h o 
h av e r ec ei v e d t w o d os es of t h e M o d er n a or Pfiz er -Bi o N T ec h  v acci n e a n d s u bs e q u e ntl y s h o w n a n e g ati v e or 
w e a kl y p ositi v e a nti b o d y r es p o ns e. T h e st u dy is a si n gl e -ar m, n o n -r a n d o miz e d i nt erv e nti o n st u dy i n w hic h 
all p artici p a nts r ec eiv e a t hir d d os e of t h e v acci n e f or w hic h t h e y h av e pr evi o usl y r ec eiv e d t w o d os es.  
1 3. 2 
E n d p oi nts  
T h e pri m ary e n d p oi nt is pr ot ectiv e a nti b o d y r es p o ns e m e as ur e d at 3 0 d a ys aft er t h e t hir d v acci n e d os e, 
m e as ur e d usi n g t h e F D A v ali d at e d M S D 3 pl ex ( W u -1 f ull l e n gt h s pik e, R B D a n d N pr ot ei ns) ass a y . K e y 
s ec o n d ary e n d p oi nts i ncl u d e v acci n e r e act o g e nicit y, tr e at e d ac ut e all o gr aft r ej ecti o n wit hi n 6 0 d a ys of t h e 
d os e, s eri o us a dv ers e ev e nts wit hi n 3 0 d a ys of t h e d os e, gr aft l oss wit hi n 6 0 d a ys, a n d d e at h wit hi n 6 0 d a ys.  
1 3. 3 
M e as ur es t o Mi ni miz e Bi as  
T his is a n u nr a n d o miz e d, u n bli n d e d, si n gl e -ar m st u dy. T o mi ni miz e m e as ur e m e nt bi as, b as eli n e ex p os ur es 
will b e m e as ur e d b ef or e t h e t hir d d os e is r ec eiv e d. T o mi ni miz e bi as i n asc ert ai n m e nt of o utc o m es, al l 
o utc o m e d efi niti o ns will b e st a n d ar diz e d a n d all ass a ys will b e pr oc ess e d i n a c e ntr aliz e d l a b or at ory.  
1 3. 4 
A n al ysis Pl a n  
1 3. 4. 1
A n al ysis P o p ul ati o ns  
A n al ysis will b e p er -pr ot oc ol. All i n divi d u als w h o r ec eiv e t h e i nt erv e nti o n a n d h av e a nti b o d y 
r es p o ns e m e as ur e d at 3 0 d a ys aft er t h e i nt erv e nti o n will b e i ncl u d e d i n t h e a n al ysis of t h e m ai n 
o utc o m e. F or s ec o n d ary a n d ex pl or at ory o utc o m es, all i n divi d u als w h o r ec eiv e t h e i nt erv e nti o n a n d 
h av e t h at o utc o m e m e as ur e d will b e i ncl u d e d. I n t h e e v e nt t h at d at a f o r a n y o utc o m e ar e missi n g 
f or m or e t h a n 2 0 % of i n divi d u als w h o r ec eiv e t h e i nt erv e nti o n, w e will us e a w ei g hti n g a p pr o ac h t o 
esti m at e t h e distri b uti o n of t h at o utc o m e a m o n g all i n di vi d u als ( m e as ur e d a n d u n m e as ur e d) w h o 
r ec ei v e t h e i nt erv e nti o n. 
1 3. 4. 2
Pri m ar y A n a l ysis of Pri m ar y E n d p oi nt  
T h e pri m ary o utc o m e is bi n ary: w h et h er or n ot a p ositiv e r es p o ns e is d et ect e d at 3 0 d a ys aft er t h e 
i nt erv e nti o n. W e will c alc ul at e a n ex act bi n o mi al c o nfi d e nc e i nt erv al ar o u n d t his pr o p orti o n. I n t h e 
e v e nt t h at o utc o m e d at a ar e m issi n g f or m or e t h a n 2 0 % of i n divi d u als, w e will us e a w ei g hti n g 
a p pr o ac h t o esti m at e t h e distri b uti o n of t h e o utc o m e a m o n g all i n divi d u als ( m e as ur e d a n d 
u n m e as ur e d) w h o r ec eiv e t h e i nt erv e nti o n. S p ecific all y, w e will us e l o gistic r e gr essi o n t o m o d el t h e 
p r o b a bilit y of a p ositiv e r es p o ns e a dj usti n g f or a g e, y e ars si nc e tr a ns pl a nt, a nti m et a b olit e us a g e, 
a n d t y p e of v acci n e ( M o d er n a vs Pfiz er -Bi o N T ec h ) a m o n g i n divi d u als wit h a m e as ur e d r es p o ns e. 
T his m o d el will b e a p pli e d t o i n divi d u als wit h n o m e as ur e d r es p o ns e t o pr e dict t h e n u m b er of t h os e 
i n divi d u als w h o w o ul d h av e h a d a p ositiv e r es p o ns e h a d it b e e n m e as ur e d. W e will us e a b o otstr a p 
t o d eriv e a n e m piric al 9 5 % c o nfi d e nc e i nt erv al ar o u n d t his esti m at e. T his pr oc e d ur e will b e r u n 
usi n g t h e e nti r e s a m pl e of 2 0 0 i n divi d u als, a n d als o s e p ar at el y i n t h e t w o str at a (n e g ativ e  r es p o ns e 
vs w e a k pri or a nti b o d y r es p o ns e). 

 
C o nfi d e nti al  
P a g e 4 6  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
1 3. 4. 3
S u p p orti v e A n al ys es of t h e Pri m ar y E n d p oi nt  
W e will c h ar act eriz e risk f act ors ass oci at e d wit h t h e pri m ary o utc o m e usi n g l o gistic r e gr e ssi o n. Risk 
f act ors ( a g e, s ex, r ac e/ et h nicit y, y e ars si nc e tr a ns pl a nt, a nti m et a b olit e us a g e, v acci n e t y p e) will 
a n alyz e d i n divi d u all y usi n g u niv ari a bl e l o gistic r e gr essi o n. A d diti o n ally, w e will a n al yz e all risk 
f act ors i n a si n gl e m ultiv ari a bl e l o gistic re gr essi o n m o d el.   
 
1 3. 4. 4
A n al ys es of S ec o n d ar y a n d Ot h er E n d p oi nt s 
S ec o n d ary e n d p oi nts will b e a n alyz e d usi n g ex act bi n o mi al c o nfi d e nc e i nt erv als a n d l o gistic 
r e gr essi o n as p er t h e m et h o ds d escri b e d i n 1 3. 4. 2 a n d 1 3. 4. 3. W e will a n al yz e ex pl or at ory 
m ec h a nistic a n d ot h er e n d p oi nts b y r e p orti n g pr o p orti o n wit h bi n o mi al ex act c o nfi d e nc e i nt erv al 
f or bi n ary v ari a bl es, pr o p orti o ns f or c at e g oric al v ari a bl es, a n d m e di a n (I Q R) f or c o nti n u o us 
v ari a bl es. W e will als o r e p ort t h es e o utc o m es str atifi e d b y t h e pri m ary o utc o m e, wit h Fis h er ex act 
t ests f or bi n ary a n d c at e g oric al v ari a bl es a n d r a nks u m t ests f or c o nti n u o us v ari a bl es. 
1 3. 4. 5
D escri pti v e A n al ys es  
W e will d escri b e d e m o gr a p hics a n d ot h er b as eli n e ( pr e -i nt erv e nti o n) c h ar act eristics ( m e dic ati o n 
us e, ti m e si nc e tr a ns pl a nt, t y p e of v acci n e) i n t h e st u dy p o p ul ati o n by r e p orti n g pr o p orti o n f or 
bi n ary a n d c at e g oric al v ari a bl es, a n d m e di a n (I Q R) f or c o nti n u o us v ari a bl es. W e will r e p ort t h es e 
ov er all a n d str atifi e d b y t h e pri m ary o utc o m e.  
1 3. 5 
I nt eri m A n al ys es  
N o i nt eri m a n al ys es ar e pl a n n e d f or t his st u dy.  
1 3. 6 
St atistic al H y p ot h es es  
T his is a si n gl e -ar m pil ot st u dy t o esti m at e t h e pr o p orti o n of i n divi d u als wit h a p ositiv e a nti b o d y r es p o ns e 
t o a t hir d d os e of v acci n e. F or t h e pri m ary e n d p oi nt, w e d o n ot t est a n y s p ecific h y p ot h esis. R at h er, o ur 
g o al is t o esti m at e t h e pr o p orti o n of i n divi d u als wit h a p ositiv e r es p o ns e. W e will esti m at e t his pr o p orti o n, 
wit h 9 5 % c o nfi d e nc e i nt erv al, usi n g a n ex act bi n o mi al c o nfi d e nc e i nt erv al.  
1 3. 7 
S a m pl e Siz e C o nsi d er ati o ns  
I n t h e c o nt ext of esti m ati n g a si n gl e pr o p orti o n, t h e 
r el e v a nt c o nsi d er ati o n f or s a m pl e siz e is t h e 
diff er e nc e b et w e e n t h e tr u e pr o p orti o n ( w h at 
pr o p orti o n of all i n divi d u als w o ul d h av e a p ositiv e 
r es p o ns e if o ur s a m pl e siz e w as i nfi nit e) a n d t h e 
o bs erv e d pr o p orti o n ( w h at pr o p orti o n i n t h e act u al 
st u dy h a v e a p ositiv e r es p o ns e). F or a r a n g e of tr u e 
pr o p orti o ns ( 5 % -7 5 %), w e r a n 2 0, 0 0 0 si m ul ati o ns of 
t h e st u dy, a n d c alc ul at e d t h e " m ar gi n of err or": t h at 
is, h alf of t h e diff er e nc e b et w e e n t h e 2. 5t h p erc e ntil e 
of t h e o bs erv e d pr o p orti o n a n d t h e 9 7. 5t h p erc e ntil e 
of t h e o bs erv e d pr o p orti o n. D e p e n di n g o n t h e tr u e 
pr o p orti o n, t h e m ar gi n of err or t h us d efi n e d r a n g e d fr o m 3 % t o 7 % ov er all ( N = 2 0 0), a n d fr o m 5 % t o 1 0 % 
p er str at u m  w h e n t h e t w o str at a ar e t h e s a m e siz e  ( N = 1 0 0) (fi g ur e). If t h e s m all er str at u m h as o nly 5 0 

 
C o nfi d e nti al  
P a g e 4 7  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
p artici p a nts, t h e m ar gi n of err or will r a n g e fr o m 6 % t o 1 4 %. O ur s a m pl e siz e, t h er ef or e, will b e s uffici e nt t o 
pr ovi d e a n acc ur at e esti m at e of t h e tr u e pr o p orti o n.   

 
C o nfi d e nti al  
P a g e 4 8  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
1 4. 
I d e ntific ati o n a n d Acc ess t o S o urc e D at a 
1 4. 1 
S o urc e D at a  
S o urc e d oc u m e nts  a n d s o urc e d at a ar e  t h e ori gi n al d oc u m e nt ati o n w h er e s u bj ect i nf or m ati o n, visits 
c o ns ult ati o ns, ex a min ati o ns a n d ot h er i nf or m ati o n  ar e r ec or d e d .   D oc u m e nt ati o n of s o urc e d at a is 
n ec ess ary f or t h e r ec o nstr ucti o n, ev al u ati o n a n d v ali d ati o n of cli nic al fi n d i n gs, o bs erv ati o ns,  a n d ot h er 
acti viti es d uri n g a cli nic al tri al.   
1 4. 2 
Acc ess t o S o urc e D at a  
T h e sit e i nv esti g at ors a n d sit e st aff will m a k e all s o urc e d at a av ail a bl e t o t h e D AI T/ NI AI D  a n d t h eir 
r e pr es e nt ati v es as w ell as t o r el ev a nt h e alt h a ut h oriti es ( F o o d an d Dr u g A d mi nistr ati o n). A ut h oriz e d 
r e pr es e nt ati v es as n ot e d a b ov e ar e b o u n d t o m ai nt ai n t h e strict c o nfi d e nti alit y of m e dic al a n d r es e arc h 
i nf or m ati o n t h at m ay b e li n k e d t o i d e ntifi e d i n divi d u als. 

 
C o nfi d e nti al  
P a g e 4 9  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
1 5. 
Q u alit y Ass ur a nc e a n d Q u alit y C o ntr ol  
Q u alit y c o ntr ol ( Q C) pr oc e d ur es will b e i m pl e m e nt e d b e gi n ni n g wit h t h e d at a e ntry s yst e m a n d d at a Q C 
c h ec ks. A n y missi n g d at a or d at a a n o m ali es will b e c o m m u nic at e d t o t h e sit e f or cl arific ati o n/r es ol uti o n.  
 
F oll o wi n g writt e n St a n d ar d O p er ati n g Pr oc e d ur es (S O Ps), t h e m o nit ors will v erify t h at t h e cli nic al tri al is 
c o n d uct e d, d at a ar e g e n er at e d,  a n d bi ol o gic al s p eci m e ns ar e c oll ect e d, d oc u m e nt e d (r ec or d e d), a n d 
r e p ort e d i n c o m pli a nc e wit h t h e pr ot oc ol, I nt er n ati o n al C o nf er e nc e o n H ar m o nis ati o n G o o d Cli nic al 
Pr actic e (I C H G C P), a n d a p plic a bl e r e g ul at ory r e q uir e m e nts . 
 
T h e i nv esti g ati o n al sit e will pr ovi d e dir ect acc ess t o all tri al r el at e d sit es, s o urc e d at a/ d oc u m e nts, a n d 
r e p orts f or t h e p ur p os e of m o nit ori n g a nd a u diti n g b y t h e s p o ns or, a n d i ns p ecti o n by l oc al a n d r e g ul at ory 
a ut h oriti es.  

 
C o nfi d e nti al  
P a g e 5 0  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
1 6. 
Pr ot oc ol D e vi ati o ns  
1 6. 1 
Pr ot oc ol D e vi ati o n  D efi niti o ns  
Pr ot oc ol D e vi ati o n  –  T h e i nv esti g at ors a n d sit e st aff will c o n d uct t h e st u dy i n acc or d a nc e wit h  t h e pr ot oc ol; 
n o d e vi ati o ns fr o m t h e pr ot oc ol ar e p er mitt e d .  A n y c h a n g e, div er g e nc e, or d e p art ur e fr o m t h e st u dy 
d esi g n or pr oc e d ur es c o nstit ut es a pr ot oc ol d evi ati o n .  As a r es ult of a ny d evi ati o n, c orr ectiv e acti o ns will 
b e d e v el o p e d by t h e sit e a n d i m pl e m e nt e d pr o m ptl y.  
 
M aj or Pr ot oc ol D e vi ati o n ( Pr ot oc ol Vi ol ati o n) - A P r ot oc ol V i ol ati o n is a d evi ati o n fr o m t h e I R B a p pr ov e d 
pr ot oc ol t h at m ay aff ect t h e s u bj ect's ri g hts, s af et y, or w ell -b ei n g a n d/ or t h e c o m pl et e n ess, acc ur ac y a n d 
r eli a bilit y of t h e st u dy d at a.  I n a d diti o n, pr ot oc ol vi ol ati o ns i ncl u d e willf ul or k n o wi n g br e ac h es  of h u m a n 
s u bj ect pr ot ecti o n r e g ul ati o ns, or p olici es, a n y acti o n t h at is i nc o nsist e nt wit h t h e NI H H u m a n R es e arc h 
Pr ot ecti o n Pr o gr a m’s r es e arc h, m e dic al, a n d et hic al pri nci pl es , a n d a s eri o us or c o n ti n ui n g n o nc o m pli a nc e 
wit h f e d er al, st at e, l oc al or i nstit uti o n al h u m a n s u bj ect pr ot ecti o n r e g ul ati o ns, p olici es, or pr oc e d ur es .  
 
N o n -M aj or  Pr ot oc ol D e vi ati o n  - A n o n -m aj or  pr ot oc ol d evi ati o n is a n y c h a n g e, div er g e nc e, or d e p art ur e 
fr o m t h e st u dy d esi g n or pr oc e d ur es of a r es e arc h pr ot oc ol t h at d o es n ot  h av e a m aj or i m p act o n t h e 
s u bj ect's ri g hts, s af et y or w ell-b ei n g, or t h e c o m pl et e n ess, acc ur ac y,  a n d r eli a bilit y of t h e st u d y d at a.  
1 6. 2 
R e p orti n g a n d M a n a gi n g Pr ot oc ol D e vi ati o ns  
T h e st u dy sit e pri nci p al i nv esti g at or  h as t h e r es p o nsi bilit y t o i d e ntify, d oc u m e nt a n d r e p ort pr ot oc ol 
d e vi ati o ns  as dir ect e d b y t h e st u dy S p o ns or .  H o w ev er, pr ot oc ol d evi ati o ns m ay als o b e i d e ntifi e d d uri n g 
sit e m o nit ori n g visits or d uri n g ot h er f or ms of st u dy c o n d uct r evi e w.  

 
C o nfi d e nti al  
P a g e 5 1  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
1 7. 
Et hic al C o nsi d er ati o ns a n d C o m pli a nc e wit h G o o d Cli nic al Pr actic e  
1 7. 1 
St at e m e nt of C o m pli a nc e  
T his cli nic al st u dy will b e c o n d uct e d usi n g g o o d cli nic al pr actic e ( G C P), as d eli n e at e d i n G ui d a nc e f or 
I n d ustry: E 6 G o o d Cli nic al Pr actic e C o ns oli d at e d G ui d a nc e, a n d acc or di n g t o t h e crit eri a s p ecifi e d i n t his 
st u dy pr ot oc ol.  B ef or e st u dy i niti ati o n, t h e pr ot oc ol a n d t h e i nf or m e d c o ns e nt d oc u m e nts will b e r evi e w e d 
a n d a p pr ov e d by  I nstit uti o n al R e vi e w B o ar d (I R B) .  A n y a m e n d m e nts t o t h e pr ot oc ol or t o t h e c o ns e nt 
m at eri als will  als o b e a p pr ov e d b y t h e I R B b ef or e t h e y ar e i m pl e m e nt e d.  
1 7. 2 
I nf or m e d C o ns e nt Pr oc ess 
T h e c o ns e nt pr oc ess will pr ovi d e i nf or m ati o n a b o ut t h e st u dy t o a pr os p ectiv e p artici p a nt a n d will all o w 
a d e q u at e ti m e f or r evi e w a n d disc ussi o n pri or t o his/ h er  d ecisi o n. T h e pri nci p al i nv esti g at or or d esi g n e e 
list e d o n t h e F D A F or m 1 5 7 2  will r evi e w t h e c o ns e nt a n d a ns w er q u esti o ns. T h e pr os p ectiv e p artici p a nt will 
b e t ol d t h at b ei n g i n t h e tri al is v ol u nt ary a n d t h at h e or s h e m ay wit h dr a w fr o m t h e st u dy at a n y ti m e, f or 
a ny r e as o n.  All p artici p a nts will  r e a d, si g n, a n d d at e a c o ns e nt f or m b ef or e u n d er g oi n g a n y st u dy 
pr oc e d ur es.   C o ns e nt m at eri als will  b e pr es e nt e d i n  t h e p artici p a nts’ pri m ary l a n g u a g e. A c o p y of t h e si g n e d 
c o ns e nt f or m will  b e giv e n t o t h e p artici p a nt.  
T h e c o ns e nt pr oc ess will b e  o n g oi n g,  a n d a ny n e w fi n di n gs will b e c o m m u nic at e d t o t h e p artici p a nts. T h e  
c o ns e nt f or m will  b e r evis e d w h e n i m p ort a nt n e w s af et y i nf or m ati o n is av ail a bl e, t h e pr ot oc ol is a m e n d e d, 
a n d/ or n e w i nf or m ati o n b ec o m es av ail a bl e t h at m ay aff ect p artici p ati o n i n t h e st u dy.  
1 7. 3 
Pri v ac y a n d C o nfi d e nti alit y  
A p artici p a nt’s priv ac y a n d c o nfi d e nti alit y will b e r es p ect e d t hr o u g h o ut t h e st u dy.  E ac h p artici p a nt will b e 
assi g n e d a u ni q u e i d e ntific ati o n n u m b er a n d t h es e n u m b ers r at h er t h a n n a m es will b e us e d t o c oll ect, 
st or e, a n d r e p ort p artici p a nt i nf or m ati o n.  Sit e p ers o n n el will  n ot tr a ns mit d oc u m e nts c o nt ai ni n g p ers o n al 
h e alt h i d e ntifi ers ( P HI) t o t h e st u dy s p o ns or or t h eir r e pr es e nt ativ es.  

 
C o nfi d e nti al  
P a g e 5 2  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
1 8. 
P u blic ati o n P olic y  
T h e p u blic ati o n g ui d eli n es a n d p olici es sti p ul at e d i n t h e gr a nt will a p pl y t o t his pr ot oc ol.  
 
 
 

 
C o nfi d e nti al  
P a g e 5 3  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
1 9. 
R ef er e nc es  
1.
F a v a A, C ucc hi ari D, M o nt er o N, T o a p a nt a N, C e nt ell as FJ, Vil a -S a nt a n dr e u A, C ol o m a A, M e n e g hi ni M, 
M a n o n ell es A, S ell ar es J, T orr es I, G el pi R, L or e nz o I, V e nt ur a -A g ui ar P, C of a n F, T orr e gr os a J V, P er ell o M, 
F ac u n d o C, S er o n D, O p p e n h ei m er F, B est ar d O, Cr uz a d o J M, M or es o F, M elilli E. Cli nic al c h ar act eristics a n d risk 
f act ors f or s ev er e C O VI D-1 9 i n h os pit aliz e d ki d n e y tr a ns pl a nt r eci pi e nts: A m ultic e ntric c o h ort st u dy. A m J 
Tr a ns pl a nt. 2 0 2 0; 2 0( 1 1): 3 0 3 0 -4 1. E p u b 2 0 2 0/ 0 8/ 1 1. d oi: 1 0. 1 1 1 1/ ajt. 1 6 2 4 6. P u b M e d P MI D: 3 2 7 7 7 1 5 3; P M CI D: 
P M C 7 4 3 6 9 0 8.  
2.
Hil br a n ds L B, D uiv e nv o or d e n R, V art P, Fr a nss e n C F M, H e m m el d er M H, J a g er KJ, Ki e n e k er L M, N o or dzij M, P e n a 
MJ, Vri es H, Arr oy o D, C ovic A, Cr es p o M, G offi n E, Isl a m M, M assy Z A, M o nt er o N, Oliv eir a J P, R oc a M u n oz A, 
S a nc h ez J E, Sri d h ar a n S, Wi nz el er R, G a ns ev o ort R T, C oll a b or at ors E. C O VI D -1 9 -r el at e d m ort alit y i n ki d n e y 
tr a ns pl a nt a n d di alysis p ati e nts: r es ults of t h e E R A C O D A c oll a b or ati o n. N e p hr ol Di al Tr a ns pl a nt. 
2 0 2 0; 3 5( 1 1): 1 9 7 3 -8 3. E p u b 2 0 2 0/ 1 1/ 0 6. d oi: 1 0. 1 0 9 3/ n dt/ gf a a 2 6 1. P u b M e d P MI D: 3 3 1 5 1 3 3 7; P M CI D: 
P M C 7 6 6 5 6 2 0.  
3.
R a v a n a n R, C all a g h a n CJ, M u mf or d L, Us hir o -L u m b I, T h or b ur n D, C as e y J, Fri e n d P, P ar a m es h w ar J, C urri e I, 
B ur n a p p L, B a k er R, D u dl e y J, O nisc u G C, B er m a n M, As h er J, H arv e y D, M a n ar a A, M a n as D, G ar di n er D, 
F orsyt h e JL R. S A R S -C o V -2 i nf ecti o n a n d e arl y m ort alit y of w aitlist e d a n d s oli d or g a n tr a ns pl a nt r eci pi e nts i n 
E n gl a n d: A n ati o n al c o h ort st u dy. A m J Tr a ns pl a nt. 2 0 2 0; 2 0( 1 1): 3 0 0 8 -1 8. E p u b 2 0 2 0/ 0 8/ 1 2. d oi: 
1 0. 1 1 1 1/ ajt. 1 6 2 4 7. P u b M e d P MI D: 3 2 7 8 0 4 9 3;  P M CI D: P M C 7 4 3 6 9 1 9.  
4.
R aj a M A, M e n d oz a M A, Vill avic e nci o A, A nj a n S, R e y n ol ds J M, Kitti pi b ul V, F er n a n d ez A, G u err a G, C a m ar g o J F, 
Si mki ns J, M orris MI, A b b o L A, N at ori Y. C O VI D -1 9 i n s oli d or g a n tr a ns pl a nt r eci pi e nts: A syst e m atic r e vi e w a n d 
m et a -a n alysis o f c urr e nt lit er at ur e. Tr a ns pl a nt R ev ( Orl a n d o). 2 0 2 1; 3 5( 1): 1 0 0 5 8 8. E p u b 2 0 2 0/ 1 1/ 2 8. d oi: 
1 0. 1 0 1 6/j.trr e. 2 0 2 0. 1 0 0 5 8 8. P u b M e d P MI D: 3 3 2 4 6 1 6 6; P M CI D: P M C 7 6 6 6 5 4 2.  
5.
W a d ei H M, G o n w a T A, L e o ni J C, S h a h S Z, Asl a m N, S p eic h er LL. C O VI D -1 9 i nf ecti o n i n S oli d Or g a n Tr a ns pl a nt 
R eci pi e nts aft er S A R S -C o V -2 v acci n ati o n. A m J Tr a ns pl a nt. 2 0 2 1. E p u b 2 0 2 1/ 0 4/ 2 4. d oi: 1 0. 1 1 1 1/ ajt. 1 6 6 1 8. 
P u b M e d P MI D: 3 3 8 9 0 4 1 0.  
6.
P ol ac k F P, T h o m as SJ, Kitc hi n N, A bs al o n J, G urt m a n A, L oc k h art S, P er ez JL, P er ez M arc G, M or eir a E D, Z er bi ni 
C, B ail e y R, S w a ns o n K A, R oyc h o u d h ury S, K o ury K, Li P, K ali n a W V, C o o p er D, Fr e nc k R W, Jr., H a m mitt LL, T ur eci 
O, N ell H, Sc h a ef er A, U n al S, Tr es n a n D B, M at h er S, D or mitz er P R, S a hi n U, J a ns e n K U, Gr u b er W C, Gr o u p C C T. 
S af et y a n d Effic ac y of t h e B N T 1 6 2 b 2 m R N A C o vi d-1 9 V ac ci n e. N E n gl J M e d. 2 0 2 0; 3 8 3( 2 7): 2 6 0 3 -1 5. E p u b 
2 0 2 0/ 1 2/ 1 1. d oi: 1 0. 1 0 5 6/ N EJ M o a 2 0 3 4 5 7 7. P u b M e d P MI D: 3 3 3 0 1 2 4 6; P M CI D: P M C 7 7 4 5 1 8 1.  
7.
T h o m ps o n M G, B ur g ess JL, N al e w a y AL, Ty n er HL, Y o o n S K, M e ec e J, Ols h o L E W, C a b a n -M arti n ez AJ, 
F o wl k es A, L utric k K, K u ntz JL, D u n ni g a n K, O d e a n MJ, H e g m a n n K T, St ef a nski E, E d w ar ds LJ, Sc h a ef er -
S oll e N, Gr a nt L, Elli n gs o n K, Gr o o m H C, Z u ni e T, T hi es e M S, Iv acic L, W esl e y M G, L a m b ert e J M, S u n X, 
S mit h M E, P hilli ps AL, Gr o ov er K D, Y o o Y M, G er al d J, Br o w n R T, H erri n g M K, J os e p h G, B eit el S, M orrill 
T C, M a k J, Riv ers P, H arris K M, H u nt D R, Arv a y ML, K utt y P, Fry A M, G a gl a ni M. I nt eri m Esti m at es of 
V acci n e Eff ectiv e n ess of B N T 1 6 2 b 2 a n d m R N A -1 2 7 3 C O VI D -1 9 V acci n es i n Pr ev e nti n g S A R S -C o V -2 
I nf ecti o n A m o n g H e alt h C ar e P ers o n n el, First R es p o n d ers, a n d Ot h er Ess e nti al a n d Fr o ntli n e W ork ers - 
Ei g ht U. S. L oc ati o ns, D ec e m b er 2 0 2 0 -M arc h 2 0 2 1. M M W R M or b M ort al W kly R e p. 2 0 2 1 A pr 
2; 7 0( 1 3): 4 9 5 -5 0 0. d oi: 1 0. 1 5 5 8 5/ m m wr. m m 7 0 1 3 e 3. P MI D: 3 3 7 9 3 4 6 0; P M CI D: P M C 8 0 2 2 8 7 9.  
8.
B a d e n L R, El S a hl y H M, Essi n k B, K otl off K, Fr e y S, N ov a k R, Di e m ert D, S p ect or S A, R o u p h a el N, Cr e ec h C B, 
Mc G etti g a n J, K h et a n S, S e g all N, S olis J, Br osz A, Fi err o C, Sc h w artz H, N e uzil K, C or e y L, Gil b ert P, J a n es H, 
F oll m a n n D, M ar ovic h M, M asc ol a J, P ol ak o wski L, L e d g er w o o d J, Gr a h a m B S, B e n n ett H, P aj o n R, K ni g htl y C, 
L e a v B, D e n g W, Z h o u H, H a n S, Iv arss o n M, Mill er J, Z a ks T, Gr o u p C S. Effic ac y a n d S af et y of t h e m R N A -1 2 7 3 
S A R S -C o V -2 V acci n e. N E n gl J M e d. 2 0 2 1; 3 8 4( 5): 4 0 3 -1 6. E p u b 2 0 2 0/ 1 2/ 3 1. d oi: 1 0. 1 0 5 6/ N EJ M o a 2 0 3 5 3 8 9. 
P u b M e d  P MI D: 3 3 3 7 8 6 0 9; P M CI D: P M C 7 7 8 7 2 1 9.  
9.
D a g a n N, B ar d a N, K e pt e n E, Mir o n O, P erc hik S, K atz M A, H er n a n M A, Li psitc h M, R eis B, B alic er R D. B N T 1 6 2 b 2 
m R N A C ovi d -1 9 V acci n e i n a N ati o n wi d e M ass V acci n ati o n S etti n g. N E n gl J M e d. 2 0 2 1; 3 8 4( 1 5): 1 4 1 2 -2 3. E p u b 
2 0 2 1/ 0 2/ 2 5. d oi: 1 0. 1 0 5 6/ N EJ M o a 2 1 0 1 7 6 5. P u b M e d P MI D: 3 3 6 2 6 2 5 0; P M CI D: P M C 7 9 4 4 9 7 5.  

 
C o nfi d e nti al  
P a g e 5 4  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
1 0. B e n ot m a n e I, G a uti er -V ar g as G, C o g n ar d N, Ol a g n e J, H ei b el F, Br a u n -P arv ez L, M artzl off J, P erri n P, M o uli n B, 
F afi -Kr e m er S, C aill ar d S. L o w i m m u niz ati o n r at es a m o n g ki d n e y tr a ns p l a nt r eci pi e nts w h o r ec eiv e d t w o d os es 
of t h e m R N A -1 2 7 3 S A R S -C o V -2 v acci n e. Ki d n e y I nt. 2 0 2 1. E p u b 2 0 2 1/ 0 4/ 2 3. d oi: 1 0. 1 0 1 6/j. ki nt. 2 0 2 1. 0 4. 0 0 5. 
P u b M e d P MI D: 3 3 8 8 7 3 1 5; P M CI D: P M C 8 0 5 5 9 2 1.  
1 1. B o y arsk y BJ, W er b el W A, Av ery R K, T o bi a n A A R, M assi e A B, S e g ev DL, G ar o nzi k -W a n g J M. I m m u n o g e nicit y of a 
Si n gl e D os e of S A R S -C o V -2 M ess e n g er R N A V acci n e i n S oli d Or g a n Tr a ns pl a nt R eci pi e nts. J A M A. 2 0 2 1. E p u b 
2 0 2 1/ 0 3/ 1 6. d oi: 1 0. 1 0 0 1/j a m a. 2 0 2 1. 4 3 8 5. P u b M e d P MI D: 3 3 7 2 0 2 9 2; P M CI D: P M C 7 9 6 1 4 6 3.  
1 2. B o y arsk y BJ, W er b el W A, Av ery R K , T o bi a n A A R, M assi e A B, S e g ev DL, G ar o nzi k-W a n g J M. A nti b o d y R es p o ns e t o 
T w o -D os e S A R S -C o V -2 M ess e n g er R N A V acci n e S eri es i n S oli d Or g a n Tr a ns pl a nt R eci pi e nts. J A M A. Acc e pt e d 2 6 
A pril 2 0 2 1.  
1 3. M ari n a ki S, A d a m o p o ul os S, D e gi a n nis D, R o uss os S, P avl o p o ul o u I D , H atz a kis A, B ol etis I N. I m m u n o g e nicit y of 
S A R S -C o V -2 B N T 1 6 2 b 2 v acci n e i n s oli d or g a n tr a ns pl a nt r eci pi e nts. A m J Tr a ns pl a nt. 2 0 2 1. E p u b 2 0 2 1/ 0 4/ 1 8. 
d oi: 1 0. 1 1 1 1/ ajt. 1 6 6 0 7. P u b M e d P MI D: 3 3 8 6 4 7 2 2.  
1 4. Gr u p p er A, R a bi n o wic h L, Sc h w artz D, Sc h w artz I F, B e n -Y e h oy a d a M, S h as h ar M, K atc h m a n E, H al p eri n T, T ur n er 
D, G oy k h m a n Y, S hi b ol et O, L ev y S, H o uri I, B ar uc h R, K atc h m a n H. R e d uc e d h u m or al r es p o ns e t o m R N A S A R S -
C ov -2 B N T 1 6 2 b 2 v acci n e i n ki d n e y tr a ns pl a nt r eci pi e nts wit h o ut pri or ex p os ur e t o t h e vir us. A m J Tr a ns p l a nt. 
2 0 2 1. E p u b 2 0 2 1/ 0 4/ 1 9. d oi: 1 0. 1 1 1 1/ ajt. 1 6 6 1 5. P u b M e d P MI D: 3 3 8 6 6 6 7 2.  
1 5. C h av ar ot N, O u e dr a ni A, M ari o n O, L er u ez -Vill e M, Vill ai n E, B a aziz M, D el B ell o A, B ur g er C, S b err o -S o uss a n R, 
M arti n ez F, C h at e n o u d L, A br av a n el F, A n glic h e a u D, Iz o p et J, C o u at C, Z u b er J, L e g e n dr e C, L a nt er ni er F, K a m ar 
N, Sc e ml a A. P o or A nti -S A R S -C o V -2 H u m or al a n d T -c ell R es p o ns es Aft er 2 I nj ecti o ns of m R N A V acci n e i n Ki d n e y 
Tr a ns pl a nt R eci pi e nts Tr e at e d wit h B el at ac e pt. Tr a ns pl a nt ati o n. 2 0 2 1. E p u b 2 0 2 1/ 0 4/ 0 9. d oi: 
1 0. 1 0 9 7/ T P. 0 0 0 0 0 0 0 0 0 0 0 0 3 7 8 4. P u b M e d P MI D: 3 3 8 3 1 9 4 1.  
1 6. Ri nc o n -Ar ev al o H, C h oi M, St ef a nski AL, H all ec k F, W e b er U, Sz eli nski F, J a hrs d örf er B, Sc hr ez e n m ei er H, L u d wi g 
C, S attl er S, K otsc h K, P ot e k hi n A, C h e n Y, B ur m est er G R, Ec k ar dt K U, G u err a G M, D ur e k P, H ei nric h F, F e rr eir a-
G o m es M, R a d br uc h A, B u d d e K, Li n o A C, M as hr e g hi M F, Sc hr ez e n m ei er E, D ör n er T. I m p air e d a nti g e n -s p ecific 
m e m ory B c ell a n d pl as m a c ell r es p o ns es i ncl u di n g l ac k of s p ecific I g G u p o n S A R S -C o V -2 B N T 1 6 2 b 2 v acci n ati o n 
a m o n g Ki d n e y Tr a ns pl a nt a n d Di al ysi s p ati e nts. m e d Rxiv 2 0 2 1. 0 4. 1 5. 2 1 2 5 5 5 5 0; d oi: 
htt ps:// d oi. or g/ 1 0. 1 1 0 1/ 2 0 2 1. 0 4. 1 5. 2 1 2 5 5 5 5 0 1 7.  
1 7. N at ori Y, S hi ots u k a M, Sl o m ovic J, H osc hl er K, F err eir a V, As ht o n P, R otst ei n C, Lill y L, Sc hiff J, Si n g er L, H u m ar A, 
K u m ar D. A D o u bl e -Bli n d, R a n d o miz e d Tri al of  Hi g h -D os e vs St a n d ar d -D os e I nfl u e nz a V acci n e i n A d ult S oli d -
Or g a n Tr a ns pl a nt R eci pi e nts. Cli n I nf ect Dis. 2 0 1 8; 6 6( 1 1): 1 6 9 8 -7 0 4. E p u b 2 0 1 7/ 1 2/ 1 9. d oi: 1 0. 1 0 9 3/ci d/cix 1 0 8 2. 
P u b M e d P MI D: 2 9 2 5 3 0 8 9.  
1 8. N e v e ns F, Z uc k er m a n J N, B urr o u g hs A K, J u n g M C, B a y as J M, K all i n o wski B, Riv as E F, D uv o ux C, N e u h a us P, 
S ali b a F, B uti M, Z arski J P, P o ns F, V a nl e m m e ns C, H a mti a ux V, St off el M. I m m u n o g e nicit y a n d s af et y of a n 
ex p eri m e nt al a dj uv a nt e d h e p atitis B c a n di d at e v acci n e i n liv er tr a ns pl a nt p ati e nts. Liv er Tr a ns pl. 
2 0 0 6; 1 2( 1 0): 1 4 8 9 -9 5. E p u b 2 0 0 6/ 0 9/ 1 2. d oi: 1 0. 1 0 0 2/lt. 2 0 8 3 6. P u b M e d P MI D: 1 6 9 6 4 5 9 5.  
1 9. Vi nk P, R a m o n T orr ell J M, S a nc h ez Fr uct u os o A, Ki m SJ, Ki m SI, Z altz m a n J, Ortiz F, C a m pist ol Pl a n a J M, 
F er n a n d ez R o dri g u ez A M, R e b oll o R o dri g o H, C a m pi ns M arti M, P er ez R, G o nz al ez  R o nc er o F M, K u m ar D, 
C hi a n g YJ, D o uc ett e K, Pi p el e ers L, A g u er a M or al es ML, R o dri g u ez -F err er o ML, S ecc hi A, Mc N eil S A, C a m p or a L, 
Di P a ol o E, El I drissi M, L o p ez -F a u q u e d M, S al a u n B, H ei n e m a n T C, O ost v o g els L, Gr o u p Z S. I m m u n o g e nicit y a n d 
S af et y of t h e A d j uv a nt e d R ec o m bi n a nt Z ost er V acci n e i n C hr o nic all y I m m u n os u p pr ess e d A d ults F oll o wi n g R e n al 
Tr a ns pl a nt: A P h as e 3, R a n d o miz e d Cli nic al Tri al. Cli n I nf ect Dis. 2 0 2 0; 7 0( 2): 1 8 1 -9 0. E p u b 2 0 1 9/ 0 3/ 0 8. d oi: 
1 0. 1 0 9 3/ci d/ciz 1 7 7. P u b M e d P MI D: 3 0 8 4 3 0 4 6; P M CI D: P M C 6 9 3 8 9 8 2.  
2 0. B o e y L, C uri nc kx A, R o el a nts M, D er d eli nc kx I, V a n Wij n g a er d e n E, D e M u nt er P, V os R, K u y p ers D, V a n 
Cl e e m p ut J, V a n d er m e ul e n C. I m m u n o g e nicit y A n d S af et y Of T h e Ni n e -V al e nt H u m a n P a pill o m avir us V acci n e I n 
S oli d Or g a n Tr a ns pl a nt R eci pi e nts A n d Hiv -I nfect e d A d ults. Cli n I nf ect Dis. 2 0 2 0. E p u b 2 0 2 0/ 1 2/ 3 0. d oi: 
1 0. 1 0 9 3/ci d/ci a a 1 8 9 7. P u b M e d P MI D: 3 3 3 7 3 4 2 9.  
2 1. C h a pi n -B ar d al es J, G e e J, M y ers T. R e act o g e nicit y F oll o wi n g R ec ei pt of m R N A -B as e d C O VI D -1 9 V acci n es. J A M A. 
2 0 2 1. E p u b 2 0 2 1/ 0 4/ 0 6. d oi: 1 0. 1 0 0 1/j a m a. 2 0 2 1 . 5 3 7 4. P u b M e d P MI D: 3 3 8 1 8 5 9 2. 

 
C o nfi d e nti al  
P a g e 5 5  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
2 2. O u M T, B o y arsk y BJ, M ott er J D, Gr e e n b er g R S, T el es A T, R u d d y J A, Kr ac h M R, J ai n V S, W er b el W A, Av ery R K, 
M assi e A B, S e g ev DL, G ar o nzi k -W a n g J M. S af et y a n d R e act o g e nicit y of 2 D os es of S A R S -C o V -2 V acci n ati o n i n 
S oli d Or g a n Tr a n s pl a nt R eci pi e nts. Tr a ns pl a nt ati o n. 2 0 2 1. E p u b 2 0 2 1/ 0 4/ 1 7. d oi: 
1 0. 1 0 9 7/ T P. 0 0 0 0 0 0 0 0 0 0 0 0 3 7 8 0. P u b M e d P MI D: 3 3 8 5 9 1 5 1.  
2 3. L euri d a n E, V a n D a m m e P. H e p atitis B a n d t h e n e e d f or a b o ost er d os e. Cli n I nf ect Dis. 2 0 1 1 J ul 
1; 5 3( 1): 6 8 -7 5. d oi: 1 0. 1 0 9 3/ci d/cir 2 7 0. P MI D : 2 1 6 5 3 3 0 6. 
2 4. N a k as hi m a I, Ot a F, K o b ay as hi T, K at o O, K at o N. T h e eff ect of a nti g e n d os es a n d ti m e i nt erv als b et w e e n 
a nti g e n i nj ecti o ns o n s ec o n d ary, t erti ary a n d q u at er n ary a nti b o d y r es p o ns es. Est a blis h m e nt of 
h y p eri m m u niz ati o n wit h b ovi n e s er u m al b u mi n i n  mic e tr e at e d wit h c a ps ul ar p ol ys acc h ari d e of 
Kl e bsi ell a p n e u m o ni a e. I m m u n ol o g y. 1 9 7 4 M ar; 2 6( 3): 4 4 3 -5 4. P MI D: 4 1 3 7 2 5 3; P M CI D: P M C 1 4 2 3 2 0 4.  
2 5. B er e k C, Milst ei n C. M ut ati o n drift a n d r e p ert oir e s hift i n t h e m at ur ati o n of t h e i m m u n e r es p o ns e. 
I m m u n ol R e v. 1 9 8 7 Apr; 9 6: 2 3 -4 1. d oi: 1 0. 1 1 1 1/j. 1 6 0 0 -0 6 5x. 1 9 8 7.t b 0 0 5 0 7.x. P MI D: 3 2 9 8 0 0 7.  
2 6. M as o p ust D, H a SJ, V ezys V, A h m e d R. Sti m ul ati o n hist or y dict at es m e m ory C D 8 T c ell p h e n ot y p e: 
i m plic ati o ns f or pri m e-b o ost v acci n ati o n. J I m m u n ol. 2 0 0 6 J ul 1 5; 1 7 7( 2): 8 3 1 -9. d oi: 
1 0. 4 0 4 9/ ji m m u n ol. 1 7 7. 2. 8 3 1. P MI D: 1 6 8 1 8 7 3 7. 
2 7. J A M A o nli n e h e a d of pri nt M a y 5, 2 0 2 1, d oi: 1 0. 1 0 0 1/j a m a. 2 0 2 1. 7 4 8 9 
2 8. C h av ar ot et al, Tr a ns pl a nt ati o n o nli n e a h e a d of pri nt, D OI: 1 0. 1 0 9 7/ T P. 0 0 0 0 0 0 0 0 0 0 0 0 3 7 8 4.  
2 9. W u K, W er n er A P, M oliv a JI, K oc h M, C h oi A, St e w art -J o n es G B E, Be n n ett H, B o y o gl u -B ar n u m S, S hi W, Gr a h a m 
B S, C arfi A, C or b ett K S, S e d er R A, E d w ar ds D K. m R N A -1 2 7 3 v acci n e i n d uc es n e utr alizi n g a nti b o di es a g ai nst s pik e 
m ut a nts fr o m gl o b al S A R S -C o V -2 v ari a nts. bi o Rxiv. 2 0 2 1. E p u b 2 0 2 1/ 0 1/ 2 8. d oi: 1 0. 1 1 0 1/ 2 0 2 1. 0 1. 2 5. 4 2 7 9 4 8 . 
P u b M e d P MI D: 3 3 5 0 1 4 4 2; P M CI D: P M C 7 8 3 6 1 1 2.  
3 0. Xi e X, Li u Y, Li u J, Z h a n g X, Z o u J, F o nt es -G arfi as C R, Xi a H, S w a ns o n K A, C utl er M, C o o p er D, M e n ac h ery V D, 
W e a v er S C, D or mitz er P R, S hi P Y. N e utr aliz ati o n of S A R S -C o V -2 s pik e 6 9/ 7 0 d el eti o n, E 4 8 4 K a n d N 5 0 1 Y v ar i a nts 
b y B N T 1 6 2 b 2 v acci n e -elicit e d s er a. N at M e d. 2 0 2 1; 2 7( 4): 6 2 0 -1. E p u b 2 0 2 1/ 0 2/ 1 0. d oi: 1 0. 1 0 3 8/s 4 1 5 9 1 -0 2 1 -
0 1 2 7 0 -4. P u b M e d P MI D: 3 3 5 5 8 7 2 4.  
3 1. Bl u m e nt h al K G, R o bi ns o n L B, C a m ar g o C A, Jr., S h e n oy E S, B a n erji A, L a n d m a n A B, Wic k n er P. Ac ut e All er gic 
R e acti o ns t o m R N A C O VI D-1 9 V acci n es. J A M A. 2 0 2 1; 3 2 5( 1 5): 1 5 6 2 -5. E p u b 2 0 2 1/ 0 3/ 0 9. d oi: 
1 0. 1 0 0 1/j a m a. 2 0 2 1. 3 9 7 6. P u b M e d P MI D: 3 3 6 8 3 2 9 0; P M CI D: P M C 7 9 4 1 2 5 1.  
3 2. W u K, W er n er A P, K oc h M, C h oi A, N ar a y a n a n E, St e w art -J o n es G B E, C ol pitts T, B e n n ett H, B o y o gl u-B ar n u m S, 
S hi W, M oliv a JI, S ulliv a n NJ, Gr a h a m B S, C arfi A, C or b ett K S, S e d er R A, E d w ar ds D K. S er u m N e utr alizi n g Acti vit y 
Elicit e d b y m R N A -1 2 7 3 V acci n e. N E n gl J M e d. 2 0 2 1. E p u b 2 0 2 1/ 0 3/ 1 8. d oi: 1 0. 1 0 5 6/ N EJ Mc 2 1 0 2 1 7 9. P u b M e d 
P MI D: 3 3 7 3 0 4 7 1.  
3 3. F A C T S H E E T F O R H E AL T H C A R E P R O VI D E R S A D MI NI S T E RI N G V A C CI N E ( V A C CI N A TI O N P R O VI D E R S) E M E R G E N C Y 
U S E A U T H O RI Z A TI O N ( E U A) O F T H E M O D E R N A C O VI D -1 9 V A C CI N E T O P R E V E N T C O R O N A VI R U S DI S E AS E 2 0 1 9 
( C O VI D-1 9). F o u n d at: htt ps:// w w w. m o d er n atx.c o m/c ovi d 1 9v acci n e -e u a/ e u a -f act-s h e et-pr ovi d ers. p df .  
3 4. F A C T S H E E T F O R H E AL T H C A R E P R O VI D E R S A D MI NI S T E RI N G V A C CI N E ( V A C CI N A TI O N P R O VI D E R S) 
E M E R G E N C Y U S E A U T H O RI Z A TI O N ( E U A) O F T H E P FI Z E R -BI O N T E C H C O VI D -1 9 V A C CI N E T O P R E V E N T 
C O R O N A VI R U S DI S E AS E 2 0 1 9 ( C O VI D -1 9). F o u n d at: htt ps:// w w w.f d a. g ov/ m e di a/ 1 4 4 4 1 3/ d o w nl o a d .  
3 5. Ts a p e p as D, P a g et K, M o h a n S, C o h e n DJ, H us ai n S A, Cli nic all y Si g nific a nt C O VI D -1 9 F oll o wi n g S A R S -
C o V -2 V acci n ati o n i n Ki d n e y Tr a ns pl a nt R eci pi e nts, A m eric a n J o ur n al of Ki d n e y Dis e as es ( 2 0 2 1), d oi : 
htt ps:// d oi. or g/ 1 0. 1 0 5 3/j. aj k d. 2 0 2 1. 0 5. 0 0 4 . 
3 6. O u M T, B o y arsk y BJ, M ott er J D, Gr e e n b er g R S, T el es A T, R u d d y J A, Kr ac h M R, J ai n V S, W er b el W A, 
Av ery R K, M assi e A B, S e g ev DL, G ar o nzi k -W a n g J M. S af et y a n d R e act o g e nicit y of 2 D os es of S A R S -C o V -2 
V acci n ati o n i n S oli d Or g a n Tr a ns pl a nt R eci pi e nts. Tr a ns pl a nt ati o n. 2 0 2 1 A pr 9. d oi: 
1 0. 1 0 9 7/ T P. 0 0 0 0 0 0 0 0 0 0 0 0 3 7 8 0. E p u b a h e a d of pri nt. P MI D: 3 3 8 5 9 1 5 1.  
3 7. J ac ks o n L A, A n d ers o n EJ, R o u p h a el N G, et al. A n m R N A V acci n e ag ai nst S A R S -C o V -2 - Pr eli mi n ary 
R e p ort. N E n gl J M e d. 2 0 2 0; 3 8 3( 2 0): 1 9 2 0 -1 9 3 1.  

 
C o nfi d e nti al  
P a g e 5 6  of 5 8  
C P A T -P St u d y
V er si o n 3. 0 /J a n u ar y 1 4 , 2 0 2 2
3 8. A m a n at F, St a dl b a u er D, Str o h m ei er S, et al. A s er ol o gic al ass a y t o d et ect S A R S -C o V -2 s er oc o nv ersi o n i n 
h u m a ns. m e d Rxiv. 2 0 2 0.  
3 9. D e p art m e nts of R es e arc h & D ev el o p m e nt a n d Pr o d uct M a n a g e m e nt, f or R oc h e Di a g n ostics S ol uti o ns, 
C or e L a b. C orr el ati o n b et w e e n El ecsys ® A nti -S A R S -C o V -2 S ass a y r es ults a n d t h e d et ecti o n of f u ncti o n al 
S A R S -C o V -2 n e utr alizi n g a nti b o di es. M e m o. 8 F e b 2 0 2 1.  
4 0. R es m a n R us K, K orv a M, K n a p N, Avsic Z u p a nc T, P olj a k M . P erf or m a nc e of t h e r a pi d hi g h-t hr o u g h p ut 
a ut o m at e d el ectr oc h e mil u mi n esc e nc e i m m u n o ass a y t ar g eti n g t ot al a nti b o di es t o t h e S A R S -C o V -2 s pik e 
pr ot ei n r ec e pt or bi n di n g d o m ai n i n c o m p aris o n t o t h e n e utr aliz ati o n ass a y. J Cli n Vir ol. 
2 0 2 1; 1 3 9: 1 0 4 8 2 0.  
4 1. K h o ury D S , Cr o m er D, R e y n al di A, et al. N e utr alizi n g a nti b o d y l ev els ar e hi g hly pr e dictiv e of i m m u n e 
pr ot ecti o n fr o m sy m pt o m atic S A R S -C o V -2 i nf ecti o n. N at M e d. 2 0 2 1.